Differences Between Cystatin C- and Creatinine-Based Estimated Glomerular Filtration Rate and Association with Mortality and Cardiovascular Events: Results from Three Cohorts of Adults with Diabetes.

BACKGROUND AND HYPOTHESIS: To explore the association between the differences between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) with the risk of mortality and cardiovascular (CV) events in individuals with diabetes. METHODS: Three prospective cohorts analyzed data of adults with diabetes from the Incident, Development, and Prognosis of Diabetic Kidney Disease (INDEED) study (2016-2017 to 2020) in China, the National Health, Nutrition Examination Survey (NHANES, 1999-2004 to 2019) in the United States, and UK Biobank (UKB, 2006-2010 to 2022). Baseline eGFRdiff was calculated using both absolute difference between cystatin C- and creatinine-based calculations (eGFRabdiff), and the ratio between them (eGFRrediff). Cox proportional hazards regression models were used to investigate the association between eGFRdiff and outcomes including all-cause mortality and incident CV events. RESULTS: A total of 8,129 individuals from the INDEED (aged 60.7±10.0 years), 1,634 from the NHANES (aged 62.5±14.4 years), and 29,358 from the UKB (aged 59.4±7.3 years;) were included. At baseline, 43.6%, 32.4% and 42.1% of participants in the INDEED, NHANES and UKB had an eGFRabdiff value ≥15 ml/min/1.73 m2. During a median follow-up of 3.8 years for the INDEED, 15.2 years for the NHANES, and 13.5 years for the UKB, a total of 430, 936 and 6143 deaths and a total of 481, 183 and 5583 CV events occurred, respectively. Each 1-standard deviation higher baseline eGFRabdiff was independently associated with a lower risk of all-cause mortality and CV events, with hazard ratios (HRs) of 0.77 and 0.82 in the INDEED, 0.70 and 0.68 in the NHANES, and 0.66 and 0.78 in the UKB. Similar results were observed for eGFRrediff. CONCLUSIONS: eGFRdiff represents a marker of adverse events for diabetes among general population. Monitoring both eGFRcys and eGFRcr yields additional prognostic information and has clinical utility in identifying high-risk individuals for mortality and CV events.

Surgical procedure and recurrence of upper urinary tract stone: a national-wide study based on hospitalized patients.

PURPOSE: This study aimed to investigate the influence of surgical intervention on recurrence risk of upper urinary tract stone and compare the medical burden of various surgical procedures. METHODS: This study analyzed data from patients with upper urinary tract stone extracted from a national database of hospitalized patients in China, from January 2013 to December 2018. Surgical recurrence was defined as patients experience surgical procedures for upper urinary tract stone again with a time interval over 90 days. Associations of surgical procedures with surgical recurrence were evaluated by Cox regression. RESULTS: In total, 556,217 patients with upper urinary tract stone were included in the present analysis. The mean age of the population was 49.9 ± 13.1 years and 64.1% were men. During a median follow-up of 2.7 years (IQR 1.5-4.0 years), 23,012 patients (4.1%) had surgical recurrence with an incidence rate of 14.9 per 1000 person-years. Compared to patients receiving open surgery, ESWL (HR, 1.59; 95% CI 1.49-1.70), URS (HR, 1.38; 95% CI 1.31-1.45), and PCNL (HR, 1.11; 95% CI 1.06-1.18) showed a greater risk for surgical recurrence. Patients receiving ESWL had the shortest hospital stay length and the lowest cost among the 4 procedures. CONCLUSIONS: Compared with open surgery, ESWL, URS, and PCNL are associated with higher risks of surgical recurrence for upper urinary tract stone, while ESWL showed the least medical burden including both expenditure and hospital stay length. How to keep balance of intervention efficacy and medical expenditure is an important issue to be weighed cautiously in clinic practice and studied more in the future.

Ambient PM2.5 components and prevalence of chronic kidney disease: a nationwide cross-sectional survey in China.

