BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

To improve the consistency of outcome documentation and address the potential for outcome reporting bias in clinical trials involving integrative Chinese and Western medicine (ICWM) for ulcerative colitis (UC), we aim to develop a customized core outcome set (COS) that incorporates input from various stakeholders. The study design of this COS has been informed by the Core Outcome Measures in Effectiveness Trials Initiative Handbook, with adherence to the guidelines from the Core Outcome Set-STAndards for Reporting statement and Core Outcome Set-STAndardised Protocol Items recommendations. Five groups of stakeholders will be invited to participate in the development of COS for clinical trials with ICWM for UC, including healthcare professionals, patients, COS developers, COS users, and methodologists. The process will involve five stages: (1) conducting a systematic review of outcomes reported in clinical trials and protocols to develop a list of potential outcome domains; (2) conducting semi-structured interviews to obtain important outcomes; (3) choosing the most important outcomes by conducting three-round Delphi surveys; (4) achieving a consensus in a face-to-face meeting to discuss the final COS; and (5) publication, dissemination and implementation of COS. Consequently, this specialized COS will be applicable to clinical trials involving both traditional Chinese medicine (TCM) and ICWM interventions. Please cite this article as: Zhang X, Zhang L, Wang J, Lau CT, Wang N, Zhang X, Wang P, Li J, Han F, Bian Z. A protocol for developing, disseminating and implementing a core outcome set for clinical trials of integrative Chinese and Western medicine for ulcerative colitis. J Integr Med. 2025; 23(6):654-659.
Colitis, Ulcerative/therapy* ; Humans ; Medicine, Chinese Traditional ; Clinical Trials as Topic ; Integrative Medicine ; Research Design ; Outcome Assessment, Health Care ; Delphi Technique

ObjectiveTo explore the effects of Guiqi Yiyuan ointment combined with cisplatin on mice with Lewis lung cancer through the endoplasmic reticulum stress pathway and mitochondrial apoptosis pathway. MethodFifty SPF male C57BL/6 mice were randomly divided into the model group， cisplatin group （0.005 g·kg^-1）， and low， medium， and high dose groups of Guiqi Yiyuan ointment combined with cisplatin （0.005+1.6 g·kg^-1， 0.005+3.3 g·kg^-1， and 0.005+6.6 g·kg^-1）. Lewis cell suspension was inoculated under the axilla of mice in each group to construct the Lewis lung cancer xenograft mouse model. After continuous administration for 14 days， the mice were sacrificed. The body weight of the mice was measured， and the tumor weight was measured after the tumors were removed. The organ index and tumor inhibition rate were calculated. Hematoxylin-eosin （ HE） staining was used to observe the pathological changes in tumor tissue. Flow cytometry was used to detect the apoptosis rate of tumor cells and the ratio of reactive oxygen species （ROS）. Western blot was used to detect the expression of glucose-regulated protein 78 （GRP78）， phosphorylated activated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， activated transcription factor 4 （ATF4）， and apoptosis protein C/EBP homologous protein （CHOP） in the endoplasmic reticulum stress pathway， as well as cysteine aspartate protease-9 （Caspase-9）， B-cell lymphoma-2（Bcl-2）， and Bcl-2 associated X protein（Bax） in the mitochondrial apoptosis pathway. ResultCompared with those in the model group， the mice in the groups of Guiqi Yiyuan Ointment combined with cisplatin had shinier fur and better mental response status. Tumor mass was reduced in all treatment groups （P<0.05）， and tumor inhibition rate was increased in all treatment groups （P<0.05）. The thymus and spleen indices of the combined group were increased （P<0.05）， and obvious pathological changes were observed in the tumor tissue of all treatment groups， with a gradual decrease in heteromorphism. Destruction of massive tumor tissue was observed in the high-dose combined group， and the apoptosis rate and ROS generation rate of tumor cells were increased in all treatment groups （P<0.05）. The protein expression level of Bcl-2 in the tumor tissue gradually decreased （P<0.05）， while the protein expression levels of GRP78， p-PERK， ATF4， CHOP， Bax， and Caspase-9 were significantly increased （P<0.05）. Compared with the cisplatin group， tumor mass was reduced in the combined group （P<0.05）， and tumor inhibition rates in the low and high-dose combined groups were increased （P<0.05）. The thymus index， spleen index， apoptosis rate of tumor cells， and ROS ratio in the combined group were significantly increased （P<0.05）， while the protein expression levels of GRP78， p-PERK， Bax， and Caspase-9 were increased in the low and high-dose combined groups （P<0.05）. The protein expression levels of ATF4 and CHOP were increased in the combined group （P<0.05）， while the expression level of Bcl-2 protein gradually decreased （P<0.05）. ConclusionGuiqi Yiyuan ointment combined with cisplatin can exert anti-tumor effects in mice with Lewis lung cancer， reduce tumor mass， increase tumor inhibition rate， and induce apoptosis of lung cancer cells. Its mechanism may be related to the regulation of the endoplasmic reticulum stress pathway and mitochondrial apoptosis pathway.

