Bronchial asthma （BA） is a common chronic inflammatory airway disease characterized by airway hyperresponsiveness and reversible airflow limitation. Lung macrophages （LMs）， as important effector cells of the innate immune system， play an important role in recognizing and engulfing pathogens， clearing harmful particles， and regulating immune responses. LMs can be polarized to M1 （pro-inflammatory） or M2 （anti-inflammatory） in different immune environments and participate in promoting or inhibiting inflammatory response， as well as lung parenchyma injury and repair （airway remodeling）， playing a key role in the BA occurrence and development. Regulating the polarization balance of macrophages can not only inhibit the inflammatory response in the airway and reduce airway hyperresponsiveness， but also improve airway remodeling and immune regulation， reduce airway mucus secretion， and alleviate the clinical BA symptoms. Traditional Chinese medicine and its active ingredients， especially polysaccharides and saponins， can regulate the polarization balance of M1/M2 macrophages. Traditional Chinese medicine compounds can balance the secretion of anti-inflammatory and pro-inflammatory factors by staging treatment and targeting the polarization state of M1/M2 macrophages， inhibit inflammatory response in the airway， reduce airway remodeling， and improve the BA symptoms. This paper summarized the research progress on the regulation of M1/M2 macrophage polarization by traditional Chinese medicine and its active ingredients， aiming to provide scientific evidence for the precise targeted therapy of BA.

Bronchial asthma （BA） is a common chronic inflammatory airway disease characterized by airway hyperresponsiveness and reversible airflow limitation. Lung macrophages （LMs）， as important effector cells of the innate immune system， play an important role in recognizing and engulfing pathogens， clearing harmful particles， and regulating immune responses. LMs can be polarized to M1 （pro-inflammatory） or M2 （anti-inflammatory） in different immune environments and participate in promoting or inhibiting inflammatory response， as well as lung parenchyma injury and repair （airway remodeling）， playing a key role in the BA occurrence and development. Regulating the polarization balance of macrophages can not only inhibit the inflammatory response in the airway and reduce airway hyperresponsiveness， but also improve airway remodeling and immune regulation， reduce airway mucus secretion， and alleviate the clinical BA symptoms. Traditional Chinese medicine and its active ingredients， especially polysaccharides and saponins， can regulate the polarization balance of M1/M2 macrophages. Traditional Chinese medicine compounds can balance the secretion of anti-inflammatory and pro-inflammatory factors by staging treatment and targeting the polarization state of M1/M2 macrophages， inhibit inflammatory response in the airway， reduce airway remodeling， and improve the BA symptoms. This paper summarized the research progress on the regulation of M1/M2 macrophage polarization by traditional Chinese medicine and its active ingredients， aiming to provide scientific evidence for the precise targeted therapy of BA.

Objective: To investigate the status of condom use and its influencing factors among men who have sex with men (MSM), so as to provide a basis for improving condom utilization rates and AIDS prevention and control in this population. Methods: From May to October 2024, a snowball sampling method was employed to recruit MSM in Songjiang District, Shanghai Municipality. Self-administered questionnaires were used to collect data on demographic characteristics, AIDS-related knowledge, sexual behaviors, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), and condom use in the past six months. Multivariable logistic regression model was used to analyze the influencing factors for consistent condom use. Results: A total of 921 MSM were surveyed, with a median age of 29.00 (interquartile range, 9.00) years. Among them, 697 (75.68%) were aware of AIDS-related knowledge, 826 (89.69%) expressed willingness to use PrEP, and 835 (90.66%) were willing to use PEP. Additionally, 787 (85.45%) MSM reported their age at first homosexual intercourse as ≥18 years, while 519 (56.35%) reported consistent condom use in the past six months. Multivariable logistic regression analysis revealed that MSM who were aware of AIDS-related knowledge (OR=0.582, 95% CI: 0.423-0.801), willing to use PrEP (OR =0.611, 95% CI: 0.385-0.969), and whose age at first homosexual intercourse was <18 years (OR=0.480, 95% CI: 0.330-0.700) were less likely to consistent use condoms. Conclusion The proportion of consistent condom use among the MSM remains relatively low, which is primarily associated with AIDS-related knowledge, willingness to use PrEP, and the age at first homosexual intercourse.

