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Background Pleuropulmonary blastomas (PPB) are rare aggressive paediatric lung malignancies and are among the most common DICER1-related disorders: it is estimated that 75–80% of children with a PPB have the DICER1 mutation. DICER1 mutations are responsible for familial tumour susceptibility syndrome with an increased risk of tumours. In approximately 35% of families with children manifesting PPB, further malignancies may be observed. Symptoms of DICER1 syndrome may vary, even within monozygotic twins. Preventive screening of carriers with DICER1 mutations is important and follow-up is undertaken as recommended by the 2016 International PPB Register. Case presentation We present two pairs of monozygotic twins. In one pair of 4-year, 2-month old girls, both with DICER1 mutation, one developed PPB(II) and her identical sibling had acute transient hepatitis. In the other pair of 19-month-old female babies, one had a history of bronchopulmonary hypoplasia and developed PPB(III) without DICER1 mutation, and her identical sibling had allergic asthma. Both patients with PPB were treated with R0 resection and received 12 cycles of postoperative chemotherapy. At the most recent review, the twins had been followed up for six and eight years, respectively, and they all remained healthy. However, the height and weight of the patients with PPB were lower than those of their respective identical sister. Conclusions PPB is rare, especially in monozygotic twins. We emphasise the importance of genetic testing and follow-up in monozygotic twins with PPB. During the follow-up, children surviving PPB should be monitored closely for growth and development disorders which caused by chemotherapy.

Background Tuberculous pleural effusion (TPE) is often misdiagnosed as severe Mycoplasma pneumoniae pneumonic effusion (SMPPE) in children at early stage. The aim of this study was to develop a predictive model based on clinical and laboratory indices to make accurate differential diagnosis. Methods Patients included in this study were 167 children (83 patients with TPE and 84 with SMPPE), containing 117 patients for predictive model development and 50 patients for external validation. Multivariate logistic regression analysis was conducted to select potentially useful characteristics for discrimination of TPEs. External validation was performed for model evaluation. Results Multivariate analysis revealed that blood neutrophils and serum lactate dehydrogenase were significant independent factors to discriminate between TPEs and SMPPEs. The results indicated that blood neutrophils ≤69.6% and concentration of serum lactate dehydrogenase ≤297 U/L were the extremely important discrimination factors of TPEs. The area under the receiver operating characteristic curve of the model was 0.9839. The accuracy rate, sensitivity and specificity of the model were 94.02%, 98.28% and 89.83%, respectively. Meanwhile, the accuracy rate of the external validation from the 50 patients was 94.0%. Conclusions Applying a predictive model with clinical and laboratory indices can facilitate the differential diagnosis of TPE from SMPPE in children, which seems helpful when a microbiologic or histologic diagnosis of pleural tuberculosis could not be established.

Background Immune tolerance induction (ITI) therapy is currently unaffordable in China. Management of hemophilia A children with high‐titer inhibitor is therefore a challenge. Aim To describe the ITI strategy using plasma‐derived factor VIII/von Willebrand factor concentrate (pdFVIII/VWF) +/− immunosuppression and to report its efficacy in children with hemophilia A having poor‐risk status for ITI success. Methods A prospective pilot study on children with hemophilia A having poor‐risk status (all with at least inhibitor titer > 10 BU pre‐ITI initiation). Patients received ~50 IU/kg FVIII every other day using domestic intermediate purity pdFVIII/VWF products, either alone or in combination with rituximab +/− prednisone. Results Sixteen patients with median age 2.9 (range, 2.2‐13.2) years and median pre‐ITI inhibitor titer 30.7 (range, 10.4‐128) BU were enrolled. Analysis at median 14.7 (range, 12.4‐22.6) months’ follow‐up showed a total response rate of 87.5%. This included success (achieving inhibitor 0.6BU) in 1 (6.3%). Compared to the pre‐ITI period, the mean bleeds/month during ITI was 0.51 (64.0% reduction), and joint bleeds/month was 0.34 (64.3% reduction). This low‐dose ITI strategy cost less by 70% to 87% than that for the high‐dose FVIII regimen. No severe adverse events were observed. Conclusion This low‐dose ITI strategy of pdFVIII/VWF +/− immunosuppression achieved relatively satisfactory outcomes in children with hemophilia A inhibitor having poor‐risk status. This low‐dose regimen showed economic advantages and is therefore suitable for using in China. However, further study in a larger cohort with a longer follow‐up time is needed.

