ObjectiveTo investigate the therapeutic mechanism of artemether in diabetic sarcopenia（DS）using network pharmacology and animal experiments. MethodsPotential active components and therapeutic targets were screened using artemisinin as the parent compound. The predicted targets were intersected with DS-related targets， followed by construction of a protein-protein interaction （PPI） network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed to identify the key biological processes and signaling pathways. Molecular docking was further used to evaluate the binding affinity between artemether and core targets. The DS mouse model was established using db/db mice， followed by artemether intervention. Fasting blood glucose， body weight， diabetes-related symptoms， body composition， grip strength， serum and skeletal muscle triglyceride levels， and muscle fiber cross-sectional area （CSA） were assessed. The expression levels of forkhead box O1 （FoxO1）， Atrogin-1， muscle RING finger protein 1 （MuRF1）， acyl-CoA synthetase short-chain family member 2 （ACSS2）， carnitine palmitoyltransferase 2 （CPT2）， and fatty acid-binding protein 3 （FABP3） in skeletal muscle were detected by qRT-PCR， Western blot， immunofluorescence， and immunohistochemistry. In addition， metabolomics was performed to analyze changes in acylcarnitine metabolites in skeletal muscle. ResultsA total of 68 overlapping targets between artemether and diabetic sarcopenia （DS） were identified. The core targets included AKT1， FoxO1， NFKB1， FBXO32， and TRIM63， which were mainly enriched in the phosphoinositide 3-kinase/protein kinase B （PI3K-Akt） signaling pathway， forkhead box O （FoxO） signWaling pathway， tumor necrosis factor （TNF） signaling pathway， and insulin resistance-related pathways. Molecular docking analysis showed that artemether exhibited favorable binding affinity with the core targets. Animal experiments demonstrated that artemether reduced fasting blood glucose， ameliorated metabolic symptoms， increased lean mass and grip strength， decreased serum and skeletal muscle triglyceride levels， and increased muscle fiber cross-sectional area （CSA） in DS mice. In addition， artemether downregulated the mRNA and protein expression levels of FoxO1， FBXO32/Atrogin-1， TRIM63/MuRF1， ACSS2， CPT2， and FABP3， and improved the disturbance of acylcarnitine metabolism in skeletal muscle. ConclusionArtemether improves metabolic and skeletal muscle phenotypes in DS mice. Its effects may be associated with the amelioration of lipid metabolic disorders and the downregulation of FoxO1 and its downstream ubiquitin-proteasome pathway-related factors Atrogin-1 and MuRF1 in skeletal muscle.

Objective: To explore the association of physical activity and sugar sweetened beverage consumption with psychological sub health among middle school students in Bao an District, Shenzhen, so as to provide a reference for adolescent mental health promotion. Methods: A questionnaire survey was conducted in November 2024 by a stratified cluster random sampling method to select 6 926 junior and senior middle school students from 5 middle schools in Shenzhen. The questionnaire from Youth Risk Behavior Surveillance System was used to assess the consumption of sugar sweetened beverages, and physical activity Rating Scale was used to assess the level of physical activity, and Brief Instrument on Psychological Health of Youths was used to evaluate the psychological sub health status. The Chi -square test was used to analyze the differences in the detection rates of psychological sub health among different groups of middle school students, and a multivariate Logistic regression model was established to analyze the effects of physical activity and sugar sweetened beverage consumption and their combined effects on the psychological sub health of middle school students. Results: The detection rate of psychological sub health among middle school students in Bao an District, Shenzhen was 18.93%. Multivariate Logistic regression analysis showed that, after controlling for confounding factors such as gender, school stage, family residence, family economic status, parental literacy, academic stress and number of friends, lack of physical activity or excessive sugar sweetened beverage consumption were associated with increased risks of psychological sub health among middle school students ( OR =1.36, 1.45); and the highest risk of psychological sub health was found in middle school students who were lack of physical activity and excessive sugar sweetened beverage consumption ( OR =2.59) ( P <0.01). Further analysis by school stages showed that junior high school students with sufficient physical activity and excessive intake of sugary drinks ( ROR =2.10), lack of physical activity and excessive intake of sugary drinks ( ROR =2.31) were at higher risks of psychological sub health than senior high school students( P <0.05). Conclusions Insufficient physical activity and excessive sugar sweetened beverage consumption are closely associated with an increased risk of psychological sub health among middle school students. Effective interventions should be targeted to reduce the risk of psychological sub health problems among middle school students.

Objective To explore the anesthesia management experience in the interventional treatment of pediatric congenital heart diseases (CHD) percutaneously guided by transthoracic echocardiography (TTE) on a mobile operating platform. Methods From March to July 2023, a total of 13 patients from remote areas underwent interventional treatment for CHD on the mobile operating platform of Fuwai Yunnan Cardiovascular Hospital. Patients who received non-tracheal intubation general anesthesia were retrospectively included. Results Eight children who had difficulty cooperating with the surgery (due to young age, emotional tension, crying) received monitored anesthesia care with local anesthesia supplemented by sedative and analgesic drugs while maintaining spontaneous breathing under the monitoring and management of an anesthesiologist (i.e., non-tracheal intubation general anesthesia). Among them, there were 5 males and 3 females, with an age of (6.95±3.29) years and a body weight of (19.50±6.04) kg. Through transthoracic echocardiography, they were diagnosed with atrial septal defect (6 patients), residual shunt after patent ductus arteriosus ligation (1 patient), and severe pulmonary valve stenosis (1 patient). The surgery proceeded smoothly, with satisfactory anesthesia and surgical effects, complete analgesia, and satisfactory postoperative recovery. There was 1 patient of body movement and 1 patient of respiratory depression during the operation, and both patients completed the surgery successfully after treatment. All children had no serious surgery- and anesthesia-related complications. The anesthesia time was 40.5 (34.5, 47.5) min, the surgery time was 39.0 (33.0, 45.5) min, and the recovery time was 43.0 (28.0, 52.5) min Conclusion Interventional surgery for CHD guided by TTE at a mobile platform is a minimally invasive approach without radiation damage. Non-tracheal intubation general anesthesia with spontaneous breathing can be safely and effectively implemented in children who cannot cooperate.

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

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged