[Establishment of acute graft-versus-host disease model after non-myeloablative haploidentical peripheral blood stem cell transplantation in aged mice].

Objective: To establish an acute graft-versus-host disease (aGVHD) model in aged mice after non-myeloablative haploidentical peripheral blood stem cell transplantation (haplo-PSCT). Methods: C57BL/6 (H-2b) male mice aged 6-8 weeks were used as donor mice, and CB6F1 (H-2b×d) female mice aged 14-16 months were used as recipient mice. The donor mice were injected subcutaneously with rehuman granulocyte-colony stimulating factor (rhG-CSF) 5 days before transplantation for hematopoietic stem cell mobilization.The recipient mice were divided into control group (CG), spleen cell low-dose group (SL), spleen cell medium-dose group (SM) and spleen cell high-dose group (SH) according to random number table method, with 16 rats in each group, all of which received total linear accelerator X-ray irradiation (TBI) with a total dose of 6 Gy. Peripheral blood mononuclear cells (PBMC) and spleen cells of different doses (0.5×107/each, 1.0×107/each and 2.0×107/each in SL group, SM group and SH group, respectively) were transfused through the tail vein within 4 hours after TBI, and only the same amount of normal saline was transfused in CG group. After transplantation, the survival and weight changes of mice in each group were observed for 30 days, and the changes of blood routine were monitored regularly. Mice peripheral blood was collected 21 days after transplantation to detect the chimerism rate of the donor. Hematoxylin-eosin staining was performed on the skin, liver and colon of mice 21 days after transplantation to analyze the histopathological changes of aGVHD target organs. Results: All the mice in each group were successfully transplanted. After TBI, the weight and activity of mice in all groups decreased, and the phenomenon of bone marrow suppression appeared. During the observation period, all mice in CG group and SL group survived, 3 mice in SM group died with survival time of (26.0±5.8) days, and 6 mice in SH group died with survival time of (20.9±7.3) days. The body weight of mice in SH group was lower than that in CG group, SL group and SM group 21days after transplantation [(25.0±0.7), (25.5±0.4), (25.0±1.4) vs (20.8±0.8) g, all P<0.05]. Compared with CG group, SL group and SM group, the levels of leukocyte, erythrocyte, hemoglobin and platelet in SH group decreased 21 days after transplantation (all P<0.05). There was no significant difference in donor chimerism rate among SL group, SM group and SH group [(95.8%±0.8%), (95.5%±1.4%) and (95.1%±1.3%), respectively, all P>0.05]. Compared with CG group, SL group and SM group, the tissue structure of aGVHD target organs in SH group was severely damaged, with a large number of inflammatory cells infiltratedand higher histopathological scores than SL group and SM group (all P<0.05). Conclusion: For aging CB6F1 mice, after 6 Gy TBI pretreatment with linear accelerator X-ray, PBMC (1×107/each) and spleen cells (2.0×107/each) were injected to successfully induce aGVHD model after non-myelablative haplo-PSCT.

miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signaling.

INTRODUCTION: Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid ß (Aß)1-42. METHODS: To create a model of AD, SH-SY5Y cells were treated with Aß1-42 and mice received intracerebroventricular injections of Aß1-42. Then, the transcriptional levels of miR-146a were estimated by real-time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and reactive oxygen species (ROS) was studied by using specific inhibitors. Aß and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aß expression was analyzed by immunofluorescence and histochemical examinations. RESULTS: Aß1-42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the animals treated with Aß1-42, in which miR-146a upregulation increased the expression of Aß, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aß deposition and ROS accumulation via the p-p38 signaling pathway. CONCLUSIONS: Our research demonstrates that miR-146a-5pa increases Aß deposition by triggering oxidative stress through activation of MAPK signaling.

miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signalingmi / R-146a empeora el deterioro cognitivo y la patología tipo Alzheimer al promover el estrés oxidativo a través de la vía de señalización MAPK

