ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

Bone metastases are a common and serious complication of solid tumors such as breast cancer, prostate cancer, lung cancer, and kidney cancer, and occur at a high rate in patients with advanced cancer. This pathological process not only frequently leads to skeletal-related events such as severe bone pain, pathological fractures, spinal cord compression, and hypercalcemia—conditions that severely impact patients’ quality of life—but may also significantly increase the risk of death. Cancer bone metastasis is a complex, multistage cascade involving key steps such as the detachment of tumor cells from the primary tumor, their invasion and entry into the bloodstream, and their colonization, dormancy, and reactivation within the bone microenvironment. In recent years, exercise—as a safe and easily implementable non-pharmacological intervention—has demonstrated significant potential in inhibiting bone metastasis, improving the bone microenvironment, and alleviating related clinical symptoms. Its mechanisms of action may involve multiple levels. First, at the mechanical load level, mechanical signals generated by exercise can directly act on bone cells, inhibiting tumor cell infiltration and colonization by regulating endothelial cell permeability and osteoclast activity. Second, at the endocrine and paracrine levels, exercise can alter the expression profiles of microRNAs (such as miR-486 and miR-34b) carried by extracellular vesicles and particles (EVPs) in the circulation, thereby inhibiting tumor cell proliferation and migration by targeting cell cycle-related genes. Furthermore, exercise can remodel the immune microenvironment, enhance the cytotoxic activity of antitumor immune cells, and improve oxygen supply to tumor tissues, thereby alleviating hypoxia-induced immunosuppression. Finally, at the metabolic intervention level, exercise can induce systemic metabolic reprogramming, increasing the nutritional demands of normal tissues, thereby competing with tumor cells for nutrients and forming a “metabolic barrier” in distal organs such as bones. This article reviews the pathogenesis and classification of bone metastases, including osteolytic, osteogenic, and mixed types, and elaborates in detail on the complex processes by which tumor cells undergo colonization, dormancy, and reactivation within the bone microenvironment. Furthermore, based on a comprehensive analysis of human and animal studies on exercise interventions for bone metastases, this paper highlights the mechanisms by which exercise inhibits tumor formation, growth, and spread through the regulation of mechanical loading, extracellular vesicles and granules, as well as via immune and metabolic pathways, thereby interfering with bone metastasis. However, the array of exercise modalities and intensities available for patients grappling with the challenges of cancer-related bone metastases remains markedly constrained, and the formulation of tailored exercise prescriptions continues to be devoid of robust, evidence-based medical backing. This review aims to explore the effects of exercise on bone health in patients with bone metastases, analyze the factors and considerations that should be taken into account in exercise prescriptions, and provide new theoretical support and insights for developing personalized exercise programs for these patients and further advancing relevant clinical research. Future research directions should include the development of evidence-based, personalized exercise prescriptions and further clarification of the safety boundaries and best practice standards for exercise interventions, thereby promoting the advancement of relevant clinical research and ultimately improving patients’ clinical outcomes and quality of life.

ObjectiveTo investigate the effect of kynurenine-3-monooxygenase （KMO） on the function of fibroblast-like synoviocytes （FLS） in rheumatoid arthritis （RA）. MethodsKMO expression in synovial tissues from RA patients and healthy controls （HC） was analyzed using bioinformatics. Synovial tissues from RA patients and HC were collected， and KMO expression in FLS within synovial tissues was detected by immunofluorescence （IF）. In vitro experiments were performed using human rheumatoid arthritis fibroblast-like synoviocytes （MH7A）. Following KMO overexpression， KMO knockdown， and KMO inhibition with the specific inhibitor Ro61-8048 in MH7A cells， Western blot， CCK-8， EdU， Transwell and ELISA assays were used to evaluate alterations in cell viability， proliferation， migration and secretory function. ResultsBioinformatic analysis revealed significantly higher KMO gene expression in RA synovial tissue compared to the HC group （P<0.001）. IF results showed increased KMO expression in FLS from RA synovial tissues relative to the HC group （P<0.01）. Overexpression of KMO led to enhanced viability， proliferation， migration， and secretory capabilities of MH7A cells （all P<0.05）， whereas knockdown or inhibition of KMO with Ro61-8048 markedly suppressed these functions （all P<0.05）. ConclusionThe expression of KMO is upregulated in the synovial tissues of RA patients and promotes the activation of RA-FLS， suggesting that KMO may serve as a potential therapeutic target for RA treatment.

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective To explore the factors that influence major adverse cardiovascular events(MACE)in atrial fibrillation(AF)patients undergoing radiofrequency ablation(RFA),as well as to compare the prognosis of patients with advanced AF to that of the general population.Methods We prospectively recruited AF patients who underwent RFA treatment at Peking University Third Hospital between January 2021 and March 2023.General patient data were collected through the hospital's inpatient system,and MACE were tracked through outpatient visits and telephone follow-ups.Patients were categorized into three age groups:Group 1(under 65 years),Group 2(65 to 75 years),and Group 3(over 75 years).In this study,MACE was defined as include cardiovascular death,all-cause death,readmission for heart failure,acute coronary syndrome(ACS),grade 2 or higher bleeding and stroke.Results A total of 431 patients were included in this study,with an average age of(66.17±12.22)years.Among these patients,259 were male(60.09％),and the mean of CHA2DS2-VASc score was(1.79±1.30).The median follow-up period was 16.0(11.3,21.3)months,during which 28(6.50％)patients experienced MACE,with ACS and stroke being the most common events.Variables were selected using LASSO regression,and a LASSO-Cox regression model was constructed.Age(HR 1.06,95％CI 1.02-1.10,P=0.006)and hypertrophic cardiomyopathy(HR 3.70,95％CI 1.27-8.68,P=0.008)were identified as independent predictors of MACE after RFA for AF.Subgroup analysis revealed that patients under 65 had significantly better prognoses compared to older AF patients(P=0.030 compared with group 2;P=0.021 compared with group 3).Conclusions Age and hypertrophic cardiomyopathy are independent risk factors for MACE in AF patients undergoing RFA.The prognosis for younger patients is better than that for older patients,while the prognosis for advanced patients is comparable to that of patients aged 65-75 years.

