简介：AbstractPreeclampsia (PE) is a principal cause of maternal and newborn mortality that poses financial and physical burdens to tens of thousands of families each year. Unfortunately, there is no effective management to arrest the progression of this disease unless delivery. Therefore, standardized management or preventive treatments are needed urgently. PE is closely associated with placental hypoxia, which increases the secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) as well as soluble endoglin (sEng) into the maternal circulation. Metformin has been found to inhibit those anti-angiogenic factors so it might be a candidate to prevent or treat PE. Women who are diagnosed with gestational diabetes mellitus (GDM) are more likely to have complications of hypertension or PE, so this review aims to demonstrate that the application of metformin in GDM might prevent the onset or progression of PE complicated with GDM.

简介：AbstractPancreatic ductal adenocarcinoma is the main cause of cancer-related mortality, with a lack of effective treatments and overall survival rates far lower than other solid cancers. This clinical challenge is related to late diagnosis as well as primary or acquired resistance to therapy-induced apoptosis. Targeting nonapoptotic cell death pathways may provide alternative therapeutic strategies to overcome drug resistance. In particular, recent studies have suggested that ferroptosis, a type of iron-dependent nonapoptotic cell death, is a promising target for pancreatic ductal adenocarcinoma. Ferroptosis can be triggered by inhibiting or activating the redox or iron metabolism-related pathways, mediated by extrinsic/membrane transports (e.g., solute carrier family 7 member 11) or intrinsic/enzymes (e.g., glutathione peroxidase 4). Although the exact effector molecule remains obscure, reactive oxygen species-induced lipid peroxidation and subsequent plasma membrane damage appears to play a central role in mediating ferroptotic death. While treatment-induced ferroptosis is beneficial to suppress tumor growth, inflammation-related immunosuppression caused by ferroptotic damage may promote the occurrence of pancreatic ductal adenocarcinoma. In this review, we outline the latest knowledge about the regulation and function of ferroptosis in pancreatic tumorigenesis and therapy.

简介：AbstractPancreatic neuroendocrine tumors (pNET) are heterogenous tumors originated from the diffuse neuroendocrine cells of pancreas, which show the function of synthesis, storage and secretion of peptide hormones and biomimetic amines. Biomarkers play a crucial role in the diagnosing, evaluating prognosis and predicting treatment response for pNET patients. Traditional NET markers such as chromogranin A and Neuron Specific Enolase, as a diagnostic biomarker, have relatively low sensitivity and specificity in pNET patients. The emergence of new types of biomarkers provides more reliable indicators for diagnosis and prognosis evaluation. Among them, NETest score is a promising biomarker with the highest diagnostic sensitivity (80%) and specificity (94%). In addition, this molecule can be also used as a prognostic biomarker, which can predict disease progression and shorter overall survival. Biomarkers related to therapeutic targets, such as vascular endothelial growth factor, vascular endothelial growth factor receptor, and key molecules of mTOR signaling pathway, have capability to predict response of treatment. With the development of next-generation sequencing, chip array, and digital droplet PCR, novel biomarkers such as circulating tumor cells, tumor-derived exosomes, and circulating tumor DNA and mRNA are expected to provide more accurate diagnosis, prognostic information, and prospective therapeutic targets. In this paper, biomarkers of pancreatic neuroendocrine tumor and their role in diagnosis, prognosis, diagnosis, treatment and monitoring are systematically introduced. Our conclusions can provide new basis for clinicians in the diagnosis and treatment process.

简介：AbstractAtopic dermatitis (AD) is a chronic inflammatory skin disease with xerosis, itchiness, as well as interconnection with immunoglobulin E (Ig E), mediated foods including airborne allergies. AD is not only related to the diminished stratum corneum barrier but also presents with an unusual expression of tight junctions (TJs) proteins. TJ barrier dysfunction leads to impairment in the stratum corneum (SC) barrier. The significant role of TJs in the epidermal barrier as indicated by Claudin-1 (Cldn-1) deficient mice that undergo high transepidermal water loss (TEWL) and skin dehydration. In atopic dermatitis, downregulation of Cldn-1 was observed due to inflammation. Still, a lack of distinct understanding exists in considering tight junction barrier impairment as a cause or outcome in atopic dermatitis. This review summarizes TJs main role in skin barrier function and TJ proteins (TJPs) expression observed in AD patients.

