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.

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 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.

Objective:To explore the effect of functional exercise rehabilitation bridging mode on the functional exercise and self-management ability of patients after breast cancer surgery, so as to provide reference for guiding patients to achieve full process management and self-management and rehabilitation.Methods:Using a non randomized grouping quasi experimental design, 202 patients with breast cancer undergoing surgical treatment were selected from the breast surgery department of Yuhuangding Hospital in Yantai from March to July 2021 through convenient sampling. The control group received routine nursing and rehabilitation guidance. The intervention group adopted a rehabilitation bridging mode for postoperative functional exercise on the basis of routine nursing care. The functional exercise compliance rate and self management ability of the two groups of patients after the intervention were evaluated.Results:In the intervention group, the rate of functional exercise reaching the standard, the rate of functional exercise knowledge awareness, correctness and compliance in self-management ability of breast cancer patients were as follows: 93.1%(95/102), 71.6%(73/102), 80.4%(82/102), 73.5%(75/102), which were higher than the control group 84.0%(84/100), 46.0%(46/100), 52.0%(52/100), 17.0%(17/100). The differences were statistically significant ( χ2 values were 4.18-65.06, all P<0.05). Conclusions:The rehabilitation bridging mode could connect the functional exercise needs of patients at different stages of rehabilitation, provide personalized, continuous, and standardized functional exercise guidance for patients, help them improve the effect of functional exercise, and improve their self management ability.

Corni Fructus, as a commonly used Chinese materia medica in clinical practice, has the efficacy of tonifying and replenishing the liver and kidney as well as stopping collapse with astringent therapy. Given the controversy among medical experts through the ages over its medicinal parts, the author conducted a textual research on the name, origin, changes in producing areas and quality, medicinal parts, collecting, harvesting and processing, natures, tastes, efficacy, usage and dosage of Corni Fructus by consulting materia medica and medical classics of past ages, and combining relevant modern literature and standards, to ensure the precision medication of classic formulas containing it and provide a reference for further development and utilization. According to the textual research, it can be concluded that Corni Fructus has originated from Cornus officinalis Sieb.et Zucc. since ancient times. It was first produced in Shandong and Shaanxi, and later extended to Henan, Zhejiang, and other places for large-scale cultivation. Currently, the quality of products produced in Zhejiang is recommended. Initially, the whole fruit of Corni Fructus was used for medicine, but due to the influence of “the core causes spontaneous seminal emission” theory, the flesh of Corni Fructus(flesh with removing the core from the fruit) has become the mainstream product standard throughout the ages. However, in clinical practice, both specifications exist and should be used in accordance with syndrome differentiation and patient types. There are also many processing methods for Corni Fructus recorded in materia medica and medical classics of past ages, but the mainstream processing varieties are raw medicinal materials of Corni Fructus and flesh of Corni Fructus processed by wine. In terms of the properties and flavors of Corni Fructus, initially priority have been given to “taste sour, mild, lukewarm without toxicity in nature”, now have been switched to “taste sour, astringent, lukewarm in nature”. Moreover, its dosage range of medication of past ages varies greatly from that specified in the pharmacopoeia. It is recommended that clinical doctors choose the appropriate dosage recorded in classic prescriptions according to the patient and disease type, as conditions permit, to maximize the clinical efficacy of Corni Fructus.

Objective:To systematically review the impact of resistance training on body weight and body composition in breast cancer patients.Methods:Randomized controlled trials of the impact of resistance training on body weight and body composition in breast cancer patients were searched through computers in Cochrane Library, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) , China Biomedical Literature Database, VIP and WanFang Data. The search period was from the establishment of the database to April 20, 2022. Two researchers independently screened the article, evaluated the quality of the article, and extracted the data. Meta-analysis was conducted using RevMan 5.4 software.Results:A total of 11 articles were included, including 1 077 patients with breast cancer. Meta-analysis results showed that resistance training could reduce body fat rate [ SMD=-1.21, 95% CI (-1.92, -0.50) , P<0.01] , fat mass [ SMD=-0.64, 95% CI (-1.13, -0.14) , P<0.01] , and increase lean body weight [ SMD=1.31, 95% CI (0.54, 2.07) , P<0.01] in breast cancer patients compared with conventional nursing or flexibility training, but there was no statistical difference in the impact on body weight ( P>0.05) . Conclusions:Resistance training can improve the body composition, and has positive impacts on the body weight and body composition in breast cancer patients.

