女性致密性骨炎血清骨转换生化标志物水平变化研究

背景 致密性骨炎（OCI）和其他疾病有时难以鉴别，探讨血清骨转换生化标志物可为OCI的鉴别诊断提供依据。 目的 探索女性OCI患者的血清骨转换生化标志物的水平变化及临床意义。 方法 回顾性选取2013年6月至2022年2月在北京积水潭医院门诊及住院诊断为OCI的61例女性患者作为观察组，年龄15~50岁，平均（33.8±6.6）岁，病程2周~15年。选择同期61例女性体检健康者作为对照组，年龄15~48岁，平均（35.6±7.6）岁。比较两组一般临床资料和血清骨转换生化标志物水平，并对血清骨转换生化标志物与病情相关指标进行相关性分析。 结果 观察组血清白蛋白（45.4±2.9）g/L低于对照组（46.5±2.8）g/L（t=2.190，P<0.05）。血清骨转换生化标志物比较结果显示，观察组血清1型胶原羧基末端肽β特殊序列（β-CTX）〔0.28（0.23，0.37）μg/L〕、N-端骨钙素（OC）〔13.1（11.2，16.2）μg/L〕、25-羟维生素D3〔25-（OH）VD3〕〔（14.1±5.1）μg/L〕低于对照组〔0.36（0.29，0.48）μg/L，15.6（13.7，17.3）μg/L，（17.5±6.6）μg/L〕（Z=-2.983、-3.255，t=3.081，P<0.05）。长病程亚组OC水平〔14.6（12.4，18.5）μg/L〕高于短病程亚组〔11.7（10.2，14.0）μg/L〕（Z=-2.407，P<0.05）。多孕亚组β-CTX〔0.25（0.22，0.32）μg/L〕、OC水平〔12.2（10.3，15.0）μg/L〕低于非多孕亚组〔0.33（0.26，0.44）μg/L、13.4（12.0，18.8）μg/L〕（Z=-2.486、-1.897，P<0.05）。相关性分析显示，观察组血清1型前胶原氨基端延长肽（tP1NP）与妊娠次数、生产次数均呈负相关（rs=-0.276、-0.298，P<0.05），OC与体质指数（BMI）、视觉模拟评分法（VAS）评分、妊娠次数均呈负相关（rs=-0.284、-0.374、-0.360，P<0.05），25-（OH）VD3水平与BMI呈正相关（rs=0.275，P<0.05）。 结论 女性OCI患者血清OC、β-CTX水平明显降低，可为鉴别其他疾病提供依据；血清OC水平可以反映OCI患者的严重程度，同时OC水平与患者妊娠次数相关；tP1NP与妊娠次数、生产次数相关。     

Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.     

Diagnostic pitfalls in needle core biopsy of the breast

Breast core biopsies are a standard component of the triple approach that includes clinical examination, imaging and tissue sampling. Conventional cores, diagnostic vacuum assisted biopsy and vacuum assisted excisions are established methods for sampling and managing breast lesions. It is important to be aware of the potential pitfalls in the technical handling and interpretation of the limited core biopsy samples. Here, we present a clinically oriented, well illustrated overview of the common diagnostic pitfalls based on the author's diagnostic and second opinion practice, emphasize the value of clinicopathological correlation and provide histological tips and clues with useful immunohistochemistry to aid the reporting pathologists in their daily interpretation of breast core biopsies.     

Marmoset cytochrome P450 2B6, a propofol hydroxylase expressed in liver

1. The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.

2. Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.

3. Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.

4. Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low K_m value was relatively comparable to that for marmoset livers.

5. These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.

     

Resistin is elevated in cystic fibrosis sputum and correlates negatively with lung function

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Interferon-induced Transmembrane Protein 3 Prevents Acute Influenza Pathogenesis in Mice

Objective Interferon-induced transmembrane protein 3(IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.Methods We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer(NK) cell numbers, their activation, and their immune function in the lungs of Ifitm3-/-and wild-type mice.Results Ifitm3-/-mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of Ifitm3-/-mice during acute influenza infection.Conclusions Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in Ifitm3-/-mice.     

乙肝孕妇血清标志物模式与HBV-DNA载量及肝功能关系研究

目的探讨乙肝孕妇血清标志物模式、HBV-DNA载量及肝功能三者之间的关系,为孕期乙肝病毒感染情况的监控和乙肝病毒母婴传播的预防提供参考。方法选取2019年1月-11月在我院产检的767例乙肝表面抗原阳性孕妇的乙肝血清标志物模式、肝功能指标的丙氨酸氨基转移酶(alamine aminotransferase,ALT)及HBVDNA载量进行研究,探讨三者间的关系。结果HBsAg、HBeAg、HBcAb阳性组孕妇HBV-DNA阳性率及病毒载量均高于其余两组(P<0.05);ALT升高程度与HBV-DNA载量具有一定相关性(r=0.255,χ^2=80.150,P=0.000);HBeAg阳性组和HBeAg阴性组间HBV-DNA阳性率、ALT异常率差异均有统计学意义。结论HBV-M、HBV-DNA与肝功能之间有一定的相关性,大三阳孕妇中高病毒载量比例高,应加强乙肝孕妇孕期各项指标的监测,必要时进行干预治疗。     

High dose trivalent influenza vaccine compared to standard dose vaccine in patients with rheumatoid arthritis receiving TNF-alpha inhibitor therapy and healthy controls: Results of the DMID 10-0076 randomized clinical trial

IntroductionSubjects with rheumatoid arthritis (RA) receiving tumor necrosis factor-inhibiting (TNFi) therapies are at risk for severe influenza, and may respond less well to influenza vaccine. We examined the safety and immunogenicity of high dose influenza vaccine (HD) compared to standard dose vaccine (SD) in participants with RA receiving stable TNFi.MethodsA randomized, double-blinded, Phase II study was conducted in adults with RA receiving TNFi, and healthy, gender and age-matched control subjects. Participants were immunized with HD (Sanofi Pasteur Fluzone High Dose [60 mcg × 3 strains]) or SD (Sanofi Pasteur Fluzone® [15 mcg × 3 strains]) intramuscularly (IM). A self-administered memory aid recorded temperature and systemic and local adverse events (AEs) for 8 days, and safety was evaluated and serum obtained to measure HAI activity on days 7, 21 and 180 days following vaccination.ResultsA greater proportion of RA subjects who received HD seroconverted at day 21 compared to SD, although this was not statistically significant. GMT antibody responses in RA subjects who received HD compared to SD were greater for all strains on day 21, and this was significant for H1N1. Seroconversion rates and GMT values were not different between RA subjects and control subjects. There were no safety concerns for HD or SD in RA subjects, and RA-related symptoms did not differ between SD and HD recipients by a RA-symptom questionnaire (RAPID 3).ConclusionsTNF-inhibitor therapy in people with RA did not appear to influence the immunogenicity of either SD or HD. Influenza seroconversion and GMT values were higher among RA subjects receiving HD compared to SD; however, differences were small and a larger study is needed to validate these findings. Given the apparent risk of increased influenza-related morbidity and mortality among immune compromised subjects, the higher GMT values generated by HD may be beneficial.