[Research Progress of Helicobacter pylori-Associated Extragastric Diseases].

Helicobacter pylori (Hp) is a common Gram-negative bacillus causing gastrointestinal infections.It mainly exists on the surface of gastric epithelial cells and in mucus and is associated with gastric ulcers,gastric cancer,and gastric mucosa-associated lymphomas.Studies have shown that Hp can induce or exacerbate certain extragastric diseases and is associated with the occurrence of coronavirus disease 2019.It is hypothesized that Hp may be indirectly or directly involved in the occurrence and development of diseases by stimulating the production of inflammatory cytokines or inducing cross-immune reactions.In addition,Hp can enter Candida to release toxins continuously and play a role in escaping the recognition of the host immune system and the bactericidal effect of drugs.This article reviews the research progress in Hp-associated extragastric diseases in recent years,aiming to draw the attention of clinical workers to Hp-associated extragastric diseases and enrich the knowledge about Hp infection for formulating countermeasures to avoid the aggravation or triggering of other diseases by Hp.

Circular RNA circ-ERBB2 promotes HER2-positive breast cancer progression and metastasis via sponging miR-136-5p and miR-198.

BACKGROUND: Circular RNAs (circRNAs) are pivotal regulators of various human cancers and circ-ERBB2 is abnormally expressed in breast cancer cells. However, the role and mechanism of circ-ERBB2 in HER2-positive breast cancer are still unknown. METHODS: The circ-ERBB2 expressions in the tumor tissues of HER2-positive breast cancer patients were tested using quantitative real-time PCR. The circ-ERBB2 function was investigated by cell counting kit 8 assay, Transwell, flow cytometry and Western blot. Mechanistically, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter gene assays were conducted to confirm the interaction between circ-ERBB2 and miR-136-5p or miR-198 in HER2-positive breast cancer cells. RESULTS: Circ-ERBB2 was elevated in the tumor tissues of HER2-positive breast cancer patients. Functionally, the interference with circ-ERBB2 repressed HER2-positive breast cancer cell proliferation, migration, invasion and accelerated cell apoptosis. Furthermore, the mechanistic analysis corroborated that circ-ERBB2 acted as a competing endogenous RNA for miR-136-5p or miR-198 to relieve the repressive influence of miR-136-5p or miR-198 on its target transcription factor activator protein 2C (TFAP2C). Meanwhile, in vivo assays further corroborated the oncogenic function of circ-ERBB2 in HER2-positive breast cancer. CONCLUSIONS: Circ-ERBB2 accelerated HER2-positive breast cancer progression through the circ-ERBB2/miR-136-5p/TFAP2C axis or the circ-ERBB2/miR-198/TFAP2C axis.

Optimal Dosing of Meropenem in a Small Cohort of Critically Ill Children Receiving Continuous Renal Replacement Therapy.

Severe sepsis is an important cause of mortality and morbidity in critically ill children. Meropenem is a broad-spectrum antibiotic commonly used to treat sepsis. Current meropenem dosage recommendations for children on continuous renal replacement therapy are extrapolated from pharmacokinetic (PK) studies done in adults. Our study aims to determine the optimal dosing in critically ill septic children receiving continuous renal replacement therapy. A prospective single-center PK study was performed in 9 children in the intensive care unit on continuous renal replacement therapy. Meropenem concentrations were measured from blood and effluent fluid samples. A population PK model was developed using nonlinear mixed-effects modeling software (NONMEM, AstraZeneca UK Ltd, Cheshire, UK). Monte Carlo simulations were performed. The PK/pharmacodynamic target aimed for plasma concentrations above minimum inhibitory concentration of 4 mg/L for 100% of dosing interval (100%ƒT>MIC ). A 2-compartment model best characterized meropenem PK. Mean (range) clearance and elimination half-life was 0.091 L/h/kg (0.04-0.157) and 3.9 hours (2.1-7.5), respectively. Dosing of 40 mg/kg/dose every 12 hours over 30 minutes achieved PK/PD target in only 32% while 20 mg/kg every 8 hours over 4 hours or 40 mg/kg every 8 hours over 2 hours achieved 100% ƒT>MIC target for at least 90% of simulated patients.

