OBJECTIVE To provide a basis for aligning Chinese pharmacoeconomic research on heart failure （HF） with international standards. METHODS A qualitative comparison o f domestic and global HF pharmacoeconomic studies was conducted across four dimensions： research methods and model application， research perspectives and endpoints， data sources and parameter selection， and policy translation and practical impact. RESULTS & CONCLUSIONS Global studies predominantly utilize long-term dynamic models， societal perspectives， real-world data integration， and directly inform reimbursement decisions. Conversely， domestic research often relies on short-term simplified models， a single healthcare system perspectives， literature-derived data， and individual medicine recommendations. Future domestic studies should transition to long-term dynamic modeling， develop localized disease-specific utility databases via big data， establish reimbursement-linked closed-loop mechanisms， and foster multidisciplinary collaboration to optimize healthcare resource allocation.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Objective To investigate the differences in acute mountain sickness between individuals en-tering the plateau for the first time and those with multiple plateau experiences,and to examine the impact on psychological stress.Methods A total of 2 337 young plateau-acclimatized individuals from an acclimatization rotation area during November 2023 to January 2024 were selected as the study subjects.Those entering the plateau for the first time were classified into Group A(n=425),while those with previous plateau experience(at least one prior visit)were classified into Group B(n=1 912).Differences were analyzed between the two groups in terms of general characteristics,as well as acute mountain sickness(AMS)scores,Self-Rating De-pression Scale(SDS)scores,Symptom Checklist-90(SCL-90)scores,and various vital signs at the following time points:before entering the plateau(T0),on the 1st day(T1),4th day(T2),7th day(T3),and 10th day(T4)after entering the plateau.Results Group A was younger than Group B,with a statistically significant difference(P<0.05).At T1,T2,and T3,AMS scores in Group A were significantly higher than those in Group B(P<0.05).At T4,there was no statistically significant difference in AMS scores between the two groups(P>0.05).At T1,T2,and T3,blood oxygen saturation was lower and heart rate higher in Group A than in Group B,with statistically significant differences(P<0.05).After high-altitude acclimatization,no statistically significant differences in blood oxygen saturation or heart rate were observed between the groups at T4(P>0.05).At T1,there were no statistically significant differences in systolic or diastolic blood pres-sure between the groups(P>0.05).At T2,both systolic and diastolic blood pressure were higher in Group A than in Group B(P<0.05).At T3 and T4,after high-altitude acclimatization,systolic blood pressure de-creased in both groups but remained higher in Group A than in Group B(P<0.05).On the SDS scale,men-tal-emotional and somatic symptom scores were significantly higher in Group A than in Group B(P<0.001).On the SCL-90,all nine symptom factor scores were higher in Group A than in Group B(P<0.05).Conclusion Indi-viduals entering high-altitude areas for the first time experience more severe acute mountain sickness and more pronounced psychological stress.Therefore,enhanced monitoring,psychological counseling,and tailored pre-vention and treatment strategies should be implemented.

Objective To identify the key biomarkers for diagnosing chronic obstructive pulmonary disease(COPD)complicated with pulmonary arterial hypertension(PAH)using bioinformatics,and validate their clinical significance.Methods High-throughput sequencing data analysis was employed to identify differentially expressed genes(DEGs)in COPD-PAH.Functional enrichment analysis was then conducted to explore the biological functions of these DEGs.Machine learning methods,including least absolute shrinkage and selection operator(LASSO),random forest(RF),and support vector machine-recursive feature elimination(SVM-RFE),were utilized to screen 5 potential biomarkers.Single-cell analysis was performed to reveal the expression patterns of these key genes in macrophages.The clinical significance of these biomarkers was further validated using peripheral blood mononuclear cells(PBMC)data.A mouse model of COPD-PAH was established using hypoxia exposure.Sixteen mice(either sexes,8 weeks old,weighing 20～22 g)were randomly divided into a hypoxia group[O2(10.0±0.5)%,COPD-PAH,n=8]and a normoxia group(COPD,n=8).Immunofluorescence assay was used to label the key biomarkers,and their expression levels were quantified.Results A total of 28 DEGs(|Log2FC|≥2,P<0.05)were identified in COPD-PAH patients.Functional enrichment analysis indicated that DEGs in COPD were primarily associated with major histocompatibility complex(MHC)Ⅱ and cell division,and involved in lysosomes,oxidative phosphorylation,and cell cycle pathways(P<0.05).Machine learning identified 5 potential biomarkers(GRN,KLF4,SHTN1,LRP1,and GPNMB),and subsequent single-cell analysis revealed that these markers exhibited reverse expression patterns during disease progression.A nomogram model constructed based on PBMC data yielded an area under the curve(AUC)of 0.907 in diagnosing COPD-PAH.GRN,KLF4,SHTN1,LRP1 and GPNMB were significantly upregulated in the COPD-PAH group(P<0.05).Conclusion GRN,KLF4,SHTN1,LRP1 and GPNMB are identified as key biomarkers for the prediction and diagnosis of COPD-PAH,which providing new insights for the clinical and treatment of the condition.

