Circular RNAs:implications of signaling pathways and bioinformatics in human cancer

Circular RNAs(circRNAs)form a class of endogenous single-stranded RNA transcripts that are widely expressed in eukaryotic cells.These RNAs mediate post-transcriptional control of gene expression and have multiple functions in biological processes,such as transcriptional regulation and splicing.They serve predominantly as microRNA sponges,RNA-binding proteins,and templates for translation.More importantly,circRNAs are involved in cancer progression,and may serve as promising biomarkers for tumor diagnosis and therapy.Although traditional experimental methods are usually time-consuming and laborious,substantial progress has been made in exploring potential circRNA-disease associations by using computational models,summarized signaling pathway data,and other databases.Here,we review the biological characteristics and functions of circRNAs,including their roles in cancer.Specifically,we focus on the signaling pathways associated with carcinogenesis,and the status of circRNA-associated bioinformatics databases.Finally,we explore the potential roles of circRNAs as prognostic biomarkers in cancer.

Deep Neural Network Based Behavioral Model of Nonlinear Circuits

With the rapid growth of complexity and functionality of modern electronic systems, creating precise behavioral models of nonlinear circuits has become an attractive topic. Deep neural networks (DNNs) have been recognized as a powerful tool for nonlinear system modeling. To characterize the behavior of nonlinear circuits, a DNN based modeling approach is proposed in this paper. The procedure is illustrated by modeling a power amplifier (PA), which is a typical nonlinear circuit in electronic systems. The PA model is constructed based on a feedforward neural network with three hidden layers, and then Multisim circuit simulator is applied to generating the raw training data. Training and validation are carried out in Tensorflow deep learning framework. Compared with the commonly used polynomial model, the proposed DNN model exhibits a faster convergence rate and improves the mean squared error by 13 dB. The results demonstrate that the proposed DNN model can accurately depict the input-output characteristics of nonlinear circuits in both training and validation data sets.

Role of gut microbiota via the gut-liver-brain axis in digestive diseases

The gut-brain axis is a bidirectional information interaction system between the central nervous system(CNS) and the gastrointestinal tract, in which gut microbiota plays a key role. The gut microbiota forms a complex network with the enteric nervous system, the autonomic nervous system, and the neuroendocrine and neuroimmunity of the CNS, which is called the microbiota-gut-brain axis. Due to the close anatomical and functional interaction of the gut-liver axis, the microbiota-gut-liver-brain axis has attracted increased attention in recent years. The microbiota-gut-liver-brain axis mediates the occurrence and development of many diseases, and it offers a direction for the research of disease treatment. In this review, we mainly discuss the role of the gut microbiota in the irritable bowel syndrome, inflammatory bowel disease, functional dyspepsia, non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and hepatic encephalopathy via the gut-liver-brain axis, and the focus is to clarify the potential mechanisms and treatment of digestive diseases based on the further understanding of the microbiota-gut-liver-brain axis.

Effect of Danzhi decoction on expression of angiogenesis factors in patients with sequelae of pelvic inflammatory disease

Objective:To investigate the efteets of traditional Chinese medicine.Danzhi decoction,on the expression angiogenesis factors in human endometrial cells during the sequelae of pelvic inflammatoty disease(SPID) and explore the role of Danzhi decction in improving the blood stasis microenvironment of SPID.Methods:A three-dimensional(3D) co—culture system including human vascular endothelial cells(VECs),endometrial stromal cells and glandular epithelial cells was established in vitro and treated with Danzhi decoction,sterilized water and aspirin respectively.A Milliplex multifunctional liquid chip technique was used to measure the expression levels of vascular endothelial growth factor(VEGF)—A/C/D,fibroblast growth factor-1/2.angiopoietin-2.epidermal growth factor(EGF) HB-EGF,bone morphogenetic protein-9.endoglin.endothehn-l.granulocyte colony stimulating factor,hepatocyte growth factor,interleukin-8,follistatin.placenta growth factor and leptin.The location of angiogenesis factors was monitored by immunofluorescence labeling and confocal laser scanning microscope3 D reconstruction.Results:Endometrial stromal cells and glandular epithelial cells were isolated and primary cultured for establishing a 3D co-culture system.The levels of VEGF—A/C/D in Danzhi decoction group and aspirin group were significantly lower than those in mock group(P<0.05).while there was no significant difference between Danzhi decoction group and aspirin group(P>0.05).Furthermore,the alterative location of VEGF—A/C/D was observed in the cytoplasm of endometrial glandular epithelial cells.Conclusions:Danzhi decoction mav inhibit the expression of VEGF in the blood stasis microenvironment of SPID by targeting the cytoplasm of endometrial glandular epithelial cell.

