Publications by authors named "Yanjun Wang"

226 Publications

Shexiang Baoxin Pills Inhibited Proliferation and Migration of Human Coronary Artery Smooth Muscle Cells PI3K/AKT/mTOR Pathway.

Front Cardiovasc Med 2021 25;8:700630. Epub 2021 Aug 25.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Proliferation and migration of smooth muscle cells in the coronary artery contribute to the deterioration of coronary artery disease (CAD). This research was designed to study the function of Shexiang Baoxin pills (SBPs) on the proliferation and migration of human coronary artery smooth muscle cells (HCASMCs) and their mechanism. Oxidized low-density lipoprotein (ox-LDL) was applied to stimulate the proliferation and migration of HCASMCs. The function of ox-LDL and SBP on HCASMCs was evidenced by the cell counting kit-8 assay, cell cycle, and Transwell assay. Network pharmacology was employed to predict the potential targets and pathways of SBP on CAD. Western blot assay and molecular docking were conducted to validate the potential targets and pathways. The current research revealed that 2.5 mg/L SBP significantly inhibited the proliferation and migration of HCASMCs. Besides, network pharmacology revealed 11 candidate targets. Molecular docking and Western blot assay validated that the activation of the top 2 targets STAT3 and MAPK14 was associated with the inhibition of HCASMCs. Moreover, the Western blot assay also detected that HCASMCs treated with ox-LDL promoted the phosphorylation of the PI3K/AKT/mTOR pathway, and SBP inhibited the activation of the PI3K/AKT/mTOR pathway in HCASMCs stimulated by ox-LDL. This study demonstrated that the treatment of CAD using SBP may result from the suppression of the proliferation and migration of HCASMCs. The mechanism of this function partly resulted from relieving the phosphorylation of targets STAT3 and MAPK14 and the PI3K/AKT/mTOR pathway. This study enhanced our comprehension of SBP and provides new targets for the treatment of CAD.
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http://dx.doi.org/10.3389/fcvm.2021.700630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425485PMC
August 2021

Deep Learning-Based Image Automatic Assessment and Nursing of Upper Limb Motor Function in Stroke Patients.

J Healthc Eng 2021 24;2021:9059411. Epub 2021 Aug 24.

Department of Nursing, The Second Hospital of Jilin University, Changchun 130041, China.

This paper mainly introduces the relevant contents of automatic assessment of upper limb mobility after stroke, including the relevant knowledge of clinical assessment of upper limb mobility, Kinect sensor to realize spatial location tracking of upper limb bone points, and GCRNN model construction process. Through the detailed analysis of all FMA evaluation items, a unique experimental data acquisition environment and evaluation tasks were set up, and the results of FMA prediction using bone point data of each evaluation task were obtained. Through different number and combination of tasks, the best coefficient of determination was achieved when task 1, task 2, and task 5 were simultaneously used as input for FMA prediction. At the same time, in order to verify the superior performance of the proposed method, a comparative experiment was set with LSTM, CNN, and other deep learning algorithms widely used. . GCRNN was able to extract the motion features of the upper limb during the process of movement from the two dimensions of space and time and finally reached the best prediction performance with a coefficient of determination of 0.89.
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http://dx.doi.org/10.1155/2021/9059411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407988PMC
August 2021

A novel germline BRCA2 mutation in a Chinese patient with prostate cancer sensitive to platinum chemotherapy: a case report.

BMC Urol 2021 Aug 23;21(1):114. Epub 2021 Aug 23.

Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.

Background: Germline BRCA2 mutation is associated with an aggressive prostate cancer phenotype and indicates higher risk for hereditary cancer. Recently, numerous studies have attempted to identify the genomic landscape of prostate cancer to better understand the genomic drivers of this disease and look for the molecular targets to guide treatment selection.

Case Presentation: We report a 67-year-old patient diagnosed with prostate cancer who experienced rapid disease progression after androgen deprivation therapy and subsequent docetaxel treatment. The patient had a strong family history of malignancy as his mother was diagnosed with breast cancer and his father was died of lung cancer. Next generation sequencing demonstrated a novel pathogenic germline BRCA2 mutation (p.Gly2181Glufs*10) in the patient. His mother with breast cancer and his son were found to have the same BRCA2 mutation. The patient experienced impressive and durable responses to carboplatin treatment.

Conclusions: This case demonstrated that the carboplatin could have a dramatic antitumor effect on patients with prostate cancer with germline BRCA2 mutations and family history will help to ensure that patients and their families can be provided with proper genetic counseling.
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http://dx.doi.org/10.1186/s12894-021-00879-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381549PMC
August 2021

hsa‑miR‑15a‑5p inhibits colon cell carcinoma via targeting CCND1.

Mol Med Rep 2021 10 20;24(4). Epub 2021 Aug 20.

Department of Integrated Traditional Chinese and Western Medicine, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China.

Colon carcinoma is one of the most common cancers worldwide. Epidemiological studies have revealed that colon cancer is the third leading cause of cancer‑related deaths, which is due to the increased incidence and mortality rates. However, the treatment strategies for colon cancer remain unsatisfactory for patients, especially for those with advanced or recurrent colon cancer. Dysregulated microRNAs (miRNAs) are considered to influence tumor development and metastasis. However, the molecular mechanism through which miRNAs affect cancer progression is not yet completely understood. The aim of the present study was to investigate the expression levels of has‑miR‑15a‑5p and its molecular mechanism in colon cell carcinoma. In the present study, the expression levels of hsa‑miR‑15a‑5p were found to be decreased in colon tumor tissues and cancer cell lines. Hsa‑miR‑15a‑5p overexpression inhibited colon cell proliferation and migration. Mechanistically, the G1/S‑specific cyclin‑D1 (CCND1) gene was predicted as a target of hsa‑miR‑15a‑5p, as evidenced by bioinformatics and dual‑luciferase reporter assay analyses. CCND1 overexpression significantly increased the progression of colon cancer. Furthermore, CCND1 was demonstrated to mediate the effects of hsa‑miR‑15a‑5p on colon cancer cells. The present study demonstrated that hsa‑miR‑15a‑5p alleviated the proliferation, migration and invasion of colon cancer by targeting the CCND1 gene, which represents a potential molecular target for the diagnosis and treatment of colon cancer.
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http://dx.doi.org/10.3892/mmr.2021.12375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404101PMC
October 2021

Corticosteroid switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients with biochemical progression on abiraterone acetate plus prednisone.

