Aim To explore the effect and mechanism of resveratrol (Res) on proliferation and differentiation of murine 3T3-L1 preadipocytes.Methods 3T3-L1 preadipocytes were cultured and treated with resveratrol in different dosages.Cell proliferation was analyzed by WST-1 method. Oil red O staining method and spectrophotography were applied to analyze the degree of differentiation. Real-time PCR was applied to detect the mRNA expression of adiponectin and leptin. Western blot was applied to detect the expression of silent information regulator 1 (Sirt1),peroxisome proliferator activated receptor γ (PPARγ) and CCTTA enhancer binding proteinα (C/EBPα).Results Res inhibited proliferation of murine 3T3-L1 preadipocytes in a time-dose dependent manner.The expression levels of adiponectin and leptin mRNA were decreased, and Res also inhibited 3T3-L1 preadipocytes to differentiate into mature adipocytes. Res increased the expression levels of Sirt1 and decreased the expression levels of PPARγ and C/EBPα.Conclusions Resveratrol can inhibit the proliferation and differentiation of 3T3-L1 preadipocytes.The underlying mechanisms may include enhancing expression of Sirt1 and inhibiting expression of PPARγ,C/EBPα which are related to cell differentiation.

Objective To detect the expression change of ETFβin diabetic nephropathy rats and study the role of ETFβin fatty acid-induced apoptosis in renal tubules.Methods Diabetic nephropathy model was established by intraperitoneal injection of streptozotocin and unilateral nephrectomy.In vivo ETFβexpression was detected in renal cortex, as well as tubular injury evaluated.In vitro fatty acid-induced apoptosis in renal tubular cells NRK 52E model was established and ETFβrecombinant plasmid was constructed to be transfected into NRK 52E cells and furtherly to observe the effect of ETFβover-expression on the fatty acid-induced apoptosis.Results In the rats model of diabetic nephropathy induced by streptozotocin injection and unilateral nephrectomy, ETFβmRNA and protein expression were decreased as obvious tubular damage occurred.Fatty acids could induce apoptosis in NRK 52E, and ETFβover-expression reduced the apoptosis.Conclusion The expression of ETFβis decreased in diabetic nephropathy model , and ETFβover-expression can reduce apoptosis induced by fatty acid in renal tubular cells.

Objective To investigate the effects of dihydropteridine reductase (QDPR) on regulating apoptosis induced by plamitic acid(PA). Methods The transfection of HEK293T cells experiment was divided into 3 groups. A group was the control vector group. B group was the control vector group induced by PA. C group was the recombinant plasmid QDPR group induced by PA. First, control vector and recombinant plasmid QDPR was respectively transfected into HEK293T cells. After 24 h, PA with concentration of 0. 5 mmol/L was added into the medium of above cells. The cells of control vector group, the cells of control vector group induced by PA and the cells of recombinant plasmid QDPR group induced by PA were cultured for another 24 hours. At last, cells were harvested to detect tetrahydrobiopterin (BH4) and reactive oxygen species(ROS) generation, Beclin 1, Caspase 3 and Beclin 2 expression. Results ① After transfection, the recombinant plasmid QDPR was successfully constructed and expressed in cells.② There was no significant difference between A group and B group in BH4 generation. Compared with B group, BH4 generation increased in C group (P < 0. 05).③ ROS generation was increased in B group compared with A group, and decreased ROS generation in C group compared with B group (P < 0. 05).④ Western blot analysis revealed that Beclin 1 and Caspase 3 increased (P < 0. 05 ) while Beclin 2 decreased in B group compared with A group (P < 0. 05). Compared to B group, Beclin 1 and Caspase 3 decreased while Beclin 2 increased in C group (P < 0. 05 ). Conclusion QDPR may regulate apoptosis induced by fatty acids by decreasing the generation of ROS and increasing the level of BH4 and the expression of Beclin 2 associated with anti-apoptosis.

Objective:To analyze the characteristics of patients with Takayasu arteritis (TA) in the east China Takayasu arteritis (ECTA) cohort and their subgroups, and evaluate the disease characteristics.Methods:Patients diagnosed with TA in ECTA cohort from January 2009 to October 2019 were enrolled and their data were analyzed. The characteristics were analyzed and compared within subgroups using t-test or Wilcoxon rank sum test or Chi-square test. Results:A total of 454 patients were included, with the male to female ratio of 1∶4.75(79/375), and the main complaint were dizziness/headache, fatigue, and chest tightness/pain. The type Ⅴ and Ⅰ were the most common angiographic pattern, among which the subclavian artery and carotid artery were most vulnerable, manifested as vascular stenosis. Hypertension, tuberculosis and hepatitis B were common complications. In subgroup comparison, symptoms and inflammation index were much more evident in the active group, female group, <40 years old, and newly diagnosed group. C-reactive protein (CRP)[10(2, 33) mg/L vs 3(1, 14) mg/L, Z=-4.49, P<0.01), erythrocyte sedimentation rate (ESR) [(45±33) mm/1 h vs (25±23) mm/1 h, t=-5.82, P<0.01), in the active group were significantly higher than those in the inactive group, while the ESR in female patients was only higher than that in males, but without statistical significant difference. SAA in the young age group, ESR in the newly diagnosed group was significantly higher than that in the other subgroups [19(6, 95) mg/L vs 10(4, 39) mg/L, Z=2.06, P<0.05] [(44±34) mm/1 h vs (32±28) mm/1 h, t=3.77, P<0.01]. Conclusion:The TA patients are mainly young women, and are in active disease when first being diagnosed. The type Ⅴ and Ⅰ are the most common artery involve-ment pattern. Hypertension and tuberculosis are the most frequent complications.

