To explore the expression of programmed death-1 （PD-1） in the infiltrating CD4+ and CD8+ T lymphocytes in non-small cell lung cancer （NSCLC） tissue， and to illuminate the influence of prostaglandin E2（PGE2） on the PD-1 expression and its related mechanism.

A total of 75 patients diagnosed as NSCLC were enrolled and divided into stages Ⅰ-Ⅳ according to the TNM staging criteria for NSCLC issued by the Union Internationale Against cancer （UICC）.The infiltrating mononuclear cells in NSCLC tissue homogenate were separated by density gradient centrifugation. The percentages of CD4+ and CD8+ T lymphocytes in the infiltrating lymphocytes were analyzed by flow cytometry. Real-time fluorescence quantitative polymerase chain reaction（RT-qPCR） and Western blotting methods were used to detect the expression levels of PD-1 mRNA and protein in the infiltrating T lymphocytes. The PGE2 level in serum was detected by ELISA.

The percentages of infiltrating CD8+ T lymphocytes in the NSCLC patients at stages Ⅲ and Ⅳ were obviously higher than those of the NSCLC patients at stages Ⅰ and Ⅱ（P<0.05）， but the percentages of CD4+ T lymphocytes showed no significant differences among the patients at different stages（P>0.05）. The expression level of PD-1 mRNA in the CD8+ T lymphocytes in the NSCLC patients at stage Ⅳ was higher than those of the patients at other stages （P<0.05）， but the expression levels of PD-1 mRNA in the CD4+ T lymphocytes had no significant differences among the patients at different stages （P>0.05）. The serum levels of PGE2 in the NSCLC patients at stages Ⅲ and Ⅳ were obviously higher than those in the NSCLC patients at stages Ⅰ and Ⅱ （P<0.05）. The expression levels of EP2 and EP4 mRNA in the CD8+ T lymphocytes were obviously increased after PGE2 stimulating（P<0.05）；the PD-1 mRNA expression levels in the CD8+ T lymphocytes were significantly decreased after adding EP2 and EP4 antagonists （P<0.05），and the PD-1 protein expression amounts were decreased.

PGE2 can promote the PD-1 expression in infiltrating CD8+ T lymphocytes in NSCLC tissue through PGE2/EP2 and PGE2/EP4 signaling pathways， resulting in the decreased immune function of CD8+ T lymphocytes.

To investigate the protective effect of calcitriol on liver fibrosis induced by common bile duct ligation （BDL） in the mice， and to explain its possible mechanism.

Forty-five male C57BL/6 mice aged 8 to 10 weeks were randomly divided into sham operation group， liver fibrosis model group （model group） and calcitriol treatment group （treatment group）， with 15 mice in each group. The mice in sham operation group received the surgical line around the common bile duct without ligation； in model group， the common bile ducts of the mice were double-ligated and severed， and the mice in treatment group were injected intraperitoneally with calcitriol （2.5 μg·kg^－1） 3 times a week after operation. The mice in sham operation group and model group were injected with an equal volume of saline. The administration was continued until 4 weeks after the operation. On the 28th day， blood was taken from the orbit and the liver of the mouse was taken. On the second day after the operation， the activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） and the levels of total bile acid （TBA）， total bilirubin （TBIL） and hydroxyproline （Hyp） in the serum of the mice in various groups were detected. The pathomorphology and fibrosis degrees of liver tissue were observed with hematoxylin and eosin （HE） and Sirius red staining. Western blotting method was used to detect the expression levels of vitamin D receptor（VDR），extracellular signal-regulated protein kinase （ERK），phosphorylated extracellular signal-regulated protein kinase （pERK）， α-smooth muscle protein （α-SMA），transforming growth factor-β1 （TGF-β1），type Ⅰ collagen （Col Ⅰ） and Desmin in liver tissue of the mice in various groups. Immunohistochemistry method was used to detect the expressions of α-SMA and TGF-β1 in liver tissue of the mice in various groups.

Compared with sham operation group， the serum activities of ALT and AST and the levels of TBA， TBIL and Hyp of the mice in model group were significantly increased （P<0.05）； compared with model group， the serum activities of ALT and AST and the levels of TBA， TBIL and Hyp in treatment group were significantly reduced （P<0.05）. The HE staining results showed that the liver lobules of the mice in sham operation group were normal， the tissue structure was relatively complete， and no inflammatory cell infiltration was seen； the liver tissue of the mice in model group had inflammatory cell infiltration， and necrosis and collagen deposition were more obvious； compared with model group， the necrotic area of ??liver tissue of the mice in treatment group was significantly reduced， and the inflammatory infiltration was improved. The Sirius red staining results showed that only a small amount of collagen deposition in liver tissue of the mice in sham operation group appeared around the central vein； the central vein and portal area of liver tissue of the mice in model group showed obvious collagen deposits； compared with model group， the collagen deposition in treatment group was significantly reduced. The Western blotting results showed that compared with sham operation group， the expression levels of ERK， p-ERK， α-SMA， TGF-β1， Col Ⅰ and Desmin in liver tissue of the mice in model group were significantly increased （P<0.05）； compared with model group， the expression levels of ERK， p-ERK， α-SMA， TGF-β1， Col Ⅰ and Desmin in liver tissue of the mice in treatment group were significantly reduced （P<0.05）. The immunohistochemical staining results showed that the expressions of α-SMA and TGF-β1 proteins in liver tissue of the mice in model group were higher than those in sham operation group， and the expressions of α-SMA and TGF-β1 proteins in treatment group were significantly lower than those in model group.

Calcitriol can reduce the activation of hepatic stellate cells （HSCs） by activating VDR， down-regulating the ERK protein expression， reducing the expression of TGF-β1，and inhibiting the deposition of collagen in tissue， thereby alleviate the BDL-induced liver fibrosis in the mice.

To investigate the effect of prunus tomentosa thunb total flavone （PTTTF） on the formation of skin hypertrophic scar （HS） in the mice， and to elucidate its possible mechanism.

A total of 96 male ICR mice were randomly divided into blank control group， model control group （given same amount of blank matrix as the plastics）， low， middle and high doses of prunus tomentosa thunb plastics （PTTP） groups （given 0.4， 0.8， and 1.6 g·L^－1）PTTP and positive control （DXM） group； there were 16 mice in each group. Except for blank control group， the mice in other groups were used to set up two full-thickness skin defect models with diameter of 10 mm made on both sides of the back by using a skin punch with the spine as the midline. The drug was given once a day and smeared with 0.1 mL each time. The wound healing was observed every day and the wound healing rate was calculated. Four mice in each group were killed on the 10th day， 20th day， 30th day and 40th day， respectively， and the full-thickness skin tissue of the wound was taken.The pathomorphology of HS skin tissue was observed by HE staining. Western blotting method was used to detect the protein expression levels of cysteinyl aspartats specific proteinase-3（Cleaved caspase-3）， B cell lymphoma-2（Bcl-2） and Bcl-2 associated X protein（Bax） in skin tissue of the mice in various groups.

Compared with model control group， on the 40th day， the healing rates of the mice in low， middle and high doses of PTTP groups were 98.94%， 99.14%， and 99.04%， respectively； there were significant differences （P<0.05）. The results of HE staining showed that compared with model control group， the wound in different doses of PTTP groups healed faster and gradually recovered to the normal skin structure， with the formation of skin appendages such as sebaceous glands， hair follicles， sweat glands and so on. The results of Western blotting method showed that compared with model control group， the expression levels of Cleaved caspase-3 and Bax proteins in different doses of PTTP groups were increased significantly （P<0.05 or P<0.01）， while the expression levels of Bcl-2 protein were decreased significantly （P<0.05 or P<0.01）.

PTTTF can promote wound healing and has a certain inhibitory effect on the formation of HS in the mice； and its mechanism may be related to inducing apoptosis.

To observe the effect of glucagon like peptide-1 （GLP-1） receptor agonist liraglutide on the expressions of the mRNA and protein of related proteins after podocyte injury induced by high glucose， and to explore its mechanism.

The differentiated mature podocytes were randomly divided into control group， high glucose group， mannitol control group， liraglutide group， high glucose + liraglutide group. The RNA was extracted from cells in each group. Real-time PCR（RT-PCR） was used to detect the expression levels of Nephrin， Podocin and ZO-1 mRNA in the podocytes in various groups. Western blotting method was used to detect the expression levels of Nephrin， Podocin， ZO-1， Bcl-2 and caspase-3 proteins in the podocytes in various groups. The Synaptopodin expression in the podocytes was observed by immunofluorescence method. The apoptotic rate was measured by flow cytometry. The differentiated mature podocytes were randomly divided into control group， high glucose group， high glucose + liraglutide group， high glucose+liraglutide+LY294002 group. The expression levels of the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway proteins were observed by Western blotting method.