Salivary virome is important for oral ecosystem, but there are few reports on people living with HIV. We performed metagenomic sequencing to compare composition and functional genes of salivary virobiota between one HIV-negative and four HIV-positive groups in which participants were all men who have sex with men (MSM) with different immunosuppression statuses (five samples per group) to find the evidence that salivary virobiota plays a role in the pathogenesis of oral disease. Acute-stage subjects achieved a positive result of HIV RNA, but HIV antibody negative or indeterminate, whereas individuals with mild, moderate, and severe immunosuppression exhibited CD4+ T-lymphocyte counts of at least 500, 200–499, and less than 200 cells/μL or opportunistic infection, respectively. The results showed the composition of salivary virus genera in subjects with mild immunosuppression was the most similar to that in healthy people, followed by that in the acute stage; under severe immunosuppression, virus genera were suppressed and more similar to that under moderate immunosuppression. Furthermore, abnormally high abundance of Lymphocryptovirus was particularly obvious in MSM with HIV infection. Analysis of KEGG Pathway revealed that Caulobacter cell cycle, which affects cell duplication, became shorter in HIV-positive subjects. It is worth noting that in acute-stage participants, protein digestion and absorption related to the anti-HIV-1 activity of secretory leukocyte protease inhibitor was increased. Moreover, in the severely immunosuppressed subjects, glutathione metabolism, which is associated with the activation of lymphocytes, was enhanced. Nevertheless, the ecological dysbiosis in HIV-positive salivary virobiota possibly depended on the changes in blood viral load, and salivary dysfunction of MSM infected with HIV may be related to CD4 counts. Ribonucleoside diphosphate reductase subunit M1 in purine metabolism was negatively correlated, though weakly, to CD4 counts, which may be related to the promotion of HIV-1 DNA synthesis in peripheral blood lymphocytes. 7-Cyano-7-deazaguanine synthase in folate biosynthesis was weakly positively correlated with HIV viral load, suggesting that this compound was produced excessively to correct oral dysfunction for maintaining normal cell development. Despite the limited number of samples, the present study provided insight into the potential role of salivary virome in the oral function of HIV infected MSM.

Accurate assessments of potassium intake in children are important for the early prevention of CVD. Currently, there is no simple approach for accurate estimation of potassium intake in children. We aim to evaluate the accuracy of 24-h urinary potassium excretion (24UKV) estimation in children using three common equations: the Kawasaki, Tanaka and Mage formulas, in a hospital-based setting. A total of 151 participants aged 5–18 years were initially enrolled, and spot urine samples were collected in the whole 24-h duration to measure the concentrations of potassium and creatinine. We calculated the mean difference, absolute and relative difference and misclassification rate between measured 24UKV and the predicted ones using Kawasaki, Tanaka and Mage formulas in 129 participants. The mean measured 24UKV was 1193·3 mg/d in our study. Mean differences between estimated and measured 24UKV were 1215·6, −14·9 and 230·3 mg/d by the Kawasaki, Tanaka and Mage formulas, respectively. All estimated 24UKV were significantly different from the measured values in all the time point (all P < 0·05), except for the predicted values from Tanaka formula using morning, afternoon and evening spot urine. The proportions with relative differences over 40 % were 87·2%, 32·5% and 47·3 % for Kawasaki, Tanaka and Mage formulas, respectively. Misclassification rates were 91·5 % for Kawasaki, 44·4 % for Tanaka and 58·9 % for Mage formula at the individual level. Our findings showed that misclassification could occur on the individual level when using Kawasaki, Tanaka and Mage formulas to estimate 24UKV from spot urine in the child population.

Background:No previous study explored the association between serum calcium levels and dyslipidemia in children. This study aimed to explore this relationship in children, based on a multicenter cross-sectional study population in China.Methods:Cross-sectional data was derived from the Pediatric Reference Intervals in China (PRINCE) study conducted between 2017 and 2018 involving 5,252 males and 5,427 females with a mean age of 10.0 ± 4.6 years. Multivariable logistic regression models were applied to calculate odds ratios (ORs), with 95% confidence intervals (CIs), for dyslipidemia of each serum calcium level and albumin-corrected calcium levels, which were sorted into quartiles. The restricted cubic spline model was fitted for the dose-response analysis. An L-shaped dose-response relation between calcium levels and the probability of dyslipidemia was found after the adjustment for multiple potential confounding factors,pfor non-linear < 0.001.Results:Using the middle category of calcium level as the reference, multivariable-adjusted ORs and 95% CIs of the lowest and the highest quartile categories were 0.96 (0.82–1.12) and 1.29 (1.12–1.48), respectively, for total serum calcium levels and 1.06 (0.91–1.23) and 1.39 (1.21–1.60) for albumin-corrected calcium levels.Conclusions:Individuals with higher levels of serum calcium were associated with increased risk of dyslipidemia in a sample of a healthy Chinese pediatric population. The association between serum calcium levels and dyslipidemia needs to be examined prospectively in future studies.

Background In developing countries, children with hemophilia A (HA) with high‐titer inhibitor and poor immune tolerance induction (ITI) prognostic risk(s) cannot afford the recommended high‐ or intermediate‐dose ITI. Objectives To determine the efficacy of low‐dose ITI (plasma‐derived factor VIII [FVIII]/von Willebrand factor at 50 FVIII IU/kg every other day) by itself (ITI‐alone) or combined with immunosuppressants rituximab and prednisone (ITI‐IS) in children with HA with high‐titer inhibitor. Methods All enrolled patients had pre‐ITI inhibitor ≥10 BU. We used ITI‐alone if inhibitor titer was

