The plateau region is known for its unique environmental characteristics of low oxygen, low pressure, strong radiation, cold and dryness. Under the low oxygen environment, human physiological functions and drug metabolism are significantly affected. In order to gain a deeper understanding of drug metabolism in the plateau hypoxic environment and to guide the rational use of drugs in the plateau region, the effects of plateau hypoxia on drug metabolism were reviewed in this paper, which focused on changes in metabolic profiles, enzyme activity and expression, and probed the relevant mechanisms in depth.

The plateau region is known for its unique environmental characteristics of low oxygen, low pressure, strong radiation, cold and dryness. Under the low oxygen environment, human physiological functions and drug metabolism are significantly affected. In order to gain a deeper understanding of drug metabolism in the plateau hypoxic environment and to guide the rational use of drugs in the plateau region, the effects of plateau hypoxia on drug metabolism were reviewed in this paper, which focused on changes in metabolic profiles, enzyme activity and expression, and probed the relevant mechanisms in depth.

“Zinc overload” has emerged as a promising strategy in tumor nanomedicine, wherein exogenous modulation of metal ion homeostasis selectively triggers cancer cell death. Among various bioactive ions, zinc (Zn²⁺) stands out due to its unique ability to simultaneously disrupt energy metabolism, damage mitochondria, degrade mutant p53, and activate antitumor immunity. Notably, tumor cells exhibit greater sensitivity to Zn²⁺ overload while normal cells maintain higher tolerance. This review systematically summarizes design strategies for achieving “zinc overload” using biodegradable zinc-based nanomaterials, focusing on two fundamental questions: how to specifically deliver Zn²⁺ to tumors (targeted delivery), and how to trigger controlled release at the tumor site (release strategies). Current challenges are critically analyzed and future perspectives are offered. For targeted delivery, the strategies are categorized into passive, active, and biomimetic approaches. Passive targeting relies on the enhanced permeability and retention (EPR) effect but suffers from poor enrichment efficiency and rapid clearance. Active targeting conjugates ligands (e.g., folic acid, hyaluronic acid) to recognize overexpressed receptors, significantly enhancing cellular uptake. It is emphasized that hyaluronic acid-modified ZIF-8 can co-deliver siRNA for GLUT1 silencing, achieving systematic energy exhaustion. Biomimetic delivery using cell membranes confers immune evasion, prolonged circulation, and homologous targeting, exhibiting the lowest off-target toxicity. This approach is considered to guide future nanocarrier design. For Zn²⁺ release, 4 mechanisms are discussed. Endogenous environment-responsive release exploits acidic pH to degrade materials like ZIF-8 or ZnO, causing mitochondrial dysfunction, reactive oxygen species (ROS) burst, and autophagic blockade. Incorporation of other ions (Ca²⁺, Mn²⁺, Ni²⁺) enables synergistic metabolic interference and immune activation. Exogenous responsive release using near-infrared light offers spatiotemporally precise activation. For example, a nanorobot combining black phosphorus with ZIF-8 accelerates Zn²⁺ release under dual acid and light stimuli. Ion exchange represents an elegant trigger: zinc complexes (e.g., Zn-carnosine) have higher affinity for Cu²⁺; competitive coordination releases Zn²⁺ while depleting Cu²⁺, dually inhibiting oxidative phosphorylation and glycolysis. This mechanism is proposed to hold promise for overcoming metabolic reprogramming. Finally, biological regulation—silencing the ZnT1 zinc transporter to block Zn²⁺ efflux—represents a paradigm shift from passive delivery to active homeostatic disruption. This “block and attack” strategy may prevent acquired resistance. The therapeutic consequences of zinc overload are multifaceted. Zn²⁺ causes lysosomal membrane permeabilization and impaired SNARE complex formation, blocking autophagic flux and inducing a distinct cell death termed “zincosis”. In mitochondria, Zn²⁺ inhibits glutathione reductase, causing oxidative stress and electron transport chain blockade. Meanwhile, Zn²⁺ suppresses glycolytic enzymes (GAPDH, LDHA), leading to ATP depletion and reversing drug resistance by downregulating P-glycoprotein. Moreover, zinc overload triggers immunogenic cell death, promoting dendritic cell maturation and CD8⁺ T cell infiltration. Combined with cGAS-STING activation, this reshapes the immunosuppressive tumor microenvironment and inhibits distant metastasis. These interconnected mechanisms endow zinc overload with a unique advantage over single-modality treatments. Despite remarkable preclinical efficacy, challenges remain: systemic toxicity from off-target release, potential zinc tolerance via metallothionein upregulation, and insufficient pharmacokinetic data. Future directions should prioritize: (1) intelligent stimuli-responsive materials; (2) combination with immune checkpoint inhibitors;(3) theragnostic integration; (4) deeper mechanistic studies; and (5) artificial intelligence-assisted screening. Zinc overload therapy is expected to become an indispensable component of integrated tumor treatment.

