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 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.

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

To achieve rapid and visual detection of Plasmodium vivax,a detection method based on recombinase polymerase amplification(RPA)technology and lateral flow dipstick(LFD)was established and evaluated.Targeting the conserved sequence of the P.vivax 18S rRNA gene(GenBank:DQ660817.1)as the target sequence,primers and probes were designed with Primer Premier 5,and the P.vivax recombinant plasmid(pUCPv)was constructed as the standard.A sensitive and specific RPA-LFD-based rapid visual detection method for P.vivax nucleic acids was established.The plasmid standard was serially diluted 10-fold to concentrations of 1×103,1×102,1×101,1×10?,and 1×10?1 copies/μL for sensitivity testing.To evaluate specificity,whole blood DNA samples from patients infected with Plasmodium falciparum,Plasmodium malariae,Plasmodium ovale,or Leishmania donovani,as well as healthy participants,were tested by RPA-LFD.Additionally,The assay′s accuracy was evaluated by testing whole blood DNA samples from 24 confirmed P.vivax-infected patients.This study successfully established a sensitive,specific,and rapid visual RPA-LFD method for detecting P.vivax nucleic acids.The assay can complete P.vivax detection within 20 minutes under isothermal conditions at 39 ℃,achieving a sensitivity of 1 copy/μL.There is no significant cross reaction with parasites such as other Plasmodium species and L.donovani,and the specificity is 100%.All 24 DNA samples from confirmed P.vivax patients were detected,showing a 100%detection rate.The developed RPA-LFD assay exhibits excellent sensitivity and specificity,requires only simple heating equipment,and is user-friendly.This rapid visual detection method is particularly suitable for P.vivax screening in low-resource settings.

Objective:To investigate the relationship between Ig class switch recombination(CSR)and mismatch repair(MMR)protein,microsatellite phenotype in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue(MALT lymphoma).Methods:Forty cases of MALT lymphoma archived in the Department of Pathology,Jiading District Central Hospital,Shanghai University of Medicine & Health Sciences were selected as the observation group,and twenty cases of benign lymphoid tissue hyperplasia were as the control group.The expressions of IgG,IgM,IgD,and IgA in both groups were detected by immunohistochemical double staining,and MMR proteins including MLH1,MSH2,MSH6,and PMS2 in both groups were detected by immunohistochemistry.Multiplex fluorescence PCR capillary electrophoresis was used to detect microsatellite phenotype in tumor and adjacent tissues of the experimental group.Results:In the observation group,the proportions of single Ig heavy chain expression(mode Ⅰ),negative expression(mode Ⅱ),and multiple expression(mode Ⅲ)were 65％(26/40),27.5％(11/40),and 7.5％(3/40),respectively,while in the control group were 0(0/20),5％(1/20),and 95％(19/20).The proportion of Ig heavy chain expression mode Ⅰ+Ⅱ in the observation group was 92.5％,which was significantly higher than 5％in the control group(P＜0.0 1).In the observation group,partial deletion of MMR protein was observed in 3 cases(7.5％),including 2 cases of MSH6 deletion and 1 case of both MSH6 and PMS2 deletion.In the control group,there was 1 case(5％)with PMS2 deletion.There was no significant difference in the deletion rate of MMR protein between the two groups(P＞0.05).A total of 5 cases of microsatellite instability(MSI)were detected in the observation group,including 1 case of low-frequency MSI(MSI-L),4 cases of high-frequency MSI(MSI-H),and 2 cases of MSI-H with MSH6 deletion.When the loss expression of MSI-H or MMR protein was counted as a positive result,the MSI-H rate detected by PCR capillary electrophoresis was 10％(4/40),which was slightly higher than the MMR protein deletion rate detected by immunohistochemistry(7.5％,3/40),but there was no statistically significant difference between the two groups(P＞0.05).The MMR protein deletion rates among the Ig heavy chain protein expression mode Ⅰ,mode Ⅱ,and mode Ⅲ groups were 0(0/26),18.2％(2/11),and 33.3％(1/3),respectively.There was a statistically significant difference in the constituent ratios among the three groups(P＜0.05).The MMR protein deletion rates among the MSS,MSI-L,and MSI-H groups were 2.9％(1/35),0(0/1),and 50％(2/4),respectively.There was a statistically significant difference in the constituent ratios among the three groups(P＜0.05).MMR protein deficiency was positively correlated with Ig heavy chain expression pattern and MSI(r=0.41,P＜0.05;r=0.48,P＜0.05),but Ig heavy chain expression pattern was not correlated with MSI(r=0.02,P＞0.05).Conclusion:Ig heavy chain CSR detection is helpful for the differential diagnosis of MALT lymphoma.Low frequency MMR protein deletion and MSI-H phenotype exist in MALT lymphoma,which may be of certain value for the study of its occurrence,development and clinical treatment.

Objective To investigate the effect of individual pretreatment of preoperative medical multi-dimensional carbohydrates on intraoperative body temperature in elderly patients with hip replacement under general anesthesia. Methods A total of 81 elderly patients who underwent unilateral hip replacement in Yancheng Third People's Hospital from January 2022 to June 2024 were selected as the study subjects,and they were randomly divided into the conventional group and the pretreatment group. Both groups of patients were given routine fasting and drinking restriction before operation,and patients in the pretreatment group were given individual pretreatment of 5 mL/kg medical multi-dimensional carbohydrates 2 hours before anesthesia. The perioperative related indicators,body temperature,intraoperative hypothermia,adverse reactions during the recovery period,and pre-anesthesia gastric antral ultrasound examination results of patients in the two groups were compared. Results There was no statistically significant difference in the surgical time or intraoperative intravenous fluid infusion between the two groups (P>0.05). The anesthesia recovery time,tracheal extubation time and intraoperative bleeding volume of patients in the pretreatment group were significantly shorter/less than those in the conventional group (P<0.05). At 30 minutes,60 minutes and the end of the surgery,the body temperature of patients in the pretreatment group was significantly higher than that in the conventional group (P<0.05),and the incidences of intraoperative hypothermia and shivering in the pretreatment group were significantly lower than those in the conventional group (P<0.05). There was no statistically significant difference in the cross-sectional area (CSA) of gastric antrum,gastric volume (GV) or ratio of gastric volume/weight (GV/W) between the two groups of patients (P>0.05). Conclusion The individual pretreatment of 5 mL/kg medical multi-dimensional carbohydrates before surgery can significantly reduce the incidence of intraoperative hypothermia in elderly patients with hip replacement under general anesthesia,promote anesthesia recovery,reduce intraoperative bleeding volume and adverse reactions,and not increase the risk of reflux aspiration.