简介：AbstractAlthough considerable advances have been made in the field of assisted reproductive technology (ART), millions of couples still suffer from infertility and miscarriage. In a large number of cases, the etiology of these common reproductive failures remains unknown. However, the significance of autoantibodies in infertility and miscarriage has sparked extensive interest because of their pleiotropic roles in disrupting normal pregnancy. This review discusses the pleiotropic roles of a series of autoantibodies in infertility and miscarriage. A brief recapitulation of how the autoantibodies interfere with ART outcomes and treatments for this type of idiopathic infertility or miscarriage is also provided. While several disputes remain to be resolved, further studies employing better designs and larger sample sizes are required in view of the therapeutic potential of autoantibody inhibitors and the future of contraceptive vaccines.

简介：AbstractIn December of 2019, several cases of atypical pneumonia caused by an unknown agent were reported in Wuhan, the capital city of Hubei Province in China. In early January 2020, it was announced that these cases were caused by a novel coronavirus. The virus was later named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes a disease associated with atypical pneumonia termed Corona virus disease 2019 (COVID-19). Several respiratory viruses, including coronaviruses and influenza viruses tend to have prominent peaks of infection during colder seasons, especially in temperate regions. The cold temperatures, along with accompanying dry conditions can drive respiratory tract infections by assisting with viral transmission, weakening the human immune system, and increasing viral molecular stability. Though the topic of SARS-CoV-2 transmission and warm weather has been associated with misinformation campaigns, it is worth investigating since an informative answer may give an indication of the future behavior of SARS-CoV-2.

简介：AbstractIncreasing evidence suggests that long non-coding RNAs (lncRNAs) are of vital importance for various biological processes, and dysregulation of lncRNAs is frequently associated with various diseases such as psoriasis. LncRNAs modulate gene expression at the transcriptional, post-transcriptional, and translational levels; however, the specific regulatory mechanisms of lncRNAs in psoriasis remain largely unexplored. This review provides an overview of recent studies investigating mechanisms and functions of lncRNAs in psoriasis, especially focusing on the role of lncRNAs in keratinocytes, T cells, and dendritic cells.

简介：[摘要]Role-play作为单元示范对话，在听说课教学中有着重要的作用。本文从Role-play文本的特殊性出发，结合人教版中的对话文本从语音语调、话语者的情感色彩、话轮功能、语用知识和文化价值方面谈谈如何对role-play对话文本进行解读。希望对初中英语Role-play对话文本解读提供一定的借鉴。

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简介：AbstractBackground:Although osteopontin (OPN) is expressed in the liver and pigment gallstones of patients with hepatolithiasis, its role in pigment gallstone formation remains unclear. This study aimed to explore the function of OPN in pigment gallstone formation.Methods:Rats were fed a chow diet (CD) or lithogenic diet (LD) for 10 consecutive weeks; blocking tests were then performed using an OPN antibody (OPN-Ab). Incidence of gallstones and levels of several bile components, OPN, tumor necrosis factor alpha (TNF-α), and cholesterol 7 alpha-hydroxylase (CYP7A1) were analyzed. To determine TNF-α expression in hepatic macrophages and both CYP7A1 and bile acid (BA) expression in liver cells, recombinant rat OPN and recombinant rat TNF-α were used to treat rat hepatic macrophages and rat liver cells, respectively. Chi-square or Fisher exact tests were used to analyze qualitative data, Student t-test or one-way analysis of variance were used to analyze qualitative data.Results:Incidence of gallstones was higher in LD-fed rats than in CD-fed rats (80% vs. 10%, P < 0.05). BA content significantly decreased in bile (t= -36.08, P < 0.01) and liver tissue (t= -16.16, P < 0.01) of LD-fed rats. Both hepatic OPN protein expression (t= 9.78, P < 0.01) and TNF-α level (t= 8.83, P < 0.01) distinctly increased in the LD group; what’s more, CYP7A1 mRNA and protein levels (t= -12.35, P < 0.01) were markedly down-regulated in the LD group. Following OPN-Ab pretreatment, gallstone formation decreased (85% vs. 25%, χ2 = 14.55, P < 0.01), liver TNF-α expression (F = 20.36, P < 0.01) was down-regulated in the LD group, and CYP7A1 expression (F = 17.51, P < 0.01) was up-regulated. Through CD44 and integrin receptors, OPN promoted TNF-α production in macrophage (F= 1041, P < 0.01), which suppressed CYP7A1 expression (F = 48.08, P < 0.01) and reduced liver BA synthesis (F= 119.4, P < 0.01).Conclusions:We provide novel evidence of OPN involvement in pigmented gallstone pathogenesis in rats.

