1.Electrophysiological Abnormalities and Pharmacological Corrections of Pathogenic Missense Variants in KCNQ3.
Xiaorong WU ; Jili GONG ; Li QIU ; Guimei YANG ; Hui YUAN ; Xiangchun SHEN ; Yanwen SHEN ; Fuyun TIAN ; Zhaobing GAO
Neuroscience Bulletin 2025;41(9):1511-1521
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. V1/2, 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 V1/2 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 V1/2 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*
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Humans
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Mutation, Missense/genetics*
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KCNQ2 Potassium Channel/genetics*
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Patch-Clamp Techniques
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HEK293 Cells
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Animals
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Phenylenediamines/pharmacology*
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Carbamates
2.Study on the application value of telmisartan combined with calcium dobesilate in patients with non-dipper hypertension complicated with type 2 diabetes mellitus
Weiwei HU ; Xiaorong LI ; Chunhui TIAN ; Zhifen LIU ; Junqi YING ; Chunyan GAO
Chinese Journal of Diabetes 2024;32(5):331-335
Objective To explore the application value of telmisartan combined with calcium dobesilate in patients with non-dipper hypertension complicated with type 2 diabetes mellitus(T2DM).Methods A total of 260 patients with non-dipper hypertension complicated with T2DM in the endocrinology department of our hospital were selected in this study from January 2021 to December 2022.All the patients were randomly divided into telmisartan group(Tel,n=110)and telmisartan+calcium dobesilate group(Tel+Cal-dob,n=150).The blood pressure level,blood pressure rhythm changes,brachial flow mediated dilatation(FMD),carotid radial pulse wave velocity(crPWV),vasomotor factors[nitric oxide(NO),endothelin-1(ET-1),vascular endothelial growth factor(VEGF)]and the incidence of adverse reactions were compared between the two groups.Results There was no significant difference in general data and biochemical indexes between the two groups(P>0.05).After 3,6 and 12 months of treatment,the FMD and NO were higher,while the dSBP,dDBP,24 hSBP,24 hDBP,nSBP,nDBP,crPWV,ET-1 and VEGF were lower than before treatment in both groups(P<0.05).After 3,6 and 12 months of treatment,the FMD and NO were higher,while dSBP,dDBP,24 hSBP,24 hDBP,nSBP,nDBP,crPWV,ET-1 and VEGF were lower in Tel+Cal-dob group than in Tel group(P<0.05).After 3,6 and 12 months of treatment,the conversion rates of dipper blood pressure were higher in Tel+Cal-dob groupthan in Tel group(P<0.05).There was no significant difference in the incidence of adverse effects between the two groups(P>0.05).Conclusion Telmisartan combined with calcium dobesilate is effective in the treatment of patients with non-dipper hypertension complicated with T2DM.
3.Prevalence and associated factors of diabetic retinopathy among type 2 diabetes in Dongcheng District and Tongzhou District, Beijing City: a cross-sectional study
Xiaorong ZHU ; Fangyuan YANG ; Lin ZHANG ; Rongrong XIE ; Jianping FENG ; Zhong XIN ; Wei TIAN
Chinese Journal of Preventive Medicine 2024;58(9):1324-1330
Objective:Diabetic retinopathy (DR) is the most common cause of adult blindness in China. Screening of DR is important for early detection, prevention, and treatment. However, there is still controversy in the research on the prevalence and risk factors of DR in China. This study was designed to evaluate the prevalence of DR and related risk factors in patients with type 2 diabetes mellitus in Beijing City.Methods:A cross-sectional survey was conducted in in Dongcheng District and Tongzhou District, Beijing City. Patients with type 2 diabetes aged 18-80 years were selected from four communities, and all subjects underwent questionnaires, physical examinations, laboratory examinations and fundus photography. The logistic regression model was used to analyze the associated factors of DR.Results:A total of 1 531 subjects were included, with the median age of 66 years old and the average age of (65.6±7.4) years old, and the glycosylated hemoglobin level in the subjects was 7.2%±1.3%, and the glycosylated hemoglobin compliance rate was 56.0%(857/1 531). A total of 254 patients with diabetic retinopathy were detected, and the prevalence of DR was 16.6%(254/1 531). Among them, there were 218 cases of non-proliferative diabetic retinopathy and 36 cases of proliferative diabetic retinopathy. Compared with the non-DR group, there were statistically significant differences in