[Impact of Smoking on the Histological Subtype and Outcome of the Primary Lung Adenocarcinoma].

OBJECTIVE: To explore the effect of smoking on the histological subtype and prognosis of patients with lung adenocarcinoma (LAC) in China. METHODS: According to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society(IASLC/ATS/ERS)classification, 266 donors with primary LAC were reclassified. The correlation between clinicopathological factors including smoking status and the histological subtype was analyzed, and survival analysis was used to analyze the prognosis of primary LAC. RESULTS: There were four main histological subtypes including acinar predominant adenocarcinoma (APA) 30.1%, papillary predominant adenocarcinoma (PPA) 26.7%, solid predominant adenocarcinoma (SPA) 25.9%, and lepidic predominant adenocarcinoma (LPA) 11.7%.Smoking was associated with the histological subtype.The proportion of smokers was significantly higher than non-smokers in the SPA group, and the proportion of non-smokers was higher in other subtypes group. Cox regression model showed that the histological subtype and TNM stage were the independent predictors of prognostic in all patients.TNM stage was the predictor of postoperative survival in both smokers and non-smokers, and histological subtypes was the predictor only in smokers (ß=0.898, RR=2.455). Compared with the non-SPA group, the prognosis of the SPA group was significantly worse. CONCLUSION: Smoking is associated with SPA subtype, which affect the prognosis of primary LAC.

MicroRNA Expression Profile on Solid Subtype of Invasive Lung Adenocarcinoma Reveals a Panel of Four miRNAs to Be Associated with Poor Prognosis in Chinese Patients.

According to the reclassification of lung adenocarcinoma (LAC) proposed in 2011, solid predominant lung adenocarcinoma (SPA) has been associated with poor outcomes for LAC patients. However, the prognostic value of the presence of solid subtype remains unclear. Besides, there is little data about the roles of microRNA (miRNA) in solid subtype of LAC. In this study, 243 LAC patients were classified into solid subtype positive and negative groups (S+ LAC, n=134 and S- LAC, n=109) according to whether the solid subtype was more than 5% of the tumor component or not. We analyzed the relationship between solid subtype and patients' outcome by univariate and multivariate analyses. Solid subtype was proved to be significantly associated with the 5-year overall survival and played as an independent prognostic factor for stage I-III invasive LAC patients. Then miRNA microarray was used to identify differentially expressed miRNAs in solid subtype, resulting in 31 differential miRNAs. Quantitative reverse transcription-PCR (QRT-PCR) was used to validate 4 key miRNAs (miR-133b, miR-155-5p, miR-124-3p, miR-145-5p). Further, CCK-8 and transwell assays were performed to validate the impact of one dysregulated miRNA (miR-133b) on LAC cell function. Interestingly, while miR-133b could significantly inhibit the proliferation of A549 and SPC-A1, it showed no effect on the migration or invasion of LAC cell lines. These results suggest that solid subtype can exert independent prognostic impact on LAC patients, and 4 important dysregulated miRNAs in solid subtype of LAC may be involved in the malignancy of S+LAC, thus may further have clinical perspective for S+ LAC in the future.

The complete mitochondrial genome of black-footed ferret, Mustela nigripes (Mustela, Mustelinae).

In this study, the complete mitochondrial genome sequence of black-footed ferret, Mustela nigripes, is determined for the first time. This mitogenome is 16,556 bp in length and contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 control region (D-loop). The overall base composition is A (32.9%), C (26.1%), G (13.8%), and T (27.2%), so the percentage of A and T (60.1%) is higher than that of G and C. Most of the genes are encoded on H-strand, except for the ND6 subunit gene and six tRNA genes. The complete mitochondrial genome sequence reported here would be useful for further phylogenetic analysis and conservation genetic studies in M. nigripes.

Use of Magnesium Sulfate Infusion for the Management of Febrile Illness-Related Epilepsy Syndrome: A Case Series.

