BACKGROUND:Chondrocyte apoptosis is an important factor in the development of osteoarthritis,and Complanatoside A has a flavonoid effect,which can inhibit apoptosis of various cells,but its effect on chondrocyte apoptosis and the mechanism of action are not clear. OBJECTIVE:To investigate the intrinsic association and mechanism of Complanatoside A in chondrocyte apoptosis based on the Wnt/β-catenin signaling pathway. METHODS:(1)The cartilage tissues of the femur and tibia transected during knee arthroplasty were collected,and chondrocytes were isolated,cultured in vitro,and identified.(2)Cell counting kit-8 was used to detect the optimal intervention concentration of Complanatoside A in the concentration range of 0-160 μmol/L.(3)Chondrocytes were divided into blank group,sodium nitroprusside(1.5 mmol/L)-induced group,and sodium nitroprusside(1.5 mmol/L)+Complanatoside A(5 μmol/L)group.The viability and apoptosis rate of the cells in each group were detected by cell counting kit-8 and flow cytometry.The expression of type Ⅱ collagen and SOX9 was detected by immunofluorescence staining.The expression of apoptosis-related proteins and Wnt/β-catenin pathway proteins was detected by western blot assay. RESULTS AND CONCLUSION:The cells extracted in vitro were cultured and stained,and were clearly identified as chondrocytes.Complanatoside A had no obvious cytotoxicity to chondrocytes in the concentration range of 0-80 μmol/L,and significantly improved the chondrocyte viability in the concentration range of 2.5-10 μmol/L,especially when the concentration was 5 μmol/L.The apoptotic rate of chondrocytes was higher in the sodium nitroprusside-induced group than the blank control group,while the apoptotic rate was lower in the sodium nitroprusside+Complanatoside A group than the sodium nitroprusside-induced group.The fluorescence intensity of type Ⅱ collagen and SOX9 in chondrocytes was weaker in the sodium nitroprusside-induced group than the blank control group,while the fluorescence intensity of type Ⅱ collagen and SOX9 in the sodium nitroprusside+Complanatoside A group was higher than that of the sodium nitroprusside-induced group.In the sodium nitroprusside-induced group,the protein expression of Bax,Caspase-3,matrix metalloproteinase 13,Wnt3a,Wnt5a and β-catenin was higher than that of the blank control group,while the protein expression of Bcl-2 was lower than that of the blank control group.In the sodium nitroprusside+Complanatoside A group,except for the protein expression of Bcl-2 which was higher than that of the sodium nitroprusside-induced group,the expression of the other aforementioned proteins was lower than that of the sodium nitroprusside-induced group.To conclude,Complanatoside A has a certain inhibitory effect on chondrocyte apoptosis,which could regulate apoptosis-related proteins and promote the expression of chondrocyte regulatory factors,and presumably might play a role through inhibiting the Wnt/β-catenin signaling pathway.

Objective Human facial morphology is an appearance phenotype with high heritability,high diversity,and complexity.Traditional facial morphological genetic analysis is mostly based on facial landmark measurements,using linear regression for genome-wide association studies,but this method extracts limited facial morphological feature information.This study established an extraction method for multidimensional facial representations and validated the correlation between 473 single-nucleotide polymorphisms(SNPs)previously reported to be significantly associated with facial features and facial representations in the Han Chinese population.Methods After acquiring facial 3D images,3D morphable face models and HR-net network were used to align and quantify the 3D images,obtaining high-density 3D facial point cloud data.After unsupervised clustering of the point cloud,principal component analysis was applied to reduce dimensionality and extract multidimensional morphological phenotypes for each facial region.Based on these multidimensional phenotypes,partial least squares regression(PLSR)and canonical correlation analysis(CCA)were used for genetic association analysis.Results A total of 10 SNPs were validated to be significantly associated with facial morphology in Han Chinese,of which 7 SNPs were validated by the PLSR method,2 SNPs were validated by the CCA method,and 1 SNP was validated by both methods.Conclusion Among the 10 significantly associated SNP sites,9 related facial morphological regions were consistent with previous reports in other populations,indicating that genes affecting complex facial morphology have cross-population effects.

