Characteristics of circulating immune cells in HBV-related acute-on-chronic liver failure following artificial liver treatment.

BACKGROUND AND AIM: Liver failure, which is predominantly caused by hepatitis B (HBV) can be improved by an artificial liver support system (ALSS). This study investigated the phenotypic heterogeneity of immunocytes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) before and after ALSS therapy. METHODS: A total of 22 patients with HBV-ACLF who received ALSS therapy were included in the study. Patients with Grade I according to the ACLF Research Consortium score were considered to have improved. Demographic and laboratory data were collected and analyzed during hospitalization. Immunological features of peripheral blood in the patients before and after ALSS were detected by mass cytometry analyses. RESULTS: In total, 12 patients improved and 10 patients did not. According to the immunological features data after ALSS, the proportion of circulating monocytes was significantly higher in non-improved patients, but there were fewer γδT cells compared with those in improved patients. Characterization of 37 cell clusters revealed that the frequency of effector CD8+ T (P = 0.003), CD4+ TCM (P = 0.033), CD4+ TEM (P = 0.039), and inhibitory natural killer (NK) cells (P = 0.029) decreased in HBV-ACLF patients after ALSS therapy. Sub group analyses after treatment showed that the improved patients had higher proportions of CD4+ TCM (P = 0.010), CD4+ TEM (P = 0.021), and γδT cells (P = 0.003) and a lower proportion of monocytes (P = 0.012) compared with the non-improved patients. CONCLUSIONS: Changes in effector CD8+ T cells, effector and memory CD4+ T cells, and inhibitory NK cells are associated with ALSS treatment of HBV-ACLF. Moreover, monocytes and γδT cells exhibited the main differences when patients obtained different prognoses. The phenotypic heterogeneity of lymphocytes and monocytes may contribute to the prognosis of ALSS and future immunotherapy strategies.

New Insight into the Function of Dopamine (DA) during Cd Stress in Duckweed (Lemna turionifera 5511).

Dopamine (DA), a kind of neurotransmitter in animals, has been proven to cause a positive influence on plants during abiotic stress. In the present study, the function of DA on plants under cadmium (Cd) stress was revealed. The yellowing of duckweed leaves under Cd stress could be alleviated by an exogenous DA (10/20/50/100/200 µM) supplement, and 50 µM was the optimal concentration to resist Cd stress by reducing root breakage, restoring photosynthesis and chlorophyll content. In addition, 24 h DA treatment increased Cd content by 1.3 times in duckweed under Cd stress through promoting the influx of Cd2+. Furthermore, the gene expression changes study showed that photosynthesis-related genes were up-regulated by DA addition under Cd stress. Additionally, the mechanisms of DA-induced Cd detoxification and accumulation were also investigated; some critical genes, such as vacuolar iron transporter 1 (VIT1), multidrug resistance-associated protein (MRP) and Rubisco, were significantly up-regulated with DA addition under Cd stress. An increase in intracellular Ca2+ content and a decrease in Ca2+ efflux induced by DA under Cd stress were observed, as well as synchrony with changes in the expression of cyclic nucleotide-gated ion channel 2 (CNGC2), predicting that, in plants, CNGC2 may be an upstream target for DA action and trigger the change of intracellular Ca2+ signal. Our results demonstrate that DA supplementation can improve Cd resistance by enhancing duckweed photosynthesis, changing intracellular Ca2+ signaling, and enhancing Cd detoxification and accumulation. Interestingly, we found that exposure to Cd reduced endogenous DA content, which is the result of a blocked shikimate acid pathway and decreased expression of the tyrosine aminotransferase (TAT) gene. The function of DA in Cd stress offers a new insight into the application and study of DA to Cd phytoremediation in aquatic systems.

Lower level of IL-28A as a predictive index of the artificial liver support system in effective treatment of patients with HBV-ACLF.

