This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.

Hepatitis B virus (HBV)-specific CD8⁺ T cells play a central role in controlling HBV infection; however, their function is impaired during chronic HBV infection, manifesting as a state of dysfunction. Recent studies have revealed that CD8⁺ T cell dysfunction in chronic HBV infection differs from the classical exhaustion observed in other viral infections or tumors. In 2024, several pivotal studies further elucidated novel mechanisms underlying CD8⁺ T cell dysfunction in chronic HBV infection and identified new therapeutic targets, including 4-1BB and transforming growth factor-beta (TGF-β). This review, while elucidating the dysfunction of CD8⁺ T cells in chronic HBV infection and its underlying mechanisms, focuses on summarizing the key findings from these latest studies and explores their translational value and clinical significance.
Humans ; Hepatitis B, Chronic/virology* ; CD8-Positive T-Lymphocytes/immunology* ; Hepatitis B virus/physiology* ; Animals ; Transforming Growth Factor beta/immunology*

OBJECTIVES: The major histocompatibility complex class I chain-related gene A (MICA), a component of the human leukocyte antigen (HLA) gene complex, is involved in the pathogenesis of various diseases including cancers and autoimmune disorders. Rosacea, a chronic inflammatory skin disease with a complex pathogenesis, potentially influenced by genetic and autoimmune factors. This study aims to investigate the relationship among MICA gene polymorphisms, single nucleotide polymorphisms (SNPs), and susceptibility to rosacea, thereby offering new insights into the disease mechanism. METHODS: Peripheral blood DNA samples were collected from 84 patients with rosacea (rosacea group) and 223 healthy volunteers (control group) who visited the Dermatology Outpatient Department of Xiangya Hospital of Central South University between November 2017 and November 2019. MICA genotyping was performed using polymerase chain reaction-sequencing-based typing (PCR-SBT) and the next-generation sequencing (NGS), and the accuracy of the 2 methods was compared. The frequency distributions of MICA alleles between the 2 groups were analyzed. Amino acid clustering and SNP site analyses were conducted to identify haplotype-linked SNPs and to classify MICA polymorphic variants. Distribution differences of these classifications between groups were also examined. RESULTS: Blood tests in rosacea patients showed mildly elevated, with no significant changes in lymphocyte counts. Both PCR-SBT and NGS accurately identified MICA alleles. The most common alleles in the rosacea group were MICA*010:01, MICA*008:04, and MICA*019:01. The frequencies of MICA*002:01 and MICA*027 were significantly lower in the rosacea group compared to controls (6.55% vs 18.16% and 1.19% vs 5.38%, respectively), while and MICA*010:01 were significantly higher (7.74% vs 3.36% and 31.55% vs 18.61%, respectively; all P<0.05). Five short tandem repeat (STR) alleles were identified. Frequencies of MICA-A4 and MICA-A9 were lower in the rosacea group than in the control group (16.07% vs 23.32% and 7.74% vs 17.26%, respectively), whereas MICA-A6 was higher (10.12% vs 4.03%; all P<0.05). Clustering and SNP analysis identified 6 linked SNP sites, classifying MICA variants into Type I (C₃₆+M₁₂₉+K₁₇₃+G₂₀₆+W₂₁₀+S₂₁₅) and Type II (Y₃₆+V₁₂₉+E₁₇₃+S₂₀₆+R₂₁₀+T₂₁₅). Type I MICA variants were significantly associated with rosacea susceptibility. CONCLUSIONS MICA gene polymorphisms are associated with susceptibility to rosacea, and there are 6 linked SNP sites within the MICA gene. Based on this, MICA polymorphic variants are classified into Type I and Type II, with Type I being more closely associated with disease development of rosacea.
Humans ; Polymorphism, Single Nucleotide ; Histocompatibility Antigens Class I/genetics* ; Rosacea/genetics* ; Genetic Predisposition to Disease/genetics* ; Female ; Male ; Adult ; Middle Aged ; Genotype ; Alleles ; Gene Frequency ; Haplotypes ; Case-Control Studies ; Aged ; High-Throughput Nucleotide Sequencing

