OBJECTIVE: To investigate the effects and mechanisms of hydroxysafflor yellow A (HSYA) on replicative senescence in human umbilical cord mesenchymal stem cells (hUC-MSCs). METHODS: hUC-MSCs were cultured to construct a replicative senescence model through continuous amplification in vitro. Cells at passage 2 served as the control group, while cells at passage 10 were designated as the senescence group. The senescent cells were cultured in a culture medium containing HSYA. Cell viability was detected by the CCK-8 assay, and cell confluence was analyzed using the Incucyte S3 live-cell analysis system. The optimal concentration and time point were determined and utilized for subsequent experiments. Senescent cells were pretreated with 0.01 mg/ml HSYA, and the proportion of senescence-associated β-galactosidase (SA-β-gal) positive cells was detected to assess the senescence state. The relative telomere length was detected by qPCR. Reactive oxygen species (ROS) levels were measured using the fluorescent probe DCFH-DA. Mitochondrial membrane potential was assessed by JC-1 staining. The expression of p53, p16, p21, OCT4, and SOX2 genes was detected by qPCR. The expression of p16, p53, OCT4, and SOX2 proteins was analyzed by Western blot. RESULTS: HSYA significantly decreased the SA-β-gal positive staining rate, inhibited telomere attrition, reduced the ROS accumulation, increased mitochondrial membrane potential in senescent cells. Additionally, HSYA downregulated the expression of p53 and p16, and upregulated the expression of OCT4. HSYA decreased p16 protein level and increased OCT4 and SOX2 protein levels. CONCLUSION HSYA may ameliorate replicative senescence in hUC-MSCs by modulating the p53 and p16 signaling pathways and suppressing oxidative stress.
Humans ; Mesenchymal Stem Cells/drug effects* ; Cellular Senescence/drug effects* ; Chalcone/pharmacology* ; Oxidative Stress/drug effects* ; Quinones/pharmacology* ; Umbilical Cord/cytology* ; Reactive Oxygen Species/metabolism* ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Membrane Potential, Mitochondrial ; Cell Proliferation

Objective To explore the accumulated effects of physical activity,sedentary behavior,and sleep on cardiorespiratory fitness(CRF)among college students and provide effective measures for enhancing their CRF. Methods From May to June in 2023,223 college students aged 18 to 24 years old were recruited from Tianjin University of Science and Technology for a 24 hours activity behavior survey and CRF testing.Compositional analysis was employed to investigate the relationships of physical activity,sedentary behavior,and sleep with CRF.Isotemporal substitution models were established to predict the effects of substituting various activity behaviors on CRF.Results The proportion of time spent on moderate-to-vigorous physical activity(MVPA)was positively correlated with CRF of college students(β=6.40,P=0.002),while the proportion of time spent on sedentary behavior was negatively correlated with CRF(β=-3.02,P=0.004).Light physical activity(LPA)and sleep were not correlated with CRF(β=-1.06,P=0.504).Isotemporal substitution results for 15-min increments showed that replacing other activity behaviors with MVPA significantly increased the CRF of college students[SB:1.72 mL/(kg·min),95% CI=0.94-2.51;LPA:1.82 mL/(kg·min),95% CI=0.95-2.68;sleep:1.64 mL/(kg·min),95% CI=0.84-2.45].In the dose-response relationship from -30 min to 30 min,reallocating time from other behaviors to MVPA had greater adverse effect on CRF than reallocating time from MVPA to other behaviors.Among all the substitutions,replacing LPA with MVPA had the most beneficial effect on improving CRF.Additionally,a 5-min increment was considered the optimal tipping point for MVPA replacing other activities.Conclusions This study underscores the importance of participating in MVPA for improving the CRF of college students.The isotemporal substitution model provides clear goals for the allocation of time for these behaviors,aiding in future intervention measure development and policy-making.
Humans ; Sedentary Behavior ; Sleep ; Students ; Cardiorespiratory Fitness ; Exercise ; Young Adult ; Adolescent ; Universities ; Male ; Female

