Predicting the 28-day prognosis of acute-on-chronic liver failure patients based on machine learning.

BACKGROUND: We aimed to establish a prognostic predictive model based on machine learning (ML) methods to predict the 28-day mortality of acute-on-chronic liver failure (ACLF) patients, and to evaluate treatment effectiveness. METHODS: ACLF patients from six tertiary hospitals were included for analysis. Features for ML models' development were selected by LASSO regression. Models' performance was evaluated by area under the curve (AUC) and accuracy. Shapley additive explanation was used to explain the ML model. RESULTS: Of the 736 included patients, 587 were assigned to a training set and 149 to an external validation set. Features selected included age, hepatic encephalopathy, total bilirubin, PTA, and creatinine. The eXtreme Gradient Boosting (XGB) model outperformed other ML models in the prognostic prediction of ACLF patients, with the highest AUC and accuracy. Delong's test demonstrated that the XGB model outperformed Child-Pugh score, MELD score, CLIF-SOFA, CLIF-C OF, and CLIF-C ACLF. Sequential assessments at baseline, day 3, day 7, and day 14 improved the predictive performance of the XGB-ML model and can help clinicians evaluate the effectiveness of medical treatment. CONCLUSIONS: We established an XGB-ML model to predict the 28-day mortality of ACLF patients as well as to evaluate the treatment effectiveness.

Impact of Onset Time, Number, Type, and Sequence of Extrahepatic Organ Failure on Prognosis of Acute-on-chronic Liver Failure.

Background and Aims: The impact of the characteristics of extrahepatic organ failure (EHOF) including the onset time, number, type, and sequence on the prognosis of acute-on-chronic liver failure (ACLF) patients remains unknown. This study aimed to identify the association between the characteristics of EHOF and the prognosis of ACLF patients. Methods: ACLF subjects enrolled at six hospitals in China were included in the analysis. The risk of mortality based on the characteristics of EHOF was evaluated. Survival of study groups was compared by Kaplan-Meier analysis and log-rank tests. Results: A total of 736 patients with ACLF were included. EHOF was observed in 402 patients (54.6%), of which 295 (73.4%) developed single EHOF (SEHOF) and 107 (26.6%) developed multiple EHOF (MEHOF). The most commonly observed EHOF was coagulation failure (47.0%), followed by renal (13.0%), brain (4.9%), respiratory (4.3%), and circulatory (2.3%) failure. Survival analysis found that MEHOF or SEHOF patients with brain failure had a worse prognosis. However, no significant outcome was found in the analysis of the effect of onset time and sequence of failed organs on prognosis. Patients were further divided into three risk subgroups by the EHOF characteristics. Kaplan-Meier analysis showed that risk stratification resulted in the differentiation of patients with different risks of mortality both in the training and validation cohorts. Conclusions: The mortality of ACLF patients was determined by the number and type, but not the onset time and sequence of EHOF. Risk stratification applicable to clinical practice was established.

A novel laboratory-based nomogram for assessing infection presence risk in acute-on-chronic liver failure patients.

Accurate assessment of infection presence risk level, timely diagnosis, and effective control are critical for decreasing mortality of Acute­on­chronic liver failure (ACLF). We aimed to develop and validate a novel diagnostic model to accurately assess infection presence risk level in ACLF patients. 185 ACLF patients with/without infection were enrolled, and their demographic, physical findings, immune-inflammatory, hepatic function, metabolism, and coagulation-fibrinolysis indicators were analyzed. Regression analysis was performed to identify the independent diagnostic parameters, which were further used to establish diagnostic models with a nomogram for visual. An area under receiver operating characteristic curve (AUROC), calibration plots, clinical impact curves, decision curve analysis, and net reclassification index were used to evaluate and identify the best model. An external validating cohort was introduced to verify the diagnostic accuracy. We screened out white blood cell (WBC) count, LYM%, blood urea nitrogen (BUN), and D-dimer for assessing infection presence risk levels in ACLF patients. WBD (WBC + BUN + D-dimer) was established and proposed as a novel diagnostic model for infection presence risk levels assessment in ACLF patients with an AUROC of 0.803 (95%CI 0.723-0.883), 0.885 (95%CI 0.786-0.984) in training and external cohorts, respectively. In stratification analysis by ACLF etiology and stages, WBD achieved an AUROC of 0.791 (95%CI 0.691-0.891) and 0.873 (95%CI 0.78-0.966) in HBV-related and early-stage patients, respectively. Whereas a higher AUROC of 0.905 (95%CI 0.807-1.00) in the early-stage of HBV-related ACLF patients indicated its optimum application scope. WBD, a novel laboratory-based nomogram, can serve as a decision-making support tool for clinicians to assess infection presence risk levels in ACLF patients.

