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.

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.

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.

Objective To explore the effects and the underlying mechanisms by which paired associative stimulation ( PAS) of tibial nerve electrostimulation and M1 cortex transcranial magnetic stimulation ( TMS) in pro-moting the recovery of forelimb dysfunction in rats with cerebral ischemic stroke. Methods Resting motor thresholds of left extensor carpi radialis muscle ( ECR) were determined 5 min before and 5 min, 30 min, 60 min after PAS,respectively, in 8 male Sprague-Dawley ( SD) rats. Then 48 male SD rats were divided into a sham group ( n=16) subject to sham surgery, an experimental group (n=32) which was further divided into a MCAO group (n=16) and a PAS group (n=16) after cerebral ischemic stroke model was established successfully by occluding the right middle cerebral artery. 24 hours after surgery, PAS consisting of left tibial nerve stimulation and right M1 cortex area TMS was applied to PAS group once daily for 7 consecutive days. The corner tests and grip strength tests were per-formed before and after 7 days of PAS treatment in each group. The RMTs of left ECR were determined, metabolites of the left area tissue of cervical spinal cord were measured by nuclear magnetic resonance spectrum, and expressions of Bcl-2 and Bax of left and right area tissue of cervical spinal cord enlargement were detected by Western Blot tech-nique after 7 days of intervention. Results The average RMTs of left ECR at 5 min, 30 min, 60 min after PAS were significantly lower than those at 5 min before PAS ( P<0.05) . All rats in experimental group showed significant higher turning scores and lower grip strength when compared with sham group (P<0.001 or P<0.01). After PAS interven-tion, PAS group demonstrated lower turning scores, higher grip strength and lower RMT of left ECR as compared with MCAO group ( P<0.05 or P<0.01) . The expression of GABA of left cervical enlargment was significantly decreased in MCAO group when compared with the sham group ( P<0.05) , and there was no significant difference between MCAO group and PAS group. Meanwhile, other metabolites showed no significant difference among the three groups. The av-erage expression level of Bcl-2 and Bax proteins in both sides of cervical spinal cord enlargment showed no significant difference among three groups either. Conclusions Tibial nerve-M1 cortex area PAS may increase the excitability of motor cortical representation of forelimbs in rats, by which PAS promotes the recovery of forelimb dysfunction in rats with cerebral ischemic stroke.

Objective: To explore the effects of exercise rehabilitation on the depression and anxiety state and quality of life in patients with chronic heart failure. Methods: 400 cases of chronic heart failure patients were selected as the research objects.They were randomly divided into control group(n=200)and exercise rehabilitation group(n=200) by random number table.Two groups were given symptomatic treatment and routine care on a regular basis, and exercise rehabilitation group again on this foundation to give rehabilitation therapy for 3 weeks.Self-rating anxiety scale(SAS) and Self-rating depression scale(SDS)were used to score the anxiety and depression of the two groups before and after rehabilitation.The SF-36 was used to assess the quality of life of patients.Rehabilitation satisfaction questionnaire was used to investigate the satisfaction degree of rehabilitation. Results: There was no significant difference in SAS and SDS scores between the two groups before intervention (P>0.05). After intervention, the SAS and SDS scores of the two groups were significantly lower than those before intervention (P<0.05). SAS and SDS scores in exercise rehabilitation group ((27.47±4.82)vs(45.63±5.61))were significantly lower than those in control group ((43.17±4.81) vs (59.61±4.18))(P<0.05). Before intervention, there was no significant difference in the scores of SF-36 scale between the two groups (P>0.05). After intervention, the scores of SF-36 scale were significantly increased in the two groups, and the difference was statistically significant compared with that before intervention (P<0.05). All the factors of SF-36 in exercise rehabilitation group were significantly higher than those in control group (mental health: (72.06±7.48)vs(64.34±7.01), emotional function: (81.06±7.01)vs(76.05±6.92), social function: (81.14±7.83)vs(71.26±7.65), overall health: (70.14±8.05)vs(61.26±7.95), energy: (74.56±7.81)vs(69.46±7.40), the body pain: (68.51±7.36)vs(60.26±7.51), physical limitations: (64.99±7.31)vs(59.62±7.53 ), physiological function: (69.71±7.63)vs(63.84±7.04), all P<0.05). The satisfaction of the exercise rehabilitation group (92.5%)was significantly higher than that of the control group(75.0%) (P<0.05). Conclusion Exercise rehabilitation training can not only improve the anxiety and depression of patients with chronic heart failure, but also effectively improve the quality of life of patients.Exercise rehabilitation training has a high degree of recognition, and is worthy of extensive application in clinical practice.

Objective:To investigate the open method(OC) and laparoscopic cholecystectomy (LC) after bile duct dilation incidence of contrast.Methods:collected from 2006 December to 2014 December in the department of hepatobiliary surgery requires 412 patients underwent cholecystectomypatients hospitalized with cholecystolithiasis,chronic cholecystitis,gallbladderpolyps,were randomly divided into LC group and OC group,LC group of 207 cases,205 cases in OC group,and were respectively treated with LC and OC.Start regular follow-up after a month,the comparison of 2 surgical operation time,blood loss and postoperative application of antibiotics time,anus exhaust time,eating time and hospitalization time.And to observe the two groups the incidence of patients after bile duct dilatation in follow-up after operation.Results:207 cases of LC patients were 89 patients had bile duct dilation,205 cases of OC patients were 41 patients had bile ductdilation,statistically significant differences between the two groups (P＜0.05).In group LC,the diameter of common bile duct in operation half months began to increase,the increase continued until 3 months after operation.After 3 months of little change in the diameter of common bile duct.The averagepreoperative bile duct diameter is 5.3 mm,after 6.1 mm,there was significant difference(P＜0.01).Conclusion:LC is a safe and reliable operation method,Identifying cause dilatation of common bile duct after LC operation and attention as soon as possible to give the corresponding prevention and treatment,further can reduce complications occur.