Objective To explore the clinical efficacy of Liuwei Dihuang Capsules for type 2 diabetes mellitus(T2DM)with yin deficiency syndrome and the effects on intestinal flora and inflammatory factors.Methods Totally 60 patients of T2DM with yin deficiency syndrome in Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2022 to June 2023 were selected as the study objects,and were divided into control group and observation group according to the method of block randomization,with 30 cases in each group.Both groups received basic treatment.The control group was given a simulated agent of Liuwei Dihuang Capsules,while the observation group was given Liuwei Dihuang Capsules.The treatment course for both groups was 4 weeks.Clinical efficacy,blood glucose levels[fasting plasma glucose(FPG),2-hour postprandial plasma glucose(2 hPG),glycated albumin(GA)],serum insulin levels[fasting insulin(FINS)and insulin resistance index(HOMA-IR)],changes in gut microbiota,and serum inflammatory cytokine levels[interleukin(IL)-6,tumor necrosis factor(TNF)-α]of both groups were compared.Results The total effective rate of the observation group(76.67%)was better than that of the control group(50.00%)(P<0.05).Compared with before treatment,the FPG,2 hPG,GA,FINS and HOMA-IR decreased in the observation group,while the FPG,2 hPG and FINS decreased in the control group(P<0.05);after treatment,the Shannon index of the observation group increased after treatment(P<0.05),and the diversity of the microbiota increased;the abundance of the microbial communities such as Coprococcus 3,Cutibacterium,Pseudomonas,Faecalibaculum,Dubosiella and Mucispirillum significantly increased(P<0.05);the abundance of Sphingomonas,Corynebacterium 1,Ileibacterium,Ruminiclostridium and other microbiota communities significantly decreased(P<0.05).Compared with before treatment,the levels of IL-6 and TNF-α in both groups were significantly reduced after treatment(P<0.01,P<0.05).After treatment,the levels of IL-6 and TNF-α in the observation group were significantly lower than those in the control group(P<0.05).Conclusion Liuwei Dihuang Capsules can effectively reduce blood glucose levels in patients of T2DM with yin deficiency syndrome,improve insulin resistance,increase gut microbiota diversity,increase beneficial bacterial abundance,reduce harmful bacterial abundance,and alleviate inflammatory cytokine levels.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective:To investigate the treatment and management of patients with endemic fluorosis (referred to as fluorosis) in Ankang City, Shaanxi Province, and to provide a scientific basis for adjusting and optimizing treatment and management strategies for fluorosis patients.Methods:A retrospective analysis was conducted on patient information collected from county-level disease prevention and control centers in Ankang City from 2019 to 2023. Data included demographic information, clinical treatment, chronic disease management, treatment records, work reports, and summaries. The study aimed to learn about the treatment willingness, methods, and effects of patients with fluorosis, and to evaluate the disease management situation of patients with fluorosis.Results:From 2019 to 2023, the proportion of fluorosis patients who were willing to receive treatment in Ankang City had increased from 76.80% (1 089/1 418) in 2019 to 100% (1 408/1 408) in 2023, showing an upward trend year by year (χ 2trend = 971.15, P < 0.001). A total of 6 876 patients received treatment, with a treatment rate of 100%. The majority of patients received drug treatment (99.64%, 6 851/6 876), with an effective rate of 94.90% (6 525/6 876). The effective rate of treatment for patients with fluorosis had increased from 88.71% (966/1 418) in 2019 to 94.67% (1 333/1 408) in 2023, showing an upward trend (χ 2trend = 1 002.92, P < 0.001). The adverse reaction rate of drug treatment was 0.36% (25/6 876). The combination of oral medication and local treatment had the highest effective rate (97.62%, 3 566/3 653). The management rate and contracted service rate of fluorosis patients were 100% each year, and the standardized management rate was above 99%. Conclusions:Fluorosis patients in Ankang City have a high willingness to receive treatment, with good treatment outcomes. The contracted services and management of patients are well implemented. In the future, continuous efforts should be made to improve the prevention, management, and health education of fluorosis patients.

