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 investigate the correlation between serum homocysteine(Hcy),hemoglobin(HGB)and hematocrit(HCT)levels and the severity of condition and inflammatory factor levels in patients with chronic atrophic gastritis.Methods A total of 122 patients with chronic atrophic gastritis admitted to a hospital from January 2022 to December 2023 were selected as the disease group,and the disease group was di-vided into mild group(n=63)and severe group(n=59)according to pathological grades,and 106 healthy volunteers who underwent physical examination in a hospital during the same period were selected as the con-trol group.Clinical data of patients were collected and binary Logistic regression analysis was performed to an-alyze the factors affecting the severity of patients'condition,and Pearson correlation analysis was used to ana-lyze the correlation between Hcy,HGB,HCT and the levels of inflammatory factors.Receiver operating char-acteristic(ROC)curve was drawn to analyze the diagnostic value of Hcy,HGB and HCT on the severity of patients'condition.Results Compared with the control group,the serum Hcy level in the diseased group was increased,the serum HGB and HCT levels were decreased,the difference was statistically significant(P<0.05).Compared with the mild group,the serum Hcy level in the severe group was increased,the HGB and HCT levels were decreased,and the difference was statistically significant(P<0.05).Compared with mild group,the levels of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in se-vere group were increased,and the levels of IL-10 were decreased,with statistical significance(P<0.05).Bi-nary Logistic regression analysis showed that Hcy and CRP were the risk factors affecting the severity of pa-tients'condition(P<0.05),and HCT,HGB and IL-10 were the protective factors affecting the severity of pa-tients'condition(P<0.05).Hcy was positively correlated with CRP,TNF-α and IL-6,and negatively correla-ted with IL-10(P<0.05).HGB and HCT were negatively correlated with CRP,TNF-α and IL-6,and posi-tively correlated with IL-10(P<0.05).ROC curve analysis showed that the area under the curve of serum Hcy,HGB,HCT and the combined diagnosis of the severity of patients'condition were 0.834,0.814,0.822 and 0.923,respectively,and the combined diagnosis value of the three was significantly better than that of Hcy(Z=2.519,P=0.012),HGB(Z=2.660,P=0.008)and HCT(Z=2.596,P=0.009)alone.Conclusion The increase of serum Hcy and the decrease of serum HGB and HCT in patients with chronic atrophic gastritis are correlated with the severity of the patient's condition and the level of inflammatory factors.The combined de-tection of the three can be used for the diagnosis of the severity of chronic atrophic gastritis.

Objective To explore the effect of tongue pressure resistance feedback training in the rehabilitation of dysphagia in patients with ischemic stroke(IS).Methods A total of 100 pa-tients with dysphagia after IS were randomly divided into control group(receiving conventional reha-bilitation therapy and oral motor training)and experimental group(receiving tongue pressure resist-ance feedback training on the basis of conventional rehabilitation therapy),with 50 patients in each group.The treatment duration was 4 weeks for both groups.During the study,3 patients dropped out due to personal reasons,and ultimately 49 patients in the control group and 48 patients in the experi-mental group completed the study.Before and after treatment,tongue muscle function was measured in both groups;videofluoroscopic swallowing studies(VFSS)were used to measure temporal and kinemat-ic parameters of swallowing;the Rosenbek Penetration-Aspiration Scale(PAS)was used to assess aspi-ration risk;the Stroke and Aphasia Quality of Life Scale(SWAL-QOL)was used to evaluate quality of life;and occurrence of complications in both groups were compared.Results After 4 weeks of treat-ment,peak tongue pressure,mean tongue pressure,and tongue pressure duration increased inboth groups,with these indicators being higher in the experimental group than in the control group;oral transit time,soft palate elevation time,and hyoid bone displacement time shortened,while upper esoph-ageal sphincter(UES)opening time and laryngeal closure time prolonged,hyoid and thyroid cartilage movement(upward and anterior displacement)and UES opening degree increased,and pharyngeal contractile ratio(PCR)decreased in both groups,with these indicators being superior in the experi-mental group compared to the control group;PAS scores decreased and SWAL-QOL scores increased in both groups,with PAS scores being lower and SWAL-QOL scores being higher in the experimental group compared to the control group;the differences between the two groups in the aforementioned indicators were statistically significant(P＜0.05).The complication rate was 4.17％(2/48)in the experimental group and 10.20％(5/49)in the control group,with no statistically significant difference(P＞0.05).Conclusion Tongue pressure resistance feedback training can improve tongue function and swallowing function,effectively reduce the risk of aspiration after swallowing,and enhance the quality of life of patients with dysphagia after IS during their rehabilitation treatment.

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

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.

【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.

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.