Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

Association Between Serum Glycated Hemoglobin Levels at Early Gestation and the Risk of Subsequent Pregnancy Loss in Pregnant Women Without Diabetes Mellitus: Prospective Cohort Study.

BACKGROUND: As a severe morbidity during pregnancy, the etiology of spontaneous pregnancy loss (SPL) remains largely unknown. Serum glycated hemoglobin (HbA1c) level is an established predictor of SPL risk among women with diabetes, but little is known about whether such an association exists among pregnant women without diabetes when glycemic levels are within the normal range. OBJECTIVE: This study aimed to quantify the association between maternal HbA1c levels in early pregnancy and subsequent SPL risk in a cohort of pregnant women without diabetes. METHODS: This prospective cohort study involved 10,773 pregnant women without diabetes enrolled at their first antenatal care visit at a hospital's early pregnancy clinic from March 2016 to December 2018 in Shanghai, China. HbA1c and fasting blood glucose (FBG) levels were examined at enrollment. Participants with diabetes before or pregnancy or those diagnosed with gestational diabetes were excluded. Diagnosis of SPL, defined as fetal death occurring before 28 gestational weeks, was derived from medical records and confirmed via telephone interviews. We used generalized linear models to quantify the associations of continuous and dichotomized maternal HbA1c levels with SPL risk and reported crude and adjusted risk ratios (RRs) and 95% CIs. A restricted cubic spline (RCS) regression model was used to assess the potential nonlinear dose-response relationship. Adjusted covariates included maternal age, education level, preconception BMI, gestational weeks, gravidity, history of adverse pregnancy outcomes, family history of diabetes, folic acid supplementation, and smoking and drinking during the periconception period. RESULTS: In total, 273 (2.5%) SPL cases occurred. Every 0.5% increase in HbA1c levels was linearly associated with a 23% increase in SPL risk (adjusted RR [aRR] 1.23; 95% CI 1.01-1.50). The RCS model revealed that this association was linear (P=.77 for the nonlinearity test). Analyses based on dichotomized HbA1c levels showed a significantly increased risk of SPL when HbA1c levels were ≥5.9% (aRR 1.67; 95% CI 0.67-3.67), and the significance threshold was ≥5.6% (aRR 1.60; 95% CI 1.01-2.54). Sensitivity analyses showed similar results when including the participants with missing SPL records or HbA1c data. Linear associations of HbA1c levels remained significant even in the subgroups without overweight, alcohol consumption, and a family history of diabetes and adverse pregnancy outcomes. Every 1 mmol/L increment in maternal FBG levels was associated with a >2-fold higher risk of SPL (aRR 2.12; 95% CI 1.61-2.80; P<.001). CONCLUSIONS: Higher HbA1c levels in early pregnant women without diabetes are associated with an increased SPL risk in a dose-response manner. Pregnant women with an HbA1c level above 5.6% at early gestation need attention for its potentially increased risk for SPL. Our findings support the need to monitor HbA1c levels to identify individuals at high risk of subsequent SPL in the general population of pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737644; https://clinicaltrials.gov/study/NCT02737644.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IB3 and IIA2): study protocol of the LAUNCH 3 trial.

BACKGROUND: Cervical cancer is and will remain to be an important health problem in China, especially with an increasing proportion of younger patients who has more specific needs. In China, surgery to remove tumor burden followed by postoperative treatment with radiotherapy and chemotherapy based on clinicopathologic factors may be the best choice for stages IB3 and IIA2 patients. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology. The current trial is designed to evaluate whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB3 and IIA2) patient survival under stringent operation standards and consistent surgical oncologic principles. This paper reports the rationale, design, and implementation of the trial. METHODS/DESIGN: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 1104 patients with stage IB3 and IIA2 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary end point will be 5-year overall survival, and secondary endpoints include 5-year progression-free survival, recurrence, and quality of life measurements. DISCUSSION: The study results will provide more convincing evidence-based information for stages IB3 and IIA2 cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04939831 , retrospectively registered on 25 June 2021.

