Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

OBJECTIVE To formulate the Hazardous Drug List in China， and provide a scientific basis for standardizing the management of hazardous drugs， preventing and controlling occupational exposure risks in medical institutions at all levels in China. METHODS Under the joint organization of the Intravenous Medication Admixture Management Professional Committee of the Chinese Pharmaceutical Association and the National Medical Quality Control Center for Pharmaceutical Management， based on literature research and international hazardous drug lists and their development procedures， the scope of hazardous drug selection， selection principles， and evidence confirmation criteria were determined through expert panel seminars and expert questionnaire survey method （Delphi method）. Chemical drugs， biological agents， and Chinese patent medicines marketed in China that met the selecti on principles were screened to form the Chinese Expert Consensus on the Hazardous Drug List . RESULTS Five principles for selecting hazardous drugs were established （including protective labeling in package inserts， carcinogenicity， reproductive toxicity， genotoxicity， and organ toxicity at low doses）， along with the corresponding evidence confirmation criteria. The Hazardous Drug List containing 210 drugs was formulated， covering anti-tumor drugs， endocrine system drugs， nervous system drugs， immunomodulators， anti-infective drugs， cardiovascular system drugs， hematological system drugs， urinary system drugs， obstetrics and gynecology drugs， dermatological drugs and other categories. Compared with international hazardous drug lists， 25 newly included hazardous drugs were added， including 15 anti-tumor drugs， 6 Chinese patent medicines and 4 biological agents. In addition， 88 Chinese patent medicines that may have potential occupational exposure risks are listed in the appendix for reference by medical institutions in management. CONCLUSIONS The development of this consensus closely aligns with the actual clinical drug use in China， with a scientific and rigorous methodology， and can serve as a reference for medical institutions at all levels to standardize the management of hazardous drugs and prevent and control occupational exposure risks.

ObjectiveTo explore the effect of respiratory training based on core stabilization training on lumbar disc herniation. MethodsFrom January, 2023 to October, 2024, 96 patients with lumbar disc herniation admitted to the First Affiliated Hospital of Bengbu Medical University were divided into control group (n = 32), core group (n = 32) and respiratory group (n = 32). All the groups underwent conventional rehabilitation therapy, with core stabilization training in the core group and respiratory training combined with core stabilization training in the respiratory group, additionally, for four weeks. Before and after training, the scores of Visual Analogue Scale, Japanese Orthopaedic Association (JOA) and Oswestry Dysfunction Index (ODI) were compared, the average electromyographic value (AEMG) and root mean square (RMS) value of the multifidus and transversus abdominis were detected by surface electromyography (sEMG); and the thickness of the multifidus and transversus abdominis were measured by musculoskeletal ultrasonography bilaterally. ResultsThe intra-group effect (F > 597.796, P < 0.001), inter-group effect (F > 16.535, P < 0.001) and interaction effect (F > 49.622, P < 0.001) were significant in the scores of VAS, JOA and ODI; which were better in the respiratory group than in the control group and the core group (P < 0.05), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 7971.631, P < 0.001), inter-group effect (F > 177.760, P < 0.001) and interaction effect (F > 478.771, P < 0.001) were significant in the thickness of the transversus abdominis and multifidus; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 144303.007, P < 0.001), inter-group effect (F > 1495.458, P < 0.001) and interaction effect (F > 3121.361, P < 0.001) were significant in the RMS of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 1890.532, P < 0.001), inter-group effect (F > 607.132, P < 0.001) and interaction effect (F > 824.923, P < 0.001) were significant in the AEMG of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). ConclusionCore training combined with respiratory training can more effectively reduce pain and improve dysfunction by enhancing the strength and control of the core muscles， thus improving the quality of life of patients with lumbar disc herniation.

