This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

ObjectiveThis paper aims to observe the protective effect of Huamoyan granules on knee osteoarthritis （KOA） and explore whether its protective effect is oriented toward an anti-inflammatory direction by regulation of macrophage polarization， which can effectively inhibit the progression of pathological inflammatory response， reduce the release of inflammatory pain mediators， and downregulate the protein expression level of transient receptor potential vanilloid 1 （TRPV1）， so as to provide experimental evidence for its clinical application and investigate its action mechanism. MethodsAfter adaptive feeding， Sprague-Dawley （SD） rats were randomly divided into six groups： sham group， model group， celecoxib group， and high， medium， and low-dose synovitis granule groups （9.6， 4.8， 2.4 g·kg^-1）. The administration dose of celecoxib capsules was 20 mg·kg^-1. There were 10 rats in the sham group and 12 rats in the model group and each administration group. A KOA animal model was established by means of intra-articular injection of sodium iodoacetate into the knee joint. From the 10^th day of the experiment， each administration group was given intragastric administration at a dose of 10 mL·kg^-1 for 4 weeks. General conditions of rats in each group were assessed daily. The pressure pain threshold （PPT） to mechanical stimulation and joint diameter were recorded. X-ray examination was performed on the right knee joints of rats for imaging analysis. Enzyme linked immunosorbent assay （ELISA） was performed to detect the tumor necrosis factor-α （TNF-α）， serum interleukin-1β （IL-1β）， and other pro-inflammatory cytokines in rat serum samples， as well as the expression levels of neurogenic inflammatory mediators such as nerve growth factor （NGF） and calcitonin gene-related peptide （CGRP）. Histopathological changes in the knee joint synovial tissues were examined by hematoxylineosin （HE） staining. Safranin O-fast green staining was performed to observe and evaluate the degree of knee cartilage lesions. Western blot was employed to quantitatively analyze TRPV1， p38 mitogen-activated protein kinase （p38 MAPK）， and phosphorylated （p）-p38 MAPK in rat knee synovial tissues. Immunofluorescence （IF） was used to measure and assess M1/M2 macrophage polarization. ResultsCompared with those in the sham group， the circumference and joint diameter of the right knee were markedly enlarged in the model group （P<0.01）， while PPTs of rats showed a significant reduction （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in rats' serum were significantly elevated （P<0.01）， and the synovial Krenn score was increased （P<0.01）. The Mankin score of cartilage tissue was increased （P<0.01）， and the protein expressions of TRPV1 and p-p38 MAPK/p38 MAPK were significantly upregulated （P<0.01）. The experimental intervention significantly reduced the proportion of pro-inflammatory M1 macrophages in the total macrophage population （P<0.01）， and the percentage of M2 macrophages was decreased （P<0.01）. The M1/M2 macrophage ratio was significantly elevated （P<0.01）. Knee joint diameters of all dose groups of Huamoyan granules and the celecoxib group were reduced （P<0.01） compared with those of the model group， and the PPT recovery speeds in the high and medium-dose groups of Huamoyan granules were more obvious （P<0.05）. The contents of IL-1β， CGRP， and NGF in the rats' serum in all administration groups were significantly reduced （P<0.05， P<0.01）， and the content of TNF-α in rats' serum was significantly reduced （P<0.01）. All dose groups of Huamoyan granules demonstrated significant reductions in both synovial Krenn score （P<0.05， P<0.01） and protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in rats' synovial tissues （P<0.01）. The percentage of M1 macrophages in the synovial tissues of the celecoxib group and all dose groups of Huamoyan granules was decreased （P<0.01）. The percentage of M2 macrophages was increased （P<0.05）， and the M1/M2 ratio was decreased （P<0.01）. ConclusionHuamoyan granules can alleviate the inflammatory response of KOA， reduce the release of inflammatory pain mediators， and downregulate TRPV1 protein expression by regulating macrophage polarization. Its mechanism may be related to the TRPV1/p38 MAPK signaling pathway， thereby achieving the effect of improving peripheral pain hypersensitivity in KOA.

