Genistein Alleviates Intestinal Oxidative Stress by Activating the Nrf2 Signaling Pathway in IPEC-J2 Cells.

In the weaning period, piglets often face oxidative stress, which will cause increased diarrhea and mortality. Genistein, a flavonoid, which is extracted from leguminous plants, possesses anti-inflammatory and antioxidative bioactivities. However, little is known about whether genistein could attenuate the oxidative stress that occurs in porcine intestinal epithelial cells (IPEC-J2). Herein, this experiment was carried out to investigate the protective effects of genistein in the IPEC-J2 cells oxidative stress model. Our results disclosed that H2O2 stimulation brought about a significant diminution in catalase (CAT) activity and cell viability, as well as an increase in the levels of reactive oxygen species (ROS) in IPEC-J2 cells (p < 0.05), whereas pretreating cells with genistein before H2O2 exposure helped to alleviate the reduction in CAT activity and cell viability (p < 0.05) and the raise in the levels of ROS (p = 0.061) caused by H2O2. Furthermore, H2O2 stimulation of IPEC-J2 cells remarkably suppressed gene level Nrf2 and CAT expression, in addition to protein level Nrf2 expression, but pretreating cells with genistein reversed this change (p < 0.05). Moreover, genistein pretreatment prevented the downregulation of occludin expression at the gene and protein level, and ZO-1 expression at gene level (p < 0.05). In summary, our findings indicate that genistein possesses an antioxidant capacity in IPEC-J2 cells which is effective against oxidative stress; the potential mechanism may involve the Nrf2 signaling pathway. Our findings could offer a novel nutritional intervention strategy to enhance the intestinal health of piglets during the weaning process.

Silybin Alleviated Hepatic Injury by Regulating Redox Balance, Inflammatory Response, and Mitochondrial Function in Weaned Piglets under Paraquat-Induced Oxidative Stress.

Silybin (Si) is the main element of silymarin isolated from the seeds of Silybum marianum L. Gaernt., which has superior antioxidant properties. However, the protective role of Si in maintaining liver health under oxidative stress remains ambiguous. This study aimed to investigate the underlying mechanism of the beneficial effect of dietary Si against hepatic oxidative injury induced by paraquat (PQ) in weaned piglets. A total of 24 piglets were randomly allocated to four treatments with six replicates per treatment and 1 piglet per replicate: the control group; Si group; PQ group; and Si + PQ group. Piglets in the control group and PQ group were given a basal diet, while piglets in the Si and Si + PQ groups were given a Si-supplemented diet. On the 18th day, the pigs in the PQ treatment group received an intraperitoneal injection of PQ, and the others were intraperitoneally injected with the same volume of saline. All piglets were sacrificed on day 21 for plasma and liver sample collection. The results showed that dietary Si supplementation mitigated PQ-induced liver damage, as proven by the reduction in liver pathological changes and plasma activity of alanine transaminase and aspartate transaminase. Si also improved superoxide dismutase and glutathione peroxidase activities and total antioxidant capacity, as well as decreased malondialdehyde and hydrogen peroxide concentration in the liver, which were closely related to the activation of the nuclear factor-erythroid 2-related factor 2 signaling pathway. Meanwhile, Si reduced tumor necrosis factor-α and interleukin-8 production and their transcript levels as well as abrogated the overactivation of nuclear factor-κB induced by PQ. Importantly, Si improved mitochondrial function by maintaining mitochondrial energetics and mitochondrial dynamics, which was indicated by the elevated activity of mitochondrial complexes I and V and adenosine triphosphate content, decreased expression of dynamin 1 protein, and increased expression of mitofusin 2 protein. Moreover, Si inhibited excessive hepatic apoptosis by regulating the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated-X-protein signaling pathway. Taken together, these results indicated that Si potentially mitigated PQ-induced hepatic oxidative insults by improving antioxidant capacity and mitochondrial function and inhibiting inflammation and cell apoptosis in weaned piglets.

