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

Objective: To explore the factors affecting carotid plaque formation among high-risk populations for stroke, so as to provide the reference for early intervention for carotid atherosclerosis among the populations. Methods: Permanent residents were selected from Minhang District, Shanghai Municipality using the multi-staged cluster random sampling method from April to September 2021. Basic information, family history of stroke and past medical history were collected by the Community and Township Population Screening Scale for Cardiovascular and Cerebrovascular Disease Risk Factors. High-risk populations for stroke were identified according to the Technical Specifications for Stroke Screening and Prevention. Carotid plaque status was assessed using carotid ultrasonography. Factors affecting carotid plaque formation were analyzed using a multivariable logistic regression model. Results: Among the 25 666 permanent residents surveyed, 8 459 were identified as high-risk populations for stroke, including 3 362 males and 5 097 females, with a male-to-female ratio of 0.66︰1. The median age was 66.00 (quartile range, 11.00) years. Carotid plaque were detected in 4 305 cases among high-risk population for stroke, accounting for 50.89%. Multivariable logistic regression analysis showed that advanced age (OR=1.052, 95%CI: 1.043-1.061), family history of stroke (OR=1.297, 95%CI: 1.103-1.526), hypertension (OR=1.245, 95%CI: 1.025-1.512) and diabetes (OR=1.439, 95%CI: 1.241-1.669) were associated with a higher risk of carotid plaque formation in male high-risk population for stroke, advanced age (OR=1.058, 95%CI: 1.051-1.066), lack of exercise (OR=1.138, 95%CI: 1.001-1.294), family history of stroke (OR=1.201, 95%CI: 1.062-1.357), significant overweight or obesity (OR=1.269, 95%CI: 1.127-1.430) and hypertension (OR=1.169, 95%CI: 1.003-1.362) were associated with a higher risk of carotid plaque formation in female high-risk population for stroke. Conclusion The main influencing factors for carotid plaque formation among high-risk populations for stroke include age, family history of stroke, exercise, significant overweight or obesity, hypertension and diabetes, with gender differences observed.

Objective:To investigate the protective effects of an anti-inflammatory mixture on acute lung injury (ALI) induced by sepsis in rats, as well as its possible mechanisms.Methods:A total of 40 Sprague-Dawley (SD) rats were randomly divided into the sham group, septic ALI model group (model group), 3-methyladenine (3-MA) control group, and anti-inflammatory mixture pretreatment group, with 10 rats in each group. Cecal ligation and perforation (CLP) was performed to reproduce a septic ALI model. The rats in the sham group only underwent opening and closing the abdomen without perforation and ligation. Both groups were given saline gavage and intraperitoneal injection for 3 consecutive days before surgery. The 3-MA control group was given intraperitoneal injection of saline and autophagy inhibitor 3-MA 15 mg/kg for 3 consecutive days before modeling. The anti-inflammatory mixture pretreatment group was given 8.8 mL/kg of anti-inflammatory mixture by gavage [the composition of anti-inflammatory mixture: rhubarb 15 g (after the next), coptis chinensis 15 g, baical skullcap root 12 g, magnoliae cortex 12 g, dahurian patrinia herb 30 g] and saline intraperitoneal injection for 3 consecutive days before modeling. The rats in each group were anesthetized 24 hours after surgery and died due to abdominal aortic blood collection. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum inflammatory cytokines interleukins (IL-1β and IL-6). Lung tissue was taken and then the bronchoalveolar lavage fluid (BALF) was collected, and the levels of IL-1β and IL-6 were detected by ELISA. Lung wet/dry weight (W/D) ratio was measured. After hematoxylin-eosin (HE) staining, the histopathological changes of the lungs were observed under light microscopy. Western blotting was used to detect the expression of autophagy markers microtubule-associated protein 1 light chain 3-Ⅱ/Ⅰ (LC3-Ⅱ/Ⅰ) and Beclin-1 protein in lung tissue. Autophagosomes in lung tissue were observed with transmission electron microscopy.Results:Compared with the sham group, the rats in the model group exhibited severe destruction of lung tissue structure, with significant infiltration of inflammatory cells, the lung W/D ratio and the levels of IL-1β and IL-6 in serum and BALF were significantly increased, the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 protein were down-regulated, the autophagosomes were more. The rats in the 3-MA control group exhibited more severe lung tissue injury as compared with the model group, the lung W/D ratio and the levels of inflammatory cytokines in serum and BALF were further increased, the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 protein still showed a decrease tendency as compared with the sham group, and the autophagosomes were less than that in the model group. Compared with the model group, the anti-inflammatory mixture pretreatment group showed milder lung tissue injury with a minimal amount of inflammatory cell infiltration, the lung W/D ratio was significantly reduced (7.07±1.02 vs. 11.33±1.85, P < 0.05), the levels of IL-1β and IL-6 in both serum and BALF were significantly decreased [IL-1β (ng/L): 26.04±3.86 vs. 40.83±5.46 in serum, 17.75±2.02 vs. 26.86±4.32 in BALF; IL-6 (ng/L): 91.28±10.15 vs. 129.44±13.05 in serum, 76.06±7.51 vs. 120.91±7.47 in BALF, all P < 0.05], and the ratio of LC3-Ⅱ/Ⅰ and Beclin-1 protein expression were significantly increased [LC3-Ⅱ/Ⅰ ratio: 1.23±0.02 vs. 0.60±0.02, Beclin-1 protein (Beclin-1/GAPDH): 2.37±0.33 vs. 0.62±0.05, both P < 0.05]. Furthermore, an increase in the number of autophagosomes was observed. Conclusion:The anti-inflammatory mixture improves lung injury in rats with sepsis induced by CLP and reduce inflammation levels, potentially through upregulation of Beclin-1-mediated autophagy.

