JD-02, a novel Hsp90 inhibitor, induces ROS/SRC axis-dependent cytoprotective autophagy in colorectal cancer cells.

Heat shock protein 90 (Hsp90) is a tumor marker that accelerates cancer growth by disrupting protein homeostasis. However, concerns such as low clinical efficacy and drug resistance continue to be obstacles to the successful marketing of Hsp90 inhibitors. The cytoprotective function of autophagy has been identified as one of the mechanisms by which tumor cells gain resistance to chemotherapy. JD-02 was identified as a new Hsp90 inhibitor that suppressed colorectal cancer (CRC) growth by lowering client protein levels in vivo and in vitro. We found that JD-02 increased cellular autophagy, which inhibited apoptosis. JD-02 enhanced cytoprotective autophagy and regulated apoptotic suppression by increasing intracellular reactive oxygen species and inhibiting SRC protein levels, as demonstrated by quantitative proteomics, bioinformatic analysis, western blotting, and flow cytometry. This effect was reversed by autophagy inhibition. Therefore, due to the synergistic effects of Hsp90 and autophagy inhibitors in efficiently activating apoptotic pathways, they could potentially serve as promising therapeutic options for CRC.

Reduced pests, improved grain quality and greater total income: benefits of intercropping rice with Pontederia cordata.

BACKGROUND: Intercropping, which is growing two or more different crops in the same field simultaneously, is an effective traditional agricultural practice for productivity, resource utilization, and pest control. However, study on intercropping in paddy fields is limited. So in this study, field experiments of 2 years/four seasons (early and late seasons in 2016 and 2017) were conducted to examine the effects of rice-Pontederia cordata intercropping on rice plant growth, pest control, yield, income, and grain quality. RESULTS: We found rice-P. cordata intercropping significantly decreased the occurrence of rice diseases and pests, with a 22.0-45.9% reduction in sheath blight and a 33.8-34.4% reduction in leaf folders. The mean land equivalent ratio (LER) (1.09) result indicates that intercropping rice and P. cordata generated positive yield effects. In addition, due to the economic profit from the replacement stripe of P. cordata in the rice paddy field, intercropping rice with P. cordata could greatly enhance farmer income. The average total income of rice intercropped with P. cordata was 2.5-fold higher than that of rice monoculture. Furthermore, intercropping significantly improved grain quality compared with the rice monoculture. It significantly increased the milled rice rate and whole milled rice rate by 11.2% and 12.8%, respectively, but decreased the chalky rice rate by 30.9-39.8% and chalkiness degree by 32.2%. CONCLUSIONS: We suggest that rice-P. cordata intercropping provides an environmentally effective way to control rice diseases and pests, results in higher overall productivity and total income, and improves grain quality. © 2021 Society of Chemical Industry.

SHOX CNE9/10 Knockout in U2OS Osteosarcoma Cells and Its Effects on Cell Growth and Apoptosis.

BACKGROUND Osteosarcoma is a common malignant tumor of musculoskeletal stromal cells. Osteosarcoma clinical behavior depends mostly on the histologic grade, the site of primary tumor, the response to chemotherapy, and the presence of pulmonary metastases. The aim of this study was to knockout SHOX CNE9/10 in U2OS osteosarcoma cells and to analyze the effects on cell growth and apoptosis. MATERIAL AND METHODS U2OS cells with CNE9 knockout and U2OS cells with CNE10 knockout were established via the CRISPR/Cas9 system. Sanger sequencing was used to detect the success of the knockdown experiment. Western blotting and quantitative polymerase chain reaction were used to detect the expression levels of short stature homeobox-containing gene (SHOX) protein and messenger RNA (mRNA) after knockdown of CNE9 and CNE10. The cell viability and apoptotic rate were detected by the Cell Counting Kit-8 method and by flow cytometry. RESULTS The Sanger sequencing results showed that the knockdown experiment was successful. The levels of SHOX mRNA and protein were significantly reduced after knocking down CNE9 and CNE10. Knockdown of CNE9 and CNE10 significantly increased the growth and inhibited the apoptosis of U2OS osteosarcoma cells. CNE9/CNE10 knockdown U2OS cells were successfully constructed. CONCLUSIONS Knockdown of CNE9 and CNE10 promoted U2OS cell growth and inhibited apoptosis by decreasing SHOX expression. This CNE9/CNE10 knockout U2OS cell model could provide a bridge for the research on SHOX and CNEs in osteosarcoma.

