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 characteristics of Xin'an doctors in the syndrome differentiation and treatment of liver cirrhosis from the dimensions of symptoms,syndromes and medication using data mining methods.Methods Medical cases and prescriptions for liver cirrhosis were collected from Xin'an medical literature.Data mining was performed using frequency analysis,complex network analysis,Louvain clustering analysis and factor analysis to investigate syndromes,symptoms,and medicines.Results A total of 363 prescriptions were analyzed,involving 15 syndromes and 325 kinds of Chinese materia medica,with 33 identified as core medications.Tonifying herbs were the most frequently used;the primary syndromes were liver qi stagnation and water retention;core symptoms of liver qi stagnation included emotional distress,reduced appetite and hypochondriac pain,with core medications such as Bupleuri Radix and Poria;core symptoms of water retention included lower limb edema and abdominal distension,with core medications such as Pinelliae Rhizoma,Citri Reticulatae Pericarpium,Magnoliae Officinalis Cortex and Poria.Factor analysis of core medications identified 12 common factors.Conclusion The pathogenesis of liver cirrhosis involves deficiency in nature and excess in superficiality,primarily affecting the liver and closely related to the spleen and kidneys.Xin'an doctors emphasize treating the symptoms with qi-regulating,blood-activating,dampness-drying and heat-clearing strategies,while simultaneously addressing the root with qi-tonifying,spleen-strengthening,liver-nourishing and kidney-replenishing therapies.

Objective To explore the characteristics of Xin'an doctors in the syndrome differentiation and treatment of liver cirrhosis from the dimensions of symptoms,syndromes and medication using data mining methods.Methods Medical cases and prescriptions for liver cirrhosis were collected from Xin'an medical literature.Data mining was performed using frequency analysis,complex network analysis,Louvain clustering analysis and factor analysis to investigate syndromes,symptoms,and medicines.Results A total of 363 prescriptions were analyzed,involving 15 syndromes and 325 kinds of Chinese materia medica,with 33 identified as core medications.Tonifying herbs were the most frequently used;the primary syndromes were liver qi stagnation and water retention;core symptoms of liver qi stagnation included emotional distress,reduced appetite and hypochondriac pain,with core medications such as Bupleuri Radix and Poria;core symptoms of water retention included lower limb edema and abdominal distension,with core medications such as Pinelliae Rhizoma,Citri Reticulatae Pericarpium,Magnoliae Officinalis Cortex and Poria.Factor analysis of core medications identified 12 common factors.Conclusion The pathogenesis of liver cirrhosis involves deficiency in nature and excess in superficiality,primarily affecting the liver and closely related to the spleen and kidneys.Xin'an doctors emphasize treating the symptoms with qi-regulating,blood-activating,dampness-drying and heat-clearing strategies,while simultaneously addressing the root with qi-tonifying,spleen-strengthening,liver-nourishing and kidney-replenishing therapies.

Objective:To test the reliability and validity of the general procrastination scale (GPS) in the application of middle school students.Methods:The Chinese version of GPS, the irrational procrastination scale(IPS), and the Maslach burnout inventory(MBI) were utilized to survey 10 825 middle school students in Harbin City through stratified random sampling, and 4 498 students were retested after 4 weeks. Statistical analysis was performed using SPSS 27.0 and Mplus 8.0.Results:The entries were well differentiated.Exploratory and confirmatory factor analysis indicated that GPS was composed of two factors, including active avoidance and lack of planning.The model fit was good (CFI=0.914, TLI=0.901, RMSEA=0.069, SRMR=0.072). GPS was positively correlated with the total scores of IPS and MBI ( r=0.753, 0.677, both P<0.001). The Cronbach's α coefficient of GPS was 0.864, the folded half reliability was 0.870, and the retest reliability after 4 weeks was 0.756. Conclusion:The GPS has good reliability and validity among middle school students, which provides a standard for measuring the procrastination level of middle school students and carrying out related research.

Objective To explore the histomorphology and related indicators in a rat model of skeletal muscle injury in an artificial experimental chamber as special environment in Northwest China to stimulate a hot and dry desert environment in order to screen the evaluation indicators of skeletal muscle injury in a hot and dry environment.Methods Eighteen male SD rats (8 weeks old)were randomly divided into blank control group (room temperature,free movement),room temperature exercise group,and hot and dry exercise group,with 6 rats in each group.After the rats were subjected to adaptation training for 3 d (a 3-D exercise treadmill,speed:16 m/min,slope:-16°,time:5～10 min),the rats in the 2 exercise groups were subjected to a treadmill once per day at a speed of 19.3 m/min and a slope of-16°till the end of exhaustion,and those in the hot and dry exercise group were housed in an artificial experimental chamber at a temperature of (40±1 )℃,a humidity of (10±2)％.After 6 d of continuous exercise,the rat soleus muscle tissue was taken to observe the pathological changes,and the serum samples were detected for skeletal muscle injury markers,inflammatory factors,oxidative stress related factors,hormones and other related indicators. Results When compared with the blank control group and the room temperature exercise group,the hot and dry exercise group had significantly higher concentrations of creatine kinase (CK),creatine kinase isoenzyme (CK-MB)and muscle-specific creatine kinase (CK-MM)(P<0.05 ),elevated contents of TNF-α,IL-1βand IL-6 (P<0.05),raised malondialdehyde (MDA)content and lower superoxide dismutase (SOD)activity (P<0.05 ),lower testosterone (T)but higher corticosterone (Cort)levels and thus lower testosterone/corticosterone (T/Cort)ratio (P<0.05 ).The markers of skeletal muscle injury,CK,CK-MB and CK-MM were positively correlated with the pro-inflammatory cytokines,TNF-α,IL-1βand IL-6 (P<0.05),positively with the antioxidant indicator MDA but negatively with SOD (P<0.05 ),and positively correlated with Cort level and negatively with T level and T/Cort ratio (P<0.05).Conclusion A stable rat model of skeletal muscle injury in a hot and dry desert environment is successfully constructed.The severity of skeletal muscle injury is greater in rats in a hot and dry desert environment than those in a normal temperature environment. TNF-α and IL-1β are found to be indirect indicators to evaluate skeletal muscle injury in the environment.

