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Background: Although the human adenovirus infection is common, adenovirus infection with liver dysfunction is rare. Methods: To retrospectively analyze and compare the clinical characteristics and outcomes of pediatric patients diagnosed with severe adenovirus pneumonia with and without liver dysfunction, who were admitted to the pediatric intensive care unit of Hunan Children’s Hospital (South China University) between January 2018 and June 2022. Results: Of the 330 severe adenovirus pneumonia cases analyzed (mean age, 19.88 ± 18.26 months), 102 were girls and 228 were boys. They were divided into two groups: those with liver dysfunction (n = 54) and without liver dysfunction (n = 276). Comparison analysis showed no significant between-group differences in body mass index and levels of white blood cells, neutrophils, platelets, albumin, total bilirubin, direct bilirubin, indirect bilirubin, creatine kinase, procalcitonin, creatinine, and urea nitrogen. However, the levels of alanine aminotransferase (175.99 U/L vs 30.55 U/L) and aspartate transaminase (215.96 U/L vs 74.30 U/L) were significantly higher in patients with liver dysfunction compared to those without liver dysfunction. Further analysis showed that pediatric patients with liver dysfunction had a significantly lower percentage of natural killer (NK) cells (6.93% vs 8.71%) and higher mortality rate (22% vs 9%) than those without liver dysfunction. Conclusion: A decrease in serum NK cell levels in pediatric patients with severe adenovirus pneumonia could serve as a marker for monitoring the onset or progression of hepatic damage.

Background. Sepsis can lead to multiple organ damage, of which the heart is one of the most vulnerable organs. Vagal nerve stimulation can reduce myocardial injury in sepsis and improve survival rates. However, the potential impact of low-level tragus stimulation and disparate cell populations on sepsis-induced myocardial dysfunction remains undetermined. Methods. A cardiac single-cell transcriptomic approach was used for characterizing cardiac cell populations that form the heart. Single-cell mRNA sequencing data were used for selecting all cardiac macrophages from CD45+ cells. Then, echocardiography, western blot, flow cytometry, immunofluorescence, and immunohistochemistry were performed to verify the single-cell mRNA sequencing results. Results. Using single-cell mRNA sequencing data, we uncovered the multiple cell populations contributing to myocardial injury in sepsis under low-level tragus stimulation, thereby illustrating a comprehensive map of the cardiac cellular landscape. Pseudotiming analysis in single-cell sequencing showed that low-level vagal nerve stimulation played an anti-inflammatory role by promoting cardiac monocytes into M2 macrophages, which significantly increased α7nAChR expression in heart tissues. Echocardiography assessment indicated that low-level vagal nerve stimulation could also improve cardiac functions in mice with sepsis-induced myocardial dysfunction. In addition, the heart tissues of mice from the sepsis group with low-level tragus stimulation had significantly lower interleukin-1β expression levels than those from the sepsis group. Flow cytometry analysis showed that different acetylcholine concentrations promoted cardiac monocytes into M2 macrophages in in vitro experiments. Conclusion. Low-level tragus stimulation could improve sepsis-induced myocardial dysfunction by promoting cardiac monocytes to M2 macrophages.

Objective: To identify the platelet-related biomarkers in Proliferative diabetic retinopathy (PDR). Methods: Two mRNA expression profiles of PDR (GSE102485 and GSE60436) were downloaded from the Gene Expression Omnibus (GEO) database with the platelet-related genes from gene set enrichment analysis (GSEA) database. A protein-protein interaction (PPI) network was established to screen out hub genes based on the interaction between differentially expressed platelet-related genes (DEPRGs), followed by the prediction of the associated microRNAs (miRNAs), transcription factors (TFs) and drugs, which were taken to establish the regulatory networks of miRNA-hub gene, TF-hub gene and drug-hub gene. To verify the expression of Hub genes, both retinal samples from experimental diabetes mouse models and human retina microvascular endothelial cells (HRMECs) treated with high glucose (HG) were subjected to quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: A total of 168 DEPRGs were determined, with 146 genes for upregulation and 22 for downregulation. 9 hub genes (CDC42, GNAI2, LCK, LCP2, LYN, PLCG2, PTPN6, RAC1 and SYK) were eventually screened. 446 miRNAs, 46 TFs and 138 hub gene targeted by drugs were presented after prediction. RAC1 and GNAI2 respectively targeted by 156 miRNAs and 19 TFs lied the most connected hub genes in the miRNA-hub gene and TF-hub gene regulatory networks. Based on the drug-hub gene regulatory network, LCK was targeted by 52 drugs. qRT-PCR results indicated that the expression of LPC2 and PTPN6 was upregulated in both diabetes mouse models and HRMECs treated with HG. Conclusions: Nine hub genes were screened with the prediction of miRNAs, which were targeted by TFs and drugs, and may play an essential role in the progression of PDR, utilized as potential biomarkers and therapeutic targets.

