To investigate the effects of different concentrations of retinoic acid （RA） on the proliferation of hippocampal neural stem cells after hypoxic-ischemic brain damage （HIBD） in the rats， and to investigate its possible mechanism.

The primary hippocampal neural stem cells were cultured and identified by immunofluorescence. The neural stem cells were injured by oxygen and glucose deprivation （OGD） to simulate the HIBD injury in vivo. The cells were divided into control group， OGD group （0 μmol·L^-1 RA intervention） and different concentrations （0.5， 1， 5， 10 and 50 μmol·L^-1） of RA intervention groups. The proliferation activities of cells in various groups were measured by CCK-8 method at 12， 24， 48 and 72 h after OGD. Real-time fluorescence quantitative PCR （RT-qPCR） and Western blotting methods were used to detect the expression levels of retinoic acid receptor alpha（RARα），glycogen synthase kinase-3β（GSK-3β） and CyclinD1 mRNA and the protein expression amounts in the hippocampal neural stem cells in various groups. After different concentrations（0， 0.5， 5.0 and 50.0 μmol·L^－1） of RA intervention， the hippocampal neural stem cells were treated with GSK-3β inhibitor CHIR99021 and divided into control group， 5 μmol·L^－1 RA intervention group， and 0， 0.5， 5.0 and 50.0 μmol·L^－1 RA+20 μmol·L^－1 CHIR99021 intervention groups. The cell proliferation rates were detected by CCK-8 assay at 24 h after OGD. RT-qPCR and Western blotting methods were used to detect the expression levels of RARα， GSK-3β and CyclinD1 mRNA and the protein expression amounts in the hippocampal neural stem cells in various groups.

The immunofluorescence identification results showed that the primary hippocampal neural stem cells were successfully extracted and cultured.The CCK-8 method detection results after RA intervention showed that the proliferation activities of cells in 1.0 and 5.0 μmol·L^－1 RA intervention groups were significantly increased at each time point after OGD compared with OGD group（P<0.05）.Compared with OGD group， the expression levels of RARα，GSK-3β，and CyclinD1 mRNA in 5.0 and 10.0 μmol·L^－1 RA intervention groups were significantly increased （P<0.05），and the expression amounts of RARα and GSK-3β proteins in 1.0，5.0 and 10.0 μmol·L^－1 RA intervention groups were increased.After GSK-3β inhibitor CHIR99021 intervention， compared with 5.0 μmol·L^－1 RA intervention group， the cell proliferation rate in 5.0 μmol·L^－1 RA+20 μmol·L^－1 CHIR99021 intervention group was significantly decreased （P<0.01）， the expression levels of RARα mRNA in 0 and 0.5 μmol·L^－1 RA+20 μmol·L^－1 CHIR99021 intervention groups were significantly decreased （P<0.01），the expression levels of GSK-3β and CyclinD1 mRNA in 0， 0.5， 5.0 and 50.0 μmol·L^－1 RA+20 μmol·L^－1 CHIR99021 intervention groups were significantly decreased （P<0.05），and the expression amounts of GSK-3β and CyclinD1 were decreased.

There is an appropriate concentration window for RA to promote the proliferation of neural stem cells after HIBD injury，and its mechanism may be that RA regulates the transcription of CyclinD1 through the activation of GSK-3β， thus promotes the proliferation of neural stem cells.

To investigate the effect of Sanjiao acupuncture on the permeability of the blood brain barrier （BBB） of the SAM mice and RhoA/Rho associated protein kinase（ROCK）， and to clarify its mechanism.

A tolal of 36 SAMP8 senile dementia mice were randomly divided into model group， non-acupoint group （parallel to the midline of the abdomen，inserted the needle 2 mm above the tip of the iliac crest，used a 1.5-inch needle to obliquely puncture about 3 mm downward，with angle of 90°－180°，frequency of 60－120 min^－1，and 105 s on each side）， acupoint group ［Xuehai point （double） straight puncture 2－3 mm， large amplitude（angle>180°），low frequency （frequency <60 min^－1） twisting and purging method for 30 s， Tanzhong， Zhongwan， Qihai， Zusanli （Double） Direct puncture 2－3 mm， small amplitude （angle<90°）， high frequency （frequency>120 min^－1） twirling and purging for 30 s］，12 mice per group； 12 SAMR1 normal aging mice were set as controls group. Morris water maze experiment was used to evaluate the learning and memory function of the mice； Evans blue staining method was used to detect the contents of Evans blue in the brain tissue of the mice in various groups（representing the BBB permeability）， and the BBB ultrastructures of the mice in various groups were observed under electron microscope； Western blotting method was performed to detect the expression levels of Occludin，Claudin-5， zonula occludens-1 （ZO-1），RhoA， ROCK proteins in hippocampus tissue of the mice in various groups.

In model group and non-acupoint group， the boundary of vascular endothelial cells of the mice was blurred， the basement membrane was thickened， some of them were broken， and the vascular edema was obvious； in acupoint group， the perivascular edema of the mice was significantly relieved， the endothelial cells were basically in normal state， and BBB was improved. Compared with control group， the escape latency of the mice， the content of Evans blue in the brain tissue，and the expression levels of RhoA and ROCK proteins in the hippocampus tissue were increased（P<0.05）； the expresion levels of Occludin， Claudin-5， and ZO-1 proteins in the hippocampus tissue and the space exploration time were decreased （P<0.05）. There were no statistically significant differences in the indication mentioned above between model group and non-acupoint group （P>0.05）. Compared with non-acupoint group， the escaped latency of the mice in acupoint group， the content of Evans blue in the brain tissue， and the expression levels of RhoA and ROCK proteins in hippocampus tissue were decreased（P<0.05）；the expression levels of Occludin， Claudin-5， ZO-1 proteins in hippocampus tissue and the space exploration time were increased （P<0.05）.

Sanjiao acupuncture can improve the BBB permeability in the SAM mice， which may be related to the inhibition of RhoA/ROCK pathway.

To explore the gene expressions related to skeletal muscle regeneration and repair and vesicle transport in the process of pelvic floor muscle injury caused by vaginal delivery， and to preliminarily clarify the potential role of effector molecules such as ADP ribosylation factor GTPase activated protein 3（ARFGAP3） in the regeneration and repair of pelvic floor muscles after injury.

Thirty-two female healthy 12-week-old C57 BL/6 mice were selected， and the pelvic floor muscle injury models were constructed by vaginal expansion and distal traction. They were divided into control group， modeling 1 d group， and modeling 3 d group and modeling 5 d group. In the Gene Expression Omnibus （GEO）， “muscle regeneration” was used as a keyword to search for information related to skeletal muscle regeneration and repair， three data sets GSE5413， GSE45577 and GSE469 were selected， and GEO2R online analysis tool and R software were used to screen for the differential expression genes； among the co-differentially expressed genes， 10 genes related to intracellular vesicle transport were selected （ArfGAP3， LGALS3， KDELR3， CSF1R， ANXA4， STMN1， THBS2， PLXNB2， KIF20A， EMR1）. Real-time fluorescence quantitative PCR（RT-qPCR） method was used to detect the expression levels of the above-mentioned vesicle transport-related differential genes in pelvic floor muscle of the mice during the repair of pelvic floor muscle injury.

The genes whose expression levels were increased after pelvic floor muscle injury were ARFGAP3， STMN1， THBS2 and PLXNB2. Compared with control group， the expression levels of ARFGAP3， STMN1 and THBS2 in the pelvic floor muscle tissue of the mice in modeling 1 d group were increased after injury（P<0.05 or P<0.01）， and the expression levels of ARFGAP3 and PLXNB2 in modeling 3 d group were increased after injury （P<0.01）. CSF1R， ANXA4 and EMR1 were the genes whose expression levels were reduced after pelvic floor muscle injury. Compared with control group， the expression levels of CSF1R and EMR1 in modeling 1 d group were decreased after injury（P<0.05 or P<0.01）； the expression levels of CSF1R and ANAX4 in modeling 3 d group after injury were decreased（P<0.05）；the expression level of ANAX4 in modeling 5 d group was decreased（P<0.05）. The expression levels of LGARLS3， KDELR3 and KIF20A remained unchanged after pelvic floor muscle injury.

ARFGAP3 may play an important regulatory role in the repair process of pelvic floor muscles after injury.

The expression levels of miR-762 and NCOR1 mRNA in cancer tissue and paracancerous normal tissue of 48 patients with TSCC were detected by Real-time fluorescence quantitative PCR（RT-qPCR）， and the correlation between the their expressions was analyzed by Pearson correlation analysis. The expression levels of miR-762 and NCOR1 mRNA and proteins in human normal tongue epithelial cells Hacat and TSCC cells （TCA-8113， CAL-27， SCC-15 and SCC-9） were detected by RT-qPCR and Western blotting methods.miR -762 inhibitor or si-NCOR1 was transfected into the CAL-27 cells separately or simultaneously；the experiment was divided into blank control group， inhibitor-NC group， miR-762 inhibitor group， si-NC group， si-NCOR1 group and miR-762 inhibitor+si-NCOR1 group. The expression levels of miR-762 and NCOR1 mRNA in the CAL-27 cells were detected by RT-qPCR method. The cell proliferation activities in various groups were detected by MTT assay； the proportions of EdU positive staining cells in various groups were detected by EdU assay， and the apoptotic rates were detected by flow cytometry. The expression levels of NCOR1， cleaved-Caspase-3， Bax and Bcl-2 proteins in the cells in various groups were detected by Western blotting method. The targeted regulatory relationship between miR-762 and NCOR1 was verified by luciferase report assay.

