Rutaecarpine protects podocytes in diabetic kidney disease by targeting VEGFR2/NLRP3-mediated pyroptosis.

OBJECTIVE: Diabetic kidney disease (DKD) is the most common cause of the end-stage renal disease, which has limited treatment options. Rutaecarpine has anti-inflammatory effects, however, it has not been studied in DKD. Pyroptosis is a newly discovered mode of podocyte death related to inflammation. This study aimed to explore whether Rutaecarpine can ameliorate DKD and to clarify its possible mechanism. METHODS: In this study, we investigated the effects of Rutaecarpine on DKD using diabetic mice model (db/db mice) and high glucose (HG)-stimulated mouse podocyte clone 5 (MPC5) cells. Quantitative reverse transcription polymerase chain reaction and western blot were performed to detect the related gene and protein levels. We applied pharmacological prediction, co-immunoprecipitation assay, cellular thermal shift assay, surface plasmon resonance to find the target and pathway of the substances. Gene knockdown experiments confirmed this view in HG-stimulated MPC5 cells. RESULTS: Rutaecarpine significantly reduced proteinuria, histopathological damage, and pyroptosis of podocytes in a dose-dependent manner in db/db mice. Rutaecarpine also protected high glucose induced MPC5 injury in vitro experiments. Mechanistically, Rutaecarpine can inhibit pyroptosis in HG-stimulated MPC5 by reducing the expression of VEGFR2. VEGFR2 is a target of Rutaecarpine in MPC5 cells and directly binds to the pyroptosis initiation signal, NLRP3. VEGFR2-knockdown disrupted the beneficial effects of Rutaecarpine in HG-stimulated MPC5 cells. CONCLUSION: Rutaecarpine inhibits renal inflammation and pyroptosis through VEGFR2/NLRP3 pathway, thereby alleviating glomerular podocyte injury. These findings highlight the potential of Rutaecarpine as a novel drug for DKD treatment.

Research progress of mitochondria in chronic obstructive pulmonary disease: a bibliometric analysis based on the Web of Science Core Collection.

Background: Due to its high morbidity and mortality, chronic obstructive pulmonary disease (COPD) has become a major global healthcare issue. Although there is abundant research regarding COPD, a bibliometric analysis of the literature related to mitochondria and COPD is lacking. Thus this study aimed to summarize the research status, research direction, and research hotspots of the published articles concerning COPD and mitochondria. Methods: A literature search for included publications related to COPD and mitochondria was carried out on the Web of Science Core Collection from the date of database establishment to December 15, 2022. A subsequent bibliometric and visual analysis of the included publications was conducted via Microsoft Excel, R software, CiteSpace, and VOSviewer. Results: A total of 227 published articles on COPD and mitochondria from 139 journals were included. Over the study period, the annual publication number and citation frequency in this field both showed a trend of continuous growth. The United States had the highest centrality and was the most productive country. The frequently occurring keywords were "oxidative stress", "obstructive pulmonary disease", "dysfunction", "mitochondria", "inflammation", and "cigarette smoke", among others. Recent research hotspots included autophagy, model, mitochondria, health, and extracellular vesicles (EVs). Despite an abundance and variety of research, there is still relatively little academic communications between scholars and institutions. Conclusions: This bibliometric study can help researchers gain a quick overview of the research into mitochondria and COPD and thus inform novel ideas and directions for future research in this field.

Sparse Bayesian learning based on spatio-temporal structure-aware for matched field processing.

In the application of the matched field processing (MFP) algorithm for underwater acoustic source localization, the measurements at each time step are conventionally processed independently. This study incorporates the prior information about the continuous spatial changes of the source over time under realistic conditions, a factor anticipated to improve localization performance. In this paper, a sparse Bayesian learning (SBL) algorithm based on the spatio-temporal structure-aware is described. We exploit a structure prior for sparse coefficients to capture the continuous spatial structure between adjacent time steps. Moreover, the sparse coefficient can automatically select the update method, utilizing the statistical information from adjacent neighbors or updating independently. The hidden variables in the hierarchical Bayesian framework are inferred via variational Bayesian inference (VBI). Additionally, we extend the proposed method to the multi-frequency case. This method inherits the advantages of the SBL and further reduces position estimation errors. Compared to other approaches, the construction of an accurate motion model is not required. The efficacy of the proposed algorithm is demonstrated through simulation examples and an analysis of the SWellEx-96 experimental data.