Early Antibiotic Use and Neonatal Outcomes Among Preterm Infants Without Infections.

OBJECTIVES: To determine whether use, duration, and types of early antibiotics were associated with neonatal outcomes and late antibiotic use in preterm infants without infection-related diseases. METHODS: This cohort study enrolled infants admitted to 25 tertiary NICUs in China within 24 hours of birth during 2015-2018. Death, discharge, or infection-related morbidities within 7 days of birth; major congenital anomalies; and error data on antibiotic use were excluded. The composite outcome was death or adverse morbidities. Late antibiotic use indicated antibiotics used after 7 days of age. Late antibiotic use rate was total antibiotic use days divided by the days of hospital stay after the first 7 days of life. RESULTS: Among 21 540 infants, 18 302 (85.0%) received early antibiotics. Early antibiotics was related to increased bronchopulmonary dysplasia (BPD) (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.05-1.56), late antibiotic use (aOR, 4.64; 95% CI, 4.19-5.14), and late antibiotic use rate (adjusted mean difference, 130 days/1000 patient-days; 95% CI, 112-147). Each additional day of early antibiotics was associated with increased BPD (aOR, 1.07; 95% CI, 1.04-1.10) and late antibiotic use (aOR, 1.41; 95% CI, 1.39-1.43). Broad-spectrum antibiotics showed larger effect size on neonatal outcomes than narrow-spectrum antibiotics. The correlation between early antibiotics and outcomes was significant among noncritical infants but disappeared for critical infants. CONCLUSIONS: Among infants without infection, early antibiotic use was associated with increased risk of BPD and late antibiotic use. Judicious early antibiotic use, especially avoiding prolonged duration and broad-spectrum antibiotics among noncritical infants, may improve neonatal outcomes and overall antibiotic use in NICUs.

Comparison of biochemical characteristics and gel properties of chicken myofibrillar protein affected by heme-iron and nonheme-iron oxidizing systems.

In this study, the effect of hemin and non-heme iron on the biochemical and gelling properties of chicken myofibrillar protein (MP) was compared. Results revealed that free radicals from hemin incubated MP were significantly higher than that in FeCl3 incubated samples (P < 0.05), and had higher ability to initiate protein oxidation. The carbonyl content, surface hydrophobicity, random coil increased with oxidant concentration, whereas the total sulfhydryl and α-helix content decreased in both oxidizing systems. The turbidity and particle size were increased after oxidant treatment, indicating oxidation promoted the cross-linking and aggregation of protein, and the degree of aggregation was higher in hemin treated MP compared with that incubated with FeCl3. The biochemical changes of MP resulted in an uneven and loose gel network structure, which significantly reduced the gel strength and water holding capacity (WHC) of the gel.

Effect of Adjuvant Steroid Therapy in Type 3 Biliary Atresia: A Single-Center, Open-Label, Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy and side effects of additional postoperative steroid therapy for type 3 BA versus the current routine care. SUMMARY BACKGROUND DATA: Whether steroid therapy post-Kasai portoen-terostomy improves the outcomes of BA remains controversial. Clinical evidence from 2 randomized trials in the UK and USA do not support the routine use of steroid in the treatment of BA. METHODS: In this open-label randomized controlled trial, patients with type 3 BA were randomized to routine postoperative treatment with or without 10 to 12 weeks of adjuvant steroid treatment. The primary outcome was the postoperative jaundice clearance rate with native liver at 6 months. The secondary outcomes included postoperative jaundice clearance rate at 3, 12, and 24 months, survival with native liver at 12 and 24 months, and SAEs within 3 months. RESULTS: Overall, 200 participants were randomized and allocated into either steroid or control group (n = 100/group). The proportion of participants that are jaundice free without liver transplantation was significantly higher in the steroid group than in the control group at 6 months (54.1% vs 31.0%, P = 0.0015). The native liver survival rate was higher postoperatively in the steroid group than in the control group at 12 (66.3% vs 50.0%, P = 0.02) and 24 (57.1% vs 40.0%, P = 0.02) months. The survival time with native liver was significantly longer in the steroid group than in the control group (median survival, steroid vs control: not reached vs 1.21 years, P = 0.02). There were no significant differences between the 2 groups in the mean occurrence of SAEs within 3 months (steroid vs control: 0.63 vs 0.45, P = 0.20). CONCLUSIONS: Postoperative adjuvant steroid intervention improved bile drainage and survival with native liver in type 3 BA patients, without increasing early-stage SAEs.

