The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events

Objective To explore associations between lipoprotein-associated phospholipase A2(Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up.Methods A random sample of 2,031 participants(73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study(APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay(ELISA). The composite endpoint was a combination of first-eve...     

Angiotensin (1−7) peptide replacement therapy with plasma transfusion in COVID-19

AimTo determine whether convalescent angiotensin (1?7) peptide replacement therapy with plasma (peptide plasma) transfusion can be beneficial in the treatment of critically ill patients with severe coronavirus 2 (SARS-CoV-2) infection.Study designCase series of 9 critically ill patients with laboratory-confirmed COVID-19 who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment.Peptide plasma: Plasma with angiotensin (1?7) content 8–10 times higher than healthy plasma donors was obtained from suitable donors. Peptide plasma transfusion was applied to 9 patients whose clinical status and/or laboratory profile deteriorated and who needed intensive care for 2 days.ResultsIn our COVID-19 cases, favipiravir, low molecular weight heparin treatment, which is included in the treatment protocol of the ministry of health, was started. Nine patients with oxygen saturation of 93% and below despite nasal oxygen support, whose clinical and/or laboratory deteriorated, were identified. The youngest of the cases was 36 years old, and the oldest patient was 85 years old. 6 of the 9 cases had male gender. 3 cases had been smoking for more than 10 years. 4 cases had at least one chronic disease.In all of our cases, SARS CoV2 lung involvement was bilateral and peptide plasma therapy was administered in cases when oxygen saturation was 93% and below despite nasal oxygen support of 5 liters/minute and above, and intensive care was required. Although it was not reflected in the laboratory parameters in the early period, 8 patients whose saturations improved with treatment were discharged without the need for intensive care. However, a similar response was not obtained in one case. Oxygen requirement increased gradually and, he died in intensive care process. An increase of the platelet count was observed in all cases following the peptide plasma treatment.ConclusionIn this preliminary case series of 9 critically ill patients with COVID-19, administration of plasma containing angiotensin (1?7) was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.     

微创和传统开放后路腰椎椎间融合术治疗腰椎退行性疾病的远期预后

目的探讨微创后路腰椎椎间融合术(MIS-PLIF)和传统开放PLIF对腰椎退行性疾病(LDD)远期疗效及安全性的影响。方法 2011年1月-2014年12月收治LDD患者182例,其中96例采用传统开放PLIF治疗(PLIF组),86例采用MIS-PLIF治疗(MIS-PLIF组)。比较2组腰椎矢状位参数、多裂肌横截面积及萎缩率、融合率、疼痛视觉模拟量表(VAS)评分、日本骨科学会(JOA)评分、Oswestry功能障碍指数(ODI)及术后并发症发生情况,分析多裂肌萎缩率与顽固性腰背痛的相关性。结果 2组术后各随访时间点椎间隙高度恢复值和节段性前凸角恢复值差异均无统计学意义(P > 0.05)。2组术后1年腰椎前凸角恢复值差异无统计学意义(P > 0.05);但术后5年和末次随访时,MIS-PLIF组腰椎前凸角恢复值显著高于PLIF组,差异均有统计学意义(P < 0.05)。MIS-PLIF组术后各随访时间点多裂肌横截面积大于PLIF组,多裂肌萎缩率低于PLIF组,差异均有统计学意义(P < 0.05)。2组术后随访6个月融合率差异无统计学意义(P > 0.05)。2组术后各随访时间点下肢痛VAS评分差异无统计学意义(P > 0.05);MIS-PLIF组术后各随访时间点腰痛VAS评分、JOA评分及ODI均优于PLIF组,差异有统计学意义(P < 0.05)。MIS-PLIF组顽固性腰背痛发生率显著低于PLIF组,差异有统计学意义(P < 0.05)。合并顽固性腰背痛患者多裂肌萎缩率高于未合并顽固性腰背痛的患者,差异有统计学意义(P < 0.05)。结论术后多裂肌萎缩可能是导致顽固性腰背痛的重要原因,相较于传统开放PLIF,MIS-PLIF治疗LDD能够更有效地保持腰椎生理曲度,改善肢体活动功能,降低多裂肌萎缩程度,有助于避免顽固性腰背痛的发生。     

HBV基因型的研究现状与发展趋势探讨

[摘要]?目前研究已知HBV有多种基因型，不同基因型在不同的种族、地域方面分布特点不同且HBV基因型是造成慢性感染自然史差异的原因之一，它们在感染的临床表现和抗病毒治疗的反应中起着重要作用。检测HBV基因型和了解HBV不同基因型对疾病预后的影响，对评估患者疾病结局和指导临床规划最佳治疗方案具有重要意义。 　　[关键词]　乙型肝炎病毒；基因型；基因突变；治疗     

Young age,female sex,and presence of systemic adverse reactions are associated with high post-vaccination antibody titer after two doses of BNT162b2 mRNA SARS-CoV-2 vaccination: An observational study of 646 Japanese healthcare workers and university staff