A simple and efficient clinical prediction scoring system to identify malignant pleural effusion.

BACKGROUND: Early diagnosis of malignant pleural effusion (MPE) is of great significance. Current prediction models are not simple enough to be widely used in heavy clinical work. OBJECTIVES: We aimed to develop a simple and efficient clinical prediction scoring system to distinguish MPE from benign pleural effusion (BPE). DESIGN: This retrospective study involved patients with MPE or BPE who were admitted in West China Hospital from December 2010 to September 2016. METHODS: Patients were divided into training, testing, and validation set. Prediction model was developed from training set and modified to a scoring system. The diagnostic efficacy and clinical benefits of the scoring system were estimated in all three sets. RESULTS: Finally, 598 cases of MPE and 1094 cases of BPE were included. Serum neuron-specific enolase, serum cytokeratin 19 fragment (CYFRA21-1), pleural carcinoembryonic antigen (CEA), and ratio of pleural CEA to serum CEA were selected to establish the prediction models in training set, which were modified to the scoring system with scores of 6, 8, 10, and 9 points, respectively. Patients with scores >12 points have high MPE risk while ⩽12 points have low MPE risk. The scoring system has a high predictive value and good clinical benefits to differentiate MPE from BPE or lung-specific MPE from BPE. CONCLUSION: This study developed a simple clinical prediction scoring system and was proven to have good clinical benefits, and it may help clinicians to separate MPE from BPE.

Single-cell RNA sequencing reveals immune microenvironment of small cell lung cancer-associated malignant pleural effusion.

We used 10 × genomics single-cell transcriptome sequencing technology to reveal the tumor immune microenvironment characteristics of small cell lung cancer (SCLC) in a patient with malignant pleural effusion (MPE). A total of 8008 high-quality cells were finally obtained for subsequent bioinformatic analysis, which were divided into 10 cell clusters further identified as B cells, T cells, myeloid cells, NK cells, and cancer cells. Such SCLC related genes as NOTCH1, MYC, TSC22D1, SOX4, BLNK, YBX3, VIM, CD8A, CD8B, and KLF6 were expressed in different degrees during differentiation of T and B cells. Different ligands and receptors between T, B and tumor cells almost interact through MHC II, IL-16, galectin, and APP signaling pathway.

Prevalence and clinical characteristics of sleep disorders in chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: Sleep disorders, including obstructive sleep apnea (OSA), restless leg syndrome (RLS) and insomnia, are present in chronic obstructive pulmonary disease (COPD) with varied prevalence. The aim of this systematic review and meta-analysis was to investigate prevalence of OSA, RLS and insomnia in patients with COPD and summarize their clinical characteristics. METHODS: We searched PubMed, Web of Science and Scopus for eligible articles reporting the prevalence of OSA, RLS, and insomnia in COPD patients. The Newcastle‒Ottawa scale was applied for quality assessment. Odds ratios or mean differences with 95 % confidence intervals (CIs) were applied for the overall prevalence calculation and clinical characteristics assessment. Sensitivity analysis, subgroup analysis and meta-regression were conducted to evaluate the heterogeneity of the results. RESULTS: Sixty articles reporting the prevalence of sleep disorders in patients with COPD were included, and the prevalence of OSA, RLS, and insomnia reached 29.1 %(95%CI 27.2%-30.9 %), 21.6 %(95%CI 11.8%-33.3 %) and 29.5 %(95%CI 16.9%-44.0 %), respectively. COPD patients with OSA were characterized by male sex (OR 1.631 95 % CI: 1.231-2.161), obesity(kg/m2) (MD 4.435, 95 % CI 3.218-5.652), higher Epworth Sleepiness Scale (MD: 3.741, 95 % CI: 0.655-6.828, p = 0.018), better pulmonary function (MD 5.66, 95 % CI 3.546-7.774) and higher risks of hypertension (OR 1.933 95 % CI 1.382-2.70) and diabetes (OR 1.898 95 % CI 1.264-2.849). COPD patients with RLS were associated with a higher Epworth sleepiness scale (ESS) score (MD 3.444, 95 % CI 1.880-5.008) and a longer COPD duration(year) (MD: 3.656, 95 % CI: 2.209-5.103). COPD patients with insomnia were characterized by female sex(OR 0.556, 95%CI 0.545,0.567, p < 0.001). CONCLUSION: Our study suggests that OSA, RLS and insomnia are common in COPD patients with specific clinical characteristics. Further studies are needed to explore the interactions between COPD and sleep disorders.