Compared with control group， the expression levels of mRNA and protein of the podocytes marker proteins Nephrin， Podocin and ZO-1 in the podocytes in high glucose group were reduced（P<0.05）， the expression level of Bcl-2 proein was reduced（P<0.05）， the expression level of caspase-3 protein was increased（P<0.05）， the fluorescence intensity of specific skeleton protein Synaptopodin was decreased significantly（P<0.05）， and the apoptotic rate of podocytes was increased significantly（P<0.05）. Compared with high glucose group， the expression levels of mRNA and protein of Nephrin， Podocin and ZO-1 in the podocytes in high glucose + liraglutide group were increased（P<0.05）， the expression level of Bcl-2 proein was increased （P<0.05）， the expression level of caspase-3 protein was decreased（P<0.05）， the fluorescence intensity of podocyte specific skeleton protein Synaptopodin was increased significantly（P<0.05）， and the apoptotic rate of podocytes was decreased significantly（P<0.05）. Compared with control group， the expression levels of PI3K and phosphorylated（p-Akt） proteins in the podocytes in high glucose group were decreased significantly （P<0.05）， the expression level of Bcl-2 protein was decreased（P<0.05）， and the expression level of caspase-3 protein was increased（P<0.05）. Compared with high glucose group， the expression levels of PI3K and p-Akt proeins in high glucose + liraglutide group were increased significantly（P<0.05）， the expression level of Bcl-2 proein was increased（P<0.05）， and the expression level of caspase-3 protein was decreased significantly（P<0.05）. Compared with high glucose + liraglutide group， the expression levels of PI3K and p-Akt proteins in the podocytes in high glucose + liraglutide + LY294002 group were decreased（P< 0.05），the expression level of Bcl- 2 protein was decreased（P<0.05），and the expression level of caspase-3 protein was increased（P<0.05）.

Liraglutidecan inhibit the apoptosis of podocytes by activating the PI3K/Akt signaling pathway and alleviates the podocyte injury induced by high glucose.

A total of 20 healthy SPF male BALB/C mice aged 6－8 weeks were randomly divided into control group and model group， with 10 mice in each group. The IgAN model was constructed by the combined administration of bovine serum albumin （BSA）， lipopolysaccharide （LPS）， and carbon tetrachloride （CCl₄）.IgA deposits in glomeruli were detected by immunofluorescence method， and hematoxylin-eosin （HE） staining was used to observe the pathomorphology of kidney tissue of the mice to evaluate whether the model was successfully constructed.The body weights and kidney weights of the mice were weighed， and the kidney index was caculated.The levels of serum creatinine and urea nitrogen of the mice were detected by enzyme activity method.The levels of tumor necrosis factor-α （TNF-α）， interleukin 1-β （IL-1β） and interleukin 6 （IL-6） in serum of the mice in each group were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （RT-qPCR） was used to detect the mRNA expression levels of the key genes that regulated mitochondrial fission and fusion， including dynamic related protein 1 （Drp1）， mitofusin 1 （Mfn1） and mitofusin 2 （Mfn2）. The expression levels of Drp1， Mfn1， and Mfn2 proteins in kidney tissue of the mice were detected by Western blotting method.

Compared with control group， the glomerulus of the mice in model group showed that IgA deposition was obvious， accompanyied by glomerular atrophy， the hyperplasia of glomerular mesangial cells and stroma led to widening of the mesangial area， and a portion of renal tubule cells presented swelling and necrosis， indicating that the IgAN model was successfully constructed. Compared with control group， the kidney index and the serum creatinine and urea nitrogen levels of the mice in model group were obviously increased（P<0.05），the levels of serum TNF-α， IL-1β and IL-6 of the mice were increased significantly（P<0.05 or P<0.01），the expression levels of Drp1 mRNA and protein in kidney tissue of the mice were obviously increased（P<0.05）， while the expression levels of Mfn1 and Mfn2 mRNA and proteins in kidney tissue of the mice were obviously reduced（P<0.05）.

The imbalance of mitochondrial fission/fusion protein expression may be one of the mechanisms of the development and progression of IgAN， and the research of fission and fusion homeostasis as a target may provide new ideas for the therapy of IgAN.

To investigate the effect of CRISPR/Cas9 gene-editing knockout of programmed cell death ligand 1（PD-L1） on the geffitinib resistance sensitivity in the non-small cell lung cancer （NSCLC） cells with T790M mutation， and to clarify the mechanism of the effect of PD-L1 on the drug resistance sensitivity of PC-9/T790M cells.

The PC-9 cells and PC-9/T790M cells were cultured in vitro. After CRISPR/ Cas9 gene editing technology was used to knock out PD-L1 in the PC-9/T790M cells， the cells were divided into three groups： PC-9 group， PC-9/T790M group and Cas9 PC-9/sgRNA group.The expression levels of PD-L1 protein in the cells in various groups were detected by Western blotting method， and CCK-8 method was used to determine the survival rates of the cells in various groups after 24，48 and 72 h of intervention with 5，10 and 20 mmol·L^－1 gefitinib. In vivo experiments，the tumor volumes in vorious groups were detected after gefitinib intervention， and the pathomorphology of transplanted tumor tissue in various groups was observed.

The Western blotting results showed that the expression level of PD-L1 protein in sgRNA1# group edited by CRISPR/ Cas9 was the lowest compared with PC-9， PC-9/T790M， sgRNA2# and sgRNA3# groups. There were no statistically significant differences in the cell proliferation activities in Cas9 PC-9 /sgRNA group compared with other two groups before drug intervention detected by CCK-8 method （P>0.05）. After 10 mmol·L^－1 gefitinib intervention for 72 h， the survival rates of cells in PC-9 and Cas9 PC-9/sgRNA1# groups were significantly lower than that in PC-9/T790M group （P<0.01）.In vivo experiment， compared with PC-9/T790M group， the tumor volumes in PC-9 group and Cas9 PC-9/sgRNA1# group were significantly reduced after gefeitinib intervention （P<0.05）；moderate to severe cell necrosis was found in PC-9 group and Cas9 PC-9/sgRNA1 group， while no significant changes in transplanted tumor tissue were found in PC-9/T790M group.

Using CRISPR/ Cas9 editing technique to knock out PD-L1 in the drug-resistant PC-9/T790M cells can significantly improve the sensitivity of gefitinib.

To investigate the anti-tumor effect of Shuganhuazheng Formula and the influence in the tumor angiogenesis in the mice with breast cancer， and to clarify its posible mechanism.

Forty female BALB/c mice were randomly divided into model group and 0.01， 0.10， 1.00 and 10.00 g·kg^－1 Shuganhuazheng Formula groups， with 8 mice in each group. The mouse models of three-negative breast cancer （TNBC） were established by inoculation of 4T1 cells at the breast fat pad of the anterior axillary sternum in the mice. After the models were built successfully， the mice in Shuganhuazheng Formula groups were given the corresponding doses of Shuganhuazheng Formula by gavage， and the mice in model group were given the same amount of distilled water， lasted for 21 d. The food intakes and body weights of the mice were measured daily. On the 3rd， 7th， 14th and 21st days after the modeling， vernier calipers were used to measure the long and short diameters of the tumor， and the tumor volumes and the inhibitory rate of tumor of the mice in various groups were calculated. After 21 d， the mice were sacrificed and tumor tissue was taken. Immunohistochemistry and Western blotting methods were used to detect the expression levels of vascular endothelial growth factor （VEGF） and angiogenin-like protein-2 （Ang-2） proteins in tumor tissue of the mice in various groups.

Compared with model group， the daily food intakes of the mice in different doses of Shuganhuazheng Formula groups were decreased with the increase of time， but the difference was not statistically significant （P>0.05）. On the 14th and 21st days， the body weight of the mice in model group was increased slowly， but the weights of the mice in 10.00 g·kg^－1 Shuganhuazheng Formula group were significantly increased，and the difference was statistically significant compared with model group （P<0.01）. Compared with model group， the inhibitory rates of tumor of the mice in 0.10， 1.00 and 10.00 g·kg^－1 Shuganhuazheng Formula groups were significantly increased on the 21st day （P<0.05 or P<0.01）.The immunohistochemical results showed that the cytoplasm of the mice in model group had darker brownish yellow color， while the staining was gradually decreased with the increase of dose in each Shuganhuazheng Formula group. The brownish yellow color in cytoplasm in each Shuganhuazheng Formula group was decreased gradually， while the pale blue color in nucleus was increased gradually.The positive signal absorbance（A） value detection results showed that the expression levels of VEGF and Ang-2 proteins in tumor tissue of the mice in different doses of Shuganhuazheng Formula groups were significantly decreased compared with model group （P<0.05 or P<0.01），especially in 10.00 g·kg^－1 Shuganhuazheng Formula group. The Western blotting results showed that compared with model group， the expression levels of VEGF and Ang-2 proteins in tumor tissue of the mice in different doses of Shuganhuazheng Formula groups were decreased （P<0.05 or P<0.01） in a does-dependent manner.

Shuganhuazheng Formula has an inhibitory effect on the tumor growth of the breast cancer-bearing mice， and its mechanism may be related to inhibition of VEGF and Ang-2 protein expressions in tumor tissue.

To study the protective effect of selenomethionine（Se-Met） on the brain tissue damage in the rats exposed to lead， and to explore its mechanism.

