2.Clinical outcomes of acute stroke thrombolysis in neurologist and non-neurologist centres – A comparative study in Malaysia
Sin Hong Chew ; Irene Looi ; Kar Keong Neoh ; Joshua Ooi ; Wee-Kooi Cheah ; Zariah Binti Abdul Aziz
The Medical Journal of Malaysia 2021;76(1):12-16
Acute ischaemic stroke (AIS) is a devastating disease and one
of the leading causes of disabilities worldwide. From 2010 to
2014, the incidence of stroke in Malaysia had increased from
65 to 187 per 100,000 population.1 Thrombolytic therapy
with intravenous recombinant tissue plasminogen activator
(rtPA) within 4.5 hours of symptom onset has been shown to
be an effective treatment for AIS. Patients who receive
thrombolysis are 30 percent more likely to achieve excellent
functional outcome (modified Rankin scale of 0 to 1) at 3
months compared to placebo.2
Unfortunately, the delivery of stroke thrombolysis service in
Malaysia is often limited by the availability of neurologists.
To date, the ratio of neurologists capable of performing
thrombolysis serving in public hospitals to the Malaysian
population is 1:1.4 million.3 To counteract this disparity
and to cope with the increasing stroke burden in Malaysia,
there has been an advocacy for greater involvement of
non-neurologists, i.e., general and emergency physicians
in performing of stroke thrombolysis.4 Emerging data based
on short term outcomes appear to support this notion.
Based on a 2015 single center study on 49 AIS patients in
Australia, A. Lee et al., reported that there was no significant
difference in door to needle time, rates of symptomatic
intracranial bleeding (SICH), and mortality between patients
thrombolysed by neurologists versus stroke physicians.5
In
2016, a larger multicentre study in Thailand reported that
patients thrombolysed in hospitals without neurologists had
lower National Institute of Health Stroke Scale (NIHSS) scores
at discharge and lower inpatient mortality rate compared to
patients treated in neurologist hospitals.6 Based on these
short term outcomes, both studies suggest that nonneurologists are able to thrombolyse AIS patients safely and
effectively. Data comparing long term functional outcomes
in thrombolysis prescribed by neurologists and nonneurologists are still very limited.
The primary objective of this study was to evaluate and
compare the 3-month functional outcomes of thrombolytic
therapy between hospitals with and without on-site
neurologists. The secondary objective was to assess the doorto-needle time and complication rates of thrombolysis service
in both hospitals
3.Single-cell analysis of angiotensin-converting enzyme II expression in human kidneys and bladders reveals a potential route of 2019 novel coronavirus infection.
Wei LIN ; Jue FAN ; Long-Fei HU ; Yan ZHANG ; Joshua D OOI ; Ting MENG ; Peng JIN ; Xiang DING ; Long-Kai PENG ; Lei SONG ; Rong TANG ; Zhou XIAO ; Xiang AO ; Xiang-Cheng XIAO ; Qiao-Ling ZHOU ; Ping XIAO ; Yong ZHONG
Chinese Medical Journal 2021;134(8):935-943
BACKGROUND:
Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.
METHODS:
We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.
RESULTS:
Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression.
CONCLUSION
This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.
Angiotensin-Converting Enzyme 2/metabolism*
;
COVID-19
;
Gene Expression
;
Humans
;
Kidney/metabolism*
;
SARS-CoV-2
;
Sequence Analysis, RNA
;
Single-Cell Analysis
;
Urinary Bladder/metabolism*
4.High levels of platelet-to-lymphocyte ratio may predict reduced risk of end stage of renal disease in Chinese patients with MPO-ANCA associated vasculitis.
Li HUANG ; Chanjuan SHEN ; Yong ZHONG ; Joshua D OOI ; Peter J EGGENHUIZEN ; Ya'ou ZHOU ; Jinbiao CHEN ; Ting WU ; Ting MENG ; Zhou XIAO ; Wei LIN ; Rong TANG ; Xiang AO ; Xiangcheng XIAO ; Qiaoling ZHOU ; Ping XIAO
Journal of Central South University(Medical Sciences) 2022;47(2):211-218
OBJECTIVES:
Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality.
METHODS:
The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality.
RESULTS:
A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801).
CONCLUSIONS
PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis*
;
Antibodies, Antineutrophil Cytoplasmic/analysis*
;
China/epidemiology*
;
Humans
;
Kidney Failure, Chronic/complications*
;
Lymphocytes
;
Peroxidase
;
Retrospective Studies
5.Single-cell RNA sequencing reveals the transcriptomic landscape of kidneys in patients with ischemic acute kidney injury.
Rong TANG ; Peng JIN ; Chanjuan SHEN ; Wei LIN ; Leilin YU ; Xueling HU ; Ting MENG ; Linlin ZHANG ; Ling PENG ; Xiangcheng XIAO ; Peter EGGENHUIZEN ; Joshua D OOI ; Xueqin WU ; Xiang DING ; Yong ZHONG
Chinese Medical Journal 2023;136(10):1177-1187
BACKGROUND:
Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys.
METHODS:
In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining.
RESULTS:
15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI.
CONCLUSION
Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
Humans
;
Mice
;
Animals
;
Transcriptome/genetics*
;
Ligands
;
Kidney/metabolism*
;
Acute Kidney Injury/metabolism*
;
Ischemia/metabolism*
;
Reperfusion Injury/metabolism*
;
Sequence Analysis, RNA
;
Adaptor Proteins, Signal Transducing/metabolism*
;
Tumor Suppressor Proteins/metabolism*