The pathogenesis of metabolic dysfunction-associated steatotic liver disease （MASLD） is fundamentally rooted in spleen deficiency and is closely associated with phlegm turbidity， damp-heat and blood stasis. Clinically， liver constraint with spleen deficiency and internal retention of damp turbidity represent the predominant traditional Chinese medicine （TCM） syndrome patterns. Researches have indicated intrinsic connections between the syndrome patterns and biological indicators such as gut microbiota and metabolic profiles. Regarding treatment， classical famous formulas， modern empirical formulas， and newly developed TCM drugs show positive effects in regulating glucose and lipid metabolism， improving insulin resistance， and alleviating metabolic inflammation， exhibiting multi-target mechanisms of action； acupuncture and other external therapies also provide adjunctive value. Nevertheless， current researches still have limitations such as the lack of high-quality clinical evidence and insufficient systematic elucidation of the uncerlying mechanisms. Future efforts should focus on conducting high-quality TCM clinical trials with hard endpoint outcomes such as hepatic histology outcomes， and utilizing modern technologies like multi-omics to elucidate TCM's mechanisms of action， thereby advancing the position of TCM as a first-line therapeutic strategy for MASLD.

Objective: To develop a clinical decision and prescription generation system (CDPGS) specifically for diarrhea in traditional Chinese medicine (TCM), utilizing a specialized large language model (LLM), Qwen-TCM-Dia, to standardize diagnostic processes and prescription generation. Methods: Two primary datasets were constructed: an evaluation benchmark and a fine-tuning dataset consisting of fundamental diarrhea knowledge, medical records, and chain-of-thought (CoT) reasoning datasets. After an initial evaluation of 16 open-source LLMs across inference time, accuracy, and output quality, Qwen2.5 was selected as the base model due to its superior overall performance. We then employed a two-stage low-rank adaptation (LoRA) fine-tuning strategy, integrating continued pre-training on domain-specific knowledge with instruction fine-tuning using CoT-enriched medical records. This approach was designed to embed the clinical logic (symptoms → pathogenesis → therapeutic principles → prescriptions) into the model’s reasoning capabilities. The resulting fine-tuned model, specialized for TCM diarrhea, was designated as Qwen-TCM-Dia. Model performance was evaluated for disease diagnosis and syndrome type differentiation using accuracy, precision, recall, and F1-score. Furthermore, the quality of the generated prescriptions was compared with that of established open-source TCM LLMs. Results: Qwen-TCM-Dia achieved peak performance compared to both the base Qwen2.5 model and five other open-source TCM LLMs. It achieved 97.05% accuracy and 91.48% F1-score in disease diagnosis, and 74.54% accuracy and 74.21% F1-score in syndrome type differentiation. Compared with existing open-source TCM LLMs (BianCang, HuangDi, LingDan, TCMLLM-PR, and ZhongJing), Qwen-TCM-Dia exhibited higher fidelity in reconstructing the “symptoms → pathogenesis → therapeutic principles → prescriptions” logic chain. It provided complete prescriptions, whereas other models often omitted dosages or generated mismatched prescriptions. Conclusion By integrating continued pre-training, CoT reasoning, and a two-stage fine-tuning strategy, this study establishes a CDPGS for diarrhea in TCM. The results demonstrate the synergistic effect of strengthening domain representation through pre-training and activating logical reasoning via CoT. This research not only provides critical technical support for the standardized diagnosis and treatment of diarrhea but also offers a scalable paradigm for the digital inheritance of expert TCM experience and the intelligent transformation of TCM.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Gastric cancer remains a highly prevalent malignancy worldwide, with surgical resection currently constituting the cornerstone of treatment aimed at improving long-term patient survival. Owing to their notable advantages, including reduced surgical trauma and accelerated postoperative recovery, minimally invasive procedures are progressively supplanting conventional open surgery and have become the mainstream approach in gastric cancer management. Concurrently, the rapid advancement of artificial intelligence (AI) technologies has enabled real-time intraoperative monitoring of surgical scenes, thereby furnishing novel technical support for adjunctive decision-making, surgical navigation, and skill assessment during gastrectomy. This article provides a systematic review of the current status of AI applications in minimally invasive gastric cancer surgery, with a particular focus on research progress pertaining to instrument recognition, surgical phase identification, delineation of normal anatomical structures, detection of metastatic foci, and early warning of intraoperative adverse events. Furthermore, we discuss the potential value of AI in enhancing surgical efficiency, ensuring patient safety, and optimizing surgical education. On this basis, we further analyze the principal challenges and inherent risks confronting current AI systems, with the aim of informing future technological innovation and facilitating clinical translation.

