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1.
BMJ Open ; 9(8): e027201, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471431

RESUMO

OBJECTIVES: This study aimed to elucidate the status of hypertension and to analyse the hypertension changes in prevalence, awareness, treatment and control rate among the portion of Chinese nursing staff based on the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) High Blood Pressure Guideline and the 2010 Chinese Guideline for the Management of Hypertension. DESIGN: Cross-sectional study. SETTING: 512 medical institutions in 13 cities in Hebei Province. PARTICIPANTS: The candidates of registered nurses from 512 medical institutions in 13 cities in Hebei Province (N=143 772) were invited to participate in the survey, and few of them who refused to participate were excluded from the research group based on the reasons that 93 603 incumbent nurses at the age of 18-65 accepted to the survey and submitted questionnaires online. Undoubtedly, a response rate of 65.11% was achieved. After excluding 788 individuals with incomplete information in the questionnaires, 92 815 participants were included in the final analysis. MAIN OUTCOME MEASURES: The prevalence, awareness, treatment and control rates of hypertension. RESULTS: 92 815 participants were included in the final analysis, among which consisted of 3677 men (3.96%) and 89 138 women (96.04%). The mean age of the participants was 31.65 (SD=7.47) years.We demonstrated that 26 875 nursing staff were diagnosed as having hypertension according to the new standard by the 2017 ACC/AHA guideline, more than 20 551 cases compared with the previous threshold on the 2010 Chinese guideline. The prevalence of hypertension among nursing staff was 28.96% in the context of the 2017 ACC/AHA guideline, 3.25 times higher than that (6.81%) evaluated by the criteria of the 2010 Chinese guideline. However, the awareness, treatment and control rate (13.50%, 10.73% and 0.81%) were 3.25, 3.22 and 17.48 times lower than those (57.37%, 45.30% and 14.97%) based on the 2010 Chinese guideline, respectively. CONCLUSIONS: This research illustrated that it was crucial to improve the awareness rate, drug treatment rate and control rate of hypertension for nurses. Meanwhile, according to the 2017 ACC/AHA guideline, the prevalence of hypertension in China will increase significantly, which poses a more severe challenge to the management of hypertension in China.

2.
J Biol Chem ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462534

RESUMO

Macrophages play an essential role in skeletal muscle regeneration. The phagocytosis of muscle cell debris induces a switch of pro-inflammatory macrophages into an anti-inflammatory phenotype, but the cellular receptors mediating this phagocytosis are still unclear. In this paper, we reported novel roles for SRB1 (scavenger receptor class BI) in regulating macrophage phagocytosis and macrophage phenotypic transitions for skeletal muscle regeneration. In a mouse model of cardiotoxin-induced muscle injury/regeneration, infiltrated macrophages expressed high level of SRB1. Using SRB1 knockout mice, we observed muscle regeneration was impaired along with decreased myogenin expression and increased matrix deposit. Bone marrow transplantation experiments indicated that SRB1 deficiency in bone marrow cells was responsible for impaired muscle regeneration. Compared with WT mice, SRB1 deficiency increased pro-inflammatory macrophage number and pro-inflammatory gene expression, and decreased anti-inflammatory macrophage number and anti-inflammatory gene expression in injured muscle. In vitro, SRB1 deficiency led to the strong decrease in macrophage phagocytic activity on myoblast debris. SRB1 deficiency macrophages easily acquired an M1 phenotype and failed to acquire an M2 phenotype in LPS/myoblast debris activation. Furthermore, SRB1 deficiency promoted activation of ERK1/2 MAPK signaling in macrophages stimulated with LPS/myoblast debris. Taken together, SRB1 in macrophages regulates phagocytosis and promotes M1 switch into M2 macrophages, contributing to muscle regeneration.

