Publications by authors named "Ying Yao"

251 Publications

Risk Factors and Outcomes of Acute Kidney Injury in Critically Ill Patients with Coronavirus Disease 2019.

Kidney Dis (Basel) 2021 Mar 26;7(2):111-119. Epub 2020 Oct 26.

Department of Nephrology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Coronavirus disease 2019 (COVID-19) has emerged as a major global health threat with a great number of deaths worldwide. Acute kidney injury (AKI) is a common complication in patients admitted to the intensive care unit. We aimed to assess the incidence, risk factors and in-hospital outcomes of AKI in COVID-19 patients admitted to the intensive care unit.

Methods: We conducted a retrospective observational study in the intensive care unit of Tongji Hospital, which was assigned responsibility for the treatments of severe COVID-19 patients by the Wuhan government. AKI was defined and staged based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Mild AKI was defined as stage 1, and severe AKI was defined as stage 2 or stage 3. Logistic regression analysis was used to evaluate AKI risk factors, and Cox proportional hazards model was used to assess the association between AKI and in-hospital mortality.

Results: A total of 119 patients with COVID-19 were included in our study. The median patient age was 70 years (interquartile range, 59-77) and 61.3% were male. Fifty-one (42.8%) patients developed AKI during hospitalization, corresponding to 14.3% in stage 1, 28.6% in stage 2 and 18.5% in stage 3, respectively. Compared to patients without AKI, patients with AKI had a higher proportion of mechanical ventilation mortality and higher in-hospital mortality. A total of 97.1% of patients with severe AKI received mechanical ventilation and in-hospital mortality was up to 79.4%. Severe AKI was independently associated with high in-hospital mortality (OR: 1.82; 95% CI: 1.06-3.13). Logistic regression analysis demonstrated that high serum interleukin-8 (OR: 4.21; 95% CI: 1.23-14.38), interleukin-10 (OR: 3.32; 95% CI: 1.04-10.59) and interleukin-2 receptor (OR: 4.50; 95% CI: 0.73-6.78) were risk factors for severe AKI development.

Conclusions: Severe AKI was associated with high in-hospital mortality, and inflammatory response may play a role in AKI development in critically ill patients with COVID-19.
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http://dx.doi.org/10.1159/000512270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649690PMC
March 2021

Carbothermal Reduction Synthesis of Aluminum Nitride from Al(OH)/C/PVB Slurries Prepared by Three-Roll Mixing.

Materials (Basel) 2021 Mar 12;14(6). Epub 2021 Mar 12.

College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China.

Polyvinyl butyral (PVB) was used in the Al(OH)/carbon black/ethanol slurries by the three-roll mixing to prepare AlN powder using the carbothermal reduction-nitridation (CRN) process in the experiments. The effects of PVB addition on the synthesis of AlN powder were studied by viscosity, tap density, XRD, SEM and TG measurements. The results showed that the PVB layer covering on the surface of Al(OH) particles reduced the viscosity of Al(OH)/carbon/ethanol slurry and increased the dispersion homogeneity of Al(OH)/carbon raw powder. The tap densities of the Al(OH)/carbon mixtures after three-roll milling could be increased with the increase in PVB addition. In the CRN process, most of the PVB covering Al(OH) particles evaporated and supplied the passage for nitrogen removal to the particles. Based on the experimental data, the role of PVB on the mixing and CRN process was discussed.
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http://dx.doi.org/10.3390/ma14061386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998097PMC
March 2021

Fructose-functionalized polymers to enhance therapeutic potential of p-boronophenylalanine for neutron capture therapy.

J Control Release 2021 Feb 24;332:184-193. Epub 2021 Feb 24.

Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan; Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan; Innovation Center of Nanomedicine (iCONM), Kawasaki Institute of Industrial Promotion, 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan. Electronic address:

In boron neutron capture therapy (BNCT), boron drugs should accumulate selectively within a tumor and be quickly cleared from blood and normal organs. However, it is usually challenging to achieve the efficient tumor accumulation and the quick clearance simultaneously. Here we report the complex composed of a fructose-modified poly(ethylene glycol)-poly(l-lysine) block copolymer and p-boronophenylalanine, termed PEG-P[Lys/Lys(fructose)]-BPA, as a boron delivery system permitting selective accumulation within the target tumor with quick clearance from normal organs as well as blood. Our PEG-P[Lys/Lys(fructose)]-BPA could be internalized into tumor cells through LAT1 amino acid transporter-mediated endocytosis and retain in the targeted cells, thereby accomplishing more efficient accumulation and retention in a subcutaneous tumor than clinically used fructose-BPA complexes. Importantly, the moderately cationic property of the polymer facilitated renal clearance and PEG-P[Lys/Lys(fructose)]-BPA exhibited high accumulation contrast between the target tumor and the blood/normal organ. Finally, upon thermal neutron irradiation, PEG-P[Lys/Lys(fructose)]-BPA significantly inhibited the tumor growth in mice. PEG-P[Lys/Lys(fructose)]-BPA may be a promising boron delivery system for BNCT.
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http://dx.doi.org/10.1016/j.jconrel.2021.02.021DOI Listing
February 2021

The glucagon-like peptide-1 (GLP-1) analog exenatide ameliorates intrauterine adhesions in mice.

Peptides 2021 Mar 12;137:170481. Epub 2021 Jan 12.

The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou, China; Gansu Key Laboratory of Reproductive Medicine and Embryo, Gansu International Scientific and Technological Cooperation Base of Reproductive Medicine Transformation Application, Lanzhou, China. Electronic address:

Objective: The purpose of the experiments in this study was to explore the effect of exenatide on intrauterine adhesions (IUAs) and to elucidate its mechanism to provide new ideas for the clinical treatment of IUAs.

Methods: In this study, an animal model of IUAs was established by double stimulation using mechanical curettage and inflammation. After modeling, the treatment group was injected subcutaneously with three doses of exenatide for two weeks. The model group was injected with sterile ultrapure water, and the sham operation group was treated the same as the normal group, except for the observation of abdominal wound changes. Two weeks later, all mice were sacrificed by cervical dysfunction. The obtained mouse uterine tissue was used for subsequent experimental detection, using HE and Masson staining for histomorphological and pathological analysis; qRT-PCR for the detection of TGF-β1, α-SMA, and MMP-9 gene expression in uterine tissue; and western blotting analysis of TGF-β1, α-SMA, and collagen 1 protein expression to verify whether exenatide has a therapeutic effect on IUAs in mice.

Results: In the high-dose exenatide treatment group, the endometrial glands significantly increased in size, and the deposition area of collagen fibers in the endometrial tissue was significantly reduced. We observed that the mRNA expression of TGF-β1 and α-SMA in the endometrial tissue of IUAs mice in this group was significantly reduced, while the expression of MMP-9 was significantly increased. In addition, we found that the protein expression of TGF-β1, α-SMA, and collagen 1 remarkably decreased after treatment with exenatide.