OBJECTIVES: Chronic kidney disease (CKD) is a global public health concern, and accumulating evidence has indicated that air pollution increases the odds of CKD. However, a limited number of studies have examined the long-term effects of ambient fine particulate matter (PM2.5) components on the risk of CKD among general population; thus, major knowledge gaps remain. METHODS: Using data from a nationwide representative cross-sectional survey in China and a validated PM2.5 composition dataset, we established generalized linear models to quantify the association between five major components of PM2.5 and CKD prevalence. RESULTS: There were significant associations between long-term exposure to three PM2.5 components [including black carbon (BC), sulfate (SO42-), organic matter (OM)] and increased odds of CKD prevalence. Along with an interquartile range (IQR) increment in BC (3.3 µg/m3), SO42- (9.7 µg/m3), and OM (16.2 µg/m3) at a 4-year moving average, the odds ratios (ORs) for CKD prevalence were 1.28 (95% CI 1.07, 1.54), 1.23 (95% CI 1.03, 1.45), and 1.23 (95% CI 1.02, 1.47), respectively. We did not detect any significant association of the other two PM2.5 components [nitrate (NO3-) or ammonium (NH4+)] with CKD prevalence. Stratified analyses revealed no differences (P ≥ 0.05) in the effect estimates of subgroups based on administrative region, sex, age, and other demographic characteristics. For instance, along with an IQR increment in BC at a 4-year moving average, the ORs of CKD prevalence among males and females were 1.30 (95% CI 0.98, 1.73) and 1.29 (95% CI 1.01, 1.65), respectively. The odds of CKD were generally higher with increasing PM2.5 composition concentration. CONCLUSIONS: Our study demonstrated that long-term exposure to specific PM2.5 components including BC, SO42-, and OM increased CKD risk in the general population. This study could provide new insights into source-directed PM2.5 control and CKD prevention.

A modified renal risk score for Chinese patients with antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: The renal risk score (RRS) is a useful tool to predict end-stage renal disease (ESRD) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to validate the predictive performance of RRS and to further modify this model in Chinese AAV patients. METHODS: Two hundred and seventy-two patients diagnosed with AAV confirmed by renal biopsies were retrospectively enrolled from a single center. The RRS was calculated based on 3 categorical variables, i.e., the proportion of normal glomeruli, the proportion of interstitial fibrosis and tubular atrophy (IF/TA), and eGFR at biopsy, classifying these patients into low-, medium-, and high-risk groups. In addition, a modified model was developed based on the RRS and was further validated in another independent cohort of 117 AAV patients. The predictive performance of each model was evaluated according to discrimination and calibration. RESULTS: Patients were classified by the RRS into low- (26.5%), medium- (46.7%), and high-risk (26.8%) groups, with 120-month renal survival rates of 93.3%, 57.2%, and 18.4%, respectively (P < 0.001). The RRS showed good discrimination but less satisfactory calibration. Therefore, a modified model with improved discrimination and calibration was developed in Chinese AAV patients, with eGFR, proportion of normal glomeruli (both as continuous variables), and IF/TA (< 25%, 25-50%, > 50%) included. Internal and external validation of the modified model were performed. Finally, an online risk prediction tool was developed based on the modified model. CONCLUSIONS: The RRS was an independent predictor of ESRD of AAV patients. The modified model could predict the probability of ESRD for AAV patients with improved performance in Chinese AAV patients.

High-Quality Axions in a Class of Chiral U(1) Gauge Theories.

We show that there are many candidates for the quintessence and/or the QCD axions in a class of chiral U(1) gauge theories. Their qualities are high enough to serve as the dark energy and/or to solve the strong CP problem. Interestingly, the high quality of axion is guaranteed by the gauged U(1) and Z_{2N} symmetries and hence free from the nonperturbative quantum gravity corrections. Furthermore, our mechanism can be easily applied to the Fuzzy dark matter axion scenarios.