BACKGROUND: HBV-related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure with high mortality. Artificial liver support system (ALSS) is an important mean to reduce the mortality of HBV-ACLF but lacking index to assess its effectiveness. The cytokines are closely related to the prognosis of HBV-ACLF patients with ALSS treatment, however, which is not fully understood. METHODS: One hundred forty-two patients with HBV-ACLF and 25 healthy donors were enrolled. The cytokine profile of peripheral blood was determined in the patients before and after ALSS treatment, and their relationship with effectiveness of ALSS treatment in HBV-ACLF was analyzed. RESULTS: Serum IL-28A levels were markedly lower in ALSS-effective patients than those in non-effective patients pre-ALSS treatment. Similarly, serum IL-6 was significantly lower in ALSS-effective patients. Furthermore, for patients with effective treatment, serum IL-28A levels were positively related with IL-6 levels post-ALSS (r = 0.2413, p = 0.0383). The ROC curve analysis showed that serum levels of IL-28A (AUC = 0.6959 when alone or 0.8795 when combined with total bilirubin, platelet count and INR, both p < 0.0001) and IL-6 (AUC = 0.6704, p = 0.0005) were useful indices for separating effective from non-effective ALSS treatment of HBV-ACLF patients. Multivariate logistic regression analysis demonstrated that lower level of IL-28A was independently associated with higher effective rate of ALSS treatments. CONCLUSIONS: Lower level of IL-28A is a predictive biomarker for ALSS in effective treatment of HBV-ACLF patients and IL-28A may be potential target for the treatment of HBV-ACLF.

First morning voided urinary gonadotropins in children: verification of method performance and establishment of reference intervals.

OBJECTIVES: Urinary luteinizing hormone (uLH) and urinary follicle-stimulating hormone (uFSH) have been shown to be useful screening and management tools for children with central precocious puberty. However, studies on uLH and uFSH reference intervals are scarce. Therefore, we aimed to establish reference intervals for uLH and uFSH, according to age, sex, and pubertal status in apparently healthy children aged 6-11 years. METHODS: We performed detection capability, precision, accuracy by recovery, linearity, agreement analysis, and stability testing to analyze the method performance of uLH and uFSH. The Clinical Laboratory Standards Institute's C28-A3 criteria was used to establish the reference intervals. RESULTS: Both uLH and uFSH were stable at 4 °C for 52.6 h and 64.8 days, respectively. The total imprecision of uFSH is within the manufacturer's claim, while the total imprecision of uLH remained within tolerable bias. Both uLH and uFSH could be measured with acceptable detection capability. The recovery rates of the hormones were 87.6-98.8% and 102.8-103.4%, respectively, and therefore within acceptable limits. There were significant correlations between the serum and urine concentrations (LH: r=0.91, p<0.001; FSH: r=0.90, p<0.001). The reference intervals of uLH and uFSH were established according to age, sex, and pubertal status. CONCLUSIONS: We established reference intervals for uLH and uFSH based on age, sex and pubertal status to provide a non-invasive clinical screening tool for precocious puberty in children aged 6-11 years.

Lower testosterone levels predict increasing severity and worse outcomes of hepatitis B virus-related acute-on-chronic liver failure in males.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a serious liver disease with pathogenesis remaining unclear. This study aims to investigate the association between testosterone levels, stage (early, middle, or late, categorized according to clinical manifestation), severity scores, and clinical outcomes of HBV-ACLF. METHODS: This single-center observational study involved 160 male patients with HBV-ACLF, 151 chronic hepatitis B patients without liver failure (CHB) and 106 healthy controls (HC). Morning blood samples were collected and androgen levels analyzed by chemi-bioluminescent immunoassay. Time to death or liver transplantation within 90 days comprised the primary composite outcome. RESULTS: Serum levels of total testosterone (TT), free testosterone index (FTI), dehydroepiandrosterone sulfate and cortisol were significantly lower among HBV-ACLF than CHB and HC, while androstenedione was higher. Low TT, sex hormone binding globulin and FTI were associated with increased stage (of HBV-ACLF, ascites, and hepatic encephalopathy) and severity scores (Model for End-stage Liver Disease and Chinese Group on the Study of Severe Hepatitis B-ACLF scores). Low TT (< 142.39 ng/dL) was a risk factor for both the composite outcome and for death alone within 90 days. Multivariate analysis revealed TT to be an independent predictor for the composite outcome (hazard ratio 2.57, 95% CI 1.09-6.02; P = 0.030). CONCLUSION: Low serum testosterone is common among male patients with HBV-ACLF and predictive of increased severity and worse outcome of the disease and may play an important role in the progression of HBV-ACLF.

Effects of Different Recovery Positions on the Postpercutaneous Liver Biopsy Complications: A Metaanalysis.

