Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.

Objective:To study the clinical characteristics and differences between clinical subtypes of neonates with SARS-CoV-2 infection.Methods:From December 11, 2022 to January 10, 2023, neonates with SARS-CoV-2 infection admitted to our hospital were retrospectively studied. The neonates were assigned into two groups according to the clinical classification: the mild group (including asymptomatic, mild and moderate disease) and the severe group (including severe and critical disease). The clinical characteristics were summarized and compared between the groups.Results:Among 162 confirmed cases, 91 (56.2%) were male, 27 (16.7%) were preterm infants and 26 (16.0%) were low birth weight infants (LBWIs). The average age of onset was 15(8,21)d with 125 cases (77.2%) had onset after 7 d of birth. The main clinical manifestations included fever (79.0%), cough (59.3%) and nasal congestion (42.6%). 70 cases (43.2%) had abnormal complete blood count (CBC) with neutropenia most common. 136 cases (84.0%) were in the mild group and 26 in the severe group. The severe group showed higher proportion of male, preterm and LBWIs than the mild group ( P<0.05). The most common clinical manifestation was fever in the mild group and cyanosis in the severe group. Compared with the mild group, the severe group had higher incidence of poor response and longer duration of fever ( P<0.05). No significant difference existed in CBC between the two groups ( P>0.05). 127 neonates received chest X-ray and 77(60.6%) showed pneumonia. 157 neonates were discharged with improvement or full-recovery. The length of hospital stay was 5(3,6)d. 5 patients were discharged refusing further treatment. Conclusions:Most SARS-CoV-2 infections in neonates are mild and moderate types with mild symptoms and fever. A few are severe or critical types with cyanosis the most common symptom. Neonates with poor responses and prolonged fever need to be alerted to the possibility of severe disease, especially for male, preterm and LBWIs. Most neonates have a favorable prognosis.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Objective:To study the predictive value of total serum bilirubin (TSB) and the ratio of bilirubin to albumin (B/A) in neonatal acute bilirubin encephalopathy (ABE).Methods:Neonates with extremely severe hyperbilirubinemia (TSB≥425 μmol/L) treated in the Nanjing Maternal and Child Health Hospital, Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Northwest Women and Children's Hospital, Yinchuan Maternal and Child Health Hospital and Liaocheng People's Hospital from March 2018 to August 2019 were selected as prospective subjects for this study. According to the score of brain injury induced by bilirubin, the subjects were divided into ABE group and non-ABE group, and the predictive value of TSB peak and B/A for neonatal ABE were analyzed.Results:A total of 194 infants with extremely severe hyperbilirubinemia were recruited in this study, including 20 in ABE group and 174 in non-ABE group. The peak value of bilirubin ranged from 427 to 979 μmol/L. The optimal critical values of TSB peak value and B/A for ABE prediction were 530 μmol/L and 9.48, respectively. The sensitivity and specificity of ABE prediction were 85.0% and 92.8% when combined with TSB peak and B/A values.Conclusions:TSB peak combined with B/A value can effectively identify neonatal ABE. When the TSB peak value was greater than 530 μmol/L and the B/A value was greater than 9.48, the neonates had a higher risk of neonatal ABE.