Objective To analyze the impact of the National Centralized Drug Procurement Policy(hereinafter referred to as the"centralized procurement policy")on the utilization of breast cancer treatment drugs in a specialized cancer hospital.Methods The defined daily dose(DDD)method was used to compare the daily drug cost(DDC),drug utilization frequency(DDDs),and affordability of letrozole,anastrozole,and capecitabine before and after the implementation of the centralized pro-curement policy in a tertiary specialized cancer hospital in Guangzhou.Results and Conclusion After the policy implementa-tion,the DDC of all three drugs decreased.The out-of-pocket DDC for the selected drugs remained stable or decreased,while the out-of-pocket DDC for both originator drugs and generic drugs increased,with a more pronounced increase for originator drugs.The proportion of DDDs for the selected drugs increased post-policy.The centralized procurement policy not only reduced the prices of selected drugs but also drove down the prices of generic and originator drugs.It is recommended to further expand the scope of centralized procurement for anticancer drugs and the types of cancers covered,as well as to establish a transitional mech-anism for medical insurance payment standards.

Objective:To investigate the efficacy of rigid ureteroscopic laser lithotripsy combined with N-trap(RULL+N-trap),which is scoop-shaped,in the treatment of ureteral stones with a maximum diameter ≥1.5 cm.Methods:This retrospective cohort study included patients diagnosed with ureteral calculi who underwent rigid ureteroscopic lithotripsy(RULL)combined with N-Trap stone entrapment system at the Department of Urology,Peking University Third Hospital,by the same surgical team between June 2021 and September 2024.A total of 364 patients were initially enrolled.After excluding 21 patients due to missing critical outcome variables,two distinct cohorts were established:38 patients with ureteral stones measuring ≥1.5 cm in maximum diameter,and 305 patients with stones＜1.5 cm in maximum diameter.To minimize selection bias and control for confounding variables,propensity score matching(PSM)was employed.This resulted in two well-balanced groups:31 patients with stones 1.5 cm in maximum diameter and 31 patients with stones＜1.5 cm in maximum diameter,matched on baseline demographic and clinical characteristics.The primary outcomes assessed between the two groups included stone clearance.Secondary outcomes included changes in renal function indicators,specifically serum creatinine(SCr)and estimated glomerular filtration rate(GFR),and other factors like postopera-tive hospital stay and operative time.Results:In the matched cohort,the patients with stones ≥1.5 cm in maximum diameter had significantly longer operative time compared with those with smaller stones:(85.8±28.8)min vs.(62.4±24.6)min(P＜0.05).Postoperative length of hospital stay showed no significant difference:(2.26±1.79)d vs.(2.03±0.80)d(P＞0.05).The stone clearance on postoperative day one was 90.3％in the study group vs.100.0％in the control group(P＞0.05).One month postoperatively,the stone clearance was 93.5％vs.100.0％,respectively(P＞0.05).Changes in SCr were(-6.58±16.10)μmol/L vs.(-13.70±12.50)μmol/L,and changes in GFR were(5.92±14.90)mL/(min·1.73 m2)vs.(7.47±11.20)m L/(min·1.73 m2),with no statistically significant differences observed between the two groups for either renal function marker(P＞0.05).Conclusion:Ureteroscopic lithotripsy combined with N-trap is an optional method for treating ureteral stones with a maximum diameter ≥1.5 cm.The overall therapeutic efficacy is comparable,with the added benefit of significantly reducing the economic burden on patients.

Aim To investigate the effect of triptolide(TP)on corticosterone(CORT)-induced depression-like behaviors in mice and explore the antidepressant mechanism of TP based on the CREB/BDNF/TrkB sig-naling pathway.Methods Sixty 8-week-old male C57BL/6J mice were randomly divided into five groups:control group,CORT group,TP groups of low and high doses(10,30 μg·kg-1),and fluoxetine(FLU)group(10 mg·kg-1).Except for the control group,the other groups received subcutaneous injec-tions of CORT for three consecutive weeks to establish the model of depression.During the last two weeks of modeling,normal saline,TP and FLU were adminis-tered via intraperitoneal injection respectively.After the administration,depression-like behaviors in mice were assessed using forced swimming test,tail suspen-sion test,and sucrose preference test.Biochemical methods were used to measure the levels of SOD and MDA in the hippocampus and prefrontal cortex(PFC).Cell apoptosis was detected by TUNEL meth-od.Immunohistochemistry,immunofluorescence,and Western blotting were employed to detect the expres-sion of apoptosis/autophagy-related proteins,synaptic structure markers,and proteins related to the CREB/BDNF/TrkB signaling pathway.Results TP signifi-cantly ameliorated CORT-induced depression-like be-haviors in mice,mainly manifested by reduced immo-bility time in the tail suspension test and forced swim-ming test,and increased sucrose preference rate.TP alleviated CORT-induced oxidative stress by increasing SOD levels and reducing MDA production in brain tis-sue.Additionally,TP also inhibited apoptosis and ex-cessive autophagy of neurons in the hippocampus and prefrontal cortex,maintained synaptic plasticity,and significantly upregulated the expression of p-CREB,BDNF,and TrkB.Conclusions TP exhibits potential antidepressant effect in mice by upregulating the CREB/BDNF/TrkB signaling pathway,reducing oxida-tive stress,inhibiting excessive neuronal apoptosis and autophagy,and improving synaptic plasticity.