Patients with lung cancer experience a heavy symptom burden during the perioperative period, which seriously affects their recovery and quality of life. Traditional symptom management models rely mainly on scheduled ward rounds during hospitalization and outpatient follow-up after discharge. However, they have limitations such as delayed symptom recognition, lack of post-discharge monitoring, and non-quantitative symptom assessment, which often lead to delayed interventions and low patient satisfaction. In recent years, the symptom management model based on electronic patient-reported outcomes (ePRO) has been increasingly valued in clinical practice. Existing high-level evidence from both domestic and international studies indicates that, through proactive monitoring, real-time alerts, and remote interventions, this model enables dynamic and continuous symptom management and helps improve patient recovery and healthcare experience. As a supplement to routine medical care, the ePRO-based symptom management model aims to enhance the quality of care rather than replace existing medical processes. To promote the standardized application of this model in perioperative lung cancer care, this consensus integrates domestic and international evidence. After multiple rounds of voting by more than 50 experts, it formulates 12 consensus statements covering the three core components, symptom monitoring, alerting, and intervention, to provide scientific and practical recommendations for clinical practice.

The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.
Humans ; Extracellular Vesicles/physiology* ; Oocytes/cytology* ; Female ; Animals ; Cell Communication/physiology*

Objective:To investigate the clinical manifestations, therapeutic strategies and prognostic outcomes in pediatric patients with severe Mycoplasma pneumoniae pneumonia (SMPP) complicated by cardiac thrombosis. Methods:This case series study retrospectively analyzed 15 pediatric patients with SMPP complicated by cardiac thrombosis. The patients was recruited from the Department of Pediatric Respiratory Medicine at Shandong Provincial Hospital Affiliated to Shandong First Medical University between July 2018 and January 2025. Comprehensive clinical data and follow-up information were collected.Results:Among the 15 children, 10 were male and 5 were female, and the age of onset was 8.0 (6.3, 10.0) years. All 15 children presented with fever and cough, while additional symptoms included dyspnea in 7 cases, chest pain in 6 cases, hemoptysis in 3 cases, and chest tightness in 1 case. The white blood cell count was 11.7 (9.5, 15.9)×10 9/L, C-reactive protein was 31.6 (17.5, 64.8) mg/L and lactate dehydrogenase was 548.2 (410.4, 768.3) U/L. A total of 14 children underwent testing for the Mycoplasma pneumoniae drug resistance genes 2063A>G and 2064A>G, of which 13 tested positive. The plasma D-dimer levels of 15 children were 8.77 (7.23, 12.50) mg/L, all of which were higher than normal. Among the 15 children, 5 had decreased activity of anticoagulant proteins (protein C, protein S, antithrombin Ⅲ), and 8 tested positive for antiphospholipid antibodies. Chest CT scans of all 15 children showed pulmonary consolidation and (or) atelectasis, with pleural effusion present in 12 cases. In the 15 children, thrombosis was detected at 14.0 (11.0, 18.0) days after the onset of illness. The locations of cardiac thrombosis included the right ventricle in 9 cases, the right atrium in 5 cases, and the left atrium in 1 case. Additionally, 10 cases had pulmonary vascular embolism, comprising 9 cases of pulmonary artery thrombosis and 1 case of pulmonary vein thrombosis. After anticoagulant treatment, cardiac thrombi disappeared in 10 children. Five children who did not show improvement with anticoagulation underwent surgical thrombectomy. In the follow-up of 15 children, lung imaging basically returned to normal, with no major hemorrhagic events or other adverse events. Conclusions:In children with Mycoplasma pneumoniae pneumonia, the presence of clinical symptoms such as shortness of breath, chest pain and hemoptysis, along with elevated plasma D-dimer levels, should raise suspicion for the possibility of cardiac thrombosis. SMPP complicated by cardiac thrombosis, prognosis is good following anticoagulation or surgical treatment.