Current therapeutic strategies for premature ejaculation and future perspectives

Premature ejaculation （PE） is a common sexual disorder in men that is mediated by disturbances in the peripheral and central nervous systems. Although all pharmaceutical treatments for PE are currently used ＇off-label＇, some novel oral agents and some newer methods of drug administration now provide important relief to PE patients. However, the aetiology of this condition has still not been unified, primarily because of the lack of a standard animal model for basic research and the absence of a widely accepted definition and assessment tool for evidence-based clinical studies in patients with PE. In this review, we focus on the current therapeutic strategies and future treatment perspectives for PE.

An open, comparative, multicentre clinical study of combined oral therapy with sildenafil and doxazosin GITS for treating Chinese patients with erectile dysfunction, and lower urinary tract symptoms secondary to benign prostatic hyperplasia

This study sought to investigate the clinical efficacy and safety of combined oral therapy with sildenafil and doxazosin GITS compared to sildenafil monotherapy in treating Chinese patients with erectile dysfunction （ED） and lower urinary tract symptoms secondary to benign prostatic hyperplasia （BPH/LUTS）. The trial was conducted in hospitals in Beijing, Shanghai, Changsha, Wuhan and Guangzhou, five major cities in China. A total of 250 patients diagnosed with ED and BPH/LUTS aged 50-75 years, and who had International Index of Erection Function-5 （IIEF-5） scores ≤ 21 and International Prostate Symptom Score （IPSS） ≥ 10 points, were enrolled and randomly divided into Group A （168 cases; doxazosin GITS 4 mg once daily plus sildenafi125-100 mg on demand） and Group B （82 cases; sildenafi125-100 mg on demand）. Efficacies were evaluated by IIEF-5 and IPSS scores and a quality of life （QoL） questionnaire, and adverse effects were evaluated during the treatment period. There were no statistically significant differences in mean age, and IIEF-5, IPSS and QoL scores pre-treatment between the two groups. After treatment, IIEF-5, IPSS and QoL scores were significantly improved in Group A, while only IIEF-5 scores were significantly improved in Group B compared with pre-treatment. There were no significant differences in side effects between the two groups. The results indicated that combined therapy with sildenafil and doxazosin GITS for the treatment of ED and BPH/LUTS is safe and effective compared to sildenafil monotherapy.

Feasibility of establishing cerebral ischemia models by using aerocyst-blocking bilateral ascending pharyngeal artery of piglets Imaging assessment

BACKGROUND： The cerebral ischemia and ischemia/reperfusion animal models are used to simulate the human cerebrovascular diseases is one of the popular topics of neurological science recently. To study the pathophysiology, pathogenesis, prophylaxis and treatment of ischemic cerebrovascular diseases and to establish the ideal animal model that is the most similar to the human cerebral ischemia, are the topics that the people generally cared about. OBJECTIVE： To evaluate the effects of aerocyst-blocking bilateral ascending pharyngeal artery on the establishment of cerebral ischemia models by using digital subtraction angiography （DSA）, magnetic resonance diffusion-weighted imaging （DWI） and magnetic resonance perfusion-weighted imaging （PWI）. DESIGN： Repetitive measure animal experiment. SETTING： Zhongshan Hospital Affiliated to Dalian University. MATERIALS： The experiment was carried out in the Animal Laboratory （Provincial Laboratory）, Zhongshan Hospital of Dalian Univeristy from January to May 2006. A total of 14 domestic piglets, of 6 months old, weighing 12-15 kg, of either gender, were selected from Animal Experimental Center, Dalian University. Multistar T.O.P digital subtraction angiography machine was provided by Siemens Company, German. METHODS： Aerocyst-blocking bilateral ascending pharyngeal artery was used to establish cerebral ischemia models. And then, Multistar T.O.P. DSA was used for imaging of cerebral vessels before blocking, during blocking and at 0.5 and 2 hours after ischemia perfusion. GE Signa 1.5 T supraconduction magnetic resonance imaging was used for DWI examination; in addition, PWI was used based on focal sites and areas. Otherwise, magnetic resonance imaging （MRI） was used to detect signal changes of T1WI and T2WI in ischemic areas. MAIN OUTCOME MEASURES： Analytic results of DSA, DWI, PWI and MRI. RESULTS： All 14 experimental piglets were involved in the final analysis. ① DSA： The blood flow of bilateral ascending pharyngeal arteries and its branch were blocked at blocking phase, which restored 0.5 and 2 hours after reperfusion. ② DWI and PWI： There were no observable abnormalities in PWI and DWI at pre-blocking. Abnormal increased signals were found on both DWI and PWI at during and post-blocking. There were reduction in ADC and rCBF and delay in rTTP at all time points except pre-blocking. ③ MRI： There were no abnormal signals observable at any time of pre- and post-blocking in T1WI and T2WI. CONCLUSION： It is feasible to establish this kind of animal experimental models, and it can simulate the ischemic state; meanwhile, the existence and extent can be showed directly by DSA, DWI, and PWI.

