ObjectiveTo investigate the current situation of mutual recognition for ethical review outcomes in multicenter clinical research across 10 contracting medical institutions in Guangdong Province， analyze existing issues and propose improvement recommendations， thereby promoting the standardized management of mutual recognition for ethical review outcomes in medical institutions. MethodsData from 381 multicenter clinical studies conducted in these 10 medical institutions from January 24 to October 31， 2024， were collected. Text visualization was performed using Python and the WordCloud library， and statistical analyses were conducted with SPSS 25.0. ResultsOf the 381 studies investigated， industry-sponsored clinical trials （ISTs） accounted for 51.71%， while investigator-initiated clinical trials （IITs） constituted 48.29%. The proportions of ethical committees serving as primary reviewers and collaborative reviewers were 33.33% and 66.67%， respectively. The confirmation methods of mutual recognition outcomes were primarily expedited reviews （50.66%） and meeting reviews （49.34%）， and no cases of “direct confirmation” were found. The Chi-square test revealed statistically significant differences in review confirmation methods based on project type （χ²=14.851， P<0.001） and ethics committee role （χ²= 69.435， P<0.001）. The frequency distribution trend of the contingency table showed that IST projects and primary ethics committees preferred to employ meeting review （58.88% and 79.53% respectively， both higher than the average level of 49.34%）， while IIT projects and the collaborative ethics committees more frequently utilized expedited review （60.87% and 65.75% respectively， both higher than the average level of 50.66%）. ConclusionThe confirmation methods of mutual recognition for ethical review outcomes in multicenter clinical research are significantly associated with the role of the ethics committee and the type of project. It is recommended to improve management systems， enhance information construction and personnel training， as well as clarify mutual recognition responsibilities and strengthen supervision. This aims to ensure review quality while improving mutual recognition efficiency， thereby safeguarding the rights and interests of research participants.

Mitochondrial quality control （MQC） homeostasis serves as a fundamental mechanism in maintaining the mitochondrial structure and function. Dysregulation of MQC contributes to the progression of acute ischemic stroke （AIS） through multiple pathways including disturbances in energy metabolism， increased oxidative stress， and imbalances in mitochondrial fusion and fission. Drawing upon the traditional Chinese medicine （TCM） theory of the kidney governing Yin and Yang， this study innovatively proposes an integrative model of "Yin-Yang dynamic balance-MQC homeostasis" to elucidate the underlying pathophysiological mechanisms. Specifically， kidney Yang deficiency and decline result in reduced driving force， thereby inhibiting mitochondrial fusion. This leads to decreased efficiency of oxidative phosphorylation and impaired adenosine triphosphate （ATP） production. Conversely， when kidney Yin is dysfunctional and excessive phlegm-blood stasis accumulates， mitochondrial fission becomes hyperactive， causing rapid accumulation of reactive oxygen species （ROS） and intensified oxidative stress. The interplay between these two pathological states culminates in the central TCM pathogenesis—Yin-Yang imbalance and disordered Qi and blood-of AIS. To address this pathogenesis， a therapeutic strategy is proposed： tonifying the kidney as the primary intervention to restore MQC homeostasis， supplemented by resolving phlegm and removing blood stasis to interrupt the deleterious cycle of cerebral vascular damage. This work integrates the holistic perspective of TCM with contemporary molecular insights， offering precise intervention targets along the "kidney-mitochondria axis" for the prevention and treatment of AIS， while establishing a novel integrative paradigm for stroke management that bridges traditional and modern medicine. Future research should focus on elucidating the molecular mechanisms through which TCM regulates MQC in AIS and integrating classical TCM theories with evidence-based medicine to facilitate the translation of theoretical insights into clinical applications.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