BMC Cancer 2021 Aug 13;21(1):919. Epub 2021 Aug 13.

Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

Background: To assess the efficacies and potential predictors of a corticosteroid switch in metastatic castration-resistant prostate cancer (mCRPC) patients with biochemical progression on abiraterone acetate plus prednisone (A + P).

Methods: Patients with mCRPC treated between April 2016 and August 2020, who experienced biochemical progression on A + P and then switched to A plus dexamethasone (D), were retrospectively identified. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were PSA response, overall survival (OS), and safety.

Results: One hundred and thirty consecutive cases were enrolled. The median PFS and OS on A + D were 5.0 and 18.7 months, respectively. The best PSA decline of ≥50% (PSA50) and ≥ 30% (PSA30) were observed in 29.2 and 46.2% patients, respectively. Lower PSA at corticosteroid switch (≤ 20 ng/mL; median PFS, HR 0.63, p = 0.019; median OS, HR 0.38, p = 0.001) and longer mCRPC-free survival (≥ 18 months; median PFS, HR 0.61, p = 0.013; median OS, HR 0.51, p = 0.015) were identified as independent prognostic predictors associated with longer PFS and OS. A risk stratification tool was developed to select candidates for corticosteroid switch based on the independent prognostic predictors of PFS and OS.

Conclusions: A corticosteroid switch from prednisone to dexamethasone is effective for mCRPC which progressed on A + P treatment. Patients with lower PSA at corticosteroid switch and/or longer mCRPC-free survival may gain more benefits by the corticosteroid switch.
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http://dx.doi.org/10.1186/s12885-021-08670-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364094PMC
August 2021

Multifunctional MOF-based probes for efficient detection and discrimination of Pb, Fe and CrO/CrO.

Dalton Trans 2021 Sep 14;50(35):12197-12207. Epub 2021 Sep 14.

College of Chemistry Engineering and Technology, Tiangong University, Tianjin, 300387, China.

Developing metal-organic framework (MOF)-based fluorescent probes for efficient detection and discrimination of polluting ions in groundwater is vital for environmental protection and human health. In this paper, we prepared two luminescence-active transition MOFs, namely, Zn-MOF and Cd-MOF, and conducted sensing experiments. The results show that they both exhibit multiple-target detection for Fe, Pb and Cr(VI) with high sensitivity, good anti-interference ability and good recyclability even with different frameworks. In addition, Eu-incorporated samples, [email protected], with dual-emission have been fabricated efficient encapsulation of Eu ions into the MOF host. As expected, [email protected] hybrids also act as multi-target and self-calibrated probes to selectively detect Fe and Cr(VI) ions. However, the quenching efficiencies of the original MOFs towards Fe are higher than those of [email protected] Thus, we could differentiate Fe, Pb and Cr(VI) ions by comparing the changes of fluorescence emission between [email protected] and the original MOFs. The recognition mechanism may be attributed to the competitive energy absorption between MOFs or [email protected] and the analytes.
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http://dx.doi.org/10.1039/d1dt01446cDOI Listing
September 2021

Characterizing ammonia emissions from water bodies using dynamic floating chambers.

Sci Total Environ 2021 Nov 10;796:148978. Epub 2021 Jul 10.

Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Qingdao 266200, Shandong, China; Sino-French Research Institute for Ecology and Environment (ISFREE), Shandong University, Qingdao 266200, Shandong, China. Electronic address:

Ammonia (NH) is the most important alkaline gas in the atmosphere and plays a central role in atmospheric pollution and the global N cycle. Water bodies receive increasing nitrogen inputs from effluents and atmospheric deposition due to anthropogenic activities and are regarded as the major natural NH and NH sinks. In this work, floating dynamic flux chambers were deployed at four types of freshwater (rivers, large reservoirs, medium-sized reservoirs and ponds) systems and a coastal seawater system to estimate the water-air NH emission fluxes. The NH emission fluxes of rivers (26.4 μg NH m h) were significantly higher than those of other types of freshwater systems, and the NH flux of offshore water was unexpectedly high (3.9 μg NH m h). The ammonium content and water temperature were the most important factors driving NH emissions from water bodies. The global NH emissions from water bodies reached 8.88 TgN a, and this value will increase persistently with global warming and water quality deterioration. Water bodies that are relatively eutrophic and directly affected by anthropogenic activities should be considered reservoirs of inputted N instead of permanent sinks.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148978DOI Listing
November 2021

NOX4-Derived ROS Mediates TGF-1-Induced Metabolic Reprogramming during Epithelial-Mesenchymal Transition through the PI3K/AKT/HIF-1 Pathway in Glioblastoma.

Oxid Med Cell Longev 2021 27;2021:5549047. Epub 2021 Jun 27.

Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.

Current studies on tumor progression focus on the roles of cytokines in the tumor microenvironment (TME), and recent research shows that transforming growth factor-1 (TGF-1) released from TME plays a pivotal role in tumor development and malignant transformation. The alteration in cellular metabolism is a hallmark of cancer, which not only provides cancer cells with ATP for fuel cellular reactions, but also generates metabolic intermediates for the synthesis of essential cellular ingredients, to support cell proliferation, migration, and invasion. Interestingly, we found a distinct metabolic change during TGF-1-induced epithelial-mesenchymal transition (EMT) in glioblastoma cells. Indeed, TGF-1 participates in metabolic reprogramming, and the molecular basis is still not well understood. NADPH oxidases 4 (NOX4), a member of the Nox family, also plays a key role in the biological effects of glioblastoma. However, the relationship between NOX4, TGF-1, and cellular metabolic changes during EMT in glioblastoma remains obscure. Here, our findings demonstrated that TGF-1 upregulated NOX4 expression accompanied by reactive oxygen species (ROS) through Smad-dependent signaling and then induced hypoxia-inducible factor 1 (HIF-1) overexpression and nuclear accumulation resulting in metabolic reprogramming and promoting EMT. Besides, inhibition of glycolysis reversed EMT suggesting a causal relationship between TGF-1-induced metabolic changes and tumorigenesis. Moreover, TGF-1-induced metabolic reprogramming and EMT which modulated by NOX4/ROS were blocked when the phosphoinositide3-kinase (PI3K)/AKT/HIF-1 signaling pathways were inhibited. In conclusion, these suggest that NOX4/ROS induction by TGF-1 can be one of the main mechanisms mediating the metabolic reprogramming during EMT of glioblastoma cells and provide promising strategies for cancer therapy.
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http://dx.doi.org/10.1155/2021/5549047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257383PMC
June 2021

CircCA12 Promotes Malignant Process via Sponging miR-1184 and Upregulating RAS Family in Bladder Cancer.

