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 evaluate the noise hazard level of a coal mining enterprise, and identify high-risk operation types and people, and to provide a basis for preventing and controlling the health damage caused by noise. Methods A large coal mining enterprise in Shaanxi Province was selected as the research object. The noise monitoring data of the coal mine over the years was used to calculate the noise exposure matrix of each post in the enterprise, and the classification of occupational hazards at workplaces (GBZ/T 229.4-2012) was used to assess the occupational health risk levels. Results Among the 22 noise-exposed positions in the enterprise, the 8-hour working day equivalent sound level in positions of shearer driver, horseshoe driver, crusher driver, shuttle driver, relaxation screen driver, and grading screen driver were all higher than the occupational exposure limit of noise. In 2021, the noise exposure levels of shearer drivers, crusher drivers, and coal-selecting workers were all higher than 90 dB (A), and the occupational hazard level was moderate hazard level. In addition, the noise exposure levels of most other jobs also exceeded the occupational exposure limit. Conclusion The noise hazards in the coal mine industry are mainly concentrated in the posts of the coal mining system, tunneling system, and screening workshop. Among them, the shearer driver, the crusher driver, and the coal preparation workers have higher noise exposure levels. It is recommended to take corresponding noise reduction measures and strengthen the protection level to reduce the noise exposure risk of workers.

Objective:To validate and compare the value of the Status Epilepticus in Pediatric Severity Score (STEPSS) versus PEDSS in assessing the short-term prognosis of children with status epilepticus (SE).Methods:Clinical data of 152 children with SE hospitalized at the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were retrospectively analyzed.According to the STEPSS and PEDSS scores, children with SE were scored and their prognosis was predicted.Receiver operating characteristic (ROC) curves of the 2 scales in assessing the short-term prognosis of SE in children were plotted, and the area under the curve (AUC), optimal cut-off, sensitivity and specificity were calculated, thus validating and comparing the value of the STEPSS versus PEDSS in assessing the short-term prognosis of children with SE.Results:Of the 152 children with SE, 90 were male and 62 were female, with the age of (5.8±3.9) years (1 month to 15 years). There were 112 cases with good prognosis and 40 cases with poor prognosis, involving 13 deaths.The AUC of STEPSS and PEDSS scores in predicting the death in children with SE were 0.908(95% CI: 0.848-0.967) and 0.887(95% CI: 0.831-0.942), respectively, both with the optimal cut-off value of 4.The sensitivity of STEPSS and PEDSS scores in predicting the death in children with SE were 0.740 and 0.846, respectively, and the specificity were 0.745 and 0.835, respectively.There was no significant difference in predicting the death in children with SE between the 2 scales ( P>0.05). In predicting adverse outcomes, the AUC of the STEPSS and PEDSS scores were 0.869(95% CI: 0.800-0.937) and 0.926(95% CI: 0.873-0.979), respectively, both with the optimal cut-off value of 3.The sensitivity of STEPSS and PEDSS scores in predicting adverse outcomes in children with SE were 0.827 and 0.900, respectively, and the specificity were 0.732 and 0.866, respectively.There was significant difference in predicting the adverse outcomes in children with SE between the 2 scales ( P<0.05). Conclusions:Compared with the STEPSS, the PEDSS has a higher application in predicting the short-term treatment outcome of children with SE, which can be used as a routine method to assess the prognosis of children with SE.

AIM:To investigate the protective effect of total flavonoids from Patrina villosa Juss(PJF)on the lung in an experimental rat model of acute lung injury(ALI),and to elucidate the potential mechanism.METHODS:The ALI rat model was established by instilling 5 mg/kg of lipopolysaccharide(LPS)into the airway.Sixty male SD rats were randomly divided into 4 groups:control,LPS,LPS+low-dose PJF(receiving 100 mg/kg PJF one hour before ALI modeling)and LPS+high-dose PJF(receiving 300 mg/kg PJF one hour before ALI modeling).Each group consisted of 15 animals.Lung tissues and bronchoalveolar lavage fluid(BALF)were collected from all groups 24 h after modeling.For as-sessment of lung tissue morphology,HE staining was performed.The wet/dry weight ratio of the lung tissue was deter-mined using the wet/dry weighing method.Evans blue staining was conducted to assess epithelial barrier permeability in lung tissues.ELISA was used to detect the levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in the BALF,as well as oxidative stress markers including superoxide dismutase(SOD),myeloperoxi-dase(MPO)and glutathione peroxidase(GSH-Px)activity,and malondialdehyde(MDA)content in the lung tissue.The expression levels of C/EBP homologous protein(CHOP),glucose-regulated protein 78(GRP78)and X-box binding pro-tein 1(XBP1)in the lung tissue were analyzed by Western blotting.RESULTS:Compared with control group,the rats in LPS group exhibited a blurred alveolar structure with a significant infiltration of inflammatory cells.The ALI score and the wet/dry weight ratio of the lung tissue were increased(P<0.05).Concurrently,the levels of IL-6,IL-1β and TNF-α in the BALF,along with MDA content and MPO activity in the lung tissue,were elevated(P<0.05).Additionally,the pro-tein levels of CHOP,GRP78 and XBP1 were up-regulated in the lung tissue(P<0.05),while the SOD and GSH-Px activi-ty was significantly decreased(P<0.05).Compared with LPS group,PJF intervention exerted beneficial effects on the lung tissue morphology with reduced ALI score and lower lung wet/dry weight ratio(P<0.05).Moreover,the levels of IL-6,IL-1β and TNF-α in BALF,as well as MDA content,MPO activity and the protein levels of CHOP,GRP78 and XBP1 in the lung tissue were all significantly decreased(P<0.05),while the SOD and GSH-Px activity was significantly in-creased(P<0.05).The efficacy in high-dose group exceeded that in low-dose group.CONCLUSION:The PJF have pro-tective effect on the lungs of rats with ALI,and its mechanism may be related to the inhibition of inflammation,oxidative stress and endoplasmic reticulum stress.