Rats ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Luteolin/metabolism* ; Down-Regulation ; Rats, Sprague-Dawley ; MicroRNAs/metabolism* ; Reperfusion Injury ; Apoptosis

【Objective】 To investigate the relationship between serum reproductive hormones and sperm parameters and outcomes of micro-testicular sperm extraction (Micro-TESE). 【Methods】 Clinical data of 1 091 patients treated in our hospital during Jan. and Dec.2021 were retrospectively analyzed. According to the sperm concentration,the patients were divided into non-obstructive azoospermia (NOA) group (group A,n=418),normal sperm concentration group (group B,n=615),mild to moderate oligospermia group (group C,n=18),severe oligospermia group (group D,n=18),and obstructive azoospermia group (group E,n=22). In group A,244 cases treated with Micro-TESE were grouped into the sperm-acquired group (Micro-TESE positive group,n=82) and non-sperm-acquired group (Micro-TESE negative group,n=162),and according to the pathological types of testicular tissue,the patients were divided into normal testicular tissue with hypospermatogenesis group (HYPO group,n=129),maturation arrest group (MA group,n=10),and support-only cell syndrome group (SCO group,n=122). Differences in semen parameters and reproductive hormone levels were compared,and relationship between reproductive hormones and sperm parameters and Micro-TESE outcomes was determined with Pearson correlation analysis. 【Results】 In the sperm concentration subgroup,the testicular volume of group A was lower than that of group B and group E (P<0.05); the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in group A were the highest (P<0.05),but the level of testosterone (T) was the lowest (P<0.05); the levels of anti-mullerian hormone (AMH) and serum inhibin B (INHB) in group A were lower than those in group B and group E (P<0.05),the normal sperm morphology rate in group B was higher than that in group A and group E (P<0.05); the percentage of forward moving sperm in group B was the highest (P<0.05). Pearson correlation analysis revealed that sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm were negatively correlated with age,FSH,LH (P<0.05),and positively correlated with testicular volume,T,AMH,and INHB (P<0.05). NOA patients were grouped according to testicular histology and pathology. The INHB in the SCO group was the smallest of the three groups (P<0.05); the FSH and LH levels in the SCO group were higher than those in the MA group (P<0.05),while the 17β-estradiol (E2) levels in the HYPO group were higher than those in the SCO group (P<0.05). NOA patients were grouped according to the results of Micro-TESE surgical treatment. There was a statistically significant difference in AMH and INHB levels between the Micro-TESE positive and negative groups (P<0.05). The binary logistic regression analysis of factors affecting the Micro-TESE outcomes of NOA patients showed AMH was negatively correlated with the Micro-TESE outcome (OR=0.904,95%CI:0.91-1.08,P<0.05). 【Conclusion】 Age,FSH,LH,AMH,and INHB are correlated with sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm. The INHB level was the lowest in the SCO group. The results of Micro-TESE in patients with NOA can be predicted by serum AMH level.

Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.