Conclusion: Exenatide may reduce the deposition of collagen fibers in the uterus of IUAs mice and promote the proliferation of endometrial glands in mice.
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http://dx.doi.org/10.1016/j.peptides.2020.170481DOI Listing
March 2021

Tertiary lymphoid organs are associated with the progression of kidney damage and regulated by interleukin-17A.

Theranostics 2021 1;11(1):117-131. Epub 2021 Jan 1.

Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Tertiary lymphoid organs (TLOs) occur after multiple chronic kidney injuries. interleukin-17A (IL-17A) has been reported to associate with the development of TLOs in inflammatory diseases. However, regulation of the renal TLOs and its clinical significance to the pathogenesis of chronic kidney injury are unknown. To evaluate the clinical significance and regulation of renal TLOs, we analyzed the progression of patients with kidney damage based on the existence and absence of TLOs in a larger multicenter cohort. We also blocked the recruitment of lymphocyte cells into the kidney by FTY720 (fingolimod) . Besides, we used aged IL-17A genetic knocked out mice and IL-17A-neutralizing antibody to explore the role of IL-17A in renal TLOs formation. : We demonstrated that renal TLOs of IgA nephropathy patients were associated with disease severity and were independent risk factors for renal progression after adjustment for age, sex, mean arterial pressure, proteinuria and, baseline eGFR and MEST-C score, especially in the early stage. Plasma levels of TLO-related chemokines CXCL13, CCL19, and CCL21 were higher in patients with renal TLOs. Inhibiting the formation of renal TLOs by FTY720 could reduce the intrarenal inflammation and fibrosis, and early intervention was found to be more effective. IL-17A was increased in renal TLOs models, and genetic depletion of IL-17A or treatment with anti-IL-17A antibody resulted in a marked reduction of the TLOs formation as well as alleviation of renal inflammation and fibrosis. These results indicate that TLOs are associated with the progression of kidney damage and regulated by IL-17A and may be effective targets for the treatment of kidney damage.
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http://dx.doi.org/10.7150/thno.48624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681089PMC
January 2021

Reactive electrically conducting membranes for phosphorus recovery from livestock wastewater effluents.

J Environ Manage 2021 Mar 30;282:111432. Epub 2020 Dec 30.

Department of Civil and Environmental Engineering, Temple University, USA. Electronic address:

We present a novel 'proof-of-concept' electrochemically based membrane filtration process for the recovery of nitrogen and phosphorus from livestock wastewater following an anaerobic digestion step. Reactive electrically conducting membranes are shown to precipitate and separate struvite, an eco-friendly fertilizer from synthetic livestock wastewater, resulting in the production of a solid fertilizer and a high-quality water stream, fit for irrigation. The recovery process is based on electrochemical hydrolysis and control of local pH in proximity to the surface of the membrane, and therefore, does not require chemical additives for pH adjustment. The system was assessed at varying concentrations of nitrogen and phosphorus corresponding to diluted and concentrated livestock wastewater (up to 1000 mg/L of N and P). Experimental results show up to 65% removal of phosphorus and nitrogen in the first 30 min of electrochemical filtration, and the precipitates were analytically confirmed to be struvite. In addition, the recovery process was shown efficient as it resulted in limited membrane fouling and flux reduction. Fouling and precipitation results were explained by a mathematical model describing the concentration of N, P, Mg ions in the presence of an external electric field. Accordingly, precipitation takes place in proximity to the membrane's surface but not directly on it, thus, limiting surface fouling. The electrochemical filtration system does not require chemical additives for pH adjustment, and the cost associated with electrochemical membrane-based struvite recovery was calculated to be $158 per ton of dry struvite, which is about 1.4 times lower in comparison to conventional recovery approaches. Overall, the electrochemical filtration system may be a promising alternative for nutrient recovery from livestock wastewater in terms of operational costs, recovery efficiency, and fouling mitigation.
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http://dx.doi.org/10.1016/j.jenvman.2020.111432DOI Listing
March 2021

Characterization of ovarian morphology and reproductive hormones in Zhedong white geese (Anser cygnoides domesticus) during the reproductive cycle.

J Anim Physiol Anim Nutr (Berl) 2020 Dec 30. Epub 2020 Dec 30.

College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

Zhedong white goose (Anser cygnoides domesticus) is a native Chinese breed with strong broodiness and low egg production, which is related to the physiology of reproduction. However, thus far, the physiology of goose reproduction has not been well elucidated. In the present study, the ovarian morphology and reproductive hormones of Zhedong white geese were investigated during the reproductive cycle (the laying and brooding periods). The results showed that the surface of the ovary was atrophied and follicular atresia appeared to some extent in the brooding period compared with the laying period. The concentrations of follicle-stimulating hormone, progesterone and luteinizing hormone were significantly higher than those in the brooding period (p < 0.05). In contrast, the concentrations of prolactin (PRL) and anti-Müllerian hormone (AMH) in the laying period were significantly lower than those in the brooding period (p < 0.05). In addition, the mRNA expression levels of PRL, AMH, dopamine-β-hydroxylase (DβH) and cytochrome P450 side-chain cleavage enzyme (P450scc) were detected in the hypothalamus, pituitary and ovaries by using real-time polymerase chain reaction. The results showed that AMH mRNA was expressed specifically in ovary tissue. The expression levels of DβH and PRL in the brooding period was significantly higher than those in the laying period in the three tissues, especially in the early and middle stages of the brooding period. Moreover, AMH mRNA expression in the ovaries presented the same trend. In addition, P450scc mRNA was highly expressed in both the ovary and pituitary in the laying period. These results revealed the remarkable features of ovarian morphology and characterized the hormonal pattern and expression profile during the reproductive cycle, all of which contribute to understanding the differences in reproductive physiology between the laying and brooding periods in Zhedong white geese.
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http://dx.doi.org/10.1111/jpn.13494DOI Listing
December 2020

Sequential CD19 and BCMA-specific CAR T-cell treatment elicits sustained remission of relapsed and/or refractory myeloma.

Cancer Med 2021 Jan 23;10(2):563-574. Epub 2020 Dec 23.

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Suzhou, China.

