Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

[Objective]To deepen the understanding of the history of ethnic exchanges and integration in the Western Regions,and fully establish the concept of ethnic exchanges,interaction and integration,by collating and analyzing the textual materials in Xuanquan Han bamboo slips,especially the content of traditional Chinese medicine.[Methods]The content of three Xuanquan Han medical slips(Ⅱ 0216②:767,Ⅰ 90DXT0112③:118,Ⅱ 90DXT0111①:51)was analyzed by using the method of interpreting the slips,the historical materials of the interaction and integration between the Han Dynasty and the Kucha was classified and analyzed with the literature combing method.Finally,the"triple evidence method"was used to explore the historical facts of medical exchanges between the Central Plains and the Western Regions.[Results]Three Xuanquan Han medical slips clearly recorded the content of Han Dynasty physicians going to the Western Regions to treat the monarch's illness,and the initial era of literature that traditional Chinese medicine participated in ethnic exchanges and integration had been advanced to the Western Han Dynasty.Historical documents from different periods all reflected that the friendly exchanges between Han Dynasty and Kucha were long-lasting and multifaceted.Xuanquan Han medical slips,Japanese unearthed medical slips and inherited literature confirmed the exchange and mutual learning of medical culture between the ancient Western Regions and the central government.[Conclusion]As unearthed materials,Xuanquan Han bamboo slips have filled the gap in the details of medical exchanges and integration between Han Dynasty and Western Regions in inherited literature.The medical content confirms the unique role of traditional Chinese medicine in the formation of the diverse and integrated Chinese civilization.Traditional Chinese medicine can keep long term prosperity and bring forth the new through the old,which is also the result of the exchange,interaction and integration of cultural elements of various nationalities.

Objective To investigate the efficacy and safety of tirofiban in the treatment of branch atheromatous disease(BAD)in elderly patients.Methods A retrospective analysis was conducted on 215 elderly BAD patients admitted to our department from June 2021 to June 2023.According to their treatment,they were divided into tirofiban group 1(55 cases)and control group 1(160 ca-ses).Using propensity score matching in a ratio of 1∶1 algorithm for adjustment,the differences in baseline features between the two groups were eliminated,and there were finally 53 cases in the tirofiban group 2 and 53 cases in the control group 2 after matching.The NIHSS scores before treatment and at 24 h and 7 d after treatment were collected.All of them were followed up for 90 d,and modified Rankin scale(mRS)was applied to evaluate the prognosis.Results The tirofiban group 1 had significantly lower NIHSS score at 24 h and 7 d after treatment and shorter length of hospital stay than the control group 1(P＜0.05,P＜0.01),so were in the tirofiban group 2 than the control group[3(1,4)vs 3(2,6),1(0,3)vs 1(1,4),8(6,10)d vs 9(8,11)d,P＜0.05].The proportion of mRS score ≤1 was obviously larger in the tirofiban group 1 than the control group 1(P＜0.01).The tirofiban group 2 obtained notably larger proportions of mRS score≤1 and≤2(71.7％vs 43.4％,P=0.003;79.2％vs 60.4％,P=0.034),and smaller proportion of mRS≥4(5.7％vs 20.8％,P=0.045)when compared with the control group 2.Logistic regression analysis indicated that in the patients without diabetes and those non-smoking,tirofiban was associated with increased good outcomes(OR=0.266,95％CI:0.090-0.788,P=0.017;OR=0.341,95％CI:0.107-0.931,P=0.046).Conclusion Tirofiban may effectively improve the clinical outcomes in the elderly BAD patients.But further randomized controlled trials are needed for verification.

