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Abstract Although decreasing body mass index (BMI) is associated with higher mortality risk in patients undergoing hemodialysis (HD), BMI neither differentiates muscle and fat mass nor provides information about the variations of fat distribution. It remains unclear whether changes over time in fat and muscle mass are associated with mortality. We examined the prognostic significance of trajectory in the triceps skinfold (TSF) thickness and mid-upper arm circumference (MUAC). In this multicenter prospective cohort study, 972 outpatients (mean age, 54.5 years; 55.3% men) undergoing maintenance HD at 22 treatment centers were included. We calculated the relative change in TSF and MUAC over a 1-year period. The outcome was all-cause mortality. Kaplan–Meier, Cox proportional hazard analyses, restricted cubic splines, and Fine and Gray sub-distribution hazards models were performed to examine whether TSF and MUAC trajectories were associated with all-cause mortality. During follow-up (median, 48.0 months), 206 (21.2%) HD patients died. Compared with the lowest trajectory group, the highest trajectories of TSF and MUAC were independently associated with lower risk for all-cause mortality (HR = 0.405, 95% CI 0.257–0.640; HR = 0.537; 95% CI 0.345–0.837; respectively), even adjusting for BMI trajectory. Increasing TSF and MUAC over time, measured as continuous variables and expressed per 1-standard deviation decrease, were associated with a 55.7% (HR = 0.443, 95% CI 0.302–0.649), and 97.8% (HR = 0.022, 95% CI 0.005–0.102) decreased risk of all-cause mortality. Reduction of TSF and MUAC are independently associated with lower all-cause mortality, independent of change in BMI. Our study revealed that the trajectory of TSF thickness and MUAC provides additional prognostic information to the BMI trajectory in HD patients.

Abstract Early insulin therapy is capable to achieve glycemic control and restore β-cell function in newly diagnosed type 2 diabetes (T2D), but its effect on cardiovascular outcomes in these patients remains unclear. In this nationwide real-world study, we analyzed electronic health record data from 19 medical centers across China between 1 January 2000, and 26 May 2022. We included 5424 eligible patients (mean age 56 years, 2176 women/3248 men) who were diagnosed T2D within six months and did not have prior cardiovascular disease. Multivariable Cox regression models were used to estimate the associations of early insulin therapy (defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients) with the incidence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization for heart failure (HF). During 17,158 persons years of observation, we documented 834 incident CHD cases, 719 stroke cases, and 230 hospitalized cases for HF. Newly diagnosed T2D patients who received early insulin therapy, compared with those who did not receive such treatment, had 31% lower risk of incident stroke, and 28% lower risk of hospitalization for HF. No significant difference in the risk of CHD was observed. We found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting models. These findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is predominant in young adults and children. Corticosteroid therapy has been controversial over several past decades. TESTING (Therapeutic Effects of Steroids in IgA Nephropathy Global) study, initiated in 2012, is an international, multicenter, double-blinded, randomized and placebo-controlled trial for evaluating oral methylprednisolone’s safety and long-term efficacy under conditions of optimized supportive treatment in IgAN patients at an elevated risk of progression. After one decade of efforts, successful completion of TESTING indicated that a 6 to 9 month course of oral methylprednisolone has been an effective regimen of protecting kidney function in high-risk IgAN patients. Some safety concerns persisted. Compared with a full-dose regimen, reduced-dose regimen was beneficial with higher safety. Overall, the TESTING trial provided more robust data regarding the treatment dosage and safety of corticosteroids. It has important implications for IgAN children. With a deeper pathogenetic understanding of IgAN, ongoing studies of novel therapeutic regimens shall further optimize the benefit-risk ratio.

Abstract The mortality rates for patients undergoing hemodialysis (HD) remain unacceptably high compared to the general population, and more specific information about the causes of death is not known. The study aimed to develop and validate a risk prediction model that uses common clinical factors to predict the probability of cardiovascular events in maintenance hemodialysis (MHD) patients. The study involved 3488 adult patients who received regular scheduled hemodialysis treatment at 20 hemodialysis centers in southwest China between June 2015 and August 2020, with follow-up until August 2021. The optimal parameter set was identified by multivariable Cox regression analyses and Cross-LASSO regression analyses and was used to establish a nomogram for predicting the risk of cardiovascular events in maintenance hemodialysis patients at 3 and 5 years. The performance of the model was evaluated using the consistency index (Harrell’s C-index), the area under the receiver operating characteristic (ROC) curve, and calibration plots. The model was validated by tenfold cross-validation and bootstrapping with 1000 resamples. In the derivation cohort, the model yields an AUC of 0.764 [95% confidence interval (CI), 0.737–0.790] and 0.793 [CI, 0.757–0.829] for predicting the risk of cardiovascular events of MHD patients at 3 and 5 years. In the internal validation cohort AUC of 0.803 [95% CI, 0.756–0.849], AUC of 0.766 [95% CI, 0.686–0.846], and the external validation cohort AUC of 0.826 [95% CI, 0.765–0.888], AUC of 0.817 [95% CI, 0.745–0.889] at 3 and 5 years. The model’s calibration curve is close to the ideal diagonal. By tenfold cross-validation analyses, the 3- and 5-year risk of cardiovascular events (AUC 0.732 and 0.771, respectively). By the bootstrap resampling method, the derivation cohort and validation cohort (Harrell’s C-index 0.695 and 0.667, respectively) showed good uniformity with the model. The constructed model accurately predicted cardiovascular events of MHD patients in the 3rd and 5th years after dialysis. And the further research is needed to determine whether use of the risk prediction tool improves clinical outcomes.

Abstract Background Gut microbiota alterations have been implicated in sepsis and related infectious diseases, but the causal relationship and underlying mechanisms remain unclear. Methods We evaluated the association between gut microbiota composition and sepsis using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics. Sensitivity analyses were conducted to validate the robustness of the results. Reverse MR analysis and integration of GWAS and expression quantitative trait loci (eQTL) data were performed to identify potential genes and therapeutic targets. Results Our analysis identified 11 causal bacterial taxa associated with sepsis, with increased abundance of six taxa showing positive causal relationships. Ten taxa had causal effects on the 28-day survival outcome of septic patients, with increased abundance of six taxa showing positive associations. Sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis did not provide evidence of reverse causality. Integration of GWAS and eQTL data revealed 76 genes passing the summary data-based Mendelian randomization (SMR) test. Differential expression of these genes was observed between sepsis patients and healthy individuals. These genes represent potential therapeutic targets for sepsis. Molecular docking analysis predicted potential drug-target interactions, further supporting their therapeutic potential. Conclusion Our study provides insights for the development of personalized treatment strategies for sepsis and offers preliminary candidate targets and drugs for future drug development.

Abstract Nocturnal hypertension is highly prevalent among Chinese and Asian populations, which is mainly attributed to high salt intake and high salt sensitivity. Nocturnal hypertension increases the risk of cardiovascular and all‐cause mortality, independent of daytime blood pressure (BP). However, it can usually be detected by 24‐h ambulatory BP monitoring, rather than routine office or home BP measurement, thus is often underdiagnosed in clinical practice. Currently, no specific guidance is available for the management of nocturnal hypertension in China or worldwide. Experts from the Chinese Hypertension League summarized the epidemiologic and pathophysiologic characteristics and clinical phenotype of nocturnal hypertension and provided consensus recommendations on optimal management of nocturnal hypertension, with the goal of maximally reducing the cardiovascular disease risks. In this consensus document, 24‐h ABPM is recommended for screening and diagnosis of nocturnal hypertension, especially in the elderly, patients with diabetes, chronic kidney diseases, obstructive sleep apnea and other conditions prone to high nocturnal BP. Lifestyle modifications including salt intake restriction, exercise, weight loss, sleep improvement, and mental stress relief are recommended. Long‐acting antihypertensive medications are preferred for nocturnal and 24‐h BP control. Some newly developed agents, renal denervation, and other device‐based therapy on nocturnal BP reduction are evaluated.

