Durability of immune response after SARS-CoV-2 vaccination in patients with chronic liver disease.

Aim: The present study aimed to evaluate the durability of immune response after basic and booster immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with chronic liver disease (CLD). Methods: Patients with CLD and complete basic or booster immunization with SARS-CoV-2 vaccines were included in this study. Based on the vaccination situation, they were divided into the basic immunity group (Basic) and the booster immunity group (Booster), which were then subdivided into four groups according to the time interval from completion of basic immunization or booster immunization to serological specimen collection. The positive rates and antibody titers of novel coronavirus neutralizing antibody (nCoV NTAb) and novel coronavirus spike receptor-binding domain antibody (nCoV S-RBD) were analyzed. Results: A total of 313 patients with CLD were enrolled in this study, including 201 in Basic and 112 in Booster. The positive rates of nCoV NTAb and nCoV S-RBD within 30 days of completing basic immunization were 80.4% and 84.8%, respectively, but decreased rapidly with the extension of vaccination time, and only 29% and 48.4% of patients with CLD remained positive for nCoV NTAb and nCoV S-RBD, respectively, after 120 days of completing basic immunization. Within 30 days of booster immunization, the positive rates of nCoV NTAb and nCoV S-RBD in patients with CLD rapidly increased from 29.0% and 48.4% at the end of basic immunization to 95.2% and 90.5%, and maintained a high level (defined as the positive rate >50%) until 120 days when the positive rates of nCoV NTAb and nCoV S-RBD were still high at 79.5% and 87.2%, respectively. After basic immunization, the time for nCoV NTAb and nCoV S-RBD to turn negative was 120 and 169 days, respectively, and the negative time of nCoV NTAb and nCoV S-RBD was significantly prolonged to 266 days and 329 days, respectively. Conclusion: It is safe and effective for patients with CLD to complete basic and booster immunization with SARS-CoV-2 vaccines. After booster immunization, the immune response of patients with CLD was further improved and the durability of the SARS-CoV-2 antibody was significantly prolonged.

Nontoxic Tb3+-induced hyaluronic nano-poached egg aggregates for colorimetric and luminescent detection of Fe3+ ions.

This study demonstrates that a luminescent Tb3+ complex with green emission can be complexed with hyaluronic (hya) to form nanoparticles. The structure of complexation is composed of a Tb(acac)2phen core with a hya surface, similar to those of the nano-poached eggs. What makes the structure unique is that Tb(acac)2phen and hya are connected by chemical bonds. To confirm their utility, we illustrate that the luminescence is rapidly and selectively quenched in the presence of Fe3+. Initial cytotoxicity experiments with human liver carcinoma cells show that the luminescent lanthanide complexes are cytotoxic, however, complexing lanthanides to hya renders them cytocompatible. The new complex integrates the advantages of superior lanthanide luminescence, the unique shape of nano-poached eggs, compatibility with aqueous systems, and cytocompatibility. Tb3+-induced hyaluronic nano-poached eggs (THNE) can, therefore, be used for Fe3+ detection in aqueous systems.

Efficacy and safety of anticoagulants in liver cirrhosis patients with portal vein thrombosis: A meta-analysis.

OBJECTIVE: To investigate the efficacy and safety of anticoagulants in liver cirrhosis patients with portal vein thrombosis (PVT). METHODS: PubMed, BioMed Central, Cochrane Library and Web of Science were retrieved to identify relevant literature. Forest plots were applied to display the results of the meta-analysis. The odds ratios (ORs) were used as the effect index for the enumeration data, and the effect size was expressed as 95% confidence intervals (CIs). Publication bias was evaluated by funnel plots and Egger's test. RESULTS: Eight articles included 225 patients with liver cirrhosis and PVT receiving anticoagulants and 232 not receiving anticoagulants. The data demonstrated that the recanalization rate of PVT was significantly higher in patients with anticoagulant treatment than in patients without anticoagulant treatment (OR=5.60; 95% CI: 3.40-9.22; P<0.001). The exacerbation risk of PVT was significantly lower in patients with anticoagulant treatment than in patients without anticoagulant treatment (OR=0.15; 95% CI: 0.04-0.54; P<0.001). A significantly lower portal hypertension bleeding effect was observed in patients with anticoagulant treatment than in patients without anticoagulant treatment (OR=0.21; 95% CI: 0.10-0.45; P<0.001). Low molecular weight heparins (LMWH) were more effective in preventing the PVT exacerbation in liver cirrhosis patients with PVT than warfarin (OR=0.16; 95% CI: 0.08-0.35). CONCLUSIONS: Anticoagulants were effective and safe in treating patients with liver cirrhosis and PVT as they could increase the PVT recanalization rate and decrease the risks of PVT exacerbation and portal hypertension bleeding.

Diagnosis and Treatment of Cirrhosis with Duodenal Variceal Bleeding: a Case Report.

