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

ObjectiveTo establish a qualitative and quantitative analysis method for chemical constituents in Liu Junzitang（LJZT）， and to clarify its material basis. MethodThe chemical constituents in LJZT were analyzed by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， and the resulting compounds were identified by using databases， such as MassBank， PubChem， ChemSpider， Traditional Chinese Medicine Systems Pharmacology Database and Analytical Platform（TCMSP）， and by combining with relevant literature. UPLC was used to establish a quantitative method for analysis of 9 compounds in LJZT， including liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ. ResultBy combining the relevant literature， database and MS information， a total of 79 compounds were identified from LJZT， including 31 flavonoids， 15 terpenoids， 14 nitrogen-containing compounds， 6 phenylpropanoids， 6 organic acids and 7 other compounds. The established quantitative analytical method for the nine representative components showed good linearity within their respective linear ranges， and the precision， stability， reproducibility and recovery were in accordance with the requirements. The quantitative results showed that the contents of liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ in LJZT were 0.376 5， 2.602 1， 0.082 6， 0.128 1， 1.778 6， 0.015 7， 0.006 7， 0.030 4， 0.003 2 mg·g^-1， respectively. ConclusionThe established method can quickly， sensitively and accurately analyze the chemical constituents in LJZT， clarify that the material basis of LJZT is mainly flavonoids， terpenoids and nitrogen-containing compounds， and simultaneously determine the contents of the 9 components， which can lay a foundation for the research on quality control， mechanism and clinical application of LJZT.

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 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 changes of skeletal muscle-derived microparticles (SKMPs) and their scaving proteins lactadherin in peripheral blood of patients with perihip fractures and their effects on blood coagulation. It provides a theoretical basis for clinical evaluation of hypercoagulability in patients with perioperative hip fractures.Methods:A total of 44 patients (72.87±13.9 years old) with perihip fractures from October 2020 to January 2021 were included in the fracture group, and 40 healthy people were included in the group without fracture. Activated clotting time (ACT) in fracture group and control group was measured by coagulation and platelet function analyzer. The level of SKMPs in peripheral venous blood was determined by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of MPs scaving proteins lactadherin in peripheral blood of fracture group and control group.Results:A total of 44 patients with perihip fractures were included. There were 33 (75%) femoral neck fractures and 11 (25%) intertrochanteric fractures. SKMPs concentration in peripheral blood of perihip fracture group 175.73/μl; postoperative fracture group 124.28/μl; Normal control group 90.69/μl. ACT was (377.5±76.2) s in the perihip fracture group, (498.1±97.1) s in the post-fracture group, and (505.7±44.0) s in the control group. Correlation analysis showed that there was a linear relationship between SKMPs count and ACT value in fracture patients ( r=-0.52, P<0.001). There was no significant correlation between SKMPs concentration and ACT value in peripheral venous blood of the post-fracture group ( P>0.05); Lactadherin protein concentration in perihip fracture group: 2 779.61 pg/ml; Fracture postoperative group 1 985.38 pg/ml; Normal control group 1 651.19 pg/ml. There is a positive correlation between Lactadherin concentration and SKMPs concentration with a correlation coefficient of 0.70. Conclusion:SKMPs plays a role in the hypercoagulability of patients with perihip fractures. Decompensation of lactadherin protein may be one of the causes of perioperative hypercoagulation in patients with hip fractures.