Objective:To explore the status and correlates of sleep quality in hospitalized patients with schizophrenia.Methods:A total number of 269 schizophrenia inpatients were recruited from 7 hospitals including Peking University Sixth Hospital, Zhumadian Second People′s Hospital and Liaocheng Fourth People′s Hospital from August 2019 to March 2021. The Brief Psychiatric Rating Scale (BPRS), the Pittsburgh Sleep Quality Index (PSQI), the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the suicide module of Mini-International Neuropsychiatric Interview were evaluated. Poor sleep quality was determined by the score of more than 5 according to PSQI, all patients were divided into groups of poor and normal sleep quality. The general demographic data and clinical characteristics of two groups were compared, and the correlates of sleep quality were obtained by Spearman correlations and multiple logistic regression.Results:The prevalence of poor sleep quality in schizophrenia inpatients was up to 44.6% (120/269). Compared with normal sleep quality group, inpatients with poor sleep quality had higher rates of alcohol consumption history, use of benzodiazepines (BZDs) and current suicide risk, and BPRS total score, factor scores (thinking disorders, anxious-depression, hostile-suspiciousness and activation), PHQ-9 and GAD-7 scores were also higher (all P<0.05). Spearman correlation analyses showed that PSQI total score were significantly positively correlated with BPRS total score ( r=0.323), PHQ-9 score ( r=0.553), GAD-7 score ( r=0.456) and current suicide risk level ( r=0.320) (all P<0.001). Multiple logistic regression showed that history of alcohol consumption ( OR=2.897, 95% CI: 1.002-8.372), use of BZDs ( OR=3.181, 95% CI: 1.548-6.534), thinking disorders ( OR=1.563, 95% CI: 1.015-2.406), comorbidity with depression ( OR=4.968, 95% CI: 1.869-13.202), and current suicide risk ( OR=2.496, 95% CI: 1.360-4.581) were independently correlated with poor sleep quality (all P<0.05). Conclusion:Poor sleep quality is common in hospitalized patients with schizophrenia, and history of alcohol consumption, use of BZDs, thinking disorders, comorbidity with depression and current suicide risk are independent correlates of poor sleep quality.

ObjectiveThe type 2C protein phosphatases （PP2C） are involved in numerous plant signal transduction pathways. They mainly participate in plant stress response and regulate second metabolites biosynthesis via negatively regulating MAPK signaling pathway. Herein，we were to identify and analyze PP2C （CsPP2C） gene family from hemp genome，in hope of providing comprehensive insights for studying CsPP2C function during the development of hemp. MethodMolecular Evolutionary Genetics Analysis （MAGA）-X was used to construct phylogenetic tree. Expert Protein Analysis System （ExPASy），WoLF PSORT，Multiple EM for Motif Elicitation （MEME），Batch Conserved Domain Search （Batch-CD-Search），PlantCare，and TBtools were used，respectively，to predict CsPP2C physicochemical properties，subcellular localization，conserved motifs，protein structure，cis-element in promoter and collinearity with Arabidopsis PP2C. Cannabis sativa transcriptome and Real-time polymerase chain reaction（Real-time PCR） were used to analyze and verify gene expressions，respectively. ResultFifty-two CsPP2C with conserved domains were identified from the entire genome of hemp，encoding proteins ranging from 244 to 1 089 aa in length and with molecular weights ranging from 26.76 to 122.53 kDa. Those genes were mainly distributed in the nucleus，cytoplasm and chloroplast. The 47 CsPP2C were divided into 10 subfamilies，and the remaining 5 were not clustered. Seven pairs of homologous genes between hemp and Arabidopsis thaliana were identified according to collinear analysis. The light-responsive elements and abscisic acid elements are most abundant in the prediction. The gene expression heat map showed varied expression pattern of CsPP2C in different tissues. Real-time PCR results of three CsPP2C were consistent with transcriptome data. Moreover，alternative splicing analysis showed that some CsPP2C had alternative-splicing genes during evolution. ConclusionWe predicted and analyzed CsPP2C gene family in genomic scale and showed that CsPP2C are involved in many biological processes，whereby provides foundation for CsPP2C functional study.

Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.