The KCNQ potassium channels play a crucial role in modulating neural excitability, and their dysfunction is closely associated with epileptic disorders. While variants in KCNQ2 have been extensively studied, KCNQ3-related disorders have rarely been reported. With advances in next-generation sequencing technologies, an increasing number of cases of KCNQ3-related disorders have been identified. However, the correlation between genotype and phenotype remains poorly understood. In this study, we established a variant library consisting of 24 missense mutations in KCNQ3 and introduced these mutations into three different template types: KCNQ3, KCNQ3-A315T (Q3*), and KCNQ3-KCNQ2 tandem (Q3-Q2). We then analyzed the effects of these mutations on the KCNQ3 channel function using patch-clamp recording. The most informative parameter across all three backgrounds was the current density of the mutant channels. The current density patterns in the Q3* and Q3-Q2 backgrounds were similar, with most mutations resulting in an almost complete loss of function (LOF), they were concentrated in the pore-forming domain of KCNQ3. In contrast, mutations in the voltage-sensing domain or C-terminus did not show significant differences from the wild-type channel. Interestingly, these LOF mutations were typically associated with self-limited familial neonatal epilepsy, while neurodevelopmental disorders (NDD) were more closely associated with mutations that did not significantly differ from the wild-type. V_1/2, another important parameter of the electrophysiological properties, could not be accurately determined in the majority of KCNQ3 mutations due to its nearly complete LOF in the Q3* and Q3-Q2 backgrounds. Intriguingly, the V_1/2 of functional mutations were primarily leftward shifted, indicating a gain-of-function (GOF) effect, which was typically associated with NDD. In addition to previously reported mutations, we identified G553R as a novel GOF mutation. In the co-transfection background, parameters such as V_1/2 could be determined, but the dysfunctional effects of these mutations were mitigated by the co-expression of wild-type KCNQ3 and KCNQ2 subunits, resulting in no significant differences between most mutations and the wild-type channel. Furthermore, we applied KCNQ modulators to reverse the electrophysiological abnormalities caused by KCNQ3 variants. The LOF mutations were reversed by the application of Pynegabine (HN37), a KCNQ opener, while the GOF mutation responded well to Amitriptyline (AMI), a KCNQ inhibitor. These findings provide essential insights into the pathogenic mechanisms underlying KCNQ3-related disorders and may inform clinical decision-making.
KCNQ3 Potassium Channel/genetics* ; Humans ; Mutation, Missense/genetics* ; KCNQ2 Potassium Channel/genetics* ; Patch-Clamp Techniques ; HEK293 Cells ; Animals ; Phenylenediamines/pharmacology* ; Carbamates

ObjectiveTo analyze the literature related to traditional Chinese medicine （TCM） pharmacology of Institute of Chinese Materia and Medica， China Academy of Chinese Medical Sciences （hereinafter referred to as "Institute of Chinese Materia and Medica"）， and evaluate the research status， development trend， influence of discipline members， and patent technology of this field. MethodThe papers from 2002 to 2024 in the databases of CNKI and Web of Science （WOS） were searched， whose first authors or corresponding authors are from the Institute of Chinese Materia and Medica， and CiteSpace 6.3.R6 was adopted for visual analysis of the annual number of publications and keywords. Additionally， the total number of published papers， citation times， and other measurement parameters of discipline members of TCM pharmacology in the institute were counted. After obtaining the h index， the academic track was calculated， and the academic influence of discipline members was quantitatively evaluated from the aspects of the academic track T and highly cited papers. Meanwhile， patent data from 2005 to 2024 of TCM pharmacology in the studied institute were retrieved from the HimmPat patent database， and Excel 2022 and Origin 2021 were utilized to conduct visual analysis on the overall patent application trend and technology composition. ResultIn the past 20 years or more， the annual publication of academic papers has been on the rise generally， and the key words include "animal model"， "mechanism of action"， "network pharmacology" and so on. The studies focus on the innovative methods of TCM pharmacological mechanisms， basic research on TCM prevention and treatment of major non-infectious diseases， and the prevention and treatment of respiratory viral diseases. The academic track T of the discipline members of TCM pharmacology in the Institute of Chinese Materia and Medica is positive， with sound personal influence. In recent years， the patent application trend has increased significantly， mainly concentrating on A61K patents and G01N subcategories， and IPC large-group analysis shows that the main technical applications are mainly in A61K36， A61K31， and other fields. ConclusionTCM pharmacology in the institute develops steadily and the academic influence of the discipline members is still sound， with fruitful patent achievements. In the future， research on pharmacological discipline innovation and new drug research and development can be enhanced， and multidisciplinary integration studies should be carried out to promote TCM modernization.