Objective:To analyze the clinical characteristics of patients with different types of coronavirus disease 2019 (COVID-19).Methods:A total of 272 eligible COVID-19 patients who were admitted to Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 22 to February 15, 2020 were retrospectively enrolled. General characteristics, the first laboratory examination and imaging data of these patients were collected. According to the clinical classification, there were 236 cases in non-severe group (mild+ common type) and 36 cases in severe group (severe+ critical type). Comparisons between groups were performed by t test, chi-square test or rank-sum test when appropriate. Results:There were 23 males and 13 females in the severe group, 103 males and 133 females in the non-severe group, and the difference was statistically significant ( χ2=5.149, P=0.023). The age of severe group was (60.5±11.2) years, which was higher than that of non-severe group (46.8±15.7) years. The difference was statistically significant ( t=6.43, P<0.01). The lymphocyte (LYM) count, platelet (PLT) count and arterial partial pressure of oxygen (PaO 2) in the severe group were 0.90(0.55, 1.10)×10 9/L, 170.00(143.50, 198.00)×10 9/L and 73.50(69.70, 83.00) mmHg(1 mmHg=0.133 kPa), respectively, which were all lower than those in the non-severe group (1.42(1.09, 1.95)×10 9/L, 187.00(148.00, 230.00)×10 9/L and 96.00(83.20, 108.00) mmHg, respectively). The differences were all statistically significant ( Z=5.59, 2.00 and 5.00, respectively, all P<0.05). The levels of creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), C reaction protein (CRP) and procalcitonin (PCT) in the severe group were 123.00(79.00, 212.00) U/L, 32.10(27.00, 47.40) U/L, 305.50(216.00, 396.00) U/L, 37.02(23.92, 63.66) mg/L and 0.09(0.05, 0.19) μg/L, respectively, which were all higher than those in the non-severe group (68.00(48.00, 103.00) U/L, 20.10(16.70, 26.20) U/L, 179.00(150.00, 222.00) U/L, 26.55(18.11, 36.96) mg/L and 0.04(0.03, 0.06) μg/L respectively), and the differences were all statistically significant ( Z=3.89, 5.60, 5.12, 2.85 and 5.43, respectively, all P<0.01). No significant differences were observed in white blood cell count, creatine kinase isoenzyme and blood lactate between the two groups ( Z=1.53, 0.41 and 1.00, respectively, all P>0.05). Conclusion:Gender, age, LYM count, PLT count, PaO 2, CK, AST, LDH, CRP and PCT could be used to provide reference for clinical classification of COVID-19 patients.

OBJECTIVETo observe the protective effect of acupuncture preconditioning at "Jiaji" (EX-B 2) on acute myocardial ischemia-reperfusion injury (MIRI) in the rats and explore the mechanism.

METHODSFifty Wistar rats were randomly divided into a control group, a model group, a Jiaji group, a Neiguan group and a Quchi group, 10 rats in each one. In the Jiaji group, the Neiguan group and the Quchi group, electroacupuncture was given for preconditioning at "Jiaji" T4~T5 (EX-B 2), "Neiguan" (PC 6) and "Quchi" (LI 11) for 7 days before modeling. In the control group and the model group, the regular feeding was given, without any acupuncture. At the end of acupuncture, except the control group, ligating the left anterior descending coronary artery (LAD) was adopted to duplicate MIRI models in the rest groups. Electrocardio-gram (ECG) was monitored and ST-segment shift was analyzed. HE staining method was adopted to observe the morphology of cardiac tissue in the rats of the groups. The transmission electron microscope was used to observe myocardial cell ultrastructure. WST-1 method was used to determine the activity of serum superoxide dismutase (SOD), TBA method was used to determine the content of serum malondialehyde (MDA) and the real-time fluorescent quantitative PCR method to determine the expressions of Nrf 2 in ischemic myocardial tissue and downstream HO-1 gene.

RESULTSCompared with the control group, after LAD ligation, ST-segment was elevated and depressed in ECG apparently after reperfusion in the rest groups (all<0.05). The ST-segment elevation in the Jiaji group and the Neiguan group was less than that in the model group (both<0.05). Compared with the model group, SOD activity was increased apparently in the Jiaji group and the Neiguan group (both<0.05), and MDA content was reduced apparently (both<0.05). The effects in the Jiaji group were better than those in the Neiguan group (both<0.05). Pathologically, "Jiajia" (EX-B 2) and "Neiguan" (PC 6) all improved the morphology of cardiac tissue and cell ultrastructure. The effects in the Jiaji group were much more significant and the improvements in the Quchi group were not apparent. Compared with the control group, the expressions of Nrf 2 and HO-1 gene in myocardial tissue were down-regulated in the model group (both<0.05). Those were up-regulated apparently in the Jiaji group and the Neiguan group as compared with the model group (<0.05,<0.01). The up-regulation times of the expressions of Nrf 2 and HO-1 gene in the Jiajia group were the highest in comparison.

