Causal associations between thyroid cancer and IgA nephropathy: a Mendelian randomization study.

BACKGROUND: The incidence of kidney disease caused by thyroid cancer is rising worldwide. Observational studies cannot recognize whether thyroid cancer is independently associated with kidney disease. We performed the Mendelian randomization (MR) approach to genetically investigate the causality of thyroid cancer on immunoglobulin A nephropathy (IgAN). METHODS AND RESULTS: We explored the causal effect of thyroid cancer on IgAN by MR analysis. Fifty-two genetic loci and single nucleotide polymorphisms were related to thyroid cancer. The primary approach in this MR analysis was the inverse variance weighted (IVW) method, and MR‒Egger was the secondary method. Weighted mode and penalized weighted median were used to analyze the sensitivity. In this study, the random-effect IVW models showed the causal impact of genetically predicted thyroid cancer across the IgAN risk (OR, 1.191; 95% CI, 1.131-1.253, P < 0.001). Similar results were also obtained in the weighted mode method (OR, 1.048; 95% CI, 0.980-1.120, P = 0.179) and penalized weighted median (OR, 1.185; 95% CI, 1.110-1.264, P < 0.001). However, the MR‒Egger method revealed that thyroid cancer decreased the risk of IgAN, but this difference was not significant (OR, 0.948; 95% CI, 0.855-1.051, P = 0.316). The leave-one-out sensitivity analysis did not reveal the driving influence of any individual SNP on the association between thyroid cancer and IgAN. CONCLUSION: The IVW model indicated a significant causality of thyroid cancer with IgAN. However, MR‒Egger had a point estimation in the opposite direction. According to the MR principle, the evidence of this study did not support a stable significant causal association between thyroid cancer and IgAN. The results still need to be confirmed by future studies.

Comparative efficacy of intravenous and oral iron supplements for the treatment of iron deficiency in patients with heart failure: A network meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed at comparing the efficacy of intravenous and oral iron supplementations for the treatment of iron deficiency (ID) in patients with heart failure (HF). METHODS: We searched the PubMed, Cochrane, and Embase databases from inception to January 15, 2022. We included randomized controlled trials enrolling patients with HF who were treated for ID with intravenous iron supplements, oral iron supplements, or placebo. The primary outcomes were all-cause death, cardiovascular mortality, and hospitalization for heart failure. The secondary outcomes were evaluated through the six-minute walking test (6MWT) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: The network meta-analysis included sixteen studies. Compared to placebo/control groups, intravenous iron supplements did not decrease all-cause death (0.69, 0.39-1.23) or cardiovascular mortality (0.89, 0.66-1.20). After 12 weeks, a reduced hospitalization for heart failure was associated with the administration of intravenous iron supplementations (0.58, 0.34-0.97). The most significant improvements regarding 6MWT (44.44, 6.10-82.79) and KCCQ (5.96, 3.19-8.73) were observed with intravenous iron supplements. Oral iron supplements reduced hospitalization for heart failure (0.36, 0.14-0.96) and all-cause death (0.34, 0.12-0.95), but did not influence the 6MWT (29.74, -47.36 to 106.83) and KCCQ (0.10, -10.95 to 11.15). CONCLUSIONS: Administering intravenous iron supplements for ID in patients with HF improves their exercise capacity and quality of life. In order to reduce hospitalizations for heart failure, the supplementation should be administered for more than 12 weeks. Although oral iron supplements did not improve exercise capacity and quality of life, they could reduce all-cause death and hospitalizations for heart failure.

Epicardial adipose tissue is associated with higher recurrence risk after catheter ablation in atrial fibrillation patients: a systematic review and meta-analysis.

OBJECTIVE: Our study aimed to investigate the association between epicardial adipose tissue (EAT) and atrial fibrillation (AF) recurrence risk after catheter ablation. METHODS: We searched PubMed, Embase, and Cochrane Library databases up to November 30, 2021 without language restrictions. Outcome was the relative risk (RR) of EAT contributes to AF recurrence after catheter ablation. The RR and 95% confidence interval (CI) was pooled by the random-effect model. RESULTS: 10 studies that contained 1840 AF patients were included in our study. The result of this study showed that EAT amount was associated with higher risk of AF recurrence after catheter ablation (RR = 1.06, 95% CI 1.02-1.11, P = 0.005) and EAT related thickness was a risk factor for AF recurrence after catheter ablation (RR = 1.73, 95% CI 1.04-2.87, P = 0.040). Sub-analysis showed that EAT was strongly associated with higher risk of AF recurrence common in Asian population (RR = 1.25, 95% CI 1.10-1.43, P < 0.001), patients aged ≤ 60 years old (RR = 2.01, 95% CI 1.18-3.44, P = 0.010), and follow-up more than 1 year (RR = 1.06, 95% CI 1.01-1.11, P = 0.020). CONCLUSION: The meta-analysis demonstrated that EAT related thickness seems to be the marker most strongly associated with a greater risk of AF recurrences after catheter ablation. It should be included into risk stratification for predicting AF recurrent before catheter ablation.