RUNX1 promotes liver fibrosis progression through regulating TGF-ß signalling.

Liver fibrosis is caused by chronic liver injury. There are limited treatments for it, and the pathogenesis is unclear. Therefore, there is an urgent need to explore the pathogenesis of liver fibrosis, and to try to identify new potential therapeutic targets. For this study we used the carbon tetrachloride abdominal injection induced liver fibrosis animal model in mice. Primary hepatic stellate cell isolation was performed by a density-gradient separation method, and this was followed by immunofluorescence stain analyses. Signal pathway analysis was performed by dual-luciferase reporter assay and western blotting. Our results showed that RUNX1 was upregulated in cirrhotic liver tissues compared with normal liver tissues. Besides, overexpression of RUNX1 caused more severe liver fibrosis lesions than control group under CCl4 -induced conditions. Moreover, α-SMA expression in the RUNX1 overexpression group was significantly higher than in the control group. Interestingly, we found that RUNX1 could promote the activation of TGF-ß/Smads in a dual-luciferase reporter assay. Thus we demonstrated that RUNX1 could be considered as a new regulator of hepatic fibrosis by activating TGF-ß/Smads signalling. Based on this, we concluded that RUNX1 may be developed as a new therapeutic target in the treatment of liver fibrosis in the future. In addition, this study also provides a new insight about the aetiology of liver fibrosis.

Risk Factors for Mortality in Severe Fever with Thrombocytopenia Syndrome Patients with Central Nervous System Complications.

BACKGROUND Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic viral hemorrhagic fever caused by the SFTS virus (SFTSV), which is a newly identified tick-borne bunyavirus, recently named Dabie bandavirus. In rural China, SFTSV or Dabie bandavirus is commonly transmitted by Haemaphysalis longicornis, the Asian longhorned tick. In recent years, SFTS has been of great concern due to its high morbidity and mortality. The present study investigated the risk factors for mortality in patients with SFTS complicated by central nervous system involvement. MATERIAL AND METHODS We studied 69 SFTS patients hospitalized between 2013 and 2020. We analyzed the laboratory test results and clinical data through univariate and multivariate regression. RESULTS Neurological complications occurred in 59 patients in the survival group and 10 in the mortality group. No significant gender difference was found between the 2 groups. No significant difference was found in age, hospitalization duration, or occurrence of encephalitis between the 2 groups. The mean duration of hospitalization and course of the disease in the mortality group were significantly shorter than those in the survival group (P<0.01). The mean values of platelet count, potassium, and sodium in the mortality group were significantly lower, while the mean values of aspartate aminotransferase, lactic dehydrogenase, creatine kinase-MB (CK-MB) and procalcitonin were higher than those in the survival group. Low platelet count and high CK-MB were independent risk factors for mortality in patients. For each unit increase in platelet count, the risk of mortality decreased by 24.2%, and for each unit increase in CK-MB, the probability of mortality increased by 118.6%. CONCLUSIONS Decreased platelets and increased CK-MB were independent risk factors for mortality in encephalitis patients. SFTS patients with encephalitis should be monitored for changes in these 2 indicators.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

SARS-CoV-2 and Emerging Variants: Unmasking Structure, Function, Infection, and Immune Escape Mechanisms.

