Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

Objective:To explore the RH genotype for a female with RhD(-) blood type and its molecular basis. Methods:A 26-year-old female who had attended the outpatient clinic of the First Affiliated Hospital of Zhengzhou University in August 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents for Rh phenotyping with gel card method. PCR-sequence-based typing (PCR-SBT) and DNA sequencing were used to determine the RHD zygosity and RH genotype of the proband and her parents. Homology modeling of Rh proteins was performed with bioinformatic software, and protein structural alterations caused by the variant was simulated by molecular dynamics. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2023-KY-0870-003). Results:Serological tests showed that the proband and her father both had weakened e antigen of the Rh phenotype. PCR-SBT and DNA sequencing showed that the genotypes of the proband and her parents were dce/ dCE, dce/ DcE and dCE/ DcE, respectively. And the genotypes of the RHD and RHCE of the proband were RHD*01N.01/ RHD*01N.16, RHCE*01.01/RHCE*04, respectively. Protein simulation and molecular dynamics analysis revealed that the ce_16C variant resulted from RHCE* ce (c.48G>C) may alter the structure of intracellular and extracellular loops, mainly affecting the mobility of extracellular loops 2, 6 and intracellular loops 3, 4. Conclusion:Variant of the RHCE* ce allele c. 48G>C probably underlay the weakened e antigen in this proband.

Objective To explore the expression of homeobox gene-A7(HOXA7)in glioma tissue and its effect on proliferation and apoptosis of glioma cells.Methods A total of 46 glioma specimens removed during neurosurgery and 10 normal brain tissues surgically removed from craniocerebral trauma in the Department of Neurosurgery of the First Affiliated Hospital of Xinxiang Medical University from September 2010 to August 2016 were selected.The relative expression of HOXA7 mRNA in glioma tissue and normal brain tissue was examined by real-time quantitative polymerase chain reaction.U251 cells in the logarithmic growth phase were randomly divided into the blank control group,the nonsense sequence control group and the HOXA7 siRNA group.The U251 cells in the blank control group were not transfected,the U251 cells in the nonsense sequence control group were transfected with scrambled small interfering RNA(siRNA),and the U251 cells in the HOXA7 siRNA group were transfected with HOXA7 siRNA.The expression of HOXA7 mRNA in U251 cells in the three groups was measured by using the real-time quantitative polymerase chain reaction,the proliferation activity of U251 cells in the three groups was detected by using the cell counting kit-8 assay,and the cell cycle and apoptosis rate of U251 cells in the three groups were detected by using the flow cytometry.Results The relative expression of HOXA7 mRNA in high-grade glioma was significantly higher than that in the low-grade glioma and normal brain tissue,and the relative expression of HOXA7 mRNA in low-grade glioma was significantly higher than that in normal brain tissue(P＜0.05).The relative expression of HOXA7 mRNA in U251 cells in the HOXA7 siRNA group was significantly lower than that in the blank control group and the nonsense sequence control group(P＜0.05).There was no statistically significant difference in the relative expression of HOXA7 mRNA in U251 cells between the blank control group and the nonsense sequence control group(P＞0.05).At 24,48,72,and 96 hours of culture,the proliferation activity of U251 cells in the HOXA7 siRNA group was significantly higher than that in the blank control group and the nonsense sequence control group(P＜0.01);and there was no significant difference in the proliferation activity of U251 cells between the blank control group and the nonsense sequence control group(P＞0.05).The proportion of U251 cells in the G0/G1 phase in the HOXA7 siRNA group was significantly higher than that in the blank control group and the nonsense sequence control group(P＜0.05),and there was no significant difference in the proportion of U251 cells in the G0/G1 phase between the blank control group and the nonsense sequence control group(P＞0.05).The proportion of U251 cells in the S phase in the HOXA7 siRNA group was significantly lower than that in the blank control group and the nonsense sequence control group(P＜0.05),and there was no significant difference in the proportion of U251 cells in S phase between the blank control group and the nonsense sequence control group(P＞0.05).The proportion of U251 cells in the G2/M phase in the HOXA7 siRNA group was significantly higher than that in the blank control group and the nonsense sequence control group(P＜0.05),and there was no significant difference in the proportion of U251 cells in the G2/M phase between the blank control group and the nonsense sequence control group(P＞0.05).The apoptosis rate of U251 cells in the HOXA7 siRNA group was significantly higher than that in the blank control group and the nonsense sequence control group(P＜0.05),and there was no significant difference in the apoptosis rate of U251 cells between the blank control group and the nonsense sequence control group(P＞0.05).Conclusion HOXA7 is highly expressed in glioma tissues,and its expression significantly increases with the glioma grade.HOXA7 may be involved in the occurrence and development of glioma by promoting the proliferation of glioma cells and inhibiting the apoptosis of glioma cells.