PURPOSE Chemoresistance remains the primary obstacle threatening the prognosis of retinoblastoma (RB). microRNAs (miRNAs) are acknowledged as critical regulators of drug resistance. This study explored the molecular mechanism of miR-130a-3p affecting the chemosensitivity of RB to vincristine (VCR). METHODS miR-130a-3p expression of human retinal astrocytes and RB cell lines (Y79, WERI-Rb-1, SO-Rb50, and SO-Rb70) was detected using RT-qPCR. VCR-resistant RB cell line Y79/VCR was induced. miR-130a-3p expression of Y79/VCR cell line and its corresponding parental cell line was detected. Y79/VCR cells were subjected to miR-130a-3p overexpression treatment. The cell proliferation was measured using MTT assay, and the IC50 value and drug resistance index were examined using CCK-8 assay. The targeting relationship between miR-130a-3p and PAX6 was predicted through bioinformatics analysis and verified using dual-luciferase assay. Functional rescue experiments were conducted to confirm the role of PAX6 in chemosensitivity of RB cells. The effect of miR-130a-3p on tumorigenesis and VCR sensitivity was observed in vivo. RESULTS miR-130a-3p was downregulated in VCR-resistant RB cells. Overexpression of miR-130a-3p repressed the proliferation of Y79/VCR cells and enhanced chemosensitivity. miR-130a-3p targeted PAX6 expression. Overexpression of PAX6 reversed the effect of miR-130a-3p on chemosensitivity of Y79/VCR cells. Overexpression of miR-130a-3p suppressed tumor growth and reduced VCR resistance in vivo. CONCLUSIONS miR-130a-3p enhanced the chemosensitivity of Y79 RB cells to VCR by targeting PAX6 expression.

Mutations in CSNK2B lead to Poirier-Bienvenu neurodevelopmental syndrome (POBINDS), a rare neurodevelopmental disorder. Only 14 cases of POBINDS have been reported worldwide. The main manifestations are seizures, often tonic–clonic, with or without intellectual disability, growth retardation, and developmental language retardation. We conducted a comprehensive phenotypic mining and trio-whole exome sequencing on six children with POBINDS for gene diagnosis and analyzed the different variants using bioinformatics analysis software and related experiments. This paper reviews previous literature and discusses two common missense variants that lead to structural changes. Among the six patients, four, one, and one had tonic–clonic, myoclonic, and febrile seizures, respectively. Language development disorder, motor development disorder, and developmental delay/intellectual disability (DD/ID) are the main clinical features. All children had de novo mutations in CSNK2B, including three missense variants (c.410G > T/p.(Cys137Phe), c.494A > G/p.(His165Arg), and c.3G > A/p.(Met1Ile)), two splice variants (c.292-2A > T, c.558-3 T > G), and one frameshift variant (c.499delC/p.(Leu167Serfs*60)). Three missense variants were predicted to be harmful by various software programs, and two splicing variants were found to produce new exonic splicing enhancers by the minigene assay. Western blot analysis showed that the frameshift variant resulted in decreased protein expression. According to a literature review, c.3G > A/p.(Met1Ile), c.292-2A > T, c.558-3 T > G, and c.499delC/p.(Leu167Serfs*60) are novel variants of CSNK2B. The decrease or loss of protein function caused by CSNK2B mutations may be a pathogenic factor in this cohort. The severity of the POBINDS phenotype differs, and refractory epilepsy may be accompanied by a more serious DD/ID, language disorder, and motor retardation. At present, there is no specific treatment, and antiepileptic therapy usually requires the combination of two or more anti-epileptic drugs.

