[摘 要] 目的：探讨异位表达血红蛋白亚基（HBA/HBB）对缺氧条件下嵌合抗原受体T细胞（CAR-T细胞）功能障碍的改善作用及其对肿瘤细胞的杀伤效应。方法：全基因合成技术合成靶向HER2的CAR序列，构建共表达HBA或HBB的CAR慢病毒载体，包装慢病毒后感染人原代T淋巴细胞，制备异位表达HBA/HBB的CAR-T细胞，命名为HBA CAR-T和HBB CAR-T。采用缺氧探针检测小鼠实体瘤缺氧状态。通过流式细胞术检测瘤内CAR-T细胞占比、异位表达血红蛋白亚基的CAR-T细胞阳性率及CAR-T细胞的活性氧、凋亡水平。WB法检测HBA CAR-T和HBB CAR-T内相关血红蛋白亚基表达情况，采用细胞计数板计数检测细胞增殖水平，通过萤光素酶报告基因法检测CAR-T细胞对肿瘤细胞的杀伤能力，qPCR检测CAR-T细胞中缺氧诱导因子-1α（HIF-1α）表达水平，利用MitoXpress Intra试剂盒检测CAR-T细胞内氧气含量。结果：不同细胞构建的实体瘤模型均存在明显缺氧情况，且CAR-T细胞浸润水平与缺氧程度呈显著负相关（P < 0.000 1）。HBA CAR-T与HBB CAR-T构建成功（阳性率 > 60%），相应血红蛋白亚基可稳定表达。缺氧环境下HBA CAR-T和HBB CAR-T的ROS水平、凋亡水平显著下降，增殖、对肿瘤细胞的体外杀伤能力显著强于传统CAR-T细胞（均P < 0.05）。HBA CAR-T与HBB CAR-T内HIF-1α表达降低（均P < 0.001），且缺氧程度显著降低（均P < 0.001）。结论：异位表达血红蛋白亚基可改善缺氧条件下CAR-T细胞功能障碍并增强其对肿瘤细胞的体外杀伤作用。

Ulcerative colitis（UC） is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulceration of the colonic mucosa and submucosa， and its complex pathogenesis involves immune abnormality， oxidative stress and other factors. The nuclear transcription factor E₂-related factor 2（Nrf2）， encoded by the Nfe212 gene， plays a central role in antioxidant responses. It not only activates various antioxidant response elements such as heme oxygenase-1（HO-1） and quinone oxidoreductase 1（NQO1）， but also enhances the activity of glutathione-S-transferase（GST） and superoxide dismutase 1（SOD1）， effectively eliminating reactive oxygen species（ROS） accumulated in the body， and mitigating oxidative stress-induced damage to intestinal mucosa. In addition， Nrf2 can reduce the release of inflammatory factors and infiltration of immune cells by regulating immune response， cell apoptosis and autophagy pathways， thereby alleviating intestinal inflammation and promoting the repair and regeneration of damaged mucosa. Based on this， this paper reviews the research progress of Chinese materia medica in the prevention and treatment of UC by modulating the Nrf2 signaling pathway. It deeply explores the physiological role of Nrf2， the molecular mechanism of activation， the protective effect in the pathological process of UC， and how active ingredients in Chinese materia medica regulate the Nrf2 signaling pathway through multiple pathways to exert their potential mechanisms. These studies have revealed in depth that Chinese materia medica can effectively combat oxidative stress by regulating the Nrf2 signaling pathway. It can also play a role in anti-inflammatory， promoting autophagy， inhibiting apoptosis， protecting the intestinal mucosal barrier， and promoting intestinal mucosal repair， providing new ideas and methods for the multi-faceted treatment of UC.

