Publications by authors named "Kang Yu"

664 Publications

[The feasibility of zygomatic implant quad approach in patients with tooth agenesis: a radiographic analysis].

Shanghai Kou Qiang Yi Xue 2021 Apr;30(2):196-200

Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology. Shanghai 200011, China.

Purpose: The aim of this study was to analyze the feasibility of zygomatic implant quad approach in patients with tooth agenesis.

Methods: Based on the data from cone-beam CT (CBCT), twenty one patients with tooth agenesis who were planned to receive zygomatic implant quad approach were enrolled. The radiographic bone-to-implant contact (rBIC) of each zygomatic implant placed virtually in patients' zygomatic segment was measured. SPSS 25.0 software package was used for statistical analysis.

Results: Twenty patients' plans of zygomatic implant quad approach were completed (12 men and 8 women). A total of 80 zygomatic implants were placed virtually and the average rBIC of zygomatic segment was (13.85±3.29) mm. The rBIC values of 40 mesial zygomatic implants and 40 distal zygomatic implants were (13.80±3.74) mm and (13.90±2.81) mm, respectively(P>0.05). The average rBIC in male of 24 mesial zygomatic implants and 24 distal zygomatic implants were(14.21±4.08) mm and(14.31±3.18) mm, respectively, slightly higher than those in female of 16 mesial zygomatic implants and 16 distal zygomatic implants, which were (13.18±3.18) mm and (13.29±2.10) mm, respectively. There was no significant difference between the two groups (P>0.05). The average rBIC of 15 extra sinus zygomatic implants, 46 against sinus lateral wall zygomatic implants and 19 intra-sinus zygomatic implants were (16.27±2.95), (13.87±3.10) and (11.88±2.78) mm, respectively. There was significant difference between the extra sinus zygomatic implants and the other two(P<0.05).

Conclusions: It is feasible to plan zygomatic implant quad approach for patients with tooth agenesis. Zygomatic implants can get adequate rBIC in zygomatic segment and to provide sufficient support and retention of the superstructure.
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April 2021

Activities of daily living associated with postoperative intensive care unit survival in elderly patients following elective major abdominal surgery: An observational cohort study.

Medicine (Baltimore) 2021 Jun;100(22):e26056

Department of Geriatric Medicine.

Abstract: Elderly patients who undergo major abdominal surgery are being in increasing numbers. Intensive care unit (ICU) survival is critical for surgical decision-making process. Activities of daily living (ADL) are associated with clinical outcomes in the elderly. We aimed to investigate the relationship between ADL and postoperative ICU survival in elderly patients following elective major abdominal surgery.We conducted a retrospective cohort study involving patients aged ≥65 years admitted to the surgical intensive care unit (SICU) following elective major abdominal surgery. Data from all patients were extracted from the electronic medical records. The Barthel Index (BI) was used to assess the level of dependency in ADL at the time of hospital admission.ICU survivors group had higher Barthel Index (BI) scores than non-survivors group (P < .001). With the increase of BI score, postoperative ICU survival rate gradually increased. The ICU survivals in patients with BI 0-20, BI 21-40, BI 41-60, BI 61-80 and BI 81-100 were 55.7%, 67.6%, 72.4%, 83.3% and 84.2%, respectively. In logistic regression, The Barthel Index (BI) was significantly correlated with the postoperative ICU survival in elderly patients following elective major abdominal surgery (OR = 1.33, 95% CI: 1.20-1.47, P = .02). The area under the receiver operating characteristic (ROC) curve of Barthel Index in predicting postoperative ICU survival was 0.704 (95% CI, 0.638-0.771). Kaplan-Meier survival curve in BI≥30 patients and BI < 30 patients showed significantly different.Activity of daily living upon admission was associated with postoperative intensive care unit survival in elderly patients following elective major abdominal surgery. The Barthel Index(BI) ≥30 was associated with increased postoperative ICU survival. For the elderly with better functional status, they could be given more surgery opportunities. For those elderly patients BI < 30, these results provide useful information for clinicians, patients and their families to make palliative care decisions.
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http://dx.doi.org/10.1097/MD.0000000000026056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183836PMC
June 2021

Raman Spectroscopy Study on Ternary Model Coal Mine Methane Hydrates.

ACS Omega 2021 Apr 14;6(16):10709-10714. Epub 2021 Apr 14.

School of Safety Engineering, Heilongjiang University of Science and Technology, Harbin 150022, China.

The microfeatures of coal mine methane (CMM) hydrates, synthesized with three gas samples (CH/CH/N, G1 = 43 : 47 : 10, G2 = 60 : 30 : 10, and G3 = 74 : 16 : 10) in a self-made transparent high-pressure cell at 275.15 K and 5 MPa were investigated using Raman spectroscopy. As a discriminator, the vibrational band frequencies in the C-C regions of the recorded hydrate Raman spectra for CH show that G1∼G3 hydrates are structure I. The three principal parameters used to study the microfeatures of the model CMM hydrates, including cavity occupancies, hydrate guest compositions, and hydration numbers, were calculated. The large cavity occupancies for CH constantly decrease from 85.12 to 79.32%, while the small cavity occupancies for CH have a continuous increase from 73.75 to 96.42%. However, CH competes with CH on entering the large cavities for their large cavity occupancies of 12.79-17.31%. The cavity occupancies of N are less than 1.2%. The hydrate composition calculations show that the molar fractions of CH are the maximum. The hydration numbers range from 6.221 to 6.00. Based on the hydrate guest compositions and hydration numbers, the molecular formulas of the three CMM hydrates are presented.
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http://dx.doi.org/10.1021/acsomega.1c00216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153790PMC
April 2021

Interaction between CD9 and PI3K‑p85 activates the PI3K/AKT signaling pathway in B‑lineage acute lymphoblastic leukemia.