The low rate of durable response against relapsed and/or refractory multiple myeloma (RRMM) in recent studies indicates that chimeric antigen receptor T-cell (CART) treatment is yet to be optimized. This study aims to investigate the safety and efficacy of sequential infusion of CD19-CART and B-cell maturation antigen (BCMA)-CARTs for RRMM with a similar 3 + 3 dose escalation combined with a toxicity sentinel design. We enrolled 10 patients, among whom 7 received autologous infusion and 3 received allogeneic infusion. The median follow-up time was 20 months. The most common grade 3/4 treatment-emergent toxicities were hematological toxicities. Cytokine-release syndrome (CRS) adverse reactions were grade 1/2 in 9 out of 10 subjects. No dose-limited toxicity (DLT) was observed for BCMA-CAR-positive T cells ≤5 × 10 /kg), while two patients with dose-levels of 5-6.5 × 10 /kg experienced DLTs. The overall response rate was 90% (five partial responses and four stringent complete responses). Three out of four patients with stringent complete responses to autologous CART had progression-free survival for over 2 years. The three patients with allogeneic CART experienced disease progression within 2 months. These results evidence the sequential infusion's preliminarily tolerability and efficacy in RRMM, and present a simple and safe design applicable for the establishment of multiple CART therapy.
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http://dx.doi.org/10.1002/cam4.3624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877347PMC
January 2021

Severe glomerular C3 deposition indicates severe renal lesions and a poor prognosis in patients with immunoglobulin A nephropathy.

Histopathology 2020 Dec 17. Epub 2020 Dec 17.

Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Aims: Glomerular complement 3 (C3) deposition is often observed in renal biopsies of patients with IgA nephropathy (IgAN); however, the relationship between the intensity of C3 deposition and the long-term prognosis of IgAN has rarely been reported. In this retrospective study, we aimed to evaluate the prognostic value of glomerular C3 deposition for IgAN progression.

Methods And Results: From June 2009 to June 2010, a total of 136 adult patients with IgAN were enrolled in the study. According to the intensity of glomerular C3 deposition, patients were divided into a glomerular C3 group (34 patients) and a glomerular C3 group (102 patients). The levels of clinical parameters, glomerular immune complexes, histopathological features, and serum cytokines of the two groups were compared. On the basis of an average of 105 months of follow-up, the predictive value of glomerular C3 deposition for IgAN progression was also investigated. Patients in the C3 group had more severe glomerular IgA, IgG, IgM, and complement factor H deposition, a higher percentage of mesangial hypercellularity (M1), and higher levels of segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T2), and crescents (C2) than those in the C3 group. Renal biopsies in the C3 group showed higher densities of interstitial inflammatory cells and higher levels of serum interferon-γ than those in the C3 group. Multivariate Cox regression analysis revealed that a higher intensity of glomerular C3 deposition remained as an independent predictor of serum creatinine doubling and end-stage renal disease.

Conclusions: A high intensity of glomerular C3 deposition is associated with the severity of renal lesions, and predicts long-term poor renal survival for IgAN patients.
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http://dx.doi.org/10.1111/his.14318DOI Listing
December 2020

Gut microbiota composition and metabolomic profiles of wild and captive Chinese monals (Lophophorus lhuysii).

Front Zool 2020 Dec 3;17(1):36. Epub 2020 Dec 3.

Chengdu Research Base of Giant Panda Breeding, Chengdu, 610081, China.

Background: The Chinese monal (Lophophorus lhuysii) is an endangered bird species, with a wild population restricted to the mountains in southwest China, and only one known captive population in the world. We investigated the fecal microbiota and metabolome of wild and captive Chinese monals to explore differences and similarities in nutritional status and digestive characteristics. An integrated approach combining 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high performance liquid chromatography (UHPLC) based metabolomics were used to examine the fecal microbiota composition and the metabolomic profile of Chinese monals.

Results: The results showed that the alpha diversity of gut microbes in the wild group were significantly higher than that in the captive group and the core bacterial taxa in the two groups showed remarkable differences at phylum, class, order, and family levels. Metabolomic profiling also revealed differences, mainly related to galactose, starch and sucrose metabolism, fatty acid, bile acid biosynthesis and bile secretion. Furthermore, strong correlations between metabolite types and bacterial genus were detected.

Conclusions: There were remarkable differences in the gut microbiota composition and metabolomic profile between wild and captive Chinese monals. This study has established a baseline for a normal gut microbiota and metabolomic profile for wild Chinese monals, thus allowing us to evaluate if differences seen in captive organisms have an impact on their overall health and reproduction.
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http://dx.doi.org/10.1186/s12983-020-00381-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713318PMC
December 2020

Early versus late acute kidney injury among patients with COVID-19-a multicenter study from Wuhan, China.

Nephrol Dial Transplant 2020 12;35(12):2095-2102

Department of Medicine, Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.

Background: Acute kidney injury (AKI) is an important complication of coronavirus disease 2019 (COVID-19), which could be caused by both systematic responses from multi-organ dysfunction and direct virus infection. While advanced evidence is needed regarding its clinical features and mechanisms. We aimed to describe two phenotypes of AKI as well as their risk factors and the association with mortality.

Methods: Consecutive hospitalized patients with COVID-19 in tertiary hospitals in Wuhan, China from 1 January 2020 to 23 March 2020 were included. Patients with AKI were classified as AKI-early and AKI-late according to the sequence of organ dysfunction (kidney as the first dysfunctional organ or not). Demographic and clinical features were compared between two AKI groups. Their risk factors and the associations with in-hospital mortality were analyzed.

Results: A total of 4020 cases with laboratory-confirmed COVID-19 were included and 285 (7.09%) of them were identified as AKI. Compared with patients with AKI-early, patients with AKI-late had significantly higher levels of systemic inflammatory markers. Both AKIs were associated with an increased risk of in-hospital mortality, with similar fully adjusted hazard ratios of 2.46 [95% confidence interval (CI) 1.35-4.49] for AKI-early and 3.09 (95% CI 2.17-4.40) for AKI-late. Only hypertension was independently associated with the risk of AKI-early. While age, history of chronic kidney disease and the levels of inflammatory biomarkers were associated with the risk of AKI-late.

Conclusions: AKI among patients with COVID-19 has two clinical phenotypes, which could be due to different mechanisms. Considering the increased risk for mortality for both phenotypes, monitoring for AKI should be emphasized during COVID-19.
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http://dx.doi.org/10.1093/ndt/gfaa288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798799PMC
December 2020

Exogenous bone marrow derived-putative endothelial progenitor cells attenuate ischemia reperfusion-induced vascular injury and renal fibrosis in mice dependent on pericytes.

Theranostics 2020 25;10(26):12144-12157. Epub 2020 Oct 25.

Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei, 430030, China.