3.
Eur Spine J ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31428860

RESUMO

PURPOSE: To investigate the adjacent segment kinematics, including the instantaneous axis of rotation (IAR) and range of motion (ROM), after anterior cervical discectomy and fusion (ACDF), and to compare between ACDF with zero-profile anchored spacer (ACDF-Z) and ACDF with plate (ACDF-P). METHODS: Eighty-seven patients (ACDF-Z = 63; ACDF-P = 24) were included. Flexion, extension and neutral cervical radiographs were obtained before operation and at 1-year follow-up. C2-C7 ROM, adjacent segment ROMs, and IARs were measured. Clinical evaluation was based on the Visual Analogue Scale, Neck Disability Index, and Japanese Orthopaedic Association score. RESULTS: After ACDF-Z, location of the superior IAR-AP reduced 1.60 mm, which represents 8% of the vertebral body (P < 0.001), and location of the inferior IAR-SI reduced 2.19 mm, 17% of the vertebral body (P = 0.02). After ACDF-P, location of the superior IAR-AP increased 0.8 mm, which means 6% of the vertebral body (P = 0.008), location of the inferior IAR-AP increased 3.34 mm, 22% of the vertebral body (P = 0.03), and location of the inferior IAR-SI reduced 3.14 mm, 25% of the vertebral body (P = 0.002). C2-C7 ROM significantly decreased after both ACDF-Z and ACDF-P (P < 0.001). Neither ACDF-Z nor ACDF-P significantly affected the adjacent segment ROMs (P > 0.05). CONCLUSIONS: Both ACDF-Z and ACDF-P significantly impacted cervical kinematics, although both procedures obtained satisfactory clinical results in the treatment of cervical spondylosis. After both ACDF-Z and ACDF-P, C2-C7 ROM decreased significantly, while adjacent segment ROMs were preserved. ACDF-Z and ACDF-P impact the location of adjacent segment IAR-SI in similar way, while impact the location of adjacent segment IAR-AP in diverse ways. These slides can be retrieved under Electronic Supplementary Material.

4.
Xenobiotica ; : 1-9, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31368836

RESUMO

Jatrorrhizine possesses a wide spectrum of pharmacological activities. However, the mechanism underlying hepatic uptake of jatrorrhizine remains unclear. Rat liver slices, isolated rat hepatocytes and human embryonic kidney 293 (HEK293) cells stably expressing human organic anion-transporting polypeptide (OATP) and organic cation transporter (OCT) were used to evaluate the hepatic uptake of jatrorrhizine in this study. Uptake of jatrorrhizine in rat liver slices and isolated rat hepatocytes was significantly inhibited by glycyrrhizic acid (Oatp1b2 inhibitor) and prazosin (Oct1 inhibitor), but not by ibuprofen (Oatp1a1 inhibitor) or digoxin (Oatp1a4 inhibitor). Uptake of jatrorrhizine in OATP1B3 and OCT1-HEK293 cells indicated a saturable process with the Km of 8.20 ± 1.28 and 4.94 ± 0.55 µM, respectively. However, the transcellular transport of jatrorrhizine in OATP1B1-HEK293 cells was not observed. Rifampicin (OATP inhibitor) for OATP1B3-HEK293 cells and prazosin for OCT1-HEK293 cells could inhibit the uptake of jatrorrhizine with the IC50 of 5.49 ± 1.05 and 2.77 ± 0.72 µM, respectively. The above data indicate that hepatic uptake of jatrorrhizine is involved in both OATP and OCT, which may have important roles in jatrorrhizine liver disposition and potential drug-drug interactions.

5.
Clin Chem Lab Med ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415235

RESUMO

Background Although laboratory information system (LIS) is widely used nowadays, the results of routine urinalysis still need 100% manual verification. We established intelligent verification criteria to perform the automated verification process and reduce manual labor. Methods A total of 4610 urine specimens were obtained from the patients of three hospitals in Beijing, China. Firstly, 895 specimens were measured to establish the reference intervals of formed-element parameters in UF5000. Secondly, 2803 specimens were analyzed for setting up the intelligent verification criteria (including the microscopic review rules and manual verification rules). Lastly, 912 specimens were used to verify the efficacy and accuracy of the intelligent verification criteria. Phase-contrast microscopes were used for the microscopic review. Results Employing a results level corresponding relationship in specific parameters including hemoglobin (red blood cell [RBC]), leukocyte esterase (white blood cell [WBC]) and protein (cast) between the dry-chemistry analysis and formed-element analysis, as well as instrument flags, we established seven WBC verification rules, eight RBC verification rules and four cast verification rules. Based on the microscopy results, through analyzing the pre-set rules mentioned earlier, we finally determined seven microscopic review rules, nine manual verification rules and three auto-verification rules. The microscopic review rate was 21.98% (616/2803), the false-negative rate was 4.32% (121/2803), the total manual verification rate was 35.71% (1001/2803) and the auto-verification rate was 64.29% (1802/2803). The validation results were consistent. Conclusions The intelligent verification criteria for urinary dry-chemistry and urinary formed-element analysis can improve the efficiency of the results verification process and ensure the reliability of the test results.