Front Genet 2021 21;12:663982. Epub 2021 Jun 21.

Department of Urology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.

Circular RNAs (circRNAs) are a panel of non-coding RNAs that mediate the regulation of gene expression, as well as pathological responses. Nonetheless, the function and expression pattern of circRNAs in urinary bladder cancer (UBC) remain unclear. Herein, we examined the function of circCA12 in UBC development. qRT-PCR results demonstrated remarkable circCA12 upregulation in UBC cell lines, as well as tissues. CCK-8, colony formation, and xenograft assays were employed to determine the effect of circCA12 on UBC. Our data illustrated silencing circCA12 repressed the proliferation along with the colony-formation capability of UBC cells. The migration and metastasis potential of UBC cells were remarkably abated , as well as after transfection with si-cirCA12 or sh-circCA12. Moreover, luciferase reporter and RIP assays indicated that circCA12 binds to miRNA-1184 through sponging miRNA, thereby up-regulating the expression of RAS family genes (, , and ). In conclusion, the circCA12/miRNA-1184/RAS family was identified as a regulatory axis in UBC progression.
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http://dx.doi.org/10.3389/fgene.2021.663982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257087PMC
June 2021

[Functional discovery and production technology for natural bioactive peptides].

Sheng Wu Gong Cheng Xue Bao 2021 Jun;37(6):2166-2180

Department of Chemical Engineering, Key Laboratory for Industrial Biocatalysis of the Ministry of Education, Tsinghua University, Beijing 100084, China.

Bioactive peptides play important roles in promoting human health, such as lowering blood pressure, blood sugar and blood lipid, anti-obesity, and anti-cancer. Thus, exploring functional bioactive peptides and developing efficient production technologies are of crucial importance. Herein, we review the development of function discovery and production technology for natural bioactive peptides. Presently, the top-down and bottom-up approaches are mainly used for the function discovery and production of natural active peptides. The top-down approach includes the direct extraction and identification for functional discovery, and the direct extraction, enzymatic hydrolysis and microbial fermentation for production. The bottom-up approach includes the polypeptide modification and database mining for functional discovery, and the chemical synthesis, enzyme synthesis, recombinant expression and cell-free synthesis for production. The top-down approach is usually associated with complicated process, lower efficiency, higher cost, harder quality control, and uncertain functionality, while the bottom-up approach is more suitable for the development of peptide drugs but difficult to be used for functional foods. With the technology development of sequencing and mass spectrometry, it is easier to obtain the proteomic information of various organisms at the molecular level. Based on the proteomic information, the top-down and bottom-up approaches can be combined to overcome the disadvantages of using these two approaches alone, thus providing a new strategy for the rapid development and production of natural active peptides.
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http://dx.doi.org/10.13345/j.cjb.210047DOI Listing
June 2021

Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China.

Front Psychiatry 2021 14;12:566990. Epub 2021 Jun 14.

Department of Emergency Medicine, The First Affiliate Hospital of Xinjiang Medical University, Wulumuqi, China.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.
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http://dx.doi.org/10.3389/fpsyt.2021.566990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236535PMC
June 2021

Risk factors for developing high-output ileostomy in CRC patients: a retrospective study.

BMC Surg 2021 Jun 26;21(1):300. Epub 2021 Jun 26.

Department of Surgery, Anyang Tumor Hospital, No. 1 Huanbin North Road, Anyang, 455000, Henan, China.

Background: Anastomotic leakage is one of the most serious postoperative complications of rectal cancer. Prophylactic ileostomy has been widely used to reduce the risk and severity of complications of anastomotic leakage. However, prophylactic ileostomy itself has some complications, and ileostomy high output syndrome (HOS) is one of them. This study was performed to explore the risk factors of HOS in ileostomy.

Methods: A total of 114 patients with HOS were screened out from 494 eligible ileostomy patients in the last 5 years. The relationship between HOS and the clinicopathological data was analyzed using the Chi-square test and Fisher's exact probability. Multivariate analysis was performed by logistic regression.

Results: The incidence of HOS was 23.07% in this study. Dehydration was the most common symptom of HOS (37.7%). There was no clear correlation between HOS occurrence with sex, age, gross typing, histological grade, tumor location, lymph node metastasis, and TNM stage (p > 0.05). The incidence of HOS was 14/18 in inflammatory bowel disease patients, 18/28 in diabetes mellitus patients, and 23/72 in neoadjuvant chemoradiotherapy patients, 13/17 in total colectomy and abdominal infection patients. Multivariate analysis showed that they are risk factors for HOS (p < 0.05).

Conclusion: HOS occurred occasionally but rarely studied and lacks attention. Inflammatory bowel disease, diabetes mellitus, neoadjuvant radiotherapy chemotherapy, total colectomy and abdominal infection are the risk factors for HOS.
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http://dx.doi.org/10.1186/s12893-021-01288-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235810PMC
June 2021

Improving Hospital Based Medical Procurement Decisions with Health Technology Assessment and Multi-Criteria Decision Analysis.

Inquiry 2021 Jan-Dec;58:469580211022911

The First Affiliated Hospital of University of Sciences and Technology of China, Hefei, P.R. China.

This research proposes a new medical procurement decision-making tool named Evaluation of Medical Technology Procurement (EMTP), which combines Mini-health Technology Assessment (Mini HTA) with the analytic hierarchy process (AHP), as well as the intuitionistic linguistic multi-criteria group decision model for multi-criteria decision analysis (MCDA). This tool was applied to a medical device procurement decision in a large provincial general hospital with more than 5000 beds in China as a case study. Specifically, the AHP evaluation framework is first established to determine the evaluation dimensions and criteria. This goal is achieved by applying the AdHopHTA Mini-HTA template and gathering data from questionnaires completed by experts from 33 major public hospitals in Anhui Province, China. The professionals within the application hospital were invited to evaluate the alternative products in a pairwise comparison and obtain a ranking of their advantages and disadvantages. This goal is achieved using the intuitionistic linguistic fuzzy model to deal with the subjectivity and uncertainty that may be present in the professional evaluation by experts in different fields. At the same time, the Keeney-Raiffa MCDA (KRM) method was used to demonstrate the accuracy of the application results. The results show that our tool can achieve the same effect as the verification method while being more efficient, easier to use, and requiring fewer participants. The advantages and disadvantages of several evaluation methods combined with multi-criteria methods are discussed, including verification methods, pointing out the advantages and limitations of this research tool as well as the prospects for the future.
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http://dx.doi.org/10.1177/00469580211022911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202291PMC
June 2021

LncRNA Landscape of Coronary Atherosclerosis Reveals Differentially Expressed LncRNAs in Proliferation and Migration of Coronary Artery Smooth Muscle Cells.

