OBJECTIVE To evaluate the cost-effectiveness of lecanemab for early Alzheimer disease （AD） from a whole-society perspective. METHODS Based on data from the Clarity AD study， a global multicenter， randomized， double-blind， placebo-controlled study of lecanemab for early AD， a Markov model was developed according to the disease progression of AD， with a monthly cycle and a time horizon extending to 99% patient mortality. Quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER） were used as outcome indicators， with a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product （GDP） for 2025 （199 330.00 yuan/QALY）. The model simulated the cost-effectiveness of lecanemab plus standard of care （SoC） versus placebo plus SoC for early AD. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were employed to test the robustness of the results. RESULTS Compared with placebo plus SoC， the ICER for lecanemab plus SoC was 4 364 711.54 yuan/QALY. One-way sensitivity analysis showed that the hazard ratio for disease progression， the price of lecanemab， body weight， the monthly progression probability of mild cognitive impairment， and the discount rate were key parameters affecting model robustness. Results of the probabilistic sensitivity analysis showed that the probability of lecanemab being cost-effective was 0 at the current WTP threshold. Scenario analysis indicated that a price reduction of at least 94.88% would be required for lecanemab to fall below the WTP threshold. CONCLUSIONS At the current WTP threshold， lecanemab plus SoC is not cost-effective compared with placebo plus SoC for early AD.

OBJECTIVE To evaluate the cost-effectiveness of lecanemab for early Alzheimer disease （AD） from a whole-society perspective. METHODS Based on data from the Clarity AD study， a global multicenter， randomized， double-blind， placebo-controlled study of lecanemab for early AD， a Markov model was developed according to the disease progression of AD， with a monthly cycle and a time horizon extending to 99% patient mortality. Quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER） were used as outcome indicators， with a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product （GDP） for 2025 （199 330.00 yuan/QALY）. The model simulated the cost-effectiveness of lecanemab plus standard of care （SoC） versus placebo plus SoC for early AD. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were employed to test the robustness of the results. RESULTS Compared with placebo plus SoC， the ICER for lecanemab plus SoC was 4 364 711.54 yuan/QALY. One-way sensitivity analysis showed that the hazard ratio for disease progression， the price of lecanemab， body weight， the monthly progression probability of mild cognitive impairment， and the discount rate were key parameters affecting model robustness. Results of the probabilistic sensitivity analysis showed that the probability of lecanemab being cost-effective was 0 at the current WTP threshold. Scenario analysis indicated that a price reduction of at least 94.88% would be required for lecanemab to fall below the WTP threshold. CONCLUSIONS At the current WTP threshold， lecanemab plus SoC is not cost-effective compared with placebo plus SoC for early AD.

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.

Chronic prostatitis,a common condition in andrology,is clinically characterized by a prolonged course,resistance to treatment,and frequent recurrence.In traditional Chinese medicine,it is classified under the categories of"turbid sperm,""overstrain strangury,"and"vaginal pain."Based on the"host-guest interaction-collateral disease"theory,we believe that healthy qi deficiency,latent pathogenic factors,and collateral obstruction are the primary pathological factors of this disease,which run through the entire process of chronic prostatitis occurrence and development.Accordingly,we propose that obstruction of collaterals and apathesia of the semen chamber are the core pathogenesis.The disease progression can be divided into three pathological stages:"deficiency,depression,and blood stasis."Spleen and kidney deficiency and malnutrition of collaterals form the pathological foundation.In the deficiency stage,treatment strategies involve reinforcing qi and nourishing the collaterals,using Fuzheng Yangrong Decoction.During disease progression,dampness and heat invasion,as well as collateral stagnation qi,are key contributors to disease progression.Thus,treatment focuses on clearing heat and dampness,promoting qi flow,and smoothing the collaterals,achieved with a modified Qiantongding Decoction.In the final stage,blood stasis and collateral obstruction dominate,warranting therapeutic strategies aimed at tonifying and removing blood stasis,addressing both the body and the collaterals simultaneously using the modified Guiling Huayu Decoction.Overall,the clinical treatment generally focuses on the concept of function through free flow,combination of unblocking and tonifying.This study provides a novel perspective and reference for clinical differentiation and treatment of chronic prostatitis.