Introduction: Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid β (Aβ)1–42. Methods: To create a model of AD, SH-SY5Y cells were treated with Aβ1–42 and mice received intracerebroventricular injections of Aβ1–42. Then, the transcriptional levels of miR-146a were estimated by real-time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and reactive oxygen species (ROS) was studied by using specific inhibitors. Aβ and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aβ expression was analyzed by immunofluorescence and histochemical examinations. Results: Aβ1–42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the animals treated with Aβ1–42, in which miR-146a upregulation increased the expression of Aβ, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aβ deposition and ROS accumulation via the p-p38 signaling pathway. Conclusions: Our research demonstrates that miR-146a-5pa increases Aβ deposition by triggering oxidative stress through activation of MAPK signaling.(AU)

Introducción: miR-146a-5p es un elemento regulador clave en la respuesta inmune. Sin embargo, estudios recientes sugieren que miR-146a-5p también está involucrado en el desarrollo de la enfermedad de Alzheimer (EA), aunque aún no se conoce con exactitud el mecanismo por el que esto sucede. Analizamos los efectos de miR-146a en un modelo animal y en células SH-SY5Y expuestas a β-amiloide (Aβ)1-42. Métodos: Tratamos células SH-SY5Y con Aβ1-42 e inyectamos Aβ1-42 en los ventrículos cerebrales de ratones para generar un modelo celular y otro animal de EA. Estimamos los niveles transcripcionales de miR-146a mediante PCR en tiempo real. Al mismo tiempo, transfectamos temporalmente las células y los ratones con imitador/inhibidor de miR-146a-5p para evaluar el papel de miR-146a. Estudiamos el papel de algunas vías de señalización, como la de p38, y los niveles de especies reactivas de oxígeno (ERO) con inhibidores específicos. Los niveles de Aβ y de proteína precursora amiloidea (APP) se determinaron con inmunoblot. También se analizó la expresión de Aβ mediante inmunofluorescencia y análisis histoquímico. Resultados: Las células SH-SY5Y expuestas a Aβ1-42 mostraron altos niveles transcripcionales de miR-146a y APP. La vía de señalización p-38 MAPK y la producción de EROs se activaron al utilizar un imitador de miR-146a-5p. Sin embargo, el bloqueo de miR-146a-5p con un inhibidor redujo los niveles de APP, EROs y p-p38 MAPK. Se observó un fenómeno similar en los ratones tratados con Aβ1-42: la sobrerregulación de miR-146a aumentó la expresión de Aβ, p-p38 y EROs, mientras que la inhibición de miR-146a tuvo el efecto contrario. Esto sugiere que miR-146a está involucrado en el aumento de acumulación de Aβ y de producción de EROs por medio de la vía de señalización p-p38. Conclusiones: Nuestro estudio muestra que miR146a-5p aumenta la acumulación de Aβ al promover el estrés oxidativo a través de la activación de la vía de señalización MAPK.(AU)

Broadband photoresponse arising from photo-bolometric effect in quasi-one-dimensional Ta2Ni3Se8.

In this paper, we report the synthesis of high-quality Ta2Ni3Se8crystals free of noble or toxic elements and the fabrication and testing of photodetectors on the wire samples. A broadband photoresponse from 405 nm to 1550 nm is observed, along with performance parameters including relatively high photoresponsivity (10 mA W-1) and specific detectivity (3.5 × 107Jones) and comparably short response time (τrise= 433 ms,τdecay= 372 ms) for 1064 nm, 0.5 V bias and 1.352 mW mm-2. Through extensive measurement and analysis, it is determined that the dominant mechanism for photocurrent generation is the photo-bolometric effect, which is believed to be responsible for the very broad spectral detection capability. More importantly, the pronounced response to 1310 nm and 1550 nm wavelengths manifests its promising applications in optical communications. Considering the quasi-one-dimensional structure with layered texture, the potential to build nanodevices on Ta2Ni3Se8makes it even more important in future electronic and optoelectronic applications.

[Clinical value of inflammatory biomarkers in predicting prognosis of patients with ureteral urothelial carcinoma].

