Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Objective:To investigate the clinical effectiveness of Du Meridian moxibustion combined with brisk walking on negative symptoms, cognitive function, and social function in patients with stable schizophrenia, aiming to provide a feasible adjunctive treatment for clinical practice.Methods:A randomized controlled trial was conducted using convenience sampling to recruit 140 patients with stable schizophrenia hospitalized at the Affiliated Brain Hospital of Guangzhou Medical University from April 1, 2023, to March 31, 2024. Patients were randomly assigned to a control group, Du Meridian moxibustion group, brisk walking group, or combined group, with 35 patients in each group. The control group received standard care. On this basis, the Du Meridian moxibustion group received moxibustion on the Du Meridian, the brisk walking group participated in slow walking exercises, and the combined group received both interventions for 12 weeks. Assessments were conducted at baseline, at 6 and 12 weeks during the intervention, and at 12 weeks post-intervention using the Scale for the Assessment of Negative Symptoms, Mini-Mental State Examination, and Social Functioning Scale for Inpatient Psychiatric Patients.Results:A total of 134 patients completed the study: control group ( n = 34), Du Meridian moxibustion group ( n = 34), brisk walking group ( n = 35), and combined group ( n = 31). The combined group demonstrated significantly lower SANS scores at the 12th week of intervention (49.71 ± 4.66) and at 12 weeks post-intervention (53.45 ± 5.34) compared to the Du Meridian moxibustion group (54.91 ± 4.79) and (59.56 ± 5.84), the brisk walking group (56.69 ± 5.59) and (58.51 ± 5.42), control group (65.71 ± 4.95) and (66.21 ± 4.33), with statistically significant differences ( t values were 3.81-13.37, all P<0.05). Regarding cognitive function, the MMSE scores in the combined group at the 12th week of intervention (28.23 ± 1.28) and at 12 weeks post-intervention (27.35 ± 1.76) were higher than those in the Du Meridian moxibustion group (26.79 ± 1.85) and (25.59 ± 2.27) and the brisk walking group (25.88 ± 2.23) and (25.43 ± 1.84), control group (23.65 ± 2.17) and (22.32 ± 2.14), with statistically significant differences ( t values were - 10.28 to - 3.48, all P<0.001). For social function, the SSPI scores in the combined group at the 12th week of intervention (35.71 ± 3.63) and at 12 weeks post-intervention (32.58 ± 3.71) were also significantly higher than those in the Du Meridian moxibustion group (32.21 ± 3.91) and (28.47 ± 3.70) and the brisk walking group (31.83 ± 3.54) and (30.31 ± 3.59), control group (24.53 ± 4.12) and (24.15 ± 3.50) with statistically significant differences ( t values were - 11.56 to - 2.52, all P<0.05). Conclusions:The combination of Du Meridian moxibustion and brisk walking is an effective adjunctive intervention for patients with stable schizophrenia, as it significantly reduces negative symptoms, enhances cognitive function, and improves social functioning.

