Northwest Women's and Children's Hospital

Since December 2019, there has been an outbreak of novel coronavirus (2019-nCoV) infection in China. Two cases of neonates with positive 2019-nCoV tests have been reported. Due to the immature immune system and the possibility of vertical transmission from mother to infant, neonates have become a high-risk group susceptible to 2019-nCoV, which emphasize a close cooperation from both perinatal and neonatal pediatrics. In neonatal intensive care unit (NICU), to prevent and control infection, there should be practical measures to ensure the optimal management of children potentially to be infected. According to the latest 2019-nCoV national management plan and the actual situation, the Chinese Neonatal 2019-nCoV expert working Group has put forward measures on the prevention and control of neonatal 2019-nCoV infection.

None of the authors has any conflicts of interest relevant to the subject matter of the article. The peer review history for this article is available at https://publons.com/publon/10.1111/pedi.13406. This article is an invited review/consensus statement. Data sharing is not applicable.

AIMS: Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries. METHODS: Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex. RESULTS: Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15-24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. CONCLUSION: These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.

Background Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. Methods We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. Results We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. Conclusions TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.).

Blood-based protein biomarkers have recently shown as simpler diagnostic modalities for colorectal cancer, while their association with clinical pathological characteristics is largely unknown. In this study, we not only examined the sensitivity and reliability of single/multiple serum markers for diagnosis, but also assessed their connection with pathological parameters from a total of 279 colorectal cancer patients. Our study shown that glycoprotein carcinoembryonic antigen (CEA) owns the highest sensitivity among single marker in the order of CEA > cancer antigen 72-4 (CA72-4) > cancer antigen 19-9 9 (CA19-9) > ferritin > cancer antigen 125 (CA125), while the most sensitive combined-markers for two to five were: CEA + CA72-4; CEA + CA72-4 + CA125; CEA + CA19-9 + CA72-4 + CA125; and CEA + CA19-9 + CA72-4 + CA125 + ferritin, respectively. We also demonstrated that patients who had positive preoperative serum CEA, CA19-9, or CA72-4 were more likely with lymph node invasion, positive CA125 were prone to have vascular invasion, and positive CEA or CA125 were correlated with perineural invasion. In addition, positive CA19-9, CA72-4, or CA125 was associated with poorly differentiated tumor, while CEA, CA19-9, CA72-4, CA125 levels were positively correlated with pathological tumor-node-metastasis stages. We here conclude that combined serum markers can be used to not only diagnose colorectal cancer, but also appraise the tumor status for guiding treatment, evaluation of curative effect, and prognosis of patients.

Intrauterine hepatitis B virus (HBV) infection has been suggested to be caused by transplacental transmission that cannot be blocked by hepatitis B vaccine. This would decrease the effectiveness of hepatitis B vaccine. This study examined the risk factors and mechanism of transplacental HBV transmission. A case-control study included 402 newborn infants from 402 HBsAg-positive pregnant women. Among these, 15 newborn infants infected with HBV by intrauterine transmission were selected as cases, and the rest as controls. A pathology study included 101 full-term placentas from the HBsAg-positive pregnant women above and 14 from HBsAg-negative pregnant women. Immunohistochemistry staining and HBV DNA in situ hybridization were used to estimate the association of intrauterine HBV infection and HBV infection in the placentas. HBeAg positivity in mothers' sera (OR = 17.07, 95%CI 3.39-86.01) and threatened preterm labor (OR = 5.44, 95%CI 1.15-25.67) were found to be associated with transplacental HBV transmission. The intrauterine infection rate increased linearly and significantly with maternal serum HBsAg titers (trend test P = 0.0117) and HBV DNA concentration (trend test P < 0.01). Results of the pathology study showed that HBV infection rates decreased gradually from the maternal side to the fetal side (trend test P = 0.0009) in the placental cell layers. There was a significant association between intrauterine HBV transmission and HBV infection in villous capillary endothelial cells (VCEC) in the placenta (OR = 18.46, P = 0.0002). The main risk factors for intrauterine HBV infection are maternal serum HBeAg positivity, history of threatened preterm labor, and HBV in the placenta especially the villous capillary endothelial cells. Previous reports of transplacental leakage of maternal blood causing intrauterine infection are confirmed. In addition, there appears to be a "cellular transfer" of HBV from cell to cell in the placenta causing intrauterine infection. This latter hypothesis needs to be confirmed.

Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a phenolic compound found in many medicinal plants traditionally used in China or patent medicine such as Feiyangchangweiyan capsule (FY capsule) for the treatment of gastrointestinal diseases for decades. However, the evidence for the gastroprotective effect of GA is deficient and the pharmacological mechanisms remain limited. The present investigation was initiated to demonstrate the gastroprotective effect and to understand potential underlying mechanism of GA on ethanol-induced gastric ulcer in rats. Gastric ulcers were induced by absolute ethanol (5 mL/kg, i.g.) in male Sprague-Dawley rats, GA (10, 30, and 50 mg/kg), FY capsule (0.4 g/kg) and 30 mg/kg Lansoprazole was administered orally. Physiological saline and lansoprazole were used as negative and positive control, respectively. Induction of rats with ethanol resulted in a significant rise in ulcer index, serum levels of inflammatory cytokines markers (IL-1β, IL-6 and TNF-α), TBARS, protein expression of Bax and Caspase-3 and a significant reduction in the activities or levels of endogenous antioxidants (SOD, CAT and GSH), gastric mucosal protective factors (PGE2 and NO) and protein expression of Bcl-2. Pretreatment with GA showed a remarkable decrease in ulcer index, inflammatory cytokines markers, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants, levels of PGE2 and NO, and protein expression of Bcl-2, Nrf2 and HO-1 when compared with ethanol treated groups. This study demonstrated the gastroprotective effect of Gallic acid and FY capsule on ethanol-induced gastric ulcer in rats. The underlying mechanism of GA and FY capsule against gastric ulcer in rats caused by ethanol might be involved in Nrf2/HO-1 anti-oxidative pathway and ultimately played an anti-apoptotic role through regulating Bax, Bcl-2 and Caspase-3.

Importance: A randomized clinical trial is needed to determine whether the second-generation Abl-tyrosine kinase inhibitor dasatinib is more effective than the first-generation inhibitor imatinib mesylate for childhood Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). Objective: To determine whether dasatinib given at a daily dosage of 80 mg/m2 is more effective than imatinib mesylate at a daily dosage of 300 mg/m2 to improve event-free survival of children with Philadelphia chromosome-positive ALL in the context of intensive chemotherapy without prophylactic cranial irradiation. Design, Setting, and Participants: This open-label, phase 3 randomized clinical trial was conducted at 20 hospitals in China. Enrollment occurred from January 1, 2015, through September 18, 2018, and randomization was stopped on October 4, 2018, when the early stopping criterion of the trial was met. Patients aged 0 to 18 years were recruited. Of the 225 patients with the diagnosis, 35 declined participation and 1 died before treatment, leaving 189 patients available for analysis. Data were analyzed from January 1 through August 4, 2019. Interventions: Patients were randomized to receive daily dasatinib (n = 92) or imatinib (n = 97) continuously for the entire duration of ALL therapy from the time of diagnosis made during remission induction to the end of continuation therapy. Main Outcomes and Measures: The primary outcome was event-free survival, analyzed based on intention to treat. The secondary outcomes were relapse, death due to toxic effects, and overall survival. Results: Among the 189 participants (136 male [72.0%]; median age, 7.8 [interquartile range (IQR), 5.2-11.3] years) and a median follow-up of 26.4 (IQR, 16.3-34.1) months, the 4-year event-free survival and overall survival rates were 71.0% (95% CI, 56.2%-89.6%) and 88.4% (95% CI, 81.3%-96.1%), respectively, in the dasatinib group and 48.9% (95% CI, 32.0%-74.5%; P = .005, log-rank test) and 69.2% (95% CI, 55.6%-86.2%; P = .04, log-rank test), respectively, in the imatinib group. The 4-year cumulative risk of any relapse was 19.8% (95% CI, 4.2%-35.4%) in the dasatinib group and 34.4% (95% CI, 15.6%-53.2%) in the imatinib group (P = .01, Gray test), whereas the 4-year cumulative risk of an isolated central nervous system relapse was 2.7% (95% CI, 0.0%-8.1%) in the dasatinib group and 8.4% (95% CI, 1.2%-15.6%) in the imatinib group (P = .06, Gray test). There were no significant differences in the frequency of severe toxic effects between the 2 treatment groups. Conclusions and Relevance: Intensive chemotherapy including dasatinib at a dosage of 80 mg/m2 per day yielded superior results in the treatment of Philadelphia chromosome-positive ALL compared with imatinib mesylate at a dosage of 300 mg/m2 per day and provided excellent control of central nervous system leukemia without the use of prophylactic cranial irradiation. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-14005706.

