ObjectiveTo observe the short-term and long-term efficacy of traditional Chinese medicine （TCM） surgical operations in treating mixed hemorrhoids. MethodsA multi-center retrospective cohort study was conducted， collecting clinical data from 17，831 mixed hemorrhoid surgery patients in 8 top-tier TCM hospitals in Jiangsu Province. Standardized and structured datasets were obtained through artificial intelligence models. Patients who underwent western surgical treatment were categorized into the western surgery group （11,646 cases）， and those receiving TCM surgical operations were categorized into the TCM surgery group （6185 cases）. Propensity score matching （1∶1 matching） was used to balance baseline data between groups. The primary outcome was the one-year recurrence rate， and secondary outcomes included the main symptoms （rectal bleeding， degree of prolapse） and secondary symptoms （anal distension， anal edema， wound secretion and exudation， anal stenosis， residual skin tags， perianal itching， and anal pain） measured on days 7， 28， and 60 after discharge. ResultsAfter matching， 2194 patients were included in each group. Symptom scores showed that at 28 days after discharge， the TCM surgical group had superior improvement in rectal bleeding ［OR=5.786， 95%CI （3.092，10.827）］， degree of prolapse ［OR=4.510， 95%CI （1.649，12.333）］， and anal edema ［OR=3.188， 95%CI （1.295，7.845）］ compared to the western surgical group. At 60 days post-discharge， the TCM group still showed advantages in improving rectal bleeding ［OR=5.237， 95%CI （1.077，25.464）］ and anal pain ［OR=11.697， 95%CI （1.186，115.336）］ （P＜0.05）. Long-term follow-up showed that the one-year recurrence rate in the TCM surgery group was 1.1% （8/726）， while that in the western surgery group was 2.3% （10/444）， with no statistically significant difference between the two groups （P＞0.05）. ConclusionBased on real-world data， TCM surgical treatment for mixed hemorrhoids shows significant short-term symptom improvement， particularly in terms of hemostasis， reducing swelling， and alleviating prolapse of anal masses.

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 investigate the expression characteristics of c-MET protein in colorectal cancer (CRC) and its associations with clinicopathological parameters, MET gene amplification status, and prognosis, and to evaluate the concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) detection strategies, thereby providing evidence for patient selection for MET-targeted therapy. Methods A total of 193 formalin-fixed paraffin-embedded (FFPE) tissue samples from CRC patients were collected. Immunohistochemistry (IHC) was used to detect c-MET protein expression, and fluorescence in situ hybridization (FISH) was performed to evaluate MET gene amplification status. The associations between c-MET protein expression and clinicopathological characteristics, including KRAS, NRAS, and BRAF mutation status, as well as progression-free survival (PFS), were analyzed. The concordance between IHC and FISH detection results was also evaluated. Results c-MET protein expression was significantly higher in tumor tissues than in adjacent normal tissues (P<0.05). Significant differences in c-MET expression were observed between primary tumors and liver or peritoneal/pelvic metastatic lesions (P<0.05). The proportion of high c-MET expression was significantly higher in KRAS-mutant patients than in KRAS wild-type patients (41.38% vs. 16.92%, P<0.05). The MET gene amplification rate was 8.29% (16/193), including clustered or diffuse amplification in 1.55% (3/193) and heterogeneous amplification in 6.74% (13/193). No MET exon 14 skipping mutation or amplification was detected by next-generation sequencing (NGS). Using an IHC H-Score≥150 as the threshold, the positive percent agreement (PPA) between IHC-detected c-MET protein expression and FISH-detected MET gene amplification was 100%. All clustered MET amplification regions exhibited diffuse strong c-MET expression (IHC 3+). No statistically significant association was observed between c-MET expression level and PFS (P>0.05). Conclusion High c-MET expression may represent a potential therapeutic target for KRAS-mutant CRC patients. An H-Score ≥150 is recommended as the initial screening threshold to rapidly identify patients suitable for MET-targeted therapy, with FISH testing when necessary. Diffuse strong c-MET expression (IHC 3+) shows high concordance with clustered MET gene amplification.