Oncol Rep 2021 Jul 26;46(1). Epub 2021 May 26.

Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

Our previous study has shown that knockdown could suppress cell proliferation, adhesion, migration and invasion, and promote apoptosis and the cytotoxicity of chemotherapeutic drugs in the B‑lineage acute lymphoblastic leukemia (B‑ALL) cell line SUP‑B15. In this study, we further investigated the molecular mechanism underlying the effects of CD9 on leukemic cell progression and the efficacy of chemotherapeutic agents in B‑ALL cells. Using the CD9‑knockdown SUP‑B15 cells, we demonstrated that the silencing of the gene significantly reduced the expression of phosphorylated‑phosphatidylinositol‑3 kinase (p‑PI3K), phosphorylated‑protein kinase B (p‑AKT), P‑glycoprotein (P‑gp), multidrug resistance‑associated protein 1 (MRP1), breast cancer resistance protein (BCRP), matrix metalloproteinase 2 (MMP2) and phosphorylated‑focal adhesion kinase (p‑FAK). In addition, glutathione S‑transferase (GST) pull‑down assay showed the binding between CD9 and both PI3K‑p85α and PI3K‑p85β , while co‑immunoprecipitation assay showed the binding between CD9 and both PI3K‑p85α and PI3K‑p85β . Furthermore, the PI3K/AKT inhibitor LY294002 mirrored the effects of knockdown in SUP‑B15 cells. Taken together, these findings demonstrated that CD9 activates the PI3K/AKT signaling pathway through direct interaction with PI3K‑p85 in B‑ALL cells. Our data provide evidence for the inhibition of the PI3K/AKT pathway as a novel therapeutic option in CD9 antigen‑positive B‑ALL.
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http://dx.doi.org/10.3892/or.2021.8091DOI Listing
July 2021

Normal Absolute Monocyte Count in Combination with Normal/High Absolute Lymphocyte Count at the Time of Relapse is Associated with Improved Survival in Patients with Early Relapsed Acute Myeloid Leukemia.

Cancer Invest 2021 Jun 9:1-9. Epub 2021 Jun 9.

Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China.

This study aimed to examine the prognostic significance of peripheral absolute monocyte count (AMC) in combination with absolute lymphocyte count (ALC) at the time of relapse in a cohort of 57 patients with early relapsed (first complete remission <12 months) acute myeloid leukemia (AML). Both univariate and multivariate Cox proportional hazard regression analyses revealed that normal AMC in combination with normal/high ALC (versus low/high AMC in combination with low ALC) was significantly associated with improved OS. We concluded that the combination of AMC and ALC could be used as a prognostic marker for survival outcomes in early relapsed AML.
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http://dx.doi.org/10.1080/07357907.2021.1933013DOI Listing
June 2021

Multiple Enhanced Lesions in the Brain MRI of a Patient with COVID-19.

Dement Neurocogn Disord 2021 Apr 8;20(2):13-15. Epub 2021 Apr 8.

Department of Neurology, Myongji Hospital, College of Medicine, Hanyang University, Goyang, Korea.

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http://dx.doi.org/10.12779/dnd.2021.20.2.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093011PMC
April 2021

Exploring the impact of number and type of comorbidities on the risk of severe COPD exacerbations in Korean Population: a Nationwide Cohort Study.

BMC Pulm Med 2021 May 6;21(1):151. Epub 2021 May 6.

International Healthcare Center, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.

Background: It is difficult to assess the impact of multiple comorbidities on clinical outcomes in chronic obstructive pulmonary disease (COPD). In this study, we aimed to investigate exacerbation-associated comorbidities, determine whether the number of comorbidities is an independent risk factor for exacerbation, and identify other exacerbation-associated factors in a Korean COPD population using a nationwide population-based cohort. This study focused on severe exacerbations that required hospitalisation or emergency room visits.

Methods: The National Health Insurance Service-National Sample Cohort, version 2.0, data sampled between 2002 and 2015 were analysed. Data from two years after the diagnosis of COPD were analysed for each participant (N = 12,554, entire cohort). Moreover, 42% of the participants underwent additional health examinations (N = 5306, health-screening cohort). Fifteen comorbidities that were previously reported as risk factors for exacerbations were examined. A logistic regression model was used to analyse association with exacerbations.

