Publications by authors named "Yanhua Wu"

130 Publications

Temporal transcriptomic landscape of postnatal mouse ovaries reveals dynamic gene signatures associated with ovarian aging.

Hum Mol Genet 2021 Jun 17. Epub 2021 Jun 17.

Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), State Key Laboratory of Genetic Engineering at School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200011, China.

The ovary is the most important organ for maintaining female reproductive health, but it fails before most other organs. Aging-associated alterations in gene expression patterns in mammalian ovaries remain largely unknown. In this study, the transcriptomic landscape of postnatal mouse ovaries over the reproductive lifespan was investigated using bulk RNA sequencing in C57BL/6 mice. Gene expression dynamics revealed that the lifespan of postnatal mouse ovaries comprised four sequential stages, during which 2517 genes were identified as differentially enriched. Notably, the DNA repair pathway was found to make a considerable and specific contribution to the process of ovarian aging. Temporal gene expression patterns were dissected to identify differences in gene expression trajectories over the lifespan. In addition to DNA repair, distinct biological functions (including hypoxia response, epigenetic modification, fertilization, mitochondrial function, etc.) were overrepresented in particular clusters. Association studies were further performed to explore the relationships between known genes responsible for ovarian function and differentially expressed genes identified in this work. We found that the causative genes of human premature ovarian insufficiency were specifically enriched in distinct gene clusters. Taken together, our findings reveal a comprehensive transcriptomic landscape of the mouse ovary over the lifespan, providing insights into the molecular mechanisms underlying mammalian ovarian aging and supporting future etiological studies of aging-associated ovarian disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddab163DOI Listing
June 2021

M2 Macrophage Subpopulations in Glomeruli Are Associated With the Deposition of IgG Subclasses and Complements in Primary Membranous Nephropathy.

Front Med (Lausanne) 2021 21;8:657232. Epub 2021 May 21.

Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, China.

The role of M2 macrophages in the pathogenesis and progression of primary membranous nephropathy (PMN) remains unknown. In this study, we aimed to investigate the relationship between M2 subsets and clinicopathological features of patients with PMN. A total of 55 patients with PMN confirmed by biopsy were recruited. The clinical and pathological data were recorded, respectively. Immunohistochemistry was used to detect the markers of M2 macrophages, including total macrophages (CD68+), M2a (CD206+), M2b (CD86+) and M2c (CD163+). The numbers of glomerular macrophages, M2a, M2b, and M2c macrophages were 1.83 (1.00, 2.67), 0.65 (0.15, 1.15), 0.67 (0.33, 1.50), and 0.80 (0.05, 2.30) per glomerulus, respectively. Higher number of glomerular macrophages was found in stage II compared with stage III (2.08 vs. 1.16, = 0.008). These macrophages also were negatively correlated with serum albumin level ( = -0.331, = 0.014), while positively associated with complement 3 (C3) deposition ( = 0.300, = 0.026) and the severity of glomerulosclerosis ( = 0.276, = 0.041). Moreover, glomerular M2a macrophages were significantly correlated with the deposition of C3 ( = 0.300, = 0.026), immunoglobulin G1 (IgG1) ( = 0.339, = 0.011), immunoglobulin G2 (IgG2) ( = 0.270, = 0.046) and immunoglobulin G3 (IgG3) ( = 0.330, = 0.014) in glomerular basement membrane (GBM). In addition, M2b macrophages were positively associated with IgG1 ( = 0.295, = 0.029) and IgG2 ( = 0.393, = 0.003), while M2c macrophages were negatively correlated with complement 4d (C4d) ( = -0.347, = 0.009) in GBM. Our results showed that M2 macrophage subpopulations in glomeruli are associated with the deposition of IgG subclasses and complements in renal tissue of PMN, which indicate that M2 macrophages may be involved in the pathogenesis and progression of PMN. Moreover, M2a and M2c macrophages might show different tendencies in the pathogenesis of PMN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.657232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175664PMC
May 2021

Reply to the Letter to the Editor.

J Card Surg 2021 May 28. Epub 2021 May 28.

Division of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.15675DOI Listing
May 2021

Microsatellite instability and Epstein-Barr virus combined with PD-L1 could serve as a potential strategy for predicting the prognosis and efficacy of postoperative chemotherapy in gastric cancer.

PeerJ 2021 18;9:e11481. Epub 2021 May 18.

Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin Province, China.

Background: Microsatellite instability (MSI) and Epstein-Barr virus (EBV)-positive molecular subtypes exhibit complex immune responses in gastric cancer (GC), and PD-L1 has emerged as a prognostic biomarker associated with the cancer immune microenvironment. This study aimed to determine the prognostic value of molecular subtypes and whether the addition of PD-L1 would accurately predict the prognosis and guide postoperative chemotherapy for GC patients.

Methods: We performed molecular subtyping of tissue microarray slides from 226 GC patients who were treated with radical gastrectomy. The MSI status and PD-L1 expression were evaluated through immunohistochemistry (IHC) and EBV status through situ hybridization. Multiplex polymerase chain reaction (PCR) was also performed on 50 cases to validate the accuracy of IHC in defining MSI status. Differences in overall survival (OS) were assessed using the Kaplan-Meier method, log-rank test and Cox proportional hazards regression model.

Results: Among the 226 GC patients, 52 (23.2%) patients were classified as the MSI subtype, 11 (4.9%) were EBV subtype, and 161 (71.9%) were MSS (Microsatellite stable) /EBV subtype according to TCGA analysis. Two patients were both positive for MSI and EBV infection. EBV cases showed higher PD-L1 positivity than MSI cases and MSS/EBV cases (81.8% 50.0% 35.4%, = 0.003). Compared with the non-MSS/EBV (MSI or EBV cases) subgroup, GC patients with MSS/EBV were associated with the worst outcomes (HR = 1.610, 95% CI [1.0462.479], = 0.031). MSS/EBV GCs alone could benefit from postoperative chemotherapy (HR = 0.452, 95% CI [0.2990.682], <0.001), and PD-L1-positive expression could also predict a better prognosis (HR = 0.612, 95% CI [0.3890.962], = 0.033) in this subgroup. Considering both chemotherapy efficacy and PD-L1 expression in the MSS/EBV subgroup, chemotherapy could improve the prognosis for PD-L1-negative MSS/EBV GCs (HR = 0.357, 95% CI [0.2170.587], <0.001) but not PD-L1-positive MSS/EBV GCs.

