Effects of enhanced education for patients with the Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori (H. pylori) infections are of serious concern due to the associated risk of gastric cancer. However, many patients have poor medication and therapy compliance, which makes it difficult to eradicate their infections. This points to the need for stronger educational interventions aimed at enhancing compliance, thus increasing the potential for treatment success. As such, this study conducted a meta-analysis to clarify the effects of enhanced patient education (EPE) programs for H. pylori. MATERIALS AND METHODS: We searched electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library) for randomized controlled trials (RCTs) on health education for patients infected with H. pylori from inception to June 2021. The primary outcome was the eradication rate of H. pylori, while the secondary outcomes included the incidence of individual adverse symptoms, treatment compliance, clinical symptom remission after treatment, and patient satisfaction. We used the fixed or random-effects model to pool the risk ratio (RR), with 95% confidence interval. We also conducted sensitivity and subgroup analyses. RESULTS: Our search returned seven relevant studies across a total of 1,433 patients. Compared with controls, EPE was significantly associated with improved H. pylori eradication rates (RR = 1.16, 95%CI: 1.04-1.29, p = 0.006) and patient compliance (RR = 1.48, 95%CI: 1.14-1.93, p = 0.003). A subgroup analysis also showed that EPE benefits were consistent across patients with different eradication programs, WeChat intervention plans, and intervention frequencies (p < 0.05). However, there were no significant differences in the total adverse effects, common side effects (diarrhea, nausea, abdominal pain, taste disorder, and skin rash), or discontinuation rate (p > 0.05). CONCLUSIONS: Patient education is inexpensive, safe, and convenient. In this context, our findings suggest that enhanced educational interventions have positive effects on both the H. pylori eradication rate and adherence among infected patients, and thus constitute promising complements to clinical treatment regimens.

HMGCS2 promotes autophagic degradation of the amyloid-ß precursor protein through ketone body-mediated mechanisms.

HMGCS2 (mitochondrial 3-hydroxy-3-methylglutaryl-COA synthase 2) is a control enzyme in ketogenesis. The mitochondrial localization and interaction with APP (ß-amyloid precursor protein) suggest that HMGCS2 may play a role in the pathophysiology of AD (Alzheimer's disease). Here we report that overexpression of HMGCS2 decreased levels of APP and related CTFs (carboxy-terminal fragments), which was largely prevented by an autophagic inhibitor chloroquine. In addition, HMGCS2 enhancement of autophagic marker LC3II was diminished by rapamycin, an inhibitor of mechanistic target of rapamycin. Moreover, deprivation of EBSS (Earle's Balanced Salt Solution) significantly augmented the effect of HMGCS2 on LC3II, while acetoacetate reversed the reduction of LC3II, APP and CTFs which was induced by HMGCS2 knockdown. In the presence of acetoacetate, rapamycin failed to induce further increase of LC3II, which mimicked the effect of HMGCS2 overexpression. Finally, HMGCS2 enhanced the antioxidant response. Collectively, HMGCS2 shares with ketone bodies common features in autophagic clearance of APP and CTFs, suggesting that ketone bodies play an important role in HMGCS2 regulation of the autophagy.

SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 5'UTR-dependent ADAM10 Translation Initiation.

It is long been suggested that one-carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small-molecule kenpaullone (KEN) promoted ADAM10 translation via the 5' untranslated region (5'UTR) and improved cognitive functions in APP/PS1 mice is found. SHMT2, which is identified as a target gene of KEN and the 5'UTR-interacting RNA binding protein (RBP), mediated KEN-induced ADAM10 translation in vitro and in vivo. SHMT2 controls AD signaling pathways through binding to a large number of RNAs and enhances the 5'UTR activity of ADAM10 by direct interaction with GAGGG motif, whereas this motif affected ribosomal scanning of eukaryotic initiation factor 2 (eIF2) in the 5'UTR. Together, KEN exhibits therapeutic potential for AD by linking OCM with RNA processing, in which the metabolic enzyme SHMT2 "moonlighted" as RBP by binding to GAGGG motif and promoting the 5'UTR-dependent ADAM10 translation initiation.