Inter-basin water transfer projects play an important role in allocating water resources that vary both in temporal and spatial scale while supporting regional development. In the practical operation of inter-basin water transfer projects, high water level and less inflow runoff would result in water supply destruction, while low water level and more inflow runoff would cause abandoned water. How to play the compensation roles of hydrological characteristics and storage capacities of multi-reservoirs to maximize the utilization efficiency of water resources, the key is to select the basis for the decision-making of starting water transfer process. In this paper, we selected the “Datong-Huangshui” water transfer project as the research subject, analyzed the composition of the inter-basin water transfer system, and constructed a dispatching rule extraction model including water transfer rules, water diversion rules, and water supply rules. Then the NSGA-II was used to solve the multi-objective optimization model to obtain the Pareto frontier solution set of the dispatching rules. Finally, the optimal operation scheme was determined and discussed according to the scheduling scheme decision model. The model itself was based on the gray target model and prospect theory. We found that: (1) The optimal target frontier obtained by the two-dimensional scheduling diagram and the hedging rules for water supply was closer to the theoretical optimal frontier of the multi-objective problem. This result indicated that the two-dimensional scheduling diagram and the hedging rules for water supply could better guide the water diversion operation of inter-basin water transfer projects. (2) Based on the multi-objective optimal operation schemes set, the OPT scheme obtained by the scheduling scheme decision model using gray target model and prospect theory could generate 359 million Kwh. At the same time, it could guarantee 90% of municipal and industrial water supply and 85% of agricultural water supply.

Background The delayed diagnosis of neuroblastoma (NB) is common in China, which results in the prognosis of NB in China lagging behind that in developed countries. Methods A referral flowchart for suspected NB was implemented in nononcology clinics at Beijing Children's Hospital (BCH). Patients with symptoms of suspected NB were referred from nononcology clinics in BCH to oncology clinics and confirmed NB cases were regarded as referral group. The control group comprised patients initially diagnosed with NB who came directly to oncology clinics in BCH from other regions nationwide. The age at NB diagnosis was compared as primary outcome, and the 5-year overall survival (OS) and event-free survival (EFS) were compared via the Kaplan-Meier method and log-rank tests. Results In total, 3337 children with suspected NB were screened consecutively from 687 070 pediatric patients. Through examination of urine vanillylmandelic acid and homovanillic acid, or B-ultrasound, 102 of 3337 patients were referred to oncologists for comprehensive evaluations. Eventually, 29 referred patients were diagnosed as NB and the hospital-based diagnosis rate of NB was 4.2 per 100 000 visits. The median age at diagnosis in the referral group was 21.0 months, which was 9 months earlier than that of the control group (30.0 months, P = .026). The 5-year OS rate was 72.4% in the referral group, which was higher than that of the control group (66.7%) but without statistical significance (P = .664). Conclusion Delayed NB detection could be avoided by training pediatricians in nononcology clinics to detect suspected NB and refer these patients to oncologists.

Although retinoblastoma (Rb) is considered to have a good prognosis, economical stress is still a huge problem for patients' families. Besides, doctors, the government, and social foundation staff do not precisely know how much is truly required for complete Rb therapy, especially the non-medical costs and indirect costs. This study was conducted to estimate the economic burden of Rb patients.This was a retrospective study. Fifty Rb patients were finally enrolled in the study. The questionnaire survey was conducted with surviving Rb patient' main family caregivers to collect the information on costs during illness through the phone. Costs included direct and indirect cost; direct costs included medical and non-medical costs. Medical costs include drug costs, surgery costs, treatment fees, lab tests, non-lab tests costs, and medical consumptive stuff costs (including hospital expenses and outpatient fees).The total direct cost was $27,814.62 ± 15,137.73, and the average medical cost was $15,034.48 ± 8,224.19 ($3,963.99-36,826.53). The total non-medical expenses averaged $12,252.93 ± 9,872.64 ($728.86-48,104.95). The average reduced working time was 11.50 ± 8.06 months, and the average lost income was $13,512.23 ± 11,545.83. Among the non-medical expenses, the average non-medical expenses for children in Beijing and surrounding areas was $6,557.68 ± 6,385.42, and the average non-medical expenses for children in other provinces and was $14,502.29 ± 10,484.86,Children with Rb have a heavy economic burden. Direct non-medical expenses are higher. Getting medical treatment nearby can help reduce the economic burden of the disease. Besides, work-related issues are also a major financial problem for families with Rb, and the government should properly provide economic subsidies. Simplifying the national health insurance process and purchasing commercial supplementary medical insurance will increase the family's ability to afford the cost of cancer treatment.

Background: To identify the risk factors and reasons for discharge against medical advice (DAMA) for newborns with neonatal surgical diseases in a tertiary care hospital in China. Methods: A retrospective study was conducted on all newborn patients admitted to the neonatal surgery department of Beijing Children's Hospital between January 1, 2016 and January 1, 2020. Medical records were compared between DAMA and non-DAMA patients. Univariate and multivariate logistic regression analyses were conducted to identify potentially useful characteristics for predicting DAMA. Results: During the study period, 854 newborns were admitted to the neonatal surgery department. A total of 68 DAMA patients (68/854, 7.96%, 47 boys), with a median age at diagnosis of 1 day (range, from birth to 21 days), were included in this study. After multivariate analysis, we found that emergency admission, age at admission ≤5 days, rejection for surgery, and admission to the neonatal intensive care unit were significant independent risk factors for DAMA. According to the electronic medical records, the reasons for DAMA included belief in incurability and concerns about the prognosis of the disease (n = 31), multiple malformations with poor prognosis (n = 8), severe postoperative complications (n = 5), financial difficulties (n = 3), refusal of further examinations (n = 2), assumption of clinical improvement (n = 1), and unknown (n = 18). Conclusions: This preliminary study showed that neonatal surgical patients in critical conditions were high-risk groups for DAMA, and the main possible reasons for DAMA were the parents' belief in incurability and concerns about the prognosis of the disease.

