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

Objective:To analyze the potential risk factors for early relapse/progression in patients with multiple myeloma(MM)and develop a risk prediction model based on these factors.Methods:A retrospective analysis was conducted on 187 newly diagnosed multiple myeloma(NDMM)patients who treated at the Affiliated Hospital of North Sichuan Medical College from February 2014 to December 2020.The clinical,laboratory examination,and follow-up data of patients experiencing relapse/progression within 24 months after treatment(ER/EP24)were analyzed using univariate and multivariate analyses,and a nomogram prediction model was established.Results:Among the 187 patients,58(31.0％)experienced ER/EP24,with a median survival time of only 24 months.The results of multivariate logistic regression analysis showed that failure to achieve partial response(PR)or better after 3-4 cycles of chemotherapy and albumin(ALB)levels＜35 g/L were independent risk factors for ER/EP24(P＜0.05).These factors,along with other clinically relevant variables,were further incorporated into the nomogram prediction model.The model demonstrated a concordance index(C-index)of 0.784,indicating strong predictive accuracy.Conclusion:MM patients experiencing ER/EP24 exhibit poor outcome,and the nomogram model developed in this study effectively predicts the risk of ER/EP24 in NDMM patients,providing a valuable tool for clinical risk assessment.

ObjectiveTo evaluate the efficacy and safety of acupoint application for post-stroke depression (PSD) by regulating gastrointestinal function. A secondary objective is to explore the potential mechanism underlying this approach from the perspective of gut microbiota.MethodsThis multicenter, randomized, double-blind (patients and assessors), placebo-controlled trial will enroll 80 patients with PSD, and include a 1-week run-in period, a 4-week treatment phase, and a 12-week follow-up. Eligible participants will randomly be assigned in a 1:1 ratio to either the acupoint application or placebo (non-acupoint) groups. Treatments will be administered thrice weekly for 4 weeks. The primary outcome is change in the Hamilton Rating Scale for Depression (HAMD) score. Secondary outcomes include the Beck Depression Inventory (BDI), 36-Item Short-Form Health Survey (SF-36), Barthel Index of Activities of Daily Living, Social Adaptation Self–Evaluation Scale (SASS), and gut microbiota profiling. All outcomes will be assessed at baseline (prior to treatment), during treatment (weeks 2 and 4), and during follow-up (weeks 8, 12, and 16). The Treatment Emergent Symptom Scale (TESS) will be used for evaluation throughout the 4-week treatment phase.DiscussionThe results of this study will provide important evidence supporting a novel treatment strategy for PSD that targets gastrointestinal regulation, potentially informing future clinical practice.

Aim To explore the action mechanism of isoquercitrin(IQ)in ameliorating anxiety based on network pharmacology,cellular transcriptomics,molecu-lar docking and animal experiments.Methods The common targets of anxiety disorders and IQ were ob-tained by using relevant databases.The protein-protein interaction network,the biological function and signa-ling pathway enrichment analysis were conducted by u-sing the common targets.Primary hippocampal neurons were cultured in vitro,and corticosterone was added to induce neurons to establish a corticosterone injury mod-el.IQ treatment was added to the culture system,and transcriptomics was used to screen for differentially ex-pressed genes and enrich for differentially expressed pathways.Subsequently,the results were validated by quantitative real-time polymerase chain reaction(qRT-PCR).Possible targets and signaling pathways for IQ treatment on anxiety were speculated and screened u-sing network pharmacology,transcriptomics and molec-ular docking.The anxiety rat model was constructed,and the anxiety state of rats was evaluated after IQ in-tervention,and the protein expression level of hippo-campus was detected to verify the relevant mechanism.Results Network pharmacology,cellular transcrip-tome,and molecular docking analyses revealed that the key mechanism of IQ for anxiety may be related to the BDKRB2/PI3K/Akt signaling pathway.Animal exper-iments showed that IQ was effective in improving anxie-ty behaviour and learning memory ability in rats.IQ increased the movement distance and residence time in the central area of the open field,the time and number percentage of entries into the open arm in the elevated plus maze,and the spontaneous alternations score in the Y maze in rats,and significantly elevated protein expression of BDKRB2,PI3K,Akt and decreased pro-tein expression of NF-κB in the hippocampus.Conclu-sions Isoquercitrin can effectively treat anxiety,and the mechanism of action may be related to the regula-tion of BDKRB2/PI3K/Akt signaling pathway in hip-pocampus.