Incidence and prognostic role of pleural effusion in patients with acute pancreatitis: a meta-analysis.

BACKGROUND: Pleural effusion (PE) is reported as a common complication in acute pancreatitis (AP), while the incidence of PE in AP varies widely among studies, and the association between PE and mortality is not clear. This study aimed to comprehensively analyze the pooled incidence of PE in patients with AP and to evaluate the influence of PE on mortality through a meta-analysis. METHOD: Six databases (PubMed, Web of Science, EMBASE, Cochrane, Scopus, and OVID) were searched thoroughly for relevant studies. Data were extracted, and Stata SE 16.0 software was applied to compute the pooled incidence of PE and assess the association between PE and mortality, taking the risk ratio (RR) as the effect size. RESULTS: Thirty-five articles involving 7,675 patients with AP were eventually included in this meta-analysis. The pooled incidence of PE was 34% (95% CI: 28%-39%), with significant heterogeneity among studies (I2=96.7%). Further analysis revealed that the pooled incidence of unilateral and small PE occupied 49% (95% CI: 21%-77%) and 59% (95% CI: 38%-81%) of AP patients complicated by PE, respectively. The subgroup analysis revealed that "region" and "examination method" may contribute to heterogeneity. PE may be associated with increased mortality in AP patients (RR 3.99, 95% CI: 1.73-9.2). CONCLUSION: This study suggested that PE is a common complication with high pooled incidence and that PE may be associated with increased mortality in AP patients. More studies should be performed to validate our findings.

Incidence and Prognostic Role of Pleural Effusion in Patients with Pulmonary Embolism: A Systematic Review and Meta-Analysis.

BACKGROUND: Pleural effusion is a common pulmonary embolism (PE) complication, which has been documented to increase the risk of death in PE and relate to disease progression. However, the incidence of pleural effusion varies among studies and its association with PE outcome is still unclear. This study sought to determine the pooled incidence and prognostic value of pleural effusion events in patients with PE. METHODS: We systematically searched the PubMed, EMBASE, SCOPE, Web of Science, Cochrane, LILACS, CINAHL, EBSCO, AMED, and OVID databases from the inception of each database to 7 September 2022 with a restriction on human studies, to identify studies assessing the association between pleural effusion and PE including all prospective and retrospective clinical studies. An exploratory meta-analysis was performed using a random-effects model. We evaluated the heterogeneity and performed subgroup analyses. RESULTS: The final meta-analysis included 29 studies involving 13,430 PE patients. The pooled incidence of pleural effusion in PE patients was 41.2% (95% CI: 35.7-46.6%), which tended to be unilateral (pooled incidence: 60.8%, 95% CI: 45.7-75.8%) and small (pooled incidence: 85.9%, 95% CI: 82.6-89.1%). Pooled analysis using a random-effects model (I2 = 53.2%) showed that pleural effusion was associated with an increased risk of 30-day mortality (RR 2.19, 95% CI: 1.53-3.15, p < 0.001, I2 = 67.1%) and in-hospital mortality (RR 2.39, 95% CI: 1.85-3.09, p < 0.001, I2 = 37.1%) in patients with PE. CONCLUSIONS: Our meta-analysis found that PE patients had a high incidence of pleural effusion, which was usually unilateral and small. Pleural effusion generally increases 30-day and in-hospital mortality in patients with PE, and it is recommended that physicians be aware of the risk of death from PE, especially when patients have pleural effusion. Further investigations focusing on PE with pleural effusion are warranted.