Capillaries are composed of endothelial cells and the surrounding mural cells, pericytes. Microvascular repair after injury involves not only the proliferation of endothelial cells but also pericyte-based vessel stabilization. Exogenous bone marrow derived-putative endothelial progenitor cells (b-pEPCs) have the potential for vascular repair; however, their effect on vascular structure stabilization and pericyte-related pathobiological outcomes in the injured kidney has not been fully examined. We applied ischemia-reperfusion (IR) to induce renal vascular injury and renal fibrosis in mice. Platelet-derived growth factor receptor β (PDGFR-β)-DTR-positive mice were generated to deplete pericytes, and exogenous b-pEPCs and the PDGFR-β ligand, PDGF chain B (PDGF-BB), were employed to explore the relationship among b-pEPCs, pericytes, vascular repair, and early renal fibrosis. Administration of b-pEPCs reduced IR-induced pericyte-endothelial detachment, pericyte proliferation, and myofibroblast transition via a paracrine mode, which preserved not only vascular stabilization but also ameliorated IR-initiated renal fibrosis. PDGF-BB upregulated the expression of PDGFR-β, exacerbated vascular abnormality, and pericyte-myofibroblast transition, which were ameliorated by b-pEPCs administration. The exogenous b-pEPCs and their culture medium (CM) induced vascular injury protection, and renal fibrosis was blocked by selective deletion of pericytes. Exogenous b-pEPCs directly protect against IR-induced vascular injury and prevent renal fibrosis by inhibiting the activation of PDGFR-β-positive pericytes.
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http://dx.doi.org/10.7150/thno.48562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667688PMC
October 2020

T cell receptor repertoire as a potential diagnostic marker for celiac disease.

Clin Immunol 2021 Jan 13;222:108621. Epub 2020 Nov 13.

Department of Immunology, Institute of Clinical Medicine, University of Oslo, Norway; K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Norway. Electronic address:

An individual's T cell repertoire is skewed towards some specificities as a result of past antigen exposure and subsequent clonal expansion. Identifying T cell receptor signatures associated with a disease is challenging due to the overall complexity of antigens and polymorphic HLA allotypes. In celiac disease, the antigen epitopes are well characterised and the specific HLA-DQ2-restricted T-cell repertoire associated with the disease has been explored in depth. By investigating T cell receptor repertoires of unsorted lamina propria T cells from 15 individuals, we provide the first proof-of-concept study showing that it could be possible to infer disease state by matching against a priori known disease-associated T cell receptor sequences.
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http://dx.doi.org/10.1016/j.clim.2020.108621DOI Listing
January 2021

MicroRNA‑138 modulates glioma cell growth, apoptosis and invasion through the suppression of the AKT/mTOR signalling pathway by targeting CREB1.

Oncol Rep 2020 Dec 15;44(6):2559-2568. Epub 2020 Oct 15.

Department of Neurosurgery, Changzheng Hospital, Navy Medical University, Shanghai 200003, P.R. China.

Alterations in the expression of microRNA (miR)‑138 have been demonstrated to result in the development of several malignant tumours. However, the possible function of miR‑138 in human glioma cells remains unclear. The present study demonstrated that miR‑138 was significantly downregulated in 48 human glioma specimens by quantitative PCR analysis. The upregulation of miR‑138 exerted significant antiproliferative and anti‑invasive effects on glioma cells and promoted their apoptosis. In addition, cAMP response element‑binding protein 1 (CREB1) was confirmed as a direct target gene of miR‑138 by luciferase gene reporter assay, and the antitumour effect of miR‑138 on glioma cells was significantly reversed by CREB1 overexpression. Moreover, the molecular mechanisms underlying the tumour‑suppressive role of miR‑138 in malignant glioma may be associated with the dephosphorylation of AKT/mTOR caused by the miR‑138 upregulation‑induced decrease in CREB1 expression in glioma cells. The results of the present study indicated that miR‑138 may affect CREB1/AKT/mTOR signalling to regulate the proliferation, apoptosis and invasion of glioma cells and the malignant progression of glioma, thereby suggesting that miR‑138 may be a potential target for the treatment of gliomas.
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http://dx.doi.org/10.3892/or.2020.7809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640360PMC
December 2020

Sexually Inactive Status in Women With Pelvic Organ Prolapse Before Colpocleisis and Postoperative Satisfaction and Regret Rate.

Female Pelvic Med Reconstr Surg 2020 Oct 26. Epub 2020 Oct 26.

From the Peking University Third Hospital, Beijing.

Purpose: The aim of the study was to investigate the sexually inactive status of patients with pelvic organ prolapse before colpocleisis and postoperative satisfaction and regret rate.

Methods: A retrospective study of patients with pelvic organ prolapse who underwent colpocleisis was conducted in our hospital from January 2007 to April 2019. Records were reviewed before surgery for general clinical characteristics, duration, and reasons for being sexually inactive. Follow-up was conducted by telephone about patient satisfaction, Patient Global Impression of Improvement score, and regret rate after surgery.

Results: The mean age of the 247 patients was 73.8 ± 5.58 years. A total of 76.9% (190/247) described the duration of being sexually inactive, and the mean time was 12.6 ± 8.69 years. The 247 patients gave the following reasons for being sexually inactive: 52.2% (129/247) were widowed and 37.2% (92/247) reported the physical health factors of their spouses or sexual partners. The first male factor was nervous system disease (37.0%, 34/92). A total of 5.3% (13/247) were patient-related factors and 5.3% (13/247) were factors of both the male and female. A total of 195 patients underwent follow-up, the rate was 78.9% (195/247), and the follow-up time was 39.7 ± 37.5 (2-140) months. A total of 98.5% (192/195) of patients were very satisfied. A total of 98.9% (193/195) of patients were very much improved or improved in Patient Global Impression of Improvement score. A total of 1.02% (2/195) of patients regretted having colpocleisis nearly 2 years later.

Conclusions: The main reason for being sexually inactive was having been widowed. Colpocleisis was associated with high satisfaction rates and low regret rate.
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http://dx.doi.org/10.1097/SPV.0000000000000974DOI Listing
October 2020

Pre-ischemic renal lavage protects against renal ischemia-reperfusion injury by attenuation of local and systemic inflammatory responses.

FASEB J 2020 Dec 21;34(12):16307-16318. Epub 2020 Oct 21.

Department of Nephrology, Hannover Medical School, Hannover, Germany.