ABSTRACTIn China, a nation facing farmland scarcity, accurate mapping of winter fallow arable lands is crucial for enhancing crop rotation and land use efficiency. The Dynamic Threshold (DT) method commonly used in phenology and winter fallow land studies often employs empirically set subjective thresholds. This approach tends to uniformly apply a single threshold across diverse vegetation types and geographical regions, neglecting the variations in physiological traits and spatial heterogeneity. This study developed a multitemporal overlapping area minimization threshold method (MOAMT). This approach constructed Normalized difference vegetation index (NDVI) probability density functions for both winter fallow and non-winter fallow arable land across a time series to attain a statistically significant threshold. We use MOAMT and DT methods for winter fallow arable land extraction in southern China, respectively. And then, comparison of identification accuracy between MOAMT and DT has been implemented by using confusion matrix method. Compared to the DT method, MOAMT exhibits better performance. The mapping of winter fallow arable lands highlighted their predominant distribution in the middle and lower reaches of the Yangtze River (MLR-YR) Basin, covering approximately 20.8 million hectares, with potential for development. This study will provide information support for the optimization of planting layouts in China, offering new opportunities for further increasing grain production. While in the sense of research approach, this study indicates the superiority of threshold obtained through statistical probability calibration over empirical universal thresholds for classification accuracy. We advocate for prioritizing threshold calibration in future applications of threshold classification methods.

This study was performed to determine the status and ecological risk as well as provide a basis for the prevention and control of antibiotic contamination in the drinking water sources of Anhui Province. Ultra Performance Liquid Chromatography (UPLC-MS/MS) was used to measure the detection rate and concentrations of nine antibiotics, classified as sulfonamides (SAs) or tetracyclines (TCs), in water collected from 51 sampling points and from areas with different seasonal characteristics. The risks of the main antibiotics (Sulfamethoxazole (SMZ), Doxycycline (DOC), Sulfadiazine (SDZ), Sulfamerazine (SM2), Sulfadimethoxine (SDM), Doxycycline (DOC), Tetracycline (TC), Oxytetracyline (OTC), and Chlortetracycline (CTC). to the ecosystem and human beings were evaluated using risk quotients (RQs) and target hazard quotients (THQs), respectively. Nine antibiotics were detected in tap water and surface water at concentrations ranging from 1.71 ng L−1–21.92 ng L−1 and 1.54 ng L−1–78.74 ng L−1, respectively. SMZ and DOC were detected in both tap water and surface water. Their highest detection rates in tap water were 59.1% and 63.6%, respectively, and those in surface water were 81.25% and 43.8%, respectively. SDZ, SMZ, SM2, SDM, DOC, TC, OTC, and CTC were detected in the dry and flood seasons, with levels ranging from 2.43 ng L−1–49.43 ng L−1. Among the detected target antibiotics, SMZ, SM2, TC, OTC, and CTC had higher detection rates. The total concentrations of detected antibiotics were higher in fall than in the other seasons. TC and OTC present in different water sources posed a moderate risk. SDZ present in surface water posed a higher ecological risk than that present in tap water and ground water. Meanwhile, the presence of DOC in tap water and the low risk caused by SDM in surface waters should be emphasized.

Purpose: Renal interstitial fibrosis is a pathological manifestation of the progression of diabetic kidney disease (DKD). Dendrobium officinale polysaccharides (DOP), one of the major active components of Dendrobium officinale, have hypoglycemic and hypolipidemic effects and are used clinically to treat diabetes. However, the role of DOP in delaying DKD progression remains unclear. This study aimed to explore the potential mechanisms by which DOP delays DKD renal interstitial fibrosis. Methods: Using db/db mice as a model of DKD, we administered DOP by gavage and observed its therapeutic effectiveness. Employing ASO technology, we knocked down lncRNA XIST expression in kidney tissues and detected the expression of lncRNA XIST, TGF-β1, and renal interstitial fibrosis-related molecules. Results: DOP was primarily composed of monosaccharides, with 91.57% glucose and 1.41% mannose, forming a spheroid-like structure. It has a high polydispersity index with an Mw/Mn of 6.146, and the polysaccharides are mainly connected by 4-Man(p) and 4-Glc(p) linkages. In the kidneys of db/db mice, lncRNA XIST and TGF-β1 are highly expressed; however, their expression is significantly reduced after gastric infusion with DOP, and upon knockdown of lncRNA XIST, it might delay the progression of renal interstitial fibrosis in DKD. Conclusion: DOP may delay the progression of DKD renal interstitial fibrosis through the regulation of the LncRNA XIST/TGF-β1 related fibrotic pathway. This provides a new perspective for clinical strategies to delay the progression of DKD renal interstitial fibrosis.

The use of organic fertilizers instead of chemical fertilizers can improve soil pH, help to maintain soil health and enable landowners to achieve organic or ecological-status agriculture. Rapeseed cake, sheep manure, and biofungal fertilizer are considered to be effective amendments to improve soil quality. However, there have been few studies on the effects of the three fertilizers on strawberry production, soil physicochemical properties, and inter-root soil microbial community structure. In this study, field experiments were conducted to investigate the differences in strawberry growth, quality, yield, and the structure and diversity of strawberry soil bacterial and fungal communities under four treatments: no organic fertilizer (CK), rapeseed cake organic fertilizer (T1), sheep manure organic fertilizer (T2) and bio-organic fertilizer (algae-optimized bacteria) (T3), the relationship between soil physicochemical properties and soil microbial diversity were analyzed. Our results have shown that these three amendments promoted the growth of strawberry to some extent. The effects of available phosphorus, ammonium nitrogen, sucrase, protease and urease under T2 treatment were significantly increased by 50.62%, 54.14%, 276.50%, 129.47%, 232.61%, and 232.00%, respectively, compared with the control. The soil bacterial and fungi community were the most abundant and diversified under the T2 treatment. Soil physicochemical properties and soil key enzyme activities varied significantly under different fertilizer treatments, with the soil nutrient content and soil carbon and nitrogen metabolizing enzyme activities being highest under T2 treatment. A Pearson correlation analysis showed that soil organic matter was closely related to the diversity of soil microbial communities. A redundancy analysis (RDA) showed that the main variables of the bacterial community included nitrate nitrogen (NN) and rapidly available potassium (RAP), while the main variables of the fungal community included alkaline dissolved nitrogen (ADN) and ammonium nitrogen (AN). Overall, different fertilizers promoted the release and transformation of soil nutrients by affecting the structure and diversity of bacterial and fungal communities in strawberry soils, which was beneficial to the supply of soil nutrients and the improvement of soil quality. The application of sheep manure organic fertilizer had the best soil improvement effect.

BackgroundThe relationship between basal metabolic rate (BMR) and Chronic kidney disease (CKD) remains unclear and controversial. In this study, we investigated the causal role of BMR in renal injury, and inversely, whether altered renal function causes changes in BMR.MethodsIn this two-sample mendelian randomization (MR) study, Genetic data were accessed from published genome-wide association studies (GWAS) for BMR ((n = 454,874) and indices of renal function, i.e. estimated glomerular filtration rate (eGFR) based on creatinine (n =1, 004, 040), CKD (n=480, 698), and blood urea nitrogen (BUN) (n =852, 678) in European. The inverse variance weighted (IVW) random-effects MR method serves as the main analysis, accompanied by several sensitivity MR analyses. We also performed a reverse MR to explore the causal effects of the above indices of renal function on the BMR.ResultsWe found that genetically predicted BMR was negatively related to eGFR, (β= −0.032, P = 4.95*10-12). Similar results were obtained using the MR-Egger (β= −0.040, P = 0.002), weighted median (β= −0.04, P= 5.35×10-11) and weighted mode method (β= −0.05, P=9.92×10-7). Higher BMR had a causal effect on an increased risk of CKD (OR =1.36, 95% CI = 1.11-1.66, P =0.003). In reverse MR, lower eGFR was related to higher BMR (β= −0.64, P = 2.32×10-6, IVW analysis). Bidirectional MR supports no causal association was observed between BMR and BUN. Sensitivity analyses confirmed these findings, indicating the robustness of the results.ConclusionGenetically predicted high BMR is associated with impaired kidney function. Conversely, genetically predicted decreased eGFR is associated with higher BMR.