Objective To predict the intervention targets of empagliflozin(EMPA),a specific inhibitor of sodium-glucose cotransporter 2(SGLT2),in gastric adenocarcinoma through comprehensive network pharmacology,and to validate the effects and the molecular mechanisms of EMPA through cellular and molecular biology experiments.Methods Bioinformatics analysis of gastric adenocarcinoma was conducted to assess the correlation between gastric adenocarcinoma prognosis and SGLT2 expression.Network pharmacology was utilized to identify shared targets of EMPA and gastric adenocarcinoma.AGS cells,a human gastric adenocarcinoma cells line,were incubated with EMPA at different concentrations for 24 h and,then,cell proliferation was assessed using the CCK8 assay.After AGS cells were incubated with EMPA at the doses of 0,3,and 6 mmol/L,real-time cell analysis(RTCA)and 5-ethynyl-2-deoxyuridine(EdU)incorporation were used to evaluate EMPA's inhibitory effects on the proliferation of the AGS cells.In addition,wound healing and Transwell assays were performed to assess the inhibitory effect of EMPA on the migration and invasion of the APC cells and Western blot analysis was conducted to examine the expression of mammalian target of rapamycin(mTOR)and phosphorylated mTOR(p-mTOR).BALB/c(nu/nu)nude mice were implanted with 5x106 AGS cells in the axilla.The mice were divided into three groups,a control group,a low-dose group,and a high-dose group,each consisting of 7 mice.After one week,the control group received daily intraperitoneal injections of normal saline,while the low-dose group and high-dose group received daily intraperitoneal injections of EMPA at the doses of 3 mg/kg and 5 mg/kg,respectively.The tumor volume was measured one week after the drug intervention started.Results Gastric adenocarcinoma patients with low expression of SGLT2 exhibited longer survival time and higher survival rate than those with high expression of SGLT2 did.A total of 104 EMPA-related potential targets and 2028 targets associated with gastric adenocarcinoma were identified.Among these,45 targets associated with gastric adenocarcinoma overlapped with potential targets of EMPA.Further analysis revealed 10 relevant pathways and 4 core genes.The core genes were cyclin-dependent kinase 4(CDK4),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),mTOR,and cyclin El(CCNE1).CCK-8 assay revealed that EMPA at concentrations ranging from 0.39 to 50 mmol/L effectively inhibited the proliferation of AGS cells.RTCA results indicated a downward shift in the cell growth curve.In comparison to the findings for the control group,EdU assay demonstrated that EMPA at the concentrations of 3 mmol/L and 6 mmol/L significantly inhibited AGS cell proliferation(P＜0.05).Results from wound healing and Transwell assays indicated a decrease in the levels of cell migration and invasion(P＜0.05)and,notably,there was a significant difference between the high and low-dose EMPA groups(P＜0.05).Western blot showed no statistically significant difference in the expression of total mTOR protein between the groups.However,the expression of p-mTOR in the 3 mmol/L and 6 mmol/L EMPA groups decreased compared to that of the control group(P＜0.05),with the 6 mmol/L EMPA group exhibiting a more pronounced reduction(P＜0.05).Nude mice xenograft tumor experiment demonstrated that,compared to that of the control group,the tumor volumes in the EMPA-treatment groups were significantly reduced(P＜0.05),with the high-dose group showing a more pronounced reduction(P＜0.05).Conclusion EMPA inhibits the abnormal proliferation and migration of gastric adenocarcinoma cells,potentially through the modulation of mTOR protein activation.This study provides new potential medication and intervention targets for gastric adenocarcinoma treatment.