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 evaluate the clinical utility of dual-layer detector CT integrated with virtual monoenergetic imaging (VMI) and an orthopedic metal artifact reduction (O-MAR) algorithm in improving the image quality of patients after lumbar pedicle screw fixation surgery, and to analyze its impact on different types of artifacts and image quality of different tissues.Methods:The study was a prospective study, The study enrolled patients who underwent lumbar pedicle screw fixation at West China Hospital of Sichuan University between March and September 2024. All patients underwent lumbar CT scans using a dual-layer detector system, and four image sets were reconstructed. CLumbar routine scans were performed using dual-layer detector CT, and four image sets were reconstructed:onventional images (CI non-O-MAR), conventional images with O-MAR (CI O-MAR), virtual monoenergetic images (VMI non-O-MAR), and VMI with O-MAR (VMI O-MAR). Objective metrics including artifact index (AI), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were quantified, alongside subjective image quality assessment. One-way ANOVA or Friedman test were used to compare the objective evaluation indicators of image quality between VMI non-O-MAR and VMI O-MAR at different energy levels. Paired t-test or Wilcoxon signed-rank test was used for CI non-O-MAR/VMI non-O-MAR versus CI O-MAR/VMI O-MAR comparisons. Results:A total of 30 patients were included, and all underwent internal fixation with titanium alloy pedicle screws. Objective analysis revealed that in both high-and low-density artifact regions, the AI values of the VMI O-MAR group decreased with the increase of energy levels, and were significantly lower than those of the corresponding VMI non-O-MAR group, with a statistically significant difference (all P<0.001). When the energy level≥140 keV, the AI value of the VMI O-MAR group was simultaneously lower than that of the CI non-O-MAR group and the CI O-MAR group, with statistically significant differences (all P<0.05). The SNR and CNR on the vertebral bodies in the VMI non-O-MAR group and the VMI O-MAR group showed a decreasing trend with increasing energy levels, and were always lower than those in the CI group at high energy levels (100-180 keV) (all P<0.05). At high energy levels (100-180 keV), the SNR of VMI O-MAR in the intervertebral disc and intraspinal tissues was higher than that of the VMI non-O-MAR group, with statistically significant differences (all P<0.05). Compared to other groups, subjective analysis indicated that the 140 keV VMI combined with O-MAR group received the highest image quality scores ( P<0.05). Conclusions:The combined application of VMI and O-MAR technology effectively reduces metal artifacts in post-lumbar fixation CT images. The 140 keV VMI with O-MAR reconstruction provides superior image quality and enhances diagnostic confidence.

Objective:To investigate the diagnostic value of metagenomic next-generation sequencing (mNGS) for pyogenic spinal infections.Methods:A total of 255 patients diagnosed with pyogenic spinal infections were enrolled between September 2022 and September 2024 at Qingdao University Affiliated Hospital, Fuzhou Second General Hospital, First Affiliated Hospital of Nanchang University, Shandong University Affiliated Public Health Clinical Center, and the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Among them, 155 were male and 100 were female, with an average age of 62.5±14.2 years (ranging from 13 to 90 years). All patients had samples of infected tissue and/or pus collected for microbial culture and mNGS testing. The number, types, and positive rates of pathogens detected by microbial culture and mNGS were compared. Using culture results as the gold standard, receiver operating characteristic (ROC) curve analysis was performed for mNGS testing and the combined method of mNGS and microbial culture, calculating the area under the curve (AUC) and 95% CI. Results:All 255 cases were clinically diagnosed as pyogenic spinal infections, with 194 cases providing microbiological evidence. The most common Gram-positive bacterium was Staphylococcus aureus, while the most common Gram-negative bacterium was Escherichia coli. A total of 33 pathogenic microorganisms were detected by mNGS, while microbial culture detected 18 pathogenic microorganisms. The positive rate of mNGS was 72.2% (184 out of 255), which was significantly higher than that of 30.2% (77 out of 255) for microbial culture, showing a significant difference (χ 2=90.150, P<0.001); the positive rate of mNGS combined with microbial culture was 76.1% (194 out of 255) with significant difference compared to mNGS alone (χ 2=8.100, P<0.001). Among 178 culture-negative samples, the detection rate of mNGS was 65.7% (117 out of 178); among 77 culture-positive samples, the detection rate of mNGS was 87.0% (67 out of 77), and 97.0% (65 out of 67) of the detected pathogens matched the culture results at the species level. The AUCs of the ROC curves for mNGS testing and the combination of mNGS with microbial culture were 0.606 [95% CI (0.534, 0.678)] and 0.671 [95% CI (0.606, 0.736)], respectively, with significant differences compared to microbial culture ( P=0.007; P=0.007). Conclusions:mNGS demonstrates superior performance over conventional culture in identifying pathogens in pyogenic spinal infections. Moreover, combining mNGS with culture further improves diagnostic yield, supporting its integration into clinical practice.