Although fertility-preserving treatment strategies have demonstrated significant clinical efficacy in patients with early-stage endometrial cancer(EC)and atypical endometrial hyperplasia(AEH),some patients who experience recurrence still express a strong desire for fertility and request conservative retreatment.This poses new challenges for clinical management.This article reviews the latest research advances in retreatment for recurrent patients and synthesizes findings from previous studies to draw the following conclusions.First,before formulating a retreatment plan,it is crucial to comprehensively evaluate key factors such as tumor characteristics,fertility intentions,and overall health status of the patient.These factors collectively determine the feasibility and appropri-ateness of an individualized retreatment strategy.Second,studies have shown that retreatment options for AEH/EC are diverse,with high-dose oral progestin remaining the primary approach.Combining progestin with metformin,GnRH-a,and hysteroscopic resection can enhance treatment outcomes.Individualized treatment plans should be tailored to the specific conditions of each patient.Based on literature analysis,the complete remission(CR)rate of retreatment ranges from 81.1%to 88.6%,with a pregnancy rate of 26.5%-50.0%and a live birth rate of 14.3%-29.0%.However,the recurrence rate remains high at 24.5%-45.5%,significantly higher than that of initial treatment.This indicates that while retreatment has achieved some success in disease control and fertility preservation,the risk of recurrence still requires significant attention.Therefore,a strict monitoring and follow-up system must be established during retreatment.Additionally,studies have identified factors associated with a higher risk of recurrence,including age over 35,overweight or obesity,polycystic ovarian syndrome,metabolic syndrome,high pathological grade,and advanced clinical stage.On the other hand,pregnancy following CR,weight loss,and maintenance therapy serve as protective factors against disease recurrence.Patients are encouraged to actively engage in weight management during treatment and consider initiating assisted reproductive technology promptly after achieving CR to optimize pregnancy outcomes while minimizing the risk of recurrence.Future research should prioritize investigating precision treatment strategies informed by molecular classification and identifying predictive biomarkers,thereby enabling the development of more personalized and precise treatment plans tailored to indi-vidual patients.

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 explore the causal relationship between air pollution and the risk of Alzheimer's disease(AD)by using two-sample Mendelian randomization(MR).Methods·Based on the data from the genome-wide association study(GWAS),a two-sample MR analysis was conducted to evaluate the causal relationship between air pollution and the risk of AD.Air pollution indicators,including particulate matter 2.5(PM2.5),particulate matter 2.5-10(PM2.5-10),particulate matter 10(PM10),nitrogen dioxide and nitrogen oxides,were used as exposure factors,and summarized data were aggregated from the UK Biobank database.The PM2.5 dataset included 423 796 cases,with correlation analysis conducted on 9 851 867 single nucleotide polymorphisms(SNPs);the PM2.5-10 dataset included 423 796 cases,with correlation analysis conducted on 9 851 867 SNPs;the PM10 dataset included 455 314 cases,with correlation analysis conducted on 9 851 867 SNPs;the nitrogen dioxide dataset included 456 380 cases,with correlation analysis conducted on 9 851 867 SNPs;the nitrogen oxides dataset included 456 380 cases,with correlation analysis conducted on 9 851 867 SNPs.AD was used as the outcome factor,and data were obtained from the International Genomics of Alzheimer's Project(IGAP).The AD dataset included 25 580 cases and 48 466 controls,with correlation analysis of 7 067 513 SNPs.SNPs significantly associated with AD were used as instrumental variables.The main analysis was conducted by using the inverse variance weighted(IVW)method,and four methods including weighted median,MR-Egger regression,mode-based simple estimation and mode-based weighted estimation were used for quality control.Heterogeneity testing,gene pleiotropy testing and sensitivity analysis were conducted to assess the reliability of the study results.Results·Heterogeneity testing indicated no evidence of heterogeneity among SNPs associated with air pollution indicators and AD(both IVW and MR-Egger results,P＞0.05).Gene pleiotropy testing did not detect any pleiotropic effects(MR-Egger results,P＞0.05).Sensitivity analysis confirmed the stability of the PM2.5 results.IVW analysis revealed a statistically significant association between PM2.5 and AD in European populations(P＜0.001),while no statistically significant associations were observed between PM2.5-10(P=0.664),PM10(P=0.664),nitrogen dioxide(P=0.284),nitrogen oxides(P=0.567)and AD.Conclusion·There is a significant causal relationship between PM2.5 exposure and the risk of AD,with PM2.5 exposure increasing the incidence of AD.However,no evidence has been found to suggest that PM2.5-10,PM10,nitrogen dioxide or nitrogen oxides cause an increased risk of AD.

Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy（RAPN）for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was（54.3±10.7）years，and the average clinical tumor diameter was（4.9±1.8）cm. Of all the patients，35（77.8%）were asymptomatic，7（15.6%）presented with hematuria，and 3（6.7%）presented with lumbar pain. Preoperative imaging assessed 34 patients（75.6%）as having clinical stage T 3a，all suspected of involving the collecting system or perirenal fat invasion；the remaining 11 patients（24.4%）were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0（7.0，10.0）. A history of hypertension，diabetes，or chronic kidney disease was present in 18 patients（40.0%）. The primary endpoint was progression-free survival，and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method，and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients（71.1%），with a median estimated blood loss of 150.0（50.0，300.0）ml. Seven（15.6%）patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0（4.0，6.0）days. Postoperative complications occurred in 6 patients（13.3%），including 5（11.1%）with mild complications and 1（2.2%）with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients（61.5%），while 3 patients（7.7%）developed surgery-related chronic kidney disease 3 to 12 months postoperatively，but none required dialysis. The median follow-up time was 31.8（22.7，50.9）months，12（26.7%）patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up，3 patients experienced tumor recurrence，the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma，RAPN performed by experienced surgeons is a feasible and safe option，providing excellent short-term oncological outcomes，complication control，and renal function recovery. The long-term efficacy remains to be seen.

Although fertility-preserving treatment strategies have demonstrated significant clinical efficacy in patients with early-stage endometrial cancer(EC)and atypical endometrial hyperplasia(AEH),some patients who experience recurrence still express a strong desire for fertility and request conservative retreatment.This poses new challenges for clinical management.This article reviews the latest research advances in retreatment for recurrent patients and synthesizes findings from previous studies to draw the following conclusions.First,before formulating a retreatment plan,it is crucial to comprehensively evaluate key factors such as tumor characteristics,fertility intentions,and overall health status of the patient.These factors collectively determine the feasibility and appropri-ateness of an individualized retreatment strategy.Second,studies have shown that retreatment options for AEH/EC are diverse,with high-dose oral progestin remaining the primary approach.Combining progestin with metformin,GnRH-a,and hysteroscopic resection can enhance treatment outcomes.Individualized treatment plans should be tailored to the specific conditions of each patient.Based on literature analysis,the complete remission(CR)rate of retreatment ranges from 81.1%to 88.6%,with a pregnancy rate of 26.5%-50.0%and a live birth rate of 14.3%-29.0%.However,the recurrence rate remains high at 24.5%-45.5%,significantly higher than that of initial treatment.This indicates that while retreatment has achieved some success in disease control and fertility preservation,the risk of recurrence still requires significant attention.Therefore,a strict monitoring and follow-up system must be established during retreatment.Additionally,studies have identified factors associated with a higher risk of recurrence,including age over 35,overweight or obesity,polycystic ovarian syndrome,metabolic syndrome,high pathological grade,and advanced clinical stage.On the other hand,pregnancy following CR,weight loss,and maintenance therapy serve as protective factors against disease recurrence.Patients are encouraged to actively engage in weight management during treatment and consider initiating assisted reproductive technology promptly after achieving CR to optimize pregnancy outcomes while minimizing the risk of recurrence.Future research should prioritize investigating precision treatment strategies informed by molecular classification and identifying predictive biomarkers,thereby enabling the development of more personalized and precise treatment plans tailored to indi-vidual patients.

Objective:To develop the Nurse Parenting Stress Scale and evaluate its reliability and validity.Methods:Based on Abidin's Parenting Stress Theory, scale items were generated through literature review and semi-structured interviews. The initial version was constructed via Delphi expert consultation. Using a convenience sampling method, nurses from six hospitals in Shandong Province were surveyed between August and October 2024. The first survey collected 314 questionnaires (308 valid, effective recovery rate 98.1%) for item analysis and exploratory factor analysis (EFA). The second survey collected 458 questionnaires (447 valid, effective recovery rate 97.6%) for confirmatory factor analysis (CFA) .Results:The Nurse Parenting Stress Scale consists of 4 dimensions and 31 items. The Cronbach's α coefficient of the total scale was 0.951, split-half reliability was 0.782, and test-retest reliability was 0.926. EFA extracted four common factors explaining 70.241% of the cumulative variance. CFA demonstrated a good model fit. The item-level content validity index ( I- CVI) ranged from 0.889 to 1.000, the scale-level universal agreement content validity index ( S- CVI/ UA) was 0.903, and the scale-level average content validity index ( S- CVI/ Ave) was 0.989. Conclusions:The Nurse Parenting Stress Scale shows strong reliability and validity and can serve as an effective tool for assessing parenting stress among nurses.