Publications by authors named "Xuefeng Sun"

123 Publications

Safety and Efficacy of Roxadustat for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis.

Front Med (Lausanne) 2021 31;8:724456. Epub 2021 Aug 31.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), has been used to treat anemia in patients with chronic kidney disease (CKD). However, its safety and efficacy remain controversial. The PubMed, EMBASE, Science Citation Index, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries databases were searched for relevant studies published up to April 2021. We identified randomized controlled trials (RCTs) comparing roxadustat with placebo or erythropoiesis-stimulating agents (ESAs) in anemia patients with CKD with or without dialysis. Eleven studies including 6,631 patients met the inclusion criteria. In non-dialysis-dependent (NDD-) and dialysis-dependent (DD-) CKD patients, the total adverse events were not significantly different between the roxadustat and control (placebo for NDD-CKD patients and ESA for DD-CKD patients) groups [relative risk (RR) = 1.02, 95% confidence interval (CI) = 1.00, 1.04, = 0.08, and RR = 1.22, 95% CI = 0.91, 1.64, = 0.18, respectively], and the trial sequential analysis (TSA) confirmed the result in the NDD-CKD groups. No significant differences in hyperkalemia and infection incidences were found between roxadustat and placebo in the DD-CKD groups. The pooled results showed that roxadustat significantly increased the hemoglobin response rate compared with placebo in the NDD-CKD group and had an effect similar to that of ESA in the DD-CKD group. However, iron metabolism parameters did not seem to be obviously optimized by roxadustat. Roxadustat can be safely used in CKD patients. Oral roxadustat was more effective than placebo as a therapy for anemia in NDD-CKD patients and non-inferior to ESA in correcting anemia in DD-CKD patients. However, additional clinical trials are still needed to further prove whether roxadustat can optimize iron metabolism.
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http://dx.doi.org/10.3389/fmed.2021.724456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438137PMC
August 2021

Preparation and Directed Evolution of Anti-Ciprofloxacin ScFv for Immunoassay in Animal-Derived Food.

Foods 2021 Aug 20;10(8). Epub 2021 Aug 20.

China College of Public Health, Zhengzhou University, 100#Kexue Avenue, Zhengzhou 450001, China.

An immunized mouse phage display scFv library with a capacity of 3.34 × 10 CFU/mL was constructed and used for screening of recombinant anti-ciprofloxacin single-chain antibody for the detection of ciprofloxacin (CIP) in animal-derived food. After four rounds of bio-panning, 25 positives were isolated and identified successfully. The highest positive scFv-22 was expressed in BL21. Then, its recognition mechanisms were studied using the molecular docking method. The result showed the amino acid residue Val160 was the key residue for the binding of scFv to CIP. Based on the results of virtual mutation, the scFv antibody was evolved by directional mutagenesis of contact amino acid residue Val160 to Ser. After the expression and purification, an indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) based on the parental and mutant scFv was established for CIP, respectively. The IC50 value of the assay established with the ScFv mutant was 1.58 ng/mL, while the parental scFv was 26.23 ng/mL; this result showed highly increased affinity, with up to 16.6-fold improved sensitivity. The mean recovery for CIP ranged from 73.80% to 123.35%, with 10.46% relative standard deviation between the intra-assay and the inter-assay. The RSD values ranged between 1.49% and 9.81%. The results indicate that we obtained a highly sensitive anti-CIP scFv by the phage library construction and directional evolution, and the scFv-based IC-ELISA is suitable for the detection of CIP residue in animal-derived edible tissues.
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http://dx.doi.org/10.3390/foods10081933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394695PMC
August 2021

Effects of Donor-Recipient Age Difference in Renal Transplantation, an Investigation on Renal Function and Fluid Proteome.

Clin Interv Aging 2021 27;16:1457-1470. Epub 2021 Jul 27.

Department of Urology, Chinese PLA General Hospital, Beijing, People's Republic of China.

Introduction: Our previous study revealed that a young internal environment ameliorated kidney aging by virtue of an animal model of heterochronic parabiosis and a model of heterochronic renal transplantation. In this research, we used proteome to investigate the effects of donor-recipient age difference in clinical renal transplantation.

Methods: This study included 10 pairs of renal transplantation donors and recipients with an age difference of greater than 20 years to their corresponding recipients/donors. All recipients have received transplantation more than 3 years ago. Renal function and the serum/urine proteomes of the donors and recipients were analyzed.

Results: The renal function was similar between the young recipients and the old donors. In contrast, the renal function of the young donors was significantly superior to that of the old recipients. Furthermore, 497 and 975 proteins were identified in the serum and urine proteomes, respectively. The content of SLC3A2 in the blood was found to be related to aging, while the contents of SERPINA1 and SERPINA3 in the urine were related to immune functions after renal transplantation.

Conclusion: This study demonstrated that, in the human body, a younger internal environment could ameliorate kidney aging and provided not only clinical evidence for increasing the age limit of kidney transplant donors but also new information for kidney aging research.
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http://dx.doi.org/10.2147/CIA.S314587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326938PMC
July 2021

Association between higher serum uric acid levels within the normal physiological range and changes of lumbar spine bone mineral density in healthy Chinese postmenopausal women: a longitudinal follow-up study.

Menopause 2021 Aug 2. Epub 2021 Aug 2.

Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, China Department of Kidney, General Hospital of Chinese People's Liberation Army, Beijing, China.

Objectives: The aim of this study was to investigate whether higher serum uric acid (SUA) levels within the physiological range were associated with changes in lumbar spine bone mineral density (LBMD) in postmenopausal women without existing lumbar spine osteoporosis after a longitudinal follow-up of 3.09 years, and to further confirm the relationship between SUA and bone mineral density (BMD) in other sites such as femoral neck, total hip, and trochanter at follow-up.

Methods: A longitudinal study of 175 healthy postmenopausal women without osteoporosis was conducted in Shenyang, China. BMD of the lumbar spine, femoral neck, total hip, and trochanter were measured using dual-energy x-ray absorptiometry at each visit. Pearson's correlation analysis and regression analyses were performed to determine any associations.

Results: There were positive correlations between baseline SUA and BMD of the lumbar spine (P = 0.03), total hip (P = 0.04), and trochanter (P = 0.04). Moreover, higher baseline SUA levels were independently associated with LBMD decline and the odds ratio of the baseline SUA of the third quartile group was 0.12 (95% confidence interval, 0.02-0.70, P < 0.05), with P = 0.23 for the trend in baseline SUA when compared with participants in the lowest, first quartile group after adjustment for many potential confounding variables.

