To explore the protective effect of 12/15-lipoxygenase （12/15-LO） gene knockout（12/15-LOKO） on the kidney tissue of the obese mice induced by high-fat diet （HFD）， and to clarify its role in the progression of kidney disease.

A total of 16 12/15-LOKO mice and 16 WT mice were randomly divided into HFD group and standard diet （SFD） group，respectively，and there were 8 mice in each group. The mice in HFD group were fed with HFD，and the mice in SFD were fed with SFD， namely WT+HFD group， WT+SFD group， LOKO+HFD group， and LOKO+SFD group.The 24 h urine of mice in various groups was collected after feeding for 1， 8， and 14 weeks. The body weights， double kidney weights and tibia lengths of hind legs of mice in various groups were detected.The 24 h urine of the mice in various groups was collected after 1，8， and 14 week，the urinary protein level，urinary perotein creatinine ratios（PCR）， and urinary microalbumin creartinine ratio（ACR） of the mice were detected.The blood glucose levels of the mice in various groups were detected by glucose tolerance test （GTT），and the mRNA levels of adiponectin， tumor necrosis factor-α （TNF-α），interleukin-6 （IL-6），monocyte chemoattractant protein-1 （MCP-1）， plasminogen activator inhibitor-1 （PAI-1），and transforming growth factor-β1（TGF-β1） in kindey cortex tissue of the mice in various groups were detected by Real-time fluorescence quantitative PCR （RT-qPCR）method.ELISA method was used to detect the levels of adiponectin，TNF-α，IL-6，angioteinsinⅡ（AngⅡ）and insulin in serum of the mice in various groups.PAS staining was used to observe the pathomorphology of kidney tissue and glomerularareas of the mice in various groups，and Western blotting method was used to detect the expressions of TGF-β1 and PAI-1β proteins in kidney tissue of the mice in various groups.

The body weight， kidney weight and glomerular area of the mice in HFD group were significantly higher than those in SFD group （P<0.01），and the ACR and PCR of the mice in WT+HFD group were higher than those in SFD group （P<0.05）； compared with LOKO+HFD group， the fasting blood glucose level of the mice in WT+HFD group was increased （P<0.05）. The expression levels of TNF- α，IL-6，and MCP-1 mRNA in kidney cortex tissue of the mice in WT+HFD group were significantly higher than those in WT+SFD group （P<0.05）. Compared with LOKO+HFD group，the expression levels of IL-6 and MCP-1 mRNA in kidney cortex tissue of the mice in WT+HFD group were increased（P<0.05）， while the expression level of adiponectin mRNA was decreased significantly （P<0.05）. The expression levels of PAI-1 and TGF-β1 mRNA in kidney cortex tissue of the mice in WT+HFD group were higher than those of the mice in WT+SFD group（P<0.05）.The expression levels of PAI-1 and TGF-β1 mRNA in kidney cortex tissue of the mice in LOKO+HFD group were lower than those of the mice in WT+HFD group（P<0.01）.

12/15-LOKO can improve insulin resistance， proteinuria level and degree of glomerular hypertrophy of the obese mice， and its mechanism may be related to the inhibition the expressions of inflammatory factors such as TNF- α and IL-6 in kidney tissue and affecting the expressions of PAI-1 and TGF-β1 mRNA，so as to play a protective role in kidney.

To observe the effect of the sevoflurane exposure during pregnancy period on changes of the maternal behaviors of the offsprings of the mice， and to explore its possible mechanism.

Forty pregnant C57BL / 6 mice（gestational age： 15－16 d） were randomly divided into normal control group， 2% sevoflurane group， 2% sevoflurane + 1% H₂ group and 2% sevoflurane + 4% H₂ group， and there were 10 mice in each group. The mixed gas of 50% O₂ + 50% N₂ was used as the carrier gas. The treatment time of the mice in each group was 6 h·d^－1. After continuous treatment for 3 d，the pregnant mice in various groups were continued to be fed. The score of nest quality of the 1st-generation mice， the time of the mother mice to first sniff the pups， the time to retrieve the pubs and put into the nest and the survival rates of 2nd-generation exchange pups in various groups were observed. The levels of oxytocin and vasopressin in plasma of the mice in various groups were detected by ELISA method. The expression levels of c-Fos proto-oncogene （c-Fos），poly ADP ribose polymerase 1 （PARP1），cleaved PARP1， Caspase 3，and cleaved Caspase 3 proteins in the medial preoptic area in hypothalamus tissue of the 1st-generation mice in various groups were detected by Western blotting method.

The maternal behavioral observation results showed that there were no milk-fed-2nd-generation pups and unclean 2nd-generation pups in various groups. There was no significant difference in the scores of nest quality of the mother mice among various groups （P>0.05）. The time of the mother mice to first sniff the pups and the time to retriev the pups and put into the nest in 2% sevoflurane group was significantly longer than those in normal control group （P<0.05）. Compared with 2% sevoflurane group， the time of the mother mice to first sniff the pups and the time to retrieve the pups and put into the nest of the mice in 2% sevoflurane + 1% H₂ group were significantly decreased （P<0.05）. There were no significant differences in the time of the mother mice to first sniff the pups and the time to retrieve the pups and put into the nest of the mice between 2% sevoflurane + 4% H₂ group and normal control group （P>0.05）. There were no significant differences in the plasma levels of oxytocin and vasopressin of the pregnant mice among various groups （P>0.05）. There were no significant differences in the expression levels of c-Fos，PARP1， cleaved PARP1， Caspase 3，and cleaved Caspase 3 proteins in medial preoptic area in hypothalamus tissue of the 1st-generation mice among various groups （P>0.05）.

The exposure to clinical doses of sevoflurane during pregnancy period of the mice could not significantly affect the apoptosis in the medial preoptic area in hypothalamus tissue， but it does have an impact on the maternal behavior of the mice. In addition， H₂ has a protective effect against the sevoflurane-mediated abnormal maternal behavior.

To investigate the effect of Shenxianshengmai Oral Liquid on the release of reactive oxygen species （ROS） in sinoatrial node tissue of the sinoatrial node syndrome （SSS） mice and its regulation on cyclic nucleotide regulated cation channel protein subtype 4 （HCN4） ion channel， and to explore the mechanism of Shenxianshengmai Oral Liquid in improving the SSS.

A total of 30 C57B6 mice were randomly divided into sham operation group，SSS group，and Shenxianshengmai Oral Liquid treatment （SXSM） group， and there were 10 mice in each group. The SSS mice model was established by pumping angiotensinⅡ（ANGⅡ） with the Alzet osmotic pressure pump.The mice in SXSM group were given 0.2 mL of Shenxianshengmai Oral Liquid per day for 28 d. The electrocardiogram of the mice in various groups was observed and the heart rates were analyzed； HE and Masson staining methods were used to observe the pathomorphology of sinoatrial node tissue of the mice in various groups，immunofluorescence method was uesd to detect the levels of ROS and HCN4 in sinoatrial node tissue of the mice in various groups； Real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of voltage-gated Na⁺α subunit （SCN5A）， L-type voltage dependent calcium channels α 1C subunit protein （CACNα1C） and voltage dependent calcium channel α1G subunit protein （CACNα1G） mRNA in sinoatrial node tissue of the mice in various groups； Western blotting method was used to detect the expression levels of SCN5A，CACNα1C，CACNα1G，and HCN4 proteins in sinoatrial node tissue of the mice in various groups.

Compared with sham operation group， the heart rate of the mice in SSS group was decreased significantly （P<0.05）， the cells were dissolved and necrotic， there was no nucleus， and there was a large number of connective fiber tissue； the ROS level in sinoatrial node tissue was increased （P<0.05），the HCN4 level in sinoatrial node tissue was decreased （P<0.05）， the expression levels of SCN5A mRNA and protein in sinoatrial node tissue were decreased significantly （P<0.05），the expression levels of CACNα1C and CACNα1G mRNA and proteins in sinoatrial node tissue were increased significantly （P<0.05），and the expression level of HCN4 protein in sinoatrial node tissue was decreased significantly （P<0.05）；compared with SSS group， the heart rate of the mice in SXSM group was increased significantly（P<0.05），a small amount of connective fiber tissue showed hyperplasia， partial of the cells showed necrosis and dissolution， the ROS level in sinoatrial node tissue was decreased （P<0.05），the HCN4 level in sinoatrial node tissue was increased （P<0.05），the expression levels of SCN5A mRNA and protein in sinoatrial node tissue were increased （P<0.05），the expression levels of CACNα1C and CACNα1G mRNA and proteins in sinoatrial node tissue were decreased significantly （P<0.05），and the expression level of HCN4 protein in sinoatrial node tissue was increased significantly （P<0.05）.

Shenxianshengmai Oral Liquid can increase the heart rate， inhibit the release of ROS in sinoatrial node tissue of the SSS mice， and inhibit the fibrosis of the sinoatrial nodes. The mechanism is related to the regulation of HCN4 ion channels.

To explore the effect of microRNA-34a（miR-34a）on the osteogenic differentiation of the human periodontal ligament stem cells （PDLSCs）， and to clarify its mechanism.

The primary cultured PDLSCs were isolated and induced osteogenic differentiation. Then the PDLSCs were collected 0， 7 and 14 d after osteogenic differentiation. The expression levels of alkaline phosphatase （ALP）， Runt-related transcription factor 2 （Runx2）， and osteocalcin （OCN） mRNA in the PDLSCs were detected by Real-time fluorescence quantitative PCR（RT-qPCR） method.The expression level of a disintegrin and metalloprotease 10（ADAM10） protein in the PDLSCs was detected by Western blotting method. The PDLSCs were divided into blank control group， vector group，and miR-34a over-expression group. The expression levels of miR-34a in the PDLSCs in various groups were detected by RT-qPCR method， the targeted relationship between miR-34a and ADAM10 genes was verified by dual luciferase report system， and the expression levels of ADAM10 protein in the PDLSCs in various groups were detected by Western blotting method. After the PDLSCs were differentiated by osteogenesis， the formations of mineralized nodules in the PDLSCs in various groups were observed by Alizarin red staining， the expression levels of ALP， Runx2， and OCN mRNA in the PDLSCs in various groups were detected by RT-qPCR method， the ALP activities in the PDLSCs in various groups were detected by colorimetric method， the expression levels of Notch1， Notch intracellular domain （NICD）， and Hes1 proteins in the PDLSCs in various groups were detected by Western blotting method.