Summary We investigated changes in anastomotic stricture indexes (SIs) and stricture diameter (SD) between before and 6 months after the first dilatation in children with anastomotic stricture after esophageal atresia (EA) repair and identified predictors of medium-term dilatation success (success for at least 3 months). We retrospectively reviewed the records and measurement indexes of patients who underwent post-EA repair endoscopic balloon dilatation between November 2017 and August 2019 in our hospital. We identified diagnostic and performance indicators that predicted medium-term dilatation success by univariate and multivariate analyses and receiver operator characteristic (ROC) curve analysis. Sixty patients (34 boys and 26 girls) showed post-EA repair anastomotic stricture. Paired sample t-tests showed that SD (P

Neuroblastoma (NB) is notorious in childhood cancer because of its high incidence and poor prognosis. The Children's Oncology Group reported that the 3-year OS in the high-risk (HR) group is 50%, and the HR-NB with bone marrow metastasis in our center is 43.1%. Thousands of families in China suffer from the cost of NB, but the true costs of therapy are unknown; to date, no study has ever performed a detailed therapy costs analysis for NB. The objective of this study was to assess the economic burden of NB treatment in children to the family, to ultimately reduce related expenses for patients and promote the establishment of NB management policy.Data in this cross-sectional study were collected via questionnaires completed by parents at the outpatient clinic and was verified via a computer system. Therapy costs of children with NB of differing risks were analyzed through descriptive statistics (1 CNY ≈ 0.1412 USD).Median direct medical costs of low risk (LR), middle risk (MR), and HR NB during treatment were 180.0 (120.0, 300.0), 200.0 (166.0, 300.0), and 650.0 (415.5, 850.0) thousand Chinese yuan (CNY), respectively. Direct non-medical costs including transportation, food, and accommodation were 60.0 (37.0, 100.0), 80.0 (60.0, 120.0), and 100.0 (80.0, 157.5) thousand CNY in the LR, MR, and HR groups, respectively. Additionally, parents accrued work absences to attend treatment, and lost a total of 100.0 (50.0, 150.0) thousand CNY in indirect costs.Families whose children had relapsed or died were excluded from this analysis and therefore limited the conclusions drawn. Parents were asked to recall costs since initial diagnosis (1-6 years in the past), but this extended time period may have introduced recall bias.Direct non-medical and indirect costs play an important role in the total treatment costs of NB. Children with NB treated in local hospitals and followed up in hospital specialized in childhood oncology may save many unnecessary expenses. China's healthcare system should establish mechanisms and provide financial support for children with NB.

Background Neuroblastoma (NB) tumor rupture is a rare oncology emergency with a poor prognosis. We aimed to evaluate patient clinical characteristics and risk factors for ruptured NB. Methods A retrospective study of 47 patients with confirmed NB rupture between January 2009 and January 2019 at Beijing Children’s Hospital was conducted. To identify tumor rupture risk factors in high-risk NB patients, we included 93 consecutive non-ruptured high-risk NB patients from January 2017 to January 2019. Results The median age at presentation was 29 months (adrenal and retroperitoneum origin) for 47 ruptured NB patients. Spontaneous tumor rupture occurred in 22 cases; 18 cases occurred during or after the first chemotherapy cycle, and 7 occurred after core needle biopsy. Five patients died of tumor rupture, and 17 patients’ parents refused further antitumor therapy. Among the 25 remaining patients, 6 survived without disease, 5 received ongoing treatment and achieved stable disease, and 14 died. According to multivariate logistic regression analysis, a maximum primary tumor diameter > 13.20 cm and MYCN gene amplification were independent risk factors for tumor rupture within high-risk NB. Conclusions Tumor rupture is an uncommon, life-threatening event for NB patients; these patients are most likely to have poor outcomes due to tumor recurrence or rapid progression. Several treatment modalities, including symptomatic support therapy and chemotherapy, are important for saving lives and for developing NB risk-based treatment in the future.

Background: Spiritual support should be offered to all patients and their families regardless of their affiliated status with an organized religion. Aim: To understand nonreligious theistic parents’ spirituality and to explore how parents discuss death with their terminally ill children in mainland China. Design: Qualitative study. Setting/participants: This study was conducted in the hematology oncology center at Beijing Children’s Hospital. Participants in this study included 16 bereaved parents. Results: Participants described themselves as nonreligious but showed a tendency toward a particular religion. Parents sought religious support in the face of the life-threatening conditions that affected their child and regarded the religious belief as an important way to get psychological and spiritual comfort after experiencing the death of their child. Religious support could partially address parents’ spiritual needs. Parents’ spiritual needs still require other supports such as bereavement services, death education, and family support groups. Some parents stated that it was difficult to find a way to discuss death with their children. For patients who come from nonreligious theistic families, their understanding of death was more complex and may be related to atheism. Conclusion: Religious support could be an element of spiritual support for nonreligious theistic parents of terminally ill children. Multiple strategies including religious supports and nonreligious supports should be rationally integrated into spiritual support of nonreligious theistic family. Patient’s personal belief in death should be assessed before discussing death with them.

