Osteoarthritis （OA） is characterized by articular cartilage degeneration， synovial hyperplasia， hyperosteogeny， and narrowing of joint space， which can be caused by trauma， inflammation， and other factors. With the increasing global population aging， the incidence of OA is rising year by year， making it a major public health problem that urgently needs to be addressed. Exploring effective treatment schemes is particularly important. The pathogenesis of OA is complex， including oxidative stress， autophagy， and apoptosis. Recent studies have found that ferroptosis， a new type of cell death， is also an important pathogenic factor in OA， characterized by a series of complex changes such as iron ion accumulation， glutathione （GSH） depletion， and mitochondrial dysfunction. Research shows that inhibiting ferroptosis in chondrocytes can promote chondrocyte proliferation， delay extracellular matrix （ECM） degradation， and reduce synovial hyperplasia and inflammation. Targeting ferroptosis is a new direction in the treatment of OA. OA treatment includes intra-articular injections of steroids or hyaluronic acid and artificial joint replacement， but there are limitations. Traditional Chinese medicine （TCM） has been widely used in the treatment of various diseases because of its low cost， low drug resistance， and few side effects. Cell and animal experiments have further confirmed that TCM can intervene in the treatment of OA with ferroptosis from multiple targets， multiple levels， and aspects， but the mechanism of its treatment of OA based on ferroptosis has not been clarified. This paper discussed iron metabolism， lipid peroxidation， cysteine/glutamate transporter system Xc^- （system Xc^-）/GSH/glutathione peroxidase 4 （GPX4） pathway， nicotinamide adenine dinucleotide phosphate（NADPH）/ferroptosis suppressor protein 1 （FSP1）/coenzyme Q₁₀ （CoQ₁₀） pathway， tumor protein p53 in OA， and related molecular targets of Chinese medicine monomers and compounds on ferroptosis inhibition. Their potential therapeutic mechanisms were further analyzed to provide theoretical guidance for the treatment of OA by TCM and useful reference for the research and development of related drugs.

Background China's manufacturing industry is still labor-intensive, and assembly employees in manufacturing industry are facing a great risk of work-related musculoskeletal disorders (WMSDs). Objective To investigate and analyze the prevalence and distribution of WMSDs among assembly workers in manufacturing enterprises and explore the relationship between WMSDs and ergonomic exposure factors such as posture load and mental load. Methods From July to September 2017, by convenient sampling, a cross-sectional survey was conducted to select 670 workers engaged in electronic accessories assembly and railway vehicle manufacturing in three manufacturing enterprises in two cities in northern China as the research participants. The posture load assessment was based on the Chinese Musculoskeletal Questionnaire independently developed by our research group. The mental load assessment was based on a revised Chinese version of the Subjective Workload Assessment Technique. An unconditional logistic regression model was used to explore the relationship between ergonomic exposure and WMSDs. Results The overall prevalence rate of WMSDs was 39.6% (265/670) with 43.8% in males and 25.2% in females; the highest prevalence rate was 47.7% in the group aged 40 years and over. The prevalence rate of WMSDs in the electronic accessories assembly workers was 16.9%, that in the railway vehicle manufacturing workers was 57.3%, and the difference was statistically significant (\begin{document}$ {\chi ^2} $\end{document}=112.63, P<0.001). The mental load score [median (first quartile, third quartile)] was 55.6 (51.9, 83.3) points, and the posture load score was 27.1 (16.0, 41.5) points. The results of unconditional logistic regression model showed that women (OR=3.152, 95%CI: 1.458-6.813), drinkers (OR=1.934, 95%CI: 1.124-3.326), and railway vehicle manufacturing worker (OR=3.416, 95%CI: 1.756-6.644) had a higher risk of reporting WMSDs; The higher the mental load (OR=1.019, 95%CI: 1.007-1.031) and posture load (OR=1.034, 95%CI: 1.019-1.050), the higher the risk of reporting WMSDs. The hierarchical analysis results showed that the risk of reporting WMSDs was higher among the electronic accessories assembly workers who were older (compared with those aged <30 years, OR_30-39=2.526 and OR_≥40=12.263, respectively) and with higher posture load (OR=1.025, 95%CI: 1.002-1.049), as well as among the railway vehicle manufacturing workers who were drinking (OR=2.035, 95%CI: 1.155-3.583), obese (OR=3.094, 95%CI: 1.185-8.078), with higher mental load (OR=1.013, 95%CI: 1.001-1.025) and posture load (OR=1.033, 95%CI: 1.018-1.049). Conclusion There is a significant correlation between reporting WMSDs and ergonomic exposures such as posture load and mental load, and drinking is also a risk factor of WMSDs. The risk of reporting WMSDs in female workers in assembly manufacturing industry is higher than that in male workers. The overall prevalence rate of WMSDs in railway vehicle manufacturing workers is higher than that in electronic accessories assembly workers.

Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.

OBJECTIVE: To explore the influencing factors of neck work-related musculoskeletal disorders( WMSDs) and their effects in airport porters. METHODS: A total of 413 airport porters were chosen as study subjects using judgment sampling method. Chinese version of Musculoskeletal Questionnaire was used to investigate the prevalence of WMSDs.Then structural equation model was constructed and used to analyze the influencing factors of neck WMSDs. RESULTS: The prevalence of neck WMSDs in airport porters was 37. 3%( 154/413). Postural load,mental workload and length of service had a direct effect on neck WMSDs of porters( path coefficients were 0. 405,0. 166,0. 296,P < 0. 05),and mental workload also had an indirect effect on neck WMSDs through postural load( path coefficient was 0. 103,P < 0. 01).CONCLUSION: Posture load,mental workload and length of service are risk factors of neck WMSDs in airport porters.

OBJECTIVE: To investigate the correlation of mental workload and prevalence of work-related musculoskeletal disorders musculoskeletal disorders( WMSDs) in railway vehicle manufacturing workers.METHODS: A total of 362 male workers in assembling and welding workshop from a railway vehicle manufacturing enterprise were selected as study subjects by cluster sampling method.The level of mental workload and prevalence of WMSDs were investigated using a revised Subjective Workload Assessment Technique and China Musculoskeletal Questionnaire.RESULTS: The median score of mental workload was 67 and the prevalence rate of WMSDs was 56.9%.The multivariate logistic regression analysis results indicated that the higher the mental workload of railway vehicle manufacturers,the higher their risk for WMSDs after excluding the influence of confounding factors( P < 0.05).Workers in welding work showed a higher risk than those in assembling work( P < 0.01).Workers with fast work rhythm showed higher risk of WMSDs than those with regular working rhythm( P < 0.01).Workers with comfortable working environment and temperature showed lower risk of WMSDs than those with uncomfortable working environment and temperature( P < 0.01).CONCLUSION: The mental workload can increase the risk of WMSDs,with a dose-effect relationship in railway vehicle manufacturing workers.The type of work,work frequency and the temperature in working environment are also influencing factors of WMSDs.

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.

After the infection with HBV, the host′s antiviral immune response is a key factor for the outcome of infection. At present, it is widely believed that the host′s innate immunity and acquired immunity are impaired during chronic HBV infection, because of which HBV clearance cannot be achieved. To achieve a long-lasting immune control of HBV infection, we need to comprehensively understand the mechanisms of dysfunction of innate immune response and specific immune response in chronic HBV infection. This article summarizes the research advances in the immune response mechanism of chronicity of HBV infection.

OBJECTIVEThe aim of this study was to clarify whether the fusion of bone marrow mesenchymal stem cells (MSCs) with tumor cells can promote tumor angiogensis.

METHODSHuman glioma stem/progenitor cells (GSPCs) (SU3 cells) were transfected with red fluorescent protein (RFP) gene. Bone marrow mesenchymal stem cells (MSCs) were harvested from nude mice with whole-body green fluorescent protein (GFP) gene expression. Then the two kinds of cells were co-cultured in vitro. At the same time SU3-RFP was transplanted into the brain of GFP-expressing nude mice to establish xenograft tumors. The co-cultured cells, GFP/RFP double positive (yellow) cells and blood vessels obtained from the xenograft tumors were observed under fluorescent microscope and laser scanning confocal microscope.