ObjectiveTo develop a standardized classification model for traditional Chinese medicine （TCM） syndrome patterns of mixed hemorrhoids using multi-center real-world data， and unveil their distribution patterns and core risk factors， thereby providing evidence-based support for standardizing TCM syndrome differentiation and implementing precision interventions. MethodsA multi-center cross-sectional study was conducted， enrolling 13 283 mixed hemorrhoid patients from eight hospitals in Jiangsu Province between September 1st， 2023 and December 31st， 2024. DeepSeek-R1-Distill-Qwen-7B and LLaMA-3.3 large language models （LLM） were integrated with latent class analysis （LCA） to perform unsupervised learning and latent class modeling of TCM symptomatology. Potential risk factors were screened via univariate analysis， followed by logistic regression to identify independent risk factors for each syndrome pattern. ResultsThe model's performance indicators were stable and reliable across different clinical data types，i.e. in the outpatient records， past medical history （F1=99.7%）， current medical history （F1=94.9%）， and specialist examination （F1=90.7%）； in inpatient records， past medical history （F1=98.2%）， current medical history （F1=91.2%）， specialist examination （F1=90.3%）， and discharge status （F1=90.6%）. Latent class mode-ling identified four core TCM syndrome patterns including spleen deficiency and qi sinking syndrome （915 cases， 6.89%）， damp-heat pouring downward syndrome （10 820 cases， 81.46%）， qi stagnation and blood stasis syndrome （1252 cases， 9.43%）， and wind injuring intestinal collaterals syndrome （296 cases， 2.22%）， with respective latent class probabilities of 0.069， 0.815， 0.094， and 0.022. Logistic regression demonstrated that gender， age， disease duration， hypertension， diabetes， hyperlipidemia， constipation， smoking history， and alcohol consumption were independent risk factors for pattern differentiation （P＜0.05）. The efficacy validation evaluation revealed that the cure rates for patients with spleen deficiency and qi sinking syndrome and qi stagnation and blood stasis syndrome were higher than those for patients with damp-heat pouring downward syndrome （adjusted P＜0.05）， with no statistically significant differences among other syndrome patterns. ConclusionDamp-heat pouring downward syndrome is the predominant syndrome in mixed hemorrhoids. Gender， age， disease duration， hypertension， diabetes， hyperlipi-demia， constipation， smoking history， and alcohol consumption are independent risk factors for the differentiation of syndrome types.

This paper has constructed a traditional Chinese medicine （TCM） specialized disease dataset platform for mixed hemorrhoids based on a multimodal large model， and the preliminary application has been validated. The platform uses StarRocks to establish a four-level data warehouse system， enabling the aggregation， cleaning， and standardization of multi-source heterogeneous data. Using DeepSeek-R1-Distill-Qwen-7B as the base model， domain fine-tuning is performed through low-rank adaptation （LoRA） technology. Combined with LLaMA-3.3 natural language processing and reasoning chain techniques， the platform enables intelligent parsing and structured extraction of unstructured TCM medical records. It accurately identifies six major categories and 28 subcategories of entities， including symptoms and syndromes， with a fine-tuned model F1 score of 93.8%. The platform has established a high-quality specialized disease dataset containing more than 50,000 medical records and has been applied in a real-world study involving 17,831 patients， preliminarily verifying the efficacy of TCM heritage surgery.

Objective To compare the performance of 7 Chinese-developed GenAI models (DeepSeek, Wenxin Yiyan, Tongyi, Doubao, Kimi, Hunyuan, and iFLYTEK Spark) in responding to common diseases of the pediatric genitourinary system and to explore their potential applications.Methods A total of 80 questions covering basic disease information, diagnosis, treatment, and prognosis related to “hypospadias, hydronephrosis, and cryptorchidism” were developed as prompts.The models were tested under 3 modes:“quick thinking, ”“deep thinking, ” and “deep thinking + internet access.” The results were evaluated in a blinded review by two pediatric urologists.The responses were graded into 4 levels—A, B, C, and D—based on accuracy, completeness, and relevance.The proportions of responses rated as A and A+B were statistically analyzed and compared across the different models/modes.Results The “deep thinking” mode of DeepSeek demonstrated the best performance, with 88% of responses rated as A and 96% rated as A+B.DeepSeek (deep thinking + internet access), Doubao (quick thinking), Hunyuan (deep thinking), and Doubao (deep thinking + internet access) followed closely, also showing excellent response capabilities.Among the top 5 models/modes, significant differences were observed in the proportion of Alevel responses (P＜0.05), while differences in the proportion of A+B-level responses were not statistically significant (P＞0.05).Conclusion Certain Chinese-developed GenAI models, represented by DeepSeek (deep thinking), demonstrate significant application potential.However, they still cannot consistently provide recommendations rated at the A+B level (recommended grade or higher) with 100% accuracy.In clinical practice, both doctors and patients should view GenAI as an auxiliary tool for education and information acquisition rather than as a final decision-making authority.All information must be reviewed and confirmed by professional physicians.

