Objective To study the cause of protective immunodeficiency of patients with hepatitis C. Methods An antigen capture ELISA in which HCV synthetic peptides SP42, CP10 and CP9 derived from HCV NS4 and core gene region, respectively, were used as solid-phase antigens was used to detect the differences in light chain isotype expression of anti-HCV antibodies. Results Antibodies in 84 sera of HCV-infected patients against HCV SP42, CP10 and CP9 were characterized by a skewed light chain isotype expression. Eighty-two out of 84 sera of HCV infection (97 62%) showed at least one of the three anti-HCV antibodies skewed from the normal ratio of light chain isotype kappa/lambda. The kappa/lambda ratios of anti-HCV antibodies in all patients with hepatitis C were found to be unique and constant during one year follow-up, and 11 of them received two years follow-up. Conclusions Anti-HCV response was stable and clonally restricted in HCV infection. B-cell clonal dominance may be the cause of human protective immunodeficiency after HCV infection.

Based on the CT data, a medical treatment FE model of hip joint prosthesis with stepped stem was rebuilt according the anatomy of the hip joint. Under the loads of 1.5 times standard body weight (70kg), the mechanical behavior of the treatment model was calculated, and the influence of step structure and distribution for stepped stem on femur stress and stability of total hip replacement were analyzed by three-dimensional finite element analysis (3D-FEA). The results show that the step structure changs the bone stress transmission on the interface of stepped stem and femur, and benefits to reduce stress-shielding in the femur. For the same distribution of step, the reduction of stress-shielding for raised stepped stem is better than that for concave stepped stem. The raised stepped stem of which the steps is distributed one of third part of the stem is of the best effect of reduction of stress shielding in all of the analysis models, and is a beneficial mechanical design to relieves osteoporosis or osteopenia of femur caused by stress-shielding and improve the reliability of it in clinic.
Adult ; Arthroplasty, Replacement, Hip ; methods ; Biomechanical Phenomena ; Computer Simulation ; Equipment Failure Analysis ; Finite Element Analysis ; Hip Prosthesis ; Humans ; Imaging, Three-Dimensional ; Male ; Models, Biological ; Prosthesis Design ; Stress, Mechanical ; Tomography, Spiral Computed ; Weight-Bearing ; physiology

Objective To observe the effect of myocardial transcription factor MRTF-A on myocardium inflammation and its mechanism.Methods Totally 30 rats were randomly divided into the sham,ischemia-reperfusion (myocardial ischemia 30 min and reperfusion 2 h),and MRTF-A groups(myocardial ischemia 30 min and reperfusion 2 h & Lentivirus infection MRTF-A) (n=10 each group).Serum myocardial enzyme activity was detected by biochemical analysis,myocardial infarct size detected by TTC,and degree of myocardial injury was measured by HE staining.The TLR4 and TRIF expression was analyzed by immunohistochemistry and qPCR.Results Compared with the sham group,the MRTF-A group significantly increased the activity of serum myocardial enzymes CK-MB and LDH (P＜0.05).The infarct area of myocardial tissue was gray-white,and the infarct area was (54.31±3.07)％ (P ＜ 0.05).Myocardial fibrosis was disorder,myocardial cell was swollen and burst,and inflammatory cell infiltration was obvious.Protein and mRNA expressions of TRL4 and TRIF were significantly up-regulated (P＜0.05).Compared with the ischemia-reperfusion group,the levels of CK-MB and LDH were significantly reduced after myocardial infection with MRTF-A (P＜0.05).The myocardial infarction area was significantly reduced to (16.74±4.26)％ (P＜ 0.05).The myocardial structure was nearly normal with mild edema.Protein and mRNA expression of TRL4 and TRIF decreased significantly (P＜0.05).Conclusions The overexpression of transcription factor MRTF-A in myocardial cells alleviates the myocardial ischemia reperfusion injury by inhibiting the TLR4/TRIF signaling pathway and reducing the serum myocardial enzyme activity and myocardial damage.

Objective To observe the impact of mesenchymal stem cells (BMSCs) transplantation on myocardial myocardin-related transcription factor-A (MRTF-A) and bcl-2 expression in rats with experimental myocardial infarction (MI).Methods Thirty rats were randomly divided into sham,MI and MI + BMSCs (1 × 106 injected into 4 infarct points immediately post coronary artery ligation) groups (n =10 each).One week later,TUNEL was used to detect cardiomyocyte apoptosis,the myocardial expression of MRTF-A and bcl-2 was detected by laser scanning confocal microscope and Western blot.In vitro plasmid of MRTF-A and co-transfection with plasmids of MRTF-A and bcl-2 or mutated bcl-2 transfection into cardiomyocyte was applied to evaluate the relationship between MRTF-A and bcl-2.Results The number of apoptotic cardiomyocytes in the sham group,MI group and MI + BMSCs group were (4.05 ± 1.56) ％,(62.38 ± 8.41) ％ and (22.36 ±+ 6.17) ％,respectively (P ＜ 0.05).The protein expression of MRTF-A and bcl-2 in the MI group were significantly lower than those in sham group,while significantly upregulated in MI + BMSCs group (P ＜ 0.05 vs.MI).In cultured neonatal rat cardiomyocyte,the expression of bcl-2 protein was significantly upregulated after transfection with MRTF-A plasmid,and bcl-2-luciferase activity significantly increased after co-transfection with plasmids of MRTF-A and bcl-2-luciferase,however,the positive regulatory effect of MRTF-A was abolished after transfection with mutated bcl-2.Conclusion Mesenchymal stem cells transplantation can effectively reduce cardiomyocyte apoptosis in this rat MI model,and upregulate the expression of MRTF-A.Consequent up-regulated bcl-2 expression might be involved in the beneficial effects of BMSCs transplantation in this model.

Objective To systematically review the sex differences in efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) patients. Methods We conducted a computer search of Medline, The Cochrane Library, and EMbase from inception to November 2022 to identify randomized controlled trials (RCTs) assessing the efficacy of ICIs in patients with NSCLC. A meta-analysis was performed using RevMan 5.4 software. Results Finally 16 RCTs with a total of 9 653 patients were included, and the modified Jadad scale score was≥4 points. Meta-analysis results showed that in female NSCLC patients receiving immune therapy, the median overall survival (OS) [HR=0.72, 95%CI (0.61, 0.85), P<0.001] was longer than that in males [HR=0.73, 95%CI (0.69, 0.78), P<0.001]. Males [HR=0.64, 95%CI (0.58, 0.71), P<0.001] had an advantage over females [HR=0.76, 95%CI (0.57, 1.03), P=0.760] in median progression-free survival (PFS). Conclusion Females receiving ICIs have an advantage over males in terms of median OS. However, males tend to derive greater benefit from ICIs in terms of median PFS.