Objective To study the clinical and genetic characteristics of congenital hyperinsulinism (CHI).Method From November 2016 to November 2018,a cohort of 21 patients with CHI were retrospectively reviewed in our hospital.The second generation sequencing was performed on Ion torrent platform to identify the genetic etiology of this disease.Result The average birth weight was 3 748 g.Overall,11 of the 21 patients (52.4％) were large for gestational age (＞ Pg0),and 90.5％ (19/21) onset within 3 days after birth.Seizures occurred in 7 cases (33.3％).Diazine was effective in alleviation in 6 patients,octreotide was effective in 8 patients,and diazine and octreotide were ineffective in 7 patients.11 patients underwent 18-fluoro-l-dopa PET-CT scan,indicating focal islet cell proliferation in 8 patients and diffuse islet cell proliferation in 3 patients.8 focal cases accepted the partial pancreatectomy (7 cases who failed to respond to drug therapy,1 case who received octreotide had significant liver damage),and all of these 8 cases were confirmed with focal islet cell proliferation by postoperative pathology.7 cases had normal glucose level after surgery,while 1 case developed insulin-dependent diabetes.Patients of 3 cases with diffuse islet cell proliferation had no consent for surgery.Gene mutations were identified in 61.9％ (13/21) of patients (12 cases of ABCC8 gene and 1 case of KCNJ11 gene).15 sequence changes were identified (14 in ABCC8 and 1 in KCNJ11).3 new ABCC8 gene mutations (exon13:c.1822C ＞ T,p.Q608X;exon22:c.2691delC,p.W898Gfs*5;exon33:c.4039C ＞T,p.Q1347X),and 1 new KCNJJ11 gene mutation (exon1:c.629T ＞ A,p.H315Y) were firstly reported.Conclusion Partial pancreatectomy is an effective treatment for those CHI not responsive to drug,however,with an attendant risk of developing diabetes.Mutations of ABCC8 gene and KCNJJ11 gene are the main pathogenic genes of CHI.Patients with different gene mutations may have different responses to drug treatment.Therefore,it is necessary to improve gene testing in clinical practice to guide treatment and prognosis.3 new ABCC8 gene mutations and 1 new KCNJJ11 gene mutation were first reported,which expand the spectra of gene mutation.

Objective To explore the physical development and immune function of infants without human immunodeficiency virus(HIV)infection who were delivered by HIV_infected mothers. Methods Two hundred and ninety_seven infants delivered HIV_infected mothers in Guangxi province from January 2008 to November 2011 were selected as observation group. According to whether infants had HIV infection or not,the children were further divided into the HIV_infection group and the infants in the non_HIV infection group according to the presence or absence of HIV infection,and the infants in the non_HIV infection group were divided into the antiretroviral drug(ART)treatment group and the non_ART treatment group according to whether the mother had used ART during pregnancy. Ninety_one healthy children born at the same time were selected as the healthy control group. The physical examination,T lympho_cyte subgroup analysis and humoral immunity test were performed on all infants. Results The weight and body length at birth of infants born from HIV_infected mothers were all significantly lower than those in the healthy control group [(2. 86 ± 0. 49)kg vs.(3. 15 ± 0. 52)kg;(47. 05 ± 2. 20)cm vs.(50. 01 ± 2. 58)cm],and the differences were sta_tistically significant(t﹦2. 652,2. 247,all P〈0. 05). The CD8 level and CD4∕CD8 ratio of infants delivered by HIV_infected mothers had no significant differences statistically compared with those in the healthy control group[(21. 31 ± 6. 49)% vs.(22. 01 ± 5. 43)%;1. 82 ± 0. 79 vs. 1. 82 ± 0. 67,t﹦0. 933,0. 033,all P〉0. 05];the CD3 and CD4 levels were lower than those in the healthy control group[(62. 36 ± 7. 94)% vs.(65. 70 ± 6. 32)%;(4. 83 ± 7. 62)% vs.(37. 02 ± 5. 69)%],and the differences were statistically significant(t﹦3. 66,2. 946,all P〈0. 01). The immunoglobulin(Ig)M,IgG and IgA levels of children born to HIV_infected mothers had no statistically significant differences compared with those in the healthy control group[(1. 79 ± 0. 66)g∕L vs.(1. 76 ± 0. 66)g∕L;(8. 96 ± 2. 74)g∕L vs.(8. 80 ± 1. 97)g∕L;(0. 85 ± 0. 57)g∕L vs.(0. 86 ± 0. 41)g∕L,t﹦0. 341,0. 619,0. 173,all P〉0. 05). The weight and body length at birth of non_HIV infected children born from HIV_infected mothers were all significantly lower than those in healthy control group[(2. 92 ± 0. 43)kg vs.(3. 15 ± 0. 52)kg;(49. 03 ± 2. 22)cm vs.(50. 01 ± 2. 