OBJECTIVE: To evaluate the clinical value of inflammation-related markers in predicting the prognosis of patients with ureteral urothelial carcinoma. METHODS: 200 patients with ureteral urothelial carcinoma were randomly divided into two groups by split sample validation: modeling group and validation group. Paraffin embedded pathological specimens of the patients were reviewed. Immunohistochemical method was used to detect tumor-infiltrating neutrophil (TIN) (CD66b+), tumor-associated macrophage (TAM) (CD163+), lymphocyte (CD+, CD4+, CD8+) counts, peripheral blood neutrophil / lymphocyte ratio (NLR) and tumor tissue neutrophil/monocyte ratio (NMR). According to the results of pathological staging, the patients were divided into non-muscle-invasive and muscle-invasive ureteral urothelial carcinoma group. The resolution of the models was evaluated, and the prognostic nomogram models including only peripheral blood parameters and all parameters were established to compare the accuracy of the two models in predicting the prognosis of patients with urothelial carcinoma of the ureter. RESULTS: The median follow-up time was 36 months, the progression-free survival was 40 months, and 42 cases (21.0%) showed tumor progression within 3 years. Tumor size, pathological stage and pathological grade were all single-factor variables predicting the first recurrence of ureteral urothelial carcinoma three years after operation. Tumor size, pathological stage, pathological grade, TIN, TAM, NLR and NMR were multi-factor variables predicting the first recurrence three years after operation. Among 104 cases of non-muscle-invasive ureteral urothelial carcinoma, 10 cases (9.6%) recurred for the first time 3 years after operation, 96 cases (33.3%) of muscle invasive ureteral urothelial carcinoma, and the diffe-rence between the two groups was statistically significant (χ2=15.53, P < 0.05). The predictive nomogram model of progression free survival was established. The concordance index of progression free survi-val was 0.722 (95%CI: 0.70-0.78) in non-muscle-invasion group, and 0.725 (95%CI: 0.71-0.79) in muscle-invasion group, which was in good agreement with the observed 3-year survival rate. The results of discrimination test showed that the concordance index of the whole parameter prediction model of ureteral urothelial carcinoma was 0.726, which was higher than that of peripheral blood parameters (consistency index 0.672). The immune microenvironment of ureteral urothelial carcinoma improved the prediction accuracy of the model. CONCLUSION: The prognosis prediction model based on immune inflammation-related markers was established as a perfection and supplement for the existing pathological grading and staging system, providing a basis for accurate individualized treatment of patients with urete-ral urothelial carcinoma. The prognosis prediction model based on the relevant indicators of peripheral blood samples is established, which is easy to obtain specimens, and the detection method is simple and economical, which is more conducive to clinical application.

miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signaling.

INTRODUCTION: Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid ß (Aß)1-42. METHODS: To create a model of AD, SH-SY5Y cells were treated with Aß1-42 and mice received intracerebroventricular injections of Aß1-42. Then, the transcriptional levels of miR-146a were estimated by real-time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and reactive oxygen species (ROS) was studied by using specific inhibitors. Aß and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aß expression was analyzed by immunofluorescence and histochemical examinations. RESULTS: Aß1-42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the animals treated with Aß1-42, in which miR-146a upregulation increased the expression of Aß, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aß deposition and ROS accumulation via the p-p38 signaling pathway. CONCLUSIONS: Our research demonstrates that miR-146a-5pa increases Aß deposition by triggering oxidative stress through activation of MAPK signaling.

[Analysis on incidence and mortality of ovarian cancer in Jiangsu province, 2006-2015].

