Objective: To evaluate the current situation of thermal environment in primary and secondary school classrooms during winter, and to analyze students thermal comfort needs, so as to provide a basis for improving classroom thermal environment. Methods: From December 16 to 26, 2024, a stratified cluster random sampling method was used to select 90 classrooms from 15 primary and secondary schools in centralized/air conditioned heating areas(Liaoning Province, Tianjin City, Shanghai City) and naturally ventilated areas(Anhui Province and Jiangxi Province)for on site environmental measurement. A questionnaire survey was conducted among 743 students. The differences between groups using the χ 2 test were compared. Based on actual measurement data, a predicted mean vote prepared percentage of dissatisfied (PMV-PPD) model for centralized/air conditioned classrooms and an adaptive model for naturally ventilated classrooms were established, and the thermal neutral temperature and comfort interval were calculated. Results: The average outdoor temperature during on site measurement was 4.00(0.20，7.00)℃. In classrooms with centralized or air conditioned heating systems, the measured average temperature was (19.33±2.59)℃, with a thermal comfort range of 20.35-25.35 ℃ and a thermal neutral temperature of 22.85 ℃. And 13.92% of students reported feeling cold, while 80.80% felt comfortable. In classrooms with natural ventilation, the measured average temperature was (12.26±1.83)℃, with a thermal neutral temperature of 19.67 ℃ and a thermal comfort range of 16.17-23.17 ℃. About 48.33% of students reported feeling cold, and 49.81 % felt comfortable.The results of univariate analysis showed that there were statistically significant differences in shoe thickness, temperature sensation, relative humidity sensation and wind speed sensation between centralized/air conditioned heating areas ( χ 2= 7.01 , 31.47, 13.57, 13.80,all P <0.05). There were also statistically significant differences in school stage for primary and secondary school students, body mass index, classroom location for seat, temperature sensation, relative humidity sensation and wind speed sensation between naturally ventilated areas ( χ 2=42.13, 11.13, 11.04, 60.39, 29.27, 38.46,all P <0.05). Conclusions There are differences in thermal environment and students subjective thermal comfort in primary and secondary schools under different ventilation modes in winter. The temperature standards for heated classrooms should be revised, and differentiated environmental regulation strategies should be adopted based on different ventilation methods to improve students health and comfort levels.

Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Objective To investigate the changes and diagnostic value of serum hypoxia inducible factor 1 subunit alpha(HIF-1α)and Toll-like receptor 4(TLR4)levels in patients with chronic obstructive pulmonary disease(COPD)complicated with pulmonary Aspergillosis infection.Methods A total of 240 COPD patients who visited Xi'an Qinhuang Hospital(hereinafter referred to as the hospital)from December 2020 to Decem-ber 2023 were selected as the study subjects in the study,and another 218 volunteers who underwent physical examinations at the hospital were selected as the control group.The COPD patients were separated into an in-fected group(124 cases)and an uninfected group(116 cases)based on whether they had pulmonary Aspergil-losis infection.Enzyme-linked immunosorbent assay was applied to detect the levels of HIF-1α and TLR4 in patients.Fully automated biochemical analyzer was applied to detect lactate dehydrogenase(LDH)and albu-min(ALB)levels.Multivariate Logistic regression was applied to analyze the influencing factors of infection in COPD patients.Pearson correlation was applied to analyze the correlation between HIF-1α and TLR4 levels in the infected group.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic val-ue of HIF-1α and TLR4 levels for the occurrence of infection in COPD patients.Results Compared with the control group,the COPD group showed an increase in HIF-1α and TLR4 levels(P＜0.05).Compared with the uninfected group,the proportion of dyspnea,antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,mechanical ventilation procedures,the longer glucocorticosteroid(GC)use time,and levels of LDH,HIF-1α,TLR4 in the infected group were higher(P＜0.05),while the level of ALB was lower(P＜0.05).The types of antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,the duration of GC use,and elevat-ed levels of LDH,HIF-1α,and TLR4 were independent risk factors for infection in COPD patients(P＜0.05),while elevated level of ALB was an independent protective factor for infection in COPD patients(P＜0.05).The levels of HIF-1α and TLR4 in the infected group were positively correlated(r=0.453,P＜0.001).The area under the curve(AUC)of HIF-1α and TLR4 in diagnosing infection in COPD patients alone was 0.816 and 0.813,and the AUC of their combined diagnosis was 0.930,which was better than their indi-vidual diagnoses(Zcombination-HIF-1α=4.923,Z combination-TLR4=5.192,P＜0.001,P＜0.001).Conclusion The levels of HIF-1α and TLR4 increase in COPD patients,and further increase after infection with pulmonary Aspergil-lus.They are independent risk factors for infection in patients,and the two are positively correlated.The combined di-agnosis of pulmonary aspergillosis has certain value and provides a theoretical basis for clinical diagnosis.