Compared with 0 d after osteogenic differentiation， the expression level of miR-34a and the expression levels of ALP， Runx2 and OCN mRNA in the PDLSCs at 7 and 14 d after osteogenic differentiation were gradually increased （P<0.05）， while the expression levels of ADAM10 protein were gradually decreased（P<0.05）.Compared with blank control group and vector group， the expression level of miR-34a in miR-34a over-expression group was significantly increased（P<0.05），while the expression level of ADAM10 protein was significantly decreased（P<0.05）. The results of dual luciferase reporter gene system showed that ADAM10 was a target gene of miR-34a in the PDLSCs. Compared with blank control group and vector group， the formation amount of calcified nodules， the ALP activity， and the expression levels of ALP， Runx2， and OCN mRNA in the PDLSCs in miR-34a over-expression group were significantly increased（P<0.05）， while the expression levels of Notch1， NICD， and Hes1 proteins were significantly decreased（P<0.05）.

Over-expression of miR-34a can inhibit the activity of Notch signaling pathway by targeting down-regulation of ADAM10， thus promote the osteogenic differentiation of the PDLSCs.

To investigate the intervention effect of astragalus polysaccharide （APS） on the pulmonary vascular inflammation of the rats with pulmonary hypertension （PAH） induced by monocrotaline （MCT）， and to clarify its mechanism.

Sixty male SD rats were randomly divided into control group， PAH group， Calpain-1 inhibitor group， NOD like receptor family protein 3 （NLRP3） inhibitor group， low dose of APS group（400 mg·kg^－1 APS），and high dose of APS group（800 mg·kg^－1 APS）.The PAH rat model was established by intraperitoneal injection of 60 mg·kg^－1MCT.The serum levels of interleukin-18 （IL-18） and interleukin-1 β（IL-1 β）of the rats in various groups were detected by ELISA method. HE staining was used to observe the pathomorphology of lung tissue of the rats in various groups.The right ventricular systolic pressure （RVSP）， right ventricular hypertrophy index （RVHI），the percentage of pulmonary arteriole wall thickness in total vessel diameter （WT%） and the percentage of pulmonary arteriole wall area in total vessel area （WA%）of the rats in various groups were measured.Immunohistochemistry staining was used to detect the expressions of Calpain-1 in lung tissue of the rats in various groups.The expression levels of B-cell lymphoma-2（Bcl-2），Bcl-2 assaciated X protein（Bax）， Caspase-3， NLRP3， apoptosis related particulate protein （ASC），Caspase-1， and Calpain-1 in lung tissue of the rats in various groups were detected by Western blotting method.

Compared with PAH group， the serum levels of IL-18 and IL-1β in low and high doses of APS groups and Calpain-1 inhibitor group were decreased （P<0.05）. The HE staining results showed that the morphology of lung tissue of the rats in control group was normal， and the cells did not fall off and proliferate， and there was no inflammatory cell infiltration； in PAH group， the endothelium of pulmonary arterioles fell off， the smooth muscle cells proliferated seriously， and a large number of inflammatory cells infiltrated in the alveolar cavity；the endothelium of pulmonary arterioles in low and high doses of APS groups， Calpain-1 inhibitor group and NLRP3 inhibitor group fell off slightly， the proliferation of smooth muscle cells and inflammatory cell infiltration were decreased. Compared with PAH group， the RVSP and RVHI of the rats in low and high doses of APS groups， Calpain-1 inhibitor group and NLRP3 inhibitor group were decreased significantly （P<0.05）.The immunohistochemistry staining results showed that compared with PAH group， the expression amounts of Calpain-1 in lung tissue of the rats in low and high doses of APS groups and Calpain-1 inhibitor group were decreased.Compared with PAH group，the Calpain-1 activities in lung tissue of the rats in low and high doses of APS groups and Calpain-1 inhibitor group were decreased（P<0.05）. The Western blotting results showed that compared with PAH group， the expression levels of Bax，Caspase-3，NLRP3， ASC，Caspase-1，and Calpain-1 proteins in lung tissue of the rats in low and high doses of APS groups， Calpain-1 inhibitor group， and NLRP3 inhibitor group were decreased （P<0.05）， and the expression levels of Bcl-2 protein were increased （P<0.05）.

APS has a protective effect on the pulmonary arteries of the PAH rats induced by MCT， and its mechanism may be related to the effect of APS on the expression of Calpain-1 protein in lung tissue of the PAH rats.

To explore the effect of palmitic acid （PA） on the lipid deposition in the skeletal muscle cells，and to discuss the optimum action concentration and time.

The C2C12 cells were divided into control group and different concentrations （50，75，100，and 125 μmol·L^－1） of PA groups when the C2C12 cells grew to 70%－80%. The C2C12 cells in different concentrations of PA groups were given growth media containing different concentrations of PA， while the C2C12 cells in control group were not treated with PA（0 μmol·L^－1 PA）.CCK-8 method was used to detect the cell proliferation activities of cells in various groups，the triglyceride （TG） levels in the C2C12 cells in various groups were detected， Oil Red O staining was used to observe the formation of lipid droplets in the C2C12 cells in various groups， and 2% horse serum was used to induce the cell differentiation and evaluate the differentiation of C2C12 cells in various groups.

Compared with control group， there were no significant differences in the proliferation activities of the C2C12 cells in 50， 75， and 100 μmol·L^－1 PA groups（P>0.05）， the proliferation activity of the C2C12 cells in 125 μmol·L^－1 PA group was decreased（P<0.01），the TG levels in the C2C12 cells in 50， 75 and 100 μmol·L^－1 PA groups were increased （P<0.01）， and the TG level in the C2C12 cells in 100 μmol·L^－1 PA group was increased significantly （P<0.01）.Compared with cultured for 24 h， the TG level in the C2C12 cells after treated with 100 μmol·L^－1 PA for 48 h was increased （P<0.01）. After differentiation and culture， more myotubes were formed in the C2C12 cells in PA groups and control group.

The lipid deposition in the C2C12 cells could be effectively promoted after cultured with 100 μmol·L^－1 PA for 48 h.

To explore the promotion effect of polygonum multiflorum （PM） extract on the differentiation of bone marrow mesenchymal stem cells（BMSCs） into osteoblasts and bone formation in the mice and its mechanism， and to provide the potential therapeutic targets and drugs for the treatment of osteoporosis （OP） caused by weightlessness in the astronauts.

Thirty 12-week-old male C57BL/6 mice were randomly divided into control group， weightlessness group and weightlessness + PM （200 mg·kg^－1·d^－1） group， and there were 10 mice in each group. After 4 weeks， the ratio of bone volume/tissue volume， the trabecular number， trabecular thickness，and trabecular space of the mice in various groups was detected by micro CT；the BMSCs of the weightlessness mice were obtained by flow sorting.The BMSCs were divided into control group（0 μmol·L^－1 PM） and 10，20，and 40 μmol·L^－1 PM groups.The expression levels of Runx family transcription factor 2 （Runx-2）， alkaline phosphatase （ALP） and Osterix， peroxisome proliferator activated receptor γ （PPARγ）mRNA in BMSCs of the mice in various groups were detected by Real-time fluorescence quantitative PCR（RT-qPCR）method，and the expression levels of Runx-2， ALP， Osterix， PPARγ，mitogen activated protein kinase （MEK）， phosphorylated MEK 1/2（p-MEK1/2）， extracellular regulated protein kinase （ERK） and phosphorylated ERK 1/2（p-ERK1/2） proteins in BMSCs of the mice in various groups were detected by Western blotting method.

Compared with control group， the ratio of bone volume / tissue volume of the mice in weightlessness group was decreased （P<0.01）， the trabecular number was decreased （P<0.01）， the trabecular thickness was decreased （P<0.05）， and the trabecular space was increased （P<0.01）. Compared with weightlessness group， the ratio of bone volume/tissue volume of the mice in weightlessness+PM group was increased （P<0.05），the trabecular number was increased （P<0.01）， the trabecular thickness was increased （P<0.05）， and the trabecular space was decreased （P<0.01）. Compared with weightlessness group， the number of BMSCs of the mice in weightlessness+PM group was increased （P<0.01）， the number of osteoblasts was increased （P<0.01）， the number of adipocytes was decreased （P<0.05）， and the number of osteoclasts was decreased （P<0.05）. Compared with control group， the expression levels of Runx-2， ALP， and Osterix mRNA in BMSCs of the mice in 10， 20， and 40 μmol·L^－1 PM groups were increased （P<0.05）， and the expression level of PPARγ mRNA was decreased （P<0.05）， the expression levels of Runx-2， ALP， and Osterix proteins were increased （P<0.05）， and the expression level of PPARγ protein was decreased （P<0.05）. Compared with control group， the expression levels of p-MEK1/2 and p-ERK1/2 proteins in BMSCs of the mice in 10 μmol·L^－1 PM group were increased （P<0.05）； compared with 10 μmol·L^－1PM group，the expression levels of p-MEK1 / 2 and p-ERK1 / 2 proteins in BMSCs of the mice in 20 μmol·L^－1 PM group were increased （P<0.05）； compared with 20 μmol·L^－1　PM group， the expression levels of p-MEK1/2 and p-ERK1 / 2 proteins in BMSCs of the mice in 40 μmol·L^－1 PM group were increased （P<0.05）.

