Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective To predict the target and molecular mechanism of Huayu Xiaopi decoction in the intervention of Precancerous lesions of gastric cancer(PLGC)based on network pharmacology and molecular docking technology,and to conduct experimental verification.Methods A total of 60 SPF SD male rats were randomly selected as blank control,and the other rats were replicated in PLGC model.After successful modeling,the rats were randomly divided into model group,folic acid group(2 mg·kg-1·d-1),Huayu Xiaopi decoction high,medium and low dose groups(24.8,12.4,6.2 g·kg-1·d-1),which were continuously administered for 90 days.The body mass and food intake of rats at 3 h were recorded,and the gastric histopathology was observed by HE staining.Network pharmacology and molecular docking techniques were used to predict the potential targets of Huayu Xiaopi decoction in PLGC intervention,and the core targets were verified by Western blot technique.Results Compared with the blank group,the body mass and 3 h food intake of rats in the model group were significantly decreased(P<0.05),the gastric mucosa of rats was significantly thinner,the glands were significantly reduced and disordered,and the intestinal metaplasia goblet cells and a large number of inflammatory cells were visible in some areas.Compared with the model group,the body mass and 3 h food intake of rats in each administration group were improved to varying degrees.Huayu Xiaopi Decoction improved significantly in medium and high doses(P<0.05),the gastric mucosa was repaired in different degrees,the glandular arrangement tended to be orderly,and the inflammatory cells in the interstitial were gradually reduced.The results of network pharmacology and molecular docking showed that TP53,JUN and MAPK3/1(ERK1/2)were the core targets of Huayu Xiaopi decoction in the intervention of PLGC.Molecular biological detection results showed that compared with blank group,the protein phosphorylation levels of TP53,c-Jun and ERK1/2 in gastric tissue of model group were significantly increased(P<0.05).Compared with model group,the protein phosphorylation levels of TP53,c-Jun and ERK1/2 in gastric tissue of rats in all administration groups were decreased to different degrees,and significantly decreased in Huayu Xiaopi decoction high-dose and medium-dose groups(P<0.05).Conclusion Huayu Xiaopi Decoction can significantly improve the survival condition of PLGC rats and promote gastric mucosal repair,the specific mechanism of which may be related to the decrease of ERK1/2,c-Jun and TP53 protein phosphorylation levels in gastric tissue of PLGC rats,and then regulate the downstream signaling molecular response.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Myeloid neoplasms (MNs) belong to a group of hematological malignancies characterized by the abnormal biological functions of hematopoietic stem progenitor cells. The abnormal immune and hematopoietic microenvironment of patients with MN interact with malignant clonal hematopoietic stem cells, promoting the occurrence and development of their diseases. MN large granular lymphocyte proliferation (MN-LGLP) is a special and rare clinical phenomenon in this type of disease. Currently, research on this disease in domestic and international cohorts is limited. This study analyzes the clinical and laboratory characteristics of this type of patient and explores the impact of LGLP on the clinical characteristics and survival of patients with MN. Patients with MN-LGLP are prone to neutropenia and splenomegaly. The presence of LGLP is not a risk factor affecting the survival of patients with MN-LGLP. STAG, ASXL1, and TET2 are the most common accompanying gene mutations in MN-LGLP, and patients with MN-LGLP and STAG2 mutations have poor prognoses.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To explore the in vitro and in vivo antimicrobial activity of antipsychotic agent pimozide against Staphylococcus aureus(S.aureu).Methods The minimal inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of pimozide were determined by micro-dilution assay.Biofilm was cultured in 96-well cell culture plate,and the anti-biofilm activity of pimozide was detected by turbidimetry.The effect of pimozide on biofilm was further observed through laser confocal microscopy and SYTO9/PI staining.Combined antimicrobial effect of pimozide and other antimicrobial agents was detected by chessboard dilution method,and cytotoxicity of pimozide was detected by CCK-8 assay kit.A model of skin abscess was constructed,in vivo antimicrobial activity and toxicity of pimozide was tested.Results Pimozide showed significant dose-dependent antimicrobial activity against S.aureu,with a MIC of 8-16 μg/mL.It could significantly inhibit the formation of S.aureu biofilm and disperse the formed biofilm.The combination of pimozide and doxycycline has a synergistic antimicrobial effect in vitro,with a synergistic antimicrobial index of 0.5.It can significantly reduce the bacterial load in mouse abscess tissue in vivo,and reduce the live bacterial count from(8.25±0.13)lgarithmic value of CFU/abscess to(3.31± 0.81)logarithmic value of CFU/abscess(q=3.74,P＜0.05).The cytotoxicity of pimozide was extremely low,with a half inhibitory concentration of 64 μg/mL on cells.Conclusion Pimozide exhibits significant antimicrobial activity in vitro and in vivo with extremely low toxicity,thus is promising for the treatment of S.aureu-related local infection in psychiatric patients.

