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 analyze the positioning error and the overall setup errors (OSEs) of patients undergoing gamma knife pain-free face mask fractionated treatment for head tumors based on kV orthogonal image guidance.Methods:A total of 58 patients who received image-guided fractionated gamma knife treatment for head tumors with a pain-free face mask at the Gamma Knife Treatment Center of Xi'an International Medical Center Hospital from July 1, 2022 to May 31, 2024 were included in the study. A kV-class orthogonal X-ray IGPS image-guided positioning system was used to collect positioning errors in three translational directions: left-right (X), anterior-posterior (Y), and head-foot (Z), as well as in three rotational directions: left-right (P), anterior-posterior (R), and head-foot ( Y) before correction. After online correction and combined with manual positioning verification, the corrected positioning errors were recalculated. The OSEs in translational and rotational directions were calculated before and after correction. The positioning errors in all six directions (X, Y, Z, P, R, Y) before and after correction were plotted. And the OSE scatter plots in translational and rotational directions were created accordingly. Errors in the six directions and OSEs in translational and rotational directions were compared. The OSEs in translational and rotational directions were analyzed across different age groups and genders. Results:The pre-correction positioning errors in the X, Y, Z, P, R, Y directions for patients were (0.45±1.54) mm, -0.96 (-1.70, -0.28) mm, 1.67 (-0.15, 3.07) mm, (0.70±1.60) °, 0.65 (0.30, 1.19) °, (0.59±0.87) °, and the post-correction positioning errors were (-0.02±0.18) mm, 0.15 (0.10, 0.21) mm, 0.06 (-0.04, 0.16) mm, (0.20±0.79) °, 0.42 (0.19, 0.78) °, (0.20±0.63) °. There were statistically significant differences between before and after correction ( t=2.30, P=0.025; Z=-5.43, P<0.001; Z=-4.10, P<0.001; t=2.56, P=0.013; Z=-3.21, P=0.001; t=3.21, P=0.002). The OSEs in translational (X, Y, Z) and rotational (P, R, Y) directions before correction were 3.07 (1.93, 4.35) mm, 1.90 (1.28, 2.66) °, and the OSEs after correction were 0.27 (0.21, 0.33) mm, 1.08 (0.70, 1.54) °, with statistically significant differences ( Z=-6.60, P<0.001; Z=-5.52, P<0.001). For patients aged 18-44 years, the OSEs in translational (X, Y, Z) and rotational (P, R, Y) directions before and after correction were 3.65 (1.62, 3.95), 0.21 (0.21, 0.31) mm, 3.25 (2.24, 3.96) °, 0.92 (0.59, 1.45) °; for patients aged 45-59 years, the OSEs were 3.57 (2.17, 5.22), 0.29 (0.22, 0.35) mm, 1.89 (1.30, 2.30) °, 1.08 (0.62, 1.51) °; for patients aged 60-74 years, the OSEs were 2.92 (1.74, 4.06), 0.24 (0.19, 0.35) mm, 2.16 (1.09, 2.95) °, 0.98 (0.78, 1.75) °; for patients aged 75-89 years, the OSEs were 3.24 (2.12, 4.37), 0.29 (0.22, 0.47) mm, 1.73 (1.01, 1.83) °, 0.60 (0.47, 1.51) °. There were no statistically significant differences in OSEs of translational and rotational directions before and after correction among the four age groups ( H=1.23, P=0.747; H=1.74, P=0.627; H=7.45, P=0.059; H=2.80, P=0.424). For male patients, the OSEs before and after correction in translational (X, Y, Z) and rotational (P, R, Y) directions were (3.19±1.59), 0.27 (0.27, 0.33) mm, 1.89 (1.27, 2.75) °, (0.84±0.59) °; for female patients, the OSEs were (3.22±1.99), 0.26 (0.25, 0.35) mm, 1.90 (1.34, 2.41) °, (1.04±0.46) °. There were no statistically significant differences in OSEs of translational and rotational directions before and after correction between genders ( t=-0.07, P=0.949; Z=-0.48, P=0.632; Z=-0.02, P=0.161; t=-2.80, P=0.424) . Conclusions:The image-guided system, which is based on the kV orthogonal X-ray stereoscopic imaging, can significantly reduce the positioning errors between fractions of pain-free face mask gamma knife treatment for head tumor patients and improve the positioning accuracy of the gamma knife through the dual verification process of "automatic correction and manual review".