BACKGROUND:Radiotherapy for head and neck tumors can easily cause xerostomia,seriously affecting the quality of life of patients.In recent years,engineered stem cells and their paracrine factors have shown therapeutic potential in the repair of salivary gland injury.However,there is currently no experimental study on the application of amniotic mesenchymal stem cell-derived exosome in radiation-induced salivary gland injury.OBJECTIVE:To preliminarily explore the repair effect of exosome derived from human amniotic mesenchymal stem cells on radiation-induced submandibular gland injury.METHODS:H uman amniotic mesenchymal stem cell exosomes were extracted and identified by ultrafiltration and ultracentrifugation.SD rats were randomly divided into a control group,a radiation injury group,and a radiation injury+exosome group.An in vitro model of radiation-induced submandibular gland injury was constructed using the submandibular gland tissue of SD rats irradiated with 18 Gy of radiation.One day after radiation modeling,exosome derived from human amniotic mesenchymal stem cells was injected into the submandibular gland in situ.Samples are taken at 1,3,7,and 14 days to detect the resting salivary flow rate.The structure of the submandibular gland tissue was observed by hematoxylin-eosin staining.The expression of glycogen particles in the submandibular gland tissue was observed by Periodic Acid-Schiff staining.Fibrosis in the submandibular gland tissue was observed by Masson staining.The secretion of salivary amylase was detected by enzyme-linked immunosorbent assay.The expression of aquaporin and tight junction proteins in submandibular gland tissue was observed by immunofluorescence staining.Real-time fluorescence quantitative PCR was used to detect the relative expression levels of aquaporins and salivary amylase mRNA in submandibular gland tissue.TUNEL assay was used to detect the apoptosis rate of submandibular gland tissues in each group.RESULTS AND CONCLUSION:After radiomodeling,compared with the radiation injury group,(1)hematoxylin-eosin staining observed that the submandibular gland tissue structure in the radiation injury+exosome group was restored,the nucleoli increased,the number of acinus increased,and the acinar atrophy improved.(2)Glycogen staining observed that the number and density of positive zymogen granules in the acinar cytoplasm of the radiation injury+exosome group gradually increased.(3)Masson staining results observed that the number and density of positive collagen fibers in the interstitium and around the ducts in the radiation injury+exosome group gradually decreased,the degree of fibrosis decreased,and the collagen deposition decreased.(4)The salivary flow rate in the radiation injury+exosome group increased(P＜0.05).The fluorescence intensity of aquaporin-5 was enhanced(P＜0.05)and the gene expression was significantly enhanced(P＜0.01).The fluorescence distribution of tight junction protein 4 was weakened and the fluorescence intensity decreased(P＜0.05,P＜0.01).The content of salivary amylase increased(P＜0.05)and gene expression were significantly increased(P＜0.01).The number of positive apoptotic cells decreased(P＜0.05,P＜0.01).It is indicated that local injection of exosome derived from human amniotic mesenchymal stem cells could improve the pathological morphology of submandibular gland tissue,promote saliva flow rate and amylase expression,and may play a functional repair role in radioactive submandibular gland injury by inhibiting acinar apoptosis.