Background The coronavirus disease 2019 (COVID-19) pandemic brought remarkable disruption to the ways in which healthcare was delivered. This study aimed to examine changes in pediatric healthcare utilization in Hunan Province, China, during the COVID-19 pandemic. Methods An electronic survey was conducted among 142 hospitals in Hunan Province, China. Using data from January 1 to April 30, 2019 as a reference, the changes in the number of visits for different types of pediatric healthcare between January 1 and April 30, 2020 were calculated. Changes in the number of admissions for infections and injuries were also evaluated. Results The total number of pediatric healthcare presentations decreased by 53.3% in the first four months of 2020. The most remarkable reductions were observed in the utilization of emergency room (ranging from -45.7% to -94.9% among three hospital levels) and observation room (-55.8% to -77.7%); neonatal inpatient care experienced the smallest decreases (-21.2% to -25.5%). Approximately 85% of the total reduction in the number of pediatric inpatient admissions was attributable to the reduction in admissions for infections. A 13.3% increase in the number of admissions for injuries was observed among third-level hospitals. Conclusions The utilization of all types of pediatric healthcare services in Hunan Province declined markedly after the outbreak of COVID-19. The reasons, consequences, and responses to these changes should be addressed in future studies and actions.

OBJECTIVES Pancreatic injury is multifactorial and potentially devastating for critically ill children. We aimed to evaluate whether serum amylase and lipase among critically ill children could serve as an independent biomarker to predict pancreatic injury. DESIGN Retrospective cohort. SETTING PICU of a tertiary, pediatric medical center. PATIENTS Seventy-nine autopsies. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A group of 79 children who died of different causes were investigated by autopsy. They were divided into pancreatic injury group and pancreatic noninjury group according to autopsy findings. Data based on patients' demographics, vital signs, laboratory findings, and clinical features at admission were collected and compared. Logistic regression was used to identify predictive factors for pancreatic injury. Receiver operating characteristic curve was constructed for assessing serum amylase and serum lipase to predicting pancreatic injury. Forty-one patients (51.9%) exhibited the pathologic changes of pancreatic injury. The levels of lactate, erythrocyte sedimentation rate, alanine transaminase, aspartate transaminase, and troponin-I in the injury group were significantly higher than that in the noninjury group, whereas the level of calcium was significantly lower than that in the noninjury group (p < 0.05). Multivariable logistic regression analysis showed that serum amylase, serum lipase, and septic shock were significantly associated with the occurrence rate of pancreatic injury. The statistically significant area under the curve results were as follows: serum amylase: area under the curve = 0.731, at a cutoff value of 97.5, sensitivity = 53.7, and specificity = 81.6; and serum lipase: area under the curve = 0.727, at a cutoff value of 61.1, sensitivity = 36.6, and specificity = 92.1. CONCLUSIONS Serum amylase and lipase could serve as independent biomarkers to predict pancreatic injury in critically ill children.

Patients with hemophagocytic lymphohistiocytosis (HLH) have high risk of early mortality. The purpose of this study was to test the hypothesis that the elevated level of serum myoglobin among patients with HLH is associated with disease severity and increased risk of mortality. We retrospectively investigated the serum myoglobin levels from 155 pediatric patients diagnosed with HLH in the Hunan Children's Hospital, China. The levels of myoglobin and creatine kinase at hospital admission among non-survivors and survivors were compared. The myoglobin level was dichotomized for the estimation of hazard ratio (HR) for mortality. Patients who died within 7 and 30 days of hospitalization had significantly higher myoglobin levels than did survivors (p 0.05). The myoglobin level was negatively associated with the days of survival among non-survivors (Spearman correlation coefficient = - 0.29, p = 0.04). An elevated myoglobin level ( 90 ng/mL) was significantly associated with increased mortality (unadjusted HR = 2.66, 95%CI: 1.41, 5.00, p = 0.0024) and persisted after adjusting for age, Epstein-Barr virus infection, admission department, acute kidney injury, myocardial damage, and shock. In conclusion, an elevated serum myoglobin level was associated with increased risk of early death among pediatric patients with HLH, suggesting the potential of myoglobin to be used as a reference indicator for monitoring and managing of HLH.