Front Cell Dev Biol 2021 18;9:656636. Epub 2021 May 18.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

We aimed to investigate differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in atherosclerosis and validate the expression of lncRNAs and co-expressed target genes in proliferation and migration models of human coronary artery smooth muscle cells (HCASMCs). Ten coronary artery specimens from a subject who died from a heart attack were employed. The pathological analysis was analyzed by hematoxylin and eosin (H&E) staining, and the lncRNAs and mRNAs were identified by RNA sequencing. Bioinformatic analyses were performed to predict possible mechanisms. The proliferation and migration of HCASMCs were induced with oxidized low-density lipoprotein (ox-LDL). Differentially expressed lncRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In this study, 68 lncRNAs and 222 mRNAs were identified differentially expressed in atherosclerosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the Fanconi anemia pathway may be involved in atherosclerosis. was found to be the co-localized target gene of LNC_000439, and 14 genes had high correlations with the expression of seven lncRNAs. In addition, nine lncRNA-miRNA-mRNA networks were constructed, and 53 co-expressed gene modules were detected with weighted gene co-expression network analysis (WGCNA). LNC_000684, LNC_001046, LNC_001333, LNC_001538, and LNC_002115 were downregulated, while LNC_002936 was upregulated in proliferation and migration models of HCASMCs. In total, six co-expressed mRNAs were upregulated in HCASMCs. This study suggests that the differentially expressed lncRNAs identified by RNA sequencing and validated in smooth muscle cells may be a target for regulating HCASMC proliferation and migration in atherosclerosis, which will provide a new diagnostic basis and therapeutic target for the treatment of cardiovascular diseases.
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http://dx.doi.org/10.3389/fcell.2021.656636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168468PMC
May 2021

Thermal Stability and Decomposition Kinetics of 1-Alkyl-2,3-Dimethylimidazolium Nitrate Ionic Liquids: TGA and DFT Study.

Materials (Basel) 2021 May 14;14(10). Epub 2021 May 14.

College of Safety Science and Engineering, Nanjing Tech University, Nanjing 211816, China.

The thermal stability and decomposition kinetics analysis of 1-alkyl-2,3-dimethylimidazole nitrate ionic liquids with different alkyl chains (ethyl, butyl, hexyl, octyl and decyl) were investigated by using isothermal and nonisothermal thermogravimetric analysis combined with thermoanalytical kinetics calculations (Kissinger, Friedman and Flynn-Wall-Ozawa) and density functional theory (DFT) calculations. Isothermal experiments were performed in a nitrogen atmosphere at 240, 250, 260 and 270 °C. In addition, the nonisothermal experiments were carried out in nitrogen and air atmospheres from 30 to 600 °C with heating rates of 5, 10, 15, 20 and 25 °C/min. The results of two heating modes, three activation energy calculations and density functional theory calculations consistently showed that the thermal stability of 1-alkyl-2,3-dimethylimidazolium nitrate ionic liquids decreases with the increasing length of the alkyl chain of the substituent on the cation, and then the thermal hazard increases. This study could provide some guidance for the safety design and use of imidazolium nitrate ionic liquids for engineering.
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http://dx.doi.org/10.3390/ma14102560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155988PMC
May 2021

Projected changes in temperature, precipitation and potential evapotranspiration across Indus River Basin at 1.5-3.0 °C warming levels using CMIP6-GCMs.

Sci Total Environ 2021 Oct 20;789:147867. Epub 2021 May 20.

State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China; Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters, Institute for Disaster Risk Management, School of Geographical Science, Nanjing University of Information Science & Technology, Nanjing 210044, China. Electronic address:

The projections of mean temperature, precipitation (P), and potential evapotranspiration (PET) reflect the probabilities of long-term changes of hydrologic processes and induced extreme events. In this paper, we investigated the future changes in some pivotal climatic variables (mean temperature, precipitation, and potential evapotranspiration) under 1.5 °C, 2.0 °C, and 3.0 °C specific warming levels (SWLs) across the Indus River Basin of South Asia. The seven global climate models output under seven different emission scenarios (SSP1-1.9, SSP1-2.6, SSP2-4.5, SSP3-7.0, SSP4-3.4, SSP4-6.0, and SSP5-8.5) from the latest Sixth phase of Coupled Model Intercomparison Project (CMIP6) are used for this purpose. The Penman-Monteith approach is applied to estimate PET, and the water balance equation is for reflecting water surplus/deficit. Results indicate that except for precipitation, the greater increases in temperature and PET are inclined to happen with continued global warming. The highest increase in temperature is accounted for 14.6% (2.4 °C), and the enhanced PET is estimated at 5.2% higher than the reference period (1995-2014) under 3.0 °C SWL. While the precipitation is projected to increase by the highest 4.8% for 2.0 °C warming level. The differences in regional climate for an additional 0.5 °C (2.0-1.5 °C) and 1.0 °C (3.0-2.0 °C) of warming, the temperature is projected to increase by 0.4 °C and 0.9 °C in the entire IRB respectively. The highest increase in mean temperature (5.1%) and PET (2.4%) in the IRB are predicted to intensify for an additional 1.0 °C than that of 0.5 °C of warming, but precipitation is intended to decrease by 0.4%. Spatially, the increase in temperature, precipitation, and PET are dominated towards high elevation in the upper basin (north) under all the SWLs. The increased variability in climatological parameters across IRB depicts an evident occurrence of both wet events (upper basin) as well as dry events (lower basin) with the increase in global average temperature rise. However, these findings provide an insightful basis for water resource management as well as initiating mitigation and adaptation measures in the IRB related to water surplus (floods) and water deficit (droughts).
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http://dx.doi.org/10.1016/j.scitotenv.2021.147867DOI Listing
October 2021

Age-specific markers of adiposity in patients with obstructive sleep apnea.