fasting blood glucose ( Z=-3.74, P<0.001), glycosylated hemoglobin( Z=-10.664, P<0.001), urinary microalbumin excretion rate( Z=-7.767, P<0.001), low-density lipoprotein cholesterol( Z=-2.589, P=0.01), and duration of diabetes( Z=-10.189, P<0.001) between the DR group and the non-DR group. Multivariate regression analysis showed that the duration of diabetes ( OR=1.08, 95% CI: 1.06-1.10, P<0.001), glycosylated hemoglobin ( OR=1.38, 95% CI: 1.23-1.55, P<0.001), and FPG ( OR=1.11, 95% CI: 1.03-1.19, P=0.008) were associated factors for DR. Conclusion:In this study, the prevalence of DR in 4 communities of type 2 diabetes in Beijing City was 16.6%. Besides, this study further confirmed that the duration of diabetes, fasting blood glucose levels, and glycosylated hemoglobin are associated factors for DR in patients with type 2 diabetes.
4.Analysis of the baseline investigation results of the conformity rate of bacterial culture examination records in a tertiary specialized hospital in 2022
Kexin GUO ; Jinying TONG ; Yang LUO ; Yuting LIU ; Xiaorong LI ; Xin ZHOU ; Lisi XU ; Junchen HUANG ; Qing'e TIAN
Modern Hospital 2024;24(5):733-736
Objective This paper aims to investigate and analyze the baseline conformity rate of bacterial culture exami-nation records in a tertiary specialized hospital.By doing this,this paper seeks to understand the current situation of medical re-cord writing of bacterial culture examination and explore the improvement path and relevant measures for enhancing the conformity rate of bacterial culture examination records.Methods According to the requirements of"Quality Control Index of Medical Re-cord Management(2021 Edition)",a retrospective analysis was conducted on 6 317 medical records that underwent bacterial culture examination in 2022.Results The execution rate of medical orders was 100.00%,the completeness rate of the report sheet was 100.00%,the record rate of medical records was 81.05%,the analysis rate of results was 33.07%,and the conformi-ty rate of bacterial culture examination records was 33.07%.Conclusion It is imperative to enhance the conformity rate of bac-terial culture examination records and improve the quality of medical records in terms of content.
5.Prevalence and associated factors of diabetic retinopathy among type 2 diabetes in Dongcheng District and Tongzhou District, Beijing City: a cross-sectional study
Xiaorong ZHU ; Fangyuan YANG ; Lin ZHANG ; Rongrong XIE ; Jianping FENG ; Zhong XIN ; Wei TIAN
Chinese Journal of Preventive Medicine 2024;58(9):1324-1330
Objective:Diabetic retinopathy (DR) is the most common cause of adult blindness in China. Screening of DR is important for early detection, prevention, and treatment. However, there is still controversy in the research on the prevalence and risk factors of DR in China. This study was designed to evaluate the prevalence of DR and related risk factors in patients with type 2 diabetes mellitus in Beijing City.Methods:A cross-sectional survey was conducted in in Dongcheng District and Tongzhou District, Beijing City. Patients with type 2 diabetes aged 18-80 years were selected from four communities, and all subjects underwent questionnaires, physical examinations, laboratory examinations and fundus photography. The logistic regression model was used to analyze the associated factors of DR.Results:A total of 1 531 subjects were included, with the median age of 66 years old and the average age of (65.6±7.4) years old, and the glycosylated hemoglobin level in the subjects was 7.2%±1.3%, and the glycosylated hemoglobin compliance rate was 56.0%(857/1 531). A total of 254 patients with diabetic retinopathy were detected, and the prevalence of DR was 16.6%(254/1 531). Among them, there were 218 cases of non-proliferative diabetic retinopathy and 36 cases of proliferative diabetic retinopathy. Compared with the non-DR group, there were statistically significant differences in fasting blood glucose ( Z=-3.74, P<0.001), glycosylated hemoglobin( Z=-10.664, P<0.001), urinary microalbumin excretion rate( Z=-7.767, P<0.001), low-density lipoprotein cholesterol( Z=-2.589, P=0.01), and duration of diabetes( Z=-10.189, P<0.001) between the DR group and the non-DR group. Multivariate regression analysis showed that the duration of diabetes ( OR=1.08, 95% CI: 1.06-1.10, P<0.001), glycosylated hemoglobin ( OR=1.38, 95% CI: 1.23-1.55, P<0.001), and FPG ( OR=1.11, 95% CI: 1.03-1.19, P=0.008) were associated factors for DR. Conclusion:In this study, the prevalence of DR in 4 communities of type 2 diabetes in Beijing City was 16.6%. Besides, this study further confirmed that the duration of diabetes, fasting blood glucose levels, and glycosylated hemoglobin are associated factors for DR in patients with type 2 diabetes.
