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.

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.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is one of the most prevalent chronic liver diseases worldwide， and currently there is still a lack of effective therapies. Bacteriophages are an important component of gut microbiota， and recent studies have shown that bacteriophages play a pivotal role in the pathological progression of MAFLD by reshaping microbiota structure， modulating intestinal barrier function， and regulating gut-liver axis signaling. Studies have also shown that there is a reduction in the diversity of bacteriophages in MAFLD patients， and the abundance of specific bacteriophages is closely associated with disease severity. The underlying mechanisms of bacteriophages involve the regulation of intestinal barrier， targeted clearance of pathogenic bacteria， promotion of the colonization of probiotic bacteria， and modulation of immune responses and the release of inflammatory cytokines. Animal models and preclinical trials have shown that targeted bacteriophage intervention strategies are expected to alleviate liver inflammation， improve steatosis， and ameliorate metabolic disorders. However， there are still challenges such as drug resistance of bacteriophage， the complexity of host-bacteriophage interactions， and safety issues in clinical translation. This article systematically elaborates on the regulatory mechanisms of bacteriophages in MAFLD and their application prospects in treatment， in order to provide a theoretical reference for future research and the development of bacteriophage-based therapies in this field.

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.

OBJECTIVE To investigate the cognition， attitudes， and current practices of Chinese physicians regarding biosimilars and their clinical switching， so as to provide a basis for the rational clinical application of biosimilars in China and the improvement of related policies.METHODS A national cross-sectional online questionnaire survey was conducted in 2025. Quota sampling was adopted， with quotas based on physicians’ sex， city tier， and specialty. Questionnaire invitations were distributed to licensed physicians， and physicians who had prescribed monoclonal antibody biosimilars were included for analysis. The questionnaire covered their familiarity with biosimilars， attitudes， clinical switching practices， and reasons. Data were processed using reliability and validity tests， dispersion analysis， and cross-tabulation analysis.RESULTS The questionnaire scale showed good reliability and validity， with Cronbach’s α coefficient ＞0.7 and KMO value ＞0.6. A total of 2 071 survey invitations were distributed， and 300 valid questionnaires were returned， with an effective response rate of 14.5%. Among the respondents， 75.3% had prescribed 3-5 types of monoclonal antibody biosimilars； only 35.3% were aware that China currently has no clear regulatory provisions on biosimilar switching； 46.3% and 47.3% of respondents believed that there was no difference in safety and efficacy， respectively， between biosimilars and originator products； 63.0% of respondents were concerned about the immunogenicity risk of long-term switching between originator drugs and biosimilars. A total of 92.3% of respondents had experience with biosimilar switching， 87.7% of which involved switching from originator products to biosimilars， and 28.2% of respondents had completed three or more switches in the same patient. Among the primary reasons for switching， non-medical factors accounted for 57.4%， higher than medical factors at 42.6%； “lower treatment cost after switching” was the most important reason for switching； 95.3% of respondents believed that informed consent should be obtained from patients before switching.CONCLUSIONS The surveyed physicians had basic knowledge of biosimilars， but their understanding of the relevant regulations of the national drug regulatory authority was insufficient. Although most physicians were concerned about the risks of non-medical switching， clinical switching was mostly driven by non-medical factors. It is recommended to strengthen policy education for medical professionals and standardize clinical switching behavior. The National Medical Products Administration should also promptly improve the interchangeability review standards and post-marketing surveillance system for biosimilars, so as to promote the rational use of biosimilars.

ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

ObjectiveTo analyze the epidemiological characteristics and influencing factors of SARS-CoV-2 reinfection by conducting follow-up investigations among community residents who experienced their first SARS-CoV-2 infection between March and June 2022, so as to provide a scientific basis for predicting future epidemic trends and adjusting prevention and control strategies. MethodsA cohort study was conducted in Xuhui District, Shanghai. A total of 1 208 individuals with a documented primary SARS-CoV-2 infection between March and June 2022 were enrolled and followed-up longitudinally. Data were collected using structured questionnaire surveys to assess the reinfection rate, incidence density, and clinical manifestations of SARS-CoV-2 reinfection. A logistic regression model was used to analyze the influencing factors of SARS-CoV-2 reinfection. ResultsA total of 497 SARS-CoV-2 reinfection cases were observed among the 1 208 research subjects, with a reinfection rate of 41.14% and an incidence density of 0.63 cases per 1 000 person-days. The cumulative reinfection rates at 6, 9, 12, 15, and 18 months following the initial infection were 0.08%, 15.31%, 19.04%, 33.53%, and 38.25%, respectively. Compared with the primary infection, reinfection was more likely to be symptomatic, with a greater severity of fever, dry cough, sore throat, and runny nose. Being female, younger age, and symptom duration ≥7 days during the primary infection were identified as influencing factors for SARS-CoV-2 reinfection, while a higher socioeconomic status can reduce the risk of SARS-CoV-2 reinfection. ConclusionSARS-CoV-2 reinfection is relatively common and often symptomatic. Age, gender, income level, and the duration of symptoms during the primary infection are identified as infuencing factors for SARS-CoV-2 reinfection. Continuous monitoring of reinfection in the population is recommended, along with the development of effective strategies to mitigate the impact of reinfection.

Objective:To investigate the multiple mediating effects of anxiety and depression on the relationship between dietary nutri-tion and perimenopausal symptoms in middle-aged and elderly women.Methods:A total of 1129 middle-aged and older women were surveyed using a dietary nutrition status questionnaire,the modified Kupperman Index,the Patient Health Questionnaire-9,and the Generalized Anxiety Disorder 7-item scale.The multiple mediating effect analysis was performed using the PROCESS macro in SPSS.Results:Dietary nutrition,anxiety,and depression were all significantly associated with perimenopausal symptoms(P<0.01).Dietary nutrition had a significant direct impact on perimenopausal symptoms(β=0.06,95%CI=0.002-0.119),and also exerted indirect nega-tive effects through three pathways:anxiety(β=0.059,95%CI=0.031-0.091),accounting for 29.65%of the total effect;depression(β=0.034,95%CI=0.017-0.054),accounting for 17.29%of the total effect;and anxiety-depression(β=0.045,95%CI=0.024-0.073),accounting for 22.76%of the total effect.Conclusion:Dietary nutrition not only directly affects perimenopausal symptoms,but also influences them through the mediating effects of anxiety and depression.

Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P＜0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P＜0.05 or P＜0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P＞0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P＜0.05 or P＜0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P＜0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P＜0.05 or P＜0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.