Abstract Background The value of radiomics features from the adrenal gland and periadrenal fat CT images for predicting disease progression in patients with COVID-19 has not been studied extensively. We assess the value of radiomics features from the adrenal gland and periadrenal fat CT images in predicting COVID-19 disease exacerbation. Methods A total of 1,245 patients (685 moderate and 560 severe patients) were enrolled in a retrospective study. We proposed a 3D V-net to segment adrenal glands in onset CT images automatically, and periadrenal fat was obtained using inflation operation around the adrenal gland. Next, we built a clinical model (CM), three radiomics models (adrenal gland model [AM], periadrenal fat model [PM], and fusion of adrenal gland and periadrenal fat model [FM]), and radiomics nomogram (RN) after radiomics features extracted. Results The auto-segmentation framework yielded a dice value 0.79 in the training set. CM, AM, PM, FM, and RN obtained AUCs of 0.717, 0.716, 0.736, 0.760, and 0.833 in the validation set. FM and RN had better predictive efficacy than CM (P

Abstract Background Our study aimed to evaluate change in sarcopenia, its defining components over 1 year follow‐up and investigate associations with subsequent cognitive decline, incident mild cognitive impairment (MCI) and dementia among patients undergoing haemodialysis (HD). Methods In the multicentre, longitudinal study, 1117 HD patients aged 56.8 ± 14.3 years (654 men; and 463 women) from 17 dialysis centres in Guizhou Province, China, were recruited in 2019 and followed up for 1 year in 2020. Sarcopenia was diagnosed with Asian Working Group for Sarcopenia criteria using appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS). Body composition was measured using body composition monitor; body water, weight, and height were corrected to calculate ASMI. HGS was measured by mechanical handgrip dynamometer. Cognitive function was measured with Mini Mental State Examination. Multivariate linear, logistic regression models and subgroup analyses were employed to examine the associations of changes in sarcopenia, ASMI, and HGS with Mini Mental State Examination score change, and incident MCI, dementia. Results Four hundred fourteen (37.1%) patients had sarcopenia at baseline; during 1 year follow‐up, 257 (23.0%) developed MCI and 143 (12.8%) developed dementia. According to changes in sarcopenia, patients were stratified into four groups: non‐sarcopenia; non‐sarcopenia to sarcopenia; sarcopenia; and sarcopenia to non‐sarcopenia. HD patients in sarcopenia and non‐sarcopenia to sarcopenia groups had higher risk of MCI (34.8%, 32.0%, vs. 17.4%) and dementia (20.6%, 19.8%, vs. 8.7%), compared non‐sarcopenia group (P 60 years, and with low educational level. Conclusions Longitudinal associations were observed between new‐onset, persistent sarcopenia, and cognitive impairment. Early detection and intervention should be implemented to delay the onset of sarcopenia and improve cognitive health among HD patients.

Abstract Objective To explore the association between intracellular water (ICW) and sarcopenic obesity in patients undergoing chronic haemodialysis (HD). Methods A multicentre, cross-sectional study of 3354 adult chronic HD patients was conducted in 20 haemodialysis centres from June 1, 2021, to August 30, 2021. The diagnosis of sarcopenic obesity was made according to the revised Asian Working Group’s definition of sarcopenia combined with obesity per the body fat percentage definition. Body composition was evaluated by a body composition monitor using bioimpedance spectroscopy. Multiple logistic regression models, stratified analyses, interactive analyses, and receiver-operating characteristic analyses were conducted. Results A total of 752 patients were diagnosed with sarcopenic obesity among 3354 participants. The patients were grouped by sex-specific ICW median levels, and the prevalence of sarcopenic obesity was significantly higher in the low ICW group than in the high ICW group (41.3%vs 3.0%). Decreased ICW was significantly associated with sarcopenic obesity. The association remained statistically significant even after adjusting for dialysis vintage, age, body mass index, biochemical indicators, and various medical histories. The odds ratios of the low ICW group were much higher than those of the high ICW group in both males and females (P for trend

Drought stress can reduce strawberry yield and quality and is one of the main abiotic factors restricting strawberry production in China. Nano-agricultural technology has significant regulatory effects in improving crop yield and quality and reducing agricultural environmental pollution. We performed a pot experiment using FenYu No. 1 strawberry and applied copper nanoparticles (CuNPs) and selenium NPs (SeNPs) to study their effects on the growth, quality, photosynthetic parameter indexes, and physiological characteristics of strawberry plants under drought stress. The growth and photosynthesis of strawberry plants were significant adversely affected by moderate drought stress (DS, 60% field capacity (FC)) and severe drought stress (SS, 25% FC). Compared with normal water-holding conditions, the application of CuNPs, SeNPs, and their combination effectively increased the agronomic traits of strawberry plants; improved fruit quality; and enhanced the content of photosynthetic pigments (chlorophyll a, chlorophyll b, and total chlorophyll), photosynthetic characteristic parameters, chlorophyll fluorescence parameters, and water-use efficiency. In addition, the exogenous application of CuNPs and SeNPs improved the drought tolerance of plants by increasing the activities of antioxidant enzymes catalase, peroxidase, and superoxide dismutase, and decreasing the malondialdehyde content, with the following overall trend among the treatments: control < CuNPs < SeNPs < CuNPs + SeNPs. The results of the principal component analysis showed that the two extracted principal components could reflect 85.54% of the information of the original data, leaf photosynthetic pigments, photosynthetic characteristic parameters, chlorophyll fluorescence parameters, and strawberry agronomic traits indexes and could be used as the primary indexes for evaluating the improvement of strawberry growth by nanofertilizers under drought-stress conditions. Taken together, our results indicate that nanofertilizers have potential for improving the growth, quality, and physiological characteristics of strawberries under drought stress.

Soil organic carbon stock (SOCS) changes caused by land use changes are still unclear, and understanding this response is essential for many environmental policies and land management practices. In this study, we investigated the temporal–spatial and vertical distribution characteristics of the SOCS in the Western Sichuan Plateau (WSP) using the sparrow search algorithm–random forest regression (SSA-RFR) models with excellent model applicability and accuracy. The temporal–spatial variations in the SOCS were modeled using 1080 soil samples and a set of nine environmental covariates. We analyzed the effect of land use changes on the SOCS in the WSP. The total SOCS increased by 18.03 Tg C from 1990 to 2020. The results of this study confirmed a significant increase in the SOCS in the study area since 2010. There was a 27.88 Tg C increase in the SOCS in 2020 compared to the total SOCS in 2010. We found that the spatial distribution of the SOCS increased from southeast to northwest, and the vertical distribution of the SOCS in the study area decreased with increasing soil depth. Forests and grasslands are the main sources of SOCS the total SOCS in the forest and grassland accounted for 37.53 and 59.39% of the total soil organic carbon (SOC) pool in 2020, respectively. The expansion of the wetlands, forest, and grassland areas could increase the SOCS in the study area. A timely and accurate understanding of the dynamics of SOC is crucial for developing effective land management strategies to enhance carbon sequestration and mitigate land degradation.

Abstract Acute kidney injury (AKI) is prevalent and a leading cause of in-hospital death worldwide. Early prediction of AKI-related clinical events and timely intervention for high-risk patients could improve outcomes. We develop a deep learning model based on a nationwide multicenter cooperative network across China that includes 7,084,339 hospitalized patients, to dynamically predict the risk of in-hospital death (primary outcome) and dialysis (secondary outcome) for patients who developed AKI during hospitalization. A total of 137,084 eligible patients with AKI constitute the analysis set. In the derivation cohort, the area under the receiver operator curve (AUROC) for 24-h, 48-h, 72-h, and 7-day death are 95·05%, 94·23%, 93·53%, and 93·09%, respectively. For dialysis outcome, the AUROC of each time span are 88·32%, 83·31%, 83·20%, and 77·99%, respectively. The predictive performance is consistent in both internal and external validation cohorts. The model can predict important outcomes of patients with AKI, which could be helpful for the early management of AKI.

Abstract Background In the general population, metabolic syndrome (MetS) is associated with increased risk of cognitive impairment, including global and specific cognitive domains. These associations are not well studied in patients undergoing hemodialysis and were the focus of the current investigation. Methods In this multicenter cross-sectional study, 5492 adult hemodialysis patients (3351 men; mean age: 54.4 ± 15.2 years) treated in twenty-two dialysis centers of Guizhou, China were included. The Mini-Mental State Examination (MMSE) was utilized to assess mild cognitive impairment (MCI). MetS was diagnosed with abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. Multivariate logistic and linear regression models were used to examine the associations of MetS, its components, and metabolic scores with the risk of MCI. Restricted cubic spline analyses were performed to explore the dose–response associations. Results Hemodialysis patients had a high prevalence of MetS (62.3%) and MCI (34.3%). MetS was positively associated with MCI risk with adjusted ORs of 1.22 [95% confidence interval (CI) 1.08–1.37, P = 0.001]. Compared to no MetS, adjusted ORs for MCI were 2.03 (95% CI 1.04–3.98) for 22.51 (95% CI 1.28–4.90) for 3, 2.35 (95% CI 1.20–4.62) for 4, and 2.94 (95% CI 1.48–5.84) for 5 components. Metabolic syndrome score, cardiometabolic index, and metabolic syndrome severity score were associated with increased risk of MCI. Further analysis showed that MetS was negatively associated with MMSE score, orientation, registration, recall and language (P