6.A consensus on the management of allergy in kindergartens and primary schools
Chinese Journal of School Health 2023;44(2):167-172
Abstract
Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.
7.Value of Charlson comorbidity index in predicting the prognosis of patients with acute-on-chronic liver failure
Fuchun WANG ; Wanjie ZHANG ; Ziyi LI ; Yongwu MAO ; Aiping TIAN ; Xiaorong MAO ; Junfeng LI
Journal of Clinical Hepatology 2023;39(5):1098-1104
Objective To investigate the value of Charlson comorbidity index (CCI) in predicting the short- and long-term risks of death in patients with acute-on-chronic liver failure (ACLF). Methods A total of 317 patients with ACLF who attended The First Hospital of Lanzhou University from December 1, 2016 to December 1, 2021 were enrolled, and according to their prognosis, they were divided into death group with 169 patients and survival group with 148 patients. The two groups were analyzed in terms of clinical data and follow-up data. The group t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for the prognosis of ACLF patients. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison of survival time between patients with different CCI scores. The receiver operating characteristic (ROC) curve was used to evaluate the performance of CCI and other indices in assessing the prognosis of ACLF patients. Results Among the 317 patients, there were 225 (71.0%) male patients. There were significant differences between the death group and the survival group in age, hemoglobin, white blood cell count, total bilirubin, albumin, Model for End-Stage Liver Disease (MELD) score, prothrombin time activity, CCI, age-adjusted Charlson co-morbidity index (ACCI), and follow-up time (all P < 0.05). The multivariate Cox regression analysis showed that the CCI (hazard ratio [ HR ]=1.351, 95% confidence interval [ CI ]: 1.112-1.641, P =0.002), ACCI ( HR =1.200, 95% CI : 1.011-1.423, P =0.037), and MELD score ( HR =1.076, 95% CI : 1.054-1.099, P < 0.001) were independent risk factors for the prognosis of ACLF patients. Based on CCI score, the patients were divided into CCI ≤4 group with 167 patients, CCI=5 group with 64 patients, and CCI ≥6 group with 86 patients, with a 3-year mortality rate of 26.5%, 83.2%, and 96.9%, respectively, and there was a significant difference in survival time between any two groups after 3 years of follow-up and at the time of follow-up till September 2022 (all P < 0.001). CCI, ACCI, and MELD scores had an area under the ROC curve of 0.845, 0.811, and 0.790, respectively, in predicting the prognosis of ACLF patients. Conclusion As commonly used comorbidity assessment indices, CCI and ACCI scores have certain value in evaluating the short- and long-term prognosis of ACLF patients.
8.A machine learning-based predictive model of nonsuicidal self-injurious behavior among college students in Guizhou Province
PAN Chan, LIU Xiaorong, SHI Xiangzi, ZHAO Wenxin, TIAN Meng, CHEN Siyuan, ZHANG Wanzhu
Chinese Journal of School Health 2023;44(8):1198-1202
Objective:
To explore the effectiveness of machine learning algorithms in predicting non-suicidal self-injury (NSSI) behavior among college students, and to analyze the influencing factors of NSSI behavior, thus providing a reference for promoting psychological well-being.