Objective:To investigate the predictive value of preoperative coagulation function and inflammation response biomarkers for postoperative recurrence of non-muscle-invasive bladder cancer (NMIBC) patients.Methods:The clinical data of 390 NMIBC patients underwent surgical treatment from May 2014 to May 2021 in the Second Affiliated Hospital of Xi′an Jiaotong University were retrospectively analyzed. The baseline characteristics coagulation function, inflammation response indexes and tumor characteristics were recorded. The baseline characteristics included gender, age and smoking history; the coagulation function included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and D-dimer; the inflammation response indexes included neutrophil count, lymphocyte count, platelet count and monocyte count, and the systemic inflammatory response index (SIRI) and systemic immune-inflammation index (SII) were calculated; tumor characteristics included TNM stage, pathological grade, tumor length, tumor amount and postoperative instillation drugs. The patients were followed up until May 2022, with recurrence records and grouping. The "pROC" package was used to draw the receiver operating characteristic (ROC) curve, and calculate the optimal cutoff values of biomarkers. Multivariate Cox regression analysis was used to analyze the independent risk factors of recurrence in patients with NMIBC (variables were selected with P<0.1). The nomogram and its calibration curve were drawn by the "survival" and "rms" packages, and the area under the curve (AUC) was calculated with the "pROC" package for assessing the predictive ability of the model. The "caret" package was used for ten-fold cross-validation to evaluate the external applicability of the nomogram. Results:The ROC curve analysis result showed that the optimal cutoff values of PT, APTT, FIB, D-dimer, SIRI and SII were 11.95 s, 17.65 s, 0.233 mg/L, 565 ng/L, 0.62 and 291.5, respectively. The 390 patients with NMIBC were followed up 29 to 71 months, with a median follow-up time of 49 months. Among them, 113 patients experienced postoperative recurrence (recurrence group), and the recurrence rate was 29.0%; while 277 patients did not experience recurrence (non-recurrence group). The rate of FIB≥0.233 mg/L, D-dimmer ≥565 ng/L, SIRI≥0.62 and SII≥291.5, T 1 stage, high-grade tumor, tumor length ≥2.3 cm and multiple tumor in recurrence group were significantly higher than those in non-recurrence group: 90.3% (102/113) vs. 71.5% (198/277), 33.6% (38/113) vs. 23.5% (65/277), 74.3% (84/113) vs. 56.7% (157/277), 84.1% (95/113) vs. 60.6% (168/277), 77.9% (88/113) vs. 38.6% (107/277), 25.7% (29/113) vs. 8.3% (23/277), 49.6% (56/113) vs. 32.1% (89/277) and 41.6% (47/113) vs. 19.9% (55/277), and there were statistical differences ( P<0.01 or <0.05); there were no statistical differences in gender ratio, age, smoking history, PT, APTT and postoperative instillation drugs between the two groups ( P>0.05). Multivariate Cox regression analysis result showed that FIB≥0.233 mg/L, SII≥291.5, T 1 stage, high pathological grade, tumor length≥2.3 cm and multiple tumor were independent risk factors of postoperative recurrence in patients with NMIBC ( HR = 2.186, 1.627, 3.182, 1.675, 1.775 and 2.052; 95% CI 1.149 to 4.159, 0.913 to 2.902, 1.988 to 5.095, 1.067 to 2.630, 1.208 to 2.608 and 1.388 to 3.033; P<0.1). A nomogram model was constructed to predict postoperative 1-, 3- and 5-year non-recurrence based on FIB, SII, T stage, tumor length, pathological grade and tumor amount. The calibration curve analysis result showed that the nomogram model predicted good consistency between the postoperative 1-, 3-, 5-year non-recurrence rates and the actual incidence rate in patients with NMIBC. ROC curve analysis result showed that the AUC of the nomogram model for predicting postoperative 1-, 3- and 5-year non-recurrence in patients with NMIBC were 0.746, 0.789 and 0.835 (95% CI 0.695 to 0.832, 0.703 to 0.875 and 0.756 to 0.915). The ten-fold cross-validation result showed that the nomogram model had good external applicability for predicting postoperative 1-, 3- and 5-year non-recurrence in patients with NMIBC, with AUC of 0.754, 0.781 and 0.832 (95% CI 0.689 to 0.817, 0.724 to 0.832 and 0.778 to 0.879). Conclusions:The nomogram model based on FIB, SII, T stage, tumor length, pathological grade and tumor amount can accurately predict the postoperative 1-, 3- and 5-year recurrence risks in patients with NMIBC. The model helps clinical doctors early identify high-risk recurrent NMIBC patients, and provides reference for the development of individualized treatment plans.

