Highly heterogeneous residual malaria risk in western Thailand

Over the past decades, the malaria burden in Thailand has substantially declined. Most infections now originate from the national border regions. In these areas, the prevalence of asymptomatic infections is still substantial and poses a challenge for the national malaria elimination program. To determine epidemiological parameters as well as risk factors for malaria infection in western Thailand, we carried out a cohort study in Kanchanaburi and Ratchaburi provinces on the Thailand-Myanmar border. Blood samples from 999 local participants were examined for malaria infection every 4 weeks between May 2013 and Jun 2014. Prevalence of Plasmodium falciparum and Plasmodium vivax was determined by quantitative PCR (qPCR) and showed a seasonal variation with values fluctuating from 1.7% to 4.2% for P. vivax and 0% to 1.3% for P. falciparum. Ninety percent of infections were asymptomatic. The annual molecular force of blood-stage infection (_molFOB) was estimated by microsatellite genotyping to be 0.24 new infections per person-year for P. vivax and 0.02 new infections per person-year for P. falciparum. The distribution of infections was heterogenous, that is, the vast majority of infections (>80%) were found in a small number of individuals (<8% of the study population) who tested positive at multiple timepoints. Significant risk factors were detected for P. vivax infections, including previous clinical malaria, occupation in agriculture and travel to Myanmar. In contrast, indoor residual spraying was associated with a protection from infection. These findings provide a recent landscape of malaria epidemiology and emphasize the importance of novel strategies to target asymptomatic and imported infections.     

奥利司他联合维生素E对肥胖多囊卵巢综合征不孕患者的代谢指标及免疫功能的影响

摘要 目的：探讨奥利司他联合维生素E对肥胖多囊卵巢综合征不孕患者的代谢指标及免疫功能的影响 。方法：选取2018年9月至2020年12月于我院进行多囊卵巢综合征治疗的61例患者,将其随机分为观察组和对照组,观察组31例,对照组30例。对照组采用常规治疗,观察组采用奥利司他联合维生素E治疗。比较两组患者空腹胰岛素（FINS)、空腹血糖（FPG)、三酰甘油（TG),免疫球蛋白（IgA、IgM、IgG)水平,排卵率、妊娠率、卵泡未破裂黄素化综合征（LUFS) 率。结果：两组患者经治疗3个月后,FINS、FPG、TG代谢指标均有所变化,且变化规律一致,组间比较差异无统计学意义（P＞0.05 );治疗前,两组IgA、IgM、IgG水平对比,差异无统计学意义（P＞0.05);治疗3个月后,两组IgA、IgM、IgG水平均明显高于治疗前（P＜0.05) ,且观察组明显高于对照组（P＜0.05) ;观察组排卵率、妊娠率均明显高于对照组（P＜0.05) ,LUFS率明显低于对照组（P＜0.05)。结论：应用奥利司他联合维生素E治疗肥胖多囊卵巢综合征不孕患者,可有效改善患者代谢水平,提高免疫功能,提高患者的排卵率、妊娠率,降低LUFS率,可应用于临床。     

无充气腋窝入路腔镜下单侧甲状腺癌根治术与开放性手术的疗效比较及对免疫功能和颈部功能的影响

摘要 目的：比较无充气腋窝入路腔镜下单侧甲状腺癌根治术与开放性手术的疗效及对免疫功能和颈部功能的影响。方法：回顾性分析我院2020年8月～2021年8月期间收治的行单侧甲状腺癌根治术患者80例的临床资料。根据手术方式的不同将患者分为开放组（开放性手术）和腔镜组（无充气腋窝入路腔镜下单侧甲状腺癌根治术）,例数分别为37例和43例。对比两组疗效、免疫功能、颈部功能、美容学满意度和并发症情况。结果：与开放组相比,腔镜组术中出血量更少,手术时间、住院时间更长,引流液总量更多（P<0.05）,两组中央组淋巴结清扫数组间对比无统计学差异（P>0.05）。两组CD3⁺、CD4⁺、CD4⁺/CD8⁺下降,但腔镜组高于开放组;CD8+升高,但腔镜组低于开放组（P<0.05）。两组术后3d视觉疼痛模拟评分法（VAS）评分、颈部损伤指数对比,差异无统计学意义（P>0.05）。腔镜组吞咽障碍指数低于开放组（P<0.05）。腔镜组的总满意率高于开放组（P<0.05）。两组并发症发生率组间对比无统计学差异（P>0.05）。结论：与开放性手术治疗单侧甲状腺癌相比,无充气腋窝入路腔镜下单侧甲状腺癌根治术的手术时间和住院时间虽然延长,但其对患者免疫功能影响更轻,同时还可减轻患者吞咽障碍,获得更好的美容学满意度。     

Single-cell transcriptomics reveals cell type diversity of human prostate

Extensive studies have been performed to describe the phenotypic changes occurring during malignant transformation of the prostate. However, the cell types and associated changes that contribute to the development of prostate diseases and cancer remain elusive, largely due to the heterogeneous composition of prostatic tissues. Here, we conduct a comprehensive evaluation of four human prostate tissues by single-cell RNA sequencing (scRNA-seq) to analyze their cellular compositions. We identify 18 clusters of cell types, each with distinct gene expression profiles and unique features; of these, one cluster of epithelial cells (Ep) is found to be associated with immune function. In addition, we characterize a special cluster of fibroblasts and aberrant signaling changes associated with prostate cancer (PCa). Moreover, we provide insights into the epithelial changes that occur during the cellular senescence and aging. These results expand our understanding of the unique functional associations between the diverse prostatic cell types and the contributions of specific cell clusters to the malignant transformation of prostate tissues and PCa development.     

