Liver sinusoidal endothelial S1pr2 regulates experimental liver fibrosis through YAP/TGF-ß signaling pathway.

The hepatic vascular niche plays an important role in the pathological process of liver fibrosis. Liver sinusoidal endothelial cells (LSECs) predominantly compose hepatic vascular niches. Endothelial cell (EC)-expressing sphingosine 1-phosphate receptor 2 (S1pr2) plays an essential role in the regulation of vascular functions. Nevertheless, it remains unknown whether liver LSEC-S1pr2 might modulate pathological liver fibrosis. In this study, liver fibrosis was induced by hepatotoxin carbon tetrachloride (CCl4 ). The expression of S1pr2 is significantly downregulated in liver sinusoidal endothelial cells after CCl4 treatment. The loss of S1pr2 in LSECs significantly alleviated liver fibrosis after chronic insult, whereas the overexpression of S1pr2 in LSECs accentuated liver fibrogenesis. In vivo experiments further revealed that the deficiency of S1pr2 in LSECs dampened hepatic stellate cell (HSC) activation, while overexpression of S1pr2 in LSECs enhanced HSC activation with more extracellular matrix component production. Mechanistically, LSEC-S1pr2 activates the YAP signaling pathway to potentiate the transactivation of TGF-ß, which acts on HSCs in a paracrine manner, and thus aggravated liver fibrosis. Taken together, our results uncover a novel pathological mechanism of liver fibrosis in which LSEC-S1pr2 plays an important role in modulating the development of liver fibrosis, providing a future novel therapy target against liver fibrogenesis.

Evening versus morning dosing regimen drug therapy for hypertension.

BACKGROUND: Variation in blood pressure levels display circadian rhythms. Complete 24-hour blood pressure control is the primary goal of antihypertensive treatment and reducing adverse cardiovascular outcomes is the ultimate aim. This is an update of the review first published in 2011. OBJECTIVES: To evaluate the effectiveness of administration-time-related effects of once-daily evening versus conventional morning dosing antihypertensive drug therapy regimens on all-cause mortality, cardiovascular mortality and morbidity, total adverse events, withdrawals from treatment due to adverse effects, and reduction of systolic and diastolic blood pressure in people with primary hypertension. SEARCH METHODS: We searched the Cochrane Hypertension Specialised Register via Cochrane Register of Studies (17 June 2022), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2022); MEDLINE, MEDLINE In-Process and MEDLINE Epub Ahead of Print (1 June 2022); Embase (1 June 2022); ClinicalTrials.gov (2 June 2022); Chinese Biomedical Literature Database (CBLD) (1978 to 2009); Chinese VIP (2009 to 7 August 2022); Chinese WANFANG DATA (2009 to 4 August 2022); China Academic Journal Network Publishing Database (CAJD) (2009 to 6 August 2022); Epistemonikos (3 September 2022) and the reference lists of relevant articles. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in people with primary hypertension. We excluded people with known secondary hypertension, shift workers or people with white coat hypertension. DATA COLLECTION AND ANALYSIS: Two to four review authors independently extracted data and assessed trial quality. We resolved disagreements by discussion or with another review author. We performed data synthesis and analyses using Review Manager Web for all-cause mortality, cardiovascular mortality and morbidity, serious adverse events, overall adverse events, withdrawals due to adverse events, change in 24-hour blood pressure and change in morning blood pressure. We assessed the certainty of the evidence using GRADE. We conducted random-effects meta-analysis, fixed-effect meta-analysis, subgroup analysis and sensitivity analysis. MAIN RESULTS: We included 27 RCTs in this updated review, of which two RCTs were excluded from the meta-analyses for lack of data and number of groups not reported. The quantitative analysis included 25 RCTs with 3016 participants with primary hypertension. RCTs used angiotensin-converting enzyme inhibitors (six trials), calcium channel blockers (nine trials), angiotensin II receptor blockers (seven trials), diuretics (two trials), α-blockers (one trial), and ß-blockers (one trial). Fifteen trials were parallel designed, and 10 trials were cross-over designed. Most participants were white, and only two RCTs were conducted in Asia (China) and one in Africa (South Africa). All trials excluded people with risk factors of myocardial infarction and strokes. Most trials had high risk or unclear risk of bias in at least two of several key criteria, which was most prominent in allocation concealment (selection bias) and selective reporting (reporting bias). Meta-analysis showed significant heterogeneity across trials. No RCTs reported on cardiovascular mortality and cardiovascular morbidity. There may be little to no differences in all-cause mortality (after 26 weeks of active treatment: RR 0.49, 95% CI 0.04 to 5.42; RD 0, 95% CI -0.01 to 0.01; very low-certainty evidence), serious adverse events (after 8 to 26 weeks of active treatment: RR 1.17, 95% CI 0.53 to 2.57; RD 0, 95% CI -0.02 to 0.03; very low-certainty evidence), overall adverse events (after 6 to 26 weeks of active treatment: RR 0.89, 95% CI 0.67 to 1.20; I² = 37%; RD -0.02, 95% CI -0.07 to 0.02; I² = 38%; very low-certainty evidence) and withdrawals due to adverse events (after 6 to 26 weeks active treatment: RR 0.76, 95% CI 0.47 to 1.23; I² = 0%; RD -0.01, 95% CI -0.03 to 0; I² = 0%; very low-certainty evidence), but the evidence was very uncertain. AUTHORS' CONCLUSIONS: Due to the very limited data and the defects of the trials' designs, this systematic review did not find adequate evidence to determine which time dosing drug therapy regimen has more beneficial effects on cardiovascular outcomes or adverse events. We have very little confidence in the evidence showing that evening dosing of antihypertensive drugs is no more or less effective than morning administration to lower 24-hour blood pressure. The conclusions should not be assumed to apply to people receiving multiple antihypertensive drug regimens.