6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(8): 991-995, 2019 Aug 15.
Artigo em Chinês | MEDLINE | ID: mdl-31407559

RESUMO

Objective: To investigate the feasibility and effectiveness of modified replanting posterior ligament complex (PLC) applying piezoelectric osteotomy in the treatment of primary benign tumors in thoracic spinal canal. Methods: The clinical data of 38 patients with primary benign tumors in thoracic spinal canal between March 2014 and March 2016 were retrospectively analyzed. There were 16 males and 22 females, aged from 21 to 72 years (mean, 47.1 years). The disease duration ranged from 6 to 57 months (mean, 32.6 months). Pathological examination showed 24 cases of schwannoma, 6 cases of meningioma, 4 cases of ependymoma, 2 cases of lipoma, and 2 cases of dermoid cyst. The lesions located in 18 cases of single segment, 15 cases of double segments, and 5 cases of three segments. The length of the tumors ranged from 0.7 to 6.5 cm. There were boundaries between the tumors and the spinal cord, cauda equina, and nerve roots. The preoperative Japanese Orthopaedic Association (JOA) score was 12.2±2.3 and the thoracic Cobb angle was (11.7±2.7)°. Modified PLC replantation and microsurgical resection were performed with piezoelectric osteotomy. Continuity of uniside supraspinal and interspinous ligaments were preserved during the operation. The PLC was exposed laterally. After removing the tumors under the microscope, the pedicled PLC was replanted in situ and fixed with bilateral micro-reconstruction titanium plate. X-ray film, CT, and MRI examinations were performed to observe spinal stability, spinal canal plasty, and tumor resection after operation. The effectiveness was evaluated by JOA score. Results: The operation time was 56-142 minutes (mean, 77.1 minutes). The intraoperative blood loss was 110-370 mL (mean, 217.2 mL). The tumors were removed completely and the incisions healed well. Three cases complicated with cerebrospinal fluid leakage, and there was no complications such as spinal cord injury and infection. All the 38 patients were followed up 24-28 months (mean, 27.2 months). There was no internal fixation loosening, malposition, or other related complications. At last follow-up, X-ray films showed no sign of kyphosis and instability. CT showed no displacement of vertebral lamina and reduction of secondary spinal canal volume, and vertebral lamina healed well. MRI showed no recurrence of tumors. At last follow-up, the thoracic Cobb angle was (12.3±4.1)°, showing no significant difference when compared with preoperative value ( t=0.753, P=0.456). JOA score increased to 23.7±3.8, showing significant difference when compared with preoperative value ( t=15.960, P=0.000). Among them, 14 cases were excellent, 18 were good, 6 were fair, and the excellent and good rate was 84.2%. Conclusion: Modified replanting PLC applying piezoelectric osteotomy and micro-reconstruction with titanium plate for the primary benign tumors in thoracic spinal canal can reconstruct the anatomy of the spinal canal, enable patients to recover daily activities quickly. It is an effective and safe treatment.