Objective:To explore the correlation between the total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio during pregnancy and the onset of gestational metabolic syndrome (GMS), as well as its association with pregnancy outcomes.Methods:Clinical data of 153 pregnant women diagnosed with GMS in the third trimester admitted to Women′s Hospital of Nanjing Medical University from January 2020 to December 2022 (observation group) were collected, and data of 153 healthy pregnant women (control group) were randomly selected for a comparative study. Indicators of the two groups were observed and compared. Multiple linear regression and restricted cubic spline analysis were used to analyze the correlation between TC/HDL-C in the first and second trimesters and metabolic indicators in the third trimester and GMS risk, respectively. According to the pregnancy outcomes of GMS pregnant women with different TC/HDL-C ratios, the association between TC/HDL-C ratio and preterm birth subtypes was analyzed.Results:There were statistically significant differences between the two groups in age, gestational week, pre-pregnancy body mass index (BMI), weight gain during pregnancy, abdominal circumference in the third trimester, whether to deliver vaginally, history of preterm birth, history of cesarean section, history of abortion, neonatal birth weight, and neonatal length (all P<0.05). There were statistically significant differences in blood pressure and BMI between the two groups in the second and third trimesters (all P<0.01). In the first trimester (gestational week <14 weeks), there were statistically significant differences in fasting plasma glucose (FPG), HDL-C, and TC/HDL-C ratio between the two groups (all P<0.05). In the second trimester (gestational weeks 14-27) and third trimester (gestational week ≥28 weeks), the levels of FPG, fasting insulin (FINS), triglyceride (TG), TC, low-density lipoprotein cholesterol (LDL-C), and TC/HDL-C ratio in the observation group were higher than those in the control group, while HDL-C was lower (all P<0.05). There were statistically significant differences between the two groups in postpartum abnormal blood pressure, abnormal BMI, abnormal glucose metabolism, and abnormal lipid metabolism (all P<0.05). After adjusting for age, gestational week, and BMI, first-trimester TC/HDL-C ratio was correlated with third-trimester FPG, systolic blood pressure, diastolic blood pressure, TG, TC, and HDL-C (all P<0.05); second-trimester TC/HDL-C ratio was correlated with third-trimester FPG, FINS, systolic blood pressure, diastolic blood pressure, TG, TC, HDL-C, and LDL-C (all P<0.05), and both were linearly related to third-trimester GMS risk ( Pfor trend<0.01). The TC/HDL-C ratio was positively correlated with the preterm birth rate ( RR>1). Conclusions:An increased TC/HDL-C ratio is closely related to the occurrence of GMS, which is prone to cause preterm birth and affect fetal growth and development.

Objective To investigate the effects of extracellular vesicles(EVs)derived from synovial fluid of rheumatoid arthritis(RA)patients on angiogenesis of human umbilical vein endothelial cells,and to preliminarily explore the underlying mechanisms.Methods Synovial fluid samples of knee joint were collected from 20 patients with RA and 20 patients with osteoarthritis(OA)in this study.EVs were purified using ultracentrifugation.The morphology and size of EVs were observed by transmission electron microscopy and nanoparticle tracking analysis.CD9,CD63,cytochrome c(Cyt-c),vascular endothelial growth factor(VEGF),lysyl oxidase(LOX),matrix metalloproteinase 2(MMP2),tumour necrosis factor alpha(TNF-α),transforming growth factor beta1(TGF-β1)in EVs were detected using Western blot.Human umbilical vein endothelial cells(HUVEC)were treated with the EVs.The growth,migration and angiogenesis of HUVEC were observed by CCK8 assay,TranswellTM chamber assay,scratch test and matrigel angiogenesis assay,respectively.The effect of EVs on the PI3K/AKT pathway in HUVEC was assessed using Western blot.Results Both EVs from RA synovial fluid(RA-EVs)and OA synovial fluid(OA-EVs)were cup-shaped,mainly between 30-400 nm in diameter,expressing CD63 and CD9,but not Cyt-c.RA-EVs carried more VEGF,LOX,MMP2,TNF-α and TGF-β1 than OA-EVs.Compared with the OA-EVs intervention,RA-EVs significantly promoted the proliferation,migration,and angiogenesis of HUVECs,as well as upregulated PI3K/AKT phosphorylation.The inhibitor of PI3K suppressed angiogenesis induced by EVs.Conclusion EVs in synovial fluid of RA carried more cytokines and enzymes that related angiogenesis and inflammation.These EVs exert their pro-angiogenic effects by activating the PI3K/AKT pathway,then contributing to the pathological progression of RA.