Purpose Our aim was to investigate the age-associated plasma protein profiles in pneumonia-derived sepsis between infants and toddlers and identify potential age-adapted prognostic markers for poor outcome of pneumonia-derived pediatric sepsis. Experimental design A nested case-control study strategy was applied. The plasma proteomes of pneumonia-derived pediatric septic patients with different outcomes between infants and toddlers were respectivly analysed compared to their age-matched controls. Results Compared to toddlers, pneumonia-derived sepsis in infants was characterized by increased upregulation of protein processing in the ER, proteasome and antigen processing and presentation; and reduced downregulation in complement and coagulation cascades and cholesterol metabolism. Among them, the pentose phosphate pathway as well as the complement and coagulation cascades were possibly associated with poor outcome of pneumonia-derived sepsis. Furthermore, we confirmed that HP, THBS1, and SAA1/2 were potential prognostic markers for poor outcome of pneumonia-derived sepsis in infant patient groups. Conclusions and clinical relevance Age-associated plasma protein profiles of pneumonia-derived pediatric septic patients provided potential age-adapted biomarkers for a more precise prognosis of poor outcome in pneumonia-derived pediatric sepsis and helped to improve the survival of septic children. This article is protected by copyright. All rights reserved.

Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder. How to stratify high risk patients is one of the current challenges for the treatment of HLH. HLH patients usually fulfill multiple but not all eight diagnostic criteria. Different combinations of the fulfilled criteria may naturally cluster into previously undescribed subsets or phenotypes that may have different pathophysiology and demonstrate different risks for a poor outcome. The objectives of this study were to identify HLH subgroups according to the fulfillment of diagnostic criteria and evaluate the risk of multiple organ dysfunction syndrome (MODS) and 30-day mortality for subgroups. We retrospectively collect medical records of patients with discharge diagnosis of HLH between June 2015 and October 2018 from a tertiary children’s hospital in China. Latent class analysis was used to identify class defining variables from HLH diagnostic items, and subgroups were defined according to different combinations of the class defining variables. Results Triglyceride and fibrinogen were identified as the class defining variables. When evaluated in combinations, patients with hypertriglyceridemia and normal fibrinogen levels during hospitalization had the lowest risks for MODS (27.8%, OR = 1) and 30-day mortality (18.8%, OR = 1), and patients with normal triglyceride and hypofibrinogenemia had the highest risks for MODS (86.2%, OR = 16.24, P = 0.0002) and 30-day mortality (57.1%, OR = 5.78, P = 0.0187). The fulfillment status of hypertriglyceridemia and hypofibrinogenemia within 72 h of hospital admission was also associated with the risk of adverse outcomes. Conclusions The fulfillment status of hypertriglyceridemia and hypofibrinogenemia were associated with the risks of MODS and 30-day mortality among pediatric HLH patients. Further studies are needed to validate this association and investigate its clinical utility in the severity evaluation for HLH.

Purpose Chemoresistance remains the primary obstacle threatening the prognosis of retinoblastoma (RB). microRNAs (miRNAs) are acknowledged as critical regulator of drug resistance. This study explored the molecular mechanism of miR-130a-3p affecting the chemosensitivity of RB to vincristine (VCR). Methods miR-130a-3p expression of VCR-sensitive and VCR-resistant RB tissues was detected using RT-qPCR. VCR-resistant RB cell line Y79/VCR was induced. miR-130a-3p expression of Y79/VCR cell line and its corresponding parental cell line was detected. Y79/VCR cells were subjected to miR-130a-3p overexpression treatment. The cell proliferation was measured using MTT assay, and the IC50 value and drug resistance index were examined using CCK-8 assay. The targeting relationship between miR-130a-3p and PAX6 was predicted through bioinformatics analysis and verified using dual-luciferase assay. Functional rescue experiments were conducted to confirm the role of PAX6 in chemosensitivity of RB cells. The effect of miR-130a-3p on tumorigenesis and VCR sensitivity was observed in vivo. Results miR-130a-3p was downregulated in VCR-resistant RB tissues and cells. Overexpression of miR-130a-3p repressed the proliferation of VCR-resistant RB cells and enhanced chemosensitivity. miR-130a-3p targeted PAX6 expression. Overexpression of PAX6 reversed the effect of miR-130a-3p on chemosensitivity of RB. Overexpression of miR-130a-3p suppressed tumor growth and reduced VCR resistance in vivo. Conclusion miR-130a-3p enhanced the chemosensitivity of RB cells to VCR by targeting PAX6 expression.

