Publications by authors named "Xin Wan"

145 Publications

[Retracted] PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells.

Mol Med Rep 2021 Sep 19;24(3). Epub 2021 Jul 19.

Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the western blotting data shown in Fig. 1B were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in 10: 399‑404, 2014; DOI: 10.3892/mmr.2014.2150].
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http://dx.doi.org/10.3892/mmr.2021.12299DOI Listing
September 2021

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18 years or older: A randomized, double-blind, placebo-controlled, phase 1/2 trial.

EClinicalMedicine 2021 Aug 7;38:101010. Epub 2021 Jul 7.

National Engineering Technology Research Centre for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd., Wuhan, Hubei, China.

Background: We aimed to assess the safety and immunogenicity of an inactivated vaccine against COVID-19 in Chinese adults aged ≥18 years.

Methods: This is an ongoing randomized, double-blind, placebo-controlled, phase 1/2 clinical trial among healthy adults aged ≥18 years in Henan Province, China. Participants ( = 336 in 18-59 age group and  = 336 in ≥60 age group) were enrolled between April 12 and May 17 2020, and were equally randomized to receive vaccine or placebo (aluminum hydroxide adjuvant) in a three-dose schedule of 2·5, 5, or 10 µg on days 0, 28, and 56. Another 448 adults aged 18-59 years were equally allocated to four groups (a one-dose schedule of 10 µg, and two-dose schedules of 5 µg on days 0 and 14/21/28) and received vaccine or placebo (ratio 3:1 within each group). The primary outcomes were 7-day post-injection adverse reactions and neutralizing antibody titres on days 28 and 90 after the whole-course vaccination. Trial registration: www.chictr.org.cn #ChiCTR2000031809.

Findings: The 7-day adverse reactions occurred in 4·8% to 32·1% of the participants in various groups, and most adverse reactions were mild, transient, and self-limiting. Twenty participants reported 68 serious adverse events which were judged to be unrelated to the vaccine. The 90-day post-injection geometric mean titres of neutralizing antibody ranged between 87 (95% CI: 61-125) and 129 (99-169) for three-dose schedule among younger and older adults; 20 (14-27), 53 (38-75), and 44 (32-61) in 5 µg days 0 and 14/21/28 groups, respectively, and 7 (6-9) in one-dose 10 µg group. There were no detectable antibody responses in all placebo groups.

Interpretation: The inactivated vaccine against COVID-19 was well tolerated and immunogenic in both younger and older adults. The two-dose schedule of 5 µg on days 0 and 21/28 and three-dose schedules on days 0, 28, and 56 could be further evaluated for long-term safety and efficacy in the phase 3 trials.
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http://dx.doi.org/10.1016/j.eclinm.2021.101010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260504PMC
August 2021

Indoleamine-2,3-Dioxygenase Activates Wnt/β-Catenin Inducing Kidney Fibrosis after Acute Kidney Injury.

Gerontology 2021 Jun 15:1-9. Epub 2021 Jun 15.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.

Introduction: As disorder of tryptophan metabolism is common in CKD, the rate-limiting enzyme of tryptophan, indoleamine-2,3-dioxygenase (IDO), has been reported to be involved in CKD, while the accurate mechanism remains unknown. This study was designed to explore correlations between IDO and kidney fibrosis after ischemia-reperfusion injury (IRI).

Methods: Wild-type (WT) mice and IDO knockout (IDO-/-) mice were divided into the sham group and acute kidney injury (AKI) group. Mice in the sham group underwent dorsal incision and exposure of renal pedicle without clamping renal artery, while mice in the AKI group received unique renal artery IRI, and the contralateral kidney was removed at day 13 after IRI. Blood and IRI kidneys were collected at day 14. Kidney function was analyzed by measuring serum Cr and BUN. Morphology was analyzed by tissue periodic acid-Schiff (PAS) staining and Masson staining. Further, fibrosis markers and Wnt/β-catenin pathway proteins were determined by Western blot. Prostaglandin E2 (PGE2) was administrated for 2 weeks after the IRI mice model was established to observe whether it ameliorates kidney fibrosis after IRI.

Results: WT AKI mice revealed elevated expression of IDO compared with WT sham mice. Kidney function of IDO-/- AKI mice showed better than that of WT AKI mice. PAS staining exhibited less loss of tubular epithelial cells and atrophy tubules in IDO-/- AKI mice. Furthermore, kidney fibrosis areas and the expressions of fibrosis markers, including α-SMA, fibronectin, and vimentin, were increased in WT AKI mice. In addition, GSK-3β and β-catenin were significantly declined in IDO-/- AKI mice. On top of that, PGE2 administration revealed inhibited IDO expression and that reducing GSK-3β and β-catenin resulting in lower expressions of α-SMA, fibronectin, and vimentin in WT AKI mice.

Conclusions: IRI could increase IDO expression to activate Wnt/β-catenin pathway resulting kidney fibrosis. PGE2 could ameliorate kidney fibrosis via inhibiting IDO expression.
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http://dx.doi.org/10.1159/000515041DOI Listing
June 2021

[Retracted] Methylation‑induced downregulation and tumor-suppressive role of microRNA‑98 in glioma through targeting Sal‑like protein 4.

Int J Mol Med 2021 Jul 20;48(1). Epub 2021 May 20.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell Transwell assay data in the article (featured in Figs. 4D and 6D) were strikingly similar to data appearing in different form in other articles by different authors at different research institutions, which were already under consideration for publication or had already been published elsewhere at the time of the present article's submission. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 41: 2651-2659, 2018; DOI: 10.3892/ijmm.2018.3464].
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http://dx.doi.org/10.3892/ijmm.2021.4962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136121PMC
July 2021

Impact of acute kidney injury on in-hospital outcomes in Chinese patients with community acquired pneumonia.