Results: Asthma (1.57 [1.39-1.76] and 1.24 [1.06-1.44]), lung cancer (1.84 [1.30-2.59] and 2.28 [1.54-3.37]), and heart failure (1.39 [1.16-1.67] and 1.52 [1.18-1.97]) were associated with exacerbation in both cohorts (odds ratio [95% confidence interval] in the entire cohort and health-screening cohort, respectively). The number of comorbidities was an independent risk factor, and old age, male sex, low body mass index, and current smoking were also independent risk factors. High cholesterol levels and body mass index exerted protective effects against exacerbation.

Conclusions: The number of comorbidities, certain comorbidities such as asthma, lung cancer and heart failure, and low BMI were associated with an increased risk of severe exacerbation in COPD patients.
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http://dx.doi.org/10.1186/s12890-021-01497-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101227PMC
May 2021

The MYB family transcription factor TuODORANT1 from Triticum urartu and the homolog TaODORANT1 from Triticum aestivum inhibit seed storage protein synthesis in wheat.

Plant Biotechnol J 2021 May 5. Epub 2021 May 5.

State Key Laboratory of Plant Cell and Chromosome Engineering, National Center for Plant Gene Research, Institute of Genetics and Developmental Biology/Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, China.

Seed storage proteins (SSPs) are determinants of wheat end-product quality. SSP synthesis is mainly regulated at the transcriptional level. Few transcriptional regulators of SSP synthesis have been identified in wheat and this study aims to identify novel SSP gene regulators. Here, the R2R3 MYB transcription factor TuODORANT1 from Triticum urartu was found to be preferentially expressed in the developing endosperm during grain filling. In common wheat (Triticum aestivum) overexpressing TuODORANT1, the transcription levels of all the SSP genes tested by RNA-Seq analysis were reduced by 49.71% throughout grain filling, which contributed to 13.38%-35.60% declines in the total SSP levels of mature grains. In in vitro assays, TuODORANT1 inhibited both the promoter activities and the transcription of SSP genes by 1- to 13-fold. The electrophoretic mobility shift assay (EMSA) and ChIP-qPCR analysis demonstrated that TuODORANT1 bound to the cis-elements 5'-T/CAACCA-3' and 5'-T/CAACT/AG-3' in SSP gene promoters both in vitro and in vivo. Similarly, the homolog TaODORANT1 in common wheat hindered both the promoter activities and the transcription of SSP genes by 1- to 112-fold in vitro. Knockdown of TaODORANT1 in common wheat led to 14.73%-232.78% increases in the transcription of the tested SSP genes, which contributed to 11.43%-19.35% elevation in the total SSP levels. Our data show that both TuODORANT1 and TaODORANT1 are repressors of SSP synthesis.
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http://dx.doi.org/10.1111/pbi.13604DOI Listing
May 2021

Women with peripartum cardiomyopathy have normal ejection fraction, but abnormal systolic strain, during pregnancy.

ESC Heart Fail 2021 May 4. Epub 2021 May 4.

Division of Cardiology, Perelman Center for Advanced Medicine, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Boulevard, 2-East Pavilion, Philadelphia, PA, 19104, USA.

We report a case series of six women with peripartum cardiomyopathy (PPCM) who incidentally underwent echocardiography prior to the clinical presentation of PPCM. For comparison, we identified controls, matched 2:1 on age, race, body mass index, gestational age, and hypertensive disorder. Among the six cases, all were diagnosed with PPCM during the post-partum period. Pre-PPCM echocardiograms were performed between 17.7 weeks of gestation and 13 days post-partum. Baseline left ventricular ejection fraction and size were normal and similar to the 12 matched controls (60% ± 6.6% vs. 61.4% ± 6.3%, P = 0.63) or left ventricular end-diastolic dimension (4.6 cm ± 0.2 cm vs. 4.5 cm ± 0.4 cm, P = 0.689). There was a trend towards a less negative (more abnormal) mean global longitudinal strain in cases compared with controls (-14% ± 4% vs. -18.3% ± 4.5%, P = 0.0658). Mean global circumferential strain was significantly less negative (more abnormal) in cases compared with controls (-21.5% ± 5% vs. -29.3% ± 7.6%, P = 0.0329). We conclude that women who develop PPCM have normal left ventricular ejection fraction during gestation preceding PPCM, indicating that the disease develops acutely in the peripartum period. Abnormal strain can be detected, however, suggesting that strain imaging could represent a screening method in populations at high risk for PPCM if confirmed in future studies.
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http://dx.doi.org/10.1002/ehf2.13323DOI Listing
May 2021

Efficacy of Immunosuppressants in High Rejection Risk Keratoplasty: A Meta-Analysis of Comparative Studies.

Cornea 2021 Jun;40(6):800-807

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.

Purpose: To evaluate the prophylactic effects of immunosuppressants in corneal graft rejection after high-risk penetrating keratoplasty.