Phenotypes of some rare genetic diseases are atypical and it is a challenge for pediatric intensive care units (PICUs) to diagnose and manage such patients in an emergency. In this study, we investigated 58 PICU patients (39 deceased and 19 surviving) in critical ill status or died shortly without a clear etiology. Whole exome sequencing was performed of 103 DNA samples from their families. Disease-causing single-nucleotide variants (SNVs) and copy number variants (CNVs) were identified to do genotype-phenotypes analysis. In total, 27 (46.6%) patients received a genetic diagnosis. We identified 34 pathogenic or likely pathogenic SNVs from 26 genes, which are related to at least 19 rare diseases. Each rare disease involved an isolated patient except two patients caused by the same gene ACAT1. The genotypic spectrum was expanded by 23 novel SNVs from gene MARS1, PRRT2, TBCK, TOR1A, ECE1, ARX, ZEB2, ACAT1, CPS1, VWF, NBAS, COG4, and INVS. We also identified two novel pathogenic CNVs. Phenotypes associated with respiratory, multiple congenital anomalies, neuromuscular, or metabolic disorders were the most common. Twenty patients (74.1%) accompanied severe infection, 19 patients (70.1%) died. In summary, our findings expanded the genotypes and phenotypes of 19 rare diseases from PICU with complex characteristics.

The difficulties and challenges of applying the HLH-2004 diagnostic criteria to early identification and diagnosis of haemophagocytic lymphohistiocytosis have been fully addressed in previous studies. However, the distribution of the diagnostic time lag of haemophagocytic lymphohistiocytosis and related patient characteristics remain unclear. This study investigated the time lags between symptom onset and diagnosis and between hospital admission and diagnosis among pediatric patients with haemophagocytic lymphohistiocytosis, and identified factors that associated with a shorter or longer diagnostic time lag. The cohort of patients with haemophagocytic lymphohistiocytosis was drawn from a tertiary children's hospital and consisted of 122 pediatric patients. The distributions of symptom-to-diagnosis and admission-to-diagnosis time lags were assessed. Clinical characteristics within 48 h of admission and the fulfillment of HLH-2004 diagnostic criteria were compared among admission-to-diagnosis time lag categories. Logistic regression analyses were conducted to identify factors associated with an admission-to-diagnosis time lag >3 days. The median interval from first symptom onset to HLH diagnosis was 12 days (range 4–71 days) and the median interval from hospital admission to HLH diagnosis was 2 days (range 0–23 days). The following factors were negatively associated with admission-to-diagnosis > 3 days: Epstein–Barr virus infection; admission through pediatric intensive care unit; diagnosis established without NK-cell activity and soluble CD25 tests; the performance of all readily available diagnostic tests for HLH (within 48 and 72 h); concurrent fever, splenomegaly, and cytopenias within 48 h; hemophagocytosis, hypertriglyceridemia and/or hypofibrinogenemia within 48 h; and elevated ferritin, total bilirubin, alanine aminotransferase, and prothrombin time within 48 h. Our findings suggest that performance of adequate diagnostic tests for HLH is essential for early diagnosis of HLH. Once suspected, immediate and adequate diagnostic tests for HLH should be arranged for PICU patients. Improvements in diagnostic procedures and monitoring plans are needed to promote early diagnosis of HLH.

Background: Extracorporeal membrane oxygen (ECMO) has used for rescuing severe pediatric acute respiratory distress syndrome (PARDS) for half a century. Prone position ventilation (PPV) has been suggested according to the surviving sepsis campaign (SSC) guideline in children in 2020. We aimed to compare the outcomes and effect of PARDS patients with ECMO+PPV and ECMO only.Design: Retrospective Multicenter pair-matched StudySetting: In the present study, propensity score matching was conducted and the outcomes of severe PARDS patients were analyzed. The effect of PPV was compared as well. The efficiency of PPV included PaO2, Oxygen Index (OI), PaO2/FiO2, compliance of respiratory system and resistance of airway. The primary outcome was hospital mortality. Secondary outcomes included ECMO running time, PICU time, hospital days and mechanical ventilation time of survivors. Patients: 137 PARDS patients with criteria of ECMO from 11 hospitals in 5 years.Interventions: No interventions.Measurements and Main Results: Among 137 patients, 93 patients received ECMO+PPV at the same time and 44 patients didn’t. After matching, we got 34 pairs. For the survivors receiving ECMO+PPV, the PaO2, OI and PaO2/FiO2 increased significantly during the PPV period (PConclusions: By far, there has been no ECMO+PPV efficiency study in PARDS patients. This study found that PPV was associated with improved oxygen state during ECMO. However, PPV was not associated with survival rate with PARDS patients on ECMO. Clinical Trial Registration: This study was registered at http://www.chictr.org.cn/index.aspx (chiCTR.gov; Identifier: ChiCTR1800019555). Registered 18 November 2018. Name of the registry: Extracorporeal membrane oxygenation in critical ill children with severe acute respiratory distress syndrome - A multicenter study.Take Home Message:1. Our study investigated prone position ventilation (PPV) could improve the oxygen state during ECMO for patients with severe PARDS.2. The results indicated PPV had no influence on the mortality of PARDS with ECMO.

