The SMAD2/miR-4256/HDAC5/p16^(INK4a) signaling axis contributes to gastric cancer progression

The dysregulation of exosomal microRNAs(miRNAs)plays a crucial role in the development and progression of cancer.This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer(GC)and the underlying mechanisms.The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics.Next,the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues,and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments.Then,the effect of miR-4256 on its downstream target genes HDAC5/p16^(INK4a) was studied in GC cells,and the underlying mechanisms were evaluated using dual luciferase reporter assay and Chromatin Immunoprecipitation(ChIP).Additionally,the role of the miR-4256/HDAC5/p16^(INK4a) axis in GC was studied using in vitro and in vivo experiments.Finally,the upstream regulators SMAD2/p300 that regulate miR-4256 expression and their role in GC were explored using in vitro experiments.miR-4256 was the most significantly upregulated miRNA and was overexpressed in GC cell lines and GC tissues;in vitro and in vivo results showed that miR-4256 promoted GC growth and progression.Mechanistically,miR-4256 enhanced HDAC5 expression by targeting the promoter of the HDAC5 gene in GC cells,and then restrained the expression of p16^(INK4a) through the epigenetic modulation of HDAC5 at the p16INK4a promoter.Furthermore,miR-4256 overexpression was positively regulated by the SMAD2/p300 complex in GC cells.Our data indicate that miR-4256 functions as an oncogene in GC via the SMAD2/miR-4256/HDAC5/p16^(INK4a) axis,which participates in GC progression and provides novel therapeutic and prognostic biomarkers for GC.

Annual cost of illness of stomach and esophageal cancer patientsin urban and rural areas in China： A multi-center study

Objective： Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereasthere were few studies on the financial burden of the two cancers.Methods： Costs per hospitalization of all patients with stomach or esophageal cancer discharged betweenSeptember 2015 and August 2016 in seven cities/counties in China were collected, together with their demographicinformation and clinical details. Former patients in the same hospitals were sampled to collect information onannual direct non-medical cost, indirect costs and annual number of hospitalization. Annual direct medical cost wasobtained by multiplying cost per hospitalization by annual number of hospitalization. Annual cost of illness （ACI）was obtained by adding the average value of annual direct medical cost, direct non-medical cost and indirect cost,stratified by sex, age, clinical stage, therapy and pathologic type in urban and rural areas. Costs per hospitalizationwere itemized into eight parts to calculate the proportion of each part. All costs were converted to 2016 US dollars（1 USD：6.6423 RMB）.Results： Totally 19,986 cases were included, predominately male. Mean ages of stomach cancer and urbanpatients were lower than that of esophageal cancer and rural patients. ACI of stomach and esophageal cancerpatients were $10,449 and $13,029 in urban areas, and $2,927 and $3,504 in rural areas, respectively. Greater ACIwas associated with male, non-elderly patients as well as those who were in stage I and underwent surgeries.Western medicine fee took the largest proportion of cost per hospitalization.Conclusions： The ACI of stomach and esophageal cancer was tremendous and varied substantially among thepopulation in China. Preferential policies of medical insurance should be designed to tackle with this burden andfurther reduce the health care inequalities.

Study on Extraction Technology of Theabrownine from Liubao Tea and Its Antioxidant Activity

[ Objective] This study aimed to provide theoretical reference for the extraction of theabrownine from Liubao tea, determination of the biological activity, and development and utilization of theabrownine. [Method] Orthogonal experimental design was adopted to investigate the effects of solid-liquid ratio, extraction temperature, extraction duration, and extraction frequency on the yield of theabrownine extracted from Liubao tea. The extraction technology was optimized, and the antioxidant activity of theabrownine was analyzed. [ Result] The results showed that extraction frequency and extraction temperature had significant effects on the yield of theabrownine extracted from Liubao tea, while solid-liquid ratio and extraction duration had no significant effect. The optimal conditions for extracting theabrownine from Liubao tea were determined as follows ： solid-liquid ratio was 1 ： 30, extraction temperature was 100℃, extraction duration was 80 min, and extraction frequency was 4 times. Under these conditions, the yield of theabrownine reached 22.92%. Results of antioxidant activity determination showed that hydroxyl radical-scavenging activity of theabrownine was as high as 74%, and the scavenging effects was significantly higher than that of Vitamin C under low concentrations; nitroso-scavenging activity of theabrownine reached 73%, with no significant difference from that of Vitamin C; superoxide anion free radical-scavenging activity of theabrownine could be above 60%, which was lower than that of Vitamin C. [Condusion] Liubao tea contains abundant theabrownine that has relatively high antioxidant activity with good prospects in antioxidant application, which lays solid foundation for in-depth development of Liubao tea.

