ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

ObjectiveTo investigate the clinical effects and safety of Shuhe Granules （舒和颗粒） in patients with rheumatoid arthritis （RA） comorbid with insomnia. MethodsA single-arm prospective exploratory design was adopted. Thirty RA patients comorbid with insomnia and diagnosed with the traditional Chinese medicine （TCM） syndrome of kidney-heart deficiency and qi-blood disharmony were enrolled. On the basis of maintaining their original RA treatment regimens， all patients received oral Shuhe Granules， one dose per day， for 12 consecutive weeks. The outcomes were assessed before treatment and at weeks 4， 8， and 12 after treatment. Sleep and related psychosomatic function were evaluated using the insomnia severity index （ISI）， Pittsburgh sleep quality index （PSQI）， fatigue severity scale （FSS）， patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， and Montreal cognitive assessment （MoCA） scores. RA-related assessments included the 28-joint disease activity score based on C-reactive protein （DAS28-CRP）， pain visual analog scale （VAS）， tender joint count （TJC28）， swollen joint count （SJC28）， morning stiffness duration， and health assessment questionnaire （HAQ） score. Laboratory parameters included erythrocyte sedimentation rate （ESR）， serum C-reactive protein （CRP）， anti-cyclic citrullinated peptide antibody （anti-CCP）， and rheumatoid factor （RF） levels. A literature-based historical control group was established through literature retrieval and meta-analysis. The ISI， PSQI， DAS28-CRP， and pain VAS scores were compared between the treatment group in the present study and the historical control group. Safety assessments were also performed. ResultsCompared with baseline before treatment， ISI and PSQI scores decreased at weeks 4， 8， and 12， while MoCA scores increased at weeks 4， 8， and 12. FSS scores decreased at weeks 4 and 12. At weeks 8 and 12， GAD-7 scores， DAS28-CRP scores， duration of morning stiffness， TJC28， and SJC28 were reduced. At week 12， PHQ-9， pain VAS， and HAQ scores significantly decreased （P＜0.05）. FSS and DAS28-CRP scores at week 12 were lower than those at week 4， and CRP levels at week 8 were lower than those at week 4 （P＜0.05）. Compared with the historical control group， the treatment group showed superior improvement in ISI and PSQI scores （P＜0.001）； however， no statistically significant differences were observed between the two groups in DAS28-CRP or pain VAS scores （P＞0.05）. No serious adverse events occurred during the study， and the 4 reported mild adverse events were all considered unrelated to the study medication. ConclusionShuhe Granules significantly improve sleep quality， fatigue， emotional status， cognitive function， RA-related symptoms， and joint function in patients with RA comorbid insomnia， with good safety and tolerability.

Objective To evaluate the effect of remimazolam premedication on emergence delirium （ED） in children undergoing tonsillectomy and/or adenoidectomy. Methods Children aged 3-6 years who underwent tonsillectomy and/or adenoidectomy with general anesthesia in Zhongshan Hospital Affiliated to Xiamen University from July 2023 to September 2024 were randomly divided into 0.1 mg/kg remimazolam group （group R1）, 0.2 mg/kg remimazolam group group R2） and normal saline group （group P）. Three groups were sedated preoperatively with remimazolam 0.1 mg/kg, remimazolam 0.2 mg/kg and normal saline, respectively. The primary outcome was the incidence of ED. The secondary outcomes included the parental separation anxiety scale （PSAS） score when entering the operating room, the induction compliance checklist （ICC） score at induction, the anesthetic recovery time, the incidence of rescue propofol for ED, the face, legs, activity, cry, and consolability （FLACC） score and the incidence of postoperative pain during the recovery period, the incidence of adverse reactions during the operation and postoperatively, and the incidence of negative postoperative behavioral changes （NPOBCs） at first day, 7th day, 30th day postoperatively. Results A total of 119 children completed the study, including 41 children in group R1, 38 children in group R2, and 40 children ingroup P. The incidence of ED and propofol rescue, the PSAS scores and ICC scores of group R1 and R2 were lower than that of group P （P<0.05）, and the above results in group R2 was better than those in group R1 （P<0.05）. The FLACC score, the incidence of postoperative pain, and the incidence of adverse reactions among the three groups had no difference （P>0.05）. The incidence of NPOBCs at 1st day and 7th day postoperatively in group R1 and group R2 was lower than that in group P （P<0.05）, but no difference was detected at 30th day postoperatively among the three groups （P>0.05）. Conclusion Remimazolam used for preoperative sedation could reduce the incidence of ED in children undergoing tonsillectomy and/or adenoidectomy, and had a positive effect on alleviating the preoperative anxiety and preventing NPOBCs.

