Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory ( Star ) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor ( Ar ) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.
Animals ; Male ; Leydig Cells/metabolism* ; Mice ; Dependovirus/genetics* ; Sertoli Cells/metabolism* ; Gene Silencing ; Genetic Vectors ; Testis/cytology*

Bronchial asthma (asthma) is a complex inflammatory airway disease affecting approximately 100 million children worldwide, imposing a heavy burden on society and families. Studies have shown that the gut microbiota plays a significant role in the occurrence and development of childhood asthma. This paper reviews the research progress on the relationship between gut microbiota and childhood asthma. By elucidating the composition, function, and relationship with the host of gut microbiota, the impact of changes in its composition and function on the development of asthma is revealed. Furthermore, the potential value and application prospects of modulating gut microbiota as a new strategy for asthma treatment are discussed, providing a theoretical reference for in-depth research on the relationship between gut microbiota and the onset of childhood asthma and the development of new therapeutic approaches.
Humans ; Asthma/etiology* ; Gastrointestinal Microbiome/physiology* ; Child

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

OBJECTIVE: This study aimed to reexplore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis. METHODS: Data from 171 Chinese adults (19-21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11-26 μg/day) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI). RESULTS: The minimum iodine excretion was estimated as 57, 58, and 51 μg/day in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg/day for iodine EAR, and 80, 81, and 71 μg/day for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg/(day·kg) of body weight. CONCLUSION The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Humans ; Iodine/administration & dosage* ; Male ; Female ; China ; Young Adult ; Diet ; Adult ; Nutritional Requirements ; East Asian People

Objective:To investigate the efficacy and safety of glofitamab in the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 patients with relapsed/refractory DLBCL who were treated with glofitamab in Sichuan Provincial People's Hospital from March 2024 to October 2024 were retrospectively analyzed. All patients received glofitamab monotherapy. Dose escalation was required in the first course, and glofitamab at a dose of 30 mg was administered from the second to the 12th course. The general data, clinical manifestations, laboratory examination results, Eastern Cooperative Oncology Group (ECOG) performance score, previous treatment history, therapeutic effect after medication and adverse reactions were collected.Results:Among 11 patients, there were 8 males and 3 females, with the median age [ M ( Q1, Q3)] of 60 (51, 76) years; 1 case was primary central nervous system DLBCL. The median number of prior treatment lines was 3 (2, 3) lines, and 6 cases received ≥3 lines of therapy; 1 case was double DLBCL and 3 cases was complicated with p53 mutations. The median follow-up time was 5 months (2-7 months). After treatment of the median number of glofitamab, 3 cases achieved complete remission, among which 1 case successfully bridged to autologous hematopoietic stem cell transplantation; 1 case had the stable disease and 7 cases achieved partial remission. Grade 1-2 adverse events included mild leukopenia in 3 patients, mild anemia in 4 patients, thrombocytopenia in 1 patient, and lymphopenia in 8 patients. Grade 3 hematologic adverse events included thrombocytopenia in 1 patient and severe lymphopenia in 1 patient. Non-hematological toxicities included mild rash in 1 patient, grade 1 liver dysfunction in 3 patients and inflammatory factor storm in 4 patients. No medication stop or deferral was found in patients due to severe adverse events. Conclusions:Glofitamab demonstrates a high response rate in the treatment of relapsed/refractory DLBCL, with manageable adverse events and a favorable safety.

Objective To develop a system for retrieving information from clinical records of Traditional Chinese Medicine(TCM)based on generative large language models(LLMs).Methods Applicational needs of the system were analyzed,and entity types to be retrieved were identified.The functions,workflows,and architecture of the system were designed by combining the automatic retrieval capabilities of LLMs with human-in-the-loop(HITL).The software was developed using such frameworks as vLLM and Node.js.Interaction of multiple commercial/open source LLMs was implemented using OpenAI-compatible interfaces.The quality of information retrieved from LLMs was enhanced by prompt engineering.Results This system supported task allocation,automatic retrieval of structured information,and manual review.To evaluate its performance,the moonshot-v1-8k model was used to retrieve clinical records of TCM before manual edition was performed.Combining large language model pre-annotation with meticulous annotator edits improved accuracy by 26.6％compared to the BERT-BiLSTM-CRF model,and enhanced extraction efficiency by 1.6-fold relative to purely manual methods.Conclusion General generative LLMs can retrieve a wide range of entity information from TCM records with high accuracy and scalability.The design and implementation of this system approach may provide a useful reference for developing other biomedical information retrieval systems.