BMC Pulm Med 2021 May 1;21(1):143. Epub 2021 May 1.

Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, Jiangsu, China.

Background: Acute kidney injury (AKI) is a frequent complication of community acquired pneumonia (CAP). However, the impact of AKI on in-hospital outcomes of patients with CAP in the Chinese population remains unclear.

Methods: Patients diagnosed with CAP were evaluated in this retrospective observational study. Multiple Cox regression models were employed to identify the association between AKI and in-hospital mortality and 30-day mortality, respectively.

Results: A total of 4213 patients were recruited; 950 (22.5%) patients were diagnosed with AKI. Independent risk factors for AKI were age, male gender, hypertension, cardiac dysfunction, diabetes, chronic kidney disease, acute respiratory failure, use of diuretics, use of vasoactive drugs, and CURB-65. Cox proportional hazards regression revealed AKI, use of angiotensin receptor blocker, hypertension, CURB-65, acute respiratory failure, and use of vasoactive drugs to be independent risk factors for both in-hospital and 30-day mortality. Compared to patients without AKI, those suffering AKI were found to have 1.31-fold (HR 1.31, 95% CI, 1.04-1.66; P = 0.023) and 1.29-fold (HR 1.29, 95% CI, 1.02-1.62; P = 0.033) increased in-hospital and 30-day mortality risks, respectively. In addition, patients with AKI were likely to require admission to intensive care unit (ICU) (42.9% versus 11.4%; P < 0.001), mechanical ventilation (33.8% versus 9.3%; P < 0.001), invasive mechanical ventilation (25.9% versus 5.8%; P < 0.001), non-invasive mechanical ventilation (25.4% versus 7.1%; P < 0.001), and experienced a longer duration of hospital stay (14 days versus 10 days; P < 0.001) than those without AKI. However, no significant difference in ICU stay (11 days versus 10 days; P = 0.099) and duration of mechanical ventilation (8 days versus 8 days; P = 0.369) between AKI and non-AKI groups was found.

Conclusion: AKI was common in Chinese patients with CAP. Patients with CAP who developed AKI had worse in-hospital outcomes.
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http://dx.doi.org/10.1186/s12890-021-01511-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088559PMC
May 2021

Influence of HLA Class II Alleles and DRB1-DQB1 Haplotypes on Rheumatoid Arthritis Susceptibility and Autoantibody Status in the Chinese Han Population.

Immunol Invest 2021 Apr 30:1-13. Epub 2021 Apr 30.

Department of Prenatal Diagnosis Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Human leukocyte antigen (HLA) class II alleles are considered to play a key role in the progress of rheumatoid arthritis (RA). This study was carried out to investigate the presence of HLA class II alleles and their influence on disease risk and autoantibody status in Chinese Han patients with RA. Here, HLA-DRB1, DQB1 and DPB1 genotyping was performed in 125 RA patients and 120 healthy controls by using the next-generation sequencing (NGS). Strong positive associations were shown between high-resolution typed HLA-DRB1*04:05:01, DRB1*10:01:01, DQB1*04:01:01, DPB1*02:01:02 and RA patients. Moreover, the haplotypes HLA-DRB1*04:05:01~ DQB1*04:01:01 and HLA-DRB1*10:01:01~ DQB1*05:01:01 were found to be more frequent in RA populations than in healthy controls. These possible susceptible HLA alleles (HLA-DRB1*04:05:01, DRB1*10:01:01, DQB1*04:01:01 and DPB1*02:01:02) also showed higher frequencies in seropositive RA patients as compared to normal controls. The present study provided evidence that alleles HLA-DRB1*04:05:01, DRB1*10:01:01, DQB1*04:01:01 and DPB1*02:01:02 constituted RA risk alleles, and haplotypes HLA-DRB1*04:05:01~ DQB1*04:01:01, HLA-DRB1*10:01:01~ DQB1*05:01:01 also showed prevalence in Chinese Han patients with RA. Serological results preliminary demonstrated patients carrying RA-risk HLA alleles might elevate the serum level of anti-citrullinated protein antibodies and rheumatoid factor and affect RA progression.
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http://dx.doi.org/10.1080/08820139.2021.1918708DOI Listing
April 2021

Protective Efficacy of Inactivated Vaccine against SARS-CoV-2 Infection in Mice and Non-Human Primates.

Virol Sin 2021 Apr 9. Epub 2021 Apr 9.

Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans.
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http://dx.doi.org/10.1007/s12250-021-00376-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034048PMC
April 2021

Correlation of Indoleamine-2,3-Dioxygenase and Chronic Kidney Disease: A Pilot Study.

J Immunol Res 2021 6;2021:8132569. Epub 2021 Jan 6.

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

Objective: To explore the correlation of indoleamine-2,3-dioxygenase (IDO) and chronic kidney disease (CKD).

Methods: A total of 154 CKD patients and 42 non-CKD patients were recruited. Patients were grouped into ACR1~ACR3 (<30 mg/g, 30-300 mg/g, and >300 mg/g). Biomarkers in different groups were compared by ANOVA. Correlation was calculated by Pearson or Spearman analysis and binary logistic regression. The ROC curve was also performed.

Results: The levels of albumin, serum creatinine (sCr), and IDO in non-CKD patients were significantly different from those in CKD3-CKD5 stages ( < 0.05). IDO was correlated with age, proteinuria, ACR, and eGFR ( < 0.01). After adjusting for CKD-related indices, ln(IDO) was an independent risk factor for CKD (3.48, < 0.05). The analysis of ROC curve revealed a best cut-off for IDO was 0.0466 and yielded a sensitivity of 83.8% and a specificity of 75%. Hemoglobin, total protein, and albumin in the ACR1 group were significantly higher than those in the ACR2 and ACR3 groups ( < 0.01), while sCr and IDO levels were significantly lower than those in the ACR2 and ACR3 groups ( < 0.01 or < 0.05). After adjusting for CKD-related indices, ln(IDO) was still an independent risk factor for ACR (OR = 2.7, < 0.05). The analysis of ROC curve revealed a best cut-off for IDO was 0.075 and yielded a sensitivity of 71.9% and a specificity of 72.2%.