A nomogram to predict hyperkalemia in patients with hemodialysis: a retrospective cohort study.

BACKGROUND: Hyperkalemia increases the risk of mortality and cardiovascular-related hospitalizations in patients with hemodialysis. Predictors of hyperkalemia are yet to be identified. We aimed at developing a nomogram able to predict hyperkalemia in patients with hemodialysis. METHODS: We retrospectively screened patients with end-stage renal disease (ESRD) who had regularly received hemodialysis between Jan 1, 2017, and Aug 31, 2021, at Lishui municipal central hospital in China. The outcome for the nomogram was hyperkalemia, defined as serum potassium [K+] ≥ 5.5 mmol/L. Data were collected from hemodialysis management system. Least Absolute Shrinkage Selection Operator (LASSO) analysis selected predictors preliminarily. A prediction model was constructed by multivariate logistic regression and presented as a nomogram. The performance of nomogram was measured by the receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis (DCA). This model was validated internally by calculating the performance on a validation cohort. RESULTS: A total of 401 patients were enrolled in this study. 159 (39.65%) patients were hyperkalemia. All participants were divided into development (n = 256) and validation (n = 145) cohorts randomly. Predictors in this nomogram were the number of hemodialysis session, blood urea nitrogen (BUN), serum sodium, serum calcium, serum phosphorus, and diabetes. The ROC curve of the training set was 0.82 (95%CI 0.77, 0.88). Similar ROC curve was achieved at validation set 0.81 (0.74, 0.88). The calibration curve demonstrated that the prediction outcome was correlated with the observed outcome. CONCLUSION: This nomogram helps clinicians in predicting the risk of PEW and managing serum potassium in the patients with hemodialysis.

Preparation, characterization, and antibacterial activity of tigecycline-loaded, ultrasound-activated microbubbles.

Central nervous system infectious disease caused by the multidrug-resistant Acinetobacter baumannii (AB) seriously threatens human life in clinic. Tigecycline has good sensitivity in killing AB, but due to its wide tissue distribution and blood-brain barrier, concentration in cerebrospinal fluid is low, therefore, the clinical effect is limited. Herein, we designed micro-bubbled tigecycline, aimed to enhance its anti-MDRAB effects under ultrasound. The lipid microbubbles with different ratios of lipids to drugs (a ratio of 10:1, 20:1, and 40:1) were prepared by the mechanical shaking method. The morphology, zeta potential and particle size of microbubbles were tested to screen out the much better formulation. Encapsulation efficiency and drug loading amount were determined by ultracentrifugation combined with high-performance liquid chromatography. Then the in vitro antibacterial activity against AB was conducted using the selected ultrasound-activated microbubble. Results showed the selected microbubbles with high encapsulation efficiency and good stability. The mechanical shaking method is feasible for preparation of drug-loaded and ultrasound-activated lipid microbubbles. Using 0.2 mg/mL microbubbles, combined with 1 MHz, 2.5 W/cm2 and 1 min of ultrasound exhibited a potent anit-AB in vitro. This study indicates that tigecycline treatment in form of ultrasound-activated microbubble is a promising strategy against AB infections.

Development and validation of a prognostic nomogram for Takotsubo syndrome patients in the intensive care units: a retrospective cohort study.