As of April 1, 2022, over 468 million COVID-19 cases and over 6 million deaths have been confirmed globally. Unlike the common coronavirus, SARS-CoV-2 has highly contagious and attracted a high level of concern worldwide. Through the analysis of SARS-CoV-2 structural, non-structural, and accessory proteins, we can gain a deeper understanding of structure-function relationships, viral infection mechanisms, and viable strategies for antiviral therapy. Angiotensin-converting enzyme 2 (ACE2) is the first widely acknowledged SARS-CoV-2 receptor, but researches have shown that there are additional co-receptors that can facilitate the entry of SARS-CoV-2 to infect humans. We have performed an in-depth review of published papers, searching for co-receptors or other auxiliary membrane proteins that enhance viral infection, and analyzing pertinent pathogenic mechanisms. The genome, and especially the spike gene, undergoes mutations at an abnormally high frequency during virus replication and/or when it is transmitted from one individual to another. We summarized the main mutant strains currently circulating global, and elaborated the structural feature for increased infectivity and immune evasion of variants. Meanwhile, the principal purpose of the review is to update information on the COVID-19 outbreak. Many countries have novel findings on the early stage of the epidemic, and accruing evidence has rewritten the timeline of the outbreak, triggering new thinking about the origin and spread of COVID-19. It is anticipated that this can provide further insights for future research and global epidemic prevention and control.

Identification of Immune-Related Prognostic Markers in Gastric Cancer.

Gastric cancer (GC) is a malignant tumor with a high fatality rate. Poor prognosis is the main cause of death caused by GC. In this study, the gene expression difference between GC and the control group was analyzed. Differentially expressed genes (DEGs) related to immunity were screened for enrichment analysis. The differences in immune cell infiltration and immune function between GC and normal were identified. Cox regression analysis and survival analysis were used to determine the prognostic genes of GC in TCGA and GSE62254. The potential prognostic role of genes was further evaluated by risk score. Difference genes in GC were analyzed in TCGA. Candidate genes in TCGA and GSE62254 are analyzed, and prognostic genes are determined. The potential prognostic role of genes was further evaluated by risk score. The immune-related prognostic markers in GC were determined. FABP4, LBP, LCN1, CMA1, INHBA, ANGPTL1, ACKR1, GHR, and OGN may be used as markers for monitoring the prognosis of GC in the future.

Attitudes of Chinese Patients with Non-alcoholic Fatty Liver Disease Toward Participation in Clinical Trials from a National Multicenter Survey.

BACKGROUND: Many new therapies of non-alcoholic fatty liver disease are being evaluated in clinical trials (CTs), but few of these trials involved sites in China. We evaluated influencing factors of Chinese patients' perspectives in participation in CTs of non-alcoholic fatty liver disease. METHODS: A questionnaire was designed to be completed by patients with non-alcoholic fatty liver disease at eight affiliated hospitals across China. RESULTS: 428 patients were included in this analysis, 63% were male and median age was 37.9 years (30.0-44.0). 54% patients rated "to help others" and 30% "to improve my health status" as the greatest benefit from CTs. The most important concerns were safety (43%) and patients' benefit (26%). Improving liver fibrosis or cirrhosis (53%) and reducing fat in liver (21%) were desired efficacy of new drugs. Possibility of being treated with a placebo for up to 2-6 years played an influential (21%) or very influential (73%) role on participation. Lower education level, lower body mass index, and cirrhosis were positively associated with acceptance of liver biopsies. Anxiety of adverse effects of the new drug and requirement of 2-3 liver biopsies were negatively associated with patients' attitudes toward participating in the trial. CONCLUSION: More than one-third of Chinese patients with NAFLD in this survey are willing to participate in CTs of NASH. For CTs of NASH treatment, potential effects on reversing fibrosis or cirrhosis would positively influence, while adverse effects of the new drug and requirement of multiple liver biopsies would negatively influence participation in our study.

Risk Factors of Neurological Complications in Severe Fever Patients with Thrombolytic Syndrome: A Single-Center Retrospective Study in China.

