Acute kidney injury following the use of different proton pump inhibitor regimens: A real-world analysis of post-marketing surveillance data.

BACKGROUND AND AIM: Recent evidence has concerned acute kidney injury (AKI) after the proton pump inhibitor (PPI) application. There are few real-world studies to compare the occurrences, clinical features, and prognosis of AKI related to various PPI regimens. We aimed to evaluate and compare the links between different PPIs and AKI in a large population by investigating the Food and Drug Administration Adverse Event Reporting System (FAERS) until recently. METHODS: Disproportionality analysis and Bayesian analysis were used in data mining to screen the suspected AKI after different PPIs based on the FAERS from January 2004 to December 2019. The times to onset, fatality, and hospitalization rates of PPI-associated AKI were also investigated. RESULTS: We identified 19 522 PPI-associated AKIs, which appeared to influence more middle-aged patients than elderly ones (53.04% vs 33.94%). Women were more affected than men (55.42% vs 44.58%). Lansoprazole appeared a stronger AKI association than other PPIs, based on the highest reporting odds ratio (reporting odds ratio = 20.8, 95% confidence interval = 20.16, 21.46), proportional reporting ratio (proportional reporting ratio = 15.55, χ2  = 73 899.68), and empirical Bayes geometric mean (empirical Bayes geometric mean = 15.15, 95% confidence interval = 14.76). The median time to AKI onset was 446 (interquartile range [IQR] 16-2176) days after PPI administration. PPIs showed a significant difference in average time to AKI onset (P < 0.001), with the shortest of 9 (IQR 3-25) days for rabeprazole and the longest of 1221 (IQR 96.5-2620) days for esomeprazole. PPI-associated AKI generally led to a 5.69% fatality rate and an 8.94% hospitalization rate. The highest death rate occurred in rabeprazole (15.35%). CONCLUSIONS: Based on the FAERS database, we profiled AKI related to various PPIs with more details in occurrences, clinical characteristics, and prognosis. Concern should be paid for PPIs when applied to patients with a tendency for AKI.

Transport of coupled particles in rough ratchet driven by Lévy noise.

This paper studies the transport of coupled particles in a tilted rough ratchet potential. The relationship between particles transport and roughness, noise intensity, external force, coupling strength, and free length is explored numerically by calculating the average velocity of coupled particles. Related investigations have found that rough potential can accelerate the process of crossing the barrier by increasing the particles velocity compared with smooth potential. It is based on the fact that the roughness on the potential surface is like a "ladder," which helps particles climb up and blocks them from sliding down. Moreover, superimposing an appropriate external force on the coupled particles or strengthening the Lévy noise leads to the particles velocity to increase. It is worth emphasizing that when the external force is selected properly, an optimal roughness can be found to maximize the particles velocity. For a given roughness, an optimal coupling coefficient is discovered to match the maximum velocity. And once the coupling coefficient is greater than the optimal value, the particles velocity drops sharply to zero. Furthermore, our results also indicate that choosing an appropriate free length between particles can also speed up transport.

Dietary quercetin attenuates depressive-like behaviors by inhibiting astrocyte reactivation in response to stress.

The mechanisms underlying the antidepressant activity of quercetin are unknown. We investigated the effect of a quercetin-enriched diet (2 g/kg and 0.5 g/kg doses) on chronic social defeat stress (CSDS)-induced depressive-like behaviors in mice. The 2 g/kg quercetin-enriched diet attenuated depressive-like behaviors when introduced before CSDS (long-term). The long-term 0.5 g/kg quercetin-enriched diet showed a trend toward behavioral improvement. The frequencies of spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs) in the mPFC and hippocampus were significantly higher in mice fed the long-term 2 g/kg quercetin-enriched diet compared with the normal diet; no difference was found in the amygdala. Quercetin-enriched diets administered concurrently and after stress induction failed to trigger these effects. A1-specific astrocyte reactivity was markedly suppressed in the microglia and astrocytes isolated from the mPFC and hippocampus of mice fed the long-term quercetin-enriched diet, but not in those who received quercetin supplementation concurrently or after CSDS. To confirm the role of astrocytes in the neuroprotective effect of quercetin, we activated astrocytes by injecting a chemogenic AAV stimulus into the mPFC and hippocampus and found that astrocyte activation during administration of the long-term quercetin-enriched diet significantly deceased the frequency of sEPSCs and sIPSCs in the mPFC and hippocampus and further attenuated quercetin-induced behavioral improvements. These findings highlight the key role of astrocyte reactivation in the regulation of quercetin neuroprotective activity and suggest that a diet high in quercetin, whether as a fruit- and vegetable-rich diet or food additive may help cope with stress.

Risk Factors and Predictive Nomogram for Carbapenem-Resistant Klebsiella pneumoniae in Children in a Grade 3 First-Class General Hospital in Central China.