OBJECTIVE: To report the performance of massively parallel sequencing (MPS) based prenatal noninvasive fetal trisomy test based on cell-free DNA sequencing from maternal plasma in a routine clinical setting in China. METHOD: The MPS-based test was offered as a prenatal screening test for trisomies 21 and 18 to pregnant women in 49 medical centers over 2 years. A total of 11,263 participants were recruited and the MPS-based test was performed in 11,105 pregnancies. Fetal outcome data were obtained after the expected date of confinement. RESULTS: One hundred ninety cases were classified as positive, including 143 cases of trisomy 21 and 47 cases of trisomy 18. With the karyotyping results and the feedback of fetal outcome data, we observed one false positive case of trisomy 21, one false positive case of trisomy 18 and no false negative cases, indicating 100% sensitivity and 99.96% specificity for the detection of trisomies 21 and 18. CONCLUSION: Our large-scale multicenter study proved that the MPS-based test is of high sensitivity and specificity in detecting fetal trisomies 21 and 18. The introduction of this screening test into a routine clinical setting could avoid about 98% of invasive prenatal diagnostic procedures.

// Shulan Lv 1, * , Qing Wang 1, * , Wanqiu Zhao 2, * , Lu Han 1 , Qi Wang 1 , Nasra Batchu 1 , Qurat Ulain 1 , Junkai Zou 1 , Chao Sun 1 , Jiang Du 1 , Qing Song 1, 3, 4 and Qiling Li 1, 4 1 Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi&rsquo;an Jiaotong University, Xi&rsquo;an, Shaanxi, China 2 Northwest Women&rsquo;s and Children&rsquo;s Hospital, Xi&rsquo;an, Shaanxi, China 3 Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, GA, USA 4 Center of Big Data and Bioinformatics, First Affiliated Hospital, Xi&rsquo;an Jiaotong University, Xi&rsquo;an, Shaanxi, China * Co first authors Correspondence to: Qiling Li, email: liqiling@mail.xjtu.edu.cn Keywords: lymphatic leakage, postoperation, complication, chylous ascites, chylothorax Received: January 04, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: April 11, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: April 20, 2017 ABSTRACT Lymphatic complications are rare, but well-known phenomena, and have been described by many researchers. However, many diagnoses of lymphatic complications are found confusing due to different definition. A literature search in Pubmed was performed for studies postoperative lympatic complications. These complications divided into two parts: lymphatic leakage and lymphatic stasis. This review is about lymphatic leakage, especially, postoperative lymphatic leakage due to the injury of lymphatic channels in surgical procedures. According to polytrophic consequences, many types of postoperative lymphatic leakage have been presented, including lymph ascites, lymphocele, lymphorrhea, lymphatic fistula, chylous ascites, chylothorax, chyloretroperitoneum and chylorrhea. In this review, we focus on the definition, incidence and treatment about most of these forms of lymphatic complications to depict a comprehensive view of postoperative lymphatic leakage. We hold the idea that the method of treatment should be individual and personal according to manifestation and tolerance of patient. Meanwhile, conservative treatment is suitable and should be considered first.