Objective: To analyze the structural changes in whole blood and apheresis platelet donations in Chinese Society of Blood Transfusion (CSBT) sentinel units from 2021 to 2025, and to provide evidence for donor recruitment and blood service management. Methods: Aggregated data reported by sentinel sites were collected and stratified according to six indicators: age, sex, donation history, donation volume, donation site, and organization mode. Pearson χ test, Cramer′V coefficient, Cochran-Armitage trend test and simple linear regression were adopted for analysis. Results: A total of 16 256 973 whole blood donations and 1 576 546 apheresis platelet donations were included. Among whole-blood donations, the proportion of donors aged 18-22 years decreased from 27.30% to 10.60%. The proportion of male donors increased from 58.81% to 63.13%; the proportion of people aged 30 and above increased from 58.40% to 75.30%; the proportion of fixed locations rose from 28.37% to 36.57%; the proportion of social groups increased from 21.69% to 39.69%. The 400-mL donations decreased from 62.12% to 53.46%, while individually initiated voluntary donations remained above 50%. Apheresis platelet donations were predominantly from males, individuals aged 30-39 years, and repeat donors; 2-treatment-unit apheresis platelet donations increased from 67.19% to 74.93%, and individually initiated donations accounted for 92.97%-96.02%. Statistically significant overall annual compositional differences were observed for all six indicators (all P<0.001), whereas linear trends for some sub-categories were not statistically significant. Conclusion: In the participating CSBT sentinel units, among whole blood donations, the proportions of donors aged 18-22 years, university-organized group donations, and donations at blood mobiles decreased, whereas the proportions of organizational group donations and donations at fixed venues increased. The apheresis platelet donation cohort is relatively mature and is evolving toward a high-efficiency donation model. Individual voluntary donation remains the primary organization mode for both donation types. Strategies such as youth donor recruitment, optimized layout of fixed donation sites, and retention of repeat donors should be strengthened to improve the resilience of blood supply.

ObjectiveTo investigate the patterns of chronic disease comorbidity among permanent elderly residents in Xuhui District of Shanghai, and to analyze the impact of different comorbidity patterns on the elderly’s ability to perform activities of daily living. MethodsBased on data from the 2015 and 2021 Surveys on Health Status and Health Service Utilization among Permanent Residents in Xuhui District of Shanghai, the study included permanent residents who fully participated in both surveys, were aged 60 years or older at the 2015 survey, self-reported having a chronic disease, and reported no significant changes in their chronic disease status between the two surveys. A prospective cohort study design was adopted, using the 2015 data as the baseline and the 2021 survey data as follow-up data. Physical examinations and questionnaire surveys were conducted by the Shanghai Xuhui District Center for Disease Control and Prevention in the subdistricts and towns within the jurisdiction from April to July in both 2015 and 2021. Latent class analysis (LCA) was used to classify comorbidity patterns across 11 types of chronic diseases. The smaller the values of the Akaike information criterion (AIC), the Bayesian information criterion (BIC), and the sample-corrected Bayesian information criterion (aBIC), the better the model fits. The Barthel index (BI) and the Lawton and Brody Instrumental Activities of Daily Living Scale (LB-IADL) were used to assess the participants’ activities of daily living (ADL) and instrumental activities of daily living (IADL). Multiple linear regression and multivariate logistic regression models were used to analyze the association between different comorbidity patterns and ADL and IADL. ResultsA total of 1 608 study participants were enrolled. Among them, 671 (41.73%) self-reported having no chronic diseases. The prevalence of 11 types of chronic diseases was as follows: hypertension in 743 participants (46.21%), heart disease in 148 participants (9.20%), cerebrovascular disease in 37 participants (2.30%), diabetes or abnormal blood glucose in 310 participants (19.28%), other endocrine system diseases (non-diabetic) in 39 participants (2.43%), malignant tumors in 37 participants (2.30%), chronic lung disease in 16 participants (1.00%), gout in 8 participants (0.50%), musculoskeletal disorders in 34 participants (2.11%), gastric or digestive system diseases in 27 participants (1.68%), and dyslipidemia in 15 participants (0.93%). LCA was used to classify comorbidity patterns of chronic diseases among older adults into 1 to 9 latent category combinations. Model 5 (i.e., 5 latent categories) had the lowest BIC (7 112.69) and aBIC (6 909.38), with a relatively low AIC (6 768.20), indicating the best model fit; thus, five latent categories represented the optimal combination in this study. The five latent categories (and their respective proportions of study participants) were the healthy control group (41.73%), the hypertension group (31.28%), the diabetes-hypertension group (19.28%), the severe illness group (5.29%), and the other metabolic diseases group (2.43%). According to multiple linear regression analyses, compared with the healthy control group, the diabetes-hypertension group had significantly lower BI-20 scores (b=-0.952, 95%CI: -1.317‒ -0.587, P<0.001) and lower IADL scores (b=-0.744, 95%CI: -0.999‒ -0.489, P<0.001); the severe illness group (b=-0.644, 95%CI: -1.072‒ -0.217, P=0.003) and the hypertension group (b=-0.344, 95%CI: -0.562‒ -0.125, P=0.002) had lower IADL scores. According to multivariate logistic regression analyses, compared with the healthy control group, older adults in the diabetes-hypertension group had a higher risk of disability (OR=2.835, 95%CI: 1.392‒5.774), impaired ADL function (OR=2.470, 95%CI: 1.637‒3.726), and impaired IADL function (OR=1.739, 95%CI: 1.264‒2.392); older adults in the severe illness group had a higher risk of impaired ADL function (OR=2.206, 95%CI: 1.171‒4.155). ConclusionAmong the elderly participating in the Survey on Health Status and Health Service Utilization of Permanent Residents in Xuhui District of Shanghai, diabetes-hypertension is one of the key chronic disease comorbidity combinations and has adverse effects on both ADL and IADL. Community health management should prioritize the elderly with diabetes-hypertension comorbidity, and strengthen early screening and comprehensive interventions to slow the decline in ADL and IADL.