Sleep Med 2021 07 3;83:196-203. Epub 2021 Mar 3.

Department of Geriatrics, Peking University First Hospital, Beijing, 100034, China.

Objectives: Adiposity can have varying effects on the individual depending upon its distribution pattern. We assessed age-related distribution of adipose tissue by anthropometric measures and bioelectrical impedance analysis, as well as their association with obstructive sleep apnea (OSA) severity.

Methods: Participants were 169 elderly (aged ≥ 65 years) and 142 non-elderly (aged < 65 years) referred for overnight polysomnography. The associations between obesity parameters and apnea-hypopnea index (AHI) were determine by univariate and multivariate linear regression analyses. Area under receiver operating characteristic curve (AUC) was used to access the predicting performance of some parameters.

Results: Compared with non-elderly, elderly showed higher conicity index and visceral adiposity (VA)/subcutaneous adiposity (SA), lower body mass index (BMI), neck circumference, waist circumference, hip circumference and SA. Multiple regression analyses revealed that VA and VA/SA were independently associated with AHI in elderly (explained 17.2% of the AHI variability), while BMI and VA/SA were independently associated with AHI in non-elderly (explained 25.9% of the AHI variability), after adjusting for age, sex, cigarette smoking, alcohol drinking and main comorbidities. In elderly, VA over 128 cm and VA/SA less than 0.41 resulted in sensitivity, specificity and AUC of 0.382, 0.790, 0.580 and 0.176, 0.947, 0.553 in predicting moderate-to-severe OSA, respectively. In non-elderly, BMI over 24.7 kg/m and VA/SA over 0.54 resulted in sensitivity, specificity and AUC of 0.883, 0.484, 0.704 and 0.550, 0.710, 0.667 in predicting moderate-to-severe OSA, respectively.

Conclusions: VA is strongly associated with OSA severity in elderly, independently of general obesity as per BMI standards, while general adiposity appears to be more strongly associated with OSA severity in non-elderly. Our study supports age-specific approaches should be developed with respect to prediction and treatment of OSA.
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http://dx.doi.org/10.1016/j.sleep.2021.02.051DOI Listing
July 2021

Role of P2X7R in eosinophilic and non‑eosinophilic chronic rhinosinusitis with nasal polyps.

Mol Med Rep 2021 07 26;24(1). Epub 2021 May 26.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammation‑mediated disease of the nasal mucosa. P2X7R has been reported to be a potential biomarker for inflammation. The aim of the present study was to explore the role of P2X7R in CRSwNP, and the interaction between P2X7R and the NLRP3 inflammasome in the development of CRSwNP. Firstly, the expression profiles of P2X7R in nasal mucosa were investigated using western blotting (WB), polymerase chain reaction (PCR) and immunofluorescence (IF) staining. Next, the effect of inflammatory stimulation with lipopolysaccharides (LPS) combined with 2'(3')‑O‑(4‑benzoylbenzoyl) adenosine 5'‑triphosphate triethylammonium salt (BzATP) on primary human nasal epithelial cells (HNECs) was determined. Then, the therapeutic effect of the selective P2X7R antagonist, A740003, on P3X7R, NOD‑like receptor pyrin domain containing 3 (NLRP3) inflammasome and IL‑1β alterations in HNECs was explored using enzyme‑linked immunosorbent assay, WB and PCR. It was found that P2X7R was overexpressed in CRSwNP, especially in eosinophilic CRSwNP, the expression of P2X7R, NLRP3 and IL‑1β were upregulated in HNECs after induction by LPS combined with BzATP; but the expression of NLRP3 and IL‑1β were downregulated after stimulation with A740003. The aforementioned results indicate that P2X7R‑mediated NLRP3 inflammasome activation may have a role in the pathogenesis of CRSwNP.
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http://dx.doi.org/10.3892/mmr.2021.12160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160476PMC
July 2021

Disrupted rhythms of life, work and entertainment and their associations with psychological impacts under the stress of the COVID-19 pandemic: A survey in 5854 Chinese people with different sociodemographic backgrounds.

PLoS One 2021 17;16(5):e0250770. Epub 2021 May 17.

Army Medical Center of PLA, Daping Hospital, Army Medical University, Chongqing, P.R. China.

Background & Aim: The coronavirus disease 2019 (COVID-19) pandemic has affected the life and work of people worldwide. The present study aimed to evaluate the rhythm disruptions of life, work, and entertainment, and their associations with the psychological impacts during the initial phase of the COVID-19 pandemic.

Method: A cross-sectional study was conducted from the 10th to 17th March 2020 in China. A structured e-questionnaire containing general information, the Chinese version of Brief Social Rhythm Scale, and Zung's self-rating scales of depression and anxiety (SDS and SAS) was posted and collected online through a public media (i.e. EQxiu online questionnaire platform). Scores in sleeping, getting up, and socializing (SGS) rhythm and eating, physical practice, and entertainment (EPE) rhythm were compared among and between participants with different sociodemographic backgrounds including gender, age, education, current occupation, annual income, health status, and chronic disease status. Correlations of SDS and SAS with SGS-scale and EPE-scale were also analyzed.

Results: Overall, 5854 participants were included. There were significant differences in the scores of SGS-scale and EPE-scale among people with different sociodemographic backgrounds. The scores were significantly higher in the groups with female gender, low education level, lower or higher than average income, poor health status, ages of 26-30 years or older than 61 years, nurses and subjects with divorce or widow status. There were also significant differences in SAS and SDS scores among people with different sociodemographic backgrounds (all P< 0.05). The overall prevalence of depression and anxiety was 24.3% and 12.6%, respectively, with nurses having the highest rates of depression (32.94%) and anxiety (18.98%) among the different occupational groups. SGS-scale was moderately correlated with SDS and SAS, and disruption of SGS rhythm was an independent risk factor for depression and anxiety.

Conclusion: Social rhythm disruption was independently associated with depression and anxiety. Interventions should be applied to people vulnerable to the rhythm disruption during the COVID-19 pandemic.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250770PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128272PMC
May 2021

Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis.

