A Case Report of Cutaneous Anthrax Diagnosed by Using a Metagenomic Next-Generation Sequencing (mNGS) Approach.

Anthrax is caused by Bacillus anthracis. Humans are mainly infected through contact with the fur and meat of livestock. The cutaneous form is the most common form. The skin lesions of typical cutaneous anthrax are characterized by shallow ulcers with black crusts, surrounded by small blisters and nonpitting edema of nearby tissues. Metagenomic next-generation sequencing (mNGS) is a new pathogenic detection method which is rapid and unbiased. We reported the first case of cutaneous anthrax diagnosed by mNGS. Ultimately, the man received prompt antibiotic therapy and had a good prognosis. In conclusion, mNGS is proved to be a good method for etiological diagnosis, especially for rare infectious diseases.

Registered Trials of Artificial Intelligence Conducted on Chronic Liver Disease: A Cross-Sectional Study on ClinicalTrials.gov.

Background: Artificial intelligence (AI) has been widely applied in the diagnosis and therapy of chronic liver disease (CLD), but there is currently little insight into the trials registered on ClinicalTrials.gov. Thus, this cross-sectional study was focused on analyzing the progress in the use of AI in CLD. Methods: Registered trials of AI applied in CLD on ClinicalTrials.gov were searched firstly. All available information was downloaded to Excel (Microsoft Excel, Rong, Rong, China), and duplicates were removed. We extracted the data of the included trials, then analyzed the characteristics of them finally. Results: Up to the 27th of May 2021, 6835 trials were identified following an initial search, and 20 registered trials were included after screening for inclusion and exclusion criteria. Among those trials, hepatocellular carcinoma (HCC, 40.0%) and nonalcoholic fatty liver disease (NAFLD, 20.0%) were the most widely applied CLDs for AI. Trials started in 2013 until 2021, with 17 trials (85%) registered after 2016. There was a large trend in trial enrolment, with 40% of them including samples more than 500. Five trials (25%) have been completed, but only one of these had available results. The most frequent sponsors and collaborators were both hospitals at 55%, followed by universities at 35% and institutes at 11%, respectively. Of the 20 trials included, 35% (7 trials) were interventional trials and 65% (13 trials) were observational trials. Among 7 interventional trials, most trials were for diagnosis purpose (42.86%, 3 trials); 4 trials (57.14%) were randomized; 3 trials (42.86%) applied behavioral intervention, 1 trial (14.29%) was in device intervention, 2 trials (28.57%) were in diagnostic test, and 1 trial intervention was unknown. Among 13 observational trials, 8 (61.54%) were cohort studies; 6 (46.15%) were prospective studies, 4 (30.77%) were retrospective studies, 2 (15.38%) were cross-sectional studies, and 1 (7.69%) did not involve a temporal perspective. Conclusion: The study is the first to focus on AI registration trials in CLD, which will aid relevant scholars in understanding the current state of the subject. This study demonstrates that additional research on AI used in the diagnosis and treatment of CLD is required, and timely publication of accessible results from registered trials is essential.

Risk factors and prognostic model for HBV-related subacute liver failure.

Background: The prognosis for patients with chronic hepatitis B virus (HBV)-related subacute liver failure is poor. Thus, accurate prognostication would facilitate management and optimize liver allocation. This study aimed to explore the risk factors for HBV-related subacute liver failure and establish a risk model. Methods: A total of 192 patients with HBV-related subacute liver failure treated at the First Affiliated Hospital of Xi'an Jiaotong University during January 2018 to January 2019 were selected and divided into the survival group (n=113) and the death group (n=79) based on their status within 6 months. Patient information were collected, including age, sex, body mass index, complications, hepatitis B e antigen (HBeAg), hepatic encephalopathy, hepatorenal syndrome, infections, ascites, HBV-DNA, Model for End-Stage Liver Disease (MELD), liver function tests, international normalized ratio (INR), serum creatinine and total cholesterol. Binary logistic regression was employed to identify risk factors for risk model establishment. The predictive value of the risk model was assessed with a receiver operating characteristic (ROC) curve. Results: Compared with the survival group, the patient age, incidence of hepatic encephalopathy and hepatorenal syndrome, infection and ascites rate, MELD score, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), INR, and serum creatinine levels were significantly elevated, whereas the total cholesterol level was significantly decreased in the death group (all P<0.05). Patient age [odds ratio (OR) =1.11, P=0.03], hepatic encephalopathy (OR =8.31, P=0.02), infection (OR =4.27, P=0.005), ascites (OR =4.54, P=0.006), MELD score (OR =1.39, P<0.001), INR (OR =5.89, P=0.001), and total cholesterol (OR =0.31, P=0.002) were identified as prognostic factors affecting patient mortality. Although both the MELD score and the risk model established in the present study could differentiate patient outcomes, the area under the curve (AUC) (0.94 vs. 0.82, P<0.001) and sensitivity (91.1% vs. 58.2%, P<0.001) of the established risk model were significantly higher than those of the MELD score. Conclusions: Patient age, hepatic encephalopathy, infection, ascites, MELD score, INR, and total cholesterol level were independent prognostic factors. The prognostic model established based on these risk factors may have favorable predictive value.