7.
Eur J Pharmacol ; 861: 172612, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31421088

RESUMO

Denervation caused by sciatic nerve injury has brought great harm to the patients, especially denervation-induced muscle atrophy. The body stress produces a large number of Schwann cells when the sciatic nerve is injured, and the cells secrete some cytokines including ciliary neurotrophic factor (CNTF) that not only play a role in promoting the repair of sciatic nerve, but also maintain the normal physiological function of the muscles surrounding the damaged nerves. CNTF upregulates janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) signals in myoblasts, and consequently accelerates the proliferation and differentiation of myoblasts. This effect on myoblasts is the most effective way to relieve muscle atrophy. Therefore, increasing CNTF is a promising direction to improve muscle atrophy. In the present study, an oleanolic acid derivative, HA-19, increased the proliferation of Schwann cells, and elevated CNTF production of the cells. HA-19 up-regulated the phosphorylation of JAK2 and STAT3 not only by directly acting on myoblasts, but also by increasing the secretion of CNTF of Schwann cells; and consequently, promoted the proliferation and differentiation of myoblasts. In denervation-induced muscle atrophy mice model, treatment with HA-19 significantly increased the weights of tibialis anterior (TA), gastrocnemius (Gastroc.), extensor digitorum longus (EDL), soleus and quadriceps (Quad.) under atrophied state. And, very interestingly, these muscles under normal condition were also strengthened by HA-19. Our finding demonstrated that HA-19 has a great potential as a lead compound for the drug discovery of anti-denervation-induced muscle atrophy.

8.
Zhongguo Gu Shang ; 32(7): 598-603, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31382715

RESUMO

OBJECTIVE: By comparing the clinical efficacy of short-segment and long-segment fixation for single-segment thoracic and lumbar spine III stage Kümmell disease to explore a more suitable fixed segment for the disease. METHODS: The clinical data of 46 patients with single-segment thoracic and lumbar spine III stage Kümmell disease treated from July 2013 to December 2016 were retrospectively analyzed. Forty-six patients were divided into short-segment fixation group(one vertebra above and below the diseased vertebra) and long-segment fixation group(two vertebrae on the upper and lower of the diseased vertebra) according to different methods of cement stick fixation. There were 25 patients in the short-segment fixation group, including 9 males and 16 females, with an average age of (75.3±4.5) years old, lumbar spine bone mineral density T-value of (-3.1±0.3) g/cm³, follow-up time of (13.0±2.3) months; there were 21 patients in long-segment fixation group, 6 males and 15 females, with an average age of (74.5±3.9) years old, lumbar spine bone mineral density T-value of (-3.2±0.3) g/cm³, follow-up time of (14.7±3.6) months.The gender, age, follow-up time, operation time, intraoperative blood loss, cement leakage, and the rate of adjacent vertebrae fractures were compared between two groups, as well as pain VAS score, ODI, and kyphosis angle before and after surgery. RESULTS: There were no significant differences in age, gender, bone density, pain VAS score, ODI, and kyphosis between two groups before surgery. The operation time and intraoperative blood loss of short-segment fixation group were less than that of long-segment fixation group. The pain VAS score, ODI and kyphosis of the two groups were significantly improved at 7 days after the operation and at the latest follow-up, there was no significant difference between two groups. There were no significant differences in bone cement leakage(9/25 vs 11/21) and adjacent vertebrae fractures(4/25 vs 3/21). CONCLUSIONS: Both long-segment fixation and short-segment fixation can effectively relieve pain, correct kyphosis, improve functional index, and achieve better clinical results, but short-segment fixation has less operation time and less intraoperative blood. So single-segment thoracic and lumbar spine III stage Kümmell disease does not need to extend the fixed segment, short-segment fixation is more in line with clinical needs and worthy of further study.


Assuntos
Cifose , Fraturas da Coluna Vertebral , Idoso , Feminino , Fixação Interna de Fraturas , Humanos , Vértebras Lombares , Masculino , Estudos Retrospectivos , Vértebras Torácicas , Resultado do Tratamento
9.
Cancer Biol Ther ; : 1-5, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31306053

RESUMO

Epithelial growth factor-like 7 (EGFL7) is a secretory protein with a well-characterized role in angiogenesis and the oncogenesis of certain solid tumors. Overexpression of EGFL7 is associated with adverse prognosis in patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, whether this association persists after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To further clarify the prognostic role of EGFL7, seventy-one AML patients with EGFL7 expression data who underwent allo-HSCT from The Cancer Genome Atlas database were included and divided into either EGFL7high or EGFL7low group based on the median EGFL7 expression level. Two groups had similar clinical and molecular characteristics except that the EGFL7high group had less frequent NPM1 mutations (P= .001). Kaplan-Meier survival curves showed that high EGFL7 expressers had shorter OS than the low expressers (P= .040). Univariate analysis showed that high EGFL7 expression, MLL-PTD, RUNX1 and TP53 mutations were associated with short OS (all P< .05). Multivariate analysis indicated that high EGFL7 expression, FLT3-ITD, RUNX1 and TP53 mutations were independent risk factors for OS (all P< .05). Collectively, our study suggested that EGFL7, like the other widely-used risk stratification factors, could serve as a prognostic tool and therapeutic target in AML, even after allo-HCST.