The blue fluorescent carbon dots(TMCDs)and cyan fluorescent carbon dots(TMCDs-H2O)were synthesized fromm-phenylenediamine and tricarballylic acid through air-assisted melting polymerization and one-step hydrothermal method,respectively.Air purging could effectively inhibit the side reactions and reduce the derivative structures in the carbon dots product.The structure and morphology of these two materials were systematically characterized using liquid nuclear magnetic resonance spectroscopy(NMR),mass spectrometry(MS),and transmission electron microscopy.Compared to TMCDs-H2O((3.12±0.63)nm),TMCDs showed a smaller average particle size(approximately(1.85±0.02)nm).The NMR and MS analysis revealed that although the main structure of both types of carbon dots was similar,TMCDs exhibited a simpler structure with higher degree of polymerization.These results suggested that supramolecular interactions might introduce numerous small molecule derivatives into TMCDs-H2O particles,resulting in lower polymerization degree,multiple substructures,and larger particle size characteristics for this material.When employed as chemical sensors for metal ion detection,in the linear range of 1×10-5-5×10-4 mol/L,the detection limits of Fe3+by TMCDs and TMCDs-H2O were 3.3×10-6 mol/L and 3.8×10-6 mol/L,respectively.The experimental results demonstrated that the recoveries of CDs and inductively coupled plasma optical emission spectrometer(ICP-OES)were similarity,whereas TMCDs displayed a considerable relative standard deviation.This study demonstrated that endogenously derived structures in CDs could enhance the performance of metal ion sensing.

Water-soluble silver nanoclusters(DHLA-AgNCs)with red fluorescence emission were synthesized using silver nitrate(AgNO3)as silver source,dihydrolipoic acid(DHLA)as ligand and sodium borohydride(NaBH4)as reducing agent by one-pot method.Based on the selective quenching of DHLA-AgNCs by tetracycline(TC),a rapid and selective fluorescence analysis method for detection of TC was constructed by monitoring the fluorescence intensity change at 650 nm.Under the optimal detection conditions,the fluorescence quenching efficiency of DHLA-AgNCs showed good linear relationship with concentration of TC within the range of 10.0-120.0 μmol/L,and the limit of detection(LOD)was 0.39 μmol/L.This method was successfully applied to detection of TC in milk samples,with spiked recoveries ranging from 99.5%to 102.5%,and relative standard deviations(RSDs)less than 5%.This method had the advantages of simplicity,rapidity,strong specificity and low cost,and thus provided a simple and feasible strategy for selective detection of TC.

Pectus excavatum (PE) is a common congenital chest malformation in children, manifested by inward depression of the anteriorthorax wall, which can compress the normal tissues and organs in the chest and cause adverse effects on the physiology and psychology of patients. Surgery is the most important means of treating PE, and with the invention of Nuss surgery, the surgical treatment of PE has entered the minimally invasive era. At present, there are many indexes to evaluate the severity of thoracic malformations in PE patients, and selecting appropriate evaluation indexes is of great significance for the formulation of surgical protocols. As a physical and mental disease, PE's deformed thoracic appearance not only affects the function of thoracic organs, but also affects the psychological state of patients. Therefore, there is still controversy over whether the role of orthopedic surgery is to improve function or cosmetic plastic surgery. At the same time, the orthopedic efficacy and postoperative complications of the existing modified and novel surgical methods need to be further observed and evaluated. In addition, the design of surgical plan and the selection of surgical timing for PE combined with other diseases are also critical and controversial issues in clinical practice. Therefore, this article explores and reviews the controversial points in the current surgical treatment of PE.

Objective To investigate the feasibility of a "pericardial lining" modified Bentall procedure for the treatment of patients with aortic root aneurysm. Methods This was a retrospective study that consecutively enrolled patients treated at the Affiliated Suzhou Hospital of Nanjing Medical University, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, and the First People's Hospital of Guangyuan from January 2023 to February 2024. Preoperative clinical data, imaging findings (including echocardiography and CT scans of the aortic root and the entire aorta), details of coronary artery management, surgical outcomes, and postoperative follow-up results were collected. All patients underwent the "pericardial lining" modified Bentall procedure: the aortic valve was replaced, and an autologous pericardial patch was divided into three equal leaflets based on the circumference of the aortic annulus measured by a valve sizer. These leaflets were then sutured to the aortic annulus. Fenestrations were created in two of the pericardial leaflets for anastomosis with the left and right coronary ostia. The pericardial leaflets were sutured to the wall of the aortic sinuses to form an integrated structure, thereby narrowing the sinus portion. A prosthetic vascular graft was anastomosed to the proximal and distal aorta, and no aortic root-to-right atrium shunt was created. Results A total of 5 patients, aged 37 to 68 years, were included. The preoperative Society of Thoracic Surgeons (STS) risk scores ranged from 2.8% to 3.9%. The diameter of the ascending aorta was 40-73 mm, the left ventricular end-diastolic diameter (LVEDD) was 45-71 mm, and the left ventricular ejection fraction (LVEF) was 47%-64%. Intraoperatively, the aortic cross-clamp time ranged from 85 to 180 min, and the cardiopulmonary bypass time ranged from 110 to 302 min. Postoperative follow-up echocardiography revealed that the ascending aortic diameter was 27-35 mm, LVEDD was 39-57 mm, and LVEF was 43%-61%. All surgeries were completed successfully with satisfactory immediate outcomes and no intraoperative complications. During the follow-up period, there was no mortality or reoperation. Conclusion For patients with aortic root aneurysm, the "pericardial lining" modified Bentall procedure yields satisfactory preliminary results, and the technique is demonstrated to be feasible.

