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 explore and establish the working mechanism for prevention and control of hospital-as-sociated infections in regional oral medical institutions so as to standardize the prevention and control of the hospi-tal-associated infections in the regional oral medical institutions.METHODS Taking an administrative division of Chongqing as example,the matrix evaluation was carried out based on the quality control mode for management of hospital-associated infections in oral medical institutions' action planning,training guidance,quality control super-vision,summary review' organically in combination with'quality control plus law enforcement',a color-co-ded management of the oral medical institutions in the region was implemented,and the effectiveness of improved work in infection control was examined.RESULTS From the perspective of the grade of medical institution,the qualified rates of hospital infection management system construction,architectural layout and process,cleaning,disinfection and sterilization of oral instruments,environmental cleaning and disinfection,isolation,safe injection,use of occupational protection supplies and disposal of medical waste of the primary and unrated medical institu-tions were respectively 26.51％,49.40％,24.10％,37.35％,31.33％,46.99％,67.47％and 51.81％before the improvement and were respectively increased to 67.47％,63.86％,45.78％,66.27％,63.86％,73.49％,84.34％and 66.27％after the improvement,and there were significant differences(P＜0.05).From the perspec-tive of the property of the medical institution,the qualified rates of the above items of the private medical institu-tions were respectively 24.66％,47.95％,21.92％,34.25％,31.51％,45.21％,69.86％and 50.68％before the improvement and were respectively increased to 65.75％,61.64％,42.47％,64.38％,63.01％,71.23％,84.93％and 63.01％after the improvement,and there were significant differences(P＜0.05).CONCLUSION The working mechanism on prevention and control of hospital-associated infections in regional oral medical institu-tions that is established based on'quality control plus law enforcement'with the introduction of social credit can effectively raise the qualified rates of the infection prevention and control measures,which achieves more remarka-ble improvement effectiveness in grass-roots oral medical institutions such as the private,primary and unrat-ed medical institutions.

Objective To explore the relationship between insulin resistance and idiopathic central precocious puberty(ICPP)in girls and the diagnostic value of insulin resistance.Methods Clinical data of 245 girls aged 4 to 7.5 years with low luteinizing hormone(LH)levels(0.2-0.83 IU/L),normal body weight(body mass index standard deviation score between-2 and+2),and early breast development who visited the Department of Pediatric Endocrinology,Henan Provincial Maternal and Child Health Hospital from January 2022 to March 2025 were retrospectively analyzed.According to the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty(2022),patients were assigned to an ICPP group(n=123)or a control group(n=122).Correlations between the homeostasis model assessment of insulin resistance(HOMA-IR)and selected indices were assessed.Multivariable logistic regression was used to evaluate the association between HOMA-IR and ICPP,and the diagnostic performance of various indices for ICPP was evaluated.Results HOMA-IR was higher in the ICPP group than in the control group(P<0.001)and was positively correlated with LH peak(rs=0.467,P<0.05)and the LH peak/FSH peak ratio(rs=0.444,P<0.05).The multivariable logistic regression model including age,BMI,and basal LH showed that HOMA-IR was closely associated with ICPP(OR=2.756,95%CI:1.940-3.913).Receiver operating characteristic curve analysis showed that the areas under the curve for basal LH,HOMA-IR,and their combination in diagnosing ICPP were 0.735,0.735,and 0.805,respectively(P<0.05),and the combined model had a greater area under the curve than either basal LH or HOMA-IR alone(both P<0.05).Conclusions HOMA-IR is closely associated with ICPP in girls with low LH and normal body weight,and combining HOMA-IR with basal LH improves early identification and diagnostic efficiency in this population.

Human Respiratory Stem Cells (RSCs) play a crucial role in the maintenance, repair and regeneration of the respiratory system. As a novel therapeutic method, stem cell therapy is a popular research direction in the medical field. And with the in-depth research on the mechanism of pneumonia caused by respiratory infections in recent years, the use of RSCs to explore pneumonia caused by respiratory infections and its therapeutic strategies has become a hot topic. In this paper, we firstly outlined the types of RSCs, summarized the mechanism of pneumonia caused by respiratory tract infections, discussed the advantages of RSCs application and the progress of culture differentiation, and elaborated the therapeutic exploration of RSCs in pneumonia caused by respiratory tract infections.

