Objective: To investigate the microbial mechanisms of Banxia Xiexin Decoction (半夏泻心汤, BXXXD) in the treatment of esophageal precancerous lesions. Methods: A total of 30 specific pathogen-free (SPF) grade female C57BL/6J mice were randomly assigned to a control group (n = 6) and a 4-nitroquinoline 1-oxide (4-NQO)-exposed group (n = 24). Esophageal precancerous lesions were induced by providing the 4-NQO-exposed group with 4-NQO in drinking water (100 μg/mL) for 17 consecutive weeks, whereas control group received sterile drinking water. After model establishment, the mice in 4-NQO-exposed group were further randomized into model group and three BXXXD-treated groups: low-dose (BXXXD-L, 3.7 g/kg), medium-dose (BXXXD-M, 7.4 g/kg), and high-dose (BXXXD-H, 14.8 g/kg) groups (n = 6 per group). During the subsequent intervention period, mice in control and model groups were gavaged with sterile water, while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks. Histopathological changes in esophageal tissues were observed by hematoxylin and eosin (HE) staining. The fecal and esophageal microbiota were profiled via 16S rDNA high-throughput sequencing to evaluate bacterial diversity, community structure, and co-occurrence networks. BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry (UHPLC-QE-MS). Serum short-chain fatty acids (SCFA) level was quantified by targeted metabolomics using gas chromatography-mass spectrometry (GC-MS). Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles. Results: Compared with model group, BXXXD-M group exhibited reduced mucosal hyperplasia and more orderly epithelial cell arrangement, with superior therapeutic effects in comparison with both BXXXD-L and BXXXD-H groups (P < 0.01). Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Escherichia-Shigella in the esophagus. In the gut, BXXXD elevated the relative abundance of beneficial taxa, including Lactobacillus, Dubosiella, Bacteroides, and Faecalibacterium. Targeted metabolomics showed that BXXXD significantly reduced total serum SCFA level (P < 0.01). Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression, migration, and invasion of esophageal cancer, which were identified as kallikrein-related peptidase 6 (Klk6), defensin beta 4 (Defb4), family with sequence similarity 3 member B (Fam3b), carboxypeptidase A4 (Cpa4), serum amyloid A1 (Saa1), and chitinase-like 1 (Chil1) (P < 0.05). Conclusion BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.

Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Objective:To clarify the complex network structure between self-management levels and supportive care needs of patients undergoing maintenance hemodialysis, utilizing network analysis methods to identify the core and bridging nodes among the variables, thereby defining targets for nursing interventions to implement more precise care strategies.Methods:A cross-sectional survey was conducted from May to November 2023 among 302 outpatient maintenance hemodialysis patients at the hemodialysis centers of two healthcare institutions in Harbin (the Second Affiliated Hospital of Harbin Medical University and Heilongjiang Changjiang Nephrology Specialist Hospital). This involved the use of general information questionnaires, the Hemodialysis Patient Self-Management Scale, and the Supportive Care Needs Scale for Hemodialysis Patients. R language was employed for the network analysis.Results:A total of 300 valid questionnaires were collected, including 186 males and 114 females, with an age range of 23 to 88 years (mean age 55.00 ± 13.78 years). The scores for the dimensions of self-management among dialysis patients were as follows: problem-solving (3.38 ± 0.63), execution of self-care (3.16 ± 0.52), partnership (2.56 ± 0.69), and emotional processing (1.89 ± 0.63). The scores for the dimensions of supportive care needs among dialysis patients were: physiological needs (2.82 ± 1.08), psychological needs (1.51 ± 1.02), social needs (1.97 ± 1.07), emotional needs (1.67 ± 1.12), spiritual needs (2.22 ± 0.77), informational needs (2.83 ± 1.08), and practical needs (2.82 ± 1.03). In network analysis, the strongest intensity was found in the execution of self-care (1.753), and the highest closeness was in psychological needs (0.017). The top three dimensions ranked by bridge strength were social needs (1.463), partnership (1.462), and execution of self-care (1.384). The root mean square error was lowest for psychological needs (0.518) and emotional needs (0.538). The stability and accuracy of the network structure were found to be good.Conclusions:The key intervention targets for nursing care in maintenance hemodialysis patients were identified as executing self-care, psychological needs, emotional needs, and social needs. Among these, executing self-care served as the core intervention focus, while psychological and emotional needs had dominant influences, and social needs exhibited the strongest bridging role. Nursing staff should prioritize these key targets and tailor personalized comprehensive nursing intervention plans to enhance patients′self-management levels and fully meet their care needs.