Massive gastric bleeding-perforation of pancreatic pseudocyst into the stomach: A case report and review of literature

BACKGROUND Pancreatic pseudocyst may cause serious gastrointestinal complications including necrosis,infection,and perforation of the gastrointestinal tract wall,but massive gastric bleeding is very rare.CASE We report a rare case of a 49-year-old man with life-threatening gastric bleeding from a pseudoaneurysm of the splenic artery perforating the stomach induced by pancreatic pseudocyst.During hospitalization,gastroscopy revealed a bare blood vessel in an ulcer-like depression of the greater gastric curvature,and computed tomography scan confirmed a pancreatic pseudocyst invading part of the spleen and gastric wall of the greater curvature.Arteriography showed that the bare blood vessel originated from a pseudoaneurysm of the splenic artery.The bleeding was controlled by the trans-arterial embolization,the patient’s recovery was rapid and uneventful.CONCLUSION Massive gastrointestinal bleeding could be a rare complication of pancreatic pseudo aneurysm.

Hi-Tag:a simple and efficient method for identifying protein-mediated long-range chromatin interactions with low cell numbers

Protein-mediated chromatin interactions can be revealed by coupling proximity-based ligation with chromatin immunoprecipitation.However,these techniques require complex experimental procedures and millions of cells per experiment,which limits their widespread application in life science research.Here,we develop a novel method,Hi-Tag,that identifies high-resolution,long-range chromatin interactions through transposase tagmentation and chromatin proximity ligation(with a phosphorothioate-modified linker).Hi-Tag can be implemented using as few as 100,000 cells,involving simple experimental procedures that can be completed within 1.5 days.Meanwhile,Hi-Tag is capable of using its own data to identify the binding sites of specific proteins,based on which,it can acquire accurate interaction information.Our results suggest that Hi-Tag has great potential for advancing chromatin interaction studies,particularly in the context of limited cell availability.

针对中国陆地碳汇反演的大气二氧化碳浓度观测网络最优化设计

精准估算陆地生态系统碳汇对中国制定碳减排措施、实现碳中和目标有重要科学支撑作用.大气反演方法基于大气二氧化碳浓度观测数据,可有效估算地面二氧化碳通量的时空分布.目前中国陆地生态系统碳汇的大气反演估算仍有巨大不确定性,其中一个重要瓶颈在于缺乏足够的二氧化碳观测站点.本文研发了针对中国区域的大气反演框架,提出了二氧化碳观测网络的站点布设方案以最大程度降低中国陆地碳汇反演估算的不确定性.研究表明,在现有站点基础上,亟需在生长季植被生产力较高的东南、东北、华北和青藏高原地区增设二氧化碳观测站点.若在中国建设30个大气二氧化碳观测站点可将碳汇估算不确定性从每年10亿吨碳降低至3亿吨碳;建设60个站点可将不确定性进一步降低至每年2亿吨碳.这些站点将是“天-空-地”综合碳观测系统的重要组成部分,服务于中国二氧化碳收支反演和精准核算.

Constraint of satellite CO_(2)retrieval on the global carbon cycle from a Chinese atmospheric inversion system

