Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD), leading to a high incidence of surgical interventions and significant disability. Despite its clinical relevance, no targeted pharmacological therapies are currently available. This review aims to explore the underlying mechanisms driving intestinal fibrosis and address unresolved scientific questions, offering insights into potential future therapeutic strategies. We conducted a literature review using data from PubMed up to October 2024, focusing on studies related to IBD and fibrosis. Intestinal fibrosis results from a complex network involving stromal cells, immune cells, epithelial cells, and the gut microbiota. Chronic inflammation, driven by factors such as dysbiosis, epithelial injury, and immune activation, leads to the production of cytokines like interleukin (IL)-1β, IL-17, and transforming growth factor (TGF)-β. These mediators activate various stromal cell populations, including fibroblasts, pericytes, and smooth muscle cells. The activated stromal cells secrete excessive extracellular matrix components, thereby promoting fibrosis. Additionally, stromal cells influence the immune microenvironment through cytokine production. Future research would focus on elucidating the temporal and spatial relationships between immune cell-driven inflammation and stromal cell-mediated fibrosis. Additionally, investigations are needed to clarify the differentiation origins of excessive extracellular matrix-producing cells, particularly fibroblast activation protein (FAP) + fibroblasts, in the context of intestinal fibrosis. In conclusion, aberrant stromal cell activation, triggered by upstream immune signals, is a key mechanism underlying intestinal fibrosis. Further investigations into immune-stromal cell interactions and stromal cell activation are essential for the development of therapeutic strategies to prevent, alleviate, and potentially reverse fibrosis.
Humans ; Fibrosis/metabolism* ; Inflammatory Bowel Diseases/pathology* ; Animals ; Transforming Growth Factor beta/metabolism* ; Intestines/pathology*

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Objective: To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa (Schenk) Wight (C. tubulosa, Rou Cong Rong), focusing on central and exercise-induced fatigue in mice. This study investigated the pharmacological effects of the total oligosaccharides, polysaccharides, and phenylethanoid glycosides (CPhGs) extracted from C. tubulosa. Methods: Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue. The mice were treated with different extracts of C. tubulosa, and their effects were assessed using behavioral tests to measure exercise capacity, learning, and memory function. Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels, liver and muscle glycogen storage, and various fatigue-related biomarkers. Results: This study found that treatment with C. tubulosa extract improved exercise capacity, learning, and memory in mice. Total oligosaccharides from C. tubulosa enhanced adrenocorticotropic hormone, cholinesterase, and thyroid-stimulating hormone levels, reduced cortisol levels in central fatigue models, and ameliorated biochemical markers of exercise-induced fatigue, including lowering lactic acid, blood urea nitrogen, and malondialdehyde levels. Among the tested extracts, the total oligosaccharides showed the most comprehensive anti-fatigue effects. Conclusion The anti-fatigue effects of C. tubulosa, particularly those of its total oligosaccharides, are pronounced in both central and exercise-induced fatigue. These effects are mediated by the regulation of neurotransmitter levels, enhancement of glycogen storage, and improvement of antioxidant enzyme activity, suggesting potential therapeutic benefits in fatigue-related conditions.

To explore the application value of endoscopic ultrasound fine-needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and treatment ofpatients with pancreatic cancer combined with obstructive jaundice.

Objective To analyze the effectiveness and safety of bisphosphonates in the treatment of pa-tients with calcification defense.Methods PubMed,Embase databases,CNKI and Wanfang were searched to collect the case reports and clinical studies of bisphosphonates for calcification defense.Then,the relevant infor-mation of patients was extracted for statistical analysis.Results A total of 18 case reports were selected involving 20 patients.Thirteen patients(65.0％)were treated with pamidronate,four(20.0％)were treated with etidr-onate,two(10.0％)were treated with alendronate,and one(5.0％)was treated with zoledronic acid.Thirteen patients(65.0％)recovered completely,the recovery time of whom ranged from half month to nine months.The tolerance of bisphosphonates in most patients(90.0％)was good,while one patient who did not tolerate pamidr-onate recovered after the frequency of administration was adjusted and one patient with high dosage of etidronate returned to normal after the discontinuation of the usage.Conclusions Bisphosphonates,an inhibitor of bone resorption,is effective and safe in the treatment of patients with calcification defense.