Discovery of novel whitefly vector proteins that interact with a virus capsid component mediating virion retention and transmission.

Specificity and efficiency of plant virus transmission depend largely on protein-protein interactions of vectors and viruses. Cucurbit chlorotic yellows virus (CCYV), transmitted specifically by tobacco whitefly, Bemisia tabaci, in a semi-persistent manner, has caused serious damage on cucurbit and vegetable crops around the world. However, the molecular mechanism of interaction during CCYV retention and transmission are still lacking. CCYV was proven to bind particularly to the whitefly foregut, and here, we confirmed that the minor coat protein (CPm) of CCYV is participated in the interaction with the vector. In order to identify proteins of B. tabaci that interact directly with CPm of CCYV, the immunoprecipitation (IP) assay and DUALmembrane cDNA library screening technology were applied. The cytochrome c oxidase subunit 5A (COX), tubulin beta chain (TUB) and keratin, type I cytoskeletal 9-like (KRT) of B. tabaci shown strong interactions with CPm and are closely associated with the retention within the vector and transmission of CCYV. These findings on whitefly protein-CCYV CPm interactions are crucial for a much better understanding the mechanism of semi-persistent plant virus transmission by insect vectors, as well as for implement new strategies for effective management of plant viruses and their vector insects.

Clinical implications of respiratory ciliary dysfunction in heterotaxy patients with congenital heart disease: elevated risk of postoperative airway complications.

Objective: Cardiac surgery in Congenital Heart Disease-Heterotaxy (CHD-HTX) patients often leads to increased postoperative airway complications. Abnormal respiratory ciliary function, resembling primary ciliary dyskinesia, has been observed. We expanded the sample size by retrospectively reviewing Ciliary Dysfunction (CD) in CHD-HTX patients to verify the increased risk of post-surgical respiratory complications. Methods: We conducted a retrospective review of 69 CHD-HTX patients undergoing cardiac surgery, assessing abnormal respiratory function using nasal nitric oxide (nNO) levels and nasal ciliary motion observed in video microscopy. Data collected included demographics, surgical details, postoperative complications, length of stay, ICU hours, salvage procedures, intubation duration, and mortality. Results: The CD and no-CD cohorts exhibited notable similarities in risk adjustment in Congenital Heart Surgery-1 (RACHS-1) risk categories, age at the time of surgery, and the duration of follow-up evaluations. We observed a trend toward an increased length of post-operative stay in the CD group (15.0 vs. 14.0; P = 0.0017). CHD-HTX patients with CD showed significantly higher rates of respiratory complications (70% vs. 44.4%; P = 0.008). There were no notable variances observed in postoperative hospitalization duration, mechanical ventilation period, or surgical mortality. Conclusion: Our findings suggest that CHD-HTX patients with CD may face an elevated risk of respiratory complications. These results offer guidance for perioperative management and serve as a reference for further pathological studies.

A multicenter non-inferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stages IB1, IB2, and IIA1): study protocol of the LAUNCH 2 trial.

