This study aims to investigate the mechanism by which resveratrol(RES) alleviates cerebral vascular endothelial damage in sepsis-associated encephalopathy(SAE) through network pharmacology and animal experiments. By using network pharmacology, the study identified common targets and genes associated with RES and SAE and constructed a protein-protein interaction( PPI) network. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed to pinpoint key signaling pathways, followed by molecular docking validation. In the animal experiments, a cecum ligation and puncture(CLP) method was employed to induce SAE in mice. The mice were randomly assigned to the sham group, CLP group, and medium-dose and high-dose groups of RES. The sham group underwent open surgery without CLP, and the CLP group received an intraperitoneal injection of 0. 9% sodium chloride solution after surgery. The medium-dose and high-dose groups of RES were injected intraperitoneally with 40 mg·kg-1 and 60 mg·kg~(-1) of RES after modeling, respectively, and samples were collected 12 hours later. Neurological function scores were assessed, and the wet-dry weight ratio of brain tissue was detected. Serum superoxide dismutase(SOD), catalase( CAT) activity, and malondialdehyde( MDA) content were measured by oxidative stress kit. Histopathological changes in brain tissue were examined using hematoxylin-eosin(HE) staining. Transmission electron microscopy was employed to evaluate tight cell junctions and mitochondrial ultrastructure changes in cerebral vascular endothelium. Western blot analysis was performed to detect the expression of zonula occludens1( ZO-1), occludin, claudins-5, optic atrophy 1( OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), fission 1(Fis1), and hypoxia-inducible factor-1α(HIF-1α). Network pharmacology identified 76 intersecting targets for RES and SAE, with the top five core targets being EGFR, PTGS2, ESR1, HIF-1α, and APP. GO enrichment analysis showed that RES participated in the SAE mechanism through oxidative stress reaction. KEGG enrichment analysis indicated that RES participated in SAE therapy through HIF-1α, Rap1, and other signaling pathways. Molecular docking results showed favorable docking activity between RES and key targets such as HIF-1α. Animal experiment results demonstrated that compared to the sham group, the CLP group exhibited reduced nervous reflexes, decreased water content in brain tissue, as well as serum SOD and CAT activity, and increased MDA content. In addition, the CLP group exhibited disrupted tight junctions in cerebral vascular endothelium and abnormal mitochondrial morphology. The protein expression levels of Drp1, Fis1, and HIF-1α in brain tissue were increased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were decreased. In contrast, the medium-dose and high-dose groups of RES showed improved neurological function, increased water content in brain tissue and SOD and CAT activity, and decreased MDA content. Cell morphology in brain tissue, tight junctions between endothelial cells, and mitochondrial structure were improved. The protein expressions of Drp1, Fis1, and HIF-1α were decreased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were increased. This study suggested that RES could ameliorate cerebrovascular endothelial barrier function and maintain mitochondrial homeostasis by inhibiting oxidative stress after SAE damage, potentially through modulation of the HIF-1α signaling pathway.
Animals ; Mice ; Network Pharmacology ; Resveratrol/administration & dosage* ; Male ; Sepsis-Associated Encephalopathy/genetics* ; Signal Transduction/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Endothelium, Vascular/metabolism* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Humans ; Sepsis/complications* ; Oxidative Stress/drug effects*

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-β1 (TGF-β1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-β1, and polidocanol (POL) combined with TGF-β1. The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-β1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-β1 combination produced pathological changes and curvature comparable to STS + TGF-β1 and led to fewer complications. In conclusion, fibrin, STS + TGF-β1, and POL + TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
Animals ; Male ; Penile Induration/drug therapy* ; Rats ; Transforming Growth Factor beta1/metabolism* ; Disease Models, Animal ; Fibrin ; Penis/drug effects* ; Polidocanol/administration & dosage* ; Rats, Sprague-Dawley ; Polyethylene Glycols/administration & dosage* ; Injections