Recent studies have reported that the imbalance of T helper 1 cell (Th1), Th17 and regulatory T cell (Treg) have been confirmed to play a vital role in the development of sepsis and other inflammatory diseases. Baicalin (BA) has anti-inflammatory properties and improves survival in sepsis. We investigated whether baicalin could regulate Th1, Th17 and Treg responses to ameliorate sepsis-associated pancreatic injury through the ras homolog family member A (RhoA)-Rho kinase (ROCK) pathway. The sepsis model was established by using the cecal ligation and puncture (CLP) method. Fifty mice were randomly divided into five groups (n = 10): sham group, model group, low-dose group (BA-L, 100 mg/kg of baicalin), medium-dose group (BA-M, 200 mg/kg of baicalin) and highdose group (BA-H, 300 mg/kg of baicalin). The effects of baicalin on the pancreatic injury, on changes of Th1, Th17 and Treg cells in vivo and in vitro, on RhoA, ROCK1 and signal transducer and activator of transcription (STAT) signaling pathways, and on levels of interferon-γ (IFN-γ), interleukin-17 (IL-17) and IL-10 were examined. Treatment of the CLP mice with baicalin significantly reduced the extent, scope and severity of the pathological changes of sepsis-associated pancreatic injury. Baicalin evidently reduced Th1 and Th17 cells and increased Treg cells in peripheral blood, spleen, pancreatic tissue and significantly inhibited T-box protein expressed in T cells (T-bet), retinoic acid receptor-related orphan receptor γt (RORγt) and increased forkhead/winged helix transcription factor (Foxp3) expressions in the pancreatic tissue. Baicalin reduced the expressions of RhoA, ROCK1, phosphorylated STAT4 (p-STAT4), p-STAT3 and increased the expression of p-STAT5 in peripheral blood, spleen and pancreatic tissue. Baicalin reduced the expressions of IFN-γ and IL-17 and increased the IL-10 in serum and pancreatic tissue. Baicalin is capable of ameliorating sepsis-associated pancreatic injury and regulating Th1, Th17 and Treg responses in sepsis. The present study provided a potential adjunctive therapy for treating pancreatic injury in sepsis, and further study is needed to reveal its deeper mechanisms.

Hand, foot, and mouth disease (HFMD) is endemic in the Pacific region, especially in mainland China. The case-fatality ratio of HFMD is increasing steadily. Knowledge of the changing epidemiology of HFMD in different regions is necessary for implementing appropriate intervention strategies. In this study, we describe the clinical and epidemiological characteristics of HFMD in Hunan Children’s Hospital between 2013 and 2017. A total of 7203 patients with HFMD were admitted, with complication and mortality rates of 35.62% and 0.78%, respectively. The total number of children with HFMD, proportion of severely ill children, and HFMD mortality rate were the highest in 2014. The number of cases caused by EV-A71 and CV-A16 decreased continuously, while the number of cases caused by ‘other enteroviruses’ increased yearly since 2014, suggesting that other enteric viruses will gradually replace EV-A71 and CV-A16 as the main pathogenic HFMD agents. Furthermore, EV-A71 and mixed infections accounted for the high case fatality rates in children with severe HFMD, among whom EV-A71 infection resulted in the highest complication and mortality rates; the mild form of the disease was dominated by ‘other enteroviruses’. In conclusion, the changing etiological pattern highlights the need to improve pathogen surveillance and vaccine strategies for HFMD control.

Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder characterized by a defect in the liver-specific peroxisomal enzyme alanine-glyoxylate and serine-pyruvate aminotransferase (AGT). This disorder results in hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. Three forms of PH1 have been reported. Data on the infantile form of PH1 are currently limited in literature. Despite the fact that China is the most populated country in the world, only a few AGXT mutations have been reported in several Chinese PH1 patients. In the present study, we investigated a Chinese family in which two siblings are affected by the infantile form of PH1. Sanger sequencing was carried out on the proband, but the results were misleading. Two novel missense mutations (c.517T > C/p.Cys173Arg and c.667A > C/p.Ser223Arg) of the AGXT gene were successfully detected through whole-exome sequencing. These two mutations occurred in the highly conserved residues of the AGT. Four software programs predicted both mutations as the cause of the disease. A postmortem examination was performed and revealed the occurrence of global nephrocalcinosis on both kidneys. The crystals were collected and analyzed as calcium oxalate monohydrate. This study extends the knowledge on the clinical phenotype–genotype correlation of the AGXT mutation. That is, (i) two novel missense mutations were identified for the infantile form of PH1 and (ii) the same AGXT genotype caused the same infantile form of PH1 within the family.

Outbreaks of hand, foot and mouth disease (HFMD) have increased recently, as has the case fatality rate in severe cases. No scoring system currently exists to predict mortality risk for severe HFMD in previous study. We retrospectively collected laboratory parameters for 546 patients with severe HFMD (a derivation and a validation cohort) at Hunan Children’s Hospitals between January 2012 and December 2014. We developed a mortality risk score comprising four laboratory parameters: blood glucose (GLU), white blood cells (WBC), lactate (LAC), and N-terminal-probrain natriuretic peptide (NT-proBNP). Using an “optimal” cutoff score of 4, the sensitivity, specificity, positive predictive value and negative predictive value was 88.00%, 96.14%, 62.86% and 99.08%, respectively, in the derivation cohort. Among severe HFMD patients with low- and high-risk scores in the validation cohort, case fatality rates were 1.49% and 74.07%, respectively. According to the “optimal” cut-off in the derivation cohort, the sensitivity, specificity, positive predictive value, and negative predictive value were 80.95%, 93.83%, 62.96% and 97.44%, respectively, in the derivation cohort. The mortality risk score demonstrated good discrimination (AUC > 0.9) and calibration (P > 0.05) in both cohorts. The mortality risk score, comprising WBC, GLU, LAC and NT-proBNP, has been demonstrated good discrimination and calibration in the both cohorts.

Pediatric sepsis is a burdensome public health problem. Assessing the mortality risk of pediatric sepsis patients, offering effective treatment guidance, and improving prognosis to reduce mortality rates, are crucial. We extracted data derived from electronic medical records of pediatric sepsis patients that were collected during the first 24 hours after admission to the pediatric intensive care unit (PICU) of the Hunan Children's hospital from January 2012 to June 2014. A total of 788 children were randomly divided into a training (592, 75%) and validation group (196, 25%). The risk factors for mortality among these patients were identified by conducting multivariate logistic regression in the training group. Based on the established logistic regression equation, the logit probabilities for all patients (in both groups) were calculated to verify the model's internal and external validities. According to the training group, 6 variables (brain natriuretic peptide, albumin, total bilirubin, D-dimer, lactate levels, and mechanical ventilation in 24 hours) were included in the final logistic regression model. The areas under the curves of the model were 0.854 (0.826, 0.881) and 0.844 (0.816, 0.873) in the training and validation groups, respectively. The Mortality Risk Model for Pediatric Sepsis we established in this study showed acceptable accuracy to predict the mortality risk in pediatric sepsis patients.