Background: Hypothalamic neuroinflammation is associated with disorders of lipid metabolism. Considering the anti-neuroinflammation effects of sodium-glucose cotransporter 2(SGLT2) inhibitors, a central administration of Dapagliflozin is postulated to provide hypothalamic protection and change lipid metabolism in kidney against diabetic kidney disease (DKD). Methods: Blood samples of DKD patients were collected. Male Sprague-Dawley (SD) rats with 30 mg/kg streptozotocin and a high-fat diet, db/db mice and palmitic acid (PA)-stimulated BV2 microglia were used for study models. 0.28 mg/3ul dapagliflozin was injected into the lateral ventricle in db/db mice. Genes and protein expression levels were determined by qPCR, western blotting, immunofluorescence, and immunohistochemistry staining. Secreted IL-1β and IL-6 were quantified by ELISA. Oil red O staining, lipidomic, and non-targeted metabolomics were performed to evaluate abnormal lipid metabolism in kidney. Results: The decrease of serum MCPIP1 was an independent risk factor for renal progression in DKD patients (OR=1.22, 95 %CI: 1.02–1.45, P = 0.033). Higher microglia marker IBA1 and lower MCPIP1 in the hypothalamus, as well as lipid droplet deposition increasing in the kidney were observed in DKD rats. Central dapagliflozin could reduce the blood sugar, hypothalamic inflammatory cytokines, lipid droplet deposition in renal tubular. Lipidomics and metabolomics results showed that dapagliflozin changed 37 lipids and 19 metabolites considered on promoting lipolysis. These lipid metabolism changes were attributed to dapagliflozin by upregulating MCPIP1, and inhibiting cytokines in the microglia induced by PA. Conclusions: Central administrated Dapagliflozin elicits an anti-inflammatory effect by upregulating MCPIP1 levels in microglia and changes lipid metabolism in kidney of DKD.

Background Functional impairment, malnutrition and fluid overload are prevalent in patients undergoing maintenance hemodialysis (MHD). The extracellular water/body cell mass ratio (ECW/BCM) is a new indicator reflecting fluid overload and malnutrition. A previous study has suggested that it performs better than other indices in assessing fluid status. This study investigates the relationship between pre-dialysis whole-body ECW/BCM and physical function in MHD patients.Methods We conducted a multicenter, cross-sectional study in Guizhou Province in Southwest China. The Karnofsky Performance Status (KPS) was used to evaluate patients’ functional status. Patients with KPS scores of ≤ 80 were considered to have a functional impairment. The body composition was measured using the body composition monitor (BCM), and the value of the ECW/BCM ratio was calculated. The subjects were classified into three groups according to ECW/BCM tertiles. Multiple logistic regression models and interactive analyses were conducted.Results The final analysis included 2818 subjects. Multivariate logistic regression analyses showed that compared with the lowest tertile (tertile 1), the adjusted odds ratio of functional impairment were 1.95 (95% CI: 1.21–3.13, p 0.05).Conclusions Elevated ECW/BCM is independently linked to an increased risk of functional impairment in patients with MHD.

Background Peritoneal dialysis (PD) patients have a high incidence of cardiovascular events (CVEs). Left ventricular fraction shortening (LVFS), one of the echocardiographic parameters, is an independent risk factor for mortality in previous studies. The aim of this study was to evaluate associations between LVFS and CVEs in PD patients.Methods This was a single-center observational cohort study. Seven hundred and eighty-four PD patients were enrolled from 1 January 2012 to 1 June 2021 and followed until 1 June 2022. The primary outcome was the incidence of CVEs. PD patients were categorized into three groups according to the tertiles of LVFS levels (tertile 1-tertile 3). Kaplan-Meier method, Cox proportional hazard models and competing risk regression models were used for survival analysis. The areas under the curve (AUC) of receiver-operating characteristic analysis was used to determine the predictive values of LVFS for CVEs. A preplanned subgroup analysis was assessed according to age, gender, and the presence of hypertension and dyslipidemia, etc.Results During a median follow-up period of 42.3 months (interquartile range 24.0–79.0 months), 259 CVEs occurred. Compared to the other two groups respectively, patients in tertile 3 group had the lowest incidence of CVEs (24.5% vs 31.6% vs 43.0%, respectively, p

AbstractBackground The optimal serum magnesium level of patients undergoing hemodialysis (HD) with cognitive impairment is still unclear. This study aimed to evaluate the association between serum magnesium levels and mild cognitive impairment among HD patients.Methods This was a multicenter observational study. Patients undergoing hemodialysis from 22 dialysis centers in Guizhou Province, China were recruited into the study. HD patients were divided into five groups according to serum magnesium quintile. Cognitive function was measured with Mini Mental State Examination. The outcome was an incident mild cognitive impairment (MCI). Multivariate logistic regression analysis, restricted cubic spline and subgroup analysis were applied to explore the association of serum magnesium level with MCI.Results Among 3562 HD patients (mean age 54.3 years, 60.1% male), the prevalence of MCI was 27.2%. After adjusting for confounders, serum magnesium 0.41–0.83 mmol/L [odds ratios (OR) 1.55, 95% confidence interval (CI): 1.10–2.18] had a higher risk of MCI compared with serum magnesium of 1.19–1.45 mmol/L. A U-shaped association was identified between the serum magnesium and incident MCI (P for non-linearity = 0.004). The optimal range of magnesium level with the lowest risk of MCI was 1.12–1.24 mmol/L. As the serum magnesium level was lower than 1.12 mmol/L, the risk of MCI decreased by 24% per standard deviation (SD) increase in serum magnesium (OR 0.76, 95%CI: 0.62–0.93); when the serum magnesium level exceeds 1.24 mmol/L, a rise per SD increased the risk of MCI by 21% (OR = 1.20, 95%CI: 1.02–1.43). Subgroup analyses demonstrated that the associations were robust among individuals with low educational level, smoking, living alone, no working, and without hypertension or diabetes.Conclusions Serum magnesium has a U-shaped association with MCI among HD patients. Both lower and higher serum magnesium can increase the risk of MCI for this population specifically. The optimal serum magnesium range with the lowest risk of MCI was 1.12–1.24 mmol/L.

The widespread use of antibiotics in animal and human medication has raised global concerns over environmental contamination caused by antibiotic residues. This research investigated the occurrence of 12 kinds of antibiotics belonging to three groups, sulfonamides (SAs), tetracyclines (TCs), and fluoroquinolones (FQs), in chicken manure and the surrounding soil from different chicken farms in Hangzhou, South China, were detected in the samples via ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and the contamination characteristics of each type of antibiotic and the correlations between each antibiotic and environmental factors were analyzed to identify the key influencing factors. An ecological risk assessment of antibiotics in the soil environment was conducted using the risk quotient (RQ) method to analyze the potential hazard level. The results indicated that: the total concentration of FQs was much higher than those of SAs and TCs in chicken manures and the soil samples. The mean concentration of FQs (39.17 μg·kg–1), TCs (34.37 μg·kg–1), and SAs (20.24 μg·kg–1) in chicken manure were significantly higher than those in the soil samples. Ciprofloxacin (CIP) was the main antibiotics detected in manure (19.42 μg·kg–1) and the soils samples (near soil: 18.42 μg·kg–1, far soil: 10.29 μg·kg–1), followed by enrofloxacin (ENR), tetracycline (TC), and ofloxacin (OFL). The redundancy analysis (RDA) showed that moisture content (MS), total organic carbon (TOC) and total nitrogen (TN) had a greater influence on the antibiotic concentration in the soil samples. Basis on the calculated risk quotient (RQs) values, the risk assessment indicated Sulfamerazine (SD) and Sulfamethoxazole (SMX) in soil posed a high risk, while trimethoprim (TMP), TC, CIP, and OFL in soils posed a medium or low risk. This research provides control and environmental monitoring data about chicken farms and scientific information that can be used to alleviate antibiotics pollution.

Spatiotemporal assessment and a comprehensive understanding of cropland sustainability are prerequisites for ensuring food security and promoting sustainable development. However, a remote sensing-based approach framework that is suitable for large-scale and high-precision assessment and can reflect the overall sustainability of cropland has not yet been developed. This study considered a typical lateritic red soil region of Guangdong Province, China, as an example. Cropland sustainability was examined from three aspects: natural capacity, management level, and food productivity. Ten typical indicators, including soil organic matter, pH, irrigation guarantee capability, multiple cropping index, and food productivity, among others, were constructed using remote sensing technology and selected to represent these three aspects. Based on the indicator system, we assessed the spatiotemporal patterns of cropland sustainability from 2010 to 2020. The results showed that the natural capacity, management level, and food productivity of cropland had improved over the 10 years. The cropland sustainability score increased from 67.95 to 69.08 over this period. The sustainability scores for 68.64% of cropland were increased and were largely distributed in the eastern and western region of the study area. The croplands with declining sustainability scores were mostly distributed in the central region. The prefecture-level regions differed in cropland sustainability, with Zhongshan, Zhuhai, and Qingyuan cities exhibiting the highest values, and Zhanjiang the lowest. Exploring the underlying mechanisms of cropland sustainability and proposing improvement measures can guide decision-making, cropland protection, and efficient utilization, especially in similar lateritic red soil regions of the world.

