ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective To investigate the therapeutic potential of human umbilical cord-derived mesenchymal stem cells(hUCMSCs)in modulating the cGAS-STING-NF-κB signaling pathway in chronic intermittent hypoxia(CIH)mice.Methods Twenty-four C57BL/6 mice were divided into the control group,the model group,the hUCMSCs group and the hUCMSCs+STING agonist(DMXAA)group,with 6 mice in each group.Except for the control group,the other groups were exposed to hypoxic conditions for 8 hours daily for a total of 8 weeks to establish the CIH mouse model.After 8 weeks,mice were anesthetized for cardiac blood collection followed by euthanasia and lung tissue collection.Serum levels of IL-6,TNF-α,IL-1β and IL-17A were measured by ELISA.Pulmonary inflammatory infiltration and collagen deposition were assessed by HE and Masson staining.E-Cadherin and α-SMA expression levels were evaluated by immunohistochemistry.Expression levels of cGAS,STING and NF-κB mRNA were detected by RT-qPCR,while protein expression levels of E-Cadherin,N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB were analyzed by Western blot assay.Results Compared with the control group,levels of IL-6,IL-1β,TNF-α and IL-17A increased in the model group,inflammation and fibrosis scores increased,mRNA expression levels of cGAS,STING and NF-κB increased,and protein expression levels of N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB increased.In contrast,E-Cadherin protein expression was significantly decreased(P＜0.05).Compared with the model group,IL-6,IL-1β,TNF-α and IL-17A decreased in the hUCMSCs group,mRNA expression levels of cGAS,STING and NF-κB were decreased,protein expression levels of N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB were also decreased.Meanwhile,E-Cadherin protein expression was significantly increased(P＜0.05).STING activator DMXAA reversed the protective effects of hUCMSCs in CIH mice(P＜0.05).Conclusion Intravenous administration of hUCMSCs alleviates pulmonary inflammatory infiltration and epithelial-mesenchymal transition in mouse model of intermittent hypoxia,which may be related to the down-regulation of the cGAS-STING-NF-κBsignaling pathway.

Objective:To analyze the dynamic changes of serum exosome miR-552 and miR-653 levels in pa-tients with gastric cancer before and after chemotherapy and their relationship with clinical benefit.Methods:IA total of 128 patients with gastric cancer received chemotherapy from January 2022 to January 2024.According to the chemo-therapy effect,the two groups were divided into disease progression group and disease remission group.The levels of serum exosome miR-552 and miR-653 before and after chemotherapy were detected in the two groups,the risk fac-tors affecting the chemotherapy effect of gastric cancer patients were screened,the risk nomogram model was con-structed,and the efficacy was evaluated.Results:The proportion of TNM stage(Ⅲ+Ⅳ),lymph node metastasis,dis-tant metastasis,tumor size(>5 cm),invasion depth(T3/T4)and tumor growth pattern(invasive type)in disease progres-sion group was higher than that in disease remission group(P<0.05).The levels of serum exosomes miR-552 and miR-653 in disease progression group were higher than those in remission group before and after chemotherapy(P<0.05).Compared with before chemotherapy,miR-552 and miR-653 levels in both groups decreased(P<0.05).Logistic regres-sion analysis showed that TNM stage,lymph node metastasis,distant metastasis,tumor size,invasion depth,miR-552 and miR-653 were all risk factors affecting the chemotherapy efficacy of gastric cancer(P<0.05).ROC curve results showed that the AUC,95%CI,sensitivity and specificity of risk nomogram model to predict chemotherapy efficacy of gastric cancer were 0.867,0.672～0.991,92.80%and 80.40%,respectively(P<0.001).Calibration curve results showed that both predicted and actual predicted values were near the ideal curve,and the Hosmer-Lemeshow goodness of fit curve test χ2=1.869,P=0.782.Conclusion:The levels of serum exosomes miR-552 and miR-653 are closely related to the chemotherapy efficacy of gastric cancer,and dynamic monitoring of the above indexes is helpful for the evaluation of the disease and prognosis of gastric cancer.In this study,the risk nomogram model constructed based on the above indexes and other risk factors has high predictive value and clinical practicability for chemotherapy efficacy in patients with gastric cancer.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective:To observe the morphological characteristics of dome-shaped macula (DSM) and macular hole (MH) in high myopia by optical coherence tomography (OCT), to further explore the correlation between DSM and MH.Methods:A retrospective case-control study. From April 2021 to December 2023, 963 eyes of 503 patients with high myopia (myopic diopter ≥6.00 D) in Department of Ophthalmology of the Fourth Hospital of Hebei Medical University were enrolled in the study. The age of patients ranged from 5 to 89 years old, with the mean age of (48.91±16.69) years. Diopter was -6.00 to -26.00 (-10.49±3.15) D. All eyes were examined by OCT. The width and height of DSM, subfoveal choroidal thickness (SFCT), inner port diameter and base diameter of MH were measured by software on OCT. According to the OCT image features, DSM was divided into horizontal and vertical oval-shaped DSM, and symmetrical round DSM. According to the presence or absence of DSM, the eyes were divided into DSM group and non-DSM group. Then, the affected eyes with MH were divided into DSM with MH group and non-DSM with MH group. The incidence of DSM, the incidence of MH in the DSM group and the non-DSM group, the inner port diameter of MH, the base diameter of MH, SFCT, and the location of retinoschisis (RS) in the DSM with MH group and the non-DSM with MH group were observed. Independent sample t test or non-parametric Mann-Whitney U test was used for comparison between groups. Pearson correlation analysis was used to analyze the related factors of MH inner port diameter, base diameter and DSM width, height, height/width ratio. Results:Among the 963 eyes, the DSM group and the non-DSM group were 266 (27.6%, 266/963) and 697 (72.4%, 697/963) eyes. Compared with the non-DSM group, patients in the DSM group were older ( Z=-11.302), had higher degree of myopia ( Z=-8.944), thinner SFCT ( Z=-16.244), and higher incidence of MH ( χ2=8.828), and the differences were statistically significant ( P<0.05). Compared with non-DSM with MH group, the patients in DSM with MH group were older ( t=2.610), higher myopia diopter ( t=3.593), and thinner SFCT ( t=3.505), the differences were statistically significant ( P<0.05). There was no significant difference in the number of eyes in the epiretinal membrane between the two groups ( χ2=0.119, P=0.730). In the DSM with MH group, RS mostly occurred in the outer retina with a large range, while in the non-DSM with MH group, RS mostly occurred in the outer and inner retina with a small range. There was a statistically significant difference in the number of eyes at different positions of RS between the two groups ( χ2=25.131, P<0.05). The results of correlation analysis showed that there was no correlation between the inner port and base diameter of MH and the width, height, height/width ratio of DSM ( P>0.05). Conclusions:Compared with high myopia patients without DSM, patients with DSM are older, have more severe myopia and thinner SFCT. In DSM patients with MH, RS often occurs in the outer retina and has a large range. There was no significant association between DSM morphology and MH size.