Evaluation of the Prognostic Role of Neutrophil-Lymphocyte Ratio, C-Reactive Protein-Albumin Ratio, and Platelet-Lymphocyte Ratio in Patients with the Co-Presentation of Coronary Artery Disease and COVID-19.

Aim: The purpose of this study was to investigate the role of neutrophil-lymphocyte ratio (NLR), C-reactive protein-albumin ratio (CAR), and platelet-lymphocyte ratio (PLR) in the prognosis of patients with coronary artery disease (CAD) complicated with coronavirus disease 2019 (COVID-19). Methods: This study included 265 patients. A receiver operating characteristic (ROC) curve analysis was performed to preliminarily evaluate the predictive ability of NLR, CAR, and PLR for all-cause death. The primary outcome was all-cause death during hospitalization, while the secondary outcomes were cardiovascular death and respiratory failure death. The Cox proportional hazard model with adjusted covariates was used to analyze the cumulative risk of outcomes. We also conducted subgroup analyses based on the acute and chronic characteristics of CAD. Propensity score matching (PSM) was used to further evaluate the robustness of the primary outcome. Results: The ROC curve analysis results showed that the area under curve (AUC) values were 0.686 (95% CI 0.592-0.781, P<0.001) for NLR, 0.749 (95% CI 0.667-0.832, P<0.001) for CAR, and 0.571 (95% CI 0.455-0.687, P=0.232) for PLR. The Cox proportional hazard model showed that trends in NLR and PLR did not affect the risk of all-cause death (P=0.096 and P=0.544 for trend, respectively), but a higher CAR level corresponded to a higher risk of all-cause death (P<0.001 for trend). Similarly, The trends of NLR and PLR did not affect the risk of cardiovascular death and respiratory failure death, while a higher CAR level corresponded to a higher risk of cardiovascular death and respiratory failure death. The results of subgroup analyses and PSM were consistent with the total cohort. Conclusion: In patients with CAD complicated with COVID-19, a higher CAR level corresponded to a higher risk of all-cause death, cardiovascular death, and respiratory failure death, while trends in NLR and PLR did not.

Birth Outcomes of Pregnant Women Infected with COVID-19 in Highland Areas of China from 2020 to 2022: A Retrospective Analysis.

Purpose: To explore the effect of coronavirus disease 2019 (COVID-19) infection on neonates in plateau regions. Methods: Cases of newborns born to pregnant women infected with COVID-19 who received prenatal care or treatment at the Women and Children's Hospital of the Tibet Autonomous Region and the Lhasa People's Hospital between January 2020 and December 2022 (infected group) and newborns born to healthy pregnant women (non-infected group) who were included by age, underlying disease and length of hospital stay were retrospectively collected. According to the inclusion and exclusion criteria, 381 patients in the infected group and 314 patients in the non-infected group were included in the study. Results: The results of multivariate analysis showed that admission to the neonatal intensive care unit (OR = 3.342, 95% CI = 1.564-6.764), shortness of breath (OR = 2.853, 95% CI = 1.789-3.154), irregular breathing (OR = 2.465, 95% CI = 1.879-4.112) and neonatal jaundice (OR = 2.324, 95% CI = 1.989-2.445) were the factors influencing the low Apgar scores of neonates in the infected group (all P < 0.05). Conclusion: Neonates born to pregnant women infected with COVID-19 had lower Apgar scores and higher incidences of complications, such as shortness of breath, groaning, irregular breathing and neonatal jaundice, than newborns born to pregnant women not infected with COVID-19.

Inflammatory risk of albumin combined with C-reactive protein predicts long-term cardiovascular risk in patients with diabetes.

