Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

Spatiotemporal diffractive deep neural networks.

A spatiotemporal diffractive deep neural network (STD2NN) is proposed for spatiotemporal signal processing. The STD2NN is formed by gratings, which convert the signal from the frequency domain to the spatial domain, and multiple layers consisting of spatial lenses and space light modulators (SLMs), which conduct spatiotemporal phase modulation. An all-optical backpropagation (BP) algorithm for SLM phase tuning is proposed, with the gradient of the loss function computed by the inner product of the forward propagating optical field and the backward propagating conjugated error field. As a proof of concept, a spatiotemporal word "OPTICA" is generated by the STD2NN. Afterwards, a spatiotemporal optical vortex (STOV) beam multiplexer based on the STD2NN is demonstrated, which converts the spatially separated Gaussian beams into the STOV wave-packets with different topological charges. Both cases illustrate the capability of the proposed STD2NN to generate and process the spatiotemporal signals.

PARG Promotes Esophagus Cancer Cell Metastasis by Activation of the Wnt/ß-Catenin Pathway.

Esophagus cancer (EC) is a highly malignant and metastatic cancer. Poly(ADP-ribose) glycohydrolase (PARG), a DNA replication and repair regulator, inhibits cancer cell replication defects. This study aimed to explore the role of PARG in EC. The biological behaviors were analyzed using MTT assay, Transwell assay, scratch test, cell adhesion assay, and western blot. PARG expression was detected using quantitative PCR and immunohistochemical assay. The regulation of the Wnt/ß-catenin pathway was assessed using western blot. The results showed that PARG was highly expressed in EC tissues and cells. Knockdown of PARG suppressed cell viability, invasion, migration, adhesion, and epithelial-mesenchymal transition. Conversely, overexpression of PARG promoted the biological behaviors mentioned above. Moreover, overexpression of PARG promoted the activation of the Wnt/ß-catenin pathway rather than the STAT and Notch pathways. XAV939, the Wnt/ß-catenin pathway inhibitor, partly abolished the biological behaviors mediated by PARG overexpression. In conclusion, PARG promoted the malignant advancement of EC via activating the Wnt/ß-catenin pathway. These findings suggested that PARG might be a new therapeutic target for EC.

Combination of Paper and Electronic Trail Making Tests for Automatic Analysis of Cognitive Impairment: Development and Validation Study.

BACKGROUND: Computer-aided detection, used in the screening and diagnosing of cognitive impairment, provides an objective, valid, and convenient assessment. Particularly, digital sensor technology is a promising detection method. OBJECTIVE: This study aimed to develop and validate a novel Trail Making Test (TMT) using a combination of paper and electronic devices. METHODS: This study included community-dwelling older adult individuals (n=297), who were classified into (1) cognitively healthy controls (HC; n=100 participants), (2) participants diagnosed with mild cognitive impairment (MCI; n=98 participants), and (3) participants with Alzheimer disease (AD; n=99 participants). An electromagnetic tablet was used to record each participant's hand-drawn stroke. A sheet of A4 paper was placed on top of the tablet to maintain the traditional interaction style for participants who were not familiar or comfortable with electronic devices (such as touchscreens). In this way, all participants were instructed to perform the TMT-square and circle. Furthermore, we developed an efficient and interpretable cognitive impairment-screening model to automatically analyze cognitive impairment levels that were dependent on demographic characteristics and time-, pressure-, jerk-, and template-related features. Among these features, novel template-based features were based on a vector quantization algorithm. First, the model identified a candidate trajectory as the standard answer (template) from the HC group. The distance between the recorded trajectories and reference was computed as an important evaluation index. To verify the effectiveness of our method, we compared the performance of a well-trained machine learning model using the extracted evaluation index with conventional demographic characteristics and time-related features. The well-trained model was validated using follow-up data (HC group: n=38; MCI group: n=32; and AD group: n=22). RESULTS: We compared 5 candidate machine learning methods and selected random forest as the ideal model with the best performance (accuracy: 0.726 for HC vs MCI, 0.929 for HC vs AD, and 0.815 for AD vs MCI). Meanwhile, the well-trained classifier achieved better performance than the conventional assessment method, with high stability and accuracy of the follow-up data. CONCLUSIONS: The study demonstrated that a model combining both paper and electronic TMTs increases the accuracy of evaluating participants' cognitive impairment compared to conventional paper-based feature assessment.

