OBJECTIVE To investigate the regulatory effects of tofacitinib combined with methotrexate （MTX） on gut microbiota and the clinical efficacy of this regimen in patients with rheumatoid arthritis （RA）. METHODS A retrospective analysis was conducted on the clinical data of 182 patients with RA admitted to Xingtai People’s Hospital from January 2022 to June 2025. The patients were divided into a control group （ n ＝88， treated with MTX monotherapy） and an observation group （ n ＝94， treated with tofacitinib combined w ith MTX） based on their treatment regimen. Gut microbiota abundance， inflammatory and immunological indicators [C-reactive protein （CRP）， erythrocyte sedimentation rate （ESR）， rheumatoid factor （RF）， and anti-cyclic citrullinated peptide antibody （anti-CCP） ] ， clinical efficacy indicators [American College of Rheumatology 20% response rate （ACR20）， Disease Activity Score in 28 Joints （DAS28）， and Health Assessment Questionnaire （HAQ） score ] ， and adverse reactions during treatment were compared between the two groups before and after 12 weeks of treatment. RESULTS After treatment， the abundance of Lactobacillus and Bifidobacterium were significantly increased in both groups compared with before treatment， whereas the abundances of Enterococcus and Enterobacter ， as well as the levels of CRP， ESR， RF， anti-CCP， DAS28 score， and HAQ score， were significantly decreased （ P ＜0.05）. The degree of improvement in the observation group was significantly greater than that in the control group （ P ＜0.05）. The ACR20 response rate in the observation group was significantly higher than that in the control group （81.91% vs. 56.82%， P ＜0.05）. There was no statistically significant difference in the incidence of adverse reactions between the two groups （ P ＞0.05）， and the main adverse reactions were gastrointestinal reactions and abnormal liver function. CONCLUSIONS Tofacitinib combined with MTX can effectively improve gut microbiota balance in patients with RA by increasing the abundance of probiotics and reducing the abundance of opportunistic pathogenic bacteria， thereby improving immune and inflammatory status. In addition， this combination regimen can enhance clinical efficacy， reduce disease activity， and improve functional status， with a favorable safety profile.

This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

Objective:To compare the clinical efficacy and adverse events of chemoradiotherapy (CRT) combined with immunotherapy versus CRT alone in patients with locally recurrent esophageal squamous cell carcinoma (ESCC) after surgery.Methods:A total of 221 patients with postoperative locally recurrent ESCC who underwent CRT at the Affiliated Huai′an No. 1 People′s Hospital of Nanjing Medical University from January 2020 to December 2022 were retrospectively analyzed. Patients were divided into two groups according to treatment modality: the CRT group ( n=118) and the CRT plus immunotherapy group (combined group, n=103). Among the combined group, 39 patients received camrelizumab, 33 received sintilimab, and 31 received tislelizumab. Short-term efficacy, survival outcomes, and treatment-related adverse events were compared between the two groups. The Cox proportional hazards model was used to analyze prognostic factors for overall survival (OS). Results:No statistically significant differences were observed in baseline clinicopathological characteristics between the two groups. The objective response rate (ORR) in the combined group was 72.8%, significantly higher than 55.9% in the CRT group ( P=0.009). The 1- and 2-year OS rates in the CRT group were 68.6% and 41.5%, respectively, while the 1- and 2-year progression-free survival (PFS) rates were 56.8% and 30.5%, respectively. In the combined group, the 1- and 2-year OS rates were 84.5% and 55.3%, and the 1- and 2-year PFS rates were 67.0% and 42.7%, respectively. The differences in both OS and PFS between the two groups were statistically significant ( P=0.001 and 0.023, respectively). Multivariate analysis showed that Karnofsky performance status score of 70, TNM stage III, and CRT alone were independent risk factors for OS ( P=0.035, 0.031, and 0.002, respectively). The incidence of grade ≥3 adverse events did not differ significantly between the two groups ( P=0.550). A total of 85 grade 1-2 immune-related adverse events (irAEs) and 7 grade ≥3 irAEs occurred in 65 patients in the combined group. Subgroup analysis suggested that tislelizumab combined with CRT showed the most favorable efficacy and safety profile. Conclusion:For patients with locally recurrent ESCC after surgery, concurrent chemoradiotherapy combined with immunotherapy demonstrates promising efficacy with tolerable safety, and may offer a potential therapeutic advantage.

