Transmission Dynamics and Effectiveness of Control Measures during COVID-19 Surge,Taiwan, April–August 2021

An unprecedented surge of COVID-19 cases in Taiwan in May 2021 led the government to implement strict nationwide control measures beginning May 15. During the surge, the government was able to bring the epidemic under control without a complete lockdown despite the cumulative case count reaching >14,400 and >780 deaths. We investigated the effectiveness of the public health and social measures instituted by the Taiwan government by quantifying the change in the effective reproduction number, which is a summary measure of the ability of the pathogen to spread through the population. The control measures that were instituted reduced the effective reproduction number from 2.0–3.3 to 0.6–0.7. This decrease was correlated with changes in mobility patterns in Taiwan, demonstrating that public compliance, active case finding, and contact tracing were effective measures in preventing further spread of the disease.     

Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE) have accelerated atherosclerosis. The underlying mechanisms are poorly understood, and investigations have been hampered by the absence of animal models that reflect the human condition of generalized atherosclerosis and lupus. We addressed this problem by transferring lupus susceptibility to low-density lipoprotein (LDL) receptor-deficient (LDLr-/-) mice, an established model of atherosclerosis, creating radiation chimeras with NZM2410-derived, lupus-susceptible, B6.Sle1.2.3 congenic or C57BL/6 control donors (LDLr.Sle and LDLr.B6, respectively). LDLr.Sle mice developed a lupus-like disease characterized by production of double-stranded DNA autoantibodies and renal disease. When fed a Western-type diet, LDLr.Sle chimeras had increased mortality and atherosclerotic lesions. The plaques of LDLr.Sle mice were highly inflammatory and contained more CD3+ T cells than controls. LDLr.Sle mice also had increased activation of CD4+ T and B cells and significantly higher antibody to oxidized LDL and cardiolipin. Collectively, these studies demonstrate that the lupus-susceptible immune system enhances atherogenesis and modulates plaque composition.     

Retention of low-density lipoprotein in atherosclerotic lesions of the mouse: evidence for a role of lipoprotein lipase

Direct binding of apolipoprotein (apo)B-containing lipoproteins to proteoglycans is the initiating event in atherosclerosis, but the processes involved at later stages of development are unclear. Here, we investigated the importance of the apoB-proteoglycan interaction in the development of atherosclerosis over time and investigated the role of lipoprotein lipase (LPL) to facilitate low-density lipoprotein (LDL) retention at later stages of development. Atherosclerosis was analyzed in apoB transgenic mice expressing LDL with normal (control LDL) or reduced proteoglycan-binding (RK3359-3369SA LDL) activity after an atherogenic diet for 0 to 40 weeks. The initiation of atherosclerosis was delayed in mice expressing RK3359-3369SA LDL, but they eventually developed the same level of atherosclerosis as mice expressing control LDL. Retention studies in vivo showed that although higher levels of 131I-tyramine cellobiose-labeled control LDL (131I-TC-LDL) were retained in nonatherosclerotic aortae compared with RK3359-3369SA 131I-TC-LDL, the retention was significantly higher and there was no difference between the groups in atherosclerotic aortae. Lower levels of control 125I-TC-LDL and RK3359-3369SA 125I-TC-LDL were retained in atherosclerotic aortae from ldlr-/- mice transplanted with lpl-/- compared with lpl+/+ bone marrow. Uptake of control LDL or RK3359-3369SA LDL into macrophages with specific expression of human catalytically active or inactive LPL was increased compared with control macrophages. Furthermore, transgenic mice expressing catalytically active or inactive LPL developed the same extent of atherosclerosis. Thus, retention of LDL in the artery wall is initiated by direct LDL-proteoglycan binding but shifts to indirect binding with bridging molecules such as LPL.     

Lymphocyte reconstitution following non-myeloablative hematopoietic stem cell transplantation follows two patterns depending on age and donor/recipient chimerism

The effect of mixed chimerism on the pace of post-transplant immune reconstitution is unknown. Using flow cytometry, recall and neo-antigen vaccine responses, and T cell receptor recombination excision circle (TREC) quantification, we evaluated phenotypic and functional characteristics of T and B cells in nine patients following non-myeloablative, HLA-identical peripheral blood stem cell transplantation for chronic granulomatous disease. Engraftment of T cell, B cell, and myeloid lineages proceeded at similar paces within each patient, but engraftment kinetics segregated patients into two groups: adults, who became full donor T cell chimeras before 6 months (rapid engrafters) and children, who became full donor T cell chimeras after 6 months or not at all (slow engrafters). Quantitative B cell recovery was achieved by 6 weeks after transplantation in children, but was delayed until 1 year in adults. Early quantitative B cell recovery was not accompanied by an early humoral immune response to tetanus toxoid (TT). Emergence of TT-specific T cell responses coincided with naive T cell reconstitution, as measured by CD4/CD45RA T cell recovery and TREC quantification. These data suggest that immune reconstitution occurs faster in pediatric patients who have prolonged mixed hematopoietic chimerism compared to adults, who have rapid donor stem cell engraftment.     

