Objective: To develop QingNangTCM, a specialized large language model (LLM) tailored for expert-level traditional Chinese medicine (TCM) question-answering and clinical reasoning, addressing the scarcity of domain-specific corpora and specialized alignment. Methods: We constructed QnTCM_Dataset, a corpus of 100 000 entries, by integrating data from ShenNong_TCM_Dataset and SymMap v2.0, and synthesizing additional samples via retrieval-augmented generation (RAG) and persona-driven generation. The dataset comprehensively covers diagnostic inquiries, prescriptions, and herbal knowledge. Utilizing P-Tuning v2, we fine-tuned the GLM-4-9B-Chat backbone to develop QingNangTCM. A multi-dimensional evaluation framework, assessing accuracy, coverage, consistency, safety, professionalism, and fluency, was established using metrics such as bilingual evaluation understudy (BLEU), recall-oriented understudy for gisting evaluation (ROUGE), metric for evaluation of translation with explicit ordering (METEOR), and LLM-as-a-Judge with expert review. Qualitative analysis was conducted across four simulated clinical scenarios: symptom analysis, disease treatment, herb inquiry, and failure cases. Baseline models included GLM-4-9B-Chat, DeepSeek-V2, HuatuoGPT-II (7B), and GLM-4-9B-Chat (freeze-tuning). Results: QingNangTCM achieved the highest scores in BLEU-1/2/3/4 (0.425/0.298/0.137/0.064), ROUGE-1/2 (0.368/0.157), and METEOR (0.218), demonstrating a balanced and superior normalized performance profile of 0.900 across the dimensions of accuracy, coverage, and consistency. Although its ROUGE-L score (0.299) was lower than that of HuatuoGPT-II (7B) (0.351), it significantly outperformed domain-specific models in expert-validated win rates for professionalism (86%) and safety (73%). Qualitative analysis confirmed that the model strictly adheres to the “symptom-syndrome-pathogenesis-treatment” reasoning chain, though occasional misclassifications and hallucinations persisted when dealing with rare medicinal materials and uncommon syndromes. Conclusion Combining domain-specific corpus construction with parameter-efficient prompt tuning enhances the reasoning behavior and domain adaptation of LLMs for TCM-related tasks. This work provides a technical framework for the digital organization and intelligent utilization of TCM knowledge, with potential value for supporting diagnostic reasoning and medical education.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

Objective To investigate serum HCV-RNA detection rate in patients with positive hepatitis C virus (HCV) immunoglobulin G (IgG) antibody, and to analyze the related factors of HCV-RNA detection in patients with positive HCV IgG antibody by logistic regression analysis. Methods A retrospective study was conducted on 500 patients with positive HCV IgG antibody. The positive rate of HCV-RNA was counted. Logistic regression analysis was adopted to analyze the related factors of HCV-RNA detection in HCV IgG antibody positive population. Results A total of 317 patients with positive HCV-RNA detection were included in serum HCV-RNA positive group (n=317), and 183 patients with negative HCV-RNA detection were enrolled as serum HCV-RNA negative group (n=183). The diagnosis rate of HCV infection was 63.40% (317/500). Logistic regression analysis showed that abnormal levels of serum ALT, AST, GGT, TBIL, HCV IgG antibody, prothrombin time, and the presence of clinical symptoms were independently correlated with the detection of HCV-RNA in HCV IgG antibody positive individuals (P<0.05). Established 7-factor prediction models and created a nomogram. The chi-square value was 0.586, and P = 0.89 > 0.05. The ROC curve was plotted using pROC, and the area under the ROC curve was 0.912. Conclusion Among the population positive for HCV IgG antibody, the detection rate of serum HCV-RNA is high. Abnormal levels of ALT, AST, GGT, TBIL, IgG antibody, prothrombin time and clinical symptoms are the related factors for the detection of HCV-RNA. These indicators provide a reference for the clinical judgment of the real infection risk of HCV IgG positive individuals.

OBJECTIVE To evaluate the cost-effectiveness of fluzoparib monotherapy versus combination with apatinib as second-line or later-line treatment for patients with germline BRCA1 / 2 -mutated human epidermal growth factor receptor 2-negative （HER2－） metastatic breast cancer， from the perspective of the Chinese healthcare system. METHODS Based on the FABULOUS trial， a partitioned survival model was developed to simulate disease progression， with a cycle length of 21 days and a time horizon of 10 years. A discount rate of 4.5% per annum was applied. Model outputs included total costs and quality-adjusted life years （QALYs）. Cost-utility analysis was conducted by comparing the incremental cost-effectiveness ratio （ICER） between the two regimens against a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product in 2025 （199 330 yuan/QALY）. Robustness of the base-case results was tested through one-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analyses. RESULTS For patients with germline BRCA1/2 -mutated HER2－ metastatic breast cancer， fluzoparib combination with apatinib provided greater health benefits （1.91 QALYs vs. 1.69 QALYs） and incurred lower total costs （1 634 119.3 yuan vs. 1 855 264.2 yuan） compared with fluzoparib monotherapy， thus representing a dominant strategy. One-way sensitivity and probabilistic sensitivity analyses confirmed the robustness of the base-case findings. Scenario analyses showed that the conclusion remained robust when the time horizon was shortened to 5 years or when the discount rate was changed to 3%； however， the results reversed when the extrapolation distribution model was altered. CONCLUSIONS Under the current WTP threshold， compared with fluzoparib monotherapy， the combination of fluzoparib and apatinib is more cost-effective as a second-line or later-line treatment for Chinese patients with germline BRCA1 / 2 -mutated HER2－ metastatic breast cancer.