OBJECTIVES: To investigate the regulatory role of the NLRP3 signaling pathway in hepatocyte pyroptosis in nonalcoholic steatohepatitis (NASH) under hypoxia. METHODS: Twenty-four male C57BL/6 mice were randomized equally into hypoxic control (A), hypoxic NASH model (B), hypoxic NASH+NLRP3 inhibitor (C), and hypoxic NASH+caspase-1 inhibitor (D) groups. In groups B-D, the mice were fed a methionine choline-deficient (MCD) diet under hypoxic conditions (to simulate a 5000 m altitude) for 6 weeks; the mice in groups C and D received intraperitoneal injections of the respective inhibitors every other day. RESULTS: Compared with those in group A, the mice in group B showed significantly elevated serum levels of FBG, TC, TG, ALT and AST, increased liver lipid content, inflammatory cell infiltration and collagen fiber deposition, and enhanced hepatic expressions of NLRP3, caspase-1, IL-1β and GSDMD proteins, with obvious swelling, cristae breakage, vacuolization, and outer membrane disruption of the mitochondria, ribosome loss in the cytoplasm, destruction of the nuclear membrane, and pathological changes of the rough endoplasmic reticulum. Treatment with NLRP3 inhibitor and caspase-1 inhibitor both significantly lowered serum levels of TC, TG, ALT and AST (but without significantly affecting FBG) in the mouse models, and reduced liver lipid content, inflammatory cell infiltration, collagen deposition, and expression levels of NLRP3, caspase-1, GSDMD and IL-1β. The treatments also significantly improved pathological changes in the mitochondria, ribosomes and endoplasmic reticulum in liver tissues of the mice. CONCLUSIONS NLRP3 signaling pathway plays a key role in promoting hepatocyte pyroptosis in NASH mice under hypoxic condition, and inhibiting this pathway can effectively reduce liver inflammation, suggesting its potential as a therapeutic target for NASH treatment.
Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Mice, Inbred C57BL ; Male ; Hepatocytes/pathology* ; Signal Transduction ; Mice ; Hypoxia/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

The mechanism of Tibetan medicine Zuotangkaca pills (ZTKCW) for the treatment of hypertension was explored by network pharmacology and in vivo experiments. 68 active ingredients of ZTKCW and 518 drug-disease targets were screened by network pharmacology. Eight core components of ZTKCW (vasicolinone, luteolin, (–)-isocorypalmine, esculetin, liquiritigenin, etc.) and eight key targets (AKT1, TNF, IL6, and STAT3, etc.) were screened by network topology analysis. KEGG enrichment analysis showed that the core targets were mainly enriched in lipids and atherosclerosis, JAK/STAT, and inflammation-related pathways. An in vivo experiment was conducted using spontaneously hypertensive rats (SHR), which were gavaged with ZTKCW at doses of 0.41, 0.82, and 1.64 g/kg for 12 weeks, respectively. The results showed that ZTKCW at a dose of 1.64 g/kg significantly reduced both systolic and diastolic pressure in SHR rats and decreased the phosphorylation levels of AKT1, PI3K, STAT3, and JAK2 in the thoracic aorta and heart tissues. This study demonstrates that ZTKCW may exert its antihypertensive effects through PI3K/AKT and JAK2/STAT3 pathways, providing some insights and a theoretical basis for the use of ZTKCW in hypertension.

Objective To investigate the relationship between systemic lupus erythematosus(SLE)and hypothyroidism using bidirectional two-sample Mendelian randomization(MR)method.Methods The Genome-Wide Association Study data of SLE and hypothyroidism were obtained online.Independent single nucleotide polymorphisms closely related to SLE were screened as instrumental variable(Ⅳ),and outlier values were tested and eliminated by MR-PRESSO tool of R 4.3.1 software.The inverse variance weighted(IVW),MR-Egger,weighted mode(WM),weighted median(WME)and simple mode(SM)were used for MR analysis,and the values of odds ratio(OR)and 95％confidence interval(95％CI)were used to evaluate whether there was an association between SLE and hypothyroidism.The Cochran's Q heterogeneity test was performed for the results of IVW and MR-Egger,the pleiotropy test was performed by Egger-intercept method,and the sensitivity analysis was performed by elimination test one by one.F value was calculated to evaluate whether there was a weak Ⅳ bias.Results MR analysis results showed that there was a positive causal relationship between SLE and hypothyroidism in the overall population,and the results calculated by IVW,MR-Egger,WM and WME were statistically significant,with OR(95％CI)being 1.004(1.002-1.005),1.004(1.001-1.008),1.004(1.002-1.007),and 1.004(1.002-1.006),respectively.The heterogeneity test results for IVW and MR-Egger were P=0.086 and P=0.098,respectively,indicating no heterogeneity;the Egger-intercept result was P=0.295,indicating no pleiotropy;sensitivity analysis showed MR results were stable;and all F values were greater than 10,indicating no weak Ⅳ bias.Conclusion Compared with healthy people,the risk of hypothyroidism in patients with SLE is significantly higher.