BACKGROUND: A retrospective study and a randomized controlled trial published in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early-stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology; therefore, this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB1, IB2, and IIA1) patient survival under stringent operation standards and consistent surgical oncologic principles. METHODS/DESIGN: This is an investigator-initiated, Prospective, Randomized, Open, Blinded End-point (PROBE)-controlled non-inferiority trial. A total of 780 patients with stage IB1, IB2, and IIA1 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary endpoint will be 5-year progression-free survival, and secondary endpoints include 5-year overall survival, recurrence, and quality of life measurements. DISCUSSION: The debate on laparoscopic versus abdominal RH is still ongoing, and high-quality evidences are needed to guide clinical practice. The study results will provide more convincing evidence-based information for early-stage cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. TRIAL REGISTRATION: ClinicalTrials.gov NCT04929769 . Registered on 18 June 2021.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IA1 with LVSI, IA2): study protocol of the LAUNCH 1 trial.

BACKGROUND: A retrospective study and a randomized controlled trial published in a high quality journal in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology, therefore this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stage IA1 with LVSI, IA2) patient survival under stringent operation standards and consistent tumor-free technique. This paper reports the rationale, design, and implementation of the trial. METHODS: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 690 patients with stage IA1 (with intravascular), and IA2 cervical cancer will be enrolled over a period of three years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed-up for at least five years. The primary endpoint will be 5-year progression-free survival. Secondary endpoints will include 5-year overall survival rates, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and quality of life. DISCUSSION: The results of the trial will provide valuable evidence for guiding clinical decision of choosing appropriate treatment strategies for stage IA1 (LVSI) and stage IA2 cervical cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04934982 , Registered on 22 June 2021).

RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort.

BACKGROUND: The protective effects of maternal folate on neural tube defects are well-established. Emerging evidence has shown paternal folate also is related to pregnancy outcome and offspring health. OBJECTIVES: This study aimed to assess the status of red blood cell (RBC) folate and serum folate, vitamin B-12, and homocysteine (Hcy) and their associated factors in a cohort of pregnancy-preparing couples. METHODS: This was a cross-sectional study involving 14,178 participants from the extension of the Shanghai Preconception Cohort conducted in 2018-2021. Circulating biomarker concentrations were measured, and the prevalence of abnormal status was reported. Linear and logistic regression analyses were conducted to examine associations of demographic factors (age, education, and income), lifestyle factors (smoking, drinking, and folic acid supplement use), and BMI with concentrations of the folate-related biomarkers, abnormal status of folate (deficiency and insufficiency) and vitamin B-12 (deficiency and marginal deficiency), and hyperhomocysteinemia. RESULTS: The geometric mean (95% CI) concentrations of RBC folate, serum folate, vitamin B-12, and Hcy were 490 nmol/L (485, 496 nmol/L), 20.1 nmol/L (19.8, 20.3 nmol/L), 353 pmol/L (350, 357 pmol/L), and 7.54 µmol/L (7.48, 7.60 µmol/L) in females, respectively, and 405 nmol/L (401, 409 nmol/L), 13.5 nmol/L (13.4, 13.7 nmol/L), 277 pmol/L (274, 279 pmol/L), and 12.0 µmol/L (11.9, 12.2 µmol/L) in males, respectively. Prevalence of abnormal status was higher in males than females for the 4 folate-related biomarkers: RBC folate deficiency (<340 nmol/L, 32.2% compared with 18.9%), serum folate deficiency (<10.0 nmol/L, 26.5% compared with 7.3%), RBC folate insufficiency (<906 nmol/L, 96.6% compared with 90.1%), serum folate insufficiency (<15.9 nmol/L, 65.5% compared with 31.4%), vitamin B-12 marginal deficiency (148-221 pmol/L, 21.4% compared with 8.8%), and hyperhomocysteinemia (>15.0 µmol/L, 22.1% compared with 2.5%). CONCLUSIONS: Most pregnancy-preparing couples failed to achieve the optimal RBC folate status (>906 nmol/L) as recommended by the WHO. These findings call for attention to the insufficiency status of folate and promising strategies to improve the folate status of the pregnancy-preparing population not exposed to folic acid fortification.