Methods: We searched PubMed, Embase, and the Cochrane Library for comparative studies published between 1989 and 2019 that evaluated the efficacy of immunosuppressants for high-risk corneal graft. The primary outcomes were the 1- and 3-year rejection rates. A fixed-effects or random-effects model was used on the basis of the I2 value, and the results were reported as odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Topical tacrolimus (FK506) was more effective than topical cyclosporine A (CsA) at reducing the 1-year graft rejection rate (OR: 0.17; 95% CI, 0.08-0.37, P<0.01). However, the combination of steroid with either topical FK506 (OR: 0.4; 95% CI, 0.16-1.04, P = 0.09) or CsA (OR: 0.74; 95% CI, 0.32-1.71, P= 0.48) did not show significant superiority in preventing immune rejection compared with steroid monotherapy. Mycophenolate mofetil (MMF) was more effective than CsA at reducing the 1-year graft rejection rate (OR: 2.67; 95% CI, 1.50-4.76, P<0.01). However, MMF was not significantly superior to CsA at reducing the 3-year graft rejection rate (OR: 1.21; 95% CI, 0.45-3.25, P = 0.71). For reducing the 1-year rejection rate, MMF (OR: 0.12; 95% CI, 0.03-0.39, P < 0.01) and CsA (OR: 0.28; 95% CI, 0.10-0.76, P = 0.01) were each more effective than the control groups.

Conclusions: FK506 eye drops, MMF, and systemic CsA were considered to be promising management to prevent rejection in high-risk penetrating keratoplasty in the present study.
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http://dx.doi.org/10.1097/ICO.0000000000002709DOI Listing
June 2021

Spectroscopic Estimation of N Concentration in Wheat Organs for Assessing N Remobilization Under Different Irrigation Regimes.

Front Plant Sci 2021 9;12:657578. Epub 2021 Apr 9.

College of Agronomy and Biotechnology, China Agricultural University, Beijing, China.

Nitrogen (N) remobilization is a critical process that provides substantial N to winter wheat grains for improving yield productivity. Here, the remobilization of N from anthesis to maturity in two wheat cultivars under three irrigation regimes was measured and its relationship to organ N concentration was examined. Based on spectral data of organ powder samples, partial least squares regression (PLSR) models were calibrated to estimate N concentration () and validated against laboratory-based measurements. Although spectral reflectance could accurately estimate , the PLSR-based -spectra predictive model was found to be organ-specific, organs at the top canopy (chaff and top three leaves) received the best predictions ( > 0.88). In addition, N remobilization efficiency (NRE) in the top two leaves and top third internode was highly correlated with its corresponding N concentration change (Δ) with an of 0.90. Δ of the top first internode (TIN1) explained 78% variation of the whole-plant NRE. This study provides a proof of concept for estimating N concentration and assessing N remobilization using hyperspectral data of individual organs, which offers a non-chemical and low-cost approach to screen germplasms for an optimal NRE in drought-resistance breeding.
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http://dx.doi.org/10.3389/fpls.2021.657578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062884PMC
April 2021

A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model.

Acta Biomater 2021 Apr 22. Epub 2021 Apr 22.

Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jie Fang Road, Hangzhou 310009, China. Electronic address:

Osteochondral regeneration is an orchestrated process of inflammatory immunity, host cell response, and implant degradation in tissue engineering. Here, the effects of a platelet-rich plasma (PRP)-gelatin methacryloyl (GelMA) hydrogel scaffold fabricated using the digital micro-mirror device (DMD) technique for osteochondral repair were investigated in a rabbit model. GelMA hydrogels with different PRP concentrations were fabricated, and their roles in bone marrow mesenchymal stem cells (BMSCs) and macrophage polarization in vitro were investigated. The incorporation of 20% PRP into the hydrogel showed optimal effects on the proliferation, migration, and osteogenic and chondrogenic differentiation of BMSCs. The 20% PRP-GelMA (v/v) hydrogel also promoted M2 polarization with high expression of Arg1 and CD206. Compared to the 20% PRP group, the 50% PRP group showed similar biological roles in BMSCs but less extent of osteogenesis. In the vivo study, the 20% PRP-GelMA composite was used for osteochondral reconstruction and showed more cartilage and subchondral bone regeneration than that observed using the pure GelMA hydrogel. The PRP-GelMA group exhibited more M2 macrophage infiltration and less M1 macrophage presentation at three time points as compared to the nontreatment group. The expression of Arg1 in the PRP-GelMA group increased significantly at 6 weeks but decreased to a lower level at 12 weeks, while CD163 showed sustained high expression until 18 weeks. Our findings demonstrated that the 3D-printed PRP-GelMA composite could promote osteochondral repair through immune regulation by M2 polarization and could be a potential candidate for osteochondral tissue engineering. STATEMENT OF SIGNIFICANCE: PRP-GelMA hydrogels promoted the migration and osteogenic and chondrogenic differentiation of BMSCs. PRP-GelMA hydrogels participated in immune regulation and M1-to-M2 transition of macrophages. PRP-GelMA hydrogels coordinated and promoted several overlapping osteochondral repair events, including dynamic immune regulation, chemotaxis of MSCs, and osteochondral differentiation. PRP-GelMA hydrogels showed superior cartilage and subchondral bone repair properties.
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http://dx.doi.org/10.1016/j.actbio.2021.04.010DOI Listing
April 2021

Ralstonia solanacearum type III effector RipJ triggers bacterial wilt resistance in Solanum pimpinellifolium.

Mol Plant Microbe Interact 2021 Apr 21. Epub 2021 Apr 21.