Objective Human facial morphology is an appearance phenotype with high heritability,high diversity,and complexity.Traditional facial morphological genetic analysis is mostly based on facial landmark measurements,using linear regression for genome-wide association studies,but this method extracts limited facial morphological feature information.This study established an extraction method for multidimensional facial representations and validated the correlation between 473 single-nucleotide polymorphisms(SNPs)previously reported to be significantly associated with facial features and facial representations in the Han Chinese population.Methods After acquiring facial 3D images,3D morphable face models and HR-net network were used to align and quantify the 3D images,obtaining high-density 3D facial point cloud data.After unsupervised clustering of the point cloud,principal component analysis was applied to reduce dimensionality and extract multidimensional morphological phenotypes for each facial region.Based on these multidimensional phenotypes,partial least squares regression(PLSR)and canonical correlation analysis(CCA)were used for genetic association analysis.Results A total of 10 SNPs were validated to be significantly associated with facial morphology in Han Chinese,of which 7 SNPs were validated by the PLSR method,2 SNPs were validated by the CCA method,and 1 SNP was validated by both methods.Conclusion Among the 10 significantly associated SNP sites,9 related facial morphological regions were consistent with previous reports in other populations,indicating that genes affecting complex facial morphology have cross-population effects.

Objective:To examine the clinical outcomes of patients undergoing total thoracoscopic aortic-mitral double-valve replacement.Methods:This is a retrospective case series study. The clinical data of 50 patients who underwent double-valve replacement under a total thoracoscopic two-port approach from November 2021 to August 2022 in the Department of Cardiovascular Surgery, Fujian Medical University Union Hospital were retrospectively analyzed. There were 32 males and 18 females, with an age of (55.3±8.8) years (range: 21 to 62 years). Among them, 36 cases had rheumatic heart disease and 14 cases had infective endocarditis. The 3 rd intercostal space between the right anterior axillary line and the midclavicular line was selected as the main operating hole, the total thoracoscopic double-valve replacement were successfully carried out. Baseline data, intraoperative information, surgical outcomes, and postoperative complications were collected for all patients. Results:The cardiopulmonary bypass time was (168.2±30.9) minutes (range: 125 to 187 minutes), the aortic cross-clamping time was (118.8±16.5) minutes (range: 96 to 147 minutes). Five patients received bioprosthetic valves, and 45 received mechanical prosthetic valves. Postoperative mechanical ventilation lasted (9.6±3.4) hours (range: 5.1 to 14.2 hours), the ICU stay was (24.8±7.3) hours (range: 16.3 to 30.1 hours), and the postoperative hospital stay was (6.5±1.2) days (range: 5.0 to 8.0 days). Four patients received red blood cell transfusions of (2.7±0.9) units (range: 2 to 4 units), and the postoperative chest drainage volume was (222.1±56.3) ml (range: 175 to 289 ml). No deaths occurred intraoperatively or in the early postoperative period. One patient required reoperation due to bleeding in the aortic incision. Three patients had mild to moderate paravalvular leakage around the prosthetic aortic valve, with no cases of third-degree atrioventricular block or conversions to median sternotomy.Conclusions:The early outcomes of total thoracoscopic double valve replacement surgery are satisfactory, demonstrating safety and efficacy. This surgical approach expands the scope of total thoracoscopic cardiac surgery, which warrants further investigation and research.

Objective:To examine the clinical outcomes of patients undergoing total thoracoscopic aortic-mitral double-valve replacement.Methods:This is a retrospective case series study. The clinical data of 50 patients who underwent double-valve replacement under a total thoracoscopic two-port approach from November 2021 to August 2022 in the Department of Cardiovascular Surgery, Fujian Medical University Union Hospital were retrospectively analyzed. There were 32 males and 18 females, with an age of (55.3±8.8) years (range: 21 to 62 years). Among them, 36 cases had rheumatic heart disease and 14 cases had infective endocarditis. The 3 rd intercostal space between the right anterior axillary line and the midclavicular line was selected as the main operating hole, the total thoracoscopic double-valve replacement were successfully carried out. Baseline data, intraoperative information, surgical outcomes, and postoperative complications were collected for all patients. Results:The cardiopulmonary bypass time was (168.2±30.9) minutes (range: 125 to 187 minutes), the aortic cross-clamping time was (118.8±16.5) minutes (range: 96 to 147 minutes). Five patients received bioprosthetic valves, and 45 received mechanical prosthetic valves. Postoperative mechanical ventilation lasted (9.6±3.4) hours (range: 5.1 to 14.2 hours), the ICU stay was (24.8±7.3) hours (range: 16.3 to 30.1 hours), and the postoperative hospital stay was (6.5±1.2) days (range: 5.0 to 8.0 days). Four patients received red blood cell transfusions of (2.7±0.9) units (range: 2 to 4 units), and the postoperative chest drainage volume was (222.1±56.3) ml (range: 175 to 289 ml). No deaths occurred intraoperatively or in the early postoperative period. One patient required reoperation due to bleeding in the aortic incision. Three patients had mild to moderate paravalvular leakage around the prosthetic aortic valve, with no cases of third-degree atrioventricular block or conversions to median sternotomy.Conclusions:The early outcomes of total thoracoscopic double valve replacement surgery are satisfactory, demonstrating safety and efficacy. This surgical approach expands the scope of total thoracoscopic cardiac surgery, which warrants further investigation and research.