58)cm],and the differences were statistically significant( F﹦4. 163,2. 87,all P〈0. 05). The birth weight,birth length and head circumference of the ART group were all significant lower than those in the healthy control group[(2. 90 ± 0. 43)kg vs.(3. 15 ± 0. 52)kg;(48. 27 ± 1. 89)cm vs.(50. 01 ± 2. 58)cm;(31. 80 ± 1. 47)cm vs. (34. 88 ± 3. 21)cm],and the differences were statistically significant( F﹦3. 711,2. 970,3. 689,all P〈0. 05). The CD8 level and CD4∕CD8 ratio of non _ HIV infected children born to HIV _ infected mothers had no significant differences statistically compared with those in the healthy control group[(20. 77 ± 5. 60)% vs.(22. 01 ± 5. 43)%, 1. 85 ± 0. 76 vs. 1. 82 ± 0. 67,F﹦43. 568,11. 705,all P〉0. 05];the CD3 and CD4 levels were lower than those in the healthy control group[(62. 27 ± 7. 94)% vs.(65. 70 ± 6. 32)%;(35. 30 ± 6. 86)% vs.(37. 02 ± 5. 69)%],and the differences were statistically significant(F﹦7. 083,28. 06,all P〈0. 05). Conclusions The humoral immune func_tion of the non_HIV infected infants delivered by HIV_infected mothers is not significantly affected,but the physical development at birth and cellular immune function are significantly affected. ART during pregnancy is not a major factor in the limitation of physical development at birth. Therefore,the nutrition support for the infants delivered by HIV_in_fected mothers and prevention of infection are especially necessary clinically.

Objective To explore the clinical characteristics and genetic mutation types of the Mediterranean anemia in Guangxi region in the early neonatal period.Methods The observation group was the children who hospitalized in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomons Region during the period of January 2013 and November 2015,and diagnosed Mediterranean anemia were 85 cases.And 85 newborns that were in the hospital at the same time were selected as the control group.The matching condition between the observation group and the control group was the gestational age.We retrospectively analyzed the general situation (birth weight and gender) and the treatment procedure (the characteristic of blood routine examinations;the day-old of the onset of anemia;the endurance of jaundice;assisted ventilation;the time of oxygen therapy;the dayold of enteral feeding;the blood transfusion times) of the two groups.And the gene was detected in the observation group.Results The observation group's days of life [(13.00 ± 3.79) d] of the oral feeding were higher than that [(9.33 ± 1.95) d] of the control group's (t =2.730,P ＜ 0.05);the observation group's frequency [(3.0 ± 1.0) times] of the blood transfusion was higher than that [(1.0 ± 0.2) times] of the control group's (t =4.268,P ＜ 0.05).The observation group's days of life [(4 ± 1) d] of anaemic onset was shorter than that [(8 ± 2) d] of the control group's (t =-3.258,P ＜ 0.05).The mean corpuscular volume [(80 ± 12) fl] in the blood routine of the observation group was smaller than that [(91 ± 28) fl] of the control group (t =6.712,P ＜ 0.05).In the observation group,the mother's age of pregnancy was (29.19 ± 0.91) years,the birth weight of the newborns was (2.356 ± 0.748) kg,the service time of the ventilator was (7.11 ± 5.07) h,the time of continue positive airway pressure was (27.40 ± 15.17) h,the time of the oxygen provision was (84.98 ± 30.65) h,the time of duration of the jaundice last was (10 ± 3) d;and in the control group,the mother's age of pregnancy was (27.9i ± 0.88) years,the birth weight of the newborns was (2.507 ± 0.783) kg,the service time of the ventilator was (6.21 ± 2.55) h,the time of continue positive airway pressure was (9.64 ± 4.89) h,the time of the oxygen provision was(63.07 ± 21.87) h,the time of duration of the jaundice last was (15 ± 2) d.The parameters showed above were not statistically different between the two groups (all P ＞ 0.05).In 85 cases the detection of α-thalassemia in 60 cases,24 patients with β-thalassemia,1 cases of α-thalassemia combined with β-thalassemia.The logistic regression analysis showed that the age of the oral feeding completely (OR =0.233,95％ CI =0.081-0.673) and the times of blood transfusion (OR =6.621,95％ CI =2.777-15.784) were the independence factors of the Mediterranean anemia.Conclusion The early clinical performance of Mediterranean anemia is lack of specificity,and we must improve genetic testing and regulate blood transfusion as soon as possible to the one who has anemia and other clinical manifestations within a week immediately following birth or who is suspected of Mediterranean anemia patients by the blood routine examination.