Objective:To explore the risk factors of perioperative outcomes of lung transplantation and establish a predictive model for delayed extubation after lung transplantation.Methods:From January 1, 2020 to December 31, 2022, 104 lung transplantation recipients were retrospectively collected to identify the risk factors of early post-operative outcome.According to the timing of extubation post-lung transplantation, they were assigned into two groups of normal(77 cases)and delayed(27 cases). Baseline profiles, type of primary diagnosis, cold ischemic duration and lung transplantation approach were compared between two groups.The factors with significant difference were examined by univariate and multivariate Logistic regression.Furthermore, multivariate logistic model was visualized by a nomogram.Receiver operating characteristic(ROC)curve and decision curve analysis(DCA) were performed for evaluating the model's predictive performance and its value for clinical utilization.Results:The postoperative mortality rate was 9.6%.Delayed extubation was a strong predictor for postoperative mortality.Cold ischemic time outperformed others variates in terms of delayed extubation prediction.AUC of cold ischemic time and multivariate logistic model was 0.75(95% CI: 0.69-0.81)and 0.87(95% CI: 0.82-0.91). Conclusions:Delayed postoperative extubation is a key predictor of early post-lung transplantation mortality.The established predictive model may effectively identify high-risk patients for preventive intervention and survival improvement post-lung transplantation.

Alcoholic liver disease(ALD)is the most frequent liver disease worldwide,resulting in severe harm to personal health and posing a serious burden to public health.Based on the reported antioxidant and anti-inflammatory capacities of scutellarin(SCU),this study investigated its protective role in male BALB/c mice with acute alcoholic liver injury after oral administration(10,25,and 50 mg/kg).The results indicated that SCU could lessen serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels and improve the histopathological changes in acute alcoholic liver;it reduced alcohol-induced malondialdehyde(MDA)content and increased glutathione peroxidase(GSH-Px),catalase(CAT),and superoxide dismutase(SOD)activity.Furthermore,SCU decreased tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1β messenger RNA(mRNA)expression levels,weakened inducible nitric oxide synthase(iNOS)activity,and inhibited nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome activation.Mechanistically,SCU suppressed cytochrome P450 family 2 subfamily E member 1(CYP2E1)upregulation triggered by alcohol,increased the expression of oxidative stress-related nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)pathways,and suppressed the inflammation-related degradation of inhibitor of nuclear factor-κB(NF-κB)-α(IκBα)as well as activation of NF-κB by mediating the protein kinase B(AKT)and p38 mitogen-activated protein kinase(MAPK)pathways.These findings demonstrate that SCU protects against acute alcoholic liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and suppressing inflammation by regulating the AKT,p38 MAPK/NF-κB pathways.

Drinking culture has high significance in both China and the world, whether in the entertainment sector or in social occasions; according to the World Health Organization's 2018 Global Alcohol and Health Report, about 3 million people died from excessive drinking in 2016, accounting for 5.3% of the total global deaths that year. Oxidative stress and inflammation are the most common pathological phenomena caused by alcohol abuse (Snyder et al., 2017). Scutellarin, a kind of flavonoid, is one of the main active ingredients extracted from breviscapine. It exerts anti-inflammatory, antioxidant, and vasodilation effects, and has been used to treat cardiovascular diseases and alcoholic liver injury. Although scutellarin can effectively alleviate multi-target organ injury induced by different forms of stimulation, its protective effect on alcoholic brain injury has not been well-defined. Therefore, the present study established an acute alcohol mice brain injury model to explore the effect of scutellarin on acute alcoholic brain injury. The study was carried out based on the targets of oxidative stress and inflammation, which is of great significance for the targeted therapy of clinical alcohol diseases.
Animals ; Apigenin/therapeutic use* ; Brain Injuries/drug therapy* ; Glucuronates/therapeutic use* ; Humans ; Mice ; Oxidative Stress

Based on the experimental teaching reform of health information management courses in Capital Medical University, this paper has explored the paths of experimental teaching suitable for the health management profession and provided suggestions for the teaching reform. The research was carried out in three stages. In the first stage, the needs of experimental teaching of health information management course were investigated. In the second stage, the experimental teaching practice was carried out based on the hospital information system platform. In the third stage, the experimental teaching effect was evaluated. The results showed that medical undergraduates have a great demand for the experimental teaching of the course. The experimental teaching method can greatly improve the interest of students in learning. The experimental teaching effect is good, and it is helpful to improve the students' practical ability and logical analysis ability. Furthermore, it is necessary and feasible to introduce experimental teaching into the specialty of health management, and better teaching effects will be achieved by closely combining the teaching reform practice with hardware and software configuration, personnel quality training and management.

