Beclin-1 is the firstly-identified mammalian protein of the autophagy machinery, which functions as a molecular scaffold for the assembly of PI3KC3 (class III phosphatidylinositol 3 kinase) complex, thus controlling autophagy induction and other cellular trafficking events. Notably, there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes, including tumor suppression and progression as well as resistance to cancer therapeutics and CSC (cancer stem-like cell) maintenance. More importantly, Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers. In this review, we provide a comprehensive survey of the structure, functions, and regulations of Beclin-1, and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology. Moreover, we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy, providing novel insights into a promising strategy for regulating Beclin-1 to improve cancer therapeutics in the future.

Sequencing-based spatial transcriptomics(ST)is an emerging technology to study in situ gene expression patterns at the whole-genome scale.Currently,ST data analysis is still complicated by high technical noises and low resolution.In addition to the transcriptomic data,matched histopathological images are usually generated for the same tissue sample along the ST experiment.The matched high-resolution histopathological images provide complementary cellular phenotypi-cal information,providing an opportunity to mitigate the noises in ST data.We present a novel ST data analysis method called transcriptome and histopathological image integrative analysis for ST(TIST),which enables the identification of spatial clusters(SCs)and the enhancement of spatial gene expression patterns by integrative analysis of matched transcriptomic data and images.TIST devises a histopathological feature extraction method based on Markov random field(MRF)to learn the cellular features from histopathological images,and integrates them with the transcrip-tomic data and location information as a network,termed TIST-net.Based on TIST-net,SCs are identified by a random walk-based strategy,and gene expression patterns are enhanced by neighborhood smoothing.We benchmark TIST on both simulated datasets and 32 real samples against several state-of-the-art methods.Results show that TIST is robust to technical noises on multiple analysis tasks for sequencing-based ST data and can find interesting microstructures in dif-ferent biological scenarios.TIST is available at http://lifeome.net/software/tist/and https://ngdc.cncb.ac.cn/biocode/tools/BT007317.

BACKGROUND: A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure. METHODS: We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan. RESULTS: Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups. CONCLUSIONS From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.
Adolescent ; Adult ; Aged ; Aspartate Aminotransferases ; blood ; Betacoronavirus ; Case-Control Studies ; Child ; Child, Preschool ; China ; epidemiology ; Coronavirus Infections ; epidemiology ; physiopathology ; therapy ; Female ; Humans ; Infant ; Infant, Newborn ; L-Lactate Dehydrogenase ; blood ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; epidemiology ; physiopathology ; therapy ; Retrospective Studies ; Young Adult

Background: To evaluate the facial asymmetry, three-dimensional computed tomography (3D-CT) has been used widely. This study proposed a method to quantify facial asymmetry based on 3D-CT. Methods: The normal standard group consisted of twenty-five male subjects who had a balanced face and normal occlusion. Five anatomical landmarks were selected as reference points and ten anatomical landmarks were selected as measurement points to evaluate facial asymmetry. The formula of facial asymmetry index was designed by using the distances between the landmarks. The index value on a specific landmark indicated zero when the landmarks were located on the three-dimensional symmetric position. As the asymmetry of landmarks increased, the value of facial asymmetry index increased. For ten anatomical landmarks, the mean value of facial asymmetry index on each landmark was obtained in the normal standard group. Facial asymmetry index was applied to the patients who had undergone orthognathic surgery. Preoperative facial asymmetry and postoperative improvement were evaluated. Results: The reference facial asymmetry index on each landmark in the normal standard group was from 1.77 to 3.38. A polygonal chart was drawn to visualize the degree of asymmetry. In three patients who had undergone orthognathic surgery, it was checked that the method of facial asymmetry index showed the preoperative facial asymmetry and the postoperative improvement well. Conclusions The current new facial asymmetry index could efficiently quantify the degree of facial asymmetry from 3D-CT. This method could be used as an evaluation standard for facial asymmetry analysis.