Conclusions: Higher SUA levels within the normal physiological range were independently associated with decreased LBMD, and SUA levels were positively related to the BMD of the lumbar spine, total hip, and trochanter in healthy Chinese postmenopausal women.
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http://dx.doi.org/10.1097/GME.0000000000001821DOI Listing
August 2021

Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury.

Front Med (Lausanne) 2021 28;8:655787. Epub 2021 May 28.

State Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese People's Liberation Army (PLA) Institute of Nephrology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Rhabdomyolysis (RM) is a clinical syndrome characterized by breakdown of skeletal muscle fibers and release of their contents into the circulation. Myoglobin-induced acute kidney injury (AKI) is one of the most severe complications of RM. Based on our previous research, exogenous biological renal support alleviates renal ischemia-reperfusion injury in elderly mice. This study aimed to determine whether exogenous biological renal support promotes renal recovery from RM-induced AKI and to preliminarily explore the mechanisms involved. A parabiosis animal model was established to investigate the effects of exogenous biological renal support on RM-induced AKI. Mice were divided into three groups: the control group (in which mice were injected with sterile saline), the RM group (in which mice were injected with 8 mL/kg glycerol), and the parabiosis + RM group (in which recipient mice were injected with glycerol 3 weeks after parabiosis model establishment). Blood samples and kidney tissue were collected for further processing 48 h after RM induction. Bioinformatics analysis was conducted via Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, functional enrichment analysis, and clustering analysis. No mice died within 48 h after the procedure. Exogenous biological renal support attenuated the histological and functional deterioration in mice with RM-induced AKI. Bioinformatics analysis identified key pathways and proteins involved in this process. We further demonstrated that exogenous biological renal support ameliorated AKI through multiple mechanisms, including by suppressing the complement system; attenuating oxidative stress, inflammation, and cell death; and increasing proliferation. Exogenous biological renal support provided by parabiosis can improve renal function in RM-induced AKI by suppressing the complement system; decreasing oxidative stress, inflammation, and cell death; and promoting tubular cell proliferation. Our study provides basic research evidence for the use of bioartificial kidneys to treat RM-induced AKI.
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http://dx.doi.org/10.3389/fmed.2021.655787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193099PMC
May 2021

Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway.

Front Cell Dev Biol 2021 22;9:630412. Epub 2021 Mar 22.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing, China.

Cardiorenal syndrome type 3 (CRS-3) is damage to the heart following acute kidney injury (AKI). Although many experiments have found that inflammation, oxidative stress, and cardiomyocyte death are involved in cardiomyocyte pathophysiological alterations during CRS-3, they lack a non-bias analysis to figure out the primary mediator of cardiac dysfunction. Herein proteomic analysis was operated in CRS-3 and growth factor receptor-bound protein 2 (Grb2) was identified as a regulator involving AKI-related myocardial damage. Increased Grb2 was associated with cardiac diastolic dysfunction and mitochondrial bioenergetics impairment; these pathological changes could be reversed through the administration of a Grb2-specific inhibitor during AKI. Molecular investigation illustrated that augmented Grb2 promoted cardiomyocyte mitochondrial metabolism disorder through inhibiting the Akt/mTOR signaling pathway. Besides that, Mouse Inflammation Array Q1 further identified IL-6 as the upstream stimulator of Grb2 upregulation after AKI. Exogenous administration of IL-6 induced cardiomyocyte damage and mitochondrial bioenergetics impairment, whereas these effects were nullified in cardiomyocytes pretreated with Grb2 inhibitor. Our results altogether identify CRS-3 to be caused by the upregulations of IL-6/Grb2 which contribute to cardiac dysfunction through inhibiting the Akt/mTOR signaling pathway and inducing cardiomyocyte mitochondrial bioenergetics impairment. This finding provides a potential target for the clinical treatment of patients with CRS-3.
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http://dx.doi.org/10.3389/fcell.2021.630412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019825PMC
March 2021

Interpretable Machine Learning Model for Early Prediction of Mortality in ICU Patients with Rhabdomyolysis.

Med Sci Sports Exerc 2021 Sep;53(9):1826-1834

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, CHINA.

Purpose: Rhabdomyolysis (RM) is a complex set of clinical syndromes that involves the rapid dissolution of skeletal muscles. Mortality from RM is approximately 10%. This study aimed to develop an interpretable and generalizable model for early mortality prediction in RM patients.

Method: Retrospective analyses were performed on two electronic medical record databases: the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care III database. We extracted data from the first 24 h after patient ICU admission. Data from the two data sets were merged for further analysis. The merged data sets were randomly divided, with 70% used for training and 30% for validation. We used the machine learning model extreme gradient boosting (XGBoost) with the Shapley additive explanation method to conduct early and interpretable predictions of patient mortality. Five typical evaluation indexes were adopted to develop a generalizable model.

Results: In total, 938 patients with RM were eligible for this analysis. The area under the receiver operating characteristic curve (AUC) of the XGBoost model in predicting hospital mortality was 0.871, the sensitivity was 0.885, the specificity was 0.816, the accuracy was 0.915, and the F1 score was 0.624. The XGBoost model performance was superior to that of other models (logistic regression, AUC = 0.862; support vector machine, AUC = 0.843; random forest, AUC = 0.825; and naive Bayesian, AUC = 0.805) and clinical scores (Sequential Organ Failure Assessment, AUC = 0.747; Acute Physiology Score III, AUC = 0.721).

Conclusions: Although the XGBoost model is still not great from an absolute performance perspective, it provides better predictive performance than other models for estimating the mortality of patients with RM based on patient characteristics in the first 24 h of admission to the ICU.
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http://dx.doi.org/10.1249/MSS.0000000000002674DOI Listing
September 2021

Fabrication of self-aligning convergent waveguides of microlens arrays to collect and guide light.

Opt Express 2021 Feb;29(3):3327-3341

The optical properties of microlens arrays may be significantly affected by the optical crosstalk effect between adjacent lenses. Recently, this issue has triggered increasing attention in the scientific community. In this study, an integrated microlens array (MLA) consisting of self-aligning convergent waveguides of microlenses was fabricated. The optical crosstalk effect does not influence the performance of such system. Based on the self-focusing effect principle, self-writing of the waveguide array was achieved in a photosensitive polymer. The light collection and guiding performance of the MLA with and without thermal cross-linking treatment was analyzed in depth. The relation between the stray light and the filling rate of the MLA shows that a high filling rate decreases the optical crosstalk. Finally, an integrated MLA with a large area, high uniformity, and excellent optical performance was fabricated.
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http://dx.doi.org/10.1364/OE.413243DOI Listing
February 2021

Development and validation of a model for the early prediction of the RRT requirement in patients with rhabdomyolysis.