Postischemic acute kidney injury (AKI) is a common clinical complication and often fatal, with no effective treatment available. Little is known about the role of leukocytes trapped in renal vessels during ischemia-reperfusion injury (IRI) in the postischemic AKI. We designed a new animal model in rats with preforming renal artery lavage prior to IRI to investigate the effect of diminishing the residual circulating leukocytes on kidney damage and inflammation. Moreover, the functional changes of macrophages in hypoxia reoxygenation condition were also analyzed. We found pre-ischemic renal lavage significantly decreased the serum creatinine and blood urea nitrogen levels, and downregulated the mRNA and protein expressions in kidneys and urinary secretion of kidney injury molecule-1 of rats after IRI. The renal pathological damage caused by IRI was also ameliorated by pre-ischemic renal lavage, as evidenced by fewer cast formation, diminished morphological signs of AKI in the tissue at 24 hours after IRI. Pre-ischemic renal lavage reduced the numbers of infiltrating CD68 macrophages and MPO neutrophils. The mRNA expression of pro-inflammatory mediator in IRI kidneys and the levels of pro-inflammatory cytokines in circulatory system and urine were also reduced due to pre-ischemic lavage. Compared with nontreated rats with IRI, pre-ischemic renal lavage significantly reduced the phosphorylation levels of ERK and p65 subunit of NF-κB in the kidney after IRI. In addition, we found hypoxia/reoxygenation could promote the expression of pro-inflammatory mediators and inhibit the expression of anti-inflammatory factors by regulating ERK/NF-κB signaling pathway. Thus, pre-ischemic renal lavage could clearly reduce the renal damage after IRI by attenuating inflammation, and macrophages trapped in renal vessels during IRI could be important pathogenic factors driving tissue injury.
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http://dx.doi.org/10.1096/fj.201902943RDOI Listing
December 2020

Long noncoding RNA LINC01189 is associated with HCV-hepatocellular carcinoma and regulates cancer cell proliferation and chemoresistance through hsa-miR-155-5p.

Ann Hepatol 2020 Oct 12;22:100269. Epub 2020 Oct 12.

Anaesthesiology department, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China. Electronic address:

Introduction And Objectives: Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) may be closely associated with Hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC). In this study, we investigated the expression and functions of a lncRNA, LINC01189, in HCV-associated HCC.

Patients Or Materials And Methods: LINC01189 expression was measured in HCC tumors, HCV-infected HCC tumors and HCV-infected HCC cells. LINC01189 was overexpressed in HCV-infected HepG2 cells to measure its function on HCV-correlated cancer proliferation. In HCC cell lines of Huh7 and Hep3B, LINC01189 was upregulated to investigate its effects on cancer cell proliferation and 5-FU chemoresistance. The competing endogenous RNA (ceRNA) target of LINC01189, human microRNA-155-5p (hsa-miR-155-5p) was probed by dual-luciferase assay and qRT-PCR. Hsa-miR-155-5p was upregulated in LINC01189-overexpessed Huh7 and Hep3B cells to investigate their epigenetic correlation on HCC development regulation.

Results: LINC01189 is downregulated in HCV-infected HCC tumors and cell lines. LINC01189 overexpression inhibited HCC cancer cell proliferation and 5-FU chemoresistance. Hsa-miR-155-5p was confirmed to be a ceRNA target of LINC01189 in HCC. Upregulating hsa-miR-155-5p reversed the LINC01189-mediated inhibition on HCC proliferation and 5-FU chemoresistance.

Conclusions: LINC01189 downregulation is associated with HCV infection in HCC, and it has tumor-suppressing effects on HCC development through hsa-miR-155-5p.
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http://dx.doi.org/10.1016/j.aohep.2020.09.013DOI Listing
October 2020

[Relationship between sleep architecture and severity of obstructive sleep apnea].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2020 Aug;49(4):455-461

Electroencephalogram Unit, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.

Objective: To investigate the effect of obstructive sleep apnea (OSA) on different sleep stages, and the relationship between N3 stage of non-rapid eye movement sleep and respiratory abnormal events.

Methods: A total of 188 adult patients who underwent overnight polysomnography(PSG)monitoring in Sir Run Run shaw Hospital of Zhejiang University from June 24th to December 26th 2019 were enrolled in the study. OSA patients were classified into 3 groups (mild, moderate and severe) according to the apnea-hypopnea index (AHI). PSG data, AHI and the lowest SPO in each stage of sleep were compared among three groups.

Results: There was no significant difference in total sleep time and sleep efficiency among patients with different severity of OSA (all >0.05). The proportion of N3 stage in moderate and severe OSA groups were significantly smaller than that in mild OSA group (all <0.05). The proportion of N3 stage in severe OSA group was also smaller than that in moderate OSA group (<0.05). In addition, severe OSA group had a longer latency of N3 stage than mild and moderate OSA groups (all <0.05). The latency of N3 stage in moderate OSA group was longer than that in mild OSA group (<0.05). The AHI in N3 stage was markedly lower than that in other sleep stages (all <0.01), regardless of the severity of OSA. Supine AHI in N3 stage in mild and moderate groups was significantly lower than that in N1, N2 and rapid eye movement (REM) stages (all <0.01). Supine AHI in N3 stage in severe group was also lower than that in N2 and REM stages (<0.05 or <0.01). The lowest SPO in N3 stage was significantly higher than that in N1, N2 and REM stages (<0.05 or <0.01), regardless of the severity of OSA.

Conclusions: s The proportion of N3 stage is lower in OSA patients, and N3 stage has less sleep respiratory events than non-N3 stages. The results suggest that the increased N3 stage proportion may indicate less severity of OSA.
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http://dx.doi.org/10.3785/j.issn.1008-9292.2020.08.02DOI Listing
August 2020

The Incidence, Risk Factors, and Prognosis of Acute Kidney Injury in Adult Patients with Coronavirus Disease 2019.

Clin J Am Soc Nephrol 2020 10 22;15(10):1394-1402. Epub 2020 Sep 22.

Department of Nephrology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Background And Objectives: Since December 2019, coronavirus disease 2019 (COVID-19) outbreak occurred and has rapidly spread worldwide. However, little information is available about the AKI in COVID-19. We aimed to evaluate the incidence, risk factors, and prognosis of AKI in adult patients with COVID-19.

Design, Setting, Participants, & Measurements: This was a retrospective cohort study of 1392 patients with COVID-19 admitted to a tertiary teaching hospital. Clinical characteristics and laboratory data were extracted from electronic hospitalization and laboratory databases. AKI was defined and staged according to the 2012 Kidney Disease: Improving Global Outcomes criteria. Risk factors for AKI and the association of AKI with in-hospital mortality were assessed.

Results: A total of 7% (99 of 1392) of patients developed AKI during hospitalization, 40% (40 of 99) of which occurred within 1 week of admission. Factors associated with a higher risk of AKI include severe disease (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.37 to 3.67), higher baseline serum creatinine (OR, 2.19; 95% CI, 1.17 to 4.11), lymphopenia (OR, 1.99; 95% CI, 1.12 to 3.53), and elevated D-dimer level (OR, 2.68; 95% CI, 1.07 to 6.70). The in-hospital mortality in patients with AKI stage 1, stage 2, and stage 3 was 62%, 77%, and 80%, respectively. AKI was associated with in-hospital mortality even after adjustment for confounders (OR, 5.12; 95% CI, 2.70 to 9.72).

Conclusions: AKI is uncommon but carries high in-hospital mortality in patients with COVID-19.
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http://dx.doi.org/10.2215/CJN.04650420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536762PMC
October 2020

The influence of socioeconomic status on menarcheal age among Chinese school-age girls in Tianjin, China.