Objective To investigate the effects of extracellular vesicles(EVs)derived from synovial fluid of rheumatoid arthritis(RA)patients on angiogenesis of human umbilical vein endothelial cells,and to preliminarily explore the underlying mechanisms.Methods Synovial fluid samples of knee joint were collected from 20 patients with RA and 20 patients with osteoarthritis(OA)in this study.EVs were purified using ultracentrifugation.The morphology and size of EVs were observed by transmission electron microscopy and nanoparticle tracking analysis.CD9,CD63,cytochrome c(Cyt-c),vascular endothelial growth factor(VEGF),lysyl oxidase(LOX),matrix metalloproteinase 2(MMP2),tumour necrosis factor alpha(TNF-α),transforming growth factor beta1(TGF-β1)in EVs were detected using Western blot.Human umbilical vein endothelial cells(HUVEC)were treated with the EVs.The growth,migration and angiogenesis of HUVEC were observed by CCK8 assay,TranswellTM chamber assay,scratch test and matrigel angiogenesis assay,respectively.The effect of EVs on the PI3K/AKT pathway in HUVEC was assessed using Western blot.Results Both EVs from RA synovial fluid(RA-EVs)and OA synovial fluid(OA-EVs)were cup-shaped,mainly between 30-400 nm in diameter,expressing CD63 and CD9,but not Cyt-c.RA-EVs carried more VEGF,LOX,MMP2,TNF-α and TGF-β1 than OA-EVs.Compared with the OA-EVs intervention,RA-EVs significantly promoted the proliferation,migration,and angiogenesis of HUVECs,as well as upregulated PI3K/AKT phosphorylation.The inhibitor of PI3K suppressed angiogenesis induced by EVs.Conclusion EVs in synovial fluid of RA carried more cytokines and enzymes that related angiogenesis and inflammation.These EVs exert their pro-angiogenic effects by activating the PI3K/AKT pathway,then contributing to the pathological progression of RA.

Objective:To analyze the potential risk factors for early relapse/progression in patients with multiple myeloma(MM)and develop a risk prediction model based on these factors.Methods:A retrospective analysis was conducted on 187 newly diagnosed multiple myeloma(NDMM)patients who treated at the Affiliated Hospital of North Sichuan Medical College from February 2014 to December 2020.The clinical,laboratory examination,and follow-up data of patients experiencing relapse/progression within 24 months after treatment(ER/EP24)were analyzed using univariate and multivariate analyses,and a nomogram prediction model was established.Results:Among the 187 patients,58(31.0％)experienced ER/EP24,with a median survival time of only 24 months.The results of multivariate logistic regression analysis showed that failure to achieve partial response(PR)or better after 3-4 cycles of chemotherapy and albumin(ALB)levels＜35 g/L were independent risk factors for ER/EP24(P＜0.05).These factors,along with other clinically relevant variables,were further incorporated into the nomogram prediction model.The model demonstrated a concordance index(C-index)of 0.784,indicating strong predictive accuracy.Conclusion:MM patients experiencing ER/EP24 exhibit poor outcome,and the nomogram model developed in this study effectively predicts the risk of ER/EP24 in NDMM patients,providing a valuable tool for clinical risk assessment.

