In recent years,the incidence of heat-related diseases has been on a steady upward trend,which is closely associated with environmental factors such as climate change and air pollution.Exposure to a hot environment and/or strenuous physical activities can progress to heat stroke(HS),an acute disease that can lead to death.Current research indicates that gut injury occupies the most crucial initiating position in the pathophysiological changes and pathogenesis of HS.Probiotics can reduce the incidence and mortality of HS through maintaining the health of the gut microbiota,regulating the intestinal immune system,and other effects.In addition,the gut microbiota can construct axis systems to interact with multiple organs such as the liver,lungs,and brain,which is of great significance for alleviating the damage to distant organs caused by HS.This paper reviews the regulation of the gut microbiota by probiotics to improve the intestinal heat tolerance ability and barrier function,aiming to provide references for the prevention and treatment of heat stroke in clinical practice.

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 investigate the clinical features and prognostic factors of pediatric patients with acute hyperleukocytic leukemia (AHL).Methods:A retrospective case series study was conducted. The clinical data of 99 pediatric patients diagnosed with AHL who admitted to the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University between May 2015 and November 2020 were retrospectively analyzed. The enrolled children were grouped based on the following factors including gender, age, initial white blood cell count (WBC), initial lactate dehydrogenase (LDH), whether tumor lysis syndrome (TLS) occurred, immunophenotype, fusion gene, whether complete remission (CR) was achieved on the 19th day (D19) after transplantation, and whether CR was achieved on the 46th day (D46) after transplantation. All the patients were treated with the chemotherapy regimen of Shanghai Children's Medical Center - Acute Lymphoblastic Leukemia - 2015 (SCMC-ALL-2015). Flow cytometry was used to monitor the minimal residual disease (MRD); fluorescence in situ hybridization (FISH) was used to screen out the mutant genes. The median follow-up time was 47 months. The Kaplan-Meier method was used for survival analysis, and the log-rank test was used for intergroup comparisons. Multivariate Cox proportional hazard regression model was used to screen out the the prognostic factors.Results:Among 99 AHL patients, there were 65 males and 35 females; the median age was 7.71 (3.32, 11.20) years. At the initial diagnosis, 48 cases had WBC≤100×10 9/L, and 51 cases had WBC>100×10 9/L; 36 cases had LDH ≤ 2 000 U/L, and 63 cases had LDH > 2 000 U/L; 3 cases had TLS, 5 cases had MLL::AF4 positive, 7 cases had BCR::ABL positive, 7 cases had E2APBX1 positive, and 10 cases had TEL::AML1 positive; 28 cases were acute T-cell lymphoblastic leukemia (T-ALL), and 71 cases were acute B-cell lymphoblastic leukemia (B-ALL). At D19, 74 cases achieved bone marrow CR; at D46, 82 cases achieved bone marrow CR; 3-year and 5-year OS rates were 74.5% and 71.3%, respectively. During the follow-up, 14 cases relapsed and 15 died, including 12 dying of relapse, 2 dying of infection and 1 case dying of pulmonary graft-versus-host disease (GVHD). There were statistically significant differences in the 3-year OS rate in patients with different age, initial WBC, initial LDH, immunophenotyping, whether bone marrow CR at D19 was achieved, whether MRD at D19 occurred, whether bone marrow CR at D46 was achieved, whether MRD at D46 occurred, the presence of TLS, MLL::AF4 positive and TEL::AML1 positive (all P < 0.05). Furthermore, multivariate Cox regression analysis showed that LDH(>2 000 U/L), MLL::AF4 positive, T immunophenotyping, relapse, not achieving bone marrow CR at D19, not achieving bone marrow CR at D46, and MRD positive at D46 were independent risk factors influencing 3-year OS rate (all P < 0.05). Conclusions:Pediatric patients with AHL have high tumor burden at early stage, and TLS may cause death. Patients treated with the SCMC-ALL-2015 protocol can achieve favorable therapeutic effects and prognosis. LDH, MLL::AF4, immunophenotyping and relapse are prognostic factors.