Heart transplantation is one of the most effective strategies to treat end-stage heart failure. Multiple challenges, such as difficulty in preservation of heart allograft, rejection and postoperative complications, emerge in heart allotransplantation. After decades of research and practice, most problems have been resolved. Nevertheless, the shortage of donor organs has become increasingly prominent. To alleviate the shortage of donor organs, artificial heart and heart xenotransplantation have captivated attention, and obtained significant progress in recent years. The application of artificial heart in clinical practice has significantly enhanced the survival rate of patients with end-stage heart failure, which is expected to become the standard treatment for end-stage heart failure. Heart xenotransplantation still faces many challenges, which is still far from clinical application. In this article, the history of heart transplantation, development of heart allotransplantation, use of artificial heart and research progress on heart xenotransplantation were reviewed, and the future development direction of heart transplantation was predicted.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Anti-Bacterial Agents ; chemistry ; pharmacology ; Drug Resistance, Bacterial ; drug effects ; Humans ; Mycobacterium tuberculosis ; chemistry ; drug effects ; Tuberculosis, Multidrug-Resistant ; drug therapy ; microbiology

Objective To investigate the relationship between interventricular septum thickness(IVS) and renal function in patients with diabetes mellitus.Methods Two hundred and sixty-five patients of type 2 diabetes without dialysis were enrolled in a cross-sectional study.According to their IVS,the patients were divided into normal group (IVS≤ 11 mm) and higher IVS group (IVS ＞ 11 mm).All patients according to evaluated glomerular filtration rate (eGFR) level were divided into eGFR≥60 ml· min-1 · (1.73 m2) 1 group and eGFR ＜ 60 ml· min-1 · (1.73 m2)-1 group.The demographic characteristic,biochemical examination,eGFR,and proteinuria of different groups were compared.Pearson or spearman correlation was used to analyze the relationship between eGFR,IVS and other parameters.eGFR ＜ 60 ml · min-1 · (1.73 m2)-1 and IVS thickening were analyzed by binary logistic regression.Risk factors affect the prognosis of renal function in patients with diabetes mellitus were analyzed by Cox regression analysis.Results Compared with normal group,patients in the higher IVS group had higher systolic pressure (P=0.002),their level of Scr,BUN,24 h urinary protein were increased (all P ＜ 0.05),while the level of eGFR,albumin (ALB),hemoglobin (Hb) and fasting blood glucose were decreased (all P ＜ 0.05).The prevalence of hypertension was increased (81.16％ vs 58.67％,x2=11.273,P=0.001),and there was also a difference in the proportion of patients in each stage of CKD (x2=34.593,P ＜ 0.001).Correlation analysis showed that IVS was positively correlated with BMI,systolic BP,Scr,BUN,24 h urinary albumin,24 h urinary protein (all P ＜ 0.05),while negative correlation was observed between the thickened degree of IVS and Hb,albumin,eGFR and total calcium (all P ＜ 0.05).It's worth noting that IVS also correlated with history of hypertension and degree of renal injury (all P ＜ 0.01).Logistic regression analysis showed that longer duration of diabetes,higher systolic pressure and BUN were independent risk factors for eGFR ＜ 60 ml·min-1·(1.73 m2)-1 (all P ＜ 0.05),while higher Hb and Alb were independent protective factors for eGFR ＜ 60 ml· min-1· (1.73 m2)-1 (all P ＜ 0.05).Logistic regression analysis also showed that the baseline increased Scr was independent risk factor for interventricular thickening (P ＜ 0.05),while the increase of fasting blood-glucose was independent protective factor for interventricular thickening (P ＜ 0.05).Cox regression analysis showed that interventricular thickening was an independent risk factor in predicting the progression of type 2 diabetes (HR=1.396,95％ CI=1.098-1.774,P=0.006).Conclusion Interventricular septum thickness is closely related to the state of renal function,as well as is an independent risk factor to predict kidney function decline in patients with type 2 diabetes.