Objective:To observe changes in intestinal flora in children with anorexia and the effects of pediatric Tuina(Chinese therapeutic massage)on their intestinal flora,and to explore the relationship between alterations in intestinal flora and anorexia,as well as the therapeutic mechanisms of pediatric Tuina in treating children with anorexia.Methods:A total of 60 healthy children who underwent physical examinations were recruited as the blank group.One hundred and twenty children with anorexia were randomly divided into a Tuina group and a medication group,with 60 children in each group,according to the random number table method.The blank group received no intervention;the Tuina group was treated with pediatric Tuina therapy;the medication group was treated with Jian Wei Xiao Shi(stomach-invigorating and digestion-promoting)tablets.Both groups underwent continuous treatment for 7 d as one course,with a 1-day rest period between courses,for a total of 4 courses.Fecal samples were collected from the three groups.The intestinal flora was detected using the 16S rDNA method.Results:Before treatment,compared to the blank group,the abundance of Firmicutes in the Tuina and medication groups was significantly lower(P<0.05).After treatment,the abundance of Firmicutes in the Tuina group was significantly increased compared to before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05);in the medication group,there was a trend of increased abundance of Firmicutes,but there was no significant difference compared to that before treatment in the same group(P>0.05),and the difference compared to the blank group remained significant(P<0.05).Before treatment,compared to the blank group,the abundance of Faecalibacterium prausnitzii(F.prausnitzii)in the Tuina and medication groups was significantly lower(P<0.05).After treatment,the abundance of F.prausnitzii in the Tuina group was significantly increased compared to before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05);in the medication group,there was a trend of increased abundance of F.prausnitzii,but no significant difference was showed compared to before treatment in the same group(P>0.05),and the differences compared to the blank and Tuina groups were significant(P<0.05).Before treatment,compared to the blank group,the abundance of Eubacterium in the Tuina and medication groups was significantly lower(P<0.05);after treatment,the abundance of Eubacterium in both Tuina and medication groups was significantly increased compared to that before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05).Before treatment,compared to the blank group,the abundance of Roseburia in the Tuina and medication groups was significantly lower(P<0.05);after treatment,the abundance of Roseburia in both Tuina and medication groups was significantly increased compared to that before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05).Conclusion:The reduction of beneficial intestinal flora may be involved in the pathogenesis of pediatric anorexia.Pediatric Tuina can promote the recovery of intestinal flora balance by increasing the abundance of beneficial flora.

Objective:To observe changes in intestinal flora in children with anorexia and the effects of pediatric Tuina(Chinese therapeutic massage)on their intestinal flora,and to explore the relationship between alterations in intestinal flora and anorexia,as well as the therapeutic mechanisms of pediatric Tuina in treating children with anorexia.Methods:A total of 60 healthy children who underwent physical examinations were recruited as the blank group.One hundred and twenty children with anorexia were randomly divided into a Tuina group and a medication group,with 60 children in each group,according to the random number table method.The blank group received no intervention;the Tuina group was treated with pediatric Tuina therapy;the medication group was treated with Jian Wei Xiao Shi(stomach-invigorating and digestion-promoting)tablets.Both groups underwent continuous treatment for 7 d as one course,with a 1-day rest period between courses,for a total of 4 courses.Fecal samples were collected from the three groups.The intestinal flora was detected using the 16S rDNA method.Results:Before treatment,compared to the blank group,the abundance of Firmicutes in the Tuina and medication groups was significantly lower(P<0.05).After treatment,the abundance of Firmicutes in the Tuina group was significantly increased compared to before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05);in the medication group,there was a trend of increased abundance of Firmicutes,but there was no significant difference compared to that before treatment in the same group(P>0.05),and the difference compared to the blank group remained significant(P<0.05).Before treatment,compared to the blank group,the abundance of Faecalibacterium prausnitzii(F.prausnitzii)in the Tuina and medication groups was significantly lower(P<0.05).After treatment,the abundance of F.prausnitzii in the Tuina group was significantly increased compared to before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05);in the medication group,there was a trend of increased abundance of F.prausnitzii,but no significant difference was showed compared to before treatment in the same group(P>0.05),and the differences compared to the blank and Tuina groups were significant(P<0.05).Before treatment,compared to the blank group,the abundance of Eubacterium in the Tuina and medication groups was significantly lower(P<0.05);after treatment,the abundance of Eubacterium in both Tuina and medication groups was significantly increased compared to that before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05).Before treatment,compared to the blank group,the abundance of Roseburia in the Tuina and medication groups was significantly lower(P<0.05);after treatment,the abundance of Roseburia in both Tuina and medication groups was significantly increased compared to that before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05).Conclusion:The reduction of beneficial intestinal flora may be involved in the pathogenesis of pediatric anorexia.Pediatric Tuina can promote the recovery of intestinal flora balance by increasing the abundance of beneficial flora.