AIMS: The purpose of this study was to evaluate the predictive value of inflammatory risk as defined by the Glasgow Prognostic Score (GPS) for cardiovascular death in patients with diabetes. METHODS: This study included 4956 patients (≥18 years old) with diabetes in the National Health and Nutrition Survey from 1999 to 2010. The mortality rate was determined by the correlation with the national death index on December 31, 2019. The GPS was composed of the serum C-reactive protein and the albumin. The primary outcome was cardiovascular death and the secondary outcome was all-cause death. The Cox proportional risk model adjusted for demographic factors and traditional cardiovascular risk factors was used to analyze the cumulative risk of outcomes. RESULTS: Among 4956 diabetes patients with a median follow-up of 10.9 years, 601 cardiovascular deaths and 2187 all-cause deaths were recorded. After adequate model adjustment, compared with the low GPS group, the high GPS group (HR, 1.257 (1.007-1.570), P = 0.043) had a higher cardiovascular mortality. Compared with the low GPS group, the all-cause mortality of the high GPS group (HR, 1.394 (1.245-1.560), P < 0.001) was higher. The results of subgroup analyses were similar with that of the overall cohort. CONCLUSIONS: The inflammatory risk as defined by the GPS was closely related to the increased risk of cardiovascular and all-cause death in patients with diabetes. It may be a convenient and efficient clinical practical risk assessment tool for patients with diabetes.

The impact of urinary albumin-creatinine ratio and glomerular filtration rate on long-term mortality in patients with heart failure: The National Health and Nutrition Examination Survey 1999-2018.

BACKGROUND AND AIMS: The urinary albumin‒creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are important markers of renal dysfunction, but few studies have simultaneously examined their impact on long-term mortality in patients with heart failure (HF). METHODS AND RESULTS: This study included patients with HF from the National Health and Nutrition Survey from 1999 to 2018. The fully adjusted Cox proportional risk model was adopted, and propensity score matching (PSM) was also used for risk adjustment. Among 988 patients, a median follow-up of 7.75 years was recorded. A higher UACR corresponded to a higher risk of cardiovascular death (P < 0.001 for trend). No statistically significant difference was found in the trend of eGFR risk stratification on the risk of cardiovascular death (P = 0.09 for trend). After PSM, the results showed that when grouped by UACR, the high-risk group had a higher risk of cardiovascular death regardless of a cutoff value of 30 or 300 mg/g (all P < 0.05). When grouped by eGFR, regardless of a cutoff value of 45 or 30 mL/min/1.73 m2, compared to the low-risk group, the high-risk group did not have a statistically significant increase in cardiovascular death (P = 0.086 and P = 0.093, respectively). The subgroup analysis of the main outcome showed an interaction between the UACR and eGFR (P = 0.044). CONCLUSIONS: Both the UACR and eGFR are markers for predicting the progression of HF, but the UACR may be a more important indicator than the eGFR, and they synergistically and complementarily reflect the long-term cardiovascular risk of HF patients.

Prevalence of Pelvic Floor Disorders in Parous Women from the Tibet Autonomous Region: A Cross-Sectional Study.

Purpose: Pelvic floor disorder (PFD) seriously affects the everyday life of women. This cross-sectional study aimed to evaluate the prevalence and risk factors for postpartum PFD in women living in the Tibet Autonomous Region (TAR). Methods: Parous women who attended the outpatient gynaecology clinic at our hospital between June 2022 and August 2022 were screened in this study. The demographic and clinical data of these women were collected. Their pelvic floor functions were evaluated via a pelvic organ prolapse (POP) quantification examination, the Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) and the Overactive Bladder Symptom Score (OABSS). Results: A total of 201 women were included in this study, of whom 81.09% (163/201) were Tibetan. Twenty-seven women (13.43%) were diagnosed with POP stage ≥2 and 27 women (13.43%) with an OABSS score ≥3. The median PFDI-20 total score was 4.17 (range 0-43.75). Han women (n = 38) in the TAR had much lower PFDI-20 total scores, compared with Tibetan women (n = 163) (p < 0.05). The results of the multiple linear regression models showed that the PFDI-20 scores obtained from women living in the TAR were closely related to parity, history of heavy weight lifting, age, history of instrumental deliveries, ethnicity and number of caesarean sections. Conclusion: Pelvic floor disorder is common among parous women living in the TAR. Ethnicity, parity, history of heavy weight lifting, age, history of instrumental deliveries and number of caesarean sections are the factors closely related to the PFDI-20 scores.