Fifty healthy male Wistar rats were randomly divided into normal control group， Pb injury model group（Pb group）， Pb+low， medium and high doses of Se-Met groups（Pb+L Se-Met group， Pb+M Se-Met group， Pb+H Se-Met group）（n=10）. In addition to normal control group， the rats in other 4 groups were fred to drink lead acetate solution with a concentration of 1 g·L^－1 （546.2 mg·L^－1 Pb） to establish the lead-damaged rat models. After 4 weeks the rats in low， medium， and high doses of Pb+Se-Met groups received 0.1，0.2^{and 0.4 g·kg－1 Se-Met and administrated with 5 mL distilled water suspension by gavage every day；the rats in normal control group and Pb group were given equal volume of distilled water every day for 6 weeks. After 6 weeks， the bone lead content of the rat was measured by graphite furnace atomic absorption spectrometry；Morris water maze experiment was carried out to detect the behavior indexes of the rats. The activities of glutathione peroxidase（GSH-Px）， superoxide dismutase （SOD） and cholinesterase（CHE） and the levels of malondialdehyde （MDA）and nitric oxide （NO）in brain tissue of the rats were detected by chemical colorimetry. HE staining was used to observe the patholmorphology of the rat hippocampus CA1 region. Immunohistochemistry was used to observe the expressions of B cell lymphoma-2（Bcl-2）， Bcl-2 associated X protein（Bax）， and selenoprotein S（Sel S） in the rat hippocampus CA1 region in various groups.}

Compared with normal control group， the bone lead contents of the rats in Pb group， Pb+L Se-Met group， Pb+M Se-Met group and Pb+H Se-Met group were significantly increased（P<0.01）， the escape latencies and the movement distance of the rats in Morris water maze experiment rats were significantly increased （P<0.01），the residence time in target quadrant and the across times were significantly reduced （P<0.05），the activities of GSH-Px， SOD and CHE in brain tissue of the rats were significantly decreased（P<0.01）， and the levels of MDA and NO were significantly increased （P<0.01）. Compared with normal control group，the nerve cells in hippocampal CA1 region of the rats in Pb group didn’t arrange neatly， the morphology of cells was irregular，presenting polygon，and the nuclei were concentrated and hyperchromatic.Compared with Pb group， the bone lead contents of the rats in Pb+L Se-Met group， Pb+M Se-Met group and Pb+H Se-Met group were significantly reduced（P<0.01），the escape latencies and the movement distance of the rats in Morris water maze experiment were significantly reduced （P<0.01）， the residence time in taget quadrant and the across times were significantly increased（P<0.05），the activities of GSH-Px， SOD and CHE were increased（P<0.01），and the levels of MDA and NO were significantly reduced（P<0.01）； the pathological changes in hippocampal CA1 region of the rats were improved， the expression amounts of SelS and Bcl-2 proteins were increased，and the Bax protein expression amounts were reduced.

Se-Met has a protective effect on the brain tissue damage of the rats exposed to lead， and its mechanism may be related to reducing the lead load in the body of the rats exposed to lead， reducing oxidative damage， apoptosis in hippocampus CA1 region of brain， and increasing the expression of SelS in CA1 region in hippocampus of the rats.

Fifteen rats were randomly selected from 100 SD rats as sham operation group ［without injection of Aspergillus funmigatus （AF） spore suspension］， and the other 85 rats were injected with spore suspension of AF to establish the AFK models. Seventy-two rats were successfully established and randomly divided into model group （14 rats）， low dose of luteolin group （14 rats）， medium dose of luteolin group （14 rats）， high dose of luteolin group （15 rats）， LPS + luteolin group （15 rats）. The rats in low， medium and high doses of luteolin groups were given local eye drop of 50 μL luteolin with concentrations of 5， 10 and 20 g·L^－1；the rats in sham operation group and model group were given the same amount of 1% DMSO solution；the rats in LPS + luteolin group were given 20 g·L^－1 luteolin solution and 1.0 μg LPS solution for local eye drops；lasted for 7 d. The general changes of cornea of the rats in various groups were observed and the cornea inflammation index was evaluated. The corneal tissue samples were obtained， and the pathomorphology of cornea tissue was observed by HE staining method. The levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interleukin-12 （IL-12） in cornea tissue of the rats in various groups were detected by enzyme-linked immunosorbent assay （ELISA）. The expression levels of TLR4， MyD88， and nuclear transcription factor-κB （NF-κB） proteins in cornea tissue of the rats in various groups were detected by Western blotting method.

The cornea tissue epithelium of the rats in sham operation group was intact without inflammatory cell infiltration.The cornea of rats in model group and LPS + luteolin group showed white dense ulcers， edema and dull surface， the iris was not visible， and the area of ulcers in LPS + luteolin group was larger. In low， medium and high doses of luteolin groups， the areas of ulcer focus were gradually decreased and the lesions were alleviated. The HE staining results showed that the collagen fibers were swollen and disordered in model group and LPS + luteolin group， a large number of inflammatory cells were infiltrated， and the above changes were alleviated in low， middle and high doses of luteolin groups， especially in high dose of luteolin group. Compared with model group， the cornea inflammation index， the levels of IL-1β， TNF-α， IL-12 and the experssion levels of TLR4， MyD88， NF-κB proteins in corneal tissue in low， medium and high doses of luteolin groups were decreased （P<0.05）.The above indexes of the rats in LPS + luteolin group were higher than those in model group and low， medium and high doses of luteolin groups （P<0.05）.

Luteolin has a therapeutic effect in the AFK rats and can effectively inhibit corneal inflammation， and its mechanism may be ralated to inhibiting the expressions of TLR4 / MyD88 signaling pathway-related proteins and its down-stream inflammatory factors.

A total of 32 pregnant ICR mice were selected and randomly divided into different doses of DEHP groups and corn oil control group. From the 3rd day of pregnancy to the 17th day of pregnancy， the mice were given by gavage with low dose （10 mg?kg^－1） of DEHP， medium dose （50 mg?kg^－1） of DEHP， high dose （250 mg?kg^－1） of DEHP and corn oil， respectively. The neurodevelopmental indicators were observed after birth， and neurobehavioral tests were performed after 7 weeks of age； the expression levels of cofilin and Pak1 proteins in the prefrontal cortex tissue of the offsprings were detected by Western blotting method. The in vitro cultured Neuro-2A cells were divided into different doses of DEHP groups and DMSO control group；the Neuro-2A cells were incubated respectively with 1 nmol?L^－1， 10 nmol?L^－1， 1 μmol?L^－1 DEHP and DMSO. After 0， 6， 12， 24， and 48 h of incubation， cell scratch test was used to observe the migration abilities of cells， and the neurite outgrowth of cells were observed under phase-contrast microscope.

Compared with corn oil control group， the neurodevelopmental indicators of the newborn mice in different doses of DEHP groups had no significant differences（P>0.05），and the ability to freely explore new environments of the female offsprings in medium dose of DEHP exposure group was significantly decreased （P<0.01）. The Western blotting results showed that compared with corn oil control group， the expression level of cofilin protein in prefrontal cortex tissue of the offsprings in medium dose of DEHP group was significantly decreased （P<0.05）， but the expression level of Pak1 had no significant difference （P>0.05）. The results of cell scratch test showed that compared with DMSO control group， the cell migration rates in different doses of DEHP groups were reduced after 12 h of incubation （P<0.05）， the mean neurite lengths were also shortened after 6 h of incubation in 1 μmol?L^-1 DEHP group （P<0.05）， and the percentage of neurite-bearing cells was decreased after 48 h of incubation in 1 μmol?L^－1 DEHP group （P<0.05）.

Exposure of the ICR mice to DEHP at a dose of 50 mg?kg^－1 or more during pregnancy can lead to the abnormal neurobehaviors of the offsprings； to incubate the Neuro-2A cells with 1 μmol?L^－1 DEHP for 12 h can significantly inhibit the cell migration and neurite growth； its mechanism may be related to inhibiting the expression of cytoskeleton regulatory protein cofilin.

To investigate the effect of carnosine on the inflammatory cytokine release in the astrocytes （AS） induced by lipopolysaccharide （LPS）， and to clarify its mechanism.

The neonatal rat cerebral cortex AS were cultured and purified in vitro. The AS were randomly divided into control group， LPS group and LPS+carnosine groups （10，30，and 90 mmol·L^-1 carnosine ）.The cells in control group were only cultured with complete medium； the cells in LPS group were stimulated in vitro with 1 mg·L^－1 LPS for 24 h to construct the inflammatory injury model； the cells in LPS+carnosine groups were cultured with 10，30， and 90 mmol·L^－1carnosine， respectively； in complete medium for 1 h， then treated with LPS with a final concentration of 1 mg·L^－1 for 24 h.The survival rates of AS in various groups were determined by MTT assay. The levels of interleukin-1β（IL-1β） and tumor necrosis factor-α（TNF-α） in the AS culture medium were detected by ELISA. DCFH-DA fluorescence probe was used to detect the reactive oxygen species（ROS） levels in AS in various groups； Hoechst 33258 fluorescence staining was used to detect the apoptotic rates of AS in various groups. The expressions of phosphorylated nuclear transcription factor-κB p65（p-NF-κB p65） in the AS and the number of p-NF-κB p65 positive cells in various groups were determined by immunofluorescence staining. The expression levels of p-NF-κB p65 protein in the AS in various groups were detected by Western blotting method.

Compared with control group， the survival rate of AS in LPS group was significantly decreased（P<0.05）， the levels of IL-1β and TNF-α in AS culture medium were increased（P<0.05）， the ROS level in AS was significantly increased（P<0.05），the apoptotic rate and the number of p-NF-κB p65 positive AS were increased significantly（P<0.05），and the expression level of p-NF-κB p65 protein in the AS was increased（P<0.05）.Compared with LPS group， the survival rates of AS in LPS+carnosine groups were significantly increased（P<0.05）， the levels of IL-1β and TNF-α in AS culture medium were decreased（P<0.05）， the ROS levels in the AS were decreased（P<0.05）， the apoptotic rates and the number of p-NF-κB p65 positive AS were decreased significantly（P<0.05），and the expression levels of p-NF-κB p65 protein in the AS were decreased（P<0.05）.

