Publications by authors named "Zhen-Yu Zhang"

207 Publications

Glomerular function in relation to fine airborne particulate matter in a representative population sample.

Sci Rep 2021 Jul 19;11(1):14646. Epub 2021 Jul 19.

Non-Profit Research Institute Alliance for the Promotion of Preventive Medicine, Mechlin, Belgium.

From 1990 until 2017, global air-pollution related mortality increased by 40%. Few studies addressed the renal responses to ultrafine particulate [≤ 2.5 µm (PM2.5)], including black carbon (BC), which penetrate into the blood stream. In a Flemish population study, glomerular filtration estimated from serum creatinine (eGFR) and the urinary albumin-to-creatinine ratio were measured in 2005-2009 in 820 participants (women, 50.7%; age, 51.1 years) with follow-up of 523 after 4.7 years (median). Serum creatinine, eGFR, chronic kidney disease (eGFR < 60 mL/min/1.73 m) and microalbuminuria (> 3.5/> 2.5 mg per mmol creatinine in women/men) were correlated in individual participants via their residential address with PM [median 13.1 (range 0.3-2.9) μg/m] and BC [1.1 (0.3-18) μg/m], using mixed models accounting for address clusters. Cross-sectional and longitudinally, no renal outcome was associated with PM or BC in models adjusted for sex and baseline or time varying covariables, including age, blood pressure, heart rate, body mass index, plasma glucose, the total-to-HDL serum cholesterol ratio, alcohol intake, smoking, physical activity, socioeconomic class, and antihypertensive treatment. The subject-level geocorrelations of eGFR change with to BC and PM2.5 were 0.13 and 0.02, respectively (P ≥ 0.68). In conclusion, in a population with moderate exposure, renal function was unrelated to ultrafine particulate.
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http://dx.doi.org/10.1038/s41598-021-94136-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290004PMC
July 2021

Normal-tension glaucomatous optic neuropathy is related to blood pressure variability in the Maracaibo Aging Study.

Hypertens Res 2021 Jul 12. Epub 2021 Jul 12.

Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.

Hypoperfusion of the optic nerve might be involved in the pathogenesis of normal-tension glaucomatous optic neuropathy (GON). Mean arterial pressure (MAP) drives ocular perfusion, but no previous studies have addressed the risk of GON in relation to blood pressure (BP) variability, independent of BP level. In a cross-sectional study, 93 residents of Maracaibo, Venezuela, underwent optical coherence tomography, visual field assessments and 24-h ambulatory BP monitoring between 2011 and 2016. We investigated the association of normal-tension GON with or without visual field defects with reading-to reading variability of 24-h MAP, as captured by variability independent of the MAP level (VIM). Odds ratios (ORs) were adjusted for 24-h MAP level and for a propensity score of up to five risk factors. Among the 93 participants (87.1% women; mean age, 61.9 years), 26 had open-angle normal-tension GON at both eyes; 14 had visual field defects; and 19 did not have visual field defects. The OR ratios for normal-tension GON, expressed per 1-SD increment in VIM (2 mm Hg), were 2.17 (95% confidence interval, 1.33-3.53) unadjusted; 2.20 (1.35-3.61) adjusted for 24-h MAP level only; 1.93 (1.10-3.41) with additional adjustment for age, educational attainment, high-density lipoprotein (HDL) cholesterol and office hypertension; and 1.95 (1.10-3.45) in models including intraocular pressure. We confirmed our a priori hypothesis that BP variability, most likely operating via hypoperfusion of the optic nerve, is associated with normal-tension GON. 24-H ambulatory BP monitoring might therefore help stratify the risk of normal-tension GON.
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http://dx.doi.org/10.1038/s41440-021-00687-1DOI Listing
July 2021

A nomogram for predicting feasibility of laparoscopic anterior resection with trans-rectal specimen extraction (NOSES) in patients with upper rectal cancer.

BMC Surg 2021 Jun 17;21(1):296. Epub 2021 Jun 17.

Department of General Surgery, Department of Colorectal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, No. 150 Jimo Road, Pudong New District, Shanghai, 200120, China.

Background: Laparoscopic anterior resection with trans-rectal specimen extraction (NOSES) has been demonstrated as a safe and effective technique in appropriate patients with upper rectal cancer (RC). However, improper selection of RC candidates for NOSES may lead to potential surgical and oncological unsafety as well as complications such as bacteria contamination and anastomotic leak. Unfortunately, no tools are available for evaluating the risk and excluding improper cases before surgery. This study aims to estimate its clinical relevancy and to investigate independent clinical-pathological predictors for identifying candidates for NOSES in patients with upper RC and to develop a validated scoring nomogram to facilitate clinical decision making.

Methods: The study was performed at Shanghai East hospital, a tertiary medical center and teaching hospital. 111 eligible patients with upper RC who underwent elective laparoscopic anterior resection between February and October of 2017 were included in the final analysis. Univariate and multivariate analyses were performed to compare characteristics between the two surgical techniques. Odds ratios (OR) were determined by logistic regression analyses to identify and quantify the clinical relevancy and ability of predictors for identifying NOSES candidate. The nomogram was constructed and characterized by c-index, calibration, bootstrapping validation, ROC curve analysis, and decision curve analysis.

Results: Upper RC patients with successful NOSES tended to be featured with female gender, negative preoperative CEA/CA19-9, decreased mesorectum length (MRL), ratio of diameter (ROD) and ratio of area (ROA) values, while no significant statistical correlations were observed with age, body mass index (BMI), tumor location, and tumor-related biological characteristics (ie., vascular invasion, lymph node count, TNM stages). Furthermore, the two techniques exhibited comparably low incidence of perioperative complications and achieved similar functional results under the standard procedures. The nomogram incorporating three independent preoperative predictors including gender, CEA status and ROD showed a high c-index of 0.814 and considerable reliability, accuracy and clinical net benefit.

Conclusions: NOSES for patients with upper RC is multifactorial; while it is a safe and efficient technique if used properly. The nomogram is useful for patient evaluation in the future.
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http://dx.doi.org/10.1186/s12893-021-01290-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212478PMC
June 2021

Tumor suppressor miR-192-5p targets TRPM7 and inhibits proliferation and invasion in cervical cancer.

Kaohsiung J Med Sci 2021 May 27. Epub 2021 May 27.

Department of Gynecology, Affiliated Hospital of Jiangnan University, Wuxi, China.

Cervical cancer is the fourth highest mortality cancer among women worldwide. Many researchers have discovered the major anticancer role of miR-192-5p. However, no study has revealed the effect of miR-192-5p on cervical cancer and its molecular mechanism. Therefore, in this study, we aimed to explore the role of miR-192-5p in proliferation, invasion of cervical cancer, and its regulatory mechanism. Firstly, the expression level of miR-192-5p was examined by real-time quantitative polymerase chain reaction. Cell counting kit-8 analysis was applied to detect the proliferation of transfected Caski and SiHa cells. Flow cytometry assay was applied to detect the apoptosis of transfected Caski and SiHa cells. Our result showed that miR-192-5p restrained cervical cancer cell proliferation and induced apoptosis. Then we employed wound healing and transwell assays to analyze the migration and invasion abilities of Caski and SiHa cells in vitro. The results showed that miR-192-5p had an inhibitory effect on cervical cancer migration and invasion. The results of in vivo experiment demonstrated that miR-192-5p also inhibited tumor development in nude mice. We further detected that the binding of transient receptor potential melastatin-subfamily member 7 (TRPM7) to miR-192-5p using bioinformatic methods and dual-luciferase reporter assay. Finally, we found that TRPM7 overexpression reversed the inhibitory effects of miR-192-5p on proliferation, migration, and invasion on cervical cancer cells. In conclusion, the findings of the present study revealed that miR-192-5p performs an inhibitory role in cervical cancer proliferation and invasion by targeting TRPM7.
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http://dx.doi.org/10.1002/kjm2.12398DOI Listing
May 2021

Two-Year Responses of Heart Rate and Heart Rate Variability to First Occupational Lead Exposure.

Hypertension 2021 May 29;77(5):1775-1786. Epub 2021 Mar 29.

From the Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium (Y.-L.Y., L.T., J.D.M., D.-M.W., Z.-Y.Z.).

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16545DOI Listing
May 2021

Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas.

Mod Pathol 2021 Jul 10;34(7):1245-1260. Epub 2021 Mar 10.

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

WHO 2016 classified glioblastomas into IDH-mutant and IDH-wildtype with the former having a better prognosis but there was no study on IDH-mutant primary glioblastomas only, as previous series included secondary glioblastomas. We recruited a series of 67 IDH-mutant primary glioblastomas/astrocytoma IV without a prior low-grade astrocytoma and examined them using DNA-methylation profiling, targeted sequencing, RNA sequencing and TERT promoter sequencing, and correlated the molecular findings with clinical parameters. The median OS of 39.4 months of 64 cases and PFS of 25.9 months of 57 cases were better than the survival data of IDH-wildtype glioblastomas and IDH-mutant secondary glioblastomas retrieved from datasets. The molecular features often seen in glioblastomas, such as EGFR amplification, combined +7/-10, and TERT promoter mutations were only observed in 6/53 (11.3%), 4/53 (7.5%), and 2/67 (3.0%) cases, respectively, and gene fusions were found only in two cases. The main mechanism for telomere maintenance appeared to be alternative lengthening of telomeres as ATRX mutation was found in 34/53 (64.2%) cases. In t-SNE analyses of DNA-methylation profiles, with an exceptional of one case, a majority of our cases clustered to IDH-mutant high-grade astrocytoma subclass (40/53; 75.5%) and the rest to IDH-mutant astrocytoma subclass (12/53; 22.6%). The latter was also enriched with G-CIMP high cases (12/12; 100%). G-CIMP-high status and MGMT promoter methylation were independent good prognosticators for OS (p = 0.022 and p = 0.002, respectively) and TP53 mutation was an independent poor prognosticator (p = 0.013) when correlated with other clinical parameters. Homozygous deletion of CDKN2A/B was not correlated with OS (p = 0.197) and PFS (p = 0.278). PDGFRA amplification or mutation was found in 16/59 (27.1%) of cases and was correlated with G-CIMP-low status (p = 0.010). Aside from the three well-known pathways of pathogenesis in glioblastomas, chromatin modifying and mismatch repair pathways were common aberrations (88.7% and 20.8%, respectively), the former due to high frequency of ATRX involvement. We conclude that IDH-mutant primary glioblastomas have better prognosis than secondary glioblastomas and have major molecular differences from other commoner glioblastomas. G-CIMP subgroups, MGMT promoter methylation, and TP53 mutation are useful prognostic adjuncts.
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http://dx.doi.org/10.1038/s41379-021-00778-xDOI Listing
July 2021

Relative and Absolute Risk to Guide the Management of Pulse Pressure, an Age-Related Cardiovascular Risk Factor.

Am J Hypertens 2021 Mar 4. Epub 2021 Mar 4.

Laboratory of Neurosciences, Faculty of Medicine, University of Zulia, Maracaibo, Zulia, Venezuela.

Background: Pulse pressure (PP) reflects the age-related stiffening of the central arteries, but no study addressed the management of the PP-related risk over the human lifespan.

Methods: In 4663 young (18-49 years) and 7185 older adults (≥50 years), brachial PP was recorded over 24-hour. Total mortality and all major cardiovascular events combined (MACE) were co-primary endpoints. Cardiovascular death, coronary events and stroke were secondary endpoints.

Results: In young adults (median follow-up, 14.1 years; mean PP, 45.1 mmHg), greater PP was not associated with absolute risk; the endpoint rates were ≤2.01 per 1000 person-years. The adjusted hazard ratios expressed per 10mmHg PP increments were less than unity (P≤0.027) for MACE (0.67; 95% CI, 0.47-0.96) and cardiovascular death (0.33; 95% CI, 0.11-0.75). In older adults (median follow-up, 13.1 years; mean PP, 52.7 mmHg), the endpoint rates, expressing absolute risk, ranged from 22.5 to 45.4 per 1000 person-years and the adjusted hazard ratios, reflecting relative risk, from 1.09 to 1.54 (P<0.0001). The PPrelated relative risks of death, MACE and stroke decreased >3-fold from age 55 to 75 years, whereas absolute risk rose by a factor 3.

Conclusions: From 50 years onwards, the PP-related relative risk decreases, whereas absolute risk increases. From a lifecourse perspective, young adulthood provides a window of opportunity to manage risk factors and prevent target organ damage as forerunner of premature death and MACE. In older adults, treatment should address absolute risk, thereby extending life in years and quality.
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http://dx.doi.org/10.1093/ajh/hpab048DOI Listing
March 2021

Modulation of Autophagy Through Regulation of 5'-AMP-Activated Protein Kinase Affects Mitophagy and Mitochondrial Function in Primary Human Trophoblasts.