10.
J Cell Biochem ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31297863

RESUMO

Ischemic heart disease (IHD) is the most occurring cardiovascular-associated disease, which is a primary leading cause of cardiac disability and death worldwide. Myocardial ischemia/reperfusion injury (MI/RI) has been linked to IHD-induced cardiomyocytes apoptosis and tissue damage. The clinical studies have indicated that pathophysiologic mechanisms of MI/RI are associated with reactive oxygen species generation, calcium overload, energy metabolism disorder, neutrophil infiltration, and others. However, the genetic mechanism of MI/RI remains unclear. In this study, we successfully established the reproducing abnormal heart observed in rat, of IHD-induced MI/RI post operation. By using these rats, we illustrated that expression of miR-181b-5p was increased not only in both hypoxia/reoxygenation-cultured H9C2 but also heart of myocardial ischemia/reperfusion (MI/R) rat. Suppression of the miR-181b-5p cardiomyocytes apoptosis and rescued myocardial infarction. Additionally, our data indicated that miR-181b-5p negatively regulates the expression of AKT3 and PIK3R3 through directly binding with its 3'-untranslated region. More importantly, suppression of miR-181b-5p protects the cardiomyocytes apoptosis and tissue damage from MI/R via regulation of PIK3R3 and AKT3. Hence, our study indicates that miR-181b-5p is essential for MI/RI via regulation of PI3K/Akt signaling pathway and could be a potential therapeutic target in IHD.

11.
Ital J Pediatr ; 45(1): 78, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288826

RESUMO

BACKGROUND: Diagnostic value of procalcitonin (PCT) for acute appendicitis (AA) has been evaluated in adult patients, but the application in children remains controversial. The aim of this study was to evaluate the diagnostic value of PCT for overall and complicated AA in children. METHODS: The PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, Chinese National Knowledge Infrastructure, and Wanfang were searched along with reference lists of relevant articles up to January 2018 without language restrictions. Original articles that reported the performance of PCT in the diagnosis of pediatric AA and associated complications were selected. To assess the diagnostic value of PCT, sensitivity, specificity, diagnostic odds ratios (DORs), summary receiver operating characteristic (ROC) curves, area under the curve (AUC), and 95% confidence intervals (95% CIs) were estimated. RESULTS: Seven qualifying studies (504 confirmed AA and 368 controls) from 6 countries for overall AA and 4 studies (187 complicated AA and 185 uncomplicated AA) for complicated AA from 3 countries were identified. The pooled sensitivity and specificity of PCT for the diagnosis of pediatric AA were 0.62 (95% CI: 0.57-0.66) and 0.86 (95% CI: 0.82-0.89), respectively. The DOR was 21.4 (95% CI: 3.64-126.1) and the AUC was 0.955. PCT was more accurate in diagnosing complicated appendicitis, with a pooled sensitivity of 0.89 (95% CI: 0.84-0.93), specificity of 0.90 (95% CI: 0.86-0.94), and DOR of 76.73 (95% CI: 21.6-272.9). CONCLUSION: This meta-analysis showed that PCT may have potential value in diagnosing pediatric AA. Moreover, PCT had greater diagnostic value in identifying pediatric complicated appendicitis.