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简介：AbstractThere have been recent extensive studies and rapid advancement on the pathogenesis underlying idiopathic pulmonary fibrosis (IPF), and intricate pathogenesis of IPF has been suggested. The purpose of this study was to clarify the logical relationship between these mechanisms. An extensive search was undertaken of the PubMed using the following keywords: "etiology," "pathogenesis," "alveolar epithelial cell (AEC)," "fibroblast," "lymphocyte," "macrophage," "epigenomics," "histone," acetylation," "methylation," "endoplasmic reticulum stress," "mitochondrial dysfunction," "telomerase," "proteases," "plasminogen," "epithelial-mesenchymal transition," "oxidative stress," "inflammation," "apoptosis," and "idiopathic pulmonary fibrosis." This search covered relevant research articles published up to April 30, 2020. Original articles, reviews, and other articles were searched and reviewed for content; 240 highly relevant studies were obtained after screening. IPF is likely the result of complex interactions between environmental, genetic, and epigenetic factors: environmental exposures affect epigenetic marks; epigenetic processes translate environmental exposures into the regulation of chromatin; epigenetic processes shape gene expression profiles; in turn, an individual’s genetic background determines epigenetic marks; finally, these genetic and epigenetic factors act in concert to dysregulate gene expression in IPF lung tissue. The pathogenesis of IPF involves various imbalances including endoplasmic reticulum, telomere length homeostasis, mitochondrial dysfunction, oxidant/antioxidant imbalance, Th1/Th2 imbalance, M1-M2 polarization of macrophages, protease/antiprotease imbalance, and plasminogen activation/inhibition imbalance. These affect each other, promote each other, and ultimately promote AEC/fibroblast apoptosis imbalance directly or indirectly. Excessive AEC apoptosis and impaired apoptosis of fibroblasts contribute to fibrosis. IPF is likely the result of complex interactions between environmental, genetic, and epigenetic factors. The pathogenesis of IPF involves various imbalances centered on AEC/fibroblast apoptosis imbalance.