CpG site hypomethylation at ETS1­binding region regulates DLK1 expression in Chinese patients with Tetralogy of Fallot.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart malformation accounting for ~10% of cases. Although the pathogenesis of TOF is complex and largely unknown, epigenetics plays a huge role, specifically DNA methylation. The protein δ like non­canonical Notch ligand 1 (DLK1) gene encodes a non­canonical ligand of the Notch signaling pathway, which is involved in heart development. However, the epigenetic mechanism of DLK1 in the pathogenesis of TOF is yet to be elucidated. Therefore, the present study aimed to clarify its specific mechanism. In this study, immunohistochemistry was used to detect the protein expression of DLK1 and the methylation status of the DLK1 promoter was measured via bisulfite sequencing PCR. Dual­luciferase reporter assays were performed to examine the influence of transcription factor ETS proto­oncogene 1 (ETS1) on DLK1 gene expression. The electrophoretic mobility shift assay and chromatin immunoprecipitation assay, both in vivo and in vitro, were used to verify the binding of the ETS1 transcription factor to the DLK1 promoter as well as the influence of methylation status of DLK1 promoter on this binding affinity. The expression of DLK1 in the right ventricular outflow tract was significantly lower in patients with Tetralogy of Fallot (TOF) than that in controls (P<0.001). Moreover, the methylation level of CpG site 10 and CpG site 11 in the DLK1_R region was significantly decreased in TOF cases compared with controls (P<0.01). The integral methylation levels of DLK1_R and the methylation status of the CpG site 11 were both positively associated with DLK1 protein expression in TOF cases. ETS1 was found to inhibit DLK1 transcriptional activity by binding to the CpG site 11 and this affinity could be influenced by the methylation level of the DLK1 promoter. These findings demonstrated that the hypomethylation of the DLK1 promoter could increase the binding affinity of ETS1 transcription factor, which in turn inhibited DLK1 gene transcriptional activity and contributed to the development of TOF.

Epidemiological characteristics and risk factors of biliary atresia: a case-control study.

OBJECTIVES: Biliary atresia (BA) is regarded as a serious neonatal hepatobiliary disease, and its aetiology and pathogenesis remain unclear. Epidemiological studies are limited, especially for the data from China. This study aims to explore risk factors of BA and provide new evidence to improve understanding of its aetiology. DESIGN: This is a case-control study from 1 January 2015 to 31 December 2016. SETTING: Cases were consecutively recruited from an urban tertiary care academic children's hospital in Shanghai, China, while the controls were recruited from a community hospital in Shanghai through a random sampling system. PARTICIPANTS: 721 patients suspected for BA who planned to take the diagnostic surgery were enrolled preoperatively. 613 were diagnosed with BA and recruited into the case group. Meanwhile, 688 infants without any observed major congenital anomalies or jaundice were enrolled. Finally, 594 valid questionnaires from the case group and 681 from the control group were obtained. PRIMARY AND SECONDARY OUTCOME MEASURES: Standardised questionnaires were used for data collection. Multivariate logistic regression analysis was performed to evaluate associations reported as ORs and precision, by adjusting covariates. RESULTS: Anxiety or stress during pregnancy was strongly associated with increased risk of BA (OR 8.36 (95% CI: 4.08 to 17.15); p<0.001), respectively. Lower birth weight, fathers from ethnic minorities of China, older age of fathers, lower income of parents, and exposure to infection, diseases and medication during pregnancy all made differences. CONCLUSIONS: Social factors including the educational and economic background and its related anxiety and stress during pregnancy might be noticed in the occurrence of BA. Maternal infections during pregnancy in the prevalence of BA were demonstrated. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-15005885.

Association of short-term fine particulate matter exposure with pulmonary function in populations at intermediate to high-risk of cardiovascular disease: A panel study in three Chinese cities.