Rare diseases have a low morbidity, include a wide variety of diseases, and involve a large number of people. However, because of the small sample size, high heterogeneity, and difficulty in recruiting, the research of rare diseases is difficult to carry out. This dilemma results in the lack of effective treatments for many rare diseases and the lack of high-quality efficacy and safety evidence of limited treatments. Therefore, it is of great significance to explore the design methods of clinical trials of rare disease. Recently, the breakthrough in methodology and the generation of new design methods provide a new clue for the clinical trials of rare diseases. The purpose of this paper is to introduce the innovative methods suitable for the clinical trials of rare diseases. We introduce four design methods according to their characteristics for researchers’ reference.

Background This study aims to explore the diagnostic accuracy of the combination of gamma-glutamyl transferase (GGT) and liver stiffness measurement (LSM) for biliary atresia (BA) screening at different ages. Methods Our retrospective study involved 282 infants under the age of 120 days with jaundice who were admitted into Beijing Children’s Hospital between January 2016 to December 2018. The GGT and LSM levels of infants were obtained. A parallel test was used, and ROC curve was created to obtain cutoff values of GGT and LSM for BA infants at different ages. Results Of the 282 infants, 135 were diagnosed with BA and 147 were non-BA infants. In all age groups (A: ≤60 days; B: 61–90 days; C: 91–120 days), the LSM and GGT levels of the BA group were significantly higher than that of the non-BA group, P Conclusions Cutoff values of GGT and LSM to screen BA increased with age. Parallel testing of GGT and LSM in infants who are younger than 90 days old can decrease the rate of BA misdiagnosis.

Importance: Childhood solid tumors account for the highest proportion of childhood cancers and are one of the leading causes of death in childhood. However, their pathogenesis is unclear. Objective: To explore prenatal and perinatal risk factors for solid malignancies in children. Methods: We enrolled 71 consecutive pediatric patients (44 boys and 27 girls; median age, 30 months) with solid tumors who were diagnosed and treated at our center from January 2013 to December 2016 as the case group. We also enrolled 211 age- and residence-matched healthy children (ratio of approximately 3:1 with the case group) as the control group. We conducted a questionnaire-based survey with the parents of these 282 children. Univariate and multivariate conditional logistic regression analyses of the collected data were performed. Results: Confirmed solid malignancies included neuroblastoma (n = 32), rhabdomyosarcoma (n = 18), retinoblastoma (n = 7), renal tumors (n = 3), and other tumors (n = 11). Risk factors for solid childhood tumors in the univariate analysis were the parents’ age, gravidity, parity, abortion history, vaginal bleeding, family history of malignancy, and prenatal use of folic acid or hematinics/iron supplements (P < 0.05), and those in the multivariate analysis were higher parity (odds ratio [OR], 2.482; 95% confidence interval [CI], 1.521–4.048), family history of malignancy (OR, 3.667; 95% CI, 1.679–8.009), and prenatal use of hematinics/iron supplements (OR, 2.882; 95% CI, 1.440–5.767). In contrast, use of prenatal folic acid was protective (OR, 0.334; 95% CI, 0.160–0.694). Interpretation: A family history of malignancy, use of prenatal hematinics/iron supplements, and higher parity are risk factors for solid childhood tumors, whereas use of prenatal folic acid is a protective factor. Key words: Case-control study; Children; Maternal; Perinatal; Risk factors; Solid malignancies

Background Different confounder adjustment strategies were used to estimate odds ratios (ORs) in case-control study, i.e. how many confounders original studies adjusted and what the variables are. This secondary data analysis is aimed to detect whether there are potential biases caused by difference of confounding factor adjustment strategies in case-control study, and whether such bias would impact the summary effect size of meta-analysis. Methods We included all meta-analyses that focused on the association between breast cancer and passive smoking among non-smoking women, as well as each original case-control studies included in these meta-analyses. The relative deviations (RDs) of each original study were calculated to detect how magnitude the adjustment would impact the estimation of ORs, compared with crude ORs. At the same time, a scatter diagram was sketched to describe the distribution of adjusted ORs with different number of adjusted confounders. Results Substantial inconsistency existed in meta-analysis of case-control studies, which would influence the precision of the summary effect size. First, mixed unadjusted and adjusted ORs were used to combine individual OR in majority of meta-analysis. Second, original studies with different adjustment strategies of confounders were combined, i.e. the number of adjusted confounders and different factors being adjusted in each original study. Third, adjustment did not make the effect size of original studies trend to constringency, which suggested that model fitting might have failed to correct the systematic error caused by confounding. Conclusions The heterogeneity of confounder adjustment strategies in case-control studies may lead to further bias for summary effect size in meta-analyses, especially for weak or medium associations so that the direction of causal inference would be even reversed. Therefore, further methodological researches are needed, referring to the assessment of confounder adjustment strategies, as well as how to take this kind of bias into consideration when drawing conclusion based on summary estimation of meta-analyses. Electronic supplementary material The online version of this article (10.1186/s12874-017-0454-x) contains supplementary material, which is available to authorized users.