Transfected Poly(I:C) Activates Different dsRNA Receptors,Leading to Apoptosis or Immunoadjuvant Response in Androgen-independent Prostate Cancer Cells

Despite the effectiveness of surgery or radiation therapy for the treatment of early-stage prostate cancer (PCa), there is currently no effective strategy for late-stage disease. New therapeutic targets are emerging; in particular, dsRNA receptors Toll-like receptor 3 (TLR3) and cytosolic helicases expressed by cancer cells, once activated, exert a pro-apoptotic effect in different tumors. We previously demonstrated that the synthetic analog of dsRNA poly(I:C) induces apoptosis in the androgen-dependent PCa cell line LNCaP in a TLR3-dependent fashion, whereas only a weak apoptotic effect is observed in the more aggressive and androgen-independent PCa cells PC3 and DU145. In this paper, we characterize the receptors and the signaling pathways involved in the remarkable apoptosis induced by poly(I:C) transfected by Lipofectamine (in-poly(I:C)) compared with the 12-fold higher free poly(I:C) concentration in PC3 and DU145 cells. By using genetic inhibition of different poly(I:C) receptors, we demonstrate the crucial role of TLR3 and Src in in-poly(I:C)-induced apoptosis. Therefore, we show that the increased in-poly(I:C) apoptotic efficacy is due to a higher binding of endosomal TLR3. On the other hand, we show that in-poly(I:C) binding to cytosolic receptors MDA5 and RIG-I triggers IRF3-mediated signaling, leading uniquely to the up-regulation of IFN-β, which likely in turn induces increased TLR3, MDA5, and RIG-I proteins. In summary, in-poly(I:C) activates two distinct antitumor pathways in PC3 and DU145 cells: one mediated by the TLR3/Src/STAT1 axis, leading to apoptosis, and the other one mediated by MDA5/RIG-I/IRF3, leading to immunoadjuvant IFN-β expression.     

Effects of Supplemental Fructooligosaccharides Plus Mannanoligosaccharides on Immune Function and Ileal and Fecal Microbial Populations in Adult Dogs

The goal of this study was to examine whether supplemental fructooligosaccharides (FOS) plus mannanoligosaccharides (MOS) influenced immune function and ileal and fecal microbial populations of adult dogs. Eight adult dogs surgically fitted with ileal cannulas were used in a crossover design. Dogs were fed 200g of a dry, extruded, kibble diet twice daily. At each feeding, dogs were dosed with either 1g sucrose (placebo) or 2g FOS plus 1g MOS orally via gelatin capsule. Fecal, ileal, and blood samples were collected at the end of each 14-d period to measure microbial populations and immune characteristics. Treatment least squares means were compared using the GLM procedure of SAS. Supplementation of FOS plus MOS increased fecal bifidobacteria and fecal and ileal lactobacilli concentrations. Dogs fed FOS plus MOS also tended to have lower blood neutrophils and greater blood lymphocytes vs placebo. Serum, fecal, and ileal immunoglobulin concentrations were unchanged by treatment. Supplementation of FOS plus MOS beneficially altered indices of gut health by improving ileal and fecal microbial ecology. Supplementation of FOS plus MOS also altered immune function by causing a shift in blood immune cells.     

Emerging roles for scavenger receptor SREC-I in immunity

SREC-I is a class F scavenger receptor with key role in the immune response, particularly in antigen presenting cell (APC) such as macrophages and dendritic cells (DC). This receptor is able to mediate engulfment of dead cells as well as endocytosis of heat shock protein (HSP)–antigen complexes. SREC-I could thus potentially mediate the tolerizing influence of apoptotic cells or the immunostimulatory effects of HSP–peptide complexes, depending on context. This receptor was able to mediate presentation of external antigens, bound to HSPs through both the class II pathway as well as cross presentation via MHC class I complexes. In addition to its recently established role in adaptive immunity, emerging studies are indicating a broad role in innate immunity and regulation of cell signaling through Toll Like Receptors (TLR). SREC-I may thus play a key role in APC function by coordinating immune responses to internal and external antigens in APC.     

microRNA参与脓毒症免疫调控机制研究进展

脓毒症是重症监护病房(ICU)患者死亡的重要原因之一,因其高患病率、高死亡率、高治疗费用的特点,以及缺乏有效的救治策略,使它成为人类健康的巨大威胁。免疫炎症反应失衡与脓毒症的发生发展密切相关,但其关键调控机制尚不清楚。微小RNA(micro RNA,mi RNA)在固有免疫反应和适应性免疫反应中起着重要作用。mi RNA通过调控炎症信号通路中关键分子的表达,从而影响脓毒症相关炎症因子的表达。因此,mi RNA可能成为在基因转录后水平诊断和治疗脓毒症的新靶点。