Objective: To estimate the incidence/mortality of ovarian cancer in 2015 and the incidence/mortality trend of ovarian cancer from 2006 to 2015 in Jiangsu province, and provide evidence for prevention and treatment of ovarian cancer in Jiangsu. Methods: The incidence and death data of cancer in Jiangsu from 2006 to 2015 collected from 35 cancer registries and verified by Jiangsu provincial CDC in 2018 were used for the extraction of ovarian cancer data. The data were stratified by urban and rural, gender and age groups. The crude rates of incidence and mortality, age-standardized incidence/mortality rates (ASIR/ASMR), cumulative incidence/mortality rates (0-74 years) and truncated incidence/mortality rates (35-64 years) of ovarian cancer were calculated. Chinese population census in 2000 and world Segi's standard population were used for the calculations of age-standardized incidence/mortality rates. Software Joinpoint 4.7.0.0 was used to analyze the annual percentage changes (APCs) of two rates from 2006 to 2015. Results: It was estimated that 2 229 ovarian cancer cases occurred in Jiangsu in 2015, accounting for 2.23% of all cancer cases and ranking 12(th) of cancer incidence in women. The crude incidence rate was 5.91/100 000, the age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 4.01/100 000 and 3.81/100 000, respectively. The cumulative incidence rate (0-74 years) was 0.42%. It was estimated that 1 239 deaths of ovarian cancer occurred in Jiangsu in 2015, accounting for 2.18% of all cancer deaths and ranking 13(th) of cancer mortality in women. The crude mortality rate was 3.29/100 000, the ASMRC and ASMRW were 1.99/100 000 and 1.96/100 000, respectively. The cumulative mortality rate (0-74 years) was 0.24%. The APCs of crude incidence rate and crude mortality rate were 4.66% (95%CI: 2.11%-7.29%) and 7.45% (95%CI: 5.46%-9.47%) (all P<0.05). The APCs of ASIRC and ASIRW were 2.30% (95%CI: -0.32%-4.99%) and 2.41% (95%CI: -0.29%-5.20%) (all P>0.05), and the APCs of ASMRC and ASMRW were 4.43% (95%CI: 2.54%-6.36%) and 4.55% (95%CI: 2.58%-6.57%) (all P<0.05). Conclusions: The incidence and mortality of ovarian cancer in Jiangsu were at low levels, and were higher in urban areas than in rural areas. The crude incidence and mortality rates increased, and age-standardized incidence rate was stable, but age-standardized mortality rate increased obviously.

[Influence of comprehensive incubational measures on the perioperative treatment of extensively burned patients who underwent escharectomy and skin grafting].

Objective: To explore the influence of standardized and comprehensive incubational measures on perioperative treatment of extensively burned patients who underwent escharectomy and skin grafting. Methods: From January 2017 to November 2018, 50 patients with extensive burn who underwent escharectomy and skin grafting in the First Affiliated Hospital of Air Force Medical University and met the inclusion criteria of this study, were recruited in this retrospective cohort study. According to the incubational measures at that time, 20 patients (14 males and 6 females, aged (33.5±5.2) years) who received routine incubation during the perioperative period from January to October 2017 were set as routine incubation group, and 30 patients (23 males and 7 females, aged (35.8±1.4) years) who received standardized comprehensive incubational measures during the perioperative period from November 2017 to November 2018 were set as comprehensive incubation group. Their body temperature was controlled mainly in 4 stages: preoperative preparation and transfer from intensive care unit (ICU) to operating room, preoperative preparation in operating room, intraoperative operating room management, as well as postoperative transfer from operating room to ICU. The initial body temperature in operating room and intraoperative hypothermia duration, intraoperative blood loss, postoperative recovery time, postoperative chill, blister, and ulcer, and wound healing rate on post operation day (POD) 10 were recorded and calculated. Data were statistically analyzed with two independent samples t test and chi-square test. Results: (1) The initial body temperature in operating room of patients in comprehensive incubation group was (36.3±0.4) ℃, which was significantly higher than (35.6±0.4)℃ in routine incubation group, t=6.658, P<0.01; the intraoperative duration of hypothermia was (205±38) min, which was significantly shorter than (234±42) min in routine incubation group, t=2.564, P<0.05. (2) The intraoperative blood loss of patients in comprehensive incubation group was (323±114) mL, which was significantly less than (490±162) mL in routine incubation group, t=4.272, P<0.01; the postoperative recovery time was (36±8) min, which was significantly shorter than (49±17) min in routine incubation group, t=3.229, P<0.01. (3) The incidence of postoperative chill of patients in comprehensive incubation group was significantly lower than that in routine incubation group (χ(2)=28.626, P<0.01). The incidences of postoperative blister and ulcer of patients between the 2 groups were close. (4) On POD 10, the wound healing rate of patients in comprehensive incubation group was (78.08±0.06)%, which was significantly higher than (71.03±0.08)% in routine incubation group, t=3.694, P<0.01. Conclusions: The standardized and comprehensive incubational measures can effectively improve the initial body temperature of patients entering the operating room, shorten the intraoperative duration of hypothermia, reduce the amount of blood loss and postoperative complications, as well as shorten the postoperative recovery time, thus improve the wound healing rate.

