Objective To study the variations in lower limb muscle strength and gait after long-distance load marching in soldiers and to investigate the effects of muscle fatigue of the lower limbs on the walking and running gait.Methods Fifteen male soldiers completed a 15 km march with a 17.5 kg load carriage.The isometric muscle strength of the hip,knee,and ankle joints under flexion and extension were tested.The walking and running gait parameters were collected with a Vicon motion capture system and AMTI force platform.Results After load marching,the peak moment of the hip decreased significantly(P＜0.05),the mean power of the right knee decreased significantly(P＜0.05),and the relative peak moment and mean power of the ankle plantar flexion decreased significantly(P＜0.05).During walking,the left hip flexion,knee flexion and extension,ankle dorsiflexion,and inversion angles(P＜0.05)decreased significantly in conjunction with a significant increase in the knee inversion angle(P＜0.05).Additionally,the moments of left hip flexion,knee flexion,ankle plantar flexion,and bilateral knee inversion(P＜0.05)decreased significantly,coupled with a significant increase in the moments of right hip extension and vertical ground reaction forces(P＜0.05).During running,the step frequency decreased significantly(P＜0.01),and the left step width increased(P＜0.05).Both left and right ankle dorsiflexion angles decreased significantly(P＜0.05),whereas the knee adduction angle increased significantly(P＜0.05).Additionally,the moment of bilateral hip flexion,left knee flexion,right ankle dorsiflexion,and knee adduction decreased significantly(P＜0.05),and the ground reaction force on the right side increased significantly(P＜0.05).Conclusions The lower limb muscle strength decreased after long-distance marching.This was particularly so in the hip joint.The hip drive mechanism was used in the walking gait after marching.However,knee hyperextension and valgus occurred owing to the decreased muscle strength.The ankle joint was used more frequently during running.This increased the risk of ankle injury.It is necessary to strengthen the hip and hamstring muscle groups to optimize the gait,increase the load capacity,and prevent injury.

The novel coronavirus(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2),classified as a single-stranded RNA virus,replicates and transcribes its genome through the action of an RNA-dependent RNA polymerase,which is itself comprised of numerous non-structural pro-teins(non-structural proteins,Nsps).The present study delineates the development of a detection system founded on a bicistronic reporter plasmid in conjunction with an array of Nsp plasmids,ai-ming to investigate the influence of SARS-CoV-2 Nsps on the virus's replication and expression profiles.Specifically,a bicistronic reporter gene plasmid along with twelve distinct Nsp plasmids(encompassing Nsp3C-Flag,Nsp4,Nsp6-Nsp10,Nsp12-Nsp16)were meticulously constructed via molecular cloning techniques.The successful expression of these Nsps was subsequently confirmed through Western blot analysis.Initially,the activity of the RNA-dependent RNA polymerase was assessed by co-transfection of the reporter plasmid with Nsp12,in the presence of its auxiliary fac-tors Nsp7 and Nsp8,with careful regulation of the co-transfection ratio,culturing temperature,and the timing of activity determination for the triad of Nsp plasmids.The normalized NLuc fluorescein value,in reference to the FLuc fluorescein value of the housekeeping gene,served as a metric for determining the polymerase activity.Building upon this foundation,the co-transfection concentra-tions of Nsp9-16 were fine-tuned,followed by the incremental addition of varying doses of Nsp3C,Nsp4,and Nsp6,to further elucidate the activity of RNA-dependent RNA polymerase(RdRp).The findings indicated that upon transfection with varying ratios of Nsp7,Nsp8,and Nsp12 at a propor-tion of 1∶8∶24,the polymerase activity was markedly elevated compared to the control group,with a statistical significance level(P＜0.001).Furthermore,in the absence of Nsp3,Nsp4,and Nsp6,the inclusion of Nsp10-16 substantially augmented the activity of the RdRp,particularly in scenarios where Nsp9 was not introduced,achieving statistical significance(P＜0.001).In the pres-ence of Nsp3 and Nsp4,the RdRp activity was augmented further upon the addition of Nsp9,reac-hing a level of significance(P＜0.05).The data imply that Nsp9 is capable of enhancing the RdRp activity of SARS-CoV-2 exclusively in the context of Nsp3 and Nsp4 coexistence,suggesting that the stimulatory influence of Nsp9 on viral replication may be contingent upon the formation of double-membrane vesicles.

