ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

Fatigue driving is a major cause of traffic accidents,which poses a great threat to public safety and property.In order to reduce the losses caused by fatigue driving,many researchers have devoted themselves to the study about fatigue driving,such as driver behavior monitoring,brainwave monitoring,eye tracking and facial expression analysis.Each of these methods has its own advantages and disadvantages.Behavioral monitoring reflects the fatigue state by analyzing the driver's driving habits and facial expression,which is easy to operate but prone to be affected by the external environment.Brainwave monitoring is more accurate and can detect the fatigue state in real time,but the equipment is complicated and costly,which limits its large-scale application.The detection based on eye-tracking and facial expression analysis also has a certain potential for application,but errors may occur under different light conditions.Herein the review introduces the effects of fatigue on driving ability and compares the research results of various fatigue driving detection methods by searching,collating,analyzing and summarizing the relevant literatures at home and abroad.Various detection methods are analyzed and summarized,and it is pointed out that the fatigue driving detection method based on multi-feature information fusion will become a research hotspot.

Fatigue driving is a major cause of traffic accidents,which poses a great threat to public safety and property.In order to reduce the losses caused by fatigue driving,many researchers have devoted themselves to the study about fatigue driving,such as driver behavior monitoring,brainwave monitoring,eye tracking and facial expression analysis.Each of these methods has its own advantages and disadvantages.Behavioral monitoring reflects the fatigue state by analyzing the driver's driving habits and facial expression,which is easy to operate but prone to be affected by the external environment.Brainwave monitoring is more accurate and can detect the fatigue state in real time,but the equipment is complicated and costly,which limits its large-scale application.The detection based on eye-tracking and facial expression analysis also has a certain potential for application,but errors may occur under different light conditions.Herein the review introduces the effects of fatigue on driving ability and compares the research results of various fatigue driving detection methods by searching,collating,analyzing and summarizing the relevant literatures at home and abroad.Various detection methods are analyzed and summarized,and it is pointed out that the fatigue driving detection method based on multi-feature information fusion will become a research hotspot.

BACKGROUND:To investigate the prognostic value of the peripheral perfusion index(PPI)in patients with septic shock. METHODS:This prospective cohort study,conducted at the emergency intensive care unit of Peking University People's Hospital,recruited 200 patients with septic shock between January 2023 and August 2023.These patients were divided into survival(n=84)and death(n=116)groups based on 28-day outcomes.Clinical evaluations included laboratory tests and clinical scores,with lactate and PPI values assessed upon admission to the emergency room and at 6 h and 12 h after admission.Risk factors associated with mortality were analyzed using univariate and multivariate Cox regression analyses.Receiver operator characteristic(ROC)curve was used to assess predictive performance.Mortality rates were compared,and Kaplan-Meier survival plots were created. RESULTS:Compared to the survival group,patients in the death group were older and had more severe liver damage and coagulation dysfunction,necessitating higher norepinephrine doses and increased fluid replacement.Higher lactate levels and lower PPI levels at 0 h,6 h,and 12 h were observed in the death group.Multivariate Cox regression identified prolonged prothrombin time(PT),decreased 6-h PPI and 12-h PPI as independent risk factors for death.The area under the curves for 6-h PPI and 12-h PPI were 0.802(95%CI 0.742-0.863,P<0.001)and 0.945(95%CI 0.915-0.974,P<0.001),respectively,which were superior to Glasgow Coma Scale(GCS),Sequential Organ Failure Assessment(SOFA)scores(0.864 and 0.928).Cumulative mortality in the low PPI groups at 6 h and 12 h was significantly higher than in the high PPI groups(6-h PPI:77.52%vs.22.54%;12-h PPI:92.04%vs.13.79%,P<0.001). CONCLUSION:PPI may have value in predicting 28-day mortality in patients with septic shock.

At present, the research on Global Health Competencies is mainly conducted in the field of the establishment of competency models and application of indicators. This review summarizes the research progress of the Global Health Competency and its models, and focuses on cutting-edge research from the aspects of target audience, purpose, content, classical model, methods and future development. The competency model is suggested to be adjusted and updated according to the practices of different countries and regions. The research and funding of the competency model in the field of public health is suggested to be strengthened, and the global health and diplomacy are suggested to be combined to enrich and improve the competency model. Finally, this review aims to promote Global Health Competencies research in China, especially to improve the global health talent training system and relevant policies in further research.

Multimorbidity is significantly associated with life quality decline, disability, and increased mortality risk. Additionally, it leads to greater consumption of healthcare resources, presenting substantial challenges to healthcare systems globally. To better assess the burden of multimorbidity, its impact on patient health outcomes and healthcare services, and to explore the underlying mechanisms in its development, this paper summarizes the existing methods used for measuring and analyzing multimorbidity in research and practice, including disease count, disease-weighted indices, multimorbidity pattern recognition (such as disease association analysis, clustering analysis, and network analysis) and longitudinal methods to provide references for the accurate assessment of the prevalence of multimorbidity and its changes and improve the validity and universality of research findings.

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after long-term use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saiko-saponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-KB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to sai-kogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NF-κB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosa-ponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chro-matography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine mono-phosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mecha-nism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of puri-nergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic re-ceptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.

Objective To study the effects and mechanisms of molecular targeted drug combination on multi-driven proliferation hepatocellular carcinoma SK-Hep-1 cells. Methods Four molecular targeted drugs (HG6-64-1, Dasatinib, Crizotinib, and Sunitinib) were used to treat SK-Hep-1 cells, and the monophasic kinetic analysis curve and two-phase analysis curve were drawn. Western blot analysis was used to detect the effects of the above drugs on key signaling pathways in SK-Hep-1 cells. MTT assay was used to detect the effects of the above drugs and their combination on the proliferation of SK-Hep-1 cells. Results Compared with the monophasic kinetic analysis curve, the biphase analysis curve could better fit the effects of molecular targeted drugs on SK-Hep-1 cells, which predicted that the combination of HG6-64-1, Dasatinib, and MK-2206 could effectively inhibit the proliferation of SK-Hep-1 cells. Conclusion Two-phase kinetic analysis can quantitatively describe the response of multi-driven proliferation hepatocellular carcinoma SK-Hep-1 cells to molecular targeted therapy. The combination of HG6-64-1, Dasatinib, and MK-2206 is a potential drug combination for the treatment of hepatocellular carcinoma.