The extract of PM can promote the differentiation of BMSCs into osteoblasts in the weightlessness mice by activating the MEK/ERK signaling pathway，and improve the bone mass and the micro-structure of trabeculae，relieve the OP caused by weightlessness.

To investigate the effects of angiotensin Ⅱ type 1 receptor （AT1R） blocker losartan on the myocardial injury and myocardial repair of the acute myocardial infarction （AMI） rats，and to clarify their mechanisms.

Forty-five rats were used to establish the AMI rat models by using the coronary artery ligation. A total of 39 rats were successfully modeled and were randomly divided into model group， AT1R blocker group， and carvedilol group， and there were 13 rats in each group. Another 13 rats were selected as sham operation group. The rats in AT1R blocker group were given 10 mg·kg^－1 losartan by gavage， and the rats in carvedilol group were given 10 mg·kg^－1 carvedilol by gavage. The left ventricular end systolic diamension（LVESD）， left ventricular end diastolic diamension （LVEDD） and left ventricular ejection fraction （LVEF） of the rats in various groups were detected by the small animal ultrasonic diagnostic system. The serum levels of creatine kinase isozyme-MB （CK-MB）， cardiac troponin I（cTnI）， lactate dehydrogenase （LDH） and brain natriuretic peptide precursors （Pro-BNP） of the rats in various groups were detected by ELISA method. 2，3，5-triphenyltetrazolium chloride （TTC） method was used to detect the percentages of myocardium infarction areas of the rats in various groups. HE staining was used to observe the morphology of myocardium tissue of the rats in various groups.TUNEL staining was used to detect the percentages of TUNEL positive cells of the rats in various groups. Immunohistochemical staining was used to detect the expressions of thioredoxin 1 （Trx1） and thioredoxin reductase 1 （TrxR1） in myocardium tissue of the rats in various groups.The protein expression levels of Trx1， TrxR1， nicotinyl adenine dinucleotide phosphate （NADPH）， cleaved Caspase 3， B-cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax） in myocardium tissue of the rats in various groups were detected by Western blotting method.

Compared with sham operation group， the LVESD and LVEDD of the rats in model group were increased（P<0.05）， while the LVEF was decreased （P<0.05）； the serum levels of CK-MB， cTnI， LDH， and Pro-BNP were increased （P<0.05）； the percentage of myocardium infarction area was increased （P<0.05）； the pathological phenomena appeared in the myocardium tissue， and the percentage of TUNEL positive cells was increased （P<0.05）； the expression level of Trx1 protein in the myocardium tissue was decreased （P<0.05）， while the expression levels of TrxR1， cleaved Caspase 3， and Bax proteins in the myocardium tissue were increased （P<0.05）， and the expression level of Bcl-2 protein in the myocardium tissue was decreased （P<0.05）. Compared with model group， the LVESD， LVEDD， and LVEF of the rats in AT1R blocker group and carvedilol group were decreased （P<0.05），and the LVEF of the rats was increased （P<0.05）； the serum levels of CK-MB， cTnI， LDH and Pro-BN were decreased （P<0.05）， the percentages of myocardium infarction areas were decreased （P<0.05），the pathomorphology of myocardium tissue was significantly improved， and the percentages of TUNEL positive cells were decreased （P<0.05）， the expression levels of Trx1 and Bcl-2 proteins in the myocardium tissue were increased（P<0.05）， and the expression levels of TrxR1，cleaved Caspase 3， and Bax proteins in the myocardium tissue were decreased （P<0.05）.

The ATIR blocker losartan can protect the rats with AMI， and its mechanism may be related to the regulation of Trx system.

To study the effect of bisphenol A （BPA） on the mRNA molecule expression profile in ovarian tissue of the prepubertal female rats， and to explore the potential effect of BPA on the structure and function of ovarian tissue.

A total of 32 female SD rats were randomly divided into control group and low，middle，and high doses of BPA groups，and there were 8 rats in each group.The rats in low，middle，and high doses of BPA groups were given 50，100，and 200 mg·kg^－1 BPA，and the rats in control group were given ethanol-corn oil（1∶100）. HE staining was used to observe the morphology of ovarian tissue of the rats in various groups. RNA sequencing （RNA-seq） and bioinformatic analyses were used to predict the differential expression genes and their biological functions between high dose of BPA group and control group. The mRNA expression levels of Hapln3， Nr4a1， Arc， Ccl2， Ccn5， Egr2，and Rab33a in ovarian tissue of the rats in various groups were detected by Real-time fluorescence quantitative PCR （RT-qPCR）method.

The HE staining results showed that compared with control group， there were no obvious abnormalities in ovarian tissue of the rats in low and middle doses of BPA groups. The number of primordial follicles， pre sinus follicles and sinus follicles in ovarian tissue of the rats in high dose of BPA group were decreased， the number of atretic follicles was increased， and the cystic follicles were appeared.The RNA-seq detection results showed that there were 14 differential expression genes in ovarian tissue of the rats in control group and high dose of BPA group. The bioinformatics analysis results showed that 14 mRNA molecules were involved in a variety of biological processes such as reproduction， metabolism and apoptosis， as well as p53， MAPK， PI3K-Akt，and other signal pathways. Compared with control group， the expression levels of Hapln3， Nr4a1， Arc， Ccl2， Ccn5，and Egr2 mRNA in ovarian tissue of the rats in high dose of BPA group were decreased （P<0.05），and the expression level of Rab33a mRNA was increased （P<0.05）.

BPA changes the mRNA molecule expression profile in ovarian tissue of the prepubertal female rats， which may potentially influence the structure and function of ovarian tissue.

To establish the experimental peri-implantitis sheep models and investigate the expressions of inflammatory factors interleukin 17 （IL-17）， interleukin 23 （IL-23）， interleukin-1α （IL-1α）， and cyclooxygenase-2（COX-2） in gingival crevicular fluid and gingival tissue of the experimental peri-implantitis sheep models， and to clarify their pathogenic roles in peri-implantitis.

Nine sheep were randomly divided into blank group， control group， and model group （n=3）.The sheep in blank group were not treated； the right maxillary bicuspid teeth of the sheep in control group and model group were removed， and the sheep received immediate implantation. After three months，when the implant bone bonding formed，the implant neck of the sheep in model group were ligated by the No.6 silk loop. The sheep in blank group were sacrificed at day 0，the sheep in control group were sacrificed after 3 months， and the sheep in model group were sacrificed 4 weeks after the ligation of No.6 silk loop. The gingival crevicular fluid was obtained before sacrifice and the gingival tissue samples were obtained after sacrifice.The morphology of gingival tissue of the sheep in control group and model group was observed.The gingival index（GI），attachment loss （AL），and periimplant pocket（PD） deep of the sheep in control group and model group were detected.The bone densities around the implants of the sheep in various groups were observed by special X-ray machine. The levels of IL-17 and IL-23 in gingival crevicular fluid of the sheep in various groups were determined by ELISA method，the expression amount of IL-1α mRNA in gingival tissue of the sheep in various groups were determined by Real-time fluorecence quantificative PCR（RT-qPCR） method，and the expression amounts of COX-2 protein in gingival crevicular fluid of the sheep in various groups were determined by Western blotting method.

The morphology observation results showed that the gingival tissue around implants of the sheep in model group presented redness and swelling and bleeding on probing， and the texture became soft with exudation.Compared with control group，the PD and AL of the sheep in model group were increased（P<0.05），while there were no significant inflammation of the sheep in blank group and control group. The X-ray detection results showed that the shadow around of implant of the sheep in model group was found， but it was not found in control group.Compared with blank group， the levels of IL-23 in gingival crevicular fluid of the sheep in control group and model group were significantly increased（P<0.05）. Compared with blank group and control group， the level of IL-17 in gingival crevicular fluid of the sheep in model group was significantly increased（P<0.05）. Compared with blank group and control group， the expression amounts of IL-1α mRNA and COX-2 protein in gingival tissue of the sheep in model group were significantly increased.

The peri-implantitis sheep models are successfully established by using the silk loop ligation. The high expression of inflammatory factors in gingival crevicular fluid and gingival tissue of the model sheep indicates that the inflammatory factors may play a certain role in promoting the development of peri-implantitis.

To prepare the intracellular membrane vesicles （NVs） loaded with oxaliplatin （OXA） and obtain the nano drugs NVs@OXA， and to discuss the endocytosis and killing effects of NVs@OXA on colon cancer cells of the mice.

The cell membrane of HEK-293T cells was separated by ultracentrifugation，and the NVs were prepared by liposome extrusion instrument； the particle size of NVs was detected by dynamic light scattering， and the ultrastructure of NVs was observed under transmission electron microscope. The surival rates of dendritic DC2.4 cells of the mice after treated with different concentrations （5， 10， 20， 50， 75 and 100 mg·L^－1）of NVs were detected. The endocytosis of the vesicles was analyzed under laser confocal fluorescence microscope. The OXA was loaded into the lumen of the vesicles by electrioporation or incubation to obtain the nano drugs NVs@OXA.The loading efficiency and changes of particle sizes of the nano drugs NVs@OXA were detected.The free OXA was selected as control（free OXA group），the survival rates of colon cancer CT26 cells treated with different concentrations （1.0， 2.5， 5.0， 10.0 and 15.0 μmol·L^－1） of NVs@OXA （NVs@OXA groups）were detected by MTT method， and the apoptotic rates of the colon cancer CT26 cells in various groups was detected by flow cytometry.

The NVs with an average particle size of 222.2 nm were prepared by cell membrane.The cytocompatibility test results showed that the survival rates of all the dendritic DC2.4 cells of the mice treated with NVs were >100%； the loading efficiency of OXA prepared by electrioporation method was higher than that prepared by incubation method. There was no significant change in the particle size of OXA during 12 d after the preparation of nano drugs. Under laser confocal fluorescence microscope， the NVs@OXA could successfully enter the colon cancer CT26 cells. The MTT detection results showed that the survival rates of the colon cancer cells in NVs@OXA groups were lower than that in free OXA group when the concentrations of OXA were 10 and 15 μ mol·L^－1 （P<0.05）.The flow cytometry results showed that the apoptotic rates of the colon cancer cells in NVs@OXA group was higher than that in free NVs group （P<0.05）.