Am J Emerg Med 2021 08 8;46:38-44. Epub 2021 Mar 8.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, China. Electronic address:

Introduction: Rhabdomyolysis (RM) is a complex set of clinical syndromes involving the rapid dissolution of skeletal muscles. The early detection of patients who need renal replacement therapy (RRT) is very important and may aid in delivering proper care and optimizing the use of limited resources.

Methods: Retrospective analyses of the following three databases were performed: the eICU Collaborative Research Database (eICU-CRD), the Medical Information Mart for Intensive Care III (MIMIC-III) database and electronic medical records from the First Medical Centre of the Chinese People's Liberation Army General Hospital (PLAGH). The data from the eICU-CRD and MIMIC-III datasets were merged to form the derivation cohort. The data collected from the Chinese PLAGH were used for external validation. The factors predictive of the need for RRT were selected using a LASSO regression analysis. A logistic regression was selected as the algorithm. The model was built in Python using the ML library scikit-learn. The accuracy of the model was measured by the area under the receiver operating characteristic curve (AUC). R software was used for the LASSO regression analysis, nomogram, concordance index, calibration, and decision and clinical impact curves.

Results: In total, 1259 patients with RM (614 patients from eICU-CRD, 324 patients from the MIMIC-III database and 321 patients from the Chinese PLAGH) were eligible for this analysis. The rate of RRT was 15.0% (92/614) in the eICU-CRD database, 17.6% (57/324) in the MIMIC-III database and 5.6% in the Chinese PLAGH (18/321). After the LASSO regression selection, eight variables were included in the RRT prediction model. The AUC of the model in the training dataset was 0.818 (95% CI 0.78-0.87), the AUC in the test dataset was 0.794 (95% CI 0.72-0.86), and the AUC in the Chinese PLAGH dataset (external validation dataset) was 0.820 (95% CI 0.70-0.86).

Conclusions: We developed and validated a model for the early prediction of the RRT requirement among patients with RM based on 8 variables commonly measured during the first 24 h after admission. Predicting the need for RRT could help ensure appropriate treatment and facilitate the optimization of the use of medical resources.
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http://dx.doi.org/10.1016/j.ajem.2021.03.006DOI Listing
August 2021

Regulation of connective tissue growth factor expression by miR-133b for the treatment of renal interstitial fibrosis in aged mice with unilateral ureteral obstruction.

Stem Cell Res Ther 2021 03 10;12(1):171. Epub 2021 Mar 10.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, China.

Introduction: Renal interstitial fibrosis, an important pathological feature of kidney aging and chronic renal failure, is regulated by mesenchymal stem cells (MSCs). We have previously demonstrated low expression of miR-133b in MSC-derived extracellular vesicles (MSC-EVs) in aged rats. However, miR-133b can mediate the inhibition of epithelial-mesenchymal transition (EMT) of renal tubules induced by transforming growth factor-β1 (TGF-β1). We investigated the effect of miR-133b for the treatment of geriatric renal interstitial fibrosis and evaluated its target genes.

Methods: We performed real-time polymerase chain reaction to detect miR-133b expression induced during EMT of HK2 cells by TGF-β1 at different concentrations (0, 6, 8, and 10 ng/mL) and at different time points (0, 24, 48, and 72 h). The target genes of miR-133b were validated using the dual-luciferase reporter assay. In vitro experiments were performed to evaluate mRNA and protein expression of miR-133b targets, E-cadherin, α-smooth muscle actin (SMA), fibronectin, and collagen 3A1 (Col3A1), in HK2 cells transfected with miR-133b under TGF-β1 stimulation. A 24-month-old unilateral ureteral obstruction (UUO) mouse model was established and injected with transfection reagent and miR-133b into the caudal vein. The target gene of miR-133b and other parameters mentioned above such as mRNA and protein expression levels and renal interstitial fibrosis were detected at 7 and 14 days.

Results: miR-133b expression gradually decreased with an increase in TGF-β1 concentration and treatment time, and the miR-133b mimic downregulated connective tissue growth factor (CTGF) expression. The dual-luciferase reporter assay confirmed CTGF as a direct target of miR-133b. Transfection of the miR-133b mimic inhibited TGF-β1-induced EMT of HK2 cells; this effect was reversed by CTGF overexpression. miRNA-133b expression significantly increased (approximately 70-100 times) in mouse kidney tissues after injection of the miRNA-133b overexpression complex, which significantly alleviated renal interstitial fibrosis in mice with UUO.

Conclusion: miR-133b exerted targeted inhibitory effects on CTGF expression, which consequently reduced TGF-β1-induced EMT of HK2 cells and renal interstitial fibrosis in aged mice with UUO.
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http://dx.doi.org/10.1186/s13287-021-02210-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944614PMC
March 2021

Evaluating the safety and efficacy of argatroban locking solution in the prevention of the dysfunction of haemodialysis central venous catheters: a study protocol for a randomized controlled trial.

Ann Palliat Med 2021 Feb 25;10(2):2260-2270. Epub 2021 Jan 25.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Background: Use of anticoagulant as lock solutions is an important method to maintain the function of haemodialysis (HD) central venous catheters (CVCs), and the common anticoagulants heparin and citrate are not suitable for some patients. Argatroban can inhibit thrombin directly, has a definite anticoagulant effect, and is expected to be a new anticoagulant for CVC lock solutions.

Methods: A total of 60 HD patients with non-tunnelled or tunnelled CVCs will be randomly assigned to two groups: an argatroban group and a control group. The participants will be given argatroban 0.5 mg/mL or unfractionated heparin (UFH) 1,000 U/mL locked post-dialysis instilled into the CVC lumens and followed up for 2 weeks. Data on demographic and general clinical information, laboratory examination, adverse events, adverse reactions and serious adverse events in the two groups will be collected. The differences in coagulation indexes at 30 min following catheter lock will be compared. The thrombosis rate, infection rate and percentage of catheter-days in the two groups will be observed. The primary outcomes include: efficacy assessments of combined outcome events: (I) rates of cumulative catheter survival in the 2-week HD session (the standard of catheter survival was catheter mean blood flow ≥250 mL/min); (II) rates of cumulative survival free of catheter thrombosis in the 2-week HD session. The second outcomes include: catheter dysfunction, the variation value (seconds) in activated partial thromboplastin time (aPTT) at 30 min following catheter locking and aPTT before next dialysis, catheter-associated bleeding, and catheterassociated infections.