Objective To compare imaging quality and detection capability of bone metastases between Insight NM/CT Pro SPECT/CT(Insight SPECT/CT)and Siemens Symbia T16 SPECT/CT(Symbia T16 SPECT/CT)scanners.Methods Totally 40 patients with diagnosed or suspected bone metastases were prospectively enrolled.Whole-body bone imaging and local tomographic fusion imaging were performed using Symbia T16 and Insight SPECT/CT scanners with same method and parameters,and imaging quality and detection capability were compared between 2 devices.Results Among whole-body bone imaging acquired with Symbia T 16 SPECT/CT,the imaging quality score was 5 in 35 cases and 4 in 5 cases,and detected 118 positive bone lesions,including 36 lesions involved chest,28 involved spinal cord,30 involved pelvic bones,20 involved limbs and 4 involved cranial bones.The imaging quality score of local tomographic fusion imaging obtained with Symbia T16 SPECT/CT was 5 in all 40 cases,and 59 positive lesions involved bone regions were detected,including 14 lesions presented as bone destruction,11 presented as increased bone density and 34 showed uneven bone density on CT.Meanwhile,the whole-body bone imaging quality score acquired with Insight SPECT/CT was 5 in 35 cases,4 in 4 cases and 3 in 1 case,and both the detected positive lesions and the involved bone regions were consistent with those of Symbia T 16 SPECT/CT.Furthermore,the imaging quality,detected positive lesions and their involved regions,as well as CT manifestations on local tomographic fusion imaging obtained with Insight SPECT/CT scanner were all consistent with those of Symbia T 16 scanner.Conclusion The imaging quality of whole-body bone imaging and local tomographic fusion imaging of bone metastases of domestic Insight SPECT/CT were comparable to those of Siemens Symbia T16 SPECT/CT.

Objective To mine and analyze signals of acute kidney injury(AKI)related to drugs,comprehensively summarize the potential risk drugs,and provide a reference for clinically safe medication.Methods The AKI reports from January 2004 to September 2023 in the US FDA Adverse Event Reporting System(FAERS)were retrieved.Disproportionality methods were used to explore the relationship between drugs and AKI,and demographic information,time to onset,and patient outcomes were analyzed.Results Out of 1 253 drugs,159 were identified as AKI signal drugs.Among these,there were 49 antimicrobial agents(30.82%),including 35 antibiotics and 14 antiviral agents;33 antineoplastic agents(20.75%);and 25 hypotensive agents(15.72%).Drug-related AKI occurred mostly in the elderly,and the male-to-female ratio was 124∶100.The median time to onset for AKI related to antibiotics was≤8 d,with the third quartile≤21 d.Rivaroxaban and aspirin had higher proportions of death reports,with 33.03%and 31.44%respectively.Conclusions A multitude of drugs pose a risk for acute kidney injury,necessitating caution in their clinical application and the implementation of monitoring of renal function.The elderly are a high-risk group for drug-related AKI,and there are more males than females.For antibiotics,the first 21 days are the key monitoring period.For drugs that require long-term use,regular monitoring is necessary.