Biochar is a versatile, carbon-rich, organic material that can effectively immobilize Cd in the soil. In this study, peanut shell biochar (SP), maize straw biochar (MS), and bamboo straw biochar (BS) were applied in different proportions to evaluate their effects on the remediation of Cd-contaminated farmland soil and plant growth. The results revealed that both single and mixed applications of biochar substantially increased corn biomass and chlorophyll content compared to the unamended control treatment, while the malondialdehyde (MDA) and proline contents were largely unaffected. The bamboo straw block biochar with maize straw biochar at a mass ratio of 2:1 (DBM) significantly increased the dry total biomass of maize (+107.24% compared to the unamended soil). SP application has highly increased the SPAD value. PB with BS application at a mass ratio of 1:1 (MSB) significantly decreased the soluble sugar content (+21.81% compared to the unamended control soil). Soil pH was increased by the application of biochar alone and in combination with feedstocks. The soil content of Fe/Mn oxide-bound (OX) and exchangeable-bound Cd (EX) was decreased, whereas that of carbonate-bound Cd (CA), residue-bound Cd (RE), and organic-bound Cd (OM) contents increased. The Cd content in corn grains under MSB and SP application was markedly reduced by 42.62% and 31.48%, respectively, compared to the unamended control soil. Overall, MSB and SP applications were effective in improving soil quality and crop growth.

Background Ambient fine particulate matter ≤ 2.5 µm (PM2.5) air pollution exposure has been identified as a global health threat, the epidemiological evidence suggests that PM2.5 increased the risk of chronic kidney disease (CKD) among the diabetes mellitus (DM) patients. Despite the growing body of research on PM2.5 exposure, there has been limited investigation into its impact on the kidneys and the underlying mechanisms. Past studies have demonstrated that PM2.5 exposure can lead to lipid metabolism disorder, which has been linked to the development and progression of diabetic kidney disease (DKD). Methods In this study, db/db mice were exposed to different dosage PM2.5 for 8 weeks. The effect of PM2.5 exposure was analysis by assessment of renal function, pathological staining, immunohistochemical (IHC), quantitative real-time PCR (qPCR) and liquid chromatography with tandem mass spectrometry (LC–MS/MS) based metabolomic analyses. Results The increasing of Oil Red staining area and adipose differentiation related protein (ADRP) expression detected by IHC staining indicated more ectopic lipid accumulation in kidney after PM2.5 exposure, and the increasing of SREBP-1 and the declining of ATGL detected by IHC staining and qPCR indicated the disorder of lipid synthesisandlipolysis in DKD mice kidney after PM2.5 exposure. The expressions of high mobility group nucleosome binding protein 1 (HMGN1) and kidney injury molecule 1 (KIM-1) that are associated with kidney damage increased in kidney after PM2.5 exposure. Correlation analysis indicated that there was a relationship between HMGN1-KIM-1 and lipid metabolic markers. In addition, kidneys of mice were analyzed using LC–MS/MS based metabolomic analyses. PM2.5 exposure altered metabolic profiles in the mice kidney, including 50 metabolites. In conclusion the results of this study show that PM2.5 exposure lead to abnormal renal function and further promotes renal injury by disturbance of renal lipid metabolism and alter metabolic profiles.

Introduction: Comprehensive data on the risk of hospital-acquired (HA) acute kidney injury (AKI) among adult users of opioid analgesics are lacking. This study aimed to systematically compare the risk of HA-AKI among the users of various opioid analgesics. Methods: This multicenter, retrospective real-world study analyzed 255265 adult hospitalized patients who received at least one prescription of opioid analgesic during the first 30 days of hospitalization. Primary outcome was the time from the first opioid analgesic prescription to HA-AKI occurrence. 12 subtypes of opioid analgesics were analyzed, including 9 for treating moderate-to-severe pain and 3 for mild-to-moderate pain. We examined the association between the exposure to each subtype of opioid analgesic and the risk of HA-AKI using Cox proportional hazards models, using the most commonly used opioid analgesic as the reference group. Results: As compared to dezocine, the most commonly used opioid analgesic treating moderate-to-severe pain, exposure to morphine, but not the other 7 types of opioid analgesics, was associated with a significantly increased risk of HA-AKI (adjusted hazard ratio 1.56, 95% confidence interval [CI] 1.40–1.78). The association was consistent in stratified analyses and in a propensity-matched cohort. There were no significant differences in the risk of HA-AKI among the opioid analgesics users with mild-to-moderate pain after adjusting for confounders. Conclusion: The use of morphine was associated with an increased risk of HA-AKI in adult patients with moderate-to-severe pain. Opioid analgesics other than morphine should be chosen preferentially in adult patients with high risk of HA-AKI when treating moderate-to-severe pain.

Abstract Kidney functions, including electrolyte and water reabsorption and secretion, could be influenced by circulating hormones. The pituitary gland produces a variety of hormones and cytokines; however, the influence of these factors on the kidney has not been well explained and explored. To provide more in-depth information and insights to support the pituitary–kidney axis connection, we used mouse pituitary and kidney single-cell transcriptomics data from the GEO database for further analysis. Based on a ligand–receptor pair analysis, cell–cell interaction patterns between the pituitary and kidney cell types were described. Key ligand–receptor pairs, such as GH-GHR, PTN-SDC2, PTN-SDC4, and DLK1-NOTCH3, were relatively active in the pituitary–kidney axis. These ligand–receptor pairs mainly target proximal tubule cells, principal cells, the loop of Henle, intercalated cells, pericytes, mesangial cells, and fibroblasts, and these cells are related to physiological processes, such as substance reabsorption, angiogenesis, and tissue repair. Our results suggested that the pituitary gland might directly regulate kidney function by secreting multiple hormones or cytokines and indicated that the above ligand–receptor pairs might represent a new research focus for studies on kidney function or kidney disease.

Differentiated nitrogen (N) application styles and dosages can directly affect crop yield and planting costs. To maximize the efficiency of N fertilizer utilization and solve the problem of increasing production without increasing income, the Decision Support Systems for Agrotechnology Transfer (DSSAT) model was used in this study to carry out experiments simulating different N application styles and dosages for potatoes at 15 meteorological observation stations in the northeast region of China during 2013–2017. The present study aims to analyze the relationship among yield, cost, and net gains under different N fertilizer management scenarios by combining the cost-benefit method. The main conclusions are as follows: (1) the staged and incremental application of N fertilizer during the potato growth period can promote a yield increase. The lowest yield was achieved by a one-time basal application of N fertilizer at sowing, and the highest yield was observed when N fertilizer was applied in a 1:1 ratio at sowing and the end of tuber formation, respectively. (2) The range for N fertilizer application to achieve the highest potato yield at each station is 275–330 kg·ha−1. (3) The highest potato yield under sufficient N application treatments did not correspond to the highest net gains. Potato net gains at all stations showed an increasing-then-decreasing trend with the increase in N application. The highest gains were obtained when 220 kg·ha−1, 220 kg·ha−1, and 275 kg·ha−1 of N fertilizer were applied in a 1:1 ratio as a basal fertilizer and supplementary fertilizer at sowing, and the end of tuber formation in Heilongjiang, Jilin, and Liaoning provinces, respectively. This study provides a reference program for potato planting with the highest benefits for regional governments, farmers, and enterprises and aims to improve the status quo of potato planting, increasing production without increasing income.

Generic parameter calibration for crop growth models is a very important step in model use. However, studies of the effect of sample size and sampling methods on the calibration and validation of genotypic parameters have seldom been conducted. Scientists commonly apply the hold-out (HO) method, by default, to deal with samples for calibration and validation in the practice of model use. In this paper, we applied the hold-out, cross-validation (CA), and bootstrapping (BS) methods with different sample sizes to analyze the influence of sampling methods and sample size on the final calibration results of genotypic parameters. The results showed that, (1) overall, CA and BS performed better than HO at most observation stations. However, there was great variability in the calibration and validation results obtained from the three methods. (2) Because of data quality differences, we could not conclude that the more samples there were, the greater the validation accuracy of the three methods. (3) The CV of the genotypic parameter values for the three methods and sample sizes varied greatly. Thus, when genotypic parameter calibration is performed, both sampling methods and sample size should be considered.