Aim To explore the action mechanism of isoquercitrin(IQ)in ameliorating anxiety based on network pharmacology,cellular transcriptomics,molecu-lar docking and animal experiments.Methods The common targets of anxiety disorders and IQ were ob-tained by using relevant databases.The protein-protein interaction network,the biological function and signa-ling pathway enrichment analysis were conducted by u-sing the common targets.Primary hippocampal neurons were cultured in vitro,and corticosterone was added to induce neurons to establish a corticosterone injury mod-el.IQ treatment was added to the culture system,and transcriptomics was used to screen for differentially ex-pressed genes and enrich for differentially expressed pathways.Subsequently,the results were validated by quantitative real-time polymerase chain reaction(qRT-PCR).Possible targets and signaling pathways for IQ treatment on anxiety were speculated and screened u-sing network pharmacology,transcriptomics and molec-ular docking.The anxiety rat model was constructed,and the anxiety state of rats was evaluated after IQ in-tervention,and the protein expression level of hippo-campus was detected to verify the relevant mechanism.Results Network pharmacology,cellular transcrip-tome,and molecular docking analyses revealed that the key mechanism of IQ for anxiety may be related to the BDKRB2/PI3K/Akt signaling pathway.Animal exper-iments showed that IQ was effective in improving anxie-ty behaviour and learning memory ability in rats.IQ increased the movement distance and residence time in the central area of the open field,the time and number percentage of entries into the open arm in the elevated plus maze,and the spontaneous alternations score in the Y maze in rats,and significantly elevated protein expression of BDKRB2,PI3K,Akt and decreased pro-tein expression of NF-κB in the hippocampus.Conclu-sions Isoquercitrin can effectively treat anxiety,and the mechanism of action may be related to the regula-tion of BDKRB2/PI3K/Akt signaling pathway in hip-pocampus.

Objective:To explore the correlation between the total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio during pregnancy and the onset of gestational metabolic syndrome (GMS), as well as its association with pregnancy outcomes.Methods:Clinical data of 153 pregnant women diagnosed with GMS in the third trimester admitted to Women′s Hospital of Nanjing Medical University from January 2020 to December 2022 (observation group) were collected, and data of 153 healthy pregnant women (control group) were randomly selected for a comparative study. Indicators of the two groups were observed and compared. Multiple linear regression and restricted cubic spline analysis were used to analyze the correlation between TC/HDL-C in the first and second trimesters and metabolic indicators in the third trimester and GMS risk, respectively. According to the pregnancy outcomes of GMS pregnant women with different TC/HDL-C ratios, the association between TC/HDL-C ratio and preterm birth subtypes was analyzed.Results:There were statistically significant differences between the two groups in age, gestational week, pre-pregnancy body mass index (BMI), weight gain during pregnancy, abdominal circumference in the third trimester, whether to deliver vaginally, history of preterm birth, history of cesarean section, history of abortion, neonatal birth weight, and neonatal length (all P<0.05). There were statistically significant differences in blood pressure and BMI between the two groups in the second and third trimesters (all P<0.01). In the first trimester (gestational week <14 weeks), there were statistically significant differences in fasting plasma glucose (FPG), HDL-C, and TC/HDL-C ratio between the two groups (all P<0.05). In the second trimester (gestational weeks 14-27) and third trimester (gestational week ≥28 weeks), the levels of FPG, fasting insulin (FINS), triglyceride (TG), TC, low-density lipoprotein cholesterol (LDL-C), and TC/HDL-C ratio in the observation group were higher than those in the control group, while HDL-C was lower (all P<0.05). There were statistically significant differences between the two groups in postpartum abnormal blood pressure, abnormal BMI, abnormal glucose metabolism, and abnormal lipid metabolism (all P<0.05). After adjusting for age, gestational week, and BMI, first-trimester TC/HDL-C ratio was correlated with third-trimester FPG, systolic blood pressure, diastolic blood pressure, TG, TC, and HDL-C (all P<0.05); second-trimester TC/HDL-C ratio was correlated with third-trimester FPG, FINS, systolic blood pressure, diastolic blood pressure, TG, TC, HDL-C, and LDL-C (all P<0.05), and both were linearly related to third-trimester GMS risk ( Pfor trend<0.01). The TC/HDL-C ratio was positively correlated with the preterm birth rate ( RR>1). Conclusions:An increased TC/HDL-C ratio is closely related to the occurrence of GMS, which is prone to cause preterm birth and affect fetal growth and development.