Carnosine can inhibit the release of the inflammatory factors IL-1β and TNF-α in the AS induced by LPS， and its mechanism may be related to inhibiting the ROS production in AS induced by LPS and then inhibiting the activation of NF-κB p65.

To observe the inhibitory effect of Nedd4 family interacting protein 1（Ndfip1）overexpression on the apoptosis of nerve cells under the conditions of iron overload， and to explore the protective mechanism of Ndfip1 in nerve cells.

The SH-SY5Y cells in experimental group were transfected with Ndfip1 plasmid， and the SH-SY5Y cells in control group were transfected with empty plasmid. MTT method was used to determine the survival rates of SH-SY5Y cells in two groups under the condition of iron overload. The levels of reactive oxygen species（ROS） and malondialdehyde （MDA） in the cells in two groups were detected by ROS and MDA detection kits. The expression levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax） and cysteinyl aspartate specific proteinase-3 （caspase-3） proteins in the cells were detected by Western blotting method.

Compared with control group， the survival rate of cells in experimental group was significantly increased （P<0.05）；compared with control group， the fluorescence of cells in experimental group was significantly weakened， indicating that the ROS level was reduced.Compared with control group， the level of MDA in experimental group was significantly reduced（P<0.05）；the expression level of Bcl-2 protein in the cells in experimental group was increased（P<0.05），and the expression levels of Bax protein and caspase-3 protein in the cells in experimental group were decreased（P<0.05）.

Ndfip1 could reduce the apoptosis induced by iron overload， improve the survival rate of nerve cells，and has protective effect on the nerve cells；its mechanism may be related to reducing the oxidative stress response and inhibiting the apoptosis pathway.

To explore the effects of new vascular endothelial growth factor （VEGF） monoclonal antibody， all-trans retinoic acid （ATRA）， new VEGF monoclonal antibody combined with ATRA on the breast cancer MCF-7 cells， and to provide a new clinical approach for the treatment of breast cancer.

The breast cancer MCF-7 cells were divided into control group （without any treatment）， VEGF antibody group （20 mg·L^－1 VEGF antibody）， ATRA group （10 μmol·L^－1 ATRA） and VEGF antibody + ATRA group （20 mg·L^－1 VEGF antibody+10 μmol·L^－1 ATRA）， each with 5 replicates. After the MCF-7 cells were treated with different drugs for 48 h，the VEGF antibody concentration was determined by ELISA， the proliferation rate of MCF-7 cells was determined by MTT assay， the apoptotic rate of MCF-7 cells was determined by flow cytometry， and the expression levels of B cell lymphoma-2（Bcl-2），Bcl-2 associated X protein（ Bax） and nuclear factor-κB（NF-κB） proteins in the MCF-7 cells were determined by Western blotting method.

The ELISA results showed that the new human recombinant VEGF monoclonal antibody had good quality compared with positive antibody control and its concentration was 200 μg·L^-1.The MTT results showed that the prolifenation rate of MCF-7 cells in VEGF antibody + ATRA group was decreased obviously compared with control group （P<0.01）.The flow cytometry results showed that compared with control group，VEGF antibody group and ATRA group， the apoptotic rate of MCF-7 cells in VEGF antibody + ATRA group was significantly increased （P<0.01）；compared with control group，the apoptotic rates of MCF-7 cells in VEGF antibody group and ATRA group were significantly increased（P<0.01）；compared with VEGF antibody group，the apototic rate of MCF-7 cells in ATRA group was significantly increased（P<0.01）. The results of Western blotting method showed that compared with control group， VEGF antibody group and ATRA group， the expression level of Bcl-2 protein in VEGF antibody+ATRA group was significantly decreased （P<0.05）；compared with control group and VEGF antibody group， the expression level of NF-κB protein in MCF-7 cells in ATRA group was decreased （P<0.05 or P<0.01）， and the expression level of Bax protein was increased （P<0.01）.

The new VEGF monoclonal antibody and ATRA can inhibit the cell proliferation and promote apoptosis of breast cancer MCF-7 cells， and the effect of their combination is significantly better than each drug used alone.

To investigate the effects of membrane associated RING-CH 1 （MARCH1） on the migration and invasion of gastric cancer cells， and to clarify its possible molecular mechanism.

A total of 20 cases of gastric cancer tissue and adjacent tissue obtained from gastrectomy were collected， and the expression levels of MARCH1 mRNA and protein in the different tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （RT-qPCR） method and Western blotting method. The expression levels of MARCH1 mRNA in the human gastric mucosal normal epithelial cells GES-1 and the human gastric cancer cells BGC-823， BGC-803， AGS and SGC-7901 were detected by RT-qPCR method. The SGC-7901 cells in logarithmic growth phase were divided into siNC group（transfected with siNC）， siMARCH1-1 group（transfected with siMARCH1-1） and siMARCH1-2 group（transfected with siMARCH1-2）. RT-qPCR method and Western blotting method were used to detect the expression levels of MARCH1 mRNA and protein in the cells in various groups. CCK-8 method was used to detect the cell proliferation activities in various groups； cell scratch test was used to detect the scratch healing rates of the cells in various groups； Transwell chamber test was used to detect the cell invasion abilities in various groups. The expression levels of phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B（p-AKT） and protein kinase B （AKT） proteins in various groups were detected by Western blotting method.

Compared with the adjacent tissue， the expression levels of MARCH1 mRNA and protein in the gastric cancer tissue were increased （P<0.05）. Compared with the human gastric mucosal normal epithelial cells GES-1， the expression levels of MARCH1 mRNA in human gastric cancer cells BGC-823， BGC-803， AGS， and SGC-7901 were all increased （P<0.05 or P<0.01）. Compared with siNC group， the expression levels of MARCH1 mRNA and protein in siMARCH1-1 group and siMARCH1-2 group were significantly reduced （P<0.01）. Compared with siNC group， the cell proliferation activities in siMARCH1-1 group and siMARCH1-2 group had no significant differences（P>0.05）； the cell scratch healing rates and the number of invasion cells in siMARCH1-1 group and siMARCH1-2 group were significantly reduced （P<0.01 ）. The expression levels of p-PI3K and p-AKT proteins in siMARCH1-1 group and siMARCH1-2 group were significantly reduced compared with siNC group （P<0.01）， and the expression levels of AKT protein had no significant differences（P>0.05）.

MARCH1 can promote the migration and invasion of gastric cancer cells， and its mechanism may be related to the regulation of PI3K/AKT signaling pathway.

To investigate the effect of miRNA-138-5p overexpression on cisplatin （DDP） resistance of the human breast cancer MCF-7 cells， and to elucidate its possible mechanism.

The MCF-7 cells were induced by concentration gradient increasing method to establish the DDP cell strain MCF-7/DDP.Then miR-138-5p mimics or hypoxia inducible factor-1α（HIF-1α） overexpression plasmid were transfected into the MCF-7/DDP cells separately or simultaneously. The MCF/DDP cells were divided into negative control group（NC group，transfected with miR-138-5p mimics negative control），miR-138-5p mimics group（transfected with mir-138-4p mimics），miR-138-5p mimics+Vector group （transfected with miR-138-5p mimics and empty plasmid）and miR-138-5p mimics+HIF-1α group（tranfected with miR-138-5p mimics and HIF-1α overexpression plasmid）；and the other MCF-7/DDP cells without transfection were used as blank control group.The cells were treated with different concentrations （0， 10， 20， 40， 80 and 100 μmol·L^－1） of DDP for 24 h and the proliferation activity of cells was detected by MTT， and half inhibitory concentration （IC₅₀） and drug resistance index （RI） were calculated. The expression levels of miR-138-5p and HIF-1α mRNA in the cells were detected by Real-time fluorescence quantitative polymerase chain reaction （qRT-PCR）； flow cytometry was used to detect the apoptotic rate of cells； Western blotting method was used to detect the expression levels of HIF-1α，P-gp and MRP1 proteins in the cells. TargetScan software was used to predict the target binding sites of miR-138-5p and HIF-1α， and the dual luciferase reporter system was used to verify the targeting relationship between miR-138-5p and HIF-1α.

The IC₅₀ of drug-resistant cell strain MCF-7/DDP for DDP was significantly higher than that of its parent MCF-7 cells （P<0.01）， and the RI value was 5.72. Compared with parental MCF-7 cells， the miR-138-5p expression level in drug-resistant cell strain MCF-7/DDP was markedly reduced （P<0.01）， while the HIF-1α mRNA and protein expression levels were significantly increased （P<0.01）. Compared with blank control group and NC group， the miR-138-5p expression level and apoptotic rate in miR-138-5p mimics group were significantly increased （P<0.01），while the HIF-1α protein expression level and the proliferation activity of cells were significantly decreased （P<0.01）. Compared with NC group， the luciferase activity of wild-type HIF-1α cells in miR-138-5p mimics group was markedly decreased （P<0.01）. Compared with miR-138-5p mimics+Vector group， the proliferation activity of cells in miR-138-5p mimics+HIF-1α group was significantly increased （P<0.05）， the apoptotic rate of cells was significantly decreased （P<0.01），and the expression levels of HIF-1α， P-gp and MRP1 proteins in the cells were significantly increased （P<0.05）.

miRNA-138-5p inhibits the expression of HIF-1α and down-regulates the expression levels of resistance-related proteins P-gp and MRP1， thereby enhances the sensitivity of MCF-7/DDP cells to DDP.

