The efficacy and safety of vonoprazan-amoxicillin dual therapy in eradicating Helicobacter pylori: a systematic review and meta-analysis.

AIM: To evaluate the efficacy and safety of vonoprazan-amoxicillin (VA) dual therapy for radically eradicating Helicobacter pylori (H. pylori). METHODS: The PubMed, Cochrane Library, Embase, China National Knowledge  Infrastructure (CNKI) and Wanfang databases were searched up to July 7, 2022, to identify clinical trials comparing the efficacy of VA dual therapy and triple therapy for H. pylori eradication. After evaluating the quality of the included studies, random effects models were conducted, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to estimate the efficacy and safety of each approach. RESULTS: Six publications (including four randomized controlled trials) involving 2019 patients were included in this meta-analysis. Overall, the eradication rate for VA dual therapy was 89.9%, while it was 85.2% for triple therapy based on other acid inhibitors. The eradication rate of H. pylori in the VA dual regimen group was higher than that in the PPI-based (omeprazole or lansoprazole) triple therapy group (RR = 1.15, 95% CI 1.07-1.23, p < 0.0001). However, the efficacy of VA dual therapy was comparable with VA-Clarithromycin (VAC) triple therapy (RR = 0.97, 95% CI 0.93-1.02). Besides, the incidence of adverse reactions in VA dual therapy was also lower than that in triple therapy (RR = 0.80, 95% CI 0.70-0.91, p = 0.0009). CONCLUSION: Compared with PPI-based triple therapy, VA dual therapy showed a better therapeutic effect, safety and patient compliance rate for eradicating H. pylori, which should be used as a novel curative strategy in the future.

Prognosis value of serum chloride on 1-year mortality in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt.

BACKGROUND AND PURPOSE: Emerging researches have regarded serum chloride as a capable predictor of mortality in liver cirrhosis. We aim to investigate the clinical role of admission chloride in cirrhotic patients with esophagogastric varices receiving transjugular intrahepatic portosystemic shunt (TIPS), which is unclear. METHODS: We retrospectively analyzed data of cirrhotic patients with esophagogastric varices undergoing TIPS in Zhongnan Hospital of Wuhan University. Mortality outcome was obtained by following up for 1-year after TIPS. Univariate and multivariate Cox regression were used to identify independent predictors of 1-year mortality post-TIPS. The receiver operating characteristic (ROC) curves were adopted to assess the predictive ability of the predictors. In addition, log-rank test and Kaplan-Meier (KM) analyses were employed to evaluate the prognostic value of predictors in the survival probability. RESULTS: A total of 182 patients were included ultimately. Age, fever symptom, platelet-to lymphocyte-ratio (PLR), lymphocyte-to-monocyte ratio (LMR), total bilirubin, serum sodium, chloride, and Child-Pugh score were related to 1-year follow-up mortality. In multivariate Cox regression analysis, serum chloride (HR = 0.823, 95%CI = 0.757-0.894, p < 0.001) and Child-Pugh score (HR = 1.401, 95%CI = 1.151-1.704, p = 0.001) were identified as independent predictors of 1-year mortality. Patients with serum chloride <107.35 mmol/L showed worse survival probability than those with serum chloride ≥107.35 mmol/L no matter with or without ascites (p < 0.05). CONCLUSION: Admission hypochloremia and increasing Child-Pugh score are independent predictors of 1-year mortality in cirrhotic patients with esophagogastric varices receiving TIPS.

Molecular and Clinical Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Isolates at a Tertiary Hospital in Wuhan, China.