Free Radic Biol Med 2021 08 8;171:55-68. Epub 2021 May 8.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China. Electronic address:

Ferroptosis and pyroptosis have not been fully studied in atherosclerosis. We aimed to investigate the expression of ferroptosis-related and pyroptosis-related proteins in human coronary arteries and analyse correlation with severity of atherosclerosis and clarify the interactions between proteins and possible mechanisms of atherosclerosis. 40 human coronary artery specimens were employed. The atherosclerotic lesions were characterized by Haematoxylin and Eosin (H&E) staining. The expression of prostaglandin-endoperoxide synthase 2 (PTGS2), anti-acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), caspase-1, and NOD-like receptor protein 3 (NLRP3) were analysed by immunohistochemical assay. Correlations between expression of proteins and severity of atherosclerosis were assessed using Spearman correlation analysis. Bioinformatic and coexpression analyses were performed to study the possible pathways and interactions. In the present study, PTGS2, ACSL4, caspase-1, and NLRP3, were upregulated, while GPX4 was downregulated in the advanced stages of atherosclerosis. The severity of atherosclerosis was positively associated with the expression of PTGS2, ACSL4, caspase-1, and NLRP3 and negatively associated with the expression of GPX4. Biological processes of lipid metabolism and inflammation and C-type lectin receptor signaling pathway were enriched. The five proteins interacted with each other directly or indirectly and PTGS2 might be the hub gene of atherosclerosis. Ferroptosis and pyroptosis may regulate the occurrence and development of atherosclerosis. These findings may shed light on new ideas and potential targets for the prevention and treatment of coronary artery atherosclerosis and the proteins may be used as biomarkers for the severity of atherosclerosis.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.05.009DOI Listing
August 2021

Dysregulation of miR-374a is involved in the progression of diabetic retinopathy and regulates the proliferation and migration of retinal microvascular endothelial cells.

Clin Exp Optom 2021 May 3:1-6. Epub 2021 May 3.

Department of Ophthalmology, Qingdao Chengyang People's Hospital, Shandong, China.

microRNAs (miRNAs) have been reported to be involved in the progression of various diseases. This study evaluated the expression and clinical value of miR-374a in diabetic retinopathy (DR) patients and analysed the effects of miR-374a on the progression of DR. Subjects were divided into four groups: healthy control, type 2 diabetes mellitus without DR (NDR), proliferation DR (PDR) and non-proliferation DR (NPDR). Real-time polymerase chain reaction (qRT-PCR) was detected in the serum miR-374a levels of the subjects. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-374a in DR patients. Pearson correlation was used to analyse the correlation between miRNA and clinical indicators of patients. High glucose (HG) in treatment of human retinal microvascular endothelial cells (HRMECs). The effects of miR-374a on cell proliferation and migration induced by HG were detected. Serum miR-374a was progressively accelerated in patients with NDR, NPDR and PDR than in healthy controls. Moreover, miR-374a can significantly distinguish between NDR and DR patients. Among DR patients, miR-374a can differentiate PDR patients from NPDR patients. Serum miR-374a was positively correlated with diabetes duration, fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), and homoeostasis model assessment of insulin resistance (HOMA-IR) in DR patients. HG-induced proliferation and migration of HRMECs was inhibited by reduction of miR-374a. Dysregulation of miR-374a is involved in the progression of DR and serves a regulatory role in retinal, which can be used as a promising diagnostic biomarker for DR.
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http://dx.doi.org/10.1080/08164622.2021.1913043DOI Listing
May 2021

Box Experiment Study of Thermally Enhanced SVE for Benzene.

Int J Environ Res Public Health 2021 04 12;18(8). Epub 2021 Apr 12.

Jiangsu Design Institute for Mineral Resources, Xuzhou 221000, China.

In order to describe the changes of soil temperature field, air flow field and remediation situation with time during the process of thermally enhanced SVE (soil vapor extraction), a remediation experiment of benzene contaminated soil with single extraction pipe was carried out in a box device. The results showed that the whole temperature of the system was raised to 80 °C in 4 h. 43% of benzene were removed in the first 2% of the extraction time. After 24 h, the repair efficiency was close to 100%. The device can efficiently remove benzene from soil. By continuously monitoring the parameters in the operation process of the system, the spatial distribution of temperature and soil gas pollutant concentration with time was plotted. It showed the benzene concentration distribution in the soil gas was more consistent with the temperature distribution before the start of ventilation, and the concentration of benzene in the soil gas dropped rapidly after ventilation, while the temperature distribution was almost unaffected. In the treatment of soil with a benzene content of 17.8 mg∙kg, when the soil gas benzene concentration is the highest at 180 min, the peak value is 11,200 mg∙m, and the average concentration is 7629.4 mg∙m.
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http://dx.doi.org/10.3390/ijerph18084062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070305PMC
April 2021

Identification of MicroRNAs as potential biomarkers for detecting ischemic stroke.

Genes Genomics 2021 Apr 5. Epub 2021 Apr 5.

Epidemiology and Biostatistics, School of Public Health, Jilin University, No. 1163 Xinmin Street, ChangchunJilin, 130021, China.

Background: Increasing epidemic of ischemic stroke (IS) makes it urgent to understand the pathogenesis and regulatory mechanism, previous studies have described microRNAs (miRNAs) is part of the brain's response to ischemia.

Objective: The aim of this study was to screen potential biomarkers for the prediction and novel treatment of IS.

Methods: Differentially expressed miRNAs were screened from three newly diagnosed IS patients and three controls by RNA sequencing technology. Furthermore, target prediction databases were then used to analysis the target genes of different expressed miRNAs, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database were used to identify the functions and the main biochemical and signal pathways of differentially expressed target genes.

Results: Our results revealed that 27 miRNAs were differentially expressed in IS, among which, hsa-miR-659-5p was the most highly increased and was first found to be associated with IS. In addition, KEGG pathway analyses showed that differentially expressed miRNAs were mainly significantly enriched in lysosome pathway, cytokine-cytokine receptor interaction pathway, spliceosome pathway, base excision repair pathway.

Conclusions: miRNAs were involved in IS pathogenesis, and hsa-miR-659-5p, hsa-miR-151a-3p and hsa-miR-29c-5p as the three highest |log2FoldChange| regulation in this study, which may be the biomarkers of IS and need further study.
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http://dx.doi.org/10.1007/s13258-021-01060-9DOI Listing
April 2021

[A preliminary study on the biomarkers of local inflammation in allergic rhinitis].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Apr;35(4):306-311;315

Department of Otolaryngology Head and Neck Surgery,Union Hospital of Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China.