BACKGROUND: The outcome of preterm infants has been varied in different hospitals and regions in developing countries. Regular clinical monitor are needed to know the effects of health care. This study aimed to describe the survival and morbidity rates of extreme to very preterm infants in 15 neonatal-intensive care hospitals in China. METHODS: Data were collected from January 1, 2013 to December 31, 2014 for preterm neonates with gestational age (GA) between 24 and 31 complete weeks born in hospitals from our collaborative study group. The primary outcomes were survival and major morbidities prior to hospital discharge. Major morbidities included bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) and sepsis. Mutivariate logistic regression was used to analyze the risk factor influencing on the outcomes. RESULTS: The preterm birth rate was 9.9 % (13 701/138 240). The proportion of extreme to very preterm infants was 1.1 % and 11.8 % respectively. The survival rate prior to discharge was increased with increasing GA (0, 24 weeks; 28 %, 25 weeks; 84.8 %, 26 weeks; 83.5 %, 27 weeks; 87.4 %, 28 weeks; 90.7 %, 29 weeks; 93.9 %, 30 weeks; 96 %, 31 weeks). Rate of survival and without severe morbidity according to GA were 0 at 24 weeks, 8 % at 25 weeks, 60.6 % at 26 weeks; 53.2 % at 27 weeks; 62.3 % at 28 weeks; 67.9 % at 29 weeks; 79.1 % at 30 weeks, 85.8 % at 31 weeks respectively. Rate of antenatal steroid use was 56 %. The antenatal steroid use was lower in GA < 28 weeks infants than that in GA between 28 and 32 weeks (28-44.3 % vs 49.7-60.1 %, P < 0.05). Infants at the lowest GAs had a highest incidence of morbidities. Overall, 58.5 % had respiratory distress syndrome, 12.5 % bronchopulmonary dysplasia, 3.9 % necrotizing enterocolitis, 15.4 % intraventricular hemorrhage, 5.4 % retinopathy of prematurity, 28.4 % patent ductus arteriosus, and 9.7 % sepsis. Mortality and morbidity were influenced by gestational age (OR = 0.891, 95 % CI: 0.796-0.999, p = 0.0047 and OR = 0.666, 95 % CI: 0.645-0.688, p = 0.000 respectively), birth weight (OR = 0.520, 95 % CI: 0.420-0.643, p = 0.000 and OR = 0.921, 95 % CI: 0.851-0.997, p = 0.041 respectively), SGA (OR = 1.861, 95 % CI: 1.148-3.017, p = 0.012 and OR = 1.511, 95 % CI: 1.300-1.755, p = 0.000 respectively), Apgar score <7 at 5 min (OR = 1.947, 95 % CI: 1.269-2.987, p = 0.002 and OR = 2.262, 95 % CI: 1.950-2.624, p = 0.000 respectively). The survival rate was increased with more prenatal steroid use (OR = 1.615, 95 % CI: 1.233-1.901, p = 0.033). CONCLUSION: Although most of the preterm infants with GAs ≥26 weeks survived, a high complication in survivors still can be observed. Rate of survival of GAs less than 26 weeks was still low, and quality improvement methods should be used to look into increasing the use of antenatal steroids in the very preterm births.