Compared with the paracancerous normal tissue and the normal human tongue epithelial cells Hacat，the expression levels of miR-762 in TSCC tissue and TSCC cells were significantly increased（P<0.01）， while the expression levels of NCOR1 were significantly decreased（P<0.01）；there was a negative correlation between their expressions in TSCC tissue（r=－0.711，P=0.003）. Luciferase reporting assay confirmed that NCOR1 was the target gene of miR-762. Compared with blank control and inhibitor-NC groups， the proliferation activity of cells， the proportion of EdU positive cells and the expression level of Bcl-2 protein in miR-762 inhibitor group were significantly decreased （P<0.01），and the apoptotic rate and the expression levels of cleaved-Caspase-3 and Bax proteins were significantly increased （P<0.01）；compared with miR-762 inhibitor group， the proliferation activity， the proportion of EdU positive cells and the expression level of Bcl-2 protein in miR-762 inhibitor+si-NCOR1 group were significantly increased （P<0.01），and the apoptotic rate and the expression levels of cleaved-Caspase-3 and Bax proteins were significantly decreased（P<0.01）.

Inhibition of miR-762 expression can inhibit the proliferation and promote the apoptosis of TSCC cells by targeting and upregulating the expression of NCOR1.

To observe the effect of electrical lesions of the lateral habenular nucleus （LHb） on the spatial learning and memory functions in the rats with Parkinson’s disease （PD）， and to clarify the role of LHb in the cognitive dysfunction in the PD rats and related mechanism.

Thirty adult male SD rats were randomly divided into control group， PD group and PD+LHb lesion group，and there were 10 rats in each group. Except control group， the rats in other two groups were used to establish the PD models. The PD rats in PD+LHb lesion group were lesioned using direct current stimulation two weeks after modeling，and the related tests were performed at the 4th week after modeling. The numbers of crossed squares and rearings of the rats in three groups were observed by open field test. The distances to find the hidden platform and the percentages of swimming distance in target quadrant of the rats in three groups were observed by Morris water maze test. The levels of serotonin （5-HT） in the medial prefrontal cortex （mPFC） and hippocampus tissue of the rats in three groups were assessed by neurochemical method. The degeneration of dopamine （DA） neurons in the brain tissue and LHb electrical lesioning were confirmed by the immunohistochemical and histological staining methods.

The results of open field test showed that compared with control group， the numbers of crossed squares and rearings of the rats in PD group were significantly decreased （P<0.01），and the number of crossed squares and rearings of the rts in PD+LHb lesion group had no significantly differences（P>0.05）.The results of Morris water maze test showed that compared with control group， the distances to find the hidden platform in navigation trial of the rats in PD group on the 2nd， 3rd，4th and 5th days were significantly increased （P<0.01）， and the percentages of swimming distance in target quadrant after withdrawal of platform in space exploration experiment were significantly decreased （P<0.05）； but there were no significant differences in the 5-HT levels in the mPFC and hippocampus tissues of the rats between two groups（P>0.05）. There were no significant differences in the numbers of crossed squares and rearings of the rats between PD and PD+LHb lesion groups； compared with PD group， the distances to find the hidden platform of the rats in PD+LHb group on the 2nd， 3rd，4th and 5th days were significantly increased （P<0.01），the percentages of swimming distance in target quadrant after withdrawal of platform were significantly decreased （P<0.05）， and the 5-HT levels in mPFC and hippocampus tissues were significantly decreased （P<0.01）. The immunohistochemical staining results showed the DA neurons of the lesioned side of the PD model rats in the substantia nigra pars compacta were missing， and the number of DA neurons in ventral tegmental area was lower than that in unlesioned side （P<0.01）.The histological staining results showed the LHb was partially lesioned.

LHb lesions can aggravate the impairment of spatial learning and memory functions of the rats with PD， and its mechanism may be related to the changes of levels of 5-HT transmitter in the related brain regions.

To prepare a antibacterial dentin adhesive containing cinnamaldehyde， and to evaluate the antibacterial properties， in vitro cytotoxicity and instant adhesive properties of the adhesive.

The Streptococcus mutans were selected for experiment. The minimum inhibitory concentration （MIC） and minimum bactericidal concentration （MBC） of cinnamaldehyde were determined by the micro broth dilution method. Cinnamaldehyde was added to the commercial adhesive Single Bond 2（SB2） in the mass fractions of 2%， 4%， 6%， and 8% to prepare the antibacterial adhesive. The commercial adhesive SB2 was used as control groups； the specimens were prepared and they were co-cultured with the bacteria. The plate colony counting method was used to determine the number of bacteria attached to the surface of the specimens and the antibacterial rates were calculated； the bacteria attached to the surface of the specimens were subjected to live/dead bacterial staining experiments to observe the state of bacteria attached to the surface of the specimens. The adhesive was incubated with the cell culture solution for 24 h to prepare the extract. The MTT method was used to determine the in vitro cytotoxicity of the adhesive and its cytotoxicity level was evaluated. On this basis， an experimental group with significant antibacterial properties was selected， and the micro-tensile test was used to measure the micro-tensile strength of the adhesive and evaluate its immediate adhesive performance.

The MIC and MBC of cinnamaldehyde were both 250 mg·L^－1， and cinnamaldehyde had a good antibacterial effect； when the mass fractions of cinnamaldehyde were 4%， 6% and 8%， the antibacterial rates of the adhesive were all higher than 99%. In the in vitro cytotoxicity experiment， under the same dilution ratio， compared with control group， the cytotoxicity level of the antimicrobial adhesive did not change significantly. According to the results of the antibacterial experiment， 4%， 6%， and 8% cinnamaldehyde groups were selected for the micro-tensile experiment. Compared with control group，the micro-tensile strengths in 4%，6% and 8% cinnamaldehyde groups had no statistically significant differences（P>0.05）.

Cinnamaldehyde has good antibacterial properties； when the mass fraction of cinnamaldehyde in the commercial adhesive SB2 is higher than 4%， the antibacterial adhesive has significant antibacterial properties， and its in vitro cytotoxicity and immediate bonding properties are not affected.

To investigate the influence of curcumol on the structure of liver sinusoidal endothelial cells（LSEC） of the mice， and to clarify its effect on intrahepatic angiogenesis mediated by LSEC.

Perfusion and digestion methods were used in 30 SPF KM mice to isolate the primary LSEC. The cells were divided into blank control group， model group， curcumol group， and salvianolic acid B group. The cells in blank control group were treated with ordinary culture medium only； the cells in model group were activated with 100 μg·L^－1 serotonin， and the cells were cultured for 48 h； the cells in curcumol group were treated with 45 mg·L^－1 curcumol for 30 min and then the cells were cultured with serotonin for 48 h； the cells in salvianolic acid B group were first treated with 1×10^－6 mmol·L^－1 salvianolic acid B for 30 min and then cultured with alicin for 48 h. MTT assay was used to detect the proliferation rates of the cells in various groups； Real-time fluorescence quantitative polymerase chain reaction（RT-qPCR） method was used to determine the expression levels of CD31 and vWF mRNA in the cells in various groups； Western blotting method was used to detect the expression levels of CD31 and vWF proteins in the cells in various groups； scanning electron microscope was used to observe the structure of the LSEC； angiogenesis experiment was used to observe intrahepatic angiogenesis.

The MTT test results showed that the proliferation rate of the cells in model group was significantly lower than that in blank control group （P<0.05）； the cell proliferation rates in curcumol group and salvianolic acid B group were significantly lower than that in model group （P<0.05）；there was no significant difference in the cell proliferation rate between salvianolic acid B group and curcumol group （P>0.05）. The results of RT-qPCR showed that the expression levels of CD31 and vWF mRNA in the cells in model group was significantly higher than those in blank control group （P<0.05）； the expression levels of CD31 and vWF mRNA in curcumol group and salvianolic acid B group were significantly lower than those in model group （P<0.05）；there were no significant differences in the expression levels of CD31 and vWF mRNA between salvianolic acid B group and curcumol group（P>0.05）. The results of Western blotting method showed that the expression levels of CD31 and vWF proteins in the cells in model group were significantly higher than those in blank control group （P<0.05）； the expression levels of CD31 and vWF proteins in the cells in salvianolic acid B and curcumol group group were significantly lower than those in model group （P<0.05）； there were no significant differences in the expression levels of CD31 and vWF proteins between salvianolic acid B group and curcumol group（P>0.05）. The results of scanning electron microscope showed that the number of LSEC fenestrations of LSEC in blank control group was larger； compared with blank control group， the number of LSEC fenestrations in model group was decreased； compared with model group， the number of LSEC fenestrations in curcumol group and salvianolic acid B group was increased. The angiogenesis experiment results showed that the number of blood vessels in model group was significantly increased compared with blank group （P<0.05）；the number of blood vessels in curcumol group and salvianolic acid B group was significantly lower than that in model group （P<0.05）； and there was no statistically significant difference in the number of blood vessels between salvianolic acid B group and curcumol group （P>0.05）.

Curcumol can inhibit the intrahepatic angiogenesis by regulating the fenestration structure of LSEC.