Massive Open Online Courses （MOOCs） in medical ethics play a significant role in cultivating the humanistic quality of medical students. Through quantitative analysis， this paper compared the commonalities and differences in “medical ethics” MOOC courses in different types of colleges and universities， as well as proposed new paths for optimizing the cultivation of medical students’ humanistic quality. By searching and analyzing course data from “medical ethics” offered on mainstream MOOC platforms in China from 2013 to 2024， this paper explored new paths for the integration of MOOCs and humanistic quality from the perspectives of course content， faculty construction， student participation， and comparison between traditional Chinese medicine （TCM） universities and comprehensive universities. This study found that medical MOOCs focused on theoretical foundations and medical professional ethics and spirit， medical equity and social responsibility， as well as end-of-life care and medical humanistic care， forming a multidimensional curriculum system. Faculty teams reflected interdisciplinary characteristics， gathering teachers from disciplines such as medicine， philosophy， and education. Differences were observed between TCM universities and comprehensive universities. The former focused more on the origins and inheritance of humanistic care in TCM culture and ancient Chinese medical classics， while the latter emphasized more on Western ethical spirit. This paper can provide valuable insights for the diversified development of medical humanistic quality education， contribute to the integration of TCM ethics with modern medical ethics， provide references for online medical ethics education， implement new medical concepts， promote interdisciplinary integration of medicine and the humanities， and assists the reform and development of medical education.

Objective:To investigate the association between serum thyroid-stimulating hormone(TSH) level and the 10-year risk of atherosclerotic cardiovascular disease(ASCVD) in men over 50 years old with type 2 diabetes mellitus(T2DM).Methods:This study included male T2DM patients aged≥50 years, diagnosed at the First Hospital of Lanzhou University between July 2021 and March 2022. Patients were categorized into three groups based on serum TSH level: elevated TSH group(T3, TSH>5.91 mIU/L) and normal TSH group, which was further divided into T1(0.56 mIU/L≤TSH<3.24 mIU/L) and T2(3.24 mIU/L≤TSH≤5.91 mIU/L) group. The 10-year ASCVD risk index was compared across groups. Spearman correlation and multiple linear regression analyses were used to assess the independent association between TSH level and 10-year ASCVD risk index. Results:A total of 490 male T2DM patients aged≥50 years were included(T1: 310, T2: 131, T3: 49). The 10-year ASCVD risk index was significantly higher in T3 group than that in T1 group(18.40% vs 13.90%, χ2=9.47, P<0.05). Serum TSH level showed a positive correlation with the 10-year ASCVD risk( r=0.144, P<0.05). After adjusting for confounders such as age, hypertension, lipid profile, diabetes duration, aspartate aminotransferase, albumin, lactate dehydrogenase, estimated glomerular filtration rate, creatinine, and phosphorus, multiple linear regression confirmed that TSH level was independently associated with the 10-year ASCVD risk index( β=0.23, 95% CI 0.02-0.45). Conclusions:Higher serum TSH level is independently associated with an increased 10-year ASCVD risk in men over 50 years old with T2DM. Regular TSH monitoring may aid in cardiovascular risk stratification in this population.