Objective:To explore the effects and molecular mechanisms of ginsenoside Rg1 on the expression of neuronal autophagosome-related proteins in a rat model of Alzheimer's disease(AD).Methods:Six-week-old SD rats were decapitated to prepare hippocampal brain slices.The slices were randomly divided into the blank control group, the model group, the low-concentration, medium-concentration and high-concentration Rg1 groups, with 10 in each group.In the model group, Aβ 1-42(final concentration: 5 μmol/L)was added into an artificial cerebrospinal fluid(CSF)for 2 h treatment.The low-concentration, medium-concentration and high-concentration Rg1 groups were treated with Aβ 1-42(final concentration: 5 μmol/L)for 2 h, and then treated with Rg1(final concentrations: 60 μmol/L, 120 μmol/L, 240 μmol/L, respectively)for 3 h. The blank control group was not given any intervention drugs.At the end of intervention, histological changes of hippocampal brain slices in each group were examined via hematoxylin-eosin(HE)staining.Autophagosomes in hippocampal brain slices of each group were detected using transmission electron microscopy.The expression levels of autophagy-related proteins(P62, LC3-Ⅱ/LC3-Ⅰ), Aβ 1-42and shank protein in hippocampal brain slices of each group were detected with Western blot. Results:The results of HE staining showed that the arrangement of hippocampal neurons were disordered in the model group, with death and depletion of neurons.The arrangement and depletion of hippocampal neurons in each Rg1 group were less severe compared with the model group, with most significant improvement seen in the high-concentration Rg1 group.The results of transmission electron microscopy showed that the number of autophagosomes in brain slices in the model group was significantly higher than that in the blank control group, while each Rg1 group had fewer autophagosomes than the model group.The results of Western blot showed that, compared with the blank control group, levels of Shank1, P62 and LC3-Ⅰ proteins in brain slices were decreased(all P<0.05), while levels of Aβ 1-42and LC3-Ⅱ protein were significantly increased(all P<0.05)in the model group.Compared with the model group, levels of Shank1, P62 and LC3-Ⅰ proteins in brain slices were increased(all P<0.05), while levels of Aβ 1-42and LC3-Ⅱ protein were decreased( P<0.05)in each Rg1 group.These changes were the most significant in the high-concentration Rg1 group. Conclusions:Ginsenoside Rg1 may inhibit autophagy by up-regulating the expression of Shank1, P62 and LC3-Ⅰ proteins in hippocampal brain slices of rats in the AD model, thus playing protective roles in brain neurons.

Objective:To investigate the variation characteristics and influencing factors of HIV/AIDS subtypes in Wuxi city of Jiangsu Province from 2014 to 2016.Methods:HIV/AIDS population in Wuxi city in 2014 was selected as the research object, and the HIV molecular epidemiology and follow-up study were carried out. Collect epidemiological information, extract DNA from blood samples, amplify pol gene fragment by nest-PCR and sequence, use ChromasPro 1.6 software and MEGA 7.0 software to construct the HIV-1 sequence database, and use FastTree2.1.10 software to construct the phylogenetic tree to confirm the subtype; in 2016, the same population was followed up, and the HIV subtype variation was analyzed, and the influencing factors of subtype variation were explored by multivariate logistic regression. Results:A total of 612 HIV/AIDS cases in 2014 and 2016 were collected. The age of the subjects was mainly 30 years old or above (85.46%, 523/612), and the proportion of people over 50 years old was higher (228/612, 37.25%). The main route of transmission was homosexuality, accounting for 49.67%. A total of 1224 samples were detected and CRF01 _ AE、CRF07_ BC、B、CRF08_ BC、CRF67_ 01B、CRF55_ 01B、CRF68_ 01B, 7 subtypes of HIV-1 and 5 unique recombinant types (URFs) was detected. CRF01_ AE and CRF07_ BC was still the main genotype in Wuxi, Jiangsu Province, accounting for 66.75%. There were 29 cases (3.56%) of URFs recombinant strains. During 2014-2016, the variation rate of subtypes was 14.63%, and the most common variation was CRF01_ AE changes to CRF07_ BC(13.95%). Marital status (OR=0.363, 95% CI: 0.137-0.964) and baseline CD4 level (OR=0.414, 95% CI: 0.192-0.891) were associated with subtype variation.Conclusions:The HIV-1 subtypes of HIV/AIDS patients in Wuxi city are diverse and complex, the proportion of recombinant subtypes is rising, the URFs that are difficult to determine the genotype increase significantly, and the variation rate of HIV-1 subtypes among HIV/AIDS infected people is high. It is necessary to strengthen the monitoring of HIV-1 subtypes.