ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

Objective This study investigated the impact of occupational mercury(Hg)exposure on human gene transcription and expression,and its potential biological mechanisms. Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation.Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells.PTEN gene expression was assessed using qRT-PCR,and Western blotting was used to measure PTEN,AKT,and PI3K protein levels.IL-6 expression was determined by ELISA. Results Combined findings from gene expression microarray analysis,bioinformatics,and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group.In the Hg-exposed cell model(25 and 10 μmol/L),a significant decrease in PTEN expression was observed,accompanied by a significant increase in PI3K,AKT,and IL-6 expression.Similarly,a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K,AKT,and IL-6 levels. Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene,activates the PI3K/AKT regulatory pathway,and increases the expression of inflammatory factors,ultimately resulting in kidney inflammation.

This study was aimed at understanding the genome-wide characterization and variations for three imported novel coronavirus(SARS-CoV-2)strains from different sources in the same period in Jinan at the viral genome level,to provide a sci-entific basis for further improving the prevention and control of COVID-19 outbreaks at Jinan port.We selected nasal and pha-ryngeal swab samples from three cases of imported asymptomatic COVID-19infectionat Jinan port;performed second-genera-tion whole-genome sequencing;and analyzed the variant loci and homology withvarious bioinformatics software.The whole ge-nome sequence of SARS-CoV-2 was successfully obtained from three samples of asymptomatic infected cases,and had full lengths ranging from 29 835 bp to 29 844 bp.Pangolin typing results indicated that the genotypes of the three samples were O-micron BQ.1,BQ.1.1,and BQ.1.12.Compared with the original Wuhan strain,the three samples produced mutations at 77,80,and 78 base sites,respectively,involving 60-63 non-synonymous mutations,mainly in the S and ORF1ab genes.Omicron BQ.1 is an imported variant of the SARS-CoV-2 virus and was detected for the first time at Jinan port.From a molecular biolo-gy perspective,this study provides a theoretical basis for the source tracing and prevention and control of COVID-19 at theport.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Objective:To explore the influencing factors of HIV-1 DNA and its clinical value.Methods:The relationship between HIV-1 DNA and CD4 + T cell count, CD4/CD8, HIV viral load and subtype was analyzed in 304 patients with HIV/AIDS in order to explore the factors affecting HIV-1 DNA and the value of clinical application. Results:There was no statistically significant difference in HIV-1 DNA levels between the different CD4 + T cell level groups (Z=1.194, P>0.05). HIV-1 DNA levels were higher in the CD4/CD8≤0.5 group than in the CD4/CD8>0.5 group (Z=-2.788, P<0.01). HIV-1 DNA levels were higher in the HIV viral load >100 copies/ml group than in the ≤100 copies/ml group (Z=-2.953, P<0.01). HIV-1 DNA levels were higher in those with CD4 + T cell counts ≤200 at diagnosis than in those with CD4 + T cell counts >200 at diagnosis (Z=-2.175, P<0.05). HIV-1 DNA levels were higher in patients with CD4/CD8 ≤0.2 at diagnosis than in those with CD4/CD8 between 0.2 and 0.5, but there was no significant difference between the two groups (Z=-0.893, P>0.05). HIV-1 DNA levels were higher in both groups than in the CD4/CD8≥0.5 group (Z=-2.568, Z=-1.960, P<0.05). Higher HIV-1 DNA levels were found in people with an HIV viral load >100, 000 copies/ml at diagnosis than in people with an HIV viral load ≤100, 000 copies/ml at diagnosis (Z=-3.520, P<0.001). The level of HIV-1 DNA was higher in the CRF01_AE group than in the non-CRF01_AE group, and the difference was statistically significant (Z=-2.848, P<0.01). CD4/CD8 seemed to be a protective factor for HIV-1 DNA>500 copies/ml. (OR=0.214(95%CI: 0.056~0.822, P<0.05) Conclusion:CD4 + T lymphocyte count, CD4/CD8, viral load and subtype are factors that influence HIV-1 DNA levels, while HIV-1 DNA may be informative for immune status assessment and disease progression determination.