13.
Thyroid ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31328653

RESUMO

Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its correlation with clinicopathological characteristics, structural recurrence (SR), and biochemical recurrence/persistent disease (BcR/BcPD). We also evaluated the prevalence of PD-L1 expression in patients developing distant or unresectable locoregional recurrence. Methods: In total, 201 consecutive MTC patients who underwent initial surgery in our institution from January 2006 to December 2015 were included. PD-L1 expression was evaluated by immunohistochemical staining and was considered positive in case of a combined positive score ≥1. The association of PD-L1 positivity with clinicopathological characteristics, structural recurrence-free survival (SRFS), and BcR/BcPD was retrospectively investigated. Results: The median follow-up length of the entire cohort was 73 months. We observed positive PD-L1 staining in 29 (14.4%) patients who were more likely to have a larger tumor size (p = 0.002), lymph node metastases (p = 0.036), and advanced TNM staging (p = 0.019). The five-year SRFS of the PD-L1-negative and PD-L1-positive groups was 85.4% and 57.9% (p = 0.001). Multivariate Cox analysis showed that PD-L1 positivity was independently associated with SR (hazard ratio = 2.19 [95% confidence interval (CI) 1.01-4.77], p = 0.047). Furthermore, multivariate logistic analysis showed that PD-L1 positivity was significantly associated with BcR/BcPD (odds ratio = 3.16 [CI 1.16-8.66], p = 0.025). During the study period, 20 patients developed distant or unresectable locoregional recurrence, among whom 8 (40%) were PD-L1 positive, which was much higher than in the entire MTC population. Conclusions: Using a large cohort of MTC patients, we demonstrate that PD-L1 positivity is associated with aggressive clinicopathological features and is independently predictive of SR and BcR/BcPD. Furthermore, a higher rate of PD-L1 expression in patients with incurable recurrence has been observed. Therefore, immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-L1 pathway may be a potential therapeutic strategy to treat advanced MTC.

14.
BMC Cardiovasc Disord ; 19(1): 152, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234798

RESUMO

BACKGROUND: Contrast-induced nephropathy (CIN) is common after percutaneous coronary intervention (PCI) and always leads to a poor prognosis. Compared with conventional detection methods, either high-sensitivity C-reactive protein (hs-CRP) or procalcitonin have higher sensitivity and specificity for predicting CIN, but their combination has not been explored. This prospective study investigated the value of hs-CRP combined with procalcitonin for predicting CIN after PCI. METHODS: All patients undergoing PCI admitted to our hospital during the year 2016 were consecutively enrolled (n = 343). The patients received adequate hydration before PCI and 20 mg furosemide after the procedure. CIN was diagnosed by a 25% elevation in serum creatinine or ≥ 44.2 µmol/L (0.5 mg/dL) serum creatinine within 48 to 72 h after intravenous injection of contrast media. RESULTS: Patients with high hs-CRP or procalcitonin had higher rates of CIN relative to those patients with low values. For predicting CIN, hs-CRP combined with procalcitonin showed an area under the receiver operating characteristic curve of 0.67, with optimal cut-off value 0.0643610, and the sensitivity and specificity were higher than hs-CRP or procalcitonin alone. The logistic regression analysis showed that high-risk factors of CIN were acute myocardial infarction and highly elevated hsCRP and procalcitonin. CONCLUSIONS: Prior to PCI, an elevation of the inflammatory biomarkers hsCRP and procalcitonin are a risk factor for postoperative CIN. This study suggests that the combination of hsCRP and procalcitonin is a better predictor of CIN after PCI then either hsCRP or procalcitonin alone. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-14005250. Date of registration 2014-09-24.

15.
Toxicol Appl Pharmacol ; 378: 114625, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31201822

RESUMO

Muscle atrophy refers to a decrease in the size of muscles in the body, occurs in certain muscles with inactivity in many diseases and lacks effective therapies up to date. Natural products still play an important role in drug discovery. In the present study, derivatives of a natural product, oleanolic acid, were screened with myoblast differentiation and myotube atrophy assays, respectively. Results revealed that one of the derivatives, HA-19 showed the most potent anti-muscle atrophy activity, and was used for further studies. We demonstrated that HA-19 led to the increase of the protein synthesis by activating mechanistic target of rapamycin complex 1 (mTORC1)/p70 S6K pathways, and also enhanced myoblast proliferation and terminal differentiation via up-regulating of the myogenic transcription factors Pax7, MyoD and Myogenin. The interesting thing was that HA-19 also suppressed protein degradation to prevent myotube atrophy by down-regulating negative growth factors, FoxO1, MuRF1 and Atrogin-1. The results were also supported by puromycin labelling and protein ubiquitination assays. These data revealed that HA-19 possessed a "dual effect" on inhibition of muscle atrophy. In disuse-induced muscle atrophy mice model, HA-19 treatment significantly increased the weights of bilateral tibialis anterior (TA), gastrocnemius (Gastroc.), quadriceps (Quad.), suggesting the effectiveness of HA-19 to remit disuse-induced muscle atrophy. Our finding demonstrated that HA-19 has a great potential as an inhibitor or lead compound for the anti-muscle atrophy drug discovery.