To explore the effect of Vascular Capsule Ⅱ on the limb ischemia of the rats， and to lay a theoretical foundation for the treatment of peripheral arteriopathy.

A total of 60 SPF female SD rats were randomly divided into normal control group， model group， sham operation group， positive control group （0.202 5 g·kg^－1 Compound Danshen Tablets）， low dose of Vascular Capsule Ⅱ group （30 mg·kg^－1） and high dose of Vascular Capsule Ⅱ group （90 mg·kg^－1）；there were 10 rats in each group. The models of hind limb ischemia were established by ligating the proximal， distal and main branches of femoral artery and vein. The general states of rats were observed. The pathomorphology of hind limb muscle tissue of the rats in various groups was observed by HE staining. The number of cells with positive expression of angiopoietin 1 （Ang-1）， tyrosine kinase receptor 2 （Tie2）， and CD31 in muscle tissue of the rats in various groups were detected by immunohistochemistry. The expression levels of Ang-1 and Tie2 proteins in muscle tissue of the rats in various groups were detected by Western blotting method.

The skin temperature of the hind limbs of the operation rats was low， the skin color was dark red， and cyanosis and toenail dropping occurred in the hind limbs. Compared with normal group and sham operation group， the hind limb muscle cells of the rats in model group were obviously swollen， the transverse striae disappeared， and the myofibril atrophy in the perineurium was observed；compared with model group，the symptoms mentioned above in positive control group and low and high doses of Vascular Capsule Ⅱ groups were alleviated.Compared with sham operation group，the number of cells with positive expressions of Ang-1 and Tie2 in muscle tissue of the rats in model group was significantly decreased（P<0.05）；compared with model group，the number of cells with positive expressions of Ang-1 and Tie2 in muscle tissue of the rats in positive control group and low and high doses of Vascular Capsule Ⅱgroups were significantly increases（P<0.05）. Compared with model group， the skin temperature differences of hind limbs of the rats in positive control and high dose of Vascular Capsule Ⅱ group were significantly decreased （P<0.05）， and the expression levels of CD31， Ang-1， and Tie2 proteins were significantly increased （P<0.05）.

Vascular Capsule Ⅱ can promote the vascular regeneration after limb ischemia in the rats，and its mechanism may be related to activating the Ang-1/Tie2 pathway.

To investigate the protective effect of the multiglycosides of tripterygium wilfordii （GTW） on the vascular endothelial injury in the rats with chronic kidney disease（CKD）， and to clarify its mechanism.

Sixty rats were randomly divided into control group， model group， low， medium and high doses of GTW groups， and there were 12 rats in each group. Adenine was used to induce the CKD rat models. The rats in low， medium and high doses of GTW groups were given 3.0， 6.0 and 9.0 mg·kg^－1 GTW by gavage， while the rats in control group and model group were given the same volume of normal saline. The levels of blood urea nitrogen（BUN） and serum creatinine（Scr） of the rats in various groups were measured after 4 weeks of administration. HE and Masson staining were used to observe the pathological changes of the kidney tissue and the changes of fibrosis of the rats in various groups. The levels of endothelin-1 （ET-1）， nitric oxide （NO）， angiotensinⅡ（AngⅡ），tumor necrosis factor-α （TNF-α），interleukin （IL-6） and transforming growth factor β1（TGF-β1） in serum of the rats in various groups were measured by ELISA.

Compared with control group， the levels of BUN， Scr， ET-1， AngⅡ， TNF-α， IL-6 and TGF-β1 in serum of the rats in model group were significantly increased （P<0.05）， while the NO level was significantly decreased （P<0.05）， and the degree of renal fibrosis was significantly increased （P<0.05）. Compared with model group， the levels of BUN， Scr， ET-1， AngⅡ， TNF-α， IL-6 and TGF-β1 in serum of the rats in low， medium and high doses of GTW groups were significantly decreased （P<0.05）， while the NO levels were significantly increased （P<0.05）， and the degrees of renal fibrosis were significantly decreased （P<0.05）. The results of HE staining showed that the glomeruli and tubules in the kidney tissue of the rats in control group were intact and the cells arranged orderly； in model group， edema， balloon adhesion and inflammatory cell infiltration occurred in glomeruli and tubules of the rats； the kidney tissue of the rats in low， medium and high doses of GTW groups showed different degrees of edema and inflammatory cell infiltration， and the damage degrees were less than that in model group.

GTW can improve vascular endothelial injury in the CKD rats by down-regulating the ET-1 and AngⅡ levels and up-regulating the NO levels；GTW was improvement effect on the vascular endothelial injury of the CKD rats.

To investigate the effects of oridonin on the proliferation， migration and invasion of endometrial cancer HEC-1B cells， and to elucidate its possible mechanism.

The endometrial cancer HEC-1B cells in logarithmic growth phase were divided into control group（DMSO）， positive control group（2.5 mg·L^－1cisplatin），low dose（10 μmol·L^－1）of oridonin group， medium dose （20 μmol·L^－1）of oridonin group and high dose （40 μmol·L^－1）of oridonin group. MTT assay was used to detect the inhibitory rates of proliferation of cells. Flow cytometry was used to determine the apoptotic rates of HEC-1B cells. Cell scratch test was used to detect the cell migration ability. Transwell chamber assay was used to detect the invasion ability of HEC-1B cells. Real-time fluorescence quantitative PCR（RT-qPCR） was used to detect the expression levels of lncRNA CCAT1 in the cells.

Compared with control group， the apoptotic rates of HEC-1B cells in positive control group， low，medium and high doses of oridonin groups were significantly increased （P<0.05），the scratch healing rates and the number of transmembrane cells were significantly reduced （P<0.05），and the expression levels of lncRNA CCAT1 in the HEC-1B cells were significantly decreased （P<0.05）. Compared with low dose of oridonin group， the apoptotic rates of HEC-1B cells in medium and high doses of oridonin groups were significantly increased （P<0.05），the scratch healing rates and the number of transmembrane cells were significantly reduced （P<0.05），and the expression levels of lncRNA CCAT1 in the HEC-1B cells were significantly decreased （P<0.05）. Compared with medium dose of oridonin group， the apoptotic rate of HEC-1B cells in high dose of oridonin group was significantly increased （P<0.05），the scratch healing rate and the number of transmembrane cells were significantly reduced （P<0.05），and the expression level of lncRNA CCAT1 in the HEC-1B cells was significantly decreased （P<0.05）.

Oridonin can inhibit the proliferation， migration，and invasion and promote the apoptosis of endometrial cancer HEC-1B cells， and its mechanism may be related to down-regulating the expression level of lncRNA CCAT1.

To investigate the effects of total glucosides of paeony （TGP） on joint condition， inflammatory factors and apoptosis factors in the rheumatoid arthritis （RA） rats by regulating the Toll-like receptor 4（TLR4） /nuclear factor-κB（NF-κB） signaling pathway， and to clarify its mechanism.

The collagen-induced arthritis （CIA） rat models were established with bovine type Ⅱ collagen and complete Freund’s adjuvant， and the CIA model rats were randomly divided into CIA group， low dose （25 mg·kg^－1）of TGP（TGP-LD） group， middle dose （50 mg·kg^－1） of TGP（TGP-MD） group， and high dose （100 mg·kg^－1） of TGP（TGP-HD）， with 10 rats in each group.Another 10 healthy SD rats were selected as control group . The body weights， arthritis indexes and joint swelling degrees of the rats in each group were measured， and the levels of tumor necrosis factor-α （TNF-α），interleukin-6 （IL-6） and interleukin-1β （IL-1β） in serum of the rats in each group were detected by ELISA method. The mRNA and protein expression levels of TLR4， NF-κB， Cleaved caspase-3， B cell lymphoma -2 （Bcl-2） and Bcl-2 associated X protein （Bax） in joint synovium tissue of the rats in each group were detected by Real-time fluorescence quantitative PCR（RT-qPCR） and Western blotting methods.

Compared with control group， the body weight and the expression levels of Cleaved caspase-3 and Bax mRNA and proteins in joint synovium tissue of the rats in CIA group were significantly decreased （P<0.05）， while the arthritis index， the joint swelling degree， the expression levels of Bcl-2， TLR4，and NF-κB p65 mRNA and proteins in joint synovium tissue， and the TNF-α， IL-6， and IL-1β levels in serum of the rats in CIA group were significantly increased （P<0.05）. Compared with CIA group，the body weights and the expression levels of Cleaved caspase-3 and Bax mRNA and protein in joint synovium tissue of the rats in different doses of TGP groups were significantly increased（P<0.05）， while the arthritis indexes，the joint swelling degrees， the expression levels of Bcl-2， TLR4，and NF-κB p65 mRNA and proteins in joint synovium tissue， and the TNF-α， IL-6， IL-1β levels in serum of the rats were significantly decreased（P<0.05）.Compared with TGP-LD group，the body weights and the expression levels of Cleaved caspase-3 and Bax mRNA and proteins in joint synovium tissue of the rats in TGP-MD group and TGP-HD group were significantly increased（P<0.05），while the arthritis indexes， the joint swelling degrees， the expression levels of TLR4，NF-κB，p65 and Bcl-2 in joint synovium tissue， and the TNF-α， IL-6， and IL-1β levels in serum of the rats were significantly decreased（P<0.05）.