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.
Adult ; Animals ; Humans ; Brain/physiopathology* ; Hippocampus/physiopathology* ; Mammals/physiology* ; Neurogenesis/physiology* ; Brain Hemorrhage, Traumatic/therapy* ; Ischemic Stroke/therapy* ; Recovery of Function ; Spinal Cord/physiopathology*

This study aimed to investigate the relationship between the promoting effect of Zuogui Pills on ovarian and vaginal angiogenesis in early-aging rats and mobilization factors granulocyte-macrophage colony-stimulating factor(GM-CSF), stromal cell-derived factor-1(SDF-1), and their receptors of endothelial progenitor cells(EPCs) and explore the mechanism of Zuogui Pills in improving reproductive hypofunction in early-aging rats. Ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) was used to analyze the chemical components of the extract of Zuogui Pills. Forty 14-month-old female early-aging rats with estrous cycle disorder were randomly divided into a blank group, a conjugated estrogen group(conjugated estrogen suspension, 65 μg·kg~(-1)), and low-(11 g·kg~(-1)) and high-dose(33 g·kg~(-1)) Zuogui Pills groups, with 10 rats in each group. In addition, 10 4-month-old female rats were assigned to the youth control group. The rats in the blank group and the youth control group were treated with 20 g·kg~(-1) distilled water by gavage, while those in the groups with drug intervention were treated with corresponding drugs by gavage, once a day for 15 days. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of SDF-1 and GM-CSF in the mobilization of EPCs in serum. Hematoxylin-eosin(HE) staining was used to observe the changes in the number of ovarian follicles at all levels and corpus luteum, the number of vaginal epithelial layers, the number of vaginal folds, and the blood vessels of ovarian and vaginal tissues in the groups with drug intervention. Western blot was used to detect the expression of ER, GM-CSFR, CXCR4, and CXCR7 proteins in ovarian and vaginal tissues. As revealed by the results, the blank group showed decreased number of corpus luteum, gro-wing follicles at all levels, and blood vessels(P<0.05), decreased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal folds, and the number of vessels in the lamina propria(P<0.05), reduced content of SDF-1 and GM-CSF in the peripheral blood(P<0.05), and down-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P<0.05). The groups with drug intervention showed increased number of growing follicles at all levels, corpus luteum, and blood vessels(P<0.05), decreased number of atresia follicles(P<0.05), increased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal mucosal folds, and the number of blood vessels in the lamina propria(P<0.05), increased content of SDF-1 and GM-CSF in the peripheral blood(P<0.05), and up-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P<0.05). This experiment suggests that Zuogui Pills may promote ovarian and vaginal angiogenesis and improve the reproductive function of early-aging rats by up-regulating the levels of mobilization factors SDF-1, GM-CSF, and their receptors of EPCs.
Rats ; Female ; Animals ; Granulocyte-Macrophage Colony-Stimulating Factor ; Estrogens, Conjugated (USP) ; Tandem Mass Spectrometry ; Aging ; Genitalia

Objective: To explore the impact of health management measures for entry personnel (entry management measures) against COVID-19 on the epidemiological characteristics of imported Dengue fever in Guangdong Province from 2020 to 2022. Methods: Data of imported Dengue fever from January 1, 2016 to August 31, 2022, mosquito density surveillance from 2016 to 2021, and international airline passengers and Dengue fever annual reported cases from 2011 to 2021 in Guangdong were collected. Comparative analysis was conducted to explore changes in the epidemic characteristics of imported Dengue fever before the implementation of entry management measures (from January 1, 2016 to March 20, 2020) and after the implementation (from March 21, 2020 to August 31, 2022). Results: From March 21, 2020, to August 31, 2022, a total of 52 cases of imported Dengue fever cases were reported, with an imported risk intensity of 0.12, which were lower than those before implementation of entry management measures (1 828, 5.29). No significant differences were found in the characteristics of imported cases before and after implementation of entry management measures, including seasonality, sex, age, career, and imported countries (all P>0.05). 59.62% (31/52) of cases were found at the centralized isolation sites and 38.46% (20/52) at the entry ports. However, before implementation of entry management measures, 95.08% (1 738/1 828) of cases were found in hospitals. Among 51 cases who had provided entry dates, 82.35% (42/51) and 98.04% (50/51) of cases were found within seven days and fourteen days after entry, slightly higher than before implementation [(72.69%(362/498) and 97.59% (486/498)]. There was significant difference between the monthly mean values of Aedes mosquito larval density (Bretto index) from 2020 to 2021 and those from 2016 to 2019 (Z=2.83, P=0.005). There is a strong positive correlation between the annual international airline passengers volume in Guangdong from 2011 to 2021 and the annual imported Dengue fever cases (r=0.94, P<0.001), and a positive correlation also existed between the international passenger volume and the annual indigenous Dengue fever cases (r=0.72, P=0.013). Conclusions: In Guangdong, the entry management measures of centralized isolation for fourteen days after entry from abroad had been implemented, and most imported Dengue fever cases were found within fourteen days after entry. The risk of local transmission caused by imported cases has reduced significantly.
Animals ; Humans ; COVID-19 ; Aedes ; Epidemics ; China/epidemiology* ; Dengue/epidemiology*