BACKGROUND: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. METHODS: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. RESULTS: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). CONCLUSIONS IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.
Albumins/analysis* ; Antiviral Agents/administration & dosage* ; Betacoronavirus ; C-Reactive Protein/analysis* ; COVID-19 ; Case-Control Studies ; China ; Coronavirus Infections/drug therapy* ; Glucocorticoids/pharmacology* ; Hospitalization ; Humans ; Interferon alpha-2/administration & dosage* ; Nasal Sprays ; Pandemics ; Pneumonia, Viral/drug therapy* ; Propensity Score ; Retrospective Studies ; SARS-CoV-2 ; Sodium/blood* ; Virus Shedding/drug effects* ; COVID-19 Drug Treatment

Hepatocellular carcinoma (HCC) is highly heterogeneous in nature and has been one of the most common cancer types worldwide. To ensure repeatability of identified gene expression patterns and comprehensively annotate the transcriptomes of HCC, we carefully curated 15 public HCC expression datasets that cover around 4000 clinical samples and developed the database HCCDB to serve as a one-stop online resource for exploring HCC gene expression with user-friendly interfaces. The global differential gene expression landscape of HCC was established by analyzing the consistently differentially expressed genes across multiple datasets. Moreover, a 4D metric was proposed to fully characterize the expression pattern of each gene by integrating data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). To facilitate a comprehensive understanding of gene expression patterns in HCC, HCCDB also provides links to third-party databases on drug, proteomics, and literatures, and graphically displays the results from computational analyses, including differential expression analysis, tissue-specific and tumor-specific expression analysis, survival analysis, and co-expression analysis. HCCDB is freely accessible at http://lifeome.net/database/hccdb.
Carcinoma, Hepatocellular ; genetics ; Databases, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; genetics

Aim To observe whether matrix metallo-proteinase-14 ( MMP-14) and tissue matrix metallopro-teinase inhibitor-4 ( TIMP-4) were involved in the car-diac-protection of mitochondrial aldehyde dehydrogen-ase 2 ( ALDH2) against high glucose induced rat pri-mary cardiomyocyte injury. Methods Rat primary cardiomyocytes were cultured. The cardiomyocyte via-bility was detected by MTT assay at different concentra-tion of glucose at different time point. After established high glucose-induced cardiomyocytes injury model, cardiomyocytes were randomly divided into 4 groups:normal control group ( NG, glucose at 5.5 mmol· L-1) , NG + Alda-1 group ( Alda-1 at 20 μmol·L-1) , high glucose group ( HG, glucose at 30 mmol·L-1) and HG+Alda-1 group. The cell viability at 48 h and oxidative stress level were detected by MTT and DHE staining methods. The protein expressions of ALDH2, MMP-14 and TIMP-4 were determined by Western blot. Results The cardiomyocytes injury model was established according to the cell activity result. Com-pared with NG group, the cell viability, the protein ex-pressions of ALDH2, MMP-14, the ratio of MMP-14/TIMP-4 were decreased, TIMP-4 protein expression and the level of oxidative stress were increased in HG group. Compared with HG group, in HG + Alda-1 group, the cell viability, the protein expressions of AL-DH2, MMP-14, the ratio of MMP-14/TIMP-4 were in-creased, the levels of oxidative stress and TIMP-4 pro-tein expression were decreased. Conclusion Activa-tion of mitochondrial ALDH2 may relieve high glucose induced cardiomyocytes injury. The protective effect was likely related to the inhibition of oxidative damage, down-regulation of MMP-14 and up-regulation of TIMP-4 proteins.

The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.

Objective To analyze the clinical characteristics of pituitary stalk interruption syndrome(PSIS). Methods The clinical data including clinical manifestations,laboratory tests,and imaging findings of 114 PSIS patients in our hospital were retrospectively analyzed. Results Of these 114 PSIS patients,102 cases (89.4%) were male. The average age was 21.1?6.1 years. A history of breech delivery was documented in 91 cases (91.9%). Short stature was found in 89 cases (71.8%) and bone age delayed (6.1?5.1) years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone,gonadotropins,corticotropin,and thyrotropin were 100.0%,94.0%,84.2%,and 74.6%,respectively. Hyperprolactinemia was found in 28.1% of patients. Three or more pituitary hormone abnormalities were found in 105 cases(92.1%). Compared with the 5 cases with history of cephalic delivery,no difference were found in the aspects of height(t=0.297,P=0.634),penile length(t=1.205,P=0.882),testicular volume (U=99.000,P=0.348),growth hormone peak (U=89.000,P=0.186),adrenocorticotropic hormone peak(U=131.000,P=0.967),luteinizing hormone peak(U=98.500,P=0.582),thyroid-stimulating hormone (U=82.000,P=0.162),and the height of anterior pituitary (t=1.676,P=0.107) in the 53 cases with history of breech delivery. Conclusions The clinical manifestations,symptoms,hormone deficiencies were severe in our series. The condition severities were not remarkably different in patients with different delivery ways.
Adolescent ; Adult ; Dwarfism ; etiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Pituitary Diseases ; complications ; physiopathology ; Pituitary Gland ; pathology ; Prevalence ; Retrospective Studies ; Young Adult