Conclusions: Molecular subtyping combined with PD-L1 expression could serve as a potential strategy to better predict prognosis and guide postoperative chemotherapy of GC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.11481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139270PMC
May 2021

Epidemiology of hospitalizations due to pesticide intoxication-associated acute kidney injury in China.

Int Urol Nephrol 2021 May 18. Epub 2021 May 18.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China.

Background: There is a paucity of epidemiological data regarding pesticide intoxication-associated acute kidney injury (AKI). Therefore, the aim of this study was to identify the epidemiological features, risk factors, and adverse outcomes of AKI in this population.

Methods: The data used in this multi-center, hospitalized population-based, retrospective study were retrieved from electronic medical records. AKI was defined as an acute increase in serum creatinine according to the criteria of Kidney Disease: Improving Global Outcomes. The Charlson Comorbidity Index was used to evaluate the burden of in-hospital mortality.

Results: Of 3,371 adult patients in 11 hospitals, 398 (11.8%) were diagnosed with AKI (grade 1, 218 [6.5%]; grade 2, 89 [2.6%]; grade 3, 91 [2.7%]). Herbicide intoxication was associated with the highest incidence of AKI (53.5%) and higher grades of AKI. After multivariable adjustment, pesticide categories and moderate or severe renal disease were independently associated with AKI. As compared with the referred category, insecticide and herbicide intoxications were associated with a 1.3-fold (95% CI 1.688-3.245) and 3.8-fold (95% CI 3.537-6.586) greater risk of AKI. Regardless of the pesticide category, AKI was independently associated with in-hospital mortality, with odds ratios of 3.433 (95% CI 1.436-8.203) for insecticides, 2.153 (95% CI 1.377-3.367) for herbicides, and 4.524 (95% CI 1.230-16.632) for unclassified or other pesticides.

Conclusion: AKI is common in pesticide intoxication and associated with an increased in-hospital mortality. Herbicides pose the greatest risks of AKI and death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11255-021-02885-9DOI Listing
May 2021

Upregulation of Nogo-B by hypoxia inducible factor-1 and activator protein-1 in hepatocellular carcinoma.

Cancer Sci 2021 May 8. Epub 2021 May 8.

Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China.

Nogo-B is an important regulator of tumor angiogenesis. Expression of Nogo-B is remarkably upregulated in multiple tumor types, especially hepatocellular carcinoma (HCC). Here, we show the transcriptional regulation mechanisms of Nogo-B in liver cancer. In response to hypoxia, expression of Nogo-B significantly increased in HCC tissues and cells. The distal hypoxia-responsive element in the promoter was essential for transcriptional activation of Nogo-B under hypoxic conditions, which is the specific site for hypoxia inducible factor-1α (HIF-1α) binding. In addition, Nogo-B expression was associated with c-Fos expression in HCC tissues. Nogo-B expression was induced by c-Fos, yet inhibited by a dominant negative mutant A-Fos. Deletion and mutation analysis of the predicted activator protein-1 binding sites revealed that functional element mediated the induction of Nogo-B promoter activity, which was confirmed by ChIP. These results indicate that HIF-1α and c-Fos induce the expression of Nogo-B depending on tumor microenvironments, such as hypoxia and low levels of nutrients, and play a role in upregulation of Nogo-B in tumor angiogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14941DOI Listing
May 2021

Caveolae-Mediated Endocytosis Drives Robust siRNA Delivery of Polymeric Nanoparticles to Macrophages.

ACS Nano 2021 05 29;15(5):8267-8282. Epub 2021 Apr 29.

State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200438, P.R. China.

Cytosolic delivery of small interfering RNA (siRNA) remains challenging, and a profound understanding of the cellular uptake and intracellular processing of siRNA delivery systems could greatly improve the development of siRNA-based therapeutics. Here, we show that caveolae-mediated endocytosis (CvME) accounts for the robust siRNA delivery of mannose-modified trimethyl chitosan-cysteine/tripolyphosphate nanoparticles (MTC/TPP NPs) to macrophages by circumventing lysosomes. We show that the Golgi complex and ER are key organelles required for the efficient delivery of siRNA to macrophages in which the siRNA accumulation positively correlates with its silencing efficiency ( = 0.94). We also identify syntaxin6 and Niemann-Pick type C1 (NPC1) as indispensable regulators for MTC/TPP NPs-delivered siRNA into macrophages both and . Syntaxin6 and NPC1 knockout substantially decrease the cellular uptake and gene silencing of the siRNA delivered in MTC/TPP NPs in macrophages, which result in poor therapeutic outcomes for mice bearing acute hepatic injury. Our results suggest that highly efficient siRNA delivery can be achieved CvME, which would give ideas for designing optimal delivery vectors to facilitate the clinical translation of siRNA drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.0c08596DOI Listing
May 2021

Haploinsufficiency in non-homologous end joining factor 1 induces ovarian dysfunction in humans and mice.

J Med Genet 2021 Apr 22. Epub 2021 Apr 22.

Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China

Background: Premature ovarian insufficiency (POI) is a common disease in women that leads to a reduced reproductive lifespan. The aetiology of POI is genetically heterogeneous, with certain double-strand break (DSB) repair genes being implicated in POI. Although non-homologous end joining (NHEJ) is an efficient DSB repair pathway, the functional relationship between this pathway and POI remains unknown.

Methods And Results: We conducted whole-exome sequencing in a Chinese family and identified a rare heterozygous loss-of-function variant in non-homologous end joining factor 1 (): c.532C>T (p.R178*), which co-segregated with POI and irregular menstruation. The amount of NHEJ1 protein in the proband was half of the normal level, indicating a link between haploinsufficiency and POI. Furthermore, another rare heterozygous variant c.500A>G (p.Y167C) was identified in one of 100 sporadic POI cases. Both variants were predicted to be deleterious by multiple in silico tools. In vitro assays showed that knock-down of in human KGN ovarian cells impaired DNA repair capacity. We also generated a knock-in mouse model with a heterozygous variant equivalent to p.R178* in familial patients. Compared with wild-type mice, heterozygous -mutated female mice required a longer time to first birth, and displayed reduced numbers of primordial and growing follicles. Moreover, these mice exhibited higher sensitivity to DSB-inducing drugs. All these phenotypes are analogous to the progressive loss of ovarian function observed in POI.