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective:To uncover alterations in the metabolic microenvironment of lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC) and identify potential metabolic biomarkers for the early diagnosis of LNM using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) spatial metabolomics.Methods:Six OSCC patients with LNM, who underwent neck dissection surgery at the Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangsu University between October 2020 and October 2022, were enrolled. Matched metastatically involved (positive) and benign (negative) lymph node tissue samples were collected and analyzed using DESI-MSI. Univariate and multivariate statistical analyses were employed to identify differentially abundant metabolites. The diagnostic efficacy of these metabolites was evaluated using receiver operating characteristic (ROC) curve analysis. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to determine the implicated metabolic pathways.Results:A total of 62 and 29 differentially abundant metabolites were identified in the metastatically involved lymph nodes compared to benign lymph nodes under positive-ion mode and negative-ion mode, respectively. These metabolites were predominantly amino acids and lipids. Four metabolites common to both ionization modes were selected for ROC curve analysis: phenylalanine, phosphoethanolamine, histidine, and taurine. The area under the curve values were 0.861, 0.802, 0.729, and 0.722, respectively, indicating promising diagnostic performance. Metabolic pathway analysis revealed significantly heightened activity in Amino acid metabolism ( P=0.469) and Glycerophospholipid metabolism ( P=0.006) within the LNM microenvironment. Conclusions:This DESI-MSI-based study identified disruptions in amino acid and glycerophospholipid metabolism within OSCC metastatic lymph node tissues. The associated differentially abundant metabolites represent potential candidate molecules for diagnosing OSCC LNM.

Objective:To uncover alterations in the metabolic microenvironment of lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC) and identify potential metabolic biomarkers for the early diagnosis of LNM using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) spatial metabolomics.Methods:Six OSCC patients with LNM, who underwent neck dissection surgery at the Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangsu University between October 2020 and October 2022, were enrolled. Matched metastatically involved (positive) and benign (negative) lymph node tissue samples were collected and analyzed using DESI-MSI. Univariate and multivariate statistical analyses were employed to identify differentially abundant metabolites. The diagnostic efficacy of these metabolites was evaluated using receiver operating characteristic (ROC) curve analysis. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to determine the implicated metabolic pathways.Results:A total of 62 and 29 differentially abundant metabolites were identified in the metastatically involved lymph nodes compared to benign lymph nodes under positive-ion mode and negative-ion mode, respectively. These metabolites were predominantly amino acids and lipids. Four metabolites common to both ionization modes were selected for ROC curve analysis: phenylalanine, phosphoethanolamine, histidine, and taurine. The area under the curve values were 0.861, 0.802, 0.729, and 0.722, respectively, indicating promising diagnostic performance. Metabolic pathway analysis revealed significantly heightened activity in Amino acid metabolism ( P=0.469) and Glycerophospholipid metabolism ( P=0.006) within the LNM microenvironment. Conclusions:This DESI-MSI-based study identified disruptions in amino acid and glycerophospholipid metabolism within OSCC metastatic lymph node tissues. The associated differentially abundant metabolites represent potential candidate molecules for diagnosing OSCC LNM.

Objective:To investigate the acute effects of persistent high exposure to atmospheric fine particulate matter (PM 2.5) on residents' outpatient visits for respiratory diseases. Methods:We collected daily outpatient records from 92 hospitals in 13 cities across the Beijing-Tianjin-Hebei region, along with daily PM 2.5, nitrogen dioxide (NO 2), and meteorological data from 2013 to 2018. Five persistent high PM 2.5 exposure scenarios were defined in terms of daily mean PM 2.5 concentrations (>75 μg/m 3 and >150 μg/m 3), duration (≥2 days and ≥3 days), and whether or not there was concurrent exposure to high levels of NO 2 (daily mean NO 2 concentration >50 μg/m 3). A two-stage statistical analysis strategy based on a generalized linear model was applied to conduct a time-series analysis to assess the exposure-response relationship between persistent high PM 2.5 exposure scenarios and residents' outpatient visits for a variety of respiratory diseases, and to estimate excess outpatient visits. Results:During the period, M ( Q1, Q3) PM 2.5 and NO 2 concentrations were 61.2 (42.3, 95.1) μg/m 3 and 40.2 (31.4, 54.4) μg/m 3, respectively, and the daily respiratory disease outpatient visits were 57 (52, 66) cases. When compared with non-permanent high PM 2.5 exposure periods, exposure scenarios with PM 2.5 >75 μg/m 3 and lasting for ≥2 days caused an increased risk of outpatient visits for respiratory diseases by 2.10% (95% CI: 1.44%-2.77%), and resulted in 43 787 (95% CI: 30 025-57 757) excess visits; in this scenario, the concurrent exposure to high levels of NO 2 had a greater acute effect on respiratory disease visits than the absence of exposure to high levels of NO 2 ( P<0.001). The risk of respiratory disease visits increased substantially by 4.41% (95% CI: 3.15%-5.68%) when the daily mean PM 2.5 concentration exceeded 150 μg/m 3 for ≥2 days. Subgroup disease analyses showed that scenarios with daily mean PM 2.5 concentrations exceeding 75 μg/m 3 for ≥3 days caused a significant increase in the risk of lower respiratory tract infections, chronic lower respiratory disease, and asthma visits. Conclusions:Sustained persistent high PM 2.5 exposure increases the risk of outpatient visits for various respiratory diseases; concurrent exposure to high concentrations of NO 2 leads to a greater risk of visiting the clinic, suggesting that the prevention and control of PM 2.5 pollution should be synchronized with the control of mobile source emissions, to synergistically manage the compound pollution of PM 2.5 and NO 2 in the atmosphere.

