Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective　To explore the characteristics of toxic heavy metal pollution in atmospheric PM2.5 (Particulate matter 2.5) during winter in Nanning City and to evaluate the health risks for the population. Methods　Atmospheric PM2.5 samples were continuously collected in the urban areas of Nanning from January to February 2019. The concentrations of seven toxic heavy metals, including cadmium (Cd), arsenic (As), chromium (Cr), lead (Pb), nickel (Ni), mercury (Hg), and manganese (Mn) in atmospheric PM2.5 were analyzed by X-ray fluorescence spectrometry. The pollution characteristics of toxic heavy metals were studied by geo-accumulation index and enrichment factor methods, and their health risks to children and adults were assessed using the health risk assessment model of the United States Environmental Protection Agency. Results　The mass concentration of atmospheric PM2.5 in Nanning in winter 2019 was (44±29) μg/m3, which was generally at a low level. Different degrees of pollution were found for Hg, Cd, As, Cr, and Pb in PM2.5, with Hg and Cd being more seriously polluted. Hg and Cd were highly enriched in PM2.5, followed by Pb with moderate enrichment. These three elements mainly originated from man-made pollution. As, Cr and Ni were mildly enriched and affected by both natural and anthropogenic sources. The non-carcinogenic risks were in the order of As>Pb>Hg>Cr>Cd>Mn>Ni. The total non-carcinogenic risks for the three populations were all less than 1, which is within acceptable limits. The carcinogenic risks were ranked as Cr>As>Cd>Ni, with Cr, As, and Cd posing carcinogenic risks to children and adults ranging from 1×10-6 to 1×10-4. Moreover, the total carcinogenic risks of heavy metals (Cr, As, Cd, and Ni) were higher than 1×10-4 for children, indicating a potential carcinogenic risk. Conclusions　The mass concentration of PM2.5 and heavy metal elements in Nanning City during the winter of 2019 was relatively low, but the pollution of heavy metals still exists. The non-carcinogenic risk of heavy metals is within an acceptable range, but the carcinogenic risk poses a potential danger to children.

ObjectiveTo explore the mechanism of Cangxi Tongbi capsules （CXTB） in regulating the p38 mitogen-activated protein kinase （p38 MAPK）/NOD-like receptor protein 3 （NLRP3）/cysteine protease-1 （Caspase-1） signaling pathway to inhibit pyroptosis of cartilage cells in knee osteoarthritis （KOA）. MethodSixty male SD rats were randomly divided into a sham operation group， a model group， low， medium， and high dose CXTB groups， and a positive control group， with 10 rats per group. The modified Hulth method was employed to establish a rat model of KOA. According to their respective assignments， rats were administered CXTB （0.25， 0.5， 1.0 g·kg^-1） and Celecoxib （24 mg·kg^-1） by gavage. The sham operation and model groups were given an equivalent volume of physiological saline. Treatment was performed once daily for 28 days. Micro-computed tomography （Micro-CT） was used to assess bone volume/total volume （BV/TV） and trabecular separation （Tb.Sp）. Joint degeneration was evaluated through hematoxylin-eosin （HE） staining， safranin-fast green （SO） staining， and Osteoarthritis Research Society International （OARSI） scoring. Western blot analysis was conducted to measure the expression levels of p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， NLRP3， Caspase-1， and gasdermin D （GSDMD） proteins. Real-time PCR was used to assess mRNA expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD genes. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum concentrations of inflammatory cytokines including tumor necrosis factor-alpha （TNF-α）， interleukin-1 beta （IL-1β）， and interleukin-18 （IL-18）. After knee replacement surgery， cartilage tissue was analyzed using Western blot to assess the protein expression levels of p38 MAPK， p-p38 MAPK， NLRP3， Caspase-1， and GSDMD， and Real-time PCR was used to evaluate gene expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD. ResultMicro-CT analysis revealed significant narrowing of the joint space and increased bone spur formation in KOA rats compared with the sham operation group， with a decrease in BV/TV ratio and an increase in Tb.Sp value （P<0.01）. Serum levels of TNF-α， IL-1β， and IL-18 were elevated （P<0.01）. The protein expression levels of p-p38 MAPK， NLRP3， Caspase-1， and GSDMD in cartilage were significantly increased （P<0.01）， and the mRNA expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD were also enhanced （P<0.01）. Significant differences in protein expression of p-p38 MAPK， NLRP3， Caspase-1， and GSDMD were observed between normal and diseased cartilage tissues after knee replacement surgery （P<0.05）， and the gene expression of p38 MAPK， NLRP3， Caspase-1， and GSDMD were also significantly different （P<0.01）. HE and SO staining showed roughened joint surfaces， reduced cartilage thickness， and disordered cellular arrangement in KOA rats. OARSI scores were significantly higher （P<0.01）. Compared with the model group， treatment with low， medium， and high concentrations of CXTB resulted in increased BV/TV ratios and decreased Tb.Sp values in the knee joints of rats （P<0.01）. HE and SO staining indicated a trend towards smoother joint surfaces and reduced OARSI scores （P<0.01）. The protein expression levels of p-p38 MAPK， NLRP3， Caspase-1， and GSDMD were notably decreased （P<0.05）， as were the mRNA expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD （P<0.01）. Additionally， serum concentrations of TNF-α， IL-1β， and IL-18 were significantly reduced （P<0.01）. ConclusionCXTB intervention may alleviate knee joint degeneration in KOA rats and inhibit the expression of inflammatory factors and pyroptosis of cartilage cells， thereby protecting cartilage. The underlying mechanism may involve modulation of the p38 MAPK/NLRP3/Caspase-1 signaling pathway.