The relationship between self-efficacy, resilience, and job burnout in pediatric residents: a cross-sectional study in Western China.

BACKGROUND: Burnout is prevalent among pediatric residents. Self-efficacy and resilience, as concepts of positive psychology, may be protective factors for burnout. However, no current data demonstrates the mechanism of their interaction. OBJECTIVES: To investigate the pediatric residents' status of self-efficacy, resilience, and job burnout in a university-affiliated hospital in western China. To explore relationships among them, especially the mediating effects of resilience. METHODS: The study was conducted with 190 pediatric residents from an A-Class women's and children's hospital in western China. Data included demographic characteristics, status of pediatric residents, measures of burnout (using the Physicians' Career Burnout Questionnaire), self-efficacy (using the General Self-Efficacy Scale) and resilience (using the Connor-Davidson Resilience Scale). Multiple regression analysis and mediation analysis with bootstrapping were used to identify whether resilience mediates the relationship between self-efficacy and burnout. RESULTS: Female pediatric residents exhibited significantly lower self-efficacy (t = 2.53, p<0.05) and higher levels of job burnout (t=-2.64, p<0.01) compared to male residents. Residents in the standardized training stage experienced higher levels of job burnout compared to those who had completed the training, as indicated by t-values of -3.21, -2.13, and - 2.80 (p<0.05). Significant correlations (p ≤ 0.01) were found among self-efficacy, resilience, and burnout. Additionally, our findings indicated that pediatric residents' self-efficacy can positively predict job burnout and its three dimensions through a major mediating effect of resilience. CONCLUSIONS: The findings regarding the mediating effect of resilience on the influence of self-efficacy on burnout, and their association with gender and residency status, have practical implications for interventions aimed at reducing burnout and improving the well-being of pediatric residents.

Development and validation of a model for early diagnosis of biliary atresia.