Objective:To study the clinical features and treatment strategy of neonatal ureaplasma meningitis.Methods:During 2021, the clinical data of 2 neonates with ureaplasma meningitis treated in Children's Hospital of Hunan Province were retrospectively analyzed. Literature on this subject were searched in the following databases: CNKI, Wanfang Database, Chinese Medical Journal Full-Text Database, CQVIP database, SinoMed, PubMed, Embase and Web of Science (up to March 2022). The key words included “infant”, “neonate”, “newborn”, “ureaplasma”, “mycoplasma urealytium”, “meningitis”, “central nervous system infection”, “brain”. The clinical data, treatment and prognosis of patients from the literature were summarized.Results:Case 1, female, gestational age(GA) 33 +3 weeks, intracranial hemorrhage (ICH) and ventricular dilatation were found on 2 d after birth. The cerebrospinal fluid (CSF) routine and biochemistry tests indicated meningitis, but the CSF culture was negative. No improvement after antibiotic treatment. CSF metagenomic next-generation sequencing (mNGS) and 23S rRNA showed Ureaplasma urealyticum on 30 d after birth. The patient was treated with doxycycline (DOX) for 21 d until mNGS turned negative and DOX was discontinued. However, the disease recurred 23 d later and erythromycin was added with DOX as combined therapy. The patient was followed up until 6 months without neurodevelopmental disabilities. Case 2, male, GA 26 weeks, ICH and ventricular dilatation were found on 10 d after birth. The CSF routine and biochemistry tests indicated meningitis, but the CSF culture was negative. No improvement after antibiotic treatment. CSF mNGS and 23S rRNA showed Ureaplasma parvum. The patient received erythromycin therapy for 32 d and had normal neurodevelopment at 5 months. According to the literature, 43 cases were reported including the 2 cases descirbed above, 17 cases were full-term infants and 26 cases were preterm infants. The median CSF leukocytes, glucose and proteins were 566 cells/mm 3, 0.2 mmol/L and 2.2 g/L. 27 cases were diagnosed based on CSF culture, 6 cases using mNGS, 4 cases with both CSF culture and PCR method and 6 cases with other methods. Macrolides alone were used in 14 cases, macrolides combined with another antibiotic were used in 8 cases, non-macrolide antibiotics were used in 9 cases and 12 cases didn't receive any anti-ureaplasma therapy. All 17 term infants survived, however, 8 cases with hydrocephalus. Among the 26 preterm infants, 8 patients died, 18 patients had periventricular-intraventricular hemorrhage and 15 patients had hydrocephalus. Conclusions:Neonatal ureaplasma meningitis has significantly lower CSF glucose level with hydrocephalus as the common complication. For intracranial infections of unknown etiology and no response to treatment, mNGS is helpful in determining the pathogen.Neonatal ureaplasma meningitis should be treated with macrolides alone or as add-on therapy.

Objective:To develop a self-made plasma quality control material for non-invasive prenatal testing (NIPT) and evaluate its performance.Methods:139 NIPT-negative maternal plasmas stored in the genetic department of Shaoxing maternal and child health hospital from January 1, 2019 to June 30, 2021 were divided into male groups (19 cases) and female groups (120 cases) according to the neonatal gender. 9360 cases from September 2020 to September 2021 were enrolled as clinical validation cases.First step, 200 μl plasma from a 47 years-old non-pregnant healthy women was used as a matrix. Different amounts (0.1, 0.2, 0.5, 2.5, and 5 μl) of positive DNA from fetal chromosome aneuploidy (T21, T18, T13) detection kit were added. The appropriate volume of positive DNA was 0.5 μl according to the test results. Second step,Plasma in male and female group was treated as matrix. 0.5 μl positive DNA was added per 205 μl. Plasma matrix from female group showed good repeatability and the sensitivity was 100%.Third step, evaluate the self-made plasma quality control material, including storage stability, matrix uniformity and repeatability, and the effect of different batch numbers of positive DNA, by calculating Z score and the CV of fetal DNA concentration (FF).Results:Plasma matrix from female group showed good repeatability and the sensitivity was 100%, while the sensitivity of male group was only 84%. The CV of FF in female matrix was 3.9% in the repetitive experiments. After adding 0.5 μl positive DNA, the mean FF of self-made positive plasma quality control was 5.63%±0.42%, Z values>6, and the CV was 7% after storage of three months. Considering the concentration variation of positive DNA in different lots, 1 μl of positive DNA should be added when the FF of positive DNA is lower than 10%.Used in 9360 clinical cases from September 2020 to September 2021, all positive plasma quality control materials showed positive results, and the positive predictive value of trisomy 21 was 100%.Conclusions:The NIPT self-made positive plasma quality control material has been successfully developed in this study. The preliminary experimental results show that it has good repeatability and stability, which is suitable for clinical application.

