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 This qualitative study aimed to explore the home-based exercise rehabilitation experiences of elderly patients after hip fracture surgery,in order to provide references for exercise intervention during rehabili-tation period.Methods Objective sampling method was used to select 13 elderly hip fracture patients who were hospitalized in the joint surgery department of a tertiary A hospital in Beijing from August 2023 to June 2024 as the research subjects.Semi-structured interviews were conducted,and the interview data were sorted and analyzed by content analysis method.Results The home-based exercise rehabilitation experience of elderly patients after hip fracture surgery can be summarized into 3 themes,including multi-dimensional self-empowerment,use of dynamic personalized skills,full cycle balance reconstruction.Conclusion Patients after hip fracture surgery have rich expe-riences in home exercise rehabilitation,including self-empowerment,exercise skills and balance reconstruction.Nurs-ing staff should strengthen long-term follow-up,according to the real experience and feeling of the patient's home exercise rehabilitation in the whole cycle,actively assist the patients to self-empower,and use various exercise skills to constantly rebuild balance to achieve rehabilitation.

Objective:To construct a narrative nursing intervention plan for post-traumatic growth (PTG) in breast cancer patients and evaluate its effectiveness.Methods:Based on PTG model and the core principles of narrative nursing techniques, an intervention plan was constructed, consisting of three themes. The first unit, "Me and Them, " used externalization techniques to construct deliberate rumination. The second unit, "What Kind of Person Am I, " used deconstruction and rewriting techniques to promote effective disease coping. The third unit, "We Are Together, " applied external witnesses and therapeutic documentation techniques to enhance social support and consolidate growth. Individualized face-to-face interventions were implemented, with each unit receiving one session lasting 1 to 1.5 hours, for a total of three sessions. Using purposive sampling, 42 breast cancer patients hospitalized in the Daytime Ward of Beijing Tiantan Hospital from July to October 2024 were selected. These patients were divided into an intervention group, which received the narrative nursing intervention plan, and a control group, which received routine nursing care, with 21 patients in each group. The Post-Traumatic Growth Inventory (PTGI) and the Chinese version of the Event-Related Rumination Inventory (C-ERRI) were used to assess the patients before and after the intervention.Results:After the intervention, the intervention group showed significantly higher scores on the PTGI and deliberate rumination in the C-ERRI compared to the control group, while the intervention group had significantly lower scores on intrusive rumination in the C-ERRI compared to the control group. The differences were statistically significant ( P<0.05) . Conclusions:The narrative nursing intervention plan for PTG in breast cancer patients constructed in this study is scientifically sound and feasible. It can help breast cancer patients enhance their PTG levels and develop deliberate rumination.

Objective This qualitative study aimed to explore the home-based exercise rehabilitation experiences of elderly patients after hip fracture surgery,in order to provide references for exercise intervention during rehabili-tation period.Methods Objective sampling method was used to select 13 elderly hip fracture patients who were hospitalized in the joint surgery department of a tertiary A hospital in Beijing from August 2023 to June 2024 as the research subjects.Semi-structured interviews were conducted,and the interview data were sorted and analyzed by content analysis method.Results The home-based exercise rehabilitation experience of elderly patients after hip fracture surgery can be summarized into 3 themes,including multi-dimensional self-empowerment,use of dynamic personalized skills,full cycle balance reconstruction.Conclusion Patients after hip fracture surgery have rich expe-riences in home exercise rehabilitation,including self-empowerment,exercise skills and balance reconstruction.Nurs-ing staff should strengthen long-term follow-up,according to the real experience and feeling of the patient's home exercise rehabilitation in the whole cycle,actively assist the patients to self-empower,and use various exercise skills to constantly rebuild balance to achieve rehabilitation.

Objective:To construct a narrative nursing intervention plan for post-traumatic growth (PTG) in breast cancer patients and evaluate its effectiveness.Methods:Based on PTG model and the core principles of narrative nursing techniques, an intervention plan was constructed, consisting of three themes. The first unit, "Me and Them, " used externalization techniques to construct deliberate rumination. The second unit, "What Kind of Person Am I, " used deconstruction and rewriting techniques to promote effective disease coping. The third unit, "We Are Together, " applied external witnesses and therapeutic documentation techniques to enhance social support and consolidate growth. Individualized face-to-face interventions were implemented, with each unit receiving one session lasting 1 to 1.5 hours, for a total of three sessions. Using purposive sampling, 42 breast cancer patients hospitalized in the Daytime Ward of Beijing Tiantan Hospital from July to October 2024 were selected. These patients were divided into an intervention group, which received the narrative nursing intervention plan, and a control group, which received routine nursing care, with 21 patients in each group. The Post-Traumatic Growth Inventory (PTGI) and the Chinese version of the Event-Related Rumination Inventory (C-ERRI) were used to assess the patients before and after the intervention.Results:After the intervention, the intervention group showed significantly higher scores on the PTGI and deliberate rumination in the C-ERRI compared to the control group, while the intervention group had significantly lower scores on intrusive rumination in the C-ERRI compared to the control group. The differences were statistically significant ( P<0.05) . Conclusions:The narrative nursing intervention plan for PTG in breast cancer patients constructed in this study is scientifically sound and feasible. It can help breast cancer patients enhance their PTG levels and develop deliberate rumination.

Myocardial fibrosis(MF),characterized by decreased cardiac function and myocardial compliance,is a pathological process and a progression factor in various cardiovascular diseases.The nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3)inflammasome is closely related to the development of MF.Recent studies have shown that traditional Chinese medicine(TCM)can regulate the NLRP3 inflammasome to alleviate MF.Based on this,this article systematically summarizes the research progress on the mechanisms by which TCM regulates the NLRP3 inflammasome to improve MF.It is found that active ingredients of TCM,such as alkaloids(lycorine,vincristine,bufalin),saponins(astragaloside Ⅳ,diosgenin,ginsenoside Rg3),terpenoids(celastrol,oridonin),and phenols(polydatin,curcumin,phloridzin)as well as TCM formulas(Zhachong shisanwei pills,Zhilong huoxue tongyu capsules,Luqi formula)can inhibit the activation of the NLRP3 inflammasome,thereby suppressing the release of inflammatory factors such as interleukin-1β and IL-18,reducing inflammatory damage to myocardial tissue,alleviating excessive deposition of the extracellular matrix,and thus exerting the effect of improving MF.

Objective:To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods.Methods:This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was ( M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results:The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up ( F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score ( r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score ( r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score ( r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion:Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.

Objective:To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods.Methods:This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was ( M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results:The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up ( F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score ( r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score ( r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score ( r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion:Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.