Prevalence, emotional and follow-up burden of insulin injection-related needle-stick injuries among clinical nurses in Shaanxi Province, west of China: A cross-sectional study.

AIMS AND OBJECTIVES: The aim of this study was to investigate the prevalence, emotional and follow-up burden of insulin injection-related needle-stick injuries among clinical nurses. BACKGROUND: needle-stick injures introduce statistically significant occupational hazards to healthcare workers. Although the large proportion of the needles injuries attributed to insulin injection, research evidence about the prevalence, emotional and follow-up burden of such injures is lacking. DESIGN: Cross-sectional study. METHODS: 5389 nurses were recruited from 45 hospitals in Shaanxi, China, from November 2018 to July 2019. Participants were administrated with a questionnaire specifically developed for this study. Descriptive statistics were used to present the findings. RESULTS: All 5,389 nurses responded to the survey, of which 396 (7.4%) participants experienced 620 insulin injection-related needle-stick injuries in the past year, representing an annual prevalence of 115.0 per 1000 nurses. The annual prevalence of infection caused by the injuries was 18.7 per 1000 nurses. The injuries occurred most frequently when nurses were recapping the needle (42.4%). In the majority (98.4%) of the injuries, the hurt nurses took proper immediate actions. However, only 30.3% of nurses reported the injuries to the administrative staff, and in 43.2% of the injuries, the nurses refused or discontinued the suggested follow-up. A large proportion (58.6%) of the hurt nurses experienced emotional changes. Multivariate logistic regression showed that department, removing and/or setting back needle caps with bare hands, frequency of insulin pen and syringes are associated with the incidence of insulin injection-related needle-stick injuries. This paper is reported following the STROBE recommendations. CONCLUSIONS: This survey demonstrated a considerably high prevalence of insulin injection-related needle-stick injuries among clinical nurses. Even though the majority of the hurt nurses took proper immediate actions, a large quantity of them failed to report the accidents to the administrative staff and complete the suggested follow-up. Nurses who suffered from insulin injection-related needle-stick injuries were subject to various negative emotional changes. It portends a statistically significant risk to occupational health management for nurses. RELEVANCE TO CLINICAL PRACTICE: Scientific preventive and management strategies are desirable in order to minimize the consequences of insulin injection-related needle-stick injuries.

Metagenomic Next-Generation Sequencing in the Diagnosis of HHV-1 Reactivation in a Critically Ill COVID-19 Patient: A Case Report.

Background: Secondary infections pose tremendous challenges in Coronavirus disease 2019 (COVID-19) treatment and are associated with higher mortality rates. Clinicians face of the challenge of diagnosing viral infections because of low sensitivity of available laboratory tests. Case Presentation: A 66-year-old woman initially manifested fever and shortness of breath. She was diagnosed as critically ill with COVID-19 using quantitative reverse transcription PCR (RT-qPCR) and treated with antiviral therapy, ventilator and extracorporeal membrane oxygenation (ECMO). However, after the condition was relatively stabled for a few days, the patient deteriorated with fever, frequent cough, increased airway secretions, and increased exudative lesions in the lower right lung on chest X-rays, showing the possibility of a newly acquired infection, though sputum bacterial and fungal cultures and smears showed negative results. Using metagenomic next-generation sequencing (mNGS), we identified a reactivation of latent human herpes virus type 1 (HHV-1) in the respiratory tract, blood and gastrointestinal tract, resulting in a worsened clinical course in a critically ill COVID-19 patient on ECMO. Anti-HHV-1 therapy guided by these sequencing results effectively decreased HHV-1 levels, and improved the patient's clinical condition. After 49 days on ECMO and 67 days on the ventilator, the 66-year-old patient recovered and was discharged. Conclusions: This case report demonstrates the potential value of mNGS for evidence-based treatment, and suggests that potential reactivation of latent viruses should be considered in critically ill COVID-19 patients.

Phosphatidylinositol 4-phosphate adaptor protein 2 accelerates the proliferation and invasion of hepatocellular carcinoma cells by enhancing Wnt/ß-catenin signaling.