BACKGROUND AND AIMS: Early diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. This study aimed to design and validate a predictive model for BA by using the data available at the initial presentation. METHODS: Infants presenting with NC were retrospectively identified from tertiary referral hospitals and constituted the model design cohort (n = 148); others were enrolled in a prospective observational study and constituted the validation cohort (n = 21). Clinical, laboratory, and abdominal ultrasonographic features associated with BA were assessed. A prediction model was developed using logistic regression and decision tree (DT) analyses. RESULTS: Three predictors, namely, gamma glutamyl transpeptidase (γGT) level, triangular cord sign (TC sign), and gallbladder abnormalities, were identified as factors for diagnosing BA in multivariate logistic regression, which was used to develop the DT model. The area under the receiver operating characteristic (ROC) curve (AUC) value for the model was 0.905, which was greater than those for γGT level, TC sign, or gallbladder abnormalities alone in the prediction of BA. CONCLUSION: A simple prediction model combining liver function and abdominal ultrasonography findings can provide a moderate and early estimate of the risk of BA in patients with NC.

Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system.

BACKGROUND: Evidence of drug-induced liver injury is abundant in adults but is lacking in children. Our aim was to identify suspected drug signals associated with pediatric liver injury. METHODS: Hepatic adverse events (HAEs) among children reported in the Food and Drug Administration Adverse Event Reporting System were analyzed. A descriptive analysis was performed to summarize pediatric HAEs, and a disproportionality analysis was conducted by evaluating reporting odds ratios (RORs) and proportional reporting ratios to detect suspected drugs. RESULTS: Here, 14,143 pediatric cases were reported, specifically 49.6% in males, 45.1% in females, and 5.2% unknown. Most patients (68.8%) were 6-18 years old. Hospitalization ranked first among definite outcomes (7,207 cases, 37.2%). In total, 264 disproportionate drug signals were identified. The top 10 drugs by the number of reports were paracetamol (1,365; ROR, 3.6; 95% confidence interval (CI), 3.4-3.8), methotrexate (878; ROR, 2.5; 95% CI, 2.3-2.7), vincristine (649; ROR, 3.0; 95% CI, 2.8-3.3), valproic acid (511; ROR, 3.2; 95% CI, 2.9-3.6), cyclophosphamide (490; ROR, 2.4; 95% CI, 2.2-2.6), tacrolimus (427; ROR, 2.4; 95% CI, 2.2-2.7), prednisone (416; ROR, 2.1; 95% CI, 1.9-2.3), prednisolone (401; ROR, 2.3; 95% CI, 2.1-2.5), etoposide (378; ROR, 2.3; 95% CI, 2.1-2.6), and cytarabine (344; ROR, 2.8; 95% CI, 2.5-3.2). After excluding validated hepatotoxic drugs, six were newly detected, specifically acetylcysteine, thiopental, temazepam, nefopam, primaquine, and pyrimethamine. CONCLUSIONS: The hepatotoxic risk associated with 264 signals needs to be noted in practice. The causality of hepatotoxicity and mechanism among new signals should be verified with preclinical and clinical studies.

Death from human cytomegalovirus infection in a girl with congenital thymic dysplasia.

We report the case of a girl with congenital thymic dysplasia and refractory disseminated Human Cytomegalovirus (CMV) infection diagnosed by autopsy. Additionally, she was diagnosed with T-cell lymphopenia immunodeficiency and received antiviral therapy with ganciclovir (GCV) /valganciclovir (V-GCV) and enhanced foscarnet. The CMV viral load (VL) monitoring was elevated with retinitis, interstitial pneumonia, and hepatitis. The phenotype of T-cell lymphopenia was uncertain, which limited any alternative therapy by whole-exome sequencing (WES) and lymphocyte subset panel until autopsy. The girl died of progressive respiratory failure and septic shock at ten months of age. Severe disseminated CMV infection typically develops in infants with primary maternal infections and occurs earlier during gestation and in people with a weakened host immune system. Individuals with CMV infection with initial immunodeficiency are associated with a poor prognosis, which is similar to patients with secondary immunodeficiency. This case describes the difficult treatment and prognosis of CMV infection in patients with congenital immunodeficiency, highlighting the importance of early aggressive anti-CMV antiviral therapy in immunodeficiencies, VL monitoring, drug resistance and the role of T-cells in CMV infection.