Objective To investigate the clinical efficacy and safety of intravenous thrombolysis with tenecteplase in the treatment of CWS.Methods A prospective study was conducted on 136 CWS patients consecutively admitted in Department of Neurology of Zhengzhou People's Hospital from March 2019 to March 2024.They were randomly divided into a tenecteplase group(67 cases)and a control group(69 cases).NIHSS was used to evaluate the recovery of neurological function after treatment.mRS was employed to assess long-term prognosis.Results Significantly larger proportion of white matter lesions and higher baseline SBP level were observed in the tenecteplase group than the control group(P＜0.05).The tenecteplase group obtained obviously greater ratio of overall recovery than the control group,with notably lower NIHSS score,incidence of new CWS attacks and proportion of new acute cerebral infarction at 24 and 72 h and 7 d after treat-ment(P＜0.05,P＜0.01).Moreover,the proportion of mRS score of 0-2 was notably greater,while that of the score of 3-6 was lower in the tenecteplase group than the Control group(P＜0.05).Intravenous thrombolysis with tenecteplase was an influencing factors for 90-day mRS score of 0-2 and of 3-6 in the CWS patients(OR=0.264,95％CI:0.089-0.813;OR=4.144,95％CI:1.184-14.506,P＜0.05).Conclusion Intravenous thrombolysis with tenecteplase for CWS significantly improves the proportion of patients with good prognosis.

Objective To investigate the correlation of imaging parameters of CT perfusion scan-ning combined with serum suPAR and Mac-2BP with END and poor outcomes in patients with BAD.Methods A total of 176 BAD patients admitted to Department of Neurology of Zhengzhou People's Hospital from June 2019 to March 2024 were prospectively enrolled,and according to whether END occurred within 72 h after onset,they were divided into END group(42 cases)and non-END group(134 cases).Based on their outcomes at 90 d of follow-up,they were also assigned into good outcome group(129 cases)and poor outcome group(47 cases).The serum suPAR and Mac-2BP levels were compared between the END and non-END groups,as well as the good and poor outcome groups.ROC curves were plotted to analyze the accuracies of serum suPAR and Mac-2BP in predicting END and poor outcomes.Results The END group had significantly higher suPAR and Mac-2BP levels,longer MTT and TTP,and larger proportions of DWMH,basal gan-glia EPVS and cerebral perfusion impairment,but lower CBV and CBF when compared with the non-END group(P＜0.05,P＜0.01).Obviously higher suPAR and Mac-2BP levels,NIHSS score at END,longer MTT and TTP,and larger proportions of EDN,basal ganglia EPVS and cerebral perfusion impairment,but lower CBV and CBF were observed in the poor outcome group than the good outcome group(P＜0.05,P＜0.01).suPAR and Mac-2BP levels,cerebral perfusion impair-ment and DWMH were independent risk factors for END(P＜0.05,P＜0.01).suPAR,Mac-2BP,NIHSS score at END,END,cerebral perfusion impairment,and basal ganglia EPVS were inde-pendent risk factors for poor outcomes(P＜0.05,P＜0.01).The AUC value of combined suPAR and Mac-2BP in predicting END was 0.8844(95％CI:0.822-0.947),and the value in predicting poor outcomes was 0.8742(95％CI:0.810-0.938)in BAD patients.Conclusion Cerebral perfu-sion impairment,suPAR and Mac-2BP are independent risk factors for END and poor outcome at 90 d in BAD patients.Combined detection can is helpful in evaluating the patient's condition and predicting the prognosis.

