ObjectiveTo explore the potential mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of regulating mitochondrial autophagy via the PTEN-induced kinase 1 （PINK1）/E3 ubiquitin ligase （Parkin） pathway. MethodsMale SD rats were subjected to abdominal aortic constriction to establish the CHF model. Twenty-four successfully modeled rats were randomly divided into the model group， sacubitril/valsartan group， and low- and high-dose Shenqi Jianxin Formula groups， with 6 rats in each group. Six other rats were set as the sham surgery group， which were only separated the abdominal aorta and then closed the abdomen. Rats in the low-dose and high-dose Shenqi Jianxin Formula groups were given intragastric administration of Shenqi Jianxin Formula suspension at doses of 4.41 g/（kg·d） and 17.64 g/（kg·d）， respectively； the sacubitril/valsartan group received intragastric administration of sacubitril/valsartan sodium tablet suspension at 10 mg/（kg·d）； the sham surgery group and the model group were given normal saline at 10 ml/（kg·d） via intragastric gavage. The intervention lasted for 4 consecutive weeks. Cardiac function indices including left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were detected， and serum brain natriuretic peptide （BNP） content was measured. HE staining and Masson staining were used to observe myocardial histopathological changes. Transmission electron microscopy was employed to examine the ultrastructure of cardiac tissues. Quantitative real-time polymerase chain reaction （Rt-qPCR） was performed to determine the mRNA expressions of PINK1/Parkin pathway-related factors and autophagy-associated proteins including Beclin-1， p62， and microtubule-associated protein 1 light chain 3 （LC3） in myocardial tissues. ResultsCompared with the sham surgery group， the model group showed significant decreases in LVEF and LVFS levels， an increase in serum BNP content， down-regulated mRNA and protein expressions of PINK1， Parkin and Beclin-1 in cardiac tissues， up-regulated mRNA and protein expressions of p62， as well as significant reductions in LC3B mRNA expression， phosphorylated PTEN-induced kinase 1 （p-PINK1） and phosphorylated E3 ubiquitin ligase （p-Parkin） protein levels， and the ratio of microtubule-associated protein 1 light chain 3-Ⅱ to microtubule-associated protein 1 light chain 3-Ⅰ （LC3Ⅱ/LC3Ⅰ） （P＜0.05）. Pathological results revealed obvious myocardial cell edema， necrosis and degeneration， increased disorder of myocardial fiber arrangement， extensive inflammatory cell infiltration， moderate to severe mitochondrial swelling， a few mitochondrial vacuolar changes， and no obvious autophagy in the field of vision in the model group. Compared with the model group， all the above indicators were significantly improved in the high-dose Shenqi Jianxin Formula group and the sacubitril/valsartan group （P＜0.05）. Moreover， the improvement of each index in the high-dose Shenqi Jianxin Formula group was superior to that in the low-dose group （P＜0.05）. In the high-dose Shenqi Jianxin Formula group， myocardial myofibrils were arranged regularly with orderly orientation， the striated structure was clear， and necrotic cells significantly reduced. ConclusionShenqi Jianxin Formula can activate the PINK1/Parkin signaling pathway in myocardial tissues， enhance mitochondrial autophagy， and clear dysfunctional mitochondria， thereby improving cardiac function and delaying the progression of CHF.