16.
Exp Eye Res ; 186: 107713, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31254513

RESUMO

Zellweger Spectrum Disorder (ZSD) is an autosomal recessive disease caused by mutations in any one of 13 PEX genes whose protein products are required for peroxisome assembly. Retinopathy leading to blindness is one of the major untreatable handicaps faced by patients with ZSD but is not well characterized, and the requirement for peroxisomes in retinal health is unknown. To address this, we examined the progression of retinopathy from 2 to 32 weeks of age in our murine model for the common human PEX1-p.Gly843Asp allele (PEX1-p.Gly844Asp) using electrophysiology, histology, immunohistochemistry, electron microscopy, biochemistry, and visual function tests. We found that retinopathy in male and female PEX1-G844D mice was marked by an attenuated cone function and abnormal cone morphology early in life, with gradually decreasing rod function. Structural defects at the inner retina occurred later in the form of bipolar cell degradation (between 13 and 32 weeks). Inner segment disorganization and enlarged mitochondria were seen at 32 weeks, while other inner retinal cells appeared preserved. Visual acuity was diminished by 11 weeks of age, while signal transmission from the retina to the brain was relatively intact from 7 to 32 weeks of age. Molecular analyses showed that PEX1-G844D is a subfunctional but stable protein, contrary to human PEX1-G843D. Finally, C26:0 lysophosphatidylcholine was elevated in the PEX1-G844D retina, while phopshoethanolamine plasmalogen lipids were present at normal levels. These characterization studies identify therapeutic endpoints for future preclinical trials, including improving or preserving the electroretinogram response, improving visual acuity, and/or preventing loss of bipolar cells.

17.
Mol Med Rep ; 20(2): 1085-1092, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173244

RESUMO

Alzheimer's disease (AD) is a chronic neurodegenerative disease. G protein coupled receptor 50 (GPR50) is a candidate gene for AD. The present study was designed to determine the association between GPR50 methylation and AD. The methylation levels of the GPR50 promoter in 51 patients with AD and 61 healthy controls were determined by bisulfite pyrophosphate sequencing. All participants were Han Chinese, living in Ningbo. It was identified that the GPR50 promoter methylation level was significantly decreased in the male AD group compared with the male control group (9.15 vs. 16.67%, P=0.002). In addition, it was observed that the GPR50 methylation levels of the females was significantly increased compared with that of males in both the patients with AD and the healthy control group (AD patient group: 33.00 vs. 9.15%, P<0.0001; healthy control group: 29.41 vs. 16.67%, P<0.0001). This may be explained by the fact that GPR50 is located on the X chromosome. In addition, GPR50 methylation was positively correlated with plasma cholinesterase levels in female patients with AD (r=0.489, P=0.039). The present study demonstrated that hypomethylation of the GPR50 promoter in peripheral blood may be a potential biomarker for the diagnosis of AD in Chinese Han males.