This study was aimed at preliminarily investigating the genetic and antimicrobial resistance characteristics of Salmonella Alachua isolates through whole-genome analyses.Five Salmonella Alachua isolates from various sources(both hu-man and non-human)were collected and identified.Phenotype and serotype verification,antimicrobial susceptibility testing,and whole-genome sequencing were performed.Virulence genes,antimicrobial resistance genes,and plasmid replicons were predicted according to globally available Salmonella Alachua genomic data.A phylogenetic tree was constructed to explore the genetic background.The first report of Salmonella Alachua in China emerged in Shanghai in 2015,and patients presented pri-marily with diarrhea.The isolates have been found predominantly in the eastern and southern coastal regions.Among the five i-solates analyzed,four belonged to sequence type(ST)2061,and one belonged to ST1298.All isolates were susceptible to most commonly used clinical antibiotics.Whole-genome analyses revealed that two ST2061 strains carried the blaKPC-2 gene,and one ST1298 strain carried the fosA7 gene.Phylogenetic analysis of global Salmonella Alachua populations indicated that the ST2061 clone belonged to the C1 clade,which was closely related to strains from the UK,whereas the ST1298 clone was found in the C4 clade,a globally disseminated fosA 7-positive lineage.This study provides initial insights into the genetic and antimi-crobial resistance characteristics of Salmonella Alachua in China,highlighting the presence of strains carrying blaKPC-2 and fo-sA7 genes.These findings may provide a reference for future large-scale molecular epidemiological surveillance and source-trac-ing efforts,and they underscore the importance of enhanced resistance monitoring for Salmonella Alachua.

Objective:To explore the value of serum P-selectin,Interleukin-18(IL-18),and Homocysteine(Hcy)levels in predicting the adverse outcomes of interventional therapy in elderly patients with deep vein thrombosis(DVT)in the lower extremities.Methods:A total of 165 elderly patients with DVT from January 2020 to August 2023 were se-lected.All patients underwent transcatheter intervention thrombolysis therapy.Patients were divided into good outcome group and poor outcome group according to the clinical treatment outcome.Serum P-selectin,IL-18,and Hcy levels were compared between the two groups.The correlation between serum P-selectin,IL-18,and Hcy levels and disease indicators,as well as the outcomes of interventional therapy was analyzed.The predictive value of serum P-selectin,IL-18,and Hcy levels for the outcomes of interventional therapy was evaluated.Results:The total effective rate of catheter-based interventional thrombolysis in 165 patients was 81.82%(135/165).The patients with good outcomes were included in the good outcome group,and the patients with poor outcomes were included in the poor outcome group.The difference in circumference between the affected side and the healthy side of the thigh and the difference in circumference between the affected side and the healthy side of the calf in the poor outcome group were greater than those in the good outcome group(P<0.05).The levels of serum P-selectin,IL-18,and Hcy in the poor outcome group were higher than those in the good outcome group(P<0.05).The levels of serum P-selectin,IL-18,and Hcy were posi-tively correlated with the difference in circumference between the affected and healthy thighs and the difference in cir-cumference between the affected and healthy calves,and negatively correlated with the outcome of interventional therapy(P<0.05).Before and after correcting other factors,serum P-selectin,IL-18,and Hcy were all independent risk factors for the outcome of interventional therapy in elderly patients with DVT(P<0.05).The area under the curve(AUC)of serum P-selectin,IL-18,and Hcy for predicting the outcome of interventional therapy for elderly DVT was 0.789(95%CI:0.718-0.848),0.812(95%CI:0.744-0.868),and 0.792(95%CI:0.722-0.851),respectively.The cutoff values were 44.21 ng/mL,185.73 ng/L,and 23.60 μmol/L,with sensitivities of 70.00%,70.00%,and 80.00%,and specificities of 82.22%,82.96%,and 68.15%,respectively.The AUC of the combined prediction of the outcomes of interventional therapy for elderly DVT was 0.935(95%CI:0.886-0.967),with a cutoff value of 44.08 ng/mL,185.16 ng/L,and 23.37 μmol/L for the three variables,with a sensitivity of 86.67%and a specificity of 88.15%.This was significantly better than the individual prediction values of the three variables(Z=5.817,4.753,5.206,all P<0.001).Conclusion:Serum P-selectin,IL-18,and Hcy are significantly correlated with disease indicators and interventional treatment outcomes in el-derly patients with DVT,and can effectively predict the outcome of interventional treatment,with a high combined pre-dictive value.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.