In vivo corneal confocal microscopic analysis in patients with keratoconus

AIM: To quantify corneal ultrastructure using laser scanning in vivo confocal microscopy(IVCM) in patients with keratoconus and control subjects. METHODS: Unscarred corneas of 78 keratoconic subjects without a history of contact lens use and 36age-matched control subjects were evaluated with slit-lamp examination(SLE), corneal topography and laser scanning IVCM. One eye was randomly chosen for analysis. Anterior and posterior stromal keratocyte,endothelial cell and basal epithelial cell densities and sub-basal nerve structure were evaluated.RESULTS: IVCM qualitatively demonstrated enlarged basal epithelial cells, structural changes in sub-basal and stromal nerve fibers, abnormal stromal keratocytes and keratocyte nuclei, and pleomorphism and enlargement of endothelial cells. Compared with control subjects, significant reductions in basal epithelial cell density( 5817 ± 306 cells / mm2 vs 4802 ±508 cells/mm2,P 【 0. 001), anterior stromal keratocyte density(800 ±111 cells/mm2 vs 555 ±115 cells/mm2, P 【0.001),posterior stromal keratocyte density(333±34 cells/mm2vs270 ±47 cells/mm2, P 【0.001), endothelial cell density(2875 ±223 cells/mm2 vs 2686 ±265 cells/mm2, P 【0.001),sub-basal nerve fiber density(31.2 ±8.4 nerves/mm2vs18.1 ±9.2 nerves/mm2, P 【0.001), sub-basal nerve fiber length(21.4±3.4 mm/mm2 vs 16.1±5.1 mm/mm2, P 【0.001),and sub-basal nerve branch density(median 50.0(first quartile 31.2- third quartile 68.7) nerve branches/mm2 vs median 25.0(first quartile 6.2- third quartile 45.3) nerve branches/mm2, P 【0.001) were observed in patients with keratoconus.CONCLUSION: Significant microstructural abnormalities were identified in all corneal layers in the eyes of subjects with keratoconus using IVCM. This non-invasive in vivo technique provides an important means to define and follow progress of microstructural changes in patients with keratoconus.

【特刊综述】雄激素对骨骼肌的作用：对乏力的发展和治疗的意义

雄激素对骨骼肌合成有明显影响，随着年龄增大，雄激素的下降常伴随肌量和肌力的下降。这种肌量和肌功能的下降，被称为少肌症或肌体老化，是老年人体质弱化（男性化减退）进展的关键事项。也是导致快速机能衰退及其不良后果的关键。雄激素水平下降对老年男性体质弱化（男性化减退）的潜在影响和对躯体功能的促进治疗作用无疑已经引起了相当的关注。本综述概述了近期关于肌肉老化、少肌症、老年体质弱化的概念、定义，并评估了关于雄激素和老年体质弱化的研究进展。近期源于观测性和介入性研究的证据强烈支持雄激素对老年男性肌量的作用，但雄激素对肌力和特有的躯体功能的效用并不明确。研究显示，雄激素治疗在老年男性中通常有良好的耐受性，而近期的研究则关注于雄激素的高剂量治疗和对于心血管风险较高人群的治疗。雄激素受体调节剂（SARMs）的初期试验研究显示传统雄激素治疗对于老年患者在肌量和肌功能方面有相同的效用。将来的重要研究方向包括利用这类雄激素治疗并结合适用于不同老年患者群体促进躯体功能的运动训练，同时将更多地关注近期关于激素水平、身体成分及躯体功能间关系的观测性（回顾性）研究。

Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity

Though the pathophysiology of clinical obesity is un-doubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1(GLP-1) signalling. Clinical studies assessing GLP-1 responses in normal weight and obese subjects suggest that weight gain may induce functional deficits in GLP-1 signalling that facilitates maintenance of the obesity phenotype. In addition, genetic studies implicate a possible role for altered GLP-1 signalling as a risk factor towards the development of obesity. As reductions in functional GLP-1 signalling seem to play a role in clinical obesity, the pharmacological replenishment seems a promising target for the medical management of obesity in clinical practice. GLP-1 analogue liraglutide at a high dose(3 mg/d) has shown promising results in achieving and maintaining greater weight loss in obese individuals compared to placebo control, and currently licensed antiobesity medications. Generally well tolerated, provided that longer-term data in clinical practice supports the currently available evidence of superior short- and longterm weight loss efficacy, GLP-1 analogues provide promise towards achieving the successful, sustainable medical management of obesity that remains as yet, an unmet clinical need.

【特刊综述】男性雄激素缺乏：一种多系统综合征

雄性激素对于多器官系统有重要影响，而这些器官系统对男性一生的健康比如调节性功能、身体功能和行为学功能起着决定性作用。雄激素缺乏是一种多系统综合征，表现出与明显的血清睾酮低水平相关的典型临床特征。雄激素缺乏的临床表现因年龄和其它诸如并存病、遗传因素、环境因素及社会文化因素等患者个体特性而不同。

Highlights of the 2nd International Symposium on Tribbles and Diseases: tribbles tremble in therapeutics for immunity, metabolism, fundamental cell biology and cancer

The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.

Vitamin D status and its influence on outcomes following major burn injury and critical illness

Vitamin D deficiency is common among the general population. It is also observed in up to 76% of critically ill patients.Despite the high prevalence of hypovitaminosis D in critical illness, vitamin D is often overlooked by medical staff as the clinical implications and consequences of vitamin D deficiency in acute contexts remain to be fully understood.Vitamin D has a broad range of pleotropic effects on various processes and systems including the immuneinflammatory response. 1α,25-dihydroxyvitamin D (1,25(OH)2D), has been shown to promote a tolerogenic immune response limiting deleterious inflammatory effects, modulation of the innate immune system, and enhancement of anti-microbial peptides. Vitamin D deficiency is frequently observed in critically ill patients and has been related to extrinsic causes (i.e., limited sunlight exposure), magnitude of injury/illness, or the treatment started by medical doctors including fluid resuscitation. Low levels of vitamin D in critically ill patients have been associated with sepsis, organ failure, and mortality. Despite this, there are subpopulations of critical illness, such as burn patients, where the literature regarding vitamin D status and its influence on outcomes remain insufficient. Thermal injury results in damage to both burned and non-burned tissues, as well as induces an exaggerated and persistent immune-inflammatory and hypermetabolic response. In this review, we propose potential mechanisms in which burn injury affects the vitamin D status and summarizes current literature investigating the influence of vitamin D status on outcomes. In addition, wereviewed the literature and trials investigating vitamin D supplementation in critically ill patients and discuss the therapeutic potential of vitamin D supplementation in burn and critically ill patients. We also highlight current limitations of studies that have investigated vitamin D status and supplementation in critical illness. Thermal injury influences vitamin D status. More studies investigating vitamin D depletion in burn patients and its influence on prognosis, via standardized methodology, are required to reach definitive conclusions and influence clinical practice.

Structure of SARS-CoV-2 main protease in the apo state

Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has been a global pandemic that severely threatens global health with concordant economic damage.However,there is currently no clinically approved vaccines or drugs against COVID-19(Lu et al.,2020).