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No RCT reported on clinically relevant outcome measures - all cause mortality, cardiovascular morbidity and morbidity. There were no significant differences in overall adverse events and withdrawals due to adverse events among the evening versus morning dosing regimens. In terms of BP lowering efficacy, for 24-hour SBP and DBP, the data suggests that better blood pressure control was achieved with bedtime dosing than morning administration of antihypertensive medication, the clinical significance of which is not known.

Biological clocks are intrinsic time-keeping systems that regulate behavior and physiological functions in most living organisms. Previous works suggested a possible link between the endogenous circadian clock and cell cycle regulation. The mammalian Period-2 gene (mPer2), an important component of the circadian clock mechanism, is recently demonstrated to play an important role in repressing tumor growth. In this study, we found that polyethylenimine-mediated intratumoral Per2 gene delivery had significant antitumor effects in C57BL/6 mice transplanted with Lewis lung carcinoma. Our data illustrated that the Per2 gene delivery inhibited PCNA expression and induced apoptosis. Our results support the emerging role of the circadian clock in critical aspects of tumorigenesis. These findings underscore the potential use of Per2 gene delivery as a novel therapeutic intervention for the treatment of malignant tumors.

The short-term safety of an effective and inexpensive new live attenuated Japanese encephalitis vaccine (SA14-14-2) was studied in a randomized trial, using block randomization. Of 26,239 children who were enrolled, half received the vaccine and half served as controls. Subjects were prospectively followed for 30 days for severe adverse events, such as encephalitis, meningitis, and ''all-cause'' hospitalization. No cases of encephalitis or meningitis occurred in either group. The upper 95% confidence limit for adverse events not occurring among subjects receiving their first dose was 4.1/ 10,000. Risk ratios and 95% confidence intervals for other adverse events were 0.70 (0.43-1.15) for all-cause hospitalization, 0.91 (0.37-2.22) for seizure, and 0.79 (0.56-1.11) for fever lasting §3 days. These data attest to the short-term safety of the SA14-14-2 virus strain and the hamster kidney cell substrate.Japanese encephalitis (JE) is an important public health probwith a three-dose primary vaccination series recommended and yearly boosters administered in some countries. Thus, the exlem throughout a vast region of Asia. Conservative estimates place the annual incidence at ú35,000 cases, mostly in children pense and inconvenience of mouse brain-derived JE vaccine hinder immunization efforts. Adding to this difficulty has been [1]. Among these, ú10,000 die of JE, and an equal number develop permanent neurologic sequelae. JE is caused by a flathe occurrence of rare hypersensitivity and neurologic reactions, including encephalitis and encephalopathy, that have vivirus that circulates in zoonotic cycles involving many vertebrate species and is transmitted to humans by the bite of several been associated temporally (although not necessarily causally) with the existing vaccine [3]. mosquito species. Because of its zoonotic cycle, prospects for eradicating JE from the environment are dim, and universalIn 1988, an inexpensive (US $.75/dose) live attenuated primary hamster kidney-derived JE vaccine (SA14-14-2) was childhood vaccination is likely to remain essential for its control in the foreseeable future. licensed in China [4]. Prior to licensure, trials conducted in highly endemic areas indicated 95% efficacy after a single dose A killed mouse brain-derived JE vaccine with 91% efficacy (95% confidence interval [CI], 70%-97%) [2] that is manufac- [1,5]. A recent case-control study conducted in an area less endemic for JE showed 80% effectiveness (95% CI, tured by Biken (Osaka, Japan) is available internationally, although in insufficient quantities to meet the need worldwide.44%-93%) after one dose and 97.5% effectiveness (95% CI, 86%-99.6%) after two doses administered 1 year apart [6]. Similar mouse brain-derived vaccines are produced in limited quantities by manufacturers in other countries. The price of Some information concerning the safety of this vaccine is known. Results of a nonexperimental cohort study of the candiJapanese-produced JE vaccine in Asia is about US $5/dose, date vaccine were published in the Chinese li...