Silencing of SOCS-1 and SOCS-3 suppresses renal interstitial fibrosis by alleviating renal tubular damage in a rat model of hydronephrosis.

Our study was performed to elucidate how SOCS-1/3 silencing suppresses renal interstitial fibrosis (RIF) by alleviating renal tubular damage in rat models affected by hydronephrosis. Male Wistar rats were randomly selected to establish hydronephrosis rat model, after which all rats were classified into normal, model, negative control (NC), siRNA-SOCS-1, siRNA-SOCS-3, and siRNA-SOCS-1 + siRNA-SOCS-3 groups. The levels of urine protein, serum creatinine (Scr), and blood urea nitrogen (BUN) were detected. ELISA was performed to determine levels of cystatin (CysC), ß2-microglobulin (ß2-MG), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. RT-qPCR and Western blotting were used for mRNA and protein expressions of SOCS-1, SOCS-3, α-smooth muscle actin (α-SMA), and transforming Growth Factor (TGF)-ß1. Compared with the normal group, the levels of Scr, BUN, urine protein, NAG, CysC, ß2-MG, IL-6, and TNF-α were increased in other groups, as well as elevated mRNA and protein expressions of SOCS-1, SOCS-3, α-SMA, and TGF-ß1. The siRNA-SOCS-1, siRNA-SOCS-3, and siRNA-SOCS-1 + siRNA-SOCS-3 groups were found with decreased levels of Scr, BUN, urine protein, NAG, CysC, ß2-MG, IL-6, and TNF-α, as well as mRNA and protein expressions of SOCS-1, SOCS-3, α-SMA, and TGF-ß1, including positive rates of SOCS-1 and SOCS-3 proteins in comparison with the model and NC groups. In comparison with the siRNA-SOCS-1 and siRNA-SOCS-3 groups, the siRNA-SOCS-1 + siRNA-SOCS-3 group exhibited decreased levels of Scr, BUN, urine protein, NAG, CysC, ß2-MG, IL-6, and TNF-α. Our study demonstrated that silencing of SOCS-1/3 may suppress RIF by alleviating the renal tubular damage in rat models affected by hydronephrosis.

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure.

The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8-12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health.

Exposure to Chronic Mild Stress Differentially Alters Corticotropin-Releasing Hormone and Arginine Vasopressin mRNA Expression in the Stress-Responsive Neurocircuitry of Male and Female Rats Prenatally Exposed to Alcohol.

BACKGROUND: Prenatal alcohol exposure (PAE) results in dysregulation of the offspring hypothalamic-pituitary-adrenal (HPA) axis, increasing sensitivity to stressors and vulnerability to stress-related disorders. We have previously shown that exposure to chronic mild stress (CMS) in adulthood significantly increases anxiety-like behaviors (elevated plus maze) in PAE males and females compared to controls. To explore neurobiological mechanisms linking HPA dysregulation and altered anxiety-like behavior, we investigated neuropeptide (corticotropin-releasing hormone [CRH] and arginine vasopressin [AVP]) expression in brain areas involved in the stress neurocircuitry of animals from this previous behavioral study. METHODS: Adult PAE, pair-fed (PF), and ad libitum fed control (C) male and female offspring exposed to CMS or remaining undisturbed (non-CMS) were terminated 30 minutes following behavioral testing. RESULTS: In the paraventricular nucleus, CMS increased CRH mRNA levels in PAE compared to PF and C males and increased AVP mRNA levels in PAE compared to C males, with no differential effects for CRH or AVP in females. In the central nucleus of the amygdala, there was an increase in CRH mRNA expression overall, regardless of CMS condition or sex, in PAE compared to C animals. Moreover, in PF males, CMS increased AVP mRNA levels in the paraventricular nucleus, resulting in a decreased CRH/AVP ratio compared to PAE males, and decreased amygdala CRH mRNA compared to that in the non-CMS condition. CONCLUSIONS: CMS differentially altered central HPA peptide expression in PAE and PF animals compared to their control counterparts, with a possible shift toward greater CRH mediation of HPA regulation in PAE males, and greater AVP mediation of HPA regulation in PF males. However, changes in CRH and AVP expression do not align fully with the anxiogenic profile observed in our previous behavior study, suggesting that other neuronal substrates and limbic forebrain regions also contribute to increased anxiety-like behavior following CMS.