Objective To screen and analyze the influencing factors of severity in the patients with type 2 diabetes mellitus (T2DM) complicating cerebral small vessel disease (CSVD).Methods A total of 519 pa-tients with T2DM complicating CSVD admitted and treated in Nanjing Municipal Hospital of Traditional Chi-nese Medicine from June 2018 to May 2023 were selected and divided into the mild group (n=214) and the se-vere group (n=305) according to the CSVD imageological score.The relevant demographic,laboratory and imageological indicators were collected.The influencing factors of T2DM complicating CSVD were screened out by the LASSO and Logistic regression analysis and the predictive model was established.The receiver op-erating characteristic (ROC) curve,goodness of fit evaluation and restricted cubic spline (RCS) fitting curve were drawn to analyze the dose-response relationship between Cys C,albumin/globulin (A/G) ratio with the disease severity.Results The male proportion and age in the severe group were greater than those in the mild group,neutrophil,systemic immune-inflammation index (SII),creatinine (Crea),uric acid (UA),Urea (Ure-a),D-dimer (D-D),lactate dehydrogenase (LDH),adenosine deaminase (ADA),globulin (GLB) and Cys C were higher than those in the mild group,lymphocyte,ALT,High density Lipoprotein-cholesterol (HDL-C),serum cholinesterase (CHE),prealbumin (PAB),and A/G were lower than those in the mild group,and the differences were statistically significant (P<0.05).LASSO and logistic regression analysis showed that the gender,age,A/G and Cys C were the independent influencing factors in the patients with T2DM complicating CSVD.The area under the curve (AUC) of this model was 0.658 (95%CI:0.610-0.706) with goodness of fit (P=0.520).The RCS fitting curves showed that serum Cys C≥0.618 mg/L had a linear relationship with CSVD imageological score (P=0.035),and A/G≥1.268 had a nonlinear relationship with CSVD imageologi-cal score (P=0.007).Conclusion The advanced age,male,increased Cys C level and decreased A/G in the pa-tients with T2DM complicating CSVD are the independent risk factors for the severity of whole brain damage.

Objective To screen the characteristic factors of renal impairment occurrence in the patients with hyperuricemia,and to analyze its diagnostic value and establish a diagnostic model.Methods A total of 2405 inpatients with diagnosed hyperuricemia in the Nanjing Municipal Hospital of Traditional Chinese Medi-cine,Nanjing University of Traditional Chinese Medicine from December 2018 to December 2022 were selected and divided into the kidney lesion group (n=1343) and the non-kidney lesion group (n=1062) according to eGFR.The characteristic factors of hyperuricemia caused renal impairment were screened and analyzed by Lasso and logistic regression and the diagnostic model was constructed.The diagnostic value of characteristic factors and diagnostic model were evaluated by the receiver operating characteristic (ROC) curve,and the change rule between the characteristic factors and the results was found by the restricted cubic splines (RCS) fitting.Results The age,uric acid (UA),cystatin-C (Cys-C) and retinol-binding protein (RBP) were the characteristic factors of hyperuricemia caused renal impairment.The combined diagnostic model:logit (P)=-8.70+0.602×age (10 years old)+0.033×UA (10 μmol/L)+0.277×Cys-C (0.1 mg/L)+0.189×RBP (10 mg/L),the area under the ROC curve (AUC) of the combined diagnosis model was 0.893 (95％CI:0.880-0.905).For every 10 μmol/L increase in blood UA,the risk of renal impairment occurrence in hyperurice-mia was increased by 3％;for every 10 years increase in age,the risk of renal impairment occurrence in hyperu-ricemia was increased by 83％;for every 10 mg/L increase in RBP,the risk of kidney damage occurrence of re-nal impairment in hyperuricemia was increased by 21％;for every 0.1 mg/L increase in Cys-C,the risk of re-nal impairment occurrence in hyperuricemia was increased by 32％.Conclusion The combined diagnostic model for whether the renal impairment in the patients with hyperuricemia occurring has good diagnostic val-ue,and Cys-C deserves more attention.