Design and synthesis of guaianolide-germacranolide heterodimers as novel anticancer agents against hepatocellular carcinoma.

Inspired by our previous finding that disesquiterpenoids showed more potent antihepatoma cytotoxicity than their corresponding parent monomers, natural product-like guaianolide-germacranolide heterodimers were designed and synthesized from guaianolide diene and germacranolides via a biomimetic Diels-Alder reaction to provide three antihepatoma active dimers with novel scaffolds. To explore the structure-activity relationship, 31 derivatives containing ester, carbamate, ether, urea, amide, and triazole functional groups at C-14' were synthesized and evaluated for their cytotoxic activities against HepG2, Huh7, and SK-Hep-1 cell lines. Among them, 25 compounds were more potent than sorafenib against HepG2 cells, 15 compounds were stronger than sorafenib against Huh7 cells, and 17 compounds were stronger than sorafenib against SK-Hep-1 cells. Compound 23 showed the most potent cytotoxicity against three hepatoma cell lines with IC50 values of 4.4 µM (HepG2), 3.7 µM (Huh7), and 3.1 µM (SK-Hep-1), which were 2.7-, 2.2-, and 2.8-fold more potent than sorafenib, respectively. The underlying mechanism study demonstrated that compound 23 could induce cell apoptosis, prevent cell migration and invasion, cause G2/M phase arrest in SK-Hep-1 cells. Network pharmacology analyses predicted PDGFRA was one of the potential targets of compound 23, and surface plasmon resonance (SPR) assay verified that 23 had strong affinity with PDGFRA with a dissociatin constant (KD) value of 90.2 nM. These promising findings revealed that structurally novel guaianolide-germacranolide heterodimers might provide a new inspiration for the discovery of antihepatoma agents.

The Role of BDNF, YBX1, CENPF, ZSCAN4, TEAD4, GLIS1 and USF1 in the Activation of the Embryonic Genome in Bovine Embryos.

Early embryonic development relies on the maternal RNAs and newly synthesized proteins during oogenesis. Zygotic transcription is an important event occurring at a specific time after fertilization. If no zygotic transcription occurs, the embryo will die because it is unable to meet the needs of the embryo and continue to grow. During the early stages of embryonic development, the correct transcription, translation, and expression of genes play a crucial role in blastocyst formation and differentiation of cell lineage species formation among mammalian species, and any variation may lead to developmental defects, arrest, or even death. Abnormal expression of some genes may lead to failure of the embryonic zygote genome before activation, such as BDNF and YBX1; Decreased expression of CENPF, ZSCAN4, TEAD4, GLIS1, and USF1 genes can lead to embryonic development failure. This article reviews the results of studies on the timing and mechanism of gene expression of these genes in bovine fertilized eggs/embryos.

Toripalimab Plus Paclitaxel and Carboplatin as Neoadjuvant Therapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are effective in the treatment of advanced esophageal squamous cell carcinoma (ESCC); however, their efficacy in locally advanced resectable ESCC and the potential predictive biomarkers have limited data. METHODS: In this study, locally advanced resectable ESCC patients were enrolled and received neoadjuvant toripalimab (240 mg, day 1) plus paclitaxel (135 mg/m2, day 1) and carboplatin (area under the curve 5 mg/mL per min, day 1) in each 3-week cycle for 2 cycles, followed by esophagectomy planned 4-6 weeks after preoperative therapy. The primary endpoints were safety, feasibility, and the major pathological response (MPR) rate; the secondary endpoints were the pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS). Association between molecular signatures/tumor immune microenvironment and treatment response was also explored. RESULTS: Twenty resectable ESCC patients were enrolled. Treatment-related adverse events (AEs) occurred in all patients (100%), and 4 patients (22.2%) experienced grade 3 or higher treatment-related AEs. Sixteen patients underwent surgery without treatment-related surgical delay, and the R0 resection rate was 87.5% (14/16). Among the 16 patients, the MPR rate was 43.8% (7/16) and the pCR rate was 18.8% (3/16). The abundance of CD8+ T cells in surgical specimens increased (P = .0093), accompanied by a decreased proportion of M2-type tumor-associated macrophages (P = .036) in responders upon neoadjuvant therapy. Responders were associated with higher baseline gene expression levels of CXCL5 (P = .03) and lower baseline levels of CCL19 (P = .017) and UMODL1 (P = .03). CONCLUSIONS: The combination of toripalimab plus paclitaxel and carboplatin is safe, feasible, and effective in locally advanced resectable ESCC, indicating its potential as a neoadjuvant treatment for ESCC. CLINICAL TRIAL REGISTRATION: NCT04177797.