Case of catatonia misdiagnosed with coma

Catatonia is a state of high-degree psychomotor inhibition in which patients often maintain a constant fixed posture,and generally have unconscious obstacles and various reflex preservation.Patients suffering from severe catatonia will become stiff.Catatonia generally manifests unconsciousness while various reflexes are preserved.Patients show reticence,no food or drink intake,and immobility as signs of complete suppression of speech and movement,and even incontinence.Patients are often first diagnosed in non-psychiatric departments and are more likely to be misdiagnosed as having‘coma’or‘epilepsy,,thus delaying treatment.This article reports a case of a 19-year-old female patient who was misdiagnosed with'catatonia'.A month ago,she was admitted to a general hospital of our city because of"intermittent attacks of nausea,vomiting,stupor for 15 years,with one week of exacerbation".During her hospitalisation,she suddenly appeared was mute,had no food or drink intake,and showed immobility and incontinence,presenting a'coma state'.She was transferred to a general hospital in Wuhan to further investigate the cause of her"coma".After 7 days in the hospital,no abnormal examination results were found and the symptoms were not alleviated.Later,she was transferred to the mental health centre for hospitalisation in this city.The patient was diagnosed as having(1)‘epileptic psychosis’and(2)‘catatonic stupor*.After 3 days of treatment,the patient's recovered consciousness.She was clinically cured and discharged half a month later.We hereby report this case.

甘肃省乡村振兴组态路径和发展模式

乡村振兴是实现省域高质量发展的重要环节,是打破城乡二元差异的重大战略部署。甘肃省乡村振兴受多维条件影响,为明晰影响其机制的核心条件与边缘条件,依据TOE(技术-组织-环境)理论框架,运用模糊集定性比较分析方法,深入探究甘肃省14个市州乡村振兴的内在机理与因素组合,对影响乡村振兴的5条组态路径展开分析,归纳出2种发展模式——TOE框架下数字技术引领型模式和TOE框架下政府引领型模式。为加快构建甘肃省乡村振兴发展新引擎,缩小城乡发展差距,应以数字技术嵌入乡村发展,打造和美甘肃乡村名片。应运用规制与激励手段加强基层组织建设,尤其要强化村民委员会主任书记兼任政策,优化组织利益链条,在巩固脱贫攻坚成果的基础上推动乡村振兴。

Circulating endothelial microvesicles and their carried miR-125a 5p:potential biomarkers for ischaemic stroke

Background Endothelial microvesicles(EMVs)are closely associated with the status of endothelial cells(ECs).Our earlier study has shown that EMVs could exert protective roles in ECs by transferring their carried miR-125a 5p.However,whether circulating EMVs and their carried miR-125a 5p can be used as biomarkers in ischaemic stroke(IS)are remain unknown.Methods We recruited 72 subjects with IS,60 subjects with high stroke risk and 56 age-matched controls.The circulating EMVs and their carried miR-125a 5p(EMV-miR 125a 5p)levels were detected.We used microRNA(miR)array to study expression changes of miRs in plasma EMVs samples of three IS patients and three matched healthy controls.Transient middle cerebral artery occlusion(tMCAO)was used to establish IS mouse model.Results EMVs level was obviously elevated in IS patients,with the highest level in acute stage,and was positively related to carotid plaque,carotid intima-media thickness(IMT),National Institutes of Health Stroke Scale(NIHSS),infarct volume.On the contrary,we observed that EMV-miR 125a 5p level was obviously reduced in IS,with the lowest level in acute stage,and was negatively correlated with carotid plaque,IMT,NIHSS scores,infarct volume.EMVs and EMV-miR 125a 5p levels were closely related with large artery atherosclerosis subgroup.Importantly,EMVs and EMV-miR 125a 5p levels could serve as independent risk factors,and receiver operating characteristic curve achieved an area under curve(AUC)of 0.720 and 0.832 for IS,respectively,and elevated to 0.881 after their combination.In IS mouse model,control EMVs or n-EMVs administration could decrease the infarct volume and neurological deficit score,while increase the cerebral blood flow of IS mice compared with vehicle group,while IS EMVs or oxygen and glucose deprivation(OGD)-EMVs administration aggravated the tMCAO induced ischaemic injury.In addition,we observed that OGD EMVmiR-125a 5p could partially ameliorate the OGD EMVs induced brain injury after IS.Conclusions These findings demonstrate that circulating EMVs and EMV-miR 125a 5p are closely related with the occurrence,progress,subtypes and severity of IS,and they can serve as innovative biomarkers and therapeutic targets for IS,especially when they are combined.

Strategies to improve the migration of mesenchymal stromal cells in cell therapy

Mesenchymal stromal/stem cells(MSCs) are multipotent cells under consideration as a potential new therapy for a variety of inflammatory diseases including certain neurological disorders. It is generally thought that the efficacy of cell therapy in attenuating damage after ischemia, inflammation, or injury depends on the quantity of transplanted cells recruited to the target tissue. However, only a small number of systematically infused MSCs can effectively migrate to target sites, which significantly decreases the efficacy of exogenous cell-based therapy. In this review, we discuss specific factors influencing MSC migration, and summarize current strategies that effectively promote the motility of MSCs. In addition, we describe several protocols to improve the migration of stromal cells into the nervous system and, therefore,enhance the efficiency of engraftment as means of treating neurological disorders.