OBJECTIVE: This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction (MI) in patients with both coronary heart disease (CHD) and type 2 diabetes (T2D). METHODS: We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen, China. Patients were categorized into 6 groups based on baseline fasting plasma glucose (FPG) levels and diabetes duration (from the date of diabetes diagnosis to the baseline date) to examine their combined effects on subsequent MI. Cox proportional hazards regression models were used, with further stratification by age, sex, and comorbidities to assess potential interactions. RESULTS: Over a median follow-up of 2.4 years, 2,110 patients experienced MI. Compared to those with optimal glycemic control (FPG < 6.1 mmol/L) and shorter diabetes duration (< 10 years), the fully-adjusted hazard ratio ( HR) (95% Confidence Interval [95% CI]) for those with a diabetes duration of ≥ 10 years and FPG > 8.0 mmol/L was 1.93 (95% CI: 1.59, 2.36). The combined effects of FPG and diabetes duration on MI were largely similar across different age, sex, and comorbidity groups, although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation. CONCLUSION Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D. Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
Humans ; Diabetes Mellitus, Type 2/blood* ; Male ; Female ; Middle Aged ; Aged ; Coronary Disease/complications* ; Myocardial Infarction/etiology* ; Retrospective Studies ; China/epidemiology* ; Glycemic Control ; Blood Glucose ; Adult ; Risk Factors ; Time Factors

Objective:To investigate the treatment and management of patients with endemic fluorosis (referred to as fluorosis) in Ankang City, Shaanxi Province, and to provide a scientific basis for adjusting and optimizing treatment and management strategies for fluorosis patients.Methods:A retrospective analysis was conducted on patient information collected from county-level disease prevention and control centers in Ankang City from 2019 to 2023. Data included demographic information, clinical treatment, chronic disease management, treatment records, work reports, and summaries. The study aimed to learn about the treatment willingness, methods, and effects of patients with fluorosis, and to evaluate the disease management situation of patients with fluorosis.Results:From 2019 to 2023, the proportion of fluorosis patients who were willing to receive treatment in Ankang City had increased from 76.80% (1 089/1 418) in 2019 to 100% (1 408/1 408) in 2023, showing an upward trend year by year (χ 2trend = 971.15, P < 0.001). A total of 6 876 patients received treatment, with a treatment rate of 100%. The majority of patients received drug treatment (99.64%, 6 851/6 876), with an effective rate of 94.90% (6 525/6 876). The effective rate of treatment for patients with fluorosis had increased from 88.71% (966/1 418) in 2019 to 94.67% (1 333/1 408) in 2023, showing an upward trend (χ 2trend = 1 002.92, P < 0.001). The adverse reaction rate of drug treatment was 0.36% (25/6 876). The combination of oral medication and local treatment had the highest effective rate (97.62%, 3 566/3 653). The management rate and contracted service rate of fluorosis patients were 100% each year, and the standardized management rate was above 99%. Conclusions:Fluorosis patients in Ankang City have a high willingness to receive treatment, with good treatment outcomes. The contracted services and management of patients are well implemented. In the future, continuous efforts should be made to improve the prevention, management, and health education of fluorosis patients.