Background: This study determined risk factors for Carbapenem-resistant Klebsiella pneumoniae (CRKP)in children admitted to a grade 3 first-class general hospital and developed an individualized line graph predictive model. Methods: The clinical data of 185 children infected with Klebsiella pneumoniae from January 2015 to December 2019 were analyzed retrospectively. Patients were grouped according to carbapenem resistance: CRKP group (50 cases) and CSKP (carbapenem-sensitive Klebsiella pneumoniae) group (135 cases). Risk factors for CRKP in children were screened by logistic regression analysis. The predictive model was established using R software and validated using the Bootstrap method. Results: Age (odds ratio [OR]=0.104, 95% confidence interval [CI]: 0.026-0.408), intensive care unit admission (OR =2.829, 95% CI: 1.138-7.030), mechanical ventilation (OR =7.510, 95% CI: 3.140-17.961), surgery history (OR =5.005, 95% CI: 1.507-16.618) and glucocorticoid (OR =0.235, 95% CI: 0.099-0.557) were independent risk factors for CRKP in children (P < 0.05), The total risk score of each factor was 362.5, and the risk rate was 0.1-0.9. In receiver-operating characteristic curve analysis, the area under the curve of CRKP predicted by the total risk score was 0.872 (95% CI=0.844-0.901; P < 0.001). The correction curve indicated that the consistency between the observed value and the predicted value was good. Discussion and Conclusion: This study successfully established a model based on the risk factors, with high accuracy and good predictive value for CRKP in children. Hospitals should take necessary preventive measures against the risk factors for drug-resistant bacteria, such as optimizing the configuration of ICU space, timely isolation of infected children, and adequate disinfection of ICU equipment. Which may reduce CRKP infection rate.

A predictive model combining clinical characteristics and nutritional risk factors for overall survival after umbilical cord blood transplantation.

BACKGROUND: Umbilical cord blood transplantation (UCBT) is a curable therapy for hematological disease; however, the impact of nutritional status on UCBT outcomes remains controversial. To evaluate the joint effect of clinical characteristics and nutritional status on the prognosis of patients who underwent UCBT, we screened various factors to establish a predictive model of overall survival (OS) after UCBT. METHODS: We performed an integrated clinical characteristic and nutritional risk factor analysis and established a predictive model that could be used to identify UCBT recipients with poor OS. Internal validation was performed by using the bootstrap method with 500 repetitions. RESULTS: Four factors, including disease status, conditioning regimen, calf skinfold thickness and albumin level, were identified and used to develop a risk score for OS, which showed a positive predictive value of 84.0%. A high-risk score (≥ 2.225) was associated with inferior 3-year OS post-UCBT [67.5% (95% CI 51.1-79.4%), P = 0.001]. Then, we built a nomogram based on the four factors that showed good discrimination with a C-index of 0.833 (95% CI 0.743-0.922). The optimism-corrected C-index value of the bootstrapping was 0.804. Multivariate analysis suggested that a high calf skinfold thickness (≥ 20.5 mm) and a low albumin level (< 33.6 g/L) conferred poor disease-free survival (DFS). CONCLUSION: The predictive model combining clinical and nutritional factors could be used to predict OS in UCBT recipients, thereby promoting preemptive treatment.

Screening and evaluation of key genes in contributing to pathogenesis of hepatic fibrosis based on microarray data.

BACKGROUND: Hepatic fibrosis (HF), which is characterized by the excessive accumulation of extracellular matrix (ECM) in the liver, usually progresses to liver cirrhosis and then death. To screen differentially expressed (DE) long non-coding RNAs (lncRNAs) and mRNAs, explore their potential functions to elucidate the underlying mechanisms of HF. METHODS: The microarray of GSE80601 was downloaded from the Gene Expression Omnibus database, which is based on the GPL1355 platform. Screening for the differentially expressed LncRNAs and mRNAs was conducted between the control and model groups. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze the biological functions and pathways of the DE mRNAs. Additionally, the protein-protein interaction (PPI) network was delineated. In addition, utilizing the Weighted Gene Co-expression Network Analysis (WGCNA) package and Cytoscape software, we constructed lncRNA-mRNA weighted co-expression networks. RESULTS: A total of 254 significantly differentially expressed lncRNAs and 472 mRNAs were identified. GO and KEGG analyses revealed that DE mRNAs regulated HF by participating in the GO terms of metabolic process, inflammatory response, response to wounding and oxidation-reduction. DE mRNAs were also significantly enriched in the pathways of ECM-receptor interaction, PI3K-Akt signaling pathway, focal adhesion (FA), retinol metabolism and metabolic pathways. Moreover, 24 lncRNAs associated with 40 differentially expressed genes were observed in the modules of lncRNA-mRNA weighted co-expression network. CONCLUSIONS: This study revealed crucial information on the molecular mechanisms of HF and laid a foundation for subsequent genes validation and functional studies, which could contribute to the development of novel diagnostic markers and provide new therapeutic targets for the clinical treatment of HF.