The OXA-loaded nanomedicine NVs@OXA is successfully prepared by NVs.The electroporation method has a higher OXA-loading efficiency than the incubation method. NVs@OXA can be internalized into the CT26 cells. NVs@OXA shows a stronger tumor killing effect than the free OXA.

To investigate the protective effect of ginsenoside Rg3 on spermatogenesis in the male mice with reproductive function injury induced by dibutyl phthalate （DBP）， and to elucidate its mechanism.

Thirty 6-week-old clean grade C57BL/6 mice were randomly divided into control group， DBP group（given 400 mg·kg^－1 DBP） and DBP+Rg3 group （given 400 mg·kg^－1 DBP and 20 mg·kg^－1 Rg3） and there were 10 mice in each group. At the end of the experiment， the mice were sacrificed and the sperm quality was analyzed. The pathomorphology of testis tissue of the mice in various groups were observed by HE staining. The expression of gap junction connexin 43（Cx43） protein in testis tissue of the mice in various groups was observed by immunohistochemistry. The expression levels of Src， phosphatidylinositol-3-kinase（PI3K） and protein kinase B（Akt） mRNA in testis tissue of the mice in various groups were detected by Real-time quantitative PCR（RT-qPCR）. Western blotting method was used to detect the expression levels of phosphorylated Src（p-Src）， phosphorylated PI3K（p-PI3K） and phosphorylated Akt （p-Akt） proteins in testis tissue of the mice in various groups.

Compared with control group， the sperm density and sperm motility of the mice in DBP group were significantly decreased （P<0.01）；compared with DBP group， the sperm density and sperm motility of the mice in DBP+Rg3 group were significantly increased （P<0.01）. The HE staining results showed that compared with DBP group，the histopathological injury of testis tissue of the mice in ginsenoside Rg3 group was improved. The immunohistochemical analysis results showed that the expression amont of Cx43 protein in testis tissue of the mice in DBP group was lower than that in control group； compared with DBP group， the expression amount of Cx43 protein in testis tissue of the mice in DBP+Rg3 group was increased.The RT- qPCR results showed that compared with control group， the expression levels of Src， PI3K and Akt mRNA in testis tissue of the mice in DBP group were decreased （P<0.01）； compared with DBP group， the expression levels of Src， PI3K and Akt mRNA in testis tissue of the mice in DBP+ Rg3 group were increased （P<0.01）.The Western blotting detection results showed that compared with control group，the expressions levels of p-Src，p-PI3K，and p-Akt proteins in testis tissue of the mice in DBP group were decreased （P<0.01）；compared with DBP group，the expressions levels of p-Src，p-PI3K，and p-Akt proteins in testis tissue of the mice in DBP+Rg3 group were increased （P<0.01）.

Ginsenoside Rg3 can improve the DBP-induced reproductive function injury in the mice， and the mechanism may be that Rg3 can up-regulate the expression of Cx43 by activating the Src/PI3K/Akt pathway， reduces the permeability of blood-testosterone barrier induced by DBP exposure， and plays a protective role in the spermatogenic injury.

To study the protective effect of astragaloside Ⅳ （ASⅣ） on the heart failure（HF） induced by over-expression of microRNA-1 （miRNA-1） in the rats， and to clarify the possible mechanism.

A total of 32 SD rats were randomly divided into normal control group，miRNA-1 mimics negative virus control（miRNA-1 mimics NC） group，miRNA-1 mimics group，and ASⅣ+miRNA-1 mimics group，and there were 8 rats in each group. The HF models of rats were established by injecting miRNA-1 lentivirus in left ventricular wall. Real-time fluorescence quantitative PCR（RT-qPCR） method was used to detect the expression level of miRNA-1 in myocardium tissue of the rats in various groups， and echocardiography was used to examine the left ventricular injection fraction（EF） and left ventricular fraction shortening （FS） of the rats in various groups.The H9C2 cardiomyocytes were divided into normal control group， miRNA-1 mimics negative virus control（miRNA-1 mimics NC） group， miRNA-1 mimics group and ASⅣ+miRNA-1 mimics group. The H9C2 cardiomyocytes were infected with miRNA-1 lentivirus.RT-qPCR method was used to detect the expression levels of miRNA-1 in the H9C2 cardiomyocytes in various groups，and the survival rates of the H9C2 cardiomyocytes in various groups were detected by MTT method to screen the optimal concentration of ASⅣ.The calcium test box was used to detect the expression levels of calcium ions （Ca²⁺） in the H9C2 cardiomyocytes in various groups，RT-qPCR method was used to detect the expression levels of calcium／calmodulin dependent protein kinaseⅡ（CaMKⅡ）and ryanodine receptor type 2（RyR2）mRNA in the H9C2 cardiomyocytes in various groups，and Western blotting method was used to detect the expression levels of CamKⅡ and RyR2 proteins in the H9C2 cardiomyocytes in various groups.

Compared with normal control group and miRNA-1 mimics NC group， the expression level of miRNA-1 in myocardium tissue of the rats in miRNA-1 mimics group was increased significantly （P<0.01），and the EF and FS were decreased significantly （P<0.01）； compared with miRNA-1 mimics group， the expression level of miRNA-1 in myocardium tissue of the rats in ASⅣ+miRNA-1 mimics group was decreased significantly （P<0.01），and the EF and FS were increased significantly （P<0.01）.Compared with normal control group and miRNA-1 mimics NC group， the expression level of miRNA-1 and Ca²⁺ level in the H9C2 cardiomyocytes of the rats in miRNA-1 mimics group were increased significantly （P<0.01）， the expression levels of CaMKⅡ mRNA and protein were increased significantly （P<0.01），and the expression levels of RyR2 mRNA and protein were decreased significantly （P<0.01）；compared with miRNA-1 mimics group， the expression levels of miRNA-1，Ca²⁺ level and the expression levels of CamKⅡ mRNA and protein in the H9C2 cardiomyocytes of the rats in ASⅣ+miRNA-1 mimics group were decreased significantly （P<0.01），and the expression levels of RyR2 mRNA and protein were increased significantly （P<0.01）.

ASⅣ may be involved in the regulation of Ca²⁺ level in the cardiomyocytes by down-regulation of the expression of miRNA-1， thus improves the HF and plays a protective role in the heart.

To explore the antiviral activity of remdesivir（RDV） against enterovirus 71 （EV71） in the cellular and animal levels，and to clarify its antiviral mechanism.

The anti-enterovirus activity of RDV was evaluated based on the human rhabdomyosarcoma（RD） cells. The half toxic concentration （CC₅₀） and half effective concentration （EC₅₀） of RDV for EV71， Coxackie virus 6（CA6）， enterovirus 68（EVD68），and Coxackie virus 16（CA16） were detected， and the selection index （SI） was calculated. The RD cells were divided into cell control group，virus control group（without treatment） and administration groups. The RD cells in virus control group were given EV71， and the RD cells in administration groups were given different concentrations （0.005， 0.015， 0.046， 0.137，0.410， 1.230，3.700，11.110，33.330，and 100.000 μmol·L^－1） of RDV. After 72 h， CellTiter-Glo^? Luminesent assay kit was used to determine the activities of RD cells in various groups. In the cell activity evaluation experiment of anti-EV71， the RD cells were divided into administration groups and virus control group.The RD cells in administration groups were given different concentrations（0.30， 0.10， 0.30， 0.80 and 2.50 μmol·L^－1） of RDV. After 30 h， the expression levels of EV71 RNA in the RD cells in various groups were detected by Real-time fluorescence quantitative PCR （RT-qPCR） method， and the expression levels of EV71 structural protein VP1 in various groups were detected by Western blotting and immunofluorescence methods. Time of addition assay was used to conform the antiviral stage of RDV.In anti-EV71 animal pharmacodynamics， 35 ICR suckling mice were randomly divided into placebo group （given 2% Tween 80， n=12），3.0 mg·kg^－1 RDV group （given 3.0 mg·kg^－1 RDV，n=12） and 1.5 mg·kg^－1 RDV ^{group （given 1.5 mg·kg－1 RDV， n=11）；each suckling mouse was challenged intraperitoneally with 5×103 PFU.The first dose was given after 4 h，and the treatment lasted for 2 weeks. The survival rates of the sucking mice in various groups were observed and recorded. On the 3rd day after challenge， the viral loads（copy number of EV71 RNA） in different tissues of the suckling mice in various groups were detected by RT-qPCR method.}

The EC₅₀ of RDV for EV71， CA6， EVD68，and CA16 were （0.05±0.01），（0.14±0.06），（0.02±0.01），and（0.10±0.03） μmol·L^－1， respectively. Compared with virus control group， the expression levels of EV71 RNA in the RD cells in 0.10， 0.30， 0.80，and 2.50 μmol·L^－1 RDV groups were decreased （P<0.05 or P<0.01）， and the expression levels of EV71 structural protein VP1 in the RD cells in 0.80 and 2.50 μmol·L^－1 RDV groups were decreased. Compared with virus control group， the copy numbers of EV71 RNA in the RD cells at stages Ⅲ and Ⅳ （virus replication stage） were decreased significantly （P<0.05）. There were no significant differences in the survival rates of the suckling mice between administration groups and placebo group （P>0.05），but there was a certain protective trend. Compared with placebo group， the viral loads in lung and muscle tissues of the suckling mice in 3.0 mg·kg^－1 RDV group were decreased significantly （P<0.05 or P<0.01）.

RDV has an excellent antiviral activity against enteroviruses （such as EV71）at the cellular level， and mainly acts on the replication stage of viral infection. RDV can significantly reduce the viral loads in lung and muscle tissues， suggesting its therapeutic potential at the animal level.