Objective To observe the clinical effect of acupuncture combined with Shenqi Huoxue Decoction in the treatment of adenomyosis of qi deficiency and blood stasis type.Methods Seventy patients with adenomyosis of qi deficiency and blood stasis type were randomly divided into observation group and control group,35 cases in each group.The control group was treated with Levonorgestrel-releasing intrauterine system,and the observation group was treated with acupuncture combined with Shenqi Huoxue Decoction on the basis of the treatment of the control group.One menstrual cycle was a course of treatment,and the treatment lasted for three courses.After 3 months of treatment,the clinical efficacy of the two groups was evaluated,and the changes of Endometriosis Health Profile-5(EHP-5)score,serum superoxide dismutase(SOD)and catalase(CAT)were observed in the two groups before and after treatment.The changes of serum carbohydrate antigen CA125,carbohydrate antigen 199(CA199)and human epididymis protein 4(HE4)levels were compared before and after treatment between the two groups.Results(1)The total effective rate was 97.14％(34/35)in the observation group and 77.14％(27/35)in the control group.The clinical efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the levels of serum CA125,CA199 and HE4 in the two groups were significantly improved(P＜0.05),and the improvement of serum CA1 25,CA199 and HE4 levels in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).(3)After treatment,the levels of serum SOD and CAT in the two groups were significantly improved(P＜0.05),and the improvement of serum SOD and CAT levels in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).(4)After treatment,the EHP-5 score of quality of life in the two groups was significantly improved(P＜0.05),and the EHP-5 score of quality of life in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).Conclusion Acupuncture combined with Shenqi Huoxue Decoction in the treatment of adenomyosis of qi deficiency and blood stasis type can significantly improve the clinical symptoms of patients,regulate the levels of SOD and CAT,so as to improve the quality of life of patients,and the curative effect is significant.

Objective To investigate whether Heshouwuyin can delay the aging of Leydig cells in rat testis through DNA methyltransferase 1(DNMT1).Methods Totally 40 male Wistar rats were randomly divided into 4 groups,with 10 rats in each group.Immunohistochemistry was used to detect the expression levels of DNMT1 in testis tissue of rats.Testosterone content in serum of rats in each group was detected by ELISA test.A rat Leydig cell aging model was established by free radical oxidative damage.DNMT1 was knocked down by lentivirus in Leydig cells,and the cell senescence status and the testosterone content and testosterone synthesis key enzyme 3β-hydroxysteroid dehydrogenase(3β-HSD),cytochrome P450 family member 11A1(CYP11A1)content secreted by cells were detected by β-galactosidase(β-GAL)staining,immunofluorescenct staining and ELISA.Results Compared with the young control group(YCG),the expression of P16 protein and the positive rate of β-GAL in the testis tissue of rats in the natural aging group(NAG)increased significantly,and the expression of DNMT1 and serum testosterone levels decreased(P＜0.05).However,after Heshouwuyin intervention,the expression of P16 protein and the positive rate of β-GAL in the testis of aging rats were reduced,and DNMT1 expression and the serum testosterone levels increased(P＜0.05).The same trend was observed in Leydig cells.Knockdown of DNMT1 in Leydig cells,β-GAL positivity and P16 protein expression increased significantly,and testosterone secretion and testosterone synthesis key enzymes 3β-HSD,CYP11A1 content from Leydig cells decreased significantly,compared with the normal control group(NCG)(P＜0.05).When Heshouwuyin was added,the above phenomenon was improved.Conclusion Heshouwuyin can delay the aging of rat Leydig cells through DNMT1.

Recent research has highlighted structural and functional abnormalities in the cerebral cortex of patients with premature ejaculation (PE). These anomalies could play a pivotal role in the physiological mechanisms underlying PE. This study leveraged functional magnetic resonance imaging (fMRI), a noninvasive technique, to explore these neural mechanisms. We conducted resting-state fMRI scans on 36 PE patients and 22 healthy controls (HC), and collected data on Premature Ejaculation Diagnostic Tool (PEDT) scores and intravaginal ejaculation latency time (IELT). Employing a surface-based regional homogeneity (ReHo) approach, we analyzed local neural synchronous spontaneous activity, diverging from previous studies that utilized a volume-based ReHo method. Areas with significant ReHo differences between PE and HC groups underwent surface-based functional connectivity (FC) analysis. Significant discrepancies in ReHo and FC across the cortical surface were observed in the PE cohort. Notably, PE patients exhibited decreased ReHo in the left triangular inferior frontal gyrus and enhanced ReHo in the right middle frontal gyrus. The latter showed heightened connectivity with the left lingual gyrus and the right orbital superior frontal gyrus. Furthermore, a correlation between ReHo and FC values with PEDT scores and IELT was found in the PE group. Our findings, derived from surface-based fMRI data, underscore specific brain regions linked to the neurobiological underpinnings of PE.
Male ; Humans ; Premature Ejaculation ; Brain Mapping/methods* ; Brain ; Cerebral Cortex ; Magnetic Resonance Imaging/methods*