Eur J Pediatr 2021 Mar 12;180(3):825-832. Epub 2020 Sep 12.

Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.

The association between socioeconomic status and the onset age of menarche is still not conclusive. This cross-sectional study was conducted among primary and middle school girls aged 7 to 16 years old in Tianjin, China, to explore the distribution of menarcheal age and its association with socioeconomic status. A self-designed structured questionnaire was completed by students and their parents to collect information on socioeconomic status (i.e., family income, parental education level, living residence), menarcheal status, and covariates (weight status of girls and their parents, sleeping hours per day, physical activity). Information on menarcheal status included whether or not menarche had occurred (Yes/No) and the exact age at menarche. Linear regression analysis was used to explore the association between socioeconomic status and menarcheal age before and after covariate adjustment. Among 1485 eligible girls with complete information, 445 had experienced menarche, with an overall menarche rate of 30%. The mean age at menarche was 12.9 years (95% confidence interval 12.8-13.0). Urban girls experienced menarche earlier than rural girls did (12.1 years vs. 13.5 years). Univariate analysis showed that urban residence and higher parental education were associated with earlier onset of menarche. After covariate adjustment, the significance still existed. However, after adjusting further for residence, the significant association with the parental education disappeared. Only urban residence was still significantly associated, even after further adjustment for parental education and family income, with adjusted regression coefficients (95% confidence interval) of - 1.087 (- 1.340,-0.834), indicating that the onset age of menarche among urban girls was 1.087 years (0.834, 1.340) younger than that among rural girls. Family income was not related to the onset age of menarche in any analyses.Conclusion: Urban-rural differences played a more important role in the early onset of menarche than socioeconomic differences between families. What is Known: • The age at menarche varies by race and country, but the global trend is towards earlier onset as a result of changes in nutrition, family structure, socioeconomic status, and physical condition. What is New: • Urban girls experienced menarche earlier than rural girls, but this urban-rural difference could not be explained by family income, parental education, weight status of the participants and their parents, participants' physical exercise and sleeping hours. • Higher parental education was associated with earlier onset of menarche, but this association disappeared after adjustment for living residence.
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http://dx.doi.org/10.1007/s00431-020-03803-4DOI Listing
March 2021

Aggressive Quarantine Measures Reduce the High Morbidity of COVID-19 in Patients on Maintenance Hemodialysis and Medical Staff of Hemodialysis Facilities in Wuhan, China.

Kidney Dis (Basel) 2020 Jul 25;6(4):271-283. Epub 2020 May 25.

Department of Nephrology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Introduction: Maintenance hemodialysis (MHD) patients are highly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Medical staff of dialysis facilities without sufficient biosecurity protection are susceptible once exposed to asymptomatic coronavirus disease 2019 (COVID-19) patients. This study evaluated the epidemiological characteristics of COVID-19 in all MHD patients and medical staff of dialysis facilities in Wuhan, China.

Methods: We collected COVID-19 morbidity and mortality data from MHD patients and medical staff from 52 hemodialysis centers in Wuhan. Then, we analyzed the symptoms and signs of patients and staff in our hospital (Tongji Hospital in Wuhan), and chest CT, SARS-CoV-2 nucleic acid detection and laboratory tests were performed. After aggressive quarantine of the COVID-19 patients, we followed up on the prognosis of them.

Results: We analyzed the hemodialysis data from Wuhan and found that 10% of MHD patients and 6.0% of medical staff were suspected of COVID-19. Further detection of SARS-CoV-2 nucleic acid showed that 1.7% of MHD patients and 2.9% of medical staff were confirmed as having COVID-19. In our facility, 18.9% (46/244) of patients and 9.5% (6/63) of medical staff were suspected of COVID-19. Among them, 2.9% (7/244) of MHD patients and 4.8% (3/63) of medical staff tested positive for SARS-CoV-2 were confirmed as having COVID-19. Interestingly, 87.0% of MHD patients suspected of COVID-19 did not have obvious symptoms, but the CT screening showed features of viral pneumonia. There were no significant differences in symptoms, CT findings, comorbidity and laboratory findings of SARS-CoV-2 nucleic-acid-positive and -negative patients. We followed up these patients and found that 57 patients with COVID-19 died (COVID-19 mortality 8.9%). Two patients from our dialysis center with COVID-19 (mortality 4.3%) died. No new infections occurred in our dialysis center after aggressive quarantine was initiated.

Conclusions: The SARS-CoV-2 infection rates in MHD patients and medical staff in dialysis facilities were both high in Wuhan. Frequent chest CT and SARS-CoV-2 nucleic acid detection were needed to screen COVID-19 patients in dialysis facilities. Through the lessons of this experience on the aggressive diagnosis and quarantine measures of COVID-19 patients, we hope medical staff avoid more infections in serious epidemic areas.
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http://dx.doi.org/10.1159/000508579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316663PMC
July 2020

Microarray assay of circular RNAs reveals cicRNA.7079 as a new anti-apoptotic molecule in spinal cord injury in mice.

Brain Res Bull 2020 11 1;164:157-171. Epub 2020 Sep 1.

Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address:

Traumatic spinal cord injury (SCI) can lead to motor disturbance, sensory deficit, or autonomic dysfunction. The role of circRNAs in the pivotal physiopathological processes of SCI has been demonstrated recently. However, no similar research has been performed to explore the circRNAs involved in apoptosis after SCI. The differentially expressed circRNAs in mice spinal cord three days after SCI were originally detected with microarray assay (n = 4/group). Subsequently, potential apoptosis-related circRNAs were predicted by comprehensive bioinformatics analysis. In total, 1131 circRNAs varied (>2-fold change, p < 0.05) in the injured mice spinal cord. The characters of these circRNAs were summarized. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was applied to predict the primary function of these circRNAs. 148 circRNAs were found to be correlated to the apoptosis injury progress in after SCI. Moreover, an apoptosis-related ceRNA network was constructed. In loss-of-function experiments, cicRNA.7079 knockdown enhanced apoptosis in NSC-34 motor neurons. This study may contribute to new insights into the mechanism of apoptosis after SCI. The anticipation of anti-apoptosis circRNA. 7079 may provide potential research targets for SCI in mice.
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http://dx.doi.org/10.1016/j.brainresbull.2020.08.004DOI Listing
November 2020

XJB-5-131 inhibited ferroptosis in tubular epithelial cells after ischemia-reperfusion injury.

Cell Death Dis 2020 08 14;11(8):629. Epub 2020 Aug 14.

Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, 430030, Wuhan, Hubei, China.