Rapid detection of Mycobacterium tuberculosis in sputum using CRISPR-Cas12b combined with cross-priming amplification in a single reaction.

IMPORTANCE: In this study, we successfully established a new One-Pot method, named TB One-Pot, for detecting Mtb in sputum by combining CRISPR-cas12b-mediated trans-cleavage with cross-priming amplification (CPA). Our study evaluated the diagnostic performance of TB One-Pot in clinical sputum samples for tuberculosis. The findings provide evidence for the potential of TB One-Pot as a diagnostic tool for tuberculosis.

Spatial transcriptomics defines injury-specific microenvironments in the adult mouse kidney and novel cellular interactions in regeneration and disease.

Kidney injury disrupts the intricate renal architecture and triggers limited regeneration, and injury-invoked inflammation and fibrosis. Deciphering molecular pathways and cellular interactions driving these processes is challenging due to the complex renal architecture. Here, we applied single cell spatial transcriptomics to examine ischemia-reperfusion injury in the mouse kidney. Spatial transcriptomics revealed injury-specific and spatially-dependent gene expression patterns in distinct cellular microenvironments within the kidney and predicted Clcf1-Crfl1 in a molecular interplay between persistently injured proximal tubule cells and neighboring fibroblasts. Immune cell types play a critical role in organ repair. Spatial analysis revealed cellular microenvironments resembling early tertiary lymphoid structures and identified associated molecular pathways. Collectively, this study supports a focus on molecular interactions in cellular microenvironments to enhance understanding of injury, repair and disease.

Potentiation and Mechanism of Berberine as an Antibiotic Adjuvant Against Multidrug-Resistant Bacteria.

The growing global apprehension towards multi-drug resistant (MDR) bacteria necessitates the development of innovative strategies to combat these infections. Berberine (BER), an isoquinoline quaternary alkaloid derived from various medicinal plants, has surfaced as a promising antibiotic adjuvant due to its ability to enhance the effectiveness of conventional antibiotics against drug-resistant bacterial strains. Here, we overview the augmenting properties and mechanisms of BER as an adjunctive antibiotic against MDR bacteria. BER has been observed to exhibit synergistic effects when co-administered with a range of antibiotics, including ß-lactams, quinolones, aminoglycosides, tetracyclines, macrolides, lincosamides and fusidic acid. The adjunctive properties of BER led to an increase in antimicrobial effectiveness for these antibiotics against the corresponding bacteria, a decrease in minimal inhibitory concentrations, and even the reversal from resistance to susceptibility sometimes. The potential mechanisms responsible for these effects included the inhibition of antibiotic efflux, the disruption of biofilm formation, the modulation of host immune responses, and the restoration of gut microbiota homeostasis. In brief, BER demonstrated significant potential as an antibiotic adjuvant against MDR bacteria and is a promising candidate for combination therapy. Further research is necessary to fully elucidate its mechanism of action and address the challenges associated with its clinical application.

The Effects of Dietary Silybin Supplementation on the Growth Performance and Regulation of Intestinal Oxidative Injury and Microflora Dysbiosis in Weaned Piglets.