Objective To find out whether photobiomodulation(PBM)can mitigate cognitive dysfunction caused by chronic stress by affecting levels of adenosine triphosphate(ATP)and adenosine receptors.Methods Twenty-four C57BL/6J mice were randomly divided into a control group,a stress group,and a treatment group.Chronic unpredictable mild stress was used to establish a mouse model of stress.Six weeks into modeling,the treatment group was subjected to one week of PBM interventions.Behavioral tests were conducted to observe behavioral changes in the mice.Western blotting(WB)was used to detect the expressions of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex of mice in the three groups.Twelve C57BL/6J mice were randomly divided into a control group and an intervention group.The intervention group received a week of PBM interventions and underwent behavioral testing.WB was used to detect the expression changes of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex in both groups.Immunofluorescence assay was adopted to detect the expression of c-Fos in the hippocampus of mice in the two groups.The ATP assay kit made by Beyotime Biotechnology Co.,Ltd.was used to measure changes in ATP contents in the hippocampus and prefrontal cortex tissues of mice.Cell experiments were conducted to verify the effect of PBM on intracellular ATP contents.Results Mice in the stress group covered a similar distance to the control group,but finished far fewer platform crossings.There was no significant difference between the treatment group and the control group in the number of times of platform crossings,but compared favorably with the stress group where the levels of adenosine receptors in the hippocampus and prefrontal cortex were lower,but were increased by PBM.After PBM interventions in normal mice,platform crossings were increased significantly compared to the control group.PBM also raised adenosine receptor levels and ATP contents in the hippocampus and prefrontal cortex,and increased hippocampal c-Fos expressions.In vitro,PBM elevated intracellular ATP levels.Conclusion PBM may improve chronic stress-induced cognitive dysfunction by regulating ATP levels and adenosine receptor expressions,thereby modulating neuronal responsiveness in the hippocampus.

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.

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.

Currently, the types of kidney stones before surgery are mainly identified by human beings, which directly leads to the problems of low classification accuracy and inconsistent diagnostic results due to the reliance on human knowledge. To address this issue, this paper proposes a framework for identifying types of kidney stones based on the combination of radiomics and deep learning, aiming to achieve automated preoperative classification of kidney stones with high accuracy. Firstly, radiomics methods are employed to extract radiomics features released from the shallow layers of a three-dimensional (3D) convolutional neural network, which are then fused with the deep features of the convolutional neural network. Subsequently, the fused features are subjected to regularization, least absolute shrinkage and selection operator (LASSO) processing. Finally, a light gradient boosting machine (LightGBM) is utilized for the identification of infectious and non-infectious kidney stones. The experimental results indicate that the proposed framework achieves an accuracy rate of 84.5% for preoperative identification of kidney stone types. This framework can effectively distinguish between infectious and non-infectious kidney stones, providing valuable assistance in the formulation of preoperative treatment plans and the rehabilitation of patients after surgery.
Humans ; Kidney Calculi/classification* ; Deep Learning ; Neural Networks, Computer ; Tomography, X-Ray Computed ; Imaging, Three-Dimensional ; Radiomics

Objective To investigate the clinical efficacy of ultrasound-guided percutaneous microwave ablation in the treatment of benign cystic/solid thyroid nodules.Methods A total of 98 patients with benign cystic/solid thyroid nodules who were treated in the Puren Hospital affiliated to Wuhan University of Science and Technology from January 2018 to July 2021 were selected as research objects.They were divided into two groups according to different treatment methods.There were 48 patients in the microwave ablation group and 50 patients in the open operation group.The operation time,hospital stay,intraoperative bleeding,inflammatory reaction indexes(C-reactive protein[CRP],interleukin 6[IL-6])one day after surgery,thyroid function indexes(FT3,FT4,and thyroid-stimulating hormone),postoperative complications,and recurrence rate during one-year follow-up were compared between the two groups.The nodule size and volume reduction rate were calculated at 6 and 12 months after operation.Results The intraoperative bleeding,operation time and length of hospital stay in the microwave ablation group were significantly less than those in the open operation group([1.65±0.64]ml vs[18.60±5.79]ml,[23.54±5.68)]min vs[99.30±17.18]min,[2.94±0.56]d vs[8.06±1.38]d).The levels of CRP and IL-6 increased after surgery in both groups,but the levels of CRP and IL-6 in the microwave ablation group were significantly lower than those in the open operation group(P<0.05).The incidence of hypothyroidism and complications in the microwave ablation group were significantly lower than those in the open operation group one day after operation(8.33%vs 64.00%,10.42%vs 66.00%).The recurrence rate in the microwave ablation group(12.50%)was higher than that in the open surgery group(10.00%)during one-year follow-up,with no significant difference(P=0.76).At 6 and 12 months after treatment,the size of the nodules was observed by ultrasound.The volume of the nodules in the microwave ablation group was reduced to(1.77±0.67)cm3 and(0.93±1.01)cm3,and the reduction rates of the nodules were(75.83±9.07)%and(88.38±11.89)%,respectively.Conclusion Compared with open surgery,ultrasound-guided percutaneous microwave ablation for benign cystic/solid thyroid nodules has shorter operation time,less trauma,fewer complications,less impact on thyroid function,and faster recovery.It is worthy of clinical application.

