Background Graves’ disease (GD) is a typical organ-specific autoimmune disease. Intestinal flora plays a pivotal role in immune homeostasis and autoimmune disease development. However, the association and mechanism between intestinal flora and GD remain elusive. Objective To investigate the association and mechanism between intestinal flora and GD. Methods We recruited 58 initially untreated GD patients and 63 healthy individuals in the study. The composition and metabolic characteristics of the intestinal flora in GD patients and the causal relationship between intestinal flora and GD pathogenesis were assessed using 16S rRNA gene sequencing, targeted/untargeted metabolomics, and fecal microbiota transplantation. Results The composition, metabolism, and inter-relationships of the intestinal flora were also changed, particularly the significantly reduced short-chain fatty acid (SCFA)-producing bacteria and SCFAs. The YCH46 strain of Bacteroides fragilis could produce propionic acid and increase Treg cell numbers while decreasing Th17 cell numbers. Transplanting the intestinal flora of GD patients significantly increased GD incidence in the GD mouse model. Additionally, there were 3 intestinal bacteria genera (Bacteroides, Alistipes, Prevotella) could distinguish GD patients from healthy individuals with 85% accuracy. Conclusions Gut dysbiosis contributes to a Treg/Th17 imbalance through the pathway regulated by propionic acid and promotes the occurrence of GD, together with other pathogenic factors. Bacteroides, Alistipes, and Prevotella have great potential to serve as adjunct markers for GD diagnosis. This study provided valuable clues for improving immune dysfunction of GD patients using B. fragilis and illuminated the prospects of microecological therapy for GD as an adjunct treatment.

Background: Hippo-Yes-associated protein (YAP) signaling is a key regulator of organ size and tumorigenesis, yet the underlying molecular mechanism is still poorly understood. At present, the significance of the Hippo-YAP pathway in diffuse large B-cell lymphoma (DLBCL) is ill-defined. Methods: The expression of YAP in DLBCL was determined in public database and clinical specimens. The effects of YAP knockdown, CRISPR/Cas9-mediated YAP deletion, and YAP inhibitor treatment on cell proliferation and the cell cycle were evaluated both in vitro and in vivo. RNA sequencing was conducted to detect dysregulated RNAs in YAP-knockout DLBCL cells. The regulatory effects of insulin-like growth factor-1 receptor (IGF-1R) on Hippo-YAP signaling were explored by targeted inhibition and rescue experiments. Results: High expression of YAP was significantly correlated with disease progression and poor prognosis. Knockdown of YAP expression suppressed cell proliferation and induced cell cycle arrest in DLBCL cells. Verteporfin (VP), a benzoporphyrin derivative, exerted an anti-tumor effect by regulating the expression of YAP and the downstream target genes, CTGF and CYR61. In vitro and in vivo studies revealed that deletion of YAP expression with a CRISPR/Cas9 genome editing system significantly restrained tumor growth. Moreover, downregulation of IGF-1R expression led to a remarkable decrease in YAP expression. In contrast, exposure to IGF-1 promoted YAP expression and reversed the inhibition of YAP expression induced by IGF-1R inhibitors. Conclusions: Our study highlights the critical role of YAP in the pathogenesis of DLBCL and uncovers the regulatory effect of IGF-1R on Hippo-YAP signaling, suggesting a novel therapeutic strategy for DLBCL.