Pohang University of Science and Technology, 34995, Department of Life Sciences, 77 CheongAm-Ro, Nam-Gu, Pohang, GyeongBuk, Korea (the Republic of), 37673;

Ralstonia solanacearum causes bacterial wilt disease in solanaceous crops. Identification of avirulence type III secreted effectors recognized by specific disease resistance proteins in host plant species is an important step towards developing durable resistance in crops. In the present study, we show that R. solanacearum effector RipJ functions as an avirulence determinant in Solanum pimpinellifolium LA2093. 10 candidate avirulence effectors were shortlisted based on the effector repertoire comparison between avirulent Pe_9 and virulent Pe_1 strain. Infection assays with transgenic Pe_1 strain individually carrying a candidate avirulence effector from Pe_9 revealed that only RipJ elicits strong bacterial wilt resistance in S. pimpinellifolium LA2093. Furthermore, we identified that several RipJ natural variants do not induce bacterial wilt resistance in S. pimpinellifolium LA2093. RipJ belongs to the YopJ family of acetyltransferases. Our sequence analysis indicated the presence of partially conserved putative catalytic residues. Interestingly, the conserved amino acid residues in the acetyltransferase catalytic triad are not required for effector-triggered immunity. In addition, we show that RipJ does not auto-acetylate its lysine residues. Our study reports the identification of the first R. solanacearum avirulence protein that triggers bacterial wilt resistance in tomato. We expect that our discovery of RipJ as an avirulence protein will accelerate the development of bacterial wilt-resistant tomato varieties in the future.
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http://dx.doi.org/10.1094/MPMI-09-20-0256-RDOI Listing
April 2021

Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo.

Cell 2021 Apr;184(8):2020-2032.e14

Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address:

Interspecies chimera formation with human pluripotent stem cells (hPSCs) represents a necessary alternative to evaluate hPSC pluripotency in vivo and might constitute a promising strategy for various regenerative medicine applications, including the generation of organs and tissues for transplantation. Studies using mouse and pig embryos suggest that hPSCs do not robustly contribute to chimera formation in species evolutionarily distant to humans. We studied the chimeric competency of human extended pluripotent stem cells (hEPSCs) in cynomolgus monkey (Macaca fascicularis) embryos cultured ex vivo. We demonstrate that hEPSCs survived, proliferated, and generated several peri- and early post-implantation cell lineages inside monkey embryos. We also uncovered signaling events underlying interspecific crosstalk that may help shape the unique developmental trajectories of human and monkey cells within chimeric embryos. These results may help to better understand early human development and primate evolution and develop strategies to improve human chimerism in evolutionarily distant species.
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http://dx.doi.org/10.1016/j.cell.2021.03.020DOI Listing
April 2021

A Web of Science-based scientometric analysis about mammalian target of rapamycin signaling pathway in kidney disease from 1986 to 2020.

Transl Androl Urol 2021 Mar;10(3):1006-1017

Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: The mammalian target of rapamycin (mTOR) signaling pathway is vital for the regulation of cell metabolism, growth and proliferation in the kidney. This study aims to show current research focuses and predict future trends about mTOR pathway in kidney disease by the methods of scientometric analysis.

Methods: We referred to publications from the Web of Science Core Collection (WoSCC) Database. Carrot2, VOSviewer and CiteSpace programs were applied to evaluate the distribution and contribution of authors, institutes and countries/regions of extensive bibliographic metadata, show current research focuses and predict future trends in kidney disease's area.

Results: Until July 10, 2020, there are 2,585 manuscripts about mTOR signaling pathway in kidney disease in total and every manuscript is cited 27.39 times on average. The big name of course is the United States. Research hot spots include "diabetic nephropathy", "kidney transplantation", "autosomal dominant polycystic kidney disease", "tuberous sclerosis complex", "renal cell carcinoma" and "autophagy". Seven key clusters are detected, including "kidney transplantation", "autosomal dominant polycystic kidney disease", "renal transplantation", "renal cell carcinoma", "hamartin", "autophagy" and "tuberous sclerosis complex".

Conclusions: Diabetic nephropathy, kidney transplantation, autosomal dominant polycystic kidney disease, tuberous sclerosis complex, renal cell carcinoma and autophagy are future research hot spots by utilizing scientometric analysis. In the future, it is necessary to research these fields.
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http://dx.doi.org/10.21037/tau-20-1469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039620PMC
March 2021

Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis.

Sci Rep 2021 04 13;11(1):8080. Epub 2021 Apr 13.

Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.

The objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.
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http://dx.doi.org/10.1038/s41598-021-87668-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044143PMC
April 2021

A Novel, Personalized Drug-Screening System for Platinum-Resistant Ovarian Cancer Patients: A Preliminary Clinical Report.

Cancer Manag Res 2021 29;13:2849-2867. Epub 2021 Mar 29.

The Obstetrics & Gynecology Hospital of Fudan University, Gynecology Department, Shanghai, People's Republic of China.

Purpose: With this study, we intended to construct a personalized drug-screening system for platinum-resistant ovarian cancer patients by consulting a patient's medical history, data derived from gene mutation detection, and drug screening results derived from mini-PDX (patient-derived xenograft) models. We also aimed to evaluate the efficacy and safety of our system.

