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.     

Preclinical evaluation of a plant-derived SARS-CoV-2 subunit vaccine: Protective efficacy,immunogenicity, safety,and toxicity

Coronavirus disease 2019 (COVID-19) is an acute respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The prevention of SARS-CoV-2 transmission has become a global priority. Previously, we showed that a protein subunit vaccine that was developed based on the fusion of the SARS-CoV-2 receptor-binding domain (RBD) to the Fc portion of human IgG1 (RBD-Fc), produced in Nicotiana benthamiana, and adjuvanted with alum, namely, Baiya SARS-CoV-2 Vax 1, induced potent immunological responses in both mice and cynomolgus monkeys. Hence, this study evaluated the protective efficacy, safety, and toxicity of Baiya SARS-CoV-2 Vax 1 in K18-hACE2 mice, monkeys and Wistar rats. Two doses of vaccine were administered three weeks apart on Days 0 and 21. The administration of the vaccine to K18-hACE2 mice reduced viral loads in the lungs and brains of the vaccinated animals and protected the mice against challenge with SARS-CoV-2. In monkeys, the results of safety pharmacology tests, general clinical observations, and a core battery of studies of three vital systems, namely, the central nervous, cardiovascular, and respiratory systems, did not reveal any safety concerns. The toxicology study of the vaccine in rats showed no vaccine-related pathological changes, and all the animals remained healthy under the conditions of this study. Furthermore, the vaccine did not cause any abnormal toxicity in rats and was clinically tolerated even at the highest tested concentration. In addition, general health status, body temperature, local toxicity at the administration site, hematology, and blood chemistry parameters were also monitored. Overall, this work presents the results of the first systematic study of the safety profile of a plant-derived vaccine, Baiya SARS-CoV-2 Vax 1; this approach can be considered a viable strategy for the development of vaccines against COVID-19.     

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.

     

基于糖脂代谢研究筋疽（糖尿病足非缺血性坏疽）湿热毒盛证

[目的]通过现代检验技术研究筋疽(糖尿病足非缺血性坏疽)湿热毒盛证的糖脂代谢指标。[方法]收集136例筋疽(糖尿病足非缺血性坏疽)患者进行不同证型间指标的比较。[结果]湿热毒盛证患者空腹血糖(FBG)、糖化血红蛋白(HbA1c)、餐后2 h血糖(2 hPBG)、晚期糖基化终末产物(AGEs)、白蛋白(ALB)、总胆固醇(TC)、高密度脂蛋白(HDL-C)与其他证型比较存在统计学差异(P<0.05)。湿热毒盛证患者C-反应蛋白(CRP)、人可溶性血管细胞黏附分子1(sVCAM-1)与其他证型组间比较存在统计学差异(P<0.01)。[结论]筋疽(糖尿病足非缺血性坏疽)湿热毒盛证形成的原因与低营养状态下糖脂代谢紊乱引起的高血糖及持续炎症反应相关。     

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.

翁连解毒汤治疗浊毒内蕴型溃疡性结肠炎的疗效观察

目的：探究翁连解毒汤治疗浊毒内蕴型溃疡性结肠炎（Ulcerative Colitis，UC）临床疗效及可能的作用机制。方法：选取2016年2月至2018年12月在攀枝花学院附属医院收治的浊毒内蕴型UC患者130例作为研究对象，按照入院先后顺序分为对照组和观察组，每组65例。对照组常规西医治疗，观察组加用翁连解毒汤，观察2组治疗前、完成治疗后T细胞、NK细胞、炎性反应因子、凝血功能、生命质量变化，完成治疗后总结疗效。结果：观察组患者在NK细胞、T淋巴细胞组成、CR、TNF-α、IL-1 β、ESR、内毒素、IL-10、FIB、PLT、APTT改善方面的效果较对照组更优，组间差异有统计学意义（P<0.05）。观察组患者完成治疗后的生命质量量表各维度评分及总评分改善效果优于对照组患者（P<0.05），且临床总有效率和组织病理学疗效率均高于对照组患者（P<0.05）。结论：翁连解毒汤能抑制浊毒内蕴型UC炎性反应，改善高凝状态，提高机体免疫功能，从而提高疗效和生命质量。     

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。