Discussion: At present, there is no clinical study of argatroban as a CVC lock solution. This study will explore the efficacy and safety of the argatroban as locking solution in the prevention of the dysfunction of HD CVCs to provide evidence for further research.

Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800017105. Registered 12 July, 2018 (prospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=29054).
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http://dx.doi.org/10.21037/apm-20-1641DOI Listing
February 2021

Tunable Synthesis of Hierarchical Yolk/Double-Shelled SiO @TiO @C Nanospheres for High-Performance Lithium-Ion Batteries.

Chemistry 2021 Feb 28;27(8):2555. Epub 2021 Jan 28.

Key Laboratory of Fine Chemicals in Universities of Shandong, School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, P. R. China.

Invited for the cover of this issue is Qinghua Gong, Guowei Zhou, and co-workers at Qilu University of Technology. The dial represents the etching time of SiO yolk in NaOH solution and the brightness of the Chinese red lantern represents the electrochemical performance of the composites. Read the full text of the article at 10.1002/chem.202003246.
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http://dx.doi.org/10.1002/chem.202004205DOI Listing
February 2021

Association between serum calcium and prognosis in patients with acute pulmonary embolism and the optimization of pulmonary embolism severity index.

Respir Res 2020 Nov 11;21(1):298. Epub 2020 Nov 11.

Department of Respiration, Peking Union Medical College Hospital, No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

Introduction: Calcium is an important coagulation factor and hypocalcemia is related to progression and poor prognosis of many cardiopulmonary diseases. However, influence of hypocalcemia on pulmonary thromboembolism (PTE) prognosis has never been reported. This study aimed to explore its prognostic value and optimize the pulmonary embolism severity index (PESI), the widely used prognosis assessment model, based on the value.

Methods: PTE patients' variables in PESI and other related clinical characteristics including admission serum calcium were collected. Associations between these variables and PTE mortality were assessed by logistic regression and cox analysis. Variables significantly associated with 30-day PTE mortality were included to develop a new prognosis prediction rule and then its validity was compared with PESI and simplified PESI (sPESI).

Results: 496 PTE patients were included and 49.48% patients had hypocalcemia (serum calcium ≤ 2.13 mmol/L) in admission, showing higher 7-day (P = 0.021), 14-day (P = 0.002), 30-day (13.03% vs 4.98%, P = 0.002) mortalities than patients without hypocalcemia. Adjusting for variables in PESI, hypocalcemia was further revealed to be an independent predictor of 30-day mortality (P = 0.014). The optimal prediction rule contained hypocalcemia and 5 variables in PESI and sPESI, showing higher predictive validity [sensitivity (Sen): 0.930, specificity (Spec): 0.390, area under curve (AUC): 0.800] than PESI (Sen: 0.814, Spec: 0.367, AUC: 0.716) and sPESI (Sen: 0.907, Spec: 0.216, AUC: 0.703).

Conclusions: Hypocalcemia is an independent predictor of the mortality following acute PTE. Based on hypocalcemia, the optimal prediction rule showed higher validity than PESI and sPESI.
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http://dx.doi.org/10.1186/s12931-020-01565-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659049PMC
November 2020

LINC00355 promoted the progression of lung squamous cell carcinoma through regulating the miR-466/LYAR axis.

Braz J Med Biol Res 2020 21;53(12):e9317. Epub 2020 Oct 21.

Department of Thoracic Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China.

LINC00355 has been reported aberrantly over-expressed and associated with poor prognosis in various types of cancer. However, reports regarding the effect of LINC00355 on lung squamous cell carcinoma (SCC) are rare. This study aimed to explore the function of LINC00355 in the development and progression of lung SCC and reveal the underlying mechanism. The expression and subcellular location of LINC00355 were determined by qRT-PCR and RNA-FISH, respectively. The lung SCC cell growth was analyzed by CCK-8 assay, transwell invasion, wound healing, colony formation, and flow cytometry assays. Reactive oxygen species level was evaluated by DCFH-DA probes. Bioinformatics online websites, luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), and RNA pull-down assays were utilized to investigate the interaction among LINC00355, miR-466, and Ly-1 antibody reactive clone (LYAR). The results showed that LINC00355 was upregulated in lung SCC and was positively associated with poor overall survival in lung SCC patients. LINC00355 was mainly located in the cytoplasm of SCC cells. Additionally, LINC0035 functioned as a competing endogenous RNA (ceRNA) to target miR-466, and LYAR was identified as a direct target of miR-466. LINC00355 expression negatively correlated with miR-466 level, and positively correlated with LYAR level. Mechanistically, knockdown of LINC00355 inhibited cell proliferation, migration and invasion, promoted cell apoptosis in vitro, and suppressed tumor growth in vivo through targeting miR-466, and thus down-regulated LYAR expression. These findings provide a new sight for understanding the molecular mechanism of lung SCC and indicate that LINC00355 may serve as a potential biomarker for the diagnosis and treatment of lung SCC.
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http://dx.doi.org/10.1590/1414-431X20209317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584152PMC
January 2021

Characterization of the key aroma compounds in Yunnan goat milk cake using a sensory-directed flavor analysis.

J Food Sci 2020 Nov 16;85(11):3981-3997. Epub 2020 Oct 16.

Department of Food Science and Technology, Shanghai Institute of Technology, Shanghai, 201418, China.