Alleviation of neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma and its relationship with expression and changes of PD-L1.

The alleviation of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT) was compared for esophageal squamous cell carcinoma (ESCC), and the correlation between the expression and changes of PD-L1 and the efficacy of NICT was evaluated in this study. Fourteen patients with ESCC who received preoperative NICT were included in group A, and fourteen patients with ESCC who received preoperative NCRT were included in group B. Next, group A was divided into CR (complete response), PR (partial response), and NR (no response) according to the degree of pathological response. Also, the expression and changes of PD-L1 (CPS, TPS, IPS) before and after treatment were compared between the groups. We observed that after the treatment, the expression of PD-L1 in both groups was higher than before treatment. In group B, the expression of PD-L1 was elevated in 92.8% of patients, which was higher than that in group A, which had significantly increased IPS (p<0.05). In group A, 9 (64.2%) patients with CPS <10 achieved partial or complete response. There was no significant difference in pathological response and reduction of tumor thickness between the two groups or significant differences in CPS and TPS among CR, PR, and NR groups before treatment. The IPS was the highest in the CR group; however, the difference was not statistically significant. The differences in IPS change were significant among the three groups (p<0.05). In conclusion, NICT and NCRT could upregulate the expression of PD-L1. NCRT more significantly upregulated the expression of PD-L1, mainly of PD-L1 in immune cells in the tumor microenvironment. NICT was not less effective than NCRT in pathological response and tumor thickness changes. The preoperative CPS and TPS scores of PD-L1 did not effectively predict the degree of pathological response, but the high IPS and high IPS downregulation could be related to the degree of pathological response. Some patients with low preoperative expression of PD-L1 could still achieve a good response by NICT. As NCRT can upregulate the expression of PD-L1, the low preoperative expression of PD-L1 is no contraindication for immunotherapy, which provides a new basis and prognostic indexes for chemoradiotherapy combined with immunotherapy.

Clinical characteristics of moderate COVID-19 patients aggravation in Wuhan Stadium Cabin Hospital: A 571 cases of retrospective cohort study.

To report the clinical characteristics and potential risk factors of patients with coronavirus disease 2019 (COVID-19) in Wuhan Stadium Cabin Hospital in Hubei Province. A total of 571 patients of COVID-19 treated in the Wuhan Stadium Cabin Hospital were selected for analysis, univariable and multivariable logistic regression methods were used to explore the risk factors associated with disease aggravation. The main clinical symptoms of moderate COVID-19 were fever, cough and dyspnea, hypertension, diabetes, and coronary heart diseases were the main comorbidities both in transferred and stable patients. Twenty-six patients (4.55%) of mild and moderate patients had disease aggravation, and most of which occurred between 36 and 48 hours after admission. Multiple regression analysis showed increasing odds of disease aggravation associated with former smoker history, diabetes, dyspnea, consolidation, and interstitial abnormalities of computed tomography scanning, lymphopenia and elevated of C-reactive protein, the time points of transferred patients mainly between 36 and 48 hours (65.38%), and the average hospital stay for stable patients was 15 days.It could help clinicians to identify patients with poor prognosis at an early stage, and provide early warning role for timely intervention.

Development of a relative potency test using ELISA for human rabies vaccines.

The NIH potency test for human rabies vaccines has disadvantages for use, especially in developing countries where rabies is endemic and prophylaxis needs ample, rapid, and reliable vaccine supplies. In China, 60-75 million doses of human rabies vaccines are administered each year. Vaccine quality control is of paramount importance, as is the release of potency-validated vaccines. We intended to design an alternative to the NIH in vivo method, and developed a relative potency test using an ELISA. Using Pearson's correlation analysis, we found a close relationship between the rabies vaccine glycoprotein content in vitro and the potency values in vivo. We suggest the relative potency test developed here as a simplified method for human rabies vaccine quality control in China and a possible alternative to the NIH method.

Complete nucleotide sequence of a norovirus GII.4 genotype: evidence for the spread of the newly emerged pandemic Sydney 2012 strain to China.