ANO1 relieves pressure overload-induced myocardial fibrosis in mice by inhibiting TGF-ß/Smad3 signaling pathway.

OBJECTIVE: The aim of this study was to measure the expression of anoctamin 1 (ANO1) in myocardial tissues of mice with pressure overload-induced myocardial fibrosis, and to further investigate the effect of ANO1 on myocardial fibrosis in mice and its mechanism. MATERIALS AND METHODS: A total of 40 male C57/B6 mice aged 6-8 weeks old were divided into 2 groups using a random number table, namely sham operation group (Sham group, n=20) and thoracic aortic constriction group (TAC group, n=20). Meanwhile, 20 ANO1 transgenic (TG) mice aged 6-8 weeks old were enrolled for TAC as TAC + ANO1 TG group. At 8 weeks after TAC, ejection fraction (EF%) and fraction shortening (FS%) in each group of mice were detected via echocardiography. Western blotting and immunofluorescence staining assays were conducted to measure the protein expression of ANO1 in myocardial tissues of mice in each group. The pathological changes in myocardial tissues of mice were evaluated through hematoxylin-eosin (H&E) staining. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay was performed to measure the messenger ribonucleic acid (mRNA) expression levels of hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in myocardial tissues of mice in each group. The deposition of collagen fibers in heart tissues was determined by Masson staining assay. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining assay was carried out to detect the apoptosis of myocardial cells and fibroblasts in heart tissues. Additionally, the protein expressions of oxidative stress markers superoxide dismutase 1 (SOD1) and 4-hydroxynonenal (4-HNE) in myocardial tissues were detected as well. Finally, Western blotting was employed to detect the effect of ANO1 overexpression on the expression of transforming growth factor-ß (TGF-ß)/Smad3 signaling pathway-related proteins in myocardial tissues of mice. RESULTS: At 8 weeks after TAC, ANO1 expression was overtly reduced in myocardial tissues of mice (p<0.05). Echocardiographic results showed that ANO1 overexpression significantly alleviated TAC-induced cardiac function deterioration in mice (p<0.05). The mRNA expression levels of ANP and BNP in myocardial tissues of TAC + ANO1 TG group were evidently lower than those in TAC group (p<0.05). Meanwhile, myocardial interstitial collagen deposition was significantly ameliorated in TAC + ANO1 TG group compared with TAC group (p<0.05). ANO1 overexpression notably mitigated the apoptosis of myocardial cells and oxidative stress in mice with cardiac pressure overload (p<0.05). Western blotting results further indicated that after overexpression of ANO1, the protein levels of TGF-ß and phosphorylated Smad3 (p-Smad3) were significantly inhibited in mice undergoing TAC (p<0.05). CONCLUSIONS: In the case of cardiac pressure overload in mice, ANO1 is lowly expressed in myocardial tissues. Meanwhile, its overexpression is able to attenuate pressure overload-induced myocardial fibrosis in mice by repressing the TGF-ß/smad3 signaling pathway. All our findings indicate that ANO1 can serve as a potential gene target for the treatment of myocardial fibrosis in the future.

[Prevalence and influencing factors of carotid plaque in population at high-risk for cardiovascular disease in Jiangsu province].