Objective:To study the clinical efficacy, safety and prognosis of systemic hypothermia therapy on neonatal hypoxic-ischemic encephalopathy (HIE)initiated at different times after birth.Method:From January 2013 to August 2018, term neonates (within 12 hours after birth) diagnosed with neonatal moderate to severe HIE and received systemic treatment in the neonatal intensive care unit of our hospital were retrospectively included. According to the starting time of hypothermia therapy, the neonates were assigned into three groups: within 6 h after birth (TH1 group), 6~12 h (TH2 group) and conventional treatment group (control group). Their clinical data during perinatal period, hospitalization period and follow-up at 6-month were reviewed. Their clinical and neurodevelopmental outcomes were compared using SPSS 25.0 statistical software.Result:A total of 147 neonates with moderate to severe HIE were enrolled. 111 received 72-hour hypothermia therapy, including 79 in the TH1 group, 32 in the TH2 group and 36 in the control group. The neurobehavioral test scores at 10-day of life in the TH1 group were significantly higher than the control group ( P<0.05). No significant differences existed among the TH2 group, the TH1 group and the control group ( P>0.05). The brain magnetic resonance imaging (MRI) showed injuries in the TH1 group and the TH2 group were significantly milder than the control group ( P<0.05). No significant differences of brain injuries existed between TH1 group and TH2 group ( P>0.05). 100 patients completed Bailey Infant Intelligence Development Scale at 6-month follow-up. 21 had abnormal scores. No statistically significant differences existed in the psychomotor development index (PDI) scores among the three groups ( P>0.05). TH1 and TH2 groups had significantly fewer cases with mental development index (MDI) <70 points than the control group ( P<0.05). No statistically significant differences existed of MDI scores between the TH1 group and the TH2 group ( P>0.05). No statistically significant differences existed of PDI scores among the 3 groups ( P>0.05). At 6-month, the mortality rate of the control group (32.1%, 9/28) was significantly higher than the TH1 group (6.6%, 4/61) ( P<0.05). No significant differences existed of mortality rate at 6-month among the TH2 group, the TH1 group and the control group ( P>0.05). Conclusion:Systemic hypothermia therapy for neonatal HIE is safe. Starting systemic hypothermia therapy at 6~12-hour after birth may also be effective in reducing mortality rate and improving neurodevelopmental outcome.

Due to low autoimmune function, imperfect development of various organs, coupled with a variety of invasive operations and other factors, premature infants are high-risk groups of invasive fungal infection.Invasive candida infection in premature infants accounts for more than 80% of invasive fungal infection. The main infection rate of invasive candida albicans was candida albicans. However, in recent years, the infection rate of non-candida albicans such as candida albicans, tropical candida, smooth candida and other non-candida albicans showed a gradual upward trend.In addition to blood culture, the latest diagnostic methods such as plasma (1-3)-β-D-glucan test and candida polymerase chain reaction are helpful for the diagnosis of invasive fungal infection. At the same time, attention should also be paid to prophylactic antifungal therapy and empirical antifungal therapy in premature infants.

High mobility group box 1 protein(HMGB1) is widely present in eukaryotic nuclei and named for its rapid migration during polyacrylamide gel electrophoresis. Studies have shown that HMGB1 playes an important role in the development of gene transcription,inflammation,cancer and other diseases. In this paper, the biological characteristics of HMGB1 and its research progress in pediatric diseases are reviewed.