Oxidative stress is the major incentive for intestinal dysfunction in weaned piglets, which usually leads to growth retardation or even death. Silybin has caught extensive attention due to its antioxidant properties. Herein, we investigated the effect of dietary silybin supplementation on growth performance and determined its protective effect on paraquat (PQ)-induced intestinal oxidative damage and microflora dysbiosis in weaned piglets. In trial 1, a total of one hundred twenty healthy weaned piglets were randomly assigned into five treatments with six replicate pens per treatment and four piglets per pen, where they were fed basal diets supplemented with silybin at 0, 50, 100, 200, or 400 mg/kg for 42 days. In trial 2, a total of 24 piglets were randomly allocated to two dietary treatments with 12 replicates per treatment and 1 piglet per pen: a basal diet or adding 400 mg/kg silybin to a basal diet. One-half piglets in each treatment were given an intraperitoneal injection of paraquat (4 mg/kg of body weight) or sterile saline on day 18. All piglets were euthanized on day 21 for sample collection. The results showed that dietary supplementation with 400 mg/kg silybin resulted in a lower feed conversion ratio, diarrhea incidence, and greater antioxidant capacity in weaned piglets. Dietary silybin enhanced intestinal antioxidant capacity and mitochondrial function in oxidative stress piglets induced by PQ. Silybin inhibited mitochondria-associated endogenous apoptotic procedures and then improved the intestinal barrier function and morphology of PQ-challenged piglets. Moreover, silybin improved intestinal microbiota dysbiosis induced by the PQ challenge by enriching short-chain fatty-acid-producing bacteria, which augmented the production of acetate and propionate. Collectively, these findings indicated that dietary silybin supplementation linearly decreased feed conversion ratio and reduced diarrhea incidence in normal conditions, and effectively alleviated oxidative stress-induced mitochondrial dysfunction, intestinal damage, and microflora dysbiosis in weaned piglets.

Analysis of genetic and chemical variability of five Curcuma species based on DNA barcoding and HPLC fingerprints.

The rhizomes of Curcuma species have a long medicinal history in Asia. In China, Curcuma species mainly be utilized to make pharmaceutical products, including C. phaecocaulis, C. aromatica, C. wenyujin, C. kwangsiensis and C. longa. In this study, twenty-four samples were selected to study the genetic and chemical variability among five Curcuma species. The ITS2 and trnK intron gene fragment were used to identify the five Curcuma species, the differences in chemical composition were computed using the Euclidean distance based on the data of HPLC characteristic peak areas and the content of six key components, and agronomic characteristics were analyzed including morphological and volatile oil characteristics. The ITS2 and trnK intron gene fragment could distinguish the five Curcuma species clearly. The genetic distance between Curcuma species ranged from 0.0085 to 0.0767 based on the data of ITS2 gene sequences with 32 variation sites, and the genetic distance between Curcuma species ranged from 0.0003 to 0.0194 based on the data of trnK intron gene sequences with 39 variation sites. Five Curcuma species showed otherness chemical composition characteristics, with the Euclidean distance ranging from 3.373 to 6.998. The C. longa showed the biggest variation compared with other species, with the Euclidean distance above 6.239. Among the samples of the original plants of Ezhu, the volatile oil yield of W1 was the highest, reached to 105.75 mL per single plant. Among all the samples, J6 showed the highest yield of volatile oil, reached to 149.42 mL per single plant. The results showed that chemical composition similarity of the medicinal plants was the primary proof for the selection of the original plants of the Curcuma medicinal materials. The genetic distance and chemical variability were important references for discovering new medicinal plant resources.

Developing a method to detect lipoarabinomannan in pleural fluid and assessing its diagnostic efficacy for tuberculous pleural effusion.

Objectives: The diagnosis of tuberculosis pleural effusion (TPE) remains challenging, traditional diagnostic tests have limited diagnostic efficacy. This study aimed to assess the diagnostic performance of pleural fluid (PF) lipoarabinomannan (LAM) in TPE. Methods: A diagnostic method for PF LAM (LAM-PF) was established using LEDBIO's AIMLAM kit. The diagnostic performance of LAM-PF was evaluated in 162 HIV-negative patients with suspected TPE. Results: The LAM-PF method established in this study exhibited good linearity and recovery rate, with a limit of detection (LOD) of 2.90 pg/mL. Using a cut-off value of 5.33 pg/mL, the sensitivity and specificity of LAM-PF in diagnosing TPE (n = 128) were 47.7% and 100.0%, respectively. The sensitivity in patients with probable TPE (n = 29) and definite TPE (n = 99) were 41.4% and 49.5%, respectively. LAM-PF displayed a significantly higher sensitivity in probable TPE compared to other tuberculosis detection methods. Combined testing of adenosine deaminase (ADA)and LAM increased the detection sensitivity of TPE to 68.0%, and the area under the curve was 0.84 (0.77-0.89). Conclusion: This study successfully established a method for detecting LAM in PF, which exhibited favorable diagnostic performance for TPE, particularly in challenging cases of probable TPE. Combined detection of LAM and ADA in PF significantly improves TPE diagnostic efficiency.