Traced back to December 2019, an unexpected outbreak of a highly contagious new coronavirus pneumonia (COVID-19) has rapidly swept around China and the globe. There have now been an estimated 2 580 000 infections and more than 170 000 fatal cases around the world. The World Health Organization (WHO) estimated that approximately 14% of infections developed into severe disease, 5% were critically ill, and the mortality rate of critically ill patients is reported to be over 50%. The shortage of specific anti-viral treatment and vaccines remains a huge challenge. In COVID-19, refractory hypoxemia is common among the critically ill with acute respiratory distress syndrome (ARDS) despite invasive mechanical ventilation, and is further complicated by respiratory and circulatory failure. This difficult situation calls for the use of extracorporeal membrane oxygenation (ECMO) for assisting respiration and circulation if necessary. This article reviews the pertinent clinical literature, technical guidance, and expert recommendations on use of ECMO in critically ill cases of COVID-19. Here, we present basic knowledge and opinions about COVID-19 and ECMO, review the evidence on ECMO use in Middle East Respiratory Syndrome (MERS) and H1N1 influenza, share the technical guidance and recommendations on use of ECMO in COVID-19, summarize the current use of ECMO against COVID-19 in China, and discuss the issues in use of ECMO in COVID-19.

Lung cancer is one of the main causes of cancer-related death in the world. The identification and characteristics of malignant cells are essential for the diagnosis and treatment of primary or metastatic cancers. Deep learning is a new field of artificial intelligence, which can be used for computer aided diagnosis and scientific research of lung cancer pathology by analyzing and learning through establishment and simulation of human brain. In this review, we will introduce the application, progress and problems of deep learning in pathology of lung cancer and make prospects for its future development.

Subclinical hypothyroidism is associated with cardiovascular diseases, yet the underlying mechanism remains largely unknown. Herein, in a common population (n = 1,103), TSH level was found to be independently correlated with both carotid plaque prevalence and intima-media thickness. Consistently, TSH receptor ablation in ApoE^−/− mice attenuated atherogenesis, accompanied by decreased vascular inflammation and macrophage burden in atherosclerotic plaques. These results were also observed in myeloid-specific Tshr-deficient ApoE^−/− mice, which indicated macrophages to be a critical target of the proinflammatory and atherogenic effects of TSH. In vitro experiments further revealed that TSH activated MAPKs (ERK1/2, p38α, and JNK) and IκB/p65 pathways in macrophages and increased inflammatory cytokine production and their recruitment of monocytes. Thus, the present study has elucidated the new mechanisms by which TSH, as an independent risk factor of atherosclerosis, aggravates vascular inflammation and contributes to atherogenesis. Graphical Abstract

Remote access and endoscopic thyroid surgery has been gaining popularity because it allows patients to avoid a visible scar in the neck. There is limited data on transoral endoscopic thyroidectomy when it relates to patients with papillary thyroid carcinoma. We aim to evaluate the safety of ipsilateral central compartment dissection for patients who undergo transoral thyroidectomy (thyroidectomy vestibular approach–compartment lymph node dissection). A total of 80 patients who underwent thyroidectomy vestibular approach–compartment lymph node dissection for papillary thyroid carcinoma from June 2015 to September 2016 were identified. Over the same period, a matched cohort of 80 patients who underwent open thyroidectomy with routine ipsilateral central compartment dissection was also identified (Open-compartment lymph node dissection). The two groups were analyzed in terms of patient characteristics, perioperative clinical results and post-operative outcomes. All patients were female with a mean age of 32-year. There was no difference in mean maximum tumor size and number of lymph nodes dissected. Moreover, there was no difference in average positive lymph nodes between thyroidectomy vestibular approach–compartment lymph node dissection and Open-compartment lymph node dissection (1.48 vs 1.08, P = 0.647). Operative time was longer in the thyroidectomy vestibular approach–compartment lymph node dissection group (193 vs 102 min, P < 0.001). Thyroidectomy specific complications were similar with rates of temporary recurrent laryngeal nerve palsy of 6.3 vs 8.8% and temporary hypocalcemia rates of 2.5 vs 5% in the thyroidectomy vestibular approach–compartment lymph node dissection and Open-compartment lymph node dissection groups, respectively. Thyroidectomy vestibular approach–compartment lymph node dissection is a feasible and safe option for select patients with papillary thyroid carcinoma who require central node dissection compared with Open-compartment lymph node dissection, and can be a viable alternative for patients wishing to avoid a visible scar.