A newly emerged pandemic Sydney GII.4-like norovirus (NoV) (Jingzhou GII.4) was isolated in Jingzhou, China in April, 2013, demonstrating the rapid spread of the variant to China. The complete nucleotide sequence was compared with the prototype Sydney 2012 variant and its VP1 gene with that of Huzhou strain (isolated in January 2013 in Huzhou, China). The result demonstrates that the new variant has evolved rapidly, including mutations in the hypervariable P2 domain of the major capsid protein VP1. Our study also shows that the new Jingzhou GII.4 variant co-circulated with GII.3 and GI.2 at the same time, supporting further monitoring of the evolution of the new NoV variant in China.

Stereoselective and controllable C3-Amination or C1,C3-di-amination of 2-nitroglycals.

Precise and selective modification of carbohydrates is a critical strategy in producing diverse carbohydrate derivatives for exploiting their functions. We disclosed a simple, efficient, and highly regioselective and stereoselective protocol to controllable amination of 2-nitroglycals under mild conditions in 5 min. A range of 3-amino-carbohydrates including 3-arylamino-2-nitro-glycals and 1,3-di-amino-carbohydrate derivatives were obtained in good to excellent yield with excellent stereoselectivity. The produced 3-amino-2-nitro-glycals can be used as a precursor for further transformation.

Association between IGF-1 levels and MDD: a case-control and meta-analysis.

Purpose: Insulin-like growth factor-1 (IGF-1) has a variety of neurotrophic effects, including neurogenesis, remyelination and synaptogenesis, and is an effective regulator of neuronal plasticity. Although multiple studies have investigated IGF-1 in depression-related disorders, few studies have focused on patients with a first episode of clearly diagnosed depression who had never used antidepressants before. Therefore, this study investigated first-episode and drug-naïve patients with depression to supplement the current evidence around IGF-1 levels in depressive disorders. Patients and methods: This study consisted of two parts. In the first part, 60 patients with first-episode and drug-naïve depression and 60 controls matched for age, sex, and BMI were recruited from the outpatient department of the Fourth Hospital of Wuhu City, and the community. The case-control method was used to compare differences in serum IGF-1 levels between the two groups. In the second part, 13 case-control studies were screened through the database for meta-analysis to verify the reliability of the results. Results: Results of the case-control study demonstrated that serum IGF-1 levels are significantly higher in patients with first-episode and drug-naïve depression compared to healthy controls (p<0.05), although there was no significant difference between men and women with diagnosed MDD, there was no significant correlation between serum IGF-1 level and age in patients with depression and no significant correlation between IGF-1 level and the severity of depression. The meta-analysis corroborates these findings and demonstrated that IGF-1 levels are significantly higher in MDD patients than in healthy controls. Conclusion: Patients with first-episode and drug-naïve depression have higher IGF-1 levels, but the exclusion of confounding factors in studies of IGF-1 as it relates to depressive disorders must be taken into consideration strictly, and additional research is needed to fully understand the critical role of IGF-1 in depression. Systematic review registration: PROSPERO, identifier CRD42023482222.

Critical role of FGF21 in diabetic kidney disease: from energy metabolism to innate immunity.

Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease (CKD) on a global scale, with its incidence witnessing a consistent annual rise, thereby imposing a substantial burden on public health. The pathogenesis of DKD is primarily rooted in metabolic disorders and inflammation. Recent years have seen a surge in studies highlighting the regulatory impact of energy metabolism on innate immunity, forging a significant area of research interest. Within this context, fibroblast growth factor 21 (FGF21), recognized as an energy metabolism regulator, assumes a pivotal role. Beyond its role in maintaining glucose and lipid metabolism homeostasis, FGF21 exerts regulatory influence on innate immunity, concurrently inhibiting inflammation and fibrosis. Serving as a nexus between energy metabolism and innate immunity, FGF21 has evolved into a therapeutic target for diabetes, nonalcoholic steatohepatitis, and cardiovascular diseases. While the relationship between FGF21 and DKD has garnered increased attention in recent studies, a comprehensive exploration of this association has yet to be systematically addressed. This paper seeks to fill this gap by summarizing the mechanisms through which FGF21 operates in DKD, encompassing facets of energy metabolism and innate immunity. Additionally, we aim to assess the diagnostic and prognostic value of FGF21 in DKD and explore its potential role as a treatment modality for the condition.

Large-Language-Model-Based AI Agent for Organic Semiconductor Device Research.