To explore the effects of insulin-like growth factors-1 receptor NVP-AEW541 on the proliferation， migration and invasion of three kind of esophageal squamous cell carcinoma （ESCC） cells KYSE30， KYSE450 and TE-1， and to preliminarily clarify their mechanisms.

The ESCC cells KYSE30， KYSE40 and TE-1 cultured in vitro were used as experimental subjects and divided into control group （0 μmol·L^－1 NVP-AEW541，1 mL RPMI 1640 complete medium + 1 μL DMSO） and experimental groups（2， 4， 6， 8 and 10 μmol·L^－1 NVP-AEW541）.After the cells in control group and experimental group were treated for 48 h， CCK-8 assay was used to detect the cell survival rates in various groups； after the cells in control group and experimental groups （4 and 6 μmol·L^－1 NVP-AEW541）were treated for 0， 6， 12 and 24 h， cell scratch test was used to detect the cell migration rates in various groups； after the cells in control group and experimental group （6 μmol·L^－1 NVP-AEW541） were treated for 48 h， Transwell test was to used detect the number of invasion cells in various groups； after the cells in control group and experimental groups （2， 4 and 6 μmol·L^－1 NVP-AEW541） were treated for 48 h， Western blotting method was used to detect the expression levels of p-IGF-1R and epithelial-mesenchymal transition （EMT）-related proteins N-Cadherin and Snail-1 proteins in the cells in various groups.

Compared with control group， the cell survival rates of KYSE30， KYSE450 and TE-1 cells in experimental groups were decreased with the increase of the concentration of NVP-AEW541 （P<0.05）； the survival rates of KYSE30， KYSE450 and TE-1 cells in experimental group （10 μmol·L^－1） were decreased（P<0.01）； the cell migration rates in experiment group （6 μmol·L^－1） were decreased with the increase of NVP-AEW541 concentration （P<0.01）； the number of invasion cells in experimental group （6 μmol·L^－1） was decreased （P<0.01）； the expression levels of p-IGF-1R，N-Cadherin and Snail-1 proteins in the cells in experimental group were significantly decreased （P<0.01）.

NVP-AEW541 can significantly inhibit the proliferation of ESCC cells，by inhibiting the expressions of N-Cadherin and Snail-1 proteins， it prevents the EMT， and inhibit the migration and invasion of ESCC cells.

To establish the polarization models of the M1 macrophages in vitro， and to investigate the effect of gallic acid（GA） on the polarization of the M1 macrophages.

The eight-week-old C57BL/6 female mice were selected for primary culture of peritoneal macrophages， and the experiment was divided into control group（untreated），M1 polarization model group［adding lipopolysaccharide （LPS， 100 μg·L^－1） and interferon-γ （IFN-γ， 20 μg·L^－1） to induce the M1 polarization of peritoneal macrophages］ and GA group ［adding GA （37.5 mg·L^－1） to co-treat the peritoneal macrophages with lipopolysaccharide and IFN-γ on the basis of M1 polarization model group］. The morphology of cells was observed by inverted microscope， Annexin Ⅴ-PE/7-AAD double dyeing method was used to detect the apoptotic rates in various groups， the positive expression rates of F4/80⁺iNOS⁺ M1 macrophages were detected by flow cytometry， and the expression levels of inducible nitric oxide synthase （iNOS） and interleukin-1β （IL-1β） in the cells in various groups were detected by Real-time fluorescence quantitative PCR （RT-qPCR） method.

The results of inverted microscope showed that the cells in control group were mainly round or oval； in M1 polarization model group， the cells were mainly spindle-shaped； compared with M1 polarization model group， the spindle cells were decreased and the round cells were increased in GA group. There were no significant differences in the apoptotic rate of macrophages between three groups （P>0.05）. Compared with control group， the positive expression rate of F4/80⁺iNOS⁺M1 macrophages in M1 polarization model group was increased significantly （P<0.01）； the positive expression rate of F4/80⁺iNOS⁺M1 macrophages in GA group increased， but the difference was not statistically significant （P>0.05）. Compared with M1 polarization model group， the positive expression rate of F4/80⁺iNOS⁺M1 macrophages in GA group was decreased significantly （P<0.01）. Compared with control group， the expression levels of iNOS and IL-1β mRNA in the cells in M1 polarization model group were significantly increased （P<0.01）； compared with M1 polarization model group， the expression levels of iNOS and IL-1β mRNA in the cells in GA group were decreased significantly （P<0.01）； but there was no significant difference in the expression levels of iNOS and IL-1β mRNA between GA group and control group （P>0.05）.

GA has no obvious effect on the macrophage apoptosis， but it can inhibit the polarization of macrophages to type M1.

To investigate the protective effect of limb ischemia training （LIT） on the neurons in the hippocampal CA1 region of the estrogen-deprived rats， and to elucidate the possible molecular mechanism.

A total of 27 SD rats aged 3－4 months were undergone bilateral ovariectomy （OVX） to induce the estrogen deprivation models， and the model rats were randomly divided into OVX group （OVX）， LIT group （OVX+LIT） and Letrozole（Let） group （OVX+LIT+ Let）； there were 9 rats in each group. On the 7th day after OVX， LIT was performed in the rats once a day for 6 weeks；the rats in Let groups were given Let by intragastric administration at a dose of 10 mg·kg^－1·d^－1 for 6 weeks. Western bloting method was used to detect the expression levels of synaptic related protein （Synapsin1）， myelin basic protein 2 （MBP2）， postsynaptic dense protein（PSD95），cyclic adenosine monophosphate response element binding protein （CREB）， phosphorylated CREB and brain-derived neurotrophic factor （BDNF）in the neurons of hippocampal CA1 region of the rats in various groups. Barns maze and novel object recognition test were used to detect the behavior indicators of the rats in various groups.

Compared with OVX group， the expression levels of Synapsin1，PSD95，and MBP2 proteins in the neurons of hippocampal CA1 region of the rats in LIT group were significantly increased （P<0.05）， and the expression levels of p-CREB and BDNF proteins were significantly increased（P<0.05）. Compared with LIT group， the expression levels of Synapsin1， PSD95，and MBP2 proteins in the neurons of hippocampal CA1 region of the rats in Let group were significantly decreased （P<0.05）， and the expression levels of p-CREB and BDNF proteins were also decreased（P<0.05）. The results of Barnes maze test showed that compared with OVX group， the residence time in target quadrant of the rats in LIT group was prolonged， but there was no significant difference between two groups （P>0.05）；compared with LIT group，the residence time in target quadrant in Let group was shortened（P<0.05）.The results of Novel object recognition test showed that compared with OVX group， the time exploring the novel and old object of the rats in LIT group was prolonged，the discrimination index was increased，but there was no significant difference between two groups （P>0.05）；compared with LIT group，the time exploring the novel object and old object of the rats in Let group was shortened， and the discrimination index was significantly decreased （P<0.05）.

LIT can preserves the hippocampal CA1 neurons and cognitive function in the rats with estrogen deprivation by up-regulating CREB phosphorglation level and the protein levels of BDNF and synaptic proteins， and Let-treatment can inhibit the neuroprotective effect of LIT.

To investigate the induction effect of panaxadiol （PD） on the apoptosis of 3T3-L1 preadipocytes， and to elucidate its possible mechanism.

The cells were divided into blank control group and different concentrations of PD treatment groups.The cell viabilities of undifferentiated 3T3-L1 adipocytes and differentiated mature adipocytes after treated 0－100 μmol·L^－1 with PD were determined by CCK-8 method.After the 3T3-L1 preadipocytes were treated with different concentrations （0， 5， 25，and 50 μmol·L^－1） of PD， DAPI staining was used to observe the morphology of apoptosis. Flow cytometry was used to detect the apoptotic rates and the percentages of 3T3-L1 preadipocytes in different cell cyeles. The protein expression levels of phosphatidylinositol 3-kinase （PI3K），phosphorylated phosphatidylinositol 3-kinase （p-PI3K），protein kinase B （AKT）， phosphorylated protein kinase B （p-AKT）， B-cell lymphoma-2 （Bcl-2），Bcl-2 associated X protein （Bax） and cleaved-Caspase 3 in each group were detected by Western blotting method， and the ratios of p-PI3K/ PI3K and p-AKT/AKT were calculated.

The CCK-8 results showed that compared with blank control group， the cell viabilities of 3T3-L1 preadipocytes in treatment groups were decreased （P<0.05 or P<0.01）， but the cell activity of mature adipocytes had no significant differences（P>0.05）. The DAPI staining results showed that compared with blank control group， the contour of 3T3-L1 preadipocytes in different concentrations of PD treatment became irregular and nuclear fragmentation was observed；the apoptotic bodies and chromatin fragments were observed.The results of flow cytometry showed that compared blank control group，the apoptotic rates of 3T3-L1 preadipocytes in different concentrations of PD treatment groups（P<0.01）， and the percentages of cells in S phase were increased （P<0.05 or P<0.01）.The Western blotting results showed that compared with blank control group， the expression levels of Bax and cleaved-Caspase 3 in different concentrations of PD treatment groups were increased （P<0.05 or P<0.01），and the expression levels of Bcl-2 were decreased （P<0.05 or P<0.01）；the ratios of p-PI3K/PI3K and p-Akt/Akt were decreased （P<0.05 or P<0.01）.

