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 safety and feasibility of uni-portal video-assisted thoracic surgery (VATS) for the treatment of bronchopulmonary sequestration (BPS). Methods    The clinical data of BPS patients with surgical resection in Shanghai Pulmonary Hospital from February 2010 to June 2021 were reviewed. The patients were divided into a VATS group and a thoracotomy group according to the operation method. The operation time, intraoperative blood loss, hospital stay and postoperative complication rate were compared between the two groups. The VATS group was subdivided into a uni-portal VATS group and a multi-portal VATS group for subgroup analysis. Results    Finally 131 patients were enrolled, including 62 males and 69 females with an average age of 39.3±13.2 years. There were 103 patients in the VATS group and 28 patients in the thoracotomy group. A total of 104 patients were diagnosed with left lower BPS, 26 with right lower BPS and 1 with bilateral lower BPS. The main symptom was cough (88 patients, 67.2%). There were 119 patients diagnosed by thoracic enhanced CT before operation. Compared with the thoracotomy group, the operation time was not statistically different (P=0.717), but the blood loss was less, the rate of postoperative complication was lower and hospital stay was shorter in the VATS group (P<0.05). The rate of conversion to open surgery in the uni-portal VATS group and multi-portal VATS group was 11.8% and 13.5%, respectively. Meanwhile, patients in the uni-portal VATS group had shorter operation time and postoperative hospital stay, less blood loss and lower postoperative complication rate than those in the multi-portal VATS group (P<0.05). Conclusion     In order to improve the rate of diagnosis, the lung enhanced CT scan should be selected as an optimal noninvasive method in adult suspected patients (especially those with solid cystic and solid lesions in the lower lobe). Uni-portal VATS is a safe and feasible method for BPS which can be widely promoted.

Objective To explore the expression of the CENP-W in gliomas and investigate the effects of its invasion. Methods The expression level of the CENP-W in gliomas with varied pathologic grade were detected by immunohistochemical analysis,RealTime PCR,and Western Blotting. U251 cells were transfected with the specific siRNA to repress the CENP-W expression level. The invasion ability of U251 cells were examined by Transwell Chamber assay ,while RAS mRNA and protein levels were detected at the same time. Results The expression levels of the CENP-W in glioma tissues were significantly high and the CENP-W gene could enhance the invasion of U251 cells . The expression of RAS was down-regulated when the expression of CENP-W was repressed. Conclusion The CENP-W has an oncogenic role in human brain gliomas and may regulate the invasion of gliomas by adjusting the RAS signaling pathways.

Objective To evaluate the apphcation value of peripheral blood neutrophil CD64 expression in early differential diagnosis of etiology in children with community-acquired pneumonia.Methods From June 2014 to June 2015 in our hospital,total of 99 cases of different pathogen infection were divided into three groups,bacterial pneumonia group (n =41),non-bacterial pneumonia group(n =38),healthy children group (n =20);and the non-bacterial pneumonia group was divided into two subgroups,viral pneumonia group (n =22) and mycoplasma pneumoniae pneumonia group(n =16).Flow cytometry was used to test the median fluorescence intensity (MFI) of peripheral blood neutrophil CD64.The levels of peripheral blood CRP,WBC and neutrophil percentage were detected.Results The levels of CD64 expression,CRP and WBC in bacterial pneumonia group were statistically higher than those of non-bacterial pneumonia group and healthy children group respectively (both P ＜ 0.01).The optimal cutoff value of CD64 was 6 519 MFI when using ROC curve,and the sensitivity and specificity of the diagnosis of bacterial pneumonia were 87.8％ and 89.7％ respectively.The levels of CD64 expression in bacterial pneumonia group were significantly higher than those in viral pneumonia group,mycoplasma pneumoniae pneumonia group and healthy children group (all P ＜ 0.01).Conclusion The expression of peripheral blood neutrophil CD64 increases in children with community-acquired pneumonia of bacteria infection.It can be used to guide early diagnosis of children with bacterial pneumonia and the using of antibiotics.

Objective To investigate the expression of CENP-W in gliomas and its relationship with clinicopathological parameters and prognosis and to explore the effects of centromere protein W (CENP-W)on the invasion of gliomas cells.Methods The expressions of CENP-W in high-grade glioma tissues,low-grade glioma tissues,and adjacent brain tissues were detected by real-time fluorescence quantitative PCR and Western blotting. The correlation of the expression of CENP-W with clinicopathological parameters and prognosis was analyzed statistically.Human gliomas U2 5 1 cells in vitro were transfected with small interfering RNA to downregulate the expression of CENP-W.The invasion and migration capabilities of gliomas cancer cells were assessed by Transwell assays.Results The expression level of CENP-W was significantly higher in glioma tissues than in normal tissues. There was a positive correlation between the three protein expression levels and the pathological grade of gliomas. CENP-W siRNA was successfully transfected into U2 5 1 cells.Compared with those of the cells transfected with the scramble siRNA and control cells,the invasive and migration activities were inhibited in the U2 5 1 cells transfected with CENP-W siRNA.The Kaplan-Meier analysis and Log-Rank test showed significant differences in progress free survival (PFS)between the CENP-W high-expression and low-expression groups.Conclusion The expression level of CENP-W was positively correlated with the pathological grade of gliomas and CENP-W can promote glioma cell invasion.It implicates that CENP-W can be a novel target in gliomas treatment.