Background: Carbapenem resistant Klebsiella pneumoniae (CRKP) is an independent risk factor for nosocomial infection which poses a serious threat to human health. How to prevent and suppress CRKP infection and explore its drug resistance mechanisms have become a huge challenge and possesses immediate significance. Methods: A total of 45 CRKP strains isolated from hospitalized patients in Zhongnan Hospital of Wuhan University were collected from August 2018-December 2020. The strain's identification and antimicrobial susceptibility tests were performed using the VITEK 2 automated identification instrument. Single molecule DNA sequencing of 45 CRKP isolates was performed by the third generation high-throughput sequencing technology. Results: The results were analyzed by multi locus sequence typing (MLST) and phylogenetic analysis. Antimicrobial susceptibility showed that 45 CRKP isolates were multi-drug resistant strains, and the resistance rates to common antibiotics were as high as 68%. Whole genome sequencing results showed that the CRKP strains carried multiple drug resistance genes and virulence factors. MLST analysis found two different sequence types (ST), of which 44 were ST11 and 1 was ST1049. Conclusion: Through whole genome sequencing (WGS), we found multiple drug-resistant genes and virulence factors, and there was obvious dominant microbiota. The source was mainly related to nosocomial infection. The ST11-KPC Klebsiella pneumoniae was the main type, which was consistent with the most common type in China. We identified several dominant microbiotas which may serve as a target in the clinical prevention and treatment of severe bacterial infections. Our finding may have a role for guiding clinical antibiotic choosing.

A novel mutation in human EMD gene and mitochondrial dysfunction in emerin knockdown cardiomyocytes.

Emerin is an inner nuclear envelope protein encoded by the EMD gene, mutations in which cause Emery-Dreifuss muscular dystrophy type 1 (EDMD1). Cardiac involvement has become a major threat to patients with EDMD1; however, the cardiovascular phenotype spectrums of emerinopathy and the mechanisms by which emerin regulates cardiac pathophysiology remain unclear. Here, we identified a novel nonsense mutation (c.C57G, p.Y19X) in the EMD gene in a Han Chinese family through high-throughput sequencing. Two family members were found to have EDMD1 with muscle weakness and cardiac arrhythmia. Mechanistically, we first discovered that knockdown of emerin in HL-1 or H9C2 cardiomyocytes lead to impaired mitochondrial oxidative phosphorylation capacity with downregulation of electron transport chain complex I and IV and upregulation of complex III and V. Moreover, loss of emerin in HL-1 cells resulted in collapsed mitochondrial membrane potential, altered mitochondrial networks and downregulated multiple factors in RNA and protein level, such as PGC1α, DRP1, MFF, MFN2, which are involved in regulation of mitochondrial biogenesis, fission and fusion. Our findings suggest that targeting mitochondrial bioenergetics might be an effective strategy against cardiac disorders caused by EMD mutations.

Identification and Verification of Feature Biomarkers Associated With Immune Cells in Dilated Cardiomyopathy by Bioinformatics Analysis.

Objective: To explore immune-related feature genes in patients with dilated cardiomyopathy (DCM). Methods: Expression profiles from three datasets (GSE1145, GSE21610 and GSE21819) of human cardiac tissues of DCM and healthy controls were downloaded from the GEO database. After data preprocessing, differentially expressed genes (DEGs) were identified by the 'limma' package in R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were then performed to identify biological functions of the DEGs. The compositional patterns of stromal and immune cells were estimated using xCell. Hub genes and functional modules were identified based on protein-protein interaction (PPI) network analysis by STRING webtool and Cytoscape application. Correlation analysis was performed between immune cell subtypes and hub genes. Hub genes with |correlation coefficient| > 0.5 and p value <0.05 were selected as feature biomarkers. A logistic regression model was constructed based on the selected biomarkers and validated in datasets GSE5406 and GSE57338. Results: A total of 1,005 DEGs were identified. Functional enrichment analyses indicated that extracellular matrix remodeling and immune and inflammation disorder played important roles in the pathogenesis of DCM. Immune cells, including CD8+ T-cells, macrophages M1 and Th1 cells, were proved to be significantly changed in DCM patients by immune cell infiltration analysis. In the PPI network analysis, STAT3, IL6, CCL2, PIK3R1, ESR1, CCL5, IL17A, TLR2, BUB1B and MYC were identified as hub genes, among which CCL2, CCL5 and TLR2 were further screened as feature biomarkers by using hub genes and immune cells correlation analysis. A diagnosis model was successfully constructed by using the three biomarkers with area under the curve (AUC) scores 0.981, 0.867 and 0.946 in merged dataset, GSE5406 and GSE57338, respectively. Conclusion: The present study identified three immune-related genes as diagnostic biomarkers for DCM, providing a novel perspective of immune and inflammatory response for the exploration of DCM molecular mechanisms.