Objective:To investigate the effects of intra-articular injection of exosomes derived from dental pulp stem cells from hu-man exfoliated deciduous teeth(SHED-EXO)on subchondral bone homeostasis in rat temporomandibular joint osteoarthritis(TMJ OA)process.Methods:36 male SD rats were randomly divided into 3 groups(n=12):control(CON),sodium iodoacetate(MIA)-induced TMJ OA(MIA),and SHED-EXO injection into TMJ OA(SHED-EXO)groups.At 2 and 6 weeks post-treatment,Micro-CT,Double labeling,TRAP staining,and immunohistochemical staining were employed to detect osteoclasts and osteoblasts in the subchondral bone.Additionally,the mRNA expression levels of ADAMTs5,IL-1β,OCN and OPG/RANKL were analyzed by qRT-PCR.Results:The MIA group exhibited significant bone loss and an enlarged bone marrow cavity.In comparison with the CON group,BV/TV and Tb.Th were lower(P＜0.001),while BS/BV,Tb.Sp,and Tb.N were higher(P＜0.01).Additionally,the bone formation rate within 5 days was low-er than that of the control group(P＜0.001).When compared to the MIA group,the SHED-EXO group showed a significant increase in bone morphology and bone mass.BV/TV and Tb.Th were increased(P＜0.01),while BS/BV,Tb.Sp and Tb.N were decreased(P＜0.05).The bone formation rate was higher(P＜0.01).Compared with both the control and treatment groups,the MIA group exhibited a significant increase in the number of osteoclasts in the subchondral bone(P＜0.01),along with a notable decrease in H-type blood vessels and OCN-positive areas(P＜0.01).Conclusion:Intra-articular injection of SHED-EXO can reg-ulate condylar subchondral bone homeostasis in TMJ OA of rats by promoting osteogenesis and inhibiting osteoclasts.

Objective To observe the effect of risperidone combined with clozapine in the treatment of vagrants with schizophrenia and its influence on social function of the patients.Methods Eighty patients with vagrant schizophrenia were selected as the study objects by a prospective randomized controlled trial,and were randomly divided into control group(40 cases)and observation group(40 cases).The control group was treated with risperidone,and the observation group was treated with risperidone and clozapine.Both groups received continuous treatment for 8 weeks.The clinical effects of the two groups were observed.The activities of daily living,rehabilitation[Inpatient Psychiatric Rehabilitation Efficacy Rating Scale(IPROS)score],social function,myocardial enzyme profile[lactate dehydrogenase(LDH),creatine kinase(CK),creatine kinase isoenzyme(CK-MB)]in the two groups before treatment and eight weeks after treatment were compared.The adverse reactions of the two groups were statistically analyzed.Results The total effective rate of treatment in the obser-vation group was higher than that of the control group(90.00％versus 72.50％,P＜0.05).After eight weeks of treatment,the abilities of daily living and social function of the two groups were stron-ger than before treatment,and the observation group was stronger than the control group.At 8 weeks of treatment,IPROS scores in two groups were lower than before treatment,and observation group was lower than control group(P＜0.05).After 8 weeks of treatment,LDH,CK and CK-MB levels in two groups were higher than before treatment(P＜0.05),but there was no statistical significant between-group difference(P＞0.05).Conclusion Risperidone combined with clozapine has a significant effect in thetreatment of vagrants with schizophrenia,which can enhance the patients'daily living ability and social ability,improve the rehabilitation status,and does not increase the adverse reactions.

Objective To observe the effect of risperidone combined with clozapine in the treatment of vagrants with schizophrenia and its influence on social function of the patients.Methods Eighty patients with vagrant schizophrenia were selected as the study objects by a prospective randomized controlled trial,and were randomly divided into control group(40 cases)and observation group(40 cases).The control group was treated with risperidone,and the observation group was treated with risperidone and clozapine.Both groups received continuous treatment for 8 weeks.The clinical effects of the two groups were observed.The activities of daily living,rehabilitation[Inpatient Psychiatric Rehabilitation Efficacy Rating Scale(IPROS)score],social function,myocardial enzyme profile[lactate dehydrogenase(LDH),creatine kinase(CK),creatine kinase isoenzyme(CK-MB)]in the two groups before treatment and eight weeks after treatment were compared.The adverse reactions of the two groups were statistically analyzed.Results The total effective rate of treatment in the obser-vation group was higher than that of the control group(90.00％versus 72.50％,P＜0.05).After eight weeks of treatment,the abilities of daily living and social function of the two groups were stron-ger than before treatment,and the observation group was stronger than the control group.At 8 weeks of treatment,IPROS scores in two groups were lower than before treatment,and observation group was lower than control group(P＜0.05).After 8 weeks of treatment,LDH,CK and CK-MB levels in two groups were higher than before treatment(P＜0.05),but there was no statistical significant between-group difference(P＞0.05).Conclusion Risperidone combined with clozapine has a significant effect in thetreatment of vagrants with schizophrenia,which can enhance the patients'daily living ability and social ability,improve the rehabilitation status,and does not increase the adverse reactions.