Aim To explore the mechanism of clar-ithromycin in treating inflammatory bowel disease(IBD)by inhibiting Kv1.3 channel protein in colonic epithelial cells.Methods A chronic IBD rat model was induced using dextran sulfate sodium(DSS)in vi-vo experiments,with clarithromycin intervention.The physical signs of each group of rats were observed,and the disease activity index(DAI)score and colonic mu-cosal damage index(CMDI)score were calculated.RT-qPCR was used to detect the levels of relevant cyto-kines in colonic tissue of rats.Flow cytometry was em-ployed to detect the relative proportions of immune cells in the peripheral blood and colonic tissue of each group of rats.Lipopolysaccharide(LPS)was used to establish an inflammation model of colon epithelial cells(NCM460)to clarify the inhibitory effect of clar-ithromycin on Kv1.3 channel protein.Results In vi-vo experiments:compared to the model group,the clar-ithromycin intervention group exhibited a reduced de-gree of weight loss(P＜0.01),and a significant de-crease in DAI scores(P＜0.01).There was an in-crease in colon length,a reduction in weight,and a de-crease in CMDI scores(P＜0.05).Levels of TNF-α,IL-1 β,and IL-6 in colon tissue were significantly re-duced(P＜0.01).The numbers of peripheral blood and colonic regulatory T lymphocytes(Th),cytotoxic T lymphocytes(CTL),natural killer cells(NK),B lym-phocytes(B),and dendritic cells(DC)were signifi-cantly decreased(P＜0.05).Clarithromycin reduced the expression of Kv1.3 channel protein in colon tissue(P＜0.05).In vitro experiments:compared to the model group,the clarithromycin group significantly pro-moted the proliferation of NCM460 cells(P＜0.01)and simultaneously significantly reduced the levels of TNF-α and IL-6 in cells(P＜0.05).Clarithromycin also reduced the expression of Kv1.3 channel protein in NCM460 cells(P＜0.05).Conclusions Clar-ithromycin may play an immunomodulatory role by in-hibiting the expression of Kv1.3 channel protein,re-ducing inflammation in the body,and playing a role in the treatment of IBD.

In 2015,the International Ascites Club proposed a new definition of hepatorenal syndrome-acute kidney injury based on the progression of hepatorenal syndrome,and studies are still being conducted to explore the exact pathogenesis of hepatorenal syndrome-acute kidney injury.Intestinal barrier plays an important bridging role in liver-kidney connection,and intestinal flora disturbance,bacterial translocation,and endotoxins entering the blood cause damage to the kidneys by releasing proinflammatory cytokines and activating immune-related cells.The entrance of bile acid into the circulation system also directly or indirectly lead to the development and progression of hepatorenal syndrome-acute kidney injury.This article reviews the crosstalk mechanism of hepatorenal syndrome-acute kidney injury from the perspective of the intestinal barrier and further clarifies the key role of the liver-gut-kidney axis in the pathogenesis of this disease,in order to provide new treatment ideas.

Objective To observe the clinical efficacy and safety of dexmedetomidine injection combined with esketamine injection in the treatment of patients with oral squamous cell carcinoma radical resection.Methods Patients with oral squamous cell carcinoma radical resection were randomly divided into treatment and control groups.The treatment group will receive intravenous administration of 0.6 μg·kg-1 dexmedetomidine 10 minutes before anesthesia induction.Subsequently,anesthesia induction will be performed with intravenous administration of 0.5 mg·kg-1 esketamine.Anesthesia maintenance will be achieved with intravenous infusion of 0.25 mg·kg-1·h-1 esketamine and 0.3 μg·kg-1·h-1 dexmedetomidine used an infusion pump.The control group will receive intravenous administration of an equivalent volume of 0.9％NaCl 10 minutes before anesthesia induction.Anesthesia induction will then be performed with intravenous administration of 2.5-5.0 μg·kg-1 fentanyl.Anesthesia maintenance will involve intravenous infusion of 0.10-0.25 μg·kg-1·min-1 remifentanil used an infusion pump.The anesthesia effectiveness,analgesic effectiveness,hemodynamics and safety were compared between the two groups.Results Treatment group were enrolled 62 cases,1 case dropped out,and 61 cases were finally included in the statistical analysis.Control group were enrolled 61 cases,1 case dropped out,and 60 cases were finally included in the statistical analysis.The recovery room stay time of treatment and control groups was(25.97±4.52)and(18.39±3.64)min,the extubation time was(16.75±4.84)and(10.16±3.18)min,and the differences were statistically significant(all P＜0.05).After operation 24 h,visual analogue scores of treatment and control groups were(0.85±0.17)and(1.39±0.25)points,adrenocorticotropin levels were(60.07±7.13)and(72.64±9.81)pg·mL-1,cortisol levels were(481.20±49.15)and(539.94±57.77)nmol·L-1,and the differences were statistically significant(all P＜0.05).The mean arterial pressure at 30 min after anesthesia induction(T1)and at the end of surgery(T2)in treatment group were(82.34±4.98)and(86.57±4.18)mmHg,while those in control group were(77.25±7.16)and(76.02±6.29)mmHg;the heart rates of T1 and T2 in treatment groups were(64.08±4.19)and(66.45±4.83)time·min-1,while those in control group were(68.44±6.02)and(72.08±7.27)time·min-1;and the differences were statistically significant(all P＜0.05).The adverse drug reactions in two groups were nausea,vomiting,bradycardia and dizziness.The total incidences of adverse drug reactions in treatment and control groups were 8.20％and 15.00％,without significant difference(P＞0.05).Conclusion Dexmedetomidine injection combined with esketamine injection has a definitive analgesia efficacy in the treatment of patients with oral squamous cell carcinoma radical resection,which can significantly reduce stress responses,maintain hemodynamic stability,without increasing the incidence of adverse drug reactions.

