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 role of metagenomic next-generation sequencing (mNGS) in the diagnosis of pathogens in primary infectious diseases of the spine (IDS) and to reveal its pathogen spectrum.Methods:This is a retrospective multi-center case series study. Clinical data of 380 patients with primary IDS who were treated at four medical centers in China from December 2019 to April 2024 were retrospectively analyzed. Among them, 82 cases were from the Department of Spine Surgery at the Affiliated Hospital of Qingdao University, 129 cases were from the Orthopedics Section Ⅱ (Bone Infection), Public Health Clinical Center Affiliated to Shandong University, 112 cases were from the Department of Spine Surgery, Fuzhou Second General Hospital, and 57 cases were from the Department of Orthopedic Surgery, Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. There were 238 males and 242 females, with an age of (61.4±13.1) years (range: 10 to 91 years). Specimens from the site of spinal infection were obtained for pathogen culture, pathological examination, and mNGS detection preoperatively or intraoperatively in all patients. The number, types, and positive rates of pathogens detected by the two methods were analyzed and compared using the Chi-square test.Results:Among the 380 patients, 320 had confirmed pathogenic bacteria, with the highest proportion being pyogenic bacterial infections, accounting for 76.9% (246/320). The most common pathogen was Staphylococcus aureus, accounting for 22.8% (73/320). Brucella accounted for 13.8% (44/320); Mycobacterium tuberculosis accounted for 6.3% (20/320). Fungal infections accounted for 3.4% (11/320), mainly Aspergillus and Candida. In addition, Mycoplasma was detected in 3 cases (0.9%) and Benacox body in 4 cases (1.2%). The pathogen spectrum constructed by mNGS covered 46 types of pathogens, higher than the 22 types detected by traditional methods. The positive rate of mNGS was 80.8% (308/381), significantly higher than the 27.9% (106/381) of traditional methods ( χ2=182.53, P<0.01). Conclusions:mNGS improves the positive rate of pathogen diagnosis in IDS, detecting a broader spectrum of pathogens, and serves as a valuable complement to traditional diagnostic methods. Combining both methods in the diagnosis of IDS can maximize detection rates, providing robust evidence for precise anti-infective treatment.

Gastric Precancerous Lesions(GPL)have the risk of developing gastric cancer,and Spasmolytic Polypeptide Expressing Metaplasia(SPEM)is the initial step of GPL,which has the risk of malignant progression to gastric precancerous lesions.Currently,the exploration of the pathogenesis during this metaplasia stage remains incomplete.Traditional Chinese Medicine(TCM),relying on its solid theoretical foundation and abundant resources of Chinese medicinal materials,possesses unique advantages in the prevention and treatment of GPL.Based on the theory of"spleen deficiency and evil stagnation",we conducts microcosmic syndrome differentiation analysis from the pathophysiological state,markers,and signal pathways of the disease,and proposes to invigorate the spleen and remove blood stasis.The detoxification method is used for treatment,and its feasibility is analyzed in combination with the literature,in order to provide new ideas and strategies for the TCM treatment of SPEM.

