Evolutionary genomics of recent clinical Bordetella pertussis isolates from Iran: wide circulation of multiple ptxP3 lineages and report of the first ptxP3 filamentous hemagglutinin-negative B. pertussis

Here we investigated nationwide clinical Bordetella pertussis isolated during 2005–2017 from different provinces of Iran, a country with more than 50 years whole cell vaccine immunisation history. Our results revealed the ongoing increase in the population of ptxP3/fim3–2 B. pertussis isolates in different provinces which were differentiated into nine clades. The largest clade (clade 8) which was previously found to be prevalent in Tehran was also prevalent across the country and clade 5 with ptxP3/prn9 genotype has also increased in frequency (14% of all ptxP3 isolates) in recent years. Furthermore, we detected the first ptxP3 B. pertussis isolates that does not express filamentous hemagglutinin (FhaB) as one of the major antigens of the pathogen and a key component of the acellular pertussis vaccine.     

Does anatomical type of proximal hip fracture affect rehabilitation outcomes among older adults?

Background and purposeNumerous studies have detailed the potential benefits of inpatient geriatric rehabilitation for older adults with hip fractures. However, data regarding effect of fracture type (femoral neck, intertrochanteric, or subtrochanteric) on rehabilitation outcomes are limited. This study assessed whether the anatomical type of proximal hip fracture affects rehabilitation outcomes among disabled older adults.MethodsA population-based study was conducted comparing all patients with a recent hip fracture who were admitted to a geriatric rehabilitation facility in Israel. Data were collected retrospectively from an electronic database during a 5-year period (2014–2019). The Functional Independence Measure (FIM) was used to assess physical and cognitive function at admission and discharge.ResultsThe analyses included 624 older adults with hip fractures. We found significant differences in motor FIM score at admission, as patients with femoral neck fracture performed better than patients with intertrochanteric and subtrochanteric fracture did. The disparity in motor FIM score remained consistent through discharge, with all groups achieving a median gain of 14 points. Within one month of rehabilitation, about a third of all patients achieved a higher functional level.ConclusionsPatients with femoral neck fracture have better motor ability than do those with intertrochanteric and subtrochanteric fractures, which were retained throughout the course of rehabilitation; yet, the level of improvement remained similar. Clinicians should be aware of such differences in functional ability when discussing goals of care with older adults with hip fractures and consider them when implementing individual rehabilitation programs .     

Determination of folic acid by capillary zone electrophoresis with indirect chemiluminescence detection

A capillary electrophoresis method with on-line inhibited chemiluminescence (CL) detection was first used to determine folic acid (FA). This method was established based on the quenching effect of FA on the CL reaction of luminol with a Ag(iii) complex in alkaline medium. The separation was conducted with a 20.0 mM sodium borate buffer containing 1.0 mmol L⁻¹ luminol. Under optimized conditions, FA was baseline separated and detected in less than 10 min. The limit of detection of FA was 1.3 mg L⁻¹, with a linear range of 5.0–150.0 mg L⁻¹ (r = 0.9953). The RSD value was 2.8% for intra-day precision and 5.4% inter-day precision. The recoveries of the standard addition of tablets and human urine ranged from 90.3% to 107.5% and from 82.0 to 105.7%, respectively. The proposed method was successfully applied to determine FA contents in commercial pharmaceutical tablets and human urine samples. Results suggested that this method was simple and robust.

A capillary electrophoresis method with on-line inhibited chemiluminescence detection was first used to determine folic acid.     

Genetic variants in IL33 and IL1RL1 genes confer susceptibility to HBV-related liver cirrhosis in Chinese Han population