Objective To investigate the effects of different timing of initiation of rivaroxaban anti-coagulation therapy on the efficacy and bleeding risk of atrial fibrillation patients after stroke.Methods A total of 336 patients with atrial fibrillation and stroke admitted in our hospital be-tween January 2021 and December 2023 were consecutively enrolled,and randomly divided into an experimental group(165 cases)and a control group(171 cases).The experimental group received rivaroxaban treatment within 48 h of symptom onset,whereas the control group initiated oral ri-varoxaban treatment on the 3rd,6th,and 12th day post-stroke onset,respectively,depending on stroke severity(mild,moderate,and severe).Their baseline clinical data were collected,and all of them were followed up till 90 d after stroke.The incidences of recurrent ischemic stroke,symp-tomatic intracranial hemorrhage and extracranial hemorrhage,mortality,and proportion of pa-tients with mRS score≤ 2 and distribution of the score were observed and analyzed in the two groups.Results During a 90-day follow-up period,the patients with moderate stroke from the ex-perimental group of patients exhibited a significantly lower rate of recurrent ischemic stroke than those in the control group(5.4％vs 15.9％,P=0.037).However,for patients with mild and se-vere stroke,no obvious difference was observed in the primary endpoint of recurrent ischemic stroke between the experimental and control groups(3.0％vs 3.2％,12.5％vs 14.8％,P＞0.05).Though no statistical differences were observed,lower rates of symptomatic intracranial hemor-rhage(1.5％vs 3.2％,5.4％vs 9.8％),reduced incidence of extracranial hemorrhage(9.0％vs 14.5％,12.2％vs 15.9％),and lower mRS score[1(0,2)vs 1(1,2),3(1,4)vs 3(2,4)]were seen in the patients with mild and moderate stroke from the experimental group when compared with the control group(P＞0.05).Similarly,there were no statistically differences for the severe stroke patients between the experimental and control groups(P＞0.05)in the incidence of extracranial hemorrhage(20.8％vs 22.2％),rate of symptomatic intracranial hemorrhage(20.8％vs 7.4％),mortality(8.3％vs 3.7％),and mRS score[4(3,4)vs 3(3,4)].Two patients from the experimen-tal group died,with one case due to secondary pulmonary infection and the other due to brainstem hemorrhage.In the control group,only one death occurred due to brainstem hemorrhage.Conclu-sion For atrial fibrillation patients,anticoagulation with rivaroxaban within 48 h after stroke has no significant increase in the risk of bleeding,reduces the proportion of recurrent ischemic stroke in patients with moderate stroke,and may improve the prognosis of patients.

Objective To investigate the clinical efficacy and safety of intravenous thrombolysis with tenecteplase in the treatment of CWS.Methods A prospective study was conducted on 136 CWS patients consecutively admitted in Department of Neurology of Zhengzhou People's Hospital from March 2019 to March 2024.They were randomly divided into a tenecteplase group(67 cases)and a control group(69 cases).NIHSS was used to evaluate the recovery of neurological function after treatment.mRS was employed to assess long-term prognosis.Results Significantly larger proportion of white matter lesions and higher baseline SBP level were observed in the tenecteplase group than the control group(P＜0.05).The tenecteplase group obtained obviously greater ratio of overall recovery than the control group,with notably lower NIHSS score,incidence of new CWS attacks and proportion of new acute cerebral infarction at 24 and 72 h and 7 d after treat-ment(P＜0.05,P＜0.01).Moreover,the proportion of mRS score of 0-2 was notably greater,while that of the score of 3-6 was lower in the tenecteplase group than the Control group(P＜0.05).Intravenous thrombolysis with tenecteplase was an influencing factors for 90-day mRS score of 0-2 and of 3-6 in the CWS patients(OR=0.264,95％CI:0.089-0.813;OR=4.144,95％CI:1.184-14.506,P＜0.05).Conclusion Intravenous thrombolysis with tenecteplase for CWS significantly improves the proportion of patients with good prognosis.