It has been reported that germline DICER1 mutations correlate with a distinctive human disease syndrome. Many published studies within this field have been conducted based on rare cases. We systematically searched bibliographic databases, including PubMed, Embase, and COSMIC for articles which are related to diseases covered by DICER1 syndrome. The weighted summary of mutation frequencies among patients with pleuropulmonary blastoma (PPB), cystic nephroma (CN), and Sertoli-Leydig cell tumor (SLCT) were calculated. Forty-nine eligible articles were included. In total, 72 cases with multimorbidity of DICER1 syndrome were identified. More females (n=46, 64%) presented with multimorbidity than males (n=18, 25%) and the remaining 8 patients' sex were unknown. Nineteen of 72 patients with multimorbidity suffered from another disease that was not yet included in DICER1 syndrome, which would provide potential phenotypes of DICER1 syndrome. The germline DICER1 mutation frequencies in PPB, CN, and SLCT were 66.9%, 73.2%, and 57.1%, respectively. The somatic DICER1 mutation frequencies of PPB, CN, and SLCT were 92.4%, 87.9%, and 43.3%, respectively. Majority of patients with multimorbidity of DICER1 syndrome were mutation positive individuals so that multimorbidity may suggest the possible germline mutation of these patients and their relatives.

The dynamic control bound of flood limited water level (FLWL) is a fundamental and key element for implementing reservoir FLWL dynamic control. Due to the uncertainty of the inflow and the dimensional increase of the reservoirs, the calculation of the dynamic control bound of FLWL becomes more and more complicated. A new model that considers capacity compensation regulation and the uncertainty of flood spatial pattern (FSP) for a serial multipurpose reservoir system is developed to calculate the dynamic control bound of FLWL. This model consists of three modules: a compensation regulation module to analyze the feasibility to raise the FLWL and calculate the probable maximum upper bound of the FLWL, a risk control module containing a risk constraint to control flood risk and a Copula function to describe the uncertainty of the FSP, and a simulation operation module to simulate the flood control operation for cascade reservoirs. The proposed model was applied to Pankou-Huanglongtan cascade reservoirs in Du River basin. The application results showed that: 1) the proposed model could give a sufficient consideration about the uncertainty of the FSP, thus a safe and reasonable dynamic control bound of FLWL was derived. 2) the upper FLWL of Huanglongtan reservoir could rise up to 247.64 m from 247.00 m without increasing flood control risk and Huanglongtan reservoir could generate 9 and 7 billion kW.h extra hydropower energy during flood season in wet year 2000 and in dry year 1994, respectively.

Background: Robust statistical designing, sound statistical analysis, and standardized presentation are important to enhance the quality and transparency of biomedical research. This systematic review was conducted to summarize the statistical reporting requirements introduced by biomedical research journals with an impact factor of 10 or above so that researchers are able to give statistical issues' serious considerations not only at the stage of data analysis but also at the stage of methodological design. Methods: Detailed statistical instructions for authors were downloaded from the homepage of each of the included journals or obtained from the editors directly via email. Then, we described the types and numbers of statistical guidelines introduced by different press groups. Items of statistical reporting guideline as well as particular requirements were summarized in frequency, which were grouped into design, method of analysis, and presentation, respectively. Finally, updated statistical guidelines and particular requirements for improvement were summed up. Results: Totally, 21 of 23 press groups introduced at least one statistical guideline. More than half of press groups can update their statistical instruction for authors gradually relative to issues of new statistical reporting guidelines. In addition, 16 press groups, covering 44 journals, address particular statistical requirements. The most of the particular requirements focused on the performance of statistical analysis and transparency in statistical reporting, including address issues relevant to research design, including participant flow diagram, eligibility criteria, and sample size estimation, and statistical methods and the reasons. Conclusions: Statistical requirements for authors are becoming increasingly perfected. Statistical requirements for authors remind researchers that they should make sufficient consideration not only in regards to statistical methods during the research design, but also standardized statistical reporting, which would be beneficial in providing stronger evidence and making a greater critical appraisal of evidence more accessible.

