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 establish a prediction model for non-curative resection in patients with early gastric cancer (EGC) who underwent endoscopic submucosal dissection (ESD), and to evaluate its predictive value.  Methods  Clinical data of EGC patients in the Second Hospital & Clinical Medical School, Lanzhou University from January 2014 to July 2023 were retrospectively collected. According to the postoperative pathological results of ESD, the patients were divided into curative resection group and non-curative resection group. Multifactorial Logistic regression analysis was used to screen the risk factors for non-curative resection after ESD surgery and establish a prediction model, and the model was evaluated using receiver operating characteristic(ROC) curves, calibration curves and clinical decision curve analysis.  Results  A total of 479 EGC patients who underwent ESD were included, with 60 cases in the non-curative resection group and 419 cases in the curative resection group. The results of multifactorial Logistic regression analysis showed that the lesion diameter > 2 cm (OR=3.017, 95% CI: 1.483-6.136, P=0.002), flat lesion morphology (OR=2.712, 95% CI: 0.774-9.497, P=0.043), undifferentiated/mixed histologic type (OR= 4.199, 95% CI: 1.621-10.872, P=0.003), and submucosal infiltration (OR=30.329, 95% CI: 13.059-70.436, P < 0.001) were independent risk factors for non-curative resection after ESD in EGC patients. The area under the curve of ROC validated within the column-line graph prediction model constructed accordingly was 0.867 (95% CI: 0.811-0.923), the calibration curve showed that the model had good calibration, and decision curve analysis showed the model had a good clinical usefulness.  Conclusions  The prediction model constructed based on lesion diameter, lesion morphology, histologic type, and depth of mucosal infiltration has good differentiation, calibration, and clinical utility. This model is expected to assist in the early clinical screening of the population at high risk for noncurative resection after ESD in patients with EGC, and to provide a basis for the development of optimal clinical decisions.

【Objective】 To explore the perioperative blood management in patients with pancreatic pseudocyst combiend with coagulation factor Ⅴ(FⅤ) deficiency. 【Methods】 Preoperative: In order to determine the effect of cryoprecipitated antihemophilic factor and fresh frozen plasma (FFP) on the elevation level of factor Ⅴ, we alternately infused cryoprecipitate and FFP in the resting state. TEG, coagulation function and coagulation factor activity were monitored before and 1 h, 24 h and 48 h after infusion, and intraoperative and postoperative blood transfusion strategies were formulated. FFP 600 mL and cryoprecipitate 10 U were supplemented preoperatively. Intraoperative: The operation procedure was performed for 7 hours with an infusion of 600 mL FFP without significant bleeding. Postoperative: FFP was infused. 【Results】 Preoperative: The coagulation factor Ⅴ activity on pre-operation was 1.9% and 1.8%. After alternating infusion cryoprecipitate 10 U and FFP 1 200 mL, the FⅤactivity increased to 5.1% and 6.0%, respectively. There was no significant difference in TEG parameters, PT and ATPP results were decreased to varying degrees. Intraoperative: The operation was successful without obvious bleeding. Postoperative: FFP 500 mL was infused 2 h after operation, and FFP 250-500 mL was injected daily from 1 to 7 days after surgery. No significant bleeding was observed in the wound, the results of TEG, PT, APTT and hemoglobin (Hb) did not change significantly compared with those before surgery. The patient was discharged successfully 12 days after surgery. The genetic test results showed that he had inherited coagulation factor Ⅴ deficiency, which was a compound heterozygous variation. 【Conclusion】 Perioperative blood management in patients with FⅤ deficiency combined with surgical disease, requiring pre-transfusion evaluation and post-transfusion evaluation in combination with laboratory investigations and clinical manifestations, cryoprecipitate and fresh frozen plasma can be effective in supplementing coagulation factors. The TEG seems to be better than the Seven items of coagulation function in judging the clotting status of patients with FⅤ deficiency.

Objective:To explore the correlation between early pupillary light reflex reduction and delirium in mechanically ventilated patients receiving sedation in the Intensive Care Unit (ICU) .Methods:From December 2020 to March 2021, convenience sampling was used to select 97 ICU patients with mechanical ventilation who received sedation in the China-Japan Union Hospital of Jilin University as the research subject. On the second to fourth days of the patient's stay in the ICU, the quantitative pupillary light reflex (q-PLR) and pupillary contraction velocity (CV) of the patients after photostimulation were measured by an automatic infrared pupillometer with a frequency of two times a day. Patients were assessed using the Richmond Agitation-Sedation Scale (RASS) . When the RASS score was≥-2, the patient was screened for delirium using the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) with a frequency of two times a day. According to the screening results, patients were divided into delirium group and non-delirium group.Results:The incidence of delirium in 97 ICU mechanically ventilated patients who received sedation was 58.76% (57/97) . Binomial Logistic regression showed that q-PLR on the second day was an influencing factor for delirium in mechanically ventilated ICU patients receiving sedation ( P<0.05) . Conclusions:Early pupillary light reflex reduction is associated with delirium in mechanically ventilated ICU patients receiving sedation.