Objective: To understand the prevalence of carotid plaque (CP) in population at high-risk for cardiovascular disease (CVD) in Jiangsu province and identify related influencing factors. Methods: Based on the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project from 2015 to 2016, a total of 11 392 persons at high-risk for CVD were selected from six project areas in Jiangsu province for the questionnaire survey, physical measurement, laboratory test and bilateral ultrasound examination of carotid arteries. The prevalence of CP and influencing factors of abnormal carotid arteries, CP and plaque burden (CP≥2) were analyzed. Results: Among the persons surveyed, 4 821 (42.3%) were males. The age of the persons surveyed was (59.4±8.9) years. There were 5 971 abnormal carotid arteries cases (52.4%), including 1 782 carotid intima-media thickness thickening cases (15.6%), 3 811 CP cases (33.5%) and 378 carotid stenosis cases (3.3%). Older age (OR=2.253, 95%CI: 2.127-2.386), urban residence (OR=2.622, 95%CI: 2.375-2.895), hypertension (OR=1.439, 95%CI: 1.195-1.732), smoking (OR=1.441, 95%CI: 1.259- 1.650), pulse pressure difference (OR=1.270, 95%CI: 1.198-1.347), fasting plasma glucose (FPG) (OR=1.109, 95%CI: 1.059-1.161) and LDL-C/HDL-C (OR=1.225, 95%CI: 1.164-1.288) were possible risk factors of CP in population at high risk for CVD. Being women (OR=0.558, 95%CI: 0.494-0.630), high BMI (OR=0.948, 95%CI: 0.904-0.994), higher levels of education (OR=0.708, 95%CI: 0.531-0.945), and higher annual household income (OR=0.773, 95%CI: 0.669-0.894) were the possible protective factors. Conclusions: Over half of the population at high-risk for CVD in Jiangsu showed abnormal carotid arteries. High blood pressure, high blood glucose, high blood lipids and smoking were the main factors that could be changed.

[Prevalence, awareness, treatment and control of hypertension in adult residents in Jiangsu province].

Objective: To investigate the prevalence, awareness, treatment and control of hypertension in adult residents in Jiangsu province and provide evidence for the prevention and control of hypertension. Methods: A population-based cardiovascular disease screening project was conducted during 2015-2018 in Jiangsu, a total of 95 348 community-dwelling adults aged 35-75 years from 6 project areas were included in the study. The prevalence rate of hypertension and rates of awareness, treatment and control of hypertension in the adults with different characteristics were analyzed. Multilevel model was applied to identify the influencing factors. Results: Among 95 348 adults surveyed, 54 407 were hypertensive, the standardized prevalence rate was 48.1%. The prevalence rate was significantly higher in males than in females (62.1% vs. 54.0%, P<0.05). Among the hypertension patients, the rates of awareness, treatment and control of hypertension were 56.6%, 45.3% and 12.0% (standardized rates: 52.2%, 41.0% and 11.2%), respectively, and all the rates were positively associated with age (all P<0.05). Multilevel model analysis showed that those who were males, at older age, lived in rural area, suffered from diabetes, had frequent alcohol drinking and those who were overweight/obese had higher risk for hypertension (all P<0.05). Among people with hypertension, those who had younger age, lower education level, lower household income level and those who had frequent alcohol drinking had lower awareness, treatment and control rates of hypertension (all P<0.05). Conclusions: The prevalence rate of hypertension was high, but related awareness, treatment and control rates were low in adult residents in Jiangsu province. Comprehensive measures should be taken to improve awareness, treatment and control of hypertension in whole population, especially in young adults, and those with low education or income levels.

Inhibition of miR-126 protects chondrocytes from IL-1ß induced inflammation via upregulation of Bcl-2.

OBJECTIVES: The aim of this study was to investigate the role of miR-126 in the development of osteoarthritis, as well as the potential molecular mechanisms involved, in order to provide a theoretical basis for osteoarthritis treatment and a novel perspective for clinical therapy. METHODS: Human chondrocyte cell line CHON-001 was administrated by different doses of interleukin (IL)-1ß to simulate inflammation. Cell viability, migration, apoptosis, IL-6, IL-8, and tumour necrosis factor (TNF)-α expression, as well as expression of apoptosis-related factors, were measured to assess inflammation. miR-126 expression was measured by quantitative polymerase chain reaction (qPCR). Cells were then transfected with miR-126 inhibitor to assess the effect of miR-126 on IL-1ß-injured CHON-001 cells. Expression of B-cell lymphoma 2 (Bcl-2) and the activity of mitogen-activated protein kinase (MAPK) / Jun N-terminal kinase (JNK) signaling pathway were measured by Western blot to explore the underlying mechanism through which miR-126 affects IL-1ß-induced inflammation. RESULTS: After IL-1ß administration, cell viability and migration were suppressed while apoptosis was enhanced. Expression of IL-6, IL-8, and TNF-α were all increased, and miR-126 was upregulated. In IL-1ß-administrated CHON-001 cells, miR-126 inhibitor suppressed the effect of IL-1ß on cell viability, migration, apoptosis, and inflammatory response. Bcl-2 expression was negatively regulated with miR-126 in IL-1ß-administrated cells, and thus affected expressions of phosphorylated MAPK and JNK. CONCLUSION: IL-1ß-induced inflammatory markers and miR-126 was upregulated. Inhibition of miR-126 decreased IL-1ß-induced inflammation and cell apoptosis, and upregulated Bcl-2 expression via inactivating the MAKP/JNK signalling pathway.Cite this article: C. D. Yu, W. H. Miao, Y. Y. Zhang, M. J. Zou, X. F. Yan. Inhibition of miR-126 protects chondrocytes from IL-1ß induced inflammation via upregulation of Bcl-2. Bone Joint Res 2018;7:414-421. DOI: 10.1302/2046-3758.76.BJR-2017-0138.R1.