Objective: We aim to evaluate the effects of different recovery positions on the adverse events and the patient acceptability in those who underwent percutaneous liver biopsy (PLB). Methods: A literature search was conducted in the Cochrane Library, Embase, Scopus, PubMed, CNKI, Sinomed, and Wanfang databases. The time for the article extraction was until July 2020. The articles were screened by two independent researchers, together with the bias risk evaluation and data extraction. The RevMan 5.4 software was utilized for the metaanalysis. Results: Finally, two articles involving 180 subjects were eligible for this study. Metaanalysis showed that at T0, the alternation between right-side and combined position (CRP) would induce an elevation of post-PLB pain compared with the dorsal/supine position (SRP) [WMD = -2.00, 95% CI (-3.54, -0.47), p = 0.01]. There were no statistical differences in the postoperative pain among the CRP, SRP, and right-side position (RRP). The patient acceptability of SRP and RRP was higher than that of the CRP. Finally, two eligible studies were included, which showed no incidence of pneumothorax and abdominal bleeding. Conclusions: CRP would induce post-PLB pain at T0. SRP was the most acceptable position for the cases that underwent PLB. There were no statistical differences in the incidence of pneumothorax and abdominal bleeding. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42020196633.

Profiling T cell receptor ß-chain in responders after immunization with recombinant hepatitis B vaccine.

BACKGROUND: T cells with edited T cell receptor ß-chain variable (TRBV) are involved in the immune response to recombinant hepatitis B surface antigen (rHBsAg) vaccine and the production of hepatitis B surface antibody (HBsAb). The immune repertoire (IR) profile and mechanism of vaccination positive responders (VPR) with rHBsAg are not fully understood. METHODS: The IR of six VPRs (HBsAb+, HbsAg-) with rHBsAg vaccination was established by the high throughput sequencing technique and bioinformatics analysis and compared with those in five vaccination negative responders (VNRs) (HbsAb-, HbsAg-) who were also inoculated with rHBsAg. The repertoire features of the BV, BJ and V (CDR3) J genes and immune diversity in peripheral blood mononuclear cells, respectively, were analyzed for each subject. RESULTS: There was no significant difference in sequencing amplification indices of each sample. However, TRBV15/BJ2-3 demonstrated significantly high expression levels in VPR compared to those in the VNR group (both p < 0.05). Further results showed that the BV15/BJ2-5 level was significantly increased for VPR compared to that of VNR group. Interestingly, the motif of CDR3 in TRBV15/BJ2-5 was mostly expressed as "GGETQ" or "GETQ". Additionally, there was no remarkable difference between the two groups of distribution with respect to the different clone expression levels of V (CDR3) J. CONCLUSIONS: The features of IR in the VPR and VNR will contribute to the exploration of the mechanism of the positive response to rHBsAg, and also contribute to development of optimized hepatitis B vaccine, in addition to providing a partial interpretation of the VNR who has a relatively low infection with HBV.

Efficiency of Double Plasma Molecular Absorption System on the Acute Severe Cholestatic Hepatitis.

BACKGROUND: Cholestasis may lead to hepatic cirrhosis and a longer hospital stay. A part of the patients with cholestasis requires liver transplantation. However, most of the treatment efficiency of cholestatic hepatitis (CH) is not satisfactory. For the patients with severe CH after artificial liver support, there was a lack of systemic evaluation on the treatment efficiency of double plasma molecular absorption system (DPMAS) for acute severe CH. OBJECTIVE: We aim to investigate the treatment efficiency of DPMAS on acute severe CH. METHODS: This retrospective study involved 309 cases diagnosed with acute severe CH admitted to the First Affiliated Hospital, Zhejiang University. We compared the prognosis of patients received standard medical therapy (SMT) and SMT + DPMAS. Besides, the effects of DPMAS on total bilirubin (TBIL) and prothrombin time (PT) were investigated. RESULTS: DPMAS could significantly reduce the requirements for liver transplantation in the CH patients. After DPMAS therapy, significant decline was noticed in the TBIL, direct bilirubin (DBIL), total bile acid, and cholesterol. The baseline ratio of neutrophil showed significant elevation in the patients received 4 or more DPMAS compared with those received less DPMAS. CONCLUSIONS: DPMAS could significantly eliminate the necessity of liver transplantation. The artificial liver support system should be conducted to bring down the bilirubin level and the ratio of cases with severe conditions. In general, DPMAS should be preferred as an artificial liver support therapy for the patients with acute severe CH.

Predictive value of insulin-like growth factor 1-Child-Turcotte-Pugh score for mortality in patients with decompensated cirrhosis.