ObjectiveTo investigate the effect of sorafenib and/or thalidomide on angiogenesis in chick chorioallantoic membrane (CAM). MethodsWhite eggs incubated for 7 days were used to establish a CAM model. The model eggs were randomly divided blank control group, sorafenib group, thalidomide group, and sorafenib/thalidomide group. After treatment, each egg was incubated for another 2 days. The CAM samples were collected and fixed to take their pictures under a microscope, and the vascular coverage of each sample was calculated. Comparison between these groups was made by analysis of variance, and comparison between each two groups was made by SNK-q test. ResultsThe thalidomide group or sorafenib group had significantly lower vascular coverage than the blank control group (30.2%±2.9% or 26.5%±2.1% vs 38.3%±2.7%, P＜0.05). The sorafenib/thalidomide group had significantly lower vascular coverage than the thalidomide group or sorafenib group (12.6%±1.5% vs 30.2%±2.9% or 26.5%±2.1%, P＜0.05). ConclusionBoth sorafenib and thalidomide have a good anti-angiogenic effect on CAM, but a combination of the two drugs shows better efficacy.

Objective To explore the expressions and correlation of RWD containing sumoylation enhancer (RSUME),small ubiquitin-like modifier (SUMO-1),hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor (VEGF)in gliomas of different pathologic grade.Methods We investigated the expression levels of RSUME mRNA,HIF-1α mRNA and VEGF mRNA with reverse transcription-polymerase chain reaction (RT-PCR),and investigated the immunohistochemical staining to determine the expressions of SUMO-1,HIF-1α and VEGF in 63 cases of human gliomas of different pathologic grade and 9 cases of normal brain tissues.We studied its correlation with the pathologic grade and the relationship between the expression of RSUME promoter sumoylation and HIF-1α/VEGF pathway in gliomas.Results There were significant differences (P <0.01)in the expressions of RSUME mRNA,HIF-1αmRNA and VEGF mRNA in glioma tissues.With the increasing degree of pathologic grade in tumor specimens,the expression levels of RSUME mRNA,HIF-1α mRNA and VEGF mRNA increased markedly (P <0.01 ).There was a positive correlation of the expression levels of RSUME mRNA with HIF-1αmRNA and VEGF mRNA.There were significant differences (P <0.01 )in the expressions of SUMO-1,HIF-1αand VEGF in glioma tissues by immunohistochemical staining.With the ascending of pathologic grade of tumor specimens,the expression levels of SUMO-1,HIF-1α and VEGF increased markedly (P < 0.01 ).There was a positive correlation between the expression level of SUMO-1 and HIF-1α(r =0.857,P <0.01).The Kaplan-Meier analysis and Log-rank test showed significant differences in progress free survival (PFS)between the RSUME high-expression and low-expression groups (χ2 =36.032,P <0.01).Conclusion RSUME may enhance HIF-1α/VEGF pathway through sumoylation in gliomas.It implicates that RSUME is related to angiogenesis in gliomas and can promote tumor invasion and progression,indicating that RSUME can be a novel target in gliomas treatment.

Objective The aim of this randomized,double-blind,placebo-controlled trial was to evaluate the efficacy of the Saccharomyces boulardii (S.boulardii) power in preventing antibiotic-associated diarrhea (AAD) in hospitalized children with pneumonia.Methods Two hundred and forty-five hospitalized children with pneumonia were randomly divided into two groups,group 1 treated with antibiotics and S.boulardii power (n =104),and group 2 with antibiotics and placebo,along with S.boulardii power and zinc when suffered from diarrhea (n =141).All children received montmorillonite powder and fluid replacement therapy for diarrhea.The stool frequency and consistency were observed.Diarrhea incidence,diarrhea and pneumonia duration of treatment,and therapeutic effect were recorded.Results AAD is more prevalent in group 2 than in group 1 (P ＜0.05).A 55.7％ relative risk reduction in AAD was seen in group 1 compared with group 2 (RR =0.443,95％CI 0.233 ～ 0.845,P =0.012).Patients with preventive treatment of S.boulardii power in broup 1 had lower AAD incidence compared with those in group 2 (P ＜ 0.05).Both the diarrhea and pneumonia duration of treatment in group 1 were shorter than that in group 2(P =0.001 for diarrhea duration,P =0.030 for pneumonia duration,respectively).No drug related adverse reactions were found during the observation period.Conclusion Preventive use of S.boulardii power may effectively reduce the risk of AAD,improve therapeutic effect,and shorten hospital stays for hospitalized children with pneumonia.

Objective To evaluate the effects of ambroxol on prevention of bronchopulmonary complications after thoracotomy in patients with chronic obstructive pulmonary disease(COPD).MethodsTotal 161 elderly patients aged ≥70 years with COPD undergoing thoracotomy were randomly allocated to two groups:ambroxol group (300 mg/d,6 d) and placebo group as control.Pulmonary complications were evaluated by clinical symptoms,radiographic changes,and blood gas analysis. Results The incidence rates of atelectasis were 8.6％ in ambroxol group and 28.8％ in placebo group,respectively.The PaO2 values after surgery in ambroxol group decreased more than in placebo group (P＜0.05) compared with the preoperative values.Side effects were not found in all patients.Conclusions Ambroxol should be considered as an alternative pharmacologic approach for the prevention of post-thoracotomy pulmonary complications in the elderly patients with COPD.

Objective To explore the relationship between methylenetetra hydrofolate reduetase (MTHFR) C677T genotypo and unstable angina pectoris(UA) in Chinese population. Methods The study consisted of 90 UA cases (UA group), and an age- and sex- matched healthy control cases (control group, n = 90). PC R-RFLP was used to analyze polymorphism of the MTHFR C677T genotypo. The relationship between MTHFR C677T genotype and UA was observed. Results MTHFR 677C→T mutation was found in 30 of 90 patients with unstable angina pectoris (33.33%) and in 15 of 90 control subjects (16.67%). This difference was statistically significant (P<0.05). Conclusion MTHFR 677C→T mutation is closely related to the unstable angina poctoris.