Objective:To investigate the application value of a multi-dimensional digital moni-toring platform for perioperative period in gastric cancer patients.Methods:The retrospective cohort study was conducted. The clinical data of 50 patients who underwent laparoscopic radical gastrec-tomy in The Affiliated Hospital of Nanjing University of Chinese Medicine from July 2022 to January 2024 were collected. There were 35 males and 15 females, aged (64±12)years. All patients followed the concept of enhanced recovery after surgery, and the multi-dimensional digital monitoring platform based on wearable monitoring equipment was used to implement perioperative management measures. Observation indicators: (1) results of heart rate variability (HRV) monitoring; (2) results of blood glucose and blood oxygen monitoring; (3) results of exercise and sleep monitoring; (4) results of body composition monitoring. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR). Repeated measurement data were analyzed using the repeated ANOVA. Measurement data with skewed distri-bution were transformed to normal distribution by SPSS transformation function before testing. For comparison between pre- and postoperation, paired sample t test was used for measurement data with normal distribution, and nonparametric Wilcoxon signed rank sum test was used for measure-ment data with skewed distribution. Results:(1) Results of HRV monitoring. From preoperation to the third day after surgery, the standard deviation normal to normal heart beat of 50 patients was changed from(103±26)ms to(101±36)ms, the mean of the standard deviations of normal to normal heart beat calculated per 5 min segment was changed from (45±16)ms to(33±12)ms, the number of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording was changed from 6.02%(4.96%) to 5.79%(4.20%), the low frequency power was changed from 376.78(468.96)ms 2 to 742.79(525.20)ms 2, the high frequency power was changed from 273.61(273.58)ms 2 to 397.48(164.87)ms 2, the ratio of low frequency power to high frequency power was changed from 1.6±0.5 to 1.6±0.6, showing significant differences in above indicators before and after operation ( F=34.43, 26.15, 24.58, 5.51, 6.11, 6.02, P<0.05). (2) Results of blood glucose and blood oxygen monitoring. From preoperation to the third day after surgery, the blood glucose of 50 patients was changed from 6.75(2.05)mmol/L to 6.90(2.63)mmol/L, showng a significant difference before and after operation ( F=45.84, P<0.05). The blood oxygen was changed from 97.00%(5.00%) to 97.50%(3.00%), showing no significant difference before and after operation ( F=2.25, P>0.05). (3) Results of exercise and sleep monitoring. From preoperation to the third day after surgery, the number of steps fo 50 pati-ents was changed from 3 043(1 224) to 1 473(767), sleep duration was changed from(8.2±1.1)hours to(7.3±0.8)hours, sleep score was changed from 80±10 to 78±5,showing significant differences in above indicators before and after operation ( F=716.46, 29.02, 47.32, P<0.05).(4) Results of body composition monitoring. The body weight of 50 patients was changed from (63±8)kg to(61±8)kg before and after operation, body fat rate was changed from 24%±8% to 22%±9%, muscle mass was changed from 43 (12)kg to 41(17)kg, body mass index was changed from (23.0±2.6)kg/m 2 to(22.1±2.5)kg/m 2, showing significant differences in above indicators before and after operation ( t=8.19, 3.00, Z=-2.78, t=7.34, P<0.05), while there was no significant difference in basal metabolic indicators from (1 390±134)kcal to (1 379±139)kcal before and after operation ( t=1.02, P>0.05). Conclusion:The multi-dimensional digital monitoring platform for preoperative period can accurately monitor the perioperative stress level and evaluate the postoperative recovery of gastric cancer patients, which can present the visual results.

Objective To investigate the clinical value of extracellular volume(ECV)based on CT delayed phase in combination with pathologic indicators in predicting early recurrence of gastric mesenchymal tumors after surgery.Methods A retrospective case-control trial was conducted on the imaging,clinical and pathological data of 110 patients with gastric mesenchymal tumors who were surgically resected at the First Affiliated Hospital of Army Medical University from January 2011 to August 2022.They were 60 males and 50 females,at a mean age of 58±10 years.All of them received preoperative multiphase dynamic CT enhancement examination of the abdomen,and ECV value was calculated with the formula:ECV=(1-hematocrit)×(△HU tumor/△HU aorta).According to the postoperative recurrence within 24 months after surgery,they were divided into early recurrence group and non early recurrence group.Statistical indexes:① Consistency analysis.