BACKGROUND: Decline in pulmonary function contributes to increasing cardiovascular disease (CVD) risk. Although adverse effects of short-term exposure to fine particulate matter (PM2.5) on pulmonary function have been recognized in healthy people or patients with respiratory disease, these results were not well illustrated among people with elevated CVD risk. MATERIALS AND METHODS: A panel study was conducted in three Chinese cities with three repeated visits among populations at intermediate to high-risk of CVD, defined as treated hypertension patients or those with blood pressure ≥ 130/80 mmHg, who met any of the three conditions including abdominal obesity, dyslipidemia, and diabetes mellitus. Individualized PM2.5 exposure and pulmonary function were measured during each seasonal visit. Linear mixed-effect models were applied to analyze the associations of PM2.5 concentrations with pulmonary function indicators, including forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC), maximal mid-expiratory flow (MMF), and peak expiratory flow (PEF). RESULTS: Short-term PM2.5 exposure was significantly associated with decreased pulmonary function and an increment of 10 µg/m3 in PM2.5 concentrations during lag 12-24 hour was associated with declines of 41.7 ml/s (95% confidence interval [CI]: 7.7-75.7), 0.35% (95% CI: 0.01, 0.69), and 20.9 ml/s (95% CI: 0.5-41.3) for PEF, FEV1/FVC, and MMF, respectively. Results from stratified and sensitivity analyses were generally similar with the overall findings, while the adverse effects of PM2.5 on pulmonary functions were more pronounced in those who were physically inactive. CONCLUSIONS: This study first identified short-term exposure to PM2.5 was associated with impaired pulmonary function and physical activity might attenuate the adverse effects of PM2.5 among populations at intermediate to high-risk of CVD. These findings provide new robust evidence on health effects of air pollution and call for effective prevention measures among people at CVD risk.

Effect of myoglobin, hemin, and ferric iron on quality of chicken breast meat.

OBJECTIVE: The objective was to evaluate the impact of different forms of iron including myoglobin, hemin, and ferric chloride on the quality of chicken breast meat. METHODS: Chicken breast muscles were subjected to 1, 2, 3 mg/mL of FeCl3, myoglobin and hemin treatment respectively, and the production of reactive oxygen species (ROS) and malondialdehyde, meat color, tenderness, water holding capacity and morphology of meat was evaluated. RESULTS: Hemin was found to produce more ROS and induce greater extent of lipid oxidation than myoglobin and ferric chloride. However, it showed that hemin could significantly increase the redness and decrease the lightness of the muscle. Hemin was also shown to be prominent in improving water holding capacity of meat, maintaining a relatively higher level of the immobilized water from low-field nuclear magnetic resonance measurements. Morphology observation by hematoxylin-eosin staining further confirmed the results that hemin preserved the integrity of the muscle. CONCLUSION: The results indicated that hemin may have economic benefit for the industry based on its advantage in improving water holding capacity and quality of meat.

Effectiveness of community-based folate-oriented tertiary interventions on incidence of fetus and birth defects: a protocol for a single-blind cluster randomized controlled trial.

BACKGROUND: Birth defects are the main cause of fetal death, infant mortality and morbidity worldwide. However, the etiology of birth defects remains largely unknown. Maternal folate status during periconception plays an important role in organogenesis and folic acid supplement reduces the risk of neural tube defects, congenital heart diseases, and several other birth defects. This trial seeks to evaluate the effectiveness of folate-oriented tertiary interventions during periconception on the incidence of fetus and birth defects. METHODS: This is a single-blind, two-arm cluster randomized controlled trial in Shanghai, China. Eligible women from 22 clusters are recruited at pre-pregnancy physical examinations clinical settings. Compared to the routine perinatal care group (control arm), folate-oriented tertiary interventions will be provided to the intervention arm. The core interventions consist of assessments of folate status and metabolism, folate intake guidance, and re-evaluation of folate status to ensure red blood cell folate level above 400 ng/ml (906 nmol/L) before pregnancy. Screening and consulting of fetus and birth defects, and treatments of birth defects during pregnancy and afterward will be provided to both arms. The primary outcome is a composite incidence of fetus defects, stillbirth, and neonatal birth defects identified from the confirmation of pregnancy to 28 days after birth. Secondary outcomes include maternal and offspring adverse complications and cost-effectiveness of folate-oriented tertiary interventions. This protocol adheres to the SPIRIT Checklist. DISCUSSION: To achieve the recommended folate status before or during pregnancy is still a challenge worldwide. This community-based cluster-randomized controlled intervention trial will evaluate the effectiveness of a package of interventions aiming at achieving recommended maternal folate status covering pre- and during pregnancy in reducing fetus and birth defects. Our study has the potential to improve the community-based practice of reducing modifiable risk factors of disease and improving primary prevention of the defects in China. The procedures would formulate the policy on folic acid supplementation during periconception against birth defects in primary care settings. TRIAL REGISTRATION: Clinical Trial Registry, NCT03725878 . Prospectively registered on 31 October 2018.