Reprod Sci 2021 08 22;28(8):2314-2322. Epub 2021 Feb 22.

Department of Obstetrics and Gynecology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.

The placenta is important for pregnancy maintenance, and autophagy is documented to be essential for placental development. Autophagy is responsible for degrading and recycling cellular misfolded proteins and damaged organelles. Mitophagy is a selective type of autophagy, where the autophagic machinery engulfs the damaged mitochondria for degradation, and there is reciprocal crosstalk between autophagy and mitochondria. Within these processes, 5'-AMP-activated protein kinase (AMPK) plays an important role. However, the role of AMPK regulation in both autophagy and mitochondria in primary human trophoblasts is unknown. In this study, we address this question by investigating changes in mRNA expression and the abundance of autophagy- and mitochondria-related proteins in isolated human trophoblasts after treatment with AMPK agonists and antagonists. We found that compared to the control group, autophagy was slightly suppressed in the AMPK agonist group and significantly enhanced autophagy in the AMPK antagonist group. However, the expressions of genes related to autophagosome-lysosome fusion were reduced, while genes related to lysosomal function were unchanged in both groups. Furthermore, mitophagy and mitochondrial fusion/fission were both impaired in the AMPK agonist and antagonist groups. Although mitochondrial biogenesis was enhanced in both groups, the function of mitochondrial fatty acid oxidation was increased in the AMPK agonist group but decreased in the AMPK antagonist group. Overall, our study demonstrates that AMPK regulation negatively modulates autophagy and consequently affects mitophagy, mitochondrial fusion/fission, and function in primary human trophoblasts.
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http://dx.doi.org/10.1007/s43032-021-00495-5DOI Listing
August 2021

Starting Antihypertensive Drug Treatment With Combination Therapy: Controversies in Hypertension - Con Side of the Argument.

Hypertension 2021 Mar 10;77(3):788-798. Epub 2021 Feb 10.

Research Institute Alliance for the Promotion of Preventive Medicine (APPREMED), Mechelen, Belgium (K.A., G.E.M., T.W.H., J.A.S).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.12858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884241PMC
March 2021

Diastolic left ventricular function in relation to the retinal microvascular fractal dimension in a Flemish population.

Hypertens Res 2021 Apr 4;44(4):446-453. Epub 2021 Feb 4.

Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.

Fractal analysis provides a global assessment of vascular networks (e.g., geometric complexity). We examined the association of diastolic left ventricular (LV) function with the retinal microvascular fractal dimension. A lower fractal dimension signifies a sparser retinal microvascular network. In 628 randomly recruited Flemish individuals (51.3% women; mean age, 50.8 years), we measured diastolic LV function by echocardiography and the retinal microvascular fractal dimension by the box-counting method (Singapore I Vessel Assessment software, version 3.6). The left atrial volume index (LAVI), e', E/e' and retinal microvascular fractal dimension averaged (±SD) 24.3 ± 6.2 mL/m, 10.9 ± 3.6 cm/s, 6.96 ± 2.2, and 1.39 ± 0.05, respectively. The LAVI, E, e' and E/e' were associated (P < 0.001) with the retinal microvascular fractal dimension with association sizes (per 1 SD), amounting to -1.49 mL/m (95% confidence interval, -1.98 to -1.01), 2.57 cm/s (1.31-3.84), 1.34 cm/s (1.07-1.60), and -0.74 (-0.91 to -0.57), respectively. With adjustments applied for potential covariables, the associations of E peak and E/e' with the retinal microvascular fractal dimension remained significant (P ≤ 0.020). Over a median follow-up of 5.3 years, 18 deaths occurred. The crude and adjusted hazard ratios expressing the risk of all-cause mortality associated with a 1-SD increment in the retinal microvascular fractal dimension were 0.36 (0.23-0.57; P < 0.001) and 0.57 (0.34-0.96; P = 0.035), respectively. In the general population, a lower retinal microvascular fractal dimension was associated with greater E/e', a measure of LV filling pressure. These observations can potentially be translated into new strategies for the prevention of diastolic LV dysfunction.
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http://dx.doi.org/10.1038/s41440-021-00623-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019655PMC
April 2021

Thoracic endometriosis presented as catamental hemoptysis: a case series of a rare disease.

Curr Med Res Opin 2021 Apr 17;37(4):685-691. Epub 2021 Feb 17.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.

Objective: Thoracic endometriosis syndrome (TES) is a rare disease in which a functioning endometrial tissue is observed in the pleura, lung, parenchyma, airways, and/or diaphragm. The optimal management of this disease remains a matter of debate. We aimed to report TES cases and their effective hormonal treatment and management.

Methods: In this retrospective study, women presented as catamenial hemoptysis (CH) diagnosed with thoracic endometriosis were included. The main outcome of measure was cessation or recurrence of the clinical manifestations of thoracic endometriosis.

Results: The mean onset age of the 14 patients was 30.21 ± 5.40 years. CH was characteristic symptom of these patients. All patients underwent chest computed tomography (CT) scan during menstruation and 2 or 3 weeks after menstruation, which showed the obvious shrinking or disappearance of the lesions. All of the patients were given Gonadotropin releasing hormone agonists (GnRHa) for 3 to 6 months, eleven of them were administered with combined oral contraceptives (COC) cyclically after GnRHa. The median follow-up duration was 24 months. Hemoptysis recurrence was observed in one patient.

Conclusions: CH is a rare clinical entity of thoracic endometriosis, the change of CT images during and after menstruation or the response to GnRHa were helpful for accurate diagnosis. Hormonal treatment with GnRHa followed by COCs cyclically could be employed for efficient management of thoracic endometriosis.
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http://dx.doi.org/10.1080/03007995.2021.1885363DOI Listing
April 2021

Risk factors for mortality of coronavirus disease-2019 (COVID-19) patients in two centers of Hubei province, China: A retrospective analysis.

PLoS One 2021 28;16(1):e0246030. Epub 2021 Jan 28.

Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Xiamen University, Fujian, China.

Purpose: Since the outbreak in late December 2019 in Wuhan, China, coronavirus disease-2019 (COVID-19) has become a global pandemic. We analyzed and compared the clinical, laboratory, and radiological characteristics between survivors and non-survivors and identify risk factors for mortality.

