The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

Drowning is a common and serious injury worldwide, especially for children and young people. Drowning occurs frequently, resulting in heavy health and economic burdens to society. This paper summarizes the progress in the research of the epidemiology of drowning both at home and abroad, including the epidemiological characteristics, risk factors and intervention measures. Through analysis on existing research literature, it is found that there are large differences in the incidence characteristics of drowning in different regions. Men and children are at high risk for drowning. Age, being man, rural environment, lack of supervision, alcohol consumption, and underlying diseases are risk factors for drowning. It is suggested to pay more attention to the problem of drowning, improve people's awareness of drowning, take appropriate intervention measures and strengthen multi-sectoral collaboration to prevent and control the incidence of drowning.

Abstract Falls are the leading cause of accidental injury deaths among the elderly. Currently, the incidence and disease burden of falls among the elderly remain high. By understanding the influencing factors of falls among the elderly and formulating targeted preventive measures, the risk of falls can be effectively reduced. Studies have found that falls among the elderly are results of the interaction of multiple factors. When formulating fall prevention strategies, attention should be paid to fall risk assessment and stratification, fall prevention exercise support and health education, living environment improvement, and primary healthcare service enhancement. Reviewing publications pertaining to the epidemiological studies of falls from January 2004 to January 2024, this article summarizes the epidemiological characteristics, risk factors, prevention and control strategies of falls among the elderly, aiming to provide the reference for prevention and control.

Background: Data on the efficacy and incidence of adverse effects associated with dexmedetomidine (DEX) as a local anesthetic adjuvant for patient-controlled epidural analgesia (PCEA) are inconclusive. This meta-analysis assessed the efficacy and risks of DEX for PCEA using opioids as a reference. Methods: Two researchers independently searched PubMed, Embase, Cochrane Library, and China Biology Medicine for randomized controlled trials comparing DEX and opioids as local anesthetic adjuvants in PCEA. Results: In total, 636 patients from seven studies were included in this meta-analysis. Postoperative patients who received DEX had lower visual analog scale (VAS) scores than those who received opioids at 4–8 h (mean difference [MD]: 0.61, 95% CI [0.45, 0.76], P < 0.001, I2 = 0%), 12 h (MD: 0.85, 95% CI [0.61, 1.09], P < 0.001, I2 = 0%), 24 h (MD: 0.59, 95% CI [0.06, 1.12], P = 0.030, I2 = 82%), and 48 h (MD: 0.54, 95% CI [0.05, 1.02], P = 0.030, I2 = 91%). Additionally, patients who received DEX had a lower incidence of itching (odds ratio [OR]: 2.86, 95% CI [1.18, 6.95], P = 0.020, I2 = 0%) and nausea and vomiting (OR: 6.83, 95% CI [3.63, 12.84], P < 0.001, I2 = 24%). In labor analgesia, no significant differences in neonatal (pH and PaO2 of cord blood, fetal heart rate) or maternal outcomes (duration of labor stage, mode of delivery) were found between the DEX and opioid groups. Conclusions Compared with opioids, using DEX as a local anesthetic adjuvant in PCEA improved postoperative analgesia and reduced the incidence of itching and nausea and vomiting without increasing the incidence of adverse events.

Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines, especially Vernonia amygdalina, a famous nature medicine for the treatment of tonsillitis, diabetes, pneumonia. The current study was designed to combine molecular networking (MN) with diagnostic ions for rapid identification of Δ^7,9(11) stigmastane-type saponins which were the α-glucosidase inhibitory active substances in V. amygdalina. First, the α-glucosidase inhibitory activities of five Δ^7,9(11) stigmastane-type steroid saponins that were previously isolated were screened, which indicated that the Δ^7,9(11) stigmastane-type steroid saponin was one of the active constituents responsible for ameliorating diabetes. Furthermore, a strategy was proposed to identify stigmastane-type steroid saponins and verify the plausibility of derived fragmentation pathways by applying MN, MolNetEnhancer and unsupervised substructure annotation (MS2LDA). Based on this strategy, other seven Δ^7,9(11) stigmastane-type steroid saponins were identified from this plant. Our research provide scientific evidence for the antidiabetic potential of the steroid saponin-rich extract of V. amygdalina leaf.
alpha-Glucosidases/metabolism* ; Vernonia/chemistry* ; Plant Extracts/chemistry* ; Plant Leaves/chemistry* ; Saponins/chemistry* ; Steroids/chemistry* ; Diabetes Mellitus