Background: To describe the characteristics, treatments, and prognosis of pediatric gastric perforation patients beyond neonatal period. Methods: Twenty pediatric patients beyond neonatal period were included in this study. Medical records were reviewed and clinical characteristics were analyzed. According to the outcomes, patients were divided into the survival group and the death group. Death time was documented, and survival patients were followed up. The degree of severity was calculated using pediatric critical illness score (PCIS). Differences between the two groups were analyzed by the Student's t-test, Mann-Whitney test and Chi-square test appropriately. Results: Gastric perforation was diagnosed in 20 pediatric patients beyond neonatal period, including 6 males (30%) and 14 females (70%), with the age of 37.18 (15.90, 107.12) months, and the range was from 4.30 months to 14.17 years old. They had different manifestations, etiologies, sites of perforation and surgery procedures. Among the 20 cases, 14 (70%) survived and 6 (30%) died. Age, gender, length and number of perforation had no statistically difference between the two groups. However, PCIS, ischemia of gastrointestinal wall, and transmural necrosis of gastric wall were statistically different. For the survival group, during a follow-up period of 50 (36, 68) months, ranging from 2 months to 8 years and 7 months, one patient had a second-time perforation, another 3 patients had brain injury symptoms, and the rest 10 patients had good quality of lives. Conclusions: Gastric perforation of pediatric patients beyond neonatal period causes a mortality of 30% on this study. Spontaneous great curvature of gastric wall perforation has the highest morbidity. Low PCIS predicts for unfavorable prognosis. Most of the survival patients have satisfactory living quality after operation. Key Words: pediatric gastric perforation, prognosis, treatment

Background The aim of this study is to add to the current knowledge regarding extracranial malignant rhabdoid tumor (MRT), a rare and highly aggressive tumor that occurs most commonly in infants and young children. Patients and methods A retrospective medical record review was conducted on 53 patients with pathologically confirmed MRT in Beijing Children's Hospital between January 2007 and October 2017. Results Fifty-three patients were diagnosed with MRT at a median age of 16 months, including 32 cases of malignant rhabdoid tumor of the kidney (MRTK) and 21 cases of extrarenal extracranial rhabdoid tumor (EERT). Fourteen (14/32, 43.75%) patients with MRTK and five (5/21, 23.81%) patients with EERT had metastases at diagnosis, and quite a few number of cases occurred tumor rupture (26.42%). Among the 53 patients, 40 (75.47%) patients died, 10 (18.87%) patients survived, and 3 patients (5.66%) were lost to follow-up. Among the 40 dead patients, 38 patients died from rapid progression of the disease or tumor recurrence, and 2 patients died of severe postoperative complications. Most of the recurrent or relapsed cases (94.11%) occurred within 8 months, with a median time of 76 days after diagnosis. The overall survival rates of 3 years and 5 years for the entire cohort were 23.71% and 18.44%, respectively. After survival analysis, it was clear that a younger age at diagnosis and distant stage patients had relatively poor outcomes. The effect of treatment was the most difficult to analyze because patients were not treated uniformly. Statistically significant differences in survival were noted among patients treated with standard chemotherapy, total resection, and radiotherapy. Conclusion Extracranial MRT is still a highly aggressive tumor in children. Younger patients and those suffering from metastatic disease were most likely to have a poor outcome because of rapid progression or recurrence of the tumor. Implications for practice This is the largest single-institutional report that investigates the clinical characteristics and outcomes of extracranial malignant rhabdoid tumor (MRT) in China. Our study showed that gross hematuria and tumor rupture were typical characteristics of malignant rhabdoid tumor of the kidney. After survival analysis, it was found that the advanced stage of the tumor and an age ≤12 months at diagnosis were significantly associated with poorer survival. Although extracranial MRT is still a highly aggressive tumor in children, multimodal treatment approach, including chemotherapy, surgery, and radiotherapy, should be employed for this disease.

The aim of this study was to discriminate the children malignant peripheral neuroblastic tumors (PNTs) from those with benign histotype ganglioneuroma (GN) based on clinical and biological characteristics in all PNTs. Four hundred and seventy-six patients were included in this study, containing 345 patients for model development and 131 patients for external validation. Multivariate logistic regression analysis was conducted to select potentially useful characteristics for discrimination of histopathology. External validation was performed for model evaluation. Compared with the main characteristics of GN (85/345, 24.6%), those of malignant PNTs (260/345, 75.4%) showed significant differences. Multivariate analysis was performed to further find the characteristics linked to histopathology. The results indicated that for the patients younger than 49 months, the primary site of adrenal and thoracic, the level of serum neuron-specific enolase (NSE) > 33 ng/mL, and tumor encasing blood vessels were the extremely important discrimination factors of malignant PNTs. The area under the receiver-operating-characteristic of the discrimination model was 0.96. The accuracy rate, sensitivity and specificity were 93.4%, 96.3% and 83.8%, respectively. Meanwhile, the accuracy rate of the external validation from the 131 patients was 97.0%. Overall, histopathologic type of childhood malignant PNTs can be discriminated based on age, primary site, NSE level and the relationship between primary tumor and blood vessels.

Pleuropulmonary blastoma (PPB) is the most common primary malignant neoplasm of the lung in children that is associated with a germline mutation in DICER1. In this report, we share an interesting case of a pair of monozygotic twins: one of them developed PPB when she was 4-year old, while the other developed acute transient hepatitis when she was 5-year old. Next-Gen sequencing for DICER1 mutations of their family revealed that both twins and their mother had c.C3675A mutation. The mother also had a history of multinodular goiter. Identification of DICER1 mutation carriers and close surveillance of individuals at risk for DICER1 syndrome may allow early detection and hence better outcome.