Aim To evaluate the tyrosine nitration modification of specific proteins in vascular endothelial cells and its impact on mitochondria-mediated apoptosis.Methods Human umbilical vein endothelial cells were cultured in vitro and divided into three groups:control group(treatment with dimethyl sulfoxide),3-morphansulam(SIN-1)group,and SIN-1+Fe(Ⅲ)5,10,15,20-(tetraphenyl)porphyrin(FeTPP)group.After 24 h,the levels of hexokinase 1(HK1)nitration modification,mitochondrial membrane potential,reactive oxygen species(ROS)production,and endothelial cell proliferation and apoptosis were assessed.A human umbilical vein endothelial cell line knockout of HK1 was constructed using gene editing technology,and its proliferation and apoptosis levels were detected.Results After treatment of hu-man umbilical vein endothelial cells with peroxynitrite generator SIN-1,the level of HK1 protein nitration modification sig-nificantly increased(P＜0.01),reactive oxygen species production significantly increased,mitochondrial membrane poten-tial significantly decreased,endothelial cell proliferation ability significantly decreased,and endothelial cell apoptosis level significantly increased(all P＜0.01).Peroxynitrite decomposition catalyst FeTPP could reverse the above effect(P＜0.01).In addition,HK1 gene knockout also exhibited similar antioxidant effects,with a significant decrease in endothe-lial cell proliferation ability and a significant increase in apoptosis levels(P＜0.01).Conclusion Peroxynitrite can induce an increase in the level of nitration modification of HK1 in vascular endothelial cells,which may be achieved by pro-moting the production of mitochondrial reactive oxygen species,thereby accelerating the process of endothelial cell apoptosis.

This study aims to establish an efficient protoplast-mediated genetic transformation sys-tem for Pochonia chlamydosporia(P.chlamydosporia)to facilitate gene transformation,genetic modification,and subsequent biological function research.Through orthogonal testing,the study systematically optimized key factors influencing electroporation,including voltage,osmotic stabi-lizer,pulse time,nucleic acid concentration,and protoplast concentration.The results showed that the optimal electroporation conditions were:voltage of 250 V,osmotic stabilizer as 0.6 mol/L su-crose solution,pulse time of 10 ms,plasmid concentration of 1％,and protoplast concentration of 1×107 protoplasts/mL,yielding a transformation efficiency of 0.4 × 103 CFU/pg.The interaction analysis revealed that the five factors affected transformation efficiency in the following order:plasmid concentration＞protoplast concentration＞pulse time＞osmotic stabilizer type＞voltage.Based on the positive transformants,the study further evaluated their colony morphology,growth rate,conidial yield,mycelial dry weight,and the ability to infect the eggs of three types of animal gastrointestinal nematodes.The results indicated that the electroporation process did not signifi-cantly affect the biological functions of P.chlamydosporia.The transformants successfully ex-pressed enhanced green fluorescent protein(EGFP),and PCR analysis confirmed the successful in-tegration of the thiostrepton resistance gene.In conclusion,this study successfully established a protoplast-based electroporation-mediated genetic transformation system for P.chlamydosporia,providing a valuable foundation for further research into the mechanism of egg parasitism and the underlying genes involved in its biocontrol activity.

Objective To compare imaging quality and detection capability of bone metastases between Insight NM/CT Pro SPECT/CT(Insight SPECT/CT)and Siemens Symbia T16 SPECT/CT(Symbia T16 SPECT/CT)scanners.Methods Totally 40 patients with diagnosed or suspected bone metastases were prospectively enrolled.Whole-body bone imaging and local tomographic fusion imaging were performed using Symbia T16 and Insight SPECT/CT scanners with same method and parameters,and imaging quality and detection capability were compared between 2 devices.Results Among whole-body bone imaging acquired with Symbia T 16 SPECT/CT,the imaging quality score was 5 in 35 cases and 4 in 5 cases,and detected 118 positive bone lesions,including 36 lesions involved chest,28 involved spinal cord,30 involved pelvic bones,20 involved limbs and 4 involved cranial bones.The imaging quality score of local tomographic fusion imaging obtained with Symbia T16 SPECT/CT was 5 in all 40 cases,and 59 positive lesions involved bone regions were detected,including 14 lesions presented as bone destruction,11 presented as increased bone density and 34 showed uneven bone density on CT.Meanwhile,the whole-body bone imaging quality score acquired with Insight SPECT/CT was 5 in 35 cases,4 in 4 cases and 3 in 1 case,and both the detected positive lesions and the involved bone regions were consistent with those of Symbia T 16 SPECT/CT.Furthermore,the imaging quality,detected positive lesions and their involved regions,as well as CT manifestations on local tomographic fusion imaging obtained with Insight SPECT/CT scanner were all consistent with those of Symbia T 16 scanner.Conclusion The imaging quality of whole-body bone imaging and local tomographic fusion imaging of bone metastases of domestic Insight SPECT/CT were comparable to those of Siemens Symbia T16 SPECT/CT.