Objective:To evaluate the long-term oncological outcomes of partial nephrectomy(PN)in patients with renal cell carcinoma(RCC)who were clinically staged as clinical T1(cT1)preoperatively but upstaged to pathological T3a(pT3a)after surgery.Methods:A total of 427 RCC patients postopera-tively diagnosed as pT3aN0M0 at Peking University Third Hospital from February 2013 to December 2022 were retrospectively reviewed.Among them,33 cT1 patients upstaged to pT3a RCC received PN(PN group),while 394 non-upstaged pT3a RCC patients underwent radical nephrectomy(RN,RN group).Propensity score matching was performed at a 1∶1 ratio based on baseline characteristics.The Kaplan-Meier method was used to assess overall survival(OS),cancer-specific survival(CSS),and disease-free survival(DFS),with Log-rank tests and Cox regression models for multivariate analysis.Results:Before matching,the PN group(n=33)had significantly higher rates of perirenal fat invasion(PFI,45.5％vs.15.2％)and segmental renal vein involvement(42.4％vs.20.8％),but lower rates of renal sinus invasion(RSI,21.2％vs.73.6％)and renal vein tumor thrombus(0％vs.15.2％)compared with the RN group(n=394,all P＜0.05).After matching,baseline characteristics were comparable between the PN group(n=33)and RN group(n=33).No significant differences were observed in operative time,blood loss,mean hospital stay,complication rate,positive margin rate,or conversion to open surgery between the two groups(P＞0.05).However,the PN group showed significantly higher estimated glomerular filtration rate(eGFR)postoperatively[76.9(55.4,87.3)mL/(min·1.73 m2)vs.61.7(56.8,73.5)mL/(min·1.73 m2),P＜0.05],indicating better renal function preserva-tion.No significant differences were found in OS,CSS,or DFS between the groups(P＞0.05).Multi-variate ana-lysis identified renal vein invasion(RVI),higher Fuhrman grades(Ⅲ-Ⅳ),and sarcoma-toid differentiation as independent risk factors for DFS and CSS in the pT3a RCC patients(P＜0.05).Conclusion:For cT1 RCC patients upstaged to pT3a,PN preserves renal function more effectively while achieving com-parable oncological outcomes to RN.RVI,higher Fuhrmann grade,and sarcomatoid differentiation are independent risk factors for pT3N0M0 RCC patients.

Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.

Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Objective:To retrieve, evaluate and summarize the best evidence for the management of oral intake in stroke patients with dysphagia.Methods:A systematic search was conducted in Chinese and English databases and subject-specific professional websites for clinical decisions, best practices, guidelines, systematic reviews, expert consensuses and evidence summaries on the management of oral intake in stroke patients with dysphagia. The retrieval time limit was from the establishment of the database to March 31, 2024. The included literatures were screened, quality-evaluated, and evidence was extracted and summarized.Results:A total of 16 articles were included, including three clinical decisions, four guidelines, four expert consensuses, four evidence summaries and one systematic review. A total of 28 pieces of evidence were summarized from eight aspects, namely, swallowing function screening, nutritional risk screening, feeding management, oral medication management, water drinking management, oral care, aspiration management, and training and education.Conclusions:This study systematically summarizes the best evidence for the management of oral intake in stroke patients with dysphagia, providing scientific guidance and strategic support for the improvement of patients' long-term quality of life.

Sphincter-preserving surgery has become the mainstream approach for mid-to-low rectal cancer, yet postoperative anal dysfunction (low anterior resection syndrome, LARS) occurs in 30%-50% of patients, significantly impacting quality of life. This review systematically elaborates the clinical value of preoperative anal function assessment (mainly digital rectal examination), proposing a multidimensional evaluation system integrating anatomical (including high-resolution anorectal MRI, 3D transrectal ultrasound and dynamic contrast-enhanced ultrasound), physiological (anorectal amnometry and anal electromyography), and neurological assessments (including Parks scale, Wexner score, MSK-BFI scale and LARS score), alongside innovative strategies such as artificial intelligence and gut microbiome analysis. We advocate incorporating preoperative functional assessment into quality control standards for sphincter preservation, promoting a paradigm shift from "anatomical preservation" to "functional preservation".