Fiber-optic drug delivery strategy for synergistic cancer photothermal-chemotherapy.

Chemotherapy is one of the conventional treatments for cancer in clinical practice. However, poor delivery efficiency, systemic toxicity, and the lack of pharmacokinetic monitoring during treatment are the critical limitations of current chemotherapy. Herein, we reported a brand-new antitumor drug delivery strategy that harnesses an optical fiber endoscopically therapeutic probe. The fiber probe carries photosensitizers in the fiber core and antitumor agents on the fiber surface mediated by a temperature-responsive hydrogel film, giving rise to an activable photothermal-chemotherapy that orchestrates the localized hyperthermia and thermal-stimuli drug release to the tumor lesion. Furthermore, the dynamical drug release and in-situ temperature can be real-time supervised through the built-in fiber sensors, including the reflective Mach-Zehnder interferometer and fiber Bragg grating, to visualize the therapy process and thus improve the safety of treatment. Compared with conventional methods, the fiber-optic drug delivery can adequately take advantage of the chemotherapeutics through collaboratively recruiting the photoheating-mediated enhanced permeability and the hydrogel particle-assisted high drug retention, shedding new light on a "central-to-peripheral" drug pervasion and retention mechanism to destroy tumors completely. The fiber-optic chemotherapy strategy incorporates precise drug delivery, accurate controllability of drug release, high drug permeability and retention in tumor, low off-target rate, and real-time drug release and temperature feedback, performing a straightforward and precise photothermal-chemotherapy pathway. More than that, the proposed strategy holds tremendous promise to provide a revolutionized on-demand drug delivery platform for the highly efficient evaluation and screening of antitumor pharmaceuticals.

Prenatal ethanol exposure delays the onset of spermatogenesis in the rat.

BACKGROUND: During late prenatal and early postnatal life, the reproductive system in males undergoes an extensive series of physiological and morphological changes. Prenatal ethanol (EtOH) exposure has marked effects on the development of the reproductive system, with long-term effects on function in adulthood. The present study tested the hypothesis that prenatal EtOH exposure will delay the onset of spermatogenesis. METHODS: Development of the seminiferous tubules and the onset of spermatogenesis were examined utilizing a rat model of fetal alcohol spectrum disorder (FASD). Male offspring from ad libitum-fed control (C), pair-fed (PF), and EtOH-fed (prenatal alcohol exposure [PAE]) dams were terminated on postnatal (PN) days 5, 15, 18, 20, 25, 35, 45, and 55, to investigate morphological changes through morphometric analysis of the testes from early neonatal life through young adulthood. RESULTS: PAE males had lower relative (adjusted for body weight) testis weights compared with PF and/or C males from PN15 through puberty (PN45). In addition, fewer gonocytes (primordial germ cells) were located on the basal lamina on PN5, while more of those touching the basal lamina were dividing in PAE compared with PF and C males, suggesting delayed cell division and migration processes. As well, the percentage of tubules with open lumena was lower in PAE compared with PF and C males on PN18 and 20, and PAE males had fewer primary spermatocytes per tubule on PN18 and round spermatids per tubule on PN25 compared with C males. Finally, the percentage of tubules at stages VII and VIII, when mature spermatids move to the apex of the epithelium and are released, was lower in PAE compared with PF and/or C males in young adulthood (PN55). CONCLUSIONS: Maternal EtOH consumption appears to delay both reproductive development and the onset of spermatogenesis in male offspring, with effects persisting at least until young adulthood.

Preparation and Characterization of Gluten/SDS/Chitosan Composite Hydrogel Based on Hydrophobic and Electrostatic Interactions.