Conclusion: IDO may be a promising biomarker to predict CKD and assess kidney function.
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http://dx.doi.org/10.1155/2021/8132569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806403PMC
January 2021

Arsenic trioxide induces macrophage autophagy and atheroprotection by regulating ROS-dependent TFEB nuclear translocation and AKT/mTOR pathway.

Cell Death Dis 2021 01 18;12(1):88. Epub 2021 Jan 18.

Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Inducing autophagy and inhibiting apoptosis may provide a therapeutic treatment for atherosclerosis (AS). For the treatment of progressive AS, arsenic trioxide (ATO) has been used to coat vascular stents. However, the effect of ATO on autophagy of macrophages is still unknown. Therefore, the aims of this study were to characterize the effects and the mechanism of actions of ATO on autophagy in macrophages. Our results showed that ATO-induced activation of autophagy was an earlier event than ATO-induced inhibition of the expression of apoptosis markers in macrophages and foam cells. Nuclear transcription factor EB (TFEB) prevents atherosclerosis by activating macrophage autophagy and promoting lysosomal biogenesis. Here, we report that ATO triggered the nuclear translocation of TFEB, which in turn promoted autophagy and autophagosome-lysosome fusion. Both the latter events were prevented by TFEB knockdown. Moreover, ATO decreased the p-AKT and p-mTOR in the PI3K/AKT/mTOR signaling pathway, thus inducing autophagy. Correspondingly, treatment with the autophagy inhibitor 3-methyladenine (3-MA) abolished the autophagy-inducing effects of ATO. Meanwhile, PI3K inhibitor (LY294002) and mTOR inhibitor (rapamycin) cooperated with ATO to induce autophagy. Furthermore, reactive oxygen species (ROS) were generated in macrophages after treatment with ATO. The ROS scavenger N-acetyl-1-cysteine (NAC) abolished ATO-induced nuclear translocation of TFEB, as well as changes in key molecules of the AKT/mTOR signaling pathway and downstream autophagy. More importantly, ATO promoted autophagy in the aorta of ApoE mice and reduced atherosclerotic lesions in early AS, which were reversed by 3-MA treatment. In summary, our data indicated that ATO promoted ROS induction, which resulted in nuclear translocation of TFEB and inhibition of the PI3K/AKT/mTOR pathway. These actions ultimately promoted macrophage autophagy and reduced atherosclerotic lesions at early stages. These findings may provide a new perspective for the clinical treatment of early-stage atherosclerosis and should be further studied.
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http://dx.doi.org/10.1038/s41419-020-03357-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814005PMC
January 2021

Low toxicity and high immunogenicity of an inactivated vaccine candidate against COVID-19 in different animal models.

Emerg Microbes Infect 2020 Dec;9(1):2606-2618

National Institutes for Food and Drug Control, Beijing, People's Republic of China.

The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.
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http://dx.doi.org/10.1080/22221751.2020.1852059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733911PMC
December 2020

Biochemical and antigenic characterization of the structural proteins and their post-translational modifications in purified SARS-CoV-2 virions of an inactivated vaccine candidate.

Emerg Microbes Infect 2020 Dec;9(1):2653-2662

Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China.

In the face of COVID-19 pandemic caused by the newly emerged SARS-CoV-2, an inactivated, Vero cell-based, whole virion vaccine candidate has been developed and entered into phase III clinical trials within six months. Biochemical and immunogenic characterization of structural proteins and their post-translational modifications in virions, the end-products of the vaccine candidate, would be essential for the quality control and process development of vaccine products and for studying the immunogenicity and pathogenesis of SARS-CoV-2. By using a panel of rabbit antisera against virions and five structural proteins together with a convalescent serum, the spike (S) glycoprotein was shown to be N-linked glycosylated, PNGase F-sensitive, endoglycosidase H-resistant and cleaved by Furin-like proteases into S1 and S2 subunits. The full-length S and S1/S2 subunits could form homodimers/trimers. The membrane (M) protein was partially N-linked glycosylated; the accessory protein 3a existed in three different forms, indicative of cleavage and dimerization. Furthermore, analysis of the antigenicity of these proteins and their post-translationally modified forms demonstrated that S protein induced the strongest antibody response in both convalescent and immunized animal sera. Interestingly, immunization with the inactivated vaccine did not elicit antibody response against the S2 subunit, whereas strong antibody response against both S1 and S2 subunits was detected in the convalescent serum. Moreover, vaccination stimulated stronger antibody response against S multimers than did the natural infection. This study revealed that the native S glycoprotein stimulated neutralizing antibodies, while bacterially-expressed S fragments did not. The study on S modifications would facilitate design of S-based anti-SARS-CoV-2 vaccines.
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http://dx.doi.org/10.1080/22221751.2020.1855945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738289PMC
December 2020

The Relationship Between Interleukin-4 Levels and Cardiovascular Events in Patients with Chronic Kidney Disease.

Risk Manag Healthc Policy 2020 2;13:2371-2377. Epub 2020 Nov 2.

Department of Critical Care Medicine, Mindong Hospital of Fujian Medical University, Fuan, Fujian 355000, People's Republic of China.

Background: Cardiovascular diseases (CVDs) are the main cause of death in patients with chronic kidney disease (CKD). Interleukin-4 (IL-4) is considered an inflammatory cytokine. However, few studies have investigated the association between serum IL-4 and cardiovascular events in CKD. This study investigated whether serum IL-4 levels were associated with an increased risk of cardiovascular (CV) events in patients with CKD.