Recombinant human thrombopoietin promotes platelet engraftment after umbilical cord blood transplantation.

Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT) accompanied by increased transplant-related complications or death. This study was designed to determine the safety and efficacy of recombinant human thrombopoietin (rhTPO) in promoting platelet engraftment after UCBT. A total of 120 patients scheduled to receive UCBT were randomly assigned to the rhTPO group (300 U/kg once daily from days 14 to 28 after UCBT, n = 60) or the control group (n = 60). The primary outcome was the 60-day cumulative incidence of platelet engraftment after single-unit cord blood transplantation. The 60-day cumulative incidence of platelet engraftment (platelet count ≥20 × 109/L) and the 120-day cumulative incidence of platelet recovery (platelet count ≥50 × 109/L) were both significantly higher in the rhTPO group than in the control group (83.1% vs 66.7%, P = .020; and 81.4% vs 65.0%, P = .032, respectively). In addition, the number of required platelet infusions was significantly lower in the rhTPO group than in the control group (6 vs 8 units, respectively; P = .026). The cumulative incidence of neutrophil engraftment and the probability of 2-year overall survival, disease-free survival, and graft-versus-host disease-free relapse-free survival did not differ between the 2 groups. Other transplant-related outcomes and complications did not differ between the 2 groups, and no severe adverse effects were observed in patients receiving rhTPO. This study demonstrated that rhTPO is well tolerated in patients and could effectively promote platelet engraftment after UCBT. This study was registered on the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) as ChiCTR-IPR-16009357.

Breathing exercises improve post-operative pulmonary function and quality of life in patients with lung cancer: A meta-analysis.

Previous research has shown that breathing exercises may improve the prognosis and health status in patients with lung cancer by enhancing pulmonary function and quality of life (QOL). However, individually published results are inconclusive. The aim of the present meta-analysis was to evaluate the clinical value of breathing exercises on post-operative pulmonary function and QOL in patients with lung cancer. A literature search of Pubmed, Embase, the Web of Science and CBM databases was conducted from their inception through to October 2012. Crude standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to assess the effect of breathing exercises. A total of eight clinical studies were ultimately included with 398 lung cancer patients. When all the eligible studies were pooled into the meta-analysis, there was a significant difference between the pre-intervention and post-intervention results of breathing exercises on post-operative pulmonary function; forced expiratory volume in 1 sec (FEV1): SMD, 3.37; 95% CI, 1.97-4.77; P<0.001; FEV1/FVC: SMD, 1.77; 95% CI, 0.15-3.39; P=0.032). Furthermore, the QOL in patients with lung cancer was significantly improved following the intervention with breathing exercises; there were significant differences between the pre-intervention and post-intervention results on the ability of self-care in daily life (SMD, -1.00; 95% CI, -1.467 to -0.52; P<0.001), social activities (SMD, -0.94; 95% CI, -1.73 to -0.15; P=0.02), symptoms of depression (SMD, -0.91; 95% CI, -1.25 to -0.57; P<0.001) and symptoms of anxiety (SMD, -0.91; 95% CI, -1.20 to -0.63; P<0.001). Results from the present meta-analysis suggest that breathing exercises may significantly improve post-operative pulmonary function and QOL in patients with lung cancer.

CASP-1, -2 and -5 gene polymorphisms and cancer risk: A review and meta-analysis.

Accumulating evidence suggests the CASP gene family is important in the development of carcinogenesis. These genetic polymorphisms have been extensively investigated as a potential risk factor for cancer, but results have been inconclusive. This Human Genome Epidemiology (HuGE) review and meta-analysis was performed to investigate the associations between CASP-1, -2 and -5 and cancer risk. A literature search of Pubmed, Embase, Web of Science and CBM databases was conducted from inception through September 1st, 2012. Four case-control studies with a total of 1,592 cancer cases and 1,833 healthy controls were included in the present meta-analysis. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Five polymorphisms were examined, including rs501192 (G>A), rs4647297 (C>G), rs507879 (T>C), rs3181320 (G>C) and rs523104 (G>C). Meta-analysis results showed that the rs3181320*C allele/carrier were associated with increased risk of various types of cancers (OR=1.26; 95% CI, 1.04-1.54; P=0.020 and OR=1.33; 95% CI, 1.00-1.75; P=0.047, respectively). However, similar associations were not found in the rs501192, rs4647297, rs507879 and rs523104 polymorphisms (all P>0.05). Results from the current meta-analysis suggest that the rs3181320*C allele/carrier in CASP-5 gene are potential risk factors for cancer.