To analyze the molecular basis of the variation of the pathogenicity of the influenza B virus, we rescued a recombinant virus with a deletion in the carboxyl terminal of the NS1 protein using reverse genetics based on the parental virus B-S9 of B/Yamagata/16/88. A mutant strain with a deletion of 171 amino acids in the carboxyl terminal of the NS1 protein was named "B-L5". BALB/c mice were inoculated with 3 X 105 EID50 of B-L5 and the parental virus B-S9, respectively. Then, weight changes, survival, and viral titers were documented. During 3 days post-inoculation (dpi) to 7 dpi, the weight of mice infected with B-S9 decreased. However, the weight of mice infected with B-L5 showed weight decreases only at 2 dpi, and quickly recovered at 3 dpi. B-S9 and B-L5 could replicate in the lungs of BALB/c mice. However, viral titers in the lungs of mice infected with B-L5 were 7900-times lower than those of mice infected with B-S9 at 3 dpi. Viral titers in the lungs of mice infected with B-L5 were not detected at 6 dpi. These results showed that, compared with the parent virus B-S9, the mutant virus B-L5 showed lower pathogenicity in BALB/c mice. Our study suggests that deletion of the carboxyl terminal of the NS1 protein decreases the pathogenicity of the influenza B virus. Establishment of a reverse-genetics system for the B influenza virus will provide a platform for studying its pathogenesis, and mechanism of transmission, and for developing live-attenuated influenza B virus vaccines.
Animals ; Body Weight ; Dogs ; Female ; HEK293 Cells ; Humans ; Influenza B virus ; genetics ; pathogenicity ; physiology ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Inbred BALB C ; Sequence Deletion ; Survival Analysis ; Viral Load ; genetics ; Viral Nonstructural Proteins ; chemistry ; genetics ; Virulence

Objective: To clarify the predictive value for long-term prognosis of GRACE score and SYNTAX score in patients with non-ST elevation acute coronary syndrome (NSTE-ACS).
Methods: A total of 784 NSTE-ACS patients treated in our hospital from 2009-01 to 2014-01 were retrospectively studied. According to the treatment, the patients were divided into 3 groups: Medication group,n=410, Stent group,n=325 and CABG group,n=49. Based on 2 scoring systems, the patients were divided into another 3 groups: Low risk group, Medium risk group and High-risk group. The relationship between GRACE score and SYNTAX score was studied by Pearson correlation analysis, survival analysis was conducted by Kaplan-Meier method, univariate and multivariate analysis were performed by Cox proportional hazard model, and the area under curve (AUC) of ROC analysis was used to compare two methods.
Results: All 784 patients completed the follow-up study at the median of 47.7 months. Pearson correlation analysis showed that there was a weak positive correlation between GRACE score and SYNTAX score (r=0.40,P<0.01). Survival analysis presented that by GRACE score system, the MACE occurrence rates in Low risk group, Medium risk group and High-risk group were elevated accordingly as 13.81%, 23.64% and 36.55% respectively. And by SYNTAX system, MACE occurrence rates in Medium risk group and High-risk group were 39.29% and 37.93%, which were both higher than that in Low risk group (23.99%), while the scores between Medium and High risk groups were similar,P>0.05. Cox proportional hazard model and ROC analysis indicated that GRACE and SYNTAX scores had the important predictive value for lone term prognosis of NSTE-ACS. ROC analysis of GRACE score, SYNTAX score, the combination of GRACE and SYNTAX scores showed that 3 of them all had good predictive value for MACE occurrence, three of 95% CI had signiifcant overlapping without statistic differences.
Conclusion: GRACE score and SYNTAX score are related, both of them have important while similar predictive value for long term prognosis in NSTE-ACS patients, the combination of 2 scores cannot increase the predictive value. GRACE score is appropriate for the risk stratiifcation in NSTE-ACS patients.

Objective To observe the effect of the active ingredient present study curcumol impact on human glioma cell line U251 proliferation and apoptosis,its effect on the detection of apoptosis-related gene expression in glioma,and explore the possible mechanism of its anti-glioma,Chinese herbal medicine for the treatment of glioma accumulation of experimental data.Methods In cultured human glioma cell line U251 as a model to medium dilution Curcumol different concentrations,observation and detection following:MTT assay at different times,different concentrations curcumol on U251 cell proliferation;microscope Effect of different concentrations of curcumol U251 cell morphology;affected by flow cytometry curcumol different concentrations on apoptosis in U251;RT-PCR method to detect different concentrations curcumol on U251 cell apoptosis-related gene bcl-2 and COX-2 expression levels of influence.Results Curcumol U251 human glioma cell proliferation inhibition effect and showed concentration-dependent and time-dependent manner (P ＜ 0.05).Conclusions Curcumol U251 human glioma cell proliferation clear.Induce apoptosis and inhibit proliferation of glioma should be an important mechanism of inhibition of proliferation effect of curcumol.Curcumol down on U251 cells bcl-2 gene expression levels and COX-2should be its induction of apoptosis,an important mechanism of inhibition of proliferation.