Patients And Methods: A total of 302 patients with stage 1-5 CKD were followed up for a mean of 32 (range=4-36) months for end points (CV events). Serum IL-4 levels were measured at baseline. The independent relationship between serum IL-4 and the risk of CV events was assessed with multivariate Cox regression analysis.

Results: The average age of this cohort (N=302) was 65.4 years. A total of 69.9% of them were male. CV events numbered 41 (13.6%) during the follow-up period. The Kaplan-Meier analysis showed that the rate of CV events was higher in patients with CKD with IL-4 levels above the mean (126.2 pg/mL) than in those with IL-4 levels below the mean. The multivariate Cox proportional hazard analysis revealed that serum IL-4 (HR=1.650, 95% CI 1.266-2.210, <0.001) was associated with CV events in these patients with CKD. Sensitivity analysis showed that the association between serum IL-4 and CV events was not affected by the use of anti-inflammatory medication. The significant association between higher IL-4 levels and increased risk of CV events existed in patients with CKD3-5 but not in patients with CKD1-2 by using the stratified analysis.

Conclusion: Higher serum IL-4 levels were associated with an increased risk of CV events during follow-up. Elevated serum IL-4 levels may help clinicians predict early CV events in patients with CKD.
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http://dx.doi.org/10.2147/RMHP.S270845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646470PMC
November 2020

Fluorescence characteristics of water-soluble organic carbon in atmospheric aerosol.

Environ Pollut 2021 Jan 20;268(Pt A):115906. Epub 2020 Oct 20.

Key Laboratory of Tibetan Environment Changes and Land Surface Processes, Institute of Tibetan Plateau Research, Chinese Academy of Sciences, Beijing, 100101, China; Center for Excellence in Tibetan Plateau Earth Sciences, Chinese Academy of Sciences, Beijing, 100101, China. Electronic address:

Fluorescence spectroscopy is a commonly used technique to analyze dissolved organic matter in aquatic environments. Given the high sensitivity and non-destructive analysis, fluorescence has recently been used to study water-soluble organic carbon (WSOC) in atmospheric aerosols, which have substantial abundance, various sources and play an important role in climate change. Yet, current research on WSOC characterization is rather sparse and limited to a few isolated sites, making it challenging to draw fundamental and mechanistic conclusions. Here we presented a review of the fluorescence properties of atmospheric WSOC reported in various field and laboratory studies, to discuss the current advances and limitations of fluorescence applications. We highlighted that photochemical reactions and relevant aging processes have profound impacts on fluorescence properties of atmospheric WSOC, which were previously unnoticed for organic matter in aquatic environments. Furthermore, we discussed the differences in sources and chemical compositions of fluorescent components between the atmosphere and hydrosphere. We concluded that the commonly used fluorescence characteristics derived from aquatic environments may not be applicable as references for atmospheric WSOC. We emphasized that there is a need for more systematic studies on the fluorescence properties of atmospheric WSOC and to establish a more robust reference and dataset for fluorescence studies in atmosphere based on extensive source-specific experiments.
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http://dx.doi.org/10.1016/j.envpol.2020.115906DOI Listing
January 2021

Higher Blood Vascular Cell Adhesion Molecule-1 is Related to the Increased Risk of Cardiovascular Events in Chronic Obstructive Pulmonary Disease.

Int J Chron Obstruct Pulmon Dis 2020 28;15:2289-2295. Epub 2020 Sep 28.

Department of Geriatrics, Mindong Hospital of Fujian Medical University, Fuan, Fujian 355000, People's Republic of China.

Background: Vascular cell adhesion molecule-1 (VCAM-1) is associated with vascular-related inflammation and atherosclerosis. This study aimed to evaluate whether VCAM-1 can be used for an indication of increased risk of CV events in patients with COPD.

Methods: Serum VCAM-1 levels were measured in 163 COPD patients. All COPD patients were prospectively followed up for a median period of 48 months (range=3-54). Cox proportional hazard analysis was performed to evaluate the prognostic value of serum VCAM-1 for predicting CV events.

Results: Serum VCAM-1 levels were higher in COPD patients with CV events than in those without CV events (1174.4±365.3 ng/mL vs 947.8±293.2 ng/mL; <0.001). The logistic regression analysis revealed that serum VCAM-1 (OR=1.750; 95% CI, 1.324-2.428; 0.0012) was independently associated with CVD (cardiovascular disease) history after adjusting for age, sex, BMI, current smoker, current drinker, admission systolic and diastolic BP, LVEF and laboratory measurements in patients with COPD at baseline. The Kaplan-Meier analysis demonstrated that the rate of CV events was higher in COPD patients with serum VCAM-1 levels above the median (517.3 ng/mL) than in those with VCAM-1 levels below the median. The Cox proportional hazard analysis revealed that serum VCAM-1 (HR=2.617; 95% CI, 1.673-5.328; 0.001) may be an independent prognostic factor for CV events in the COPD patients.

Conclusion: Our results suggested that serum VCAM-1 was significantly and independently associated with CV events in COPD patients. The inflammatory marker may help clinicians predict CV complications early.
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http://dx.doi.org/10.2147/COPD.S264889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532039PMC
June 2021

Serum cystatin C: A potential predictor for hospital-acquired acute kidney injury in patients with acute exacerbation of COPD.