Objective:To investigate the association of blood lipids and body mass index (BMI) with hyperuricemia (HUA) in the elderly.Methods:It was a cross-sectional study. A total of 114 391 elderly individuals received health examinations at primary healthcare institutions in Wujin District from January to December in 2022. The health examination included questionnaire survey, physical examination and laboratory examination. The multivariate logistic regression and restricted cubic spline (RCS) plots were used to analyze the association and dose-response relationship of blood lipid and BMI with HUA. The mediating effect model was used to explore the mediation effect of BMI on the association between blood lipid and HUA.Results:Among the 112 415 subjects, 18 506 (16.46%) were checked with HUA. After adjusting for relevant confounders, total cholesterol (TC) ( OR=1.20, 95% CI: 1.16-1.23), triglyceride (TG) ( OR=1.46, 95% CI: 1.44-1.49), high density lipoprotein cholesterol (HDL-C) ( OR=0.74, 95% CI: 0.73-0.76), low density lipoprotein cholesterol (LDL-C) ( OR=1.14, 95% CI: 1.12-1.15) and BMI ( OR=1.42, 95% CI: 1.39-1.44) were all associated with HUA (all P0.05). The RCS analysis revealed that TG, HDL-C, and LDL-C each exhibited a nonlinear dose-response relationship with HUA, the inflection points was 3.00 mmol/L, 1.57 mmol/L and 2.50 mmol/L, respectively (all P-nonlinear0.001). The results of interaction showed that there were additive interaction between high TC( S=1.27 , 95% CI: 1.17-1.37), high TG( S=1.32 , 95% CI: 1.25-1.40), high LDL-C( S=1.23 , 95% CI: 1.14-1.34) and overweight/obesity with HUA (all P0.05). The results of mediation effect analysis showed that the mediation effect of BMI on the association between blood lipids (HDL-C, LDL-C, TG and TC) and HUA, from high to low, were as follows: 22.5% (95% CI: 20.8%-24.2%), 13.9% (95% CI: 12.0%-16.2%), 13.5% (95% CI: 12.7%-14.4%) and-3.9% (95% CI:-6.6%--1.8%). Conclusion:The blood lipid levels and BMI are positively correlated with HUA in the elderly.

Oral cancer(OC)is a common malignant tumor and its incidence and mortality rate is increasing year by year.According to statistics,there are over 500,000 new cases worldwide every year,and most patients face treatment challenges.Electrospinning technology(ES)is a method for preparing nanofibers by driving the polymer in solution to form nanoscale fibers through an electric field.Since its discovery in the 1930s,it has received widespread attention and application.This article reviews the application of ES in the treatment of OC.The principles and preparation process of ES are induced,its application research in treating OC is elaborated,and the challenges faced by ES in OC treatment research are analyzed.Finally,the future development is discussed.

Objective:To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia(AML)cells.Methods:Juglone and AML targets were collected from public databases,and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML.Then wet experiments were performed to verify.AML cell lines including KG-1a,MV-411,THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h.MTT assay was used to detect cell viability and determine the IC50,and the most sensitive cell line was screened for subsequent experiments.Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone.Western blot was performed to check the expression of relevant proteins.Results:Eleven targets were obtained as potential targets for juglone in the treatment of AML,and the top ten significantly enriched pathways were intrinsic pathway of apoptosis,programmed cell death,cytochrome c-mediated apoptotic response,apoptosis,apoptotic factor-mediated response,regulated necrosis,cytokine signaling in immune system,signaling by interleukins,oncogene induced senescence,and signal transduction.The cell viability of KG-1a,MV-411,THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment(r=-0.992,-0.886,-0.956,-0.910).Among them,MOLM-13 was the most sensitive to juglone.The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone(r=0.99).At the same time point,p-RIPK1/RIPK1,p-RIPK3/RIPK3,and p-MLKL/MLK were decreased in each juglone concentration group compared with control group.Conclusion:Juglone inhibits the viability of KG-1a,MV-411,THP-1 and MOLM-13 cells,and induces apoptosis of MOLM-13 cells,the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.

Objective:To evaluate the effectiveness of remote management based on unmet health needs self-monitoring reports in patients with colorectal cancer.Methods:A total of 124 colorectal cancer inpatients admitted to the First Affiliated Hospital of Zhengzhou University from October 2022 to September 2023 were selected using convenience sampling and randomly divided into a control group and an intervention group (62 patients each). The control group received routine follow-up care, while the intervention group received remote management based on self-monitoring reports of unmet health needs in addition to routine follow-up, over a 3-month period. To evaluate the outcomes, the Health Literacy Management Scale (HeLMS), the Health Promoting Lifestyle Profile-II (HPLP-II), the Short Form of the Unmet Needs Survey (SF-SUNS), and the Self-Care Self-Efficacy Scale (SCSES) were compared between two groups.Results:After the intervention, the intervention group showed significantly higher scores in HeLMS, HPLP-II, and SCSES compared to their baseline values and the control group ( P<0.05). Additionally, the SF-SUNS score was significantly lower in the intervention group post-intervention than both its baseline and the control group post-intervention ( P<0.05) . Conclusions:Remote management based on unmet health needs self-monitoring reports effectively improves health literacy, promotes healthier lifestyles, enhances self-management efficacy, and reduces levels of unmet health needs in patients with colorectal cancer.