Objective This study aimed to establish a pre-metastatic niche mouse model utilizing luciferase-labeled Lewis (Luc-Lewis) lung cancer cells and to assess the efficacy of this model employing both qualitative and quantitative methods. Methods C57BL/6 mice were categorized into two groups: a normal control group and a model group, each containing 15 individual mice. The pre-metastatic niche model was established via tail vein injection of Luc-Lewis lung cancer cells. Body mass were measured daily for all groups. Tumor fluorescence signals within the mice were detected using a high-throughput enzyme marker instrument. Lung tissue specimens were harvested to evaluate metastatic progression. HE staining was used to assess histopathological changes. Real-time quantitative PCR and Western blot analysis were used to detect the mRNA and protein expression of lysyl oxidase (LOX), matrix metalloproteinase 9 (MMP9), versican (VCAN), and fibronectin (FN), which are the specific markers for the formation of the microenvironment of lung tissues before metastasis. Results Significant declines in body mass and observable lethargy were noted in the model group when compared to the control group. Distinct fluorescence signals were observed in the lung tissue of the model group, demonstrating a positive correlation with the duration of model establishment. By day 14, elevated mRNA and protein expression levels of LOX, MMP9, VCAN, and FN were significantly evident. In addition, histopathological evaluations revealed augmented interstitial thickness, alveolar atrophy and significant inflammatory cell infiltration within the lung tissues of the model group. By the 21st day, metastatic lesions manifested in the lung tissues of the model group, suggesting an approximate pre-metastatic niche maturation timeline of 14 days. Conclusion A pre-metastatic niche mouse model for Lewis lung cancer is successfully established.
Mice ; Animals ; Lung Neoplasms/pathology* ; Matrix Metalloproteinase 9 ; Mice, Inbred C57BL ; Carcinoma, Lewis Lung ; Disease Models, Animal ; RNA, Messenger ; Tumor Microenvironment

In order to fulfill the new requirement of educational and teaching reform in the new era, the Teaching and Research Section of Parasitology in Guangxi Medical University have constructed online courses of Parasites Invasion— Human Parasitology on the platform of Xueyin Online, providing resources in professional learning and general education. In the construction concept, we recombine teaching content to give consideration to both scientificity and interest. In terms of the curriculum content, the curriculum includes micro lecture, PPT, in-lass quiz, case analysis and other diversified teaching resources. In the curriculum management, teachers interact with students in real time with the help of various functions of the platform to fully play the role of supervision. In the assessment, teachers pay attention to students' learning process and carry out comprehensive evaluation. Since the online course was put into operation, good teaching effects has been achieved.