Detection of pulmonary tuberculosis in children using the Xpert MTB/RIF Ultra assay on sputum: a multicenter study.

Microbiological confirmation is rare in children with active tuberculosis; therefore, a more accurate test is needed to detect pulmonary tuberculosis in children. In this multicenter study, we evaluated the utility of the Xpert MTB/RIF Ultra (Ultra) on sputum, an assay recommended by the World Health Organization to test for childhood tuberculosis in high-burden settings. Children with symptoms suggestive of tuberculosis were enrolled at three hospitals in China and categorized as having active tuberculosis or nontuberculosis. The sensitivity and specificity of Ultra were 42.1% (48/114) and 99.0% (208/210), respectively. Using three MTB culture results as the reference, the sensitivity of Ultra in the subset of 38 children with culture-positive and 76 children with culture-negative was 68.4% (26/38) and 28.9% (22/76), respectively(p < 0.001). A single MTB culture combined with a single Ultra could detect 54 (54/114,47.4%) cases with active TB, while repeated MTB culture combined with a single Ultra detected 60 (60/114, 52.6%) cases with active TB(p = 0.427). Among 155 children (58 with TB and 97 with RTIs) simultaneously tested with the Ultra and Xpert MTB/RIF (Xpert), the sensitivity of the Xpert (24.1%, 14/58) was lower than that of the Ultra (41.4%, 24/58; p = 0.048). Eight children were found to have rifampin-resistant MTB strains. The Xpert MTB/RIF Ultra assay should be implemented to test for pulmonary tuberculosis in children to achieve higher confirmation rates.

Clinical profiles and antimicrobial resistance patterns of invasive Salmonella infections in children in China.

Invasive Salmonella infections result in a significant burden of disease including morbidity, mortality, and financial cost in many countries. Besides typhoid fever, the clinical impact of non-typhoid Salmonella infections is increasingly recognized with the improvement of laboratory detection capacity and techniques. A retrospective multicenter study was conducted to analyze the clinical profiles and antimicrobial resistance patterns of invasive Salmonella infections in hospitalized children in China during 2016-2018. A total of 130 children with invasive Salmonella infections were included with the median age of 12 months (range: 1-144 months). Seventy-nine percent of cases occurred between May and October. Pneumonia was the most common comorbidity in 33 (25.4%) patients. Meningitis and septic arthritis caused by nontyphoidal Salmonella (NTS) infections occurred in 12 (9.2%) patients and 5 (3.8%) patients. Patients < 12 months (OR: 16.04) and with septic shock (OR: 23.4), vomit (OR: 13.33), convulsion (OR: 15.86), C-reactive protein (CRP) ≥ 40 g/L (OR: 5.56), and a higher level of procalcitonin (PCT) (OR: 1.05) on admission were statistically associated to an increased risk of developing meningitis. Compared to 114 patients with NTS infections, 16 patients with typhoid fever presented with higher levels of CRP and PCT (P < 0.05). The rates of resistance to ampicillin, sulfamethoxazole/trimethoprim, ciprofloxacin, and ceftriaxone among Salmonella Typhi and NTS isolates were 50% vs 57.3%, 9.1% vs 24.8%, 0% vs 11.2%, and 0% vs 9.9%, respectively. NTS has been the major cause of invasive Salmonella infections in Chinese children and can result in severe diseases. Antimicrobial resistance among NTS was more common.

Toxic epidermal necrolysis after therapeutic plasma exchange in pediatric lupus patients and associated risk factors analysis.

