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Xiuhua Jiang,1,* Shiqi Chai,1,* Yan Huang,2,* Zuxiong Huang,3,* Wenting Tan,4,* Yanhang Gao,5,* Xiaobo Lu,6,* Zhongji Meng,7,* Huayou Zhou,8 Wenbing Kong,8 Xiaoting Tang,1 Yujun Tang,1 Tingting Qi,1 Chengjin Liao,2 Qiaorong Gan,3 Xiaomei Xiang,4 Yanan Zhang,5 Shuai Wang,6 Yuanyuan Chen,7 Jinjun Chen1,9 1Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 5Department of Hepatology, the First Hospital of Jilin University, Changchun, People’s Republic of China; 6Infectious Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 7Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China; 8Department of Blood Transfusion, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 9Hepatology Unit, Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinjun Chen, Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Dadao Bei, Guangzhou, 510515, People’s Republic of China, Email chjj@smu.edu.cnBackground: Acute-on-chronic liver failure (ACLF) has high short-term mortality and lacks sufficient medical therapy. Available algorithms are unable to precisely predict short-term outcomes or safely stratify patients with ACLF as emergent liver transplantation candidates. Therefore, a personalized prognostic tool is urgently needed.Purpose: Platelet function and its clinical significance in ACLF patients with chronic hepatitis B virus (HBV) infection have not been investigated. This study aimed to assess changes in platelet function using thromboelastography (TEG) and platelet mapping (TEG-PM) in HBV-related ACLF patients.Methods: Chronic liver disease patients with acute decompensation or acute hepatic injury were recruited. The derivation cohort enrolled HBV-related patients at Nanfang Hospital. HBV-related and non-HBV-related patients were both enrolled in internal and external validation cohorts at seven university hospitals. TEG and TEG-PM were performed at baseline in the derivation cohort and baseline, day 7, and day 14 in the validation cohorts. The primary outcome was all-cause 28-day mortality. Status check and new-onset complications were recorded during the 3-month follow-up, but status check will extend to 5 years.Conclusion and Future Plans: In this study, 586 participants were enrolled, including 100 in derivation cohort, 133 in internal validation cohort, and 353 in external validation cohort. Biomaterials, including plasma, serum, urine, and some explanted liver tissues, were collected from these patients. A 3-month follow-up with survival status was completed. The baseline characteristics indicated that 51% of the patients had adenosine diphosphate (ADP)-hyporesponsive circulating platelets. The prognostic potential of platelet function will be explored in the derivation cohort (HBV-related ACLF patients) and further substantiated in the validation cohorts (HBV-related and non-HBV-related ACLF patients). Biosamples are currently used to explore the underlying mechanisms related to ADP-hyporesponsive platelets. The ongoing proteomic and metabolic analyses will provide new insights into the pathogenesis of extrahepatic organ failures in ACLF patients.Keywords: acute-on-chronic liver failure, coagulopathy failure, platelet function, thromboelastography, prognosis, study design

Background There is growing recognition of natural history, complications, and outcomes of patients who develop non-acetaminophen (APAP) drug-induced acute liver failure (ALF). To clarify high-risk factors and develop a nomogram model to predict transplant-free survival (TFS) in patients with non-APAP drug-induced ALF. Methods Patients with non-APAP drug-induced ALF from 5 participating centers were retrospectively analyzed. The primary endpoint was 21-day TFS. Total sample size was 482 patients. Results Regarding causative agents, the most common implicated drugs were herbal and dietary supplements (HDS) (57.0%). The hepatocellular type (R ≥ 5) was the main liver injury pattern (69.0%). International normalized ratio, hepatic encephalopathy grades, the use of vasopressor, N-acetylcysteine, or artificial liver support system were associated with TFS and incorporated to construct a nomogram model (drug-induced acute liver failure-5, DIALF-5). The AUROC of DIALF-5 for 7-day, 21-day, 60-day, and 90-day TFS in the internal cohort were 0.886, 0.915, 0.920, and 0.912, respectively. Moreover, the AUROC of DIALF-5 for 21-day TFS had the highest AUROC, which was significantly higher than 0.725 of MELD and 0.519 of KCC (p p > 0.05). These results were successfully validated in the external cohort (147 patients). Conclusions Based on easily identifiable clinical data, the novel DIALF-5 model was developed to predict transplant-free survival in non-APAP drug-induced ALF, which was superior to KCC, MELD and had a similar prediction performance to ALFSG-PI but is more convenient, which can directly calculate TFS at multiple time points.