To identify the key aroma compounds in Yunnan goat milk cake, seven varieties of milk cake samples were subjected to sensory analysis and gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), aroma recombination, omission, and addition tests. The GC-MS results revealed 53 compounds with aroma characteristics in all the samples. A further comparison of odor activity values and aroma intensities (AI) revealed 25 of these compounds as the initial key aroma compounds. The contributions of these key aroma compounds to the sensory attributes were determined using a partial least squares regression. Of these compounds, 2-heptanone and 2-nonanone were closely related to the "milky" and "cheesy" attributes and were highly abundant in the samples from Kunming. Fatty acids, including butanoic acid, hexanoic acid, octanoic acid, and decanoic acid, were the most abundant compounds detected in the milk cakes. These fatty acids were closely related to the "rancid" and "animalic (goat)" attributes and were largely detected in the samples from Dali Dengchuan and Dali Xiaguan. Sensory-directed aroma recombination, omission, and addition tests further validated the important contributions of ethyl butyrate, benzaldehyde, 3-methyl-1-butanol, 2-heptanone, hexanoic acid, and octanoic acid to the overall sensory properties. Moreover, ethyl butyrate, benzaldehyde, and 2-heptanone, when added, had evident inhibitory or masking effects on the AI of "sour," "rancid," and "animalic (goat)" attributes. PRACTICAL APPLICATION: Goat milk cake is a popular acid-curd cheese in Yunnan, China, however, our limited knowledge to its key aroma compounds restricts its development and industrial production. In this study, a sensory-directed flavor analysis was used to characterized the key aroma compounds of Yunnan goat milk cake, which will help to enhance our understanding on the flavor profile of Yunnan goat milk cake and provide a reference for optimizing the flavor feature and organoleptic quality of this fresh goat cheese.
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http://dx.doi.org/10.1111/1750-3841.15490DOI Listing
November 2020

Preparations of NiFeO [email protected] Nanospheres and Their Performances as Anode Materials for Lithium-Ion Batteries.

Nanomaterials (Basel) 2020 Oct 9;10(10). Epub 2020 Oct 9.

Key Laboratory of Fine Chemicals in Universities of Shandong, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.

At present, lithium-ion batteries (LIBs) have received widespread attention as substantial energy storage devices; thus, their electrochemical performances must be continuously researched and improved. In this paper, we demonstrate a simple self-template solvothermal method combined with annealing for the synthesis of NiFeO yolk-shell (NFO-YS) and NiFeO solid (NFO-S) nanospheres by controlling the heating rate and coating them with a carbon layer on the surface via high-temperature carbonization of resorcinol and formaldehyde resin. Among them, [email protected] has an obvious yolk-shell structure, with a core-shell spacing of about 60 nm, and the thicknesses of the NiFeO shell and carbon shell are approximately 15 and 30 nm, respectively. The yolk-shell structure can alleviate volume changes and shorten the ion/electron diffusion path, while the carbon shell can improve conductivity. Therefore, [email protected] nanospheres as the anode materials of LIBs show a high initial capacity of 1087.1 mA h g at 100 mA g, and the capacity of [email protected] nanospheres impressively remains at 1023.5 mA h g after 200 cycles at 200 mA g. The electrochemical performance of [email protected] is significantly beyond [email protected], which proves that the carbon coating and yolk-shell structure have good stability and excellent electron transport ability.
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http://dx.doi.org/10.3390/nano10101994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600623PMC
October 2020

Free available chlorine initiated Baeyer-Villiger oxidation: A key mechanism for chloroform formation during aqueous chlorination of benzophenone UV filters.

Environ Pollut 2021 Jan 28;268(Pt A):115737. Epub 2020 Sep 28.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China.

Chloroform, a regulated disinfection by-product in water, is often generated during chlorination disinfection treatment. However, the formation of chloroform is heavily dependent on the molecular structures of precursors. Moreover, compounds containing ketone moiety are ubiquitous in water environments. However, it is unclear if they can generate chloroform during chlorination. In this study, 14 benzophenones (BPs), efficient and widely used UV filters, with different substituents were selected to explore chloroform formation during chlorination. All 14 BPs generated chloroform, with yields dependent on their molecular structures and operational conditions. Compounds 2,2',4,4'-tetrahydroxy-BP and benzophenone produced the highest and lowest chloroform of 0.313 and 0.013 g/g, respectively, corresponding to the fastest and slowest formation rate constants of 1.41 × 10 and 2.71 × 10 min. Alkaline conditions and high chlorine dosages were favorable to chloroform formation. Three reactions played key roles in chloroform formation from BPs: (1) chlorine initiated Baeyer-Villiger oxidation converted ketone moieties of BP molecules into esters; (2) the esters further underwent hydrolysis and formed phenolic and benzoic products; and (3) benzoic acids underwent decarboxylation and hydrolysis to form phenolic products. Subsequently, these phenolic products could further generate chloroform in the chlorination system. More importantly, BPs could generate chloroform in the ambient water matrices during practical chlorination treatment. This work emphasized the critical role of Baeyer-Villiger oxidation for chloroform formation, implying that pollutants containing aromatic ketone moieties generate chloroform during chlorination disinfection, and their potential risk should therefore be reviewed.
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http://dx.doi.org/10.1016/j.envpol.2020.115737DOI Listing
January 2021

Tunable Synthesis of Hierarchical Yolk/Double-Shelled SiO @TiO @C Nanospheres for High-Performance Lithium-Ion Batteries.

Chemistry 2021 Feb 3;27(8):2654-2661. Epub 2020 Dec 3.

Key Laboratory of Fine Chemicals in Universities of Shandong, School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, P. R. China.

This work reports the preparation of unique hierarchical yolk/double-shelled SiO @TiO @C nanospheres with different voids by a facile sol-gel method combined with carbon coating. In the preparation process, SiO nanosphere is used as a hard template. Etch time of SiO yolk affects the morphology and electrochemical performance of SiO @TiO @C. With the increase in etch time, the yolk/double-shelled SiO @TiO @C with 15 and 30 nm voids and the TiO @C hollow nanospheres are obtained. The yolk/double-shelled SiO @TiO @C nanospheres exhibit remarkable lithium-ion battery performance as anodes, including high lithium storage capacity, outstanding rate capability, good reversibility, and stable long-term cycle life. The unique structure can accommodate the large volume change of the SiO yolk, provide a unique buffering space for the discharge/charge processes, improve the structural stability of the electrode material during repeated Li intercalation/deintercalation processes, and enhance the cycling stability. The SiO @TiO @C with 30 nm void space exhibits a high discharge specific capacity of ≈1195.4 mA h g at the current density of 0.1 A g after 300 cycles and ≈701.1 mA h g at 1 A g for over 800 cycles. These results suggest that the proposed particle architecture is promising and may have potential applications in improving various high performance anode materials.
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http://dx.doi.org/10.1002/chem.202003246DOI Listing
February 2021

Factors Associated with Brachial-Ankle Pulse Wave Velocity in an Apparently Healthy Chinese Population.

Biomed Res Int 2020 23;2020:9795240. Epub 2020 Jul 23.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing, China.

Purpose: To investigate the factors influencing brachial-ankle pulse wave velocity (baPWV) in an apparently healthy Chinese population, especially the associations between baPWV and indices of blood pressure (BP).