Chlorine-Substituted N-Heteroacene Analogues Acting as Organic Semiconductors for Solution-Processed n-type Organic Field-Effect Transistors.

High performance solution processable n-type organic semiconductor is an essential element to realize low-cost, all organic and flexible composite logic circuits. In the design of n-type semiconducting materials, tuning the LUMO level of compounds is a key point. As a strong electron withdrawing unit, the introduction of chlorine atom into the chemical structure can increase the electron affinity of the material and reduce the LUMO energy level. Here, a series chlorine substituted N-heteroacene analogues of 6,7,8,9-tetrachloro-4,11-bis(4-((2-ethylhexyl)oxy)phenyl)-[1,2,5]thiadiazolo[3,4-b]phenazine (O4Cl), 6,7,8,9-tetrachloro-4,11-bis(4-((2-ethylhexyl)thio)phenyl)-[1,2,5]thiadiazolo[3,4-b]phenazine (S4Cl), 1,2,3,4,8,9,10,11-octachloro-6,13-bis(4-((2-ethylhexyl)oxy)phenyl)quinoxalino[2,3-b]phenazine (8Cl) and 12Cl have been synthesized and characterized. Solution-processed organic field-effect transistors (OFETs) based on these four compounds exhibit good electron mobilities of 0.04 cm2  V-1 s-1 , 0.01 cm2  V-1 s-1 , 2×10-3  cm2  V-1 s-1 and 3×10-3  cm2  V-1 s-1 , respectively, under ambient conditions. The results suggest that these chlorine substituted π-conjugated N-heteroacene analogues are promising n-type semiconductors in OFET applications.

Predicting Distant Metastasis in Young-Onset Colorectal Cancer After Surgery: A Retrospective Study.

Background: Although overall colorectal cancer (CRC) cases have been declining worldwide, there has been an increase in the incidence of the CRC among individuals younger than 50 years old, which is associated with distant metastasis (DM) and poor prognosis. Methods: Young-onset CRC patients' postoperative data were collected from the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015. Data from the SEER database were divided into early stage and advanced stage according to whether chemoradiotherapy was recommended in the guidelines. Independent risk factors for DM were explored by using univariate and multivariate logistic regression separately. A predictive model was established and presented as nomogram in the training set of advanced stage. The model was internally verified in testing set and externally validated in a cohort of 145 patients from Zhongnan Hospital of Wuhan University. The accuracy, reliability, and clinical application value were assessed using the receiver operating characteristic curve (ROC), the area under the curve (AUC), calibration curve, and decision curve analysis (DCA), respectively. Different risk subgroups of DM were classified according to the scores of the nomogram in the training set of advanced stage. Results: A total of 5,584 patients were eligible and enrolled in our study in which 1,277 were in early stage and 4,307 in advanced stage. Preoperative CEA positive was found to be an independent predictor of DM in early stage. Multivariate logistic regression analysis showed that tumor size, degree of differentiation, T stage, N stage, preoperative CEA, and whether radiation or chemotherapy performed were independent risk factors for DM (all, p < 0.05) in advanced stage. Great accuracies were achieved in our nomogram with AUC of 0.801 in training set, 0.811 in testing set, and 0.791 in the validation cohort, respectively. Calibration curves and DCA in internal validation and external validation both showed good stability and clinical utility values. Conclusions: Preoperative CEA positive was a significant predictor of DM for young-onset CRC patients. A novel nomogram containing clinical and pathological features was established for predicting DM of advanced CRC in patients younger than 50 years old. This tool may serve as an early alert for clinicians to DM and make better clinical treatment regimens.

Plasma protein profiling analysis in patients with atrial fibrillation before and after three different ablation techniques.