Patients And Methods: We selected 12 patients with platinum-resistant ovarian cancer who were treated at our hospital from January 2018 to December 2019 to design a single-arm clinical trial. The subsequent chemotherapeutic plans were selected according to a personalized drug-screening system that circulating tumor DNA (ctDNA) testing and the establishment of mini-PDX models. We then analyzed the patients for clinical benefits side-effects in response to chemotherapy in order to evaluate the clinical effects and safety of our new personalized drug-selection system.

Results: We successfully established an individualized and sensitive drug-screening system for the 12 patients. Mini-PDX models verified that potentially effective drugs were identified for 11 of the patients. Treatment resulted in complete remission (one patient), partial remission (five patients), and stable disease (three patients). The remaining three patients experienced disease progression. The overall clinical-benefit rate was 75.0%. Following treatment, the levels of CA125 levels decreased significantly in seven of the 12 patients. Severe side effects, arising from chemotherapy, were only observed in one case.

Conclusion: Constructing a personalized drug-screening system for platinum-resistant ovarian cancer patients can be used to guide clinical drug selection and improve the clinical-benefit rate for patients.

Trial Registration Number: ChiCTR1800016766 (Chinese Clinical Trial Registry Center).
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http://dx.doi.org/10.2147/CMAR.S276799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020460PMC
March 2021

Clinical risk score for predicting invasive fungal disease after allogeneic hematopoietic stem cell transplantation: Analysis of the China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study.

Transpl Infect Dis 2021 Apr 7:e13611. Epub 2021 Apr 7.

Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University, People's Hospital, Beijing, People's Republic of China.

Background And Objective: Invasive fungal disease (IFD) is associated with a high mortality for patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed not only to develop a proven/probable IFD risk-scoring model but to identify high-risk populations that would benefit from anti-fungal prophylaxis.

Methods: Data from the China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study were retrieved, and all patients (n = 1053) undergoing allo-HSCT were randomly divided into the training set (n = 685) for model development and the validation set (n = 368) for model verification. A weighted risk score for proven or probable IFD was established through multivariate logistic regression analysis.

Results: The study population had a mean age of 28.95 years and the majority underwent myeloablative transplantation in complete remission 1 (53.4%). Five risk factors of IFD were identified, namely neutropenia lasting longer than 14 days, corticosteroid use, diabetes, haploidentical donor, and unrelated donor. Based on the risk score for IFD, the patients were categorized into three groups: low risk (score 0-4, 1.5%-4.0%), intermediate risk (score 5-8, 9.8%), and high risk (score>8, 24.7%-14.0%). Anti-fungal prophylaxis may provide benefits for patients with intermediate (8.5% vs. 18.5%, P = .0085) or high risk (19.4% vs. 30.8%, P = .4651) but not low risk (2.1% vs. 3.8%, P = .6136) of IFD.

Conclusion: A practical weighted risk score for IFD in patients receiving allo-HSCT was established, which can aid decision-making regarding the administration of anti-fungal prophylaxis.
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http://dx.doi.org/10.1111/tid.13611DOI Listing
April 2021

Activity of daily living upon admission is an independent predictor of in-hospital mortality in older patients with community-acquired pneumonia.

BMC Infect Dis 2021 Apr 1;21(1):314. Epub 2021 Apr 1.

Department of Internal Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, China.

Background: Older patients hospitalized with community-acquired pneumonia (CAP) are at high risk for short-term mortality. Activity of daily living (ADL) is associated with clinical outcomes in older patients. We aimed to investigate the prognostic value of ADL upon admission on the in-hospital mortality in older patients with CAP.

Methods: We conducted a retrospective cohort study involving patients aged ≥65 years admitted to Beijing Chao-Yang hospital due to CAP between June 2012 and June 2020. ADL evaluation upon admission was performed by Barthel Index (BI). Data from all patients were extracted from the electronic medical records.

Results: Four thousand eight hundred eighty patients were included, 131 patients (2.7%) died during their hospitalization. Median BI in the Deceased group was 45 (20-65), Deceased group had lower BI scores than Survivors group (p < 0.001). Low BI (< 60) was more frequent in patients who died in the hospital than in patients discharged alive (69.5% vs. 13%, p < 0.001). In-hospital mortality was higher among patients with worse ADL upon admission (BI< 60) compared to those BI≥60 (12.6% vs. 0.9%). The worse ADL upon admission (BI< 60) was associated with an increase in the risk of death during CAP hospitalization, worse ADL upon admission (BI< 60) showed an odds ratio (OR) for in-hospital mortality of 7.53 (95%CI: 2.77-20.48; P < 0.01). This association remained significant after adjustment for age, comorbid conditions, respiratory failure, pathogens and laboratory findings (OR, 3.74; 95%CI, 2.37-5.91; P < 0.01). Receiver operating characteristic (ROC) curve revealed that BI upon admission is a predictor related to in-hospital mortality in elderly patients, the area under the ROC curve of BI in predicting in-hospital mortality was 0.81 (with 95% confidence interval: 0.78-0.85). The predictive value of ADL upon admission was better than age in our study population.

