BACKGROUND: High temperatures are known to be associated with an increased risk of self-harm, but the influence of demographic changes and country-level indicators on the burden of heat-related self-harm remains unclear. This study examined the key factors driving changes in self-harm mortality linked to high temperatures and explored their impact at the country level. METHODS: This is an ecological study that analyzes data from the 2021 Global Burden of Disease (GBD) study, the World Bank, and the Climate Research Unit (CRU) were analyzed. Decomposition analyses were used to identify key factors driving changes in high temperature-related self-harm mortality between 1990 and 2021. A panel data model assessed the impact of national indicators on heat-related self-harm mortality. RESULTS: In 2021, 14,885 deaths globally were attributed to heat-related self-harm, a 41.94% increase from 1990, with low-middle SDI regions accounting for 47.84% of these deaths. While the global death rate from heat-related self-harm declined slightly over this period, South Asia and low-middle SDI regions contributed most to the decline. However, population aging exacerbated mortality rates. Demographic and meteorological factors were also linked to heat-related self-harm. CONCLUSION The global decline in heat-related self-harm mortality is largely driven by reductions in females, low-middle SDI regions, and South Asia. However, population aging and growth in these regions have added to the mortality burden, slowing the overall decline. Factors such as population density are also associated with heat-related self-harm. Targeted measures are needed to mitigate heat-induced self-harm more effectively in future.
Humans ; Self-Injurious Behavior/etiology* ; Hot Temperature/adverse effects* ; Global Health/statistics & numerical data* ; Female ; Male ; Adult ; Middle Aged ; Aged ; Young Adult ; Adolescent

Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

Objective To investigate the role of the BNIP3-PI3K/Akt signaling pathway in mediating the inhibitory effect of Buyang Huanwu Decoction(BYHWT)on mitochondrial autophagy in human synovial fibroblasts from rheumatoid arthritis patients(FLS-RA)cultured under a hypoxic condition.Methods Forty normal Wistar rats were randomized into two groups(n=20)for daily gavage of BYHWT or distilled water for 7 days to prepare BYHWT-medicated or control sera.FLS-RA were cultured in routine condition or exposed to hypoxia(10％O2)for 24 h wigh subsequent treatment with IL-1β,followed by treatment with diluted BYHWT-medicated serum(5％,10％and 20％)or control serum.AnnexinV-APC/7-AAD double staining and T-AOC kit were used for detecting apoptosis and total antioxidant capacity of the cells,and the changes in ROS,ATP level,mitochondrial membrane potential and Ca2+homeostasis were analyzed.The changes in mRNA and protein expressions of BNIP3,PI3K and AKT and mRNA expressions of LC3,Beclin-1 and P62 were detected using RT-qPCR and Western blotting.Results Treatment with BYHWT-medicated serum dose-dependently lowered apoptosis rate of IL-1β-induced FLS-RA with hypoxic exposure.The treatment significantly decreased T-AOC concentration,increased ROS production,autophagosome formation and ATPase levels,and lowered mitochondrial membrane potential and Ca2+level in the cells.In IL-1β-induced FLS-RA with hypoxic exposure,treatment with BYHWT-medicated serum significantly increased BNIP3 protein expression,decreased the protein expressions of PI3K and AKT,increased the mRNA expressions of BNIP3 and P62,and lowered the mRNA expressions of PI3K,AKT,LC3 and Beclin-1 without significantly affecting Beclin-1 protein expression.The cells treated with 5％and 10％BYHWT-medicated serum showed no significant changes in LC3 expression.Conclusion BYHWT inhibits mitochondrial autophagy in IL-1β-induced FLS-RA with hypoxic exposure possibly by inhibiting BNIP3-mediated PI3K/AKT signaling pathway.