BACKGROUND: Therapeutic plasma exchange (TPE) is an effective means of treating systemic lupus erythematosus in children and is safe for most pediatric patients with systemic lupus erythematosus, but severe complications such as toxic epidermal necrolysis (TEN) may occur, which is a life-threatening condition. METHODS: In this study, three systemic lupus erythematosus (SLE) children developed toxic epidermal necrolysis after TPE. We analyzed their medical history, clinical manifestations, SLEDAI scores, and immunological characteristics, compared to 117 cases of SLE patients without TEN after TPE, trying to find the possible risk factors. RESULTS: The three children with TEN after plasma exchange appeared to have a higher proportion of male (male: female = 2:1), fever (100% Vs 32.5%), erythema on the cheek (100% Vs 54.7%), itching rash (100% Vs 54.7%), ruptured rash (100% Vs 54.7%), oral ulcer (100% Vs 54.7%) and higher LDH level (1826.0 ± 1113.1 Vs 721.1 ± 799.5 U/L), but lower white blood cell count (5.5 ± 3.3 Vs 7.2 ± 4.2 × 109/L), neutrophil count (4.7 ± 3.7 Vs 5.2 ± 3.6 × 109/L), lymphocyte count (0.6 ± 0.5 Vs 1.5 ± 0.8 × 109/L), platelet count (133.7 ± 58.1 Vs 178.5 ± 103.1 × 109/L) and C-reactive protein (all normal Vs 47.9% elevated). Autoantibody spectrum revealed that positive anti-SSA seemed more common (100% Vs 42.7%) in the three children. Relative risk analysis revealed that male (OR 21.4, 95%CI 1.78-257.186), ruptured skin rash (OR 56.5, 95%CI 4.199-760.196) and rash with itching (OR 24, 95%CI 1.98-290.896) are the risk factors of SLE patients developing TEN after plasma exchange. CONCLUSIONS: We should pay particular attention to TEN after plasma exchange in SLE patients (3/120, 2.5%). This condition may be related to male, ruptured skin rash and rash with itching. For SLE patients with risk factors. We should arrange plasmapheresis more carefully.

Microbiological profiles and antimicrobial resistance patterns of pediatric bloodstream pathogens in China, 2016-2018.

OBJECTIVES: This study aimed to investigate the microbiological profiles and antimicrobial resistance patterns of bloodstream pathogens in Chinese children. METHODS: This retrospective study was conducted at 13 tertiary hospitals in China during 2016-2018. The first bloodstream isolates of the same species from one pediatric patient < 18 years were included to this study for analysis. Antimicrobial susceptibility testing was determined based on minimum inhibitory concentrations or Kirby-Bauer disk diffusion methods according to the 2018 Clinical and Laboratory Standards Institute guidelines. RESULTS: Overall, 9345 nonduplicate bloodstream isolates were collected. Top 10 pathogens included Coagulase-negative staphylococcus (CoNS) (44.4%), Escherichia coli (10.2%), Klebsiella pneumoniae (5.9%), Staphylococcus aureus (5.0%), Streptococcus pneumoniae (4.9%), Pseudomonas aeruginosa(2.8%), Enterococcus faecium (2.7%), Stenotrophomonas maltophilia (2.4%), Salmonella spp. (2.3%), and Streptococcus agalactiae (2.0%). The commonest pathogens apart from CoNS in age group 0-28 days, 29 days-2 months, 3-11 months, 1-5 years, and ≥ 5 years were Escherichia coli (17.2%), Escherichia coli (14.0%), Escherichia coli (7.9%), Streptococcus pneumoniae (10.7%) ,and Staphylococcus aureus (13.6%), respectively. The overall prevalence of extended-spectrum ß-lactamases-producing Enterobacteriaceae, carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, and carbapenem-resistant Pseudomonas aeruginosa were 41.4, 28.4, 31.7, and 5.6%, respectively. The overall prevalence of methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant Enterococcus was 38.1, 28.3, and 0.7%, respectively. CONCLUSIONS: The major bacterial pathogens have differences in different age groups, ward types, and regions in Chinese children, and the commonest causing microorganism was the Escherichia coli, especially in neonates and infants. High prevalence of important resistant phenotypes is of a serious concern.