Large language models (LLMs) have attracted widespread attention recently, however, their application in specialized scientific fields still requires deep adaptation. Here, an artificial intelligence (AI) agent for organic field-effect transistors (OFETs) is designed by integrating the generative pre-trained transformer 4 (GPT-4) model with well-trained machine learning (ML) algorithms. It can efficiently extract the experimental parameters of OFETs from scientific literature and reshape them into a structured database, achieving precision and recall rates both exceeding 92%. Combined with well-trained ML models, this AI agent can further provide targeted guidance and suggestions for device design. With prompt engineering and human-in-loop strategies, the agent extracts sufficient information of 709 OFETs from 277 research articles across different publishers and gathers them into a standardized database containing more than 10 000 device parameters. Using this database, a ML model based on Extreme Gradient Boosting is trained for device performance judgment. Combined with the interpretation of the high-precision model, the agent has provided a feasible optimization scheme that has tripled the charge transport properties of 2,6-diphenyldithieno[3,2-b:2',3'-d]thiophene OFETs. This work is an effective practice of LLMs in the field of organic optoelectronic devices and expands the research paradigm of organic optoelectronic materials and devices.

Controllable 1,3-Bis-Functionalization of 2-Nitroglycals with High Regioselectivity and Stereoselectivity Enabled by a H-Bond Catalyst.

The selective modification of carbohydrates is significant for producing their unnatural analogues for drug discovery. C1-functionalization (glycosylation) and C1,C2-difunctionalization of carbohydrates have been well developed. In contrast, C3-functionalization or C1,C3-difunctionalization of carbohydrates remains rare. Herein, we report such processes that efficiently and stereoselectively modify carbohydrates. Specifically, we found that trifluoroethanol (TFE) could promote 1,3-bis-indolylation/pyrrolylation of 2-nitroglycals generated carbohydrate derivatives in up to 93% yield at room temperature; slightly reducing the temperature could install two different indoles at the C1- and C3-positions. Switching TFE to a bifunctional amino thiourea catalyst leads to the generation of C3 monosubstituted carbohydrates, which could also be used to construct 1,3-di-C-functionalized carbohydrates. This approach produced a range of challenging sugar derivatives (over 80 examples) with controllable and high stereoselectivity (single isomer for over 90% of the examples). The potential applications of the reaction were demonstrated by a set of transformations including the synthesis of bridged large-ring molecules and gram scale reactions. Biological activities evaluation demonstrated that three compounds exhibit a potent inhibitory effect on human cancer cells T24, HCT116, AGS, and MKN-45 with IC50 ranged from 0.695 to 3.548 µM.

Identifying circulating biomarkers for major depressive disorder.

Objective: To date, the current diagnosis of major depressive disorder (MDD) still depends on clinical symptomatologic criteria, misdiagnosis and ineffective treatment are common. The study aimed to explore circulating biomarkers for MDD diagnosis. Methods: A high-throughput antibody array technology was utilized to detect 440 circulating cytokines in eight MDD patients and eight age-and gender-matched healthy controls. LASSO regression was conducted for MDD-related characteristic proteins selection. Enzyme-linked immunosorbent assay (ELISA) was used to validate the characteristic proteins in 40 MDD patients and 40 healthy controls. Receiver operating characteristic (ROC) curve was employed to evaluate the diagnostic values of characteristic proteins for discriminating MDD patients from healthy controls. Correlations between the levels of characteristic proteins and depression severity (HAMD-17 scores) were evaluated using linear regression. Results: The levels of 59 proteins were found aberrant in MDD patients compared with healthy controls. LASSO regression found six MDD-related characteristic proteins including insulin, CD40L, CD155, Lipocalin-2, HGF and LIGHT. ROC curve analysis showed that the area under curve (AUC) values of six characteristic proteins were more than 0.85 in discriminating patients with MDD from healthy controls. Furthermore, significant relationship was found between the levels of insulin, CD155, Lipocalin-2, HGF, LIGHT and HAMD-17 scores in MDD group. Conclusion: These results suggested that six characteristic proteins screened from 59 proteins differential in MDD may hold promise as diagnostic biomarkers in discriminating patients with MDD. Among six characteristic proteins, insulin, CD155, Lipocalin-2, HGF and LIGHT might be useful to estimate the severity of depressive symptoms.

Efficacy and safety of non-steroidal mineralocorticoid receptor antagonists for renal outcomes: A systematic review and meta-analysis.