P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model.

BACKGROUND: The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. METHODS: We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. RESULTS: In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. CONCLUSION: P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract.

Genome-Wide Identification of Proline Transporter Gene Family in Non-Heading Chinese Cabbage and Functional Analysis of BchProT1 under Heat Stress.

Non-heading Chinese cabbage prefers cool temperatures, and heat stress has become a major factor for reduced yield. The proline transporter protein (ProT) is highly selective for proline transport, contributing to the heat tolerance of non-heading Chinese cabbage. However, there has been no systematic study on the identification and potential functions of the ProT gene family in response to heat stress in non-heading Chinese cabbage. We identified six BchProT genes containing 11-12 transmembrane helices characteristic of membrane proteins through whole-genome sequencing. These genes diverged into three evolutionary branches and exhibited similarity in motifs and intron/exon numbers. Segmental duplication is the primary driving force for the amplification of BchProT. Notably, many stress-related elements have been identified in the promoters of BchProT using cis-acting element analysis. The expression level of BchProT6 was the highest in petioles, and the expression level of BchProT1 was the highest under high-temperature stress. Subcellular localization indicated their function at cell membranes. Heterologous expression of BchProT1 in Arabidopsis plants increased proline transport synthesis under heat-stress conditions. This study provides valuable information for exploring the molecular mechanisms underlying heat tolerance mediated by members of the BchProT family.

Visual function changes of dysthyroid optic neuropathy and ROC curve analysis for early diagnostic indicators. / ç”²çŠ¶è ºåŠŸèƒ½éšœç¢æ€§è§†ç¥žç»ç— å˜çš„è§†è§‰åŠŸèƒ½æ”¹å˜åŠæ—©æœŸè¯Šæ–­æŒ‡æ ‡çš„ROC曲线分析.

OBJECTIVES: Dysthyroid optic neuropathy (DON) is a class of diseases that makes seriously endanger to the vision of patients with thyroid-associated ophthalmopathy. This study aims to observe the visual function changes in patients with DON, and to evaluate the diagnostic value of indicators diagnosing DON. METHODS: A retrospective study was conducted on 98 eyes of 49 patients with dysthyroid optic neuropathy (DON) who were treated in Xiangya Hospital of Central South University from January 2017 to December 2019. All patients were received the examination of best corrected visual acuity (BCVA), Humphrey visual field, visual evoked potential (VEP), and contrast sensitivity. Ninety-eight eyes were divided into a DON group (45 eyes) and a non-DON group (53 eyes). T-test was used to compare the related indicators between the 2 groups. The sensitivity and specificity of each indicator were analyzed by receiver operating characteristic (ROC) curve. RESULTS: The BCVA and visual field index (VFI) of the DON group were significantly lower than those of the non-DON group (all P<0.05). The mean deviation (MD) and pattern standard deviation (PSD) of the DON group were significantly higher than those of the non-DON group (all P<0.05). The low frequency contrast sensitivity (CSL), medium frequency contrast sensitivity (CSM), and high frequency contrast sensitivity (CSH) of the DON group were significantly lower than those of the non-DON group (all P<0.05), with CSH being particularly prominent. Compared with the non-DON group, at spatial frequencies of 15°, 30°, and 60°, the amplitude of N135 wave was significantly reduced, and the latency of N75 wave, P100 wave, and N135 wave was significantly prolonged in the DON group (all P<0.05); at spatial frequencies of 15° and 30°, the amplitude of P100 wave was significantly reduced in the DON group (P<0.05). The ROC curve analysis results showed that the area under the curve (AUC) of VFI, CSL, CSM, CSH and 15° P100 amplitude diagnosing DON were 0.812, 0.841, 0.880, 0.784, and 0.791, respectively, with CSM possessing the highest sensitivity and specificity. CONCLUSIONS: The visual function of patients with DON is decreased. VFI, contrast sensitivity of low, medium, and high frequency, and 15° P100 wave amplitude might be effective indicators for early diagnosis of DON.