Objective:To assess the effect of short-term exposures to atmospheric fine particulate matter (PM 2.5) and its components on cognitive function in middle-aged and older people aged 40-89 and identify key components that affect cognitive function. Methods:From October 2018 to March 2019, a cross-sectional survey of middle-aged and older people aged 40-89 was conducted across 10 cities in Beijing-Tianjin-Hebei and neighboring regions of China. Data on PM 2.5 and its components were collected from the nearest air supermonitoring stations to the residential addresses. The cognitive function was assessed using the Min-Mental State Examination (MMSE) scale. Multiple linear regression models were used to assess the effect of short-term exposures to PM 2.5 and its components on cognitive function in middle-aged and older people. The restricted cubic spline function was used to fit the exposure-response relationship between different components and changes in MMSE scores. Results:The age of the 1 978 respondents was (65.1±13.4) years, and 976 (49.34%) were males. During the study period, the daily mean concentration of PM 2.5 was (71.2±43.2) μg/m 3, and the MMSE score was (28.2±3.7). The results of the multiple linear regression model showed that short-term exposures to PM 2.5 and its components were associated with cognitive decline in middle-aged and older people after adjusting for confounding factors, and the effect was higher at lag 0-28 days. For an interquartile range (64.3 μg/m 3) increase in PM 2.5 at lag 0-28 d, the MMSE score decreased by 5.91 (95% CI: 0.04, 11.77). For an interquartile range increase in organic carbon (OC), antimony (Sb), chromium (Cr), zinc (Zn), tin (Sn), and cadmium (Cd), the MMSE scores of middle-aged and older people decreased by 5.71 (95% CI: 1.69, 9.73), 4.67 (95% CI: 2.50, 6.84), 4.49 (95% CI: 1.05, 7.92), 3.65 (95% CI: 0.89, 6.42), 2.76 (95% CI: 1.22, 4.30), and 1.72 (95% CI: 0.53, 2.92). Conclusions:Short-term exposures to atmospheric PM 2.5 and its components (OC, Sb, Cr, Zn, Sn, and Cd) are associated with cognitive decline in middle-aged and older people.

Renal cancer is a common and increasingly prevalent malignancy with a complex pathogenesis influenced by genetics,smoking,and obesity.Current treatment mainly involves surgery with adjunctive chemotherapy,radiation,and immunotherapy,but high rates of recurrence and metastasis indicate its limited effectiveness,emphasizing the need for better therapeutic targets.Growing evidence indicates that epigenetic modifications,particularly RNA modifications,play a critical role in renal cancer development and progression.This review highlights recent advances in renal cancer epigenetics,focusing on RNA modifications such as N6-methyladenosine(m6 A),N7-methylguanosine(m7G),5-methylcytosine(m5C),N1-methyladenosine(m1A),adenosine-to-inosine(A-to-I),N6,2'-O-dimethyladenosine(m6Am),and N4-acetylcytidine(ac4C),along with their regulatory factors.It also explores the diagnostic and therapeutic potential of targeting RNA modifications and associated proteins.

OBJECTIVE To evaluate the long-term cost-effectiveness of canagliflozin or semaglutide in patients with type 2 diabetes mellitus（T2DM）poorly controlled with metformin. METHODS Based on the perspective of China’s health system， a Markov model was used to calculate the long-term costs and utilities of canagliflozin or semaglutide combined with metformin for T2DM patients in China for 30 years based on the data from SUSTAIN 8 study. The incremental cost-effectiveness ratio（ICER） and incremental net monetary benefit （INMB） were calculated using one time the 2024 per capita gross domestic product（GDP） as the willingness-to-pay（WTP） threshold. One-way sensitivity analysis， probability sensitivity analysis and scenario analysis were conducted to confirm the stability of the conclusions. RESULTS Compared with canagliflozin + metformin， ICER of semaglutide combined with metformin was 260 485.67 yuan/quality-adjusted life year （QALY），which was higher than the WTP threshold set in this study （95 749 yuan/QALY），and the corresponding INMB was －61 576.24 yuan，indicating that the canagliflozin + metformin regimen was more cost-effective. The cost of diabetes without complications treatment in the semaglutide + metformin group had the greatest influence on INMB，but changes in parameters within the selected range did not drive decision reversal. With the increasing of WTP threshold，the economic acceptability of semaglutide + metformin regimen increased. Under the current WTP threshold，the annual cost of semaglutide should be reduced by 42.95% to make the semaglutide + metformin regimen more cost- effective. CONCLUSIONS From the perspective of China’s health system， canagliflozin + metformin is more cost-effective than semaglutide + metformin for T2DM patients yueru. with poor glycemic control with metformin alone.