SMYD3 induces sorafenib resistance by activating SMAD2/3-mediated epithelial-mesenchymal transition in hepatocellular carcinoma.

Drug resistance prominently hampers the effects of systemic therapy of sorafenib to hepatocellular carcinoma (HCC). Epigenetics have critical regulatory roles in drug resistance. However, the contributions of histone methylatransferase SET and MYND domain containing 3 (SMYD3) to sorafenib resistance in HCC remain largely unknown. Here, using our established sorafenib-resistant HCC cell and xenograft models, we found SMYD3 was markedly elevated in sorafenib-resistant tumors and cells. Functionally, loss- and gain-of-function studies showed that SMYD3 promoted the migration, invasion, metastasis and stemness of sorafenib-resistant HCC cells. Mechanistically, SMYD3 is required for SMAD2/3-mediated epithelial-mesenchymal transition (EMT) in sorafenib-resistant HCC cells by interacting with SMAD2/3 and epigenetically promoting the expression of SOX4, ZEB1, SNAIL1 and MMP9 genes. In summary, our data demonstrate that targeting SMYD3 is an effective approach to overcome sorafenib resistance in HCC.

Smoking is a Factor in Discordance Between QuantiFERONTB Gold Assay and Tuberculosis Etiology: Especially in Older Patients.

Purpose: Exploring whether smoking is an influencing factor for the inconsistency between QuantiFERONTB Gold assay (QFT-GIT) and tuberculosis etiology. Patients and Methods: The clinical data of patients who were confirmed positive for Mycobacterium tuberculosis (MTB) after undergoing QFT-GIT testing from September 2017 to August 2021 were retrospectively analyzed. Chi-square and rank-sum tests were used to compare the differences in characteristics between smokers and non-smokers. Logistic regression was used to adjust for confounding factors affecting smoking. Propensity score matching (PSM) was used to verify the above conclusions again. Results: Positive results of tuberculosis etiology were adopted as the standard, the incidence of inconsistent results between QFT-GIT and tuberculosis etiology was 8.90% (108/1213), of which the false negative rate was 6.27% (76/1213) and the indeterminate rate was 2.64% (32/1213). In the overall population, the smokers had a lower level of basal IFN-γ (Z=-2.079, P=0.038). Among 382 elderly (≥65 years old) patients, the smokers had lower levels of antigen-stimulated IFN-γ (Z=-2.838, P=0.005). After performing BOX-COX transformation on all non-normally distributed data, logistic stepwise regression was used to adjust confounding factors. The results showed that smoking was an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiology results (OR=1.69, P=0.020). Using PSM for 1:2 matching, the results showed that smoking was still an independent risk factor for the inconsistent results of QFT-GIT and tuberculosis etiology (OR= 1.95, P=0.019). Age-stratified analysis showed that smoking was an independent risk factor in discordance between QFT-GIT and tuberculosis etiology in patients aged ≥65 years (OR=2.40, P=0.005), but not in patients aged <65 years (P > 0.05). Conclusion: Smoking can reduce the body's IFN-γ release ability, and smoking (especially the elderly) is an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiological results.

Evaluation of the performances of InnowaveDx MTB-RIF assay in the diagnosis of pulmonary tuberculosis using bronchoalveolar lavage fluid.