Adenosine deaminase-based measurement in the differential diagnosis of pleural effusion: a multicenter retrospective study.

INTRODUCTION: The differential diagnosis of pleural effusion is difficult, and studies have reported on the potential role of adenosine deaminase (ADA) in the differential diagnosis of undiagnosed pleural effusion. This retrospective study aimed to investigate the diagnostic role of ADA in pleural effusion. METHODS: 266 patients with pleural effusion from three centers were enrolled. The concentrations of ADA and lactate dehydrogenase (LDH) were measured in pleural fluids and serum samples of the patients. The diagnostic performance of ADA-based measurement for tuberculous pleural effusion (TPE), malignant pleural effusion (MPE), and parapneumonic effusion (PPE) was examined by receiver operating characteristic (ROC) curve analysis. RESULTS: An area under the ROC curve (AUC) value of 0.909 was obtained using the pleural ADA values as the indicator for TPE identification (sensitivity: 87.50%, specificity: 87.82%). The ratio of serum LDH to pleural ADA (cancer ratio) provided the predictive capacity with an AUC of 0.879 for MPE diagnosis (sensitivity: 95.04%, specificity: 67.06%). At a cut-off value of 14.29, the pleural ADA/LDH ratio showed a sensitivity and specificity of 81.13% and 83.67%, respectively, and a high AUC value of 0.888 for the differential diagnosis of PPE from TPE. CONCLUSION: ADA-based measurement is helpful for the differential diagnosis of pleural effusion. Further studies should be performed to validate these results.

Incidence of complications from indwelling pleural catheter for pleural effusion: A meta-analysis.

Indwelling pleural catheter (IPC) is widely used in patients with pleural effusion (PE). This meta-analysis aimed to comprehensively summarize the clinical complication from IPC. We searched four large electronic databases (PubMed, EMBASE, MEDLINE, and Cochrane Library) for potentially relevant studies and assessed the included studies' quality using the methodological index for nonrandomized studies' criteria. Extracted data were used to pool rates, and to conduct subgroup and meta-regression analyses. Forty-one studies involving a cumulative 4983 patients with 5650 IPCs were included in this meta-analysis. The overall incidence of IPC complications was 20.3% (95% confidence interval [CI]: 15.0-26.3). The top four complications were: overall infection incidence 5.7% (95% CI: 0.7-2.4); overall catheter abnormality incidence 4.4% (95% CI: 2.8-6.3); pain incidence 1.2% (95% CI: 0.4-2.4); and overall loculation incidence 0.9% (95% CI: 0.1-2.1). Subgroup and meta-regression analyses for overall complications and infections by country, PE site, and PE type demonstrated these factors did not contribute significantly to heterogeneity. Further subgroup analyses for infection of benign PE showed that the overall infection incidence (12.6% [95% CI: 8.1-17.8] vs 0.7% [95% CI: 0.0-4.5]) and empyema incidence (9.1% [95% CI: 5.3-13.8] vs 0.0% [95% CI: 0.0-2.3]) of patients with liver-related PE were significantly higher than that of patients with heart-related PE. Our meta-analysis showed reliable pooled incidences of IPC-related complications, with infection being the most common. These results serve to remind clinicians about the incidence of IPC-related complications and emphasize the importance of taking corresponding preventive and therapeutic steps.

Impact of sleep disordered breathing on postoperative atrial fibrillation in patients who underwent cardiac surgery: a meta-analysis.