BACKGROUND: Previous studies have used a modified version of the Child-Turcotte-Pugh (CTP) score to include insulin-like growth factor 1 (IGF-1) concentrations, denoted the Insulin-like Growth Factor 1-Child-Turcotte-Pugh (IGF-CTP) system. We evaluated the predictive power of IGF-CTP for 1-year mortality in patients with decompensated cirrhosis (DC). METHODS: A total of 386 patients with DC were retrospectively analyzed. Comparison of distribution of patients with decompensated cirrhosis according to Insulin-like Growth Factor-1-Child-Turcotte-Pugh and Child-Turcotte-Pugh scores were performed. Area under the receiver operating characteristic curves (AUROCs) for IGF-CTP, CTP and the Model for End-stage Liver Disease (MELD) scores were evaluated to compare predictive value. Univariate and multivariate analyses were carried out to determine potential risk factors for 1-y mortality. RESULTS: During the 1-y follow-up, 94 patients died. Significantly more patients (both surviving and non-surviving) were classified as IGF-CTP stage C than CTP stage C. The AUROC of IGF-CTP was significantly higher than that of CTP and MELD in the training and validation cohorts. Multivariate analysis indicated IGF-CTP score and IGF-1 to be independently associated with mortality. CONCLUSION: The IGF-CTP score is independently associated with mortality for patients with DC, and offers more accurate prediction of 1-y mortality than either CTP or MELD score for these patients.

Diagnostic Value of Serum Biomarkers for Intrahepatic Cholangiocarcinoma.

OBJECTIVE: To explore the diagnostic value of carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) for the diagnosis of intrahepatic cholangiocarcinoma (ICC). STUDY DESIGN: Case control study. PLACE AND DURATION OF STUDY: First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, from June 2016 to March 2018. METHODOLOGY: Patients with ICC (n = 51) diagnosed by histological examination after surgery were matched 1:4 to control subjects (n = 204) based on age (±2 years), gender, and ethnicity. Serum CA 19-9 and CEA levels were determined and compared. Receiver operating characteristic (ROC) curves were generated, and areas under the receiver operating characteristic curve (AUC) were calculated. The cutoff values, sensitivities, specificities, and Youden index values were calculated and compared. RESULTS: The levels of CA 19-9 and CEA were elevated in the ICC patients relative to control subjects (p <0.001). CA 19-9 and CEA showed diagnostic efficacy for ICC, with AUC values of 0.6916 and 0.6376, respectively. The cutoff value, sensitivity, specificity, and Youden index for CA 19-9 were 26 U/ml, 58.82%, 83.82%, and 0.4262, respectively. The cutoff value, sensitivity, specificity, and Youden index for CEA were 1.95 ng/ml, 90.2%, 35.29%, and 0.2549, respectively. The combination of CA 19-9 and CEA exhibited the best diagnostic efficacy, with the sensitivity, specificity, and Youden index being 90.2%, 88.24%, and 0.7844, respectively. CONCLUSION: Combined CA 19-9 and CEA levels have diagnostic value for ICC. The combination of CA 19-9 and CEA can assist surveillance and diagnosis of ICC prior to surgery.

Risk factors for Clostridium difficile infection in cirrhotic patients.

BACKGROUND: Cirrhotic patients are susceptible to Clostridium difficile infection (CDI), however, the high risk factors are not clear. The present study aimed to identify the risk factors in cirrhotic patients with CDI. METHODS: A total of 526 cirrhotic patients admitted to our hospital between May 2015 and October 2015 were included in this study. Stool samples were collected upon admission for the detection of CDI and toxin. CDI was monitored during the hospital stay. In total, 34 cases showed CDI. Then we analyzed the effects of age, sex, C. difficile colonization (CDC), multiple hospitalization, extended hospital stay, elevation of total bilirubin (TBIL), creatinine (Cr), Child-Pugh grade C, hepatic encephalopathy, hepatorenal syndrome, upper gastrointestinal hemorrhage, and exposure of antibiotics and proton pump inhibitor (PPI) on the CDI in cirrhotic patients. RESULTS: Patients in the CDI group had more frequent CDC, multiple hospitalization, and extended hospital stay compared to those in the non-C. difficile infection (NCDI) group. Patients in the CDI group had higher TBIL and Cr, and higher frequency of Child-Pugh grade C, hepatic encephalopathy, upper gastrointestinal hemorrhage compared with those in the NCDI group. Multiple logistic regression analysis indicated that age >60 years (OR=1.689; 95% CI: 1.135-3.128), multiple hospitalization (OR=3.346; 95% CI: 1.392-8.043), length of hospital stay >20 days (OR=1.564; 95% CI: 1.113-2.563), hypoproteinemia (OR=4.962; 95% CI: 2.053-11.996), CDC (OR=18.410; 95% CI: 6.898-49.136), hepatic encephalopathy (OR=1.357; 95% CI: 1.154-2.368), and exposure of antibiotics (OR=1.865; 95% CI: 1.213-2.863) and PPI (OR=3.125; 95% CI: 1.818-7.548) were risk factors of CDI. CONCLUSIONS: Age >60 years, multiple hospitalization, length of hospital stay >20 days, hypoproteinemia, CDC, hepatic encephalopathy, and exposure of antibiotics and PPI were risk factors for CDI in cirrhotic patients. These may contribute to the early diagnosis and monitoring of CDI in clinical practice.