Objective To establish a noninvasive diagnostic model for liver fibrosis in chronic hepatitis B(CHB)patients with normal alanine aminotransferase(ALT)and an age of≤30 years by selecting specific indicators from the commonly used noninvasive indicators such as clinical,biochemical,and imaging indicators,to avoid invasive liver biopsy in such patients to some extent,and to guide the timing of antiviral therapy.Methods A total of 251 CHB patients with normal ALT and an age of≤30 years who underwent liver biopsy in Shenzhen Third People's Hospital and The First Hospital of Changsha from January 2019 to January 2022 were enrolled,with 175 patients in the model group and 76 patients in the validation group,and commonly used clinical indicators were obtained based on clinical experience and related articles.The two-independent-samples t test or the two-independent-samples Mann-Whitney U rank sum test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.A Spearman rank correlation analysis was used to investigate the correlation between each indicator and liver fibrosis and identify the indicators with correlation(P<0.01,r>0.200);a Logistic regression analysis was used to establish a noninvasive diagnostic model,and the receiver operating characteristic(ROC)curve was used to evaluate its performance and perform validation of the model;this model was then compared with the widely used models of aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB-4).The Kappa consistency test was used to investigate the consistency of pathological results.Results A total of 17 commonly used clinical indicators were obtained,among which 9 indicators(ALT,aspartate aminotransferase[AST],gamma-glutamyl transpeptidase[GGT],ferritin[FERR],platelet count[PLT],procollagen type Ⅲ amino-terminal peptide[PⅢP],collagen Ⅳ[CⅣ],HBV DNA,and spleen thickness)were correlated with liver fibrosis(P<0.01,r>0.232).Based on the above indicators,the predictive model was established as P=1/(1+e-γ),γ=-1.902+0.106×AST-0.011×PLT-0.265×HBV DNA+0.059×PⅢP,in which P was the probability for predicting≥S2 liver fibrosis and γ was the predictive index.The comparison between each indicator and the model showed that the model had the largest area under the ROC curve of 0.852,with a sensitivity of 92.7%and a specificity of 76.9%.The model was validated in 76 patients and showed an accuracy of 77.600%.The model was compared with APRI and FIB-4,and the results showed that the model has good accuracy.Conclusion Compared with the models of APRI and FIB-4 commonly used in the world,this model can more accurately judge the degree of liver fibrosis in such patients,thereby replacing liver biopsy to some extent and guiding the timing of antiviral therapy.

Objective:To develop adjustable peel force tester with peel angle from 0° to 180°,so as to realize the test for the performance of interface adhesion of wearable electronic products under multi angles.Methods:The rotating platform of angle adjustment component was used to realize free adjustment of peel angle from 0° to 180°.A method of peel test procedure based on the peel force tester with full-angle was established,and the comparative experiment between that and tensile testing machine was conducted.The peel tests of various kinds of wearable electronic products were conducted under peel angle of 45°,90° and 180°.Results:The test results of the peel force tester with full-angle were consistent with those of the tensile testing machine,which function opposed reliability.The peel test results of more than 10 wearable electronic products indicated that the peel force tester with full-angle could effectively determinate the performance of interface adhesion.Conclusion:The peel force tester with full-angle can effectively appear the performance of the interface adhesion of wearable electronic products,which provides basis for establishing the standard of peel test of wearable electronic products.

Ceria nanoparticles(CeO2 NPs)have become popular materials in biomedical and industrial fields due to theirpotential applications in anti-oxidation,cancer therapy,photocatalytic degradation of pollutants,sensors,etc.Many methods,including gas phase,solid phase,liquid phase,and the newly proposed green synthesis method,have been reported for the synthesis of CeO2 NPs.Due to the wide application of CeO2 NPs,concerns about their adverse impacts on human health have been raised.This review covers recent studies on the biomedical applications of CeO2 NPs,including their use in the treatment of various diseases(e.g.,Alzheimer's disease,ischemic stroke,retinal damage,chronic inflammation,and cancer).CeO2 NP toxicity is discussed in terms of the different systems of the human body(e.g.,cytotoxicity,genotoxicity,respiratory toxicity,neurotoxicity,and hepatotoxicity).This comprehensive review covers both fundamental discoveries and exploratory progress in CeO2 NP research that may lead to practical developments in the future.

Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders.However,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation.Corin knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion effect.Furthermore,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability.Mechanistically,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation.PD98059(a selective ERK inhibitor)blocks the corin-mediated promotion effect.With regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion effect.Furthermore,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability.To conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway.We hope this brings new insights into future clinical treatments for BRONJ.