Background: There are controversies on the pathophysiological alteration in patients with atrial fibrillation (AF) undergoing pulmonary vein isolation using different energy sources. Objectives: We evaluated the changes in plasma proteins in acute phase post-ablation in patients receiving cryoballoon ablation, radiofrequency balloon ablation, or radiofrequency ablation. Methods: Blood samples from eight healthy controls and 24 patients with AF were taken on the day of admission, day 1, and day 2 post-ablation and analyzed by the Olink proximity extension assay. Proteins were identified and performed with enrichment analysis. Protein-protein interaction network and module analysis were conducted using Cytoscape software. Results: Of 181 proteins, 42 proteins in the cryoballoon group, 46 proteins in the radiofrequency balloon group, and 43 proteins in the radiofrequency group significantly changed after ablation. Most of the proteins altered significantly on the first day after ablation. Altered proteins were mainly involved in cytokine-cytokine receptor interaction. Both balloon-based ablations showed a similar shift toward enhancing cell communication and regulation of signaling while inhibiting neutrophil chemotaxis. However, radiofrequency ablation presented a different trend. Seed proteins, including osteopontin, interleukin-6, interleukin-10, C-C motif ligand 8, and matrix metalloproteinase-1, were identified. More significant proteins associated with hemorrhage and coagulation were selected in balloon-based ablations by machine learning. Conclusion: Plasma protein response after three different ablations in patients with AF mainly occurred on the first day. Radiofrequency balloon ablation shared similar alteration in protein profile as cryoballoon ablation compared with radiofrequency ablation, suggesting that lesion size rather than energy source is the determinant in pathophysiological responses to the ablation.

Series of Highly Luminescent Macrocyclic Sm(III) Complexes: Functional Group Modifications Together with Luminescence Performances in Solid-State, Solution, and Doped Poly(methylmethacrylate) Film.

Here, we report our trials to regulate the luminescence performance of the macrocyclic samarium(III) complex and prepare four excellent luminescent Sm(III) complex-doped poly(methylmethacrylate) (PMMA) composites. Four 23-membered [1 + 1] Schiff-base macrocyclic mononuclear Sm(III) complexes, Sm-2 a -Sm-2 d , originating from dialdehydes with different pendant arms and 1,2-bis(2-aminoethoxy)ethane, have been constructed by the template method. Crystal structures reveal that every Sm(III) ion with the coordination geometry of a distorted bicapped square antiprism is capsulated by the macrocyclic cavity environment forming the "lasso-type" protection. Relative photophysical properties of macrocyclic Sm(III) complexes are carefully investigated in solid-state, methanol solution, and doped PMMA film, and all these show characteristic emissions of the Sm(III) ion associated with satisfactory lifetimes and quantum yields in all media, which could be comparable to reported outstanding examples. Especially, the luminescence performance for this type of Sm(III) complex could be regulated in the solid state by the use of different functional groups in the pendant arm while it is not achieved in solution and the doped PMMA composite. High emitting and air-stable plastic materials could be obtained when these Sm(III) complexes are doped in PMMA with 0.1 wt % mixing ratio, and the corresponding maximum lifetime and quantum yield are 61.2 µs and 0.63% in the case of complex Sm-2 a , respectively. We believe that these highly luminescent "lasso-type" Sm(III) complexes and doped PMMA composites are valuable references in the design of luminescent lanthanide(III) hybrid materials.

An excellent colorimetric and "turn off" fluorescent probe for tetrahydrofuran based on a luminescent macrocyclic samarium(iii) complex.