Objective:To evaluate the effectiveness of virtual case teaching integrating standardized patients (SP) and objective structured clinical examination (OSCE) in enhancing students' clinical thinking and practical skills in experimental exercise therapy course.Methods:In April 2023, 52 students from the 2021 cohort and 54 students from the 2022 cohort of the Rehabilitation Therapy undergraduate program at Xinjiang Medical University were selected and divided into the experimental group and control group according to their classes. In the shoulder joint mobilization experimental class of the exercise therapy course, virtual SP teaching was performed in the experimental group of both cohorts. For the control group, student-led SP teaching was performed in the 2021 cohort, while the traditional "lecture + demonstration" method was used in the 2022 cohort. Upon completion of teaching, theoretical exams, case analysis, practical exams, and a teaching satisfaction survey were conducted on the students. Data were analyzed using the t-test and chi-square test in SPSS 25.0. Results:In both cohorts, the experimental group had similar theoretical exam scores ( P=0.207 and P=0.097, respectively) to the control group, but had higher practical exam scores ( P=0.013 and P=0.002, respectively) than the control group. In the case analysis exam, the experimental group scored higher than the control group in the 2022 cohort ( t=2.84, P=0.006) but similarly to the control group in the 2021 cohort ( t=1.53, P=0.132). All students believed that virtual SP teaching was most engaging. In terms of understanding complex concepts, increasing active participation, and fostering clinical thinking, the 2022 cohort was more satisfied with virtual SP teaching, whereas the 2021 cohort experienced no significant difference between virtual SP teaching and student-led SP teaching. In addition, the 2021 cohort found that student-led SP teaching was more helpful for improving doctor-patient communication skills. Conclusions:The application of virtual SP teaching in the experimental exercise therapy course effectively enhances students' practical skills and case analysis capabilities, contributing greatly to their overall clinical management thinking.

The novel coronavirus(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2),classified as a single-stranded RNA virus,replicates and transcribes its genome through the action of an RNA-dependent RNA polymerase,which is itself comprised of numerous non-structural pro-teins(non-structural proteins,Nsps).The present study delineates the development of a detection system founded on a bicistronic reporter plasmid in conjunction with an array of Nsp plasmids,ai-ming to investigate the influence of SARS-CoV-2 Nsps on the virus's replication and expression profiles.Specifically,a bicistronic reporter gene plasmid along with twelve distinct Nsp plasmids(encompassing Nsp3C-Flag,Nsp4,Nsp6-Nsp10,Nsp12-Nsp16)were meticulously constructed via molecular cloning techniques.The successful expression of these Nsps was subsequently confirmed through Western blot analysis.Initially,the activity of the RNA-dependent RNA polymerase was assessed by co-transfection of the reporter plasmid with Nsp12,in the presence of its auxiliary fac-tors Nsp7 and Nsp8,with careful regulation of the co-transfection ratio,culturing temperature,and the timing of activity determination for the triad of Nsp plasmids.The normalized NLuc fluorescein value,in reference to the FLuc fluorescein value of the housekeeping gene,served as a metric for determining the polymerase activity.Building upon this foundation,the co-transfection concentra-tions of Nsp9-16 were fine-tuned,followed by the incremental addition of varying doses of Nsp3C,Nsp4,and Nsp6,to further elucidate the activity of RNA-dependent RNA polymerase(RdRp).The findings indicated that upon transfection with varying ratios of Nsp7,Nsp8,and Nsp12 at a propor-tion of 1∶8∶24,the polymerase activity was markedly elevated compared to the control group,with a statistical significance level(P＜0.001).Furthermore,in the absence of Nsp3,Nsp4,and Nsp6,the inclusion of Nsp10-16 substantially augmented the activity of the RdRp,particularly in scenarios where Nsp9 was not introduced,achieving statistical significance(P＜0.001).In the pres-ence of Nsp3 and Nsp4,the RdRp activity was augmented further upon the addition of Nsp9,reac-hing a level of significance(P＜0.05).The data imply that Nsp9 is capable of enhancing the RdRp activity of SARS-CoV-2 exclusively in the context of Nsp3 and Nsp4 coexistence,suggesting that the stimulatory influence of Nsp9 on viral replication may be contingent upon the formation of double-membrane vesicles.