BackgroundIt is now widely accepted that radiotherapy (RT) can provoke a systemic immune response, which gives a strong rationale for the combination of RT and immune checkpoint inhibitors (ICIs). However, RT is a double-edged sword that not only enhances systemic antitumor immune response, but also promotes immunosuppression to some extent. Nevertheless, many aspects regarding the efficacy and safety of this combination therapy remain unknown. Therefore, a systematic review and meta-analysis was performed in order to assess the safety and efficacy of RT/chemoradiotherapy (CRT) and ICI combination therapy for non-small cell lung cancer (NSCLC) patients.MethodsPubMed and several other databases were searched (according to specific criteria) to find relevant studies published prior to the 28th of February 2022.Results3,652 articles were identified for screening and 25 trials containing 1,645 NSCLC patients were identified. For stage II-III NSCLC, the one- and two-year overall survival (OS) was 83.25% (95% confidence interval (CI): 79.42%-86.75%) and 66.16% (95% CI: 62.3%-69.92%), respectively. For stage IV NSCLC, the one- and two-year OS was 50% and 25%. In our study, the pooled rate of grade 3-5 adverse events (AEs) and grade 5 AEs was 30.18% (95% CI: 10.04%-50.33%, I2: 96.7%) and 2.03% (95% CI: 0.03%-4.04%, I2: 36.8%), respectively. Fatigue (50.97%), dyspnea (46.06%), dysphagia (10%-82.5%), leucopenia (47.6%), anaemia (5%-47.6%), cough (40.09%), esophagitis (38.51%), fever (32.5%-38.1%), neutropenia (12.5%-38.1%), alopecia (35%), nausea (30.51%) and pneumonitis (28.53%) were the most common adverse events for the combined treatment. The incidence of cardiotoxicity (0%-5.00%) was low, but it was associated with a high mortality rate (0%-2.56%). Furthermore, the incidence of pneumonitis was 28.53% (95% CI: 19.22%-38.88%, I2: 92.00%), grade ≥ 3 pneumonitis was 5.82% (95% CI: 3.75%-8.32%, I2: 57.90%) and grade 5 was 0%-4.76%.ConclusionThis study suggests that the addition of ICIs to RT/CRT for NSCLC patients may be both safe and feasible. We also summarize details of different RT combinations with ICIs to treat NSCLC. These findings may help guide the design of future trials, the testing of concurrent or sequential combinations for ICIs and RT/CRT could be particularly useful to guide the treatment of NSCLC patients.

IntroductionSepsis-associated encephalopathy (SAE) is a diffuse cerebral dysfunction resulting from a systemic inflammatory response to infection; however, its pathophysiology remains unclear. Sepsis-induced neuroinflammation and blood–brain barrier (BBB) disruption are crucial factors in brain function disturbance in SAE. Mast cells (MCs) activation plays an important role in several neuroinflammation models; however, its role in SAE has not been comprehensively investigated.MethodsWe first established a SAE model by cecal ligation puncture (CLP) surgery and checked the activation of MCs. MCs activation was checked using immumohistochemical staining and Toluidine Blue staining. We administrated cromolyn (10mg/ml), a MC stabilizer, to rescue the septic mice. Brain cytokines levels were measured using biochemical assays. BBB disruption was assessed by measuring levels of key tight-junction (TJ) proteins. Cognitive function of mice was analyzed by Y maze and open field test. Transwell cultures of brain microvascular endothelial cells (BMVECs) co-cultured with MCs were used to assess the interaction of BMVECs and MCs.ResultsResults showed that MCs were overactivated in the hippocampus of CLP-induced SAE mice. Cromolyn intracerebroventricular (i.c.v) injection substantially inhibited the MCs activation and neuroinflammation responses, ameliorated BBB impairment, improved the survival rate and alleviated cognitive dysfunction in septic mice. In vitro experiments, we revealed that MCs activation increased the sensitivity of BMVECs against to lipopolysaccharide (LPS) challenge. Furthermore, we found that the histamine/histamine 1 receptor (H1R) mediated the interaction between MCs and BMVECs, and amplifies the LPS-induced inflammatory responses in BMVECs by modulating the TLR2/4-MAPK signaling pathway.ConclusionsMCs activation could mediate BBB impairment and cognitive dysfunction in septic mice in a histamine-dependent pathway.

Purpose Acteoside (Act), a phenylethanoid compound that was first isolated from mullein, has been widely used for the investigation of anti-inflammatory and anti-fibrotic effect. However, the mechanism of Act against unilateral ureteral obstruction (UUO)-mediated renal injury is largely unknown. Therefore, this study aimed to explore the effects of Act on UUO rats and possible mechanisms. Methods A total of 20 Sprague-Dawley (SD) rats were divided randomly into three groups (n ≥ 6): (i) sham-operated group (Sham); (ii) UUO group (UUO+Saline); and (iii) UUO + Act 40 mg/kg/day, (UUO+Act); Continuous gavage administration for 2 weeks postoperatively, while the rats in Sham and UUO+saline groups were given equal amounts of saline. All rats were sacrificed after 14 days, the urine and blood samples were collected for biochemical analysis, the renal tissues were collected for pathological staining and immunohistochemistry. Correlations between individual proteins were analyzed by Pearson correlation analysis. Results The results of renal function indexes and histopathological staining showed that Act could improve renal function by reducing serum creatinine, blood urea nitrogen and urine protein at the same time, Act could alleviate renal inflammation and fibrosis. In addition, the results of immunohistochemistry showed that Act could reduce the expression of inflammation and kidney injury-related proteins F4/80, Mcp-1, KIM-1 proteins, as well as the expression of fibrosis-related protein α-SMA and β-catenin. More importantly, Act can also reduce the expression of HMGN1, TLR4 and TREM-1 proteins. Conclusion These data demonstrate that Act can ameliorate UUO-induced renal inflammation and fibrosis in rats probably through triggering HMGN1/TLR4/TREM-1 pathway.

Objectives: This study involved a multi-omics analysis of glioblastoma (GBM) samples to elaborate the potential mechanism of drug treatment.Methods: The GBM cells treated with or without orexin A were acquired from sequencing analysis. Differentially expressed genes/proteins/metabolites (DEGs/ DEPs/ DEMs) were screened. Next, combination analyses were conducted to investigate the common pathways and correlations between the two groups. Lastly, transcriptome-proteome-metabolome association analysis was carried out to determine the common pathways, and the genes in these pathways were analyzed through Kaplan-Meier (K-M) survival analysis in public databases. Cell and animal experiments were performed to investigate the anti-glioma activity of orexin A.Results: A total of 1,527 DEGs, 52 DEPs, and 153 DEMs were found. Moreover, the combination analyses revealed that 6, 4, and 1 common pathways were present in the transcriptome-proteome, proteome-metabolome, and transcriptome-metabolome, respectively. Certain correlations were observed between the two data sets. Finally, 11 common pathways were discovered in association analysis, and 138 common genes were screened out in these common pathways. Six genes showed significant differences in terms of survival in both TCGA and CGGA. In addition, orexin A inhibited the proliferation, migration, and invasion of glioma in vitro and in vivo.Conclusion: Eleven common KEGG pathways with six common genes were found among different omics participations, revealing the underlying mechanisms in different omics and providing theoretical basis and reference for multi-omics research on drug treatment.

Tumor-associated macrophages (TAMs) exert integrated effects in all aspects of tumor progression, including tumor cell proliferation, angiogenesis, invasion, and metastasis. Recently, considerable preclinical and clinical trials have demonstrated that TAM-targeted therapy is an effective antitumor therapeutic approach, especially as a complementary strategy in combination with conventional chemotherapy, radiotherapy, or emerging immunotherapy. Here, we review all of the current clinical trials targeting TAMs worldwide up to May 2021 and highlight instances of the synergetic therapeutic efficacy of TAM-targeted combined therapeutic strategies. In total, 606 clinical trials were conducted, including 143 tested products. There has been explosive growth in macrophage-targeted therapy around the world during the past decade. Most trials were at early phase, and two-thirds used macrophage-targeting therapy as part of a combination approach. The most common combination is that of traditional chemotherapy with TAM-targeted therapy, followed by immune checkpoint inhibitors and targeted drugs. TAM-targeted therapeutic approaches are a newly emerging but rapidly developing area of anticancer therapy, especially as a combinatorial therapeutic approach. Further investigation of promising combination strategies will pave the way to more effective anticancer therapies.