BackgroundSARS-CoV-2 vaccination has started worldwide, including Japan. Although high rates of vaccine response and adverse reactions of BNT162b2 vaccine have been reported, knowledge about the relationship between sex differences and antibody response is limited. Furthermore, it is uncertain whether adverse reactions are associated with the vaccine response.MethodsThis prospective observational study included 673 Japanese participants working in a medical school and its affiliated hospital in Tokyo, Japan (UMIN000043340). Serum samples were collected before the first dose and three weeks after the second dose of BNT162b2 vaccine, and antibody titers against the receptor-binding domain of the spike protein of SARS-CoV-2 were measured. Answers to questionnaires about background characteristics and adverse reactions were obtained at the time of sample collection, and the relationship between antibody titers was analyzed.ResultsAfter excluding participants who did not complete receiving two doses of vaccination or two series of serum sample collection, 646 participants were analyzed. Although all participants became sero-positive after vaccination, antibody titers were highly variable among individuals (260.9–57,399.7A U/mL), with a median titer of 13478.0AU/mL. Mean titer was higher in females than in males and higher in young (≤45 years old) participants than in aged (>45 years old) participants. Participants who experienced adverse reactions demonstrated a higher antibody titer after vaccination than those without adverse reactions. Multivariable analysis demonstrated that young age, female sex, and adverse reactions after the second dose were independently related to higher antibody titers after the second dose.DiscussionA favorable antibody response was observed after two doses of BNT162b2 vaccination among mostly healthy Japanese participants, especially among female and young participants. Although further investigation is essential, our results imply that the systemic adverse reactions (i.e., fever and general fatigue) are associated with a higher antibody response that indicates the acquisition of humoral immunity.     

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.     

朝鲜淫羊藿酸性多糖的理化特性及对HepG2细胞脂质堆积的改善作用＊

目的 对比研究朝鲜淫羊藿酸性多糖酯化还原前后的理化特性，并探讨其改善油酸诱导的肝癌HepG2细胞脂质堆积活性的差异。方法 采用高效凝胶渗透色谱法测定朝鲜淫羊藿酸性多糖（EFPA）的均一性和分子量，高效液相色谱法测定EFPA和酯化还原后朝鲜淫羊藿酸性多糖（EFPA-R）的单糖组成；采用油酸（OA）处理HepG2细胞诱导建立脂质蓄积模型，不同浓度EFPA与EFPA-R（10、30、100、300 μg·mL^-1）分别和OA共同作用于细胞24 h，采用CCK-8试剂盒测定细胞存活率，油红O染色观察细胞内脂滴蓄积情况，并采用试剂盒测定细胞内总胆固醇（TC）、甘油三酯（TG）含量。结果 EFPA为成分均一的多糖组分，分子量为125.8 kDa，由甘露糖、葡萄糖、半乳糖、葡萄糖醛酸和阿拉伯糖组成，摩尔比为1.7∶7.4∶1.4∶1.8∶1.0，葡萄糖占比最大，EFPA-R由甘露糖、葡萄糖、半乳糖和阿拉伯糖组成，摩尔比为0.8∶10.6∶2.1∶1.0；在10-300 μg·mL^-1范围内，EFPA和EFPA-R对HepG2细胞的抑制作用较弱，作为给药浓度；与空白组相比，模型组细胞中TC、TG含量显著升高（P < 0.01），细胞内红色脂滴显著增多，与模型组相比，EFPA可显著降低细胞中TC、TG含量（P < 0.01），明显减少细胞内红色脂滴（P < 0.05或P < 0.01），EFPA-R干预后细胞则无明显变化。结论 EFPA可明显改善HepG2细胞脂质堆积情况，且呈现剂量依赖性，而半乳糖醛酸（GalA）的存在可能是其抑制HepG2细胞脂质蓄积的关键因素。     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

Left ventricular noncompaction associated with a pathogenic mutation in the MYH7 gene: Known mutation,different phenotype

Left ventricular noncompaction (LVNC) is a genetically heterogeneous cardiomyopathy, with familial and sporadic forms, but genetic testing only identifies a pathogenic mutation in a minority of cases. The main complications are heart failure, embolism and dysrhythmias. Herein we report a familial case of LVNC associated with a mutation in the MYH7 gene and review the literature regarding controversies in LVNC. A 50-year-old woman was referred to the cardiology clinic for palpitations. She underwent echocardiography and cardiac magnetic resonance imaging that revealed mild left ventricular systolic dysfunction and LVNC criteria. She had several episodes of non-sustained ventricular tachycardia and received an implantable cardioverter-defibrillator (ICD). Genetic testing revealed the c.1003G>C (p.Ala335Pro) mutation in the MYH7 gene. Familial screening showed clear genotype-phenotype cosegregation, which provided strong evidence for the pathogenic role of this mutation. To the best of our knowledge, this is the first report of LVNC associated with the p.Ala335Pro mutation in the MYH7 gene. This mutation has been described in hypertrophic cardiomyopathy, suggesting that the same pathogenic sarcomere mutation may be associated with different cardiomyopathies. This case also highlights the current difficulties regarding decisions on ICD implantation for primary prevention of sudden cardiac death in LVNC.     

BCL2 G quadruplex-binding small molecules: Current status and prospects for the development of next-generation anticancer therapeutics

B cell lymphoma 2 (BCL2) overexpression in a range of human tumors is often related to chemotherapy resistance and poor prognosis. GC-rich regions upstream of the P1 promoter in human BCL2 can form G-quadruplex (G4) structures through the stacking of four Hoogsteen-paired guanine bases. Stabilizing the G4 fold implies the inhibition of BCL2 expression and, thus, small molecules that selectively bind to the G4 are promising anticancer candidates. In this review, we discuss the structural aspects, binding affinity, selectivity, and biological activity of well-characterized BCL2 G4 binding ligands in vitro and in vivo. We also explore future directions in the research and development of G4-based anticancer therapeutics.