Objective To explore the mechanism of Angong Niuhuang pill on the neurological function of rats with spontaneous intracerebral hemorrhage based on the tumor necrosis factor-α/nuclear factor-κB(TNF-α/NF-κB)signaling pathway combined with network pharmacology.Methods The targets for treatment of intracerebral hemorrhage with Angong Niuhuang pill were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),High-Throughput Experiment and Refeence-guided Database of Traditional Chinese Medicine(HERB).Key targets were screened for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and molecular docking.Then,rats were randomly divided into normal control group,model group,Angong Niuhuang pill group(administered by gavage at 270 mg·kg-1·d-1),and the Western medicine group(intraperitoneal injection of 4 500 mg·kg-1·d-1+furosemide 1.8 mg·kg-1·d-1),the dosage administered was the equivalent dose ratio calculated based on the body surface area for humans and animals.The intracerebral hemorrhage model was replicated by the autologous heart blood caudate nucleus injection method.After modeling,the neurological function behavior scores,brain tissue water content,pathological changes of brain tissue,blood-brain barrier permeability,and protein expression levels of NF-κB p65,tumor necrosis factor receptor 1(TNFR1),inhibitor NF-κBα(IκBα)and TNF-α in brain tissue of each group were observed.Results A total of 216 intersection genes were selected.The results of GO enrichment analysis and KEGG pathway annotation analysis predicted that the TNF-α/NF-κB inflammatory signaling pathway was one of the main regulatory pathways.The animal experiment results showed that at 72 hours after modeling,compared with the model group,the neurological function score,brain tissue water content,and blood-brain barrier permeability index evans blue(EB)content of the Angong Niuhuang pill group were significantly decreased[neurological function score:1.62±0.62 vs.2.23±0.58,brain water content:(77.7±0.49)%vs.(79.9±0.04)%,EB content(μg/L):490.50±100.79 vs.1 966.20±94.81,all P<0.05];the pathological observation of brain tissue showed that Angong Niuhuang pill could reduce the pathological damage of brain tissue around the hematoma,repair the blood-brain barrier,and alleviate brain edema;the Western blotting results showed that Angong Niuhuang pill could inhibit the protein expression of TNF-α,TNFR1,and NF-κB p65 in brain tissue[NF-κB p65 protein expresion(NF-κB p65/β-actin):2.27±0.52 vs.5.40±0.26;TNFR1 protein expression(TNFR1/β-actin):1.49±0.33 vs.2.52±0.04,TNF-α protein expression(TNF-α/β-actin):1.40±0.13 vs.2.29±0.18,all P<0.05],promote the protein expression of IκB-α(IκB-α/β-actin):0.78±0.02 vs.0.32±0.00,P<0.05).Conclusion Angong Niuhuang pill may regulate the TNF-α/NF-κB signaling pathway by inhibiting the expression of TNFR1 and promoting the expression of IκB-α,exerting neuroprotective effects.

Objective:To explore the effectiveness and application value of focused ultrasound ablation surgery (FUAS) combined with hysteroscopic surgery in treating solitary type Ⅱ submucosal uterine fibroids with maximum diameter >5 cm.Methods:Clinical data of 35 patients with a single type Ⅱ submucosal uterine fibroid with maximum diameter greater than 5 cm who underwent FUAS combined with hysteroscopic surgery at Qingdao Women and Children′s Hospital from June 2020 to December 2023 were collected. The clinical characteristics, treatments and treatment outcomes were retrospectively analyzed.Results:(1) Clinical characteristics: the mean age of the 35 patients was (36.7±6.6) years, with a median maximum diameter of fibroids of 56 mm (range: 51-80 mm). All patients presented with symptoms of menorrhagia, median menstrual bleeding score was 5 points (ranged from 3 to 5 points), and 34 cases (97.1%, 34/35) had concomitant anemia, the mean hemoglobin was (83.1±13.8) g/L of 35 patients. (2) Treatments: all 35 patients underwent FUAS treatment initially, with a lesion ablation rate ranging from 69.7% to 97.9% (median:90.7%), and no complications occurred. After FUAS treatment, the volume of fibroids decreased in all patients, with a volume reduction rate ranging from 30.57% to 87.22% (median:76.03%). Hysteroscopic surgery was performed 3-14 months (median: 5 months) after FUAS to remove the necrotic fibroid tissue, achieving a 100.0% (35/35) fibroid resection rate. Only 1 patient developed complications of hyperhyderation syndrome during hysteroscopic surgery, and no complications occurred in the remaining patients. (3) Evaluation of efficacy: after FUAS pretreatment, the maximum diameter of fibroids in the 35 patients decreased significantly ( Z=-5.171, P<0.001), as did the volume of fibroids ( Z=-5.159, P<0.001). The hemoglobin level increased significantly compared to the level before FUAS in all cases ( t=-8.657, P<0.001), and median menstrual bleeding score decreased to 2 points (range: 1-3 points), significantly lower than original level ( Z=-5.292, P<0.001). At the 3-month follow-up after hysteroscopic surgery, all patients were free of anemia symptoms, with menstrual bleeding scores totally decreased to 1 point, significantly lower than that before hysteroscopic surgery ( Z=-4.786, P<0.001); hemoglobin level [(118.7±5.6) g/L] significantly increased compared to that before hysteroscopic surgery ( t=-9.258, P<0.001). All patients underwent gynecological transvaginal ultrasound re-examination, which did not reveal any residual fibroids. Conclusion:FUAS combined with hysteroscopic surgery is effective in treating solitary type Ⅱ submucosal uterine fibroids with maximum diameter >5 cm, providing a new treatment option for patients.