Satellite carbon dioxide(CO_(2))retrievals provide important constraints on surface carbon fluxes in regions that are undersampled by global in situ networks.In this study,we developed an atmospheric inversion system to infer CO_(2)sources and sinks from Orbiting Carbon Observatory-2(OCO-2)column CO_(2)retrievals during 2015–2019,and compared our estimates to five other state-of-the-art inversions.By assimilating satellite CO_(2)retrievals in the inversion,the global net terrestrial carbon sink(net biome productivity,NBP)was found to be 1.03±0.39 petagrams of carbon per year(Pg C yr^(-1));this estimate is lower than the sink estimate of 1.46–2.52 Pg C yr^(-1),obtained using surface-based inversions.We estimated a weak northern uptake of 1.30 Pg C yr-1and weak tropical release of-0.26 Pg C yr^(-1),consistent with previous reports.By contrast,the other inversions showed a strong northern uptake(1.44–2.78 Pg C yr-1),but diverging tropical carbon fluxes,from a sink of 0.77 Pg C yr^(-1) to a source of-1.26 Pg C yr^(-1).During the 2015–2016 El Ni?o event,the tropical land biosphere was mainly responsible for a higher global CO_(2)growth rate.Anomalously high carbon uptake in the northern extratropics,consistent with concurrent extreme Northern Hemisphere greening,partially offset the tropical carbon losses.This anomalously high carbon uptake was not always found in surface-based inversions,resulting in a larger global carbon release in the other inversions.Thus,our satellite constraint refines the current understanding of flux partitioning between northern and tropical terrestrial regions,and suggests that the northern extratropics acted as anomalous high CO_(2)sinks in response to the 2015–2016 El Nino event.

Association between adjuvant chemotherapy and survival in stage I gastric cancer patients after curative resection

Background:The efficacy of adjuvant chemotherapy(AC)on survival outcomes of patients with stage I gastric cancer(GC)after curative resection remains controversial.We aimed to determine whether these patients would benefit from AC.Methods:This retrospective study included patients with pathologically confirmed stage I GC who underwent curative resection between November 2010 and December 2020.Patients were divided into AC and non-AC groups,then a 1:1 propensity score matching(PSM)analysis was performed to minimize the selection bias.Potential risk factors including age,pN stage,pT stage,lymphovascular invasion,perineural invasion,tumor size,histological type,and carcinoembryonic antigen level were used as matching covariates.The recurrence-free survival(RFS)and disease-specific survival(DSS)were compared between groups using the Kaplan–Meier method.Results:A total of 902 consecutive patients were enrolled and 174(19.3%)patients were treated with AC.PSM created 123 pairs of patients.Before PSM,patients receiving AC had lower 10-year RFS rates(90%vs 94.6%,P=0.035)than those who did not receive AC;the two groups had similar 10-year DSS rates(93.8%vs 95.0%,P=0.240).After PSM,there were no statistical differences in the 10-year RFS(90.9%vs 93.0%,P=0.507)or DSS rates(93.5%vs 93.6%,P=0.811)between the two groups.Similar results were found in the stage IA and IB subgroups.Moreover,these findings were not affected by AC cycles.Conclusions:The addition of AC could not provide survival benefits for patients with stage I GC after surgery and follow-up is thus recommended.However,large-scale randomized clinical trials are required.

Aknowledge-guided and traditional Chinese medicine informed approach for herb recommendation

Traditional Chinese medicine(TCM)is an interesting research topic in China’s thousands of years of history.With the recent advances in artificial intelligence technology,some researchers have started to focus on learning the TCM prescriptions in a data-driven manner.This involves appropriately recommending a set of herbs based on patients’symptoms.Most existing herb recommendation models disregard TCM domain knowledge,for example,the interactions between symptoms and herbs and the TCM-informed observations(i.e.,TCM formulation of prescriptions).In this paper,we propose a knowledge-guided and TCM-informed approach for herb recommendation.The knowledge used includes path interactions and co-occurrence relationships among symptoms and herbs from a knowledge graph generated from TCM literature and prescriptions.The aforementioned knowledge is used to obtain the discriminative feature vectors of symptoms and herbs via a graph attention network.To increase the ability of herb prediction for the given symptoms,we introduce TCM-informed observations in the prediction layer.We apply our proposed model on a TCM prescription dataset,demonstrating significant improvements over state-of-the-art herb recommendation methods.

鼻咽病变的影像诊断思路

鼻咽解剖位置深在,病变种类繁多,CT及MRI是鼻咽病变治疗前主要评估手段。不同鼻咽病变影像表现不同,但也存在较多重叠,临床工作中需从病变位置、形态、边界、信号及密度特征、强化方式、与邻近组织结构关系、有无骨质破坏或淋巴结转移等方面进行综合分析,并结合临床鼻咽镜及实验室检查进一步明确诊断,从而提升诊断准确性。笔者系统总结鼻咽病变影像诊断思路,并归纳分析鼻咽病变的影像诊断要点,在治疗前明确诊断及病变范围,从而为临床治疗决策提供重要支持证据。