Continued P2X7 activation leads to mitochondrial fission and compromising microglial phagocytosis after subarachnoid haemorrhage.

Subarachnoid haemorrhage (SAH) has a high rate of disability and mortality. Extremely damaging molecules, including adenosine triphosphate (ATP), are released from extravasated red blood cells and nerve cells, which activate microglia and induce sterile tissue injury and organ dysfunction. P2X purinoceptor 7 (P2X7) is one of the most important purine receptors on the microglial surface and is involved in the proinflammatory activation of microglia. While P2X7 can also affect microglial phagocytosis, the mechanism is not clear. Here, we demonstrated that microglial phagocytosis is progressively impaired under continued BzATP exposure and P2X7 activation. Furthermore, we found that P2X7 activation leads to increased intracellular Ca2+ levels and activates Calcineurin, which dephosphorylates dynamin-related protein 1 (DRP1) S637. The dephosphorylation of DRP1 at S637 leads to increased mitochondrial fission and decreased mitochondrial function, which may be responsible for the decreased microglial phagocytosis. Finally, we pharmacologically inhibited P2X7 activation in mice, which resulted in rescue of mitochondrial function and decreased microglial proliferation, but improved phagocytosis after SAH. Our study confirmed that P2X7 activation after SAH leads to the impairment of microglial phagocytosis through mitochondrial fission and verified that P2X7 inhibition restores microglial phagocytosis both in vitro and in vivo.

Characterizing Intra-Tumor and Inter-Tumor Variability of Immune Cell Infiltrates in Murine Syngeneic Tumors.

Murine tumors are indispensable model systems in preclinical immuno-oncology research. While immunologic heterogeneity is well-known to be an important factor that can influence treatment outcome, there is a severe paucity of data concerning the nature of this heterogeneity in murine tumor models. Using serial sectioning methodology combined with IHC analysis and whole-slide image analysis, the depth-dependent variation in immune-cell abundance in tumor specimens was investigated at single-cell resolution. Specifically, intra- and intertumor variability in cell density of nine immune-cell biomarkers was quantified in multiple murine tumor models. The analysis showed that intertumor variability was typically the dominant source of variation in measurements of immune-cell densities. Statistical power analysis revealed the effect of group size and variance in immune-cell density on the predictive power of detecting a statistically meaningful fold-change in immune-cell density. Intertumor variability in the ratio of immune-cell densities showed distinct patterns in select tumor models and revealed the existence of strong correlations between select biomarker pairs. Furthermore, the relative proportion of immune cells at different depths across tumor samples was preserved in some but not all tumor models, thereby revealing the existence of compositional heterogeneity. Taken together, these results reveal novel insights into the nature of immunologic heterogeneity, which is not accessible through typical omics approaches.

Direct Detection Constraints on Blazar-Boosted Dark Matter.

We explore the possibility that relativistic protons in the extremely powerful jets of blazars may boost via elastic collisions the dark matter particles in the surroundings of the source to high energies. We concentrate on two sample blazars, TXS 0506+056, towards which IceCube recently reported evidence for a high-energy neutrino flux, and BL Lacertae, a representative nearby blazar. We find that the dark matter flux at Earth induced by these sources may be sizable, larger than the flux associated with the analogous process of dark matter boosted by galactic cosmic rays, and relevant to access direct detection for dark matter particle masses lighter than 1 GeV. From the null detection of a signal by XENON1T, MiniBooNE, and Borexino, we derive limits on dark matter-nucleus spin-independent and spin-dependent cross sections which, depending on the modelization of the source, improve on other currently available bounds for light dark matter candidates of 1 up to 5 orders of magnitude.

The level of urinary C4d is associated with disease progression in IgA nephropathy with glomerular crescentic lesions: a cohort study.