PD can significantly induce the apoptosis of 3T3-L1 preadipocytes， and its mechanism may be related to its influence in the expression levels of apoptosis-related proteins.

To prepare the composite material of nacre powder （NP） and platelet-rich fibrin （PRF） and analyze its repair effect in the cranial defect model rabbits， and to clarify its possible mechanism.

Twelve New Zealand rabbits were selected to set up the rabbit cranial defect models， the 3 cm×3 cm area around the sagittal suture at the top of the cranial was depilated. After general anesthesia， four full-thickness cranial defects with a diameter of 8 mm were created on both sides of the sagittal suture but the intact dura mater was retained. Four cranial defects of each New Zealand rabbit were divided into four groups according to different implants：blank control group（no implant material），NP group （only NP）， PRF group （only PRF），and mixed group （NP+PRF）. Four New Zealand rabbits were sacrificed at 4，8 and 12 weeks respectively， and the cranial defect specimens were collected.Micro CT scan was adopt to detect the bone mineral density（BDM） and the percentages of new bone volome/total bone volume（BV/TV）.The pathomorphology of the bone in the cranial defect areas in various groups were observed with HE staining. The expression levels of bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （VEGF） in the new bones of the New zealand rabbits in various groups were analysed by immunohistochemistry.

At 4， 8 and 12 weeks，compared with blank control group，NP group and PRF group， the bone formation of the gross specimens in mixed group was significantly plump. The results of Micro CT scan showed that compared with blank control group，NP group and PRF group， at 4， 8 and 12 weeks，a larger area of new bone was formed in mixed group， and BMD and BV/TV were significantly increased（P<0.05），especially at 12 weeks （P<0.05）.The results of HE staining showed that the bone cells， osteoid， and new blood vessels of the New Zealand rabbits in mixed group at 4 weeks were higher than those in blank control group，NP group and PRF group； at 8 weeks，bone mineralization and neonatal bone trabecula of the New Zealand rabbits in mixed group were more obvious than those in blank control group，NP group and PRF group； at 12 weeks， the neonatal bone trabecula of the rabbits in mixed group were thicker and the degree of maturity was higher than those in blank control group，NP group and PRF group. The immunohistochemical results showed that the expression levels of BMP-2 and VEGF proteins in the new bone tissue in defect areas of the New Zealand rabbits in mixed group were significantly higher than those in blank control group，NP group and PRF group （P<0.05）.

NP combined with PRF has obvious ability to promote the bone tissue growth and it can promote the bone regeneration by inducing the increase of BMP-2 and VEGF.

The A549 cells were treated with DAPT （N-［N-（3，5-Difluorophenacetyl）-l-alanyl］-S-phenylglycine t-butyl ester） as an inhibitor of Notch1 signaling pathway and divided into 0 μmol·L^－1 DAPT group（control group），10 μmol·L^－1 DAPT group and 20 μmol·L^－1 DAPT group. Transwell chamber assay was used to detect the number of invasion cells of A549 cells in various groups； ELISA assay was used to detect the levels of matrix metalloproteinase-9 （MMP-9） and vascular endothelial growth factor （VEGF） in the supernatant of cells in various groups； Western blotting method was performed to detect the expression levels of Notch1， Hes1， Vimentin， N-cadherin and E-cadherin proteins in the cells in various groups； CCK-8 method was used to detect the inhibitory rates of growth of the A549 cells after treated with cisplatin （0.625－5.000 mg·L^－1） in various groups； Western blotting method was used to detect the expression levels of Notch1 and Hes1 proteins in the A549 cells after treated with 0 and 1.250 mg·L^－1 cisplatin alone， and the expression levels of P-glycoprotein （P-gp） and multidrug resistance-associated protein 1 （MRP1） proteins in the A549 cells after treated with 1.250 mg·L^－1 cisplatin alone or combination with 10 μmol·L^－1 DAPT.

Compared with control group， the number of invasion cells in 10 and 20 μmol·L^－1 DAPT groups was significantly decreased （P<0.05 or P<0.01），the levels of MMP-9 and VEGF in in the cell supernatant were significantly decreased （P<0.05 or P<0.01）， the expression levels of Notch1， Hes1， Vimentin and N-cadherin proteins in the A549 cells were significantly decreased （P<0.05 or P<0.01），and the expression levels of E-cadherin protein were significantly increased （P<0.05）.Compared with control group， the inhibitory rates of growth of the A549 cells in 10 and 20 μmol·L^－1 DAPT groups were significantly increased after treated with different concentrations of cisplatin （P<0.05 or P<0.01）.Compared with 0 mg·L^－1 cisplatin group， the expression levels of Notch1， Hes1， P-gp and MRP1 proteins in the A549 cells in 1.250 mg·L^－1 cisplatin group were significantly increased （P<0.05 or P<0.01）. Compared with 1.250 mg·L^－1 cisplatin group， the expression levels of P-gp and MRP1 proteins in the A549 cells in 1.250 mg·L^－1 cisplatin combined with 10 μmol·L^－1 DAPT group were significantly decreased （P<0.01）.

Blocking Notch1 signaling pathway may inhibit the cell invasion and reduce the cisplatin resistance in the lung adenocarcinoma cells.

To study the role of small GTP binding protein （Rho）/Rho-related coiled-coil forming protein kinase （ROCK） signaling pathway in the occurrence of acute ischemic stroke in the rats with obstructive sleep apnea hypopnea syndrome （OSAHS），and to provide reference for the prevention and treatment of acute ischemic stroke after OSAHS.

Fifty SD rats were randomly divided into sham operation group， OSAHS group， stroke group， post-OSAHS stroke group， and Rho inhibitor group （C3 transferase 5 μg·kg^－1·d^－1 intraperitoneal injection）， with 10 rats in each group. The OSAHS model was established by chronic intermittent hypoxia， and the middle cerebral artery was blocked by the suture method to establish an acute ischemic stroke model. The general situation and pathomorphology of cerebral cortex tissue of the rats after modeling were observed and the volumes of cerebral infarction were calculated. The respiratory frequencies and the neurological impairment scores of the rats in various groups were compared. The expression levels of myosin light chain （MLC）， Rho and ROCK in brain tissue of the rats in various groups were detected by Real-time fluorescence quantitative PCR （RT-qPCR）and Western blotting methods.

Compared with sham operation group， the rats in other groups had changes such as poor mental state and cerebral cortex structure damage， among them， the rats in post-OSAHS stroke group changed the most and the rats in Rho inhibitor group changed slightly. Compared with sham operation group，the respiratory frequency of rats in OSAHS group was increased （P<0.05）；compared with OSAHS group， the respiratory frequency of rats in stroke group was decreased （P<0.05）； compared with stroke group， the respiratory rate and Longa score of rats in post-OSAHS stroke group were increased（P<0.05）， and the Longa score of rats in Rho inhibitor group were decreased （P<0.05）； compared with post-OSAHS stroke group， the respiratory frequency and Longa score of rats in Rho inhibitor group were decreased （P<0.05）. Compared with sham operation group， the escape latency of rats in OSAHS group was prolonged（P<0.05）， and the number of crossing platform was decreased （P<0.05）； compared with OSAHS group， the escape latency of rats in stroke group was prolonged（P<0.05） and the number of crossing platform was decreased （P<0.05）； compared with stroke group， the escape latency of rats in post-OSAHS stroke group was prolonged（P<0.05）， and the number of crossing platform was decreased（P<0.05）；compared with post-OSAHS stroke group， the escape latency of rats in Rho inhibitor group was shortened（P<0.05），and the times of crossing platform was decreased（P<0.05）. Compared with stroke group， the cerebral infarction volume of rats in post-OSAHS stroke group was increased（P<0.05）； compared with post-OSAHS stroke group，the cerebral infarction volume of rats in Rho inhibitor group was decreased（P<0.05）. Compared with sham operation group， the expression levels of Rho， rock mRNA and proteins and the P-MLC / MLC ratio in brain tissue of the rats in OSAHS group were increased （P<0.05）；compared with OSAHS group， the expression levels of Rho and ROCK mRNA and proteins and the p-MLC/MLC ratio in brain tissue of the rats in stroke group were increased （P<0.05）； compared with stroke group， the expression levels of Rho and ROCK mRNA and proteins in brain tissue of the rats in post-OSAHS stroke group and the p-MLC/MLC ratio were increased （P<0.05）；compared with post-OSAHS stroke group， the expression levels of Rho and ROCK mRNA and proteins in brain tissue of the rats in Rho inhibitor group and the p-MLC/MLC ratio were decreased （P<0.05）.

The intermittent hypoxia of OSAHS can damage the nerve function， and Rho/ROCK signaling pathway may play a role in the occurrence of acute ischemic stroke in the OSAHS rats.

To investigate the effect of human umbilical cord mesenchymal stem cells （MSCs） on the proliferation and apoptosis of cervical cancer HeLa cells， and to elucidate its possible mechanism.

The human umbilical cord MSCs were isolated and cultured. The morphology of cells were observed by light microscope. The expressions of surface antigen markers CD90， CD105， CD34 and CD45 were identified by flow cytometry. The MSCs were added with second antibody （without first antibody） were used as parallel control group.The conditioned medium containing 20% and 60% MSCs and cervical cancer HeLa cells were co-cultured for 72 h， colony formation experiment was used to observe the colony forming ability of HeLa cells after treated with of MSCs conditioned medium.CCK-8 experiment was used to detect the inhibitory rates of proliferation of the HeLa cells. Flow cytometry was used to detect the apoptotic rates of HeLa cells. Western blotting method was used to detect the expression levels of proliferation- and apoptosis-related gene proteins in the HeLa cellsn.