TGP can improve the symptoms of CIA， reduce the inflammatory reaction and promote the apoptosis of synovial tissue by inhibiting TLR4/NF- κB signal pathway.

To investigate the effect of alkylation repair homolog 3 （ALKBH3） knockdown on the growth， migration and tumor angiogenesis of bladder cancer cells， and to elucidate its related mechanisms.

The expression levels of ALKBH3 protein in the urothelial cell carcinoma and para-carcinoma tissues， normal bladder epithelial cells （SV-HRUC-1）， and bladder cancer cells （BIU87 and T24） were detected by immunohistochemistry and Western blotting method， respectively. The BIU87 and T24 cells were divided into sh-Con group （transfected with sh-Con） and sh-ALKBH3 group （transfected with sh-ALKBH3）. The cell viabilities and the number of colony， migration and invasion in two groups were detected by CCK-8 method， colony formation experiment and Transwell chamber assay， respectively. The number of migration cells and the tubule formation rate of human umbilical vein endothelial cells （HUVEC） induced by cell culture medium in two groups were detected by Transwell chamber and tubule formation assays， respectively. After the xenograft tumor model was constructed， the tumor volumes in two groups were measured regularly with vernier caliper， and the expression levels of CD31 protein in the tumor tissue in two groups were detected by immunohistochemistry. The expression levels of vascular endothelial growth factor-A（VEGF-A） protein in invivo and invitro experiments intwo groups were detected by Western blotting method.

Compared with para-carcinoma tissue or SV-HRUC-1 cells， the expression levels of ALKBH3 proteins in urothelial cell carcinoma tissue and bladder cancer cells （BIU87 and T24） were significantly increased （P<0.01）. The invitro experiment results showed that compared with sh-Con group， the cell activities， the number of migration and invasion BIU87 and T24 cells， as well as the number of induced migration HUVEC and the tubule formation rate of HUVEC in sh-ALKBH3 group were significantly decreased （P<0.01）. The vivo experiment results showed that compared with sh-Con group， the tumor volume in sh-ALKBH3 group was significantly reduced， and the expression level of CD31 protein in tumor tissue was significantly decreased （P<0.01）. Compared with sh-Con group， the expression levels of VEGF-A protein in invivo and in vitro experiments in sh-ALKBH3 group were significantly decreased （P<0.01）.

ALKBH3 knockdown contributes to inhibiting the growth， migration， invasion and tumor angiogenesis of bladder cancer cells， and its mechanism may be related to the down-regulation of VEGF-A expression.

To discuss the effect of celiac plexus block on the stress response and immune inflammation of the rats after partial hepatectomy， and to clarify its mechanism.

Forty rats were selected， ten rats were randomly selected as normal group， ten rats were used as blocker control group， and the other 20 rats were used to construct partial hepatectomy models. Sixteen modeling rats were randomly divided into model group and model + blocker group， and there were eight rats in each group. The rats in model + blocker group were injected with 0.5% lidocaine on both sides of the celiac plexus before abdominal closure， and the rat models were not prepared in blocker control group and the rats were injected with 0.5% lidocaine on both sides of the celiac plexus； the rats in normal group and model group were injected with the same amount of normal saline. At 12 h after of administration， the levels of cocorticoid （CORT），adrenocorticotropic hormone （ACTH）， noradrenaline （NE）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in serum of the rats in various groups were measured by ELISA method；Real-time fluorescence quantitative PCR （RT-qPCR） and Western blotting methods were used to detect the expression levels of glucocorticoid receptor （GR） and Toll-like receptor 4 （TLR4） mRNA and proteins in the peripheral blood mononuclear cells of the rats in various groups.

Compared with normal group and blocker control group， the levels of CORT， ACTH and NE in serum of the rats in model group and model + blocker group were increased （P<0.05）； compared with model group， the levels of CORT， ACTH， and NE in serum of the rats model + blocker group were decreased （P<0.05）. Compared with normal group and blocker control group， the levels of TNF-α， IL-1β and IL-6 in serum of the rats in model group and model + blocker group were increased （P<0.05）； compared with model group， the levels of TNF-α， IL-1β， and IL-6 in serum of the rats in model + blocker group were decreased （P<0.05）. Compared with normal group and blocker control group， the expression levels of GR mRNA and protein in the peripheral blood mononuclear cells of the rats in model group and model+blocker group were increased（P<0.05）， while the expression levels of TLR4 mRNA and protein were decreased （P<0.05）； compared with model group， the expression levels of GR mRNA and protein in the peripheral blood mononuclear cells of the rats in model + blocker group were increased（P<0.05）， while the expression levels of TLR4 mRNA and protein were decreased （P<0.05）. There were no significant differences in the serum levels of CORT， ACTH， NE， TNF-α， IL-1β， and IL-6， and the expression levels of GR and TLR4 mRNA and proteins in peripheral blood mononuclear cells of the rats between normal group and blocker control group （P>0.05）.

Celiac plexus block can reduce the stress response and immune inflammatory response of the rats after partial hepatectomy， and its mechanism may be related to up-regulating the GR protein expression and down-regulating the TLR4 protein expression.

To explore the prognostic factors of cervical squamous cell carcinoma by bioinformatics methods based on The Cancer Genome Atlas （TCGA） and Gene Expression Omnibus （GEO） databases.

The data of cervical squamous cell carcinoma were downloaded from TCGA and GEO databases. Perl and R software were used to screen the differential expression genes （DEGs） in normal and tumor tissues shared by the two databases. Gene Ontology （GO） function enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed to predict the mechanism of DEGs. Further， STRING database and Cytoscape software were used to construct a protein- protein interact （PPI） network， and screen the hub gene， and the survival analysis was performed combined with the clinical data.

There were 226 DEGs including 170 up-regulation genes and 56 down-regulation genes in two databases. The GO enrichment analysis results showed that DEGs were mainly related to cell nuclear division， organelle division， mitosis and DNase activity. The KEGG pathway analysis results showed that the main enrichment was in the cell cycle， DNA replication， and p53 signaling pathway， etc. The survival analysis results showed that the minichromosome maintenance proteins （MCMs） genes， including MCM2， MCM5 and MCM6， and structural maintenance of chromosome 4 （SMC4） gene were all highly expressed in tumor tissue and significantly related to the prognosis of cervical squamous cell carcinoma （P<0.05）. Additionally， the up-regulated genes MCM2， MCM5 and MCM6 prolonged the survival time of the patients with cervical squamous cell carcinoma，and they were tumor suppressor genes； while SMC4 shortened the survival time of the patients with cervical squamous cell carcinoma，and they were carcinogenic genes.

As tumor suppressors genes， MCM2， MCM5 and MCM6 genes can inhibit the tumor development； as an oncogene， SMC4 gene can promote the progression of cervical squamous cell carcinoma.

To analyze the expression levels of 20 m⁶A-related genes in uterine corpus endometrial carcinoma （UCEC） tissue with the bioinformatics methods data and to screen the hub genes related to prognosis， and to explore the correlations between the expression levels of hub genes and the immune infiltration degrees in UCEC.

The transcriptome sequencing， clinicopathological and survival data of 547 UCEC and 35 normal controls were obtained from The Cancer Genome Atlas （TCGA） database. The GSE17025 datasets that contained 81 samples of UCEC and 12 samples of adjacent cancer tissue were downloaded from Gene Expression Omnibus （GEO） database. Using the GEO2R online analysis tools and R software， the differentially expressed genes （DEGs） between UCEC tissue and adjacent normal tissue were identified. Survival analysis and Cox regression were carried out for DEGs. The genes that were significantly associated with overall survival （OS） were identified as the hub genes； protein-protein interaction （PPI） network of 20 m⁶A regulators and correlation analysis of the DEGs were performed using STRING database and R software， respectively. The correlations between the expression levels of hub genes and the clinicopathological features of UCEC were analyzed using the UALCAN database； the correlations between the target genes and immune infiltration degrees and the markers of immune cells were explored via Tumor Immune Estimation Resource （TIMER） and Gene Expression Profiling Interactive Analysis （GEPIA） database. Furthermore， survival analysis based on the expression of target genes was conducted in the related immune cell subgroup using Kaplan-Meier Plotter database.

Most of the 20 m⁶A regulators were significantly differentially expressed in UCEC tissue compared with the adjacent normal tissue （P<0.05）； the IGF2BP3 mRNA was highly expressed in UCEC tissue （P<0.05）.High IGF2BP3 expression was correlated with shorter OS （P<0.05）. Furthermore， both univariate ［hazard ratio （HR）=1.106， 95% condifence interval （CI）： 1.019－1.202， P=0.016］ and multivariate （HR=1.097， 95% CI： 1.003－1.199，P=0.043） Cox regression analysis results showed that IGF2BP3 could be used as an independent risk factor for OS evaluation. IGF2BP3 mRNA exhibited higher expression in the UCEC tissue of advanced stage and pre-menopause patients and endometrial serous adenocarcinoma tissue （P<0.05）. The expression level of IGF2BP3 mRNA was positively associated with the degrees of immune infiltration by CD8+T cells （r=0.126， P<0.05），neutrophils （r=0.324，P<0.01） and dendritic cells （DC）（r=0.120， P<0.05） in UCEC. The expression level of IGF2BP3 mRNA was positively associated with the markers of tumor-associated macrophages（TAMs）， macrophages （M1 and M2）， helper T cells （Th1， Th2， and Th17） and regulatory T cells （Treg） in UCEC （0.1≤r ≤1，P<0.05）. The patients with high expression of IGF2BP3 mRNA had a shorter OS than those with low expression of IGF2BP3 mRNA in the low infiltration subgroup of B cells， Treg cells， and Th2 cells （P<0.05）.