② The factors affecting early recurrence after resection of gastric mesenchymal stromal tumors were analyzed and a prediction model was conducted.Delong test was used to assess the predictive value of the model.Then a nomogram was plotted based on the combines model,and calibration curves were drawn to assess the efficacy of the column charts,and decision curve analysis(DCA)was adopted to assess the value of the model for clinical application.Results ① Consistency analysis.After 2 radiologists outlined the region of interest and obtained ECV value according to the above formula,The intraclass correlation coefficient(ICC)was 0.806.② For the 110 subjected patients,21 cases of them had early recurrence,and 89 one did not.Multivariate analysis showed that ECV value,risk degree,and tumor length were independent influencing factors for predicting early recurrence.Receiver operating characteristic(ROC)curve analysis indicated that the area under the curve(AUC)value of ECV,hazard degree,and tumor length diameter in predicting early recurrence was 0.838(95％CI 0.758～0.918),0.774(95％CI 0.656～0.892),and 0.700(95％CI 0.589～0.810),respectively,and the value of their combined model was 0.899(95％CI 0.811～0.987),which was higher than that of each independent model.The sensitivity and specificity of the combined model was 85.71％and 86.52％,respectively,and the optimal cutoff value was 0.19.Delong test revealed that there was statistical difference between the combined model and the clinical model established by the hazard level(Z=6.548,P＜0.001,95％CI 0.140～0.259).Calibration curve analysis suggested that the combined model had a better fit,and DCA displayed that the combined model had a better net benefit.Conclusion The model established by ECV combined with pathological indicators has good predictive performance and can be used as a more effective predictor of early recurrence of gastric mesenchymal tumors after surgery.

Objective To investigate the serum levels of microRNA-146a(miR-146a)and soluble pro-grammed death ligand 2(sPD-L2)in children with Mycoplasma pneumoniae pneumonia(MPP)and to ana-lyze their relationship with disease severity and their predictive value for prognosis.Methods A total of 89 MPP patients diagnosed and treated in Linfen People's Hospital from February 2019 to June 2021 were includ-ed,and they were divided into severe group(50 cases)and mild group(39 cases)based on disease severity.Based on the prognosis of MMP patients,they were categorized into good prognosis group(70 cases)and poor prognosis group(19 cases).Moreover,50 healthy children who underwent physical examination at the same time were setected as the control group.Real-time fluorescence quantitative PCR was performed to assess the serum miR-146a levels in each group,while serum sPD-L2 levels were measured using the enzyme-linked im-munosorbent assay.Pearson correlation analysis was conducted to evaluate the relationship between serum miR-146a and sPD-L2 levels in children with MPP.Logistic regression analysis was performed to identify fac-tors influencing poor prognosis in children with MPP.The predictive efficacy of serum miR-146a and sPD-L2 for predicting the poor prognosis in children with MPP was assessed by receiver operating characteristic curve.Results The serum miR-146a levels decreased sequentially from the control group to the mild group and the severe group(P<0.05),while the sPD-L2 levels increased sequentially(P<0.05).Serum miR-146a was negatively correlated with sPD-L2 levels in children with MPP(r=-0.735,P<0.001).Duration of fe-ver,proportion of pleural effusion,C-reactive protein(CRP)levels,proportion of severe MPP patients and ser-um sPD-L2 levels in the poor prognosis group were higher than those in the good prognosis group,while ser-um miR-146a level was lower than that in the good prognosis group(P<0.05).Severe MMP and serum sPD-L2 were identified as independent risk factors for poor prognosis in children with MPP(P<0.05),whereas miR-146a was found to be a protective factor(P<0.05).The area under the curve of the combination of ser-um miR-146a and sPD-L2 levels in predicting the poor prognosis in children with MPP was 0.915(95%CI:0.861-0.949),which was higher than 0.844 of miR-146a(95%CI:0.801-0.886)and 0.859 of sPD-L2(95%CI:0.814-0.897)alone(Z=4.780,4.023,P<0.05).Conclusion In children with MPP,serum miR-146a level decreases,while sPD-L2 level increases,and the two are associated with the disease severity of MPP.The combination of these two demonstrates high predictive value for the poor prognosis in MPP.