Objective To investigate clinical features and risk factors of childhood diabetes mellitus(DM)complicated with urinary tract infection(UTI).Methods The data of 160 children with DM in our hospital in the past 2 years were collected as the research object,and they were divided into the UTI group and the non-UTI group UTI,with 80 cases in each group.The clinical data of children with DM and UTI were collected and analyzed,including DM type,sex,age,body mass index(BMI),living environment,duration of disease,length of hospital stay,indwelling catheter,ketoacidosis,antibiotic and insulin use,the types of bacteria isolated from urine samples and various laboratory indicators on admission.Results Pathogen bacteria mainly included Escherichia coli(n=37,46.2%),Enterococci(n=21,26.2%)and Klebsiella pneumoniae(n=9,11.2%)in the UTI group.Univariate analysis showed that there were significant differences in obesity,duration of disease,length of hospital stay,indwelling catheter,ketoacidosis,antibiotic use,glycosylated hemoglobin(HbA1c),albumin(ALB)and serum creatinine(Cr)between the two groups(P＜0.05).Multivariate regression analysis showed that risk factors for DM complicating UTI included prolonged hospitalization(OR=2.087,95%CI:1.562-2.789),indwelling urinary catheter(OR=15.886,95%CI:2.336-108.007),ketoacidosis(OR=9.300,95%CI:1.169-73.992),duration of disease≥36 months(OR=20.548,95%CI:2.425-174.119),increased HbA1c(OR=16.686,95%CI:3.666-75.955)and serum Cr(OR=1.010,95%CI:1.002-1.019),while the increased serum ALB(OR=0.799,95%CI:0.702-0.910)was its protective factor.Conclusion Pathogenic bacteria in the UTI group are mainly Escherichia coli.Children with DM and UTI are closely related to the length of hospitalization,indwelling catheter,ketoacidosis,duration of disease,HbA1c,serum Cr and ALB levels.

21-hydroxylase deficiency(21-OHD) is mainly characterized by cortisol deficiency with or without aldosterone deficiency and hyperandrogenemia.The disease requires lifelong exogenous glucocorticoid/salt supplementation.Excessive doses of exogenous glucocorticoids are often needed to control hyperandrogenemia, but the effect is not satisfactory.Corticotropin releasing factor (CRF) type 1 receptor antagonist can directly block the production of adrenocorticotropin, inhibit the generation of adrenogenic androgen, reduce the dose of glucocorticoid therapy, and thus lower the incidence of adverse reactions.In this article, the current research progress on 21-OHD therapy and CRF1 receptor antagonist was reviewed.

The hypothalamic-pituitary-thyroid axis gradually becomes mature at gestational age of 30~35 weeks.With the improvement of the treatment level of premature infants, the gestational age of surviving premature infants gradually decreases, and the thyroid axis of young premature infants is immature.Meanwhile, premature infants are more prone to systemic complications, such as ischemia and hypoxia, severe infection, etc., which aggravate the influence on thyroid.Clinically, more and more premature infants are found to be complicated with congenital hypothyroidism, temporary hypothyroxemia, hyperthyrotropin, delayed thyrotropin elevation, low T 3 syndrome and other problems.Abnormal thyroid function affects the outcome of the treatment of premature infant diseases.Early detection and early treatment is the key to improve the treatment, metabolism and the development of premature infant.At present, the timing of screening and treatment of premature thyroid disease is still controversial.In this review, the thyroid function and outcome of premature infants under different pathological conditions are summarized and analyzed to provide a reliable basis for rational selection of screening opportunities and treatment strategies for thyroid diseases in clinical practice.

Antibodies, Antiphospholipid ; Antiphospholipid Syndrome ; Female ; Humans ; Killer Cells, Natural ; Pregnancy ; Pregnancy Complications

Objective:To systematically evaluate the effects of oral stimulation combined with non-nutritional sucking on premature infants feeding.Methods:From the establishment of the databases to December 14, 2020, PubMed, Embase, Cochrane Library and SinoMed, CNKI, Wanfang databases were searched for randomized controlled trials (RCT) on oral stimulation combined with non-nutritive sucking in preterm infants. The gestational age (GA) of the infants was 26~37 w.The control group received routine nursing or sham treatment and the intervention group received oral stimulation and non-nutritional sucking on the basis of routine nursing. The intervention strategy included infant oral motor intervention and oral sensorimotor intervention. The literature were reviewed and the quality of RCTs evaluated. RevMan 5.3 software was used for meta-analysis.Results:A total of 20 RCTs were included, including 1 316 premature infants (GA 26~36 w). Compared with the control group, the intervention group had significantly shorter duration of hospital stay ( WMD=-3.45, 95% CI -4.41~-2.50, P<0.001). Significant differences existed in the corrected GA of discharge ( WMD=-0.68, 95% CI -1.10~-0.26, P=0.001), the age of total oral feeding(TOF) ( WMD=-5.22, 95% CI -9.04~-1.40, P=0.007), corrected GA of TOF ( WMD=-1.02, 95% CI -1.40~-0.64, P<0.001) and the body weight on TOF day ( WMD=-59.75, 95% CI -114.55~-4.95, P=0.030). Conclusions:Oral stimulation combined with non-nutritive sucking can accelerate TOF and shorten hospital stay in premature infants. The procedure should be standardized and promoted as routine and standard care for premature infants.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Nitric oxide is an endothelium-derived relaxing factor, which has the effect of dilating pulmonary vessels and reducing pulmonary artery pressure.Currently, inhaled nitric oxide has been widely used in the treatment of persistent pulmonary hypertension in term infants and late preterm infants, but its use in the field of preterm infants is still controversial.In recent years, there have been more and more studies on inhaled nitric oxide in premature infants.This review summarized the relevant studies at home and abroad in recent years, discussed the indications of inhaled nitric oxide in premature infants, and introduced the potential adverse reactions, in order to provide guidance for clinical work.