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简介：AbstractBackground:HIV/AIDS has transformed into a chronic controllable but not yet curable infectious disease as other chronic diseases to some extent. The additional of so called fourth 90% that included the improved health-related quality of life (HRQoL) for people living with HIV (PLWHIV) required solutions beyond antiretroviral therapy and viral load suppression. This study will explore the role of personality, social economic and prevention strategy effection on HRQoL among people living with HIV/AIDS.Methods:A cross-sectional study was conducted among PLWHIV aged more than 16 years old in the 10 municipalities in Yunnan Province, China from October 2019 to May 2020, enrolling total 1997 participants. Individual-level HRQoL data were measured by 12-item Short Form Health Survey (SF-12) and EuroQol Five Dimensions Questionnaire (EQ-5D-5L). We assembled municipal-level data about social economic from Yunnan Statistical Yearbook in 2020 and strategy practice information from the self-evaluation system. We used the principal component analysis to build the social economic and strategy effect on each area respectively and one-way ANOVA was used to perform univariate analysis to identify the predictors with significant differences. Finally we used multi-level model (MLM) to explore the personality, social economic and strategy effects in health-related quality of life among PLWHIV.Results:The global score for quality of life measured using EQ-5D-5L had an estimated mean score (standard deviation, SD) of 0.901 ± 0.146. The HRQoL score measured using PCS-12 had an estimated mean score (SD) of 46.62 ± 8.55. The mean MCS-12 score (SD) was estimated to be 47.80 ± 9.71 . The area-level predictors explained a proportion of 13.6-17.2% for the between-area variation of the HRQoL scores, regardless of the total HRQoL, physical component and mental component. The impacts of stigma (P < 0.01), social support (P < 0.001), anxiety (P < 0.001), depression (P < 0.05) and social economic status (P < 0.05) on HRQoL at the individual-level were significantly different. The plots visualized the impact of individual-level factors on a respondent’s HRQoL was modified by the area-level characteristics.Conclusions:The study identified the possible strategy determinant of individual HRQoL of PLWHIV and also the area effect on HRQoL. Stigma, social support, anxiety, depression and social economic status were the individual-level determinants on HRQoL. These could be a valuable resource for evaluating the overall health of the areas and help improve local decision making.

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简介：AbstractA significant number of SARS-CoV-2 (COVID-19) pandemic patients have developed chronic symptoms lasting weeks or months which are very similar to those described for myalgic encephalomyelitis/chronic fatigue syndrome. This study reviews the current literature and understanding of the role that mitochondria, oxidative stress and antioxidants may play in the understanding of the pathophysiology and treatment of chronic fatigue. It describes what is known about the dysfunctional pathways which can develop in mitochondria and their relationship to chronic fatigue. It also reviews what is known about oxidative stress and how this can be related to the pathophysiology of fatigue, as well as examining the potential for specific therapy directed at mitochondria for the treatment of chronic fatigue in the form of antioxidants. This study identifies areas which require urgent, further research in order to fully elucidate the clinical and therapeutic potential of these approaches.

简介：AbstractBackground:Histological and functional recovery after peripheral nerve injury (PNI) is of significant clinical value as delayed surgical repair and longer distances to innervate terminal organs may account for poor outcomes. Low-intensity extracorporeal shock wave therapy (LiESWT) has already been proven to be beneficial for injured tissue recovery on various pathological conditions. The objective of this study was to explore the potential effect and mechanism of LiESWT on PNI recovery.Methods:In this project, we explored LiESWT’s role using an animal model of sciatic nerve injury (SNI). Shockwave was delivered to the region of the SNI site with a special probe at 3 Hz, 500 shocks each time, and 3 times a week for 3 weeks. Rat Schwann cells (SCs) and rat perineurial fibroblasts (PNFs) cells, the two main compositional cell types in peripheral nerve tissue, were cultured in vitro, and LiESWT was applied through the cultured dish to the adherent cells. Tissues and cell cultures were harvested at corresponding time points for a reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence staining. Multiple groups were compared by using one-way analysis of variance followed by the Tukey-Kramer test for post hoc comparisons.Results:LiESWT treatment promoted the functional recovery of lower extremities with SNI. More nerve fibers and myelin sheath were found after LiESWT treatment associated with local upregulation of mechanical sensitive yes-associated protein (YAP)/transcriptional co-activator with a PDZ-binding domain (TAZ) signaling pathway. In vitro results showed that SCs were more sensitive to LiESWT than PNFs. LiESWT promoted SCs activation with more expression of p75 (a SCs dedifferentiation marker) and Ki67 (a SCs proliferation marker). The SCs activation process was dependent on the intact YAP/TAZ signaling pathway as knockdown of TAZ by TAZ small interfering RNA significantly attenuated this process.Conclusion:The LiESWT mechanical signal perception and YAP/TAZ upregulation in SCs might be one of the underlying mechanisms for SCs activation and injured nerve axon regeneration.