Objective:To explore the psychological experience and demand of parents of children with delayed recovery after congenital heart disease surgery.Methods:This study adopted phenomenological research methods from qualitative research. Using the purposive sampling method, parents of postoperative delayed recovery children with congenital heart disease who met the inclusion criteria were selected as the research objects from October to November 2019 at Fuwai Hospital, Chinese Academy of Medical Sciences. Semi-structured interviews were conducted with the parents of the children, and the data were analyzed by Colaizzi 7-step analysis method.Results:Finally, 13 parents of children with delayed recovery after congenital heart disease surgery were included. According to the interview results, four themes were extracted, which were negative psychological experience of parents of children with delayed recovery, positive psychological experience and expectation change of parents, heavy economic burden of parents and diversified needs of parents.Conclusions:During the delayed recovery period, psychological experience of parents is complex and their needs are diverse. The nursing staff should identify and pay attention to the causes of the negative psychological experience of the parents of the children, timely channel their negative emotions and strengthen the positive psychological experience in many aspects. They can assist parents to seek social help to reduce physical and mental pressure and meet the diverse needs of parents by providing high-quality nursing services and multi-channel information support.

ObjectiveTo systematically evaluate the safety of interferon β-1a for treatment of corona virus disease 2019 （COVID-19）， and to provide references for interferon β-1a's clinical application. MethodsThis study was conducted with the database from US Food and Drug Administration adverse event reporting system （FAERS） from January 1， 2015 to March 31， 2021. Information component （IC） and reporting odds ratio （ROR） methods were applied for signal mining. ResultsA total of 463 700 records of COVID-19 were selected for analysis， and 45 positive drug adverse event signals were detected. Headache （IC₀₂₅=1.09， ROR₀₂₅=2.28）， pyrexia （IC₀₂₅=0.51， ROR₀₂₅=1.51） and multiple sclerosis relapse （IC₀₂₅=3.67， ROR₀₂₅=14.71） were positive adverse events with higher frequency. Autoimmune disorder （IC₀₂₅=4.42， ROR₀₂₅=24.03）， streptococcal infection （IC₀₂₅=4.12， ROR₀₂₅=19.82）， and multiple sclerosis relapse （IC₀₂₅=3.67， ROR₀₂₅=14.71） were positive adverse events. Acute lung injury， cardio-respiratory arrest and metabolic acidosis were associated with a higher proportion and frequency of death. ConclusionThere are certain safety issues with interferon β-1a in the treatment of COVID-19， and some adverse events with high frequency and high death rate deserve further attention by medical staffs.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.

Objective:To investigate the prevalence and predictors of delayed function independence (DFI) in patients with acute vertebrobasilar artery occlusion (VBAO) achieved successful recanalization after endovascular therapy.Methods:Patients with acute VBAO received endovascular treatment in the Departments of Neurology, the First Affiliated Hospital of University of Science and Technology and General Hospital of Eastern Theater Command, PLA from December 2015 to December 2018 were retrospectively enrolled. The demographic, clinical, laboratory and imaging data were collected. Early functional independence (EFI) was defined as the modified Rankin Scale score 0-2 at discharge, and DFI was defined as the modified Rankin Scale score 0-2 at 90 d after discharge for non-EFI patients. Multivariate logistic regression analysis was used to determine the independent predictors of DFI. Results:A total of 122 patients with acute VBAO were included. Their age was 61.8±11.9 years old and 91 (74.6%) were male. The median Glasgow Coma Scale (GCS) score was 7, the median National Institutes of Health Stroke Scale (NIHSS) score was 26.5, and the median posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) score was 9. Twenty-four patients (20.0%) had EFI; of the 98 patients with non-EFI, 18 (18.4%) had DFI. Multivariate logistic regression analysis showed that male (odds ratio [ OR] 0.038, 95% confidence interval [ CI] 0.002-0.658; P=0.025), cardiogenic embolism ( OR 0.116, 95% CI 0.023-0.579; P=0.009), baseline NIHSS score ( OR 1.136, 95% CI 1.040-1.242; P=0.005) and lung infection ( OR 6.089, 95% CI 1.451-25.562; P=0.014) were the independent predictors of DFI. Conclusions:Nearly 1/5 of the non-EFI patients have DFI. Male, cardiogenic embolism, lower baseline NIHSS score and without pulmonary infection are the independent predictors of DFI.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.