OBJECTIVE: To develop a user-friendly visualization application for the automatic annotation of Human Phenotype Ontology (HPO) terms based on large language models and retrieval-augmented generation (RAG) technology, and to validate its performance in an authoritative case dataset. METHODS: By integrating the domestic open-source large language model DeepSeek-V3 with RAG technology, an interactive web application was deployed on the Streamlit cloud platform. Using only the latest official HPO dataset as the data source, the lightweight sentence-embedding model BAAI/bge-small-en-v1.5 was employed to construct a FAISS vector index. During the online phase, a four-step closed-loop process is automatically completed: multilingual translation, phenotype phrase extraction, RAG candidate retrieval, term mapping, and official database validation. 121 English case reports publicly released by BMJ Case Reports and Oxford Medical Case Reports (with a gold-standard HPO set of 1 794 terms) were selected for application validation. Precision, recall, and F1 score were calculated and compared horizontally with traditional dictionary tools, standalone large language models, and the similar application "RAG-HPO". Finally, replace the model with the more advanced ChatGPT-5 and evaluate its performance on the newly extracted dataset. RESULTS: An HPO term automatic annotation visualization application named PhenoRAG, based on large language models and RAG technology, was successfully developed. Users can access it directly via a web link. Across the 112 cases, a total of 2 150 HPO terms were generated; 2,064 (96.0%) were fully validated by the official database, with a hallucination rate of 1.3% and an HPO ID-name mismatch rate of 2.7%. After deduplication, 1,906 terms remained for testing. The overall precision was 63.65%, recall was 67.34%, and F1 was 65.44%, significantly outperforming traditional annotation tools (F1: 0.45-0.49, P < 0.001). Although PhenoRAG's F1 was lower than that of RAG-HPO (F1 = 0.78, P < 0.001), which relies on a manually constructed synonym database of 54 000 entries plus the HPO dataset, it requires no additional dictionary maintenance and can be used without any background in computer programming. Moreover, after switching to the GPT-5 model, PhenoRAG exhibited no hallucination rate on the new dataset, and its F1 score significantly increased (P = 0.038). CONCLUSION Without constructing a synonym database, the PhenoRAG achieved high-accuracy automatic mapping from clinical text to standard HPO terms. It features a low usage threshold, free access, and a Chinese-language interface, and can directly serve rare disease diagnosis, genetic counseling, and research scenarios in China and worldwide, warranting further clinical promotion and multicenter validation.
Humans ; Phenotype ; Biological Ontologies ; Language ; Software ; Large Language Models