MicroRNAs (miRNAs) are a class of small noncoding RNA that can regulate physiological and pathological processes through post-transcriptional regulatory gene expression. As an important member of the miRNAs family, microRNA-7 (miR-7) was first discovered in 2001 to play an important regulatory role in tissue and organ development. Studies have shown that miR-7 participates in various tissue and organ development processes, tumorigenesis, aging, and other processes by regulating different target molecules. Notably, a series of recent studies have determined that miR-7 plays a key regulatory role in the occurrence of inflammation and related diseases. In particular, miR-7 can affect the immune response of the body by influencing T cell activation, macrophage function, dendritic cell (DC) maturation, inflammatory body activation, and other mechanisms, which has important potential application value in the intervention of related diseases. This article reviews the current regulatory role of miR-7 in inflammation and related diseases, including viral infection, autoimmune hepatitis, inflammatory bowel disease, and encephalitis. It expounds on the molecular mechanism by which miR-7 regulates the occurrence of inflammatory diseases. Finally, the existing problems and future development directions of miR-7-based intervention on inflammation and related diseases are discussed to provide new references and help strengthen the understanding of the pathogenesis of inflammation and related diseases, as well as the development of new strategies for clinical intervention.

Abstract Background Normal-weight maintenance hemodialysis (MHD) patients with abdominal obesity exhibited a more proatherogenic profile than overweight and obesity patients with abdominal obesity, highlighting the importance of early identification of metabolically unhealthy nonobese (MUNO) in this population. Visceral fat accumulation plays a crucial role in the development of MUNO. Lipid accumulation product (LAP), visceral adiposity index (VAI) have been proved as reliable visceral obesity markers. The Chinese visceral adiposity index (CVAI) and a body shape index (ABSI) are newly discovered indexes of visceral obesity and have been reported to be associated with multiple metabolic disorders. There are limited studies investigating the associations between different visceral obesity indices and risk of MUNO, especially in hemodialysis patients. Moreover, no general agreement has been reached to date regarding which of these obesity indices performs best in identifying MUNO. We aimed to investigate the prevalence of MUNO in MHD patients and compare the associations between different adiposity indices (CVAI, ABSI,VAI, LAP, body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHtR)) with MUNO risk in this population. Methods We conducted a multi-center cross-sectional study in Guizhou Province, Southwest China. 1302 nonobese adult MHD patients were included in our study. MUNO was defined as being nonobese and having the presence of > = 2 components of metabolic syndrome (MetS). Nonobese was defined as BMI less than 25 kg/m2. VAI, LAP, CVAI, ABSI, BMI, WC and WHtR were calculated. Logistic regression analyses and receiver operator curve (ROC) analyses were performed. Results 65.6% participants were metabolically unhealthy. The ROC curve analysis demonstrated that of the seven obesity indices tested, the VAI (AUC 0.84 for women and 0.79 for men) followed by LAP (AUC 0.78 for women and 0.72 for men) had the highest diagnostic accuracy for MUNO phenotype while ABSI exhibited the lowest AUC value for identifying MUNO phenotype Conclusions Metabolically unhealthy is highly prevalent in nonobese MHD patients. VAI and LAP outperformed CVAI in discriminating MUNO in MHD patients. Though ABSI could be a weak predictor of MUNO, it is not better than WHtR, WC and BMI.

Abstract Background The 2019 novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) is a current worldwide threat for which the immunological features after infection need to be investigated. The aim of this study was to establish a highly sensitive and quantitative detection method for SARS-CoV-2 IgG antibody and to compare the antibody reaction difference in patients with different disease severity. Results Recombinant SARS-CoV-2 nucleocapsid protein was expressed in Escherichia coli and purified to establish an indirect IgG ELISA detection system. The sensitivity of the ELISA was 100% with a specificity of 96.8% and a 98.3% concordance when compared to a colloidal gold kit, in addition, the sensitivity of the ELISA was 100% with a specificity of 98.9% and a 99.4% concordance when compared to a SARS-CoV-2 spike S1 protein IgG antibody ELISA kit. The increased sensitivity resulted in a higher rate of IgG antibody detection for COVID-19 patients. Moreover, the quantitative detection can be conducted with a much higher serum dilution (1:400 vs 1:10, 1:400 vs 1:100). The antibody titers of 88 patients with differing COVID-19 severity at their early convalescence ranged from 800 to 102,400, and the geometric mean titer for severe and critical cases, moderate cases, asymptomatic and mild cases was 51,203, 20,912, and 9590 respectively. Conclusion The development of a highly sensitive ELISA system for the detection of SARS-CoV-2 IgG antibodies is described herein. This system enabled a quantitative study of rSARS-CoV-2-N IgG antibody titers in COVID-19 patients, the occurrence of higher IgG antibody titers were found to be correlated with more severe cases.

Single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of the gouty spine is rare. We describe a 66-year-old man who presented with pain and numbness in the right lower leg; he reported a 2-month history of intermittent low back pain. Imaging revealed neoplastic lesions of the spine, which were initially regarded as tumors. Thus, the patient underwent surgical removal of the lumbar lesion. However, the postoperative pathological diagnosis was gout spondylitis. In this report, we show multimodal images of advanced gout spondylitis. The metabolic information provided by SPECT/CT, combined with the microscopic changes in bone structure revealed by dual-source thin-layer CT and the anatomical localization information provided by magnetic resonance imaging, can help clinicians to more fully understand the pathophysiological mechanisms and imaging manifestations of gout from multiple perspectives, thereby reducing the rate of misdiagnosis.

Introduction: Cognitive impairment is prevalent in patients undergoing hemodialysis (HD), which is related to the nutritional and inflammatory status of this population. Malnutrition-inflammation score (MIS) has been identified as a useful tool to evaluate nutrition and inflammation status. The aim of this study is to investigate the association between MIS and cognitive impairment in HD patients. Methods: This was a multicenter observational cohort study with 1591 patients undergoing HD. Nutritional and inflammatory status was evaluated with MIS, anthropometric measurements, and body composition assessments. Cognitive function was evaluated with the Mini Mental State Examination (MMSE). The associations between MIS and cognitive impairment were analyzed by multivariable logistic regression models. Results: Among 1591 HD patients, the mean MIS was 6.0±2.6. Patients with higher MIS had significantly lower MMSE scores. 311 patients had cognitive impairment. After adjusting clinical confounders, higher MIS was independently associated with increased rate of cognitive impairment both as a categorized variable (OR, 1.358; 95%CI, 1.010-1.825; P=0.045) and as a continuous variable (OR, 1.113; 95%CI, 1.053-1.178; P

Acute kidney injury (AKI) is a complex and common set of multifactorial clinical syndromes, and associated with increased in-hospital mortality. There is increasing evidence that Hyperhomocysteinemia (HHcy) is highly associated with the development of a variety of kidney diseases, including AKI. However, the pathogenesis of HHcy in AKI remains unclear. In this study, we investigated the effect and mechanism of HHcy on cisplatin-induced AKI in mice and NRK-52E cells cultured with HHcy. We confirmed that mice with HHcy had higher serum levels of creatinine and more severe renal tubule injury after cisplatin injection. We found that HHcy aggravated renal mitochondrial damage, mainly manifested as decreased ATP β, significantly increased cytoplasmic Cyt C expression and the ADP/ATP ratio, and a significantly decreased mitochondrial DNA (mtDNA) copy number. In addition, we found that HHcy accelerated cisplatin-induced renal DNA damage; culturing NRK-52E cells with homocysteine (Hcy) could significantly increase apoptosis and mitochondrial damage. Interestingly, we found that Mdivi-1 reduced Hcy-induced mitochondrial damage, thereby reducing the level of apoptosis. In conclusion, these results suggest that HHcy might aggravate the development of AKI by increasing mitochondrial damage and that reducing Hcy levels or inhibiting mitochondrial damage may be a potential therapeutic strategy to delay the development of AKI.

Heavy metal-containing atmospheric particulate matter (PM) and acid rain (AR) trigger molecular alteration in plants, perturbing metabolites and damaging plant growth. However, the molecular mechanisms of plants under AR along with Cd-containing atmospheric fine particulate matter (PM2.5-Cd) stress remain unknown. In this study, integrated transcriptomics and metabolomics analyses of pak choi (Brassica pekinensis (Lour.) Rupr) exposed to AR (pH3.5) and PM2.5-Cd (500 μg·m−3) stress were performed. Metabolomics analyses revealed that AR-Cd stress mainly affected 42 metabolic pathways, including 451 differentially expressed metabolites (DEMs). RNA-seq identified 735 common differentially expressed genes (DEGs: 557 upregulated and 178 downregulated). Further analysis found several important DEGs (transcription factors, metabolic pathways genes, and signal transduction genes), including WRKY11, WRKY53, WRKY41, MYB73, NAC062, NAC046, HSFA4A, ABCC3, CAXs, GSTs, AZFs, PODs, PME41, CYP707A2, and CDPK32 implying that Cd chelate sequestration into the vacuoles, the antioxidant system, cell wall biosynthesis pathway, and calcium signaling play a critical role in AR damage and Cd detoxification. Conjoint revealed phenylpropanoid and flavonoid biosynthesis pathways with different metabolism patterns, including the key DEM, chlorogenic acids. The results obtained using multiple approaches provide a molecular-scale perspective on plant response to AR-Cd stress.