Methods: Clinical and laboratory variables, radiological features, treatment approach, and complications were retrospectively collected in two centers of Hubei province, China. Cox regression analysis was conducted to identify the risk factors for mortality.

Results: A total of 432 patients were enrolled, and the median patient age was 54 years. The overall mortality rate was 5.09% (22/432). As compared with the survivor group (n = 410), those in the non-survivor group (n = 22) were older, and they had a higher frequency of comorbidities and were more prone to suffer from dyspnea. Several abnormal laboratory variables indicated that acute cardiac injury, hepatic damage, and acute renal insufficiency were detected in the non-survivor group. Non-surviving patients also had a high computed tomography (CT) score and higher rate of consolidation. The most common complication causing death was acute respiratory distress syndrome (ARDS) (18/22, 81.8%). Multivariate Cox regression analysis revealed that hemoglobin (Hb) <90 g/L (hazard ratio, 10.776; 95% confidence interval, 3.075-37.766; p<0.0001), creatine kinase (CK-MB) >8 U/L (9.155; 2.424-34.584; p = 0.001), lactate dehydrogenase (LDH) >245 U/L (5.963; 2.029-17.529; p = 0.001), procalcitonin (PCT) >0.5 ng/ml (7.080; 1.671-29.992; p = 0.008), and CT score >10 (39.503; 12.430-125.539; p<0.0001) were independent risk factors for the mortality of COVID-19.

Conclusions: Low Hb, high LDH, PCT, and CT score on admission were the predictors for mortality and could assist clinicians in early identification of poor prognosis among COVID-19 patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246030PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842894PMC
February 2021

Rapid Geographical Origin Identification and Quality Assessment of Angelicae Sinensis Radix by FT-NIR Spectroscopy.

J Anal Methods Chem 2021 12;2021:8875876. Epub 2021 Jan 12.

National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Angelicae Sinensis Radix is a widely used traditional Chinese medicine and spice in China. The purpose of this study was to develop a methodology for geographical classification of Angelicae Sinensis Radix and determine the contents of ferulic acid and Z-ligustilide in the samples using near-infrared spectroscopy. A qualitative model was established to identify the geographical origin of Angelicae Sinensis Radix using Fourier transform near-infrared (FT-NIR) spectroscopy. Support vector machine (SVM) algorithms were used for the establishment of a qualitative model. The optimum SVM model had a recognition rate of 100% for the calibration set and 83.72% for the prediction set. In addition, a quantitative model was established to predict the content of ferulic acid and Z-ligustilide using FT-NIR. Partial least squares regression (PLSR) algorithms were used for the establishment of a quantitative model. Synergy interval-PLS (Si-PLS) was used to screen the characteristic spectral interval to obtain the best PLSR model. The coefficient of determination for calibration (R2C) for the best PLSR models established with the optimal spectral preprocessing method and selected important spectral regions for the quantitative determination of ferulic acid and Z-ligustilide was 0.9659 and 0.9611, respectively, while the coefficient of determination for prediction (R2P) was 0.9118 and 0.9206, respectively. The values of the ratio of prediction to deviation (RPD) of the two final optimized PLSR models were greater than 2. The results suggested that NIR spectroscopy combined with SVM and PLSR algorithms could be exploited in the discrimination of Angelicae Sinensis Radix from different geographical locations for quality assurance and monitoring. This study might serve as a reference for quality evaluation of agricultural, pharmaceutical, and food products.
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http://dx.doi.org/10.1155/2021/8875876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815386PMC
January 2021

Ambulatory Blood Pressure Monitoring to Diagnose and Manage Hypertension.

Hypertension 2021 02 4;77(2):254-264. Epub 2021 Jan 4.

Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium (K.A., Z.-Y.Z., L.T., J.A.S).

This review portrays how ambulatory blood pressure (BP) monitoring was established and recommended as the method of choice for the assessment of BP and for the rational use of antihypertensive drugs. To establish much-needed diagnostic ambulatory BP thresholds, initial statistical approaches evolved into longitudinal studies of patients and populations, which demonstrated that cardiovascular complications are more closely associated with 24-hour and nighttime BP than with office BP. Studies cross-classifying individuals based on ambulatory and office BP thresholds identified white-coat hypertension, an elevated office BP in the presence of ambulatory normotension as a low-risk condition, whereas its counterpart, masked hypertension, carries a hazard almost as high as ambulatory combined with office hypertension. What clinically matters most is the level of the 24-hour and the nighttime BP, while other BP indexes derived from 24-hour ambulatory BP recordings, on top of the 24-hour and nighttime BP level, add little to risk stratification or hypertension management. Ambulatory BP monitoring is cost-effective. Ambulatory and home BP monitoring are complimentary approaches. Their interchangeability provides great versatility in the clinical implementation of out-of-office BP measurement. We are still waiting for evidence from randomized clinical trials to prove that out-of-office BP monitoring is superior to office BP in adjusting antihypertensive drug treatment and in the prevention of cardiovascular complications. A starting research line, the development of a standardized validation protocol for wearable BP monitoring devices, might facilitate the clinical applicability of ambulatory BP monitoring.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803442PMC
February 2021

Association of Fatal and Nonfatal Cardiovascular Outcomes With 24-Hour Mean Arterial Pressure.

Hypertension 2021 01 8;77(1):39-48. Epub 2020 Dec 8.

From the Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium (J.D.M., W.-Y. Y, L.T., F.-F.W., J.A.S., Z.-Y.Z.).

Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of <90 (normotension, n=6183), 90 to <92 (elevated MAP, n=909), 92 to <96 (stage-1 hypertension, n=1544), and ≥96 (stage-2 hypertension, n=2960) mm Hg yielded equivalent 10-year major adverse cardiovascular events risks as office MAP categorized using 2017 American thresholds for office SBP and DBP. Compared with 24-hour MAP normotension, hazard ratios were 0.96 (95% CI, 0.80-1.16), 1.32 (1.15-1.51), and 1.77 (1.59-1.97), for elevated and stage-1 and stage-2 hypertensive MAP. On top of 24-hour MAP, higher 24-hour SBP increased, whereas higher 24-hour DBP attenuated risk (<0.001). Considering the 24-hour measurements, R statistics were similar for SBP (1.34) and MAP (1.28), lower for DBP than for MAP (0.47), and reduced to null, if the base model included SBP and DBP; if the ambulatory BP indexes were dichotomized according to the 2017 American guideline and the proposed 92 mm Hg for MAP, the R values were 0.71, 0.89, 0.32, and 0.10, respectively. In conclusion, the clinical application of 24-hour MAP thresholds in conjunction with SBP and DBP refines risk estimates.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720872PMC
January 2021

Two-year neurocognitive responses to first occupational lead exposure.