ObjectiveTo investigate the mechanisms by which Jianpi Yangzheng Xiaozheng prescription （JPYZXZ） treats poorly cohesive gastric carcinoma （PC-GC） through regulation of ubiquitin-specific peptidase 51 （USP51）. MethodsIn vitro experiments： Cell viability and proliferation of PC-GC cell lines （MKN-45 and HGC-27） treated with different concentrations of JPYZXZ （2， 4， 6 g·L^-1） were assessed using Cell Counting Kit-8 （CCK-8） and colony formation assays. Cell migration was evaluated by wound healing （scratch） and Transwell assays. The mRNA and protein expression levels of USP51， zinc finger E-box-binding homeobox 1 （ZEB1）， and epithelial-mesenchymal transition （EMT）-related markers （e.g.， E-cadherin） were detected by quantitative real-time PCR （Real-time PCR） and Western blot， respectively. Subsequently， stable MKN-45 and HGC-27 cell lines with USP51 knockdown （sh-USP51） and overexpression （oe-USP51） were constructed. Their migration ability and EMT-related protein expression were further evaluated by scratch assay， Transwell assay， and Western blot. In vivo experiments： A subcutaneous xenograft model of MKN-45 human gastric cancer was established in BALB/c nude mice. Thirty mice were randomly divided into six groups （NC， NC + JPYZXZ， sh-USP51， sh-USP51 + JPYZXZ， oe-USP51， and oe-USP51 + JPYZXZ）， with five mice in each group. After successful modeling， mice in the treatment groups were administered JPYZXZ （30 g·kg^-1） by gavage for 28 days. Body weight and tumor volume were monitored during the experiment. The expression levels of USP51 and EMT-related proteins in tumor tissues were detected by Western blot and immunohistochemistry （IHC）. ResultsCompared with the blank group， the colony formation rate， wound healing rate， and number of migrated cells in MKN-45 and HGC-27 cells were significantly reduced in all JPYZXZ groups and the 5-fluorouracil （5-FU） group （P<0.05）. The mRNA and protein expression levels of USP51 were decreased （P<0.05）. The expression of ZEB1 and mesenchymal phenotype proteins （e.g.， N-cadherin and vimentin） was reduced （P<0.05）， whereas the expression of the epithelial marker E-cadherin was increased （P<0.05）. Compared with the control group， USP51 expression was decreased in the sh-USP51 group and increased in the oe-USP51 group （P<0.05）. Compared with the NC group， USP51 knockdown significantly reduced the migration and proliferation of gastric cancer cells （P<0.01）， decreased the expression of ZEB1 and EMT-related proteins， and increased E-cadherin expression （P<0.05）. In vivo results showed that JPYZXZ significantly inhibited the growth of xenograft tumors in nude mice （P<0.05） and markedly reversed the abnormal expression of EMT-related proteins in tumor tissues （P<0.05）. ConclusionThe therapeutic mechanisms of JPYZXZ in PC-GC may be associated with inhibition of the EMT process via regulation of the USP51-ZEB1 signaling pathway.

BACKGROUND:Previous studies have demonstrated that the cannabinoid type Ⅰ receptor can enhance the proliferation and neural differentiation of neural stem cells and mesenchymal stem cells.Moreover,cannabinoid type Ⅰ also governs the proliferation and mineralization capacity of human apical papilla stem cells.However,there are relatively few investigations concerning the impact of cannabinoid type Ⅰ overexpression on the neural differentiation of human apical papilla stem cells.OBJECTIVE:To investigate the effect of cannabinoid type Ⅰ on neural differentiation of human apical papilla stem cells in vitro.METHODS:Healthy third molars with immature root tips that need to be removed for orthodontic treatment were collected,and human apical papilla stem cells were isolated and cultured by tissue block method combined with enzyme digestion method.Cannabinoid type Ⅰ gene was introduced into human apical papilla stem cells by lentivirus-mediated transfection technique.A blank control group,a negative control group,and cannabinoid type Ⅰ overexpression group were set up.The transfection effect of overexpression of cannabinoid type Ⅰ lentivirus on human apical papilla stem cells was verified by Western Blot.The control group,negative control group,cannabinoid type Ⅰ overexpression group and cannabinoid type Ⅰ overexpression+AM251(cannabinoid type Ⅰ receptor antagonist)group were set up.Cell proliferation was detected by CCK-8 assay at 1,5,and 10 days after neural induction.On day 10 of neural induction,the expression levels of TH,NeuroD-1,and NCAM1 genes were detected by qRT-PCR,and the protein expression levels of Nestin and TUBB3 were detected by immunofluorescence.RESULTS AND CONCLUSION:(1)Compared with the blank control group and the negative control group,the expression of cannabinoid receptor Ⅰ protein in the cannabinoid receptor Ⅰ overexpression group was significantly increased,and the difference was significant(P＜0.05).(2)Compared with the blank control group and the negative control group,the proliferation ability of human apical papilla stem cells in the cannabinoid type Ⅰ overexpression group was the strongest at 5 and 10 days after neural induction(P＜0.05).(3)Compared with the blank control group and the negative control group,the mRNA expression of NeuroD-1,NCAM1,and TH in the stem cells of the human apical papilla in the cannabinoid type Ⅰ overexpression group was significantly increased,and the fluorescence intensity of Nestin and TUBB3 was significantly enhanced(P＜0.05).(4)Compared with the cannabinoid type Ⅰ overexpression group,the proliferation ability,mRNA expression level of NeuroD-1,NCAM1,and TH,as well as the fluorescence intensity of Nestin and TUBB3,were significantly decreased in the cannabinoid type Ⅰ overexpression+AM251 group(P＜0.05).These findings conclude that overexpression of cannabinoid type Ⅰ promoted the proliferation and neural differentiation of human apical dentin papilla stem cells.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