BACKGROUND: Positive glomerular C4d staining, representative of lectin pathway activation, has been proven to be associated with unfavorable outcomes in immunoglobulin A nephropathy (IgAN). Our previous study suggested that urinary C4d correlated positively with an increase in crescents while the relationship between urinary C4d and disease severity and progression remains unelucidated. METHODS: In this study we enrolled 168 patients diagnosed with IgAN with varying proportions of crescent formation at the time of biopsy. An independent cohort of 107 IgAN patients was enrolled for validation. Kidney biopsy specimens were stained using immunohistochemistry. Urinary C4d levels at renal biopsy were measured by enzyme-linked immunosorbent assay. The primary endpoint was end-stage kidney disease (ESKD). RESULTS: Higher urinary C4d/creatinine levels were associated with a lower estimated glomerular filtration rate (eGFR); massive proteinuria; hypertension and severe Oxford M, E, T and C scores. After a median follow-up of 19 months (interquartile range 9-27), 53 (31.5%) participants reached ESKD. High urinary C4d/creatinine levels were independently and significantly associated with a risk of developing ESKD [hazard ratio per standard deviation increment of log-transformed C4d/creatinine 7.623 (95% confidence interval 4.117-14.113)]. CONCLUSIONS: The urinary C4d/creatinine level is a potential useful biomarker that was associated with disease severity and progression in patients with IgAN and crescents.

Structure-aware siamese graph neural networks for encounter-level patient similarity learning.

Patient similarity learning has attracted great research interest in biomedical informatics. Correctly identifying the similarity between a given patient and patient records in the database could contribute to clinical references for diagnosis and medication. The sparsity of underlying relationships between patients poses difficulties for similarity learning, which becomes more challenging when considering real-world Electronic Health Records (EHRs) with a large number of missing values. In the paper, we organize EHRs as a graph and propose a novel deep learning framework, Structure-aware Siamese Graph neural Networks (SSGNet), to perform robust encounter-level patient similarity learning while capturing the intrinsic graph structure and mitigating the influence from missing values. The proposed SSGNet regards each patient encounter as a node, and learns the node embeddings and the similarity between nodes simultaneously via Graph Neural Networks (GNNs) with siamese architecture. Further, SSGNet employs a low-rank and contrastive objective to optimize the structure of the patient graph and enhance model capacity. The extensive experiments were conducted on two publicly available datasets and a real-world dataset regarding IgA nephropathy from Peking University First Hospital, in comparison with multiple baseline and state-of-the-art methods. The significant improvement in Accuracy, Precision, Recall and F1 score on the patient encounter pairwise similarity classification task demonstrates the superiority of SSGNet. The mean average precision (mAP) of SSGNet on the similar encounter retrieval task is also better than other competitors. Furthermore, SSGNet's stable similarity classification accuracies at different missing rates of data validate the effectiveness and robustness of our proposal.

Association of left ventricular hypertrophy and functional impairment with cardiovascular outcomes and mortality among patients with chronic kidney disease, results from the C-STRIDE study.

AIM: Left ventricular hypertrophy and impaired systolic and diastolic function are commonly seen in patients with chronic kidney disease (CKD), but relationships between the disorders and cardiovascular outcomes are not well established among the patients. METHODS: Totally, 2020 patients with CKD Stages 1-4 were used in the analysis. Left ventricular hypertrophy was defined by left ventricular mass index >49.2 g/m2.7 in men and > 46.7 g/m2.7 in women. Incident heart failure, non-heart failure cardiovascular events, and all-cause mortality were recorded longitudinally. Cox proportional hazards regression model was used to evaluate the association between the echo parameters and the outcomes, with death treated as the competing risk event for the cardiovascular events. RESULTS: After a median follow-up of 4.5 years, 53 heart failure, 76 non-heart failure cardiovascular events and 82 deaths occurred. No overall association was found between left ventricular hypertrophy and subsequent heart failure, but the relationship was significant among patients with no diabetes with the multivariable adjusted hazard ratio of 3.66 (95% confidence interval: 1.42-9.46). Ejection fraction<55% was associated with both heart failure and non-heart failure cardiovascular events with hazard ratios of 3.16 (1.28-7.77) and 2.76 (1.08-7.04), respectively. E/A ratio ≤ 0.75 was associated with non-heart failure cardiovascular events [hazard ratio = 2.03 (1.09-3.80)], compared with E/A ratio of 0.76-1.49. CONCLUSION: Associations of reduced left ventricular ejection fraction with both heart failure and non-heart failure cardiovascular events and of impaired left ventricular diastolic function with non-heart failure cardiovascular events were validated in a Chinese cohort of CKD.