Conclusion: Activity of daily living upon admission is an independent predictor of in-hospital mortality in older patients with community-acquired pneumonia.
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http://dx.doi.org/10.1186/s12879-021-06006-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017749PMC
April 2021

Weight-bearing exercise prevents skeletal muscle atrophy in ovariectomized rats.

J Physiol Biochem 2021 May 31;77(2):273-281. Epub 2021 Mar 31.

Department of Electronic Engineering, Fudan University, Shanghai, 200433, China.

Skeletal muscle atrophy (SMA) is a dominant symptom induced by estrogen deficiency which can lead to severe health problems of postmenopausal women. Furthermore, estrogen deficiency has severely compromised the maintenance of muscle stem cells as well as impairs self-renewal and differentiation into muscle fibers. Resistance training is commonly considered as a positive and useful intervention in accelerating the rate of muscle growth. As one of the resistance training, whether the weight-bearing exercise can alleviate SMA induced by estrogen deficiency has not been investigated. The rats were divided into 3 groups randomly: sham group, ovariectomized (OVX) group, and weight-bearing exercise (WBE) therapeutic group. The weight that rats were loaded was 35% of their body weight, and the rats were trained by treadmill training (5° slope, 20 m/min, 30 min/day, 6 days/week) for 8 weeks. After training, the quality and strength of skeletal muscle of the WBE rats were improved; meanwhile, the cross-sectional areas of the skeletal muscle were also increased. Moreover, the WBE activated Akt significantly, upregulated the expression of mTOR, and downregulated the expression of MSTN and its receptor ActRIIB and FoxO1, respectively. The SMA phenomena of rats which induced by estrogen deficiency were prevented effectively via WBE, and the MSTN/Akt/mTOR and FoxO1 signaling pathway may be the predominant way in this improvement.
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http://dx.doi.org/10.1007/s13105-021-00794-0DOI Listing
May 2021

COLGALT2 is overexpressed in ovarian cancer and interacts with PLOD3.

Clin Transl Med 2021 Mar;11(3):e370

Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People's Republic of China.

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http://dx.doi.org/10.1002/ctm2.370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989968PMC
March 2021

miR-23a-3p is involved in drug resistance by directly targeting the influx drug transporter organic anion-transporting polypeptide 2.

Childs Nerv Syst 2021 Mar 29. Epub 2021 Mar 29.

Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 136 Zhong shan Er Road, Yu Zhong District, Chongqing, 400014, China.

Objective: Drug transporters are involved in the drug resistance of individuals with drug-resistant epilepsy by influencing the intracerebral transport of antiepileptic drugs (AEDs). The expression of drug transporters is associated with microRNAs. We previously revealed that miR-23a-3p levels were elevated in the blood of patients with intractable epilepsy. Additionally, the influx drug transporter organic anion-transporting polypeptide 2 (Oatp2) is involved in the intracerebral transport of valproic acid (VPA), the most commonly used AED; repeated seizures lead to decreased expression of Oatp2. However, the role of miR-23a-3p in the expression of Oatp2 and in the development of drug resistance has not been established. Herein, we aimed to determine the potential role of miR-23a-3p in VPA-resistant epilepsy through in vivo and in vitro experiments.

Methods: Epilepsy was elicited after status epilepticus (SE) was induced by lithium-pilocarpine in adult Sprague-Dawley rats, followed by VPA treatment to select rats with VPA resistance. The expression of miR-23a-3p was detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). A miR-23a-3p inhibitor was intracerebrally injected into VPA-resistant rats, and histological staining and Morris water maze tests were performed to evaluate brain damage and learning/memory functions in these rats. Subsequently, a dual-luciferase reporter assay and a VPA uptake assay were performed in brain microvascular endothelial cells (BMECs) to investigate the underlying mechanism of action of miR-23a-3p.

Results: Our results indicated that compared to that in control rats, miR-23a-3p was elevated in VPA-resistant rats. Intracerebral injection of a miR-23a-3p inhibitor reduced brain damage and the associated deficits in learning and memory functions in rats with VPA resistance. Further investigation indicated that Oatp2 was the direct target of miR-23a-3p, and it was negatively regulated by miR-23a-3p in the brain and BMECs. Furthermore, we demonstrated that miR-23a-3p reduced VPA uptake in BMECs by regulating Oatp2 expression.

Conclusions: miR-23a-3p is involved in VPA resistance in epilepsy by directly targeting the influx drug transporter Oatp2, indicating that miR-23a-3p could be a potential therapeutic target for intractable epilepsy.
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http://dx.doi.org/10.1007/s00381-021-05146-3DOI Listing
March 2021

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

J Korean Med Sci 2021 Mar 22;36(11):e83. Epub 2021 Mar 22.

Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain.

Methods: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values.

Results: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; = 0.007).

Conclusion: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.
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http://dx.doi.org/10.3346/jkms.2021.36.e83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985289PMC
March 2021

Pleural effusion-based nomogram to predict outcomes in unselected patients with multiple myeloma: a large single center experience.

Ann Hematol 2021 Jul 14;100(7):1789-1801. Epub 2021 Mar 14.

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, China.

