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 understand the sleep quality and mental health status of nurses in public health emergencies, and analyze the correlation between them.Methods:A total of 128 first-line nursing staff participating in public health emergencies on February 22-23, 2020 in Tianjin Beichen Hospital, Tianjin First Central Hospital, Tianjin Fourth Central Hospital were investigated by the general data questionnaire, Pittsburgh Sleep Quality Index (PSQI), and Symptom Checklist 90 (SCL-90).Results:70.3%(90/128) of nursing staff had poor sleep quality, and the total score of PSQI was (9.71±4.01) points, which was statistically significant compared with the domestic norm ( t value was 16.479, P<0.01). The total score of SCL-90 was 1.59±0.52, which was statistically significant compared with the domestic norm ratio ( t value was 4.505, P<0.01). One-way ANOVA showed that the nursing staff's age had a significant impact on sleep quality, and the difference was statistically significant ( F value was 4.092, P<0.05). Pearson correlation analysis showed that the Pittsburgh sleep quality scale index scores and symptom self-assessment scale and somatization, force, sensitive interpersonal relationship, depression, anxiety, hostile, terrorist, paranoia, and psychosis were positively correlated( r values were 0.292-0.444, P< 0.01). Conclusions:The sleep quality and mental health status of nurses in public health emergencies are poor, and the sleep quality is correlated with mental health status.

Artificial intelligence (AI) is an emerging science and technology that studies and develops theories, methods, technologies, and application systems for simulating and expanding human intelligence. AI has made great breakthroughs in the field of intelligent medicine, and has shown great potential in the diagnosis and treatment of diabetic retinopathy (DR), retinopathy of prematurity, and other fundus diseases. A number of clinical trials on the application of AI technologies to DR screening have been carried out in the domestic and overseas, which not only have a high accuracy rate, but also save doctors' reading time and reduce the burden of society, medical work and patients. However, due to the lack of evaluation system for DR intelligent diagnosis technology, the accuracy of AI system still lacks of big data verification. Secondly, most of the color fundus photographs are taken in the posterior 45°, which only show the most vulnerable areas, making some lesions undetectable. In addition, the current DR screening system has not yet been applied to the clinic, most of which are in the stage of prospective research and trials. There are still many obstacles from the environment to the hospital or the clinic. Doctors cannot use real patient data to evaluate the AI system, so it is not popular in clinical practice. In the future, DR screening algorithms and diagnostic models can be further improved and established to make DR AI screening more accurate.

The number of patients with chronic diseases is increasing year by year,bring a series of chronic problems and challenges to patients and society. Western countries have formed a mature model and system for chronic disease. This paper mainly introduce chronic care models in western country,so as to help nurses and patients in our country to know the management of patients with chronic disease,and then to improve the outcome of patients with chronic disease in our country.

Objective To discuss whether mild hyperuricemia can lead to kidney damage and the protection of decreased uric acid,through observing that hyperuricemia did damage to glomerulus endothelial function and cell proliferation of vascular smooth muscle in rats. Methods Fifty-four male SD rats were divided into four groups,the control group,model group (Oxonate),allopurinol group and Oxonate+allopurinol group.Rats were administered on a low sodium diet and their systolic blood pressure (SBP) were measured each 10 days.ELISA was used to detect rat plasma markers of endothelial function damage [nitric oxide (NO),type-1 plasminogen activator inhibitor (PAI-1),endothelin 1 (ET-1)] and cell proliferation of vascular smooth muscle[plateletderived growth factor (PDGF),cycloxygenase 2 (COX2),monocyte chemotactic protein-1 (MCP-1)],and the markers of inflammatory reaction[interleukin-18 (IL-18),tumor necrosis factor α(TNF-α)].PDGF and nitric oxide synthase (NOS) levels of rats were detected by immunohistochemical method.Renal tissue pathology of rats was observed. Results Compared to the control group,the plasmic concentration of COX2,ET-1,IL-18,PAI-1,PDGF,TNF-o,MCP-1 increased,and NO decreased significantly in rats of model group (all P＜0.05),expression of NOS significantly reduced and PDGF increased (all P＜0.05).Under light microscope,vascular wall thickening,intimal proliferation and lumen slight stricture without uric acid crystals in renal tissue were found in model group,which were obviously improved by using allopurinol. Conclusion Mild hyperuricemia can do damage to endothelial function of glomerulus and lead to vascular cell proliferation,which can be improved through decreasing uric acid.

By using semi-quantitative RT-PCR method, it was found that PD-L1 mRNA but not PD-L2 mRNA was expressed in H22 hepatoma cells and both PD-L1 and PD-L2 mRNAs were expressed in tumor tissues of tumor-bearing mice and upregulated as compared with muscle tissues in normal mice and H22 hepatoma cells. PD-L1 and PD-L2 were also expressed on the surface of the activated T cells. The soluble recombinant sPD-1 expressed from the constructed eukaryotic expression vector could enhance the lysis of tumor cells by lymphocytes stimulated specifically with antigen. The expresssion of sPD-1 by local gene therapy on the inoculation site of H22 hepatoma cells could inhibit the growth of tumor. The results of this study indicate that expression of soluble receptor of negative costimulatory molecules could reduce the inhibitory effect on T cells in tumor microenvironment and enhance the cytotoxicity of T cells on tumor cells. This possibly provides a new method of improving efficacy of tumor gene therapy.
Animals ; B7-1 Antigen ; biosynthesis ; genetics ; B7-H1 Antigen ; Carcinoma, Hepatocellular ; immunology ; pathology ; Genetic Therapy ; Liver Neoplasms ; immunology ; pathology ; Male ; Membrane Glycoproteins ; biosynthesis ; genetics ; Mice ; Mice, Inbred BALB C ; Peptides ; genetics ; metabolism ; Programmed Cell Death 1 Ligand 2 Protein ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Spleen ; cytology ; T-Lymphocytes ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection ; Tumor Cells, Cultured