Cost-effectiveness of medical migration for chronic kidney disease: a national cross-sectional study in China.

BACKGROUND: The phenomenon of medical migration is common in China. Due to the limited capacity and substantial geographical variation in medical practice, patients with chronic kidney disease (CKD) travel more frequently to seek medical care. We aimed to assess the cost-effectiveness of medical migration for CKD patients in China and provide real-world evidence for the allocation of CKD resources. METHODS: Records of patients with CKD between January 2014 and December 2018 were extracted from a large national database. A patient is defined as a medical migrant if she travelled across the provincial border to a non-residential province to be admitted for inpatient care. The propensity score matching method is used to estimate the effect of medical migration on medical expenditure, length of hospital stay, and in-hospital mortality. The cost-effectiveness is evaluated by comparing the estimated cost per life saved with contemporaneous estimates of the value of a statistical life. RESULTS: Among 4,392,650 hospitalizations with CKD, medical migrants accounted for 4.9% in 2018. Migrant patients were estimated to incur a 26.35% increase in total medical expenditure, experience a 0.24-percentage-points reduction in in-hospital mortality rates, and a 0.49-days reduction in length of hospital stay compared to non-migrant patients. Overall, medical migration among CKD patients incurred an average of 1 million yuan per life saved, which accounted for 20-40% of contemporaneous estimates of the value of a statistical life. Compared with migrant patients with self-payment and commercial insurance, migrant patients with public health insurance (urban basic medical insurance and new rural co-operative medical care) incurred lower cost per life saved. Cost per life saved for CKD patients was similar between female and male, lower among older population, and varied substantially across regions. CONCLUSIONS: The medical care seeking behaviors of CKD patients was prominent and medical resources of kidney care were unevenly allocated across regions. Medical migration led to a reduction in mortality, but was associated with higher medical expenditure. It is imperative to reduce the regional disparity of medical resources and improve the clinical capacity. Our study shows that it is imperative to prioritize resource allocation toward improving kidney health and regional health care planning.

Effects of ambient temperature on hospital admissions for obstructive nephropathy in Wuhan, China: A time-series analysis.

Under the background of global warming, it has been confirmed that heat exposure has a huge impact on human health. The current study aimed to evaluate the effects of daily mean ambient temperature on hospital admissions for obstructive nephropathy (ON) at the population level. A total of 19,494 hospitalization cases for ON in Wuhan, China from January 1, 2015 to December 31, 2018 were extracted from a nationwide inpatient database in tertiary hospitals according to the International Classification of Diseases (ICD)- 10 codes. Daily ambient meteorological and pollution data during the same period were also collected. A quasi-Poisson Generalized Linear Model (GLM) combined with a distributed lag non-linear model (DLNM) was applied to analyze the lag-exposure-response relationship between daily mean temperature and daily hospital admissions for ON. Results showed that there were significantly positive associations between the daily mean temperature and ON hospital admissions. Relative to the minimum-risk temperature (-3.4 â„ƒ), the risk of hospital admissions for ON at moderate hot temperature (25 â„ƒ, 75th percentile) occurred from lag day 4 and stayed to lag day 12 (cumulative relative risk [RR] was 1.846, 95 % confidence interval [CI]: 1.135-3.005, over lag 0-12 days). Moreover, the risk of extreme hot temperature (32 â„ƒ, 99th percentile) appeared immediately and lasted for 8 days (RR = 2.019, 95 % CI: 1.308-3.118, over lag 0-8 days). Subgroup analyses indicated that the middle-aged and elderly (≥45 years) patients might be more susceptible to the negative effects of high temperature, especially at moderate hot conditions. Our findings suggest that temperature may have a significant impact on the acute progression and onset of ON. Higher temperature is associated with increased risks of hospital admissions for ON, which indicates that early interventions should be taken in geographical settings with relatively high temperatures, particularly for the middle-aged and elderly.