Objective:To detect the mRNA expression and methylation status of leucine rich repeat containing 55(LRRC55) gene in pancreatic carcinoma tissues, and discuss the clinical value.Methods:Resected pancreatic ductal adenocarcinoma and normal adjacent specimens from 37 patients admitted in General Surgery of First Affiliated Hospital of Naval Medical University were collected from May 2019 to May 2021. Another two normal pancreas specimens and two blood samples from healthy adults were also collected. All patients′ age, gender, tumor location, tumor size, tumor differentiation, TNM staging, lymphatic metastasis, CEA and CA19-9 level were recorded. Bisulfite treatment of genomic DNA and sequencing analysis was used to study methylation patterns in CpG islands of the promoter for LRRC55 gene in fresh tissues from 2 pancreatic adenocarcinoma and adjacent tissues, 2 normal pancreatic tissues, 2 pancreatic cancer cell lines (PaTu8988 and ASPC1). LRRC55 mRNA in 35 pancreatic adenocarcinoma and adjacent tissues was detected by real-time quantitative PCR and the correlations with clinical parameters were analyzed.Results:CpG islands of LRRC55 in pancreatic adenocarcinoma tissues and pancreatic cancer cell lines was highly methylated and the mean methylation rate was 53% and 71%, respectively; while LRRC55 gene in pancreatic adjacent tissues and normal pancreatic tissues was lowly methylated, and the mean methylation rate was 8% and 11%. The relative expression in the pancreatic adenocarcinoma tissues and the paired adjacent normal tissues was 0.21 (0.02, 1.00 ) and 0.98 (0.33, 3.66 ), respectively; the former was significantly lower than the later and the difference was statistically significant ( P=0.003). Correlation analysis showed that LRRC55 mRNA expression level was related to tumor differentiation and CEA, but not correlated with patients′ age, gender, tumor location and size, CA19-9 level, lymphatic metastasis and TNM staging. Conclusions:Pancreatic cancer tissue and cell lines had abnormal methylation of LRRC55 gene; LRRC55 gene hypermethylation was related with its lower mRNA expression level in pancreatic cancer, which was correlated with the tumor differentiation and CEA level. LRRC55 may be a potential suppressor gene for pancreatic cancer.

Objective To examine the reliability and validity of the Connor-Davidson resilience scale (CD-RISC) among coal miners,and explore factors structure and essence. Methods A questionnaire survey was conducted among 731 coal miners by using CD-RISC,Maslach burnout inventory( MBI-GS) and general self-efficacy scale( GSES). Results Twenty-five items of CD-RISC were retained based on the re-sults of exploratory factor analysis,including three factors of stress resistance,sense of competence and optim-ism. CD-RISC factors were significantly correlated with each other,and the correlation coefficient ranged from 0. 623 to 0. 777(P<0. 01). There was also a significant correlation between CD-RISC factors and total score, and the correlation coefficient ranged from 0. 837 to 0. 939(P<0. 01). The fitting index of confirmatory factor analysis were χ2/df=3. 76<5,GFI=0. 884,CFI=0. 909,AGFI=0. 862>0. 8,RMSEA=0. 065,proved that the measured data fitted well with the hypothesized three-factor model. Internal consistency reliability coeffi-cient of the total scale,stress resistance,sense of competence and optimism factors were 0. 942,0. 920,0. 868 and 0. 765,repectively. The CD-RISC scale was positively correlated with GSES and negatively correlated with MBI-GS and its factors named emotional exhaustion and depersonalization. Conclusion The CD-RISC of 25 items for coal miners possesses good reliability and validity.