Objective:To elucidate the molecular mechanisms through which high-dose dexamethasone exerts long-term effects on bone marrow mesenchymal stem cells (BMSCs), specifically its role in suppressing osteogenic differentiation, accelerating cellular senescence, triggering the senescence-associated secretory phenotype (SASP), and inducing apoptosis.Methods:Primary rat BMSCs were isolated and treated with high-dose dexamethasone (1×10 -4 mol/L) to establish the experimental group, while untreated cells served as the control. The gene and protein expression levels of osteogenic markers, bone alkaline phosphatase (bALP) and Runt-related transcription factor 2 (Runx2), were analyzed in both groups. Cellular senescence was evaluated using senescence-associated β-galactosidase (SA-β-gal) staining. The expression of senescence-related markers (P16 and P21), components of the senescence-associated secretory phenotype (SASP), including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-γ, as well as apoptosis-related proteins (Bcl-2, Bax, and Cleaved-Caspase-3), and key factors of the Nrf2/HO-1 signaling pathway were assessed at both transcriptional and protein levels using qRT-PCR, immunofluorescence, and Western-blot analyses. These comprehensive evaluations aimed to determine the senescent state, apoptotic features, and alterations in osteogenic differentiation of BMSCs. Results:Following treatment with dexamethasone and subsequent withdrawal, both qRT-PCR and Western blot analyses indicated a significant reduction in the expression of the osteogenic markers bALP and Runx2 at both mRNA and protein levels. The proportion of SA-β-gal positive cells was markedly higher in the dexamethasone group (74.33%±6.89%) than in the control group (20.30%±1.57%, t=17.300, P<0.001). qRT-PCR analysis revealed upregulated mRNA expression of the senescence-related genes P16 and P21 after dexamethasone treatment, which was further supported at the protein level by immunofluorescence showing increased P21 expression. Western-blot results confirmed that protein expression levels of P16 and P21 were significantly elevated in the dexamethasone group (7.025±0.255 and 6.362±0.456, respectively) compared with the control group (1.016±0.115 and 0.816±0.172; both P<0.05). Furthermore, gene expression levels of the senescence-associated secretory phenotype (SASP) factors TNF-α and IL-1β were significantly increased (TNF-α: 3.539±0.599 vs. 0.742±0.095; IL-1β: 4.469±0.331 vs. 0.799±0.175; both P<0.05), and their protein expression was consistently upregulated as validated by Western-blot. Additionally, protein expression levels of TNF-α, IL-1β, and IFN-γ were significantly higher in the dexamethasone-treated group (3.476±0.932 vs. 0.945±0.095; 4.111±0.220 vs. 0.762±0.105; 2.155±0.240 vs. 0.656±0.104; all P<0.05).Western-blot analysis also demonstrated that protein expression of Nrf2 and HO-1 was significantly suppressed in the dexamethasone group (0.21±0.07 and 0.19±0.06, respectively) compared with the control group (1.13±0.15 and 0.92±0.21; P<0.05). Moreover, Western-blot analysis revealed that the expression levels of the pro-apoptotic proteins Bax and Cleaved-Caspase-3 were significantly up, regulated in the dexamethasone, treated BMSCs (Bax: 3.673±0.397 vs. 0.453±0.111; Cleaved-Caspase-3: 3.863±0.399 vs. 0.465±0.057), while the expression of the anti-apoptotic protein Bcl-2 was markedly down, regulated (0.959±0.073 vs. 2.126±0.195), with all differences being statistically significant ( P<0.05). Conclusions:High-dose dexamethasone treatment of BMSCs, followed by withdrawal of dexamethasone, induces cellular senescence and enhances the expression of the senescence-associated secretory phenotype (SASP) through suppression of the Nrf2/HO-1 signaling pathway. Concurrently, it promotes apoptosis by activating the mitochondrial apoptotic pathway, collectively leading to impaired osteogenic differentiation of BMSCs.