Stereotactic radiotherapy is widely favored because of its high treatment precision and less fractionations.ZND-A is a new domestic gamma-ray cone-beam focused stereotactic radiotherapy system.Herein the technical characteristics of ZND-A system are described in detail from the aspects of the treatment frame,gamma-ray module,collimator module,six-dimensional treatment couch module and image-guided system module,and the main parameters are compared with the mainstream gamma knife equipments at home and abroad.With reference to Response Evaluation Criteria in Solid Tumors(RECIST 1.1),the initial efficacy of the patients treated by the ZND-A system is analyzed to evaluate the advantages and disadvantages of the ZND-A system for providing a reference for the hospital clinical use of this type of gamma knife.

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".

BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes are involved in multiple injury repair processes,and the effects and the specific mechanisms of renal ischemia/reperfusion injury have not been fully elucidated.OBJECTIVE:To investigate the molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of renal ischemia/reperfusion injury.METHODS:(1) Human umbilical cord mesenchymal stem cells were cultured and exosomes were obtained and identified using an exosome extraction kit.(2) The distribution of exosomes in the kidney of mice with renal ischemia/reperfusion injury was examined by intravital fluorescence imaging.(3) Thirty C57/BL6 male mice were divided into five groups according to the random number table method:sham operation group,renal ischemia/reperfusion group,sham operation group+Compound C group,renal ischemia/reperfusion+exosome group (exosome group),and renal ischemia/reperfusion+exosome+Compound C group (exosome+Compound C group),with 6 mice in each group.Except the sham operation group,bilateral renal pedicles were clamped for 45 minutes and a mouse model of renal ischemia/reperfusion injury was established after 24 hours of reperfusion.In sham operation+Compound C group and exosome+Compound C group,AMPK inhibitor Compound C was intraperitoneally injected 30 minutes before model establishment.In the exosome group and exosome+Copmpound C group,exosomes were injected through the tail vein 15 minutes before renal pedicle clipping.The levels of serum creatinine and urea nitrogen,interleukin 6,and tumor necrosis factor α in renal tissue,and the expression of apoptosis-related factors in renal tissue were detected after 24 hours of reperfusion in each group.RESULTS AND CONCLUSION:(1) Human umbilical cord mesenchymal stem cell exosomes had the typical tea tray morphology,with the diameter distribution in the range of 40-160 nm,and expressed the specific marker membrane protein of exosome surface.(2) Murine kidneys after renal ischemia/reperfusion injury were more likely to gather human umbilical cord mesenchymal stem cell exosomes compared with the sham operation group.(3) Exosome pretreatment reduced renal injury and the level of renal cell apoptosis in mice treated with renal ischemia/reperfusion injury.Moreover,this protective effect could be reversed by AMPK inhibitors.These findings verify that human umbilical cord mesenchymal stem cell-derived exosomes exerting a protective effect on renal ischemia/reperfusion injury may be related to the activation of the AMPK/YAP1 pathway to antiapoptosis.