OBJECTIVE: To investigate the effects of rosuvastatin combined with tirofiban on serum inflammatory factors and renal function in acute coronary syndrome patients with diabetes after percutaneous coronary intervention (PCI).METHODS: A total of 120 acute coronary syndrome patients with diabetes receiving PCI selected from cardiology department of our hospital during Apr. 2014-Mar. 2015 were divided into control group and observation group according to random number table, with 60 cases in each group. Except for routine treatment, control group was given Rosuvastatin calcium tablets orally after surgery (10 mg each day, for consecutive 7 d); observation group was given Rosuvastatin calcium tablets orally before and after surgery (20 mg before surgery; 10 mg each day after surgery, for consecutive 7 d), and then given Tirohydrochloric acid sodium chloride injection during surgery [10 μg/kg intravenously, 0. 15 μg/(kg· min) with intravenous pump for 36 h]. Clinical efficacies of 2 groups were compared. The changes of serum inflammatory factors (TNF-α, IL-6, IL-10) and renal function indexes (Scr, CysC, eGFR), the incidence of radiographic contrast nephropathy were compared before surgery and 24, 72 h after surgery. The occurrence of cardiovascular events was followed up for one year. RESULTS: There were no statistical significance in baseline information between 2 groups before treatment (P>0. 05). The number of complete remission case and total response rate in observation group were increased significantly higher than control group (P<0. 05), while number of invalid cases was significantly lower than control group (P<0. 05). Compared with before surgery, the levels of serum inflammation factor in 2 groups were decreased significantly 24, 72 h after surgery, while the levels of Scr and CysC were increased significantly in control group 24, 72 h after surgery and in observation group 24 h after surgery; the level of eGFR was decreased significantly, while the level of CysC was increased significantly in observation group 72 h after surgery, with statistical significance (P<0. 05). The improvement of serum inflammation factors and renal function indexes in observation group were more significant than control group (P<0. 05); the incidence of radiographic contrast nephropathy was significantly lower than control group (P<0. 05). The incidence of 1-year angina pectoris and total incidence of cardiovascular events were significantly lower than control group (P< 0. 05). CONCLUSIONS: Rosuvastatin combined with tirofiban can promote the recovery of renal function in acute coronary syndrome patients with diabetes after PCI, reduce the levels of serum inflammatory factors and decrease the incidence of radiographic contrast nephropathy and post-treatment cardiac events. Its effects are different from rosuvastatin alone.

Objective The F10 gene was found in the initial stage of our study to be highly expressed in hydatidiform mole. The aim of this study was to investigate the effects of theoverexpression or depletion of F10 on the invasiveness of the choriocarcinoma cell line JAR and explore the relationship of F10 expression with the invasiveness and metastasis ofchoriocarcinoma. Methods Using cell transfection and RNA interference technology, we established JAR choriocarcinoma cell lines with stablyoverexpressedor silenced F10 gene.We randomly and equally assigned 30 SPF nude mice into the three groups to receive the injection of JAR cellswith overex-pressed F10 ( F10 overexpression group) , untreated JAR cells ( control group) , and JAR cells with silenced F10( F10 silence group) . At 5 weeks after the JAR cell injection, we harvested the subcutaneous tumor tissues from the mice, determined the expressions of ma-trix metalloproteinases (MMP), tissue inhibitors of metalloproteinase-1(TIMP-1), and plasminogen activator inhibitor-1(PAI-1), and compared by Western blot and immunohistochemistry, and compared the expressions among the three groups of mice. Results Im-munohistochemistryshowed significantlyup-regulated expressions of MMP-2, -8, -11, -16, and-19 and down-regulated expressions of TIMP-1 and PAI-1 in the subcutaneous tumor tissues in the F10 overexpression group as compared with the control and F10 silence groups ( P<0.05) .Western blot also exhibitedextremely significantly up-regulated expressions of MMP-2,-8,-11,-16, and -19 pro-teins anddown-regulated expressions of TIMP-1 and PAI-1 proteins in the F10 overexpression groupin comparison with the control and F10 silence groups( P<0.01 ) . Conclusion By up-regulating the expressions of MMPs and down-regulating the expressions of TIMP-1 and PAI-1, the F10 gene might be an upstream stimulating factor involved in the proliferation, invasiveness, and metastasis of-choriocarcinoma cells.