Scand J Work Environ Health 2021 Apr 4;47(3):233-243. Epub 2020 Dec 4.

Research Institute Alliance for the Promotion of Preventive Medicine, Leopoldstraat 59, BE-2800 Mechelen, Belgium.

Objectives Lead exposure causes neurocognitive dysfunction in children, but its association with neurocognition in adults at current occupational exposure levels is uncertain mainly due to the lack of longitudinal studies. In the Study for Promotion of Health in Recycling Lead (NCT02243904), we assessed the two-year responses of neurocognitive function among workers without previous known occupational exposure newly hired at lead recycling plants. Methods Workers completed the digit-symbol test (DST) and Stroop test (ST) at baseline and annual follow-up visits. Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 µg/dL). Statistical methods included multivariable-adjusted mixed models with participants modelled as random effect. Results DST was administered to 260 participants (11.9% women; 46.9%/45.0% whites/Hispanics; mean age 29.4 years) and ST to 168 participants. Geometric means were 3.97 and 4.13 µg/dL for baseline BL, and 3.30 and 3.44 for the last-follow-up-to-baseline BL ratio in DST and ST cohorts, respectively. In partially adjusted models, a doubling of the BL ratio was associated with a 0.66% [95% confidence interval (CI) 0.03-1.30; P=0.040] increase in latency time (DST) and a 0.35% (95% CI ‑1.63-1.63; P=0.59) decrease in the inference effect (ST). In fully adjusted models, none of the associations of the changes in the DST and ST test results with the blood lead changes reached statistical significance (P≥0.12). Conclusions An over 3-fold increase in blood lead over two years of occupational exposure was not associated with a relevant decline in cognitive performance.
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http://dx.doi.org/10.5271/sjweh.3940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126443PMC
April 2021

RNA Interference-Based Silencing of the Gene for Reproductive and Developmental Disruptions in .

Insects 2020 Nov 11;11(11). Epub 2020 Nov 11.

Institute of Fruit and Tea, Hubei Academy of Agricultural Sciences, Wuhan 430064, China.

() is an essential gene regulating chitin during different developmental stages of arthropods. In the current study, we explored for the first time the role of gene regulation in the citrus red mite, (McGregor) (Acari: Tetranychidae), by silencing its expression using (RNA interference) RNAi-based strategies. The results reveal that tested in different developmental stages, including larvae, protonymphs, deutonymphs, and adults fed on sweet orange leaves dipped in various concentrations (200, 400, 600, and 800 ng/μL) of dsRNA-, resulted in a continuous reduction in their gene expression, and the extent of transcript knockdown was positively correlated with the concentration of dsRNA. Concentration-mortality response assays revealed a mortality of more than 50% among all the studied developmental stages, except for adulthood. Furthermore, the target gene dsRNA- treatment of larvae, protonymphs, deutonymphs, and females at a treatment rate of 800 ng/mL of dsRNA significantly decreased the egg-laying rates by 48.50%, 43.79%, 54%, and 39%, respectively, and the hatching rates were also considerably reduced by 64.70%, 70%, 64%, and 52.90%, respectively. Moreover, using the leaf dip method, we found that the RNA interference effectively reduced the transcript levels by 42.50% and 42.06% in the eggs and adults, respectively. The results of this study demonstrate that the RNAi of can dramatically reduce the survival and fecundity of , but the dsRNA concentrations and developmental stages can significantly influence the RNAi effects. These findings indicate the potential utility of the gene in causing developmental irregularities, which could aid in the development of effective and novel RNAi-based strategies for controlling .
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http://dx.doi.org/10.3390/insects11110786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697958PMC
November 2020

Clinical and mutational profiles of adult medulloblastoma groups.

Acta Neuropathol Commun 2020 11 10;8(1):191. Epub 2020 Nov 10.

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong.

Adult medulloblastomas are clinically and molecularly understudied due to their rarity. We performed molecular grouping, targeted sequencing, and TERT promoter Sanger sequencing on a cohort of 99 adult medulloblastomas. SHH made up 50% of the cohort, whereas Group 3 (13%) was present in comparable proportion to WNT (19%) and Group 4 (18%). In contrast to paediatric medulloblastomas, molecular groups had no prognostic impact in our adult cohort (p = 0.877). Most frequently mutated genes were TERT (including promoter mutations, mutated in 36% cases), chromatin modifiers KMT2D (31%) and KMT2C (30%), TCF4 (31%), PTCH1 (27%) and DDX3X (24%). Adult WNT patients showed enrichment of TP53 mutations (6/15 WNT cases), and 3/6 TP53-mutant WNT tumours were of large cell/anaplastic histology. Adult SHH medulloblastomas had frequent upstream pathway alterations (PTCH1 and SMO mutations) and few downstream alterations (SUFU mutations, MYCN amplifications). TERT promoter mutations were found in 72% of adult SHH patients, and were restricted to this group. Adult Group 3 tumours lacked hallmark MYC amplifications, but had recurrent mutations in KBTBD4 and NOTCH1. Adult Group 4 tumours harboured recurrent mutations in TCF4 and chromatin modifier genes. Overall, amplifications of MYC and MYCN were rare (3%). Since molecular groups were not prognostic, alternative prognostic markers are needed for adult medulloblastoma. KMT2C mutations were frequently found across molecular groups and were associated with poor survival (p = 0.002). Multivariate analysis identified histological type (p = 0.026), metastasis (p = 0.031) and KMT2C mutational status (p = 0.046) as independent prognosticators in our cohort. In summary, we identified distinct clinical and mutational characteristics of adult medulloblastomas that will inform their risk stratification and treatment.
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http://dx.doi.org/10.1186/s40478-020-01066-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656770PMC
November 2020

Two-Year Responses of Office and Ambulatory Blood Pressure to First Occupational Lead Exposure.

Hypertension 2020 10 9;76(4):1299-1307. Epub 2020 Sep 9.

From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium (Y.-L.Y., L.T., J.D.M., C.-G.Y., D.-M.W., F.-F.W., Z.-Y.Z., J.A.S.).