Objective:To investigate the factors influencing sound localization in patients with unilateral sudden sensorineural hearing loss, so as to provide the reference for hearing rehabilitation of patients with unilateral sudden hearing loss.Methods:This study was a cross-sectional study that retrospectively analyzed the clinical data and audiological examination results of 228 patients with unilateral sudden sensorineural hearing loss(103 males and 125 females; aged from 18 to 80 years, with an average age of 46.2 years; 107 cases in the left ear and 121 cases in the right ear; 8 cases of low-frequency decline type, 42 cases of high-frequency decline type, 92 cases of flat decline type, and 86 cases of total deafness type)at the Eye and ENT Hospital of Fudan University from June 2023 to April 2024. The minimum audible angle (MAA) was calculated by the angle discrimination test of 1000 Hz and 4000 Hz warble tones, which were recorded as MAA 1 000 and MAA 4 000 according to the frequency of the given sound stimulus. The root mean square error (RMSE) was calculated by the angle recognition test with daily natural sounds as the stimulus sound. Using SPSS 27.0 statistical software, correlation and multiple regression analysis were used to research the clinical factors affecting the ability of sound localization in patients with unilateral sudden sensorineural hearing loss. Results:The mean MAA 1 000, MAA 4 000, RMSE of patients with unilateral sudden deafness were (53.97±29.14)°, (46.34±28.87)° and (30.06±13.64)°, respectively. Univariate analysis of variance revealed that there were significant differences between different classifications of sudden sensorineural hearing loss for sound localization tests (MAA 1 000: F=6.338, P<0.001,MAA 4 000: F=14.334, P<0.001,RMSE: F=49.918, P<0.001), post-hoc analysis observed that all significant contrasts were included the type of total deafness and low-frequency deafness. Correlation analysis showed the age of subjects in this study was weak positively correlated to the MAA 1 000 ( r=0.165, P=0.013), the duration of sudden sensorineural hearing loss was weak negatively related to RMSE ( r=-0.144, P=0.030), there were significant positive relationships between the threshold of PTA, PTA 1kHz, PTA 4kHz for the affected side, as well as the binaural PTA difference and sound localization test (MAA 1 000,MAA 4 000,RMSE) (all P<0.001). The multiple regression analysis showed the age and the binaural PTA difference for the affected side were the significant factors for the MAA 1 000 and MAA 4 000, the binaural PTA difference was the significant factors for the RMSE. The R 2 of multivariable linear regression model for MAA 1 000, MAA 4 000 and RMSE results in unilateral sudden deafness patients were 0.149, 0.207 and 0.553, respectively. Conclusion:Age, the hearing of the affected side, and binaural PTA difference are the significant factors for sound localization ability in patients with unilateral sudden sensorineural hearing loss, hearing compensation of the affected ear for these patients is hopeful to enhance the sound localization ability.

Objective:To explore effects of tofacitinib combined with traditional disease modifying antirheumatic drugs(DMARDs)on peripheral blood IL-22,IL-23 and Th22 cell subsets in patients with rheumatoid arthritis(RA).Methods:Retrospec-tive analysis of clinical data of 100 RA patients admitted to Xingtai People's Hospital from December 2022 to December 2024.Patients were divided into conventional group(n=33,treated with traditional DMARDs),single group(n=34,treated with tofacitinib)and combination group(n=33,treated with tofacitinib combined with traditional DMARDs)by random number table method.Serum IL-22 and IL-23 levels,Th22 cell subsets proportion,recovery of joint function,disease improvement and adverse reactions were compared in three group.Results:After 3 months of treatment,IL-22,IL-23 and Th22 cell subsets proportion in three groups were decreased compared to before treatment,and combination group was significantly lower than conventional group and single group(P<0.05);levels of anti-CCP and RF in three groups were decreased compared to before treatment,and combined group was significantly lower than conventional group and single group(P<0.05);joint swelling frequency,number of tender joints,morning stiffness time and VAS scores in three groups were decreased compared to before treatment,and combination group was significantly lower than conven-tional group and single group(P<0.05);DAS28 scores and HAQ scores of three groups were decreased compared to before treatment,and combined group was significantly lower than conventional group and single group(P<0.05);there was no statistically significant difference in incidence of adverse reactions among three groups during treatment period(Z=0.290,P=0.865).Conclusion:Clinical effect of tofacitinib combined with traditional DMARDs in treatment of RA is significant,which can effectively reduce serum IL-22,IL-23 and autoantibodies levels,regulate Th22 cell subsets proportion,alleviate inflammatory reactions,and improve joint function.