// Zhanwei Zhao 1 , Quanxin Feng 1 , Zifang Yin 2 , Jianbo Shuang 3 , Bin Bai 1 , Pengfei Yu 1 , Min Guo 1 and Qingchuan Zhao 1 1 Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi&prime;an, China 2 Department of Obstetrics, Northwestern Women and Children&rsquo;s Hospital, Xi&prime;an, China 3 Department of General Surgery, Chinese PLA 323 Hospital, Xi&prime;an, China Correspondence to: Qingchuan Zhao, email: zhaoqc@fmmu.edu.cn Keywords: nutrition, red meat, processed meat, colorectal cancer, meta-analysis Received: December 28, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: June 09, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: September 06, 2017 ABSTRACT The associations between red and processed meat consumption and the risk of colorectal cancer types have not been conclusively defined. We performed a systematic review and meta-analysis to analyze these associations. We searched PubMed and EMBASE to identify studies published from inception through September 2016. Dose-response, subgroup and subtype analyses of colorectal cancer (colon cancer, proximal colon cancer, distal colon cancer and rectal cancer) were performed. We ultimately selected 60 eligible studies. Positive associations were observed for colorectal cancer in case-control studies (red meat, P &lt;0.01; processed meat, P &lt;0.01) and cohort studies (red meat, P &lt;0.01; processed meat, P &lt;0.01). However, subtype analyses yielded null results for distal colon cancer in case-control studies ( P =0.41) and cohort studies ( P =0.18) for red meat and null results for proximal colon cancer in case-control studies ( P =0.13) and cohort studies ( P =0.39) for processed meat. Additionally, although the results of case-control studies were positive (red meat, P &lt;0.01; processed meat, P =0.04) for rectal cancer, there were no positive associations between red ( P =0.34) and processed meat ( P =0.06) consumption and the risk in cohort studies. In a systematic review and meta-analysis, we found consumption of red and processed meat was associated with the risk of overall colorectal cancer but not rectal cancer. Additionally, there were no associations between the consumption of red meat and distal colon cancer risk and between the consumption of processed meat and proximal colon cancer risk.

BackgroundRelatively few studies have been made on neurobehavioral outcomes of prenatal maternal stress during the newborn period, and little research has focused on umbilical cord stress hormones including cortisol, adrenocorticotropic hormone (ACTH), norepinephrine, and epinephrine. Our objective was to investigate the effects of prenatal maternal life stressors on neonatal birth outcomes, neurobehavioral development, and stress-related hormones levels.MethodsParticipants were 142 mothers and their infants; 71 were selected as the prenatal life stressor exposed group and 71 as the control group matched on maternal age, gestational week, delivery type, socioeconomic and education status, and newborns' sex. Maternal life stressors during pregnancy were determined using the Life Events Scale for Pregnant Women. Neonatal neurobehavioral development was assessed with the Neonatal Behavioral Neurological Assessment. Umbilical cord plasma stress-related hormones, including ACTH, cortisol, norepinephrine, and epinephrine were measured using an enzyme-linked immunosorbent assay.ResultsIn the prenatal life stressors exposed group, newborns had significantly lower birth weight, smaller head circumference (p < 0.01, p < 0.01, respectively). Scores of Neonatal Behavioral Neurological Assessment were significantly reduced (p < 0.001). Cord plasma ACTH, norepinephrine, and epinephrine levels were significantly increased (p < 0.001), but cortisol levels were reduced (p < 0.001).ConclusionPrenatal maternal stress may negatively affect fetal birth outcomes, neurobehavioral development and affect neonates' cord plasma ACTH, cortisol, norepinephrine, and epinephrine. Relatively few studies have been made on neurobehavioral outcomes of prenatal maternal stress during the newborn period, and little research has focused on umbilical cord stress hormones including cortisol, adrenocorticotropic hormone (ACTH), norepinephrine, and epinephrine. Our objective was to investigate the effects of prenatal maternal life stressors on neonatal birth outcomes, neurobehavioral development, and stress-related hormones levels. Participants were 142 mothers and their infants; 71 were selected as the prenatal life stressor exposed group and 71 as the control group matched on maternal age, gestational week, delivery type, socioeconomic and education status, and newborns' sex. Maternal life stressors during pregnancy were determined using the Life Events Scale for Pregnant Women. Neonatal neurobehavioral development was assessed with the Neonatal Behavioral Neurological Assessment. Umbilical cord plasma stress-related hormones, including ACTH, cortisol, norepinephrine, and epinephrine were measured using an enzyme-linked immunosorbent assay. In the prenatal life stressors exposed group, newborns had significantly lower birth weight, smaller head circumference (p < 0.01, p < 0.01, respectively). Scores of Neonatal Behavioral Neurological Assessment were significantly reduced (p < 0.001). Cord plasma ACTH, norepinephrine, and epinephrine levels were significantly increased (p < 0.001), but cortisol levels were reduced (p < 0.001). Prenatal maternal stress may negatively affect fetal birth outcomes, neurobehavioral development and affect neonates' cord plasma ACTH, cortisol, norepinephrine, and epinephrine.