Objective To understand and evaluate the knowledge, attitude and practice of female human papillomavirus and HPV vaccine in Chinese mainland. Methods We searched the relevant studies about the knowledge, attitude and behavior factors of HPV infection and HPV vaccine published in PubMed, MEDLINE, CNKI and Wanfang databases about Chinese mainland women from January 1, 1995 to January 31, 2021.Two researchers independently screened the literatures, extracted data and the literatures with quality score≥5 points.Chi square test was used to evaluate its heterogeneity.Begg' s test was used to evaluate publication bias. Results A total of 33 literatures were included, with a total number of 46013 people.The results showed that the total awareness rate of HPV in the population was 65.9%, the lowest rates were 16.0%, 41.2% and 14.4% in Northeast, rural areas and middle school students, respectively; while the highest rates of HPV were 77.4%, 56.3% and 71.0% in Central China, cities and towns and college students, respectively.The main source of HPV knowledge was the network/WeChat official account number (38.9%), and the lowest was family/friend (4.5%).The population's awareness rate of HPV vaccine related knowledge was 41.4%, the highest rates were 51.8% and 69.7% in East China and medical staff, respectively, while the lowest were 23.6% and 12.7% in Southwest and middle school students. Conclusion In order to achieve the total elimination of cervical cancer in China by 2030 as soon as possible, people should strengthen their awareness of HPV and HPV vaccine related knowledge.

Objective:To develop a set of indexes for the assessment of healthy older adults in China, in order to provide a reference and basis for developing aging-related national policies, standardizing and guiding health management services for the elderly.Methods:A set of indexes for the assessment of healthy older adults in China was established based on a literature review, expert discussions, 2 rounds of Delphi surveys, expert consultations and a cross-sectional study assessing the indexes.Results:The positive coefficients for 2 rounds of expert consultations were 86.25%(69/80)and 94.52%(69/73), respectively.All surveyed experts(100%)specialized in the area of geriatric health and came from 22 provincial-level administrative regions in China.In the two rounds of consultations, the familiarity degree coefficients were 0.706-0.915 and 0.835-0.922, and the authority coefficients were 0.762-0.921 and 0.863-0.932, respectively.The mean importance scores of each index were 6.10-9.74 scores and 7.87-9.56 scores, with perfect score rates of 43%-99% and 75%-99%, respectively.The mean coefficients of variation(CV)were 0.19±0.05(0.07-0.34)and 0.16±0.03(0.10-0.21), respectively.The set of indexes for the assessment of healthy older Chinese adults covered multi-dimensions including physical health, mental health and social health, with 3 primary indexes, 11 secondary indexes and 17 tertiary indexes.Conclusions:The construction process of the set of indexes for the assessment of healthy Chinese adults was scientific and rigorous, and the panelists had a high level of agreement, strong authority and active participation.The set of indexes has comprehensive coverage and an inclusive framework, and indexes at each level are scientific and feasible.It can serve as a reference for the comprehensive assessment of health status of the elderly and for aging-related government policy formulation in the future.

