ObjectiveTo investigate the effect of icariin （ICA） on the phenotype of dendritic cells （DCs） in heart tissue of the Dahl salt-sensitive myocardial remodeling model of rats and its regulation on the vitamin D system. MethodsMale Dahl salt-resistant rats were divided into a normal group， and male Dahl salt-sensitive rats were divided into a model group， low-， medium-， and high-dose ICA groups （30， 60， 120 mg·kg^-1·d^-1）， and Vitamin D group （3×10^-5 mg·kg^-1·d^-1）. In addition to the normal group， the other groups were given an 8% high salt diet to establish a myocardial remodeling model and received intragastric administration after successful modelling once a day for six weeks. The dynamic changes in tail artery blood pressure were monitored， and detection of cardiac ultrasound function in rats was performed. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes in rat heart tissue. The phenotype of DCs and T helper cell 17 （Th17）/regulatory T cell （Treg） ratio were detected by flow cytometry. The mRNA and protein expression of vitamin D receptor （VDR）， 1α-hydroxylase （CYP27B1）， 24-hydroxylase （CYP24A1）， forkhead frame protein 3 （FoxP3）， solitaire receptor γt （RORγt）， myocardial type Ⅰ collagen （ColⅠ）， and type collagen （ColⅢ） in heart tissue was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the normal group， the model group showed disordered arrangement and rupture of myocardial cells， nuclear condensation， significant edema of myocardial tissue， significant proliferation of collagen fibers in a network distribution， and a significant increase in tail artery blood pressure， left ventricular end diastolic diameter （LVEDD）， and left ventricular end systolic diameter （LVESD） （P<0.05）. The phenotype of cardiac DCs was CD40， CD80， and CD86， and the levels of major histocompatibility complex Ⅱ （MHC-Ⅱ）， Th17 cells， and Th17/Treg were significantly increased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt in the heart， as well as the mRNA expression of ColⅠ and ColⅢ， were significantly increased （P<0.05）. The left ventricular ejection fraction （LVEF）， interventricular septal thickness （IVSD）， and left ventricular posterior wall thickness （LVPWD） were significantly decreased （P<0.05）. The phenotype of cardiac DCs such as CD11， CD11b， and Treg cells， were significantly reduced （P<0.05）， while the mRNA and protein expression of cardiac VDR， CYP27B1， and FoxP3 were significantly decreased （P<0.05）. Compared with the model group， the low-， medium-， and high-dose ICA groups and vitamin D group significantly reduced myocardial cell rupture and nuclear consolidation in rats. The high-dose ICA group and vitamin D group showed a small amount of myocardial cell rupture and nuclear consolidation， improving myocardial fiber arrangement to varying degrees and significantly reducing myocardial fiber rupture and proliferation. The tail artery blood pressure， LVEDD， and LVESD were significantly decreased in the low-， medium-， and high-dose ICA groups and vitamin D group （P<0.05）， and the phenotype of cardiac DCs including CD40， CD80， CD86， MHC-Ⅱ， Th17 cells， and Th17/Treg were significantly decreased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt， and the mRNA expression of ColⅠ and ColⅢ in the heart were significantly decreased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. The LVEF， IVSD， and LVPWD of myocardial remodeling model rats in the low-， medium-， and high-dose ICA groups and vitamin D group were significantly increased （P<0.05）. The phenotypes of cardiac DCs including CD11， CD11b， and Treg cells were significantly increased in the medium- and high-dose ICA groups and the Vitamin D group （P<0.05）. The mRNA and protein expressions of VDR， CYP27B1， and FoxP3 in the heart were significantly increased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. ConclusionICA can regulate tail artery blood pressure， cardiac structural and functional damage， and myocardial tissue fibrosis and inhibit phenotype and functional maturation of DCs in heart tissue in the myocardial remodeling model of Dahl salt-sensitive rats. It can also affect the gene and protein expression of VDR， CYP24A1， and CYP27B1， achieving its intervention in Th17/Treg balance in the immune process of myocardial remodeling possibly by regulating vitamin D/VDR in heart tissue.

