Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

OBJECTIVES: To investigate the correlation of PRELID1 with gastric cancer (GC) progression, prognosis, and epithelial-mesenchymal transition (EMT) and the underlying mechanisms. METHODS: We analyzed the data of 115 patients undergoing radical gastrectomy for GC in our hospital between February, 2018 and March, 2023 to explore the correlation of PRELID1 expression level in GC tissues with tumor progression and patient prognosis. In cultured GC cells, the effects of lentivirus-mediated overexpression or interference of PRELID1 were observed on cell migration, invasion and EMT. RESULTS: Immunohistochemical staining revealed significantly higher PRELID1 expression in GC tissues (P<0.001), whose expression level was positively correlated with CEA ≥5 ng/mL (P=0.007), CA199 ≥37 U/mL (P=0.007), G_3-4 stages (P=0.001), T_3-4 stages (P=0.001), and N_2-3 stages (P=0.020). Univariate and Cox multifactorial analysis showed that high PRELID1 level was an independent risk factor affecting 5-year survival of GC patients (P=0.001). In cultured GC cells, PRELID1 overexpression obviously promoted cell proliferation, migration, invasion, and the expressions of MMP2 and MMP9, and interference of PRELID1 produced the opposite changes. PRELID1 overexpression also increased the expressions of N-cadherin and vimentin and reduced the expression of E-cadherin. Mechanistic analyses showed that up-regulation of PRELID1 increased the expression of p-PI3K, p-AKT, and p-mTOR in GC cells, whereas its interference caused the opposite changes; the application of 740 Y-P, a PI3K/AKT pathway activator, significantly enhanced the migration, invasion, and EMT of GC cells with PRELID1 knockdown. CONCLUSIONS PRELID1 is highly expressed in GC and affects prognosis of the patients, and its high expression promotes migration, invasion and epithelial mesenchymal transition of GC cells possibly by activating the PI3K/AKT/mTOR pathway.
Humans ; Stomach Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Prognosis ; Cell Movement ; Cell Line, Tumor ; Male ; Female ; Middle Aged ; Signal Transduction ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism*

Temporomandibular joint osteoarthritis(TMJOA)is a chronic degenerative disorder.Although current clinical interven-tions can effectively mitigate disease progression,they remain limited in fully reversing formed pathological structural alterations.Mesenchymal stem cell-derived exosomes(MSC-Exos),which mimic the primary therapeutic functions of mesenchymal stem cells,exhibit advantages such as excellent biocompatibility,low immunogenicity,and absence of cytotoxicity.In TMJOA,MSC-Exos exert therapeutic effects by modulating chondrocytes,immune cells,and the cartilage matrix.However,the clinical application of MSC-Exos still faces certain limitations.Enhancing their therapeutic efficacy has become a central research focus in this field.This review summarizes existing therapeutic strategies for TMJOA and explores the potential applications of MSC-Exos in TMJOA management,aiming to provide insights for future research.

Objective:To explore the real experience of ICU patients during continuous renal replacement therapy (CRRT) and to inform the development of interventions.Methods:This study was a qualitative study. Using the social ecosystem theory as a theoretical framework and purposive sampling method, 15 ICU patients who received CRRT at Beijing Friendship Hospital, Capital Medical University from May 2023 to February 2024 were selected for semi-structured interviews. Colaizzi 7-step analysis was applied to analyze the data.Results:A total of three themes and 11 sub-themes were summarized, including microsystems (symptom improvement, limited mobility and self-care, sleep disorders, hypothermia, emotional overload, hope and gratitude), mesosystems (heavy financial burden, disrupted rhythm of family life, dependence on peer support), and macrosystems (information support needs to be improved, expectation of an open ICU visitation system) .Conclusions:The social ecosystem of patients with CRRT in the ICU is not optimistic. Healthcare professionals should provide appropriate support for patients to facilitate their physical and psychological recovery.