OBJECTIVE： To investigate the pratice of pharmaceutical care provided by clinical pharmacists in orthopedics department. METHODS： Based on the characteristics of orthopedic diseases and clinical drug use， combined with case analysis， the content， work focus and working methods of pharmaceutical care provided by clinical pharmacists were summarized in orthopedics department of our hospital. RESULTS： Clinical pharmacists of our hospital provided basal pharmaceutical care， such as pharmacy consultation， drug reforming， medication education. Focusing on the application standardization of antibiotics in perioperative period， pain evaluation， analgesic regimen optimization， hemostasis and anticoagulation medication safety monitoring of patients undergoing orthopaedic surgery， clinical pharmacists went deep into ward work to assist physicians in formulating treatment plans. Results of case analysis showed that the work of clinical pharmacists was recognized by doctors and promoted rational drug use in clinic. CONCLUSIONS： Clinical pharmacists should combine different specialty characteristics to carry out pharmacy services for specific groups， continuously improve the professional level and their ability to work， and improve the level of pharmaceutical care.

Objective To introduce a breast conserving surgery for reconstruction of breast shape and to demonstrate the postoperative effect.Methods Ten patients were treated with this method from Apr.2016 to Dec.2017,and the lateral thoracic wall arteriovenous vessels were used as vascular pedicle to transfer the distal compound tissue flap of the blood vessel to repair the breast defect remnant cavity which was formed after the breast conserving surgery,and a good shape was obtained.Results All the 10 cases were successfully completed.The intraoperative bleeding was 20 to 30 ml.The operative time was 2 to 3 hours.No blood transfusion was needed.The average hospital stay was 11.5 days,ranging from 10 to 15 days.No infection happened to the incision.All the 10 patients were followed up from 2 to 20 months,with 11 months as the average.No limb edema,asymmetry or local recurrence happened.Conclusion The operation method is effective,safe and economical for patients with large swelling but strong desire to conserve breast.

Objective To analyze the pathogenesis and prevention and treatment of limb deep venous thrombosis complicated by postoperative gynaecological malignant tumours.Methods A retrospective analysis of 22 cases with limb deep venous thrombosis complicated by postoperative gynaecological malignant tumours in our hospital were analyzed.According to the situation of patients,surgery or conservative treatment was conducted.The clinical efficacy after treatment was observed.Results In 22 cases,6 cases underwent surgical treatment,16 cases underwent conservative treatment.After treatment,18 cases were cured,3 cases were effective,1 case ineffective.After treatment,the TT,Pt,APTT and FBG levels were (24.17 ±2.13)s,(18.25 ±2.13)s,(31.68 ± 10.30)s and (2.26 ±0.52) g/L,which were all better than before treatment,the differences were statistically significant (t =10.362,9.774,12.281,8.462,P =0.028,0.032,0.012,0.029).Followed up for 3 months,no recurrence of LDVT was observed.Conclusion The cases of gynecological malignant tumor have higher risk of limb deep vein thrombosis,we should taken prevention actively,once diagnosed should take effective intervention measures to improve the prognosis.

Objective To establish a capillary gas chromatography method for determination of camphol and isoborneol in Shaoshang yuhe gao ( burn healing cream) . Methods The capillary gas chromatography was adopted under the following conditions: use PEG-2000 as the stationary liquid,nitrogen as carrier gas,ZB-WAX (30 m×0. 25 mm,0. 25 μm) as the chromatographic column,and the flame ionization detector. The column temperature was programmed at 80 ℃ for 5 min as the initial temperature,then raised to 180 ℃ at the rate of 5℃·min-1 and kept for 10 min. The shunt ratio was 101. Results The liner range for camphol was 0. 487 5-31. 25 μg ( r =0. 999 6),and the average recovery was 95. 95%( n =6). The liner range for isoborneol was 0. 487 5-31. 25 μg( r =0. 999 7),and the average recovery was 96. 44%( n =6). Conclusion The method is accurate,sensitive,and can be applied to quality control of shaoshang yuhe gao.

ObJective To evaluate the multi-slice spiral CT (MSCT) in the diagnosis of early small renal cell carcinoma (RCC). Methods 32 cases of small RCC proved by pathology were retrospectively analyzed. The relationship of imaging features MSCT with pathology was compared. Results Of the 32 RCC in this study, 19 patients were with low density, 6 medium density, and 5 minimal high density. In 24 patients, the lesion were seen as a mixed enhancement pattern, 8 were with the homogeneous enhancement pattern.In cortical phase, clear cell RCC (25/32) tended to be marked enhancement or mixed enhancement pattern; 2 chromophobe lesions and 2 angsarcomakoid renal cell carcinoma (2/32, 2/32 respectively) tended to enhance moderately, papillary lesions (3/32) were mostly hypovascular and homogeneous enhancement pattern. The detection and characterization as well as accuracy of staging in 32 small RCC on MSCT were 100%, 93.75%, and 84.38%, respectively. Conclusion Muhiphase enhanced MSCT scan was a reliable technique in the dectection and clinical predicting subtype of small RCC.