OBJECTIVE To investigate the mechanism through which Danggui buxue decoction regulates neutrophil extracellular traps （NETs） to improve osteoporosis （OP） in rats with premature ovarian failure （POF）. METHODS Female SD rats were randomly divided into normal group， model group， calcitriol group， and Danggui buxue decoction low-dose， medium-dose and high-dose groups， with 9 rats in each group. Except for the normal group， all other groups were administered cisplatin via intraperitoneal injection on days 1 and 8 to establish a POF complicated with OP model. Each group received the corresponding drugs or normal saline intragastrically starting from day 5， once a day， for 4 consecutive weeks. After the last medication， serum levels of estradiol （E2）， NETs， 25-hydroxyvitamin D3 [25（OH）D3]， receptor activator of nuclear factor-κB ligand （RANKL）， and osteocalcin （BGP） were measured. The histopathological changes in bone tissue were observed. The expressions of vitamin D receptor （VDR）， myeloperoxidase （MPO）， neutrophil elastase （NE） and citrullinated histone H3 （CitH3） in bone tissue were detected； the protein expressions of 25-hydroxyvitamin D-1α-hydroxylase （CYP27B1） and 1α，25-dihydroxyvitamin D3-24-hydroxylase （CYP24A1） were also determined. RESULTS Compared with the normal group， the bone tissue of rats in the model group showed a significant reduction in the number of trabeculae， which was thinner broken and poorly connected， with significant destruction of the reticular structure， and an enlarged marrow cavity. Serum levels of NETs and RANKL， the protein expressions of MPO， NE， CitH3 and CYP24A1 in bone tissue were significantly increased or upregulated， while serum levels of E2， 25（OH）D3 and BGP as well as protein expressions of VDR and CYP27B1 were significantly decreased or downregulated （P＜0.05）. Compared with the model group， the histopathological changes in the bone tissue of rats in each administration group showed some degree of recovery， with significant improvements observed in most quantitative indicators （P＜0.05）. CONCLUSIONS Danggui buxue decoction can restore the E2 level in POF complicated with OP rats， and improve OP. The mechanism may be related to its ability to upregulate VD level and inhibit the formation of NETs.

Objective Given that psychosocial stress can contribute to a series of diseases,such as inflammatory bowel disease and irritable bowel syndrome,we aimed to establish an experimental chronic restraint mouse intestinal stress injury model as a basis for exploring the pathogenic mechanism of chronic restraint stress-induced gastrointestinal diseases,and for developing preventive and curative measures.Methods Eighteen male SPF-grade BALB/c mice were acclimatized for 7 days and then divided into a control group and a chronic restraint stress group according to body weight,using a randomized numerical table method.The mice were subjected to restraint stress for 3 hours per day for 14 days to establish an intestinal injury model.The model was evaluated by observing body weight,pathological changes in intestinal histomorphology,expression of tight junction proteins,apoptosis of intestinal epithelial cells,and mRNA expression levels of inflammatory cytokines.Results After 14 days of chronic restraint stress,model mice showed weight loss,shortened duodenal villus height,abnormal crypt structure,a decreased villus/crypt ratio,colonic mucosal inflammatory cell infiltration,and irregular crypt structure.Protein immunoblotting,immunohistochemistry,and immunofluorescence staining showed that the expression levels of the duodenal and colonic tight junction proteins Occludin and Claudin-1 were significantly decreased in mice after chronic restraint stress(P＜0.05),while expression levels of the apoptotic protein cleaved-caspase-3 in intestinal epithelial cells were significantly increased(P＜0.05).Regarding the mRNA expression levels of intestinal inflammatory factors and chemokines,chronic restraint stress for 14 days significantly increased the gene expression levels of interleukin(IL)-1β,IL-6,monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α,and IL-10 in the duodenum of mice(P＜0.05),and significantly increased the gene expression levels ofIL-1β,IL-6,and MCP-1 in the colon(P＜0.001).Conclusions The use of a behavioral restriction device to restrain mice continuously for 14 days led to abnormal intestinal tissue structure,intestinal barrier dysfunction,and intestinal epithelial cell apoptosis,and triggered an intestinal inflammatory response in the stressed mice,indicating successful establishment of a mouse model of intestinal injury by chronic restraint stress.

