Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

[Objective] To evaluate the efficacy and safety of sacral neuromodulation (SNM) in the treatment of patients with benign prostatic hyperplasia (BPH) complicated with underactive bladder (UAB) who respond poorly to transurethral resection of the prostate (TURP). [Methods] A retrospective analysis was performed on 10 patients with BPH and UAB treated with TURP by the same surgeon in Zhongda Hospital Southeast University during Jan.2018 and Jan.2023.The residual urine volume was not significantly relieved after operation, and the maximum urine flow rate and urine volume per discharge were not significantly improved.All patients underwent phase I SNM, and urinary diaries were recorded before and after surgery to observe the average daily frequency of urination, volume per urination, maximum urine flow rate, and residual urine volume. [Results] The operation time was (97.6±11.2) min.During the postoperative test of 2-4 weeks, if the residual urine volume reduction by more than 50% was deemed as effective, SNM was effective in 6 patients (60.0%). Compared with preoperative results, the daily frequency of urination [(20.2±3.8) times vs. (13.2±3.2) times], volume per urination [(119.2±56.7) mL vs. (246.5±59.2) mL], maximum urine flow rate [(8.7±1.5) mL/s vs. (16.5±2.6) mL/s], and residual urine volume [(222.5±55.0) mL vs. (80.8±16.0) mL] were significantly improved, with statistical significance (P<0.05). There were no complications such as bleeding, infection, fever or pain.The 6 patients who had effective outcomes successfully completed phase II surgery, and the fistula was removed.During the follow-up of 1 year, the curative effect was stable, and there were no complications such as electrode displacement, incision infection, or pain in the irritation sites.The residual urine volume of the other 4 unsuccessful patients did not improve significantly, and the electrodes were removed and the vesicostomy tube was retained. [Conclusion] SNM is safe and effective in the treatment of BPH with UAB patients with poor curative effects after TURP.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Objective To investigate the effect of perindopril on the nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)/NOD-like receptor protein 3(NLRP3)signaling pathway in rat liver fibrosis induced by thioacetamide(TAA).Methods Thirty-two SD rats were randomly divided into the blank group,the model group(TAA 200 mg/kg,twice a week for 6 weeks)and the low/high dose group(TAA+perindopril 2/8 mg/kg),with 8 rats in each group.Two weeks after modeling,the administration group was given the corresponding dose of perindopril by gavage(for 4 weeks).At the end of the 6th week,liver pathological sections were used to observe pathological changes of liver tissue and degrees of fibrosis and inflammation.The biochemical analyzer was used to detect alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Enzyme-linked immunosorbent assay(ELISA)was used to detect NLRP3 and IL-1β.Immunohistochemistry was used to detect NOX4,NLRP3,Caspase-1,IL-1β protein and α-smooth muscle agonist protein(α-SMA).Results Compared with the blank group,liver collagen fibers were significantly proliferated in the model group,a large number of inflammatory cells infiltrated,and serum levels of ALT and AST,as well as NLRP3 and IL-1β in rats were significantly increased.The average optical density values of positive proteins such as NOX4,NLRP3,Caspase-1,IL-1β and α-SMA in rat liver tissue increased significantly(P<0.05).Compared with the model group,the proliferation of collagen fibers and inflammatory infiltration were significantly reduced in both the low-dose and high-dose groups,and serum levels of ALT and AST,NLRP3 and IL-1β in rats were significantly decreased.The average optical density values of positive proteins such as NOX4,NLRP3,Caspase-1,IL-1β and α-SMA in rat liver tissue decreased significantly(P<0.05).Moreover,the degree of liver fibrosis reduction in rats was better in the high-dose group than that in the low-dose group.Conclusion Perindopril may regulate the NLRP3 signaling pathway by inhibiting the expression of NOX4,thereby reducing oxidative stress damage and inflammatory responses and thus delaying the process of liver fibrosis.