BACKGROUND: Cases of duodenal variceal hemorrhage after cirrhosis are rare, but patients have a higher mortality rate. There is currently no clinical guideline to address how such patients should choose preferred treatment. METHODS: We retrospectively evaluated the clinical information of a 65-year-old male admitted to the Gastroenterology Department with gastrointestinal bleeding. RESULTS: The patient was eventually diagnosed with duodenal variceal bleeding after cirrhosis. We performed TIPS on the patients after the vital signs were stable. No varicose veins were seen by endoscopy during the 2-year follow-up. CONCLUSIONS: TIPS treatment is a good choice for patients with severe duodenal varices after cirrhosis.

Research on minimum detectable activity (MDA) of underwater gamma spectrometer for radioactivity measurement in the marine environment.

To improve the capability of underwater gamma spectrometer to quantify radiation levels slightly above the background radiation in the seawater, the minimum detection activity (MDA) and factors including the background count, detection efficiency and acquisition time were studied using Monte Carlo simulation and field experiments. The simulation results show that the crystal type selected in the spectrometer and its volume, enclosure materials of the spectrometer and its thickness all affect the marine detection efficiency in in-situ measurement, and thus determine MDA of the underwater gamma spectrometer. The acquisition time and the placement depth of the spectrometer in the seawater also affect the MDA in the in-situ measurement. Some research data and suggestions on design and use of underwater gamma spectrometer were presented, which are of guiding significance for the in-situ radioactivity measurement in the marine environment.

Retracted Article: MicroRNA-1271 modulates hepatitis B virus replication, cell proliferation and apoptosis in hepatitis B virus-related hepatocellular carcinoma by targeting SIRT1.

Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Certain studies have revealed that microRNAs play crucial roles in HBV-related HCC. The aim of this study was to investigate the effects of microRNA-1271 (miR-1271) on HBV replication, cell proliferation and apoptosis in HBV-related HCC. The expression of HBV DNA and miR-1271 was detected by quantitative real time-polymerase chain reaction (qRT-PCR). The mRNA and protein levels of SIRT1 were detected by qRT-PCR and western blot analysis, respectively. HBV replication was assessed by the expression of HBV DNA and the levels of HBsAg and HBeAg. Cell proliferation was assessed by cell counting kit-8 (CCK-8) and 5-bromo-2-deoxyuidine (BrdU) assay, and apoptosis was evaluated by flow cytometry assay, enzyme-linked immunosorbent assay (ELISA) and the activity of caspase-3. The relationship between miR-1271 and SIRT1 was predicated by online software and confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and pull-down assay. We first found that the expression of miR-1271 was downregulated and SIRT1 was upregulated in both HBV-related HCC tissues and cells. Overexpression of miR-1271 inhibited HBV replication and cell proliferation whilst promoting apoptosis in HBV-related HCC cells. Subsequently, SIRT1 was identified as a target of miR-1271. Moreover, overexpression of SIRT1 reversed the effects of miR-1271 overexpression on HBV replication, cell proliferation and apoptosis in HBV-related HCC cells. In conclusion, our study demonstrated that miR-1271 inhibited HBV replication and proliferation and promoted apoptosis of HBV-related HCC cells via targeting SIRT1, which might contribute to the diagnosis and therapy of HBV-related HCC.

Complete cure of a patient with HBV-associated hepatocellular carcinoma with lung metastasis using interferon and survival up to 108 months: A case report and literature review.

Hepatocellular carcinoma (HCC) has a poor prognosis due to its asymptomatic onset and susceptibility to metastasis. The survival of patients with advanced HCC is 6-12 months. As a first-line medicine for the control of hepatitis B virus, interferon (IFN) is also capable of inhibiting tumor growth and modulating immunity. However, treatment of HCC with lung metastasis using IFN has been rarely reported. The present study reports the case of one patient with HCC having lung metastasis who underwent a one-time treatment with transcatheter arterial chemoembolization (TACE) and was subsequently completely cured by single peginterferon α 2a (PEG-IFNα2a); and has survived up to 108 months. A 53-year-old male patient diagnosed with HBV-related HCC with lung metastasis underwent TACE using floxuridine (FUDR) 500 mg, cisdiamine dichloroplatinum (CDDP) 20 mg, mitomycin 10 mg, and ultrafluid lipiodol 10 ml, together with local thoracic aorta chemotherapy using FUDR 250 mg and CDDP 20 mg. His metastatic lung cancer aggravated. However, after 9 months of treatment with subcutaneous injections of PEG-IFNα 2a once per week, the metastatic lung foci gradually shrunk until disappearance and the HCC lesion stabilized without progression. According to the World Health Organization criteria for the efficacy of solid tumors, this was a case of complete response. Upon follow-up up to 108 months his metastatic lung cancer had disappeared and HCC did not recur. Therefore, IFN intervention may be an appropriate novel adjuvant therapy for patients with HCC with lung metastasis and requires further attention and study.

Different scoring systems to predict 6-week mortality in cirrhosis patients with acute variceal bleeding: a retrospective analysis of 202 patients.