Objective To study the variations in lower limb muscle strength and gait after long-distance load marching in soldiers and to investigate the effects of muscle fatigue of the lower limbs on the walking and running gait.Methods Fifteen male soldiers completed a 15 km march with a 17.5 kg load carriage.The isometric muscle strength of the hip,knee,and ankle joints under flexion and extension were tested.The walking and running gait parameters were collected with a Vicon motion capture system and AMTI force platform.Results After load marching,the peak moment of the hip decreased significantly(P＜0.05),the mean power of the right knee decreased significantly(P＜0.05),and the relative peak moment and mean power of the ankle plantar flexion decreased significantly(P＜0.05).During walking,the left hip flexion,knee flexion and extension,ankle dorsiflexion,and inversion angles(P＜0.05)decreased significantly in conjunction with a significant increase in the knee inversion angle(P＜0.05).Additionally,the moments of left hip flexion,knee flexion,ankle plantar flexion,and bilateral knee inversion(P＜0.05)decreased significantly,coupled with a significant increase in the moments of right hip extension and vertical ground reaction forces(P＜0.05).During running,the step frequency decreased significantly(P＜0.01),and the left step width increased(P＜0.05).Both left and right ankle dorsiflexion angles decreased significantly(P＜0.05),whereas the knee adduction angle increased significantly(P＜0.05).Additionally,the moment of bilateral hip flexion,left knee flexion,right ankle dorsiflexion,and knee adduction decreased significantly(P＜0.05),and the ground reaction force on the right side increased significantly(P＜0.05).Conclusions The lower limb muscle strength decreased after long-distance marching.This was particularly so in the hip joint.The hip drive mechanism was used in the walking gait after marching.However,knee hyperextension and valgus occurred owing to the decreased muscle strength.The ankle joint was used more frequently during running.This increased the risk of ankle injury.It is necessary to strengthen the hip and hamstring muscle groups to optimize the gait,increase the load capacity,and prevent injury.

Objective:To evaluate the effectiveness of virtual case teaching integrating standardized patients (SP) and objective structured clinical examination (OSCE) in enhancing students' clinical thinking and practical skills in experimental exercise therapy course.Methods:In April 2023, 52 students from the 2021 cohort and 54 students from the 2022 cohort of the Rehabilitation Therapy undergraduate program at Xinjiang Medical University were selected and divided into the experimental group and control group according to their classes. In the shoulder joint mobilization experimental class of the exercise therapy course, virtual SP teaching was performed in the experimental group of both cohorts. For the control group, student-led SP teaching was performed in the 2021 cohort, while the traditional "lecture + demonstration" method was used in the 2022 cohort. Upon completion of teaching, theoretical exams, case analysis, practical exams, and a teaching satisfaction survey were conducted on the students. Data were analyzed using the t-test and chi-square test in SPSS 25.0. Results:In both cohorts, the experimental group had similar theoretical exam scores ( P=0.207 and P=0.097, respectively) to the control group, but had higher practical exam scores ( P=0.013 and P=0.002, respectively) than the control group. In the case analysis exam, the experimental group scored higher than the control group in the 2022 cohort ( t=2.84, P=0.006) but similarly to the control group in the 2021 cohort ( t=1.53, P=0.132). All students believed that virtual SP teaching was most engaging. In terms of understanding complex concepts, increasing active participation, and fostering clinical thinking, the 2022 cohort was more satisfied with virtual SP teaching, whereas the 2021 cohort experienced no significant difference between virtual SP teaching and student-led SP teaching. In addition, the 2021 cohort found that student-led SP teaching was more helpful for improving doctor-patient communication skills. Conclusions:The application of virtual SP teaching in the experimental exercise therapy course effectively enhances students' practical skills and case analysis capabilities, contributing greatly to their overall clinical management thinking.

Objective To explore the intrinsic relationship between circadian clock and cell cycle in osteoarthritis(OA)chondrocytes,especially the regulation of cell cycle-related genes by the clock gene Bmal1.Methods The chondroid ATDC5 cells induced by insulin-transfering-selenium(ITS)were divided into control group,OA group and LV-Bmal1 group.The cell viability of each group was detected by CCK8 method.The expression of Bmal1,Per1,Wee1,Cdk1,Ccnb1 and Mmp13 mRNA in each group was detected by RT-qPCR.The expression of BMAL1,PER1,WEE1,CDK1,CCNB1 and MMP13 protein in each group was detected by Western blot.The effects of Bmal1 on different stages of cell cycle and apoptosis was analyzed by flow cytometry.The regulation of Bmal1 on Per1,Wee1,Cdk1,Ccnb1 and Mmp13 and their roles in OA were analyzed.Results Compared with the normal group,the cell viability of the OA group was increased,the relative mRNA expression of Bmal1 and Wee1 in the OA group decreased,and the relative mRNA expression of Per1,Cdk1,Ccnb1 and Mmp13 increased signif-icantly.The cell viability of LV-Bmal1 group decreased,the relative expression of Bmal1 and Wee1 mRNA in-creased,and the relative expression of Per1,Cdk1,Ccnb1 and Mmp13 mRNA decreased(P＜0.05).Correlation analysis showed that Bmal1 was positively correlated with Wee1 and they were negatively correlated with Per1,Cdk1,Ccnb1 or Mmp13.The results of Western blot showed that protein expression in different groups were con-sistent with the trend of PCR.The results of cell cycle and apoptosis showed that compared with the normal group,the S phase and G2/M phase of the OA group were shortened,the proportion of cells decreased significantly,and the proportion of early and late apoptosis increased.The S phase and G2/M phase of the LV-Bmal1 group were prolonged,the proportion of cells was increased,and the proportion of early and late apoptosis was decreased.Conclusions Circadian clock gene Bmal1 in inflammatory chondrocytes might regulate the expression of cell cycle-related genes.