Objective: To evaluate the equity of human resource allocation in centers for disease control and prevention (CDCs) in China, so as to provide insights into optimizing human resource and promoting the high-quality development of CDCs. Methods: The number, age, educational level and professional title of CDCs personnel from 2017 to 2021 were collected from China Health Statistics Yearbook and China Statistical Yearbook. General information of human resource in CDCs across different provinces (autonomous regions, municipalities) was described, and the equity of human resource allocation was assessed using agglomeration degree. Results: The number of personnel in CDCs was 190 730 in 2017, and it began to increase from 2020, reaching 209 550 in 2021, with an average annual growth rate of 2.47%. The staffing gap decreased from 52 534 to 37 655. The proportion of personnel aged 55 years and older increased from 10.74% to 16.69%, the proportion of personnel with a bachelor's degree or above increased from 36.50% to 47.80%, the proportion of personnel with senior professional titles increased from 9.75% to 13.31%, and the number of personnel per 10 000 permanent residents increased from 1.36 to 1.48. Agglomeration degree analysis indicated that the equity of human resource allocation in terms of both geography and population was relatively good among the CDCs of 12 provinces (autonomous regions, municipalities) including Beijing, Tianjin and Liaoning; the equity of human resource allocation was relatively good in terms of geography and was relatively poor in terms of population among 11 provinces (autonomous regions, municipalities) including Shanghai, Jiangsu and Zhejiang; the equity of human resource allocation was relatively poor in terms of geography and was relatively good in terms of population among the CDCs of 8 provinces (autonomous regions, municipalities) including Inner Mongolia, Heilongjiang and Hainan. Conclusions Although there was an increase in the number of personnel in CDCs from 2017 to 2021, the growth rate was low. There were differences in the equity of human resource allocation among provinces (autonomous regions, municipalities), with a relative shortage of human resource in CDCs in the east area.

Objective To evaluate the predictive value of triglyceride-glucose body mass index(TyG-BMI),atherogenic index of plasma(AIP),and postprandial glucose excursion(PPGE)for sarcopenia in patients with type 2 diabetes mellitus(T2DM).Methods An observational cohort trial was conducted on 590 hospitalized T2DM patients(322 males and 268 females)admitted to Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University between January 2023 and December 2024.General demographic data and key metabolic indicators,including fasting plasma glucose(FPG),postprandial 2-hour plasma glucose(PPG),triglyceride(TG)were collected,and then TyG-BMI,AIP,and PPGE were calculated.Based on the Asian Working Group for Sarcopenia(AWGS)2019 criteria,they were divided into a sarcopenia group(n=140)and a non-sarcopenia group(n=450).After 1∶1 propensity score matching(PSM),102 patients with sarcopenia were matched with 102 without.Differences in metabolic indicators FPG,PPG,TyG-BMI,AIP and PPGE were compared between the 2 groups.Spearman correlation analysis was conducted to assess correlations of these indicators with sarcopenia.Conditional logistic regression analysis was performed to identify independent risk factors,and receiver operating characteristic(ROC)curves were plotted to assess predictive performance.An external validation cohort consisting of 192 T2DM patients from Department of Endocrinology of Jiangbei Branch of First Affiliated Hospital of Army Medical University between January 2023 and December 2024 was included to validate the prediction model.Results After PSM,the baseline data of the 2 groups was balanced(P>0.05).The sarcopenia group showed higher levels of PPG,AIP,and PPGE,but lower TyG-BMI value than the non-sarcopenia group(all P=0.001).Spearman correlation analysis revealed that the TyG-BMI was negatively correlated(r=-0.404,P=0.001),whereas AIP and PPGE were positively correlated with concomitant sarcopenia(r=0.280,P=0.001;r=0.372,P=0.001)in the T2DM patients.Conditional logistic regression analysis identified AIP(OR=14.367)and PPGE(OR=1.245)as independent risk factors,while TyG-BMI(OR=0.966)as independent protective factors.ROC curve analysis revealed that the area under the curve(AUC)of the combined model of TyG-BMI,AIP and PPGE in predicting sarcopenia was 0.918,and the AUC value was 0.954 in external validation,with good sensitivity and specificity.Conclusion TyG-BMI,AIP,and PPGE are important metabolic predictors in T2DM patients with sarcopenia.Their combination has good screening value for sarcopenia,and can be applied in external prediction for T2DM patients.