Clinical Manifestations of Fibrosing Mediastinitis in Chinese Patients

Background：Fibrosing mediastinitis （FM） is a rare disease.FM is thought to be related to prior granulomatous mediastinal infection,such as histoplasmosis or tuberculosis.The majority of cases have been reported in endemic regions for histoplasmosis.The characteristics of cases of FM in China,where the prevalence of tuberculosis is high,have not been reported.We analyzed the clinical,imaging,and bronchoscopic features of Chinese patients with FM to promote awareness of this disease.Methods：Between January 2005 and June 2015,twenty patients were diagnosed with FM in our hospital.Medical records and follow-up data were collected.Imaging and biopsy findings were reviewed by radiologists and pathologists.Results：A total of 20 patients were analyzed （8 males and 12 females）.The age ranged from 43 to 88 years with a mean age of 69.5 years.Previous or latent tuberculosis was found in 12 cases.Clinical symptoms included dyspnea （18/20）,cough （17/20）,expectoration （7/20）,and recurrent pneumonia （3/20）.Chest computed tomography scans showed a diffuse,homogeneous,soft tissue process throughout the mediastinum and hila with compression of bronchial and pulmonary vessels.Calcification was common （15/20）.Pulmonary hypertension was present in 9 of 20 cases.Diffuse black pigmentation in the bronchial mucosa was frequently seen on bronchoscopy （12/13）.The patients＇ response to antituberculosis treatment was inconsistent.Conclusions：FM in Chinese patients is most likely associated with tuberculosis.Some characteristics of FM are different from cases caused by histoplasmosis.

Design,synthesis characterization and in vitro biological activity of a series of 3-aryl-6-(bromoarylmethyl)-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives as the novel acetylcholinesterase inhibitors

Bromination is used as a strategy to improve biological activity in medicinal chemistry.In order to study on the structure-activity relationships of the novel acetylcholinesterase inhibitors with 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one scaffold,based on our previous work and molecular modeling,a series of novel 3-aryl-6-（bromoarylrnethyl）-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were designed by molecular docking,synthesized and characterized by mass spectra,infrared spectra,proton NMR and elemental analyses.The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control.Most of all target compounds exhibited more than 45%inhibition at 10μmol/L.The preliminary structureactivity relationship was the bromine atoms and the hydroxyl group at the phenyl ring at the C6 position of the parent nucleus played significant roles in the AChE inhibitory activity of the target compounds.

Quercetin-3-O-β-D-glucuronide Inhibits Mitochondria Pathway-mediated Platelet Apoptosis via the Phosphatidylinositol-3-kinase/AKT Pathway in Immunological Bone Marrow Failure

Objective: Quercetin-3-O-β-D-glucuronide(QG) can alleviate immunological bone marrow failure(BMF) by increasing platelet counts. However, the principal mechanism is less known. This study aimed at deciphering the possible underlying mechanism of QG that is indicated in thrombocytopenic purpura. Methods: In vitro and in vivo experiments were carried out for investigating the mechanism behind QG-facilitated inhibition of mitochondrial pathway-mediated excessive apoptosis of platelets through the phosphatidylinositol-3-kinase(PI3K)/AKT pathway. Results: Our results revealed that QG, the main effective ingredient of Herba Sarcandrae, increases the number of platelets and decreases the expression of Bax, Bad, Bid, and caspase-9 in immunological BMF, indicating the inhibition of mitochondrial pathway-mediated apoptosis. Moreover, we found that the protein and m RNA expressions, as well as the phosphorylated levels of PI3K and AKT, were increased significantly by QG, suggesting the activation of the PI3K/AKT pathway. Furthermore, the inhibition of the PI3K/AKT pathway by LY294002 antagonizes the effects of QG on platelet counts and mitochondrial pathway-mediated apoptosis. Conclusion: We demonstrate that QG inhibits the mitochondria pathway-mediated platelet apoptosis via the PI3K/AKT pathway in immunological BMF. This study thus sheds light on exploring the possible regulatory mechanism of traditional Chinese medicine in the treatment of thrombocytopenia induced by BMF.

Synthesis and biological evaluation of indole-3-carboxamide derivatives as antioxidant agents

Oxidative stress results in various pathologies and as consequence antioxidant agents have attracted uninterrupted attention.In this paper,a novel series of indole-3-carboxamide derivatives(6 a-61) were designed and synthesized based on the melatonin structure as novel antioxidants.All of them were evaluated for the antioxidant activities in vitro against human neuroblastoma SH-SY5 Y cell line using H2 O2 radical scavenging assay.The target compounds 6 a,6 f and 6 i indicated better activities than the positive control,ascorbic acid,and 6 a exhibited the best antioxidant activity.In addition,the structureactivity relationships of the target compounds were also preliminarily summarized based on the obtained experimental data.