Objective:To explore the value of 18F-fluorodeoxyglucose ( 18F-FDG) PET-CT dual-modality habitat imaging technology in predicting the epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma. Methods:This study was designed as a cross-sectional study. Clinical and imaging data of 403 patients with lung adenocarcinoma who underwent 18F-FDG PET-CT imaging with definitive EGFR results from January 2018 to April 2022 at the Third Affiliated Hospital of Soochow University were retrospectively analyzed.The patients were divided into a development set (282 cases) and a validation set (121 cases) using a stratified random sampling method at a 7∶3 ratio. An adaptive clustering algorithm was used to segment the regions of interest, forming different habitats and obtaining derived parameters. Independent samples t-test or Mann-Whitney U test were used to compare clinical, imaging indicators, and habitat-derived parameters between EGFR mutant and wild-type patient. The clinical, imaging indicators, and habitat-derived parameters that showed statistically significant differences in univariate analysis were included in multivariate logistic regression to construct clinical and clinical-habitat combined models, respectively. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the model′s ability to predict EGFR mutations in lung adenocarcinoma. Additionally, the net reclassification index (NRI) was employed to assess the model′s classification improvement capability. Results:There were 249 cases of EGFR mutation and 154 cases of wild type. The optimal number of habitats was two, namely Habitat 1 and Habitat 2. The parameters included in the clinical model were smoking history, bronchial sign, pleural indentation sign, and tumor diameter. The parameters incorporated into the clinical-habitat combined model were smoking history, bronchial sign, pleural indentation sign, Habitat 2, and Habitat 1 voxel count. In the development set, the AUCs for predicting EGFR mutations in lung adenocarcinoma using the clinical model and the clinical-habitat combined model were 0.723 and 0.733, respectively, with no statistically significant difference ( Z=0.60, P=0.549); In the validation set, the AUCs were 0.684 and 0.715, respectively, with no statistically significant difference ( Z=1.32, P=0.186). The accuracy (0.694) and specificity (0.609) of the clinical-habitat combined model in the validation set were slightly higher than those of the clinical model (0.686 and 0.565, respectively). NRI analysis confirmed that the clinical-habitat combined model improved the correct classification of EGFR wild-type lung adenocarcinoma by 10.9% compared to the clinical model ( P=0.018). Conclusion:18F-FDG PET-CT dual-modality habitat imaging technology can be used to analyze the microenvironment of lung adenocarcinoma and has the potential in non-invasively predicting EGFR mutation status, providing an important basis for personalized and accurate treatment of patients with lung adenocarcinoma.

Objective:To establish an in vitro cell model simulating acute graft-versus-host disease(aGVHD)bone marrow microenvironment injury with the advantage of mouse serum of aGVHD model and explore the effect of serum of aGVHD mouse on the adipogenic differentiation ability of mesenchymal stem cells(MSCs).Methods:The 6-8-week-old C57BL/6N female mice and BALB/c female mice were used as the donor and recipient mice of the aGVHD model,respectively.Bone marrow transplantation(BMT)mouse model(n=20)was established by being injected with bone marrow cells(1 × 10'per mouse)from donor mice within 4-6 hours after receiving a lethal dose(8.0 Gy,72.76 cGy/min)of y ray general irradiation.A mouse model of aGVHD(n=20)was established by infusing a total of 0.4 ml of a mixture of donor mouse-derived bone marrow cells(1 × 107 per mouse)and spleen lymphocytes(2 × 106 per mouse).The blood was removed from the eyeballs and the mouse serum was aspirated on the 7th day after modeling.Bone marrow-derived MSCs were isolated from 1-week-old C57BL/6N male mice and incubated with 2％,5％and 10％BMT mouse serum and aGVHD mouse serum in the medium,respectively.The effect of serum in the two groups on the in vitro adipogenic differentiation ability of mouse MSCs was detected by Oil Red O staining.The expression levels of related proteins PPARy and CEBPα were detected by Western blot.The expression differences of key adipogenic transcription factors including PPARy,CEBPα,FABP4 and LPL were determined by real-time quantitative PCR(RT-qPCR).Results:An in vitro cell model simulating the damage of bone marrow microenvironment in mice with aGVHD was successfully established.Oil Red O staining showed that the number of orange-red fatty droplets was significantly reduced and the adipogenic differentiation ability of MSC was impaired at aGVHD serum concentration of 10％compared with BMT serum.Western blot experiments showed that adipogenesis-related proteins PPARy and CEBPα expressed in MSCs were down-regulated.Further RT-qPCR assay showed that the production of PPARy,CEBPα,FABP4 and LPL,the key transcription factors for adipogenic differentiation of MSC,were significantly reduced.Conclusion:The adipogenic differentiation capacity of MSCs is inhibited by aGVHD mouse serum.