Objective To investigate the correlation of imaging parameters of CT perfusion scan-ning combined with serum suPAR and Mac-2BP with END and poor outcomes in patients with BAD.Methods A total of 176 BAD patients admitted to Department of Neurology of Zhengzhou People's Hospital from June 2019 to March 2024 were prospectively enrolled,and according to whether END occurred within 72 h after onset,they were divided into END group(42 cases)and non-END group(134 cases).Based on their outcomes at 90 d of follow-up,they were also assigned into good outcome group(129 cases)and poor outcome group(47 cases).The serum suPAR and Mac-2BP levels were compared between the END and non-END groups,as well as the good and poor outcome groups.ROC curves were plotted to analyze the accuracies of serum suPAR and Mac-2BP in predicting END and poor outcomes.Results The END group had significantly higher suPAR and Mac-2BP levels,longer MTT and TTP,and larger proportions of DWMH,basal gan-glia EPVS and cerebral perfusion impairment,but lower CBV and CBF when compared with the non-END group(P＜0.05,P＜0.01).Obviously higher suPAR and Mac-2BP levels,NIHSS score at END,longer MTT and TTP,and larger proportions of EDN,basal ganglia EPVS and cerebral perfusion impairment,but lower CBV and CBF were observed in the poor outcome group than the good outcome group(P＜0.05,P＜0.01).suPAR and Mac-2BP levels,cerebral perfusion impair-ment and DWMH were independent risk factors for END(P＜0.05,P＜0.01).suPAR,Mac-2BP,NIHSS score at END,END,cerebral perfusion impairment,and basal ganglia EPVS were inde-pendent risk factors for poor outcomes(P＜0.05,P＜0.01).The AUC value of combined suPAR and Mac-2BP in predicting END was 0.8844(95％CI:0.822-0.947),and the value in predicting poor outcomes was 0.8742(95％CI:0.810-0.938)in BAD patients.Conclusion Cerebral perfu-sion impairment,suPAR and Mac-2BP are independent risk factors for END and poor outcome at 90 d in BAD patients.Combined detection can is helpful in evaluating the patient's condition and predicting the prognosis.

Objective To investigate the effects of different timing of initiation of rivaroxaban anti-coagulation therapy on the efficacy and bleeding risk of atrial fibrillation patients after stroke.Methods A total of 336 patients with atrial fibrillation and stroke admitted in our hospital be-tween January 2021 and December 2023 were consecutively enrolled,and randomly divided into an experimental group(165 cases)and a control group(171 cases).The experimental group received rivaroxaban treatment within 48 h of symptom onset,whereas the control group initiated oral ri-varoxaban treatment on the 3rd,6th,and 12th day post-stroke onset,respectively,depending on stroke severity(mild,moderate,and severe).Their baseline clinical data were collected,and all of them were followed up till 90 d after stroke.The incidences of recurrent ischemic stroke,symp-tomatic intracranial hemorrhage and extracranial hemorrhage,mortality,and proportion of pa-tients with mRS score≤ 2 and distribution of the score were observed and analyzed in the two groups.Results During a 90-day follow-up period,the patients with moderate stroke from the ex-perimental group of patients exhibited a significantly lower rate of recurrent ischemic stroke than those in the control group(5.4％vs 15.9％,P=0.037).However,for patients with mild and se-vere stroke,no obvious difference was observed in the primary endpoint of recurrent ischemic stroke between the experimental and control groups(3.0％vs 3.2％,12.5％vs 14.8％,P＞0.05).Though no statistical differences were observed,lower rates of symptomatic intracranial hemor-rhage(1.5％vs 3.2％,5.4％vs 9.8％),reduced incidence of extracranial hemorrhage(9.0％vs 14.5％,12.2％vs 15.9％),and lower mRS score[1(0,2)vs 1(1,2),3(1,4)vs 3(2,4)]were seen in the patients with mild and moderate stroke from the experimental group when compared with the control group(P＞0.05).Similarly,there were no statistically differences for the severe stroke patients between the experimental and control groups(P＞0.05)in the incidence of extracranial hemorrhage(20.8％vs 22.2％),rate of symptomatic intracranial hemorrhage(20.8％vs 7.4％),mortality(8.3％vs 3.7％),and mRS score[4(3,4)vs 3(3,4)].Two patients from the experimen-tal group died,with one case due to secondary pulmonary infection and the other due to brainstem hemorrhage.In the control group,only one death occurred due to brainstem hemorrhage.Conclu-sion For atrial fibrillation patients,anticoagulation with rivaroxaban within 48 h after stroke has no significant increase in the risk of bleeding,reduces the proportion of recurrent ischemic stroke in patients with moderate stroke,and may improve the prognosis of patients.