OBJECTIVES: To investigate the role of the BNIP3-PI3K/Akt signaling pathway in mediating the inhibitory effect of Buyang Huanwu Decoction (BYHWT) on mitochondrial autophagy in human synovial fibroblasts from rheumatoid arthritis patients (FLS-RA) cultured under a hypoxic condition. METHODS: Forty normal Wistar rats were randomized into two groups (n=20) for daily gavage of BYHWT or distilled water for 7 days to prepare BYHWT-medicated or control sera. FLS-RA were cultured in routine condition or exposed to hypoxia (10% O₂) for 24 h wigh subsequent treatment with IL-1β, followed by treatment with diluted BYHWT-medicated serum (5%, 10% and 20%) or control serum. AnnexinV-APC/7-AAD double staining and T-AOC kit were used for detecting apoptosis and total antioxidant capacity of the cells, and the changes in ROS, ATP level, mitochondrial membrane potential and Ca²⁺ homeostasis were analyzed. The changes in mRNA and protein expressions of BNIP3, PI3K and AKT and mRNA expressions of LC3, Beclin-1 and P62 were detected using RT-qPCR and Western blotting. RESULTS: Treatment with BYHWT-medicated serum dose-dependently lowered apoptosis rate of IL-1β-induced FLS-RA with hypoxic exposure. The treatment significantly decreased T-AOC concentration, increased ROS production, autophagosome formation and ATPase levels, and lowered mitochondrial membrane potential and Ca²⁺ level in the cells. In IL-1β-induced FLS-RA with hypoxic exposure, treatment with BYHWT-medicated serum significantly increased BNIP3 protein expression, decreased the protein expressions of PI3K and AKT, increased the mRNA expressions of BNIP3 and P62, and lowered the mRNA expressions of PI3K, AKT, LC3 and Beclin-1 without significantly affecting Beclin-1 protein expression. The cells treated with 5% and 10% BYHWT-medicated serum showed no significant changes in LC3 expression. CONCLUSIONS BYHWT inhibits mitochondrial autophagy in IL-1β-induced FLS-RA with hypoxic exposure possibly by inhibiting BNIP3-mediated PI3K/AKT signaling pathway.
Drugs, Chinese Herbal/pharmacology* ; Arthritis, Rheumatoid/pathology* ; Animals ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Autophagy/drug effects* ; Humans ; Fibroblasts/cytology* ; Rats, Wistar ; Membrane Proteins/metabolism* ; Rats ; Phosphatidylinositol 3-Kinases/metabolism* ; Mitochondria/metabolism* ; Cells, Cultured ; Proto-Oncogene Proteins/metabolism* ; Apoptosis/drug effects* ; Cell Hypoxia ; Synovial Membrane/cytology* ; Male ; Mitochondrial Proteins

Objective: To investigate the therapeutic effect of patchouli alcohol on mice with lung-heat syndrome based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/nuclear factor-kappa B(NF-κB) signaling pathway. Methods: First, network pharmacology was used to predict the potential targets of patchouli alcohol in the treatment of lung-heat syndrome, and a "component-disease-key target" network was constructed for pathway analysis. Then, 40 BALB/c mice were assigned to the normal, lung-heat model, honeysuckle, and low-dose and high-dose patchouli alcohol groups. All groups, except the blank group, were intranasally infected with 50 μL (103 TCID50) of influenza virus solution. After two hours of infection, mice were treated once a day for seven consecutive days. The therapeutic mechanism of patchouli alcohol was explored by measuring pulmonary inflammatory factors, the PI3K/Akt/NF-κB pathway, hypothalamic fever markers (PGE2, cAMP, cGMP levels), rectal temperature, and tissue energy metabolism. Results: Network pharmacology identified 135 target genes related to patchouli alcohol and lung-heat syndrome, with the key targets being STAT3, H1F1A, and NF-κB1. In animal experiments, patchouli alcohol significantly alleviated influenza virus-induced lung inflammatory damage in mice with lung-heat syndrome, inhibited the expression of TNF-α and IL-6 in lung tissues(P<0.01), and suppressed the activation of the PI3K/Akt/NF-κB pathway. It also reduced hypothalamic levels of PGE2 and cAMP(P<0.01), suppressed the increase in rectal temperature, significantly decreased liver glycogen and pyruvate levels(P<0.01), and increased the activities of SDH, LDH, and Na+ -K+ -ATPase in the liver(P<0.01) Conclusion Patchouli alcohol improves the symptoms of lung-heat syndrome in mice by inhibiting the activation of the PI3K/Akt/NF-κB pathway, reducing proinflammatory cytokines and inflammatory damage, and regulating hypothalamic fever markers and energy metabolism.

Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

Objective:To investigate the mid-to-long term therapeutic effects of allogeneic bone composite prosthesis reconstruction in patients with large bone defects after the resection of distal femoral tumors.Methods:From June 2013 to December 2018, a total of 19 patients with malignant tumors of the distal femur who underwent reconstruction with allogeneic bone composite prosthesis in the Department of Bone Tumor, Shanghai General Hospital were retrospectively collected. There were 10 males and 9 females, aged 22.3±11 years (range, 11-42 years). The mean body mass index was 19.3±3.4 kg/m 2 (range, 14-27 kg/m 2). There were 18 cases of osteosarcoma and 1 case of Ewing's sarcoma. According to Ennecking staging, there were 17 cases of stage IIB and 2 cases of stage III. The intraoperative blood loss and operation time were recorded, and the prosthesis and patient survival conditions and postoperative complications were observed. The limb function was evaluated by the Musculoskeletal Tumor Society (MSTS) 93 function score. Results:All patients successfully completed the operation. The operation time was 187.3±39.8 min (range, 110-260 min), the intraoperative blood loss was 284.9±87.0 ml (range, 200-500 ml), and the blood transfusion volume was 327±213 ml (range, 100-800 ml). The remaining length of the proximal femur was 153.7±26.6 mm (range, 93-190 mm), and the length of allogeneic bone was 84.1±24.6 mm (range, 39-134 mm). Among the 19 patients, 9 patients (47%) achieved bony union with an average healing time of 16.7±4.8 months (range, 10-25 months), and 7 patients had delayed healing with an average healing time of 18.4±4.0 months (range, 15-25 months). The remaining 10 cases were nonunion between allogeneic bone and host bone. All patients were followed up for 80.7±20.2 months (range, 56-121 months). During the follow-up, 3 cases died due to pulmonary metastasis of bone tumors, and the time of death was 57 months, 63 months, and 59 months after surgery, respectively. At the last follow-up, the patient survival rate was 84% (16/19), and the MSTS 93 function score of the 16 patients was (24.3±2.4) points (range, 21-28 points), with an excellent rate of 100% (16/16). Seven patients underwent revision surgery, 3 cases were aseptic loosening, 3 cases were prosthesis stem fracture at the junction of the allograft bone and the host bone, and 1 case was periprosthetic infection, among which the patient with periprosthetic infection had poor local soft tissue conditions due to preoperative radiotherapy, and the infection was controlled after two revision surgeries. Five cases were revised with allogeneic bone composite prosthesis, and 2 cases were revised with short-stem giant prosthesis with cortical steel plate or locking nail. After revision, the remaining length of the proximal femur was 143.4±31 mm (range, 91-175 mm), and the length of the allograft bone was 92.6±26.6 mm (range, 61-123 mm). The 7 revised patients were still in follow-up. There were no cases of pulmonary infection, nerve injury, deep vein thrombosis or other complications after surgery.Conclusion:The survival period of patients after the surgery to reconstruct large bone defects following the resection of malignant tumors at the distal end of the femur using allogeneic bone composite prosthesis is satisfactory, and the limb function is good. However, the incidence of prosthesis complications is high, which can be reconstructed through revision.

Chronic pain refers to pain that persists or recurs for more than 3 months and has a high comorbidity rate with emotions such as depression and anxiety. The complex pathogenesis of comorbid depressive symptoms in chronic pain poses great challenges to clinical diagnosis and treatment. This article reviews the research progress on the effect mechanism on the comorbid depressive symptoms in chronic pain by traditional Chinese medicine monomers， compound formulas， and acupuncture therapy in recent years. It is found that traditional Chinese medicine monomers （flavonoids， phenols， terpenes， coumarins， alkaloids）， traditional Chinese medicine formulas （Aconitum carmichaeli decoction， Chaihu guizhi decoction， etc.）， and acupuncture therapy （acupuncture at acupoints such as Baihui， Yintang， Hegu， and Taichong） can effectively improve comorbid depressive symptoms in chronic pain by regulating the levels of neurotransmitters， brain-derived neurotrophic factors and inflammatory factors， and the activity of glial cells in the central nervous system.

Objective To retrospectively investigate and analyze the specially permitted aeromedical evaluation results of overage military flying personnel,in order to provide references for health management and related evaluation methods improvement.Methods The clinical data and evaluation results of overage flying personnel were collected from 2012 to 2023.Disease spectrum was analyzed,and qualified rates among different airplane types and aviation duties were compared.Results 79.57%of the 509 flying personnel were detected with diseases,and the top ten were hyperlipidemia,fatty liver,thyroid nodule,renal cyst,hepatic cyst,gallbladder polyps,hyperuricemia,carotid artery arteriosclerosis,hypertension and hepatic hemangioma.96.08%of the personnel were qualified to continue flying,1.96%were disqualified and 1.96%were temporarily disqualified.The qualified rates among different airplane types and aviation duties were not significantly different(P?>?0.05).Conclusion Overage military flying personnel could apply for specially permitted aeromedical evaluation to extend their flying lifespan.Attention should be paid to metabolic and cardiovascular diseases in aeromedical support and evaluation for these experienced flying personnel.

Most solid tumors suffer from inadequate blood perfusion and oxygenation, leading to a hypoxic microenvironment that accelerates tumor progression and adversely impacts prognosis. Thus, improving oxygenation in tumor tissues is crucial for enhancing the sensitivity and efficacy of tumor therapy. Hemoglobin-based oxygen carriers (HBOCs), as a type of oxygen-carrying nanoparticles, can not only carry and release oxygen but also reach the small blood vessels of obstructive microcirculation to deliver oxygen for anoxic tissues and organs, which are difficult for normal red blood cells to pass through. Studies have demonstrated that the application of HBOCs as a potential nanoscale efficient oxygen carrier in tumor therapy can enhance tissue oxygenation and hold great promise for applications in tumor therapy.This review summarizes the impact of hypoxia in tumors and highlights the progress and potential mechanisms of using HBOCs in tumor radiotherapy, chemotherapy, new kinetic therapy and immunotherapy.