Objective To analyze the effect of Hsa-circ-0101216 on gemcitabine(GEM)chemotherapy resistance in pancreatic cancer and its mechanism.Methods Differentially expressed circRNAs between GEM-resistant pancreatic cancer cells and parent cells were screened using the GEO database.Pancreatic cancer GEM resistant cell lines(BxPC-3-GEM and Capan-1-GEM)were constructed by intermittent concentration gradient method.qRT-PCR was used to detect the expression of Hsa-circ-0101216 in cells.GEM resistant pancreatic cancer cell lines were taken and divided into sh-circ-0101216 group(knockdown of circ-0101216),sh-NC group(transfected with sh-NC),and blank control group(untreated).CCK-8 assay and EdU proliferation assay were used to detect the half inhibitory concentration(IC50)of GEM and proliferation ability of cells in each group.Western blotting was performed to detect the expression of multidrug resistance-related protein 1(MRP1),breast cancer resistance protein(BCRP),and human equilibrative nucleoside transporter-1(hENT-1).A subcutaneous xenograft tumor model of human pancreatic cancer in nude mice was constructed,and sh-NC+GEM group and sh-circ-0101216+GEM group(n=6)were set up.The volume and weight of xenograft tumor in nude mice were compared between the two groups.Western blotting and immunohistochemistry were used to detect the expression of MRP1,BCRP,and hENT-1 proteins in xenograft tumor tissues,and EDU proliferation assay was used to detect the proliferation ability of tumor cells.Results The GEO database screening showed that Hsa-circ-0101216 was up-regulated in GEM-resistant pancreatic cancer cell lines.Pancreatic cancer GEM-resistant cell lines were successfully constructed,and the expression levels of Hsa-circ-0101216 and the IC50 value in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly higher than those in parental cells(P<0.05).In sh-circ-0101216 group,the IC50 values of GEM,cell viability,EdU positivity rate,and the expression levels of MRP1 and BCRP proteins in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly lower than those in blank control group and sh-NC group,while the expression level of hENT-1 protein was significantly higher(P<0.05 or P<0.001).In sh-circ-0101216+GEM group,the weight and volume of subcutaneous xenograft tumors in nude mice,the expression levels and positive expression rates of MRP1 and BCRP proteins in tumor tissues,and the EdU positive rate were significantly lower than those in sh-NC+GEM group,while the expression level and positive expression rate of hENT-1 protein were significantly higher(P<0.05).Conclusions Hsa-circ-0101216 is highly expressed in GEM-resistant pancreatic cancer cell lines.Its knockdown can inhibit the proliferation of pancreatic cancer cells and enhance the chemosensitivity of pancreatic cancer cells to GEM.The mechanism may be related to the regulation of transmembrane transporter protein expression.