Objective To study the transport risk and factors that influence deaths of very low birth weight (VLBW) and extremely low birth weight (ELBW) infants.Method All infants transferred to our neonatal intensive care unit (NICU) by our hospital transport team or local hospital transport team from January 2014 to December 2015 were included in our study.Their clinical data were retrospectively studied.The risks of transport between hospitals were analyzed.The risk factors of deaths within and after 7 days of admission were further analyzed by multivariate Logistic regression analysis.The receiver operation characteristic (ROC) curve was used to assess the sensitivity and specificity of mortality index for neonatal transportation (MINT),transport related mortality score (TREMS),transport risk index of physiologic stability (TRIPS) for predicting mortality of preterm infants.Result (1) A total of 527 cases of ELBW/VLBW infants were included in our study.There were no deaths during transport.There were 10.2％ (54/527) died within and 8.9％ (42/473) died after 7 days of hospitalization.(2) Multivariate Logistic regression analysis showed that scleredema of newborn,secondary transport,gastrointestinal malformations,metabolic acidosis,high TREMS score,and high MINT score were risk factors of mortality within 7 days of admission for ELBW/VLBW infants;necrotizing enterocolitis,intraventricular hemorrhage ≥ three degree,high MINT score and low admission weight were risk factors of mortality after 7 days of admission.(3) The area under the ROC curve for MINT,TREMS,and TRIPS score were 0.672,0.655 and 0.665,respectively.The cut-off values for MINT score (cut-off 8,sensitivity 0.444,specificity 0.829),for TREMS score (cut-off 2,sensitivity 0.500,specificity 0.757,for TRIPS score (cut-off 20,sensitivity 0.444,specificity O.829) were selected to predict mortality within 7 days of admission.Conclusion (1) Secondary transport is the transport-related risk factor of mortality within 7 days of admission for ELBW/VLBW infants.(2) High MINT score is the risk factor of mortality within and after 7 days of admission.(3) If MINT ≥ 8,TREMS ≥2,or TRIPS ≥20,it might significantly increase the risk of mortality of ELBW/ VLBW infants within 7 days of admission after transport.

Objective To study the occurrence of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants and to determine the risk factors of severe BPD.Method From January 2007 to January 2017,ELBW infants admitted to neonatal intensive care unit (NICU) in Hunan Children's Hospital were retrospectively analyzed.They were assigned into severe and mild/moderate groups based on the severity of BPD.The general condition,maternal status,prenatal and delivery room treatment,transportation,clinical courses,therapy and outcome in NICU of the two groups were compared,and the risk factors of severe BPD were analyzed.Result A total of 367 cases were hospitalized during the 10 years.281 ELBW infants with complete medical records survived longer than 28 days were enrolled in this study.Among them,233 had BPD.Among BPD infants,116 cases were in the severe BPD group,47 cases (40.5％) died.117 cases were in the mild/moderate BPD group and 1 case (0.9％) died.The difference between the two groups was statistically significant (P ＜ 0.05).Multivariate Logistic regression analysis showed that the risk factors of severe BPD were duration of mechanical ventilation ≥ 7 days (OR =7.518,95 ％ CI 3.197 ～ 17.676),ventilator-associated pneumonia (OR =3.047,95 ％ CI 1.436 ～ 6.464),1 min Apgar score ≤7 (OR =2.341,95 ％ CI 1.142 ～ 4.796) and patent ductus arteriosus (OR =2.223,95 ％ CI 1.079 ～4.582).Conclusion The incidence and mortality of BPD,especially severe BPD,are high in ELBW infants.Avoiding asphyxia,shortening the time of mechanical ventilation,preventing infection and closing ductus arteriosus are important measures to reduce the severity of BPD.

Objective To study the effectiveness of family-integrated-care (FICare) for preterm infants with moderate to severe bronchopuhnonary dysplasia (BPD) in neonatal intensive care unit (NICU).Method Preterm infants with moderate to severe BPD in Hunan Children's Hospital from January 2015 to March 2016 were selected as the objects.These infants were assigned into two groups (FICare group and control group) in the base of whether the parents agreed to implement FICare.If the infant was enrolled into FICare group,the parents need to spend 3 hours in ward every day,and participate in nursing services under the guidance of nurses.The nursing services included bathing,cuddling,skin care,breast-feeding,and so on.If the infant was enrolled into control group,these nursing services were implemented by nurses.Oxygen exposure time,breast-feeding rate,time of begin oral feeding,time of total oral feeding,weight growth rate during hospitalization,weight of discharge,length of stay,readmission rate within 30 days,the rate of parents that mastered basic care knowledge and skills when discharge from hospital,the rate of satisfaction,and the rate of follow-up within 30 days of the two groups were compared.Result There were 106 cases in our study,54 in the FICare group and 52 in the control group.Compare the FICare group and the control group,there were statistical differences between two groups in the follow aspects (all P ＜ 0.05):oxygen exposure time [(57.1 ±20.9) d vs.(71.4 ±32.6) d],breast-feeding rate (77.8％ vs.44.2％),time of total oral feeding [(46.1 4 19.6) d vs.(59.4 ± 30.2) d,length of stay [(65.8 ± 18.4) d vs.(84.3 ±35.0) d],the rate of parents that mastered basic care knowledge and skills when discharge from hospital (96.3％ vs.82.7％),the rate of satisfaction (94.4％ vs.84.6％),the rate of follow-up within 30 days (92.6％ vs.73.1％).Conclusion FICare could significantly reduce oxygen exposure time of preterm infants with moderate to severe BPD,could improve the level of parents mastered basic care knowledge and skills of preterm infants,especially in critically ill preterm children,and could shorten length of stay of them.FICare is beneficial to the healthy growth of premature infants with BPD.