Long-Term Exposure to Ambient PM2.5 and Increased Risk of CKD Prevalence in China.

BACKGROUND: Fine particulate matter (PM2.5) is an important environmental risk factor for cardiopulmonary diseases. However, the association between PM2.5 and risk of CKD remains under-recognized, especially in regions with high levels of PM2.5, such as China. METHODS: To explore the association between long-term exposure to ambient PM2.5 and CKD prevalence in China, we used data from the China National Survey of CKD, which included a representative sample of 47,204 adults. We estimated annual exposure to PM2.5 before the survey date at each participant's address, using a validated, satellite-based, spatiotemporal model with a 10 km×10 km resolution. Participants with eGFR <60 ml/min per 1.73 m2 or albuminuria were defined as having CKD. We used a logistic regression model to estimate the association and analyzed the influence of potential modifiers. RESULTS: The 2-year mean PM2.5 concentration was 57.4 µg/m3, with a range from 31.3 to 87.5 µg/m3. An increase of 10 µg/m3 in PM2.5 was positively associated with CKD prevalence (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.22 to 1.35) and albuminuria (OR, 1.39; 95% CI, 1.32 to 1.47). Effect modification indicated these associations were significantly stronger in urban areas compared with rural areas, in males compared with females, in participants aged <65 years compared with participants aged ≥65 years, and in participants without comorbid diseases compared with those with comorbidities. CONCLUSIONS: These findings regarding the relationship between long-term exposure to high ambient PM2.5 levels and CKD in the general Chinese population provide important evidence for policy makers and public health practices to reduce the CKD risk posed by this pollutant.

The AP2 Transcription Factor BrSHINE3 Regulates Wax Accumulation in Nonheading Chinese Cabbage.

Wax is an acellular structural substance attached to the surface of plant tissues. It forms a protective barrier on the epidermis of plants and plays an important role in resisting abiotic and biotic stresses. In this paper, nonheading Chinese cabbage varieties with and without wax powder were observed using scanning electron microscopy, and the surface of waxy plants was covered with a layer of densely arranged waxy crystals, thus differentiating them from the surface of waxless plants. A genetic analysis showed that wax powder formation in nonheading Chinese cabbage was controlled by a pair of dominant genes. A preliminary bulked segregant analysis sequencing (BSA-seq) assay showed that one gene was located at the end of chromosome A09. Within this interval, we identified BraA09000626, encoding an AP2 transcription factor homologous to Arabidopsis AtSHINE3, and we named it BrSHINE3. By comparing the CDS of the gene in the two parental plants, a 35 bp deletion in the BrSHINE3 gene of waxless plants resulted in a frameshift mutation. Tissue analysis showed that BrSHINE3 was expressed at significantly higher levels in waxy plant rosette stage petioles and bolting stage stems than in the tissues of waxless plants. We speculate that this deletion in BrSHINE3 bases in the waxless material may inhibit wax synthesis. The overexpression of BrSHINE3 in Arabidopsis induced the accumulation of wax on the stem surface, indicating that BrSHINE3 is a key gene that regulates the formation of wax powder in nonheading Chinese cabbage. The analysis of the subcellular localization showed that BrSHINE3 is mainly located in the nucleus and chloroplast of tobacco leaves, suggesting that the gene may function as a transcription factor. Subsequent transcriptome analysis of the homology of BrSHINE3 downstream genes in nonheading Chinese cabbage showed that these genes were downregulated in waxless materials. These findings provide a basis for a better understanding of the nonheading Chinese cabbage epidermal wax synthesis pathway and provide important information for the molecular-assisted breeding of nonheading Chinese cabbage.