Approximately 25%of cancers worldwide are related to obesity and sedentary lifestyle.Changing behavior(exer-cise)may be a cost-effective means of prevention and treatment.Studies have found that exercise plays an important role in reducing cancer risk,inhibiting tumor growth,improving cancer-related quality of life,and improving the effectiveness of treatment.However,this protection mechanism is largely unclear.Clarifying the mechanism of action is essential to fully exploit the potential of exercise therapy,this article reviews the possible mechanisms for exercise to reduce the risk of cancer.

Objective:To develop and validate a predictive nomogram for 28-day mortality among very older patients with sepsis, to identify high-risk patients early and improve prognosis.Methods:This study was conducted from January 1, 2022, to November 30, 2022. Very older patients aged≥80 years with sepsis admitted to the emergency department of Beijing Chao-Yang Hospital, Capital Medical University were consecutively recruited. Their clinical data within 24 h of admission and 28-day mortality was recorded. The participants were divided into training (70%) and validation cohort (30%) (random number). In the training cohort, the risk factors of 28-day mortality were selected via least absolute shrinkage and selection operator (LASSO) regression analysis and multivariable Cox proportional hazard model, and a nomogram was developed. The prediction model was verified in validation cohort.Results:In total, 507 very older patients with sepsis were included, among which the mortality rate was 31.2%. In training cohort, the independent risk factors for 28-day mortality were identified: increased age [hazard ratio ( HR)=1.059, 95% confidence interval (95% CI)=1.017-1.103, P=0.005], cognitive impairment ( HR=2.100, 95% CI=1.322-3.336, P=0.002), frailty ( HR=2.561, 95% CI=1.183-5.545, P=0.017), decreased mean arterial pressure ( HR=0.987, 95% CI=0.976-0.998, P=0.017), decreased prealbumin ( HR=0.997, 95% CI=0.994-1.000, P=0.040), increased blood urea nitrogen ( HR=1.028, 95% CI=1.010-1.045, P=0.001), increased procalcitonin ( HR=1.008, 95% CI=1.001-1.016, P=0.019) via LASSO regression analysis and multivariable Cox regression analysis. The nomogram was developed using these seven predictors. In the training and validation cohorts, the calibration curves, time-dependent AUC curves, and decision curve analysis showed that the nomogram had good calibration degree, discrimination and clinical net benefits. Conclusions:Increased age, cognitive impairment, frailty, decreased mean arterial pressure, decreased prealbumin, increased blood urea nitrogen, and increased procalcitonin are independent risk factors for 28-day mortality in very older patients with sepsis. The nomogram, which included the seven predictors, have good predictive performance, and might be helpful for prognosis assessment.

In the course of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infec-tion,to verify whether ursodeoxycholic acid(UDCA)can reduce angiotensin-converting enzyme 2(ACE2)receptor in BALB/c mice and reduce the risk of infection.UDCA was administered by in-tragastric administration to BALB/c mice for 7 d.During the treatment,the turbinate bones and lungs of mice were taken every day,and the changes of ACE2 content in the turbinate bones and lungs of mice were detected by ELISA.In addition,after 1,4 and 7 d of intragastric prophylaxis,BALB/c mice were infected with SARS-CoV-2 C57MA14 mouse adapted strain and SARS-CoV-2 Omicron DY1.1,respectively,after nasal inoculation,and viral load was detected on the turnings and lungs of mice 3 d after challenge to evaluate the preventive effect.In addition,UDCA was used to treat BALB/c mice infected with SARS-CoV-2 C57MA14 mouse adapted strain after nasal drops by gavage for 3 d,and the viral load of the mouse turbinate and lung was detected to evaluate the therapeutic effect.UDCA can decrease ACE2 content in turbinate and lung of BALB/c mice.How-ever,after 1,4 and 7 d of UDCA intragastric administration,there was no statistical difference in viral load in turbinate and lung of BALB/c mice between the prevention group and the virus con-trol group.There was no significant difference in the viral load of the turbinate and lung between the UDCA treatment group and the viral control group.UDCA could reduce the ACE2 content in the turnings and lungs of aged BALB/c mice,but the daily dose and duration of UDCA treatment had no significant effect on the mice infected with SARS-CoV-2 C57MA14 mouse adapted strain and SARS-CoV-2 Omicron DY1.1.