BACKGROUND Severe fever with thrombocytopenia syndrome is a serious insect-borne infectious disease caused by the Huaiyangshanbanyang virus. We conducted a retrospective study to identify risk factors for neurological complications caused by the virus. MATERIAL AND METHODS We included 121 patients who had severe fever with thrombocytopenia syndrome and were admitted to our hospital from 2013 to 2020. Patients' laboratory test results and clinical data were collected. Univariate and multivariate regression were used for statistical analysis. RESULTS Patients with neurological complications had higher mortality rates and longer hospital stays and disease duration than did patients without neurological complications. The neurological symptoms with the highest incidence rates were involuntary tremors (tongue and mandible), cognitive disorder, and limb tremors. Patients with neurological complications had a higher incidence of abnormal heart rhythms. Subcutaneous bleeding, pulmonary rales, percentage of neutrophils, increased lactate dehydrogenase and C-reactive protein levels, and decreased chloride ion concentration were closely related to the occurrence of neurological complications. The significant decrease in chloride ion concentration within 1 to 5 days of disease onset may be a risk factor for predicting the occurrence of neurological complications in patients with severe fever with thrombocytopenia syndrome. CONCLUSIONS Early monitoring of subcutaneous bleeding, pulmonary rales, electrocardiogram changes, and biochemical indicators in patients with severe fever with thrombocytopenia syndrome can predict the occurrence of neurological complications.

Prognostic factors of adult tuberculous meningitis in intensive care unit: a single-center retrospective study in East China.

BACKGROUND: Tuberculous meningitis (TBM) is the most lethal form of tuberculosis worldwide. Data on critically ill TBM patients in the intensive care unit (ICU) of China are lacking. We tried to identify prognostic factors of adult TBM patients admitted to ICU in China. METHODS: We conducted a retrospective study on adult TBM in ICU between January 2008 and April 2018. Factors associated with unfavorable outcomes at 28 days were identified by logistic regression. Factors associated with 1-year mortality were studied by Cox proportional hazards modeling. RESULTS: Eighty adult patients diagnosed with TBM (age 38.5 (18-79) years, 45 (56 %) males) were included in the study. An unfavorable outcome was observed in 39 (49 %) patients and were independently associated with Acute Physiology and Chronic Health Evaluation (APACHE) II > 23 (adjusted odds ratio (aOR) 5.57, 95 % confidence interval (CI) 1.55-19.97), Sequential Organ Failure Assessment (SOFA) > 8 (aOR 9.74, 95 % CI 1.46-64.88), and mechanical ventilation (aOR 18.33, 95 % CI 3.15-106.80). Multivariate Cox regression analysis identified two factors associated with 1-year mortality: APACHE II > 23 (adjusted hazard ratio (aHR) 4.83; 95 % CI 2.21-10.55), and mechanical ventilation (aHR 9.71; 95 % CI 2.31-40.87). CONCLUSIONS: For the most severe adult TBM patients of Medical Research Council (MRC) stage III, common clinical factors aren't effective enough to predict outcomes. Our study demonstrates that the widely used APACHE II and SOFA scores on admission can be used to predict short-term outcomes, while APACHE II could also be used to predict long-term outcomes of adult patients with TBM in ICU.

The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease.

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China.

The Combination of Shear Wave Elastography and Platelet Counts Can Effectively Predict High-Risk Varices in Patients with Hepatitis B-Related Cirrhosis.

BACKGROUND: Baveno VI criteria, based on liver stiffness (LS) measured by transient elastography and platelet counts (PLT), have been proposed to avoid unnecessary endoscopy screening for high-risk varices (HRVs). However, the cut-off value of LS measured by 2D-SWE and PLT to predict HRVs in compensated hepatitis B-related cirrhotic patients remains unknown. AIMS: To prospectively analyze the cut-off of the combination of LS measured by 2D-SWE and PLT in predicting HRVs and the influence of antiviral therapies in its efficacy. METHODS: Serum parameters, LS, and endoscopy results were obtained from 160 compensated hepatitis B-related cirrhotic patients. The accuracy of the combined algorithm was assessed in the whole cohort and subgroups with or without consecutive antiviral therapies in the past 6 months. RESULTS: In the whole cohort, the optimal cut-off value of LS for HRVs was 14.5 kPa. Patients with a LS value < 14.5 kPa with a PLT value > 110 × 109/L can be excluded from HRVs (NPV = 0.99, endoscopy saved rates = 0.68). Conversely, a LS value of ≥14.5 kPa and a PLT value of ≤110 × 109/L indicated HRVs, with accurate rates of 82.35%, and 10.63% of patients can avoid additional endoscopy screening. Moreover, antiviral therapy had no significant effect on the accuracy and rates saved from further endoscopy screening, when comparing patients with or without antiviral therapies (all p values > 0.05). CONCLUSIONS: The combination of LS (14.5 kPa) measured by 2D-SWE and PLT (110 × 109/L) can predict HRVs accurately in compensated hepatitis B-related cirrhotic patients without significant interference of antiviral therapy histories.