Objective:To evaluate the effect of patent foramen ovale on the development of post-operative stroke in the patients undergoing non-cardiac surgery using a meta-analysis approach.Methods:A comprehensive search was conducted across multiple databases including PubMed, Embase, Web of Science, CINAHL, Cochrane Library, China Biomedical Literature Database, Wanfang Data Knowledge Service Platform, and China Journal Full Text Database.The inclusion criteria encompassed studies assessing the correlation between patent foramen ovale and post-operative stroke.The primary outcome measure focused on the incidence of post-operative stroke, and secondary outcome measures comprised mortality, myocardial infarction rate, and readmission rate within 30 days after surgery. The quality of literature meeting the inclusion criteria was evaluated and data were extracted, and then meta-analysis was conducted using RevMan 5.4 software.Results:Eight retrospective cohort studies involving 21 142 237 patients were included.The results of meta-analysis showed that patent foramen ovale was associated with post-operative stroke and readmission within 30 days after surgery.There were no significant differences in all-cause mortality and myocardial infarction rates between patent foramen ovale group and mon-patent foramen ovale group ( P>0.05). Conclusions:Patent foramen ovale can increase the risk of post-operative stroke in the patients undergoing non-cardiac surgery.

Objective By simulating acute hypoxic conditions, an experimental model of intestinal stress injury in plateau mice was established to explore the pathogenic mechanism of acute gastrointestinal diseases in plateau, and to lay foundation for preventive and therapeutic measures.MethodsThirty-six SPF-grade adult male BALB/c mice were randomly divided into four groups: normoxic 24 h, normoxic 72 h, hypoxic 24 h, and hypoxic 72 h, based on body weight using a randomized numerical table method, with nine mice in each group. Mice in the normoxic group were kept in a conventional barrier environment, while those in the hypoxic group were placed in a hypoxic chamber within the barrier environment with oxygen concentration set at 10% to simulate plateau conditions. They were subjected to stress for 24 h and 72 h, respectively, in order to establish a model of intestinal injury induced by acute hypoxia. After modeling, the mice were weighed, anesthetized with 1% pentobarbital sodium, and then euthanized by cervical dislocation. Duodenal and colonic tissues were collected. Histopathological morphology of intestinal tissues was observed after HE staining. Western blotting and immunohistochemistry were used to detect the expression levels of tight junction-related proteins in intestinal tissues. Real-time fluorescence quantitative PCR was performed to measure the expression levels of inflammatory cytokines and chemokines. TUNEL staining was used to assess apoptotic activity of intestinal epithelial cells, thus evaluating intestinal injury-related phenotypes in this model.Results Compared with the normoxic groups, mice in the 24 h and 72 h hypoxia groups showed weight loss, shortened duodenal villi, abnormal crypt structure, and decreased villus/crypt ratio. The colonic mucosa was infiltrated with inflammatory cells and irregular crypt structure. Expression levels of Occludin and zonula occludens-1 (ZO-1) were significantly decreased in duodenal and colonic tissues of mice in the 24 h and 72 h hypoxia groups (P<0.05). The expression of pro-apoptotic protein Bax was significantly up-regulated while expression of anti-apoptotic protein Bcl-2 was significantly down-regulated in duodenal tissues (P<0.05). Apoptotic activity of intestinal epithelial cells was significantly enhanced (P<0.05). In addition, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) mRNA levels were significantly increased in duodenal tissues after 24 and 72 h of hypoxic stress(P<0.05). After 24 h of hypoxic stress, there was no significant change in the expression levels of inflammatory cytokines in colon tissues (P>0.05), but after 72 h, the expression levels of pro-inflammatory factors IL-1β, TNF-α, IL-6, MCP-1, and anti-inflammatory factor IL-10 mRNAs significantly increased in colon tissues of mice (P<0.05).Conclusion The usage of a hypoxia chamber to simulate an acute hypoxic environment in plateau can lead to abnormal intestinal tissue structure, intestinal barrier dysfunction, and induce intestinal epithelial cell apoptosis, triggering an intestinal inflammatory response in stress mice. These findings indicate the successful construction of a mouse model for an acute hypoxic stress-induced intestinal injury.