After 72 h of inoculation， a small number of cells adhered to the wall， and gradually became flat monolayer cells， which grew in clusters and vortices after one week. With the increase of cell density， the cell body became slender， similar to that of fibroblasts.The MSCs showed positive expressions of CD90 and CD105， but negative expressions of CD34 and CD45， which conformed to the phenotype of stem cells.The results of colony formation test showed that the inhibitory rates of colony formation of HeLa cells were 18.56% and 37.64% respectively when the conditioned medium containing 20% and 60% MSCs were added.Compared with control group，the early apoptotic rate of HeLa cells after treated with MSCs for 48 h was increased （P<0.05）. After the HeLa cells were treated with MSCs for 0， 24 and 48 h， the expression levels of cysteinyl aspartate-specific proteinase-3 （Caspase-3） and P53 proteins were increased continuously （P<0.05）， and the expression levels of B-cell lymphoma-2 （Bcl-2） protein were decreased continuously （P<0.05）.

The MSCs can inhibit the proliferation of HeLa cells and induce the apoptosis of HeLa cells in vitro，and its mechanism may be related to up-regulating the expression of Caspase-3 and P53 and down-regulating the expression of anti-apoptotic factor Bcl-2.

To investigate the protective effect of semen plantaginis extract （SPE） on kidney of the rats with membranous nephropathy， and to elucidate its mechanism.

Fifty male SD rats were randomly divided into control group， model group， low， medium and high doses of SPE groups（ n=10）. In addition to control group， the rats in other groups were given cationic bovine serum albumin to establish the membranous nephropathy models. The rats in low， medium and high doses of SPE groups were given 1.5， 3.0 and 4.5 mg·kg^－1 SPE by gavage， and the rats in model group and control group were given the same amount of normal saline， last for 4 weeks. The levels of creatinine （Scr）， urea nitrogen （BUN） and albumin （ALB） in serum of the rats were determined. TUNEL assay was used to determine the apoptotic rates of kidney tissue cells of the rats in various groups. Real-time fluorescence quantitative PCR（RT-qPCR） and Western blotting methods were used to detect the expression levels of Bcl-2， Bax， Caspase-3 mRNA and proteins in kidney tissue.

Compared with control group， the levels of serum Scr and BUN of the rats in model group were significantly increased （P<0.05）， while the level of serum ALB was significantly decreased （P<0.05）， the expression levels of Bcl-2 mRNA and proteins in kidney tissue of the rats were significantly decreased （P<0.05）， the expression levels of Bax and Caspase-3 mRNA and proteins in kidney tissue were significantly increased（P<0.05）， and the apoptotic rates were significantly increased （P<0.05）. Compared with model group， the levels of serum Scr and BUN in low， medium and high doses of SPE groups were significantly decreased （P<0.05）， while the level of serum ALB was significantly increased （P<0.05）， the expression levels of Bcl-2 mRNA and protein and proteins in kidney tissue were significantly increased （P<0.05）， the expression level of Bax and Caspase-3 mRNA and proteins in kidney tissue were significantly increased （P<0.05），and the apoptotic rates were significantly increased （P<0.05）.Compared with low dose of SPE group， the levels of serum Scr and BUN in medium and high doses of SPE groups were significantly decreased （P<0.05），while the levels of serum ALB were significantly increased （P<0.05）， the expression levels of Bcl-2 mRNA and protein in kidney tissue were significantly increased （P<0.05）， the expression levels of Bax and Caspase-3 mRNA and proteins in kidney tissue were significantly decreased （P<0.05）， and the apoptotic rates were significantly decreased （P<0.05）.

SPE can protecte the kidney of the rats with membranous nephropathy by regulating the expression levels of Bcl-2 and Bax mRNA and proteins， and reduce the apoptosis of kidney tissue cells.

To observe the effect of fermented red ginseng total saponins（FRGTS） on the proliferation and collagen synthesis of the rat myocardial interstitial fibroblasts （cFb） cultured in high glucose， and to clarify their mechanisms.

The cFb were isolated and extracted from 1－3 old SD rats by trypsin digestion and differential adhesion method. After culture and passage， the 2－3 generations of cFb were taken for experimental study. The cells were divided into normal glucose control group （5.5 mmol·L^－1 D-glucose）， high glucose group （25 mmol·L^－1 D-glucose），high glucose +15 mg·L^－1 FRGTS group （F15 group）， and high glucose +30 mg·L^－1 FRGTS group （F30 group）. MTT assay was used to detect the proliferation activities of cFb in various groups， ELISA method was used to detect the levels of collagen Ⅰ and collagen Ⅲ proteins in the cFb supernatant in various groups， Real-time fluorescence quantitative PCR（RT-qPCR） was used to detect the expression levels of Smad3 and Smad7 mRNA， and Western blotting method was used to detect the expression levels of urotensin Ⅱ（UⅡ）， transforming growth factor beta 1 （TGF-β1）， Smad3 and Smad7 proteins in the cFb in various groups.

Compared with normal glucose control group， the proliferation activities of cFb in high glucose group was significantly increased （P<0.01）， and the levels of collagen Ⅰ and collagen Ⅲ proteins were significantly increased （P<0.01）.compared with high glucose group， the proliferation abilities of cFb in F15 and F30 groups were decreased （P<0.05）， and the inhibitory effect of F30 group was stronger than that of F15 group. After 24 h of intervention with FRGTS， the levels of collagen Ⅰ and collagen Ⅲproteins in the cFb supernatant were significantly lower than those in high glucose group （P<0.05）， and the effect of F30 group was more significant than that of F15 group. Compared with normal glucose control group， the expression levels of UⅡ and TGF-β1 proteins in the cFb in high glucose group were significantly increased （P<0.01），the mRNA and protein expression levels of Smad3 were significantly increased （P<0.01），and the mRNA and protein expression levels of Smad7 were significantly decreased （P<0.05）；compared with high glucose group， after 24 h of intervention with FRGTS， the expression levels of UⅡ and TGF-β1 proteins in the cFb in F15 group and F30 group were significantly decreased （P<0.01），the mRNA and protein expression levels of Smad3 were significantly decreased （P<0.01）， the mRNA and protein expression levels of Smad7 were significantly increased （P<0.05 or P<0.01），and the effect in F30 group was better than that in F15 group.

FRGTS can effectively inhibit the fibrosis induced by high glucose and protect the myocardium of diabetic rats， and its mechanism may be related to inhibiting the activation of UⅡ in the cFb and regulating the TGF-β1/Smads pathway.

To investigate the effects of N-acetyl-L-cysteine （NAC） on the oxidative stress and vascular endothelial function in the rats with hyperuricemia （HUA）， and to elucidate their mechanisms.

Totally 60 SD rats were randomly divided into control group， model group， low dose of NAC group and high dose of NAC group，with 15 rats in each group. Except for control group， the rats in all other groups were administered with potassium oxonate to induce the HUA models. The rats in low and high doses of NAC groups were given 75 and 300 mg·kg^－1 NAC respectively by gavage， while the rats in control group and model group were given the same amount of normal saline， once a day for 4 weeks. The blood samples of rats were collected from abdominal aorta and the serum was separated. The levels of serum uric acid （UA）， blood urea nitrogen （BUN）， serum creatinine （Scr）， endoderin-1 （ET-1）， nitric oxide （NO） and malondialdehyde （MDA）， and the activities of total superoxide dismutase （T-SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） were measured. The expression levels of endothelial nitric oxide synthase （eNOS） in thoracic aorta tissue of the rats in various groups were detected by immunohistochemistry method.

Compared with control group， the levels of UA， MDA and ET-1 of the rats in model group were obviously increased （P<0.05）， the activities of serum T-SOD， CAT and GSH-Px， the level of NO and the expression level of eNOS in thoracic aorta tissue were significantly decreased （P<0.05）， while there were no statistical differences in the levels of serum BUN and Scr （P>0.05）. Compared with model group， the levels of serum UA， MDA and ET-1 in high dose of NAC group were significantly decreased （P<0.05）， the activities of serum T-SOD， CAT， and GSH-Px， the level of NO and the expression level of eNOS in thoracic aorta tissue were markedly increased （P<0.05）， while there were no statistical differences in the levels of serum BUN and Scr （P>0.05）； there were no statistical differences in the changes of the above indexes in low dose of NAC group （P>0.05）. Compared with low dose of NAC group， the levels of serum UA， MDA and ET-1 of the rats in high dose of NAC group were significantly decreased （P<0.05）， the activities of serum T-SOD， CAT， and GSH-Px， the level of NO and the expression level of eNOS in thoracic aorta tissue were markedly increased （P<0.05），while there were no statistical differences in the levels of serum BUN and Scr （P>0.05）.

NAC can decrease the level of serum UA in the HUA rats， reduce the level of oxidative stress in the body， and improve the vascular endothelial function.

To observe the effects of velvet antler polypeptide（VAP） on the learning and memory abilities and the expressions of KELCH-like ECH related protein 1（Keap1）， nuclear factor E2 related factor 2（Nrf2） and heme oxygenase-1（HO-1） in hippocampus tissue of the rats with mild cognitive impairment（MCI）， and to explore the mechanisms.