胃缺血再灌注损伤的模型与机制

近年来,随着临床医学的一些重要进展,缺血再灌注损伤的普遍意义已引起人们的高度重视。失血性休克、败血症、胃肠道某些血管性疾病、一些重要器官(如心、脑、肾)的损伤等常可引起急性胃粘模损伤,其损伤机制与胃的缺血再灌注密切相关,现仅就近几年来国内外对胃缺血再灌注损伤(GIRI)的研究进展作一综述。 1 动物模型的制备 1.1 夹闭支配胃的有关动脉在实验室中最常用的动物是大鼠,通常是夹闭腹腔动脉30min,松开后恢复血流1h即可见到明显的胃粘膜损伤,以后,随着再灌注时间的延长,损伤逐渐加重,再灌48h～72h损伤达高峰,此时,胃粘膜肌层破坏,形成溃     

The human bile salt export pump: characterization of substrate specificity and identification of inhibitors

BACKGROUND & AIMS: The bile salt export pump (BSEP) is the major bile salt transporter in the liver canalicular membrane. Our aim was to determine the affinity of the human BSEP for bile salts and identify inhibitors. METHODS: Human BSEP was expressed in insect cells. Adenosine triphosphatase (ATPase) assays were performed, and bile salt transport studies were undertaken. RESULTS: The BSEP gene, ABCB11, was cloned and a recombinant baculovirus was generated. Infected insect cells expressed a 140-kilodalton protein that was absent in uninfected and in mock-infected cells. An ATPase assay showed BSEP to have a high basal ATPase activity. Transport assays were used to determine the Michaelis constant for taurocholate as 4.25 micromol/L, with a maximum velocity of 200 pmol x min(-1) x mg(-1) protein. Inhibition constant values for other bile salts were 11 micromol/L for glycocholate, 7 micromol/L for glycochenodeoxycholate, and 28 micromol/L for taurochenodeoxycholate. Cyclosporin A, rifampicin, and glibenclamide were proved to be competitive inhibitors of BSEP taurocholate transport, with inhibition constant values of 9.5 micromol/L, 31 micromol/L, and 27.5 micromol/L, respectively. Progesterone and tamoxifen did not inhibit BSEP. CONCLUSIONS: The human BSEP is a high-affinity bile salt transporter. The relative affinities for the major bile salts differ from those seen in rodents and reflect the different bile salt pools. BSEP is competitively inhibited by therapeutic drugs. This is a potentially significant mechanism for drug-induced cholestasis.     

Epidemiological study on obesity and its comorbidities in urban Chinese older than 20 years of age in Shanghai, China

The aim of this work was to establish the prevalence of overweight and obesity and its associated comorbidities in a Chinese population older than 20 years of age. A group of 2776 randomly selected adults (20–94 years of age) living in the Huayang Community in Shanghai, China, were investigated between 1998 and 2000. Body weight, height, waist and hip circumferences and blood pressure were measured, as were fasting blood glucose, fasting insulin and lipid profile, as well as blood glucose 2 h after a glucose load, and a 75‐g glucose tolerance test was performed. The prevalence of overweight was 29.5% and obesity was 4.3%, with a greater number of women being obese than men. More than one‐third of the population had abnormal lipid levels. Impaired glucose regulation (IGR) occurred in 10.8%; and 9.8% of the population were classified as having type 2 diabetes mellitus. Hypertension was present in 58.4% of this population. About 21% and 29.3% of the population suffered from high total cholesterol and high triglyceride, respectively. The prevalence of metabolic syndrome was 10.2%. The prevalence of diabetes, IGR and metabolic syndrome increased progressively in association with a body mass index (BMI) of >23 kg m^?2. Hence, although the prevalence of obesity is low in this Chinese population, higher BMI and waist circumference values are clearly associated with an increasing prevalence of comorbidities. The absolute risk of having diabetes, IGR and metabolic syndrome is high in adults with a BMI of ≥23 kg m^?2.