Waist-to-height ratio as a screening tool for cardiometabolic risk in children and adolescents: a nationwide cross-sectional study in China.

OBJECTIVES: To demonstrate the accuracy and flexibility of using waist-to-height ratio (WHtR) as a screening tool for identifying children and adolescents with cardiometabolic risk (CMR) across a wide range of prevalence levels among general paediatric populations. DESIGN: A nationwide population-based cross-sectional study with all data collected at school settings in six cities of China. PARTICIPANTS: A total of 8130 children and adolescents aged 7-18 years with complete anthropometric and CMR measurements based on blood tests were recruited. OUTCOME MEASURES: Elevated blood pressure, dyslipidaemia, elevated fasting blood glucose and central obesity were measured. The primary outcome, CMRs, was defined as meeting three or more of the above risk factors. The accuracy of WHtR for identifying CMRs was evaluated using areas under the curves (AUCs) with 95% CI of the receiver operating characteristic curve. The predictability of WHtR at given CMRs prevalence levels was estimated by positive predictive value (PPV) and negative predictive value. RESULTS: Overall, 6.1% of study participants were presented with CMRs. WHtR had high AUCs ranging from 0.84 (95% CI 0.81 to 0.88) to 0.88 (95% CI 0.86 to 0.90) in the total population and age-subgroup and gender-subgroup. The overall optimal WHtR cut-off value was 0.467, with boys having a higher cut-off than girls (0.481 vs 0.456). WHtR achieved an overall sensitivity of 0.89 and PPV of 18.8% at a specificity of 0.75. The screening performance of WHtR remained satisfactory across a wide range of given CMRs prevalence levels (5%, 10% and 20%). CONCLUSION: WHtR as a screening tool could accurately and flexibly identify children affected with the clusters of three or more of CMR factors from the general paediatric population with various CMR prevalence levels. Our findings provide support for policy-making on early CMR identification and management in the high-risk group of children.

Mortality and Morbidity in Infants <34 Weeks' Gestation in 25 NICUs in China: A Prospective Cohort Study.

Objectives: To describe the rates and variability of mortality and morbidity of preterm infants born in China. Methods: This prospective cohort study included infants born at <34 weeks' gestation and admitted to 25 NICUs within 7 days of birth between May 1st, 2015 and April 30th, 2016. Infants were followed until death or NICU discharge. The primary outcome was a composite of mortality or any major morbidity (sepsis, necrotizing enterocolitis, intraventricular/periventricular leukomalacia, retinopathy of prematurity, and bronchopulmonary dysplasia) in infants who received complete care following medical advice. Secondary outcomes included rate of discharge against medical advice, mortality and individual morbidities. Results: Of the 8,065 infants, 6,852 (85%) received complete care and 1,213 (15%) were discharged against medical advice. Among infants who received complete care, the rate of the composite outcome was 27% (1,827/6,852), mortality 4% (248/6,852), sepsis 14% (990/6,852), necrotizing enterocolitis 3% (191/6,550), intraventricular hemorrhage/periventricular leukomalacia 7% (422/6,307), retinopathy of prematurity 2% (67/3,349), and bronchopulmonary dysplasia 9% (616/6,852). There were significant variations between NICUs for all outcomes. Conclusions: Discharged against medical advice, mortality, and morbidity rates for preterm infants <34 weeks' gestation are high in China with significant variations between NICUs.