CONCLUSIONSAcupuncture preconditioning at "Jiaji" (EX-B 2) has the protective effect on cardiac ischemia and reperfusion damage, which is probably relevant with the up-regulation of Nrf 2-ARE pathway expression, the activation of endogenous anti-oxidative pathway, the improvement of oxygen free radical scavenging capacity and the alleviation of lipid peroxide damage.

Objective To investigate the effect of diosmin on the pain and wound healing after modified anal fissure resection .Methods 98 patients from January 2015 to July 2016 in our hospital who were admitted to meet the inclusion criteria and improved anal fissure resection patients were selected and randomly divided into control group and study group, 49 cases in each group.And the control group was given routine postoperative treatment, the study group was treated with diosmin tablets on routine postoperative therapy , two groups were treated for seven days for a course of treatment, the wound pain, wound width and wound healing were observed and recorded before and after treatment, blood samples were taken to determine changes in serum inflammatory factors, the clinical efficacy and complications were compared.Results After treatment, the two groups of wound pain, the width of the wound and wound healing rate were decreased, the serum TNF-α, IFN-γ, IL-6 levels were decreased, the difference was statistically significant (P<0.05), compared with the control group, the degree of pain, the width of the wound and wound healing rate were lower, the serum TNF-α, IFN-γ, IL-6 content were lower, the average healing time and granulation growth time and remove decay time were shorter, the difference was statistically significant (P<0.05).The effective rate of the study group was 91.83%, higher than the control group 75.51%, the difference was statistically significant (P<0.05).All patients were followed up, no case falls off phenomenon, there was no significant difference in the incidence of adverse reactions between the two groups.Conclusion Diosmin tablets on the improvement of anal fissure after resection of wound healing has a role in promoting inflammation, reduce the severity of pain conditions.

Objective To explore the application value of mammary gland remodeling to one-stage repair local defects after partial excision.Methods The clinical data of 62 breast patients undergoing mammary gland remodeling to one-stage repair local defect after partial excision between January 2011 and December 2014 were reviewed.Results All patients recovery,the average operative time was 60 min,the average hospital stay was 7 days,the average cost was 5 216 yuan,1 case with postoperative concurrent incision infection,6 cases with postoperative hematoma.The cosmetic results were excellent or good rate was 87.1％ (54/62),and fair rate was 12.9％ (8/62).The breasts showed natural and symmetrical appearance during a follow-up of 12-36 months.Conclusions The application of mammary gland remodeling to one-stage repair local defect after partial excision is a safe and economical method.

Aim Toexaminethecombinedeffectsof 5-ALA and metformin on diabetes mellitus induced by streptozotocin( STZ) in mice, and to discuss the mech-anisminitially.Methods Thediabeticmiceinduced by intraperitoneal injection of STZ were treated with 5-ALA and/or metformin for 30 days. Physical signs, fasting blood glucose ( FBG ) , fasting plasma insulin ( FIns) , plasma leptin ( Lep) , glucose tolerance, and histological changes of liver and pancreas were as-sessed. Insulin resistance was evaluated by the homeo-stasismodelassessment(HOMA).Results There were more significant effects when 5-ALA combined with metformin than only using metformin on lowering FBG, FIns and Lep. And 5-ALA combined with met-formin could improve glucose tolerance and the insulin sensitivity. Microscopic analysis demonstrated that sig-nificant changes in pancreatic islet and characteristic feature of the vacuolization phenotype in liver was ob-served on diabetic mice, and use of 5-ALA could in-hibit shrinking pancreatic islet number and hepatic morphological changes, especially in combination with metformin.Conclusions Asynergisticeffectof5-ALA and metformin is observed. Combined therapy of 5-ALA and metformin can decrease FBG and improve glucose tolerance, insulin sensitivity and islet ? cells function and morphology.