This study proposes a hedging rule model which is composed of a two-period reservior operation model considering the damage depth and hedging rule parameter optimization model. The former solves hedging rules based on a given poriod’s water supply weighting factor and carryover storage target, while the latter optimization model is used to optimize the weighting factor and carryover storage target based on the hedging rules. The coupling model gives the optimal poriod’s water supply weighting factor and carryover storage target to guide release. The conclusions achieved from this study as follows: (1) the water supply weighting factor and carryover storage target have a direct impact on the three elements of the hedging rule; (2) parameters can guide reservoirs to supply water reasonably after optimization of the simulation and optimization model; and (3) in order to verify the utility of the hedging rule, the Heiquan reservoir is used as a case study and particle swarm optimization algorithm with a simulation model is adopted for optimizing the parameter. The results show that the proposed hedging rule can improve the operation performances of the water supply reservoir.

Due to the aggravation of human activities and global climate changes in recent decades, catchment water cycle has experienced strong variation. The world is faced with profound water crisis, and water problems are especially severe and water disasters are of high frequency in China. Water problems have become significant obstacle factors for realizing sustainable development, which greatly threatens national economy and ecological safety. Given the scientific background of catchment water cycle evolution and water resources comprehensive regulation, we propose the method of solving water problems through water resources operation based on dualistic water cycle theory and discuss the developing status and existing problems of current water resources operation in China. On this basis, we also put forward the technical framework and key process of water resources regulation, which integrates the six links of monitoring, simulation, evaluation, forecasting, regulation and control. Furthermore, aiming at the background of the second phase of National Water Monitoring Capacity Building Project, we introduce a nationwide general software platform for water resources regulation. This platform will realize business collaboration and information sharing among three-scale platform of Ministry of Water Resources, basin authorities and provincial level, so as to overall improve the ability of water resources regulation and decision-making.

Artificial neural network and fuzzy inference technology have been successfully used in various fields in the last decades. In order to combine the advantages of these approaches, the previous researchers came up with a new model named adaptive neural fuzzy inference system (ANFIS), which has been applied to signal processing and the related fields. Hydrological prediction is an important aspect of hydrological services for economy and society. The prediction result not only provides decision support for generation optimization, but also is of great significance to the economical operation of hydropower systems, navigation, flood control and so on. This paper presents the application of adaptive neural fuzzy inference system (ANFIS) on daily runoff time-series prediction at Tongzilin station. To evaluate the performances of the selected ANFIS, comparison was made with the ANN and autoregressive (AR) model. Previous inflows were chosen as input vectors of the three different models. Nash-Sutcliffe efficiency coefficient (NS coefficient), root mean square error (RMSE) and mean absolute relative error (MARE) were chosen to evaluate the performances of our models. The results show that ANFIS not only keep the potential of the ANN whose advantage is to deal with nonlinear problem, but it also eases the model building process and makes the result more stable. As a result, ANFIS can be a recommended daily runoff time-series prediction model.

Data mining technology is applied to extract the water supply operation rules in this study. Five characteristic attributes—reservoir storage water, operation period number, water demand, runoff, and hydrological year—are chosen as the dataset, and these characteristic attributes are applied to build a mapping relation with the optimal operation mode calculated by dynamic programming (DP). A Levenberg-Marquardt (LM) neural network and a classification and regression tree (CART) are chosen as data mining algorithms to build the LM neural network classifier and CART decision tree classifier, respectively. In order to verify the classification effect of the LM and CART, the two classifiers are applied to the operation mode recognition for the Heiquan reservoir, which is located in the Qinghai Province of China. The accuracies of the two classifiers are 73.6% and 86.9% for the training sample, and their accuracies are 65.8% and 83.3%, respectively, for the test sample, which indicates that the classification result of the CART classifier is better than that of the LM neural network classifier. Thus, the CART classifier is chosen to guide the long-series water supply operation. Compared to the operation result with the other operation scheme, the result shows that the water deficit index of the CART is mostly closest to the DP scheme, which indicates that the CART classifier can guide reservoir water supply operation effectively.

The epidemiology, clinical presentation, and treatment of infective endocarditis (IE) has significantly changed over the past few years in developed countries. However, relevant data from developing countries are different and remain scarce. The objective of this study was to evaluate the clinical presentations, treatment and outcomes of IE patients in a tertiary hospital in East China over an 8-year period. This was a retrospective observational study of consecutive cases of definite or possible IE as per the modified Duke criteria between January 2008 and December 2015. A total of 135 definite and 39 probable IE cases were identified. The mean age was 47.8 ± 15.7 years, with a male preponderance (1.9: 1). Degenerative valve disease accounted for 30.5% cases of IE, followed by congenital heart disease (29.9%) and rheumatic heart disease (14.9%). Native cardiac valves were present in 93.7% of the IE patients. Echocardiography and blood culture were performed in all patients, of whom 55.2% were found to have large vegetations (≥10 mm) and the positive rate of blood culture was 60.3%. Streptococcus remained the chief causative agent that was identified in 61.9% of culture-positive patients. Glycopeptide antibacterials and cephalosporins were the most frequently used antimicrobial drugs for IE therapy. Seventy-six (43.7%) of the IE patients were surgically treated. The mortality rate during hospital stay was 10.9%. Our data reflected clinical and microbiological profile, and treatment of IE in a tertiary hospital located in the East China.