IntroductionPrevious studies indicate that the IL-33/ST2 pathway is involved in hepatitis B virus (HBV) -related liver diseases. This study aimed to determine the relationship between genetic variants in IL-33/ST2 pathway with susceptibility to liver cirrhosis.Materials and methodsA total of 2632 Han Chinese samples met the inclusion and exclusion criteria, including 840 negative controls (NeC), 691 chronic hepatitis B (CHB), 680 HBV-related liver cirrhosis (LC) and 421 HBV-related hepatocellular carcinoma (HCC) (without LC) patients. Four polymorphisms (IL33-rs4742170, rs1048274, rs10975519 and IL1RL1-rs1041973) were selected and genotyping was performed. All statistical analyses were performed by SPSS21.0, mainly using the Hardy-Weinberg equilibrium test, Pearson chi-square, unconditional Logistic regression and haplotype analysis.ResultsAfter adjusting for age, sex, smoking and drinking, significant associations were observed between IL33-rs4742170, rs1048274 and rs10975519 polymorphisms with LC risk. NeC with IL33-rs4742170 CC genotype was 1.80 times more likely to develop LC compared with TT genotype, while NeC with rs10975519(TC + CC) genotype was 1.32 times more likely to develop LC when compared with the TT genotype. CHB cases with rs4742170(CC + TC) genotype had 1.30 times higher susceptibility to develop LC compared with the TT genotype. The IL33-rs1048274G allele occurred more frequently in the LC group compared with the HCC group in codominant model (AG/AA: P = 0.001, OR = 1.66, 95%CI = 1.22–2.25; GG/AA: P = 0.018, OR = 1.54, 95%CI = 1.08–2.20). The IL33 haplotype CG conformed by rs10975519C and rs1048274G was more frequent in the LC group than in the NeC group and CHB group. Moreover, the IL33 haplotype CCG conformed by rs4742170C, rs10975519C and rs1048274G was found to be more frequent in the LC group than the HCC group. However, there was no association between IL1RL1-rs1041973 and LC risk.ConclusionOur findings demonstrate the association between genetic variants in IL33 with susceptibility to liver cirrhosis. IL33-rs4742170C, rs1048274G and rs10975519C could serve as biomarkers of LC.     

Circular RNA hsa_circ_0098181 inhibits metastasis in hepatocellular carcinoma by activating the Hippo signaling pathway via interaction with eEF2

Introduction and ObjectivesThe development of hepatocellular carcinoma (HCC) is a multi-step process that accumulates genetic and epigenetic alterations, including changes in circular RNA (circRNA). This study aimed to understand the alterations in circRNA expression in HCC development and metastasis and to explore the biological functions of circRNA.Materials and MethodsTen pairs of adjacent chronic hepatitis tissues and HCC tissues from patients without venous metastases, and ten HCC tissues from patients with venous metastases were analyzed using human circRNA microarrays. Differentially expressed circRNAs were then validated by quantitative real-time PCR. In vitro and in vivo assays were performed to assess the roles of the circRNA in HCC progression. RNA pull-down assay, mass spectrometry analysis, and RNA-binding protein immunoprecipitation were conducted to explore the protein partners of the circRNA.ResultsCircRNA microarrays revealed that the expression patterns of circRNAs across the three groups were significantly different. Among these, hsa_circ_0098181 was validated to be lowly expressed and associated with poor prognosis in HCC patients. Ectopic expression of hsa_circ_0098181 delayed HCC metastasis in vitro and in vivo. Mechanistically, hsa_circ_0098181 sequestered eukaryotic translation elongation factor 2 (eEF2) and dissociated eEF2 from filamentous actin (F-actin) to prevent F-actin formation, which blocked activation of the Hippo signaling pathway. In addition, the RNA binding protein Quaking-5 bound directly to hsa_circ_0098181 and induced its biogenesis.ConclusionsOur study reveals changes in circRNA expression from chronic hepatitis, primary HCC, to metastatic HCC. Further, the QKI5-hsa_circ_0098181-eEF2-Hippo signaling pathway exerts a regulatory role in HCC.     

Burden of Cirrhosis and Other Chronic Liver Diseases Caused by Specific Etiologies in China, 1990-2016:Findings from the Global Burden of Disease Study 2016

Objective To estimate the burden of cirrhosis and other chronic liver diseases caused by specific etiologies in China.Methods Data from the Global Burden of Disease Study 2016(GBD 2016) were used. We evaluated the burden by analyzing age-sex-province-specific prevalence, mortality, and disability-adjusted lifeyears(DALYs) of 33 provinces in China.Results From 1990 to 2016, prevalence cases in thousands increased by 73.7% from 6833.3(95% UI:6498.0–7180.6) to 11869.6(95% UI: 11274.6–12504.7). Age-standardized mortality and DALY rates per100,000 decreased by 51.2% and 53.3%, respectively. Male and elderly people(aged ≥ 60 years)preponderance were found for prevalence, mortality, and DALYs. The number of prevalence cases,deaths, and DALYs due to hepatitis C virus(HCV) increased by 86.6%, 8.7%, and 0.9%, respectively. Also,age-standardized prevalence rates decreased in 31 provinces, but increased in Yunnan and Shandong.The Socio-demographic Index(SDI) values were negatively correlated with age-standardized mortality and DALY rates by provinces in 2016; the correlation coefficients were-0.817 and-0.828, respectively.Conclusion Cirrhosis and other chronic liver diseases remain a huge health burden in China, with the increase of population and the aging of population. Hepatitis B virus(HBV) remains the leading cause of the health burden in China.     