Methods:
In December 2022, a stratified random cluster sampling method was used to select 835 college students from a university in Guizhou Province, China. The Adolescent Self-injury Scale, Family Function Assessment Scale, and Emotion Regulation Self-efficacy Scale were used to evaluate the participants. Demographic characteristics, family factors, and emotional factors were taken as independent variables, while the dependent variable was whether college students exhibited NSSI behavior. Machine learning algorithms, including Logistic regression, support vector machine (SVM), decision trees, algorithm gradient boosting trees, random forests, and AdaBoost, were used to construct predictive models.
Results:
The detection rate of NSSI behavior among the college students was 23.23% (194 individuals). The NSSI behavior group scored higher than the non-NSSI behavior group in total family function, emotional communication, egoism, and family rules ( t=3.02, 3.35 , 2.23,2.87, P <0.05). On the other hand, the non-NSSI behavior group scored higher than the NSSI behavior group in total emotion regulation selfefficacy, managing negative emotion self-efficacy, and expressing positive emotion self-efficacy ( t=-5.04, -5.48 , -2.43, P <0.05). The recall rates of random forests, SVM, Logistic regression, decision trees, algorithm gradient boosting trees, and AdaBoost were 84.3% , 90.6%, 73.4%, 87.5%, 95.3%, 89.0%, respectively. The F1 scores were 84.4%, 92.1%, 71.2 %, 79.4%, 91.7%, 89.1% , respectively. The respective precision rates were 84.4%, 93.5%, 69.1%, 72.7%, 88.4%, 89.1 %. The AUC scores were 0.845, 0.922, 0.706, 0.776, 0.915, and 0.891, respectively.
Conclusion
Compared to the algorithm gradient boosting tree, random forest, Logistic regression, and AdaBoost models, the SVM model has a better predictive effect on whether college students in Guizhou Province exhibits NSSI behavior. It is recommended to use an appropriate model to identify students at risk of NSSI behavior as early as possible and provide psychological crisis interventions to promote their mental health.
9.Analysis of red blood cells supply before and after the outbreak of COVID-19 from 2018 to 2021 in 18 domestic blood centers
Dongyan ZHAO ; Hongwei MA ; Dingjie TANG ; Xiaorong FENG ; Hao TIAN ; Mengzhuo LUO ; Nan WU ; Yan LIN ; Xia DU ; Qi FU ; Junlei HUANG ; Changchun LU ; Xiaoli CAO ; Yi YANG ; Lin WANG ; Ying LI ; Hai QI ; Dongtai WANG ; Yan QIU
Chinese Journal of Blood Transfusion 2023;36(10):892-898
【Objective】 To compare the supply data of red blood cells(RBCs) from 18 blood centers in China before and after the outbreak of COVID-19 during 2018 to 2021. 【Methods】 Eight indicators related to RBCs supply from 18 blood centers in China during 2018-2021 were collected retrospectively, including the storage of total amount of qualified RBCs (referred to as the total amount of storage), the distribution of total amount of RBCs (referred to as the total amount of distribution), the distribution amount of RBCs per 1 000 population (referred to as the amount of distribution per 1 000 population), the distribution amount of RBCs from 400 mL original blood per 1 000 population [referred to as the amount of distribution per 1 000 population (400 mL)], the average daily distribution amount of RBCs (referred to as the average daily distribution amount), the average daily storage amount of RBCs (referred to as the average daily storage amount), the average storage days of RBCs when distribute (referred to as the RBC storage days), and the expired amount of RBCs (referred to as the expired amount). Based on the outbreak time of COVID-19, the data of 2018 and 2019 were the pre-pandemic group, and the data of 2020 and 2021 were the post-pandemic group. 