To assess the performance of pediatric risk of mortality (PRISM), pediatric index of mortality 2 (PIM2) in predicting mortality in critically ill pediatric patients via a prospective study.The outcome and the variables required to calculate PRISM and PIM2 were collected. The efficiency of PRISM and PIM2 in differentiation between death and survival by calculating the area under the receiver operating characteristic curve (ROC). Calibration across deciles of risk was evaluated using the Hosmer-Lemeshow goodness-of-fit χ(2) test.A total of 412 critically ill pediatric patients transferred to Hunan Children's Hospital during August 1, 2012 and May 31, 2013 were enrolled in the study, and more than two-thirds of the children were suffering from respiratory and miscellaneous diseases; 45 (10.9%) inter-hospital transport of critically ill pediatric patients died at the time of hospitalization. The expected number of deaths were 45.01 by PRISM, and the expected number of deaths were 44.99 by PIM2. The expected mortality rate was 10.9% for PRISM or PIM2. The standardized mortality rate was 1.000 (0.710-1.290) for PRISM and 1.000 (0.710-1.290) for PIM2. The Hosmer-Lemeshow test gave a chi-square of 8.75 (P=0.364) for PRISM and 22.75 (P0.05) for PIM2, PRISM had better fitting with the actual mortality than PIM2. The area under the receiver-operating characteristics (ROC) curve (95% confidence intervals, CI) were 0.829 (0.768-0.890) for PRISM and 0.758 (0.667-0.849) for PIM2.Although the PIM2 test is less well calibrated overall, both PRISM and PIM2 can offer a good capacity for discriminating between survivors and moribund patients. The good performance of PRISM and PIM2 are demonstrated in predicting mortality probability in critically ill pediatric patients.

This study was designed with the aim of comparing the performances of the pediatric risk of mortality (PRISM), pediatric index of mortality (PIM), and revised version pediatric index of mortality 2 (PIM2) models in a pediatric intensive care unit (PICU) in China.A total of 852 critically ill

Although beta cell dysfunction has been proved to predict prognosis among humans and animals, its prediction on severity of disease remains unclear among children. The present study was aimed to examine the relationship between beta cell dysfunction and severity of disease among critically ill children. This prospective study included 1146 critically ill children, who were admitted to Pediatric Intensive Care Unit (PICU) of Hunan Children's Hospital from November 2011 to August 2013. Information on characteristics, laboratory tests, and prognostic outcomes was collected. Homeostasis model assessment (HOMA)-β, evaluating beta cell function, was used to divide all participants into 4 groups: HOMA-β = 100% (group I, n = 339), 80% ≤ HOMA-β < 100% (group II, n = 71), 40% ≤ HOMA-β < 80% (group III, n = 293), and HOMA-β < 40% (group IV, n = 443). Severity of disease was assessed using the worst Sequential Organ Failure Assessment (SOFA) score, Pediatric Risk of Mortality (PRISM) III score, incidence of organ damage, septic shock, multiple organ dysfunction syndrome (MODS), mechanical ventilation (MV) and mortality. Logistic regression analysis was used to evaluate the risk of developing poor outcomes among patients in different HOMA-β groups, with group I as the reference group. Among 1146 children, incidence of HOMA-β < 100% was 70.41%. C-peptide and insulin declined with the decrement of HOMA-β (P

To obtain the gene encoding retinal specific Rho promoter therefore to prepare for exogenous gene transcription and expression in retina.Extract the genomic DNA of a BLAB/c mice . The Rho promoter DNA were then amplified by PCR, the product of which was subcloned into PcDNA3.1 +vector. After identification by restriction enzymes, the recombinant PcDNA3.1+vectors were subjected to sequence analysis.The fragments of the promoter as amplified by PCR were of predicted length. Digestion with HindIII and NheI proved correct insertion of the target fragments with expected length into the recombinant PcDNA3.1+vectors. As indicated by homology analysis the Rho promoter was highly conservative, and the Rho promoter we got had hole homology as reported by Boulanger A etc.Retinal specific Rho promoter has been successfully cloned, thus making possible the subsequent research as the mechanism and gene therapy of retina.

To evaluate the nibble technology in the therapy of diabetic retinopathy.Eighty-three patients (ninety-two eyes) with proliferative diabetic retinopathy were treated in our department. All the patients received a standard pars plana vitrectomy. Fifty-two of them (fifty-eight eyes) were treated with nibble technology, while the other thirty-one (thirty-four eyes), who were treated with common procedure to tear the proliferative membrane, were served as a control group.The operative complication of iatrogenic retinal tears was observed in 2 eyes of the test group and 7 eyes of the control group (P0.05). Another operative complication of hemorrhage was observed in 4 eyes of the test group and 15 eyes of the control group (P0.01). There were 6 eyes of the test group and 5 eyes of the control group presented with grade-III postoperative responds (P0.01).The nibble technology is safe in the therapy of proliferative diabetic retinopathy and could reduce the complications during or after the operation.