Abnormal intrinsic brain functional network dynamics in patients with cervical spondylotic myelopathy.

The specific topological changes in dynamic functional networks and their role in cervical spondylotic myelopathy (CSM) brain function reorganization remain unclear. This study aimed to investigate the dynamic functional connection (dFC) of patients with CSM, focusing on the temporal characteristics of the functional connection state patterns and the variability of network topological organization. Eighty-eight patients with CSM and 77 healthy controls (HCs) were recruited for resting-state functional magnetic resonance imaging. We applied the sliding time window analysis method and K-means clustering analysis to capture the dFC variability patterns of the two groups. The graph-theoretical approach was used to investigate the variance in the topological organization of whole-brain functional networks. All participants showed four types of dynamic functional connection states. The mean dwell time in state 2 was significantly different between the two groups. Particularly, the mean dwell time in state 2 was significantly longer in the CSM group than in the healthy control group. Among the four states, switching of relative brain networks mainly included the executive control network (ECN), salience network (SN), default mode network (DMN), language network (LN), visual network (VN), auditory network (AN), precuneus network (PN), and sensorimotor network (SMN). Additionally, the topological properties of the dynamic network were variable in patients with CSM. Dynamic functional connection states may offer new insights into intrinsic functional activities in CSM brain networks. The variance of topological organization may suggest instability of the brain networks in patients with CSM.

Predictive value of CT perfusion-derived parameters in Moyamoya disease.

OBJECTIVE: To explore the applicability of CT perfusion-derived parameters and collateral index in prediction of functional and clinical outcomes in patients with Moyamoya disease (MMD) who have not been treated surgically. METHODS: All hemispheres were categorized into four groups: those with ischemic (IS) lesions, hemorrhagic (HE) lesions, subarachnoid hemorrhage (SAH) and normal hemisphere (NH). The clinical review included primary outcomes (whether a patient survived the cerebrovascular event) and secondary outcomes (the modified Rankin scale [mRS] and Katz-activity of daily living [ADL] scale). CTP-derived parameters of the frontal, temporal lobe and basal ganglia were calculated. Collateral index of the hypointensity ratio (HIR) was defined as a volume of Tmax >10 s/ Tmax >4 s. RESULTS: Between December 2020 and December 2021, 21 MMD patients (15 bilateral cases and 6 unilateral cases, for a total of 36 hemispheres) were retrospectively included. Compared with the NH group, the IS group showed obviously abnormal hemodynamics. As for the primary outcomes, HIR showed an excellent area under the curve of 0.955 (95 % CI: 0.886-1.000, p < 0.001). Significant correlations were found between CTP-derived parameters and secondary outcomes. Furthermore, HIR was significantly correlated with mRS (r = 0.576, p = 0.001) and ADL scores (r = 0.644, p < 0.001). CONCLUSION: Among different imaging types, IS hemispheres were characterized by distinct changes of hemodynamic parameters. Collateral index of HIR could be considered a clinically accessible and promising indictor of functional and clinical outcomes in MMD.

Preoperative and postoperative clinical signatures of postgastrectomy venous thromboembolism in patients with gastric cancer: A retrospective cohort study.

BACKGROUND: This study aimed to identify preoperative and postoperative risk factors of venous thromboembolism (VTE) after gastrectomy in gastric cancer (GC) patients. METHODS: 757 GC patients underwent gastrectomy at our institution and 246 patients with elevated postoperative D-dimer levels who received Doppler ultrasonography of lower/upper extremity veins were enrolled. Clinicopathological factors data were collected, and the differences in clinicopathological factors between postoperative VTE (+) and VTE (-) groups were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors of postgastrectomy VTE. RESULTS: Of 246 patients with elevated postgastrectomy D-dimer concentrations, 74 patients showed thrombosis in lower/upper extremity veins. Among preoperative factors, age, WBC level, D-dimer concentration, and blood glucose level were significantly higher in the postoperative VTE (+) group. Among the postoperative factors, hemoglobin level was significantly lower in the postoperative VTE (+) group. Among the pathological factors, tumor stage, depth of invasion and TNM classification indicated higher malignancy in the postoperative VTE (+) group. Univariate logistic regression analysis indicated age, preoperative blood glucose level, postoperative hemoglobin level, tumor stage, depth of invasion, and TNM classification as the independent risk factors for postgastrectomy VTE, whereas multivariate logistic regression analysis revealed age and tumor stage as independent risk factors for postgastrectomy VTE. CONCLUSION: Our study revealed that age, preoperative blood glucose level, postoperative anemia, and tumor malignancy were independent risk factors for GC patients exhibiting postgastrectomy VTE. Therefore, the perioperative monitoring, assessment and management of risk factors are important in achieving better outcomes after gastrectomy.