This study aimed to explore the biomarkers in nasal secretion that can assist in the diagnosis of allergic rhinitis(AR) and can be used to evaluate the therapeutic effect of AR. Thirty-three patients with AR and 21 healthy controls were included. The nasal secretion of healthy controls and patients with AR(before and after treatment) were collected. The cytology, the concentrations of cytokines(IL-5, IL-6, IL-8, IL-33, IFN-γ) and inflammatory mediators(ECP, MPO) were detected. Then, we compared the differences of various biomarkers between healthy controls and AR patients(before and after treatment group). And analyzed the correlation between each biomarkers/biomarkers difference value/the percentage of biomarkers difference value and clinical symptom score/ score difference value / the percentage of score difference value. Compared with normal controls, the levels of ECP, IL-5, IL-6, IL-8, IL-33 and IFN-γ in nasal secretion of AR patients were significantly higher than those of normal controls(<0.05). There was no significant difference in MPO. After treatment, ECP decreased significantly(<0.01), inflammatory cell grade and eosinophil percentage are also decreased(<0.01). However, MPO, IL-5, IL-6, IL-8, IL-33 and IFN-γ did not change significantly. The difference value of ECP before and after treatment was correlated with the difference value of VAS score(=0.348, =0.047). The difference value of IL-5 was correlated with the difference value of VAS score and rhinorrhea, the correlation coefficients were 0.406(=0.019) and 0.429(=0.013), respectively. The difference value of eosinophil percentage in nasal secretion before and after treatment was correlated with nasal congestion, and the correlation coefficient was 0.383. The difference value of eosinophil percentage multiplied by inflammatory cell grade before and after treatment was correlated with VAS score(=0.417, =0.016) and nasal congestion difference value(=0.519, =0.002). The percentage of difference value of IFN-γ before and after treatment was correlated with the percentage of difference value of VAS score / rhinorrhea / sneeze / total nasal symptom score. ECP, IL-6, IL-8 and IL-33 in nasal secretion are expected to be objective biomarkers for auxiliary diagnosis of AR. And ECP, IL-5, IFN-γ, eosinophil percentage multiplied by grade is expected to be an objective index to judge the improvement of patients' symptoms after treatment.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.04.005DOI Listing
April 2021

Macrophage Activation Status Rather than Repolarization Is Associated with Enhanced Checkpoint Activity in Combination with PI3Kγ Inhibition.

Mol Cancer Ther 2021 06 30;20(6):1080-1091. Epub 2021 Mar 30.

Bioscience, Early Oncology, R&D, AstraZeneca, Cambridge, United Kingdom.

Suppressive myeloid cells mediate resistance to immune checkpoint blockade. PI3Kγ inhibition can target suppressive macrophages, and enhance efficacy of immune checkpoint inhibitors. However, how PI3Kγ inhibitors function in different tumor microenvironments (TME) to activate specific immune cells is underexplored. The effect of the novel PI3Kγ inhibitor AZD3458 was assessed in preclinical models. AZD3458 enhanced antitumor activity of immune checkpoint inhibitors in 4T1, CT26, and MC38 syngeneic models, increasing CD8 T-cell activation status. Immune and TME biomarker analysis of MC38 tumors revealed that AZD3458 monotherapy or combination treatment did not repolarize the phenotype of tumor-associated macrophage cells but induced gene signatures associated with LPS and type II INF activation. The activation biomarkers were present across tumor macrophages that appear phenotypically heterogenous. AZD3458 alone or in combination with PD-1-blocking antibodies promoted an increase in antigen-presenting (MHCII) and cytotoxic (iNOS)-activated macrophages, as well as dendritic cell activation. AZD3458 reduced IL-10 secretion and signaling in primary human macrophages and murine tumor-associated macrophages, but did not strongly regulate IL-12 as observed in other studies. Therefore, rather than polarizing tumor macrophages, PI3Kγ inhibition with AZD3458 promotes a cytotoxic switch of macrophages into antigen-presenting activated macrophages, resulting in CD8 T-cell-mediated antitumor activity with immune checkpoint inhibitors associated with tumor and peripheral immune activation.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0961DOI Listing
June 2021

Doubling of the population exposed to drought over South Asia: CMIP6 multi-model-based analysis.

Sci Total Environ 2021 Jun 6;771:145186. Epub 2021 Feb 6.

Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters/Institute for Disaster Risk Management/School of Geographical Science, Nanjing University of Information Science & Technology, Nanjing 210044, China; State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China. Electronic address:

Drought has a substantial socioeconomic impact under the changing climate. The estimation of population exposure to drought could be the pivotal signal to predict future water scarcity in the climate hotspot of South Asia. This study examines the changing population exposure to drought across South Asia using 20 climate model ensembles from the latest CMIP6 and demographic data under shared socioeconomic pathways (SSPs). Underpinning the latest version of the IPCC 6th Assessment Report (AR6), this paper focuses on the 2021-2040 (near-term), 2041-2060 (mid-term), and 2081-2100 (long-term) periods to project population exposure changes relative to the reference period (1995-2014) under four SSP-RCP scenarios. Drought events are detected by adopting the standardized precipitation evapotranspiration index (SPEI) and run theory method. Model validation suggests that CMIP6-GCM performs well in projecting climate variables and capturing drought events. The results show that the projected increases in frequent drought events and affected areal coverage are stronger during the early part of the century and weaker at the end under all scenario combinations. In relative terms, the projected increase in the number of people exposed to drought is dominant (>1.5-fold) in the near-term and mid-term periods but decreases in the long-term period. Compared to the reference period, the leading increase in population exposure (2.3-fold) is projected under the newly designed gap scenario (SSP3-7.0) in the mid-term period. A surprising decline in the number of exposed populations was estimated to be 18.8% under SSP5-8.5 by the end of the century. The mitigating effect of the predicted heavy precipitation will decrease droughts in the late future. Spatially, increasing exposure will become more pronounced across India and Afghanistan. Furthermore, the population change effect is mainly responsible for the exposure changes in South Asia. However, this study strongly recommends future 'plausible world' regional rivalry pathways (SSP3) scenario-combinations into consideration for policymaking in regard to water management as well as migration planning over South Asia.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145186DOI Listing
June 2021

Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study.

Diabetologia 2021 May 9;64(5):1066-1078. Epub 2021 Mar 9.