High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b.

BACKGROUND AND AIM: Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3. METHODS: The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index). RESULTS: We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naïve, and 2.5% HBsAg+ . The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin). CONCLUSIONS: In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.

Liver stiffness as measured by two-dimensional shear wave elastography overestimates the stage of fibrosis in patients with chronic hepatitis B and hepatic steatosis.

Two-dimensional shear wave elastography (2D-SWE) is a non-invasive technique for measuring liver stiffness (LS) and is used to assess the degree of hepatic fibrosis in patients with chronic hepatitis B (CHB). Despite its usefulness, several factors, other than hepatic fibrosis, can affect its diagnostic accuracy. Hepatic steatosis (HS) is a common lesion in CHB that has increasingly been getting attention in the field of disease development; however, its influence on the measurement of LS remains unclear. We aimed to determine whether HS affects the diagnostic accuracy of 2D-SWE in patients with CHB. Serum parameters and LS values were obtained from 161 patients with CHB. The degrees of hepatic fibrosis and inflammatory activity were estimated based on the METAVIR Cooperative Study Group criteria, and the extent of HS was defined as the percentage of hepatocytes containing fat droplets using oil red staining. We found that LS values were independently correlated with HS in the early stages of hepatic fibrosis (F0-F2 or F0-3). Furthermore, LS values in patients with significant steatosis (S≥10%) were higher than the counterpart in fibrosis stages F0-2 (6.82±1.57 vs. 7.92±1.99; p=0.010) and F0-3 (7.18±1.84 vs. 8.25±1.91; p=0.007). Therefore, false positive rates (FPRs) in the diagnosis of advanced fibrosis (16.00% vs. 37.04%, p=0.037) and cirrhosis (6.67% vs. 21.62%, p=0.030) were higher in patients with significant steatosis. In conclusion, the use of 2D-SWE in the measurement of LS overestimates the stage of hepatic fibrosis in CHB patients with HS>10%. This should be taken into consideration to combine LS results with other non-invasive parameters to improve its accuracy.

Absence of SARS-CoV-2 in semen of a COVID-19 patient cohort.

BACKGROUND: Since SARS-CoV-2 infection was first identified in December 2019, the novel coronavirus-induced pneumonia COVID-19 spread rapidly and triggered a global pandemic. Recent bioinformatics evidence suggested that angiotensin-converting enzyme 2-the main cell entry target of SARS-CoV-2-was predominantly enriched in spermatogonia, Leydig and Sertoli cells, which suggests the potential vulnerability of the male reproductive system to SARS-CoV-2 infection. OBJECTIVES: To identify SARS-CoV-2 RNA in seminal plasma and to determine semen characteristics from male patients in the acute and recovery phases of infection. METHODS: From February 26 to April 2, 2020, 23 male patients with COVID-19 were recruited. The clinical characteristics, laboratory findings and chest computed tomography scans of all patients were recorded in detail. We also investigated semen characteristics and the viral RNA load in semen from these patients in the acute and recovery phases of SARS-CoV-2 infection using approved methods. RESULTS: The age range of the 23 patients was 20-62 years. All patients tested negative for SARS-CoV-2 RNA in semen specimens. Among them, the virus had been cleared in 11 patients, as they tested negative. The remaining 12 patients tested negative for SARS-CoV-2 RNA in semen samples, but were positive in sputum and fecal specimens. The median interval from diagnosis to providing semen samples was 32 days, when total sperm counts, total motile sperm counts, and sperm morphology of the patients were within normal ranges. DISCUSSION AND CONCLUSION: In this cohort of patients with a recent infection or recovering from COVID-19, there was no SARS-CoV-2 RNA detected in semen samples, which indicates the unlikely possibility of sexual transmission through semen at about 1 month after first detection.

Current directions, conceptions and viewpoints on 2019-nCoV (Review).