Methods: A total of 1123 participants with no history of hypertension were enrolled in this study, and the baPWV and BP of all four limbs were measured along with other covariates. Correlation analyses and multivariate linear regression models were used to identify factors associated with baPWV.

Results: A total of 1123 participants (male 43.3%, mean age: 58.4 ± 13.9 years) were included. The average baPWV was 14.87 ± 3.21 m/s, and no difference was found between the sexes. Age was positively correlated with baPWV ( = 0.65, < 0.01), especially in females ( = 0.71 versus 0.56 in males). The correlation coefficient between age and baPWV increased markedly after the age of 65 years. In addition, the resting heart rate (RHR), waist-hip ratio, glomerular filtration rate, and plasma glucose level were significantly correlated with baPWV ( = 0.25, 0.22, -0.43, and 0.25, respectively; < 0.01). BP parameters were highly positively correlated with baPWV, especially systolic BP (SBP) and pulse pressure (PP). Multivariate regression revealed that age, BP parameters, and RHR were independently correlated with baPWV ( < 0.01) after adjusting for confounding factors. The standardized coefficients of SBP were greater than those of PP, followed by diastolic BP (DBP).

Conclusion: BaPWV increased with age, especially after 65 years. Age, BP, and RHR were independent factors associated with baPWV. The effect of SBP on baPWV was more prominent than that of PP.
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http://dx.doi.org/10.1155/2020/9795240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396024PMC
April 2021

Neurological Manifestations in Critically Ill Patients With COVID-19: A Retrospective Study.

Front Neurol 2020 10;11:806. Epub 2020 Jul 10.

Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

The complications of coronavirus disease 2019 (COVID-19) involved multiple organs or systems, especially in critically ill patients. We aim to investigate the neurological complications in critically ill patients with COVID-19. This retrospective single-center case series analyzed critically ill patients with COVID-19 at the intensive care unit of Tongji Hospital, Wuhan, China from February 5 to April 2, 2020. Demographic data, clinical and laboratory findings, comorbidities and treatments were collected and analyzed. Among 86 patients with confirmed COVID-19, 54 patients (62.8%) were male, and the mean (SD) age was 66.6 (11.1) years. Overall, 65% patients presented with at least one neurological symptom. Twenty patients (23.3%) had symptoms involving the central nervous system, including delirium, cerebrovascular diseases and hypoxic-ischemic brain injury, while 6 patients (7%) had neuromuscular involvement. Seven of 86 patients exhibited new stroke and 6 (7%) cases were ischemic. A significantly higher prevalence of antiphospholipid antibodies was observed in patients with ischemic stroke than in those without stroke (83.3 vs. 26.9%, < 0.05). Patients with ischemic stroke were more likely to have a higher myoglobulin level, and a lower hemoglobin level. The clinical spectrum of neurological complications in critically ill patients with COVID-19 was broad. Stroke, delirium and neuromuscular diseases are common neurological complications of COVID-19. Physicians should pay close attention to neurological complications in critically ill patients with COVID-19.
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http://dx.doi.org/10.3389/fneur.2020.00806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365850PMC
July 2020

The top 100 most cited articles on rhabdomyolysis: A bibliometric analysis.

Am J Emerg Med 2020 09 17;38(9):1754-1759. Epub 2020 May 17.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, China. Electronic address:

Introduction: Over the past few decades, the incidence of Rhabdomyolysis (RM) has significantly increased. The prognosis is substantially worse if renal failure develops. Many problems remain to be addressed regarding the pathogenesis, prevention, and treatment of RM. The purpose of this study was to identify and characterize the top 100 most cited publications regarding rhabdomyolysis (RM) by performing a bibliometric analysis.

Methods: Publications focusing on RM were identified from the Science Citation Index-Expanded (SCI-E) of the Web of Science Core Collection (WoSCC). Bibliographic information was collected, including year of publication, authorship, publishing journals, institution, country of origin and keywords. CiteSpace V5.6.R2 and the Online Analysis Platform of Literature Metrology were used for descriptive analysis.

Results: The 100 most cited articles were published between 1995 and 2016, with citation numbers ranging from 116 to 904. The United States (60) has been the largest contributor to RM research. Hartford Hospital and University of Texas were found to be the most productive institutions, with five articles each. Thompson, PD, who authored six articles, was the most productive author. The American Journal of Cardiology published the most articles (5), followed by the New England Journal of Medicine (4). The top three co-cited journals were the New England Journal of Medicine (74), Lancet (59) and JAMA (54).

Conclusions: This study provides valuable information on the study of RM. These findings may be used to guide clinical decision-making and identify new research fields.
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http://dx.doi.org/10.1016/j.ajem.2020.05.031DOI Listing
September 2020

Antiphospholipid Antibodies in Critically Ill Patients With COVID-19.

Arthritis Rheumatol 2020 12 7;72(12):1998-2004. Epub 2020 Oct 7.

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Objective: Coagulopathy is one of the characteristics observed in critically ill patients with coronavirus disease 2019 (COVID-19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, though their role in COVID-19 remains unclear. This study was undertaken to determine the prevalence and characteristics of aPLs in patients with COVID-19.

Methods: Sera collected from 66 COVID-19 patients who were critically ill and 13 COVID-19 patients who were not critically ill were tested by chemiluminescence immunoassay for anticardiolipin antibodies (aCLs), anti-β -glycoprotein I (anti-β GPI) (IgG, IgM, and IgA), and IgG anti-β GPI-domain 1 (anti-β GPI-D1) and IgM and IgG anti-phosphatidylserine/prothrombin (anti-PS/PT) antibodies were detected in the serum by enzyme-linked immunosorbent assay.

Results: Of the 66 COVID-19 patients in critical condition, aPLs were detected in 31 (47% ). Antiphospholipid antibodies were not present among COVID-19 patients who were not in critical condition. The IgA anti-β GPI antibody was the most commonly observed aPL in patients with COVID-19 and was present in 28.8% (19 of 66) of the critically ill patients, followed by IgA aCLs (17 of 66, or 25.8%) and IgG anti-β GPI (12 of 66, or 18.2%). For multiple aPLs, IgA anti-β GPI + IgA aCLs was the most common antibody profile observed (15 of 66, or 22.7%), followed by IgA anti-β GPI + IgA aCL + IgG anti-β GPI (10 of 66, or 15.2%). Antiphospholipid antibodies emerge ~35-39 days after disease onset. A dynamic analysis of aPLs revealed 4 patterns based on the persistence or transient appearance of the aPLs. Patients with multiple aPLs had a significantly higher incidence of cerebral infarction compared to patients who were negative for aPLs (P = 0.023).