Regulated necrosis has been reported to exert an important role in the pathogenesis of various diseases, including renal ischemia-reperfusion (I/R) injury. Damage to renal tubular epithelial cells and subsequent cell death initiate the progression of acute kidney injury (AKI) and subsequent chronic kidney disease (CKD). We found that ferroptosis appeared in tubular epithelial cells (TECs) of various human kidney diseases and the upregulation of tubular proferroptotic gene ACSL4 was correlated with renal function in patients with acute kidney tubular injury. XJB-5-131, which showed high affinity for TECs, attenuated I/R-induced renal injury and inflammation in mice by specifically inhibiting ferroptosis rather than necroptosis and pyroptosis. Single-cell RNA sequencing (scRNA-seq) indicated that ferroptosis-related genes were mainly expressed in tubular epithelial cells after I/R injury, while few necroptosis- and pyroptosis-associated genes were identified to express in this cluster of cell. Taken together, ferroptosis plays an important role in renal tubular injury and the inhibition of ferroptosis by XJB-5-131 is a promising therapeutic strategy for protection against renal tubular cell injury in kidney diseases.
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http://dx.doi.org/10.1038/s41419-020-02871-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429848PMC
August 2020

HMGB1 in kidney diseases.

Life Sci 2020 Oct 8;259:118203. Epub 2020 Aug 8.

Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei 430030, China. Electronic address:

High mobility group box 1 (HMGB1) is a highly conserved nucleoprotein involving in numerous biological processes, and well known to trigger immune responses as the damage-associated molecular pattern (DAMP) in the extracellular environment. The role of HMGB1 is distinct due to its multiple functions in different subcellular location. In the nucleus, HMGB1 acts as a chaperone to regulate DNA events including DNA replication, repair and nucleosome stability. While in the cytoplasm, it is engaged in regulating autophagy and apoptosis. A great deal of research has explored its function in the pathogenesis of renal diseases. This review mainly focuses on the role of HMGB1 and summarizes the pathway and treatment targeting HMGB1 in the various renal diseases which may open the windows of opportunities for the development of desirable therapeutic ends in these pathological conditions.
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http://dx.doi.org/10.1016/j.lfs.2020.118203DOI Listing
October 2020

"No Pain No Gain": Evidence from a Parcel-Wise Brain Morphometry Study on the Volitional Quality of Elite Athletes.

Brain Sci 2020 Jul 17;10(7). Epub 2020 Jul 17.

EuroMov Digital Health in Motion, Univ Montpellier, IMT Mines Ales, 34090 Montpellier, France.

Volition is described as a psychological construct with great emphasis on the sense of agency. During volitional behavior, an individual always presents a volitional quality, an intrapersonal trait for dealing with adverse circumstances, which determines the individual's persistence of action toward their intentions or goals. Elite athletes are a group of experts with superior volitional quality and, thereby, could be regarded as the natural subject pool to investigate this mental trait. The purpose of this study was to examine brain morphometric characteristics associated with volitional quality by using magnetic resonance imaging (MRI) and the Scale of Volitional Quality. We recruited 16 national-level athletes engaged in short track speed skating and 18 healthy controls matched with age and gender. A comparison of a parcel-wise brain anatomical characteristics of the healthy controls with those of the elite athletes revealed three regions with significantly increased cortical thickness in the athlete group. These regions included the left precuneus, the left inferior parietal lobe, and the right superior frontal lobe, which are the core brain regions involved in the sense of agency. The mean cortical thickness of the left inferior parietal lobe was significantly correlated with the independence of volitional quality (a mental trait that characterizes one's intendency to control his/her own behavior and make decisions by applying internal standards and/or objective criteria). These findings suggest that sports training is an ideal model for better understanding the neural mechanisms of volitional behavior in the human brain.
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http://dx.doi.org/10.3390/brainsci10070459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407584PMC
July 2020

Lopinavir/ritonavir is associated with pneumonia resolution in COVID-19 patients with influenza coinfection: A retrospective matched-pair cohort study.

J Med Virol 2021 01 15;93(1):472-480. Epub 2020 Jul 15.

Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

During the early stages of the pandemic, some coronavirus disease (COVID-19) patients were misdiagnosed as having influenza, which aroused the concern that some deaths attributed to influenza were actually COVID-19-related. However, little is known about whether coinfection with influenza contributes to severity of COVID-19 pneumonia, and the optimal therapeutic strategy for these patients. We retrospectively studied 128 hospitalized patients with COVID-19 pneumonia. All patients were positive severe acute respiratory syndrome coronavirus 2 positive by nucleic acid detection. Sixty-four cases were coinfected with influenza A/B and the other 64 were influenza negative, matched by age, sex, and days from onset of symptoms. Among the 64 coinfected patients, 54 (84.4%) were coinfected with influenza A, and 10 (15.6%) with influenza B. The median duration of viral shedding time from admission was longer for patients with influenza coinfection (17.0 days) than for those without influenza coinfection (12.0 days) (P < .001). The multivariable Cox proportional hazards model showed that the hazards ratio of resolution in lung involvement was 1.878 (P = .020) for patients administered lopinavir/ritonavir, compared with those not administered lopinavir/ritonavir (95% confidence interval: 1.103-3.196). Among influenza coinfected patients, those treated with lopinavir/ritonavir exhibited faster pneumonia resolution within 2 weeks after symptom onset (37% vs 1%; P = .001). There was no difference in lung involvement between influenza coinfected and noninfected groups. Lopinavir/ritonavir eliminated the difference of lung involvement between influenza coinfected and noninfected groups, indicating that lopinavir/ritonavir is associated with pneumonia resolution in COVID-19.
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http://dx.doi.org/10.1002/jmv.26260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361199PMC
January 2021

Long-term efficacy and patient satisfaction of Le Fort colpocleisis for the treatment of severe pelvic organ prolapse.

Int Urogynecol J 2021 Apr 29;32(4):879-884. Epub 2020 Jun 29.

Peking University Third Hospital, No. 49 North Garden Road, Beijing, 100191, Haidian district, China.

Introduction And Hypothesis: The objective was to investigate the long-term efficacy and patient satisfaction of Le Fort colpocleisis for the treatment of severe pelvic organ prolapse.

Methods: This was a retrospective study of patients who underwent Le Fort colpocleisis from January 2007 to August 2018 in our hospital. Follow-up was conducted via outpatient visits or the telephone. Records were reviewed for anatomical recurrence, complications, urinary and intestinal symptoms post-operation, reoperation rate, patient satisfaction, Patient Global Impression of Improvement (PGI-I) score, regret rate etc. RESULTS: A total of 208 patients underwent follow-up. The follow-up time was 60.7 ± 34.18 (12-140) months. There were no intraoperative complications. Postoperative urinary retention occurred in 3.8% of patients (8 out of 208). There was no anatomical recurrence. New or more severe urinary symptoms occurred in 8.7% of patients (18 out of 208); new or more severe intestinal symptoms occurred in 1.9% of patients (4 out of 208). The reoperation rate was 1.44% (3 out of 208). Three cases of reoperation occurred for the following reasons: a case of severe stress urinary incontinence, a case of abscess in the vaginal septum, and a case of uterine malignancy after 2 years of colpocleisis. Patient satisfaction was as follows: 98.6% (205 out of 208) of patients were very satisfied. The PGI-I score was very much improved or improved in 99.5% (207 out of 208) of patients. A total of 0.96% (2 out of 208) of patients regretted undergoing colpocleisis.