To discuss the protective effect of exogenous nerve growth factor （NGF） in the guinea pigs with form-deprived myopia（FDM），and to charify its mechanism.

A total of 48 guinea pigs were randomly divided into control group， model group， low concentration of NGF group and high concentration of NGF group（n=12）. In addition to control group， the FDM models of guinea pigs in other groups were established by wearing lens with 10.0 diopter （D） in the right eyes， and the left eyes were not treated. The guinea pigs in low and high concentrations of NGF groups were respectively injected with 500 and 1 000 BU NGF in the right eyes for 21 d. The D and axial lengths of eyes of the guinea pigs in various groups were measured by infrared eccentric optometer and ophthalmic A/B ultrasound diagnostic apparatus. HE staining was used to observe the pathomophology of scleral tissue of the guinea pigs in various groups. Real-time fluorescence quantificative PCR （RT-qPCR） method was used to detect the expression levels of glycogen synthase kinase-3β（GSK-3β），β-catenin， and vascular endothelial growth factor （VEGF） mRNA in scleral tissue of the guinea pigs in various groups. Immunohistochemistry was used to detect the rates of GSK-3β and β-catenin positive cells in scleral tissue of the guinea pigs in various groups.Western blotting method was used to detect the expression levels of GSK-3β and β-catenin proteins in scleral tissue of the guinea pigs in various groups.

Compared with model group， the D of right eyes of the guinea pigs in low and high concentrations of NGF groups were increased significantly （P<0.05）， while the axial lengths of eyes were decreased significantly （P<0.05）.The HE staining results showed that the thickness of scleral tissue of the guinea pigs in model group were decreased， the collagen fibers were disordered， and the obvious interstitial spaces appeared between the fibers； the thickness of sclera tissue of the guinea pigs in low and high concentrations of NGF groups were increased， and the structures were relatively clear. Compared with model group， the expression levels of GSK-3β mRNA and protein in scleral tissue of right eyes of the guinea pigs in low and high concentrations of NGF groups were significantly decreased （P<0.05）， while the expression levels of VEGF and β-catenin mRNA and protein were significantly increased （P<0.05）.

The exogenous NGF can protect the scleral tissue of the guinea pigs with FDM by regulating the Wnt/β-catenin signaling pathway， inhibiting the expression of GSK-3β and increasing the expression of β-catenin.

To investigate the neuroprotective effect of ceftriaxone （CEF） in the rats with subarachnoid hemorrhage （SAH） ，and to clarify its possible mechanism.

A total of 48 male SD rats were randomly divided into sham operation group， SAH group， and CEF group， and there were 16 rats in each group. The SAH rat model was established by improved endovascular puncture. The rats in CEF group were injected intraperitoneally 5 d before the establishment of SAH model， and the drug dose of CEF was 200 mg·kg^－1.After the establishment of SAH model for 24 h， the neurological function scores of the rats in various groups were evaluated. The morphology of nerve cells in brain tissue of the rats in various groups was observed by HE staining， and the numbers of necrosis nerve cells were calculated. The numbers of activated astrocytes in brain tissue of the rats in various groups were examined by immunohistochemistry. The levels of interleukin-1β（IL-1β）， interleukin-33（IL-33）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） in brain tissue of the rats in various groups were detected by ELISA method.

Compared with sham operation group， the neurological function score of the rats in SAH group was significantly decreased （P<0.05）. Compared with SAH group， the neurological function score of the rats in CEF group was significantly increased （P<0.05）. The HE staining results showed that the distribution of nerve cells in brain tissue of the rats in sham operation group was orderly and regular，the cells were symmetrical， and the nucleus was in the middle and stained clearly； the nerve cells in brain tissue of the rats in SAH group were disordered， irregular and cone-shaped， and the nuclear were shrinkaged， ruptured and dissolved； in CEF group， the structure of nerve cells in brain tissue was intact and the nuclear pyknosis was alleviated. Compared with sham operation group， the number of necrosis nerve cells in brain tissue of the rats in SAH group was significantly increased （P<0.05）；compared with SAH group， the number of necrosis nerve cells in brain tissue of the rats in CEF group was significantly decreased （P<0.05）. The immunohistochemical staining results showed that most of the activated astrocytes were “branched” in shape， with small cell bodies， mainly cytoplasmic staining， and the processes were thickened and lengthened with different lengths. Compared with sham operation group， the number of activated astrocytes in brain tissue of the rats in SAH group was significantly increased （P<0.05）； compared with SAH group， the number of activated astrocytes in brain tissue of the rats in CEF group was significantly decreased （P<0.05）.The ELISA assay results showed that the levels of IL-1β， IL-33， IL-6 and TNF-α in brain tissue of the rats in SAH group were significantly higher than those in sham operation group （P<0.05）；compared with SAH group， the levels of IL-1β， IL-33， IL-6，and TNF-α in brain tissue of the rats in CEF group were significantly decreased （P<0.05）.

CEF can reduce the necrosis of nerve cells in brain tissue of the rats with SAH， improve the neurological function score of the rats， and has a neuroprotective effect； its mechanism may be related to inhibiting the activation of astrocytes and alleviating the inflammatory reaction.

To explore the regulatory effect of Danggui Liuhuang Decoction on the immune function of the prostate cancer （PCa）-bearing mice， and to clarify its mechanism.

Fifty mice were randomly divided into control group， model group， low dose of Danggui Liuhuang Decoction group， high dose of Danggui Liuhuang Decoction group and cisplatin group （n=10）. All the mice were vaccinated with RM-1 to establish the PCa-bearing mouse models except control group.The mice in low dose and high doses of Danggui Liuhuang Decoction groups were given 0.25 and 0.50 g·kg^－1·d^－1 Danggui Liuhuang Decoction by gavage，respectively，and the mice in cisplatin group were intraperitoneally injected with 0.2 mL cisplatin. The spleen coefficients， thymus coefficients， tumor volumes and inhibitory rates of tumor of the mice in various groups were calculated. HE staining was used to observe the pathomorphology of tumor tissue of the mice in various groups. Flow cytometry was used to detect the percentages of CD4+ and CD8+T lymphocytes in peripheral blood of the mice in various groups. Western blotting method was used to detect the expression levels of programmed cell death receptor-1 （PD-1） and programmed cell death-ligand 1 （PD-L1） proteins in spleen tissue of the mice in various groups.

Compared with control group， the spleen coefficient， thymus coefficient， and percentage of CD8+ T lymphocytes of the mice in model group were increased（P<0.05），and the percentage of CD4+ T lymphocytes was decreased （P<0.05）. Compared with model group， the spleen coefficients， thymus coefficients， tumor volumes， percentages of CD8+ T lymphocytes， expression levels of PD-1 and PD-L1 proteins in spleen tissue of the mice in low dose of Danggui Liuhuang Decoction group， high dose of Danggui Liuhuang Decoction group and cisplatin group were decreased（P<0.05），and the percentages of CD4+ T lymphocytes were increased （P<0.05）. Compared with low dose of Danggui Liuhuang Decoction group， the spleen coefficients， thymus coefficients， tumor volumes， percentages of CD8+ T lymphocytes， expression levels of PD-1 and PD-L1 proteins in spleen tissue of the mice in high dose of Danggui Liuhuang Decoction group and cisplatin group were decreased （P<0.05）， the inhibitory rate of tumor and percentages of CD4+ T lymphocytes were increased （P<0.05）.Compared with high dose of Danggui Liuhuang Decoction group， the spleen coefficient， thymus coefficient， tumor volume， percentage of CD8+ T lymphocytes， expression levels of PD-1 and PD-L1 proteins in spleen tissue of the mice in cisplatin group were decreased （P<0.05）， and the inhibitory rate of tumor and percentage of CD4+T lymphocytes were increased （P<0.05）. The HE staining results showed that the tumor cells in model group were evenly and tightly distributed， with occasional vacuoles，and the tumor cells in low dose of Danggui Liuhuang Decoction group were evenly distributed and the number of vacuoles was increased， the tumor cells in high dose of Danggui Liuhuang Decoction group were loosely arranged and the number of vacuoles was increased significantly， and the tumor cells in cisplatin group were significantly reduced， and they were separated from the vacuole.

Danggui Liuhuang Decoction can improve the immune function of the PCa-bearing mice， and its mechanism maybe related to inhibiting the PD-1/PD-L1 signaling pathway.

To investigate the promotion effect of total alkaloids of leonurus on decidual villus excretion in the drug abortion rats， and to explore its possible mechanism.

A total of 100 healthy female SD rats during estrus and 50 male SD rats were caged， and 60 pregnant female rats were selected. Nine rats were randomly selected as normal group， and the other 51 rats were used to establish the pathological models of incomplete uterine involution after drug abortion. A total of 40 successfully modeled rats were randomly divided into model group， activator group， activator +leonurus alkaloid group and leonurus alkaloid group（n=10），and the rats were given phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） signaling pathway activator insulin-like growth factor-1 （IGF-1）， PI3K/AKT activator IGF-1+total alkaloids of leonurus and total alkaloids of leonurus by gavage， and the rats in normal group were given equal volume of normal saline by gavage. The bleeding volume， coagulation time， wet weight，and coefficient of the urerus， tension and contractility of uterus smooth muscle of the rats in various groups were detected. The morphology of uterine tissue of the rats in various groups was observed by HE staining， the expression levels of estrogen receptor （ER） in decidual tissue of the rats in various groups were detected by immunohistochemistry， and Western blotting method was used to detect the expression levels of p38 mitogen activated protein kinase （p38MAPK），PI3K，phosphorylated PI3K（p-PI3K），AKT and phosphorylated AKT （p-AKT） proteins in decidual tissue of uterus of the rats in various groups.