Autism spectrum disorder in children (hereinafter called "childhood autism") is a prevalent neurodevelopmental condition; however, ancient Chinese medical texts did not provide detailed accounts of it. The concept of "the sovereign fire illuminates, while the ministerial fire occupies its position" was first introduced in the Plain Questions: The Great Treatise on the Origin of Heavenly Influences chapter. Subsequent medical practitioners have elaborated on this idea, identifying the sovereign fire as the master of the spirit and governing life activities, while the ministerial fire is the assisting minister that supports the functions of the zang-fu organs. When these two are in harmony, they complement each other, collectively sustaining the body′s normal physiological functions. In the context of this theory, the pathogenesis of childhood autism is attributed to the imbalance between the sovereign and ministerial fires. The root cause lies in the mutual antagonism of these two fires, resulting in the dysfunction of the spirit. Central to childhood autism onset is the dimming of the sovereign fire and a deficiency in the spirit, while the displacement of the ministerial fire and the impaired function of the five viscera contribute significantly to the progression of the condition. Effective treatment for childhood autism involves restoring these imbalances: dispelling yin-related obstructions to illuminate the sovereign fire, nourishing the spleen and kidney to nourish the ministerial fire, and regulating the liver and lung to harmonize the sovereign and ministerial fires. The ultimate goal is to integrate body and spirit, harmonize the sovereign and ministerial fires, and restore the interconnectedness between spirit and the function of the five zang viscera. This article, based on the "the sovereign fire illuminates, while the ministerial fire occupies its position" theory, provides a novel perspective and insights for understanding and treating childhood autism through the holistic principles of traditional Chinese medicine. Emphasizing the integration of body and spirit offers new insights and approaches for the clinical management of childhood autism in traditional Chinese medicine.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

The angiogenic response is essential for the repair of ischemic brain tissue. Integrin α6 (Itga6) expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures; however, its role in post-ischemic angiogenesis remains poorly understood. In this study, we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization, reduced pericyte coverage on microvessels, and accelerated breakdown of microvascular integrity in the peri-infarct area. In vitro, endothelial cells with ITGA6 knockdown display reduced proliferation, migration, and tube-formation. Mechanistically, we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis. Importantly, the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels, leading to improved functional recovery. Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis, and may represent a promising therapeutic target for promoting recovery after stroke.
Animals ; Nitric Oxide Synthase Type III/metabolism* ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Integrin alpha6/genetics* ; Endothelial Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Stroke/pathology* ; Vascular Remodeling/physiology* ; Vascular Endothelial Growth Factor A/metabolism* ; Mice, Knockout ; Signal Transduction/physiology* ; Mice, Inbred C57BL ; Male ; Neovascularization, Physiologic/physiology*