Acute urinary retention(AUR)occurs frequently among astronauts on orbit.The current treatment is complex and easy to damage the urethra,which seriously affects the life and work of astronauts.In contrast,acupuncture,a traditional Chinese remedy,has shown promising results in managing urinary retention.However,the specific acupoints that could potentially prevent AUR remain uncertain due to the unique physiological conditions experienced by individuals in space compared to those on Earth.To address this gap,our research delved into the mechanisms of AUR and acupuncture within both traditional Chinese medicine and modern medical practices.We conducted a thorough literature review from Pubmed,Web of Science,CNKI,Wanfang database,VIP database and Chinese Medical Code database.A hierarchical evidence-scoring approach was utilized to analyze the included literatures,thus devised acupuncture protocols for the treatment of AUR.The outcomes of our study aim to establish a foundation for the application of acupuncture in managing AUR.

This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history* ; Humans ; Medicine, Chinese Traditional/history* ; History, Ancient ; Astragalus Plant/chemistry* ; China ; Astragalus propinquus

The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals ; Gastrointestinal Microbiome/drug effects* ; Mice ; Intestinal Mucosa/microbiology* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Glycolipids/metabolism* ; Lipid Metabolism/drug effects* ; Administration, Oral ; Disease Models, Animal

Objective: To explore the effects of parenting style on emotional and behavioral problems (EBPs) of preschool children and to provide theoretical reference for promoting children s physical and mental health. Methods: In October-November 2021, a stratified cluster random sampling method was adopted to select 3 575 preschool children aged 3-6 years from 12 kindergartens in Hefei. Data on parenting styles and children s EBPs were collected through electronic questionnaires. Binary Logistic regression model was used to explore the effects of parenting styles on children s EBPs. Results: The detection rates of emotional symptoms, conduct problems, hyperactivity, peer interaction problems, and prosocial behavior problems were 15.5% ( n =554), 23.2% ( n =830), 22.4% ( n =802), 38.2% ( n =1 367), and 29.5% ( n =1 055) in preschool children, respectively. Binary Logistic regression analysis showed that after adjusting for covariates such as child s age, sex, and preterm birth, a high authoritative parenting style reduced the risk of EBPs in children ( OR =0.29-0.78), while a high authoritarian ( OR =1.36-2.15) and high permissive ( OR =1.36-1.68) parenting style in mothers increased the risk of EBPs in children (all P <0.05). Further stratified analysis indicated that among children with fathers exhibiting high authoritative, high authoritarian, or high permissive parenting styles, a high authoritative parenting style in mothers reduced the risk of peer interaction problems and prosocial behavior problems ( OR =0.51, 0.30 ; 0.44, 0.23; 0.51, 0.29, all P <0.05). Among children with fathers exhibiting a high authoritative parenting style, a high authoritarian parenting style in mothers increased the risk of emotional problems ( OR =2.59), and both high authoritarian and high permissive parenting styles in mothers increased the risk of conduct problems ( OR =3.25, 2.09) and hyperactivity problems ( OR =2.35, 2.87) (all P <0.05). Among children with fathers exhibiting high authoritarian or high permissive parenting styles, a high authoritarian parenting style in mothers increased the risk of EBPs ( OR =1.65-2.71, 1.62-2.52, all P <0.05). Conclusion Parenting style is an important factor affecting EBPs of preschool children, and appropriate parenting style is beneficial for children s psychological development.