Epidemiology, risk factors and outcomes of bloodstream infection caused by ESKAPEEc pathogens among hospitalized children.

BACKGROUND: Bloodstream infection (BSI) resulting from ESKAPEEc pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp) is relevant to high mortality and economic cost. Data concerning the impact of BSI due to ESKAPEEc in pediatric population was virtually scant. Our purpose was to summarize the epidemiology, risk factors and outcomes of ESKAPEEc BSI among hospitalized children. METHODS: Inpatients diagnosed with BSI with definite etiology between January 2016 and December 2018 were enrolled retrospectively at the West China Second University Hospital. Data were systematically reviewed on patients' clinical characteristics and laboratory findings to ascertain independent predictors, clinical features and outcomes. RESULTS: Of the 228 patients with BSI, 174 (76.3%) were caused by ESKAPEEc (124 MDR-ESKAPEEc). Multivariate analysis demonstrated that premature and/ or low birth weight (odds ratio [OR] = 2.981, P = 0.036), previous surgery and/or trauma (OR = 5.71, P = 0.029) and source of urinary tract infection (OR = 10.60, P = 0.004) were independently associated with ESKAPEEc BSI. The independent risk factor for MRD-ESKAPEEc BSI was nosocomial infection (OR = 3.314, P = 0.037). The overall mortality rate in patients with ESKAPEEc BSI was 14.4% (25/174), and no significant difference was ascertained in mortality between MRD-ESKAPEEc and non-MRD ESKAPEEc BSI groups (13.7% vs. 11.4%, P = 0.692). In addition, previous surgery and/or trauma, thrombocytopenia, and mechanical ventilation were significant risk factors for mortality caused by ESKAPEEc BSI. CONCLUSIONS: More than two-thirds of BSI among hospitalized children were caused by ESKAPEEc. Previous surgery and/or trauma, thrombocytopenia and mechanical ventilation increased the risk rate for mortality in ESKAPEEc BSI. The risk factors ascertained could assist physicians to early suspect ESKAPEEc BSI and MDR ESKAPEEc BSI.

Acute development of syringomyelia following TBM in a pediatric case.

BACKGROUND: Syringomyelia secondary to tuberculous meningitis (TBM) is rarely reported, and is usually a late complication. Acute development of syringomyelia following TBM is an exceedingly rare condition with only a few cases published in adults and no previous reports in children. CASE PRESENTATION: We present a case of syringomyelia as an acute complication of TBM in a 12-year-old boy despite appropriate chemotherapy. The patient developed spastic paraplegia of the lower limbs with fecal and urinary retention seventeen days after the initial symptoms of TBM. He was managed successfully with continued chemotherapy and high-dose intravenous immunoglobulin (IVIG). CONCLUSIONS: This case reminds us that syrinx formation may be responsible for early neurological deterioration in children being managed for TBM. IVIG may be considered as an effective treatment option for this situation.

Evaluation of Xpert MTB/RIF Ultra Assay for Diagnosis of Childhood Tuberculosis: a Multicenter Accuracy Study.

A multicenter study was performed to evaluate the value of testing gastric aspirate (GA) with Xpert MTB/RIF Ultra assay (Ultra) for childhood tuberculosis (TB) detection in China. In total, 129 children with active TB and 173 children without TB were enrolled. The sensitivity of Ultra in bacteriologically confirmed TB and probable TB cases was 87.5% (42/48) and 44.4% (36/81), respectively. The specificity of Ultra was high (99.4%, 172/173). When Ultra, culture, and acid-fast bacilli outcomes were integrated as a composite reference standard, the percentage of children with definite TB increased from 37.2% (48/129) to 67.4% (87/129). The sensitivity of Ultra is 80.0% (40/50) in children aged <4 years, which is significantly higher than that in older children (48.1%, 38/79) (P < 0.001). Ultra conducted using GA samples can provide faster results, allowing an early and accurate TB diagnosis, especially in younger children with difficulty producing sputum.