Objective:This study aims to investigate the predictive performance of serum levels of white blood cell count(WBC),D-dimer(D-D)and N-terminal pro-brain natriuretic peptide(NT-proBNP)for major adverse cardiovascular events(MACE)in elderly patients with acute ST-segment elevation myocardial infarction(ASTE-MI).Methods:A total of 70 elderly patients with ASTEMI treated in Bozhou People's Hospital between April 2020 and May 2023 were prospectively selected as observation group.Incidence of MACE during 1-year follow-up were recorded,another 50 patients with unstable angina pectoris treated in our hospital simultaneously were selected as control group.Serum levels of WBC,D-D and NT-proBNP were compared among above groups.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum WBC,D-D and NT-proBNP for MACE in elderly patients with ASTEMI.A nomogram was established,and calibration curve and deci-sion curve analysis(DCA)were used to evaluate the performance of model.Results:A total of 40 cases(59.70％)experienced MACE during one-year follow-up.Compared to those in control group,patients in observation group had significant higher serum WBC[(11.43±1.98)×109/Lvs.(6.30±1.99)× 109/L],D-D[(0.91±0.20)mg/L vs.(0.47±0.18)mg/L]andNT-proBNP[(192.31±63.19)pg/ml vs.(114.05±22.79)pg/ml](P＜0.001 all).Compared to participants without MACE,those with MACE had significantly higher serum WBC[(13.33±1.90)× 109/L vs.(10.27±0.98)× 109/L],D-D[(1.11±0.25)mg/L vs.(0.87±0.21)mg/L]and NT-proBNP[(238.73±50.22)pg/ml vs.(150.70±39.16)pg/ml](P＜0.001 all).ROC analysis showed that the ar-ea under the curve(AUC)of the combined detection of serum WBC(AUC=0.791,95％CI 0.677～0.879),D-D(AUC=0.767,95％CI 0.650～0.859)and NT-proBNP(AUC=0.733,95％CI 0.614～0.832)was 0.916(95％CI 0.825～0.969),which was significantly higher than those of single detections(Z=2.386,4.953,3.190,P=0.017,0.004,＜0.001).The total score of the nomogram model constructed based on the levels of WBC,D-D and NT-proBNP ranged from 70 to 126 points.The predicted incidence was basically consistent with the actual in-cidence.For the internal verification of the model,the AUC of ROC curve of the training set and the validation set was 0.863 and 0.926 respectively.The DCA curve was located above the critical curve,indicating that the model had a net benefit and good clinical effectiveness.Conclusion:Serum WBC,D-D and NT-proBNP significantly el-evated in elderly patients with ASTEMI.The combined detection of serum WBC,D-D and NT-proBNP levels has good predictive value for MACE in these patients.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective To investigate the brain voxel-mirrored homotopic connectivity(VMHC)alterations in patients with ves-tibular migraine(VM)by using resting-state functional magnetic resonance imaging(rs-fMRI).Methods The rs-fMRI data of 30 VM patients(VM group)and 30 healthy volunteers(control group)were prospectively collected.The brain VMHC values in all subjects were calculated and the differences between the two groups were compared.The correlations between VMHC values of significant brain regions and clinical scale scores were analyzed in the VM group.Results Compared with the control group,the VMHC values of the cerebellum region 6,orbital inferior frontal gyrus,insula,superior temporal gyrus and postcentral gyrus in the VM group were all decreased[cluster-level family wise error(FWE)corrected,Pvoxel-level<0.001,Pcluster-level<0.05].In the VM group,the VMHC values of the postcentral gyrus were negatively correlated with dizziness handicap inventory(DHI)score(r=-0.383,P=0.037).Additionally,the VMHC values of the insula were negatively correlated with headache impact test-6(HIT-6)score(r=-0.430,P=0.018).Conclusion VM patients have altered VMHC in certain brain regions,indicating related dysfunctions in vestibule,pain,hearing and emotion.