To identify the bacterial pathogens in a case of goat respiratory disease in Yunnan prov-ince,three Gram-negative,rod-shaped bacteria strains,YN240861,YN240862 and YN240863,were isolated from lung samples of three diseased goats with respiratory disease,and the identifications of the biochemical and the sequence similarity and phylogeny of 16S rDNA gene,and the analyses of the pathogenicity and antimicrobial susceptibility were studied.The results of the bacterial iden-tification indicated that the most biochemical characteristics of the three isolates were identical with those of the Histophilus somni(H.somni)type stain ATCC 43625T and the other reference strains of H.somni.The three strains had the 16S rDNA sequence similarity of 97.7％with H.som-ni type strain ATCC 43625T,and shared the 16S rDNA sequence similatiies of 99.4％-99.9％with the other H.somni reference strains.The three strains formed the same branch with all the H.som-ni reference strains in the 16S rDNA gene sequence phylogenetic tree.Based on these identification results,the three strains were identified as H.somni.The mouse pathogenicity test showed that each of the three strains had the median lethal dose(LD50)≤7.6×10 5 CFU in mice,which indica-ted that the three stains have higher pathogenicity to mice.The results of the antimicrobial suscep-tibility test indicated that the three strains were sensitive to ampicillin of penicillins,cefazolin and ceftriaxone of cephalosporins,chloramphenicol and florfenicol of chloramphenicols,kanamycin and gentamicin of aminoglycosides,and ofloxacin of quinolones.The strain YN240862 was resistant to sulfamethoxazole of sulfonamides.To our knowledge,this is the first isolation of Hi.somni in Chi-na,and confirmed the presence of H.somni infection in goats in China,which provides the basic da-ta for the prevention and treatment of H.somni infection in goats in China.

IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.

Objective To evaluate the relationship between systemic inflammation makers and bone mineral density(BMD)in male patients with type 2 diabetes(T2DM).Methods A total of 261 male patients with T2DM were selected and divided into three groups based on diagnostic criteria:the normal bone mass group(96 cases),the reduced bone mass group(111 cases)and the osteoporosis group(54 cases).Differences in systemic inflammation markers and bone metabolic markers were compared between the three groups.Multivariate ordered Logistic regression analysis was used to investigate factors influencing the progression from normal bone mass to osteoporosis in male patients with T2DM.Receiver operating characteristic(ROC)curves were used to evaluate the predictive value of inflammatory markers for osteoporosis in male patients with T2DM.Correlation analysis was conducted to investigate the correlation between inflammatory markers and BMD and bone turnover markers(BTM)in male patients with T2DM.Results Platelet count(PLT),platelet-to-lymphocyte ratio(PLR),systemic inflammatory index(SII)and neutrophil-to-lymphocyte ratio(NLR)were significantly higher in the osteoporosis group than those in the normal bone mass group(P＜0.05).Multivariate ordered Logistic regression analysis showed that PLR and SII were risk factors for the progression from normal bone mass to osteoporosis in male patients with T2DM(P＜0.05).The area under the ROC curve of PLR was 0.590,and the cut-off value was 96.67.The area under the curve of SII was 0.613,with a cut-off value of 307.9,and the area under the combined curve of the above two indicators was 0.612.In patients with osteoporosis and osteopenia,SII,PLR and PLT were negatively correlated with L1-4 BMD and left hip BMD(P＜0.05).SII was also negatively correlated with left femoral neck BMD(P＜0.05).Conclusion Inflammatory markers PLR and SII have predictive values for the progression from normal bone mass to bone loss and osteoporosis in male patients with T2DM.