Department of Endocrinology, West China Hospital Sichuan University, Sichuan, China.

Aims/hypothesis: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) such as exenatide are used as monotherapy and add-on therapy for maintaining glycaemic control in patients with type 2 diabetes mellitus. The current study investigated the safety and efficacy of once-weekly PB-119, a PEGylated exenatide injection, in treatment-naive patients with type 2 diabetes.

Methods: In this Phase II, randomised, placebo-controlled, double-blind study, we randomly assigned treatment-naive Chinese patients with type 2 diabetes in a 1:1:1:1 ratio to receive subcutaneous placebo or one of three subcutaneous doses of PB-119 (75, 150, and 200 μg) for 12 weeks. The primary endpoint was the change in HbA from baseline to week 12, and other endpoints were fasting plasma glucose, 2 h postprandial glucose (PPG), and proportion of patients with HbA < 53 mmol/mol (<7.0%) and ≤48 mmol/mol (≤6.5%) at 2, 4, 8 and 12 weeks of treatment. Safety was assessed in all patients who received at least one dose of study drug.

Results: We randomly assigned 251 patients to one of the four treatment groups (n = 62 in placebo and 63 each in PB-119 75 μg, 150 μg and 200 μg groups). At the end of 12 weeks, mean differences in HbA in the treatment groups were -7.76 mmol/mol (95% CI -9.23, -4.63, p < 0.001) (-0.72%, 95% CI -1.01, -0.43), -12.89 mmol/mol (95% CI -16.05, -9.72, p < 0.001) (-1.18%, 95% CI -1.47, -0.89) and -11.14 mmol/mol (95% CI -14.19, -7.97, p <0 .001) (-1.02%, 95% CI -1.30, -0.73) in the 75 μg, 150 μg and 200 μg PB-119 groups, respectively, compared with that in the placebo group after adjusting for baseline HbA. Similar results were also observed for other efficacy endpoints across different time points. There was no incidence of treatment-emergent serious adverse event, severe hypoglycaemia or death.

Conclusions/interpretation: All tested PB-119 doses had superior efficacy compared with placebo and were safe and well tolerated over 12 weeks in treatment-naive Chinese patients with type 2 diabetes.

Trial Registration: ClinicalTrials.gov NCT03520972 FUNDING: The study was funded by National Major Scientific and Technological Special Project for Significant New Drugs Development and PegBio.
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http://dx.doi.org/10.1007/s00125-021-05392-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012337PMC
May 2021

Prostate cryoablation combined with androgen deprivation therapy for newly diagnosed metastatic prostate cancer: a propensity score-based study.

Prostate Cancer Prostatic Dis 2021 Sep 4;24(3):837-844. Epub 2021 Mar 4.

Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.

Background: Several studies showed that androgen deprivation therapy (ADT) plus local treatment of prostate could improve metastatic prostate cancer (mPCa) patients' survival. To date there are few studies analyzed the value of prostate cryoablation in mPCa. The objective of our analysis is to evaluate the oncological results and clinical value of prostate cryoablation combined with ADT compared with ADT alone in newly diagnosed mPCa patients.

Methods: Newly diagnosed mPCa patients undergoing cryoablation plus ADT (group A) between January 2011 and November 2018 were identified. Patients receiving ADT alone (group B) were selected from the same institutional prostate cancer database by propensity score matching based on clinical characteristics. Oncological results and clinical value in symptom control and primary lesion treatment were compared.

Results: Fifty-four patients were included in each group. Prostate cryoablation was well tolerated. The median follow-up time was 40 (27-53) and 39 (31-54) months in group A and group B, respectively. Patients in group A had a lower median prostate-specific antigen (PSA) nadir (0.025 ng/mL vs. 0.230 ng/mL, p = 0.001), longer median failure-free survival (FFS) (39 months vs. 21 months, p = 0.005), and median metastatic castration-resistant prostate cancer (mCRPC)-free survival (39 months vs. 21 months, p = 0.007). No difference in cancer-specific survival and overall survival was found between the two groups. Multivariate Cox analysis showed combination therapy reduced the risk of FFS by 45.8% (HR = 0.542 [95% CI 0.329-0.893]; p = 0.016). Patients in group A had better clinical relief of urinary symptoms (79.1 vs. 59.1%, p = 0.044) and required less treatment of primary lesions for symptomatic relief (13.0 vs. 31.5%, p = 0.021).

Conclusions: Prostate cryoablation plus ADT decreases PSA nadir, prolongs FFS and mCRPC-free survival, relieves urinary symptoms and reduces the need for treating primary lesions in newly diagnosed mPCa patients compared to ADT alone.
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http://dx.doi.org/10.1038/s41391-021-00335-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384623PMC
September 2021

Mendelian Randomization Highlights the Causal Role of Normal Thyroid Function on Blood Lipid Profiles.

Endocrinology 2021 05;162(5)

Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.

The association between thyroid function and dyslipidemia has been well documented in observational studies. However, observational studies are prone to confounding, making it difficult to conduct causal inference. We performed a 2-sample bidirectional Mendelian randomization (MR) using summary statistics from large-scale genome-wide association studies of thyroid stimulating hormone (TSH), free T4 (FT4), and blood lipids. We chose the inverse variance-weighted (IVW) method for the main analysis, and consolidated results through various sensitivity analyses involving 6 different MR methods under different model specifications. We further conducted genetic correlation analysis and colocalization analysis to deeply reflect the causality. The IVW method showed per 1 SD increase in normal TSH was significantly associated with a 0.048 SD increase in total cholesterol (TC; P < 0.001) and a 0.032 SD increase in low-density lipoprotein cholesterol (LDL; P = 0.021). A 1 SD increase in normal FT4 was significantly associated with a 0.056 SD decrease in TC (P = 0.014) and a 0.072 SD decrease in LDL (P = 0.009). Neither TSH nor FT4 showed causal associations with high-density lipoprotein cholesterol and triglycerides. No significant causal effect of blood lipids on normal TSH or FT4 can be detected. All results were largely consistent when using several alternative MR methods, and were reconfirmed by both genetic correlation analysis and colocalization analysis. Our study suggested that, even within reference range, higher TSH or lower FT4 are causally associated with increased TC and LDL, whereas no reverse causal association can be found.
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http://dx.doi.org/10.1210/endocr/bqab037DOI Listing
May 2021
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