Patients with Takotsubo syndrome (TTS) admitted to the intensive care unit (ICU) always confront a higher risk of in-hospital death than those hospitalized in the cardiology unit. The prognosis of the latter was analyzed by a large number of studies. However, there was no utility model to predict the risk of in-hospital death for patients with TTS in the ICU. This study aimed to establish a model predicting in-hospital death in patients with TTS admitted to ICU. We retrospectively included ICU patients with TTS from the MIMIC-IV database. The outcome of the nomogram was in-hospital death. Least Absolute Shrinkage Selection Operator (LASSO) analysis selected predictors preliminarily. The model was developed by multivariable logistic regression analysis. Calibration, decision curve analysis (DCA), and receiver operating characteristic (ROC) measured the performance of the nomogram on the accuracy, clinical utility, and discrimination, respectively. Eventually, 368 ICU patients with TTS were enrolled in this research. The in-hospital mortality was 13.04%. LASSO regression and multivariate logistic regression analysis verified risk factors significantly associated with in-hospital mortality. They were potassium, prothrombin time (PT), age, myocardial infarction, white cell count (WBC), hematocrit, anion gap, and sequential organ failure assessment (SOFA) score. This nomogram excellently discriminated against patients with a risk of in-hospital death. The area under curve (AUC) was 0.779 (95%CI: 0.732-0.826) in training set and 0.775 (95%CI: 0.711-0.839) in test set. The calibration plot and DCA showed good clinical benefits for this nomogram. We developed a nomogram that predicts the probability of in-hospital death for ICU patients with TTS. This nomogram was able to discriminate patients with a high risk of in-hospital death and performed clinical utility.

A nomogram to predict in­hospital mortality in post-cardiac arrest patients: a retrospective cohort study.

INTRODUCTION: Nomograms of prognosis in patients with a history of cardiac arrest (CA) have been established. However, there are some shortcomings and interferences in their clinical application. OBJECTIVES: Our study aimed at developing a utility nomogram to predict the risk of in­hospital death in post­CA patients. PATIENTS AND METHODS: We retrospectively extracted data from the MIMIC­IV database. The least absolute shrinkage and selection operator logistic regression and multivariable logistic regression were used to investigate independent risk factors. A nomogram defined as a prediction model was established for these independent risk factors. The model performance was measured by examining discrimination (area under the receiver operating characteristic curve [AUC]), calibration (calibration curve analysis), and utility (decision curve analysis [DCA]). RESULTS: A total of 1724 post­CA patients were enrolled in the study. Of those, 788 survived and 936 died. The incidence of in­hospital death was 54.3%. In this nomogram, the predictors included age, malignant cancer, bicarbonate, blood urea nitrogen, sodium, heart rate, respiratory rate, temperature, SPO2, norepinephrine prescription, and lactate level. The internally validated nomogram showed good discrimination (AUC 0.801; 95% CI, 0.775-0.835). The calibration curve analysis and DCA confirmed that this prediction model can be clinically useful. CONCLUSIONS: We established a risk prediction model based on the admission characteristics to accurately predict the clinical outcome in post­CA patients. The nomogram might help with the risk identification and individual clinical interventions.

Short sleep duration and atrial fibrillation risk: A comprehensive analysis of observational cohort studies and genetic study.

BACKGROUND: Previous observational studies are inconclusive on whether an association exists between short sleep duration and the high risk of developing atrial fibrillation (AF). Understanding their potential association would be of great clinical significance. Thus, in this study, we aimed to explore their causal relationship. METHODS AND RESULTS: We meta-analyzed the association between short sleep duration and the risk of developing AF by including six observational studies. Based on genetic susceptibility analysis using the mendelian randomization (MR) method, we identified 16 genetic loci that might link short sleep duration and the high risk of developing AF. Meta-analysis showed a significant association between short sleep duration and a higher risk of developing AF (RR = 1.06, 95% CI 1.02-1.11, P = 0.005). However, the fixed-effect and random-effect inverse variance weighted (IVW) models using the MR method showed a non-obvious effect of short sleep duration on the risk of developing AF (OR, 0.979; 95% CI, 0.880-1.089, P = 0.693; OR, 0.979; 95% CI, 0.857-1.117, P = 0.750, respectively). Other models, also showed no statistical difference. No heterogeneity or asymmetry was observed, as Cochran's Q test showed. The leave-one-out sensitivity analysis demonstrated good robust results, which were not subject to directional pleiotropy. CONCLUSION: Meta-analysis and MR analysis demonstrated inconsistent results on the relationship between short sleep duration and a high risk of developing AF. Specifically, while meta-analysis confirmed that short sleep duration increases the risk of developing AF, MR analysis did not support a causal association between genetically determined short sleep and risk of AF.

A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease.