Conclusions: Our observations in both humans and mice suggest that haploinsufficiency is associated with non-syndromic POI, providing novel insights into genetic counselling and clinical prevention of POI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jmedgenet-2020-107398DOI Listing
April 2021

Sleep fragmentation and incidence of congestive heart failure: the Sleep Heart Health Study.

J Clin Sleep Med 2021 Mar 29. Epub 2021 Mar 29.

Department of Cardiology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Study Objectives: Sleep fragmentation (SF) has been reported to be associated with cardiovascular risk. The aim of this study was to explore the relationship between SF and congestive heart failure (CHF).

Methods: A total of 4,887 participants (2,256 males and 2,631 females, mean age of 63.6 ± 11.0 years) from the Sleep Heart Health Study (SHHS) were included in this study. Incident CHF was defined as the first occurrence of CHF between baseline in-home polysomnography (PSG) and the end of follow-up. Objective assessments for SF, including sleep fragmentation index (SFI), arousal index (ArI), sleep efficiency (SE), and wake after sleep onset (WASO), were determined based on in-home polysomnography records. Multivariate Cox regression analysis was used to investigate the relationship between SF and incident CHF.

Results: During an average of 10 years of follow-up, 543 participants with CHF (11.1%) were observed. Individuals with CHF had a significantly higher SFI, total ArI, and WASO and a lower SE than controls. After multivariate Cox regression analysis, SE (odds ratio [OR], 0.967; 95% confidence interval [CI] 0.955-0.978; P < 0.001), WASO (OR, 1.009; 95% CI 1.006-1.012; P < 0.001), SFI (OR, 1.046; CI 1.007-1.086; P = 0.021), and total ArI (OR, 1.018; 95% CI 1.000-1.035; P = 0.044) were found to be associated with the incidence of CHF in participants without hypertension.

Conclusions: Objectively measured SF was associated with the incidence of CHF. The role of SFI, total ArI, SE, and WASO deserves further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5664/jcsm.9270DOI Listing
March 2021

Prospective model for predicting renal recovery in cardiac surgery patients with acute kidney injury requiring renal replacement therapy.

Nephrology (Carlton) 2021 Jul 27;26(7):586-593. Epub 2021 Mar 27.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Aim: To develop a model for predicting renal recovery in cardiac surgery patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT).

Methods: Data from a prospective randomized controlled trial, conducted in a tertiary hospital to compare the survival effect of two dosages of hemofiltration for continuous RRT in cardiac surgery patients between 20 March 2012 and 9 August 2015, were used to develop the model. The outcome was renal recovery defined as alive and dialysis-free 90 days after RRT initiation. Multivariate logistic regression with a stepwise backward selection of variables based on Akaike Information Criterion was applied to develop the model, which was internally validated using bootstrapping. Model discrimination, calibration and clinical value were assessed using the concordance index (C-Index), calibration plots and decision curve analysis, respectively.

Results: Totally, 211 patients with AKI requiring RRT (66.8% male) with median age of 57 years were included. The incidence of renal recovery was 33.2% (n = 70). The model included six variables: body mass index stratification, baseline estimated glomerular filtration rate, hypertension, sepsis, mean arterial pressure and mechanical ventilation. The C-Index for this model was 0.807 (95% CI, 0.744-0.870). After correction by the bootstrap, the C-Index was 0.780 (95% CI, 0.720-0.845). The calibration plots indicated good consistency between actual observations and model prediction of renal recovery. Decision curve analysis demonstrated the model was clinical usefulness.

Conclusion: We developed and validated a model to predict the chance of renal recovery in cardiac surgery patients with AKI requiring RRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/nep.13878DOI Listing
July 2021

The effect of amiloride in decreasing albuminuria in patients with diabetic kidney diseases: a prospective, crossover, open-label study.

Ren Fail 2021 Dec;43(1):452-459

Division of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: Diabetic kidney diseases (DKD) were the leading cause of End-stage renal diseases worldwide. Albuminuria was a target for treatment in DKD and decreasing albuminuria was particularly important for improving its prognosis. However, there is still a lack of specific treatment for DKD.

Methods: We conducted a prospective, crossover, open-label study to investigate the effect of amiloride in patients with DKD. Safety and efficacy were assessed by monitoring urine protein creatinine ratio(uPCR), urinary albumin creatinine ratio (uACR), blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid, serum soluble urokinase-type plasminogen activator receptor (suPAR) and urinary suPAR. Ten subjects were enrolled in the trial.

Results: In this prospective, crossover, open-label design, amiloride could induce a significant decrease of uACR in DKD. The decrease of serum and urinary suPAR in the amiloride/hydrochlorothiazide (HCTZ) group was also significant compared with those patients using HCTZ as the control group. Correlation analysis showed that the levels of urinary suPAR were positively associated with uPCR and uACR. No significant difference in blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid was seen between the amiloride/HCTZ group and the control group.

Conclusion: In summary, among patients with DKD, amiloride could decrease albuminuria without severe side effects, which was accompanied by the significant decline of urinary suPAR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0886022X.2021.1892759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935116PMC
December 2021

Tissue inhibitor of metalloproteinase-1 (TIMP-1) as a prognostic biomarker in gastrointestinal cancer: a meta-analysis.

PeerJ 2021 16;9:e10859. Epub 2021 Feb 16.

Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin, China.

Background: Tissue inhibitor of metalloproteinase 1 (TIMP-1) has recently been shown to be dependent on or independent of Matrix metalloproteinases (MMPs) in its roles in tumorigenesis and progression. This appreciation has prompted various studies assessing the prognostic value of TIMP-1 in patients with gastrointestinal cancer, however, the conclusions were still inconsistent. The aim of this study was to assess the prognostic value of TIMP-1-immunohistochemistry (IHC) staining and pretreatment serum/plasma TIMP-1 level in gastrointestinal cancer survival as well as the association between TIMP-1 and clinicopathologic features.