Objective To explore the clinical application value of high frequency ultrasound combined with acoustic radiation force impulse in patients with diabetic sarcopenia(DSA).Methods A total of 196 patients with type 2 diabetes mellitus(T2DM)who were hospitalized in the Endocrinology Department of the First Affiliated Hospital of Longyan City,Fujian Medical University were enrolled in this study from January 2022 to February 2023.All the participants were divided into two groups:simple T2DM group(n=120)and combined DSA group(DSA,n=76)according to the limb skeletal muscle mass index(ASMI).During the same period,40 healthy individuals who underwent physical examination were selected as the normal control(NC)group.The general information and biochemical indicators were analyzed in each group.And the muscle thickness,pinnate angle,muscle bundle length and shear wave velocity of the medial head of the right gastrocnemius muscle were compared among the groups.Results The thickness,feathery angle,muscle bundle length,and shear wave velocity of the medial head muscle of the right gastrocnemius muscle were lower in DSA group than in NC and T2DM groups(P＜0.05).Pearson correlation analysis showed that ASMI was positively correlated with body weight,BMI,TC,albumin,total protein,muscle thickness,feather angle,muscle bundle length,and shear wave velocity(P＜0.05),while negatively correlated with age,FPG and HbA1c(P＜0.05).Binary logistic regression analysis showed that muscle thickness and shear wave velocity are influencing factors for DSA.The analysis of the receiver operating characteristic(ROC)curve of the subjects showed that the area under the ROC curve of muscle thickness and shear wave velocity was 0.826 and 0.877(P＜0.05).The diagnostic thresholds for DSA were 14.1 mm and 1.63 m/s,with sensitivity of 0.953 and 0.903,and specificity of 0.971 and 0.941.Conclusions Ultrasound measurement of the muscle thickness and shear wave velocity of the medial head of the right gastrocnemius muscle can be used to diagnose diabetic sarcopenia.

Objective:To explore the status and obstacle factors of exercise in elderly maintenance hemodialysis (MHD) patients, so as to provide a clinical evidence for exercise guidance and targeted intervention in elderly maintenance hemodialysispatients.Methods:A mixed method of consistent parallel design was adopted. A total of 180 elderly MHD patients in two ClassⅢ hospitals of Kunshan in December 2021 were enrolled using convenience sampling method and investigated by questionnaire. The statas of exercise and exercise self-efficacy were researched. Objective sampling method was used to interview 17 elderly MHD patients with semi-structured interviews. The obstacle factors of exercise were investigated.Results:A total of 180 valid questionnaires were collected in the quantitative study. The highest metabolicequivalent of leisure time physical activity was 1 188 MET-min/w, the lowest was 0 MET-min/w, and the median was 396 MET-min/w. Pearson correlation analysis showed that there was a positive correlation between exercise self-efficacy and physical activity in elderly MHD patients ( P<0.05). Qualitative study extracted 3 themes and 9 subthemes, including lack of exercise knowledge, low self-efficacy, family and social environment resource limitation. Conclusions:Elderly MHD patients lack ideal exercise state. In clinical practice, medical staff should popularize exercise knowledge, improve patients' exercise self-efficacy, carry out family support education, increase social support, and select suitable exercise methods and develop individualized exercise programs according to patients' disease characteristics, so as to improve their exercise status.

Objective To investigate the biological effects of bcl-2 gene on neurons. Methods The recombinant expression plasmid pc DNA3-bcl-2 was constructed from pSFFV-bcl-2,then it was introduced into PC12 cell line by liposome method.Western blotting and immunohistochemistry in situ were applied to exam the exogenous gene expression.The two groups of cells(Group A,PC12 transfected by pcDNA3-bcl-2 and Group B,PC12 transfected by pcDNA3) were exposed to cisplatin with the concentration of 10*!?mol/L,50*!?mol/L, and 100*!?mol/L 72 hours later,the survival cells were estimated.Cell cycle indexes between these two groups were also studied by FCM. Results The recombinant expression plasmid pcDNA 3-bcl-2 was constructed successfully and PC12 cell line transfected by the plasmid could express Bcl-2 protein effectively.Compared with the control(25 79%),there was a significant decrease of cells from the S phase in PC12 with bcl-2 gene(8.81%).After exposed with 10*!?mol/L,50*!?mol/L,and 100*!?mol/L cisplatin,the surviving cells in group A were 276?13,185?11 and 108?10 respectively,which increased much more than in group B while they were 100?9,12?3 and 2?2 accordingly.Conclusions bcl-2 can protect PC12 cells against cytotoxic insults of cisplatin,and it suggested that it might act via cell cycle controlling.