OBJECTIVE: To evaluate the tuberculosis diagnostic performance of the InnowaveDx MTB-RIF assay (InnowaveDx test) in bronchoalveolar lavage fluid (BALF). METHODS: A total of 213 BALF samples from suspected PTB patients were analyzed. AFB smear, culture, Xpert, Innowavedx test, CapitalBio test and simultaneous amplification and testing (SAT) were performed. RESULTS: Of the 213 patients included in the study, 163 were diagnosed with PTB, and 50 were TB negative. Using the final clinical diagnosis as the reference, the sensitivity of InnowaveDx assay was 70.6%, which was significantly higher than the values achieved using the other methods (P < 0.05), and the specificity was 88.0%, which was comparable with other methods (P > 0.05). Among the 83 PTB cases with negative culture results, the detection rate of InnowaveDx assay was significantly higher than those of AFB smear, Xpert, CapitalBio test and SAT (P < 0.05). Kappa analysis was used to compare the agreement of InnowaveDx and Xpert in detecting RIF sensitivity, and the result showed the Kappa value was 0.78. CONCLUSIONS: The InnowaveDx test is a sensitive, rapid and cost-effective tool for PTB diagnosis. In addition, the sensitivity of InnowaveDx to RIF in samples with low TB load should be interpreted with caution in light of other clinical data.

Glomerular filtration rate estimated by differing measures and risk of all-cause mortality among Chinese individuals without or with diabetes: A nationwide prospective study.

BACKGROUND: Whether estimated glomerular filtration rates (eGFRs) by differing biomarkers are differentially associated with mortality or whether the associations differ by diabetes status remains unclear, especially in Chinese population. METHODS: We included 6995 participants without diabetes (mean age: 60.4 years) and 1543 with diabetes (mean age: 61.8 years). Each eGFR measure was divided into normal (≥90 mL/min/1.73 m2 ), modestly declined (60 to <90 mL/min/1.73 m2 ), and chronic kidney disease (CKD) (<60 mL/min/1.73 m2 ) groups. Cox proportional hazards models were used to estimate hazard ratio (HR) of all-cause mortality associated with each eGFR. RESULTS: Over a follow-up of 7 years, 677 and 215 deaths occurred among individuals without or with diabetes, respectively. Among those without diabetes, all measures of modestly declined eGFR were not associated with mortality, whereas CKD defined by eGFR cystatin C (eGFRcys) and eGFR creatinine (eGFRcr)-cys (HRs were 1.71 and 1.55, respectively) but not by eGFRcr were associated with higher risk of mortality. Among diabetes, all measures of modestly declined eGFR (HRs: 1.53, 1.56, and 2.09 for eGFRcr, eGFRcys, and eGFRcr-cys, respectively) and CKD (HRs: 2.57, 2.99, and 3.92 for eGFRcr, eGFRcys, and eGFRcr-cys, respectively) were associated with higher risk of mortality. Regardless of diabetes status, an addition of eGFRcys or eGFRcr-cys to traditional risk factors lead to a larger improvement in the prediction of all-cause mortality risk than adding eGFRcr. CONCLUSIONS: The association of eGFR with mortality risk appeared to be varied by its measures and by diabetes status among middle-aged and older Chinese, which needs to be considered in clinical practice.

EPOR activation attenuates colitis via enhancing LC3B-dependent apoptotic cell clearance.

Systemic immune activation and excessive inflammatory response, induced by intestinal barrier damage, are the major characteristics of inflammatory bowel disease (IBD). Excessive apoptotic cell accumulation leads to the production of a large number of inflammatory factors, further aggravating IBD development. Gene set enrichment analysis data showed that the homodimeric erythropoietin receptor (EPOR) was highly expressed in the whole blood of patients with IBD. EPOR is specifically expressed in intestinal macrophages. However, the role of EPOR in IBD development is unclear. In this study, we found that EPOR activation significantly alleviated colitis in mice. Furthermore, in vitro, EPOR activation in bone marrow-derived macrophage (BMDMs) promoted microtubule-associated protein 1 light chain 3B (LC3B) activation and mediated the clearance of apoptotic cells. Moreover, our data showed that EPOR activation facilitated the expression of phagocytosis- and tissue-repair-related factors. Our findings suggest that EPOR activation in macrophages promotes apoptotic cell clearance, probably via LC3B-associated phagocytosis (LAP), providing a new mechanism for understanding pathological progression and a novel potential therapeutic target for colitis.