BACKGROUND: The study is intended to fill the knowledge gap about the neuropsychology and neuromotor developmental outcomes, and identify the perinatal risk factors for late preterm infants (LPIs 34~36 weeks GA) born with uncomplicated vaginal birth at the age of 24 to 30 months. METHODS: The parents/guardians of 102 late preterm infants and 153 term infants, from 14 community health centers participated in this study. The Modified Checklist for Autism in Toddlers (M-CHAT) questionnaire, the Chinese version of Gesell Development Diagnosis Scale (GDDS), and the Sensory Integration Schedule (SIS), a neurological examination for motor disorders (MD) were carried out. Infants screening positive to the M-CHAT were referred to specialist autism clinics. RESULTS: Forty-six LPIs (45.1%) scored low in GDDS. Nine LPIs (8.8%) scored positive on M-Chat. 8.8% of LPIs (9 out of 102) were diagnosed MD (p < 0.05). Compared with their full-term peers, LPIs had statistically lower scores in GDDS and the Child Sensory Integration Checklist. LPIs who had positive results on M-CHAT showed unbalanced abilities in every part of GDDS. Risk factors of twin pregnancies, pregnancy induced hypertension and premature rupture of membranes had negative correlation with GDDS (all p < 0.05). Birth weight and gestational age were positively correlated with GDDS. CONCLUSIONS: LPIs shall be given special attention as compared to normal deliveries, as they are at increased risk of neurodevelopment impairment, despite being born with no major problems. Some perinatal factors such as twin pregnancies, and pregnancy induced hypertension etc. have negative effects on their neurodevelopment. Regular neurodevelopmental follow- up and early intervention can benefit their long term outcomes.

BACKGROUND: The cross-talk between RNA binding proteins (RBPs) and microRNAs (miRNAs) in the regulation of gene expression is a complex process. Here, we describe a new mode of regulation of TRIM25 expression mediated by an antagonistic interplay between IGF2BP3 and miR-3614-3p. METHODS: The expression level of TRIM25, IGF2BP3, pri-miR-3614 and miR-3614-3p in breast cancer (BC) tissues, non-tumor tissues and BC cell lines were detected by qRT-PCR, Western blot and Immunohistochemistry (IHC). Binding of miR-3614-3p and IGF2BP3 to TRIM25 RNA was verified using luciferase activation assays, RNA immunoprecipitation (RIP) and biotin pull-down assays. In vitro and in vivo loss- and gain-of-function studies were performed to reveal the effects and related mechanism of IGF2BP3-miR-3614-3p-TRIM25 axis in in breast cancer cells proliferation. FINDINGS: We found that an intragenic miRNA-3614-3p inhibits the expression of its host gene TRIM25 by binding to its 3'- untranslated region (UTR). Interestingly, IGF2BP3 can competitively occupy this binding site and inhibit miRNA-3614 maturation, thereby protecting TRIM25 mRNA from miR-3614-mediated degradation. The overexpression of miR-3614-3p dramatically inhibited breast cancer cell growth through the downregulation of TRIM25. Furthermore, the silencing of IGF2BP3 reduced TRIM25 expression, suppressed cell proliferation, and exhibited a synergistic effect with miR-3614-3p overexpression. INTERPRETATION: Collectively, these results demonstrate that control of TRIM25 RNA by an interplay between IGF2BP3 and miR-3614-3p represents a mechanism for breast cancer cell proliferation. FUND: The scientific research and sharing platform construction project of Shaanxi Province, Opening Project of Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, China Postdoctoral Science Foundation and The National Natural Science Foundation of China.