Reconstructed rebalanced hemostasis exists in patients with liver cirrhosis, while such balance is unstable and can be easily broken by stress factors, which may lead to bleeding or thrombosis. There is a lack of effective strategies to prevent and solve the disrupted balance in clinic due to the complex pathogenesis of rebalanced hemostasis, limited testing methods, and insufficient awareness among clinicians. With reference to the articles in recent years, this article summarizes the mechanism of rebalanced hemostasis in liver cirrhosis and the causes of bleeding and thrombosis and discuss the association between blood transfusion and rebalanced hemostasis and the selection of anticoagulant drugs during thrombosis, in order to provide a theoretical basis and new ideas for solving related issues in clinical practice.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Objective:To explore the clinical value of autoantibodies in patients with liver disease.Methods:We retrospectively analyzed the data of 1 495 outpatients or inpatients with liver disease in Beijing Ditan Hospital of Capital Medical University from August 2020 to April 2021. Indirect immunofluorescence and Western blot were used to detect antinuclear antibody (ANA) and antinuclear antibodies (ANAs).Results:ANA and ANAs were positive in patients with liver diseases of various etiologies. Among 1 495 patients with liver disease, 494 cases were ANA positive, the positive rate was 33.04%; 573 cases were positive for ANAs, the positive rate was 38.33%. The positive rate of ANA in the immune liver disease group (63.37%) was higher than that in the viral, alcoholic, fatty liver, confounding factors and other liver disease groups, and the difference was statistically significant ( P<0.01). The ANA positive rate between the viral, alcoholic, fatty liver, and confounding factor groups was statistically significant ( χ2=19.823, P<0.01), the positive rate of ANAs in the immune liver disease group (80.23%) was higher than that in other liver disease groups, and the difference was statistically significant ( P<0.05). The antibody titer of immune liver disease group was mainly 1∶1000, and other liver disease etiology groups was mainly 1∶100. The two most common fluorescent karyotypes in liver disease groups of different etiologies are cytoplasmic and nuclear granular types. The most common specific antibody in the immune liver disease group was anti-mitochondrial antibody type 2 (anti-AMA-M2) antibody, the most common anti-Ro-52 antibody in viral, drug-induced, complex etiology, and other etiological groups, and the most common anti-SSA antibody in alcoholic liver disease. Anti-SSA antibody (17.44%), anti-SSB antibody (9.30%), anti-CENP-B antibody (22.09%), anti-Ro-52 antibody (41.28%), anti-AMA-M2 antibody (51.74%) were positive in immune liver disease group, The rate was higher than that of other liver disease etiology groups, and the difference was statistically significant ( P<0.01). When the ANA fluorescence karyotype is nuclear granule type, the positive rate of anti-CENP-B antibody, anti-Ro-52 antibody, and anti-AMA-M2 antibody in the immune liver disease group was higher than that in the viral liver disease group ( P<0.01), The positive rate of anti-Ro-52 antibody was higher than that of drug-induced liver disease group ( P<0.05). Conclusions:The ANA titer of autoimmune liver disease was mainly (1∶1 000). ANAs were mainly positive for anti-SSA antibody, anti-SSB antibody, anti-CENP-B antibody, anti-Ro-52 antibody, and anti-AMA-M2 antibody, especially anti-AMA-M2 antibody. When combined with ANA fluorescent karyotype and ANAs for analysis, if the fluorescent karyotype is nuclear particle type, the positive anti-Ro-52 antibody in ANAs is more valuable in distinguishing immunity from viral and drug-induced liver diseases.

OBJECTIVE: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, CONCLUSIONS Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.
Beijing/epidemiology* ; Breast Feeding ; China/epidemiology* ; Communicable Diseases/epidemiology* ; Female ; Hospitalization ; Hospitals ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Male ; Pregnancy