Objective To develop a fused model based on combined intratumor-peritumor radiomics features and clinical risk factors to accurately predict the efficacy of radiotherapy for hepatocellular carcinoma(HCC).Methods A retrospective study was conducted on 124 HCC patients(95 males and 29 females)undergoing IMRT at the radiotherapy center of some hospital,who were divided into a training set and a validation set in a 7∶3 ratio.According to relevant standards for evaluating solid tumor treatment efficacy the patients at the progressive disease phase were enrolled into a non-response group,and the ones at the phases of complete response,partial response and stable disease were included into a response group.Firstly,radiomics features were extracted from pre-radiotherapy contrast-enhanced CT images,and were screened with the least absolute shrinkage and selection operator(LASSO)regression to obtain valuable radiomics features;secondly,the scores of intratumor radiomics features,peritumor radiomics features and combined intratumor-peritumor radiomics features underwent binary Logistic regression(LR)analysis by using the glmnet package in R software(version 4.2.0),so as to construct three models for intratumor radiomics features,peritumor radiomics features and combined intratumor-peritumor radiomics features;finally,a fused model was established based on the scores of combined intratumor-peritumor radiomics features and clinical risk factors,and the corresponding Nomogram,calibration curve and clinical decision curve were plotted.R software(version 4.4.1)was used for image analysis and statistical analysis.Results The fused model based on the scores of combined intratumor-peritumor radiomics features and clinical risk factors achieved an AUC of 0.87 on both the training and validation sets,outperforming the models based solely on intratumor radiomics features,peritumor radiomics features or combined intratumor-peritumor radiomics features.The Nomogram plot showed the prediction probability of the fused model for the short-term treatment response rate was 10%-90%within the total score range of 42-93 points,and the calibration and clinical decision curves indicated that the fused model gained advantages in prediction and clinical application.Conclusion The fused model based on the scores of combined intratumor-peritumor radiomics features and clinical risk factors predicts the short-term efficacy of HCC radiotherapy effectively,providing references for formulating radiotherapy plans and guiding subsequent treatment decisions.

Objective:To evaluate the early outcomes of total hip arthroplasty (THA) and discuss the revisions post THA in the treatment for Kashin-Beck disease (KBD) with severe hip problems.Methods:This retrospective cohort study enrolled 50 patients (64 hips) with a mean age of 52.4±8.7 years, including 25 male patients and 25 female patients (36 left hips and 28 right hips), who were diagnosed as KBD with hip problems and received THA at Arthritis Clinical and Research Centre, Peking University People's Hospital from October 2019 to January 2024. The leg length discrepancy (LLD), femoral offset (FO), abduction angle and anteversion angle were calculated preoperatively and one week post-operation. The postoperative radiological indexes and the functional outcomes in the last follow-up were compared with the preoperative assessment.Results:The surgical duration was 105(80, 120) min and the bleeding amount was 300(200, 400) ml. All the cases were followed up for an average of 37 months (ranging from 21 to 44 months). Significant differences were found on postoperative radiological images, with LLD improving to 0.50±0.78 cm from a preoperative value of -1.36±0.79 cm, and FO increasing to 3.28±1.01 cm from 2.72±0.83 cm ( P<0.05). The mean postoperative abduction angle and anteversion angle were 42.5°±7.7° and 15.1°±5.9°, respectively. A total of 71.8% and 95.3% hips fell within the Lewinnek safe zones of abduction angle and anteversion angle, respectively. In terms of functional outcomes, the average range of motion improved significantly to 185°(173°, 210°) from a preoperative value of 99°(76°, 123°), and the Harris Hip Score increased from 35(26, 43) preoperatively to 70(63, 80) postoperatively ( P<0.05). During the follow-up, there were complications for two cases of femoral stem loosening, one case of periprosthetic femoral fracture, one case of hip dislocation, and one case of acetabular component loosening with hip subluxation. Additionally, seven patients exhibited Trendelenburg gait. A total of five hips required revision surgery due to severe complications, including two cases of femoral stem loosening, one case of periprosthetic femoral fracture, one case of hip dislocation, and one case of acetabular component loosening with subluxation. Conclusions:Patients with KBD demonstrated significant early improvements in both radiological and functional outcomes following THA.