Aim To investigate the effects of total flavonoids from Rosa rugosa (TFR) on cerebral ischemia reperfusion injury (CIRI) in rats, and to investigate whether TFR inhibited neuronal apoptosis by regulating phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and endoplasmic reticulum stress (ERS) pathways. Methods SD rats were randomly divided into sham operation group, model group, low-dose group (50 mg · kg

Gut microbial metabolite trimethylamine-N-oxide (TMAO) is associated with type 2 diabetes (T2DM). Decreased insulin sensitivity is a significant etiological factor of T2DM. Adipocytes, myocytes, and hepatocytes are the three major target cells for insulin. This study aims to investigate the effects and mechanisms of TMAO on the insulin sensitivity of these target cells. Research results indicate that in different ages of db/db diabetic mice, plasma TMAO levels were increased. TMAO significantly inhibits the insulin signaling pathways in these three major insulin target cells, reduces glucose uptake in 3T3-L1 adipocytes and L6 myocytes and downregulates genes related to gluconeogenesis in primary mouse hepatocytes. Furthermore, in mice with normal insulin sensitivity, elevating plasma TMAO levels to those seen in db/db mice using a minipump results in impaired glucose tolerance and hyperinsulinemia. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). Mechanistic studies suggest that TMAO exposure increases the levels of endoplasmic reticulum stress-related proteins in these three major insulin target cells. In summary, TMAO directly attenuates insulin sensitivity in insulin target cells, and its mechanism of action may involve enhancing endoplasmic reticulum stress.

ObjectiveTo explore the relationship between the kidney deficiency and governor vessel cold syndrome and the kidney deficiency damp-heat syndrome in ankylosing spondylitis （AS） patients and the five evolutive phases and six climatic factors of their birth and onset year based on the theory of five movements and six climates （FMSC）. MethodsTotally 1791 patients with AS who were admitted to China-Japan Friendship Hospital from September 2010 to September 2020 and met the diagnostic and inclusion criteria were selected in this study. The clinical data were classified into two types of syndromes， kidney deficiency and governor vessel cold syndrome and the kidney deficiency damp-heat syndrome based on the diagnostic criteria of traditional Chinese medicine syndromes. The date of birth and the year of disease onset were converted into FMSC symbols according to the perpetual almanac （《万年历》）， and the two could be converted into the terrestrial branch， year evolutive phase， host evolutive phase， guest evolutive phase， host climatic qi， guest climatic qi， celestial manager qi， guest climatic qi adding to fixed host qi， combined analysis of five evolutive phases and six climatic factors， solar terms， and season of the date of birth， as well as the terrestrial branch， year evolutive phase， and celestial manager qi of the year of disease onset. Univariate analyses were performed using the two independent samples t-test or the Mann Whitney U-test， the Pearson （Pearson） χ² test， or one-way logistic regression analyses， and variables for which statistical significance existed in the one-way analyses were included in the multivariate logistic regression analyses. General conditions， clinical manifestations， physical signs， laboratory indicators ［including C reactive protein （CRP）， erythrocyte sedimentation rate （ESR）， and humans leukocyte antigen B27 （HLA-B27）］， measurement （including occipital wall distance， jaw peduncle distance， finger-to-ground distance， thoracic range of motion， and Schober experiment）， and distribution of FMSC of birth and disease onset between AS patients with kidney deficiency and governor vessel cold syndrome and with the kidney deficiency damp-heat syndrome were compared， and the association between FMSC and AS patients with kidney deficiency and governor vessel cold syndrome and the kidney deficiency damp-heat syndrome was studied. ResultsThe differences in ESR， CRP， chest mobility， occurrence of achilles tendon enthesitis， and peripheral arthritis between the two groups of patients were statistically significant （P＜0.05）. Single factor analysis found that taking kidney deficiency and governor vessel cold syndrome as control the following FMSC factors increases the risk of developing kidney deficiency damp-heat syndrome： excess of water in year evolutive phase at birth， excess of wood in host evolutive phase at birth， excess of wood in guest evolutive phase at birth， excess of wood in year evolutive phase of onset， deficiency of metal in year evolutive phase at birth （OR = 2.000， P = 0.004）， excess of metal in host evolutive phase at birth （OR = 1.745， P = 0.024） or excess of wood （OR = 1.781， P = 0.023）， deficiency of fire in guest evolutive phase at birth （OR = 1.689， P = 0.049） or deficiency of wood （OR = 1.901， P = 0.018） or excess of metal （OR = 2.163， P = 0.004）， excess of water in year evolutive phase at the disease onset （OR = 1.880 ， P = 0.013） or deficiency of wood （OR = 1.707， P = 0.022）. Multivariate logistic regression analysis found that the risk of developing kidney deficiency damp-heat syndrome in AS was increased by deficiency of metal in year evolutive phase at birth， excess of metal in host evolutive phase at birth， higher level of ESR， greater the chest mobility， incidence of concomitant Achilles tendon enthesitis and peripheral arthritis. ConclusionThe year evolutive phase and host evolutive phase at birth play a significant role in the development of kidney deficiency and governor vessel cold syndrome AS. Risk of developing kidney deficiency damp-heat syndrome can be increased by excess of water or deficiency of metal in year evolutive phase at birth， and excess of wood or excess of metal in host evolutive phase at birth and the kidney deficiency damp-heat syndrome in ankylosing spondylitis.

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg^-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg^-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.