Starting from the inheritance and development of Chinese philosophy of life and Traditional Chinese Medicine (TCM) wisdom through the Chinese narrative medicine practice, this paper discussed the inheritance and correspondence relationship between the text reading ability in Chinese narrative medicine practice and the "four diagnostic" in TCM wisdom, narrative regulation and the "mind-body philosophy" in TCM, as well as the narrative wisdom and the "Tao produces one" in the Chinese philosophy of life. By analyzing the stories of contemporary doctors’ practice of narrative wisdom, this paper clarified that the Chinese narrative medicine system is a new model of medical education and clinical practice constructed by absorbing the essence elements of Chinese traditional life wisdom and TCM culture, and integrating the concept of western narrative medicine. It advocated for Chinese scholars to actively build the discipline of "narrative traditional Chinese medicine", constantly translate and introduce the achievements to foreign countries, and create a good narrative ecology of TCM.

Objective:To investigate the Chinese anesthesiologist′s proficiency, training experience and needs of flexible bronchoscope-guided awake flexible bronchoscopy intubation (AFBI) using a questionnaire method.Methods:The cluster sampling was used, and self-designed questionnaires that addressed 54 questions in 5 categories were distributed through WeChat and online platforms. The survey took one month, and the answers were automatically recorded by the WeChat server.Results:A total of 1 250 anesthesiologists participated in the survey in 30 provinces of China, 9 of them were not anesthesiologists, and 1 241 (99.28%) questionnaires were validated. In the valid questionnaires, 52.70% (654) of the anesthesiologists were from tertiary hospitals, and 74.78% (928) of the anesthesiologists were attending physicians or above, only 7.57% (94) of the anesthesiologists had sufficient confidence in AFBI. Twenty-five point two two percent (313) of the anesthesiologists preferred fiberoptic intubation as the first tool when dealing with the anticipated difficult airway. Forty-eight point one one percent (597) of the anesthesiologists had implemented AFBI. Among them, 80.74% (482) had experienced unsuccessful AFBI practices. Eight hundred and ninety-four anesthesiologists had received AFBI training, and the most common AFBI training strategy was theoretical lectures. In addition, the degree of satisfaction regarding the theoretical lectures quality, technical training, clinical practice relativity and non-technical skills training was 21.47% (192), 14.32% (128), 12.3% (110) and 17.90% (160), respectively. The degree of satisfaction with all the 4 training elements mentioned above was 7.27% (65).Conclusions:The awareness and practice of Chinese anesthesiologists in terms of clinical application of AFBI to treat difficult airways need to be strengthened at present, and the lack of high-quality AFBI training may be the key.

Objective:To investigate the effect of the liquid resuscitation therapy strategy using intra-abdominal pressure (IAP) and oxygenation index (PaO 2/FiO 2) as the end point in patients with severe acute pancreatitis (SAP). Methods:A retrospective study was performed, including 84 patients with SAP in emergency intensive care unit of Qingzhou Hospital Affiliated to Shandong First Medical University from January 2018 to August 2021. According to the status of fluid balance at admission, all patients were divided into the positive fluid balance group (43 cases) and the negative fluid balance group (41 cases). The clinical data including gender, age, etiology, underlying disease, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) of all patients were collected. Fluid balance, PaO 2/FiO 2, IAP, compliance rate, new mechanical ventilation rate and overall hospital stay of 1 week after admission were recorded and compared between the two groups. Results:After 72 hours of treatment, the cumulative fluid balance was (5 219.5±1 038.4) mL in the positive fluid balance group; IAP was higher than that before treatment [mmHg (1 mmHg≈0.133 kPa): 11.9±2.0 vs. 11.7±2.1], but no significant difference was found ( P > 0.05); PaO 2/FiO 2 was significantly higher than that before treatment (mmHg: 299.8±51.4 vs. 220.5±50.4, P < 0.05). After 72 hours of treatment, the cumulative fluid balance in negative fluid balance group was (-3 542.4±1 310.6) mL; IAP was significantly lower than before treatment (mmHg: 11.4±1.8 vs. 15.2±1.9, P < 0.05); PaO 2/FiO 2 was significantly higher than that before treatment (mmHg: 309.9±50.9 vs. 215.4±49.7, P < 0.05). In the fluid resuscitation goals, after 72 hours of treatment, the compliance rate in the negative fluid balance group was significantly higher than that in the positive fluid balance group [82.93% (34/41) vs. 62.79% (27/43), P < 0.05]; 1 week after admission, the new mechanical ventilation rate in the negative fluid balance group was significantly lower than that in the positive fluid balance group [21.95% (9/41) vs. 41.86% (18/43), P < 0.05]; however, there was no significant difference in overall hospital stay between the two groups (days: 41.2±10.9 vs. 39.1±11.5, P > 0.05). After treatment, 70 patients survived and 14 patients died (including 9 cases in the positive fluid balance group and 5 cases in the negative fluid balance group). Conclusions:Using IAP and PaO 2/FiO 2 to guide liquid therapy could result in effective fluid resuscitation in SAP. The treatment strategy effectively improved prognosis of patients with SAP.