Clostridium difficile colonization and infection in patients with hepatic cirrhosis.

OBJECTIVE: The aim of this study was to investigate the toxigenic Clostridium difficile colonization (CDC, colonization with toxigenic C. difficile but without symptoms) and C. difficile infection (CDI, active C. difficile infection resulting in disease symptoms) in hepatic cirrhosis patients, identify the risk factors of CDC, and determine the correlation between CDC and CDI. METHODOLOGY: The strains of toxigenic C. difficile were isolated from patients with hepatic cirrhosis within 48 h after admission, followed by multilocus sequence typing (MLST). Patients were divided into toxigenic CDC group and noncolonized (NC) group according to the colonization. Logistic regression analysis was performed to analyse the risk factors for the CDC. Besides, the CDI incidence was compared between the two groups. RESULTS: Colonization of toxigenic C. difficile was identified in 104 cases (19.8 %). Eighteen sequence types (STs) were identified, among which ST-3, ST-54, ST-35 and ST-37 were the predominant types. Child-Pugh class C(relative risk, RR, 3.025; 95 % CI: 1.410-6.488), decrease of prothrombin time activity (PTA) (RR 2.180; 95 % CI: 1.368-3.476), decrease of platelet (RR 2.746; 95 % CI: 0.931-8.103) and concurrent hepatic encephalopathy (RR 1.740; 95 % CI: 1.012-2.990) were identified as the risk factors for the hepatic cirrhosis patients with CDC. The CDI incidence in the CDC group was also significantly higher than that of the NC group (26.0 % vs 1.7 %, P<0.001). CONCLUSION: An carriage rate of 19.8 % was reported in the hepatic cirrhosis patients with C. difficile colonization. Child's class C, decrease of PTA and platelet, and concurrent hepatic encephalopathy were the risk factors for the hepatic cirrhosis patients with C. difficile colonization. Hepatic cirrhosis patients with C. difficile colonization were more susceptible to CDI.

Effects of backrest density on lumbar load and comfort during seated work.

BACKGROUND: Seated workplaces have greatly increased in China. Many researchers have found that seated work is a risk factor in the development of low-back pain. Backrest can reduce the load on the lower back by transmitting more of the weight from the upper body to the floor via the backrest so as to prevent low-back pain. To design a suitable chair backrest for seated office work, some backrest parameters must be optimized. In this study, the role of backrest density on lumbar load and comfort were investigated. The goal of the study was to help establish criteria with which backrests that alleviate and prevent low back pain during seated office work can be designed and selected. METHODS: Twenty volunteers (10 men and 10 women) were seated in three backrest conditions (10 kg/m(3), 25 kg/m(3), and 40 kg/m(3)). Pressure data, including contact pressure (CP), peak contact pressure (PCP) and contact area were collected during 15-minute trial. Subjective data were collected after each pressure test. RESULTS: Backrest density had a significant effect on backrest pressure variables. CP and PCP increased with increasing backrest density. Contact area decreased with increased density. In terms of user preference, the backrest with low density was most highly rated. CONCLUSIONS: Backrest density plays an important role in lumbar load and comfort during seated work. During designing and selecting backrests, backrest density should be focused on so as to alleviate and prevent low-back pain during seated office work. Backrest density at 10 kg/m(3) got the lowest CP and PCP and largest contact area. Backrest with low density can reduce lumbar pressure and increase support contact area, which could raise comfort feeling. Backrest density at 10 kg/m(3) is better to maintain a balance between providing effective support and alleviating excess lordosis.

[Study on effect of backrest thickness to lumbar muscle fatigue during computer work].

OBJECTIVE: To investigate the relationship between backrest thickness and lumbar muscle fatigue so as to confirm the fitting backrest thickness. METHOD: Twenty subjects coming from university seated at a computer workstation in three backrest thicknesses: 4, 7 and 10 cm. The time that the subjects reported the lumbar muscle fatigue was collected during each trial and subjective appraise was collected at the end of the entire protocol. RESULTS: The MF value decreased and lumbar muscle felt fatigue in all three backrest thickness. Subject could feel fatigue more late [(45.0 +/- 10.8) min] and subject felt more comfort at 7 cm thickness. CONCLUSION: It is better to relive computer worker lumbar muscle fatigue when the backrest thickness was kept on 7 cm. Work break was needed because one hour work could cause muscle fatigue.