Acute pancreatitis(AP)is a frequently encountered acute abdominal syndrome in clinical settings,and the integrated model of traditional Chinese and Western medicine(TCM-WM)has demonstrated notable advantages in the diagnosis and treatment of AP.To systematize and standardize clinical practices related to develop clinical pathway for integrated TCM-WM diagnosis and treatment of AP,which enhances the efficiency and quality of patient care.This pathway focuses on AP,a common acute and life-threatening disease within the digestive system,and outlines that the central pathological mechanism involves pancreatic injury and localized inflammation resulting from the abnormal activation of pancreatic enzymes.It has the characteristics of rapid onset,multiple causes,and complex manifestations.Severe cases can be life-threatening.At present,conventional treatments encompass a diverse range of modalities.Moreover,traditional Chinese medicine(TCM)holds distinct advantages in alleviating relevant symptoms,and TCM-WM is gaining increasing prevalence.To enhance the standardization and consistency of diagnostic and therapeutic practices,this clinical pathway clearly delineates the target patient population,which includes individuals diagnosed with abdominal pain disorder according to TCM and with AP in accordance with WM criteria,as well as the corresponding inclusion standards.The diagnostic framework integrates both TCM and WM guidelines,and further incorporates disease staging,severity grading,and syndrome differentiation to support a comprehensive and integrated diagnostic strategy.The treatment integrates approaches from both TCM and WM.Within the WM framework,interventions consist of basic supportive care,infection control,nutritional support,and the management of complications.In the context of TCM,the protocol includes syndrome differentiation and corresponding therapeutic strategies(Distinct syndrome patterns are identified and managed during the acute and convalescent phases),such as acupuncture and retention enema.This clinical pathway addresses multiple key components,including preventive strategies,post-treatment follow-up,criteria for evaluating therapeutic efficacy,admission and discharge,admission examination protocols,discharge criteria,and the rationale for deviations or withdrawal from the pathway.It is designed to provide a systematic and standardized reference framework for relevant clinical practices.

The menopausal age is one of the important menopausal factors, and women of different menopausal ages have different risks of diabetes. This study reviewed the evidence from prospective studies on the association between the age at natural menopause and diabetes risk, both domestically and internationally, and presented its research design and main findings. Advanced menopause, especially premature and early menopause, will increase the risk of diabetes in postmenopausal women. The research on the influence of delayed menopause on the incidence of diabetes is still insufficient. Many factors may modify the association between menopausal age and the risk of diabetes.

Objective: To analyze the disease burden of chronic obstructive pulmonary disease (COPD) and changes in its risk factors among residents in Zhejiang Province from 1990 to 2021, so as to identify key priorities for COPD prevention and control. Methods: Data on COPD mortality and disability-adjusted life years (DALY) for residents in Zhejiang Province from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Standardized mortality and standardized DALY rate were calculated using the GBD 2021 world population standard structure. Premature mortality was computed via the life table method. The average annual percent change (AAPC) was applied to analyze trends in COPD mortality, DALY rate, and premature mortality. Changes in deaths of COPD risk factors were evaluated using population attributable fraction (PAF). Results: From 1990 to 2021, the standardized COPD mortality in Zhejiang Province decreased from 272.40/100 000 to 70.56/100 000 (AAPC=-4.395%), and the standardized DALY rate declined from 4 167.37/100 000 to 1 071.89/100 000 (AAPC=-4.396%). Similar downward trends were observed in both males (AAPC=-3.933%, -4.173%) and females (AAPC=-4.785%, -4.480%), all P<0.05. Crude mortality and DALY rates increased with age, and the crude mortality and DALY rates of various age groups in Zhejiang Province showed decreasing trends from 1990 to 2021 (all P<0.05). The premature mortality declined from 4.37% to 0.60% from 1990 to 2021 (AAPC=- 6.206%), with consistent trends across males and females (AAPC=- 6.144%, - 6.379%, all P<0.05). From 1990 to 2021, particulate matter pollution showed the largest reduction in PAF (- 56.76%), while ambient ozone pollution had the largest increase (103.07%) in Zhejiang Province. By 2021, smoking became the leading risk factor for deaths of COPD (PAF=43.32%). Conclusions The standardized mortality, standardized DALY rate, and premature mortality for COPD show consistent declining trends in Zhejiang Province from 1990 to 2021. However, risk factors such as smoking and ambient ozone pollution require intensified focus to further reduce disease burden of COPD.