Background Long-term occupational health surveillance facilitates the identification of chronic health risks arising from occupational hazard exposures. However, under low-level exposure conditions in chemical enterprises, traditional workplace-centered risk assessment models are insufficient to fully explain the observed health effects among workers, highlighting the need for individual-focused health management strategies that focus on the worker. Objective To characterize long-term health trends among workers in a chemical enterprise and examine the limitations of workplace hazard monitoring and health surveillance under low-level multiple exposure scenarios, thereby providing a scientific basis for more comprehensive worker health protection measures. Methods We analyzed 972 occupational health examination records collected over a 15-year period (2010–2024) from a chemical enterprise, integrating these with enterprise hazard monitoring reports and workshop air monitoring of volatile organic compounds (VOCs). The annual counts and prevalences of abnormalities in liver function tests, metabolic syndrome-related indicators, and liver imaging were summarized. Temporal trends were evaluated using the Cochran-Armitage trend test. Time-related changes in abnormal health indicators among active workers were evaluated by generalized linear mixed-effects models (GLMMs), adjusting for age and sex. Individual longitudinal profiles were described for nine workers with continuous 15-year records. In addition, paired comparisons of health outcomes were conducted for 81 workers with both pre-employment and periodic examinations. Results Workplace hazard monitoring indicated that airborne concentrations of major occupational contaminants including VOCs, acids and bases, dust, and physical factors were below national occupational exposure limits. However, 62 VOC species—including chlorobenzene, chloromethane, and cyclohexane—were detected in workshop air, suggesting complex mixed organic solvent exposure. From 2010 to 2015, occupational health examination records were primarily based on physicians’ qualitative assessment, yielding generally low abnormality detection rates. During 2016–2024, data collection was complete, and the prevalences of abnormalities in liver function, metabolic syndrome-related indicators, and liver imaging among active workers remained relatively high. Trend analysis indicated that only the abnormality rates of total bilirubin (TBIL) and hypertension showed statistically significant temporal trends; other indicators exhibited no significant linear changes despite high prevalences. After adjusting for age and sex, the GLMMs showed that the abnormality rates of aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), TBIL, and hypertension decreased over time, whereas those of total cholesterol, triglycerides, and fatty liver increased. In a subgroup of 9 workers with continuous 15-year follow-up data, the cumulative number of abnormal health indicators increased in several individuals after 2016. Among the 81 workers with both pre-employment and periodic records, abnormalities in total cholesterol, triglycerides, body mass index, and fatty liver were significantly more prevalent after employment over time, whereas changes in liver function enzymes were not statistically significant. Conclusion With increasing age, workers exhibit a gradual deterioration in liver function and metabolic-related health indicators, reaching abnormality rates comparable to those reported in the general population. These findings suggest that both workplace-related and non-occupational factors jointly contribute to the observed health changes. Consequently, occupational health management should shift towards an "individual-centered" approach. Enhancing workers' health literacy, strengthening workplace health promotion, and extending occupational health services beyond the workplace are essential to comprehensively protect workers' health.

ObjectiveTo investigate whether Carthamus tinctorius L.-derived nanovesicles （CDNVs） can alleviate angiotensin Ⅱ （ANGⅡ）-induced cardiomyocyte （H9C2） hypertrophy by inhibiting the NF-κB signaling pathway and to elucidate the underlying molecular mechanisms. MethodsCDNVs were isolated and purified by ultracentrifugation combined with sucrose density gradient centrifugation， and their morphology and particle size distribution were identified by transmission electron microscopy and nanoparticle tracking analysis. Rat H9C2 cardiomyocytes were cultured in vitro and randomly divided into the normal control group （NC）， ANGⅡ （1.0 μmol/L） group， ANGⅡ+CDNVs group， and ANGⅡ+CDNVs+NF-κB activator 1 group. After 24 h of intervention， cell viability was detected by the CCK-8 assay， the expression of myocardial hypertrophy-related genes （ANP， BNP） was determined by qPCR， the relative cell area was measured by phalloidin staining， the expression of hypertrophy marker proteins and NF-κB pathway proteins （P-p65/p65， P-IκBα/IκBα） was examined by Western blot， and nuclear translocation of p65 was observed by immunofluorescence. Subsequently， NF-κB signaling pathway agonist activator 1 was added， and the expression of myocardial hypertrophy marker proteins and NF-κB pathway proteins was detected. ResultsCDNVs exhibited a typical round-like vesicle structure with an average particle size of 140.4 nm， which was consistent with the morphological characteristics of exosomes. ANGⅡ at concentrations of 0.1-1.0 μmol/L had no significant effect on cardiomyocyte viability. Compared with the NC group， ANGⅡ significantly upregulated the gene expression of ANP and BNP， increased the relative surface area of cardiomyocytes， elevated the levels of myocardial hypertrophy marker proteins and NF‑κB pathway proteins， and promoted the nuclear translocation of p65 （P<0.05）. Following treatment with CDNVs， all the above indicators were markedly reduced in comparison with the ANGⅡ group （all P<0.05）. However， all these experimental results were reversed after the addition of an NF‑κB agonist. ConclusionCDNVs alleviate ANGⅡ-induced H9C2 cell hypertrophy by inhibiting the NF-κB signaling pathway.

To compare psychological reactance, intention to adopt sleep-management recommendations, and intention to use sleep-support resources among students in medical and health-related disciplines exposed to sleep health messages with different outcome frames and expression styles, and to provide evidence for the design of sleep health information materials.