Prostate cancer is one of the most common malignant tumors in male genitourinary system,and it is one of the main causes of male death in Europe and America.The incidence of prostate cancer in our coun-try is increasing,the key of treatment of prostate cancer is early diagnosis and early treatment.Endoglin also known as endothelial glycoprotein,is the most reliable marker of endothelial cell proliferation,which is over-expressed in neovascularization.Soluble Endoglin was found in the serum of tumor patients,which can be used as an auxiliary diagnosis.Inhibition of Endoglin receptor can inhibit the formation of tumor blood vessels,which provides a basis for targeted therapy.Microvessel density marked by Endoglin is of great significance in the clinical and pathological grading of solid tumors and can be used to evaluate the prognosis.This article re-views the role of Endoglin in the pathogenesis,diagnosis,treatment and prognosis of prostate cancer.

Objective:To explore the role of metagenomic next-generation sequencing (mNGS) in the diagnosis of pathogens in primary infectious diseases of the spine (IDS) and to reveal its pathogen spectrum.Methods:This is a retrospective multi-center case series study. Clinical data of 380 patients with primary IDS who were treated at four medical centers in China from December 2019 to April 2024 were retrospectively analyzed. Among them, 82 cases were from the Department of Spine Surgery at the Affiliated Hospital of Qingdao University, 129 cases were from the Orthopedics Section Ⅱ (Bone Infection), Public Health Clinical Center Affiliated to Shandong University, 112 cases were from the Department of Spine Surgery, Fuzhou Second General Hospital, and 57 cases were from the Department of Orthopedic Surgery, Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. There were 238 males and 242 females, with an age of (61.4±13.1) years (range: 10 to 91 years). Specimens from the site of spinal infection were obtained for pathogen culture, pathological examination, and mNGS detection preoperatively or intraoperatively in all patients. The number, types, and positive rates of pathogens detected by the two methods were analyzed and compared using the Chi-square test.Results:Among the 380 patients, 320 had confirmed pathogenic bacteria, with the highest proportion being pyogenic bacterial infections, accounting for 76.9% (246/320). The most common pathogen was Staphylococcus aureus, accounting for 22.8% (73/320). Brucella accounted for 13.8% (44/320); Mycobacterium tuberculosis accounted for 6.3% (20/320). Fungal infections accounted for 3.4% (11/320), mainly Aspergillus and Candida. In addition, Mycoplasma was detected in 3 cases (0.9%) and Benacox body in 4 cases (1.2%). The pathogen spectrum constructed by mNGS covered 46 types of pathogens, higher than the 22 types detected by traditional methods. The positive rate of mNGS was 80.8% (308/381), significantly higher than the 27.9% (106/381) of traditional methods ( χ2=182.53, P<0.01). Conclusions:mNGS improves the positive rate of pathogen diagnosis in IDS, detecting a broader spectrum of pathogens, and serves as a valuable complement to traditional diagnostic methods. Combining both methods in the diagnosis of IDS can maximize detection rates, providing robust evidence for precise anti-infective treatment.

Aim To investigate the relationship between fibrinogen(FIB)and the progression of coronary plaque stenosis rate in patients with type 2 diabetes mellitus(T2DM).Methods Hospitalized T2DM patients who underwent two or more coronary CT angiography(CCTA)examinations in the First Affiliated Hospital of Xi'an Jiaotong U-niversity from January 2015 to December 2020 were included.The subjects were divided into high FIB and low FIB groups according to the median of FIB.The differences in the progression of coronary plaque stenosis rate and other clini-cal characteristics were compared between the two groups,and the relationship between FIB level and the progression of coronary plaque stenosis rate was analyzed by Spearman's correlation analysis and Logistic regression.Results A total of 145 patients were included,73 in the high FIB group and 72 in the low FIB group at baseline,with a median follow-up time of 25(18,40)months between CCTA.The age,proportion of women,and the progression of coronary plaque ste-nosis rate were higher in the high FIB group than those in the low FIB group,and the differences were statistically signifi-cant(P＜0.05).FIB level was positively correlated with the change in coronary plaque stenosis rate(r2=0.308,P＜0.001).Multivariate Logistic regression analysis showed that FIB level was a risk factor for the progression of coronary plaque stenosis rate in patients with T2DM(OR=5.25,95％CI:1.97～14.02,P＜0.001),after adjusting for age,sex and other clinical risk factors.Conclusion High baseline FIB level is an independent risk factor for the progression of coronary plaque stenosis rate in patients with T2DM,and monitoring FIB level is beneficial to cardiovascular risk stratifica-tion in patients with T2DM.