Gluten is a natural byproduct derived from wheat starch, possessing ideal biocompatibility. However, its poor mechanical properties and heterogeneous structure are not suitable for cell adhesion in biomedical applications. To resolve the issues, we prepare novel gluten (G)/sodium lauryl sulfate (SDS)/chitosan (CS) composite hydrogels by electrostatic and hydrophobic interactions. Specifically, gluten is modified by SDS to give it a negatively charged surface, and then it conjugates with positively charged chitosan to form the hydrogel. In addition, the composite formative process, surface morphology, secondary network structure, rheological property, thermal stability, and cytotoxicity are investigated. Moreover, this work demonstrates that the change can occur in surface hydrophobicity caused by the pH-eading influence of hydrogen bonds and polypeptide chains. Meanwhile, the reversible non-covalent bonding in the networks is beneficial to improving the stability of the hydrogels, which shows a prominent prospect in biomedical engineering.

Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltration.

Background: Autophagy plays a critical role in the progression of osteoarthritis (OA), mainly by regulating inflammatory and immune responses. However, the underlying mechanisms remain unclear. This study aimed to investigate the potential relevance of autophagy-related genes (ARGs) associated with infiltrating immune cells in OA. Methods: GSE114007, GSE169077, and ARGs were obtained from the Gene Expression Omnibus (GEO) database and the Human Autophagy database. R software was used to identify the differentially expressed autophagy-related genes (DEARGs) in OA. Functional enrichment and protein-protein interaction (PPI) analyses were performed to explore the role of DEARGs in OA cartilage, and then Cytoscape was utilized to screen hub ARGs. Single-sample gene set enrichment analysis (ssGSEA) was used to conduct immune infiltration analysis and evaluate the potential correlation of key ARGs and immune cell infiltration. Then, the expression levels of hub ARGs in OA were further verified by the GSE169077 and qRT-PCR. Finally, Western blotting and immunohistochemistry were used to validate the final hub ARGs. Results: A total of 24 downregulated genes and five upregulated genes were identified, and these genes were enriched in autophagy, mitophagy, and inflammation-related pathways. The intersection results identified nine hub genes, namely, CDKN1A, DDIT3, FOS, VEGFA, RELA, MAP1LC3B, MYC, HSPA5, and HSPA8. GSE169077 and qRT-PCR validation results showed that only four genes, CDKN1A, DDT3, MAP1LC3B, and MYC, were consistent with the bioinformatics analysis results. Western blotting and immunohistochemical (IHC) showed that the expression of these four genes was significantly downregulated in the OA group, which is consistent with the qPCR results. Immune infiltration correlation analysis indicated that DDIT3 was negatively correlated with immature dendritic cells in OA, and FOS was positively correlated with eosinophils. Conclusion: CDKN1A, DDIT3, MAP1LC3B, and MYC were identified as ARGs that were closely associated with immune infiltration in OA cartilage. Among them, DDIT3 showed a strong negative correlation with immature dendritic cells. This study found that the interaction between ARGs and immune cell infiltration may play a crucial role in the pathogenesis of OA; however, the specific interaction mechanism needs further research to be clarified. This study provides new insights to further understand the molecular mechanisms of immunity involved in the process of OA by autophagy.

Prenatal alcohol exposure alters the course and severity of adjuvant-induced arthritis in female rats.

Prenatal alcohol exposure (PAE) has adverse effects on the development of numerous physiological systems, including the hypothalamic-pituitary-adrenal (HPA) axis and the immune system. HPA hyper-responsiveness and impairments in immune competence have been demonstrated. The present study investigated immune function in PAE females utilizing an adjuvant-induced arthritis (AA) model, widely used as a model of human rheumatoid arthritis. Given the effects of PAE on HPA and immune function, and the known interaction between HPA and immune systems in arthritis, we hypothesized that PAE females would have heightened autoimmune responses, resulting in increased severity of arthritis, compared to controls, and that altered HPA activity might play a role in the immune system changes observed. The data demonstrate, for the first time, an adverse effect of PAE on the course and severity of AA in adulthood, indicating an important long-term alteration in functional immune status. Although overall, across prenatal treatments, adjuvant-injected animals gained less weight, and exhibited decreased thymus and increased adrenal weights, and increased basal levels of corticosterone and adrenocorticotropin, PAE females had a more prolonged course of disease and greater severity of inflammation compared to controls. In addition, PAE females exhibited blunted lymphocyte proliferative responses to concanavalin A and a greater increase in basal ACTH levels compared to controls during the induction phase, before any clinical signs of disease were apparent. These data suggest that prenatal alcohol exposure has both direct and indirect effects on inflammatory processes, altering both immune and HPA function, and likely, the normal interactions between these systems.

Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal function across the estrous cycle.

BACKGROUND: Rats prenatally exposed to ethanol (E) typically show increased hypothalamic-pituitary-adrenal (HPA) responses to stressors in adulthood. Importantly, prenatal ethanol may differentially alter stress responsiveness in male and female offspring, suggesting a role for the gonadal hormones in mediating the effects of ethanol on HPA activity. We investigated the role of ethanol-induced changes in hypothalamic-pituitary-gonadal (HPG) activity in the differential HPA regulation observed in E compared to control females across the estrous cycle. METHODS: Peripheral hormones and changes in central neuropeptide mRNA levels were measured across the estrous cycle in adult female offspring from E, pair-fed (PF) and ad libitum-fed control (C) dams. RESULTS: Ethanol females showed normal estrous cyclicity (vaginal smears) but delayed sexual maturation (vaginal opening). Both HPG and HPA activity were differentially altered in E (and in some cases, PF) compared to control females as a function of estrous cycle stage. In relation to HPG activity, E and PF females had higher basal and stress estradiol (E(2)) levels in proestrus compared to other phases of the cycle, and decreased GnRH mRNA levels compared to C females in diestrus. Further, E females had greater variation in LH than PF and C females across the cycle, and in proestrus, only E females showed a significant LH increase following stress. In relation to HPA activity, both basal and stress CORT levels and overall ACTH levels were greater in E than in C females in proestrus. Furthermore, AVP mRNA levels were increased overall in E compared to PF and C females. CONCLUSIONS: These data demonstrate ethanol-induced changes in both HPG and HPA activity that are estrous phase-specific, and support the possibility that changes in HPA activity in E females may reflect differential sensitivity to ovarian steroids. E females appear to have an increased HPA sensitivity to E(2), and a possible shift toward AVP regulation of HPA activity. That PF were similar to E females on some measures suggests that nutritional effects of diet or food restriction played a role in mediating at least some of the changes observed.

Targeting redox-altered plasticity to reactivate synaptic function: A novel therapeutic strategy for cognitive disorder

Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity

Status of treatment for atrial fibrillation in a community health service center in Shanghai Pudong New Area / 中华全科医师杂志

Objective To analyze the status of the treatment for atrial fibrillation (AF) in a community health service center in Shanghai Pudong New Area. Methods Clinical data of all patients with AF attended in Hudong Community Health Service Center of Shanghai Pudong from August 2016 to August 2017 were retrospectively reviewed. The gender,age,smoking history,drinking history,concomitant diseases, antithrombotic therapy, rhythm control, ventricular rate control drugs, health education, needs for setting up AF clinics in the community were analyzed. Result The study included 220 patients,with average age of (59.7±10.4) years; 34.1％(75/220)patients had hypertension and the blood pressure was controlled in 41.3％(31/75); 20.5％(45/220)patients had diabetes mellitus and glycosylated hemoglobin(HbA1c)was controlled well in 26.7％(12/45). Three cases of mitral stenosis were treated with warfarin anticoagulation. Among 217 patients without valvular atrial fibrillation,157 had thromboembolic risk score≥2,20.4％ (32/157) of whom used warfarin anticoagulation,10.8％ (17/157) used new oral anticoagulant (NOAG) and 58.1％ (91/157) had never used warfarin or NOAG anticoagulation. The reasons were as follows:doctors did not prescribe (41.9％, 39/91),patients did not accept (35.2％,32/91), and so on. There were 21.8％ (48/220) of patients undergoing drug cardioversion,and 5.9％ (13/220) undergoing electrical cardioversion. For control of ventricular rate, 55.9％ (123/220) patients used beta blockers,13.6％ (30/220) used non?dihydropyridine calcium antagonists, and 23.6％ (52 / 220) used digitalise. Less than 55％ of patients were given health education of physical exercise,weight management and medicine use. For AF clinic in community hospital,56.8％ (125/220) of patients needed,and 17.3％ (38/220) very need; 50.0％ (110/220) patients trusted and 12.3％ (27/220) very trusted in anticoagulation management in community hospitals. Conclusion The anticoagulant rate is relatively low, treatment of concomitant diseases is less satisfactory and the health education might be incomplete in the community surveyed in this study.

