Objective To detect the expression changes of citrullinated histone H3(CitH3)during the development of deep vein thrombosis(DVT)in mice,and to explore its value in estimating the time to thrombosis.Methods The inferior vena cava(IVC)of mice was ligated to establish a thrombosis model induced by congestion.Mice were sacrificed under excessive anesthesia at 0 h,1 d,3 d,5 d,7 d,10 d,14 d and 21 d after the modeling,respectively.The congested IVC segments(0 h after modeling)and the thrombosed IVC segments(1-21 days after modeling)were extracted.Immunohistochemistry and double immunofluorescence staining were used to observe the number of neutrophils and the ex-pression of CitH3 during thrombosis.Western blotting was used to detect the protein expression level of CitH3.Results During thrombosis,CitH3 was mainly expressed in neutrophils within the thrombus.A small number of neutrophils and a few CitH3-positive cells were observed at 0 h after modeling in the congested IVC.Between 1 d and 21 d after modeling,the number of neutrophils reached a peak at 1 d and gradually decreased.The number of CitH3-positive cells and their ratio to neutrophils began to increase at 1 d,reached a peak at 5 d after modeling,and then decreased.The expression level of CitH3 protein began to increase at 1 d and reached a peak at 5 d after modeling.Conclusion The expres-sion of CitH3 during DVI shows temporal changes,and is expected to become a biological marker for estimating the formation time of thrombosis.

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

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

Objective: To predict and screen potential biomarkers of systemic lupus eythematosus(SLE) based on machine learning algorithms and structural biology, and to reveal their mechanisms of action and to provide new targets for disease diagnosis and treatment. Methods: Four machine learning algorithms, random forest(RF), eXtreme gradient boosting(XGBoost), support vector machine(SVM), least absolute shrinkage and selection operator(LASSO), were used to analyze the gene expression data of SLE patients in GEO(datasets: GSE121239 and GSE11907) to analyze the gene expression data of SLE patients and screen key markers. Peripheral blood single nucleated cells(PBMCs) from SLE patients were collected and RT-qPCR was used to detect differential gene expression levels. Subsequently, GSEA enrichment analysis was used to identify biomarker-related pathways. CIBERSORT immune infiltration analysis and protein interactions network were applied to calculate the sample immune cell infiltration abundance. Single-cell data were analyzed for gene expression specificity in immune cells. Interaction relationships in combination with AlphaFold3(AF3) were predicted. Results: Multiple algorithms were screened together to identify the unique marker gene HERC5 , and expression analysis of multiple datasets showed that HERC5 was highly expressed in SLE compared to the normal group (P < 0. 05) , and RT⁃qPCR verified the same trend (P = 0. 006 2) . Functional enrichment analysis identified the major pathway promoted by HERC5 in SLE as the interferon receptor signalling pathway (P < 0. 05) . Immune infiltration analysis showed that HERC5 was closely associated with immune cells (Neutrophils : r = 0. 39 , P < 0. 05 ; Memory B cells : r = 0. 33 , P < 0. 05 ; Activated dendritic cell : r = 0. 52 , P < 0. 05) . Most HERC5 ⁃related interacting proteins were associated with SLE ,and potential transcription factors of HERC5 and its related genes were also significantly associated with immune responses. Conclusion The HERC5 gene is an important biomarker for SLE , which upregulates the interferon pathway to promote SLE progression and provides a new target for SLE diagnosis and treatment.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective:To evaluate the clinical efficacy of Tianma Xionglin Zhixuan Tablets in treating hypertension patients with liver yang hyperactivity or comorbid phlegm-stasis syndrome and explore its therapeutic mechanisms through plasma metabolomics.Methods:Thirty-six hypertension patients(4 dropouts)diagnosed with liver yang hyperactivity or phlegm-stasis syndrome were enrolled as the treatment group from June 2022 to September 2023 at the First Affiliated Hospital of Hunan University of Chinese Medicine,while 30 healthy volunteers with balanced constitutions were recruited as the blank group.Plasma samples were collected from patients pre-and post-treatment and from healthy volunteers.Clinical outcomes,including syndrome scores,office blood pressure(BP),and 24-hour ambulatory BP,were recorded.Plasma metabolomic profiling was performed using liquid chromatography-mass spectrometry(LC-MS).Results:Compared with baseline,Tianma Xionglin Zhixuan Tablets significantly reduced traditional Chinese medicine syndrome scores(P＜0.01),office systolic/diastolic BP(P＜0.01),and 24-hour ambulatory BP parameters(24-hour mean BP,daytime/nighttime mean BP;all P＜0.01).Metabolomic analysis identified 45 differential metabolites between the blank group and pretreatment patients,and 64 metabolites altered post-treatment(VIP＞1,P＜0.05).Enrichment analysis of 16 overlapping endogenous metabolites revealed that Tianma Xionglin Zhixuan Tablets primarily modulated arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion:Tianma Xionglin Zhixuan Tablets demonstrates significant clinical efficacy in hypertension patients with liver yang hyperactivity or phlegm-stasis syndrome,potentially mediated through regulation of arachidonic acid and sphingolipid metabolism.