Objective:To clarify the complex network structure between self-management levels and supportive care needs of patients undergoing maintenance hemodialysis, utilizing network analysis methods to identify the core and bridging nodes among the variables, thereby defining targets for nursing interventions to implement more precise care strategies.Methods:A cross-sectional survey was conducted from May to November 2023 among 302 outpatient maintenance hemodialysis patients at the hemodialysis centers of two healthcare institutions in Harbin (the Second Affiliated Hospital of Harbin Medical University and Heilongjiang Changjiang Nephrology Specialist Hospital). This involved the use of general information questionnaires, the Hemodialysis Patient Self-Management Scale, and the Supportive Care Needs Scale for Hemodialysis Patients. R language was employed for the network analysis.Results:A total of 300 valid questionnaires were collected, including 186 males and 114 females, with an age range of 23 to 88 years (mean age 55.00 ± 13.78 years). The scores for the dimensions of self-management among dialysis patients were as follows: problem-solving (3.38 ± 0.63), execution of self-care (3.16 ± 0.52), partnership (2.56 ± 0.69), and emotional processing (1.89 ± 0.63). The scores for the dimensions of supportive care needs among dialysis patients were: physiological needs (2.82 ± 1.08), psychological needs (1.51 ± 1.02), social needs (1.97 ± 1.07), emotional needs (1.67 ± 1.12), spiritual needs (2.22 ± 0.77), informational needs (2.83 ± 1.08), and practical needs (2.82 ± 1.03). In network analysis, the strongest intensity was found in the execution of self-care (1.753), and the highest closeness was in psychological needs (0.017). The top three dimensions ranked by bridge strength were social needs (1.463), partnership (1.462), and execution of self-care (1.384). The root mean square error was lowest for psychological needs (0.518) and emotional needs (0.538). The stability and accuracy of the network structure were found to be good.Conclusions:The key intervention targets for nursing care in maintenance hemodialysis patients were identified as executing self-care, psychological needs, emotional needs, and social needs. Among these, executing self-care served as the core intervention focus, while psychological and emotional needs had dominant influences, and social needs exhibited the strongest bridging role. Nursing staff should prioritize these key targets and tailor personalized comprehensive nursing intervention plans to enhance patients′self-management levels and fully meet their care needs.

Objective To investigate the effects of tegafur, gimeracil and oteracil potassium combined with oxaliplatin on gastric motility-related hormones, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in elderly patients with gastric cancer. Methods A total of 128 elderly patients with gastric cancer were selected as the study subjects and randomly divided into control group (n=64) and observation group (n=64). The control group was treated with tegafur, gimeracil and oteracil potassium, while the observation group received tegafur, gimeracil and oteracil potassium combined with oxaliplatin. Gastric motility-related hormones [motilin (MTL) and vasoactive intestinal peptide (VIP)], MMP-2, MMP-9, tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 19-9 (CA19-9)], clinical efficacy and occurrence of adverse reactions were observed in both groups. The correlations of gastric motility-related hormones with the levels of MMP-2, MMP-9 and tumor markers were analyzed. Results After treatment, MTL levels in both groups were significantly lower, while VIP levels were significantly higher compared to before treatment. Additionally, the observation group had significantly lower MTL and higher VIP levels compared to the control group (P < 0.05). After treatment, the levels of MMP-2, MMP-9, CEA, CA125 and CA19-9 were significantly reduced in both groups compared to pretreatment levels, with the observation group showing significantly lower levels than the control group (P < 0.05). The total effective rate in the observation group was 70.31%, which was significantly higher than the 53.13% in the control group (P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05). A negative correlation was observed between MTL and MMP-2, MMP-9, CEA, CA125 as well as CA19-9 (P < 0.05), while VIP showed a positive correlation with MMP-2, MMP-9, CEA, CA125 and CA19-9 (P < 0.05). Conclusion The combination of tegafur, gimeracil and oteracil potassium and oxaliplatin is effective and safe for the treatment of elderly patients with gastric cancer. MTL, VIP, MMP-2, MMP-9, CEA, CA125 and CA19-9 are interrelated in the development of gastric cancer in elderly patients.