Objective: An increasing number of studies suggest that sleep disordered breathing (SDB) may be associated with postoperative atrial fibrillation (POAF), but these studies present discrepant results. Thus, this meta-analysis aimed to synthesize the data associating SDB with POAF in patients who underwent cardiac surgery.Methods: A literature search was performed in the Scopus, PubMed, Web of Science, EMBASE, CENTRAL, Weipu, Wanfang Data, and China National Knowledge Infrastructure databases before August 2022. Data were extracted, and the strength of the relationship between SDB and the risk of POAF was evaluated using odds ratio (OR) and 95% confidence intervals (CIs). All statistical analysis was carried out using the Stata 12.0 software.Results: A total of 24 studies with 660,685 subjects were included in current meta-analysis. SDB was significantly associated with the risk of POAF in the patients who underwent cardiac surgery (OR = 1.49; 95% CI, 1.30-1.70; p < .001). Next subgroup analysis revealed that such association may be increased in the group with medical equipment-measured SDB (OR = 2.27; 95% CI, 1.59-3.23; p < .001), prospective studies (OR = 2.17; 95% CI, 1.55-3.03; p < .001), patients without a previous history of atrial fibrillation (OR = 2.04; 95% CI, 1.47-2.82; p < .001), and patients who received a coronary artery bypass graft (OR = 2.10; 95% CI, 1.45-3.05; p < .001). No publication bias was identified.Conclusion: The results of meta-analysis support that SDB may be associated with an increased risk of POAF in patients who had undergone cardiac surgery, and these results should be confirmed in more rigorously designed studies.KEY MESSAGESPatients with SDB who underwent cardiac surgery showed increased risk of POAF.The relationship between SDB and POAF should be explained with caution with the consideration of various covariate.The effect of pre-treatment of SDB on POAF should be examined in future.

Performance of Serum Angiotensin-Converting Enzyme in Diagnosing Sarcoidosis and Predicting the Active Status of Sarcoidosis: A Meta-Analysis.

The usefulness of serum angiotensin-converting enzyme (sACE) for diagnosing sarcoidosis and determining the active status of sarcoidosis has been reported with varying outcomes. On the basis of the majority of published data, we conducted a meta-analysis to calculate the overall predictive accuracy of sACE in sarcoidosis disease and the active status of sarcoidosis. The inclusion of related research listed in Web of Science, PubMed, Scopus, and other literature databases was assessed. SROC curves were generated to characterize the overall test results after data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were combined. Publication bias was identified using Deeks' funnel plot. Thirty-five publications with 8645 subjects met the inclusion criteria. The following are summary estimates of sACE diagnostic performance for sarcoidosis: sensitivity, 60% (95% confidence interval (CI), 52-68%); specificity, 93% (95% CI, 88-96%); PLR, 8.4 (95% CI, 5.3-13.3); NLR, 0.43 (95% CI, 0.36-0.52); and DOR, 19 (95% CI, 12-31). The area under the SROC curve (AUC) was 0.84 (95% CI, 0.80-0.87). Summary estimates for predicting the active status of sarcoidosis were as follows: sensitivity, 0.76 (95% CI, 0.61-0.87); specificity, 0.80 (95% CI, 0.64-0.90); PLR, 3.9 (95% CI, 2.1-7.3); NLR, 0.29 (95% CI, 0.17-0.49); and DOR, 13 (95% CI, 6-31). The AUC was 0.85 (95% CI, 0.82-0.88). There was no evidence of publication bias. Our meta-analysis suggests that measuring the sACE may assist in the diagnosis of sarcoidosis and predicting the active status of sarcoidosis, but the interpretation of the sACE results should be with caution. Future studies should validate our results.

The Value of Adenosine Deaminase 2 in the Detection of Tuberculous Pleural Effusion: A Meta-Analysis and Systematic Review.