【Objective】 To explore the quality of autologous platelet-rich plasma prepared by manual and automatic method and to study the clinical injection therapeutic effects in patient with knee arthritis. 【Methods】 28 patients with knee arthritis in Orthopedics Department of our hospital were enrolled. PRP was prepared manually in 12 patients and automatically in 16. The whole blood of 50~70 mL was drawn from 12 patients and prepared into PRP of 10 mL manually by centrifugation. The 20~30 mL PRP was collected by automatic apheresis. Plt, RBC, WBC and other related indexes of PRP were detected after collection. Among the 28 patients, 12 in the manual group received injection twice, while 16 in the automatic group 4 episodes, with an interval of 15~20 days. The treatment effect was evaluated after the last treatment. 【Results】 The PRP prepared by two methods can both reach the required quality standard of platelet counts..The patient′s pain symptoms relieved significantly after injection treatment and the effect was remarkable. There was no significant difference in clinical efficacy between the two groups. 【Conclusion】 The PRP prepared by manual and automatic methods can be used for injection treatment for patient with knee arthritis. The clinical therapeutic effects were good and worth promotion and application.

【Objective】 To explore the effect of allogeneic platelet gel on hemostasis and repair of vascular anastomoses and wounds in patients with giant aortic aneurysms during surgery. 【Methods】 One adult dose of allogeneic platelets, applied as platelet rich plasma (PRP), was prepared as platelet gel (PG) (about 220 mL) for spraying or smearing at the vascular anastomosis and thoracic wound during the surgery of giant aortic aneurysms. 【Results】 The gel formation was presented about 30 seconds after spraying or smearing with PG on the anastomotic and wound surface. The hemostatic effect is good, with less postoperative drainage fluid from pericardium and mediastinum than usual, and the ICU stay was 4 days. 【Conclusion】 Allogeneic platelets as a source of PRP to prepare PG may be applied to obtain the clotting and healing during surgical operation.

Objective:To evaluate the effect of angiotensin-converting enzyme (ACE) gene polymorphism on dexmedetomidine-induced inhibition of responses to endotracheal intubation in the patients with hypertension.Methods:One hundred and eighty patients with essential hypertension, aged 48-61 yr, weighing 51-66 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, in whom ACE genotype was determined using polymerase chain reaction-restriction fragment length polymorphisms method before operation, were divided into 6 groups ( n=30 each) according to whether dexmedetomidine was applied: DD genotype group (DD group), ID genotype group (ID group), II genotype group (II group), dexmedetomidine plus DD genotype group (DEX+ DD group), dexmedetomidine plus ID genotype group (DEX+ ID group), and dexmedetomidine plus II genotype group (DEX+ II group). Dexmedetomidine 0.8 μg/kg was intravenously infused over 15 min before induction of anesthesia in DEX+ DD group, DEX+ ID group and DEX+ II group.Systolic and diastolic pressure (SP, DP) and heart rate (HR) were measured before dexmedetomidine (T 0), immediately before tracheal intubation (T 1), immediately after tracheal intubation (T 2), and at 1.5 and 5.0 min after tracheal intubation (T 3, 4). The rate-pressure product (RPP) was calculated.The occurrence of myocardial ischemia and cardiovascular responses within 5 min after tracheal intubation was recorded.Blood samples from the internal jugular vein were collected at T 0 and T 2-4, and plasma concentrations of epinephrine (E) and norepinephrine (NE) were determined by high performance liquid chromatography-electrochemical detection assay. Results:Compared with group DD, the SP, DP, HR and RPP were significantly decreased at T 2-4, plasma NE and E concentrations were decreased at T 2, 3, and the incidence of myocardial ischemia and cardiovascular reactions was decreased in group Dex+ DD ( P<0.05). Compared with group ID, SP, DP, HR and RPP were significantly decreased at T 2-4, plasma NE and E concentrations were decreased at T 2, 3, and the incidence of myocardial ischemia and cardiovascular responses were decreased in group Dex+ DD ( P<0.05). Compared with group II, SP, DP, HR and RPP were significantly decreased at T 2, 3, plasma NE and E concentrations were decreased, HR and RPP were decreased at T 4, and the incidence of myocardial ischemia and cardiovascular reactions was decreased in group Dex+ II ( P<0.05). There was no significant difference in the above parameters among group Dex+ DD, group Dex+ ID and group Dex+ II ( P>0.05). Conclusion:ACE gene polymorphism does not affect dexmedetomidine-induced inhibition of responses to endotracheal intubation in the patients with hypertension.