The expression level of IGF2BP3 mRNA in UCEC tissue is significantly increased， which promotes the immune infiltration of UCEC and indicates the poor prognosis of UCEC patients. IGF2BP3 could be served as a prognostic molecular biomarker of UCEC and indicate the poor prognosis of UCEC patients， and may become a novel target for cancer therapy.

A total of 40 colon cancer specimens and paired paracancer normal mucosa tissue were collected for examination of miR-1915-3p and Bcl-2 mRNA expression levels by Real-time fluorescence quantitative polymerase chain reaction （RT-qPCR）. The correlation between the miR-1915-3p expression level and Bcl-2 mRNA expression level was analyzed by Pearson correlation analysis. The correlations between the expressions of miR-1915-3p and Bcl-2 and the clinicopathological features and prognosis of the colon cancer patients were analyzed by χ² test. The survival curve was drawn by Kaplan-Meier method， and the survival difference was tested by Log-rank test.

The RT-qPCR results showed that compared with the adjacent mucosa tissue， the expression level of miR-1915-3p in colorn cancer tissue was decreased significantly （P<0.05）， and the expression level of Bcl-2 mRNA in colon cancer tissue was increased （P<0.05）； there was a significant negative correlation between the expression level of miR-1915-3p and the expression level of Bcl-2 mRNA in colon cancer tissue （r=－0.542，P<0.05）. The expression lervels of miR-1915-3p in colon cancer tissue was significantly correlated with the degree of tumor differentiation and lymph node metastasis （P<0.05）， but not with gender， age， tumor size and TNM stage （P>0.05）. The expression level of Bcl-2 mRNA in colon cancer tissue was significantly correlated with TNM stage （P<0.05）， but was not related to other clinicopathological features （P>0.05）. The Kaplan-Meier analysis results of survival curve showed that the overall survival（OS） of the colon cancer patients in miR -1915-3p high expression group was lower than that in miR-1915-3p low expression group （χ²=3.641，P<0.05）. There was no significant relationship between the expression level of Bcl-2 mRNA and the prognosis of colon cancer patients （χ²=0.571，P>0.05）.

The miR-1915-3p expression level in tumor tissue of the colorectal cancer patients is decreased， but the expression level of Bcl-2 mRNA is significantly increased. The combined detection of them is useful for the diagnosis and prognosis evaluation of colon cancer.

To explore the effects of miR-26a-5p on the apoptosis and secretion of inflammatory factors in the rheumatoid arthritis （RA）-fibroblast-like synovial cells （FLSs）， and to clarify its mechanism of action.

The RA-FLSs from knee joint synovial tissue of patients with RA were isolated and cultured，and miR-26a-5p mimics， inhibitors and negative controls were transfected into the RA-FLSs.Real-time fluorescence quantitative polymerase chain reaction（qRT-PCR） was used to detect the effect of transfection， ELISA was used to detect the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） in cell culture fluid， CCK-8 method was used to detect the cell proliferation activity， AnnexinⅤ-FITC/PI and Hoechst 33342 staining were used to observe the apoptosis， and Western blotting method was used to detect the expression levels of apoptosis-related proteins B cell lymphoma-2（Bcl-2），Bcl-2 associated X protein（Bax） and Janus kinase 2（JAK2）/signal transducer and activator of transcription（STAT3） signaling pathway-related proteins in the cells.

Compared with blank control group and NC-mimic group， the expression level of miR-26a-5p in RA-FLSs in miR-26a-5p mimic group was increased （P<0.05）， the proliferation activity of RA-FLSs was decreased（P<0.05），the apoptotic rate of cells was increased （P<0.05），the expression levels of Bcl-2， JAK2， p-JAK2 and STAT3 proteins were decreased（P<0.05）， and the expression level of Bax protein was increased （P<0.05）.Compared with blank control group and NC-inhibitor group， the expression level of miR-26a-5p in RA-FLSs in miR-26a-5p inhibitor group was decreased （P<0.05）， the proliferation activity of RA-FLSs was increased （P<0.05）， the apoptotic rate was decreased （P<0.05）， the expression levels of Bcl-2，JAK2， p-JAK2 and STAT3 proteins were increased （P<0.05）， and the expression level of Bax protein was decreased （P<0.05）.

Overexpression of miR-26a-5p can inhibit the proliferation of RA-FLSs and promote apoptosis. Its mechanism may be related to the inhibition of the activation of JAK2/STAT3 signaling pathway.

To investigate the effects of ulinastatin pretreatment in the operation of the controllable donation after cardiac death（DCD） on the postoperative renal function of the recipients.

A total of 90 cases of controllable DCD donors and 174 cases of renal transplant recipients were selected. The donors were randomly divided into three groups. U1 group： 5 000 U·kg^－1 ulinastatin was used preoperatively； U2 group： 10 000 U·kg^－1 ulinastatin was used preoperatively； control group： no ulinastatin was used preoperatively， instead of an equal volume of normal saline. The levels of serum creatinine and blood urea nitrogen of the recipients before and 1~7 d after operation were detected， the estimated glomerular filtration rate （eGFR） was calculated， the hourly urine volumes were recorded， and the postoperative incidence rates of delayed graft function （DGF） were calculated.

The hourly urine volume showed a decreasing trend in the three groups within 7 d postoperatively. The hourly urine volumes in U1 group and U2 group on the first day after operation were higher than that in control group （P<0.05）； the hourly urine volume of the recipients on the third day after operation in U2 group was higher than that in U1 group （P<0.05）； the hourly urine volume of the recipients on the 5th day after operation in U2 group was higher than that in U1 group （P<0.05）； the hourly urine volume of the recipients on the 6th day after operation in U2 group was higher than those in U1 group and control group （P<0.05）. There were no significant differences in hourly urine volumes among three groups on the other days （P>0.05）. The eGFR of the recipients in U1 group and U2 group were higher than those in control group within 7 d after operation （P<0.05）； the eGFR of the recipientsof the recipients in U1 group was higher than that in control group on the 2nd day after operation （P<0.05）. There were no significant differences in the eGFR among three groups for the rest of time. The serum creatinine levels of the recipients in three groups were significantly decreased； the serum creatinine levels of the recipients in U1 and U2 groups were decreased more greatly than control group， but the differences among three groups were not statistically significant （P>0.05）. The blood urea nitrogen levels of the recipients in three groups were decreased first and then increased， and the blood urea nitrogen levels of the recipients in U1 and U2 groups were decreased more greatly than control group， but the differences among three groups were not statistically significant （P>0.05）. The incidence rates of DGF after operation in control group， U1 group and U2 group were 10.5%， 8.5% and 6.9%， respectively， but the differences among three groups were not statistically significant （P>0.05）.

Ulinastatin pretreatment of controllable DCD can promote the early recovery of urine volume of recipients after renal transplantation and protect the renal function to some extent.

To evaluate and compare the efficacies and safeties of moderate dose of rosuvastatin and simvastatin in the Chinese patients underwent coronary artery bypass grafting （CABG）， and to provide a reasonable strategy for secondary prevention after CABG.

The patients underwent CABG who met the study criteria in our hospital were included. According to the types of postoperatively administered statin drugs， the patients were divided into rosuvastatin group and simvastatin group， and there were 150 cases in each group. The baseline characteristics of patients and theirs blood lipid status at admission and 1 year after CABG were recorded. The occurrence of major adverse cardiovascular events （MACE） such as cardiovascular death and recurrent angina， as well as safety-related adverse events such as abnormal liver function and myopathy were noted. Meanwhile coronary computed tomography angiography（CTA） was performed 1 year after operation， and its stenosis index was calculated.

A total of 286 cases were followed up， with a follow-up rate of 95.3%， including 140 cases in rosuvastatin group and 146 cases in simvastatin group. In terms of blood lipid changes， compared with before operation， the total cholestrol（TC） and low density lipoprotein-cholesterol（LDL-C） levels in rosuvastatin grouop and simvastatin group 1 year after operation were significantly decreased （P<0.05），and the levels of high density lipoprotein-cholesterol（HDL-C） were significantly increased（P<0.05）. In terms of MACE and safety events， there were no statistically significant differences between two groups （P>0.05）. The stenosis indexes of the patients in rosuvastatin group and simvastatin group were 4.55（0 —11.86） vs 5.78（0 —13.00）， and the difference was not statistically significant （P>0.05）.

Moderate dose of rosuvastatin and simvastatin can make the serum LDL-C level meet the standard of lipid lowering. There is no difference in the efficacies or safeties between two kinds of drugs， and both drugs could be used as secondary prevention strategies after CABG in the Chinese patients with coronary heart disease.