Adenosine deaminase 2 (ADA2) is reported as a novel diagnostic biomarker for tuberculous pleural effusion (TPE) in many studies. This meta-analysis was conducted to systematically evaluate the general diagnostic performance of pleural ADA2 in TPE. After searching for relevant studies that investigated the diagnostic performance of pleural ADA2 in TPE in several databases, we assessed and selected eligible studies to calculate pooled parameters by STATA 16.0 software. A final set of thirteen studies entirely met the inclusion standards and were used to calculate pooled parameters in our meta-analysis. Among them, there were nine English studies and four Chinese studies. The pooled parameters of pleural ADA2 in diagnosing TPE were summarized as follows: sensitivity, 0.91 (95% CI: 0.86-0.95); specificity, 0.93 (95% CI: 0.92-0.95); positive likelihood ratio, 13.9 (95% CI: 10.6-18.3); negative likelihood ratio, 0.09 (95% CI:0.06-0.16); diagnostic odds ratio, 147 (95% CI: 76-284); and the area under the curve, 0.95 (95% CI: 0.93-0.97). Pleural ADA2 is a reliable indicator with excellent accuracy in TPE diagnosis. However, we need to combine pleural ADA2 with diverse examinations to diagnose TPE in clinical practice.

Melatonin Alleviates Acute Kidney Injury by Inhibiting NRF2/Slc7a11 Axis-Mediated Ferroptosis.

Acute kidney injury (AKI) is still a puzzling clinical problem; its pathophysiology is not completely understood. Up to now, an effective treatment for AKI is lacking. Ferroptosis is a novel form of regulated cell death characterized by the lethal accumulation of lipid hydroperoxides that are dependent on iron and reactive oxygen species and mitochondrial dysfunction. Recently, ferroptosis was shown to play a vital role in AKI such as ischemia-reperfusion kidney injury and folic acid-induced AKI. Melatonin (MT) is an antioxidant that regulates the sleep-wake cycle. While the therapeutic effect of melatonin on AKI has been reported, its mechanism for the treatment of renal ferroptosis remains unclear. We found that melatonin treatment significantly alleviated the serum biochemistry index and histopathological alterations in vivo AKI models induced by bilateral renal artery ischemia reperfusion and folic acid in mice. Ferroptosis induced by hypoxia and reoxygenation or erastin (Era) in mouse tubular epithelial cells (MTEC) was also rescued by melatonin treatment. RNA sequence analysis of ferroptosis-related genes showed that melatonin affects oxidative stress responses by inhibiting hypoxia and reoxygenation- (HR-) mediated downregulation of NRF2 and upregulation of Slc7a11 in MTEC. Specific knockdown of NRF2 increased the sensitivity of cells to ferroptosis, and melatonin failed to protect against ferroptosis in the HR condition. Together, our data indicate that melatonin prevents ferroptosis in AKI by acting on the NRF2/Slc7a11 axis.

METTL3-mediated m6A modification of TIMP2 mRNA promotes podocyte injury in diabetic nephropathy.

Epigenetic changes are present in many physiological and pathological processes. The N6-methyladenosine (m6A) modification is the most common modification in eukaryotic mRNA. However, the role of m6A modification in diabetic nephropathy (DN) remains elusive. Here, we found that m6A modification was significantly upregulated in the kidney of type 1 and type 2 diabetic mice, which was caused by elevated levels of METTL3. Moreover, METTL3 is increased in podocyte of renal biopsy from patients with DN, which is related to renal damage. METTL3 knockout significantly reduced the inflammation and apoptosis in high glucose (HG)-stimulated podocytes, while its overexpression significantly aggravated these responses in vitro. Podocyte-conditional knockout METTL3 significantly alleviated podocyte injury and albuminuria in streptozotocin (STZ)-induced diabetic mice. Therapeutically, silencing METTL3 with adeno-associated virus serotype-9 (AAV9)-shMETTL3 in vivo mitigated albuminuria and histopathological injury in STZ-induced diabetic mice and db/db mice. Mechanistically, METTL3 modulated Notch signaling via the m6A modification of TIMP2 in an insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2)-dependent manner and exerted pro-inflammatory and pro-apoptotic effects. In summary, this study suggested that METTL3-mediated m6A modification is an important mechanism of podocyte injury in DN. Targeting m6A through the writer enzyme METTL3 is a potential approach for the treatment of DN.