The advantages of 3D printing technique in medicine were described.The current status of 3D printing technique was introduced when applied to customized radiotherapy compensation film,printing tumor models and breast cancer surgical navigation molds,individualized postoperative implants and printing models for drug testing and research of new therapies.The problems of 3D printing technique in breast cancer therapy were analyzed,and the future direction of development was envisioned.[Chinese Medical Equipment Journal,2024,45(11):103-108]

To detect interleukin-33(IL-33)level and investigate the effect of IL-33 signaling pathway on monocytes in patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),total of 31 HBV-HCC patients,33 chronic hepatitis B(CHB)patients and 21 normal controls were enrolled in the study.Peripheral blood was collected to isolate plasma and peripheral blood mononuclear cells(PBMC),then CD14+monocytes were purified by magnetic-activated cell sorting.Intrahepatic lymphocytes(IHL)were isolated from para-tumor tissues and tumor tissues of 11 HBV-HCC patients.IL-33 and soluble suppressor of tumorigenicity 2(sST2)levels in plasma were measured by enzyme-linked immunosorbent assay;ST2 expression in CD14+monocytes was investigated by flow cytometry.Recombinant human IL-33 was used to stimulate CD14+monocytes,then the cytokine secretion and HLA-DR proportion in CD14+monocytes were assessed.Furthermore,cytotoxicity of monocytes was also investigated.Data showed that plasma IL-33 level in CHB patients and HBV-HCC patients were lower than that in controls(P<0.01).Plasma sST2 level of HBV-HCC patients was higher than those of CHB patients and controls(P<0.01).ST2+CD14+proportion in PBMC from HBV-HCC patients was lower than those of from CHB patients and controls(P<0.000 1).ST2 mean fluorescence intensity(MFI)in PBC from HBV-HCC patients was lower than those from CHB patients and controls(P<0.0001).ST2+CD14+proportion in IHL was also lower in tumor tissues than that in para-tumor tissues(P<0.05);ST2 MFI in IHL was lower in tumor tissues than that in para-tumor tissues(P<0.05).As compared with controls,monocytes activity of HBV-HCC and CHB patients were lower,especially in tumor tissues,which was presented as downregulation of HLA-DR proportion,TNF-α,IL-6,IL-1β and granzyme B secretion(P<0.05).IL-33 stimulation did not affect ST2 level in CD14+monocytes(P>0.05).Both 0.1 ng/ml and 1 ng/ml of IL-33 stimulation elevated cytokine production and HLA-DR+CD14+monocytes percentage in CD14+monocytes from HBV-HCC patients(P<0.05).However,only 1 ng/ml of IL-33 stimulation promoted monocytes-induced target cell death(P<0.000 1).Taken together,monocytes activity is down-regulated in HBV-HCC patients,and IL-33 signaling pathway could enhance monocytes function in HBV-HCC patients.

Objective To investigate the gray matter volume(GMV)changes and molecular basis underlying antipsychotic-induced weight gain(AIWG).Methods One hundred twenty-nine first-episode schizophrenia patients from October 2019 to December 2021 were enrolled in this study.Patients with≥7%weight gain(weight gain,WG)and patients with<3%weight changes(weight stable,WS)were studied.All patients underwent T1-weighted MRI scanning at baseline and after 8 week treatment.Transcriptome-neuroimaging correlations were used to investigate brain gene profiles from the Allen Human Brain Atlas and GMV changes induced by AIWG.Results Thirty-three patients with WG and 27 with WS completed the GMV measures.Compared with baseline,the WG group showed reduced GMV in right hippocampus,left basal ganglia,and right inferior parietal lobule,etc.and increased GMV in bilateral thalamus(P<0.05).The WS group showed reduced GMV in bilateral orbital gyrus,bilateral inferior frontal gyrus and bilateral hippocampus(P<0.05).These GMV changes in WG group were spatially correlated with expression levels of 354 genes,which were exclusively enriched in Cushing syndrome,neuroinflammation and glutamatergic signaling,and Pnoc+.Conclusion The study has demonstrated increased GMV in thalamus in schizophrenia patients with AIWG which may be associated with Cushing syndrome and Pnoc+.These findings may provide important insights into the molecular mechanisms of AIWG.