Antifungal activity of the bioactive substance from Bacillus atrophaeus strain HAB-5 and its toxicity assessment on Danio rerio.

The prevalence of pathogen inhibitors bacteria has motivate the study for antimicrobial compounds. Bioactive fungicide have always received considerable attention. A bacterial isolated strain HAB-5 showed antifungal activity against plant fungi. Based on morphological, physiological, biochemical and 16SrDNA sequence analysis, the strain was identified to be a Bacillus atrophaeus. This strain possessed a broad spectrum antifungal activity against various plant pathogenic fungi. Extraction of antifungal substance was performed and the crude extract had potent antifungal ability and showed great potential for swelling and inhibiting spore germination. This antifungal displayed heat stability and active in a wide pH range 5.0-10.0. Moreover no reduction was found in its activity after enzyme treatment. The toxicity test was evaluated in Danio rerio. The acute toxicity test indicated that the 24, 48, 72, 96h LC50 values of UMTLS to the zebrafish were 14.4, 13.8, 13.4, and 12.9%, respectively. Based on the results obtained in this study, antifungal substance was not toxic to zebra. Analyses of disease suppression showed that HAB-5 was effective to reduce the incidence of anthracnose symptoms on mango fruits, also prevent disease infection and protect tobacco seedling from Phytophtora nicotianae. The bioactive substance from Bacillus atrophaeus HAB-5 could be a candidate in the generation of new antifungal agents in crop.

TIA patients with higher ABCD3-I scores are prone to a higher incidence of intracranial stenosis, unstable carotid plaques and multiple-vessel involvement.

The ABCD3-I criteria have proved to be effective for use in regular clinical practice to assist in transient ischemic attack (TIA) risk stratification and treatment. In this prospective study we aimed to explore the relationships between risk stratification and arterial stenosis location, carotid plaque morphology and vessel involvement in 90 TIA patients, stratifying risk by ABCD3-I scores. Clinical variables such as total cholesterol, triglyceride, low-density lipoprotein cholesterol, glycosylated hemoglobin, homocysteine and high-sensitive C-reactive protein levels were recorded. The endpoint was subsequent stroke at seven-day follow-up. Ninety patients were divided into three risk groups on the basis of their ABCD3-I scores. The results revealed that patients with higher ABCD3-I scores showed a higher occurrence of intracranial stenosis (P < 0.05), less organized carotid plaques (P < 0.05) and multiple-vessel involvement (P < 0.05).

Autophagy attenuates the oxidative stress-induced apoptosis of Mc3T3-E1 osteoblasts.