BACKGROUND: The first 18 months of life are the most important for long-term childhood well-being. Anemia and malnutrition occurring in this key period have serious implications for individuals and societies, especially in rural areas in developing country. We conducted a cross-sectional study as the baseline survey to provide data for developing a policy-based approach to controlling infant anemia and malnutrition in rural areas of Shaanxi province in northwestern China. METHODS: We randomly sampled 336 infants aged 0-18 months in 28 rural villages from 2 counties of Shaanxi province. Anthropometric measurements and household interviews were carried out by well-trained researchers. The hemoglobin concentration was measured for 336 infants and serum concentrations of iron, zinc, and retinol (vitamin A) were measured for a stratified subsample of 55 infants. Anemia was defined using World Health Organization (WHO) standards combined with the Chinese standard for infants<6 months old. Logistic regression modeling was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for anemia with non-anemic group as a reference. RESULTS: We found that 35.12% of infants in rural Shaanxi suffered from anemia, and the malnutrition prevalence rates were 32.14% for underweight, 39.58% for stunting, and 11.31% for wasting. Anemia was significantly associated with malnutrition (underweight, OR: 2.42, 95%CI: 1.50-3.88; stunting, OR: 1.65, 95%CI: 1.05-2.61; wasting, OR: 2.89, 95%CI: 1.45-5.76). Low birth weight, more siblings, less maternal education, low family income, crowded living conditions, and inappropriate complementary food introduction significantly increased the risk for infant anemia. Serum concentrations of iron, zinc, and retinol (vitamin A) were significantly lower in anemic infants compared with non-anemic infants. CONCLUSIONS: Specific socio-demographic characteristics and feeding patterns were highly associated with infant anemia in rural areas of Shaanxi province. Health education focusing on feeding practices and nutrition education could be a practical strategy for preventing anemia and malnutrition in young children.

To evaluate the genetic variability of human parvovirus B19, the complete coding region of the VP1/VP2 structural proteins of 29 B19 isolates obtained from 25 infected patients were sequenced and compared with each other and with two previously published B19 isolates. The VP1/VP2 gene was amplified by PCR using B19-specific oligonucleotide primers and the amplification products were sequenced directly. Overall, the average nucleotide and predicted amino acid identity among B19 isolates was high. Sequential virus isolates from the same cases and isolates obtained from two cases linked by transmission in the same household were essentially identical. Sequence variation was minimal among isolates obtained from a single community-wide B19 outbreak, ranging between 0 and 10 (0.4%) base substitutions, although there appeared to be more than one genetic lineage circulating in the outbreak. A comparison with 18 additional isolates from distinct epidemiological settings found greater variability. These isolates differed from each other by between 11 (0.5%) and 112 (4.8%) base substitutions. B19 isolates from Xi'an, China, were significantly different from other isolates at both the nucleotide and amino acid levels, and were more closely related to a single isolate from Japan, obtained 10 years earlier, than to isolates from other countries. Isolates examined in this study included distinct genotypes from patients with similar clinical presentations and similar genotypes from patients with diverse clinical presentations. These data suggest that geographically defined genetic lineages of B19 may exist and that no particular B19 genotype was associated with a particular clinical outcome.

cause familial or sporadic female infertility via a phenotype that we term "oocyte death." The mutations, which are associated with oocyte death, alter the PANX1 glycosylation pattern, influence the subcellular localization of PANX1 in cultured cells, and result in aberrant PANX1 channel activity, ATP release in oocytes, and mutant PANX1 GLY1. Overexpression of a patient-derived mutation in mice causes infertility, recapitulating the human oocyte death phenotype. Our findings demonstrate the critical role of PANX1 in human oocyte development, provide a genetic explanation for a subtype of infertility, and suggest a potential target for therapeutic intervention for this disease.