Conclusion: Antiphospholipid antibodies were common in critically ill patients with COVID-19. Repeated testing demonstrating medium to high titers of aPLs and the number of aPL types a patient is positive for may help in identifying patients who are at risk of developing cerebral infarction. Antiphospholipid antibodies may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID-19 may trigger the development of an autoimmune condition similar to the antiphospholipid syndrome (APS), referred to as "COVID-19-induced APS-like syndrome." Long-term follow-up of COVID-19 patients who are positive for aPLs would be of great importance in understanding the pathogenesis of this novel coronavirus.
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http://dx.doi.org/10.1002/art.41425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361932PMC
December 2020

Efficacy and safety of Abelmoschus manihot for IgA nephropathy: A multicenter randomized clinical trial.

Phytomedicine 2020 May 18;76:153231. Epub 2020 May 18.

Department of Nephrology, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China. Electronic address:

Rationale And Objective: IgA nephropathy (IgAN) is an important cause for end-stage renal disease worldwide. The treatment for IgAN remains challenging, and few randomized and controlled clinical trials have been conducted to evaluate new therapies. The present study assesses the efficacy and safety of Abelmoschus manihot (AM) in IgAN patients.

Study Design: Randomized, non-inferiority, double-blind, double-dummy multicenter trial.

Setting And Participants: This trial was designed to recruit 1,600 biopsy-proven IgAN patients (proteinuria between 0.5-3.0 g/d and estimated glomerular filtration rate [eGFR] of ≥ 45 ml/min/1.73 m) across China.

Interventions: The participants were randomized at 1:1 to AM (2.5 g for three times per day) or losartan potassium (100 mg per day) for 48 weeks.

Outcomes: The primary outcome was the change in 24-hour proteinuria from baseline to week 48. The secondary outcomes were the change in eGFR from baseline to week 48, and the incidents of endpoint events (proteinuria ≥ 3.5 g/24 h, doubling of serum creatinine, or receiving renal replacement treatment).

Results: Among 1,470 randomized patients (mean age, 37.4 [SD, 10.6] years old; 777 [52.9%] were female; mean eGFR, 95.0 [SD, 24.3] mL/min/1.73 m; mean 24-hour proteinuria, 1.2 [SD, 0.7] g/d), the mean decline in 24-h proteinuria at week 48 was 230 mg and 253 mg in the AM and losartan potassium groups, respectively (P = 0.676). The mean difference in the change in 24-h proteinuria between these two groups was -23.32 mg (95% confident interval: -123.2 to 76.6, p = 0.647). The mean decline in eGFR was 0.41 ml/min/1.73 m and 0.76 ml/min/1.73 m in the AM and losartan potassium groups, respectively (p = 0.661). The mean difference in the change in eGFR between these two groups was -0.43 ml/min/1.73 m (95% confident interval: -1.99 to 1.13, p = 0.589). The incidence of endpoint events was 8.6% in the AM group and 8.2% in the losartan group (p = 0.851).

Limitations: The results of the trial may not be generalized to IgAN patients with a proteinuria of > 3.0 g/d and an eGFR of < 45 ml/min/1.73 m. The long-term benefits of AM in reducing the risk of progressive renal dysfunction remains unclear, based on this 48-week observation.

Conclusion: AM can be recommended as a promising treatment for IgAN patients.
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http://dx.doi.org/10.1016/j.phymed.2020.153231DOI Listing
May 2020

Evaluation of the perceptual interaction among key aroma compounds in milk fan by gas chromatography-olfactometry, odor threshold, and sensory analyses.

J Dairy Sci 2020 Jul 21;103(7):5863-5873. Epub 2020 May 21.

Department of Food Science and Technology, Shanghai Institute of Technology, Shanghai 201418, China. Electronic address:

To evaluate the perceptual interactions among key aroma compounds found in milk fan, propanoic acid, butanoic acid, octanoic acid, octanal, nonanal, 2-nonanone, and ethyl hexanoate were analyzed by threshold values, aroma addition experiments (subthreshold), Feller's additive model (threshold), and σ-τ diagrams (threshold and superthreshold) at various concentrations. Aroma addition experiments highlighted that 7 key aroma compounds had significant effects on the aroma intensity of the sensory attributes of milk fan at the concentrations measured in a milk fan sample, and they might have synergistic effects with other compounds. The components of the 7 aroma compounds in binary mixtures showed synergistic effects from 21 binary mixtures by Feller's additive model. The components of 9 mixtures showed synergistic effects in the superadditive region (σ > 1.05), and 3 mixtures showed additive effects in the additive region (0.95 < σ < 1.05) of the σ-τ diagrams for all 168 binary mixtures. The results showed that perceptual interactions among the key aroma compounds in milk fan vary with different concentrations and threshold ratios. These results are helpful for further understanding the aroma of milk fan and improving the quality of its aroma.
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http://dx.doi.org/10.3168/jds.2019-17880DOI Listing
July 2020

Better pulmonary function is associated with greater handgrip strength in a healthy Chinese Han population.

BMC Pulm Med 2020 Apr 29;20(1):114. Epub 2020 Apr 29.

Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin, China.

Background: Handgrip strength (HGS) has been widely studied in clinical and epidemiological settings, but the relationship between HGS and pulmonary function is still controversial. This study analysed pulmonary function and HGS stratified by sex and age in a healthy Chinese Han population, as well as the associations between HGS and pulmonary function parameters.

Methods: HGS was measured by a Jamar dynamometer and pulmonary function was tested using a portable spirometer. Frequencies and variables are presented as percentages and means ± standard deviations, respectively. Chi-square tests were used for comparisons of categorical variables, and Student's t-tests or Mann-Whitney U-tests were used for continuous variables. Pearson's correlation coefficients were used to analyse the normally distributed variables, and Spearman correlation coefficients were used to analyse the non-normally distributed variables. Multivariate linear regression models were employed to explore the relationships between HGS and parameters of pulmonary function. The statistical significance was set at p < 0.01.

Results: Cross-sectional data were available for 1519 subjects (59.0% females, 57.9 ± 13.3 years old). Males had higher average HGS than females (40.2 vs. 25.0 kg, p < 0.01), as well as better pulmonary function. Both HGS and pulmonary function parameters were significantly inversely correlated with age (r ≤ - 0.30, p < 0.01). The maximum value of vital capacity (VC max), forced expiratory volume in 3 s (FEV 3) and forced vital capacity (FVC) were strongly correlated with HGS among the pulmonary function indices (r = 0.72, 0.70 and 0.69, respectively, p < 0.001). In the multivariate linear regression analysis, HGS and height were positively correlated, while age and pulse pressure were negatively correlated with HGS. In males, the FVC, VC max and FEV3 increased by 0.02 L, 0.023 L and 0.03 L in per 1 kg increase in HGS, respectively. The HGS coefficients for females were smaller than those for males.