BACKGROUND: Five types of HIF-PHIs have been authorized for anemia treatment in CKD patients in China and Japan. These are enarodustat, roxadustat, daprodustat, vadadustat, and molidustat. How effectively they compare to ESAs about clinical results in CKD-DD patients is uncertain. This study examined the RCT evidence about the benefits and risks of HIF-PHIs and ESAs in dialysis CKD patients. METHODS: We conducted an extensive investigation and network meta-analysis of RCTs. In these RCTs, patients with CKD-DD received one of five different HIF-PHI or ESAs, a placebo, and no medical intervention. Outcomes included hemoglobin, iron parameters, and adverse events, and there were four weeks of follow-up at least. A frequentist framework for multivariate random effects meta-analyzed the results. The effect sizes of categorical variables were displayed as odds ratios. Mean differences were employed for computing continuous outcomes with common units; otherwise, standardized mean differences were applied. The Cochrane tool evaluated the bias risk in RCTs. RESULTS: 26 RCTs with 14945 patients were qualified for inclusion. Compared to the placebo, HIF-PHIs and ESAs dramatically boosted hemoglobin without affecting serum iron. Roxadustat performed better hemoglobin levels than ESAs (MD 0.32, 95% CI 0.10 to 0.53) and daprodustat (0.46, 0.09 to 0.84). Roxadustat (91.8%) was the top hemoglobin treatment among all medical interventions, as determined by the SUCRA ranking. However, roxadustat caused more thrombosis and hypertension than ESAs (1.61, 1.22 to 2.12) and vadadustat (1.36, 1.01 to 1.82). The lowest rates of hypertension and thrombosis were seen in molidustat (80.7%) and ESAs (88.5%). Compared with a placebo, ESAs and HIF-PHIs all affected TSAT levels. Except for molidustat, the other four HIF-PHIs impact different iron parameters. Regarding ferritin reduction, roxadustat (90.9%) and daprodustat (60.9%) came out on top. Enarodustat (80.9%) and roxadustat (74%) placed best and second in lowering hepcidin levels. The former two medicines for TIBC improvement were vadadustat (98.7%) and enarodustat (80.9%). CONCLUSION: The most effective treatment for hemoglobin correction is roxadustat. The superior efficacy of reducing hepcidin makes roxadustat and enarodustat appropriate for patients with inflammation. However, the increased risk of hypertension and thrombosis associated with roxadustat should be noted. In patients at risk for hypertension and thrombosis, molidustat and ESAs may be preferable options. When administering roxadustat and daprodustat, clinicians should check ferritin to assess iron storage. Lower TSAT in patients receiving HIF-PHIs and ESAs treatment suggests intravenous iron supplements are needed.

The synthesis of copper-modified biochar from Elsholtzia Harchowensis and its electrochemical activity towards the reduction of carbon dioxide.

Phytoremediation techniques have been widely used in the treatment of heavy metal contaminated soils in recent years, but there is no effective post-treatment method for plant tissues containing heavy metals after remediation. Elsholtzia Harchowensis is a copper hyperaccumulator, commonly distributed in copper mining areas and often used for soil remediation of mine tailings. Moreover, copper-based catalysts are widely used in electrocatalytic reduction of carbon dioxide, which aims to convert carbon dioxide into useful fuels or chemicals. In this study, copper-modified biochar was prepared from Elsholtzia Harchowensis. Its specific surface area can reach as high as 1202.9 m2/g, with a certain porous structure and even distribution of copper on the amorphous carbon. Various products (such as carbon monoxide, methane, ethanol, and formic acid) could be obtained from the electrolytic reduction of carbon dioxide by using the as-prepared catalyst. Instantaneous current density of up to 15.3 mA/cm2 were achieved in 1.0 M KHCO3 solution at a potential of -0.82 V (vs. RHE). Electrolysis at a potential of -0.32 V (vs. RHE) for 8 h resulted in a stable current of about 0.25 mA/cm2, and the Faraday efficiency (FE) of carbon monoxide can reach as high as 74.6%. In addition, electrolysis at a potential of -0.52 V (vs. RHE) for 8 h led to a stable current of about 2.2 mA/cm2 and a FE of 8.7% for the C2 product. The rich variety of elements in plants leads to catalysts with complex structural and elemental characteristics as well, which facilitates the electrolytic reduction of carbon dioxide with a variety of useful products.

Development and validation of a nomogram to predict protein-energy wasting in patients with peritoneal dialysis: a multicenter cohort study.