Febrile illness-related epilepsy syndrome is a catastrophic epileptic encephalopathy that is highly refractory to most antiepileptic drugs leading to high morbidity and mortality. The authors report the use of a pediatric infusion protocol of continuous intravenous magnesium sulfate for the control of seizures in 2 children with febrile illness-related epilepsy syndrome refractory to multiple antiepileptic drugs in a pediatric intensive care unit of a tertiary care children's hospital. Both patients, 2 and 16 years of age, respectively, were treated with continuous magnesium sulfate infusion. Serum magnesium concentrations ranging from 2.1 to 5 mmol/L were achieved. Seizure reduction and cessation were noted in 1 patient with magnesium more than 3.0 mmol/L. No significant adverse effects were observed. Magnesium sulfate infusions can be safely used in pediatric refractory status epilepticus. Magnesium sulfate can be considered in the management of children with febrile illness-related epilepsy syndrome.

Developing a nomogram for dose individualization of phenytoin in Asian pediatric patients derived from population pharmacokinetic modeling of saturable pharmacokinetic profiles of the drug.

BACKGROUND: A population pharmacokinetic model for phenytoin in Asian pediatric patients was developed to determine the influence of concurrent medications, patient demographics, and blood biochemistry on the pharmacokinetic profile of phenytoin. METHODS: Retrospective clinical data were obtained from 66 patients (age, 1-16 years) for the determination of pharmacokinetic parameters of phenytoin using WinNonmix. Data from 49 patients (74.2%) were allocated in the "index" group, and the other 17 patients (25.8%) in the "validation" group. Models were compared by final log likelihood, mean error as a measure of bias, and root-mean-squared error as a measure of precision. RESULTS: The Michaelis-Menten constant (km) and volume of distribution (V) were fixed at 9.08 mg/L and 1.23 L/kg, respectively. The saturated elimination rate (V × Vmax) of phenytoin was then found to be 0.525 mg/kg per hour (352.9 4 mg/d for a 28.0 kg individual). Patients' body surface area (in square meter) and catalytic activities of liver enzymes aspartate aminotransferase (U/L) and alkaline phosphatase (U/L) appeared to have significant correlation with Vmax, whereas coadministrating drugs with phenytoin did not yield any significant effect. The final model for the saturated elimination rate was (Equation is included in full-text article.) In validation of the final model, the mean error was found to be -0.805 (95% confidence interval, -3.67 to 2.06), and the root-mean-squared error was 7.92 (95% confidence interval, 3.41-12.43). CONCLUSIONS: The obtained results indicated the need to consider patients' body surface area and the catalytic activities of liver enzymes aspartate aminotransferase and alkaline phosphatase when dosing phenytoin. Based on the population pharmacokinetic parameters, a nomogram was subsequently developed for dose individualization of phenytoin in Asian pediatric patients.

A retrospective study on the usage of antiepileptic drugs in Asian children from 2000 to 2009 in the largest pediatric hospital in Singapore.

PURPOSE: In light of the increasing usage of the newer antiepileptic drugs (AEDs) in other countries, we reviewed the prescribing pattern of AEDs in Singapore over the last 10 years (2000-2009). METHODS: A retrospective review of pharmacy dispensing records solicited from the only children's hospital in Singapore was performed to analyze the trend in AEDs prescribing in the last 10 years. We also examined the correlation between the serum concentrations of valproic acid (VPA), the most-prescribed AED, and seizure control. Descriptive and inferential statistical analyses were then performed on the findings. RESULTS: A total of 41 671 prescriptions on AEDs were retrieved and analyzed. Despite the introduction of the second-generation AEDs, the first generation AEDs still dominate epilepsy treatment in Asian children, with VPA being the mostly prescribed AED (about 40% of the total AEDs usage). The majority of patients (62.8%) were on monotherapy. The mean VPA serum concentration in patients with good seizure control was 68.6 µg/ml (SD = 26.4 µg/ml; range = 12.2-138.0 µg/ml), which was statistically higher than the mean VPA concentration of 57.7 µg/ml (SD = 27.1 µg/ml; range = 11.1-149.0 µg/ml) in patients with poor seizure control (p < 0.0001). CONCLUSION: With VPA being the most prescribed AED in our clinical practice, and the finding in this study that with careful classification of the patients' condition, serum concentrations of VPA generally correlate well with the seizure control, the correct dose titration of VPA with therapeutic drug monitoring is still of paramount importance.