Objective: Immune inflammatory cells and cytokines play an important role in the occurrence and development of diabetic nephropathy (DN). Acteoside has been reported to regulate the inflammation and immune response. The study aims to investigate the effects of acteoside on the expressions of MCP-1 and TGF-β 1 on nephropathy in diabetic mice. Methods: C57BL/6J mice in the model group were given a single intraperitoneal injection of STZ (150 mg/kg). Model mice were divided randomly into two groups: 5 without treatment, 5 treated with acteoside. After continuous administration for 8 weeks, serum, urine, and kidney tissue were collected, then, ralated biochemical parameters, pathological characteristics and MCP-1 and TGF-β1 mRNA or protein were detected. The NRK-52E cells were divided into three groups as follows: the normal control group (NC group), the high glucose group (HS group), the high glucose+acteoside group (HS+ACT group). The expressions of MCP-1 and TGF-β 1 in the mRNA and protein levels were assessed with RT-PCR, western blot and ELISA. Results: The expressions of MCP-1 and TGF-β 1 were significantly enhanced in DN group and dramatically reduced after acteoside treatment. Compared with those in NC group, the expressions of MCP-1 and TGF-β 1 in NRK-52E cell of HS group were significantly enhanced, while both were significantly decreased in HS+ACT group compared with HS group. Conclusion: Our findings indicate that Acteoside has protective effects on DN via inhibiting the expressions of MCP-1 and TGF-β 1 .

Mitigating heavy metals (HMs) contamination and ensuring the safe production of crops is of paramount importance for sustainable agriculture development. The purpose of the current field plot study was to select maize varieties with low HMs and metalloids in their edible parts but high accumulation in other parts. The cadmium (Cd), arsenic (As), lead (Pb), and chromium (Cr) contents of 11 maize varieties were measured by atomic absorption spectrometry, and the plant growth and bioconcentration factors (BFs) were examined. Furthermore, the average daily intake (ADDi) of HMs in maize grains was calculated to assess the associated health risks. The results revealed that the growth of variety TZ23 was minimally impacted HMs and metalloids. The grains of all of the tested maize varieties contained Cr, As, and Pb contents in accordance with National Food Safety Standards (NFSSs, GB2762-2017, ≤0.1 mg·kg−1), while the Cd concentration in grains of varieties QJN1, LSCR, and JN20 were 0.084 mg·kg−1, 0.094 mg·kg−1, and 0.077 mg·kg−1, respectively, in accordance with NFSSs. The translocation factor (TF) of As, Pb and Cr in the grains of 11 maize varieties were found to be less than 1. However, the TF of grain Cd in varieties LYN9, JYN9, and QJN3 exceeded 1. For varieties HNY21, TZ23, and LYN9, the TF of Cd, As, Pb, and Cr in the stems/leaves was less than 1. Cluster analysis revealed that the grains of variety HNY21 had the lowest accumulation capacity of all four HMs. Importantly, the variety JN20 exhibited a high accumulation capacity for Pb and a low capacity for As, while both varieties SKN11 and QJN3 had high accumulation capacities for Cd and low capacities for As. Health risk (HR) indices of the different age groups displayed an overall trend of children > elderly > young adult. Among the HMs and metalloids, Cd and Cr pose the greatest health risks of maize intake. Variety QJN3 posed a significant HR due to chronic toxicity. This study provides a scientific basis for multi-element pollution control and screening of maize varieties suitable for cultivation in mining areas and the remediation of HMs-contaminated soils.

Objective(s): To explore the effect of verbascoside on renal fibrosis in unilateral ureteral obstruction (UUO) rats.Materials and Methods: Twenty Sprague-Dawley rats were randomly distributed into sham-operated, UUO, and UUO+Verbascoside groups. After two weeks of rat model construction, urine and blood samples were collected for biochemical analysis while kidney tissues were harvested for hematoxylin and eosin (H&E), Masson’s Trichrome, and immunohistochemistry staining. Pearson coefficient was used to analyze the correlation between the two proteins. Results: Verbascoside improved UUO-induced renal dysfunction as detected by decreased serum creatinine, urea nitrogen, and urinary protein excretion rate. In UUO rats, H&E staining result revealed increased total nucleated cell number, and Masson’s Trichrome staining results showed tubular interstitial fibrosis with the deposition of collagen fibrils. Besides, expressions of fibrosis-related proteins including collagen type I (COL-I), α-smooth muscle actin (a-SMA), and tissue inhibitor of metalloproteinase 2 (TIMP2) expressed higher in the UUO group. Moreover, macrophage infiltration-related factors such as CD68+, F4/80+ cells, and suppressor of cytokine signaling-3 (SOCS3) were significantly higher in the UUO group than in sham-operated rats. However, after administration with verbascoside, the accumulation of collagen fibrils and total nucleated cell numbers were mitigated. Likewise, macrophage infiltration was extenuated and fibrosis-related proteins were down-regulated in the UUO+Verbascoside rats. Correlation analysis indicated that macrophage infiltration-related markers were related to fibrosis-related factors.Conclusion: Verbascoside could alleviate renal fibrosis in UUO rats probably through ameliorating macrophage infiltration.

Abstract Background Anemia is one of the common complications in patients with chronic kidney disease (CKD). However, there is no systematic investigation on the prevalence of anemia in CKD patients and its relationship with the quality of life in China. Methods The data for this study comes from baseline data from the Chinese Chronic Kidney Disease Cohort Study (C-STRIDE), which recruited predialysis CKD patients in China. The kidney disease quality of life summary (KDQOL-TM) was used to assess health-related quality of life (HRQoL). Use linear regression model to estimate the relationship between hemoglobin level and quality of life. Results A total of 2921 patients were included in this study. The adjusted prevalence of hemoglobin (Hb) less than 100 g/L was 10.3% (95% confidence interval [CI]: 9.9,11.4%), and showed an increased trend through reduced eGFR levels from 4.0% (95%CI:2.3,5.9%) in the 45-60 ml/min/1.73m2 group to 23.4% (95%CI:20.5,26.2%) in the 15–29 ml/min/1.73m2 group. The prevalence of anti-anemia treatment was 34.0% (95%CI: 28.7,39.3%) and it is shown by reducing eGFR levels from 15.8% (95%CI:0,36.7%) in the 45-60 ml/min/1.73m2 group to 38.2% (95%CI: 30.7,45.2%) in the 15–29 ml/min/1.73m2 group. All five dimensions of the KDQOL scores in patients with CKD decreased as hemoglobin declined. After multivariable adjustments,the degrees of decrease became somewhat blunted. For example, compared with hemoglobin of ≥130 g/L, regression coefficients in the hemoglobin of

Objective(s): Acute renal ischemia may cause acute renal dysfunction due to lack of blood supply; the manifestations are renal tubular cell apoptosis, infiltration of macrophages, and microvascular destruction. Many studies have shown that erythropoietin (EPO) and vitamin D3 (VD3) can be used to prevent or treat renal ischemia-reperfusion (I/R) injury, and VD3 may interact with EPO. In the present study, the effects of the combination of VD3 and EPO in I/R acute kidney injury were studied. Materials and Methods: Rats were divided into 5 groups: sham-operated (SHAM), AKI without treatment (AKI-control), AKI treatment with VD3(AKI+VD3), AKI treatment with EPO(AKI+EPO), AKI treatment with VD3 and EPO(AKI+VD3+EPO). The effects of the combination of VD3 and EPO on AKI were assessed by histologic, inflammation, and apoptosis studies.Results: The degree of damage in renal tissue was significantly reduced in VD3, EPO, and combined groups. Combination therapy with VD3 and EPO markedly improved Creatinine clearance rate (CCr). The combined treatment group showed the lowest F4/80+ and CD68+ expressions. The expression of Bcl-2 in the combined treatment group was higher than those in VD3 group and the EPO group, while Bax’s expression goes in the opposite direction.Conclusion: This provides further evidence that VD3 and EPO have beneficial effects in I/R injury via anti-inflammatory and anti-apoptosis pathways. The synergistic protective effect of VD3 and EPO is of profound significance in the development of new strategies for the prevention and treatment of acute kidney injury (AKI).