Background Bacterial resistance leads to the dilemma in the treatment with synthetic antibiotics. A new alternative strategy is to develop some safe and non-toxic natural antibiotics as alternative therapeutic drugs. The aims of this research were to determine the saponins extracted from fresh fruit of Luffa acutangula, to evaluate their antibacterial property by inhibiting the formation of biofilm, and to reveal the mechanism in ultrastructural surface. Methods the saponin components were extracted and isolated from Fresh Fruit of Luffa acutangula by organic solvents extraction; their chemical structures were identified by HPLC-MS/MS. The growth inhibition curves and the 50% inhibitory concentrations (IC50) were used to evaluate the antibacterial activity of the extract. Then, crystal violet staining method was accepted to investigate the capacity of the saponins to inhibit biofilm formation. Anti-biofilm activity was assessed with minimum biofilm inhibitory concentration (MBIC). The interaction of the chemical compounds with saponins and biofilm were observed by SEM in ultrastructural surface. Results the extract by n-butanol was mainly saponins and the total content of saponins in the extract was 322.58 mg/g. nine saponin compounds were identified in n-butanol extract and the saponin compounds were mainly triterpene aglycone and triterpene glucosides. The extracted saponins have great bacteriostasis with IC50 value 3mg/ml, and the saponins can also inhibite the biofilm formation with MBIC value 16mg/ml. Conclusions the saponins extracted from fresh fruit of Luffa acutangula could inhibit multidrug resistance Staphylococcus aureus and substantially eradicate biofilm, it may be a potential to be developed as antibacterial agent.

Huge amounts of unstructured data including image, video, audio, and text are ubiquitously generated and shared, and it is a challenge to protect sensitive personal information in them, such as human faces, voiceprints, and authorships. Differential privacy is the standard privacy protection technology that provides rigorous privacy guarantees for various data. This survey summarizes and analyzes differential privacy solutions to protect unstructured data content before it is shared with untrusted parties. These differential privacy methods obfuscate unstructured data after they are represented with vectors and then reconstruct them with obfuscated vectors. We summarize specific privacy models and mechanisms together with possible challenges in them. We also discuss their privacy guarantees against AI attacks and utility losses. Finally, we discuss several possible directions for future research.

Background the incidence of acute-on-chronic liver disease (AoCLD) is increasing. Objective to investigate the clinical features and risk factors of AoCLD and construct an effective prognostic nomogram model for older patients with AoCLD. Methods data from 3,970 patients included in the CATCH-LIFE study were used, including 2,600 and 1,370 patients in the training and validation sets, respectively. Multivariate Cox regression analyses were performed to identify predictive risk factors in older individuals, and an easy-to-use nomogram was established. Performance was assessed using area under the curve, calibration plots and decision curve analysis (DCA). Results of the 3,949 patients with AoCLD, 809 were older with a higher proportion of autoimmune-related abnormalities, hepatitis C viral infection and schistosomiasis. In the older patient group, the incidence of cirrhosis, hepatic encephalopathy (HE), infection, ascites and gastrointestinal bleeding; neutrophil-to-lymphocyte ratio (NLR), aspartate-to-alanine transaminase ratio (AST/ALT), creatinine and blood urea nitrogen levels were higher, whereas incidence of acute-on-chronic liver failure, white blood cell, platelet and haemoglobin levels; albumin, total bilirubin (TB), AST and ALT levels; international normalised ratio (INR), estimated glomerular filtration rate and blood potassium levels were lower than in the younger group. The final nomogram was developed based on the multivariate Cox analysis in training cohort using six risk factors: ascites, HE grades, NLR, TB, INR and AST/ALT. Liver transplantation-free mortality predictions were comparable between the training and validation sets. DCA showed higher net benefit for the nomograph than the treat-all or treat-none strategies, with wider threshold probabilities ranges. Conclusions our analysis will assist clinical predictions and prognoses in older patients with AoCLD.

