ObjectiveTo explore the potential mechanism of Changji'an Formula （肠激安方） on intestinal permeability for rats with diarrhea-predominant irritable bowel syndrome （IBS-D） of liver depression and spleen deficiency syndrome by the microRNA-29b-3p （miR-29b-3p）/tumor necrosis factor receptor-associated factor 3 （TRAF3）/nuclear factor-κB （NF-κB）/myosin light chain kinase （MLCK） axis. MethodsTwenty-four 1-day-old male Sprague-Dawley （SD） suckling rats were selected， and the IBS-D rat model of liver depression and spleen deficiency syndrome was established via a three-factor method，i.e. maternal separation plus acetic acid stimulation and restraint stress， for 6 consecutive weeks. After successful modeling， the rats were randomly divided into a model group， pinaverium bromide group， low-dose and high-dose Changji'an Formula groups， with 6 rats in each group. Another 6 age-matched non-modeled SD rats were included as the control group. The low-dose and high-dose Changji'an Formula groups were given intragastric administration of Changji'an Formula solution at doses of 16.74 g/（kg·d） and 33.48 g/（kg·d）， respectively； the pinaverium bromide group received intragastric administration of pinaverium bromide tablets at 0.018 g/（kg·d）； and the control group was given distilled water at 10 ml/（kg·d） via intragastric gavage. The intervention was conducted once daily for 14 consecutive days. After the gavage treatment， the fecal water content of rats in each group was measured. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of intestinal permeability indicators， including D-lactic acid （D-LA）， diamine oxidase （DAO）， and lipopolysaccharide （LPS）. Quantitative real-time polymerase chain reaction （qRT-PCR） was conducted to determine the mRNA expression levels of miR-29b-3p， TRAF3， tumor necrosis factor-α （TNF-α）， p65， p50， and MLCK in colonic tissues. Western Blot analysis was employed to detect the protein expression levels of TRAF3， TNF-α， p65， phosphorylated p65 （p-p65）， MLCK， myosin light chain （MLC）， phosphorylated MLC （p-MLC）， and tight junction proteins including junctional adhesion molecule-A （JAM-A）， Occludin， and Claudin-1 in colonic tissues. ResultsCompared with the control group， the model group exhibited significantly increased fecal water content and serum levels of D-LA， DAO， and LPS， along with decreased protein expression levels of JAM-A， Occludin， and Claudin-1 in colonic tissues （P＜0.05 or P＜0.01）. Additionally， in the model group， the mRNA expression levels of miR-29b-3p， TNF-α， p65， p50， and MLCK in colonic tissues were up-regulated， while the mRNA and protein expression levels of TRAF3 were down-regulated； the protein levels of TNF-α and MLCK， as well as the ratios of p-p65/p65 and p-MLC/MLC， significantly elevated （P＜0.01）. Compared with the model group， all treatment groups showed reduced fecal water content and serum levels of D-LA， DAO， and LPS， along with down-regulated mRNA expression levels of miR-29b-3p， TNF-α， p65， p50， and MLCK， and up-regulated TRAF3 mRNA expression in colonic tissues. Moreover， the pinaverium bromide group and high-dose Changji'an Formula group presented increased protein levels of Occludin， Claudin-1， and TRAF3， as well as decreased protein levels of TNF-α and MLCK， and reduced ratios of p-p65/p65 and p-MLC/MLC in colonic tissues （P＜0.05 or P＜0.01）. Compared with the low-dose Changji'an Formula group， the high-dose group had lower fecal water content and serum levels of DAO and LPS （P＜0.01）. In comparison with the pinaverium bromide group， the high-dose Changji'an Formula group showed a significant decrease in serum DAO level （P＜0.01）. ConclusionsChangji'an Formula can reduce intestinal permeability and restore intestinal barrier function in IBS-D rats of liver depression and spleen deficiency syndrome by regulating the miR-29b-3p/TRAF3/NF-κB/MLCK axis.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Aim To investigate the effect of chrysoeriol on pulmonary vascular remodeling in pulmonary hyper-tension by animal experiments combined with cell ex-periments,and to explore its potential therapeutic tar-gets by network pharmacology.Methods The target of chrysoeriol was collected in Targetnet,SEA and SwissTargetPrediction database.Pulmonary arterial hy-pertension(PAH)targets were collected in the Dis-GeNET and GeneCards databases,and PPI network map was drawn in the STRING database,and key tar-gets were screened.The GO and KEGG pathway en-richment analysis was carried out through DAVID data-base and Weishengxing platform.AutoDock software was used for molecular docking of key core targets.The PAH model of rats was constructed,and the pulmo-nary hemodynamics and vascular remodeling were de-tected by echocardiography,HE and Masson staining.Primary pulmonary smooth muscle cells were extracted,and the effects of drugs on pathway proteins were de-tected in vitro.Results The results of network phar-macology showed that chrysoeriol exerted therapeutic effects on pulmonary hypertension by affecting key tar-gets such as AKT1,SRC,EGFR,MMP9 and gsk3 β,and signaling pathways such as EGFR and PI3K-AKT.Molecular docking showed that chrysoeriol had good binding ability with 5 key target genes.Animal experi-ments showed that the pulmonary hemodynamic func-tion of PAH rats was significantly improved after ad-ministration of chrysoeriol.The remodeling of small pulmonary arteries was significantly reduced.Cell ex-periments showed that chrysoeriol could inhibit the ex-pression of proliferation,migration and phenotypic transformation genes.Conclusion Chrysoeriol may play a role in the treatment of pulmonary hypertension through multiple targets.