Chron Respir Dis 2020 Jan-Dec;17:1479973120940677

Department of Nephrology, 385685Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

Hospital-acquired acute kidney injury (HA-AKI) is associated with poor prognosis. In this study, we evaluated whether serum cystatin C on admission could predict AKI in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The retrospective study was conducted using data on adult inpatients with AECOPD from January 2014 to January 2017. A total of 1035 patients were included, among which 79 (7.6%) with HA-AKI were identified. Univariate and multivariate logistic regression analyses were used to investigate predictors of HA-AKI in patients with AECOPD. HA-AKI was associated with poor prognosis, and patients with HA-AKI had higher inpatient mortality (34.2% vs. 2.6%, < 0.001). Furthermore, after adjusting for confounders, HA-AKI was an independent risk factor for inpatient mortality for patients with AECOPD (odds ratio (OR) 11.02; 95% confidence interval (CI) 4.77-25.45; < 0.001). Four independent risk factors for HA-AKI (age, levels of urea and cystatin C, and platelet count on admission) were identified in patients with AECOPD. Cystatin C (OR 5.22; 95% CI 2.49-10.95; < 0.001) was a significant independent predictor of AKI in patients with AECOPD. HA-AKI in patients with AECOPD could be identified with a sensitivity of 73.5% and a specificity of 75.9% (area under the curve (AUC) = 0.803, 95% CI 0.747-0.859) by cystatin C level (cutoff value = 1.3 mg/L) and with a sensitivity of 75.9% and a specificity of 82.0% (AUC = 0.853, 95% CI 0.810-0.896) using a model comprising all significant predictors. Serum cystatin C has the potential for use to predict the risk of HA-AKI in patients with AECOPD.
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http://dx.doi.org/10.1177/1479973120940677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493270PMC
September 2020

Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials.

JAMA 2020 09;324(10):951-960

National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co Ltd, Wuhan, Hubei, China.

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed.

Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China.

Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 μg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 μg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]).

Design, Setting, And Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020.

Main Outcomes And Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups.

Conclusions And Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials.

Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.
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http://dx.doi.org/10.1001/jama.2020.15543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426884PMC
September 2020

Retinoic Acid Alleviates Cisplatin-Induced Acute Kidney Injury Through Activation of Autophagy.

Front Pharmacol 2020 3;11:987. Epub 2020 Jul 3.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.

Cisplatin-induced acute kidney injury (CIAKI) is a common complication in patients receiving cisplatin-based chemotherapy. But the effective therapies for CIAKI are not available. Retinoic acid (RA), the main derivative of vitamin A, has the potential to reduce inflammation and fibrosis in renal injury. However, the effect and mechanism of RA on CIAKI are still unclear. The aim of this study is to investigate whether RA can alleviate CIAKI through activation of autophagy. In this study, we evaluated the effect of RA, RA's effect on autophagy and apoptosis after cisplatin-induced injury on renal tubular epithelial cells (RTECs) by LDH assay, immunoblotting and TUNEL staining. Then we established Atg5:Cagg-Cre mice in which Cagg-Cre is tamoxifen inducible, and Atg5 is conditional deleted after tamoxifen injection. The effect of RA and RA's effect on autophagy on CIAKI model were evaluated by biochemical assessment, hematoxylin and eosin (HE) staining, and immunoblotting in the control and autophagy deficient mice. , RA protected RTECs against cisplatin-induced injury, activated autophagy, and inhibited cisplatin-induced apoptosis. , RA attenuated cisplatin-induced tubular damage, shown by improved renal function, decreased renal cast formation, decreased NGAL expression, and activated autophagy in the control mice. Furthermore, the nephrotoxicity of cisplatin was aggravated, and the protective effect of RA was attenuated in autophagy deficient mice, indicating that RA works in an autophagy-dependent manner on CIAKI. RA activates autophagy and alleviates CIAKI and .Thus RA may be a renoprotective adjuvant for cisplatin-based chemotherapy.
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http://dx.doi.org/10.3389/fphar.2020.00987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348052PMC
July 2020

Mutated SASH1 promotes Mitf expression in a heterozygous mutated SASH1 knock‑in mouse model.

Int J Mol Med 2020 Sep 19;46(3):1118-1134. Epub 2020 Jun 19.

Clinical Research Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.

The SAM and SH3 domain‑containing 1 (SASH1) genes have been identified as the causal genes of dyschromatosis universalis hereditaria (DUH); these genes cause the pathological phenotypes of DUH, and SASH1 variants have been shown to regulate the abnormal pigmentation phenotype in human skin in various genodermatoses. However, investigations into the mutated SASH1 gene have been limited to in vitro studies. In the present study, to recapitulate the molecular pathological phenotypes of individuals with DUH induced by SASH1 mutations, a heterozygous BALB/c mouse model, in which the human SASH1 c.1654 T>G (p. Tyr 551Asp, Y551D) mutation was knocked in was first generated. The in vivo functional experiments on Y551D SASH1 indicated that the increased expression of microphthalmia‑associated transcription factor (Mitf) was uniformly induced in the tails of heterozygous BALB/c mice, and an increased quantity of Mitf‑positive epithelial cells was also detected. An increased expression of Mitf‑ and Mitf‑positive cells was also demonstrated in the epithelial tissues of Y551D‑SASH1 affected individuals. In the present study, Mitf expression was also found to be increased by Y551D SASH1 in vitro. Taken together, these findings indicate that the upregulation of Mitf is the bona fide effector of the Y551D SASH1‑mediated melanogenesis signaling pathway in vivo. SASH1 may function as a scaffold molecule for the assembly of a SASH1‑Mitf molecular complex to regulate Mitf expression in the cell nucleus and thus to promote the hyperpigmented phenotype in the pathogenesis of DUH and other genodermatoses related to pigment abnormalities.
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http://dx.doi.org/10.3892/ijmm.2020.4652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387086PMC
September 2020

Learning what a machine learns in a many-body localization transition.

J Phys Condens Matter 2020 Jun 22;32(41):415605. Epub 2020 Jun 22.