Empirical antibiotic therapy in patients with spontaneous bacterial peritonitis (SBP) is common as pathogen(s) are identified in only 5%-20% patients using conventional culture-based techniques. Metagenome next-generation sequencing (mNGS) test is a promising approach for the diagnosis of infectious disease. The clinical application of mNGS for infected ascites in cirrhotic patients is rarely reported. Here, we describe three cases to preliminarily explore the potential role of mNGS for microbiological diagnosis of ascites infection in an exploratory manner. The clinical performance of ascites mNGS in cirrhotic patients remains to be further evaluated.

As the application scenarios of recommendation algorithms are becoming increasingly complex, the efficiency of traditional recommendation algorithm based on accuracy is no longer satisfied. To solve this problem, an improved matrix factorization based model for many-objective optimization recommendation is proposed to simultaneously optimize the four recommendation objectives of novelty, diversity, accuracy, and recall. As a novel double-layer recommendation model, two improved algorithms are composed: 1) For the bottom layer, an improved matrix factorization algorithm with additional regularization constraints is used to predict unknown item ratings; 2) For the top layer, the recommendation list is optimized by a many-objective evolutionary algorithm . Comprehensive experiments demonstrate that the proposed model can effectively improve the four recommended evaluation metrics . And a recommended list with novel and diverse items is provided for users in a more efficient way while maintaining accuracy.

While the industrial Internet of Things (IIoT) can support efficient control of the physical world through large amounts of industrial data, data security has been a challenge due to various interconnections and accesses. Blockchain technology can support security and privacy preservation in IIoT data with its trusted and reliable security mechanism. Sharding technology can help improve the overall throughput and scalability of blockchain networks. However, the effectiveness of sharding is still challenging due to the uneven distribution of malicious nodes. By aiming to improve the performance of blockchain networks and reduce the possibility of malicious node aggregation, in this article, we propose a many-objective optimization algorithm based on the dynamic reward and penalty mechanism (MaOEA-DRP) to optimize the shard validation validity model. Then, an optimal blockchain sharding scheme is obtained. Compared with other state-of-the-art many-objective optimization algorithms, MaOEA-DRP performs better on the DTLZ test suite. The simulation results demonstrate that our proposed algorithm can significantly improve the throughput and validity of sharding for better security in the blockchain-enabled IIoT.

Background This study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD). Methods This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance. Results Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037–8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388–4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772–9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398–6.210; P = 0.004) after the adjustments of the BMI and diabetes. Conclusions Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.

Introduction Acute-on-chronic liver failure (ACLF) patients are susceptible to invasive fungal infections. We evaluated the prognosis and antifungal options in ACLF patients with invasive pulmonary aspergillosis (IPA). Methods ACLF patients with IPA from 15 hospitals were retrospectively screened from 2011 to 2018, and 383 ACLF patients without lung infections were included from a prospective cohort (NCT02457637). Demographic, laboratory, clinical data, and 28-day outcomes were documented in the two cohorts. Results ACLF patients with probable IPA (n = 145) had greater 28-day mortality (33.6% vs. 15.7%, p

BACKGROUND Chronic liver diseases (CLD), including cirrhosis and non-cirrhotic liver diseases, are globally widespread and create a serious disease burden. Platelet count is a clinically accessible and affordable prognostic indicator of liver disease. We investigated the relationship between platelet count and 90-day prognosis in patients with acute-on-chronic liver diseases (AoCLD). METHODS A total of 3,970 patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study, which included two prospective multi-center cohorts, were included in the study. We grouped the patients according to the platelet count and analyzed the 90-day adverse outcome (death or liver transplantation). RESULTS In the final analysis, 3,939 patients with AoCLD were included, of whom 2,802 had definite liver cirrhosis. The cumulative incidence of 90-day adverse outcomes in patients increased with the change of platelet group (log-rank P