BACKGROUND: Novel nonsteroidal mineralocorticoid receptor antagonists (MRAs) are noted for their potential cardiorenal benefits for patients with type 2 diabetes mellitus and chronic kidney diseases; however, the effect of this regimen on renal outcomes remains uncertain. METHODS: We performed a systematic review and meta-analysis of nonsteroidal MRAs focusing primarily on renal outcomes and safety in randomized, controlled trials. The MEDLINE, Embase, and Cochrane databases were systemically searched for trials published through April 2022. We included randomized, controlled trials assessing the effects of nonsteroidal MRAs on renal outcomes, as well as cardiovascular disease (CVD) effects in patients with chronic kidney disease (CKD). Summary estimates of risk ratios (RRs) reductions were calculated with a random-effects model. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. This study is registered with PROSPERO under number CRD42022335464. FINDINGS: In total, 11 trials and 1 pooled analysis including a total of 17,517 participants were enrolled. Nonsteroidal MRAs reduced renal composite endpoints by 17 % [HR = 0.83, 95 % (0.75, 0.91); low quality] with 16 % in kidney failure (high quality), 23 % in ESRD (high quality), 20 % in eGFR decreased to less than 15 mL/min/1.73 m2 (high quality), and 17 % with more than a 40 % decrease in eGFR (high quality); 14 % with cardiovascular composite endpoints [HR = 0.86, 95 % (0.78, 0.94); moderate quality]; and 13 % of all-cause mortality [HR = 0.87, 95 % (0.76, 0.98); moderate quality]. Nonsteroidal MRAs were also associated with additional benefits in lowering UACR levels (moderate quality) and lowering BP levels (moderate quality) compared with the control groups. However, nonsteroidal MRAs did not show a statistically significant effect on the risk of renal death (moderate quality), hospitalization for any cause (moderate quality) or change in GFR (low quality). Regarding safety, there was no significant difference in the risk of adverse events between the participants receiving nonsteroidal MRAs and the control group. INTERPRETATION: Nonsteroidal MRAs had a statistically beneficial effect on reducing the risk of the composite kidney outcome, the composite of cardiovascular outcomes, and all-cause mortality. Nonsteroidal MRAs were also associated with benefits of proteinuria remission and blood pressure lowering. Although these findings provided positive evidence for the use of nonsteroidal MRAs for cardiorenal protection in patients with or without CKD, the quality of this evidence is potentially uncertain.

Analysis of the correlation between BMI and respiratory tract microbiota in acute exacerbation of COPD.

Objective: To investigate the distribution differences in the respiratory tract microbiota of AECOPD patients in different BMI groups and explore its guiding value for treatment. Methods: Sputum samples of thirty-eight AECOPD patients were collected. The patients were divided into low, normal and high BMI group. The sputum microbiota was sequenced by 16S rRNA detection technology, and the distribution of sputum microbiota was compared. Rarefaction curve, α-diversity, principal coordinate analysis (PCoA) and measurement of sputum microbiota abundance in each group were performed and analyzed by bioinformatics methods. Results: 1. The rarefaction curve in each BMI group reached a plateau. No significant differences were observed in the OTU total number or α-diversity index of microbiota in each group. PCoA showed significant differences in the distance matrix of sputum microbiota between the three groups, which was calculated by the Binary Jaccard and the Bray Curtis algorithm. 2. At the phylum level, most of the microbiota were Proteobacteria, Bacteroidetes Firmicutes, Actinobacteria, and Fusobacteria. At the genus level, most were Streptococcus, Prevotella, Haemophilus, Neisseria and Bacteroides. 3. At the phylum level, the abundance of Proteobacteria in the low group was significantly higher than that in normal and high BMI groups, the abundances of Firmicutes in the low and normal groups were significantly lower than that in high BMI groups. At the genus level, the abundance of Haemophilus in the low group was significantly higher than that in high BMI group, and the abundances of Streptococcus in the low and normal BMI groups were significantly lower than that in the high BMI group. Conclusions: 1. The sputum microbiota of AECOPD patients in different BMI groups covered almost all microbiota, and BMI had no significant association with total number of respiratory tract microbiota or α-diversity in AECOPD patients. However, there was a significant difference in the PCoA between different BMI groups. 2. The microbiota structure of AECOPD patients differed in different BMI groups. Gram-negative bacteria (G-) in the respiratory tract of patients predominated in the low BMI group, while gram-positive bacteria (G+) predominated in the high BMI group.