Objective:To explore the effect of recombinant human brain natriuretic peptide(rhBNP)combined with dopamine on cystatin C(CysC),homocysteine(Hcy)and cardiac function in patients with severe heart failure(HF).Methods:This randomized controlled study enrolled 110 severe HF patients admitted in Aerospace Center Hospital between December 2021 and December 2022.They were divided into control group(n=55,nitroglycerin combined dopamine)and combined treatment group(n=55,rhBNP combined dopamine).Each group received corresponding therapy based on basic treatment for one week.Therapeutic effect,levels of CysC,Hcy,left ventric-ular end-systolic diameter(LVESd),left ventricular end-diastolic diameter(LVEDd),left ventricular ejection fraction(LVEF),and incidence of adverse reactions were compared between two groups.Results:Compared with patients in control group,those in combined treatment group had significant higher total effective rate(81.82％vs.58.18％)and LVEF[(54.68±4.59)％vs.(44.79±4.37)％],and significant lower CysC[(1.02±0.19)mg/L vs.(1.40±0.21)mg/L],Hcy[(15.98±2.17)μmol/L vs.(21.05±2.82)μmol/L],LVESd[(35.13±3.51)mm vs.(41.71±3.28)mm]and LVEDd[(41.33±4.26)mm vs.(50.51±4.37)mm](P＜0.01 all).There was no significant difference in total incidence of adverse reactions between two groups(16.36％vs.7.27％,P=0.180).Conclusion:rhBNP combined with dopamine could significantly improve the clinical therapeutic effect,im-prove levels of CysC,Hcy and cardiac function with good safety in the treatment of severe HF.

Objective:To explore the effect of recombinant human brain natriuretic peptide(rhBNP)combined with dopamine on cystatin C(CysC),homocysteine(Hcy)and cardiac function in patients with severe heart failure(HF).Methods:This randomized controlled study enrolled 110 severe HF patients admitted in Aerospace Center Hospital between December 2021 and December 2022.They were divided into control group(n=55,nitroglycerin combined dopamine)and combined treatment group(n=55,rhBNP combined dopamine).Each group received corresponding therapy based on basic treatment for one week.Therapeutic effect,levels of CysC,Hcy,left ventric-ular end-systolic diameter(LVESd),left ventricular end-diastolic diameter(LVEDd),left ventricular ejection fraction(LVEF),and incidence of adverse reactions were compared between two groups.Results:Compared with patients in control group,those in combined treatment group had significant higher total effective rate(81.82％vs.58.18％)and LVEF[(54.68±4.59)％vs.(44.79±4.37)％],and significant lower CysC[(1.02±0.19)mg/L vs.(1.40±0.21)mg/L],Hcy[(15.98±2.17)μmol/L vs.(21.05±2.82)μmol/L],LVESd[(35.13±3.51)mm vs.(41.71±3.28)mm]and LVEDd[(41.33±4.26)mm vs.(50.51±4.37)mm](P＜0.01 all).There was no significant difference in total incidence of adverse reactions between two groups(16.36％vs.7.27％,P=0.180).Conclusion:rhBNP combined with dopamine could significantly improve the clinical therapeutic effect,im-prove levels of CysC,Hcy and cardiac function with good safety in the treatment of severe HF.