Lead exposure causing hypertension is the mechanism commonly assumed to set off premature death and cardiovascular complications. However, at current exposure levels in the developed world, the link between hypertension and lead remains unproven. In the Study for Promotion of Health in Recycling Lead (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02243904), we recorded the 2-year responses of office blood pressure (average of 5 consecutive readings) and 24-hour ambulatory blood pressure to first occupational lead exposure in workers newly employed at lead recycling plants. Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 µg/dL). Hypertension was defined according to the 2017 American College of Cardiology/American Heart Association guideline. Statistical methods included multivariable-adjusted mixed models with participants modeled as a random effect and interval-censored Cox regression. Office blood pressure was measured in 267 participants (11.6% women, mean age at enrollment, 28.6 years) and ambulatory blood pressure in 137 at 2 follow-up visits. Geometric means were 4.09 µg/dL for baseline BL and 3.30 for the last-follow-up-to-baseline BL ratio. Fully adjusted changes in systolic/diastolic blood pressure associated with a doubling of the BL ratio were 0.36/0.28 mm Hg (95% CI, -0.55 to 1.27/-0.48 to 1.04 mm Hg) for office blood pressure and -0.18/0.11 mm Hg (-2.09 to 1.74/-1.05 to 1.27 mm Hg) for 24-hour ambulatory blood pressure. The adjusted hazard ratios of moving up across hypertension categories for a doubling in BL were 1.13 (0.93-1.38) and 0.84 (0.57-1.22) for office blood pressure and ambulatory blood pressure, respectively. In conclusion, the 2-year blood pressure responses and incident hypertension were not associated with the BL increase on first occupational exposure.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480942PMC
October 2020

Analysis of the Primary and Post-Treatment Antibiotic Resistance of Helicobacter pylori in the Nanjing Area.

Curr Pharm Biotechnol 2021 ;22(5):682-685

Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Background: Resistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide. The study was aimed to understand the current situation of antibiotic resistance in Nanjing and to provide a reasonable basis for clinical selection of antibiotics to cure H. pylori.

Objective: To investigate the current status of H. pylori antibiotics resistance in the Nanjing area, and analyze the primary and post-treatment antibiotic resistance of H. pylori in this area.

Methods: During the period from July 2017 to December 2019, 1533 gastric mucosal specimens from patients with positive H. pylori confirmed by a breath test or rapid urease test were collected for isolation and identification of H. pylori. The agar dilution method was used for the antibiotic resistance test.

Results: The result showed that the resistance rates of H. pylori to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 2.74%, 47.03%, 33.59%, 0.91%, 0.52% and 80.76%, respectively in the period of July 2017 to December 2019. The resistance rates of H. pylori (primary vs. post-treatment) to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 1.83% vs. 6.08%, 38.62% vs. 77.81%, 27.41% vs. 56.23%, 0.58% vs. 2.13%, 0.33% vs. 1.22%, 78.57% vs. 88.75%, respectively.

Conclusion: Antibiotic resistance of H. pylori remained a problem for the effective eradication of this pathogen and its associated diseases in the Nanjing area. For post-treatment eradication patients, clinicians should take into account regional antibiotic resistance rate, personal antibiotic exposure history, economic benefit ratio, adverse antibiotic reactions, antibiotic availability and other aspects.
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http://dx.doi.org/10.2174/1389201021666200722162613DOI Listing
June 2021

A Shift Pattern of Bacterial Communities Across the Life Stages of the Citrus Red Mite, .

Front Microbiol 2020 10;11:1620. Epub 2020 Jul 10.

State Key Laboratory of Agricultural Microbiology, Key Laboratory of Horticultural Plant Biology (MOE), Institute of Urban and Horticultural Entomology, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, China.

As one of the most detrimental citrus pests worldwide, the citrus red mite, (McGregor), shows extraordinary fecundity, polyphagia, and acaricide resistance, which may be influenced by microbes as other arthropod pests. However, the community structure and physiological function of microbes in are still largely unknown. Here, the high-throughput sequencing of 16S rDNA amplicons was employed to identify and compare the profile of bacterial communities across the larva, protonymph, deutonymph, and adult stages of . We observed a dominance of phylums Proteobacteria and Firmicutes, and classes α-, γ-, β-Proteobacteria and Bacilli in the bacterial communities across the host lifespan. Based on the dynamic analysis of the bacterial community structure, a significant shift pattern between the immature (larva, protonymph, and deutonymph) and adult stages was observed. Accordingly, among the major families (and corresponding genera), although the relative abundances of Pseudomonadaceae (), Moraxellaceae (), and Sphingobacteriaceae () were consistent in larva to deutonymph stages, they were significantly increased to 30.18 ± 8.76% (30.16 ± 8.75%), 20.78 ± 10.86% (18.80 ± 10.84%), and 11.71 ± 5.49% (11.68 ± 5.48%), respectively, in adult stage, which implied the important function of these bacteria on the adults' physiology. Actually, the functional prediction of bacterial communities and Spearman correlation analysis further confirm that these bacteria had positively correlations with the pathway of "lipid metabolism" (including eight sublevel pathways) and "metabolism of cofactors and vitamins" (including five sublevel pathways), which all only increased in adult stages. In addition, the bacterial communities were eliminated by using broad-spectrum antibiotics, streptomycin, which significantly suppressed the survival and oviposition of . Overall, we not only confirmed the physiological effects of bacteria community on the vitality and fecundity of adult hosts, but also revealed the shift pattern of bacterial community structures across the life stages and demonstrated the co-enhancements of specific bacterial groups and bacterial functions in nutritional metabolism in . This study sheds light on basic information about the mutualism between spider mites and bacteria, which may be useful in shaping the next generation of control strategies for spider mite pests, especially .
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http://dx.doi.org/10.3389/fmicb.2020.01620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366552PMC
July 2020

Retinal and Renal Microvasculature in Relation to Central Hemodynamics in 11-Year-Old Children Born Preterm or At Term.

J Am Heart Assoc 2020 08 31;9(15):e014305. Epub 2020 Jul 31.

Studies Coordinating Centre Research Unit Hypertension and Cardiovascular Epidemiology KU Leuven Department of Cardiovascular Sciences University of Leuven Belgium.