Compared with normal group， the bleeding volume， coagulation time， weight and coefficient of uterus of the rats in activator group， model group， activator+leonurus alkaloid group and leonurus alkaloid group were decreased （P<0.05）， the tension and contractility of uterine smooth muscle were increased （P<0.05）， the expression levels of ER in decidual tissue of uterus were increased （P<0.05）， and the ratios of P-P38MAPK / p38MAPK， p-PI3K/PI3K and p-AKT/AKT in decidual tissue of uterus were decreased （P<0.05）； compared with activator group， the bleeding volume， coagulation time， uterus weights and uterus coefficients of the rats in model group， activator+leonurus alkaloid group and leonurus alkaloid group were increased （P<0.05）， the tensions and contractilities of uterine smooth muscle were increased （P<0.05）， and the expression levels of ER in decidual tissue of uterus were increased （P<0.05） and the ratios of p-P38MAPK / p38MAPK， p-PI3K / PI3K and p-AKT/AKT in decidual tissue of uterus were decreased （P<0.05）；compared with model group， the bleeding volume of uterus of the rats in activator+leonurus alkaloid group and leonurus alkaloid group were decreased （P<0.05）， the coagulation time was prolonged， the tensions and contractility of the uterine smooth muscle were increased （P<0.05），the expression levels of ER in decidual tissue of the uterus were increased （P<0.05）， and the ratios of p-P38MAPK/p38MAPK， p-PI3K/PI3K and p-AKT/AKT in decidual tissue of uterus were decreased （P<0.05）； compared with activator+leonurus alkaloid group， the bleeding volume of uterus of the rats in leonurus alkaloid group was decreased （P<0.05）， the coagulation time was prolonged（P<0.05），the tension and contractility of uterine smooth muscle were increased （P<0.05）， and the expression level of ER in decidual tissue of uterus was increased（P<0.05），and the ratios of p-p38MAPK/p38MAPK，p-PI3K/PI3K and p-AKT/AKT in decidual tissue of uterus were decreased （P<0.05）.There were a large amount of congestion and decidual cells in the rats in activator group and model group. There was no congestion and decidual cells decreased significantly in the activator+leonurus alkaloid group and leonurus alkaloid group.

The total alkaloids of leonurus can promote the excretion of decidual villi tissue of the drug abortion rats， which may be achieved by inhibiting the MAPK/PI3-K/AKT signaling pathway.

Thirty SPF male C57BL/6 mice were randonly divided into control group （n=6）， sham operation group （n=6）， and pSNL group （n=18）. The mice in pSNL group were randomly divided into pSNL group （n=6）， pSNL+NC shRNA group （the NC shRNA was injected intrathecally on the 7th day， n=6）， and pSNL+ TRPA1 shRNA group （the TRPA1 shRNA was injected intrathecally on the 7th day， n=6） after successful intrathecal cathetering. The mechanical withdrawal threshold （MWT） and the thermal withdrawal latency （TWL） of hind limbs of the mice were measured before and 1， 7， 12， and 24 h after injection. The mice were sacrificed 2 h after the last test. The expression levels of TRPA1 protein kinase C epsilon type（Prkce），and the astrocyte activation marker glial fibrillary acidic protein （GFAP） in dorsal root ganglion （DRG） of the mice in various groups were detected by Western blotting method， and the levels of tumor necrosis factor-α（TNF-α） and monocyte chemoattractant protein-1 （MCP-1） in serum and cell superatant were detected by ELISA method. The primary astrocytes of pSNL model mice were isolated and cultured. TRPA1 was over-expressed or knocked down. The expression levels of TRPA1， Prkce， and GFAP proteins in the astrocytes and the levels of TNF-α and MCP-1 in cell supernatant were detected.The interaction between TRPA1 and Prkce was predicted and verified by STRING database and immunoprecipitation （Co-IP） method.After over-expression or knockdown of TRPA1， the expression levels of Prkce and GFAP proteins in the astrocytes in empty plasmid group， Ad-TRPA1 group， sh-NC group and sh-TRPA1 group and the levels of TNF-α and MCP-1 in the cell supernatant were detected. The astrocytes were transfected with TRPA1 shRNA alone or co-transfected with Ad-Prkce and divided into sh-TRPA1+empty vector group （transfected with empty vector）， sh-TRPA1+Ad-Prkce group （transfected with TRPA1 over-expression vector） and sh-TRPA1+Ad-Prkce group （transfected with Prkce over-expression vector）. The expression levels of TRPA1， Prkce，and GFAP proteins in the cells in various groups were detected by Western blotting method， and the levels of TNF- α and MCP-1 in the cell supernatant in various groups were detected by ELISA method.

Compared with control group， the MWT and TWL of the mice in pSNL group were decreased （P<0.01）；compared with pSNL+NC shRNA group， the MWT and TWL of the mice in pSNL+TRPA1 shRNA group were increased （P<0.01）. Compared with sham operation group， the expression levels of TRPA1 and GFAP proteins in DRG and the levels of TNF-α and MCP-1 in serum of the mice in pSNL group were increased 7 d after operation （P<0.05）. Compared with pSNL+NC shRNA group， the expression levels of TRPA1 and GFAP proteins in DRG and the levels TNF- α and MCP-1 in serum of the mice in pSNL+TRPA1 shRNA group were decreased （P<0.05）.Compared with empty plasmid group， the expression level of GFAP protein in the cells in Ad-TRPA1 group was significantly increased （P<0.01）， and the levels of TNF-α and MCP-1 in the cell supernatant were increased significantly （P<0.05）； compared with sh-NC group， the expression level of GFAP protein in the cells in sh-TRPA1 group was decreased significantly （P<0.05），and the levels of TNF-α and MCP-1 in the cell supernatant were decreased significantly （P<0.05）. Compared with sh-TRPA1+empty vector group， the expression levels of TRPA1， Prkce，and GFAP proteins in the cells in sh-TRPA1+Ad-Prkce group were increased （P<0.01），and the levels of TNF-α and MCP-1 in the cell supernatant were increased significantly （P<0.05）.

TRPA1 participates in the activation of astrocytes and the production and maintenance of neuropathic pain in the pSNL model mice through the interaction with Prkce.

To explore the improvement effect of miR-490-3p over-expression on non-alcoholic fatty liver disease （NAFLD） of the rats， and to preliminarily analyze its action mechanism.

A total of 32 male SD rats were randomly divided into control group， model group， negative control group （mimic-NC group），and miR-490-3p mimic group （miR-490-3p mimic group），and there were 8 rats in each group. The rats were fed with high-fat diet to replicate the NAFLD rat models. The rats in control group were given nothing，and the rats in mimic-NC and miR-490-3p mimic groups were injected with adenovirus containing meaningless sequence and miR-490-3p mimic plasmid through tail vein， respectively. The expression levels of miR-490-3p in liver tissue of the rats in various groups were detected by Real-time fluorescence quantitative （RT-qPCR）method. The serum levels of alanine aminotransferase （ALT），aspartate aminotransferase （AST）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） in liver tissue of the rats in various groups were detected by ELASA method. The pathomorphology of liver tissue of the rats in various groups were detected by HE staining and Oil red O staining.The expression levels of Toll-like receptor 4 （TLR4） and nuclear factor κB （NF-κB） mRNA in liver tissue of the rats in various groups were detected by RT-qPCR method.The expression levels of TLR4 and NF-κB proteins in liver tissue of the rats in various groups were detected by Western blotting method.

Compared with control group， the serum levels of ALT， AST， TNF-α， IL-6， IL-1β and MDA， the expression levels of TLR4 mRNA and protein and NF-κB mRNA in liver tissue of the rats in model group were increased（P<0.05）；while the serum levels of SOD and GSH-Px and expression level of miR-490-3p in liver tissue were decreased （P<0.05）. Compared with model group， the serum levels of ALT， AST， TNF-α， IL-6， IL-1β， and MDA and the expression levels of TLR4 mRNA and protein and NF-κB mRNA in liver tissue of the rats in miR-490-3p mimic group were decreased（P<0.05）， while the levels of serum SOD and GSH-Px， and the expression level of miR-490-3p in liver tissue were increased （P<0.05）.The HE staining results showed that the hepatocytes of the rats in control group were evenly arranged， a large amount of fat was accumulated in the hepatocytes in model group and mimic-NC group， and there was obvious inflammatory cell infiltration in the portal area， and some hepatocytes were necrotic and fibrotic； the degree of liver lesions in miR-490-3p mimic group was less than that in model group. The oil red O staining results showed that there were no obviously red stained fat droplets in liver tissue of the rats in control group，and the obviously red stained fat droplets were found in liver tissue of the rats in model group and mimic-NC group， with large quantity and volume； the volume and quantity of fat droplets in liver tissue of the rats in miR-490-3p mimic group were significantly reduced.

Over-expression of miR-490-3p can relieve the NAFLD damage，and its mechanism may be related to blocking the TLR4/NF-κB signaling pathways， reducing the inflammation response，and improving the oxidative stress.

To investigate the expression of hyaluronan-mediated motility receptor （HMMR） in the lung adenocarcinoma （LUAD） tissue and its impact on the prognosis of the LUAD patients， and to elucidate the role of HMMR in the occurrence and development of LUAD.

The expression levels HMMR mRNA and protein in the LUAD tissue were assessed by Gene Expression Omnibus （GEO）， the Cancer Genome Atlas （TCGA） and Human Protein Atlas （HPA）. The effect of HMMR expression on the overall survival （OS） and disease-free survival （DFS） of the LUAD patients was analyzed by using the GEPIA2 database. The relationships between HMMR mRNA expression and the clinicopathological parameters and prognosis of the LUAD patients were analyzed by using the TCGA database. The GSEA enrichment analysis was used to explore the pathways significantly enriched for HMMR in the LUAD tissue. The relationship between HMMR mRNA expression and TP53 gene mutations was probed by using the UALCAN database， and the interaction between HMMR and the proteins in the p53 signaling pathway was predicted by the Search Tool for Recurring Instances of Neighbouring Genes （STRING） database.