Estimation of Prevalence of Kidney Disease Treated With Dialysis in China: A Study of Insurance Claims Data.

RATIONALE & OBJECTIVE: The national prevalence of dialysis in China has not been well studied. We aimed to estimate the prevalence of kidney disease treated with dialysis and predict the trend using claims data in order to provide evidence for developing prevention strategies. STUDY DESIGN: Cross-sectional study of insurance claims. SETTING & PARTICIPANTS: Medical claims data from January 1, 2013, to December 31, 2017, were extracted from a large claims database by using a 2-stage sampling design to obtain a national sample covered by the urban basic medical insurance, the most predominant insurance program in China. EXPOSURE: Patients receiving maintenance dialysis, including hemodialysis (HD) and peritoneal dialysis (PD), were identified according to medical billing data and International Classification of Diseases, Tenth Revision (ICD-10) codes. OUTCOMES: The age- and sex-standardized population prevalence of kidney disease treated with dialysis was estimated by year and treatment modality. ANALYTICAL APPROACH: Crude and age- and sex-standardized prevalence of kidney disease treated with dialysis were calculated stratified by year and treatment modality. The gray Verhulst model was used to predict dialysis prevalence from 2018 to 2025. RESULTS: The age-and sex-standardized prevalence of dialysis patients increased from 255.11 per million population (pmp) in 2013 to 419.39 pmp in 2017. The age- and sex-standardized prevalence of HD and PD in 2017 were 384.41 pmp and 34.98 pmp, respectively, and the total number of dialysis patients in China was estimated to be 581,273. The prevalence of dialysis was predicted to rise above 2017 levels, with a predicted prevalence of 534.60 pmp in 2020 and 629.67 pmp in 2025, corresponding to 744,817 and 874,373 patients, respectively. LIMITATIONS: Claims data have potential errors in classification of patients, and population selection bias may have limited inferences to the entire Chinese population. CONCLUSIONS: The prevalence of kidney disease treated with dialysis has risen between 2013 and 2017 in China and is predicted to increase further through 2025. These findings highlight the importance of prevention and control strategies to reduce the escalating burden of kidney failure.

Effect of clinical decision support systems on clinical outcome for acute kidney injury: a systematic review and meta-analysis.

BACKGROUND: Clinical decision support systems including both electronic alerts and care bundles have been developed for hospitalized patients with acute kidney injury. METHODS: Electronic databases were searched for randomized, before-after and cohort studies that implemented a clinical decision support system for hospitalized patients with acute kidney injury between 1990 and 2019. The studies must describe their impact on care processes, patient-related outcomes, or hospital length of stay. The clinical decision support system included both electronic alerts and care bundles. RESULTS: We identified seven studies involving 32,846 participants. Clinical decision support system implementation significantly reduced mortality (OR 0.86; 95 % CI, 0.75-0.99; p = 0.040, I2 = 65.3 %; n = 5 studies; N = 30,791 participants) and increased the proportion of acute kidney injury recognition (OR 3.12; 95 % CI, 2.37-4.10; p < 0.001, I2 = 77.1 %; n = 2 studies; N = 25,121 participants), and investigations (OR 3.07; 95 % CI, 2.91-3.24; p < 0.001, I2 = 0.0 %; n = 2 studies; N = 25,121 participants). CONCLUSIONS: Nonrandomized controlled trials of clinical decision support systems for acute kidney injury have yielded evidence of improved patient-centered outcomes and care processes. This review is limited by the low number of randomized trials and the relatively short follow-up period.