Role of mono-ADP-ribosylation histone modification (Review).

The current knowledge regarding ADP-ribosylation modifications of histones, particularly mono-ADP-ribosylation modifications, is limited. However, recent studies have identified an increasing number of mono-ADP-ribosyltransferases and the role of mono-ADP-ribosylation has become a hot research topic. In particular, histones that are substrates of several mono-ADP-ribosyltransferases and mono-ADP-ribosylated histones were indicated to be involved in numerous physiological or pathological processes. Compared to poly-ADP-ribosylation histone modification, the use of mono-ADP-ribosylation histone modification is restricted by the limited methods for research into its function in physiological or pathological processes. The aim of the present review was to discuss the details regarding mono-ADP-ribosylation modification of histones and the currently known functions thereof, such as cell physiological and pathological processes, including tumorigenesis.

Occurrence and antimicrobial resistance of Salmonella isolated from retail meats in Anhui, China.

Salmonella is considered one of the major foodborne pathogens associated with severe infections. Little attempt has been focused on the distribution of Salmonella in retail meats and the analysis of its phenotypic characteristics in Anhui Province. The aim of this study was to characterize the prevalence of Salmonella serovars, antimicrobial susceptibility, antimicrobial resistance genes, and virulence genes in Salmonella recovered from retail meats in Anhui, China. Out of the 120 samples collected from supermarket chains and open-air markets, 16 samples (13.3%) were positive for Salmonella, of which Salmonella enterica serovars Enteritidis and Typhimurium were the common serotypes. Significant differences in incidence were found between supermarket chains and open-air markets (p < 0.05). Overall, all 16 isolates were resistant to at least two tested antimicrobials, while 12 isolates showed multiple antimicrobial resistant phenotypes. High resistance was observed for ampicillin (87.5%), doxycycline (75.0%), and tetracycline (62.5%). The sul2 was detected in all isolates, and the aac(6')-Ib-cr (93.8%) and the tetA (81.3%) were predominant in 10 resistance genes conferring five classes of antimicrobials. In addition, the correlation between resistance phenotypes and genes of tetracyclines and aminoglycosides was more than 80%. Interestingly, all the Salmonella isolates contained the genes mogA, mgtC, sopB, and spvB, whereas the siiE was variably represented. The findings in this study showed high prevalence, antimicrobial resistance, and the existence of virulence genes, suggesting that effective measures are required to ensure microbial safety from retail meats.

Two Different 1-Week Quadruple Therapies Given Back-to-Back Consecutive Therapy for Difficult-to-Treat Helicobacter pylori Infection: A Pilot Study.

INTRODUCTION: We aim to evaluate the efficacy of 2 different 1-week quadruple therapies given back-to-back consecutive therapy in patients with difficult-to-treat Helicobacter pylori infection. METHODS: Patients with proven H. pylori infection were recruited after >3 failed standard quadruple eradication. They received consecutive therapy consisting of esomeprazole 40 mg or rabeprazole 20 mg twice daily, amoxicillin 1,000 mg twice daily, tetracycline 500 mg 4 times daily, and furazolidone 100 mg 3 times daily for the first 7 days, followed by colloidal bismuth pectin 200 mg twice daily in place of furazolidone 100 mg for another 7 days. Eradication rates, treatment-emergent adverse events (TEAEs), and compliance were assessed. RESULTS: Sixty-five patients were enrolled. The mean number of previous eradications was 3.6 (range: 3-7). The intention-to-treat and per-protocol eradication rates were 90.8% (59/65) and 95.1% (58/61). In total, 23.4% (15/64) of patients experienced drug-related TEAEs. No serious adverse events were observed. None of the patients required treatment for TEAEs, and 95.3% (61/64) showed good compliance. Overall, 51 patients (78.5%) were with the available antimicrobial susceptibility testing results. The resistance rates to clarithromycin, metronidazole, levofloxacin, and amoxicillin were 60.8% (31/51), 100% (51/51), 70.6% (36/51), and 2.0% (1/51), respectively. No resistance was detected to either furazolidone or tetracycline. However, in 54.9% of patients (28/51), H. pylori was resistant to 3 antibiotics (metronidazole, levofloxacin, and clarithromycin). DISCUSSION: Consecutive therapy, including amoxicillin, tetracycline, and furazolidone, achieved a good eradication rate (>90%), with desirable compliance and tolerability in difficult-to-treat H. pylori infection.