Importance: Patients with hypertrophic obstructive cardiomyopathy (HOCM) and drug-refractory symptoms and outflow gradients have limited nonsurgical treatment options. The feasibility of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) has been reported previously; however, procedural and medium-term outcomes are unknown. Objective: To describe the safety and medium-term outcomes of PIMSRA in a large patient cohort with drug-refractory HOCM. Design, Setting, and Participants: This was a single-arm, open-label study of PIMSRA in patients with drug-refractory HOCM. Patients presenting to the Xijing Hospital in Xi'an, China, between October 2016 to June 2020 with hypertrophic cardiomyopathy. Of 1314 patients presenting with HOCM, 244 fulfilled inclusion criteria of severe resting/provoked outflow gradients of 50 mm Hg or higher, and symptoms of New York Heart Association functional class of II or higher refractory to maximum tolerated medications. After discussion among the heart team, 40 patients underwent surgical or alcohol septal reduction therapy and 4 required treatment of significant coronary artery disease. Interventions: PIMSRA performed in patients. Main Outcomes and Measures: The primary outcome was 30-day major adverse clinical events: death, emergency surgery, severe effusion requiring intervention, procedure-related stroke, bleeding, and stroke. Secondary outcomes included 30-day technical success and 90-day improvement in outflow obstruction. Results: The mean (SD) age of 200 patients was 46.9 (14.0) years, and 125 (62.5%) were men. Resting or provoked left ventricular outflow tract gradients were 50 mm Hg or higher. The median (IQR) follow-up for all patients was 19 (6-50) months. Thirty-day major adverse clinical events rate was 10.5% (n = 21): there were 2 in-hospital/30-day deaths (1.0%), 7 patients (3.5%) with pericardial effusion requiring mini-thoracotomy, 12 patients (6%) with pericardial effusion requiring pericardiocentesis, and no bleeding or strokes. Other periprocedural complications included permanent right bundle branch block in 5 patients (2.5%), resuscitated ventricular fibrillation in 2 (1.0%), and septal branch aneurysm in 2 (1.0%). There were no permanent pacemaker implantations. At follow-up, maximum septal thickness was reduced from a mean (SD) of 24.0 (5.1) mm to 17.3 (4.4) mm (P < .001), and left ventricular outflow tract gradient was decreased from a mean (SD) of 79.0 (53.0) mm Hg to 14.0 (24.0) mm Hg (P < .001). Overall, 190 patients (96%) with HOCM were in New York Heart Association functional class I or II at last follow-up. Conclusions and Relevance: This study found that PIMSRA in patients with drug-refractory HOCM may be an effective procedure for relief of left ventricular outflow tract obstruction and symptoms with acceptable complication rates. These results are encouraging and support the design of a randomized clinical trial against well-established septal reduction therapies.

OBJECTIVE: To evaluate the usefulness of a fasting plasma glucose (FPG) at 24-28 weeks' gestation to screen for gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The medical records and results of a 75-g 2-h oral glucose tolerance test (OGTT) of 24,854 pregnant women without known pre-GDM attending prenatal clinics in 15 hospitals in China were examined. RESULTS: FPG cutoff value of 5.1 mmol/L identified 3,149 (12.1%) pregnant women with GDM. FPG cutoff value of 4.4 mmol/L ruled out GDM in 15,369 (38.2%) women. With use of this cutoff point, 12.2% of patients with mild GDM will be missed. The positive predictive value is 0.322, and the negative predictive value is 0.928. CONCLUSIONS: FPG at 24-28 weeks' gestation could be used as a screening test to identify GDM patients in low-resource regions. Women with an FPG between ≥4.4 and ≤5.0 mmol/L would require a 75-g OGTT to diagnose GDM. This would help to avoid approximately one-half (50.3%) of the formal 75-g OGTTs in China.