In this paper we report a novel probe based on a luminescent 23-membered [1 + 1] Schiff-base macrocyclic mononuclear Sm(iii) complex Sm-2e, originating from the dialdehyde H2Qe and 1,2-bis(2-aminoethoxy)ethane precursors, which is synthesized by the Sm(iii) ion template method. X-ray structural analyses confirm that each ten-coordinate Sm(iii) center with the coordination geometry of a distorted bicapped square antiprism is fully encapsulated by a flexible macrocyclic ligand H2L2e to form a "lasso-type" architecture, and this architecture could enable efficient energy transfer in various solvents confirmed by long lifetimes (33.5-65.2 µs) and high quantum yields (0.23-0.76%) of the Sm(iii) ion. Simultaneously, complex Sm-2e could serve as a probe for sensing organic solvents. Particularly, this complex probe Sm-2e exhibits a highly selective, rapid and sensitive response to tetrahydrofuran (THF), which is easily distinguished by a large absorption shift, even visible to the naked eye, and complete fluorescence quenching. Moreover, the limit of detection for THF is about 0.20% determined by titration experiments, and good selectivity for THF could still be realized in mixture solvents. Consequently, this colorimetric and "turn off" fluorescent probe Sm-2e could be a valuable candidate as a sensor material for sensing THF which has been rarely reported.

Enhancing recovery and sensitivity studies in an unconventional tight gas condensate reservoir.

The recovery factor from tight gas reservoirs is typically less than 15%, even with multistage hydraulic fracturing stimulation. Such low recovery is exacerbated in tight gas condensate reservoirs, where the depletion of gas leaves the valuable condensate behind. In this paper, three enhanced gas recovery (EGR) methods including produced gas injection, CO2 injection and water injection are investigated to increase the well productivity for a tight gas condensate reservoir in the Montney Formation, Canada. The production performance of the three EGR methods is compared and their economic feasibility is evaluated. Sensitivity analysis of the key factors such as primary production duration, bottom-hole pressures, and fracture conductivity is conducted and their effects on the well production performance are analyzed. Results show that, compared with the simple depletion method, both the cumulative gas and condensate production increase with fluids injected. Produced gas injection leads to both a higher gas and condensate production compared with those of the CO2 injection, while waterflooding suffers from injection difficulty and the corresponding low sweep efficiency. Meanwhile, the injection cost is lower for the produced gas injection due to the on-site available gas source and minimal transport costs, gaining more economic benefits than the other EGR methods.

A systematic review of randomised controlled trials examining the therapeutic effects of adult bone marrow-derived stem cells for non-ischaemic dilated cardiomyopathy.

BACKGROUND: Certain early-phase clinical trials have suggested that bone marrow-derived stem cell transplantation might improve left ventricular function in patients with non-ischaemic dilated cardiomyopathy (NIDCM), whereas others trials have revealed no benefit from this approach. We sought to evaluate the therapeutic effects of bone marrow-derived stem cell therapy on NIDCM. METHODS: We searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases (through February 2016) for randomised controlled clinical trials that reported on bone marrow-derived stem cell transplantation for patients with NIDCM with a follow-up period ≥12 months. The co-primary endpoints were changes in mortality rate and left ventricular ejection fraction (LVEF); the secondary endpoints were changes in the 6-minute-walk test (6MWT) and left ventricular chamber size. Seven trials involving bone marrow-derived stem cell therapy that included 482 patients satisfied the inclusion and exclusion criteria. RESULTS: Subjects who received bone marrow-derived stem cell therapy exhibited a significant reduction in mortality rate (19.7% in the cell group vs. 27.1% in the control group; 95% confidence interval (CI) -0.16 to -0.00, I 2 = 52%, p = 0.04). Bone marrow-derived stem cell therapy tended to produce LVEF improvement within 6 months (1.83% increase; 95% CI -0.27 to 3.94, I 2 = 74%, p = 0.09) and significantly improved LVEF after mid-term (6-12 months) follow-up (3.53% increase; 95% CI 0.76 to 6.29, I 2 = 88%, p = 0.01). However, this therapy produced no significant benefit in the 6MWT (p = 0.18). Finally, the transplantation of increased numbers of stem cells resulted in no observable additional benefit with respect to LVEF. CONCLUSIONS: Bone marrow-derived stem cell therapy might have improved prognoses and appeared to provide moderate benefits in cardiac systolic function at mid-term follow-up. However, this therapy produced no observed improvement in exercise tolerance.