To observe the effect of glycine sandblast on peri-implantitis and investigate the assistant effect of honeysuckle and forsythia suspense extract combined with glycine subgingival sandblast in the treatment of peri-implantitis， and to analyze the feasibility of compound Chinese medicine in the treatment of peri-implantitis.

A total of 56 patients with peri-implantitis were divided into two groups according to the voluntary principle： control group（n=30） and traditional Chinese medicine group（n=26）. There were no significant differences in the age，sex， probing depth （PD），modified plaque index （mPLI） and modified sulcus bleeding index （mSBI） and the level of interleukin-6（IL-6） in peri-implant sulcular fluid （PISF） before treatment of the patients in two groups（P>0.05）；the data was comparable. After basic periodontal treatment， in traditional Chinese medicine group distilled water was replaced in the EMS subgingival sandblast machine with honeysuckle and forsythia suspense extract for glycine subgingival sandblasting； in control group the patients received subgingival sandblast with glycine granules and distilled water. The PD， mPLI and mSBI of the affected teeth of the patients in two groups were recorded at 1，2 and 4 weeks after treatment. Enzyme-linked immunosorbent assay （ELISA） was used for the detection of IL-6 in PISF of the patients in two groups.

The levels of IL-6， mPLI and mSBI of the patients in two groups after treatment were lower than before treatment and the indexes in traditional Chinese medicine group mentioned above were decreased more obviously than control group （P<0.05）.

Glycine subgingival sandblast combined with basic periodontal treatment has a good therapeutic effect on the peri-implantitis； honeysuckle and forsythia suspense extract has a good promotion effect.

To discuss the feasibility of treating thoracolumbar tuberculosis with lateral displacement using the combination of posterior 360° debridement and double titanium mesh bone graft fusion.

The clinical data of a patient of thoracolumbar tuberculosis with lateral displacement were collected and the surgical treatments and clinical efficacy of the patient were analyzed and the relative literatures were reviewed.

The 41-year-old woman patient was admitted to the hospital due to backache for half a year and aggravation with numbness and weakness of both lower limbs for half a month. The physical examination showed a bulge on the lower back， obvious percussion pain and the hypoesthesia at the level of bilateral groin. The muscle strength of each muscle group of both lower limbs was grade Ⅱand the muscle tension was normal. The physiological and pathological reflexes were not elicited. The laboratory examination results showed T cells spot test of tuberculosis infection（T-SPOT）（+），erythrocyte sedimentation rate（ESR） 76 mmHg and C-reactive protein（CRP）55.19 mg·L^-1. The imaging results indicated the pathological fracture of L1 vertebral body， damage of T12/L1 vertebral body and intervertebral space， thoracolumbar kyphosis with lateral displacement and abscess in bilateral psoas major， spinal canal and paravertebral parts. The diagnosis was thoracolumbar spinal tuberculosis （T12， L1）， lateral kyphosis of thoracolumbar， incomplete paralysis of both lower limbs and abscess in psoas major and paravertebral parts. The intervertebral and paravertebral focus were fully removed and the spinal stability was reconstructed during the operation. The operation was successful， the patient’s symptoms were obviously relieved， the physiological curvature of the thoracolumbar was recovered， and the bone graft fusion was good. One year after the operation， the Frankel Classification returned to E from preoperative B， the visual analogue score （VAS） was decreased from 7 points before the operation to 1 point， and the oswestry disability index （ODI） score was decreased from preoperative 78% to 16%. No recurrence， and the prognosis was good.

The combination of posterior 360° debridement and double titanium mesh supporting combined structural bone graft and granular bone graft can bring better effect of intervertebral support and fusion to the treatment of thoracolumbar tuberculosis with lateral displacement and fully remove the intervertebral and paravertebral focus. It can be used as a surgical method for the treatment of such diseases.

To explore the diagnosis value of three-dimensional transrectal ultrasound（3D-ERUS） in the preoperative lymph node metastasis and N-stage in middle and lower rectal cancer， and to explore the correlations between the ultrasound features and the clinicopathologic factors and lymph node metastasis of rectal cancer.

A total of 94 patients with rectal cancer confirmed by pathology were selected，and all patients were examined by 3D-ERUS and magnetic resonance imaging （MRI）. Receiver operating characteristic（ROC） curve was used to evaluate the results of 3D-ERUS and MRI in the diagnosis of lymph node metastasis；the precision，recall and F1 score were used to evaluate the results of 3D-ERUS and MRI in the diagnosis of N staging.Kappa coefficient was used to evaluate the consistency between the results of 3D-ERUS and MRI in the diagnosis of lymph node metastasis and N staging and the pathological results. Chi square test was used to compare the differences between the ultrasound features and clinicopathologic factors and lymph node metastasis of rectal cancer，and the factors with statistical differences were analyzed by multivariate Logistic regression.

The accuracy of 3D-ERUS in the diagnosis of lymph node metastasis was 80.85%（Kappa=0.615，P<0.01）， respectively， and the area under curve（AUC） was 0.831； the accuracy of MRI in the diagnosis of lymph node metastasis was 70.21%（Kappa=0.415，P<0.01），respectively， and the AUC was 0.728.The AUC of 3D-ERUS and MRI had statistical difference（Z=2.039， P=0.041），and there was no statistical difference in the accuracy of diagnosis between them（χ²=2.33，P=0.126）.The overall accuracies of 3D-ERUS and MRI in distinguishing N staging were 74.47% and 63.44%，and there was no statistical difference（χ²=2.17，P=0.141）. The univariate analysis results showed that the related factors of lymph node metastasis were pathological T stage，carcinoembryonic antigen（CEA）， histological differentiation and 3D-ERUS T stage（uT-stage）.The multivariate analysis results showed that the main risk factor of lymph node metastasis was pathological T stage（P<0.01）；compared with stage T_is-T₂ rectal cancer，stage T₄ rectal cancer［odds ratio（OR）=12.000，95% confidence interval（CI）：3.141－45.839］ had the higher risk in the occurrence of lymph node metastasis.

3D-ERUS has high accuracy and clinical value in the preoperative diagnosis of N staging of middle and lower rectal cancer， and pathological T4 rectal cancer has the highest risk of perienteral lymph node metastasis.

To analyze the influence of atmospheric pollutant exposure in stroke hospitalization risk in Changchun City， Jilin University.

The stroke cases admitted at the First Hospital of Jilin University from October 1， 2018 to October 30， 2019 and the atmospheric measurement data of Changchun city were collected. A case-cross study was conducted for Logistic regression analysis on single pollutant and multi-pollutant models.The lag effect of each air pollutant on stroke hospitalization risk was analyzed with single pollutant model， and the best lag of each air pollutant was determined according to the maximum odds ratio （OR）.Multi-pollutant model was used to analyze the influence of air pullutants in the stroke hospitalization risk.

A total of 3 633 cases were included. A single pollutatant model determined that the atmospheric abnormality for stroke admission was the best in the late stage of stay 4 d before onset. Multivariate model analysis found that atmospheric particulate matter 2.5 （PM_2.5），sulfur dioxide （SO₂）， carbon monoxide （CO）， and ozone （O₃） concentrations 4 d before the onset of illness could affect stroke admission risk. Every 10 μg?m^－3 increase in PM_2.5 concentration increased stroke admission risk by 3% ［95% confidence interval（CI） （1.007， 1.054）］； every 10 μg?m^－3 increase in SO₂ concentration increased stroke admission risk by 22.6% ［95%CI （1.165，1.291）］； every 10 mg?m^－3 increase in CO concentration increased stroke admission risk by 14% ［95%CI （1.101，1.180）］； every 10 μg?m^－3 increase in O₃ concentration increased stroke admission risk by 3.7% ［95%CI （1.029，1.046）］.

The impact of air pollutants on stroke admission risk has a lagging effect. The increase of concentrations of PM_2.5， SO₂， CO and O₃ in the atmosphere of Changchun city can increase the risk of local stroke admission.

To screen the small molecules that can inhibit the binding of neuromyelitis optica（NMO）-IgG to aquaporin 4（AQP4） by high-throughput screening method.

The FRT-AQP4 cells were divided into negative control group （no small molecule compounds） and screening group， and the horseradish peroxidase（HRP） activity was detected by chemiluminescence. The V79-AQP4 cells are divided into inhibitor group （neosutchuenenine） and DMSO group.The fluorescence intensity of each group was detected by immunofluorescence method， the water permeabilitise of cells in varions groups were detected by fluorescence quenching method， and complement dependent cytotoxicity was detected by CellTiter-Glo^? luminescence method；the cell activities were detected by water solubility tetrazole-1（WST-1） method，and the apoptosis was detected by enzyme linked immunosorbent assay（ELISA） method.

Compared with negative control group， the HRP activity in screening group was significantly increased（P<0.01）. Compared with DMSO group， the red fluorescence intensity in inhibitor group was significantly reduced， while the green fluorescence did not change significantly； compared with DMSO group， the water permeability in inhibitor group did not change significantly（P>0.05）； compared with DMSO group， the complement-dependent cytotoxicity in inhibitor group was significantly reduced （P<0.01）； compared with DMSO group， there was no significant changes in cell activities and apoptosis in inhibitor group（P>0.05）.

A high-throughput screening method for AQP4 small molecule inhibitor is successfully established， and neosutchuenenine， a small molecule inhibitor with blocking effect， is screened out.