OBJECTIVE: The oxidative stress-induced osteoblast apoptosis plays an important role in the pathological process of osteoporosis, but the roles of autophagy in oxidative stress and apoptosis of osteoblasts remain unclear. This study aimed to observe the role of autophagy in oxidative stress injury of osteoblasts and the relationship between autophagy and apoptosis. MATERIALS AND METHODS: Mc3T3-E1 cells were stimulated with different concentrations (0.1, 0.5, and 1 mM) of hydrogen peroxide. The cell viability was detected via cell counting kit 8 (CCK8) at different time points (0, 2, 6, 8, and 12 h), the apoptosis was detected via Western blotting and flow cytometry, and the autophagy was detected via macrophage-derived chemokine (MDC) and transmission electron microscope. The changes in expression of autophagy-associated protein, Beclin1, and LC3II/I ratio, were detected via Western blotting. Moreover, the intracellular reactive oxygen species (ROS) level and extracellular superoxide dismutase (SOD) level were observed using the autophagy regulators, rapamycin (Rap) and 3-methyladenine (3-MA), so as to clarify the interaction between autophagy and cellular oxidation. RESULTS: Hydrogen peroxide-induced apoptosis and autophagy of osteoblasts were in dose- and time-dependent manners; the hydrogen peroxide inhibitors could inhibit the autophagy level, and autophagy inhibitor (3-MA) could significantly enhance the hydrogen peroxide-induced ROS level and apoptosis rate in cells. Besides, Western blotting confirmed that the cleaved caspase-3 and cleaved poly adenosine diphosphate ribose polymerase (PARP) proteins were increased. The autophagy inducer (Rap) partially inhibited the hydrogen peroxide-induced oxidative stress and apoptosis. CONCLUSIONS: Autophagy inhibits the oxidative stress-mediated apoptosis of osteoblasts, which is a potential target for the osteoporosis treatment.

[Study of optic radiations in patients with primary open-angle glaucoma with diffusion tensor imaging].

Objective: To study the alteration of the optic radiations in patients with primary open-angle glaucoma (POAG) by diffusion tensor imaging (DTI) and tractography, and to reveal the correlation between the DTI derived parameters and the severity of the disease. Methods: A total of 24 patients with POAG and 20 age- and gender-matched healthy controls were enrolled in this study from January 2011 to June 2013.All subjects underwent ophthalmoscopy, standard automatic perimetry, intraocular pressure measurement and MRI scanning.All the eyes of POAG patients were evaluated by Hodapp-Anderson-Parrish (HAP) system.Then the stages of bilateral eyes were added together to evaluate the disease severity.Tractography was used to measure the fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) of the optic radiations of these subjects.The results of the two groups were compared.Partial correlation was then used to reveal the correlation between these derived DTI parameters and the severity of POAG. Results: Compared with health controls, POAG patients showed significant decreased FA (t=-3.299, P=0.002) and AD (t=-2.485, P=0.013), increased RD (t=2.365, P=0.018) in optic radiation .The alteration of MD was not significant (t=0.719, P=0.454). Mean FA values of the optic radiations were negatively correlated with POAG stages (r=-0.643, P= 0.001), while mean RD values (r=0.570, P= 0.004) and mean MD values (r= 0.448, P= 0.028) were positively correlated with POAG stages.No correlation between AD values and severity of POAG was found. Conclusion: In the optic radiations of POAG patients, the FA values and AD values decrease, while RD values increase, indicating the fiber integrity changes.The alterations of FA, RD and MD are correlated with disease severity.

Immune-camouflaged graphene oxide nanosheets for negative regulation of phagocytosis by macrophages.

Signal regulatory protein alpha (SIRPα) is highly expressed in macrophages of the reticuloendothelial system and in tumor-associated macrophages, whereas tumor cells express the surface membrane protein, CD47, which interacts with SIRPα to negatively regulate phagocytosis. In this study, we modified the surfaces of graphene oxide (GO) nanosheets with a CD47-like SIRPα-binding peptide (SP). The presence of SP on GO nanosheets reduced the macrophage uptake to a greater extent than the PEGylation of such nanosheets. This reduced uptake was found to be mediated by the activation of Src homology region 2 domain-containing phosphatase 1 (SHP-1) and the downstream inhibition of myosin assembly, which is necessary for phagosome formation. Unlike SP-coated GO nanosheets, PEGylated GO nanosheets did not affect myosin assembly or phagocytosis. After in vivo systemic administration, the clearance of SP-coated GO nanosheets was slower than that of PEGylated GO nanosheets, and this difference increased with repeated administration. Finally, SP-coated GO nanosheets showed a higher distribution to tumor tissues than PEGylated GO nanosheets or a physical mixture of SP and GO nanosheets. Our findings indicate that immune-camouflaged GO nanosheets with natural CD47-like SIRPα-binding molecules can reduce the nonspecific loss of such nanosheets through macrophage uptake, thereby enhancing their blood circulation and tumor delivery after multiple injections.