BackgroundGut microbiota plays a critical role in many important physiological processes and is linked with various pulmonary infectious diseases. The relationship between pulmonary tuberculosis (PTB) and gut microbiota has been poorly studied. The present study aimed to characterize gut microbiota in pediatric patients with PTB.MethodsA case-controlled study was executed for the characterization of gut microbiota in pediatric PTB patients. Fecal samples were collected from the PTB patients and healthy controls upon admission. In addition, a one-month follow-up assessment was performed to investigate alterations in the gut microbiota post anti-tuberculosis treatment. 16SrDNA sequencing analysis of fecal DNA was completed on the Illumina MiSeq platform.ResultsCompared with healthy controls, the gut microbiota of pediatric patients with PTB was characterized by decreased microbial diversity. PTB patients further presented an up-regulation of the pro-inflammatory bacteria Prevotella, the opportunistic pathogen Enterococcus, as well as a reduction of beneficial bacteria including Ruminococcaceae, Bifidobacteriaceae and prausnitzii. One-month after anti-tuberculosis therapy, the richness of gut microbiota in PTB patients was distinctly depleted.ConclusionsThe gut microbiota of pediatric patients with PTB was significantly distinct from healthy controls. Additionally, the richness of gut microbiota in PTB patients decreased after one-month anti-tuberculosis treatment. It is hypothesized that the homeostasis of gut microbiota in PTB patients may affect the pathogenies of PTB by de-regulation of the hosts’ immune status through the gut-lung axis.

Background Staphylococcus aureus is commonly carried asymptomatically in the human anterior nares and occasionally enters the bloodstream to cause invasive disease. Much of the global diversity of S. aureus remains uncharacterised, and is not clear how disease propensity varies between strains, and between host populations.MethodologyWe compared 147 isolates recovered from five kindergartens in Chengdu, China, with 51 isolates contemporaneously recovered from cases of pediatric infection from the main hospital serving this community. The samples were characterised by MLST, the presence/absence of PVL, and antibiotic resistance profiling.Principal FindingsGenotype frequencies within individual kindergartens differ, but the sample recovered from cases of disease shows a general enrichment of certain MLST genotypes and PVL positive isolates. Genotypes under-represented in the disease sample tend to correspond to a single sequence cluster, and this cluster is more common in China than in other parts of the world.Conclusions/SignificanceVirulence propensity likely reflects a synergy between variation in the core genome (MLST) and accessory genome (PVL). By combining evidence form biogeography and virulence we demonstrate the existence of a “native” clade in West China which has lowered virulence, possibility due to acquired host immunity.

BackgroundTo determine the correlation between obesity in school-aged children and imbalance of gut microbes by examining the ratio change of intestinal Bifidobacteria and E.coli in obese children compared to non-obese controls.MethodsA hospital-based 1:1 case–control study was performed. Fecal samples of the subjects were collected for DNA extraction and analyzed by quantitative real-time PCR (qPCR) to determine the copy number of Bifidobacteria and E.coli. The ratio of two microbes (B/E) was then calculated and statistically analyzed.ResultsSubjects of the obesity group and control group showed no significant difference in age, gender or height (P > 0.05); whereas they had significant differences in body weight and BMI. Copy numbers of Bifidobacteria and E.coli per gram of wet fecal samples were first determined using qPCR in both obese and normal groups, which were further used for the calculation of B/E ratio. We found that B/E ration in the two groups showed significant difference (P < 0.05). Corrected χ2 test was performed for the two groups against B/E < 1, and it was found that there was a positive correlation (OR = 719.2, OR 95% C.I. = 81.57-6341.18) between B/E ratio decrease with childhood obesity.ConclusionsThe obese children have a lower amount of Bifidobacteria and higher amount of E.coli (smaller B/E ratio) compared to normal non-obese children. It was suggested that obesity in children may be associated with the imbalance of gut microbes.

BackgroundIn recent years, the impact of Helicobacter pylori (H pylori) on the gut microbiota has attracted more attention; however, the relationship in pediatric population rarely was reported.MethodsEndoscopic gastric mucosal biopsy specimens from 55 children with gastrointestinal symptoms were collected, 37 of them were H pylori‐positive (23 nonpeptic ulcer and 14 peptic ulcer) and 18 were H pylori‐negative. In addition, 11 specimens were collected from H pylori‐positive children who performed second endoscopy in 4 weeks after therapy. Microbial abundance and compositions were analyzed by 16S ribosomal RNA amplification and microbial functions were predicted using the software PICRUSt.ResultsThe gastric microbiota of H pylori‐positive children were mainly dominated by Helicobacter in genus (95.43%). The microbiota richness and diversity of H pylori‐positive children were lower than that of H pylori‐negative children. No difference was found in microbiota structure between H pylori‐positive children with or without peptic ulcer. The richness and compositions after therapy were closer to the characteristics of H pylori‐negative children. For predicted functions, higher abundance in pathways of infection diseases, cancer and lower abundance in the pathways of amino acid, lipid, and carbohydrate metabolism were found in H pylori‐positive group than H pylori‐negative group.ConclusionThe characteristics of gastric microbiota were affected by H pylori infection rather than disease states, and the richness and diversity of gastric species were inverse correlation with H pylori infection in children. Eradication therapy was helpful to restore shifted gastric microbiota.