Zhejiang Institute of Modern Physics, Zhejiang University, Hangzhou 310027, People's Republic of China.

We employ a convolutional neural network to explore the distinct phases in random spin systems with the aim to understand the specific features that the neural network chooses to identify the phases. With the energy spectrum normalized to the bandwidth as the input data, we demonstrate that a network of the smallest nontrivial kernel width selects level spacing as the signature to distinguish the many-body localized phase from the thermal phase. We also study the performance of the neural network with an increased kernel width, based on which we find an alternative diagnostic to detect phases from the raw energy spectrum of such a disordered interacting system.
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http://dx.doi.org/10.1088/1361-648X/ab9f09DOI Listing
June 2020

Exosomes Secreted by Adipose-Derived Mesenchymal Stem Cells Foster Metastasis and Osteosarcoma Proliferation by Increasing COLGALT2 Expression.

Front Cell Dev Biol 2020 25;8:353. Epub 2020 May 25.

Department of Spinal Surgery, Qingdao University Affiliated Hospital, Qingdao, China.

Objectives: Homosapien collagen beta (1-O) galactosyl transferase 2 (COLGALT2) is an important enzyme during collagen glycosylation, yet its biological functions in cancer are incompletely understood. Our previous study revealed that in the osteosarcoma microenvironment, adipose-derived mesenchymal stem cells (ADSCs) demonstrate cancer-promoting effects, but the exact mechanisms remain unclear. The aim of this study was to investigate the role of COLGALT2 in the osteosarcoma-fostering effects of ADSCs.

Materials And Methods: In this study, we compared COLGALT2 expression between primary and metastatic osteosarcoma tissues and found that metastatic tissues expressed significantly higher COLGALT2 levels. Then, we isolated and identified exosomes secreted by ADSCs. Additionally, we assessed the roles of ADSC exosomes and COLGALT2 in the osteosarcoma-promoting effects of ADSCs.

Results: Our results showed that ADSC exosomes could foster the invasion, migration, and proliferation of osteosarcoma cells, together with increasing COLGALT2 expression. COLGALT2 inhibition in MG63 cells suppressed the ADSC exosome-mediated fostering of osteosarcoma cell invasion, migration and proliferation . Conversely, COLGALT2 overexpression promoted U-2OS cell invasion, migration and proliferation . Additionally, COLGALT2 inhibition attenuated metastasis and tumor growth, and ADSC exosomes promoted tumor progression, as demonstrated in a nude mouse model of osteosarcoma.

Conclusion: According to these data, ADSC exosomes foster osteosarcoma progression by increasing COLGALT2 expression in osteosarcoma cells.
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http://dx.doi.org/10.3389/fcell.2020.00353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262406PMC
May 2020

Incidence, Risk Factors, and Prognostic Implications of Acute Kidney Injury in Patients with Acute Exacerbation of COPD.

Int J Chron Obstruct Pulmon Dis 2020 15;15:1085-1092. Epub 2020 May 15.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Purpose: Little is known about the incidence, risk factors, and prognostic implications of acute kidney injury (AKI) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in China. In this study, we investigated the incidence, risk factors, and short-term outcomes of AKI in these patients.

Patients And Methods: We analyzed the records of 1768 patients admitted to Nanjing First Hospital with a principal diagnosis of AECOPD. Of these, 377 patients had AKI.

Results: AKI occurred in 377 patients (21%). Independent risk factors for AKI in patients with AECOPD were advanced age, coronary artery disease, anemia, cancer, chronic kidney disease, hypercapnic encephalopathy, acute respiratory failure, and mechanical ventilation. Patients with AKI had worse prognostic implications and were more likely to require mechanical ventilation (38.7% vs 19.1%, <0.001); non-invasive mechanical ventilation (38.2% vs 18.9%, <0.001); invasive mechanical ventilation (18.3% vs 3.1%, <0.001); intensive care unit (ICU) admission (33.7% vs 12.9%, <0.001); had a longer ICU stay (9 days vs 8 days, =0.033) and longer hospitalization (13 days vs 10 days, <0.001); and higher in-hospital mortality (18.0% vs 2.7%, <0.001) than those without AKI. Multivariable analysis indicated that compared to patients without AKI, those with stage 1, 2, or 3 AKI had a 1.9-fold, 2.1-fold, or 6.0-fold increased risk of in-hospital death, respectively.

Conclusion: AKI is common in patients with AECOPD requiring hospitalization. Patients with AKI have worse short-term outcomes. Thus, AKI may be a prognostic predictor of patient survival.
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http://dx.doi.org/10.2147/COPD.S238343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237118PMC
June 2021

Kidney injury induced by elevated histones in community-acquired pneumonia.

Mol Cell Biochem 2020 Aug 9;471(1-2):155-163. Epub 2020 Jun 9.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Road, Nanjing, 211166, Jiangsu, China.

Previous studies showed that extracellular histones could damage organs, but the role of extracellular histones in pneumonia patients with acute kidney injury (AKI) is unknown. This study aims to investigate the impact of extracellular histones on patients with community-acquired pneumonia (CAP) developed AKI. Blood samples were obtained within 24 h after admission to hospital from patients who were diagnosed with CAP. According to the discharge diagnosis, the patients were divided into 2 groups (Non-AKI and AKI). In vitro, A549 cells were treated with lipopolysaccharides (LPS) and conditioned media were collected. HK2 cells were exposed to the conditioned media or not. Cells proliferation and apoptosis of HK2 were determined. Clinically, Log Histones (OR 3.068; 95% CI 1.544-6.097, P = 0.001) and estimated glomerular filtration rate (eGFR) (OR 0.945; 95% CI 0.914-0.978, P = 0.001) were predictors of AKI in CAP patients. Compared to the lower histones group, patients in the higher histones group were more likely to be admitted to ICU, receive mechanical ventilation, and have a longer length of in-hospital stay. In vitro, A549 cells injured by LPS released extracellular histones, in conditioned media which significantly promoted HK2 cells apoptosis. Extracellular histones was a high risk factor for developing AKI in CAP patients and a predictor of worse short-term outcomes. We also showed that extracellular histones in conditioned media damaged HK2 cells.Trial registration number: KY20181102-03; Date of registration: 20181102.
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http://dx.doi.org/10.1007/s11010-020-03775-xDOI Listing
August 2020

Nanocasting SiO into metal-organic frameworks imparts dual protection to high-loading Fe single-atom electrocatalysts.