Pediatric Antibiotic Prescribing in China According to the 2019 World Health Organization Access, Watch, and Reserve (AWaRe) Antibiotic Categories.

OBJECTIVES: To assess clinical indication-specific antibiotic prescribing in pediatric practice in China based on the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) metrics and to detect potential problem areas. STUDY DESIGN: Pediatric prescription records on the 16th of each month during 2018 were sampled for all encounters at outpatient and emergency departments of 16 tertiary care hospitals via hospital information systems. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) classification. RESULTS: A total of 260 001 pediatric encounters were assessed, and antibiotics were prescribed in 94 453 (36.3%). In 35 167 encounters (37.2%), at least 1 intravenous antibiotic was administered. WHO Watch group antibiotics accounted for 82.2% (n = 84 176) of all antibiotic therapies. Azithromycin (n = 15 791; 15.4%) was the most commonly prescribed antibiotic, and third-generation cephalosporins (n = 44 387; 43.3%) were the most commonly prescribed antibiotic class. In at least 66 098 encounters (70.0%), antibiotics were prescribed for respiratory tract conditions, mainly for bronchitis/bronchiolitis (n = 25 815; 27.3%), upper respiratory tract infection (n = 25 184; 26.7%), and pneumonia (n = 13 392; 14.2%). CONCLUSIONS: Overuse and misuse of WHO Watch group antibiotics for respiratory tract conditions and viral infectious diseases is common in pediatric outpatients in China. Pediatric antimicrobial stewardship should be strengthened using WHO AWaRe metrics.

Correction to: Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts.

In the original article, Fig. 4b was published incorrectly in which four to five lanes in Pi-ERK and Pi-CREB panels look very similar to each other (Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts, Mol Cell Biochem, 2008, 313:11-18). Since this image was stored in The Experiment Center of the West China Second University Hospital, Sichuan University, which was dissoluted in 2012, the original data cannot be traced. Experiments were therefore redone to verify the result and the correct version of Fig. 4b is provided in this correction.

The relationship of gastric microbiota and Helicobacter pylori infection in pediatrics population.

BACKGROUND: In 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. METHODS: Endoscopic 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. RESULTS: The 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. CONCLUSION: The 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.

Infantile fever-triggered acute liver failure caused by novel neuroblastoma amplified sequence mutations: a case report.

BACKGROUND: Infantile liver failure syndrome-2 (ILFS2) is caused by neuroblastoma amplified sequence (NBAS) mutation. The disease is characterized by recurrent episodes of acute liver failure (ALF) or by liver crisis triggered by recurrent episodes of fever and complete recovery. CASE PRESENTATION: Here, we describe the case of a Chinese girl with typical clinical manifestation of ILFS2 without exhibition of extrahepatic involvement. The patient harbored novel compound heterozygous mutations in the NBAS region (c.3386C > T (p.Ser1129Phe), c.1A > C (p.Met1Leu) and c.875G > A (p.Gly292Glu)), mutations which have not been previously reported. After administration of antipyretics and intravenous glucose and electrolyte administration, the patient recovered fully. CONCLUSION: Through the present study, we recommend that ILFS2 should be taken into consideration during the differential diagnosis of children with recurrent, fever-triggered ALF. While the definitive diagnosis of ILFS2 remains dependent on genetic sequencing and discovery of NBAS, early antipyretic treatment is recommended to prevent liver crisis.

A new insight into acute lymphoblastic leukemia in children: influences of changed intestinal microfloras.