Effects of the novel poly(methyl methacrylate) (PMMA)-encapsulated organic ultraviolet (UV) filters on the UV absorbance and in vitro sun protection factor (SPF).

Sunscreens are thought to protect skin from many of the harmful effects of ultraviolet (UV) light and the photostability of sunscreens is thus an important concern in their application. Therefore, to discover new UV filters or to modify well-known UV filters are presents an important way for development of sunscreens. In this study, we presented several novel poly(methyl methacrylate) (PMMA) encapsulated organic UV filters, including encapsulated benzophenone-3 (TB-MS), avobenzone (TA-MS), octyl methoxycinnamate (TO-MS) and diethylamino hydroxybenzoyl hexyl benzoate (TD-MS). Our results have demonstrated that PMMA-encapsulated UV filters have improved safety, photoprotective ability and photostability. We proposed therefore that these PMMA-encapsulated UV filters can be used as ingredients for sunscreen products in the future.

Research progress on food literacy assessment tools for children and adolescents / 中国学校卫生

Abstract@#As dietary issues of children and adolescents become increasingly complex, the assessment of food literacy (FL) is increasingly importance. FL involves a comprehensive cognition and practical ability concerning food among children, playing a key role in fostering healthy eating habits and improving health levels. The article explores the definition and connotations of FL, and introduces eight FL assessment tools in terms of theoretical foundations, dimensions, assessment methods, and their reliability and validity. Moreover, it provides a comparative analysis of these tools by examining their dimensional design, evaluation indicators, strengths, and weaknesses, as well as their applicable subjects and scenarios, aiming to offer references for implementing relevant policies and developing more comprehensive and effective FL assessment tools.

The Analysis on the Influence Factors of Commercial Health Insurance Demand Based on the Model of Cross-sectional Fixed Effect / 中国卫生经济

Objective:To analyze the main influencing factors of China's commercial health insurance demand and promote the development of China's health service industry.Methods:Based on the panel data of 31 provinces and cities in China from 2009 to 2015,the model of cross-sectional fixed effect was constructed to conduct empirical analysis on the main influencing factors of China's commercial health insurance demand.Result and Conclusion:More significant influences on commercial health insurance demand factors were urban per capita disposable income,per capita urban employee basic medical insurance fund income,elderly population bring-up ratio and per capita outpatient expenses.For the basic medical insurance of urban employees,the urban employee medical insurance had significant effect on the demand of commercial health insurance.For the basic medical insurance of urban residents,the income impact was more prominent.The proportion of graduates of general institutions of higher learning had few influence commercial health insurance.

Survey on knowledge level of atrial fibrillation among general practitioners in Shanghai Pudong New Area / 中华全科医师杂志