Atherosclerosis(AS)is the major pathologic basis of cardiovascular disease,and its complications,such as myocardial infarction and stroke,are primarily triggered by rupture of atherosclerotic vulnerable plaques(VASPs).Conventional imaging techniques rely on anatomical changes,making it difficult to assess plaque vulnerability at an early stage.In recent years,molecular imaging combined with nanoprobe technology has enabled precise visualization at the cellular and molecular levels by targeting pathological features of plaques(e.g.,lipid core,inflammation,thin fibrous cap,etc.).This article reviews the pathological features of VASPs,the limitations of existing imaging techniques,and the design principles and application progress of molecular imaging probes and discusses the challenges and future directions for their clinical translation.

ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

Objective:To describe the hotspots and application trends of artificial intelligence (AI) in epidemiology in the past decade and analyze its advantages and challenges.Methods:The literatures with AI and epidemiology related keywords were systematically retrieved from Web of Science and China National Knowledge Infrastructure from 2014 to 2024. CiteSpace was used for bibliometric analysis of publication volume, keyword co-occurrence, clustering, emergence and cited literature co-occurrence analysis.Results:A total of 5 389 English papers and 1 659 Chinese papers were included, showing an increasing publication trend. High-frequency Chinese keywords included prediction, influencing factor, and machine learning, while English keywords frequently used were machine learning, prediction, and artificial intelligence. The Chinese keywords formed 14 clusters such as epidemiological characteristic, dietary pattern, and elderly individual, and the English keywords formed 21 clusters including prediction model, risk factor, and adult. In international studies, health policy, COVID-19, and digital health were the emerging frontier keywords. Eleven core papers were selected, covering key areas like traffic accident risk assessment, public health big data application, and deep learning in medical diagnosis.Conclusions:This study systematically summarized the research hotspots and development trends of AI applications in epidemiology over the past decade by using bibliometric methods, which indicated that current AI-based epidemiological studies are still in the exploratory phase, with the coexisting of both advantages and challenges. Continued attention should be paid to the future development of this field.

Atherosclerosis(AS)is the major pathologic basis of cardiovascular disease,and its complications,such as myocardial infarction and stroke,are primarily triggered by rupture of atherosclerotic vulnerable plaques(VASPs).Conventional imaging techniques rely on anatomical changes,making it difficult to assess plaque vulnerability at an early stage.In recent years,molecular imaging combined with nanoprobe technology has enabled precise visualization at the cellular and molecular levels by targeting pathological features of plaques(e.g.,lipid core,inflammation,thin fibrous cap,etc.).This article reviews the pathological features of VASPs,the limitations of existing imaging techniques,and the design principles and application progress of molecular imaging probes and discusses the challenges and future directions for their clinical translation.

Aim To investigate the changes in hepatic lactylation during liver regeneration and its impact on regeneration.Methods A partial hepatectomy(PHx)mouse model was used to study liver regenera-tion.Sodium oxamate was administered intraperitoneal-ly to inhibit lactate dehydrogenase,and blood and liver tissues were collected at different time points post-sur-gery.The histopathological status was observed using HE staining.Proliferating cell nuclear antigen(PC-NA)levels were detected by immunohistochemistry.Lactylation was assessed using immunofluorescence.Liver LDH enzyme activity,lactate levels and serum alanine aminotransferase(ALT)and aspartate trans-aminase(AST)levels were measured using assay kits.Results After PHx,the liver volume of mice gradual-ly increased,returning to preoperative size on day 7.PCNA levels peaked at 48 hours post-surgery.Liver tissue lactate levels increased to approximately 1.5 times the preoperative level at 12 hours post-surgery and remained elevated until day 7.The lactylation lev-el in hepatocytes peaked at 24 hours post-surgery,gradually declined after 48 hours,and returned to pre-operative levels on day 7.Compared to the PHx group,the sodium oxamate(750 mg·kg-1)+PHx group showed significantly reduced lactylation levels in hepa-tocytes and a smaller liver regeneration volume on day 7.Conclusion Lactylation regulates hepatocyte pro-liferation and promotes liver regeneration after PHx.