BACKGROUND: Previous studies have shown that changes in intestinal microfloras are associated with both gastrointestinal (GI) and non-GI tumors. It is not clear whether there is an association between GI microflora changes and hematological malignancies. METHODS: In the current study, we used 16S rDNA gene sequencing techniques to profile the GI microbiome in children with lymphoblastic leukemia (ALL, n = 18) and matched healthy control (n = 18). Using multiple specialized software [Heatmap, Principal coordinates analysis (PCoA), Claster and Metastates], we analyzed the sequencing data for microfloral species classification, abundance and diversity. RESULTS: A total of 27 genera between the ALL and control groups (FDR ≤ 0.05 and/or P ≤ 0.05) showed significantly different abundance between ALL patients and healthy controls: 12 of them were predominant in healthy group and other 15 species were significantly higher in ALL group. In addition, we compared the abundance and diversity of microfloral species in ALL patients prior to and during remission stage after chemotherapy, and no significant difference was detected. CONCLUSIONS: Compared to healthy controls, ALL patient showed significant changes of GI microfloras. Further explorations of the intestinal micro-ecology in ALL patients may provide important information to understand relationship between microfloras and ALL.

Dynamic construction of gut microbiota may influence allergic diseases of infants in Southwest China.

BACKGROUND: Gut microbes have been suggested as the possible targets in the management of allergic diseases. However, the way in which these microbes influence allergic diseases remain unclear. Forty-seven full-term newborns were selected from a 1000-infant birth cohort. Among them were 23 allergic infants, whereas 24 infants were healthy without allergic symptoms at 1 year of age. Two hundred and sixty-four fecal samples were collected at 7 time points following their birth. These fecal samples were microbiologically analyzed using 16S rRNA gene sequencing. The dynamic processes involved in gut microbiota diversity and composition in the tested infants were constructed. RESULTS: Healthy infants demonstrated more statistical differences in longitudinal changes in the alpha diversity of their microbiota at the time points compared with day 0 (meconium) than did allergic infants. Analysis of beta diversity showed that the fecal microbiota of days 0 and 2 comprised different communities in healthy infants, and that there were three separate communities in the fecal microbiota of day 0 of the healthy infants, those of day 2 of the healthy infants, and those of days 0-2 of the allergic infants. The relative abundance of dominant gut microbiota at phylum level varied at different time points in the healthy and diseased groups. Bifidobacterium, Escherichia-Shigella, Streptococcus, Clostridium_sensu_stricto_1, Akkermansia and Erysipelatoclostridium were significantly different between the healthy and diseased groups at a different time points. CONCLUSION: The dynamic construction processes of gut microbiota during early life might be associated with the occurrence of long-term allergic diseases, with the first month following birth potentially being the most critical.

Relationship between nasal Carrier isolates and clinical isolates in children with Staphylococcus aureus infections.

AIM: To assess the relationship between Staphylococcus aureus (S. aureus) strains colonizing the anterior nares and clinical isolate colonizing other, non-nasal infectious sites in children with S. aureus infections. METHODS: Fifty-six hospitalized children with S. aureus infection were screened and 22 pairs of nasal carrier isolates and non-nasal clinical isolates were characterized by polymerase chain reaction (PCR) assay for the detection of methicillin resistance (mecA) gene, Panton-Valentine leukocidin virulence (PVL) gene, and multilocus sequence typing (MLST) for the purpose of identifying sequence types of S. aureus. RESULTS: In this study, Sequence Type (ST) 59 was found to be the predominant clonal type in the nasal carrier isolates, with statistically significant differences in positive mecA and PVL expression compared with other STs. In general, there was consistence between the STs detected in the nose and other, non-nasal sites for each patient (Kappa = 0.950), where 19 pairs (86.4%) of colonization isolates and their corresponding non-nasal clinical isolates were indistinguishable in mecA, PVL, and ST expression. CONCLUSION: ST59 is reported here as a dominant and virulent methicillin-resistant S. aureus (MRSA) clone which may has become a leading sequence type among virulent MRSAs in Sichuan area. Overall there is a strong correlation between colonization and infection in pediatric patients that may be genetically indistinguishable and endogenous. Therefore, nasal swabs as a routine test for children, the elimination of nasal carriage may be considered as a prevention strategy for some systemic S. aureus infections.