Attention deficit hyperactivity disorder （ADHD） is often accompanied by tic disorder. The core pathogenesis is considered to be ministerial fire scorching yin and internal stirring of deficient wind， which leads to disharmony between the body and spirit， resulting in clinical manifestations. The treatment principles emphasize nourishing yin fluids， calming ministerial fire， and extinguishing endogenous wind （内风）. The method of nourishing yin fluids is applied throughout the entire treatment process， commonly using ingredients such as Shudihuang （Rehmanniae Radix Praeparata）， Shanzhuyu （Corni Fructus）， Gouqizi （Lycii Fructus）， Wuweizi （Schisandrae Chinensis Fructus）， and Tusizi （Cuscutae Semen）. These are combined with approaches to harmonize the zang-fu organs， primarily including extinguishing liver wind， clearing heart fire， nourishing kidney water， and strengthening spleen earth， thereby stabilizing ministerial fire and extinguishing endogenous wind. Additionally， emotional regulation and smoothing emotional constraint are essential to improve clinical symptoms in children with ADHD comorbid with tic disorder.

Objective To explore the application of artificial intelligence (AI) in the standardized training of thoracic surgery residents, specifically in enhancing clinical skills and anatomical understanding through AI-assisted lung nodule identification and lung segment anatomy teaching. Methods Thoracic surgery residents undergoing standardized training at Peking Union Medical College Hospital from September 2023 to September 2024 were selected. They were randomly assigned to a trial group and a control group using a random number table. The trial group used AI-assisted three-dimensional reconstruction technology for lung nodule identification, while the control group used conventional chest CT images. After basic teaching and self-practice, the ability to identify lung nodules on the same patient CT images was evaluated, and feedback was collected through questionnaires. Results A total of 72 residents participated in the study, including 30 (41.7%) males and 42 (58.3%) females, with an average age of (24.0±3.0) years. The trial group showed significantly better overall diagnostic accuracy for lung nodules (91.9% vs. 73.3%) and lung segment identification (100.0% vs. 83.70%) compared to the control group, and the reading time was significantly shorter [ (118.5±10.5) s vs. (332.1±20.2) s, P<0.01]. Questionnaire results indicated that 94.4% of the residents had a positive attitude toward AI technology, and 91.7% believed that it improved diagnostic accuracy. Conclusion AI-assisted teaching significantly improves thoracic surgery residents’ ability to read images and clinical thinking, providing a new direction for the reform of standardized training.

ObjectiveTo observe the efficacy of Sangmei Pingfeng granules combined with western medicine in the treatment of patients with allergic asthma in the chronic persistent stage， diagnosed with lung-spleen Qi deficiency syndrome in traditional Chinese medicine （TCM）. MethodsA retrospective analysis was conducted on 420 patients with allergic asthma in the chronic persistent stage and TCM-diagnosed lung-spleen Qi deficiency syndrome， treated at the Third Affiliated Hospital of Beijing University of Chinese Medicine from January 2017 to September 2024. Patients were divided into an exposed group （320 cases） and a non-exposed group （100 cases） based on whether they used Sangmei Pingfeng granules. The non-exposed group received conventional western medicine treatment， while the exposed group took Sangmei Pingfeng Granules in addition to conventional western medicine. The following indicators were observed： recurrence rate per 100 patients per year， pulmonary function tests， fractional exhaled nitric oxide （FeNO） and fractional nasal nitric oxide （FnNO） tests， serum total IgE （TIgE） detection， TCM syndrome score， and changes in asthma control test （ACT） scores between the two groups. ResultsThe annual recurrence rate per 100 people was 8.4 times/100 person-years in the exposed group， lower than the 13 times/100 person-years in the unexposed group. After treatment， the exposed group showed increases in forced vital capacity percentage predicted （FVC%pred）， forced expiratory volume in one second percentage predicted （FEV₁%pred）， the ratio of forced expiratory volume in one second to forced vital capacity （FEV₁/FVC）， and peak expiratory flow percentage predicted （PEF%pred） （P0.05）. Lung function indicators in the non-exposed group showed no statistically significant differences after treatment. Residual volume as a percentage of total lung capacity （RV%TLC） showed no statistically significant difference after treatment in either group. Compared with the non-exposed group， the exposed group had increased FVC%pred， FEV₁%pred， FEV₁/FVC， and PEF%pred， without statistically significant differences. After treatment， fractional exhaled nitric oxide （FeNO）， fractional nasal nitric oxide （FnNO）， and total immunoglobulin E （TIgE） decreased in the exposed group. FeNO decreased in the non-exposed group （P0.05）. FnNO decreased， and TIgE increased in the non-exposed group， without statistically significant differences. After treatment， compared with the non-exposed group， the treatment group had decreased FeNO （P0.05）. After treatment， traditional Chinese medicine （TCM） syndrome scores decreased， and asthma control test （ACT） scores increased in both groups （P0.01）. After treatment， compared with the non-exposed group， the exposed group had decreased TCM syndrome scores and increased ACT scores （P0.01）. ConclusionCombining Sangmei Pingfeng granules with Western medicine significantly reduces recurrence rates， enhances clinical efficacy， improves lung function， lowers serum TIgE and FeNO levels， and reduces reliance on Western medications in patients with allergic asthma. This integrated approach is worthy of clinical promotion and application.