Epidemiology and microbiology of late-onset sepsis among preterm infants in China, 2015-2018: A cohort study.

OBJECTIVE: To describe the incidence, case-fatality rate and pathogen distribution of late-onset sepsis (LOS) among preterm infants in China. To investigate risk factors and short-term outcomes associated with LOS caused by Gram-positive bacteria, Gram-negative bacteria and fungi. METHODS: This cohort study included all infants born at <34 weeks' gestation and admitted to 25 tertiary hospitals in 19 provinces in China from May, 2015 to April, 2018. Infants were excluded who died or were discharged within 3 days of being born. RESULTS: A total of 1199 episodes of culture-positive LOS were identified in 1133 infants, with an incidence of 4.4% (1133/25,725). Overall, 15.4% (175/1133) of infants with LOS died and 10.0% (113/1133) of infants died within 7 days of LOS onset. Among 1214 isolated pathogens, Gram-negative bacteria were the most common (51.8%, 629/1214) and fungi accounted for 17.1% (207/1214). Use of central lines, longer duration of antibiotics and previous carbapenem exposure were related to increased risk of fungal LOS compared with Gram-positive bacteria. Gram-negative bacteria LOS was independently associated with increased risk of death, periventricular leukomalacia, bronchopulmonary dysplasia, and necrotizing enterocolitis. Fungal LOS was independently associated with increased risk of periventricular leukomalacia, bronchopulmonary dysplasia and necrotizing enterocolitis. CONCLUSIONS: Late-onset sepsis was a significant cause of morbidity and mortality in Chinese neonatal intensive care units, with a distinct pathogen distribution from industrial countries. Clinical guidelines on the prevention and treatment of LOS should be developed and tailored to these LOS characteristics in Chinese neonatal intensive care units.

Neonatal Outcomes Following Culture-negative Late-onset Sepsis Among Preterm Infants.

BACKGROUND: Culture-negative late-onset sepsis (LOS) is commonly diagnosed in neonatal intensive care units, while the outcomes of neonatal culture-negative LOS are not reported for large cohorts. This study aimed to examine the incidence and neonatal outcomes for culture-negative LOS in a contemporary multicenter cohort of preterm infants. METHODS: We performed a retrospective analysis of data from a cluster-randomized controlled study. Infants <34 weeks of gestation and admitted to 25 neonatal intensive care units between May 1, 2015, and April 30, 2018, were included. Culture-negative LOS was diagnosed if infants had abnormal manifestations and laboratory tests but negative blood cultures. The primary outcome was a composite of mortality or morbidities including periventricular leukomalacia (PVL), retinopathy of prematurity (ROP) ≥ stage 3 or bronchopulmonary dysplasia (BPD). RESULTS: Of 22,346 eligible infants, 1505 (6.7%) infants had culture-negative and 761 (3.4%) infants had culture-positive LOS. Compared with infants without LOS, infants with culture-negative LOS had higher rates of composite outcome (24.1% vs. 9.6%), death (3.8% vs. 1.8%), PVL (4.8% vs. 2.2%), severe ROP (3.3% vs. 1.1%) and BPD (18.1% vs. 7.0%). After adjustment, culture-negative LOS was independently associated with increased risk of composite outcome {adjusted odds ratio [aOR]: 1.8 [95% confidence interval (CI): 1.5-2.1]}, PVL [aOR: 2.0 (95% CI: 1.4-2.8)] and BPD [aOR: 1.8 (95% CI: 1.5-2.2)] relative to the absence of LOS. CONCLUSION: Culture-negative LOS was frequently diagnosed in preterm infants and was associated with increased risks of adverse outcomes. There is an emerging need for more precise diagnosis and treatment strategies for culture-negative LOS.