By sorting out the differences and connections between family doctor teams and specialized disease teams, role competency and mutual collaboration, and introducing the learning health system (LHS) mechanism, a comprehensive operating system for community general practice learning organizations based on LHS was constructed, focusing on five single disease types. The system includes a combination of general and specialized medicine that links three levels of medical institutions, thereby opening up the business cooperation process between professionals in different institutions, and establishing a sustainable collaboration mechanism. This allows medical institutions at three levels to continuously tap the potential of their disciplines, achieve their own ability growth and feel higher work value, and also bring better health solutions to residents, guided by the common goal of "health centered, patient centered".

This study searched the clinical researches on traditional Chinese medicine （TCM） for cardiovascular diseases registered in Chinese Clinical Trial Registry and the US Clinical Trial Registry， the cardiovascular disease-related studies funded by the National Natural Science Foundation of China， as well as those published in China National Knowledge Infrastructure （CNKI）， Wanfang database， VIP.com， China Biology Medicine disc （CBMdisc）， Embase， Medline， Cochrane Library， and other databases published cardiovascular disease-related studies from 1 January 2021 to 30 June 2023. In order to analyse and evaluate the research progress of TCM treatment for coronary heart disease， hypertension， heart failure， and arrhythmia， this study aimed at recent research hotspots and research direction. It is found that the research on TCM for cardiovascular diseases was gradually deepening and the high-quality evidence continued to emerge. It is believed that studies related to the prevention and treatment of common cardiovascular diseases by TCM reflected the multi-angle integration of modern technology and pattern differentiation and treatment， closer integration of clinical and basic research， and further optimisation of pattern identification and interventions. On this basis， the research programme and implementation process should be further standardized， and the translation of research results should be emphasized to promote the standardized application and promotion of TCM diagnosis and treatment of cardiovascular diseases.

Objective:To investigate the related factors and prognosis of invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS). Methods:The in-patients diagnosed with Klebsiella pneumoniae liver abscess in the Department of Infectious Diseases, Huashan Hospital, Fudan University from January 2015 to February 2021 were retrospectively enrolled. The patients were divided into IKLAS group and non-IKLAS group according to whether they had IKLAS or not. The clinical data between the two groups were compared, including the prevalence of diabetes mellitus, the details of liver abscess, clinical symptoms such as fever and abdominal pain, as well as laboratory tests such as glycosylated hemoglobin and hemoglobin. Statistical analysis was performed using chi-square test or independent sample t test. Multivariate logistic regression analysis was used to analyze the factors influencing the occurrence of IKLAS. Results:A total of 75 patients with Klebsiella pneumoniae liver abscess were enrolled, including 55 patients (73.33%) in the IKLAS group and 20 patients (26.67%) in the non-IKLAS group. Fifty-two point seven three percent (29/55) of the patients had diabetes mellitus and 12.73%(7/55) of the patients had abdominal pain in the IKLAS group, which were 20.00%(4/20) and 45.00%(9/20) in the non-IKLAS group, respectively, and the differences were both statistically significant ( χ2=6.38 and 7.28, respectively, both P<0.05). Most of liver abscesses were single (50/75, 66.67%), and more likely to occur in the right liver (50/75, 66.67%). The maximum diameter of liver abscess in the IKLAS group was (4.58±2.04) cm, which was smaller than that in the non-IKLAS group ((6.49±3.11) cm), and the difference was statistically significant ( t=2.82, P=0.011). Compared with those in the non-IKLAS group, patients in the IKLAS group had higher glycosylated hemoglobin (8.69%±2.64% vs 6.18%±1.31%) and hemoglobin ((112.25±22.04) g/L vs (100.05±18.59) g/L), and the differences were both statistically significant ( t=-4.25 and -2.21, respectively, both P<0.05). The proportion of patients using antibiotics combined with abscess drainage in the IKLAS group was 38.18%(21/55), and that in the non-IKLAS group was 85.00%(17/20). The difference between the two groups was statistically significant ( χ2=12.86, P<0.001). A total of 16 patients (21 eyes) were diagnosed as endogenous Klebsiella pneumoniae endophthalmitis (EKPE), and all of them were IKLAS patients, and 14 patients underwent monocular/binocular eyeball injection and/or vitrectomy and silicone oil filling. The visual acuity of 13 patients decreased significantly. Multivariate logistic regression analysis showed that complicated with diabetes mellitus was an independent risk factor for IKLAS (odds ratio ( OR)=5.02, 95% confidence interval (95% CI) 1.01 to 25.03, P=0.049). The large diameter of liver abscess was a protective factor for IKLAS ( OR=0.64, 95% CI 0.47 to 0.86, P=0.003). Conclusions:The patients with IKLAS have less abdominal pain, and most of them complicate with diabetes mellitus. Diabetes mellitus is an independent risk factor for the occurrence of IKLAS, while the large diameter of liver abscess is a protective factor. EKPE is associated with poor visual prognosis.