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.

Objective To explore the impact of factors such as economic level,regional differences,and healthcare policies on the medical costs and the clinical treatment behaviors for benign prostatic hyperplasia(BPH)using big data technology.Methods A combination of qualitative and quantitative approaches was employed,including descriptive statistical analysis,central tendency analysis,comparative analysis,and structural analysis to explore regional differences in the treatment of BPH and the underlying causes.Results The mean medical cost per case in the provincial capital city(19 502 yuan)was significantly higher than that in the prefecture-level city(16 526 yuan),with a difference of 2 976 yuan(+18%).Moreover,the cost distribution was more dispersed in the provincial capital([8 370 yuan-26 344 yuan]vs.[9 687 yuan-21 974 yuan]in the prefecture-level city).However,the provincial capital demonstrated better hospitalization efficiency,with a significantly shorter mean length of stay(9.24 days vs 10.21 days,-10.5%).All these differences were statistically significant(P<0.01).Payment methods influenced surgical choices.In the provincial capital,43.99%of patients underwent transurethral resection of the prostate(TURP),with no cases of holmium laser enucleation of the prostate(HOLEP).In contrast,the prefecture-level city reported 22.71%of patients receiving plasmakinetic resection of the prostate(PKRP)and 19.19%undergoing HoLEP.Significant differences were observed in antibiotic utilization patterns.The most commonly used antibiotic in the provincial capital was piperacillin-tazobactam(19.96%),while cefotaxime dominated in the prefecture-level city(21.11%).Notably,ertapenem was frequently used in the provincial capital but rarely in the prefecture-level city,potentially due to cost considerations(P<0.05).Regional preferences were evident in antispasmodic medication;phloroglucinol injection was used in 80%of cases in the prefecture-level city,while anisodamine hydrobromide injection predominated in the provincial capital(P<0.05).For BPH-specific medications,although tamsulosin hydrochloride sustained-release capsules were the primary choice in both regions,the prefecture-level city showed significantly higher usage(80.11%vs 49.17%).Finasteride tablets were more commonly prescribed in the provincial capital(39.03%vs.14.14%,P<0.05).Conclusion Economic levels,healthcare policies,and different hospitals significantly influence clinical decision-making and medical expenses.Hospitals should enhance refined management,while healthcare policy reforms need to advance from multiple perspectives and levels to improve the efficiency and equity of healthcare services.

Objective To explore the impact of factors such as economic level,regional differences,and healthcare policies on the medical costs and the clinical treatment behaviors for benign prostatic hyperplasia(BPH)using big data technology.Methods A combination of qualitative and quantitative approaches was employed,including descriptive statistical analysis,central tendency analysis,comparative analysis,and structural analysis to explore regional differences in the treatment of BPH and the underlying causes.Results The mean medical cost per case in the provincial capital city(19 502 yuan)was significantly higher than that in the prefecture-level city(16 526 yuan),with a difference of 2 976 yuan(+18%).Moreover,the cost distribution was more dispersed in the provincial capital([8 370 yuan-26 344 yuan]vs.[9 687 yuan-21 974 yuan]in the prefecture-level city).However,the provincial capital demonstrated better hospitalization efficiency,with a significantly shorter mean length of stay(9.24 days vs 10.21 days,-10.5%).All these differences were statistically significant(P<0.01).Payment methods influenced surgical choices.In the provincial capital,43.99%of patients underwent transurethral resection of the prostate(TURP),with no cases of holmium laser enucleation of the prostate(HOLEP).In contrast,the prefecture-level city reported 22.71%of patients receiving plasmakinetic resection of the prostate(PKRP)and 19.19%undergoing HoLEP.Significant differences were observed in antibiotic utilization patterns.The most commonly used antibiotic in the provincial capital was piperacillin-tazobactam(19.96%),while cefotaxime dominated in the prefecture-level city(21.11%).Notably,ertapenem was frequently used in the provincial capital but rarely in the prefecture-level city,potentially due to cost considerations(P<0.05).Regional preferences were evident in antispasmodic medication;phloroglucinol injection was used in 80%of cases in the prefecture-level city,while anisodamine hydrobromide injection predominated in the provincial capital(P<0.05).For BPH-specific medications,although tamsulosin hydrochloride sustained-release capsules were the primary choice in both regions,the prefecture-level city showed significantly higher usage(80.11%vs 49.17%).Finasteride tablets were more commonly prescribed in the provincial capital(39.03%vs.14.14%,P<0.05).Conclusion Economic levels,healthcare policies,and different hospitals significantly influence clinical decision-making and medical expenses.Hospitals should enhance refined management,while healthcare policy reforms need to advance from multiple perspectives and levels to improve the efficiency and equity of healthcare services.