OBJECTIVETo explore the role of the hydatidiform mole-related gene F10 in the tumorigenicity of choriocarcinoma cell lines JEG-3 in nude mice.

METHODSChoriocarcinoma JEG-3 cell lines with stable F10 gene over-expression and F10 gene silencing were established using cell transfection and RNA interference techniques, respectively. Thirty SPF nude mice (4-5 weeks old) were equally randomized into F10 over-expression group, control group, and F10 gene-silenced group for subcutaneous injection of 0.2 ml cell suspension (5 × 10⁷ cells) of F10 gene over-expressing JEG-3 cells, non-treated JEG-3 cells, and F10 gene-silenced JEG-3 cells, respectively. The mice were observed and weighed every 3-4 days, and the tumor formation time was recorded to draw the tumor growth curve and calculate the tumor formation rate.

RESULTSThe tumor formation rates were 100% in all the 3 groups. No significant difference was found in the tumor formation time among the F10 over-expression, F10-silenced and control groups (6.2 ± 0.78 vs 7 ± 2.49 vs 6.3 ± 0.67 days; F=0.781, P=0.468). A significantly greater tumor growth rate was noted in the F10 over-expression group compared with the other two groups (P<0.05), and the growth rate was significantly slower in F10-silenced group than in the control group (P<0.05). The subcutaneous tumor weight at 5 weeks after JEG-3 cell injection differed significantly among F10 over-expression, F10-silenced and control groups (571.1 ± 221.10 vs 136.2 ± 66.25 vs 354.5 ± 116.23 mg; F=21.199, P=0.000).

CONCLUSIONF10 gene plays a role in the regulation of choriocarcinoma JEG-3 cell proliferation and might enhance its tumorigenicity in nude mice.

Animals ; Cell Line, Tumor ; Cell Proliferation ; Choriocarcinoma ; pathology ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Genes, Neoplasm ; Humans ; Hydatidiform Mole ; genetics ; Mice ; Mice, Nude ; Pregnancy ; Transfection ; Uterine Neoplasms ; pathology

Objective To explore the role of the hydatidiform mole-related gene F10 in the tumorigenicity of choriocarcinoma cell lines JEG-3 in nude mice. Methods Choriocarcinoma JEG-3 cell lines with stable F10 gene over-expression and F10 gene silencing were established using cell transfection and RNA interference techniques, respectively. Thirty SPF nude mice (4-5 weeks old) were equally randomized into F10 over-expression group, control group, and F10 gene-silenced group for subcutaneous injection of 0.2 ml cell suspension (5 × 107 cells) of F10 gene over-expressing JEG-3 cells, non-treated JEG-3 cells, and F10 gene-silenced JEG-3 cells, respectively. The mice were observed and weighed every 3-4 days, and the tumor formation time was recorded to draw the tumor growth curve and calculate the tumor formation rate. Results The tumor formation rates were 100% in all the 3 groups. No significant difference was found in the tumor formation time among the F10 over-expression, F10-silenced and control groups (6.2 ± 0.78 vs 7 ± 2.49 vs 6.3 ± 0.67 days; F=0.781, P=0.468). A significantly greater tumor growth rate was noted in the F10 over-expression group compared with the other two groups (P<0.05), and the growth rate was significantly slower in F10-silenced group than in the control group (P<0.05). The subcutaneous tumor weight at 5 weeks after JEG-3 cell injection differed significantly among F10 over-expression, F10-silenced and control groups (571.1 ± 221.10 vs 136.2 ± 66.25 vs 354.5 ± 116.23 mg; F=21.199, P=0.000). Conclusion F10 gene plays a role in the regulation of choriocarcinoma JEG-3 cell proliferation and might enhance its tumorigenicity in nude mice.