Fifty clean Wistar rats were randomly divided into normal control group， MCI group， piracetam group， low dose of VAP group and high dose of VAP group （n=10）. Except normal control group，the rats in other groups were intraperitoneally injected scopolamine for 18 d to set up the MCI models.The rats in piracetam group were given piracetam 500 mg·kg^－1， the rats in low dose of VAP group were given VAP 200 mg·kg^－1， and the rats in high dose of VAP group waere given VAP 300 mg·kg^－1. The behavioral changes of rats in various groups were observed by Morris water maze test， the pathomorphology of hippocampus tissue of the rats was observed by HE staining， the activities of superoxide dismutase （SOD） and the levels of malondialdehyde （MDA） in serum of the rats in various groups were detected by ELISA method， and the expression levels of Keap1， Nrf2and HO-1 proteins in hippocampus tissue of the rats in various groups were detected by Western blotting method.

The results of Morris water maze test showed that compared with normal control group， the escape latency and behavior path of the rats in MCI group were significantly increased （P<0.01）， while the times of crossing the platform and the residence time in the effective area were significantly decreased （P<0.01）；compared with MCI group， the escape latencies of piracetam group，low dose of VAP group and high dose of VAP group were decreased significantly （P<0.01），the behavior paths of piracetam group and high dose of VAP group were shortened significantly （P<0.01）， and the times of crossing the platform and the residence time in the effective area of the rats in piracetam group，low dose of VAP group and high dose of VAP group were increased significantly （P<0.05 or P<0.01）.The HE results showed that compared with normal control group， the number of cells in hippocampus tissue of the rats in MCI group was decreased obviously， and the arrangement mode was changed from orderly to relatively disorder； compared with MCI group， the cells in hippocampus tissue of the rats in piracetam group and high dose of VAP group were arranged more orderly and the shape was slightly regular. Compared with normal control group， the activity of serum SOD of the rats in MCI group was decreased significantly （P<0.01） and the level of MDA was increased significantly （P<0.01）；compared with MCI group， the serum SOD activities of the rats in piracetam group and high dose of VAP group were increased significantly （P<0.05 or P<0.01）， while the MDA levels were decreased significantly （P<0.05 or P<0.01）.The results of Western blotting method showed that compared with normal control group， the expression level of Keap1 protein in hippocampus tissue of the rats in MCI group was significantly increased （P<0.01），while the expression levels of Nrf2 and HO-1 proteins were significantly decreased （P<0.05 or P<0.01）；compared with MCI group， the expression levels of Keap1 protein in hippocampus tissue of the rats in piracetam group， low dose of VAP group and high dose of VAP group were decreased significantly （P<0.01）， while the expression levels of Nrf2 and HO-1 proteins were increased significantly （P<0.01）.

VAP can improve the learning and memory abilities of MCI model rats induced by scopolamine， and its mechanism may be related to increasing the expression levels of Keap1，Nrf2 and HO-1 proteins in hippocampus of the rats to play an anti-oxidative stress role.

To investigate the expressions of tight junction proteins Claudin-1 and Occludinin in the human colon adenocarcinoma cells （Caco-2） infected by Shigella， and to elucidate the effect of Shigella on the human colon adenocarcinoma Caco-2 cells and its related mechanism.

The ten nests of SPF Kunming 5-day-old suckling mice were divided into control group and experimental group，with 5 nests in each group. Each suckling mouse in control group was given 100 μL PBS per day，the mouse in experimental group was given 100 μL 1×10⁶ PFU·mL^－1 SA11 strain rotavirus.The fecal samples of suckling mice were collected，and Shigella was isolated and identified by biochemical test， serological detection and 16S rRNA sequencing.The Caco-2 cells were divided into control group and Shigella infection group. Different concentrations of Shigella were used to infect the Caco-2 cells for different time. The cell survival rates in various groups were detected by trypan blue staining， and the expression levels of Claudin-1 and Occludin mRNA and proteins in the cells in various groups were detected by Real-time PCR and Western blotting methods.

The biochemical identification of bacteria showed that the color of inclined surface of disaccharide iron medium did not change， the bottom was yellow， and the puncture line was obvious， which was suspected of pathogenic intestinal bacteria. It was negative for lactose and positive for glucose， maltose， sucrose and mannitol.The 16S rRNA sequencing results showed 99% homology with Shigella， and it was identified as Shigella. Compared with control group， there was no significant difference in the cell survival rate within 4 h of infection in Shigella group （P>0.05）； when cocultured with 1×10⁶ CFU·mL^－1 Shigella for 3 h， the expression levels of Claudin-1 and Occludin mRNA and proteins in the Caco-2 cells were decreased significantly （P<0.05）.

Shigella isolated from feces of diarrhea model mice infected with rotavirus can reduce the expression levels of Occludin and Claudin-1 in the human colon adenocarcinoma cells（Caco-2）， improve the permeability of intestinal epithelial cells， and affect the normal barrier function of intestinal epithelial cells.

To investigate the expressions of phosphoribosyl pyrophosphate synthetases 2 （PRPS2） in different subtypes of breast cancer and its relationship with the prognosis of breast cancer.

The transcription levels of PRPS2 in the pan-breast cancer and normal breast tissues were investigated using GEPIA database. Furthermore， UALCAN database was used to analyze the expressions of PRPS2 in the breast cancer and normal breast tissues on the basis of age， menopause status， different subtypes， histologic subtypes， pathological stages， and nodal metastasis status. miRTarBase database was used to predict the miRNAs binding with 3' un-translated region （3'UTR） of PRPS2. Kaplan-Meier plotter database was used to evaluate the relationships between the miRNAs binding with PRPS2 andPRPS23'UTR and the prognosis of breast cancer.

Compared with normal breast tissue，the expression levels of PRPS2 mRNA in different subtypes of breast cancer tissue was significantly increased（P<0.05）.The high expression of PRPS2 mRNA documented the poor prognosis of breast cancer. Compared with normal breast tissue，the expression levels of hsa-miR-215-5p and hsa-miR-26b-5p， the miRNAs binding with 3'UTR of PRPS2，in the different subtypes of breast cancer tissue were significantly reduced（P<0.05）；moreover， the low expression levels of hsa-miR-215 and hsa-miR-26b reflected the poor prognosis of breast cancer.

PRPS2 is of specific expression characteristics of pan-breast cancer， suggesting that the axis of miR-PRPS2-prognosis of breast cancer may exist.

To investigate the expressions of phosphatidylinositol proteoglycan 3 （GPC3） and α-smooth muscle actin （α-SMA） in the liver tissue of the biliary atresia （BA）children， and to investigate their correlations with liver function related indexes.

A total of 26 children with BA were selected as the study subjects（BA group）.All patients received Kasai surgery. Twenty children with choledochal cyst were selected as control group. Real-time fluorescence quantitative PCR （RT-qPCR） and immunohistochemistry were used to detect the expression levels of GPC3 and α-SMA mRNA and proteins in liver tissue of the patients in two groups； Pearson correlation analysis was used to analyze the correlations of the GPC3 mRNA expression level with the expression level of and α-SMA mRNA and the correlations of GPC3 and α-SMA protein expression levels in liver tissue and liver function indexes ［albumin （ALB）， total bilirubin （TB），direct bilirubin （DB），alanine aminotransferase （ALT），aspartate aminotransferase （AST）， alkaline phosphatase （ALP） and γ-glutamyl aminotransferase （γ-GGT）］ of the patients. After 6 months of postoperative follow-up， 18 patients were divided into good prognosis group and 8 patients were divided into poor prognosis group according to the level of liver function. The protein expression levels of GPC3 and α-SMA of the patients in different prognosis groups were compared. Metavir score was used to compare the degrees of liver fibrosis patients in different prognosis groups.

Compared with control group， the expression levels of GPC3 and α-SMA mRNA in liver tissue of the children in BA group were significantly increased （P<0.05）；there was a positive relationship between GPC3 and α-SMA mRNA expression levels in liver tissue of the BA children （r=0.5370， P=0.005）.GPC3 protein expression was positive in 21 （80.8%） cases of BA children， and α-SMA protein expression was positive in 20 （76.9%） cases of BA children.Compared with control group， the expression levels of GPC3 and α-SMA proteins in liver tissue of the children in BA group were increased （P<0.05）.The Pearson correlation analysis results showed that the GPC-3 protein expression level was positively correlated with ALP level （r=0.582， P=0.008） and Metavir score （r=0.468，P=0.016），and it was negatively correlated with age （r=－0.384，P=0.026），ALB level （r=－0.514，P=0.005） and AST level （r=－0.327 2，P=0.035）.The α-SMA protein expression level was positively correlated with ALP level （r=0.465，P=0.016） and Metavir score （r=0.422，P=0.010）. Compared with good prognosis group， the expression levels of GPC3 and α-SMA proteins and Metavir score in liver tissue of the children in poor prognosis group were significantly increased （P<0.05）.

The high expression levels of GPC3 and α-SMA in the liver tissue may be positively correlated with the degrees of liver dysfunction and fibrosis in the BA children， which often suggests a poor prognosis.

To investigate the relationships between the expression of Tip60 protein in the endometrial adenocarcinoma tissue and the clinicopathological parameters and prognosis of endometrial adenocarcinoma，and to clarify the effect of Tip60 protein in the occurrence and development of endometrial adenocarcinoma.