Wogonin protects glomerular podocytes by targeting Bcl-2-mediated autophagy and apoptosis in diabetic kidney disease.

Diabetic kidney disease (DKD) is one of the microvascular complications of diabetes mellitus and a major cause of end-stage renal disease with limited treatment options. Wogonin is a flavonoid derived from the root of Scutellaria baicalensis Georgi, which has shown a potent renoprotective effect. But the mechanisms of action in DKD are not fully elucidated. In this study, we investigated the effects of wogonin on glomerular podocytes in DKD using mouse podocyte clone 5 (MPC5) cells and diabetic mice model. MPC5 cells were treated with high glucose (30 mM). We showed that wogonin (4, 8, 16 µM) dose-dependently alleviated high glucose (HG)-induced MPC5 cell damage, accompanied by increased expression of WT-1, nephrin, and podocin proteins, and decreased expression of TNF-α, MCP-1, IL-1ß as well as phosphorylated p65. Furthermore, wogonin treatment significantly inhibited HG-induced apoptosis in MPC5 cells. Wogonin reversed HG-suppressed autophagy in MPC5 cells, evidenced by increased ATG7, LC3-II, and Beclin-1 protein, and decreased p62 protein. We demonstrated that wogonin directly bound to Bcl-2 in MPC5 cells. In HG-treated MPC5 cells, knockdown of Bcl-2 abolished the beneficial effects of wogonin, whereas overexpression of Bcl-2 mimicked the protective effects of wogonin. Interestingly, we found that the expression of Bcl-2 was significantly decreased in biopsy renal tissue of diabetic nephropathy patients. In vivo experiments were conducted in STZ-induced diabetic mice, which were administered wogonin (10, 20, 40 mg · kg-1 · d-1, i.g.) every other day for 12 weeks. We showed that wogonin administration significantly alleviated albuminuria, histopathological lesions, and p65 NF-κB-mediated renal inflammatory response. Wogonin administration dose-dependently inhibited podocyte apoptosis and promoted podocyte autophagy in STZ-induced diabetic mice. This study for the first time demonstrates a novel action of wogonin in mitigating glomerulopathy and podocytes injury by regulating Bcl-2-mediated crosstalk between autophagy and apoptosis. Wogonin may be a potential therapeutic drug against DKD.

Diagnostic accuracy of the cancer ratio for the prediction of malignant pleural effusion: evidence from a validation study and meta-analysis.

OBJECTIVE: This study aimed to assess the diagnostic accuracy of serum LDH to pleural ADA ratio (cancer ratio, CR)for malignant pleural effusion (MPE) through an original study and meta-analysis. METHODS: We retrospectively collected data from 145 patients with MPE and 117 cases of benign pleural effusions (BPE). The diagnostic performance of CR and a typical biomarker of MPE, carcinoembryonic antigen (CEA), were analysed using the receiver operating characteristic (ROC) curves and the area under the curve (AUC) as a measure of accuracy. The overall diagnostic accuracy of CR was summarised by a standard diagnostic meta-analysis. RESULTS: Significantly higher CR and pleural CEA values were observed in the MPE patients than in the BPE patients. At a cut-off value of 14.97, CR showed high sensitivity (0.91), low specificity (0.67), and high AUC (0.85). The combination of CEA and CR increased the AUC to 0.98. The meta-analysis included seven studies involving 2,078 patients. The pooled values for sensitivity, specificity, positive/negative likelihood ratio, and diagnostic odds ratio of CR were 0.96, 0.88, 7.70, 0.05, and 169, respectively. The AUC of the summary ROC of CR was 0.98. CONCLUSION: CR has a high diagnostic accuracy for predicting MPE, especially when used in combination with pleural CEA.