Objective:To explore the association between short-term exposures to fine particulate matter (PM 2.5) on blood lipids in the elderly. Methods:In this panel study, five repeated measurements were performed on 76 people aged 60-69 in Jinan city. Each participant had a PM 2.5 monitor for 72 hours before each health examination, including a questionnaire survey, physical examination, and biological sample collection. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were examined, and non-HDL-C concentrations were calculated by subtracting HDL-C from TC. The generalized linear mixed-effects model was used to quantify the association of personal PM 2.5 exposure at different lag with blood lipids and dyslipidemia. Results:The age of 70 participants was (65.0±2.8) years, of which 48.6% (34/70) were males. The BMI of participants was (25.0±2.5) kg/m 2. Their TC, TG, LDL-C, HDL-C, and non-HDL-C concentrations were (5.75±1.32), (1.55±0.53), (3.27±0.94), (1.78±0.52), and (3.97±1.06) mmol/L, respectively. Generalized linear mixed-effects model showed that after adjusting for confounding factors, at lag 72 hours, each 10 μg/m 3 increase in PM 2.5 was associated with the percentage change in TC, LDL-C, HDL-C and non-HDL-C about 1.77% (95% CI: 1.22%-2.32%), 1.90% (95% CI: 1.18%-2.63%), 1.99% (95% CI: 1.37%-2.60%) and 1.74% (95% CI: 1.11%-2.37%), and the OR values (95% CI) of hypercholesterolemia, hypertriglyceridemia and hyperbetalipoproteinemia were 1.11 (1.01-1.22), 1.33 (1.03-1.71) and 1.15 (1.01-1.31), respectively. Conclusion:There is a significant association of short-term PM 2.5 exposure with the concentration of blood lipids and the risk of dyslipidemia in the elderly.

Objective:To explore the association between short-term exposures to fine particulate matter (PM 2.5) on blood lipids in the elderly. Methods:In this panel study, five repeated measurements were performed on 76 people aged 60-69 in Jinan city. Each participant had a PM 2.5 monitor for 72 hours before each health examination, including a questionnaire survey, physical examination, and biological sample collection. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were examined, and non-HDL-C concentrations were calculated by subtracting HDL-C from TC. The generalized linear mixed-effects model was used to quantify the association of personal PM 2.5 exposure at different lag with blood lipids and dyslipidemia. Results:The age of 70 participants was (65.0±2.8) years, of which 48.6% (34/70) were males. The BMI of participants was (25.0±2.5) kg/m 2. Their TC, TG, LDL-C, HDL-C, and non-HDL-C concentrations were (5.75±1.32), (1.55±0.53), (3.27±0.94), (1.78±0.52), and (3.97±1.06) mmol/L, respectively. Generalized linear mixed-effects model showed that after adjusting for confounding factors, at lag 72 hours, each 10 μg/m 3 increase in PM 2.5 was associated with the percentage change in TC, LDL-C, HDL-C and non-HDL-C about 1.77% (95% CI: 1.22%-2.32%), 1.90% (95% CI: 1.18%-2.63%), 1.99% (95% CI: 1.37%-2.60%) and 1.74% (95% CI: 1.11%-2.37%), and the OR values (95% CI) of hypercholesterolemia, hypertriglyceridemia and hyperbetalipoproteinemia were 1.11 (1.01-1.22), 1.33 (1.03-1.71) and 1.15 (1.01-1.31), respectively. Conclusion:There is a significant association of short-term PM 2.5 exposure with the concentration of blood lipids and the risk of dyslipidemia in the elderly.

Objective:To develop a comprehensive ability evaluation system for general practice management post in community health service institutions.Methods:Based on the previous studies and literature search on competency of general practitioners in various clinical posts, the first draft of the comprehensive ability indicator system for general management posts was designed. From November 2019 to January 2020, the comprehensive ability indicator system, classification and scoring method and evaluation method for general management posts were determined through three rounds of Delphi consultation.Results:Seventeen experts with administrative management experiences were invited for consultation, including 3 directors in charge and 14 general practice managers. The response rate of valid questionnaires in the three rounds of consultation were all 17/17, the authority of experts were all>0.7, and the coordination coefficients of expert opinions were 0.142, 0.212, and 0.532 (all P<0.01). The 11 evaluation indexes of the comprehensive ability of community general management posts were: achievement orientation, initiative, interpersonal understanding, service consciousness, influence, organization, training others, teamwork, team leadership, professional skills and confidence. Methods suitable for evaluation the ability of psychological test indicators were achievement orientation, interpersonal understanding, service consciousness and self-confident;appropriate indicators for no-leader group discussion were initiation, influence, team work, team leadership;appropriate indicators for in-tray test ability were organized cognition, professional skills;and the appropriate indicator for the ability of the structured interview was training others. Conclusions:The comprehensive ability evaluation system for community general management posts established in this study is scientific and practical, which may provide objective standard basis for the ability evaluation of community health management talents.