Methods: The meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration NO. CRD42020185407) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A highly sensitive literature search was performed in electronic databases including PubMed, EMBASE and the Cochrane Library. Heterogeneity analysis was conducted using both chi-square-based Q statistics and the I test. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the prognostic value of TIMP-1 using the fixed-effects model. Odds ratios (ORs) with 95% CIs were calculated to evaluate the associations between TIMP-1 and clinicopathological characteristics. The meta-analysis was conducted using STATA 12.0 software.

Results: A total of 3,958 patients from twenty-two studies were included in the meta-analysis. Elevated TIMP-1 levels were significantly associated with poor survival in gastrointestinal cancer (TIMP-1-IHC staining: HR = 2.04, 95% CI [1.59-2.61],  = 35.7%, = 0.156; pretreatment serum/plasma TIMP-1 levels: HR = 2.02, 95% CI [1.80-2.28],  = 0%, = 0.630). Moreover, clinicopathological parameter data analysis showed that elevated TIMP-1 levels were significantly associated with lymph node metastasis (N1/N2/N3 vs N0: OR = 2.92, 95% CI [1.95-4.38]) and higher TNM stages (III/IV vs I/II: OR = 2.73, 95% CI [1.23-6.04]).

Conclusion: Both TIMP-1-positive IHC staining and high serum/plasma TIMP-1 levels are poor prognostic factors for the survival of gastrointestinal cancer. In addition, TIMP-1 overexpression was correlated with more advanced clinicopathological features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.10859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894117PMC
February 2021

The Incidence, Characteristics, and Use of Suspected Nephrotoxic Drugs in Elderly Patients with Community-Acquired Acute Kidney Injury.

Clin Interv Aging 2021 7;16:35-42. Epub 2021 Jan 7.

Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou 510080, People's Republic of China.

Purpose: Acute kidney injury (AKI) is a major health problem with poor prognosis. However, little is known about elderly community-acquired-AKI (CA-AKI). This study aimed to investigate the incidence, clinical characteristics, outcomes and use of suspected nephrotoxic medications after CA-AKI in the elderly.

Materials And Methods: A total of 36,445 patients aged over 60 years were recruited from 2013 to 2016. Through an electronic database, we collected the demographic and medical history data, and admission lab results from all patients.

Results: A total of 2371 patients with CA-AKI were identified. The incidence of CA-AKI was 26.03% in the elderly. The proportion of CA-AKI patients with chronic comorbidities and Charlson comorbidity index score were higher than that of non-AKI patients. After CA-AKI, the proportions of exposure to non-steroidal anti-inflammatory drugs (NSAIDs), iodine contrast agent, angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) were significantly decreased (p < 0.001). However, the proportion of other possible nephrotoxic drugs (including aminoglycosides, glycopeptide antibiotics, antifungal agents, beta lactam antibiotics, diuretic, ferralia, adrenergic receptor agonists and drugs for cardiac insufficiency therapy) still increased after CA-AKI (p < 0.001). Compared with non-AKI patients, CA-AKI patients had higher percentage of cardiogenic shock, multiple organ failure, transferring to intensive care unit, cardio-pulmonary resuscitation, hemodialysis, and mortality (p < 0.001). Moreover, CA-AKI patients had worse prognosis when more kinds of suspected nephrotoxic drugs were used (p < 0.001).

Conclusion: The incidence of CA-AKI in the elderly was high, with more complex chronic complications and poor clinical outcomes. The use of most suspected nephrotoxic drugs still increased and was associated with worse prognosis after CA-AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CIA.S286660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7800449PMC
April 2021

Is acute kidney injury age-dependent in older adults: an observational study in two centers from North China.

BMC Geriatr 2021 01 6;21(1). Epub 2021 Jan 6.

Division of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Road 2, Guangzhou, 510080, China.

Background: Although aging increases susceptibility to acute kidney injury (AKI), whether the AKI risk and the association between AKI and adverse outcomes are age-dependent remain unclear in older adults. The current study aimed to identify whether AKI risk was age-dependent in older adults and to investigate whether the association between AKI and mortality increased with increasing age.

Methods: Medical records from 47,012 adult hospital admissions, including 30,194 older adults aged 60 or older, in two tertiary general hospitals were studied retrospectively. AKI was identified based on changes in blood creatinine levels according to the Kidney Disease: Improving Global Outcomes criteria.

Results: Among the total population and 30,194 older adult patients, the raw incidences of AKI were 8.2 and 8.3%, respectively. The curve of the age-grouped AKI incidence was "U-shaped", which revealed a positive relationship between the AKI incidence and age among the older adults aged 75 years or older. This trend of the age-AKI relationship was supported by further multivariable analysis. After adjusting for the Charlson Comorbidity Index score, the AKI was associated with in-hospital mortality; however, the associations did not increase with increasing age.

Conclusion: The AKI risk does not increase with age in older adults, except for those aged 75 and above. The association between AKI and in-hospital death did not increase in an age-dependent manner in older adults.

Trial Registration: This study was retrospectively registered at clinicaltrials.gov ( NCT03054142 ) on February 13, 2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12877-020-01906-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789374PMC
January 2021

Development and validation of a model for predicting acute kidney injury after cardiac surgery in patients of advanced age.

J Card Surg 2021 Mar 12;36(3):806-814. Epub 2020 Dec 12.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Objective: To develop a clinical model for predicting postoperative acute kidney injury (AKI) in patients of advanced age undergoing cardiac surgery.

Methods: A total of 848 patients (aged ≥ 60 years) undergoing cardiac surgery were consecutively enrolled. Among them, 597 were randomly selected for the development set and the remaining 251 for the validation set. AKI was the primary outcome. To develop a model for predicting AKI, visualized as a nomogram, we performed logistic regression with variables selected by Lasso regression analysis. The discrimination, calibration, and clinical usefulness of the new model were assessed and compared with those of Cleveland Clinic score and Simplified Renal Index (SRI) score in the validation set.

