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Protective effect of human serum amyloid P on CCl4-induced acute liver injury in mice.
Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression. Moreover, CCl4-induced apoptosis in the mouse liver was inhibited by hSAP, as measured by terminal-deoxynucleotidyl transferase mediated nick-end labeling (TUNEL) assay and cleaved caspase-3 expression. hSAP significantly restored the expression of B cell lymphoma/leukemia (Bcl)-2 and suppressed the expression of Bcl-2-associated X protein (Bax) in vivo. The number of hepatocytes in early apoptosis stained with Annexin V was significantly reduced by 28-30% in the hSAP treatment group compared with the CCl4 group, and the expression of Bcl-2 was increased, whereas the expression of Bax and cleaved caspase-3 were significantly inhibited in the hSAP pre-treatment group compared with the CCl4 group. hSAP administration also inhibited the migration and activation of hepatic stellate cells (HSCs) in CCl4-injured liver and suppressed the activation of isolated primary HSCs induced by transforming growth factor (TGF)-ÎČ1 in vitro. Collectively, these findings suggest that hSAP exerts a protective effect againts CCl4-induced hepatic injury by suppressing the inflammatory response and hepatocyte apoptosis, potentially by inhibiting HSC activation
A large-scale serological survey of Akabane virus infection in cattle, yak, sheep and goats in China
Akabane virus (AKAV) is a member of the Simbu serogroup, classified in the genus Orthobunyavirus, family Bunyaviridae. AKAV infection can cause abortion, stillbirth, and congenital arthrogryposis and hydranencephaly in cattle and sheep. The distribution and prevalence of AKAV infection in China is still unknown. A total of 2731 sera collected from 2006 to 2015 in 24 provinces of China from cattle, sheep, goats and yak were examined by serum neutralisation test. The overall seroprevalence rates for AKAV antibodies were 21.3% in cattle (471/2215) and 12.0% (17/142) in sheep or goats, and 0% in yak (0/374). The results indicated widespread AKAV infection in China among cattle and sheep but yak appear to have a low risk of infection. Using a selection of 50 AKAV-positive and 25 AKAV-negative cattle sera, neutralisation tests were also conducted to detect antibodies to several other Simbu serogroup bunyaviruses and closely related Leanyer virus. Although inconclusive, the data suggest that both Aino virus and Peaton virus, which have been reported previously in Japan and Korea, may also be present in cattle in China
The Effects of Short-duration Exercise on Arterial Stiffness in Patients with Stable Coronary Artery Disease
Arterial stiffness is an important contributor to the development of cardiovascular disease. We investigated the effect of short duration exercise using the treadmill test on arterial stiffness in the presence of coronary artery disease. We enrolled patients with and without coronary artery diseases (CAD and control group, 50 patients each) referred for treadmill testing. Brachial-ankle pulse wave velocity (baPWV) were measured before and after treadmill testing. Values of baPWV were significantly reduced at 10 min after exercise in both groups, more in the CAD group than in the control group (baseline baPWV and post-exercise change [cm/sec]: 1,527±245 and -132±155 in the CAD group, 1,439±202 and -77±93 in the control group, respectively, P for change in each group <0.001, P for difference in changes between the two groups <0.001). These findings persisted after adjusting for age, body mass index, systolic blood pressure, mean arterial pressure (MAP), MAP decreases, and baseline baPWV. Significant post-exercise baPWV reductions were observed in both groups, and more prominently in the CAD group. This finding suggests that short-duration exercise may effectively improve arterial stiffness even in patients with stable coronary artery disease
A High Serum Level of Taurocholic Acid is Correlated with the Severity and Resolution of Drug-induced Liver Injury
Background & Aims
Alterations in the serum levels of bile acids are associated with drug-induced liver injury (DILI). We investigated the association between serum levels of bile acids and the severity and outcome of DILI, along with the potential role of variants in the ATP binding cassette subfamily B member 11 ( ABCB11) gene and expression of its product, ABCB11 (also called BSEP).
Methods
We performed this prospective study of 95 patients (median age, 53 years; 73.7% female) with DILI from August 2018 through August 2019. Patients were matched for age, gender, and body mass index with healthy individuals (n=100; healthy controls) and patients with chronic hepatitis B (n=105; CHB controls). We collected demographic and biochemical data at baseline and 1 week, 1 month, 3 months, and 6 months after DILI onset and at the time of biochemical recovery, liver failure or liver transplantation. Serum levels of bile acids were measured using high-performance liquid-chromatography tandem mass-spectrometry. All 27 exons of ABCB11 were sequenced and expression of BSEP were analyzed by immunohistochemistry in liver biopsy specimens.
Results
Levels of 30 of the 37 bile acids analyzed differed significantly between patients with DILI and healthy controls. Changes in levels of taurocholic acid (TCA), glycocholic acid, taurochenodeoxycholate, and glycochenodeoxycholate associated with the increased levels of bilirubin and greater severity of DILI, and were also associated with CHB. Cox regression analysis showed that only change in the levels of TCA independently associated with biochemical resolution of DILI. Combination of TCA level (â„ 1955.41 nmol/L), patient age, and DILI severity was associated with abnormal blood biochemistry at 6 months after DILI onset (area under the curve, 0.81; 95% confidence interval, 0.71â0.88; sensitivity, 0.69; specificity, 0.81). ABCB11 missense variants were not associated with differences in the serum bile acid profiles, DILI severity, or clinical resolution. However, lower levels of BSEP in bile canaliculi in liver biopsies were associated with altered serum levels of bile acids.