OBJECTIVE: To assess the feasibility of first polar body transfer (PB1T) combined with preimplantation mitochondrial genetic testing for blocking the transmission of a pathogenic mitochondrial DNA 8993T>G mutation. METHODS: A Chinese family affected with Leigh syndrome which had attended the Reproductive Medicine Centre of the First Affiliated Hospital of Anhui Medical University in September 2021 was selected as the study subject. Controlled ovarian hyperstimulation was carried out for the proband after completing the detection of the mitochondrial DNA 8993T>G mutation load among the pedigree members. Mature MII oocytes were inseminated by intracytoplasmic sperm injection (ICSI), cultured in vitro for 5 to 6 days to the blastocyst stage, and trophoblastocytes were obtained by microbiopsy. Mitochondrial DNA testing (PGT-MT) and chromosomal aneuploidy (PGT-A) analyses were carried out after whole-genome amplification, and the embryos with zero mutation load were selected for transfer. Amniotic fluid and umbilical cord blood samples were collected during middle pregnancy and after birth respectively for mitochondrial DNA testing to verify the reliability of embryo screening. As an attempt, PB1 with good morphology of MII oocytes was selected for transfer into the enucleated oocytoplasm from healthy donors, followed by ICSI fertilization, blastocyst culture and PGT of embryos using the same procedure. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University (No. 2021zhyx-B12). RESULTS: An antagonist protocol was used for ovarian stimulation, and a total of 19 oocytes were obtained, of which 14 MII were fertilized by ICSI, and 2 had developed into blastocysts. PGT-MT was carried out on biopsied trophoblastocytes, in which the mitochondrial DNA 8993T>G mutation load was not detected in one embryo, the other was 100% mutated, and the mutation loads of the remaining unfertilized eggs and developmentally arrested embryos ranged from 0% ~ 100%, presenting a clear biased distribution. With fully informed consent, one PGT-MT zero mutation load blastocyst was transferred and clinical pregnancy was achieved. Mitochondrial DNA and chromosomal testing of amniotic fluid cells during middle pregnancy had revealed no abnormalities. The proband had delivered a healthy boy through Caesarean section at 39⁺⁵ weeks of gestation, and no mutation was detected in the cord blood sample. Five well-formed PBs from 14 eggs were selected for PB1 transfer, followed by ICSI and culture, and two of the reconstituted embryos had formed blastocysts, with none of the above mutations detected in the biopsied samples. CONCLUSION The PGT-MT technology can help families affected with mitochondrial diseases to have healthy offspring. PB1 transfer in combination with ICSI and PGT-MT holds the promise of turning waste into treasure and providing an alternative means of fertility for such families.
Humans ; Preimplantation Diagnosis/methods* ; Female ; DNA, Mitochondrial/genetics* ; Genetic Testing/methods* ; Pregnancy ; Mitochondrial Diseases/genetics* ; Polar Bodies ; Adult ; Feasibility Studies ; Sperm Injections, Intracytoplasmic/methods* ; Embryo Transfer/methods* ; Mutation ; Male ; Blastocyst/metabolism* ; Pedigree

Objective:To examine the risk factors and predictive value of depression following mild acute ischemic stroke in elderly individuals.The aim is to enhance early identification and intervention, ultimately leading to improved prognosis.Methods:A case-control study was conducted on 988 elderly patients with mild acute ischemic stroke.The study collected general population and social data, as well as clinical laboratory data such as blood glucose, blood lipids, and AD7C-NTP in urine.Additionally, the patients underwent assessments using the Montreal Cognitive Assessment Scale(MoCA), National Institutes of Health Stroke Scale(NHISS), Barthel index(BI), Hamilton Anxiety Scale(HAMA), and Hamilton Depression Scale(HAMD).Based on the HAMD depression scale score, the patients were divided into a nopost-stooke depression(NPSD)group and a post-stooke depression(PSD)group.The study then analyzed the related risk factors and predictive value of PSD.Results:A total of 988 patients were eligible for inclusion, with 132 being excluded and 856 being included.The NPSD and PSD groups showed significant differences in age, hypertension, smoking history, education level, and stroke history(all P<0.05).Regarding clinical data, there were statistically significant differences between the two groups in total cholesterol(TC), triacylglycerol(TG), HDL, urinary AD7C-NTP, MoCA, and HAMA scores(all P<0.05).The results of the multi-factor logistic regression analysis revealed that gender( OR=1.975, 95% CI: 1.223-3.190, P=0.005), stroke history( OR=1.352, 95% CI: 0.877-2.086, P=0.042), and HAMA score( OR=1.216, 95% CI: 0.932-1.526, P=0.043)were identified as independent risk factors for post-stroke depression in the elderly.Conversely, MoCA score( OR=0.873, 95% CI: 0.814-0.937, P<0.001)was found to be an independent protective factor.Furthermore, the ROC curve analysis demonstrated that the HAMA score(AUC=0.892, sensitivity: 0.721, specificity: 0.854, cut-off value: 9.5)exhibited significant predictive value, while the other indexes had limited predictive value. Conclusions:Gender, stroke history, and HAMA score have been identified as potential independent risk factors for post-stroke depression(PSD)in the elderly, while MoCA score may serve as an independent protective factor.Notably, HAMA score demonstrates a strong predictive ability for PSD.Early identification of these factors and timely intervention could significantly contribute to improving prognosis.