Phosphatidylinositol 4-phosphate adaptor protein 2 (FAPP2) has been recently identified as a tumor-associated regulator that is closely related to tumorigenesis. Yet, the precise role of FAPP2 in hepatocellular carcinoma (HCC) is still largely unknown. This study was designed to determine the function and molecular mechanisms of FAPP2 in HCC. Elevated expression of FAPP2 commonly occurred in the tumor tissue of HCC compared with normal controls. High expression of FAPP2 was also detected in HCC cell lines and its knockdown markedly decreased the proliferation, colony formation and invasion of HCC cells. Upregulation of FAPP2 by using a FAPP2 expression vector markedly promoted the proliferation, colony formation and invasion of HCC cells. FAPP2 was found to promote the activation of Wnt/ß-catenin signaling. Importantly, inhibition of Wnt/ß-catenin signaling abrogated the FAPP2 overexpression-conferred oncogenic effect in HCC cells. In addition, xenograft tumor experiments revealed that knockdown of FAPP2 significantly decreased the tumorigenicity of HCC cells in vivo. Taken together, the data of our study reported a tumor-promotion function of FAPP2 in HCC and demonstrate that knockdown of FAPP2 was capable of suppressing HCC cell proliferation and invasion through downregulation of Wnt/ß-catenin signaling. This study indicated that FAPP2 might be an attractive candidate anticancer target for HCC.

TRIM66 confers tumorigenicity of hepatocellular carcinoma cells by regulating GSK-3ß-dependent Wnt/ß-catenin signaling.

Tripartite motif 66 (TRIM66) protein, a member of the tripartite motif (TRIM) protein superfamily, has emerged as an oncogenic protein that is closely related to carcinogenesis in multiple cancers. However, whether TRIM66 plays a role in the progression of hepatocellular carcinoma (HCC) remains unknown. This study was aimed to investigate TRIM66 expression and its potential biological function in HCC cell lines. Here we showed that TRIM66 expression was significantly upregulated in HCC cell lines compared with normal control cells. Loss-of-function experiments by RNA interfering knockdown of TRIM66 showed that TRIM66 inhibition significantly reduced the proliferation, colony formation, and invasion of HCC cells, whereas gain-of-function by overexpression of TRIM66 exhibited the opposite effect. Further investigation showed that TRIM66 was involved in regulating glycogen synthase kinase-3ß (GSK-3ß) phosphorylation and ß-catenin expression. Knockdown of TRIM66 impeded the activation of Wnt signaling, while overexpression of TRIM66 promoted Wnt signaling activation. Moreover, inhibition of GSK-3ß by specific inhibitor partially reversed TRIM66 inhibition-mediated antitumor effect, while knockdown of ß-catenin blocked the oncogenic effect of TRIM66 overexpression in HCC cells. Additionally, in vivo experiments using a xenograft tumor model showed that TRIM66 knockdown blunted the tumorigenicity of HCC cells associated with downregulation of ß-catenin expression. Overall, our results showed that TRIM66 functioned as an oncogenic protein in HCC by promoting the activation of Wnt/ß-catenin signaling. Our study suggests that TRIM66 is a potential target for HCC treatment.

Knockdown of FRAT1 inhibits hypoxia-induced epithelial-to-mesenchymal transition via suppression of the Wnt/ß-catenin pathway in hepatocellular carcinoma cells.

Hypoxia-induced epithelial-to-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) was investigated. Frequently rearranged in advanced T-cell lymphomas-1 (FRAT1) is a positive regulator of the Wnt/ß-catenin signaling pathway and is overexpressed in many human tumors. However, the expression and role of FRAT1 in HCC has not been elucidated. In this study, we investigated the effect of FRAT1 on EMT process in HCC cells induced by hypoxia. Our results showed that FRAT1 is highly expressed in HCC tissues and cell lines. Hypoxia significantly induced FRAT1 expression in HCC cells. FRAT1 knockdown inhibited hypoxia-induced cell migration/invasion, downregulation of epithelial markers and upregulation of mesenchymal markers. Moreover, FRAT1 knockdown suppressed the expression levels of ß-catenin, cyclin D1 and c-myc in HCC cells under the same hypoxic condition. Our results revealed that FRAT1 is a hypoxia factor that is critical for the induction of EMT in HCC cells. These data suggest a potential role for targeting FRAT1 in the prevention of hypoxia-induced HCC cancer progression and metastasis mediated by EMT.

Effects of hepatitis C virus gene NS2 on the expressions of Bcl-2 and Bax in HepG2 cells.

OBJECTIVE: To study the effects of hepatitis C virus gene nonstructural protein 2 on the expressions of Bcl-2 and Bax in liver hepatocellular cells. METHOD: The study was conducted at the Department of Infectious Diseases, the First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China, from March 2012 to April 2013. Negative controls pEGFP-C3-NS2, pEGFP-C3-C and pEGFP-C3 were transiently transfected into liver hepatocellular cells and expressions of Bcl-2 and Bax were detected by Western blot 24 h post-transfection. SPSS 13 was used for statistical analysis. RESULTS: After transfected with NS2 gene, expression of Bcl-2 in liver hepatocellular cells was slightly higher than the non-transfected cells, and the expression of Bax was significantly higher than the non-transfected cells. CONCLUSION: Hepatitis C virus non-structural protein 2 gene plays a role in adjusting the proto-oncogene Bcl-2 and tumour suppressor gene Bax.