Objective To explore the effects of time reallocation among moderate-to-vigorous physical activity(MVPA),light physical activity(LPA),sedentary behavior(SB),and sleep on a body shape index(ABSI),body roundness index(BRI),conicity index(CI),and relative fat mass(RFM)of college students by the compositional isotemporal substitution method,thus providing measures for alleviating the obesity problem of college students. Methods Two hundred and ten college students(111 males and 99 females)aged 18-22 years old were recruited from Tianjin University of Science and Technology from April to June in 2023.Three-dimensional acceleration sensors were used to collect data of MVPA,LPA,SB,and sleep of college students.The body height,body weight,and waist circumference were measured,and four novel obesity indicators(ABSI,BRI,CI,and RFM)were calculated.The effects of substituting each activity behavior for 15 min on the obesity indicators were predicted,and the dose-effect relationship was explored at intervals of 5 min from -30 to 30 min.Results MVPA was negatively correlated with ABSI(β=-0.03,P=0.001),BRI(β=-0.27,P=0.049),CI(β=-0.10,P=0.001),and RFM(β=-9.95,P=0.004).LPA was negatively correlated with CI(β=-0.05,P=0.011)and RFM(β=-8.74,P=0.007).Neither SB nor sleep had correlations with ABSI,BRI,CI,and RFM.The results of 15 min isotemporal substitutions showed that increasing the MVPA time decreased the ABSI,BRI,CI,and RFM by 0.006-0.008,0.306-0.393,0.162-0.205,and 2.468-2.897,respectively.Decreasing the MVPA time increased the ABSI,BRI,CI,and RFM by 0.012-0.014,0.548-0.632,0.286-0.328,and 4.358-4.748,respectively.In the dose-effect relationship from -30 min to 30 min,MVPA was irreplaceable,and the negative benefits from substituting MVPA for other activity behaviors were much greater than the positive benefits from substituting MVPA for other activity behaviors.Conclusions Future research should take 24 hours activity behaviors as a whole.Increasing the time spent on MVPA and LPA and decreasing the time spent on SB is one of the effective ways to alleviate the obesity problem among college students.
Humans ; Male ; Students ; Female ; Young Adult ; Obesity ; Sleep ; Adolescent ; Exercise ; Universities ; Sedentary Behavior ; Body Mass Index ; Body Weight

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Abstract: Objective　To evaluate the influence of coronavirus disease 2019 (COVID-19) prevention and control measures on the transmission and epidemic of influenza in Chongqing, so as to provide references for formulating targeted influenza prevention and control strategies. Methods　The influenza surveillance data, during the year 2018 to 2020, were collected through the "China Influenza Surveillance Information System", and the seasonal characteristics of influenza epidemic were analyzed. The percentage of influenza like cases (ILI%) and influenza virus positive rate between 2020 and 2018-2019 were compared, so as to evaluate the impact of COVID-19 prevention and control measures on influenza epidemic characteristics. Results　The annual proportions of ILI cases in Chongqing were respectively 3.53%, 2.23% and 1.2% from 2018 to 2020, while the positive rates of influenza virus were respectively 13.97%, 23.81% and 2.65%. The distribution trend of ILI% from 2018 to 2019 fluctuated were similar, but it continued to drop and remain at a low level since February 2020. The positive rate of influenza virus showed an epidemic peak from December to March in 2018-2019, also peaked from November 2019 to January 2020, but decreased to 0 in March. ILI% was positively correlated with the positive rate of influenza virus (r=0.404 8, P<0.05). In 2020, compared with the same period of 2018-2019, the growth rate of ILI% was -66.09% and -46.32%, respectively. The positive rate of influenza virus in 2020 decreased by 81.03% and 88.87% compared with the same period of 2018-2019, respectively. The growth rates of influenza virus positive rate in January 2020 were decreased with a small rate of about 39.87%, and with a significantly decline of more than 93.65% from February. No influenza epidemic was found after March. Conclusions　Since COVID-19 prevention and control measures were implemented in January 2020 in Chongqing, the ILI% and the positive rate of influenza virus in sentinel hospitals decreased significantly. In the season of high incidence of respiratory infectious diseases, personal protection and other measures can effectively reduce influenza virus infection.

Humans ; Leukemia, Mast-Cell ; Bone Marrow ; Leukemia