Objective: To investigate the current status of hyperopic reserve among preschool children and to determine the associations with genetic and behavioral factors, so as to provide evidence for early intervention strategies and the development of working protocols for myopia prevention with a forward shift of the prevention threshold. Methods: A total of 924 preschool children (3-6 years of age) from 6 kindergartens in Jiading District of Shanghai were enrolled by stratified random sampling from March to June 2024. Cycloplegic refraction using 1% atropine eye drops was performed to obtain accurate spherical equivalent (SE) values. Questionnaires were used to collect the genetic history and daily behavioral habits of the children. Refractive status was classified into three categories based on the SE:sufficient hyperopic reserve, relatively insufficient hyperopic reserve, and pre myopia. Results: The overall detection rate of insufficient hyperopic reserve among preschool children was 82.25%, consisting of 72.29% for relatively insufficient hyperopic reserve and 9.96% for pre myopia. Multivariate Logistic regression analysis showed that parental bilateral myopia was independently and positively associated with relatively insufficient hyperopic reserve ( OR =2.13) and pre myopia ( OR =4.35) compared to children with sufficient hyperopic reserve; electronic screen exposure time ≥2 h/d on school days was an independent and positive risk factor for pre myopia ( OR =2.83); all of the above associations were statistically significant (all P <0.05). No statistically significant association was noted between outdoor activity and hyperopic reserve (all P >0.05). Conclusions The insufficient hyperopic reserve detection rate is relatively high among preschool children in Jiading District, Shanghai. Early management of electronic device use with regular screening and monitoring for preschool children with a family history of myopia should be strengthened to shift the prevention threshold earlier and prevent childhood myopia.

ObjectiveTo summarize the incidence and clinical features of drug hypersensitivity reactions in children treated with sustained-releasing gonadotropin-releasing hormone agonists （GnRHa）， aiming to provide guidance for the safe clinical application of GnRHa in children. MethodsThe medical data of children diagnosed with central precocious puberty （CPP） or early and fast puberty （EFP） were retrospectively analyzed， who received GnRHa treatment at the Children's Growth Center of the First Affiliated Hospital of Sun Yat-sen University between January 1990 and July 2023. The occurrence of GnRHa-related drug hypersensitivity reactions were summarized， including the incidence and clinical features of systemic reactions and sterile abscesses. ResultsAmong the 1 684 children treated with GnRHa for CPP/EFP， the female-to-male ratio was 3.8∶1. A total of nine children （0.53%） developed 44 occurrences of drug hypersensitivity reactions. Four children （0.24%） presented with sterile abscesses （21 occurrences）， and five children （0.30%） experienced systemic hypersensitivity reactions （14 occurrences）. Four children were hypersensitive to triptorelin acetate， three were hypersensitive to leuprorelin acetate， and two were hypersensitive to both triptorelin acetate and leuprorelin acetate. The predominant hypersensitivity reactions to leuprorelin acetate were sterile abscesses， observed in four cases （4/277， 1.44%）， whereas the main reactions to triptorelin acetate were systemic hypersensitivity reactions， affecting five cases （5/1 501， 0.33%）. Case one presented with a severe and complex condition， exhibiting hypersensitivity to multiple GnRHa preparations （sustained-releasing triptorelin， sustained-releasing leuprorelin， and short-acting triptorelin）， and presenting with diverse manifestations， including induration， sterile abscesses， systemic hypersensitivity reactions， and even loss of suppression of the hypothalamic-pituitary-gonadal axis， leading to treatment failure. ConclusionsThe proportion of children experiencing drug hypersensitivity reactions to sustained-releasing GnRHa is relatively low at 0.53%， with diverse manifestations. The reactions primarily manifest as sterile abscesses and systemic hypersensitivity reactions， and in severe cases， may lead to treatment failure due to loss of suppression of the hypothalamic-pituitary-gonadal axis.