The expression levels of HMMR mRNA and protein in LUAD tissue were significantly higher than those in normal and adjacent tissues （P<0.01）. The patients with higher HMMR mRNA expression had shorter OS and DFS（P<0.01）. In LUAD tissue， the HMMR mRNA expression was associated with the patients’ TNM stage，T stage， and N stage （P<0.01）.The univariate and multivariate Cox analysis results showed that the OS of the patients with high HMMR mRNA expression was shorter. The GSEA enrichment analysis results showed that cell cycle， homologous recombination， p53 signaling pathway， bladder cancer， pancreatic cancer， small cell lung cancer， and ubiquitin-mediated proteolysis pathways were significantly enriched in the high expression phenotype of HMMR.

The expression of HMMR in LUAD tissue is significantly up-regulated，and the highly expressed HMMR mRNA is an independent evaluation indicator of poor prognosis in the LUAD patients.

To detect the expression of human interleukin-17A （IL-17A） recombinant protein in the human gastric cancer tissue and its effects on the proliferation， invasion， migration and apoptosis of gastric cancer cells， and to explore their mechanisms.

Thirty cases of postoperative paraffin specimens of the patients with gastric cancer，20 cases of intestinal metaplasia specimens， and 10 cases of normal gastric tissue were collected. The positive expression rates of IL-17A and interleukin-17 receptor A （IL-17RA） in different kinds of tissues were detected by immunohistochemical staining.The correlation between the expressions of IL-17A and IL-17RA was analyzed by Pearson correlation analysis.The BGC-823 cells in logarithmic growth phase were divided into control group and different concentrations （50，100， and 200 μg·L^－1） of IL-17A groups. The proliferation activities of the gastric cancer BGC-823 cells in various groups were detected by MTT method. The numbers of invasion cells of the gastric cancer BGC-823 cells in various groups were detected by Transwell test. The migration rates of the gastric cancer BGC-823 cells in various groups were detected by scratch test， and the expression levels of vascular endothelial growth factor （VEGF），matrix metalloproteinase-9 （MMP-9），B cell lymphoma-2 （Bcl-2）， and Bcl-2 associated X protein （Bax） in the gastric cancer BGC-823 cells in various groups were detected by Western blotting method.

The positive expression rates of IL-17A and IL-17RA in the intestinal metaplasia and gastric cancer tissue were significantly higher than those in normal gastric tissue（P<0.01）. There was positive correlation between IL-17A expression and IL-17RA expression in the gastric cancer tissue（r=0.891，P<0.01）. Compared with control group，the proliferation activities of the gastric cancer BGC-823 cells in 100 and 200 μg·L^－1 IL-17A groups were significantly increased after treated with IL-17A for 48 and 72 h （P<0.05）. Compared with control group， the apoptotic rates of gastric cancer BGC-823 cells in 100 and 200 μg·L^－1 IL-17A groups were decreased significantly （P<0.01）， the numbers of invasion cells and migration rates were increased （P<0.05）.The Western blotting method results showed that compared with control group， the expression levels of VEGF， MMP-9 and Bcl-2 proteins in the gastric cancer BGC-823 cells in 200 μg·L^－1 IL-17A group were increased （P<0.05）， and the expression level of Bax protein was decreased（P<0.05）.

The recombinant human IL-17A can promote the proliferation， migration， and invasion of the gastric cancer BGC-823 cells and inhibits the apoptosis，and its mechanism may be related to the promotion of expressions of invasion-related proteins VEGF， MMP-9， and the inhibition of apoptosis-related proteins Bcl-2 and Bax.

To detect the levels of small breast epithelial mucin （SBEM），human mammaglobin（hMAM），and carcinoembryonic antigen-related cell adhesion molecule 19（CEACAM19） in serum of the patients with breast cancer， and to clarify the significances of these indicators in the early diagnosis of breast cancer and their relationships with the clinicopathological parameters of the patients.

A total of 80 patients with breast cancer were selected as breast cancer group， 58 patients with benign breast disease were selected as benign breast disease group， and 54 healthy women were selected as healthy control group. The serum levels of SBEM， hMAM，and CEACAM19 of the subjects in three groups were measured by ELISA method.The receiver operating characteristic curve（ROC） was used to analyze the area under curve （AUC），cut-off value， sensitivity and specificity of these indexes in diagnosis of breast cancer.

The levels of serum SBEM， hMAM，and CEACAM19 of the patients in breast cancer group were significantly higher than those in benign breast lesion group and healthy control group （P<0.05）. Compared with TNM Ⅰ-Ⅱ stages， the levels of serum SBEM， hMAM，and CEACAM19 in the patients with TNM Ⅲ-Ⅳ stages breast cancer were significantly increased （P<0.05）.Compared with negative lymph node metastasis group， the serum levels of SBEM， hMAM，and CEACAM19 in the breast cancer patients with positive lymphnode metastasis were significantly increased （P<0.05）.The AUC， sensitivities，and specificities of SBEM， hMAM， CEACAM19 and SBEM+hMAM+CEACAM19 in diagnosis of the breast cancer were 0.868， 80.0% and 88.4%； 0.809， 70.0% and 80.4%； 0.756， 97.5% and 50.9%； 0.913， 82.5% and 90.2%.The combined detection had the best diagnotic efficiency.

The combined detection of serum SBEM， hMAM and CEACAM19 has high sensitivity and specificity in diagnosis of the breast cancer， which can improve the early diagnotic efficiency of the breast cancer patients.

To discuss the clinical and rehabilitation characteristics of postoperative rehabilitation in the patients with intracranial tumor， and to provide the basis for the postoperative rehabilitation treatment of the patients with intracranial tumor.

The clinical and rehabilitation data of 26 postoperative rehabilitation patients with intracranial tumor were retrospectively analyzed. The data of gender，age， pathological classification， histological grade， neurological dysfunction，history of hypertension， history of coronary heart disease， history of diabetes， postoperative time，lower extremity deep vein thrombosis， use of antiepileptic drugs， and scores of activities of daily living（ADL） on admission and discharge of all the patients were statistically analyzed.

The average age of 26 postoperative rehabilitation patients with intracranial tumor was （46.42±15.23） years， the majority of the patients was male（19 cases）.The admission time was mainly from 2 to 4 weeks after the operation. The most common dysfunctions were motor dysfunctions and balance disorder and ataxia. A total of 57.69% of the patients were complicated with the lower extremity deep venous thrombosis，80.76% of the patients took the anti-epileptic drugs，and 61.53% of the patients had the severe motor dysfunctions.There was significant difference in the ADL score of the patiens between admission and discharge （P<0.05）.

The attentions should be paid to the common clinical complications such as lower extremity deep venous thrombosis and epilepsy in the postoperative rehabilitation patients with intracranial tumor. Such patients are generally complicated with multiple types of dysfunctions. The postoperative rehabilitation therapy can effectively improve the ADL of the patients.

To observe the bleeding regression and prognosis of the acute ischemic stroke patients complicated with different degrees of cerebral microbleeds （CMBs ）after the application of dual anti-platelet therapy.

The clinical data of 160 cases of acute ischemic stroke patients were analyzed retrospectively.The patients were divided into control group（non-CMBs group，n=39） and CMBs group（n=116） acording to the head checking results detected by magnetic sensitive weighted imaging （SWI）.The patients in CMBs group were then divided into 3 subgroups： low-risk group， middle-risk group and high-risk group according to CMBs severity score—NSL score.The patients in various groups were given conventional treatment after admission， based on which they were given dual anti-platelet therapy， aspirin 100 mg orally once a day and clopidogrel 75 mg orally once a day for 21 d according to the Stroke Guidelines 2018， after which aspirin 100 mg once a day or clopidogrel 75 mg once a day was given as the monotherapy， and no other anticoagulant or antiplatelet drugs were given during the treatment period. CT and SWI examination of the head and the neurological deficit score according to the National Institute of Health Stroke Scale （NIHSS） were performed at admission. The CT of head and NIHSS scores were rechecked after 21 d of dual anti-treatment， and the number of bleeding regression cases was counted. The neurological recovery statuses of the patients in various groups were detected by modified Rankin Scale（mRS） score after 21 d， 3 months and 6 months of dual anti-treatment.

There were no significant differences in the conversion rates of cerebral hemorrhage，NIHSS scores and mRS scores of the patients after dual anti-platelet therapy between control group and CMBs group （P>0.05）； compared with control group， the conversion rates of cerebral hemorrhage， NIHSS scores and mRS scores of the patients in low-risk group and middle-risk group in CMBs group had no significant differences（P>0.05），the conversion rate of cerebral hemorrhage of the patients in high-risk group was increased（P<0.05），but there were no significant differences in the NIHSS scores and mRS scores of the patients between high-risk group and control group （P>0.05）.

The application of dual anti-platelet therapy does not increase the risk of intracranial hemorrhage， nor does it affect the neurological recovery or long-term prognosis in the acute ischemic stroke patients complicated with low-risk and middle-risk CMBs； the acute ischemic stroke patients complicated with high-risk CMBs have the risk of bleeding regression.

To set the different parameters of muscle strength ratio of flexor and extensor knee muscles to observe the efficacy of isokinetic muscle strength training in the patients with correcting knee hyperextension after stroke， and to provide the basis for treatment of the disease.

Since July 2019， 64 patients with knee hyperextension after stroke were selected and randomly divided into low ratio group， middle ratio group， high ratio group， and random ratio group according to the block random method （the length of block was 8）. During the treatment， a total of 4 patients （1 in low ratio group，1 in high ratio group and 2 in random ratio group） were withdrew from the study because of early discharge. A total of 60 patients （15 in low ratio group，16 in middle ratio group， 15 in high ratio group， and 14 in random ratio group） completed the study. On the basis of routine rehabilitation training， all the patients in various groups received isokinetic muscle strength training. The muscle strength ratio of knee flexors and extensors in low ratio group was controlled at 0.5－0.7，in middle ratio group it was controlled at 0.7－0.9，and in high ratio group it was controlled at 0.9－1.1.The ratio of flexor muscle to extensor muscles was 0.5－1.1 in random ratio group.Before treatment and 4 weeks after treatment， the knee hyperextension correction rate and simplified Fugl Meyer Assessment（FMA） scale were used to evaluate the effective rate of knee hyperextension and lower limb motor function of the patients in various groups. CON-TREX multi joint isokinetic muscle strength test and training system was used to compare the average torque of knee flexors and extensors of the patients in various groups.