Conclusions
In this prospective study performed in Chinese patients, we found that the serum levels of TCA were associated with the severity and clinical resolution of DILI. Reduced protein expression of BSEP in liver tissue, rather than variants of the ABCB11 gene were associated with altered serum levels of bile acids
Relationship between fitness and arterial stiffness according to hypertensive state
Background: There is a well-established relationship between cardiorespiratory fitness (CRF) and arterial stiffness. However, it is unclear whether this relationship differs significantly between hypertensive and non-hypertensive patients. Methods: Adults without a history of ischemic heart disease or stroke and normal exercise test results who underwent health screening were included. Cardiopulmonary function test was performed using the Bruce protocol. Peak oxygen consumption (VO2peak) was measured. Arterial stiffness was evaluated using the brachial-ankle pulse wave velocity (baPWV). Results: Study subjects were 9232 participants (M:F = 71:29%) with a mean age of 53 ± 6 years. Thirty-four percent had hypertension. There was an inverse relationship between the peak oxygen consumption and baPWV (r = - 0.21, p < 0.001) This relationship persisted after adjusting for age, gender, body mass index, smoking, diabetes mellitus, hemoglobin A1c, LDL-cholesterol, mean blood pressure, and hypertension (p < 0.0001). The regression coefficient of VO2peak was significantly more negative among hypertensive subjects than it was in non-hypertensive subjects in the regression coefficient (â9.2 vs. â4.2, p for interaction <0.001). The difference in arterial stiffness between hypertensive and non-hypertensive groups decreased as the CRF increased. Conclusion: Arterial stiffness decreased as CRF increased among participants without overt cardiovascular disease. The effect of hypertension on arterial stiffness also decreased as the CRF increased
Corrigendum to âA large-scale serological survey of Akabane virus infection in cattle, yak, sheep and goats in Chinaâ (Veterinary Microbiology (2017) 207 (7â12), (S0378113517303851) (10.1016/j.vetmic.2017.05.014))
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Detection and clinical application of VAR2 synthetic peptide specific binding to circulating tumor cells
Objective To investigate the detection and clinical application studies based on malaria protein VAR2CSA(VAR2) synthetic peptide specifically binding to circulating tumor cells (CTCs). Methods The peptide sequence of the functional structural domain of malaria protein VAR2CSA was selected to synthesize VAR2 that enriched CTCs based on nano-microfluidic technology, and used VAR2 synthetic peptide to detect enriched cells to establish a novel detection protocol for CTCs. Cellular immuno-fluorescence staining, flow cytometry and tumor cell doping recovery assays were used to analyze the specific binding and recovery efficiency of VAR2 synthetic peptide with tumor cells of different tissue sources and compare with immuno-staining-fluorescence in situ hybridization (imFISH) assay. Twenty-two colorectal cancer patients and twenty-two healthy individuals were selected, and the VAR2 synthetic peptide was used to detect peripheral blood CTCs in both. The VAR2 synthetic peptide was used to compare the positive detection rate of CTCs in patients with different TNM stages. Results The VAR2 synthetic peptide bound specifically to tumor cells collected from different tissue sources of human colon cancer cell line SW620, human breast cancer cell line MCF7 and human esophageal squamous carcinoma cell line KYSE180.The VAR2 synthetic peptide detected 100 SW620, MCF7 and KYSE180 tumor cells mixed into 3 mL of peripheral blood with recovery rates of 82.8%±8.41%, 56.2%±3.57%, 86.6%±8.19%, which were not significantly different from the imFISH assay. The VAR2 synthetic peptide assay recoveries of 50, 100, and 200 SW620 tumor cells were 80.7%, 82.8%, and 84.7%, respectively, which did not correlate significantly with the number of adulterated tumor cells. The VAR2 synthetic peptide detected 63.6% positive CTCs in peripheral blood samples from patients with clinical colorectal cancer, which was higher than the 0.0% positive CTCs rate in the group of healthy subjects, and also correlated with depth of invasion, lymph node metastasis, distant metastasis, and clinical stage (PïŒ0.05). Conclusions The VAR2-based synthetic peptide may be applied in specific and non-antibody dependent CTCs detection in different tissue samples and so has good clinical application value for clinical staging and severity evaluation of tumor patients
Systematic review on the reporting quality of randomized controlled trials in patients with hepatitis B or C in China
Background: The numbers of articles reporting randomized controlled trials (RCTs) on viral hepatitis in China have been increasing, but there have been few systematic studies evaluating the reporting quality of RCTs in this field. This study was performed to assess the reporting quality of RCTs on the treatment of hepatitis B and C in China from 1991 to 2015.
Methods: Articles published between January 1991 and December 2015 were identified via the PubMed, MEDLINE, and Embase databases using the key words ârandomized clinical trialsâ, âtreatmentâ, âtherapyâ, âhepatitis Bâ, âHBVâ, âhepatitis Câ, âHCVâ, âChinaâ, and âChineseâ. The reporting quality was assessed against the Consolidated Standards of Reporting Trials (CONSORT) checklist.
Results: In total, 211 RCTs on the treatment of hepatitis B or C were included. The number of articles focusing on these RCTs increased rapidly over time, while the reporting quality improved steadily over time. Overall, compliance with the key components of the CONSORT checklist was low, with only 8.5%, 3.8%, and 11.4% of the articles fulfilling the reporting requirements of randomization, allocation concealment, and blinding, respectively.
Conclusions: Both the number and the quality of RCT articles were found to have increased steadily over the last two decades. However, compliance with the key components of the CONSORT checklist still needs improvement. It is hoped that the results of this study will lead to improvements in the reporting quality of clinical trials on hepatitis B and C in China
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