Conclusions: Both pulmonary function and HGS were inversely correlated with age, and better pulmonary function was associated with greater handgrip strength.
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http://dx.doi.org/10.1186/s12890-020-1155-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191764PMC
April 2020

Opportunistic infections complicating immunotherapy for non-small cell lung cancer.

Thorac Cancer 2020 06 20;11(6):1689-1694. Epub 2020 Apr 20.

Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.

Immunotherapy has produced durable responses in numerous advanced and metastatic cancers, especially advanced non-small cell lung carcinoma (NSCLC). However, opportunistic infection has become a major risk for patients who have received immune checkpoint inhibitors (ICIs). Early diagnosis of infection is difficult due to an acute disease course and heterogeneity in clinical manifestation. We retrospectively analyzed four cases with NSCLC who received ICIs and developed opportunistic infections. Two of our cases received antecedent glucocorticoids to treat immune-related adverse events (irAEs), whereas immunosuppressive agents were not used beforehand in the other cases. We highlight that opportunistic infections complicating immunotherapy can be severe and even fatal. When patients deteriorate after initial remission from irAEs by glucocorticoids, infections should be thoroughly investigated and carefully distinguished from an irAE flare. Bronchoscopy and bronchoalveolar lavage (BAL) are essential. In patients where limited results from traditional microbiological tests have been obtained, next-generation sequencing (NGS) of BAL fluid is beneficial in guiding a precise antimicrobial treatment. An antipneumocystis prophylaxis may also be considered in selected patients.
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http://dx.doi.org/10.1111/1759-7714.13422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262884PMC
June 2020

Functionally heterogeneous human satellite cells identified by single cell RNA sequencing.

Elife 2020 04 1;9. Epub 2020 Apr 1.

Departments of Surgery and Orofacial Sciences, Division of Plastic and Reconstructive Surgery, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, United States.

Although heterogeneity is recognized within the murine satellite cell pool, a comprehensive understanding of distinct subpopulations and their functional relevance in human satellite cells is lacking. We used a combination of single cell RNA sequencing and flow cytometry to identify, distinguish, and physically separate novel subpopulations of human PAX7+ satellite cells (Hu-MuSCs) from normal muscles. We found that, although relatively homogeneous compared to activated satellite cells and committed progenitors, the Hu-MuSC pool contains clusters of transcriptionally distinct cells with consistency across human individuals. New surface marker combinations were enriched in transcriptional subclusters, including a subpopulation of Hu-MuSCs marked by CXCR4/CD29/CD56/CAV1 (CAV1+). In vitro, CAV1+ Hu-MuSCs are morphologically distinct, and characterized by resistance to activation compared to CAV1- Hu-MuSCs. In vivo, CAV1+ Hu-MuSCs demonstrated increased engraftment after transplantation. Our findings provide a comprehensive transcriptional view of normal Hu-MuSCs and describe new heterogeneity, enabling separation of functionally distinct human satellite cell subpopulations.
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http://dx.doi.org/10.7554/eLife.51576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164960PMC
April 2020

METTL7B Is Required for Cancer Cell Proliferation and Tumorigenesis in Non-Small Cell Lung Cancer.

Front Pharmacol 2020 28;11:178. Epub 2020 Feb 28.

Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, China.

Lung cancer remains a leading cause of cancer-associated mortality worldwide, however, molecular mechanisms underlying lung cancer tumorigenesis and progression remain unknown. Here, we report evidence showing that one member of the mammalian methyltransferase-like family (METTL), METTL7B, is a potential molecular target for treatment of non-small cell lung cancer (NSCLC). METTL7B expression was elevated in the majority of NSCLC comparing to normal tissues. Increased expression of METTL7B contributed to advanced stages of tumor development and poor survival in NSCLC patients. Lentivirus-mediated shRNA silencing of METTL7B suppressed proliferation and tumorigenesis of cancer cells and . Investigation on gene expression profiles of NSCLC cells revealed that abundant cell cycle related genes were downregulated in the absence of METTL7B. Pathway enrichment analysis indicated that METTL7B participated in cell cycle regulation. Notably, CCND1, a key regulator for G1/S transition, was significantly decreased with the depletion of METTL7B, resulting in G0/G1 arrest, indicating that METTL7B is critical for cell cycle progression. Taken together, our findings implicate that METTL7B is essential for NSCLC development and progression. METTL7B might serve as a potential therapeutic target for NSCLC.
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http://dx.doi.org/10.3389/fphar.2020.00178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059849PMC
February 2020

Experimental Identification of Electric Dipoles Induced by Magnetic Monopoles in Tb_{2}Ti_{2}O_{7}.

Phys Rev Lett 2020 Feb;124(8):087601

Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

The fundamental principles of electrodynamics allow an electron carrying both electric monopole (charge) and magnetic dipole (spin) but prohibit its magnetic counterpart. Recently, it was predicted that the magnetic "monopoles" carrying emergent magnetic charges in spin ice systems can induce electric dipoles. The inspiring prediction offers a novel way to study magnetic monopole excitations and magnetoelectric coupling. However, no clear example has been identified up to now. Here, we report the experimental evidence for electric dipoles induced by magnetic monopoles in spin frustrated Tb_{2}Ti_{2}O_{7}. The magnetic field applied to pyrochlore Tb_{2}Ti_{2}O_{7} along the [111] direction, brings out a "3-in-1-out" magnetic monopole configuration, and then induces a subtle structural phase transition at H_{c}∼2.3  T. The transition is made evident by the nonlinear phonon splitting under magnetic fields and the anomalous crystal-field excitations of Tb^{3+} ions. The observations consistently point to the displacement of the oxygen O^{''} anions along the [111] axis which gives rise to the formation of electric dipoles. The finding demonstrates that the scenario of magnetic monopole having both magnetic charge and electric dipole is realized in Tb_{2}Ti_{2}O_{7} and sheds light into the coupling between electricity and magnetism of magnetic monopoles in spin frustrated systems.
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http://dx.doi.org/10.1103/PhysRevLett.124.087601DOI Listing
February 2020
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