Objective To investigate the effect of Danshen Baoxin Cha (DBC) on a rat model of coronary heart disease combined with cognitive impairment. Methods Male Sprague-Dawley(SD) rats were randomly assigned to two groups:normal group and model group. Streptozotocin was injected into the bilateral ventricles of rats in the model group to establish cognitive impairment model,then isoproterenol hydrochloride was injected subcutaneously to model myocardial ischemia. Behavioral experiments were conducted to verify the success of the model of cognitive dysfunction. The rats of the model group were randomly divided into five groups:model control group,Tongxinluo Capsule group (TXL group,1.6 g·kg-1),and low-(4 g·kg-1),medium-(8 g·kg-1),and high-(16 g·kg-1) dose DBC groups. These groups were received the respective treatments continuously for two weeks. Subsequently,the Y-maze,novel object recognition and Morris water maze experiment were employed to assess the learning and memory abilities of rats. A kit was utilized to quantify the level of oxidative stress in the brain and the adenosine triphosphate (ATP) content in the brain and mitochondria. Hematoxylin-eosin (HE) staining and Nissl staining were employed to observe the pathological changes of neurons in hippocampus CA1 region. Electron microscopy was utilized to observe the pathological changes of mitochondria in hippocampal CA1 region. The expression levels of peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),glucose transporter type 4(GLUT4),and optic atrophy 1(OPA1) were quantified by real-time fluorescence quantitative polymerase chain reaction (PCR),and the expression of proteins related to the AMPK/OPA1 signaling pathway was determined by Western Blot analysis. Results Compared with the normal group,the spontaneous alternating reaction rate,the novel object recognition index,number of crossing the original platform,and distance ratio in the model group were obviously decreased (P<0.01). Neuronal density in the CA1 region of the hippocampus was decreased,Nissl bodies were decreased,and nucleus consolidation was increased. The ATP level in mitochondria,and the levels of ATP,SOD,and GSH-PX in brain were significantly decreased(P<0.05,P<0.01),as well as the content of ROS and MDA were significantly increased (P<0.05,P<0.01). The mitochondria of hippocampus in CA1 region were swollen,with sparse and vacuolated cristae. The mRNA expression levels of GLUT4,PGC-1α,and OPA1 were significantly decreased (P<0.01). The protein expression levels of GLUT4,SIRT1,PGC-1α and OPA1,and p-AMPK/AMPK ratio were significantly decreased (P<0.05,P<0.01). Compared with the model group,the behavioral indexes of rats in the DBC groups were significantly improved (P<0.05,P<0.01),the number of neurons in the hippocampal CA1 area,Nissl bodies and nucleus consolidation were improved. The ATP level in mitochondria and the levels of ATP,SOD,and GSH-PX in brain were significantly increased (P<0.05,P<0.01). The levels of ROS and MDA were significantly decreased (P<0.05,P<0.01). The structure of mitochondrial cristae in hippocampal CA1 region were relatively intact. The mRNA expression levels of GLUT4,PGC-1α and OPA1 were increased (P<0.05,P<0.01),and the expression of proteins related to the AMPK/OPA1 signaling pathway was significantly increased(P<0.05,P<0.01). Conclusion DBC can enhance learning and memory abilities,reduce neuronal damage in a rat model of coronary heart disease combined with cognitive impairment. The mechanism may be related to the reduction of oxidative stress damage in the brain,the activation of the AMPK/OPA1 signaling pathway,and the restoration of energy levels.