18.
Hypertens Res ; 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133681

RESUMO

To examine the association between stage 1 hypertension (at baseline and longitudinal change) defined by the 2017 ACC/AHA hypertension guidelines and risk of cardiovascular events in a Chinese Kailuan Cohort. A total of 97,126 active and retired workers aged 18 to 98 years free of cardiovascular disease at baseline were followed for up to 10 years in the Chinese Kailuan Cohort Study. Adjusted Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals of cardiovascular events among different blood pressure categories. Participants with stage 1 hypertension at baseline accounted for 31.1% of the cohort. Compared with normal blood pressure (<120/80 mmHg), stage 1 hypertension had a significantly higher risk of cardiovascular events, cerebral infarction and cerebral hemorrhage, and the hazard ratios (95% confidence intervals) were 1.25 (1.11-1.40), 1.31 (1.13-1.52), and 1.45 (1.07-1.97), respectively. Over a four-year period, 43.1% of participants maintained stage 1 hypertension. Compared with the decreased blood pressure from stage 1 hypertension to normal blood pressure, the maintained stage 1 hypertension had a significantly higher risk of cardiovascular events and cerebral infarction, and the hazard ratios (95% confidence intervals) were 1.78 (1.16-2.72) and 1.94 (1.14-3.30), respectively. People with stage 1 hypertension defined by the 2017 ACC/AHA hypertension guidelines have a relatively high risk for cardiovascular events in northern China; they should be given appropriate antihypertensive interventions.

19.
IEEE Trans Neural Syst Rehabil Eng ; 27(6): 1170-1180, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31071048

RESUMO

Motor imagery electroencephalography (EEG) decoding is an essential part of brain-computer interfaces (BCIs) which help motor-disabled patients to communicate with the outside world by external devices. Recently, deep learning algorithms using decomposed spectrums of EEG as inputs may omit important spatial dependencies and different temporal scale information, thus generated the poor decoding performance. In this paper, we propose an end-to-end EEG decoding framework, which employs raw multi-channel EEG as inputs, to boost decoding accuracy by the channel-projection mixed-scale convolutional neural network (CP-MixedNet) aided by amplitude-perturbation data augmentation. Specifically, the first block in CP-MixedNet is designed to learn primary spatial and temporal representations from EEG signals. The mixed-scale convolutional block is then used to capture mixed-scale temporal information, which effectively reduces the number of training parameters when expanding reception fields of the network. Finally, based on the features extracted in previous blocks, the classification block is constructed to classify EEG tasks. The experiments are implemented on two public EEG datasets (BCI competition IV 2a and High gamma dataset) to validate the effectiveness of the proposed approach compared to the state-of-the-art methods. The competitive results demonstrate that our proposed method is a promising solution to improve the decoding performance of motor imagery BCIs.

20.
Urol J ; 0(0): 4955, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31087322

RESUMO

PURPOSE: The aim of this study is to evaluate the impact of different pulse energy settings on dusting efficiency in flexible ureteroscopic lithotripsy (fURSL) for the treatment of upper urinary tract calculi. MATERIALS AND METHODS: Data of 88 consecutive patients who underwent fURSL for upper urinary tract calculi by a single surgeon in our department From August 2017 to August 2018 were reviewed retrospectively. Lumenis Power Suite 100W lithotripter with a 200 ?m laser fiber was used to comminute stones. According to energy settings, patients were divided into three groups- low energy group (LE: 0.3-0.6J), middle energy group (ME: 0.7-1.0J), high energy group (HE: 1.1-1.5J). Frequency was set at 30Hz in all patients. ANOVA and Chi square tests were applied to compare the difference of the mean lithotripsy and operation time, early stone-free rate (eSFR), overall stone-free rate (oSFR) and complication rate. RESULTS: A total of 32, 36 and 20 patients were included in the LE, ME and HE groups, respectively. There was no difference in the age, gender distribution or in any other stone characteristics among the three groups. The mean lithotripsy time of LE, ME, HE was 10.9±7.6, 16.1±7.0, 23.0±15.0 min respectively. The mean operation time of the three groups was 16.9±7.7, 22.3±7.1, 29.2±14.9 min respectively. There were significant differences on the mean lithotripsy time (P=0.002) and the mean operation time (P=0.001) among the three groups. The stone-free rate was 31.8% and 87.5% respectively in eSFR and oSFR. No statistical significance was detected among the three groups in terms of the eSFR (P=0.89), oSFR (P=0.86), and complication rate (P=0.97). CONCLUSION: In fURSL with dusting, low energy (0.3-0.6J) is more efficient than middle (0.7-1.0J) and high energy (1.1-1.5J). As energy increased, dusting efficiency decreased dramatically. Consequently, we recommend low pulse energy (0.3-0.6J) as the optimal dusting strategy for fURSL.

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