A toatal of 84 cases of endometrial adenocarcinoma patients were selected. The expression levels of Tip60 protein in 84 cases of endometrial adenocarcinoma tissue and 36 cases of normal endometrial tissue were selected with immunohistochemical SP method. The relationships between the expression of Tip60 protein and the clinicopathological parameters were analyzed. Kaplan-Meier curve was used to analyze the relationships between the expression of Tip60 protein and prognosis of the patients. Western blotting method was used to detect the expressions of Tip60 in the endometrial carcinoma cell lines ISHIKAWA and HEC-1A.

The immunohistochemistry results showed that the positive expression rate of Tip60 protein in the endometrial adenocarcinoma tissue was 54.76% （46/84）， which was significantly lower than that in the normal endometrial tissue （83.33%， 30/36） （χ²=8.859，P=0.003）.The expression of Tip60 protein was not associated with age of the patients（χ²=1.073，P=0.300）； the positive expression rate of Tip60 protein in endometrial adenocarcinoma tissue of the patients in grade Ⅰ of FIGO stage was significantly high than those of the patients in grade Ⅰ and grade Ⅲ（χ²=13.481，P=0.001）；the positive expression rate of Tip60 protein in the endometrial adenocarcinoma patients with high differentiation was higher than that in the patients with low and middle differentiation（χ²=8.962，P=0.013）. The median follow-up time for 84 patients with endometrial adenocarcinoma was 58 months. The results of Kaplan-Meier survival analysis and Log-rank test showed that the survival rate of the patients with high expression of Tip60 protein was significantly higher than that of the patients with low expression（χ²=64.391， P=0.002）. The expression level of Tip60 protein in the ISHIKAWA cells with high expression of estrogen receptor（ER） was significantly higher than that of HEC-1A cells with low expression of ER （P<0.05）.

The expressions of Tip60 protein in endometrial adeno carcinoma tissue and Ishikawa cells with high expression of ER are lower which suggests that Tip60 protein is involved in the occurrence and development of endometrial adenocarcinoma. The detection of Tip60 protein expression level in endometrial tissue is helpful for the diagnosis and prognosis of endometrial adenocarcinoma.

To explore the reasons for the differences in the patency rates of left internal mammary artery （LIMA）， great saphenous vein （SVG）， internal mammary artery + great saphenous vein composite bridge （LIMA+SVG） and radial artery （RA） after coronary artery bypass grafting （CABG） based on the characteristics of blood flow spectrum， and to clarify the clinical significance and application value.

The clinical materials of 132 patients underwent CABG were collected. The blood flow waveforms of patent grafts in follow-up were obtained and divided into LIMA group， SVG group， LIMA+SVG group and RA group according to the types for Fast Fourier Transform （FFT）. The differences in the frequencies and amplitudes of wave peaks （which were named H₁－H_n according to frequency from low to high） in the spectrum of grafts in various groups were compared with the statistic method and the factors affecting the differences in the long-term patency rates of different types of grafts were analyzed.

The frequency of first harmonic （H₁） in LIMA group was equal to SVG group， and the others in LIMA group were lower than those in SVG group. The frequencies of H₁ and H₂ in LIMA +SVG group were higher than those in LIMA group， the frequency of H₃ was lower， and the fourth harmonic H₄ was visible. Compared with SVG group， the frequency of H₁ in LIMA+SVG group and the frequencies of H₂ and H₃ were lower.The frequencies of H₁ and H₂ in RA group were higher than those in LIMA group and SVG group.The differences in the amplitudes between four groups were statistically significant （χ²=8.131， P=0.043）；the amplitude in SVG group was higher than that in LIMA group （P=0.006），and there were no significant differences in the amplitudes between LIMA+SVG group， RA group and LIMA group （P=0.812， P=0.977）.

The blood flow in LIMA and RA is more stable and less turbulent， which are the preferred choice in CABG operation. LIMA+SVG has partly arterial characteristics and the structural advantages compared with SVG. The flow of SVG is easier to turbulence and SVG should be reduced as much as possible.

To explore the effect of programmed intermittent epidural bolus（PIEB） mode for labor analgesia and its influence in the umbilical blood flow and umbilical artery blood gas， and to provide the basis for finding a more ideal mode of epidural labor analgesia.

Ninety cases of full-term singleton neonates who required labor analgesia were randomly divided into PIEB group and continuous epidural infusion （CEI） group by random number table method，with 45 cases in each group.The maternity patients in two groups were given the first dose （0.08 g·L^－1 ropivacaine+0.4 mg·L^－1 dexmedetomidine） 10 mL.The maternity patients in PIEB group were connected to the PIEB analgesia pump 1 h after the injection of the first dose， with the pulse dose of 8 mL·h^－1 and the speed of 7 mL·min^－1；the patients in CEI group were connected to the CEI analgesia pump immediately after the first dose injection， and the continuous background dose was 8 mL·h^－1.The VAS pain scores of the maternity patients in two groups before analgesia （T0）， 30 min after analgesia （T1），1 h after analgesia （T2）， 2 h after analgesia （T3） and full-time uterine opening （T4） were compared. The umbilical artery pulsatitly index （PI）， umbilical artery resistance index （RI） and the ratios of systolic peak to diastolic peak （S/D） of fetal umbilical artery blood flow velocity of the patients at T0－T3 were compared. The umbilical artery blood gas pH values， residual alkali （BE） values and the newborn Apgar scores immediately after delivery of the maternity patients in two group were compared.The first stage of labor， the second stage of labor， satisfaction and adverse reactions were compared between two groups.

There were no differences in the VAS scores of the patients at T0， T1， T2 and T3 between two groups （P>0.05）.The VAS score of the maternity patients in PIEB group at the T4 time point was lower than that in CEI group （P<0.05）. There were no differences in the fetal PI， RI， and S/D ratios of the maternity patients at different time points between two groups （P>0.05）.There were no statistically significant differences in the umbilical artery blood gas pH values and BE values of the maternity patients between two groups（P>0.05）， and there was no significant difference in the Apgar score between two groups （P>0.05）. There were no significant differences in the first stage of labor， the second stage of labor and the adverse reactions between two groups（P>0.05）. The score of satisfaction with analgesia of the maternity patients in PIEB group was significantly higher than that in CEI group（P<0.05）.

PIEB mode for labor analgesia has no significant effect on the umbilical blood flow and umbilical artery blood gas， and has better safety.

To investigate the associations of the neutrophil/lymphocyte ratio（NLR） and platelet/lymphocyte ratio（PLR） with the prognosis in the small-cell lung cancer（SCLC） patients received platinum-based first-line chemotherapy， and to clarify the significance of NLR and PLR in the prognosis of the SCLC patients.

Literature retrieval were conducted in PubMed， EMbase， Web of Science， Cochrane Library and China National Knowledge Internet（CNKI）databases. The retrieval period was from the establishment to March 2021. The clinical studies of patients with SCLC including limited stage SCLC （LS-SCLC） and extensive stage SCLC（ES-SCLC） received platinum-based first-line chemotherapy. Meta-analysis was performed on the literatures that met the inclusion and exclusion criteria by STATA 14.0 software， and the prognostic effects of NLR and PLR in the SCLC patients with different disease stages and pathological types were observed.

A total of 1 012 literatures were retrieved. Finally， eleven studies encompassing 3 634 SCLC patients were included. The combined outcomes demonstrated that the overall survival（OS）［hazard ratio（HR）=1.45， 95%confidence interval（95%CI）： 1.26－1.67，P<0.01］ and progression-free survival（PFS）（HR=1.53，95%CI：1.29－1.82，P<0.01） of the patients in high NLR group were lower than those in low NLR group， while there was no difference in the OS between high NLR group and low NLR group（HR=1.17， 95%CI：0.87－1.56，P=0.293）. In subgroup analysis， the OS in higher NLR group in different stages，different pathological types， different regions， analysis modes，and NLR cutoff value≥4 in subgroups were lower than those in lower NLR group（P<0.05）；the OS in LS-SCLC and PLR cutoff value<160 patients in higher NLR group were lower than those in lower PLR group.

In the SCLC patients received platinum-based first-line chemotherapy， higher NLR is associated with poor prognosis in the SCLC patients， and higher PLR is associated with poor prognosis in the LS-SCLC patients.

To explore the related factors that affects the sagittal diameter of upper airway of the children with skeletal class Ⅱ malocclusion during the growth and development period， and to provide ideas for the formulation of clinical orthodontic programs that includes airway prediction.

A total of 100 children with skeletal class Ⅱ malocclusion during the growth and development period aged 9－15 years old from 2017－2018 in the Department of Orthodontics in our hospital were selected for retrospective study. The patients’ general information （gender，height， body mass），dental arch measurement data， and X-ray cephalometric analysis data were collected， and the upper airway sagittal diameters of the children with skeletal class Ⅱ malocclusion during the growth and development period were analyzed. Through the results obtained by multiple regression analysis， the related factors affecting the size of the sagittal diameter of each segment of the upper airway were obtained.