Objective:To explore risk factors of in-stent restenosis (ISR) after vertebral artery stenting (VAS) in patients with ischemic cerebrovascular disease.Methods:Case-control studies and cohort studies on risk factors for ISR after VAS in patients with ischemic cerebrovascular disease were searched from CNKI, VIP, Wanfang, Chinese Biomedical literature Database, PubMed, Embase and Cochrane Library. The retrieval time limit was the establishment of each database until May 31, 2021. Two researchers screened the literature and extracted relevant data. Newcastle-Ottawa Scale (NOS) was used to evaluate quality of the literature and RevMan 5.3 software was used for meta-analysis.Results:A total of 30 studies were included. Meta-analysis results showed that smoking [ OR=3.76, 95% confidence interval ( CI) : 2.43-5.82, P<0.01], diabetes ( OR=2.95, 95% CI: 2.15-4.06, P<0.01) , hypertension ( OR=2.55, 95% CI: 1.50-4.34, P=0.006) , hyperlipidemia ( OR=7.12, 95% CI: 3.46-14.68, P<0.01) , coronary heart disease ( OR=3.06, 95% CI: 1.10-8.47, P=0.03) , homocysteine ( OR=2.36, 95% CI: 1.30-4.27, P=0.005) , clopidogrel drug-related gene ( CYP2C19) mutation ( OR=3.04, 95% CI: 1.63-5.68, P=0.005) , lesion vessel diameter ( OR=3.43, 95% CI: 1.30-9.05, P=0.01) , residual stenosis ( OR=6.08, 95% CI: 3.28-14.07, P<0.01) ) , stent type ( OR=2.26, 95% CI: 1.18-4.36, P=0.01) , stent length ( OR=3.52, 95% CI: 2.34-5.30, P<0.01) were associated with ISR after VAS operation in patients with ischemic cerebrovascular disease. Conclusions:Postoperative smoking, history of diabetes mellitus, history of hypertension, history of hyperlipidemia, history of coronary heart disease, high level of homocysteine, CYP2C19 mutation, shorter lesion vessel diameter, postoperative residual stenosis, use of bare metal stents and longer stent length are risk factors for ISR after VAS in patients with ischemic cerebrovascular disease. Clinical medical staff should adjust the follow-up time of postoperative patients according to risk factors and formulate individualized strategies to prevent the occurrence of ISR.

OBJECTIVES: Pseudolaric acid B (PAB) has been shown to inhibit the growth of various tumor cells, but the molecular details of its function are still unknown. This study investigated the molecular mechanisms by which PAB induces apoptosis in HeLa cells. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to investigate the effect of PAB treatment in various cervical cancer cell lines. Annexin V/propidium iodide staining combined with flow cytometry and Hoechst 33258 staining were used to assess PAB-induced apoptosis. Additionally, we performed bioinformatics analyses and identified a paired box 2 (PAX2) binding site on the BAX promoter. We then validated the binding using luciferase and chromatin immunoprecipitation assays. Finally, western blotting assays were used to investigate PAB effect on the Wnt signaling and the involved signaling molecules. RESULTS: PAB promotes apoptosis and downregulates PAX2 expression in HeLa cells in a time- and concentration-dependent manner. PAX2 binds to the promoter of BAX and inhibits its expression; therefore, PAX2 inhibition is associated with increased levels of BAX, which induces apoptosis of HeLa cells via the mitochondrial pathway. Additionally, PAB inhibits classical Wnt signaling. CONCLUSION: PAB effectively inhibits Wnt signaling and PAX2 expression, and increases BAX levels, which induce apoptosis in HeLa cells. Therefore, PAB is a promising natural molecule for the treatment of cervical cancer.
Apoptosis ; Binding Sites ; Bisbenzimidazole ; Blotting, Western ; Cell Line ; Chromatin Immunoprecipitation ; Computational Biology ; Flow Cytometry ; HeLa Cells ; Humans ; Luciferases ; Mitochondria ; Uterine Cervical Neoplasms ; Wnt Signaling Pathway

As the rapid development of minimally invasive techniques, anesthesia, and enhanced recovery after surgery (ERAS), anorectal day surgery receiving more and more attention by improving efficiency of medical care while reducing cost and hospitalized infection. However, day surgery also faces the challenge of completing the whole process from patient admission to discharge within 24 hours. Therefore, establishing a reasonable and detailed day surgery process is the cornerstone to guarantee safe medical practice and patients satisfaction. National Clinical Research Center for Geriatric Disorders (Xiangya), together with China Ambulatory Surgery Alliance formulates the clinical practice guideline for anorectal day surgery 2019 edition. Here we make some interpretations of the guidelines on the detailed process of anorectal day surgery, including indication, preoperative examination, preoperative risk evaluation, health education, assessment of day surgery anesthesia and before leaving postanesthesia care unit (PACU), postoperative management, assessment of discharge and follow-up, for the convenience of various medical centers.