Results: The incidence of AKI was 61.8% in the development set. The new model included seven variables including preoperative serum creatinine, hypertension, preoperative uric acid, New York Heart Association classification ≥ 3, cardiopulmonary bypass time > 120 min, intraoperative red blood cell transfusion, and postoperative prolonged mechanical ventilation. In the validation set, the areas under the receiver operating characteristic curves for assessing discrimination of the new model, Cleveland Clinic score, and SRI score were 0.801, 0.670, and 0.627, respectively. Compared with the other two scores, the new model presented excellent calibration according to the calibration curves. Decision curve analysis presented the new model was more clinically useful than the other two scores.

Conclusions: We developed and validated a new model for predicting AKI after cardiac surgery in patients of advanced age, which may help clinicians assess patients' risk for AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.15249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898501PMC
March 2021

Effects of temperature fluctuation on endocrine disturbance of grass carp Ctenopharyngodon idella under mercury chloride stress.

Chemosphere 2021 Jan 29;263:128137. Epub 2020 Aug 29.

Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, 430223, China.

Mercury (Hg) is considered to be one of the most toxic and ubiquitously distributed metals in the aquatic system. Meanwhile, the temperature increase of water bodies due to global climatic changes, may affect ecosystems through alterations of the metal properties or by affecting the susceptibility of organisms. To study the physiological stress of mercury chloride on grass carp Ctenopharyngodon idella at different temperatures, we investigated the effects of water temperature and/or mercury chloride (HgCl) on growth performance (SGR-the specific growth rate, HSI-hepato-somatic index, CF-condition factor) and the thyroid hormones levels (T3-triiodothyronine; T4-thyroxine), as well as the expression levels of related genes involved growth and hypothalamus-pituitary-thyroid (HPT) axis. Fish (45.37 ± 3.58 g) were acclimated to 15, 20, 25, 30 or 35 °C and co-exposed to 0.0 or 0.039 mg/L HgCl for 4 weeks in triplicates. Three-way ANOVA revealed that all variables were significantly affected by water temperature, HgCl exposure, exposure time and their interactions. It was found that fish reared in Hg-free group at 25 °C showed the optimum growth. Otherwise, T4 concentrations were decreased, while T3 levels remained constant following exposure to HgCl, which was explained by the up-regulation of the dio2 gene. Our data provide evidences that increased temperatures can potentiate HgCl toxicity, but the exact mechanism of the effects of temperature coupled HgCl on fish is not full clear, which should be give more attention in future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2020.128137DOI Listing
January 2021

Isolation and Characterization of New Anti-Inflammatory and Antioxidant Components from Deep Marine-Derived Fungus SP. Bzo-l062.

Mar Drugs 2020 Nov 26;18(12). Epub 2020 Nov 26.

Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China.

In the present study, four new compounds including a pair of 2-benzoyl tetrahydrofuran enantiomers, namely, (-)-1-myrothecol () and (+)-1-myrothecol (), a methoxy-myrothecol racemate (), and an azaphilone derivative, myrothin (), were isolated along with four known compounds (-) from cultures of the deep-sea fungus sp. BZO-L062. Enantiomeric compounds and were separated through normal-phase chiral high-performance liquid chromatography. The absolute configurations of , , and were assigned by ECD spectra. Among them, the new compound and its enantiomer exhibited anti-inflammatory activity, inhibited nitric oxide formation in lipopolysaccharide-treated RAW264.7 cells, and exhibited antioxidant activity in the 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and oxygen radical absorbance capacity assays.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md18120597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760613PMC
November 2020

Clinical features, risk factors, and clinical burden of acute kidney injury in older adults.

Ren Fail 2020 Nov;42(1):1127-1134

Division of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatrics Institute, Guangzhou, China.

Few epidemiologic studies on acute kidney injury (AKI) have focused on the older adult population. This study investigated the clinical features, risk factors, and clinical burden in this population. A retrospective observational study was performed with the clinical data of inpatients at Guangdong Geriatrics Institute from 1 August 2012, to 31 December 2016. AKI was classified into community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), and the risk factors for AKI were ranked by weight. The relationships between AKI and adverse outcomes during hospitalization were analyzed using univariate and multivariate logistic regression. In total, 6126 patients were enrolled, and 1704 patients developed AKI (27.8%): 6.3% had CA-AKI, and 21.5% had HA-AKI. In total, 1425 (23.3%), 202 (3.3%), and 77 (1.3%) patients had stage 1, 2 and 3 AKI, respectively. Age, dementia, moderate/severe renal disease, moderate/severe liver disease, metastatic solid tumor, female sex, congestive heart failure, chronic pulmonary disease, diabetes mellitus with chronic complications, non-metastatic tumor and lymphoma were independent risk factors for HA-AKI. The first five were also independent risk factors for CA-AKI. After multiple adjustment, AKI was associated with intensive care admission (CA-AKI: OR 5.688, 95% CI 3.122-10.361; HA-AKI: OR 4.704, 95% CI 3.023-7.298) and in-hospital mortality (CA-AKI: OR 5.073, 95% CI 2.447-10.517; HA-AKI: OR 13.198, 95% CI 8.133-21.419). AKI occurs in >25% of older adults in the geriatric ward. In addition to traditional risk factors, dementia and tumors were risk factors for AKI in older adults. AKI is closely related to a poor prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0886022X.2020.1843491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671701PMC
November 2020

"Response to the letter to the editor "Concerns regarding the potentially causal role of FANCA heterozygous variants in human primary ovarian insufficiency".

Hum Genet 2021 04 11;140(4):695-697. Epub 2020 Nov 11.

Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai, 200011, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00439-020-02233-4DOI Listing
April 2021

Demethylation of the RB1 promoter concomitant with reactivation of TET2 and TET3 impairs gastric carcinogenesis in K19-Wnt1/C2mE transgenic mice.

Life Sci 2020 Dec 12;263:118580. Epub 2020 Oct 12.

Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, China. Electronic address:

Aberrant methylation of promoter CpG islands (CGIs) can inactivate the expression of many tumor suppressor genes and play an important role in the carcinogenesis of gastric cancer. The tumor suppressor gene RB1, which encodes a cell cycle regulator, is hypermethylated and downregulated in multiple kinds of cancer. Activation of RB1 expression through DNA demethylation is a potential strategy for the treatment of gastric cancer. Herein, we found that the methylation status of the RB1 promoter was negatively related to the development of gastric tumors, while its expression was positively correlated with TET2 and TET3 expression. Further reactivation of RB1 expression by curcumin could inhibit gastric cell viability and carcinogenesis both in vitro and in vivo. Molecular docking and other studies confirmed that curcumin could bind to and upregulate the expression of TET2 and TET3 with hydrogen bonds and arene-H bonds, suggesting that demethylation of RB1 was attributed to reactivation of the demethylation enzymes TET2 and TET3 after curcumin treatment. Thus, our findings reveal a promising therapeutic strategy for gastric cancer prevention and treatment through RB1 demethylation and reactivation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2020.118580DOI Listing
December 2020

A heterozygous hypomorphic mutation of Fanca causes impaired follicle development and subfertility in female mice.

Mol Genet Genomics 2021 Jan 6;296(1):103-112. Epub 2020 Oct 6.

Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai, 200011, China.

Reduced fertility is a common clinical feature of the individuals with Fanconi anemia (FA), a rare autosomal recessive disorder due to deficiency in FA pathway during DNA repair. Our previous study reported that the heterozygous pathogenic variants in FANCA (Fanconi anemia complementation group A) induced premature ovarian insufficiency (POI). However, the genotype-phenotype correlation in POI caused by FANCA variants remains considerably uncertain. Herein, a heterozygous non-frameshift Fanca-mutated mouse strain (Fanca) carrying a 9-bp deletion (c.3581del9, p.QEA1194-1196del) was generated. The mutant mice exhibited slightly decreased Fanca protein level in ovaries, suggesting the non-frameshift deletion mutant is hypomorphic. Female fertility test showed decreased number of litters, litter sizes and prolonged litter interval time in the female Fanca mice compared to wild-type mice. Follicle counting revealed a consistent decreasing pattern of follicle numbers in Fanca females compared to that in wild-type mice with aging. Furthermore, embryonic fibroblasts of Fanca mice were hyper-responsive to Mitomycin C in vitro, demonstrating a partial loss of function of this hypomorphic Fanca mutant in DNA repair. Collectively, our experimental observations suggest that the hypomorphic Fanca allele is sufficient to reduce female fertility in mice, providing new insights into the genetic counseling of FANCA variants in subfertile women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00438-020-01730-5DOI Listing
January 2021

Coexpression of Matrix Metalloproteinase-7 and Tissue Inhibitor of Metalloproteinase-1 as a Prognostic Biomarker in Gastric Cancer.

Dis Markers 2020 14;2020:8831466. Epub 2020 Sep 14.

Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin Province, China.

Background: Degradation of the extracellular matrix (ECM), an essential step in tumour invasion and metastasis, is mainly dependent on the activities of both matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). This study aimed to explore whether expression of MMP-7 and TIMP-1 alone and in combination can be used as a prognostic marker for gastric cancer (GC).

Method: A total of 285 patients who had undergone tumourectomy for GC were included. Gastric tumour tissues were stained immunohistochemically to evaluate expression of MMP-7 and TIMP-1.

Results: Expression of MMP-7 was associated with tumour N stage and neural invasion. Multivariate Cox regression analysis suggested that expression of MMP-7 or TIMP-1 alone cannot serve as an indicator of patient prognosis; however, coexpression of MMP-7 and TIMP-1 was found to be an independent predictive factor of overall survival in patients with GC (HR = 1.74, 95% CI: 1.08-2.80). The results of stratified analysis also showed that the predictive value of MMP-7 and TIMP-1 coexpression was stronger in patients with N3 stage disease and not receiving chemotherapy.

Conclusions: In conclusion, coexpression of MMP-7 and its inhibitor TIMP-1 in gastric tumour tissues is a potential prognostic marker for GC. Greater knowledge of protein expression will lead to new paradigms and possible improvements in therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8831466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509560PMC
September 2020

Regulation of glutathione-dependent antioxidant defense system of grass carp Ctenopharyngodon idella under the combined stress of mercury and temperature.

Environ Sci Pollut Res Int 2021 Jan 26;28(2):1689-1696. Epub 2020 Aug 26.

Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, 430223, China.

In this study, we investigated the combined effects of temperatures fluencies and mercury (Hg) on glutathione-dependent antioxidant system in fish, by measuring the oxidative stress indicator (LPO, lipid peroxidation) and the parameters involved in the glutathione-related antioxidant defense system (GPx, glutathione peroxidase; GR, glutathione reductase; GST, glutathione S-transferase; GSH, reduced glutathione), as well as the expression of related genes in grass carp, Ctenopharyngodon idella. Fish (45.37 ± 3.58 g) were exposed to 10 test groups, e.g., 15 °C with/without Hg, 20 °C with/without Hg, 25 °C with/without Hg, 30 °C with/without Hg, 35 °C with/without Hg for 4 weeks. Three-way ANOVA was used to analyze the correlation between the measured parameters and experimental conditions (water temperature, Hg exposure, exposure time, and their interactions.). Our results show that there is no interaction between mercury and low temperature, but the combined effect at high temperature has been confirmed, which indicated the glutathione-dependent enzyme system in grass carp has a complex regulatory mechanism with temperature fluctuations. In the actual field monitoring, it is necessary to consider the impact of extreme temperature on the toxicity of pollutants in the aquatic ecosystem.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-10587-5DOI Listing
January 2021

Rare deleterious BUB1B variants induce premature ovarian insufficiency and early menopause.

Hum Mol Genet 2020 09;29(16):2698-2707

Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China.