Objective:To analyze the process of Chinese expert consensus on the core information on prevention of sarcopenia in the elderly(2021)in China, so as to realize the early diagnosis and treatment of sarcopenia and to improve the quality of life in the elderly.Methods:The index system framework was established by literature review and expert questionnaire discussion, and Delphi expert consultation method was adopted to construct the index system.Results:A total of 109 experts(128 person-times)in Geriatrics from various fields participated in Delphi expert consultation.Positive coefficient for four rounds of expert consultation were 88.9%, 100.0%, 100.0% and 100.0% respectively, with expert authority factors being concentrated on 0.78~0.90.Through 4 rounds of Delphi expert surveys, the core information index system for sarcopenia prevention in the elderly has been definitive: Chinese Expert Consensus(2021)consists of nine indicators including "enhancing public scientific awareness of myosis, and so on."Conclusions:The core information index system for sarcopenia prevention in the elderly has high levels of overall convergence, comprehensive coverage, strong authority, stability, comprehensiveness and popularity.

OBJECTIVE：To study the improvement effect and possible mechanism of Leontopodium leontopodioides combined with Astragalus membranaceus on the renal function of mesangial proliferative glomerulonephritis （MsPGN） model rats. METHODS：Totally 85 rats were randomly divided into sham operation group （n＝10）and modeling group （n＝75）. Sham operation group underwent sham operation ，and MsPGN model was induced by immunological method [Freund ’s adjuvant+BSA + lipopolysaccharide（LPS）] in modeling group. After successfully modeling ，70 rats were randomly divided into model group ，L. leontopodioides+A. membranaceus high-dose，medium-dose and low-dose groups （4.05，2.03，1.02 g/kg，by total crude drug ），L. leontopodioides alone group （2.70 g/kg，by crude drug ），Tripterygium glycosides tablet group （positive control 1，0.02 g/kg）， Lotensin tablet group （positive control 2，0.02 g/kg），with 10 rats in each group. Sham operation group and model group were given constant volume of normal saline intragastrically ； administration groups were given relevant drug solution intrasgastrcially at a volume of 15 mL/kg，once a day ，for consecutive 5 weeks. At last administration ，24 h urinary lnzyxyqy2003@163.com protein，urine creatinine and serum creatinine were determined in rats. The right kidney was weighed ，and HE staining was used to observe the pathomorpholog y changes of renal tissue. Immunohistochemistry was used to detect the protein expression of NF-κB p65 in renal tissue. Western blotting assay was used to determine the protein expressions of NF-κB p65，IκBα，ERK，p-ERK and p 38 MAPK in renal tissue. RESULTS ：Compared with sham operation group ，right kidney weight ，24 h urine protein and serum creatinine levels ，protein expressions of NF-κB p65， p-ERK and p 38 MAPK in renal tissue were increased significantly in model group （P＜0.05 or P＜0.01）；the level of urine creatinine and protein expression of IκBα in renal tissue were decreased significantly（P＜0.05 or P＜0.01）；there were obvious glomerular hypertrophy ，diffuse increase of mesangial cells ，necrosis of renal tubules and other pathomorphological changes in renal tissue. Compared with model group ，right kidney weight and serum creatinine level were decreased significantly in L. leontopodioides alone group （P＜0.05），while urine creatinine level was increased significantly （P＜0.05），but there was no statistical significance in the level of 24 h urine protein （P＞0.05）；the right kidney weight ，24 h urine protein ，serum creatinine level and protein expression levels of NF-κB p65，p-ERK and p38 MAPK in renal tissue were decreased significantly in L. leontopodioides+A. membranaceus high-dose group （P＜0.05），while the urine creatinine level and protein expression level of IκBα in renal tissue were increased significantly （P＜0.05 or P＜0.01）；there was no statistical significance in above indexes in L. leontopodioides+A. membranaceus medium-dose，low-dose groups （P＞0.05）；pathological changes of renal tissue were improved to different extents in administration groups ，especially in L. leontopodioides +A. membranaceus high-dose group. CONCLUSIONS ： High dose of L. leontopodioides +A. membranaceus can improve renal function of MsPGN model rats by inhibiting MAPK/NF-κB signal pathway.