Cosmosiin Increases ADAM10 Expression via Mechanisms Involving 5'UTR and PI3K Signaling.

The α-secretase "a disintegrin and metalloproteinase domain-containing protein" (ADAM10) is involved in the processing of amyloid precursor protein (APP). Upregulation of ADAM10 precludes the generation of neurotoxic ß-amyloid protein (Aß) and represents a plausible therapeutic strategy for Alzheimer's disease (AD). In this study, we explored compounds that can potentially promote the expression of ADAM10. Therefore, we performed high-throughput small-molecule screening in SH-SY5Y (human neuroblastoma) cells that stably express a luciferase reporter gene driven by the ADAM10 promoter, including a portion of its 5'-untranslated region (5'UTR). This has led to the discovery of cosmosiin (apigenin 7-O-ß-glucoside). Here, we report that in human cell lines (SH-SY5Y and HEK293), cosmosiin proportionally increased the levels of the immature and mature forms of the ADAM10 protein without altering its mRNA level. This effect was attenuated by translation inhibitors or by deleting the 5'UTR of ADAM10, suggesting that a translational mechanism was responsible for the increased levels of ADAM10. Luciferase deletion assays revealed that the first 144 nucleotides of the 5'UTR were necessary for mediating the cosmosiin-induced enhancement of ADAM10 expression in SH-SY5Y cells. Cosmosiin failed to increase the levels of the ADAM10 protein in murine cells, which lack native expression of the ADAM10 transcript containing the identified 5'UTR element. The potential signaling pathway may involve phosphatidylinositide 3-kinase (PI3K) because pharmacological inhibition of PI3K attenuated the effect of cosmosiin on the expression of the ADAM10 protein. Finally, cosmosiin attenuated Aß generation because the levels of Aß40/42 in HEK-APP cells were significantly reduced after cosmosiin treatment. Collectively, we found that the first 144 nucleotides of the ADAM10 5'UTR, and PI3K signaling, are involved in cosmosiin-induced enhancement of the expression of ADAM10 protein. These results suggest that cosmosiin may be a potential therapeutic agent in the treatment of AD.

Phorbol esters dPPA/dPA promote furin expression involving transcription factor CEBPß in neuronal cells.

Using high-throughput small molecule screening targeting furin gene, we identified that phorbol esters dPPA (12-Deoxyphorbol 13-phenylacetate 20-acetate) and dPA (12-Deoxyphorbol 13-acetate) significantly increased furin protein and mRNA expression in SH-SY5Y cells. This effect was prevented by PKC (protein kinase C) inhibitor calphostin C but not Ro318220, suggesting that the C1 domain, rather than the catalytic domain of PKC plays an important role. Luciferase assay revealed that nucleotides -7925 to -7426 were sufficient to mediate dPPA/dPA enhancement of furin P1 promoter activity. RNA interference of transcriptional factors CEBPß (CCAAT/enhancer-binding protein ß) and GATA1 revealed that knockdown of CEBPß significantly attenuated the effect of dPPA on furin expression. Pharmacological inhibition of ERK and PI3K but not TGFß receptor diminished the up-regulation of furin by dPPA. These results suggested that in neuronal cells, transcriptional activation of furin by dPPA/dPA may be initiated by C1 domain containing proteins including PKC; the intracellular signaling involves ERK and PI3K and transcription factor CEBPß.