OBJECTIVE: Determine the optimal scoring system for evaluation of 6-week bleeding-related mortality in liver cirrhosis patients with acute variceal bleeding (AVB). Prediction effects of six scoring systems, AIMS65 score, Glasgow-Blatchford (GBS) score, full Rockall (FRS) score, the model for end-stage liver disease (MELD), the MELD-Na model and the Child-Turcotte-Pugh (CTP) score were analyzed in this study. METHODS: A total of 202 liver cirrhosis patients with AVB were enrolled between 1 January 2014, and 31 December 2014. All subjects were scored according to AIMS65, GBS, FRS, MELD, MELD-Na and CTP scoring systems on the first day of admission. The primary endpoint of the study was 6-week mortality. The prediction effect of these scoring systems for 6-week mortality was compared by ROC curve and the area under the curve (AUC). RESULTS: The scores of nonsurvival group evaluated by the AIMS65, GBS, FRS, MELD, MELD-Na and CTP (2.6 ± 1.1, 12.9 ± 2.7, 6.6 ± 1.8, 26.9 ± 6.5, 31.6 ± 9.3, 9.6 ± 2.2, respectively) were higher than those of the survival group (1.2 ± 1.1, 10.2 ± 3.4, 5.1 ± 1.6, 21.0 ± 6.4, 22.8 ± 8.2, 7.7 ± 2.0, respectively) (p < .01). The values of AUC and Youden index of AIMS65 and MELD-Na scoring systems [(0.808, 0.453) and (0.781, 0.516), respectively] were superior to those of MELD (0.761, 0.454), CTP (0.748, 0.399), FRS (0.738, 0.358) and GBS scoring systems (0.726, 0.370). CONCLUSIONS: AIMS65 and MELD-Na scoring systems are recommended for evaluation of 6-week bleeding-related mortality in liver cirrhosis patients with AVB.

Propranolol suppresses the proliferation and induces the apoptosis of liver cancer cells.

An increasing amount of evidence indicates that the inhibition of ß adrenergic signaling can result in the inhibition of tumor growth. However, the role of propranolol in liver cancer and the underlying mechanism remain to be elucidated. The present study aimed to investigate the role of propranolol in liver cancer cell lines and provide evidence for further clinical study. Propranolol was added at different concentrations to HepG2 and HepG2.2.15 liver cancer cells and HL­7702 normal human liver cells. The proliferation of the cell lines was monitored by live­cell imaging at a range of time intervals. Immunofluorescence using DAPI and Hoechst 33342/propidium iodide (PI) staining, Annexin V­FITC/PI double­staining flow cytometry, western blotting and reverse transcription­quantitative polymerase chain reaction were used to investigate the effect of propranolol on liver cancer cell apoptosis. The proliferation of HepG2 and HepG2.2.15 cells was inhibited by 40 and 80 µmol/l propranolol. However, the proliferation of HL­7702 cells was not affected by <160 µmol/l propranolol. Propranolol treatment decreased the expression of adrenergic receptor ß­2 to a greater extent than adrenergic receptor ß­1, and induced apoptosis in the liver cancer cells. The apoptotic rates of HepG2 and HepG2.2.15 cells increased following treatment with propranolol, while the apoptotic rate of HL­7702 cells was not affected. Propranolol promoted poly (ADP­ribose) polymerase cleavage and decreased the expression of full­length caspase­3 in liver cancer cell lines; it induced S­phase arrest in HepG2 and HepG2.2.15 cell lines, while HL­7702 cells were arrested at the G0/G1 phase of the cell cycle. Thus, it was demonstrated that propranolol inhibited proliferation, promoted apoptosis and induced S-phase arrest in HepG2 and HepG2.2.15 cells.

Native chemical ligation combined with spirocyclization of benzopyrylium dyes for the ratiometric and selective fluorescence detection of cysteine and homocysteine.

Spirocyclization of xanthene dyes has become a powerful technique for developing fluorescent probes. Herein, we extend this unique fluorescence switching mechanism to a near-infrared (NIR) dye, 2-(7-diethylamino-2-oxo-2H-1-benzopyran-3-yl)-4-(2-carboxyphenyl)-7-diethylamino-1-benzopyrylium (CB), and construct a ratiometric fluorescent probe 1 for cysteine (Cys)/homocysteine (Hcy). The ratiometric sensing of probe 1 toward Cys/Hcy is realized by utilizing a tandem native chemical ligation/spirocyclization reaction to interrupt the large π-conjugated system of CB fluorophore, thereby affording remarkable blue shifts in the spectra of sensing system (from 669 to 423 nm in absorption spectra and from 694 to 474 nm in emission spectra). Probe 1 shows a high sensitivity for Cys/Hcy, and the detection limits (3 δ) for Cys and Hcy are 1.6 × 10(-7) and 1.8 × 10(-7) M, respectively. Moreover, since both the sulfhydril and the adjacent amino groups are involved in the sensing process, probe 1 is selective toward Cys/Hcy over other thiols such as glutathione. All these unique features make it particularly favorable for ratiometric Cys/Hcy sensing and bioimaging applications. It has been preliminarily used for Cys detection in rabbit serum samples and the ratiometric fluorescent imaging of Cys in living HepG2 cells.