OBJECTIVES: To investigate the risk factors of overall postoperative complications in elderly patients undergoing gastrointestinal surgeries. METHODS: This study was conducted among a total of 1388 elderly patients, who underwent elective gastrointestinal surgeries at 17 centers across China between April, 2020 and April, 2022. The primary outcome was the incidence of postoperative complications within 30 days, including procedure-related, neuropsychiatric, respiratory, cardiovascular, and gastrointestinal complications as well as acute kidney injury. Baseline characteristics, preoperative psychological and functional status, intraoperative anesthesia and surgical factors, intraoperative medication, use of nerve block, and postoperative analgesia methods were compared between the patients experiencing one or more postoperative complications and those without complications. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for postoperative complications. The relationship between postoperative acute pain and each type of complication were explored. RESULTS: The incidence of overall postoperative complications was 50.8% (705/1388) in these patients. Multivariate analysis showed that age (OR: 1.026; 95% CI: 1.006-1.046), prognostic nutritional index (OR: 0.998; 95% CI: 0.997-1.000), preoperative EuroQol-5 dimensions score (OR: 0.094; 95% CI: 0.018-0.500), blood loss (OR: 1.002; 95% CI: 1.001-1.003), and acute postoperative pain (OR: 1.308; 95% CI: 1.033-1.657) were significantly associated with the occurrence of postoperative complications. Specifically, patients experiencing severe postoperative pain had a significantly higher incidence of neuropsychiatric (27.2% vs 19.8%), procedure-related (17.3% vs 10.2%), and cardiovascular complications (3.6% vs 1.7%). CONCLUSIONS An advanced age, a low preoperative nutritional index, a poor quality of life score, a greater volume of intraoperative blood loss, and acute postoperative pain are independent risk factors for postoperative complications in elderly patients undergoing gastrointestinal surgeries. There is a significant association between acute postoperative pain and multi-system complications.
Humans ; Postoperative Complications/etiology* ; Aged ; Risk Factors ; Digestive System Surgical Procedures/adverse effects* ; Male ; Female ; China/epidemiology* ; Pain, Postoperative/epidemiology* ; Incidence ; Aged, 80 and over

Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

OBJECTIVE: To explore the effects of different endotracheal tube cuff pressure management modes on cuff sealing and the pressure exerted on the tracheal wall. METHODS: A prospective self-controlled study was conducted. Eleven patients undergoing endotracheal intubation and mechanical ventilation with an automatic airway management system (AGs) admitted to the Second Medical Centre of the Chinese People's Liberation Army General Hospital from October 1, 2020, to April 1, 2022, were enrolled as the study subjects. Within 24 hours after the establishment of artificial airway and mechanical ventilation, four cuff pressure management modes were randomly applied to each patient for 24 hours in sequence: automatic cuff pressure management mode [modeI: the safe range of cuff pressure was set at 20-35 cmH₂O (1 cmH₂O≈0.098 kPa), and the CO₂ pressure above the endotracheal tube cuff was automatically detected by AGs every 5 minutes to determine the cuff sealing status, and the cuff pressure was automatically adjusted], constant cuff pressure (25 cmH₂O) management mode (mode II: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 25 cmH₂O via a pressure pump), constant cuff pressure (30 cmH₂O) management mode (mode III: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 30 cmH₂O via a pressure pump), and manual cuff pressure management mode (mode IV: the cuff pressure was manually measured by nurses every 6-8 hours using a cuff pressure gauge to keep the cuff pressure at 25-30 cmH₂O after inflation). The CO₂ pressure above the endotracheal tube cuff (at 60-minute intervals) and the cuff pressure changes (at 50-ms intervals) were recorded to compare the differences in number of cuff leaks [no leak was defined as CO₂ pressure = 0, small leak as 0 < CO₂ pressure < 2 mmHg (1 mmHg≈0.133 kPa), and large leak as CO₂ pressure ≥ 2 mmHg] and cuff pressure among modesI-IV. RESULTS: A total of 24 CO₂ pressure measurements were taken per patient across the four modes, resulting in a total of 264 detections for each mode. Regarding the cuff leak, the total number of leak and large leak in modeIwas significantly lower than that in modes II-IV [total leak: 30 cases (11.36%) vs. 81 cases (30.68%), 70 cases (26.52%), 103 cases (39.02%); large leak: 15 cases (5.68%) vs. 50 cases (18.94%), 48 cases (18.18%), 66 cases (25.00%), all P < 0.05]. There was no significant difference in the number of cuff leak between modes II and III, and mode IV had the most severe cuff leak. In terms of cuff pressure, since mode IV required blocking the cuff tube from the AGs tube and the AGs cuff pressure management module did not actually work, real-time monitoring of cuff pressure was not possible. Therefore, cuff pressure changes were only analyzed in modes I-III. Each of the 11 patients underwent 24-hour cuff pressure monitoring under modes I-III, with 19 008 000 monitoring times for each mode. The cuff pressure in mode I was between that in modes II and III [cmH₂O: 27.09 (26.10, 28.14) vs. 26.60 (25.92, 27.47), 31.01 (30.33, 31.88), both P < 0.01]. Moreover, the number of extreme values of cuff pressure > 50 cmH₂O in mode I was significantly lower than that in modes II and III [19 900 cases (0.105%) vs. 22 297 cases (0.117%), 27 618 cases (0.145%), both P < 0.05]. CONCLUSION Dynamically monitoring the CO₂ pressure above the cuff to guide the adjustment of endotracheal tube cuff pressure can achieve better cuff sealing with a relatively lower cuff pressure load.
Humans ; Intubation, Intratracheal/instrumentation* ; Pressure ; Prospective Studies ; Respiration, Artificial ; Male ; Airway Management/methods* ; Female ; Middle Aged