Objective To evaluate the effect of angiotension-converting enzyme (ACE) gene poly-morphism on dexmedetomidine-induced inhibition of responses to extubation in the patients with hyperten-sion. Methods A total of 180 patients with primary hypertension, aged 50-63 yr, weighing 54-69 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, scheduled for elective abdominal surgery under general anesthesia, in whom ACE genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism, were divided into 6 groups (n = 30 each) according to whether dexmedeto-midine was applied: DD genotype group (DD group), ID genotype group (ID group), Ⅱ genotype group (Ⅱ group), dexmedetomidine +DD genotype group (DEX+DD group), dexmedetomidine +ID genotype group (DEX+ID group) and dexmedetomidine+Ⅱ genotype group ( DEX+Ⅱ group). Dexmedetomidine 0. 5 μg·kg-1 ·h-1 was intravenously infused starting from 30 min before the end of surgery until the end of surgery in DEX+DD, DEX+ID and DEX+Ⅱ groups. Immediately before infusing dexmedetomidine (T1 ), at 30 min of dexmedetomidine infusion (T2 ), immediately after extubation (T3 ) and at 1. 5, 5 and 15 min after extubation (T4-6 ), systolic blood pressure, diastolic blood pressure, heart rate and ECG were recor-ded, and rate-pressure product was calculated. The development of myocardial ischemia and responses to extubation was recorded within 15 min after extubation. Results Compared with the baseline at T1 , each parameter of hemodynamics was significantly increased at T3-6 in DD, ID and Ⅱ groups (P<0. 05), and no significant change was found in each parameter of hemodynamics at T2-6 in Dex+DD, Dex+ID and Dex+Ⅱ groups (P> 0. 05). Each parameter of hemodynamics was significantly lower at T3-6 , and the inci-dence of myocardial ischemia and responses to extubation was decreased in group Dex+DD than in group DD and in group Dex+ID than in group ID (P<0. 05). Compared with group Ⅱ, each parameter of he-modynamics at T3-6 and incidence of responses to extubation were significantly decreased in group Dex+Ⅱ, and each parameter of hemodynamics was significantly increased at T3-6 , and the incidence of myocardial ischemia and responses to extubation was increased in DD and ID groups (P<0. 05). There was no signif-icant difference in each parameter of hemodynamics or incidence of myocardial ischemia and responses to extubation among group Dex+DD, group Dex+ID and group Dex+I (P>0. 05). Conclusion ACE gene polymorphism does not affect dexmedetomidine-induced inhibition of responses to extubation in the patients with hypertension.

According to the personalized service needs of patients with hypertension,diabetes and other chronic diseases,the paper develops a family self-service health management system based on intelligent terminal devices,introduces the system architecture,functions of each terminal,data communication and other key technologies.This system is able to provide patients and family members with real-time and effective disease prevention knowledge and targeted online medical treatment.

Objective To identify the role of miR-124 in regulating the radiosensitivity and the epithelial-mesenchymal transition (EMT) of nasopharyngeal carcinoma (NPC). Methods Transient transfection of cells with miR-124 mimic or inhibitor was performed and wound-healing assay was used to investigate the role of miR-124 in the EMT of NPC. The apoptosis affected by miR-124 was also measured after irradiation , followed by investigating the cell proliferation by EdU assay. Finally , proteins of Akt and ERK associated with EMT and radiosensitivity, were measured by western blot. Results The migration index from NPC cell line indicated that miR-124 repressed the EMT. The results from caspase-3 activity assay showed that caspase-3 activity after irradiation significantly increased in miR-124 mimic group compared with the control group (P < 0.01). It was also confirmed that irradiation led to a higher percentage of apoptosis in miR-124 group compared with the control group in NPC cells. Cell proliferation after irradiation was significantly decreased in MiR-124 group as compared with control group . MiR-124 inhibited the protein expression of p-Akt . Conclusion MiR-124 may repress the EMT and decrease radio-resistance of NPC via p-Akt signaling pathway , which may provide a new insight into radio-resistance in NPC.