OBJECTIVE To establish the graded management standards for off-label use of Shenqi fuzheng injection. METHODS Systematic searches were conducted in databases including CNKI， PubMed and the Cochrane Library to retrieve guidelines/consensuses， systematic reviews/meta-analyses， and randomized controlled trials （RCTs） of Shenqi fuzheng injection. The quality of evidence was evaluated using AGREE Ⅱ， AMSTAR Ⅱ， and the Risk of Bias 1.0 tool recommended by Cochrane Collaboration， and the graded management standard for off-label use of Shenqi fuzheng injection was developed by using the Thomson grading system. RESULTS A total of 534 articles were involved， including 11 guidelines， 22 systematic reviews/meta-analysis， and 501 RCTs. They covered 79 off-label indications for Shenqi fuzheng injection： cancer-related fatigue， colorectal cancer and breast cancer， all with high-quality evidence were classified under grade A management （grade Ⅰ commendation）， allowing all physicians across the hospital to prescribe relevant treatments； five diseases， such as ovarian cancer， liver cancer， leukemia， heart failure and cerebral infarction， were classified under grade B management （grade Ⅱa commendation）， with prescription restricted to physicians with intermediate or higher professional titles in specific departments； eleven diseases， including sepsis， cervical cancer， esophageal cancer， etc.， were classified under grade C management （grade Ⅱb commendation）， requiring strict evaluation by senior physicians before prescription； the use of Shenqi fuzheng injection for other conditions was explicitly prohibited due to a lack of sufficient evidence. CONCLUSIONS Off-label use of Shenqi fuzheng injection is prevalent. The graded management standard established by evidence-based medical approach provides a scientific basis for standardizing the clinical application of traditional Chinese medicine injections and offers an operable paradigm for implementing differentiated drug use supervision in medical institutions.

Objective To evaluate the effect of LifePort combined with polymyxin B in preventing donor-derived infections caused by preservation solution contamination. Methods Clinical data of 110 kidney transplant recipients were retrospectively analyzed. According to the decontamination status of preservation solution, the recipients were divided into the decontamination group (n=62) and the non-decontamination group (n=48). The general data of the two groups were compared, and the preventive effect of polymyxin B on possible donor-derived infections (p-DDI) was analyzed, especially infections associated with multidrug-resistant Gram-negative bacteria (MDR GNB). Results There were no statistically significant differences in baseline data (gender, age, preservation solution contamination status, etc.) between the decontamination group and the non-decontamination group (all P > 0.05). The overall contamination rate of preservation solution was 80.0%, and 68 contaminated samples were with single microorganism and 20 with multiple microorganisms. Coagulase-negative staphylococci, Enterococcus and Klebsiella pneumoniae were the most common microorganisms in the positive samples. Fifteen cases of preservation solution were contaminated by MDR GNB, including 10 cases in the non-decontamination group and 5 cases in the decontamination group, with no statistically significant difference between the two groups (P = 0.053). Postoperative infection-related events occurred in 69 recipients, including 39 cases in the non-decontamination group and 30 cases in the decontamination group, with the incidence rate in the non-decontamination group significantly higher than that in the decontamination group (P < 0.001). Only 10 cases of infections were identified as p-DDI, all of which were positive for preservation solution culture, including 8 cases in the non-decontamination group and 2 cases in the decontamination group (P < 0.05). There were 5 cases of p-DDI related to MDR GNB in the non-decontamination group, while no such cases occurred in the decontamination group (P < 0.05). No adverse reactions related to polymyxin B were observed, and no recipient death or renal allograft dysfunction occurred in either group. Conclusions Adding polymyxin B to the preservation fluid during hypothermic machine perfusion with LifePort before renal transplantation may reduce p-DDI and its potential adverse consequences.