Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Objectives:To investigate the clinical efficacy of the smiley face rod(SFR)technique in treating lumbar spondylolysis with grade Ⅰ spondylolisthesis.Methods:A total of 22 patients(18 males,4 females)with lumbar spondylolysis and grade Ⅰ spondylolisthesis treated with the SFR segmental fixation technique in our department from January 2019 to December 2024 were retrospectively analyzed.The age of the patients was 12-55(28.7±12.6)years old,the body mass index(BMI)was 18-29kg/m2(22.7±3.4kg/m2),and preoperative symptom duration was 6-60(12.3±14.3)months.The patients were followed up for 6-19(9.1±4.5)months.The operative time and intraoperative blood loss volume were recorded.Before opearation,at 3 months and 6 months after operation,visual analogue scale(VAS)for low back pain,Oswestry disability index(ODI),and Japanese Orthopaedic Association(JOA)scores were recorded to evaluate the clinical outcomes.Imaging exami-nations(X-ray,CT)were performed before operation and at 6 months after operation to measure preoperative and postoperative disc height(DH),slip distance(SD),slip rate,lumbar lordosis angle,and range of motion(ROM)at the surgical and adjacent segments to assess the improvement of spondylolisthesis and ROM,as well as the pars defect healing status.The correlations between age,BMI,preoperative disease duration and isthmus bone healing rate were studied.Results:The operative time was 131.8±32.8min(range:86-200min),and intraoperative blood loss was 86.4±41.4mL(range:50-150mL).Significant improvements in VAS,ODI and JOA scores were observed at 3 months and 6 months versus preoperative values(P＜0.05).Slip distance,slip percentage,and lumbar lordosis angle significantly decreased at 6 months versus preoperatively(P＜0.05).No significant differences were observed in DH ratio or ROM between the surgical and adjacent segments preoperatively and at 6 months(P＜0.05).At 6-month follow-up,complete bilateral pars bony union was achieved in 18 cases(81.82％),partial union(including unilateral or other types)in 3 cases(13.63％),and nonunion in 1 case(4.55％).Age,BMI,and preoperative symptom duration showed potential influence on bone healing.Conclusions:In the treatment of lumbar spondylolysis with grade Ⅰ spondylolisthesis,SFR can effectively enhance postoperative lumbar stability,significantly alleviate low back pain symptoms,preserve lumbar mobility,and mitigate disc height collapse to a certain extent.

Objectives:To investigate the clinical efficacy of the smiley face rod(SFR)technique in treating lumbar spondylolysis with grade Ⅰ spondylolisthesis.Methods:A total of 22 patients(18 males,4 females)with lumbar spondylolysis and grade Ⅰ spondylolisthesis treated with the SFR segmental fixation technique in our department from January 2019 to December 2024 were retrospectively analyzed.The age of the patients was 12-55(28.7±12.6)years old,the body mass index(BMI)was 18-29kg/m2(22.7±3.4kg/m2),and preoperative symptom duration was 6-60(12.3±14.3)months.The patients were followed up for 6-19(9.1±4.5)months.The operative time and intraoperative blood loss volume were recorded.Before opearation,at 3 months and 6 months after operation,visual analogue scale(VAS)for low back pain,Oswestry disability index(ODI),and Japanese Orthopaedic Association(JOA)scores were recorded to evaluate the clinical outcomes.Imaging exami-nations(X-ray,CT)were performed before operation and at 6 months after operation to measure preoperative and postoperative disc height(DH),slip distance(SD),slip rate,lumbar lordosis angle,and range of motion(ROM)at the surgical and adjacent segments to assess the improvement of spondylolisthesis and ROM,as well as the pars defect healing status.The correlations between age,BMI,preoperative disease duration and isthmus bone healing rate were studied.Results:The operative time was 131.8±32.8min(range:86-200min),and intraoperative blood loss was 86.4±41.4mL(range:50-150mL).Significant improvements in VAS,ODI and JOA scores were observed at 3 months and 6 months versus preoperative values(P＜0.05).Slip distance,slip percentage,and lumbar lordosis angle significantly decreased at 6 months versus preoperatively(P＜0.05).No significant differences were observed in DH ratio or ROM between the surgical and adjacent segments preoperatively and at 6 months(P＜0.05).At 6-month follow-up,complete bilateral pars bony union was achieved in 18 cases(81.82％),partial union(including unilateral or other types)in 3 cases(13.63％),and nonunion in 1 case(4.55％).Age,BMI,and preoperative symptom duration showed potential influence on bone healing.Conclusions:In the treatment of lumbar spondylolysis with grade Ⅰ spondylolisthesis,SFR can effectively enhance postoperative lumbar stability,significantly alleviate low back pain symptoms,preserve lumbar mobility,and mitigate disc height collapse to a certain extent.