Objective:Analysis of the composition of pathogen spectrum and prevalence characteristics in throat swabs of patients with acute respiratory infections (ARI) in Yucheng city, Henan province, from March to June 2023.Methods:After 1 153 throat swabs were collected from ARI patients in Yucheng, 18 respiratory pathogens were tested using a real-time fluorescence quantitative polymerase chain reaction (qPCR) method. The characterization of pathogens spectrum was analyzed.Results:A total of 1 153 throat swabs from ARI patients were collected from March to June 2023 in Yucheng, including 171 outpatients and 982 hospitalized patients. A total of 244 positive samples for common respiratory pathogens were detected (at least one pathogen per sample was detected). The total detection rate of respiratory pathogens was 21.16%, and the top three detection rates were, in descending order, human bocavirus (HBoV), enterovirus (EV), and human parainfluenza virus (HPIV). The main detection month for pathogens was May, with a detection rate of 42.3% (60/142). The main respiratory pathogens detected are HBoV, EV, and HPIV. The detection rate of the age group under 1 year old was the highest, at 25.1% (49/195), mainly consisting of HBoV, respiratory syncytial virus (RSV), and HPIV. The main clinical manifestations of respiratory pathogen-positive patients were fever and cough, and the clinical diagnosis was mainly lower respiratory tract infection, all of which were hospitalized patients.Conclusions:The respiratory pathogens in ARI patients were mainly HBoV, EV, and HPIV from March to June, 2023 in Yucheng. The peak of the epidemic was in May, mainly infecting children under 5 years of age.

Objective To investigate the effect of G9a histone methyltransferase inhibitor BIX01294 on the proliferation of vascular smooth muscle cell(VSMC)and its underlying mechanism.Methods Twelve SD rats were divided into the control group and the treatment group,with 6 rats in each group.The rats were anesthetized by intraperitoneal injection with sodium pentobarbital,then exposed the common carotid artery and the internal and external carotid artery after disinfection and skin preparation,ligated the distal end of the internal and external jugular veins,clamped the proximal end of the common carotid artery,cut the external carotid artery,inserted the balloon catheter,blocked the blood flow by compression,and ligated the proximal end of the external carotid artery after withdrawing the balloon.The common carotid artery clamping state of rats in the treatment group was maintained after withdrawing the balloon,then restored the blood flow after perfusion with 100 μmol/L BIX01294 solution for 30 seconds;rats in the control group were restored the blood flow after perfusion with PBS for 30 seconds.VSMC were divided into the normal group and the BIX01294 groups.Cells in the normal group were cultured in low glucose medium containing 2%fetal bovine serum,and cells in the BIX01294 groups were co-treated with 2.5,5.0,7.5 and 10.0 μmol/L BIX01294 on the basis of the normal group,respectively.CCK-8 assay and EDU assay were used to detect the cell activity and proliferative ability respectively,to screen appropriate concentration of BIX01294.The cell apoptosis was detected by TUNEL assay between the normal group and the BIX01294 group,and the control group and the treatment group.Western blot was used to detect the expression levels of autophagy-and apoptosis-related proteins in the normal group and BIX01294 group.Results Compared with 0 μmol/L,the activity and proliferative ability of VSMC decreased in a concentration-dependent manner after treatment with BIX01294 at different concentrations(P<0.05).Compared with the normal group,the apoptosis level of VSMC in the BIX01294 group was increased(P<0.05),the expression of VSMC autophagy-and apoptosis-related proteins of LC3Ⅰ/Ⅱ and Bax were up-regulated(P<0.05),and the expression of Bcl-2 and p62 proteins were down-regulated(P<0.05).In vivo test results showed that BIX01294 local perfusion aggravated the apoptosis of carotid VSMC.Conclusion BIX01294 activates VSMC autophagy and apoptosis and inhibits its proliferation.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

OBJECTIVES: To evaluate and integrate evidence on the management of sleep disorders in children with attention deficit hyperactivity disorder (ADHD). METHODS: Literature was retrieved based on the 6S model, and evidence related to sleep disorder management in children with ADHD was extracted from the included references. RESULTS: A total of 17 studies were included, from which 16 pieces of evidence were extracted. Of these, 6 were classified as Level 1 evidence and 10 as Level 5. The evidence covered screening, assessment, non-pharmacological interventions, pharmacological interventions, follow-up, and multidisciplinary collaboration. CONCLUSIONS This study integrated evidence on the management of sleep disorders in children with ADHD using an evidence-based approach, providing an evidence-based foundation for managing sleep disorders in this population.
Humans ; Attention Deficit Disorder with Hyperactivity/complications* ; Sleep Wake Disorders/etiology* ; Child ; Evidence-Based Medicine

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.