ObjectiveTo investigate the mechanism by which Shengjiang Pingchuan Zhike pills （SPZP） alleviate airway injury in the rat model of cough variant asthma （CVA） via regulating autophagy through activating the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/Unc-51-like autophagy activating kinase 1 （ULK1） signaling pathway based on transcriptomics， thus providing experimental evidence for the clinical application of SPZP. MethodsForty SPF-grade SD rats were enrolled in the present study and randomly via the random number table method assigned into four groups： a blank group， a model group， a SPZP （2 160 mg·kg^-1·d^-1） group， and a positive drug （montelukast sodium， MTL， 0.9 mg·kg^-1·d^-1）group， with 10 rats in each group. After one week of adaptive feeding， the rat model of cough variant asthma （CVA） was established by two-week sensitization with ovalbumin （OVA） and aluminium hydroxide， followed by capsaicin atomization challenge. Rats in the blank group received an equal volume of normal saline during modeling. Upon successful modeling， rats in the SPZP group and positive drug group were administrated with SPZP suspension and MTL solution， respectively， while those in the blank and model groups received the same dose of normal saline by gavage. The whole intervention lasted for 21 consecutive days. After the intervention， general behaviors of rats in each group were observed. Pulmonary function indicators were subsequently detected. Hematoxylin-eosin （HE） staining was performed to visualize the pathological morphology of the lung tissue， and periodic acid-Schiff （PAS） staining was adopted to evaluate airway mucus secretion. Transcriptomic sequencing was conducted to screen differentially expressed genes in the lung tissue across groups. The levels of inflammatory cytokines including interleukin （IL）-4， IL-5， immunoglobulin E （IgE）， and interferon-γ （IFN-γ） in the bronchoalveolar lavage fluid （BALF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence staining was used for detecting the co-localization of autophagy-related protein Beclin-1 and phosphorylated mammalian target of rapamycin （p-mTOR）. Transmission electron microscopy was employed to count autophagosomes and observe mitochondrial morphological changes in the lung tissue. Western blot assay was utilized to measure the expression levels of AMPK/mTOR/ULK1 axis-related proteins， including AMPK， phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， mTOR， phosphorylated mammalian target of rapamycin （p-mTOR）， ULK1， and phosphorylated Unc-51-like autophagy activating kinase 1 （p-ULK1） as well as the autophagy biomarkers Beclin-1 and selective autophagy adaptor protein p62 in lung specimens. ResultsCompared with the blank group， the model group exhibited markedly elevated cough frequency accompanied by wheezing and stridor， dull fur， poor mental activity， diminished motor activity， accelerated respiratory rate， and weakened sensory response and mobility to external stimuli， accompanied by a declining tendency of body mass. Meanwhile， the model group exhibited decreased dynamic lung compliance， increased airway resistance （P<0.01）， severe pathological damage and excessive mucus secretion in the lung tissue （P<0.01）， and elevated levels of IL-4， IL-5， and IgE and declined level of IFN-γ in the BALF （P<0.01）. Ultrastructural observation revealed damaged mitochondrial morphology and a sharp reduction in the number of autophagosomes in the lung tissue. In addition， the expression of p-AMPK， p-ULK1， and Beclin-1 were downregulated， whereas p-mTOR and p62 were highly expressed （P<0.05， P<0.01） in the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses demonstrated significant enrichment of AMPK， mTOR， and autophagy-related pathways. Compared with the model group， both the positive drug group and SPZP group obtained visible improvements in general behavioral manifestations and obvious recovery of pulmonary function indicators （P<0.05）， alleviated pulmonary pathological lesions and suppressed excessive airway mucus secretion （P<0.05）， recovered levels of inflammatory cytokines in the BALF （P<0.05）， restored mitochondrial morphology， increased autophagosomes， upregulated expression levels of p-AMPK， p-ULK1， and Beclin-1， and downregulated expression levels of p-mTOR and p62 （P<0.05）. ConclusionSPZP can effectively ameliorate airway inflammation and improve the pulmonary function in the rat model of CVA by activating the AMPK/mTOR/ULK1 signaling pathway， enhancing autophagy in the lung tissue， and inhibiting excessive airway mucus secretion and immune inflammatory imbalance.

ObjectiveTo analyze the incidence and spatiotemporal distribution of typhus fever in Baoshan City, Yunnan Province from 2005 to 2023, to identify high-risk populations and regions, so as to provide a scientific basis for optimizing the allocation of local prevention and control resources and developing targeted intervention measures. MethodsData of typhus fever cases in Baoshan City from 2005 to 2023 were obtained from the Infectious Disease Information Management System of the Chinese Center for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the temporal, spatial and demographic distribution of typhus fever cases. Spatial clustering was assessed using spatial dynamic window scan statistics (circular and elliptical windows), flexible spatial scan statistics, and local spatial autocorrelation methods (including local Moran’s I, local Geary’s C, and Getis-Ord G_i*). Retrospective spatiotemporal scan statistics were employed to detect spatiotemporal clusters. ResultsA total of 1 099 typhus fever cases were reported in Baoshan City from 2005 to 2023. The incidence rate peaked at 6.31/ 100 000 in 2007, followed by a decline until reaching its lowest level at 0.21/100 000 in 2015 , and subsequently rebounded during 2016‒2023. The highest proportion of cases was among children under 10 years of age (31.12%), and the top three occupations of cases were farmers, students, and children, accounting for 88.62% of all cases. Cases occurred predominantly between June and September each year. The incidence was relatively high in Jiucheng Town (62.58/100 000), Yaoguan Town (57.15/100 000), and Dianyang Town (46.81/100 000) of Shidian County. Spatial clustering analyses indicated that high-risk areas were mainly located in the southern part of Baoshan City, showing a south-to-north trend. Spatiotemporal scan analyses identified five clusters, with the most likely cluster centered around Yaoguan Town, covering ten towns (subdistricts) during the period 2007‒2010. ConclusionThe incidence of typhus fever in Baoshan City exhibits a clear seasonal and spatial clustering pattern, with peak incidence occurring in summer and autumn. Spatially, cases are primarily distributed in the southern part of Baoshan City, and high-risk clusters exhibit a south-to-north trend. Farmers, students, and children are the high-risk groups.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.