In the laryngopharyngeal airway， compared with QCVM stages Ⅰ to Ⅱ，the laryngopharyngeal airway sagittal diameter （V-LPW） in QCVM stages Ⅱ to Ⅲ，and Ⅲ to Ⅳ were increased significantly.In the nasopharyngeal airway， compared with QCVM Ⅰ to Ⅱ stages and Ⅲ to Ⅳ stages， the PNS-UPW from stage Ⅱ to stage Ⅲ was significantly increased（P<0.05）. In the laryngopharyngeal airway， the sagittal diameter （V-LPW） was increased with the increase of the body mass index（BMI），and there were statistically significant differences between low-weight group and normal-weight group，low-weight group and overweight group （P<0.05）.The sagittal diameters （PNS-UPW and U-MPW） in low-weight group were lower than those in normal weight group （P<0.05）. In the nasopharyngeal airway， SNB and whether the patient was in QCVM stage Ⅱ were the influencing factors of the sagittal diameter PNS-UPW （P<0.05）. In the oropharyngeal airway， H-C3， ANB and soft palate length （SPL） were the influencing factors of U-MPW （P<0.05）. In the laryngopharyngeal airway， H-C3 and whether the patient was in low-weight were the influencing factors of V-LPW （P<0.05）. In the pharyngeal airway space， H-C3，ANB and whether the patient was in low-weight were the influencing factors of PAS （P<0.05）.

The sagittal diameter of the upper airway in the children with skeletal class Ⅱ malocclusion during the growth and development period is closely related to the surrounding soft and hard tissues. When formulating a clinical orthodontic treatment plan， it is necessary to comprehensively evaluate the upper airway and the patient’s own condition to avoid the iatrogenic factor-caused upper airway obstruction in the patients， and to provide a reference for the prognosis.

To analyze the clinical manifestation， pathological diagnosis， treatment and prognosis of the patient with alveolar soft part sarcoma （ASPS） of right buccal mucosa， and to improve the clinicians’ understanding of ASPS.

The clinicopathologic data of a patient with ASPS of right buccal mucosa were collected； the clinical characteristics， pathological diagnosis features， differential diagnosis， treatment and prognosis were summarized， and the relevant literatures were reviewed.

A 46-year-old male patient was admitted to local hospital because of right buccal mucosal tumor found 3 months ago. The tumor increased slowly without pain or other clinical symptoms. The patient was diagnosed as benign tumor and underwent surgical treatment. No definite pathological diagnosis was found after surgery. In order to conform the diagnosis， the patient came to our hospital for consultation. Histologically， the neoplastic cells were characterized by aggregates of large polygonal or round mesenchymal cells with abundant eosinophilic and granular cytoplasm. The tumor showed a solid， diffuse growth pattern， without organoid or nested architecture，and tumor thrombi could be seen. The neoplastic cells were negative for CK（p） and Vimentin， and demonstrated partly positivity for SAM and Desmin， and diffuse intense nuclear positivity for TFE3. The pathological diagnosis was ASPS （solid pattern）， with blood vessel invasion. The patient did not receive radiotherapy or chemotherapy after operation. There was no recurrence and metastasis after follow-up of 5 months.

ASPS has no specific clinical characteristics and imaging features. The diagnosis of ASPS mostly depends on the histopathological and immunohistochemical examinations. Solid ASPS is more likely to be misdiagnosed. Radical resection is the main treatment for ASPS and the patients should be given regular follow-up after operation.

To analyze the clinical diagnosis and treatement of the patients with primary hyperparathyrodism （PHPT）， papillary thyroid carcinoma （PTC） and moderate anemia， and to improve the clinicians’ understanding and knowledge to these diseases to reduce the missed diagnosis and misdiagnosis.

The clinical materials of a patient with PHPT combined with PTC and moderate anemia were collected and the relevant literatures were reviewed； the clinical characteristics， imaging appearances， diagnosis and surgery methods were discussed.

A female 42-year-old patient was admitted to hospital due to kidney stones for 15 years and PHPT for 1 month. The main manifestations of the patient included disgusted， palpitation， fatigue， mastication discomfort， and poor appetite with weight reducing 10 kg within 1 month. The patient had anemia appearance. The results of lab tests showed hypercalcemia， hyponatremia， hypopotassaemia， moderate anemia， hypoproteinemia and hyperparathyroidism. The thyroid ultrasound results showed a tumor on the left lobe of thyroid， TI-RADS4a grade； a tumor might origin from the parathyroid tissue on the right side of neck. ^{99 m}Tc MIBI dual phase imaging of parathyroid： an increased radioactivity area on the dorsal side of the upper pole of the thyroid right lobe. It was considered as hyperparathyroidism tumor. The results of abdominal ultrasound showed cholestasis， left hydronephrosis， double kidney stones. The diagnosis was parathyroid tumor， PHPT，thyroid tumor （considered as malignant），kidney stones， moderate anemia and chronic periodonititis.The patient was undergone parathyroid tumor excision and radical thyroidectomy after electrolyte disturbance and anemia was treated.

The patients with PHPT may lead to kidney stones and electrolyte disturbance because of hypercalcemia. The patient should be suspected as PHPT according to these symptoms. PHPT combined with PTC and anemia is rare even to misdiagnose. Complete examinations and correct diagnosis are necessary in order to avoid reoperation.

To discuss the clinical restoration effect of multi-disciplinary combined treatment for invasive periodontitis， and to explain the significance of multi-disciplinary combined treatment on the restoration of oral function.

The clinical data of one patient with severe invasive periodontitis resulted in loosening and disengagement of teeth were collected. After periodontium-orthodontium-implant-prosthesis multidisciplinary combined treatment， the bleeding on probing （BOP）， probing depth （PD）， attachment loss （AL） and implant osseointegration indexes of the patient were observed to determine the clinical repair effect；at the same time， literature review was conducted.

The patient， female， was conscious of the loosening and discomfort of the front and rear mandibular teeth in Jan. 2016； recently， the loosening became worse and she dared not bite on the hard objects. The clinical examination found that the patient’s oral hygiene was poor； the gingival of 31， 35， 36， 37， 41 were dark red； BOP （+）； PD 5－7 mm； AL 3－5 mm； teeth mobility： Ⅲ°.The clinical diagnosis was severe invasive periodontitis. First， periodontal treatment was performed to eliminate inflammation. After the inflammation was obviously eliminated， the affected teeth loosened by Ⅲ° were removed. In order to close the anterior teeth space， develop the lower anterior teeth and leave space for implantation， the patient was treated with orthodontic treatment. Finally， the bone defect was repaired by guided bone regeneration （GBR）. When the periodontal soft and hard tissues grew well and the alveolar ridge was plump， implant restoration was performed. During the whole treatment process， the plaque was strictly controlled， the chewing function of the patient was restored， and the anticipated aesthetic effect was achieved. One year later， the patient’s oral hygiene was good， the implant position was stable， and the radiographic examination showed no loss of bone around the implant.The gingival was pink and had not obvious inflammation.

Multidisciplinary combined treatment of the invasive periodontitis patients can not only recover the masticatory function of the patient， but also achieve the effect of aesthetic restoration.

To understand the general demographics， clinical symptoms and living conditions of the patients living in communities with severe mental disorders in Guangdong Province，to analyze the differences between them and inpatients， and to provide a basis for the further management and treatment of severe mental disorders.

From December 2018 to February 2019， 6 886 patients with severe mental disorders hospitalized or managed in mental health institutions （specialized mental health institutions and community health service centers） in 11 prefecture-level cities under the jurisdiction of Guangdong Province were investigated by multi-stage stratified sampling method.

Compared with the inpatients， the distribution differences in the general demographic characteristics， clinical symptoms and living status of the patients living in the community were statistically significant （P<0.05）. The composition ratio of inpatients at <18 years old, 18-44 years old and ≥60 years old were higher than those of the community residents, while the composition ratio of inpatients at 45-59 years old was lower than that of community patients (P<0.05). The composition ratio of male inpatients was higher than that of community patients, while the composition ratio of female patients was lower than that of community patients (P<0.05).The community patients were more married cohabitation， and the inpatients unmarried accounted for a higher proportion （P<0.05）； the community patients with education level below primary school accounted for a higher proportion than the inpatients （P<0.05）；the proportions of hallucinations， difficulty in communication， suspicion， motility，strange behaviors， excited talking，destroying things， pessimism， going out for no reason， self-amusement，solitude and lazy and other clinical symptoms in the patients living in community as well as the total number of hospitalization in the past were lower than the inpatients（P<0.05）， but the first age and the total duration of illness were higher than the inpatients （P<0.05）.The multivariate Logistic analysis of the patients from the two sources showed that the proportions of smoking ［OR （95%CI）=1.968（1.436－2.696）］，drinking［OR（95%CI）=1.776（1.105－3.105）］，risk assessment level ［OR（95%CI）=10.197（4.053－25.654）］ and actual sleep frequency ［OR（95%CI） = 1.855 （1.375－2.502）］of the patients living in the communities were higher than those of the inpatients（P<0.05）.The proportions of frequency of exercising less than 1－2 times a week ［OR（95%CI）=0.205（0.070－0.600）］ and being locked up ［OR（95%CI）= 0.566（0.425－0.755）］ in the patients living in communities were lower than those of the inpatients（P<0.05）.

The patients with severe mental disorders living in community in Guangdong Province are more likely to have hallucinations， communication difficulties， suspicion， moodiness， strange behavior and other clinical symptoms， as well as the bad behaviors such as smoking and drinking. In the future， behavioral intervention should be strengthened for the patients with severe mental disorders in the community， and the service functions of the community and the hospital should be balanced.