Nat Commun 2020 Jun 5;11(1):2831. Epub 2020 Jun 5.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.

Single-atom catalysts (SACs) have sparked broad interest recently while the low metal loading poses a big challenge for further applications. Herein, a dual protection strategy has been developed to give high-content SACs by nanocasting SiO into porphyrinic metal-organic frameworks (MOFs). The pyrolysis of [email protected] composite affords single-atom Fe implanted N-doped porous carbon (Fe-N-C) with high Fe loading (3.46 wt%). The spatial isolation of Fe atoms centered in porphyrin linkers of MOF sets the first protective barrier to inhibit the Fe agglomeration during pyrolysis. The SiO in MOF provides additional protection by creating thermally stable FeN/SiO interfaces. Thanks to the high-density Fe sites, Fe-N-C demonstrates excellent oxygen reduction performance in both alkaline and acidic medias. Meanwhile, Fe-N-C also exhibits encouraging performance in proton exchange membrane fuel cell, demonstrating great potential for practical application. More far-reaching, this work grants a general synthetic methodology toward high-content SACs (such as Fe, Co, Ni).
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http://dx.doi.org/10.1038/s41467-020-16715-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275045PMC
June 2020

Efficacy and Safety of Ureteral Catheter Use During Arteriovenous Fistula in End-Stage Renal Disease Patients with Poor Vascular Status.

Med Sci Monit 2020 May 29;26:e920421. Epub 2020 May 29.

Kidney Disease Center, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China (mainland).

BACKGROUND The aim of this study was to evaluate the efficacy and safety of use of a ureteral catheter during arteriovenous fistula in end-stage renal disease patients with poor vascular status. MATERIAL AND METHODS Fifty patients with standard arteriovenous fistulas at Sir Run Run Hospital of Nanjing Medical University from April 2018 to April 2019 were included. Based on the use of ureteral catheter exploration and tourniquet hydraulic dilatation, patients were divided into study and control groups. The operative success rate, inner diameter of cephalic vein 1 day post-operatively, blood flow in the internal fistula, patency rate and blood flow in the internal fistula 3 months post-operatively, and complications 6 months post-operatively were compared between the 2 groups. RESULTS There were 25 cases in each group, with no significant differences in sex or age between the 2 groups. The operative success rate in the study group was higher than in the control group (96% vs. 88%) (F=1.087, P=0.297). The patency rates at 3 and 6 months post-operatively in the study group were higher than in the control group. The inner diameter of the cephalic vein 1 day post-operatively, the blood flow in the internal fistula, and the complications 6 months post-operatively in the study group were significantly superior to those of the control group (P=0.002). CONCLUSIONS In standard arteriovenous fistula, especially vascular catheter exploration of unhealthy vessels, the application of a ureteral catheter can improve the operative success rate and promote internal fistula maturity, with low cost and ease of use.
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http://dx.doi.org/10.12659/MSM.920421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282533PMC
May 2020

The efficacy and safety of balloon dilation for unresectable malignant biliary obstruction before placement of self-expanding metal stents.

J Dig Dis 2020 May 11;21(5):293-300. Epub 2020 May 11.

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.

Objective: To evaluate whether patients with malignant biliary obstruction (MBO) benefit from balloon dilation before the placement of a self-expanding metal stent (SEMS) for palliative biliary drainage.

Methods: Consecutive patients who underwent endoscopic retrograde cholangiopancreatography with SEMS placement for palliative management of MBO were retrospectively included. Comparative analyses of serum bilirubin levels, post-procedural adverse events, stent patency time, stent dysfunction, and patient survival were performed between the dilation and non-dilation groups.

Results: A total of 221 patients underwent palliative endoscopic SEMS implantation for MBO from January 2014 to June 2018. Dilation significantly improved the percentage of serum bilirubin improvement (37.0% vs 14.3%, P = 0.001), with a decreasing trend in the incidence of post-procedural cholangitis (2.5% vs 7.8%, P = 0.075), while the rates of other complications such as pancreatitis and bleeding were not increased. The patency time of SEMS and patient survival did not significantly differ between patients with and without dilation. Patients had endoscopic nasobiliary drainage (ENBD) but not dilation showed similar short-term outcomes as patients underwent dilation but without ENBD.

Conclusions: Dilation with a small-caliber balloon catheter before the placement of SEMS is a safe and effective approach for MBO. Balloon dilation may improve the short-term efficacy of SEMS placement, while long-term outcomes are not obviously affected. The short-term effect of stricture dilation may be achieved by ENBD. Further studies are needed to confirm our results.
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http://dx.doi.org/10.1111/1751-2980.12864DOI Listing
May 2020

Renin-angiotensin-aldosterone system blockade is associated with higher risk of contrast-induced acute kidney injury in patients with diabetes.

Aging (Albany NY) 2020 04 2;12(7):5858-5877. Epub 2020 Apr 2.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211166, Jiangsu, China.