Background: Protein-energy wasting (PEW) is a common complication in patients with peritoneal dialysis (PD). Few investigations involved risk factors identification and predictive model construction related to PEW. We aimed to develop a nomogram to predict PEW risk in patients with peritoneal dialysis. Methods: We collected data from end-stage renal disease (ESRD) patients who regularly underwent peritoneal dialysis between January 2011 and November 2022 at two hospitals retrospectively. The outcome of the nomogram was PEW. Multivariate logistic regression screened predictors and established a nomogram. We measured the predictive performance based on discrimination ability, calibration, and clinical utility. Evaluation indicators were receiver operating characteristic (ROC), calibrate curve, and decision curve analysis (DCA). The performance calculation of the internal validation cohort validated the nomogram. Results: In this study, 369 enrolled patients were divided into development (n = 210) and validation (n = 159) cohorts according to the proportion of 6:4. The incidence of PEW was 49.86%. Predictors were age, dialysis duration, glucose, C-reactive protein (CRP), creatinine clearance rate (Ccr), serum creatinine (Scr), serum calcium, and triglyceride (TG). These variables showed a good discriminate performance in development and validation cohorts (ROC = 0.769, 95% CI [0.705-0.832], ROC = 0.669, 95% CI [0.585-0.753]). This nomogram was adequately calibrated. The predicted probability was consistent with the observed outcome. Conclusion: This nomogram can predict the risk of PEW in patients with PD and provide valuable evidence for PEW prevention and decision-making.

Efficacy of brain natriuretic peptide vs. nicorandil in preventing contrast-induced nephropathy: a network meta-analysis.

This study aimed to conduct a network meta-analysis (NMA) to compare the efficacy of brain natriuretic peptide (BNP) vs nicorandil for preventing contrast-induced nephropathy (CIN). Databases of Pubmed, Cochrane, Embase, Web of Science were searched by keywords for eligible studies of randomized controlled trials investigating different agents (BNP, nicorandil, nitroglycerin, intravenous saline) for preventing CIN. The outcomes included a change in serum creatinine level at 48 h and the incidence of CIN after percutaneous coronary intervention (PCI) or coronary angiography (CAG). A total of 13 studies with 3,462 patients were included. Compared with intravenous saline alone, except for nitroglycerin (odds ratio [OR]: 1.02, 95% CI [0.36-2.88]), the other drugs significantly reduced the CIN incidence with OR of 0.35 (95% CI [0.24-0.51]) for BNP, 0.52 (0.29, 0.94) for usual-dose nicorandil, 0.28 (0.19, 0.43) for double-dose nicorandil. BNP and double-dose nicorandil significantly decreased the change of serum creatinine (SCr) levels with mean difference (MD) of -6.98, (-10.01, -3.95) for BNP, -8.78, (-11.63, -5.93) for double-dose nicorandil. No significant differences were observed in the change of SCr levels for nitroglycerin (-4.97, [-11.46, 1.52]) and usual-dose nicorandil (-2.32, [-5.52, 0.89]) compared with intravenous saline alone. For double-dose nicorandil, the CIN incidence and the change of SCr level in group of 4-5 days treatment course were more than group of less than or equal to 24 h treatment course (OR of 1.48, [0.63-3.46] and MD of 2.48, [-1.96, 6.91]). In conclusion, BNP and double-dose nicorandil can have effects on preventing the incidence of CIN and double-dose nicorandil performed better than BNP. In double-dose nicorandil groups, a course of less than or equal to 24 h before and after procedure performed with better efficacy than a course of 4-5 days.

High-Density Genetic Map Construction and Stem Total Polysaccharide Content-Related QTL Exploration for Chinese Endemic Dendrobium (Orchidaceae).

Plants of the Dendrobium genus are orchids with not only ornamental value but also high medicinal value. To understand the genetic basis of variations in active ingredients of the stem total polysaccharide contents (STPCs) among different Dendrobium species, it is of paramount importance to understand the mechanism of STPC formation and identify genes affecting its process at the whole genome level. Here, we report the first high-density single-nucleotide polymorphism (SNP) integrated genetic map with a good genome coverage of Dendrobium. The specific-locus amplified fragment sequencing (SLAF-seq) technology led to identification of 7,013,400 SNPs from 1,503,626 high-quality SLAF markers from two parents (Dendrobium moniliforme ♀ × Dendrobium officinale ♂) and their interspecific F1 hybrid population. The final genetic map contained 8, 573 SLAF markers, covering 19 linkage groups (LGs). This genetic map spanned a length of 2,737.49 cM, where the average distance between markers is 0.32 cM. In total, 5 quantitative trait loci (QTL) related to STPC were identified, 3 of which have candidate genes within the confidence intervals of these stable QTLs based on the D. officinale genome sequence. This study will build a foundation up for the mapping of other medicinal-related traits and provide an important reference for the molecular breeding of these Chinese herb.