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.

Chemical investigation of the stems of Fritillaria unibracteata P.K. Hsiao & K.C. Hsia resulted in the isolation of nine compounds, by means of silica gel column chromatography, and preparative HPLC. Based on spectroscopic and chemical evidence, these compounds were identified as: 27-hydroxychlorogenone (1), sieboldogenin (2), (3β, 25S)-spirost-5-ene-3,17,27-triol (3), laxogenin (4), tigogenone (5), cerevisterol (6), ergosterol peroxide (7), stigmaterol (8), and β-sitosterol (9). Compound 1 was a new compound, and compounds 2-9 were isolated from the stems of Fritillaria unibracteata for the first time. The inhibitory effects of compounds 1−9 on A549 cells were determined using the MTT method. The results show that compound 6 exhibits moderate inhibitory activity with an IC50 value of (14.16 ± 1.11) μmol/L.

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 explore the influencing factors of compliance with new oral anticoagulants(NOACs)in elderly patients with nonvalvular atrial fibrillation(NVAF)and its correlation with social support.Methods The clinical data of 126 patients with NVAF treated by NOACs in Lu 'an People's Hospital of Anhui Province from January 2022 to January 2024 were selected by convenient sampling method.General data of patients were collected.According to Morisky medication compliance scale,patients were divided into two groups:the good compliance group(n=74)and the poor compliance group(n=52).Social support was investigated by Social Support Rating Scale(SSRS).General data of patients were compared between the good compliance group and the poor compliance group.The relationship between medication compliance and social support was analyzed by Pearson correlation.Multivariate Logistic regression was used to analyze the influencing factors of patient medication compliance.Results There were statistically significant differences in educational level,the proportion of patients with anxiety and depression,CHA2DS2-VASc score,HAS-BLED score and SSRS score between the good compliance group and the poor compliance group(P＜0.05).The results of the correlation analysis showed that the medication compliance of patients was positively correlated with objective support(r=0.461),subjective support(r=0.432),support utilization(r=0.323)and SSRS score(r=0.596,P＜0.05).The results of multivariate Logistic regression analysis showed that low educational level,accompanied by anxiety,low HAS-BLED and SSRS scores were risk factors for poor medication compliance in elderly NVAF patients(P＜0.05).Conclusion Improving the social support level of elderly patients with NVAF is conducive to the formation of good medication compliance.

Objective To explore the influencing factors of compliance with new oral anticoagulants(NOACs)in elderly patients with nonvalvular atrial fibrillation(NVAF)and its correlation with social support.Methods The clinical data of 126 patients with NVAF treated by NOACs in Lu 'an People's Hospital of Anhui Province from January 2022 to January 2024 were selected by convenient sampling method.General data of patients were collected.According to Morisky medication compliance scale,patients were divided into two groups:the good compliance group(n=74)and the poor compliance group(n=52).Social support was investigated by Social Support Rating Scale(SSRS).General data of patients were compared between the good compliance group and the poor compliance group.The relationship between medication compliance and social support was analyzed by Pearson correlation.Multivariate Logistic regression was used to analyze the influencing factors of patient medication compliance.Results There were statistically significant differences in educational level,the proportion of patients with anxiety and depression,CHA2DS2-VASc score,HAS-BLED score and SSRS score between the good compliance group and the poor compliance group(P＜0.05).The results of the correlation analysis showed that the medication compliance of patients was positively correlated with objective support(r=0.461),subjective support(r=0.432),support utilization(r=0.323)and SSRS score(r=0.596,P＜0.05).The results of multivariate Logistic regression analysis showed that low educational level,accompanied by anxiety,low HAS-BLED and SSRS scores were risk factors for poor medication compliance in elderly NVAF patients(P＜0.05).Conclusion Improving the social support level of elderly patients with NVAF is conducive to the formation of good medication compliance.

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.