As the incidence of diabetes and cardiovascular comorbidities continues to rise, driven by increased prevalence of obesity and an aging population, so does the demand for percutaneous coronary intervention (PCI) to restore cardiac blood flow. Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly prescribed to hypertensive diabetic patients to prevent diabetic nephropathy. However, evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of contrast-induced acute kidney injury (CIAKI) following coronary angiography (CAG) and PCI. We therefore conducted a retrospective, multicenter study applying the propensity score matching method to evaluate the impact of RAAS inhibition on CIAKI in diabetic patients undergoing CAG/PCI. Among 2240 subjects that met the inclusion criteria, 704 patients in the ACEIs/ARBs group were successfully matched to eligible control patients. The incidence of CIAKI (serum creatinine increase ≥0.5 mg/dl or ≥25% from baseline within 72 h post-CAG/PCI) was significantly higher in the ACEIs/ARBs group than in the control group (26.6% vs. 16.2%, <0.001). However, control patients showed increased risk of overall adverse cardiovascular events (4.1% vs. 1.8% for ACEIs/ARBs; =0.016). These data indicate that RAAS inhibition increases the risk of CIAKI in diabetic patients, but confers protection against early cardiovascular events.
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http://dx.doi.org/10.18632/aging.102982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185147PMC
April 2020

Protein disulfide isomerases are promising targets for predicting the survival and tumor progression in glioma patients.

Aging (Albany NY) 2020 02 5;12(3):2347-2372. Epub 2020 Feb 5.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, P. R. China.

The present study focused on the expression patterns, prognostic values and potential mechanism of the PDI family in gliomas. Most PDI family members' mRNA expressions were observed significantly different between gliomas classified by clinical features. Construction of the PDI signature, cluster and risk score models of glioma was done using GSVA, consensus clustering analysis, and LASSO Cox regression analysis respectively. High values of PDI signature/ risk score and cluster 1 in gliomas were associated with malignant clinicopathological characteristics and poor prognosis. Analysis of the distinctive genomic alterations in gliomas revealed that many cases having high PDI signature and risk score were associated with genomic aberrations of driver oncogenes. GSVA analysis showed that PDI family was involved in many signaling pathways in ERAD, apoptosis, and MHC class I among many more. Prognostic nomogram revealed that the risk score was a good prognosis indicator for gliomas. The qRT-PCR and immunohistochemistry confirmed that P4HB, PDIA4 and PDIA5 were overexpressed in gliomas. In summary, this research highlighted the clinical importance of PDI family in tumorigenesis and progression in gliomas.
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http://dx.doi.org/10.18632/aging.102748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041756PMC
February 2020

Complement C3 and Nonalcoholic Fatty Liver Disease in Chronic Kidney Disease Patients: A Pilot Study.

Kidney Blood Press Res 2020 22;45(1):61-69. Epub 2020 Jan 22.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China,

Context: Evidences have suggested complement C3 is a biomarker for nonalcoholic fatty liver disease (NAFLD) in the general population.

Objective: The present study was conducted to explore the predictive function of C3 for NAFLD in chronic kidney disease (CKD) patients.

Design, Setting, And Participants: CKD patients were recruited for evaluation of their liver function, kidney function, serum lipids, glycated hemoglobin, blood, and immune function. The glomerular filtration rate was calculated using the CKD-EPI equation. NAFLD was diagnosed according to predefined ultrasonographic criteria.

Results: A total of 648 consecutive CKD patients were included, with 216 (33.3%) patients diagnosed with NAFLD. The NAFLD group had significant higher levels of serum protein, serum albumin, triglycerides, glycated hemoglobin, complement C3, hemoglobin (p = 0.001), alanine aminotransferase (p = 0.002), estimated glomerular filtration rate (p = 0.007), and C4 (p = 0.043) and lower levels of cystatin C, β2-microglobulin, proteinuria (p = 0.001), and high-density lipoprotein cholesterol (p = 0.008). In a logistic regression model, only complement C3 (OR = 1.003; 95% CI 1.002-1.004, p = 0.001) was associated with a higher likelihood of being diagnosed with NAFLD. Finally, we constructed ROC curves for complement C3 for prediction of having NAFLD. The best cut-off for complement C3 was 993.5 mg/L and it yielded a sensitivity of 63.9% and a specificity of 70.1%.

Conclusion: Our study revealed that complement C3 can be used as a surrogate biomarker of NAFLD in CKD patients.
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http://dx.doi.org/10.1159/000504172DOI Listing
October 2020

Design and Optimization of PLGA Particles to Deliver Immunomodulatory Drugs for the Prevention of Skin Allograft Rejection.

Immunol Invest 2020 Oct 6;49(7):840-857. Epub 2019 Dec 6.

Department of Microbiology and Immunology, Medical School, Southeast University , Nanjing, Jiangsu, China.

: Recent advancements in therapeutic strategies have attracted considerable attention to control the acute organs and tissues rejection, which is the main cause of mortality in transplant recipients. The long-term usage of immunosuppressive drugs compromises the body immunity against simple infections and decrease the patients' quality of life. Tolerance of allograft in recipients without harming the rest of host immune system is the basic idea to develop the therapeutic approaches after induction of donor-specific transplant. : Controlled and targeted delivery system by using biomimetic micro and nanoparticles as carriers is an effective strategy to deplete the immune cells in response to allograft in an antigen-specific manner. Polylactic-co-glycolic acid (PLGA) is a biocompatible and biodegradable polymer, which has frequently being used as drug delivery vehicle. : This review focuses on the biomedical applications of PLGA based biomimetic micro and nano-sized particles in drug delivery systems to prolong the survival of alloskin graft. : We will discuss the mediating factors for rejection of alloskin graft, selective depletion of immune cells, controlled release mechanism, physiochemical properties, size-based body distribution of PLGA particles and their effect on overall host immune system.
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http://dx.doi.org/10.1080/08820139.2019.1695134DOI Listing
October 2020
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