【Results】 Data on RBCs supply in 18 blood centers from 2018 to 2021(comparison of the pre-pandemic group and the post-pandemic group): the amount of distribution per 1 000 population (median 14.68 U>13.92 U) decreased, the amount of distribution per 1 000 population (400 mL) (median 10.16 U>9.21 U) decreased, and the difference was statistically significant (P<0.05); data comparison between 2019 and 2020:the total amount of distribution (median 117 770.38 U>99 084.08 U) decreased, the amount of distribution per 1 000 population (median 15.04 U>12.19 U) decreased, the amount of distribution per 1000 population (400 mL) (median 10.11 U>8.94 U), the average daily distribution amount(322.66 U>270.73 U) decreased and RBC storage days (median 10.50 d<11.45 d) increased, the difference has statistical significance (P<0.05); data comparison between 2020 and 2021:the total amount of storage (median 101 920.25 U<120 328.63 U), the total amount of distribution (median 99 084.08 U<118 428.62 U), the amount of distribution per 1 000 population (median 12.19 U<15.00 U), the amount of distribution per 1 000 population (400 mL) (median 8.94 U<9.46 U), the average daily distribution amount (270.73 U>324.46 U), the average daily inventory (median 3 222.00 U<4 328.00 U) increased, the expired amount (median 1.50 U>0.00 U) decreased, the difference has statistical significance (P<0.05). The results of ANOVA showed that there were significant differences on the data related to RBCs supply (except expired amount) in different blood centers (P<0.05). The ratio of average daily stock to average daily distribution in the post-outbreak group (median 12.36 d) was higher than that in the pre-outbreak group (median 10.92 d), the difference has statistical significance (P<0.05), with significant difference among different blood centers (P <0.05). 【Conclusion】 The COVID-19 pandemic has a significant impact on RBCs supply in different blood centers. In the second year of the pandemic, the supply capability had recovered to some extent, and there were differences in RBCs supply in different blood centers.
10.Association of IL-10 and TNF-α gene polymorphisms with hepatic echinococcus granulosus infection and necrosis
Guanglei TIAN ; Lunhong CHEN ; Bofeng YU ; Xiaorong HUANG ; Jinguo WANG ; Kalifu BAHETI ; Yuan MENG ; Wei SONG ; Zhigang MA ; Xiong CHEN
Journal of Chinese Physician 2022;24(10):1504-1508
Objective:To investigate the association between hepatic echinococcus granulosus infection and necrosis with gene polymorphism of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α), and to identify the related factors at the gene level.Methods:A total of 106 patients with hepatic echinococcosis who underwent surgical treatment in the department of hepatobiliary surgery, People′s Hospital of Xinjiang Uygur Autonomous Region from January 2018 to December 2020 were selected. Patients with necrosis caused by hepatic echinococcus granulosus infection were selected as the observation group, and patients without necrosis caused by hepatic echinococcus granulosus infection were selected as the control group, with 53 cases in each group. The serum levels of IL-10 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). The polymorphisms of IL-10 (-592, -1082) and TNF-α (rsl800630) were detected by polymerase chain reaction (PCR). The levels of IL-10 and TNF-α and their gene polymorphisms were analyzed.Results:The levels of serum IL-10 and TNF-α in the observation group were significantly higher than those in the control group (all P<0.05); There was significant difference in genotype and allele frequency of IL-10 (-592, -1082) and TNF-α (rsl800630) (all P<0.05). The serum IL-10 level of CC genotype patients with IL-10 gene -592C/A locus in the observation group was higher than that of CA+ AA genotype patients, with statistically significant difference ( P<0.05). The serum IL-10 level in patients with TT genotype at -1082T>A of IL-10 gene in the observation group was higher than that in patients with TA+ AA genotype, with statistically significant difference ( P<0.05). The serum TNF-α level in patients with CC genotype at rsl800630C/A locus of TNF-α gene in the observation group was higher than that in patients with CA+ AA genotype, with statistically significant difference ( P<0.05). Conclusions:The changes of IL-10 (-592, -1082) and TNF-α (rsl800630) gene polymorphisms may be associated with hepatic echinococcus granulosus infection and necrosis.


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