Objective To observe the clinical efficacy and safety of dexmedetomidine injection combined with esketamine injection in the treatment of patients with oral squamous cell carcinoma radical resection.Methods Patients with oral squamous cell carcinoma radical resection were randomly divided into treatment and control groups.The treatment group will receive intravenous administration of 0.6 μg·kg-1 dexmedetomidine 10 minutes before anesthesia induction.Subsequently,anesthesia induction will be performed with intravenous administration of 0.5 mg·kg-1 esketamine.Anesthesia maintenance will be achieved with intravenous infusion of 0.25 mg·kg-1·h-1 esketamine and 0.3 μg·kg-1·h-1 dexmedetomidine used an infusion pump.The control group will receive intravenous administration of an equivalent volume of 0.9％NaCl 10 minutes before anesthesia induction.Anesthesia induction will then be performed with intravenous administration of 2.5-5.0 μg·kg-1 fentanyl.Anesthesia maintenance will involve intravenous infusion of 0.10-0.25 μg·kg-1·min-1 remifentanil used an infusion pump.The anesthesia effectiveness,analgesic effectiveness,hemodynamics and safety were compared between the two groups.Results Treatment group were enrolled 62 cases,1 case dropped out,and 61 cases were finally included in the statistical analysis.Control group were enrolled 61 cases,1 case dropped out,and 60 cases were finally included in the statistical analysis.The recovery room stay time of treatment and control groups was(25.97±4.52)and(18.39±3.64)min,the extubation time was(16.75±4.84)and(10.16±3.18)min,and the differences were statistically significant(all P＜0.05).After operation 24 h,visual analogue scores of treatment and control groups were(0.85±0.17)and(1.39±0.25)points,adrenocorticotropin levels were(60.07±7.13)and(72.64±9.81)pg·mL-1,cortisol levels were(481.20±49.15)and(539.94±57.77)nmol·L-1,and the differences were statistically significant(all P＜0.05).The mean arterial pressure at 30 min after anesthesia induction(T1)and at the end of surgery(T2)in treatment group were(82.34±4.98)and(86.57±4.18)mmHg,while those in control group were(77.25±7.16)and(76.02±6.29)mmHg;the heart rates of T1 and T2 in treatment groups were(64.08±4.19)and(66.45±4.83)time·min-1,while those in control group were(68.44±6.02)and(72.08±7.27)time·min-1;and the differences were statistically significant(all P＜0.05).The adverse drug reactions in two groups were nausea,vomiting,bradycardia and dizziness.The total incidences of adverse drug reactions in treatment and control groups were 8.20％and 15.00％,without significant difference(P＞0.05).Conclusion Dexmedetomidine injection combined with esketamine injection has a definitive analgesia efficacy in the treatment of patients with oral squamous cell carcinoma radical resection,which can significantly reduce stress responses,maintain hemodynamic stability,without increasing the incidence of adverse drug reactions.