OBJECTIVE To explore the influence of glucuronoxylomannan(GXM)of Trichosporon asahii on Toll-like receptor(TLR)-2,TLR-4 and TLR-6 in human myeloid leukemia mononuclear cell(THP-1)and analyze the molecular mechanisms.METHODS The THP-1 cells were randomly divided into the blank control group(without any treatment after the culture of induced and differentiated THP-1 cells for 8 and 24 hours),and the GXM group(with the induced and differentiated THP-1 cell acting by 500 μg/ml of T.asahii GXM for 8 and 24 hours)after being induced differentiation with phorbol 12-myristate 13-acetate(PMA).The expression levels of TLR-2,TLR-4 and TLR-6 messager ribonucleic acid(mRNA)were detected by real-time fluorescent quantitative polymerase chain reaction(RT-qPCR),and the expression level of TLR-2 protein was detected by means of Western Blot(WB).RESULTS The expression levels of TLR-2,TLR-4 and TLR-6 mRNA of the GXM group were 0.65±0.05,0.46±0.03 and 0.51±0.19,respectively,after the THP-1 cells were acted with GXM for 8 hours,lower than those of the blank control group(P＜0.05).After being acting with GXM for 24 hours,the expression level of TLR-2 mRNA of the GXM group was 0.83±0.05,lower than that of the blank control group(t=4.927,P=0.039),and there were no significant differences in the expression levels of TLR-4 and TLR-6 mRNA between the GXM group and the blank control group.The expression level of TLR-2 protein of the GXM group was 85.43±0.40 after the THP-1 cells were acted with GXM for 24 hours,lower than that of the blank control group(t=35.415,P＜0.001).CONCLUSION The T.asahii may possess the capabilities of escaping from the phagocytosis of white blood cells and monocytes by increasing the release of GXM,which may help a certain number of fungi escape from the killing by the immune system of the host and establish the persistent infection.

OBJECTIVE To explore the influence of glucuronoxylomannan(GXM)of Trichosporon asahii on Toll-like receptor(TLR)-2,TLR-4 and TLR-6 in human myeloid leukemia mononuclear cell(THP-1)and analyze the molecular mechanisms.METHODS The THP-1 cells were randomly divided into the blank control group(without any treatment after the culture of induced and differentiated THP-1 cells for 8 and 24 hours),and the GXM group(with the induced and differentiated THP-1 cell acting by 500 μg/ml of T.asahii GXM for 8 and 24 hours)after being induced differentiation with phorbol 12-myristate 13-acetate(PMA).The expression levels of TLR-2,TLR-4 and TLR-6 messager ribonucleic acid(mRNA)were detected by real-time fluorescent quantitative polymerase chain reaction(RT-qPCR),and the expression level of TLR-2 protein was detected by means of Western Blot(WB).RESULTS The expression levels of TLR-2,TLR-4 and TLR-6 mRNA of the GXM group were 0.65±0.05,0.46±0.03 and 0.51±0.19,respectively,after the THP-1 cells were acted with GXM for 8 hours,lower than those of the blank control group(P＜0.05).After being acting with GXM for 24 hours,the expression level of TLR-2 mRNA of the GXM group was 0.83±0.05,lower than that of the blank control group(t=4.927,P=0.039),and there were no significant differences in the expression levels of TLR-4 and TLR-6 mRNA between the GXM group and the blank control group.The expression level of TLR-2 protein of the GXM group was 85.43±0.40 after the THP-1 cells were acted with GXM for 24 hours,lower than that of the blank control group(t=35.415,P＜0.001).CONCLUSION The T.asahii may possess the capabilities of escaping from the phagocytosis of white blood cells and monocytes by increasing the release of GXM,which may help a certain number of fungi escape from the killing by the immune system of the host and establish the persistent infection.

Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer.Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were select-ed.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARH-GAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the pa-tients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expres-sion.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups.Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue(P＜0.001).The expression level of ARHGAP8 was correlated with tumor stage(P=0.024),lymph node metastasis(P=0.007),and age(P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tis-sue(P＜0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARH-GAP8 in the cancer tissue was higher than that in the rectal tissue(P=0.011).The expression of ARHGAP8 was correlated with tumor size(P=0.010)and pathological stage(P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 pa-tients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91％(29/44)patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy(P＜0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86％,which was higher than that(53.33％)in the patients with high pro-tein level of ARHGAP8(P=0.033).Conclusions ARHGAP8 is highly expressed in the rectal cancer tissue.The pa-tients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and develop-ment of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.

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.