Objective To survey the knowledge level of atrial fibrillation (AF) among general practitioners (GPs) in Shanghai Pudong New Area.Methods From July to September 2016,a stratified cluster sampling method was used to collect questionnaires from GPs who met the inclusion criteria in 12 community health service centers in Shanghai Pudong New Area.A self-made questionnaire was applied according to Current knowledge and management recommendations of atrial fibrillation-2015,which included 5 domains:antithrombotic therapy,rhythm control,ventricular rate control and evaluation of the guideline.Results A total of 377 questionnaires were distributed,and 371 were recovered.Among 371 participants there were 151 males and 220 females aged (41.3±8.3) years,including 156 (42.0％) with junior professional titles,158 (42.6％) with intermediate titles,and 57 (15.4％) with senior titles.More than 90％ of participants recognized that age,hypertension,myocardial infarction,and heart valve disease were risk factors of AF.For patient evaluation,54.2％ (201/371) of participants would use electrocardiogram,47.9％ (1 78/371) would use thyroid function,21.0％ (78/371) would use echocardiography,3.2％ (12/371) would use respiratory sleep monitoring,and 95.4％ (354/371) did not heard of cardiovascular implantable electronic devices.82.2％ (305/ 371) of participants thought rheumatic mitral stenosis,46.4％ (172/371) thought CHA2DS2-VASc score over and 2 and 12.7％ (47/371) thought hypertrophic cardiomyopathy as indications for anticoagulant;and 38.5％ (143/371) of participants rarely used CHA2DS2-VASc.The rhythm conversion would applied for the onset of atrial fibrillation in 42.9％ participants (159/371),for symptoms after the control of ventricular rate in 39.9％ (148/371) participants and for symptomatic patients in 12.7％ participants (47/371).59.8％ (222/371) of participants did not know the anticoagulation therapy for AF cardioversion,44.5％ (165/371) participants had not heard radiofrequency ablation for AF.38.5％ (143/371) of participants knew the Chinese guidelines for AF,of which 45.5％ (65/143) of the GPs used the guidelines;80.4％ (115/143) of the GPs thought the guide was very instructive.GPs with senior professional titles had better mastery of clinical evaluation,antithrombotic therapy,catheter ablation,and awareness of guideline than junior and middle-level general practitioners.Conclusion The survey shows that there is relative lack of knowledge on the risk factors,clinical assessment methods,anticoagulation indications and cardioversion anticoagulation therapy of AF,as well as lack of awareness and application of the AF guideline for GPs in Shanghai Pudong New Area.

Identification and Function of Acid-sensing Ion Channels in RAW 264.7 Macrophage Cells / 华中科技大学学报（医学）（英德文版）

Activation of acid-sensing ion channels (ASICs) plays an important role in neuroinflammation.Macrophage recruitment to the sites of inflammation is an essential step in host defense.ASIC 1 and ASIC3 have been reported to mediate the endocytosis and maturation of bone marrow derived macrophages.However,the expression and inflammation-related functions of ASICs in RAW 264.7 cells,another common macrophage,are still elusive.In the present study,we first demonstrated the presence of ASIC 1,ASIC2a and ASIC3 in RAW 264.7 macrophage cell line by using reverse transcriptase polymerase chain reaction (RT-PCR),Western blotting and immunofluorescence experiments.The non-specific ASICs inhibitor amiloride and specific homomeric ASIC 1 a blocker PcTx 1 reduced the production of iNOS and COX-2 by LPS-induced activating RAW 264.7 cells.Furthermore,not only amiloride but also PcTx 1 inhibited the migration and LPS-induced apoptosis of RAW 264.7 cells.Taken together,our findings suggest that ASICs promote the inflammatory response and apoptosis of RAW 264.7 cells,and ASICs may serve as a potential novel target for immunological disease therapy.

Identification and Function of Acid-sensing Ion Channels in RAW 264.7 Macrophage Cells / 华中科技大学学报（医学）（英德文版）

Activation of acid-sensing ion channels (ASICs) plays an important role in neuroinflammation.Macrophage recruitment to the sites of inflammation is an essential step in host defense.ASIC 1 and ASIC3 have been reported to mediate the endocytosis and maturation of bone marrow derived macrophages.However,the expression and inflammation-related functions of ASICs in RAW 264.7 cells,another common macrophage,are still elusive.In the present study,we first demonstrated the presence of ASIC 1,ASIC2a and ASIC3 in RAW 264.7 macrophage cell line by using reverse transcriptase polymerase chain reaction (RT-PCR),Western blotting and immunofluorescence experiments.The non-specific ASICs inhibitor amiloride and specific homomeric ASIC 1 a blocker PcTx 1 reduced the production of iNOS and COX-2 by LPS-induced activating RAW 264.7 cells.Furthermore,not only amiloride but also PcTx 1 inhibited the migration and LPS-induced apoptosis of RAW 264.7 cells.Taken together,our findings suggest that ASICs promote the inflammatory response and apoptosis of RAW 264.7 cells,and ASICs may serve as a potential novel target for immunological disease therapy.