ObjectiveTo investigate the effect of icariin （ICA）-mediated vitamin D system on peripheral blood dendritic cells （DCs） and helper T cells 17 （Th17）/regulatory T cells （Treg） balance in myocardial remodeling model of Dahl salt-sensitive rats. MethodFifty SPF Dahl salt-sensitive rats were divided into model group， vitamin D group （3×10^-5 mg·kg^-1·d^-1）， and high-， medium-， and low-dose ICA groups （120， 60， 30 mg·kg^-1·d^-1）， and 10 Dahl salt-resistant rats were used as normal group. The myocardial remodeling model was established by feeding rats with a high-salt diet containing 8% NaCl. After six weeks of modeling， the normal group and the model group were given an equal volume of ultrapure water by gavage， and other groups were continuously administrated for six weeks. Cardiac echocardiography， hematoxylin-eosin （HE） staining， and Masson staining were used to observe the pathological changes in cardiac structure and fibrosis. The levels of serum 25（OH）D₃， B-type N-terminal pro-brain natriuretic peptide （NT-ProBNP）， interleukin （IL）-17， transforming growth factor （TGF）-β₁， IL-12， and IL-10 were detected by enzyme-linked immunosorbent assay （ELISA）. The phenotype of peripheral blood DCs and the ratio of Th17/Treg cells of rats were detected by flow cytometry. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expressions of vitamin D receptor （VDR），1α-hydroxylase （CYP27B1）， and 24-hydroxylase （CYP24A1） in peripheral blood DCs of rats. ResultCompared with the control group， the rats in the model group had pathological changes such as disordered arrangement of myocardial cells and cytoplasmic hypertrophy and swelling. Myocardial collagen fibers proliferated significantly， and the arrangement of myocardial fibers was disordered. The levels of serum 25（OH）D₃ and IL-10 were significantly decreased， and the levels of serum IL-17， TGF-β₁， IL-6， IL-12， and NT-ProBNP were significantly increased （P<0.05）. The costimulatory molecules CD40， CD80， CD86， and MHC-Ⅱ were highly expressed in the peripheral blood DCs， and the expression of CD11 and CD11b was lower （P<0.05）. The proportion of Th17 cells in the peripheral blood was significantly increased， and the proportion of Treg cells was decreased. The ratio of Th17/Treg was increased （P<0.05）. The mRNA and protein expressions of CYP24A1 in peripheral blood DCs increased， and the mRNA and protein expressions of CYP27B1 and VDR decreased （P<0.05）. Compared with the model group， the arrangement of myocardial fibers in each drug administration group was relatively regular， and the swelling of myocardial cells was significantly reduced. The pathological morphology of myocardial tissue was improved to varying degrees. The pathological changes in myocardial tissue were improved and alleviated to varying degrees. The drug could reduce the serum levels of NT-ProBNP， IL-17， TGF-β₁， IL-6， and IL-12 and increase the level of serum 25（OH）D₃ and IL-10 （P<0.05）. The expression of costimulatory molecules CD40， CD80， CD86， and MHC-Ⅱ in the peripheral blood DCs of rats was decreased， and the expression of CD11 and CD11b molecules was increased （P<0.05）. The drug could reduce the proportion of Th17 cells in peripheral blood and the ratio of Th17/Treg cells and increase the proportion of Treg cells （P<0.05）. It could decrease the mRNA and protein expressions of CYP24A1 in peripheral blood DCs of rats and elevate the mRNA and protein expression of VDR and CYP27B1 （P<0.05）. ConclusionICA can regulate the phenotype of peripheral blood DCs and the ratio of Th17/Treg cells by regulating the vitamin D system and play a role in improving myocardial remodeling from the perspective of immune balance.

Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Vascular remodeling is a physiological and pathological process in which abnormal changes in vas-cular cells and non-cellular components lead to the remodeling of inward and outward blood vessel wall or changes in lu-men diameter.As the channels for blood flow,blood vessels are continuously affected by hemodynamic forces.When sens-ing the abnormal blood flow forces,the mechanically sensitive cell membrane structures such as G protein-coupled recep-tors,ion channels,cell surface glycocalyx,and integrins,as well as the extracellular matrix will induce the process of vas-cular endothelial dysfunction,endothelial-mesenchymal transition,smooth muscle cell phenotypic switching,pericyte morphological changes and extracellular matrix remodeling to participate in vascular remodeling.As shown by research,abnormal hemodynamics caused abnormal changes in vascular structure and function,which was the basic process for the occurrence and development of pan-vascular diseases such as atherosclerosis,hypertension,diabetes,non-alcoholic fatty liver disease,pulmonary hypertension and COVID-19.This paper reviewed the interaction and molecular mechanism be-tween abnormal hemodynamics and vascular remodeling,and analyzed its influence on the pathogenesis of pan-vascular diseases,which could provide reference for formulating prevention and treatment strategies for pan-vascular diseases.

Atherosclerosis(As)is a chronic inflammatory disease caused by lipid deposition.Panvascular disea-ses,which are mainly caused by As,have gradually attracted the attention of many scholars,and their main pathological features are vascular lesions.Vitamin D plays an important role in anti-As in panvascular diseases.It is involved in the regulation of renin-angiotensin system(RAS),endothelial cell injury,immune response,neutrophil extracellular traps(NET)regulation,apoptosis and autophagy,and is a new target in panvascular diseases research.Traditional Chinese Medicine(TCM)has certain advantages in the prevention and treatment of panvascular diseases.Among them,single herbs,active ingredients and compound prescriptions can regulate vitamin D-related metabolism,and have unique scientific value for the prevention and treatment of As.This article mainly discusses the role of vitamin D in multiple pathological links of panvascular diseases and related Chinese medicine interventions,aiming to provide effective ideas for the prevention and treatment of panvascular diseases from the perspective of vitamin D.

Objective:To evaluate the real-world safety of the domestic rotavirus attenuated live vaccine in China.Methods:Studies on the incidence of adverse event following immunization (AEFI) published from January 1, 2020 to July 31, 2023 were retrieved from National Knowledge Infrastructure (CNKI), CQVIP, Wanfang Database, PubMed, Medline, and Embase. Surveillance data about AEFI reports related to the domestic rotavirus vaccine rotavirus were collected. A meta-analysis on the safety of the rotavirus vaccine after vaccination was conducted using R software, and subgroup analyses were conducted on the incidence of AEFI in different regions and time periods.Results:A total of 36 articles were included involving 25.332 million doses of vaccine. The incidence of AEFI associated with the domestic rotavirus vaccine was 19/100 000 doses [95%CI: 15/100 000-24/100 000 doses]; the incidence was 26/100 000 doses [95%CI: 17/100 000-39/100 000 doses] in the northern regions and 16/100 000 doses [95%CI: 11/100 000-23/100 000 doses] in the southern regions; it was 24/100 000 doses [95%CI: 12/100 000-45/100 000 doses] before 2017 and 27/100 000 doses [95%CI: 18/100 000-39/100 000 doses] after 2017.Conclusions:The incidence of AEFI related to the domestic rotavirus vaccine is within the expected range, and the safety of the vaccine is good based on the real-world data.