Losing of ovarian functions prior to natural menopause age causes female infertility and early menopause. Premature ovarian insufficiency (POI) is defined as the loss of ovarian activity before 40 years of age. Known genetic causes account for 25-30% of POI cases, demonstrating the high genetic heterogeneity of POI and the necessity for further genetic explorations. Here we conducted genetic analyses using whole-exome sequencing in a Chinese non-syndromic POI family with the affected mother and at least four affected daughters. Intriguingly, a rare missense variant of BUB1B c.273A>T (p.Gln91His) was shared by all the cases in this family. Furthermore, our replication study using targeted sequencing revealed a novel stop-gain variant of BUB1B c.1509T>A (p.Cys503*) in one of 200 sporadic POI cases. Both heterozygous BUB1B variants were evaluated to be deleterious by multiple in silico tools. BUB1B encodes BUBR1, a crucial spindle assembly checkpoint component involved in cell division. BUBR1 insufficiency may induce vulnerability to oxidative stress. Therefore, we generated a mouse model with a loss-of-function mutant of Bub1b, and also employed D-galactose-induced aging assays for functional investigations. Notably, Bub1b+/- female mice presented late-onset subfertility, and they were more sensitive to oxidative stress than wild-type female controls, mimicking the clinical phenotypes of POI cases affected by deleterious BUB1B variants. Our findings in human cases and mouse models consistently suggest, for the first time, that heterozygous deleterious variants of BUB1B are involved in late-onset POI and related disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddaa153DOI Listing
September 2020

A novel supplemental maneuver to predict fluid responsiveness in critically ill patients: blood pump-out test performed before renal replacement therapy.

Ann Transl Med 2020 Jun;8(12):786

Department of Cardiology, Guangdong Provincial People's Hospital/Guangdong Academy of Medical Sciences/Guangdong Provincial Cardiovascular Institute, Guangzhou 510080, China.

Background: Passive leg raising (PLR) test, known as reversible increasing venous return, could predict hemodynamic intolerance induced by renal replacement therapy (RRT). Oppositely, blood drainage procedure at the start of RRT cuts down intravascular capacity which is likely to have changes in fluid responsiveness has been little studied. Our study aimed to determine whether blood drainage procedure, defined as blood pump-out test, which is essential and inevitable at the beginning of RRT could predict fluid responsiveness in critically ill patients.

Methods: Critically ill patients underwent RRT with pulse contour analysis were included. During PLR, an increase of cardiac output (CO, derived from pulse contour analysis) ≥10% compared to baseline was considered responders as the gold standard. BPT was performed at a constant speed after the increase of CO induced by PLR returned to baseline and the maximal of CO within 2 minutes was recorded. Then area under ROC curve of CO changes to identify responders from non-responders in BPT was calculated based on the results from PLR test.

Results: Sixty-five patients were enrolled. Thirty-one/sixty-five patients (47.7%) were considered responders during PLR. And after analysis by ROC curve, a decrease in CO greater than 11.0% during BPT predicted fluid responsiveness with 70.9% sensitivity and 76.5% specificity. The highest area under the curve (AUC) was found for an increase in CO (0.74±0.06; 95% CI: 0.62 to 0.84).

Conclusions: BPT could be a supplement to PLR, providing a novel maneuver to predict fluid responsiveness in critically ill patients underwent RRT. (Trial registration: ChiCTR-DDD-17010534). Registered 30 January 2017 (retrospective registration).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2020.04.56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333114PMC
June 2020

Chitosan derivatives as green corrosion inhibitors for P110 steel in a carbon dioxide environment.

Colloids Surf B Biointerfaces 2020 Oct 30;194:111150. Epub 2020 May 30.

China Oilfield Services Limited, Beijing 101149, PR China. Electronic address:

Two chitosan derivatives were synthesized for the first time as green corrosion inhibitors for the carbon dioxide corrosion of P110 steel. The structures of the synthesized products were characterized by infrared spectroscopy. Electrochemical and weight-loss experiments were used to test the effect of corrosion inhibitors, while SEM-EDS, AFM and other analysis methods were used to study the protection mechanism of corrosion inhibitors. The experimental results show that synthetic corrosion inhibitors CHC and CAHC are all good corrosion inhibitors for carbon dioxide corrosion inhibition. Both chitosan derivatives can form hydrophobic protective films on the metal surface. For inhibition performance, CAHC is better than CHC, which is the same conclusion drawn from practical experiments and quantum chemical calculations. Investigation into chitosan inhibitors has opened up a new area of research of environmentally friendly corrosion inhibitors, which is of great significance for metal protection without toxicity and side effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.colsurfb.2020.111150DOI Listing
October 2020

The impact of coexisting diabetes mellitus on clinical outcomes in patients with idiopathic membranous nephropathy: a retrospective observational study.

BMC Nephrol 2020 06 12;21(1):224. Epub 2020 Jun 12.

Division of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.106 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.

Background: Idiopathic membranous nephropathy (IMN) is frequently coexisted with diabetes mellitus (DM). Few researches investigate clinical outcomes in IMN patients coexisting diabetes mellitus (DM), including remission rates, renal survival and complications. Concurrent DM also pose therapeutic challenges to IMN patients due to the influence of glucocorticoids and immunosuppressant on metabolic disorders. We performed this study to investigate the impact of DM on clinical outcomes in IMN and the influence of therapeutic regime on metabolic parameters in diabetic IMN patients.

Methods: Two hundred and six adult hospitalized patients diagnosed with biopsy-proven IMN were retrospectively studied, including 42 patients coexisted with DM. Clinical outcomes including remission rates, renal outcome and complications were compared between groups. Impact of cyclophosphamide and ciclosporin on metabolism and complications were analyzed in IMN patients coexisting DM.

Results: IMN patients coexisted with DM were presented with advanced age, lower level of eGFR and hemoglobin. Patients coexisted with DM experienced worse renal function deterioration and higher incidence of infection. COX regression analysis showed that DM was an independent risk factor for renal function deterioration in IMN patients. There was no significant difference in remission rates and incidence of venous thromboembolism between two groups. Further exploration on the impact of therapeutic regimens on complications and metabolism showed that cyclophosphamide and ciclosporin had no significant difference in incidence of complications including infection and venous thromboembolism, and posed comparable influences on blood glucose, uric acid and blood lipids in IMN patients coexisted with DM.

Conclusion: Coexisting DM was an independent risk factor for renal function deterioration in IMN patients but did not influence the remission of proteinuria. Glucocorticoids in combination with cyclophosphamide or ciclosporine had similar impact on complications and metabolic index including blood glucose, uric acid and blood lipids in IMN patients coexisted with DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-020-01878-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291707PMC
June 2020

Metabolic syndrome and concomitant diabetes mellitus are associated with higher risk of cardiovascular comorbidity in patients with primary glomerular diseases: A retrospective observational study.

Clin Cardiol 2020 Sep 29;43(9):949-956. Epub 2020 May 29.