Four weeks after treatment， the FMA scores of the patients in various groups were higher than those before treatment （P<0.05）， the effective rate of knee hyperextension of the patients in middle ratio group was significantly higher than that in the other groups （P<0.0083）， and the FMA score was also significantly higher than that in the other groups （P<0.05）. Four weeks after treatment， compared with low ratio group， the ratios of knee flexor to knee extensor of the patients in middle ratio group and high ratio group were increased （P<0.05）， and the ratio of knee flexor to knee extensor of the patients in random ratio group was decreased （P<0.05）； compared with middle ratio group， the ratio of knee flexor to knee extensor of the patients in high ratio group was increased （P< 0.05）， and the ratio of knee flexor to knee extensor of the patients in random ratio group was decreased （P<0.05）； compared with high ratio group， the ratio of knee flexor to knee extensor of the patients in random ratio group was decreased （P<0.05）.

The isokinetic muscle strength training with the muscle strength ratio of knee flexor and knee extensor between 0.7 and 0.9 can more effectively correct the knee hyperextension after stroke.

To analyze the clinical characteristics and pathogenesis and of Opalski syndrome， and to improve the clinicians’s understanding of the disease.

The clinical data of 5 patients with Opalski syndrome were collected， and the literature was reviewed to summarize the etiology and pathogenesis.

All 5 patients with Opalski syndrome were male， with an average age of （58.00±15.96） years. Among them， 4 patients had a long-term history of alcohol consumption， who presented different degrees of Wallenberg syndrome combined with focal limb paralysis.The magnetic resonance diffusion-weighted imaging（DWI） detection results indicated that there was infarction in the medulla oblongata， but the magnetic resonance angiography（MRA） detection results showed that the responsible vessels were different，which was the vertebral artery dissection in patient 1，posterior inferior cerebellar artery occlusion in patient 2－4， and vertebral artery occludsion in patient 5. All 5 patients had some degrees of improvement in their symptoms after conservative treatment. The symptoms of patient 1 were improved significantly after the neurointerventional therapy.

The incidence of Opalski syndrome in men is higher than that in women， and the responsible vessels and the causes of diseases are different. The clinicians can choose different treatment methods according to the etiology in order to give the most effective treatment to the patients.

To observe the orthodontic treatment effect of micro-implant anchorage in the patients with severe mesioclination impaction of mandibular second molars， and to provide the clinical basis for the clinical orthodontists to treat the patients.

The clinical data of one patient with severe mesioclination impaction of bilateral mandibular second molars were collected. Combined with literature review， the orthodontic clinical scheme for the treatment of this kind of patient was discussed.

One 21-year-old female patient with severe mesioclination impaction of bilateral mandibular second molars with crowded dentition was diagnosed as Angle Class Ⅱ malocclusion， Mao Ⅰ¹+Ⅲ¹+Ⅴ malocclusion and skeletal Class Ⅰmalocclusion.After extraction of 15， 18， 28， 38 and 48， the micro-implants were implanted in the front edge of bilateral mandibular ramus. After surgical exposure of bilateral mandibular second molars， the mandibular second molars were uprighted by using the traction of elastic rubber line between the micro-implant and the lingual buckle of surface of the second molars. After the orthodontic treatment， a good occlusal relationship was established between the mandibular second molar and the opposite teeth， and a good adjacent relationship was built up with the mandibular first molar.

For the patients with severe mesioclination impaction of mandibular second molars， the micro-implants can provide anchorage for the orthodontic treatment， and concisely and efficiently achieve a good occlusion and abutment relationship.

To investigate the clinical features， diagnosis and treatment of the patients with spindle cell carcinoma of lung （SpCC）， in order to improve the clinicians’understanding of this disease.

The clinical data， imaging manifestations， bronchoscope findings，and pathological findings of 1 patient with SpCC were collected， the above data were analyzed， and the relevant literatures were reviewed.

A 71-year-old male patient was hospitalized due to cough and shortness of breath for 1 month.The physical examination results showed that the left thoracic cavity was depressed， the intercostal space was narrow， and the trachea shifted to the left；the dullness of left lung was detected by percussion， and the breath sounds of left lung disappeared without other obvious positive signs. The chest CT results showed the high-density shadow in the left airway and the reduced volume of left lung.The fiberoptic bronchoscope results showed that there were pedicled neoorganisms blocking the airway in the left main bronchus. The pathological examination results showed that the adenopapilloma of the bronchus was formed with scalification. After admission，the chest enhanced CT examination results showed the strip-shaped soft tissue density shadow of the left main bronchus，which showed mild enhancement in enhanced scan；the volume of left lung was reduced with strip-like soft tissue density shadow， which showed uneven enhancement in enhanced scan. After comprehensive laboratory and imaging examination， the possibility of bronchial benign tumor was considered， and two times of bronchoscopic electrical traps were performed. The final bronchoscopic lung biopsy showed a large number of spindle cells.Combined with the immunohistochemical staining results， SpCC was diagnosed.

SpCC is a special type of epithelial-derived tumor and it is easily misdiagnosed due to its similar morphology to sarcoma.The SpCC patients with main bronchial space occupying lesions accompanying with atelectasis as the main imaging manifestations are relatively rare， and SpCC should be differentiated from the bronchial benign tumor.

To explore the mental life status and risk behavior levels of the patients with bipolar disorder（BPD） in Guangdong Province and clarify the influencing factors of risk behavior levels， and to provide the basis for the development of related management and treatment policies.

By using the multi-stage sampling method， 870 BPD patients who were hospitalized or managed in the mental health institutions （specialized mental health institutions and community health service centers） in 11 prefecture-level cities in Guangdong Province from December 2018 to February 2019 were investigated by questionnaire and physical examination.The patients were divided into low risk group （grade 0－2，n=798） and high risk group （grade 3－5，n=72） according to the risk behavior assessment grade. The general demographic characteristics， clinical characteristics，and symptoms of the BPD patients in Guangdong Province were statistically analyzed. The influencing factors of risk behaviors of the BPD patients were analyzed by multivariate Logistic regression.

The avarage age of the BPD patients in low-risk group was higher than that in high-risk group （P<0.05）. The composition ratios of male BPD patients in both two groups were higher， and the composition ratio of male BPD patients in high risk group was higher than that in low risk group （P<0.05）.The composition ratio of married/cohabitant BPD patients in low risk group was higher than that in high risk group （P<0.05），while the composition ratio of single and unmarried patients in high risk group was higher than that in low risk group （P<0.05）. The percentages of clinical symptoms such as hallucination， suspicion， moodiness， weird behavior， excitement and loquacity， wounding and destroying objects， going outside without a reason of the BPD patients in high risk group were higher than those in low risk group （P<0.05）.The composition ratios of male patients ［OR （95%CI）=1.925（1.093－3.390）］，inpatients ［OR （95%CI）=6.145（2.775－13.607）］， lock-in ［OR （95%CI） =3.178（1.523－6.629）］， and drug noncompliance ［OR （95%CI） =4.390（2.500－7.708）］ of the BPD patients in high risk group were higher than those in low risk group （P<0.05）.

Age， gender， source of patients， and medication compliance are the important influencing factors for the occurrence of risk behaviors of the BPD patients.Low age， female patients， community living patients， and regular medication play positive roles in the dowregulation of occurrence of risk behaviors of the BPD patients. The comprehensive and effective management models should be developed for the BPD patients to improve their quality of life.

To screen the core driving genes of the occurrence and development of osteosarcoma （OS）， and to explore the pathogenic mechanism of OS at the molecular level as well as to construct the gene model to predict the survival time of the OS patients.

The matrix data of gene chips in OS patients were downloaded from the Gene Expression Omnibus （GEO） database： GSE12865，GSE14359 and GSE36001.The differentially expressed genes （DEGs） between the normal tissue and OS tissue were screened through the bioinformatic method. The molecular functions and pathways of DEGs were comprehensively understood through Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis. The protein-protein interaction （PPI） network was constructed by STRING data， and Cytoscape software was conducted to analyze the correlation between DEGs to identify the most related gene set in the progression of OS as well as to figure out the core pathogenic genes of OS. The clinical record information and transcriptome data of 379 samples of OS were obtained from The Cancer Genome Atlas （TCGA） database， and Kaplan-Meier （K-M） survival analysis was further performed to clarify the relationship between hub genes and survival time of the OS patients， then other factors related to prognosis such as gender and race were searched and discussed. The expression amounts of 6 gene sets were modeled to predict the survival time of the patients.

The top ten DEGs analyzed by MCC algorithm were TYROBP， LAPTM5， FCER1G， CD74， HCLS1， ARHGDIB， HLA-DPA1， CD93， GIMAP4， and LYZ，and the expression difference in these 10 DEGs between OS and normal patients showed statistical significance （P<0.05）.The GO and KEGG results revealed that the DEGs were chiefly enriched in PI3K-AKT and Notch signaling pathways.The K-M survival analysis results demonstrated that the OS patients with lower expressions of 6 genes （ARHGDIB， CD74， FCER1G， HCLS1， HLA-DPA1， and TYROBP） had longer overall survival time than those with higher expressions （P<0.05）. The C-index of the gene set composed of these 6 genes in the construction of prediction model was 0.71.

The high expressions of screened core driving genes are correlated with the occurrence and development of OS.The abnormal signaling pathways of occurrence and development of OS are PI3K-AKT and Notch signal pathways. The prediction model constituted by 6 characteristic gene sets of OS possesses a good predictive ability.