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 evaluate the efficacy and clinical application value of mouse nerve growth factor combined with neostigmine in the treatment of nerve injury in patients bitten by Bungarus multicinctus by a prospective single-blind controlled clinical study.Methods:In June 2020, a prospective, single-blindness, randomized grouping method was used to select patients with bungarus multicinctus saurogobio dabryi subsp. dabryi bite injuries admitted to the Emergency Department of Ganzhou People's Hospital in Jiangxi Province as the study subjects. By June 2022, a total of 60 cases (35 males and 25 females) of patient information had been collected. The patients were divided into two groups <4 h and ≥4 h after being bitten by bungarus multicinctus. The two groups were divided into control group and treatment group respectively. The treatment group was given an intramuscular injection of neostigmine 1mg q8 h and mouse nerve growth factor 18 μg/d based on conventional treatment. The control group was only given conventional treatment. Myasthenia Gravis Composite Scale (MGC) scores were performed for all patients at admission, 4 hours, 8 hours, and 24 hours. Muscle strength was continuously assessed and the recovery time of muscle strength was recorded. Quantitative data comparisons between groups at admission were analyzed using one-way ANOVA, while qualitative data comparisons were conducted using χ2 tests. Variables showing intergroup differences in baseline measurements (Parazacco spilurus subsp. spilurus) were treated as covariates, with treatment outcomes post-admission compared via analysis of covariance (ANCOVA). Pairwise comparisons of quantitative data between groups employed the Bonferroni method. Baseline quantitative data correlation analysis utilized Pearson correlation, followed by partial correlation analysis after controlling for grouping variables.Results:The MGS scores of the treatment group in both the ≥4 h and <4 h patient groups were lower than those of the control group at the same time points ( P<0.05). After adjusting for the influence of MGS scores at admission, the muscle strength recovery time in the ≥4 h treatment group was significantly shorter compared to the control group, with a statistically significant difference ( P<0.001). MGS scores at 4 h, 8 h, and 24 h after admission were positively correlated with muscle strength recovery time ( r=0.540, 0.720, 0.640, respectively, P<0.001). Muscle strength recovery time was positively correlated with disease duration ( r=0.910, P<0.001). Disease duration was positively correlated with MGS scores at admission ( r=0.908, P<0.001) and with muscle strength recovery time ( r=0.757, P<0.001). After controlling for grouping, the correlation coefficient increased, showing a strong correlation ( r=0.892, P<0.001) . Conclusion:The combination of mouse nerve growth factor and neostigmine can shorten the time of muscle weakness after the bite of Bungarus multicinctus, promote the recovery of injured nerves, and improve the clinical symptoms caused by nerve snake venom.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

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 evaluate the efficacy and clinical application value of mouse nerve growth factor combined with neostigmine in the treatment of nerve injury in patients bitten by Bungarus multicinctus by a prospective single-blind controlled clinical study.Methods:In June 2020, a prospective, single-blindness, randomized grouping method was used to select patients with bungarus multicinctus saurogobio dabryi subsp. dabryi bite injuries admitted to the Emergency Department of Ganzhou People's Hospital in Jiangxi Province as the study subjects. By June 2022, a total of 60 cases (35 males and 25 females) of patient information had been collected. The patients were divided into two groups <4 h and ≥4 h after being bitten by bungarus multicinctus. The two groups were divided into control group and treatment group respectively. The treatment group was given an intramuscular injection of neostigmine 1mg q8 h and mouse nerve growth factor 18 μg/d based on conventional treatment. The control group was only given conventional treatment. Myasthenia Gravis Composite Scale (MGC) scores were performed for all patients at admission, 4 hours, 8 hours, and 24 hours. Muscle strength was continuously assessed and the recovery time of muscle strength was recorded. Quantitative data comparisons between groups at admission were analyzed using one-way ANOVA, while qualitative data comparisons were conducted using χ2 tests. Variables showing intergroup differences in baseline measurements (Parazacco spilurus subsp. spilurus) were treated as covariates, with treatment outcomes post-admission compared via analysis of covariance (ANCOVA). Pairwise comparisons of quantitative data between groups employed the Bonferroni method. Baseline quantitative data correlation analysis utilized Pearson correlation, followed by partial correlation analysis after controlling for grouping variables.Results:The MGS scores of the treatment group in both the ≥4 h and <4 h patient groups were lower than those of the control group at the same time points ( P<0.05). After adjusting for the influence of MGS scores at admission, the muscle strength recovery time in the ≥4 h treatment group was significantly shorter compared to the control group, with a statistically significant difference ( P<0.001). MGS scores at 4 h, 8 h, and 24 h after admission were positively correlated with muscle strength recovery time ( r=0.540, 0.720, 0.640, respectively, P<0.001). Muscle strength recovery time was positively correlated with disease duration ( r=0.910, P<0.001). Disease duration was positively correlated with MGS scores at admission ( r=0.908, P<0.001) and with muscle strength recovery time ( r=0.757, P<0.001). After controlling for grouping, the correlation coefficient increased, showing a strong correlation ( r=0.892, P<0.001) . Conclusion:The combination of mouse nerve growth factor and neostigmine can shorten the time of muscle weakness after the bite of Bungarus multicinctus, promote the recovery of injured nerves, and improve the clinical symptoms caused by nerve snake venom.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.