Objective:To compare the effects of propofol and dexmedetomidine for sedation on the outcome in mechanically ventilated patients with severe pulmonary infection.Methods:Patients with severe pulmonary infection (Clinical Pulmonary Infection Score >7) requiring mechanical ventilation from the Medical Information Mart for Intensive Care Ⅳ database between 2008 and 2020 were selected and divided into propofol group and dexmedetomidine group based on the sedative agent used. The primary outcome was all-cause in-hospital mortality, and secondary outcomes included 90-day all-cause mortality and duration of mechanical ventilation. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders, and logistic regression and linear regression were applied to analyze the effects of the two sedative drugs on the outcomes of mechanically ventilated patients with pulmonary infection. Kaplan-Meier survival curves were used to analyze survival outcomes.Results:A total of 6 204 critically ill patients with pulmonary infection requiring mechanical ventilation were included, with 3 439 cases in propofol group and 2 765 cases in dexmedetomidine group. The baseline characteristics between the two groups were well balanced (standardized mean difference < 0.1) after IPTW adjustment. In the IPTW-adjusted cohort, the in-hospital all-cause mortality and 90-day all-cause mortality were significantly lower in dexmedetomidine group than in propofol group (439.2[18.7%] vs 563.6[24.1%], 618.0[26.3%] vs 733.6[31.3%], P<0.001), the results of Further Kaplan-Meier survival curve analysis showed that the 90-day all-cause mortality was significantly lower in dexmedetomidine group than in propofol group ( P<0.01). Conclusions:Compared with propofol, dexmedetomidine can decrease the mortality rate and improve the prognosis in mechanically ventilated patients with severe pulmonary infection when used for sedation.

Objective:To investigate the clinical demand for subcutaneous immunotherapy (SCIT) with pet allergens and explore the sensitization characteristics of patients undergoing pet SCIT.Methods:A cross-sectional retrospective analysis was conducted on patients diagnosed with pet allergies and treated with pet allergen SCIT in our outpatient clinic from January 2019 to December 2023. Patients were categorized into three groups based on the type of SCIT received: single-cat SCIT group, single-dog SCIT group, and combined cat-dog SCIT group.Results:A total of 931 patients were included, the age range was 5-65 years (median age of 30 years), with 283 male and 648 female. Among them, 67.7%( n=630) received single-cat SCIT, 10.9% ( n=102)received single-dog SCIT, and 21.4% ( n=199) received combined cat-dog SCIT. The number of patients receiving pet allergen SCIT increased annually. Patients in the single-dog SCIT group were significantly older than those in the other two groups ( H=41.329, P<0.001) and had a lower prevalence of allergic rhinitis (91.2% vs. 96.5% and 98.5%; χ2=10.400, P=0.006). In the combined cat-dog SCIT group, the allergy rate to mold allergens was significantly higher than in the single-cat SCIT group (12.6% vs. 4.9%, χ2=13.965, P=0.001). In the single-dog SCIT group, the allergy rate to spring pollen allergens was significantly higher than in the other two groups ( χ2=15.731, P<0.001), and the allergy rate to autumn pollen allergens was significantly higher than in the single-cat SCIT group ( χ2=13.459, P=0.001). There was no significant difference in the dust mite allergy rate among the three groups( χ2=4.117, P=0.129). In the single-dog SCIT group, patients with asthma were significantly older than those without asthma (41.2 vs. 35.2 years old, t=-2.073, P=0.041). In both the single-cat and single-dog SCIT groups, the proportion of allergic rhinitis in the asthma group(91.2%,78.3%) was significantly lower than that in the non-asthma group(97.4%,94.9%) ( χ2=8.863,6.158; P=0.008,0.026). In the single-cat SCIT group, non-asthmatic patients were significantly more likely to receive SCIT combined with spring pollen allergens compared to asthmatic patients (23.9% vs. 11.0%, χ2=7.586, P=0.006). Conclusions:The demand for pet allergen SCIT has steadily increased over the years, with a predominance of female patients. Sensitization profiles varied among patients receiving SCIT for different pet allergens. This study comprehensively elucidates the clinical demand and sensitization characteristics of patients undergoing pet allergen SCIT, providing valuable reference data for clinical diagnosis and treatment.