Pleural effusion (PE) is prevalent in unselected "real-life" populations of multiple myeloma (MM). However, its prognostic value on MM is currently elusive. This study aimed to explore the role of PE on MM prognosis and to develop a novel prognostic nomogram for a cohort of Chinese patients with MM. Patients diagnosed with MM form 2000 through 2017 were retrospectively enrolled. PE was evaluated by chest computed tomography (CT) scans. Independent predictors of overall survival (OS) were identified using a multivariable Cox regression model performed on variables selected by the least absolute shrinkage and selection operator (LASSO) algorithm. A nomogram was constructed based on these variables. The concordance index (C-index) and the calibration curve were used to evaluate the predictive performance of the nomogram. Among 861 patients analyzed, 368 patients developed PE. Multivariate cox regression and restricted mean survival time (RMST) analyses revealed that patients with PE experienced worse OS vs. patients without PE. A nomogram predictive of OS was constructed using PE, plasma cell proportion, international staging system (ISS) stage, Charlson comorbidity index (CCI), 1q21 gain, and autologous hematopoietic stem cell transplantation (HSCT). The nomogram showed satisfactory discrimination in the derivation cohort (C-index=0.729) and the validation cohort (C-index=0.684), outperforming the Durie-Salmon (DS) and ISS staging systems. Moreover, the nomogram accurately classified patients into two distinct high- and low-risk groups. PE is frequently encountered in the disease course for MM patients. We derivated and validated a novel nomogram for MM based on PE, outperforming the DS/ISS staging systems.
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http://dx.doi.org/10.1007/s00277-021-04484-1DOI Listing
July 2021

Aptasensor for the Detection of Ochratoxin A Using Graphene Oxide and Deoxyribonuclease I-Aided Signal Amplification.

J Nanosci Nanotechnol 2021 09;21(9):4573-4578

School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China.

In this investigation, a sensitive sensor for ochratoxin A detection was designed based on graphene oxide (GO) and DNase I for amplified fluorescence signal. The outcomes of this investigation indicated that this exploratory platform exhibited efficient sensitivity and good selectivity for ochratoxin A when existence of other toxins. The proposed sensor displayed a linear response over a range of 100-1000 nM (² = 0.986) with a low detection limit of 38.2 nM (S/N = 3) and showed remarkable convenience. In addition, the constructed sensor was examined by testing real food samples spiked with different concentrations of ochratoxin A. Results demonstrated that the constructed sensor provided an effective method for ochratoxin A evaluate in complicated food sample analyses.
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http://dx.doi.org/10.1166/jnn.2021.19348DOI Listing
September 2021

Clinical Characteristics and Risk Factors for Pleural Effusion in Patients with Multiple Myeloma.

Int J Gen Med 2021 25;14:649-657. Epub 2021 Feb 25.

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.

Purpose: Pleural effusion (PE) is prevalent in "real-life" populations of multiple myeloma (MM), a common hematologic malignancy. Development of PE likely has prognostic implications. The aim of this study was to investigate the characteristics and identify risk factors for occurrence of PE in MM.

Patients And Methods: We reviewed electronic medical records of 907 patients diagnosed with MM.

Results: Incidence of PE in MM patients was 42.7%. Small and bilateral PE in most cases. PE developed in all MM subtypes, the median time from diagnosis of multiple myeloma to pleural effusion was 6.8 months (range 0.8-33.6 months). Patients with PE showed worse survival than those without PE (unadjusted hazard ratio with 95% confidence interval: 2.249 [1.774-2.852]). No difference in survival was found between patients with small PE and those with moderate to large PE (unadjusted HR, 1.402; 95% CI, 1.037-1.896). Plasma cell proportion (OR, 1.373; 95% CI, 1.153-1.634; P = 0.009) and amyloidosis (OR, 1.791; 95% CI, 1.408-2.279; P = 0.024) were risk factors for the occurrence of PE at the initial diagnosis of MM. Plasma cell proportion (OR, 1.853; 95% CI, 1.451-2.368; P = 0.038), pneumonia (OR, 1.309; 95% CI, 1.143-1.498; P = 0.008) and heart failure (OR, 1.815; 95% CI, 1.387-2.374; P = 0.031) were risk factors for the occurrence of PE at relapse of MM.

Conclusion: The incidence of PE in MM patients is notable and PE can occur in all MM subtypes. PE indicates a poor prognosis, even small amounts of effusion. PE is a problem worthy of attention, especially in patients with high plasma cell proportion, amyloidosis or complicated with pneumonia and heart failure.
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http://dx.doi.org/10.2147/IJGM.S300337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920607PMC
February 2021

Sterol metabolism and protein metabolism are differentially correlated with sarcopenia in Asian Chinese men and women.

Cell Prolif 2021 Apr 20;54(4):e12989. Epub 2021 Feb 20.

Department of Health Care and Department of Health Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.

Objectives: Our aim was to investigate the prevalence and predictive variables of sarcopenia.

Methods: We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables.

Results: The prevalence of sarcopenia and sarcopenic obesity was 9.2%-16.2% and 0.26%-9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut-off value for age was 71 years, which departs from the commonly accepted cut-off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25-hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia.

Conclusions: Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.
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http://dx.doi.org/10.1111/cpr.12989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016649PMC
April 2021