Association between Baseline SBP/DBP and All-Cause Mortality in Residents of Shanxi,China: A Population-based Cohort Study from 2002 to 2015

Objective To investigate the association between blood pressure and all-cause mortality in Shanxi,China.Methods The‘2002 China Nutrition and Health Survey’baseline data in Shanxi province was used.A retrospective investigation was performed in 2015.The effects of SBP and DBP on the all-cause mortality were analyzed using the Cox regression model.The hazard ratio(HR)and 95%confidence interval(CI)were estimated by the sex and age groups.Results The follow-up rate was 76.52%over 13 years,while the cumulative mortality rate for all participants was 917.12/100,000 person-years.The mortality rose with an increasing SBP(χ_trend²=270.537,P<0.001)or DBP level(χ_trend²=57.240,P<0.001).After adjustment for the confounding factors,a significant association between mortality and high SBP(≥160 mm Hg)and high DBP(≥100 mm Hg),with adjusted HR ranging from 1.405-to 2.179-fold for SBP and 1.550-to 2.854-fold for DBP,was noted.Significant HRs for most DBP subgroups were found in>60-year-old participants.Males with DBP≥100 mm Hg had a significantly higher mortality,with an HR(95%CI)of 2.715(1.377–5.351).Conclusion Adults with SBP>160 mm Hg and DBP>100 mm Hg had a higher mortality risk.Sex and age difference was noted in both DBP and mortality risk.     

Disease susceptibility,transplantation and the MHC

Since his early days in the laboratory of Peter Gorer in the 1950s. Professor Richard Batchelor's distinguished research career has encompassed transplantation, tolerance, the MHC and disease susceptibility. A recent symposium     

中外循证医学课程教学模式的现状与启示：系统综述

目的 本研究运用定性系统综述的方法对国内外循证医学课程不同教学模式进行评价,为提高我国循证医学教学水平提供依据。方法 系统检索PubMed、Embase、Proquest、Cochrane和Web of Science英文数据库和SinoMed、CNKI、万方和维普中文数据库,筛选循证医学不同教学模式的研究,总结其研究现状。结果 共纳入论文52篇（中文21篇,英文31篇）,共涉及PBL等13种教学模式,其中PBL教学模式是研究最多的教学模式,而且循证医学教学效果与不同教学模式密切相关。结论 目前中外循证医学课程教学模式比较丰富,PBL是最常采用的教学方式,相关原始研究质量较高。     

Treated with interferon and the gene polymorphism of CGRP and its receptor

ObjectiveThis case-control study aims to investigate the relationship of polymorphisms of four gene loci (CGRP rs155209 and rs3781719, RAMP1 rs3754701 and rs7590387) with the prognosis of interferon therapy for chronic hepatitis B (CHB).Materials and methodsA total of 317 CHB patients receiving interferon alone for the first time were recruited in northern China, and peripheral blood samples were obtained. The single-nucleotide polymorphisms (SNPs) in rs155209, rs3781719, rs3754701, and rs7590387 were genotyped using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Univariate and multivariate logistic regression methods were employed to assess the correlation between CHB prognosis treated with interferon and polymorphisms of these gene loci.ResultsThe study clearly demonstrated the relevance of polymorphisms of rs155209, rs3781719, rs3754701, and rs7590387 with DNA response and ALT response after interferon treatment. CHB patients with CGRP rs155209C had a lower risk of developing DNA response (CT vs. TT: OR = 0.159, 95% CI = 0.086–0.294, P_adj < 0.001; CC vs. TT: OR = 0.131, 95% CI = 0.059–0.288, P_adj < 0.001), as well as a lower risk of developing ALT response (CT vs. TT: OR = 0.530, 95% CI = 0.323–0.869, P_adj < 0.05). Moreover, CHB patients with RAMP1 rs3754701T allele were more prone to develop DNA response (AT vs. AA: OR = 2.061, 95% CI = 1.237–3.435, P_adj < 0.05; TT vs. AA: OR = 5.676, 95% CI =1.247–25.837, P_adj < 0.05), and they also more likely to develop ALT response (AT vs. AA: OR = 1.766, 95% CI = 1.098–2.840, P_adj < 0.05). We did not find a significant association between CGRP rs3781719 or RAMP1 rs7590387 and DNA response or ALT response.ConclusionThis study revealed that CGRP rs155209 and RAMP1 rs3754701 polymorphisms, but not CGRP rs3781719 and RAMP1 rs7590387, were correlated with interferon therapy prognosis for CHB in Han Chinese population, and RAMP1 rs3754701T was a protective factor for ALT response and DNA response, but CGRP rs155209C carriers were less prone to DNA and ALT responses.