Melanocytes derived from neural crest cells harbor the BRAFV600E mutation,which is the predominant driver of nevus formation in humans.This mutation leads to malignant cell proliferation and subsequent cell cycle arrest,culminating in oncogene-induced senescence and nevus development.Nevertheless,emerging evidence has highlighted the heterogeneity of cellular senescence markers in BRAFV600E-induced senescent melanocytes.Moreover,the capacity of melanocytes within nevi to regain their proliferative ability raises questions about the molecular mechanisms by which BRAFV600E,via the mitogen-activated protein kinase signaling pathway,triggers nevus formation.This study provides an overview and discussion of the molecular mechanisms underpinning BRAFV600E-induced melanocyte nevus formation and the relevant animal models employed for their elucidation.It also highlights the significance of elucidating dynamic changes in cytoplasmic and nuclear substrates that interact with phosphorylated extracellular signal-regulated protein kinases 1 and 2 and underscores the value of using targeted BRAFV600E animal models created through gene editing technologies.

Objective:To study the features of adenomyomatous hyperplasia (AH) of the Vaterian system (common bile duct and ampulla of Vater) to help in the diagnosis and management of this disease.Methods:A retrospective analysis on the data of 17 patients who had a postoperative pathological diagnosis of AH of the Vaterian system treated from January 2005 to December 2021 at the First Medical Center of the PLA General Hospital was carried out with 12 males and 5 females, aged (58.4±11.3) years. The clinical presentations, treatment and postoperative pathology of these patients were analyzed. Patients with dysplasia of the tubular mucosal epithelium in the non-cancerous area around the AH under microscopy were included in the AH with dysplasia group ( n=8), and those without dysplasia were included in the control group ( n=9). The clinical characteristics of the two groups were compared. Results:The main clinical symptoms were abdominal pain in 8 patients, jaundice in 7 patients and fever in 2 patients. Preoperative imaging showed 10 cases of occupying lesions and 6 cases of abnormally dilated intrahepatic and extrahepatic bile ducts without obvious lesions or stones or biliary tract injury stenosis. Sixteen patients underwent radical pancreaticoduodenectomy, and 1 patient underwent extrahepatic biliary resection combined with choledochojejunostomy for bile duct obstruction due to biliary stones, 3 patients had combined malignant tumors, 1 patient had a carcinoma of AH origin at the ampulla of Vater, and the other 2 patients had neoplastic lesions in the mucosal epithelium adjacent to the AH (cholangiocarcinoma and ampullary carcinoma, respectively). There were no significant differences in age, gender, bile duct stones, cholangitis, combined carcinoma and liver function indexes between the two groups of patients with AH of the Vaterian system (all P>0.05). Conclusion:Adenomyomatous hyperplasia of the Vaterian system was difficult to distinguish preoperatively from malignant tumors basing on its clinical presentations or imaging findings. Such patients are recommended to be treated surgically.

Objective:To investigate the etiological mechanism in single small subcortical infarction (SSSI) with different imaging features.Methods:The patients registered in a database of ischemic stroke in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were analyzed. According to the lowest slice (LS) and the total number of involved slices (TNS) on diffusion-weighted imaging, the SSSI was divided into 3 types: proximal SSSI (pSSSI; LS≤2), distal and large SSSI (dl-SSSI; LS>2, TNS>2) and distal and small SSSI (ds-SSSI; LS>2, TNS≤2). The clinical and imaging features among 3 different lesion patterns were compared by using χ 2 test, Kruskal-Wallis H test and multiple Logistic regression analysis, etc. Results:In the 3 groups of ds-SSSI ( n=205), dl-SSSI ( n=157) and pSSSI ( n=166), the prevalences of parent artery disease (PAD)[10.7% (22/205) , 19.1% (30/157) , 42.8% (71/166), respectively, χ 2=54.89, P<0.001], coronary artery disease [8.3% (17/205), 14.0% (22/157), 16.9%(28/166), respectively, χ 2=6.44, P=0.040] and severe white matter hyperintensities (sWMHs)[58.0% (119/205), 43.3% (68/157), 41.0% (68/166), respectively, χ 2=12.94, P<0.001], the level of serum homocysteine (Hcy)[18.01 (13.54, 25.56), 16.03 (12.50, 21.09), 14.72 (11.12, 19.14) μmol/L, respectively, H=19.36, P<0.001], and the National Institutes of Health Stroke Scale (NIHSS) score[2(1, 3), 3(1, 4), 3(2, 6), respectively, H=39.53, P<0.001] showed statistically significant differences. Multiple Logistic regression analysis showed that compared with dl-SSSI patients, the lesion pattern of patients with higher proportion of PAD ( OR=3.12, 95% CI 1.86-5.24, P<0.001) was closer to pSSSI; the lesion pattern of patients with higher serum Hcy level ( OR=1.02, 95% CI 1.00-1.04, P=0.046) or higher proportion of sWMHs ( OR=1.79, 95% CI 1.12-2.86, P=0.015) was closer to ds-SSSI, and the lesion pattern of patients with higher proportion of PAD ( OR=0.50, 95% CI 0.27-0.93, P=0.029) or higher NIHSS score ( OR=0.84, 95% CI 0.77-0.92, P<0.001) was closer to dl-SSSI. Conclusions:The pathogenesis of ds-SSSI tends to be cerebral small vessel disease. The pathogenesis of pSSSI is related to atherosclerosis. The patients with dl-SSSI have the intermediate characteristics of pSSSI and ds-SSSI and may be unstable.