ObjectiveTo analyze the correlation between the clinical symptoms， signs， syndrome characteristics and laboratory indicators of cough variant asthma （CVA） and deepen the understanding of the treatment of this disease based on the theory of "Fu Feng". MethodsAn observational study was conducted. A total of 207 CVA patients who visited the respiratory department of the Third Affiliated Hospital of Beijing University of Chinese Medicine from September 2022 to November 2023 were included. The information from the four diagnostic methods and the laboratory test results of patients were collected. Factor analysis was conducted on the information obtained through the four diagnostic methods in TCM， and the nature and location of CVA were extracted. Sample cluster analysis （Q clustering） and the K-means method were used for data clustering analysis to determine the syndrome types of CVA and analyze the syndrome characteristics and differences in laboratory indicators among different syndrome types. ResultsThe main symptom of CVA patients was cough， accompanied by symptoms such as itchy throat， foreign body sensation in the throat， dry throat， shortness of breath， dry mouth， chest tightness， hoarseness， bitter mouth， poor appetite， and skin itching. Factor analysis showed that the disease was located in the lung， involving the liver， spleen， and kidney. The pathological factors involved Yin deficiency， Yang deficiency， wind factor， dampness factor， Yin factor， and Qi stagnation. Cluster analysis revealed four syndrome types： Fengfu Yinshang syndrome， Shixie Neiyun syndrome， Tanyin Zufei syndrome， and Ganhuo Fanfei syndrome. Fengfu Yinshang syndrome accounted for the highest proportion， followed by Tanyin Zufei syndrome. There were no significant differences in eosinophil count and percentage， fractional nasal nitric oxide （FnNO） level， and pulmonary function indexes among the four syndromes. The levels of serum total IgE and fractional exhaled nitric oxide （FeNO） in patients with Fengfu Yinshang syndrome were significantly higher than those in patients with Shixie Neiyun syndrome and Tanyin Zufeisyndrome. ConclusionCough is the main symptom of CVA， accompanied by pharyngeal itching， foreign body sensation in the throat， dry throat， shortness of breath， dry mouth， and allergic manifestations. The disease involves the lung， liver， spleen， and kidneys. The essence of the pathogenesis lies in a latent dormant pathogen and a disorder of the pivot mechanism. The four common syndrome types are Fengfu Yinshang syndrome， Shixie Neiyun syndrome， Tanyin Zufei syndrome， and Ganhuo Fanfei syndrome. The TCM syndrome types are correlated with laboratory indexes. The serum total IgE and FeNO of patients with Fengfu Yinshang syndrome are worse.

Based on the theory of "three regions and sanjiao" in traditional Chinese medicine (TCM), the acupuncture-moxibustion differentiation and treatment system is explored and constructed for spasm syndrome, so as to provide a clearer guiding framework for TCM treatment of spasm syndrome. This disorder is caused essentially by the invasion of pathogenic wind, and located in brain marrow. The key regions of illness cover five zang organs and five tissues, and the core pathogenesis is associated with wind disturbance in brain marrow. In differentiation, spasm syndrome refers to overall transmission (from the upper to the lower) and local transmission (from exterior to interior). This disorder can be classified into sanjiao spasm (heart-lung spasm of the upper jiao, liver-spleen spasm of the middle jiao, and liver-kidney spasm of the lower jiao) and three-region spasm (skin-vessel spasm of the upper region, tendon-muscle spasm of the middle region, and tendon-bone spasm of the lower region). Based on "three regions and sanjiao" theory of acupuncture and moxibustion, 7 "expelling-wind" points can be selected in terms of the etiology of this disease. Baihui (GV20)-toward-Taiyang (EX-HN5) needling is applied to regulate the brain marrow, focusing on the core location of illness; and regarding the key location of illness, the combination of back-shu and front-mu points and that of jing-well and xing-spring points are adopted to regulate five zang organs. The five needling techniques (half needling, leopard-spot needling, joint needling, Hegu needling and shu needling) are used to regulate five tissues.
Humans ; Acupuncture Therapy ; Spasm/diagnosis* ; Moxibustion ; Acupuncture Points ; Medicine, Chinese Traditional ; Diagnosis, Differential

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Astrocytes in the spinal dorsal horn (SDH) exhibit diverse reactive phenotypes under neuropathic conditions, yet the mechanisms driving this diversity and its implications in chronic pain remain unclear. Here, we report that spared nerve injury (SNI) induces marked upregulation of both complement component 3 (C3⁺, A1-like) and S100 calcium-binding protein A10 (S100A10⁺, A2-like) astrocyte subpopulations in the SDH, with elevated microglial cytokines including interleukin-1α, tumor necrosis factor-α, and complement component 1q. Transcriptomic, immunohistochemical, and Western blot analyses reveal co-activation of multiple reactive astrocyte states over a unidirectional shift toward an A1-like phenotype. Fibroblast growth factor 8 (FGF8), a neuroprotective factor via FGFR3, mitigated microglia-induced C3⁺ astrocyte reactivity in vitro and suppressed spinal C3 expression and mechanical allodynia following intrathecal administration in SNI mice. These findings reveal a microglia-astrocyte signaling axis that promotes A1 reactivity and position FGF8 as a promising therapeutic candidate for neuropathic pain by modulating astrocyte heterogeneity.
Animals ; Astrocytes/drug effects* ; Neuralgia/pathology* ; Receptor, Fibroblast Growth Factor, Type 3/metabolism* ; Signal Transduction/physiology* ; Male ; Mice ; Microglia/drug effects* ; Fibroblast Growth Factor 8/pharmacology* ; Mice, Inbred C57BL ; Hyperalgesia/drug therapy* ; Spinal Cord/drug effects* ; Complement C3/metabolism* ; Spinal Cord Dorsal Horn/metabolism*

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

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*