Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

As a branched chain amino acid, L-valine is widely used in the medicine and feed sectors. In this study, a microbial cell factory for efficient production of L-valine was constructed by combining various metabolic engineering strategies. First, precursor supply for L-valine biosynthesis was enhanced by strengthening the glycolysis pathway and weakening the metabolic pathway of by-products. Subsequently, the key enzyme in the L-valine synthesis pathway, acetylhydroxylate synthase, was engineered by site-directed mutation to relieve the feedback inhibition of the engineered strain. Moreover, promoter engineering was used to optimize the gene expression level of key enzymes in L-valine biosynthetic pathway. Furthermore, cofactor engineering was adopted to change the cofactor preference of acetohydroxyacid isomeroreductase and branched-chain amino acid aminotransferase from NADPH to NADH. The engineered strain C. glutamicum K020 showed a significant increase in L-valine titer, yield and productivity in 5 L fed-batch bioreactor, up to 110 g/L, 0.51 g/g and 2.29 g/(L‧h), respectively.
Valine ; Corynebacterium glutamicum/genetics* ; Metabolic Engineering ; Amino Acids, Branched-Chain ; Bioreactors

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). Conclusions SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). Conclusions SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

OBJECTIVE: To estimate the prevalence rate of bone and joint injury in China and to describe the three-dimension distribution of the disease (area, time and people). METHODS: Based on a cross-sectional design, a retrospective study was conducted by using Chinese basic medical insurance database from January 1, 2013 to December 31, 2017 to analyze the epidemiological characteristics of bone and joint injury. The prevalence rate of bone and joint injury in each city was calculated, and then using meta-analyses to estimate the pooled prevalence of each area and the whole country. The pooled prevalence rates were compared among the different groups of populations, in terms of geographical area, time and population characteristics (age and gender). RESULTS: A total of 28 419 264 subjects were included in this study, including 705 793 patients with bone and joint injury. From 2013 to 2017, in Chinese basic medical insurance database, the overall prevalence rate of bone and joint injury was 141.5(95%CI: 90.4－203.7) per 10 000 population, and the prevalence rates of non-specific or polyarticular disease, knee disease, and shoulder disease were 101.6 (95%CI: 63.5－148.4)per 10 000 population, 22.5(95%CI:15.1－31.4)per 10 000 population and 10.9 (95%CI: 6.4－16.4)per 10 000 population. The prevalence rates varied across the areas, the highest rate was observed in North China, with the prevalence of 310.6 (95%CI: 12.6－989.7) per 10 000 population, and the lowest rate was observed in Southwest China, with the prevalence of 59.0 (95%CI: 37.5－85.2) per 10 000 population. The prevalence rate of bone and joint injury increased over the study period, from 111.1 (95%CI: 56.0－182.5)per 10 000 population in 2013 to 175.5 (95%CI: 116.8－245.5)per 10 000 population in 2017. The prevalence of bone and joint injury in the female population was 149.1 (95%CI: 94.2－215.9) per 10 000 population, which was higher than that of men [133.6(95%CI: 86.2－190.9) per 10 000 population]. The higher prevalence of knee disease, unspecified or polyarticular disease, and bone and joint injury were observed in people aged 60 years and older, while the prevalence of shoulder disease peaked in 40－59 years old people [20.6 (95%CI: 12.5－30.5) per 10 000 population]. CONCLUSION This study reported a relative low prevalence of bone and joint injury in China from 2013 to 2017. The prevalence increased over the study period, and the highest prevalence rate was observed in North China. The prevalence rate showed differences among different groups of populations, and higher rates were observed in females and people aged 60 years and older.
Adult ; China ; Databases, Factual ; Female ; Humans ; Insurance, Health ; Male ; Middle Aged ; Prevalence ; Retrospective Studies ; Urban Population

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

[Abstract] Objective The purpose of this study is to construct a high-resolution model focusing on the vascular pattern of the scaphoid by using micro CT and to provide anatomical reference for the daily clinical use. Methods The lead-based contrast was perfused from the brachial artery and then the scaphoid bone was harvested. 3D models of the scaphoid bones were constructed by using micro CT to show how arteries distributed in and on the bones. Results The arteries on the surface stretched from the distal radius covered with scaphoid fossa to the radial side of the waist and then head back to the distal ulna along the dorsoradial ridge, formed like a letter “Ⅴ”. The arteries gathered at the inflection point of the letter “Ⅴ” and the dorsal region. The tubercle region was anastomosed extensively with 3 to 5 major intraosseous vessels originated from the extraosseous vessels covering the waist and the tubercle. There are only 1 to 2 major intraosseous vessels entering the bone via a long route from the ulnar side. The vessels running in the scapholunate ligament didn’t spilt into any intraosseous branches. Conclusion The superficial vascularity formes a “Ⅴ”-like pattern. The inflection point of the letter “Ⅴ” and the dorsal region display a dense vascularization and these vessels contributed a lot to the intraosseous vascularity.

Objective To observe the outcomes of no necrotic cavity lavage after debridement and drainage in patients with infected pancreatic necrosis (IPN).Methods From February 2014 to August 2017,there were 89 patients who were diagnosed as IPN undergoing minimally invasive surgery with no necrotic cavity lavage and large caliber-wide channel drainage in Department of General Surgery,Xuanwu Hospital,Capital Medical University.There were 57 male and 32 female patients aging of (49.5± 14.4)years (ranging from 23 to 84 years).The body mass index of 89 patients was (25.4± 3.8) kg/m2 (ranging from 17.6 to 36.7 kg/m2).Among the 89 patients,37 cases(41.6％) of biliary pancreatitis,10 cases (11.2％) of alcoholic pancreatitis,16 cases (18.0％) of hyperlipidemic pancreatitis,and 26 cases (29.2％) of other reasons.Results Of 89 patients,IPN in 6 patients (6.7％) resolved using only percutaneous catheter drainage;another 83 patients underwent laparoscopic debridement (n =3,3.4％) or video-assisted debridement (n =80,89.9％).No patient was conversed to laparotomy.The average operation frequency and surgery time was (2.3±1.7) times and (56.5±31.7) minutes.The median bleeding volume and total length of stay was 10(0-600) ml and 34(6-172) days separately.The complication rate(Clavien-Dindo grade ≥Ⅲ) was 9.0％ (8/89) which involved mainly abdominal hemorrhage (5/8) and digestive tract fistula formation (3/8).The overall mortality rate was 6.7％ (6/89).Among them,3 cases died of abdominal infection,bacteremia and multiple organ failure,2 cases died of pulmonary infection and bacteremia and 1 case died of fungal infection.Conclusion No necrotic cavity lavage after debridement and drainage operation is considered effective and safe for IPN patients.