Aim To investigate the differences in the role of different purinergic receptor subtypes at different sites in postoperative-hyperalgesic priming in mice. Methods A postoperative-hyperalgesic priming model was constructed by injecting PGE

Objective:To investigate the temporal trend of the mortality rate of intracerebral hemorrhage (ICH) among residents with different characteristics during the comprehensive prevention and control of hypertension in Tengzhou, Shandong Province from 2013 to 2021.Methods:Comprehensive prevention and control of hypertension was conducted in Tengzhou, Shandong Province from 2013 to 2021. ICH mortality rate was calculated from January 1, 2013 to December 31, 2021. ICH mortality monitoring data from Tengzhou, Shandong Province was used to analyze the temporal trend of ICH mortality among residents with different characteristics. The registered residence population came from the Public Security Bureau of Tengzhou, Shandong Province. The age and gender standardized mortality rate was calculated based on the data of China's seventh population census in 2020. The temporal and age trends of mortality were analyzed using Cochran Armitage Trend Tests.Results:From 2013 to 2021, the overall crude and standardized mortality rates of ICH in Tengzhou, Shandong Province decreased from 50.51/100 000 and 63.21/100 000 to 17.51/100 000 and 16.74/100 000, respectively ( Z=-11.013 and -15.426, P<0.001), with an average annual mortality rate decrease of 12.41% and 15.30%, respectively. The overall crude and standardized mortality rates in 2017 peaked compared to 2016, mainly due to an increase of 32.94% and 30.92% in male ICH crude and standardized mortality rates, respectively ( χ2=12.328 and 15.854, P<0.05). The mortality rate of ICH increased with age, and the decreasing trend over time became increasingly evident with age. The mortality rate of ICH in the ≥65 year old age group decreased by 77.94% over 9 years ( Z=-14.065, P<0.001). In 2017, the mortality rate of ICH in the male age group ≥65 years old and female 45-54 years old increased by 31.13% and 125.79% compared to 2016 respectively, there were statistically significant differences ( χ2=8.877 and 5.421, P<0.05). In 2021, the mortality rates of urban and rural ICH decreased by 93.22% and 46.40% compared to 2013, respectively ( Z=-13.279 and -5.393, P<0.001), with an average annual decrease of 28.56% and 7.50%, respectively. The ICH mortality rate in rural areas increased by 30.54% in 2017 compared to 2016 ( χ2=16.086, P<0.001); after 2018, the mortality rate of ICH began to be higher than that of urban areas ( χ2=33.400 and 67.305, P<0.001). Conclusions:The ICH mortality rate in Tengzhou, Shandong Province has shown a significant downward trend over time, with male mortality rate higher than female mortality rate and rural mortality rate higher than urban areas. This suggests that the key attention should be paid to both male and rural areas.

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.
Humans ; Fecal Microbiota Transplantation/methods* ; Treatment Outcome ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Steroids

The Ministry of Education and other four departments jointly issued the Notice on the Construction of high-level schools of public Health, proposing that "it will take ten years to build a number of high-level schools of public health, and form a high-quality education development system to adapt to the construction of modern public health system". At present, the construction of high-level public health schools in various universities in China is in full swing. The high-level School of Public Health and the CDC have played an important role in constructing the national public health system and the human health community. The high-level public health schools are of strategic significance and important value to the development of the CDC. The review presents reflections and insights on the role of high-level public health schools in the development of the CDC and the challenges they might face.
Humans ; United States ; Schools, Public Health ; Schools ; Universities ; Public Health ; Centers for Disease Control and Prevention, U.S.