Conclusions: The long-term follow-up results showed that Le Fort colpocleisis was a safe and effective surgical procedure associated with high satisfaction. There was a very low regret rate, but the procedure should be taken seriously.
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http://dx.doi.org/10.1007/s00192-020-04380-8DOI Listing
April 2021

Fixation of distal radius fracture with volar locking palmar plates while preserving pronator quadratus through the minimally invasive approach.

Technol Health Care 2021 ;29(1):167-174

Department of Orthopedics, Tongji Hospital, Tongji University, Shanghai, China.

Background: The volar locking plate technique with an L-shaped incision of the PQ muscle through the classic volar Henry approach is a popular method for treating distal radius fractures. Recently we revised and improved this traditional technique by performing mini-invasive surgery.

Objective: The purpose of this study was to evaluate the clinical effects after fixation of distal radius fracture with volar locking palmar plates while preserving the pronator quadratus through minimally invasive approach.

Methods: From May 2014 to March 2017, 58 patients (38 males and 21 females) with an age range of 22-72 years (mean age 44.6 years) and with distal radius fractures underwent open reduction and internal fixation with volar locking palmar plates. The patients were classified as 23A-2 through 23C-2 according to the Orthopedic Trauma Association fracture classification system. All surgeries were completed by one trained team. The group that received volar locking palmar plates of distal radius performed with the traditional method through Henry approach involved 33 patients (21 males and 12 females) and the group that received PQ through minimally invasive approach group involved 25 patients (16 males and 9 females). We compared the two groups for wrist pain, forearm range of motion, grip strength, preoperative complications and wrist functional recovery score.

Results: The minimum follow-up for the whole cohort was one year. The differences between the two groups were significant in terms of wrist pain, forearm range of motion, grip strength and wrist function at 1, 2, 6 weeks postoperatively, but insignificant at 3 and 12 months postoperatively. In the minimally invasive group a case of limited extension of the forefinger 3 months postoperatively was found. No significant differences were found for preoperative complications and radiographs postoperatively.

Conclusion: Fixation with volar locking palmar plates through minimally invasive approach is a satisfactory and optional method in the treatment of distal radius fractures. This technique yields better early wrist function, shortens rehabilitation time and gets high psychological satisfaction.
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http://dx.doi.org/10.3233/THC-192113DOI Listing
January 2021

High expression of ESRP1 regulated by circ-0005585 promotes cell colonization in ovarian cancer.

Cancer Cell Int 2020 19;20:174. Epub 2020 May 19.

1Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital Of Xiangya School of Medicine, Central South University, Yuelu District, 283 Tongzipo Road, Changsha, Hunan 410013 People's Republic of China.

Background: Ovarian cancer is the third most common gynecological cancer in the world but the leading cause of death among gynecological malignancies. Epithelial splicing regulatory protein-1 (ESRP1), a key negative splicing regulator in epithelial-mesenchymal transition (EMT), has been proven to be overexpressed and may plays a role in epithelial ovarian cancer (EOC) progression. However, the functional roles of ESRP1 and the underlying mechanisms in this process still remain unclear.

Methods: Tumor invasion, migration, colony formation and animal experiments were used to study the malignant biological behavior of ESRP1. A vector-based system expressing circ-0005585 was established to investigate circRNA as a microRNAs sponge. RNA-Seq and cytoskeleton staining explored underlying mechanisms of ESRP1.

Results: Our results demonstrated that circ-0005585 regulates ESRP1 overexpression via sponging miR-23a/b and miR-15a/15b/16. Overexpression of ESRP1 suppresses EOC cell migration, but promotes colonization and drives a switch from mesenchymal to epithelial phenotype (MET) in association with actin cytoskeleton reorganization, mainly by alternative splicing EPB41L5 and RAC1. Furthermore, we have shown that high ESRP1 expression may be associated with immune-suppression in tumor immune microenvironment in vivo.

Conclusions: ESRP1 overexpression promotes MET status and correlates with actin cytoskeleton reorganization in EOC. ESRP1 plays an important role in EOC colonization. In addition, a miRs panel from two miR families can inhibit ESRP1, may provide an innovative approach for cancer theranostics.
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http://dx.doi.org/10.1186/s12935-020-01254-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236301PMC
May 2020

MicroRNA-381-3p Functions as a Dual Suppressor of Apoptosis and Necroptosis and Promotes Proliferation of Renal Cancer Cells.

Front Cell Dev Biol 2020 28;8:290. Epub 2020 Apr 28.

State Key Laboratory of Radiation Medicine and Protection, Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.

Renal cell carcinoma (RCC) is the most common type of kidney cancer. It has a poor prognosis, with approximately 20-30% of patients developing recurrent and/or metastatic diseases that is relatively high resistant to conventional therapy. Resisting cell death is a hallmark of cancer cells. Apoptosis is a form of programmed cell death mediated by the activation of caspases. Necroptosis is a form of regulated necrosis that relies on the activation of receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL), the substrate of RIPK3. Cancer cells often display apoptosis resistance via upregulation of anti-apoptotic genes and defective necroptosis due to the epigenetic silence of . MicroRNAs (miRNAs) are non-coding small RNAs that are involved in numerous biological processes including cell proliferation, differentiation and death. In this study, we screened a set of ∼120 miRNAs for apoptosis-regulating miRNAs and identified miR-381-3p as a suppressor of TNF-induced apoptosis in various cancer cells. Ectopic expression of miR-381-3p inhibits the activation of caspase-8 and caspase-3. The expression level of miR-381-3p inversely correlates with the sensitivity of cancer cells to TNF-induced apoptosis. Moreover, we found that overexpression of miR-381-3p blocks TNF-induced necroptosis by inhibiting the activation of RIPK3 and MLKL. Of note, Kaplan-Meier Plotter analysis demonstrates that papillary RCC patients with high miR-381-3p expression have a lower overall survival than those with low expression level of miR-381-3p. Importantly, miR-381-3p overexpression promotes colony formation in human renal cancer cells. Thus, miR-381-3p acts as an oncogenic miRNA that counteracts both apoptotic and necroptotic signaling pathways. Our findings highlight miR-381-3p as a biomarker for predicting sensitivity to apoptosis and necroptosis, and as a possible therapeutic target for RCC.
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http://dx.doi.org/10.3389/fcell.2020.00290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198711PMC
April 2020