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 analyze the influencing factors of the success of clinical pregnancy in secondary infertility patients undergoing in vitro fertilization-embryo transfer(IVF-ET)and construct a nomogram prediction model.Methods A retrospective analysis was conducted on the clinical data of 235 patients with secondary infertility who underwent IVF-ET at Urumqi Maternal and Child Health Hospital from January 2020 to December 2023.They were divided into successful pregnancy group(n=109)and failed pregnancy group(n=1 26)based on whether clinical pregnancy was successful.The general information,ovulation induction data and embryo data of two groups of patients were compared.Multivariate Logistic regression analysis was used to screen out statistically significant indicators,and based on this,a nomogram prediction model was constructed.The receiver operating characteristic curve,calibration curve and decision analysis curve were drawn to verify the discrimination,accuracy and clinical practicability of the model.Results The results of multivariate Logistic regression analysis showed that the female's age,overweight and obesity were all risk factors for clinical pregnancy failure,while anti-Müllerian hormone(AMH)and the total amount of gonadotropins(Gn)were protective factor for clinical pregnancy outcomes.On this basis,a nomogram prediction model was successfully constructed,which has a medium degree of discrimination,good accuracy and clinical practicability.Conclusion For secondary infertility patients undergoing IVF-ET,the female's age,overweight and obesity,AMH,and the total amount of Gn have certain influences on clinical pregnancy.The clinical pregnancy outcome can be predicted through the constructed nomogram prediction model.

As a third major discipline on par with internal medicine and surgery,interventional radiology is one of the key branches of modern medicine.The unique practicality and innovation of interventional radiology make it play an irreplaceable role in the diagnosis and treatment of diseases.In recent years,with the rapid development of technology and the updating of educational concepts,the teaching mode of interventional radiology is facing new challenges and opportunities.This article combines the clinical training methods adopted by interventional physicians in Europe and Germany,integrates imaging,anatomy and pathology teaching,strengthens the foundation,uses virtual reality(VR),augmented reality(AR)technology,and simulation training to enhance the practical ability of medical students.At the same time,with the help of online education platforms,the innovative methods and optimization strategies such as personalized learning program are implemented,which can greatly improve the teaching effectiveness of interventional radiology and provide useful references for teaching reform in this field.

Objective To analyze the influencing factors of the success of clinical pregnancy in secondary infertility patients undergoing in vitro fertilization-embryo transfer(IVF-ET)and construct a nomogram prediction model.Methods A retrospective analysis was conducted on the clinical data of 235 patients with secondary infertility who underwent IVF-ET at Urumqi Maternal and Child Health Hospital from January 2020 to December 2023.They were divided into successful pregnancy group(n=109)and failed pregnancy group(n=1 26)based on whether clinical pregnancy was successful.The general information,ovulation induction data and embryo data of two groups of patients were compared.Multivariate Logistic regression analysis was used to screen out statistically significant indicators,and based on this,a nomogram prediction model was constructed.The receiver operating characteristic curve,calibration curve and decision analysis curve were drawn to verify the discrimination,accuracy and clinical practicability of the model.Results The results of multivariate Logistic regression analysis showed that the female's age,overweight and obesity were all risk factors for clinical pregnancy failure,while anti-Müllerian hormone(AMH)and the total amount of gonadotropins(Gn)were protective factor for clinical pregnancy outcomes.On this basis,a nomogram prediction model was successfully constructed,which has a medium degree of discrimination,good accuracy and clinical practicability.Conclusion For secondary infertility patients undergoing IVF-ET,the female's age,overweight and obesity,AMH,and the total amount of Gn have certain influences on clinical pregnancy.The clinical pregnancy outcome can be predicted through the constructed nomogram prediction model.

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.

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.

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.

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