RESULTSAfter five passages in vitro, MSCs maintained the proliferative activity and highly expressed CD105. CD105 was also expressed in the femurs of GFP-expressing nude mice, tumor cells, blood vessels of SU3 xenograft tumors, and clinical malignant gliomas. When MSCs were co-cultured with SU3-RFP, the ratio of yellow cells co-expressing RFP and GFP was significantly increased after extended time and continuous passages. According to the flow cytometry, yellow cells co-expressing RFP and GFP were 83.7% of the cultured cells. In tissue slices of the xenograft tumors, bundles of yellow vessel-like structure and cross-sectioned yellow vascular wall structures including vascular wall stroma cells were observed with RFP and GFP expression, and were identified as de novo formed vessels derived from fusion of MSCs with SU3-RFP cells.

CONCLUSIONCell fusion occurs between tumor cells and host MSCs and it promotes tumor angiogenesis.

Animals ; Bone Marrow Cells ; physiology ; Cell Communication ; Cell Fusion ; Cells, Cultured ; Glioma ; Green Fluorescent Proteins ; Humans ; Luminescent Proteins ; Mesenchymal Stromal Cells ; Mice ; Mice, Nude ; Microscopy, Fluorescence ; Neoplasms ; Neovascularization, Pathologic ; Stem Cells ; Transfection ; Transplantation, Heterologous

Objective The aim of this study was to clarify whether the fusion of bone marrow mesenchymal stem cells ( MSCs) with tumor cells can promote tumor angiogensis.Methods Human glioma stem/progenitor cells (GSPCs) (SU3 cells) were transfected with red fluorescent protein (RFP) gene.Bone marrow mesenchymal stem cells ( MSCs) were harvested from nude mice with whole-body green fluorescent protein (GFP) gene expression.Then the two kinds of cells were co-cultured in vitro.At the same time SU3-RFP was transplanted into the brain of GFP-expressing nude mice to establish xenograft tumors.The co-cultured cells, GFP/RFP double positive ( yellow ) cells and blood vessels obtained from the xenograft tumors were observed under fluorescent microscope and laser scanning confocal microscope.Results After five passages in vitro, MSCs maintained the proliferative activity and highly expressed CD105.CD105 was also expressed in the femurs of GFP-expressing nude mice, tumor cells, blood vessels of SU3 xenograft tumors, and clinical malignant gliomas.When MSCs were co -cultured with SU3-RFP, the ratio of yellow cells co-expressing RFP and GFP was significantly increased after extended time and continuous passages. According to the flow cytometry, yellow cells co-expressing RFP and GFP were 83.7%of the cultured cells. In tissue slices of the xenograft tumors, bundles of yellow vessel-like structure and cross-sectioned yellow vascular wall structures including vascular wall stroma cells were observed with RFP and GFP expression, and were identified as de novo formed vessels derived from fusion of MSCs with SU3-RFP cells.Conclu sion Cell fusion occurs between tumor cells and host MSCs and it promotes tumor angiogenesis.

Objective The aim of this study was to clarify whether the fusion of bone marrow mesenchymal stem cells ( MSCs) with tumor cells can promote tumor angiogensis.Methods Human glioma stem/progenitor cells (GSPCs) (SU3 cells) were transfected with red fluorescent protein (RFP) gene.Bone marrow mesenchymal stem cells ( MSCs) were harvested from nude mice with whole-body green fluorescent protein (GFP) gene expression.Then the two kinds of cells were co-cultured in vitro.At the same time SU3-RFP was transplanted into the brain of GFP-expressing nude mice to establish xenograft tumors.The co-cultured cells, GFP/RFP double positive ( yellow ) cells and blood vessels obtained from the xenograft tumors were observed under fluorescent microscope and laser scanning confocal microscope.Results After five passages in vitro, MSCs maintained the proliferative activity and highly expressed CD105.CD105 was also expressed in the femurs of GFP-expressing nude mice, tumor cells, blood vessels of SU3 xenograft tumors, and clinical malignant gliomas.When MSCs were co -cultured with SU3-RFP, the ratio of yellow cells co-expressing RFP and GFP was significantly increased after extended time and continuous passages. According to the flow cytometry, yellow cells co-expressing RFP and GFP were 83.7%of the cultured cells. In tissue slices of the xenograft tumors, bundles of yellow vessel-like structure and cross-sectioned yellow vascular wall structures including vascular wall stroma cells were observed with RFP and GFP expression, and were identified as de novo formed vessels derived from fusion of MSCs with SU3-RFP cells.Conclu sion Cell fusion occurs between tumor cells and host MSCs and it promotes tumor angiogenesis.