Background Prematurity disrupts the perinatal maturation of the microvasculature and macrovasculature and confers high risk of vascular dysfunction later in life. No previous studies have investigated the crosstalk between the microvasculature and macrovasculature in childhood. Methods and Results In a case-control study, we enrolled 55 children aged 11 years weighing <1000 g at birth and 71 matched controls (October 2014-November 2015). We derived central blood pressure (BP) wave by applanation tonometry and calculated the forward/backward pulse waves by an automated pressure-based wave separation algorithm. We measured the renal resistive index by pulsed wave Doppler and the central retinal arteriolar equivalent by computer-assisted program software. Compared with controls, patients had higher central systolic BP (101.5 versus 95.2 mm Hg, <0.001) and backward wave amplitude (15.5 versus 14.2 mm Hg, =0.029), and smaller central retinal arteriolar equivalent (163.2 versus 175.4 µm, <0.001). In multivariable analyses, central retinal arteriolar equivalent was smaller with higher values (+1 SD) of central systolic BP (-2.94 µm; 95% CI, -5.18 to -0.70 µm [=0.011]) and forward (-2.57 µm; CI, -4.81 to -0.32 µm [=0.026]) and backward (-3.20 µm; CI, -5.47 to -0.94 µm [=0.006]) wave amplitudes. Greater renal resistive index was associated with higher backward wave amplitude (0.92 mm Hg, =0.036). Conclusions In childhood, prematurity compared with term birth is associated with higher central systolic BP and forward/backward wave amplitudes. Higher renal resistive index likely moves reflection points closer to the heart, thereby explaining the inverse association of central retinal arteriolar equivalent with central systolic BP and backward wave amplitude. These observations highlight the crosstalk between the microcirculation and macrocirculation in children. Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT02147457.
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http://dx.doi.org/10.1161/JAHA.119.014305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792278PMC
August 2020

Association between cytokine profiles and lung injury in COVID-19 pneumonia.

Respir Res 2020 Jul 29;21(1):201. Epub 2020 Jul 29.

Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Xiamen University; Teaching Hospital of Fujian Medical University, No. 201, Hubin Nan Road, Siming District, Xiamen, Fujian Province, 361004, People's Republic of China.

Background: Coronavirus disease 2019 (COVID-19) is a new respiratory and systemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of the present study was to investigate the association between cytokine profiles and lung injury in COVID-19 pneumonia.

Methods: This retrospective study was conducted in COVID-19 patients. Demographic characteristics, symptoms, signs, underlying diseases, and laboratory data were collected. The patients were divided into COVID-19 with pneumonia and without pneumonia. CT severity score and PaO/FiO ratio were used to assess lung injury.

Results: 106 patients with 12 COVID-19 without pneumonia and 94 COVID-19 with pneumonia were included. Compared with COVID-19 without pneumonia, COVID-19 with pneumonia had significantly higher serum interleukin (IL)-2R, IL-6, and tumor necrosis factor (TNF)-α. Correlation analysis showed that CT severity score and PaO/FiO were significantly correlated with age, presence of any coexisting disorder, lymphocyte count, procalcitonin, IL-2R, and IL-6. In multivariate analysis, log IL6 was the only independent explanatory variables for CT severity score (β = 0.397, p < 0.001) and PaO/FiO (β = - 0.434, p = 0.003).

Conclusions: Elevation of circulating cytokines was significantly associated with presence of pneumonia in COVID-19 and the severity of lung injury in COVID-19 pneumonia. Circulating IL-6 independently predicted the severity of lung injury in COVID-19 pneumonia.
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http://dx.doi.org/10.1186/s12931-020-01465-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389162PMC
July 2020

Cardiovascular End Points and Mortality Are Not Closer Associated With Central Than Peripheral Pulsatile Blood Pressure Components.

Hypertension 2020 08 8;76(2):350-358. Epub 2020 Jul 8.

Research Unit Hypertension and Cardiovascular Epidemiology (L.T., F.-F.W., J.D.M., Z.-Y.Z., J.A.S.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium.

Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular end point occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP, and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% CI, 1.33-1.70) for cSBP, 1.36 (95% CI, 1.19-1.54) for cPP, 1.49 (95% CI, 1.33-1.67) for pSBP, and 1.34 (95% CI, 1.19-1.51) for pPP (<0.001). Further adjustment of cSBP and cPP, respectively, for pSBP and pPP, and vice versa, removed the significance of all hazard ratios. Adding cSBP, cPP, pSBP, pPP to a base model including covariables increased the model fit (<0.001) with generalized increments ranging from 0.37% to 0.74% but adding a second BP to a model including already one did not. Analyses of the secondary end points, including total mortality (204 deaths), coronary end points (109) and strokes (89), and various sensitivity analyses produced consistent results. In conclusion, associations of the primary and secondary end points with SBP and pulse pressure were not stronger if BP was measured centrally compared with peripherally.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340226PMC
August 2020

Opportunities of Antidiabetic Drugs in Cardiovascular Medicine: A Meta-Analysis and Perspectives for Trial Design.

Hypertension 2020 08 8;76(2):420-431. Epub 2020 Jul 8.

From the Department of Science and Technology, Beijing YouAn Hospital (C.Y., Y.-M.F.), Capital Medical University, China.

To identify potential application of GLP1-RAs (glucagon-like peptide-1 receptor agonists) and SGLT2-Is (sodium-dependent glucose cotrasnsporter-2 inhibitors) in cardiovascular medicine, we performed PubMed search until March 31, 2020 and selected placebo-controlled randomized trials (RCTs) in patients with type 2 diabetes mellitus. Twenty-four hour ambulatory and office blood pressure (BP), major adverse cardiovascular events (MACE), progression of chronic kidney disease (CKD), and changes in glycated hemoglobin and body weight were aggregated across RCTs using random-effect models. In 2238 patients (7 RCTs), SGLT2-Is lowered 24-hour systolic/diastolic BP by 4.4/1.9 mm Hg (95% CI, 3.4-5.5/1.2-2.6 mm Hg), whereas 2 GLP1-RAs RCTs produced contradictory BP results. Over 1.3 to 5.4 years of follow-up of 56 004 patients (7 RCTs), aggregate hazard ratios associated with GLP1-RA treatment were 0.88 (0.84-0.93) for MACE, 0.84 (0.74-0.89) for CKD, and ranged from 0.84 to 0.90 for individual MACE end points (≤0.01). Across 5 SGLT2-Is RCTs, including 43 467 patients with 1.5 to 4.2 years follow-up, hazard ratios were 0.87 (0.82-0.93) for MACE, 0.68 (0.62-0.75) for HF, 0.82 (0.72-0.93) for cardiovascular death, 0.87 (0.79-0.96) for myocardial infarction, and 0.61 (0.56-0.67) for worsening CKD. The risk of HF and CKD, but not MACE, decreased with more BP lowering. Stricter glycemic control was associated with higher HF risk, but unrelated to MACE or CKD. The aggregate effect sizes on systolic BP, body weight, and glycated hemoglobin were -1.61 mm Hg, -2.40 kg, and -0.69% for GLP1-RAs, and -2.53 mm Hg, -1.15 kg and -0.24%, for SGLT2-Is (<0.001). In conclusion, GLP1-RAs and SGLT2-Is reduced cardiovascular risk with differential benefit profiles.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14791DOI Listing
August 2020

Transthyretin increases migration and invasion of rat placental trophoblast cells.