Objective:To clarify the definition and attributes of change fatigue among nurses.Methods:A comprehensive literature search was conducted across both Chinese and international databases, including CINAHL, Cochrane Library, Web of Science, PubMed, ProQuest, ScienceDirect, Springer Link, Wanfang Data, China National Knowledge Infrastructure, VIP, and China Biology Medicine disc, from inception to December 2024. Walker and Avant's classic concept analysis method was adopted.Results:A total of 30 relevant studies were included. The defining attributes of nurse change fatigue include perception of change, negative psychological responses, and passive reactions. Antecedents involve personal and organizational factors, and the consequences affect nurses themselves, patients, and the organization.Conclusions:Concept analysis helps clarify the connotation of nurse change fatigue, enabling managers to identify its features and providing a foundation for future targeted interventions to mitigate fatigue and promote nurses' positive responses to organizational change.

Objective:To investigate the association between serum thyroid-stimulating hormone(TSH) level and the 10-year risk of atherosclerotic cardiovascular disease(ASCVD) in men over 50 years old with type 2 diabetes mellitus(T2DM).Methods:This study included male T2DM patients aged≥50 years, diagnosed at the First Hospital of Lanzhou University between July 2021 and March 2022. Patients were categorized into three groups based on serum TSH level: elevated TSH group(T3, TSH>5.91 mIU/L) and normal TSH group, which was further divided into T1(0.56 mIU/L≤TSH<3.24 mIU/L) and T2(3.24 mIU/L≤TSH≤5.91 mIU/L) group. The 10-year ASCVD risk index was compared across groups. Spearman correlation and multiple linear regression analyses were used to assess the independent association between TSH level and 10-year ASCVD risk index. Results:A total of 490 male T2DM patients aged≥50 years were included(T1: 310, T2: 131, T3: 49). The 10-year ASCVD risk index was significantly higher in T3 group than that in T1 group(18.40% vs 13.90%, χ2=9.47, P<0.05). Serum TSH level showed a positive correlation with the 10-year ASCVD risk( r=0.144, P<0.05). After adjusting for confounders such as age, hypertension, lipid profile, diabetes duration, aspartate aminotransferase, albumin, lactate dehydrogenase, estimated glomerular filtration rate, creatinine, and phosphorus, multiple linear regression confirmed that TSH level was independently associated with the 10-year ASCVD risk index( β=0.23, 95% CI 0.02-0.45). Conclusions:Higher serum TSH level is independently associated with an increased 10-year ASCVD risk in men over 50 years old with T2DM. Regular TSH monitoring may aid in cardiovascular risk stratification in this population.

Objective:To explore effects of tofacitinib combined with traditional disease modifying antirheumatic drugs(DMARDs)on peripheral blood IL-22,IL-23 and Th22 cell subsets in patients with rheumatoid arthritis(RA).Methods:Retrospec-tive analysis of clinical data of 100 RA patients admitted to Xingtai People's Hospital from December 2022 to December 2024.Patients were divided into conventional group(n=33,treated with traditional DMARDs),single group(n=34,treated with tofacitinib)and combination group(n=33,treated with tofacitinib combined with traditional DMARDs)by random number table method.Serum IL-22 and IL-23 levels,Th22 cell subsets proportion,recovery of joint function,disease improvement and adverse reactions were compared in three group.Results:After 3 months of treatment,IL-22,IL-23 and Th22 cell subsets proportion in three groups were decreased compared to before treatment,and combination group was significantly lower than conventional group and single group(P<0.05);levels of anti-CCP and RF in three groups were decreased compared to before treatment,and combined group was significantly lower than conventional group and single group(P<0.05);joint swelling frequency,number of tender joints,morning stiffness time and VAS scores in three groups were decreased compared to before treatment,and combination group was significantly lower than conven-tional group and single group(P<0.05);DAS28 scores and HAQ scores of three groups were decreased compared to before treatment,and combined group was significantly lower than conventional group and single group(P<0.05);there was no statistically significant difference in incidence of adverse reactions among three groups during treatment period(Z=0.290,P=0.865).Conclusion:Clinical effect of tofacitinib combined with traditional DMARDs in treatment of RA is significant,which can effectively reduce serum IL-22,IL-23 and autoantibodies levels,regulate Th22 cell subsets proportion,alleviate inflammatory reactions,and improve joint function.