Objective:To investigate the clinical characteristics, treatment and prognosis of QARS1 gene related glutaminyl-tRNA synthetase deficiency.Methods:To summarize and analyze the clinical manifestations, imaging, laboratory examination, genetic variant characteristics and treatment of three patients from the Fujian Medical University Affiliated Union Hospital, the 900th Hospital of People's Liberation Army, the First Medical Center of People's Liberation Army General Hsopital carrying compound heterozygous variations in QARS1 gene with a long-term follow-up in China. A literature search was conducted using Wanfang, Weipu, China National Knowledge Infrastructure (CNKI) and Pubmed databases with the keywords "QARS", "QARS1" and "glutaminyl-tRNA Synthetase"(up to December 2019). Results:Case 1, a female 53 days of age, was admitted to the Fujian Medical University Affiliated Union Hospital for treatment because of the complaint of repetitive seizures for one month after birth and fever for one day. The seizure occurred within the first 2 hours of life with multiple forms and often had a status as persisted from hours to days. The seizures were resistant to many anti-epilepsy drugs (AED) and ketogenic diet but later controlled by clonazepam. However, she died at the age of seven years. Case 2 (younger brother of case 1), a one-hour-old boy, was hospitalized because of seizures after birth for 1 hour. Intrauterine growth retardation was discovered during late-pregnancy. The boy presented seizures and microcephaly immediately after birth, and his epilepsy was pharmacoresisitant. Case 3, an 8-month-old girl, was admitted due to recurrent convulsions for nearly two months. The girl had mild developmental retardation and hypotonia after birth. The infantile spasm was observed at her age of 6 months and disappeared under treatment with Vitamin B6, vigabatrin combined with adreno-cortico-tropic-hormone and magnesium sulfate. However, the seizure pattern turned to tonic seizures later. She was seizures free now with clobazam and zonisamide treatment. All of them manifested as a syndrome composed of severe global developmental retardation, progressive microcephaly, hypotonia from the very beginning, mild hypoproteinemia and diffuse brain atrophy. Genetic studies revealed compound heterozygous variations of QARS1 gene which were not reported previously . A review of the literature reported a total of 22 patients from 18 unrelated families all over the world. Except for 5 cases without epilepsy,all the patients shared very similar clinical manifestations as classic pentalogy. The recommended effective treatment for epilepsy has not been reported yet. Conclusions:Glutaminyl-tRNA synthetase deficiency caused by QARS1 gene variations manifested as a clinical syndrome′s pentalogy, characterized by microcephaly, cerebral atrophy, intractable early-onset epileptic encephalopathy, global developmental retardation and severe muscle hypotonia.

Objective To observe the long-term clinical effect of pars plana vitrectomy combined with fovea-sparing internal limiting peeling in the treatment of macular foveoschisis in pathologic myopic. Methods A prospective case series study. Fifteen patients (15 eyes) with pathological myopic macular foveoschisis who received treatment in Eye Hospital of Wenzhou Medical University from December 2015 to December 2016 were enrolled. There were 4 males (4 eyes) and 11 females (11eyes), with an average age of 55.33±8.34 years. All patients underwent BCVA, diopter, spectral domain OCT and axial length measurement. The mean logMAR BCVA was 0.95±0.64. The mean central fovea thickness (CFT) was 576.00±185.32 μm. All patients underwent vitrectomy combined with fovea-sparing internal limiting peeling. After gas-liquid exchange, 12％ C3F8 was filled and followed up at 1, 3, 6 and 12 months after surgery. Follow-up time was more than 12 months. The structural changes of BCVA and macular area were observed.Results The foveal internal limiting membranes was successfully preserved in all eyes using the techinique. At the final follow-up, the CFT was 258.60±175.22 μm and the BCVA was 0.46±0.43, which were significantly improved compared with preoperative measurements (t=4.90, 5.20;P<0.001). Macular foveoschisis was resovled in 13 eyes. BCVA increased in 14 eyes. Internal limiting membranes proliferation and contraction occurred in 5 eyes and full-thickness macular hole occurred in 1 eye.Conclusions Pars plana vitrectomy with fovea-sparing internal limiting peeling is effective in the treatment of myopic macular retinoschisis. It can improve BCVA and CFT.