On December 31, 2019, the first case of a novel coronavirus infection was reported in Wuhan, China. The ongoing outbreak of the 2019 novel coronavirus (2019-nCoV) has caused immense global concern. According to the recommendations of the International Health Regulations Emergency Committee and the facts and cases that 215 other countries have also reported to date, the World Health Organization Director-General announced that the outbreak of 2019-nCoV constitutes a public health emergency of international concern and a severe threat to the human health worldwide. To date, the prevalence of the virus has continued in waves and is increasing globally. The present review briefly introduces the epidemiology of 2019-nCoV, as well as viral structural characteristics, and receptors and cells that may act after entering the body, laboratory examinations, imaging and pathological features, clinical manifestations, complications, treatment and management.

TRIB3 promotes hepatocellular carcinoma growth and predicts poor prognosis.

BACKGROUND: Tribbles pseudokinase 3 (TRIB3) is a member of the tribbles-related family, which is involved a lot of cellular processes and multiple cancers, such as breast cancer, colorectal cancer, renal cell carcinomas, and lung cancer. However, the expression pattern and biological function of TRIB3 in hepatocellular carcinoma (HCC) has not yet been completely elucidated. METHODS: The expression of TRIB3 and clinicopathological characteristics were evaluated by HCC tissue microarray and qPCR analysis. Lentivirus packaging and transfection were employed to establish cell lines with TRIB3 overexpression or knockdown. The biological functions of TRIB3 in the growth of HCC were determined using MTT and crystal violet assays. Tumor growth was monitored in a xenograft model in vivo. RESULTS: The expression of TRIB3 was upregulated in HCC tissue samples compared to paired normal tissues in 45 patients examined by qPCR assay. TRIB3 expression was significantly correlated with HCC tumor size and prognosis in postoperative patients by analysis of the TRIB3 expression data and HCC clinical features. Forced expression of TRIB3 significantly promoted HCC growth in vitro. In contrast, downregulation of TRIB3 inhibited cell growth in vitro. Moreover, knockdown of TRIB3 suppressed tumorigenesis of HCC cells in vivo. CONCLUSION: TRIB3 promotes growth abilities of HCC cells both in vitro and in vivo and predicts poor prognosis of HCC patients, which serves as a prognostic marker and might provide a potential therapeutic candidate for patients with HCC.

Radiofrequency ablation versus repeat resection for recurrent hepatocellular carcinoma (≤ 5 cm) after initial curative resection.

OBJECTIVES: Recurrence rate is up to 70% at 5 years for hepatocellular carcinoma (HCC) after initial resection, but the management of recurrent HCC remains unclear. To compare the efficacy and safety of radiofrequency ablation (RFA) and repeat resection as the first-line treatment in recurrent HCC. METHODS: This multicenter retrospective study analyzed 290 patients who underwent RFA (n = 199) or repeat resection (n = 91) between January 2006 and December 2016 for locally recurrent HCC (≤ 5 cm) following primary resection. We compared the overall survival (OS), progression-free survival (PFS), and complications between the two treatment groups for the total cohort and the propensity score matched (PSM) cohort. RESULTS: The 1-, 3-, and 5-year OS (90.7%, 69.04%, 55.6% vs. 87.7%, 62.9%, 38.1%, p = 0.11) and PFS (56.5%, 27.9%, 14.6% vs. 50.2%, 21.9%, 19.2%, p = 0.80) were similar in the RFA group and the repeat resection group. However, RFA was superior to repeat resection in complication rate and hospital stay (p ≤ 0.001). We observed similar findings in the PSM cohort of 48 pairs of patients and when OS and PFS were measured from the time of the primary resection. The OS of the RFA group was significantly better than repeat resection group among those with 2 or 3 recurrent tumor nodules in both the total cohort (p = 0.009) and the PSM cohort (p = 0.018). CONCLUSION: RFA has the same efficacy as repeat resection in recurrent HCC patients, but with fewer complications. RFA is more efficient and safer than repeat resection in patients with 2 or 3 recurrent tumor nodules. KEY POINTS: • Recurrence rate is up to 70% at 5 years for hepatocellular carcinoma (HCC) after initial resection. • RFA has the same efficacy as repeat resection in recurrent HCC patients, but with fewer complications. • RFA may be preferred for those with 2 or 3 recurrent HCC nodules.