FEBS Open Bio 2020 08 1;10(8):1568-1576. Epub 2020 Jul 1.

Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China.

Preeclampsia (PE) is a hypertensive disorder of pregnancy. Early diagnosis of PE is currently contingent on regular prenatal physical examinations and may be facilitated by identification of novel diagnostic markers. Transthyretin (TTR), also known as prealbumin, is primarily responsible for maintaining the normal levels of thyroxine and retinol binding protein. The expression of TTR is lower in patients with severe PE as compared with healthy controls. Here, we examined the suitability of TTR as a diagnostic marker in pregnant hypertensive rats. N'-nitro-l-arginine-methylesterhydrochloride (l-NAME) was used to generate a rat model of hypertension during pregnancy. Rat placental trophoblast cells were divided into control and TTR groups for in vitro experiments. Systolic blood pressure, diastolic blood pressure, mean blood pressure and urinary protein of hypertensive pregnant rats were higher than those of healthy pregnant rats, but these effects could be reversed by TTR treatment. There were no significant changes in blood pressure and urinary protein in healthy pregnant rats before or after TTR treatment. TTR levels in the serum and placental tissues of pregnant hypertensive rats were significantly reduced compared with those of healthy pregnant rats. Changes in placental and fetal weights in the hypertensive model could also be rescued by TTR treatment. TTR treatment significantly increased the level of matrix metalloproteinase-2/9 in hypertensive rats. Finally, in vivo and in vitro experiments demonstrated that TTR effectively increased the migration and invasion of rat placental trophoblast cells, as well as matrix metalloproteinase-2/9 levels in these cells. In conclusion, our data from a rat model suggest that TTR may have potential as a novel marker for PE diagnosis.
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http://dx.doi.org/10.1002/2211-5463.12911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396443PMC
August 2020

Factors influencing the application of transrectal natural orifice specimen extraction performed laparoscopically for colorectal cancer: A retrospective study.

Asian J Surg 2021 Jan 5;44(1):164-168. Epub 2020 Jun 5.

Department of General Surgery and Colorectal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. Electronic address:

Background: A few factors influence the feasibility of transrectal natural orifice specimen extraction (NOSE) surgery for colorectal cancers. However, little is known about the underlying factors of NOSE surgery.

Methods: Consecutive patients with rectal and sigmoid colon cancers treated laparoscopically between January 2014 and April 2017 were enrolled in this study. The transrectal NOSE performed laparoscopically was the first choice of all patients. When NOSE failed, the specimen was removed through a midline abdominal wall incision. Univariate and multivariate logistic regression analyses were performed to identify challenging factors influencing the intraoperative specimen extraction.

Results: Overall, 412 consecutive patients were included. NOSE performed laparoscopically was successful in 278 patients (75.5%) and unsuccessful in 90 patients (24.5%). The multivariate analyses indicated that body mass index (BMI; odds ratio [OR] = 3.510, 95% confidence interval [CI]: 1.333-9.243, p = 0.011), mesenteric thickness (OR = 1.069, 95% CI: 1.032-1.107, p < 0.001), maximum tumor diameter (OR = 2.827, 95% CI: 1.094-7.302, p = 0.032), and tumor T stage (OR = 2.831, 95% CI: 1.258-6.369, p = 0.012) were the factors influencing the feasibility of NOSE surgery.

Conclusion: A successful transrectal NOSE surgery was associated with a lower BMI, thinner mesentery, lesser tumor diameter, and earlier tumor T stage.
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http://dx.doi.org/10.1016/j.asjsur.2020.04.008DOI Listing
January 2021

Ambulatory Blood Pressure in Relation to Plasma and Urinary Manganese.

Hypertension 2020 04 2;75(4):1133-1139. Epub 2020 Mar 2.

From the Department of Epidemiology and Health Systems, Center for Primary Care and Public Health-Unisanté (Z.-Y.Z., C.C., B.P., D.P., M. Bochud), University of Lausanne, Switzerland.

The association of blood pressure (BP) with manganese-an essential trace element required for human health-remains poorly studied. In 734 randomly recruited Swiss participants (mean age, 47.5 years; 51.4% women), we related ambulatory BP to 2 biomarkers, plasma manganese (pMn) and the urinary manganese (uMn) excretion. To allow for diurnal variation, we assessed BP and uMn over 24 hours and during wakefulness and sleep, using split urine samples. Twenty-four-hour, daytime, and nighttime systolic/diastolic BPs averaged 119.8/78.1, 123.8/81.2, and 107.0/68.3 mm Hg; the corresponding median uMn were 199.5, 83.0, and 51.5 μmol and median pMn, 0.52 μg/L. In analyses dichotomized by the median of the biomarkers, greater pMn was associated with higher 24-hour systolic/diastolic BP (+4.1/+2.3 mm Hg; ≤0.0003), greater daytime uMn with lower daytime BP (-3.5/-1.9 mm Hg; ≤0.0067), and greater nighttime uMn with higher nighttime BP (+2.9/+1.2 mm Hg; ≤0.046). In multivariable-adjusted analyses, significance (≤0.030) was retained for the positive association of 24-hour and daytime diastolic BP with pMn and for systolic BP in relation to uMn at night. The association sizes for a 2-fold increment in the biomarkers amounting to 0.77 mm Hg (95% CI, 0.08-1.47 mm Hg), 0.97 (CI, 0.20-1.76) and 1.33 (CI, 0.20-2.50 mm Hg), respectively. In conclusion, there were positive associations between diastolic BP and pMn over 24 hours and during daytime and between systolic BP and uMn at night.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13649DOI Listing
April 2020
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