AIM:To investigate the protective ef-fect of midazolam(MID)on cardiac function and angiogenesis in myocardial infarction(MI)rats and its effect on c-Jun N-terminal kinase-signal trans-ducer and activator of transcription 3(JNK/STAT3)pathway.METHODS:MI rat model was established by left anterior descending coronary artery ligation method.A total of 68 rats were modeled.After ex-cluding the rats that died(n=3,mortality rate≈4.4％)or failed modeling(n=5),the 60 MI rats in-cluded in this experiment were randomly divided in-to the model group(Model group),MID low,medi-um and high dose group(1 mg/kg MID-L group,3 mg/kg MID-M group,6 mg/kg MID-H group),MID high dose+JNK activator Anisomycin group(6 mg/kg MID-H+Anisomycin group),12 rats in each group.Another 12 rats undergoing sham surgery were selected as the control group.All rats were echocardiographic and evaluated for cardiac func-tion.The myocardial tissue pathological morpholo-gy and the myocardial fibrosis degree were ob-served by hematoxylin-eosin(HE)staining and Mas-son staining.The serum myocardial injury markers[creatine kinase isoenzyme(CK-MB)and brain na-triuretic peptide(BNP)]and inflammatory factors[tumor necrosis fa ctor-α(TNF-α),interleukin-1β(IL-1β)and C-reactive protein(CRP)],myocardial tis-sue oxidative stress indicators[malondialdehyde(MDA),superoxide dismutase(SOD)and reduced glutathione(GSH)]levels were detected by enzyme-linked immunosorbent assay(ELISA).The vascular endothelial growth factor(VEGF),vascular endothe-lial growth factor receptor 2(VEGFR2),p-JNK,JNK,p-STAT3 and STAT3 proteins expression levels were detected by Protein blot method(Western blot).RE-SULTS:Compared with Control group,the myocar-dial tissue damage degree in Model group was more severe,the myocardial interstitial fibrosis de-gree was greatly deepened,the collagen volume fraction was significantly increased,the left ventric-ular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly in-creased,the left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),GSH and SOD levels were significantly de-creased,and the VEGF,VEGFR2 proteins expression levels were significantly decreased,the p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P＜0.05).Compared with Model group,with the MID dose increase,the myocardial tissue damage de-gree in MID-L,MID-M and MID-H groups was signif-icantly reduced,the myocardial interstitial fibrosis degree was reduced,the collagen volume fraction was decreased,the LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly decreased,the LVEF,LVFS,GSH and SOD levels were significantly increased,and the VEGF,VEGF2R protein expression levels were significantly in-creased,p-JNK/JNK and p-STAT3/STAT3 were signifi-cantly decreased(P＜0.05).Compared with MID-H group,the myocardial tissue damage degree in MID-H+Anisomycin group was more severe,the myocardial interstitial fibrosis degree was greatly deepened,the collagen volume fraction was signifi-cantly increased,the cardiac function was weak-ened,the oxidative stress and inflammation were aggravated,LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were increased,the LVEF,LVFS,GSH,SOD,VEGF and VEGFR2 proteins expres-sion levels were significantly decreased,p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P＜0.05).CONCLUSION:MID may improve myocardial tissue damage in MI rats by regulating JNK/STAT3 pathway,reduce oxidative stress and inflammatory response,promote angiogenesis,so as to play a role in cardiac protection.

Objective:To explore the value of contrast enhanced ultrasonography(CEUS) combined with shear wave elastography (SWE) in the diagnosis of urethral stricture.Methods:One hundred and twenty patients with urethral stricture were recruited, and preoperative retrograde urography, common urethral ultrasound, and CEUS were used to measure the length of the stricture site, and SWE was used to detect the elasticity value of the stricture site and its nearby spongiosum. Intraoperative urethral stricture lesion site measurements were performed to confirm the actual lesion location and length during surgery and to compare them with the lengths measured in the preoperative examination;4 months after surgery, SWE was used to detect the stiffness of the surgical site and to assess the surgical efficacy and prognosis.Results:The stenosis length measured by CEUS and intraoperative measurement had no statistical difference: (4.41 ± 1.47) cm vs. (4.37 ± 1.36) cm, t = 0.22, P>0.05. The elastic value in urethra stenosis in SWE was higher than that in normal urethra: (33.1 ± 6.7) kPa vs. (23.3 ± 4.1) kPa, there was statistical difference ( t = 13.67, P<0.05). The elastic value of unobstructed urethra and that of normal urethra after reconstruction had no statistical difference ( t = 0.95, P>0.05). Conclusions:CEUS combined with SWE is a safe, accurate and effective method to evaluate urethral stricture. SWE can be used to measure postoperative outcomes and recurrence.