Objective:To study the use of trans gastric sinus stent placement and drainage in management of persistent external pancreatic fistula.Methods:The clinical data of 12 patients who developed persistent external pancreatic fistulae after severe acute pancreatitis, pancreatic trauma or pancreatic surgery who were treated at the First Medical Center of Chinese PLA General Hospital from August 2018 to December 2020 were retrospectively analyzed. There were 10 males and 2 females, aged 30 to 65 years, median 43.5 years. These patients underwent trans gastric sinus stent placement and drainage, and were followed-up to study persistence of pancreatic fistula, new pancreatic fluid accumulation, complications and death.Results:In this study, there were 9 patients who developed persistent external pancreatic fistulae after severe acute pancreatitis, 2 patients after pancreatic trauma, and 1 patient after pancreatic surgery. The median operation time was 47 min (range 38-54 min). The technical success rate was 100.0% (12/12). The median follow-up was 22.5 months (range 2-29 months). Seven days after stenting, the percutaneous drainage tubes (urinary catheters) of all the patients were removed. One patient (8.3%) developed recurrence of pancreatic fistula 17 days after treatment. The same procedure of placing another stent was done and the patient recovered. Six months after treatment, 2 patients (16.7%) lost their stents, and 1 patient developed a pseudocyst (recurrence of pancreatic fistula). The maximum diameter of this pseudocyst increased gradually to 7cm after 9 months. A double pigtail drainage tube was placed under endoscopy in this patient, and the patients recovered. All the other patients did not develop recurrence of pancreatic fistula or pseudocyst. During the follow-up period, no patient developed any new complications including pancreatic fluid accumulation, fever, bleeding, infection and organ dysfunction, and no patients died.Conclusion:It was safe and efficacious to use trans gastric sinus stent placement for treatment of persistent external pancreatic fistula. However, the long-term outcomes require further studies.

Objective:To explore the strategy and efficacy using minimally invasive treatment for grade Ⅲ&Ⅳ blunt pancreatic injuries.Methods:Retrospective data retrieved from medical records of 13 patients with grade Ⅲ&Ⅳ blunt pancreatic injuries who underwent minimally invasive treatment at the Chinese PLA General Hospital from July 2011 to June 2019 were analysed. There were 10 males and 3 females, aged (38±9) years. Minimally invasive treatment included percutaneous catheter drainage (PCD) and minimal-access retroperitoneal pancreatic necrosectomy (MARPN). Date from enrolled patients were anylsed.Results:There were 9 patients suffering from grade Ⅲ injuries and 4 patients suffering from grade Ⅳ injuries. On initial conservative treatment of these 13 patients, all developed local complications. The local complications were treated using minimally invasive treatment strategies: 13 patients underwent PCD. The median intervention time for PCD was 25 days after trauma; 10 patients were further treated with MARPN, and the median intervention time of MARPN was 41 days after trauma. Twelve patients recovered well and were discharged home. One patient died. The mortality rate was 7.7% (1/13). The median postoperative hospital stay was 19 days.Conclusion:For patients with pancreatic grade Ⅲ&Ⅳ injuries who were hemodynamically stable and had no other associated gastrointestinal injuries, initial conservative treatment, followed by subsequent minimally invasive treatment based on MARPN technology could be used to treat local complications.