Division of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: Metabolic syndrome (MS) and diabetes mellitus (DM) are risk factors for cardiovascular diseases in general population. However, there was a paucity of studies investigating their impact in primary glomerular diseases (PGD).

Hypothesis: MS and concomitant DM are associated with higher risk of cardiovascular comorbidity in PGD.

Methods: In a retrospective observational design, we analyzed 3622 hospitalized adult PGD patients and compared the prevalence of cardiovascular comorbidity in non-MS, MS with and without DM. Risk factors for cardiovascular comorbidity were identified using univariate and multivariate logistic regression.

Results: Among 3622 PGD patients, 308 (8.5%) cases accompanied with MS, including 180 (5.0%) patients with DM and 128 (3.5%) without DM. One hundred and sixty four (4.5%) cases coexisted with cardiovascular comorbidity. Patients with MS and concomitant DM exhibited a higher prevalence of cardiovascular comorbidity than those without MS stratified by estimated glomerular filtration rate and pathological types. Logistic regression showed that MS and concomitant DM (OR: 2.496, 95% CI: 1.600-3.894, P < .001), older age (OR: 1.060, 95% CI: 1.047-1.074, P < .001), male (OR: 1.536, 95% CI: 1.072-2.200, P = .019), higher level of serum ti (OR: 1.002, 95% CI: 1.001-1.003, P < .001), hyperuricemia (OR: 1.901, 95% CI: 1.327-2.725, P < .001), idiopathic membranous nephropathy (OR: 2.874, 95% CI: 1.244-6.640, P < .001) and focal segmental glomerulosclerosis (OR: 2.906, 95% CI: 1.147-7.358, P < .001) were independently associated with a higher risk for cardiovascular comorbidity.

Conclusions: In PGD patients, MS and concomitant DM are associated with an increased risk for cardiovascular comorbidity. More evidence for the causal link between MS/DM and cardiovascular outcomes is needed to be clarified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clc.23388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101350PMC
September 2020

Feasibility of coding-based Charlson comorbidity index for hospitalized patients in China, a representative developing country.

BMC Health Serv Res 2020 May 18;20(1):432. Epub 2020 May 18.

Division of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.106 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.

Background: The Charlson Comorbidity Index (CCI) can be automatically calculated from the International Classification of Disease (ICD) code. However, the feasibility of this transformation has not been acknowledged, particularly in hospitals without a qualified ICD coding system. Here, we investigated the utility of coding-based CCI in China.

Methods: A multi-center, population-based, retrospective observational study was conducted, using a dataset incorporating 2,464,395 adult subjects from 15 hospitals. CCI was calculated using both ICD-10-based and diagnosis-based method, according to the transformation rule reported previously and to the literal description from discharge diagnosis, respectively. A κ coefficient of variation was used as a measure of agreement between the above two methods for each hospital. The discriminative abilities of the two methods were compared using the receiver-of-operating characteristic curve (ROC) for prediction of in-hospital mortality.

Results: Total agreement between the ICD-based and diagnosis-based CCI for each index ranged from 86.1 to 100%, with κ coefficients from 0.210 [95% confidence interval (CI) 0.208-0.212] to 0.932 (95% CI 0.924-0.940). None of the 19 indices of CCI had a κ coefficient > 0.75 in all the hospitals included for study. The area under the curve of ROC for in-hospital mortality of all 15 hospitals was significantly lower for ICD-based than diagnosis-based CCI [0.735 (0.732, 0.739) vs 0.760 (0.757, 0.764)], indicative of more limited discriminative ability of the ICD-based calculation.

Conclusions: CCI calculated using ICD-10 coding did not agree with diagnosis-based CCI. ICD-based CCI displayed diminished discrimination performance in terms of in-hospital mortality, indicating that this method is not promising for CCI scoring in China under the present circumstances.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12913-020-05273-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236530PMC
May 2020

Decreased B1 and B2 Lymphocytes Are Associated With Mortality in Elderly Patients With Chronic Kidney Diseases.

Front Med (Lausanne) 2020 20;7:75. Epub 2020 Mar 20.

Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, China.

Loss of renal function is associated with immune deficiency; however, few studies have addressed the role of B lymphocytes in elderly patients with chronic kidney disease (CKD). In this study, we examined the distribution and the relationship of the B lymphocyte subpopulation with clinical outcomes in elderly CKD patients. In this study, a total of 380 patients (312 CKD patients and 68 non-CKD controls) were recruited. Venous blood samples were analyzed by flow cytometry to determine the following B cell subsets: total B cells (CD19+), innate B1 cells (CD19+CD5+), and conventional B2 cells (CD19+CD5-). Correlations between the B cell subsets with clinical features and patient prognosis were analyzed. A total of 380 patients (mean age 82.29 ± 6.22 years, 76.3% male) were included. The median follow-up time was 37.0 months (range, 1-109 months); 109 (28.7%) patients died. The main causes of death were infections (59.6%) and cardiovascular diseases (22.9%). Correlation analysis showed that levels of serum creatinine (SCr), blood urea nitrogen (BUN), and CKD were negatively associated with B1 cells. However, lymphocytes, T lymphocytes, and estimated glomerular filtration rate (eGFR) were positively correlated with B1 cells (all < 0.05). B2 cells were negatively associated with age, SCr, cystatin C, BUN, and CKD, and were positively correlated with hemoglobin, lymphocytes, T lymphocytes, NK cells, and eGFR (all < 0.05). Patient survival was significantly better in patients with B cells > 0.05 × 10/L, B1 cells > 0.02 × 10/L, and B2 cells > 0.04 × 10/L. Multivariate Cox regression analysis showed that B1 cells > 0.02 × 10/L [hazard ratio (HR) = 0.502, 95% confidence interval (CI): 0.297-0.851, = 0.010] and B2 cells > 0.04 × 10/L (HR = 0.536, 95% CI: 0.319-0.901, = 0.019) were independent protective factors for all-cause mortality. Our results showed that B1 and B2 cells exhibited a significantly negative correlation with the progression of CKD in elderly patients. Moreover, B1 and B2 cells were independent prognostic factors for survival, which indicates that the decrease in B cells may be associated with the progression of kidney diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2020.00075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098909PMC
March 2020