Objective To investigate the diagnostic correlation and sensitivity of amplitude integrated electroencephalogram (aEEG),brainstem auditory evoked potential (BAEP) and cranial magnetic resonance imaging (MRI) for acute bilirubin encephalopathy (ABE) in the newborn.Method Term and near-term neonates (gestational age ≥ 35 weeks) with hyperbilirubinemia (the level of bilirubin over than 95th percentile) of high and intermediate risk group admitted in the neonatal ward of Guangxi Maternal and Child Health Care Hospital from Jan 2014 to Dec 2015 were recruited retrospectively.The infants were assigned to ABE group and non-ABE group according to the diagnostic criteria of ABE.The clinical data of the newborns were collected and the diagnostic correlation between clinical diagnosis and aEEG,BAEP and cranial MRI were analyzed.The receiver operating characteristic (ROC) curve was adopted to assess the diagnostic efficiency of the peak level of serum bilirubin,aEEG,BAEP and cranial MRI on the early diagnosis of ABE.Result A total of 152 newborns with hyperbilirubinemia were recruited,including 33 cases in the ABE group and 119 cases in non-ABE group.(1) The results of aEEG and MRI were marginally positively correlated with clinical diagnosis of ABE (aEEG:r =0.487,P ＜ 0.001;MRI:r =0.220,P=0.018),while the results of BAEP were closely related to the clinical diagnosis of ABE (r =0.593,P ＜ 0.001);(2) The results of BAEP and MRI on the diagnosis of ABE were positively correlated with those of aEEG (BAEP:r =0.424,P ＜ 0.001;MRI:r =0.307,P ＜ 0.001).(3) The area under the ROC curves for predicting the onset of ABE were 0.899 for the peak level of serum bilirubin,0.767 for BAEP,0.738 for aEEG and 0.590 for MRI.Conclusion There was the correlation on the diagnosis of ABE among the methods of aEEG,BAEP and MRI.The combined diagnosis of the three methods could play a complementary role.The aEEG contributed to the early diagnosis of ABE with high sensitivity.

Objective To study the risk factors and prognosis of very/extremely low birth weight preterm (VLBW/ELBW) infants with bronchopulmonary dysplasia (BPD) during the first three years of life.Method From January 1st to December 31st,2012,a retrospective study was conducted on the VLBW/ELBW preterm infants with ＞ 28 days of hospitalization in the NICU of our hospital.The infants were assigned into BPD group (FiO2 ＞ 21％) and non-BPD group depending on the oxygen requirement on the 28th day after birth.The incidences of bronchitis,pneumonia,wheezing and re-hospitalization during the first three years of life were analyzed.The pulmonary function tests were performed at one-year-age.Independent-sapmles t test,Kruskal-wallis test and x2 test were used to compare the results between the two groups.Result A total of 72 patients were enrolled into this study.34 patients in the BPD group and 38 in the non-BPD group.The gestational age,birth weight and the use of INSURE technique of BPD group were significantly lower than non-BPD group,while the duration of hospital stays were longer than non-BPD group (P ＜0.05).The ratio of male,neonatal respiratory distress syndrome (RDS),patent ductus arteriosus (PDA),intrauterine infection,mechanical ventilation,nosocomial infection and the inhalation of high concentrations of oxygen were significantly higher in BPD group than non-BPD group (P ＜ 0.05).Incidences of bronchitis and wheezing during 0 ～ 1,1 ～ 2 and 2 ～ 3 years of age in the BPD were significantly higher than non-BPD group,separately.No significant differences existed in the incidences of pneumonia and re-hospitalization between the two groups.Pulmonary function test showed that the respiratory rate (RR) and peak tidal expiratory flow in the BPD group were significantly higher than non-BPD group,while the tidal volume,peak expiratory time and peak expiratory volume were significantly lower in BPD group than non-BPD group (P ＜ 0.05).Conclusion BPD often occurs in preterm infants with gestational age less than 32 weeks.It may cause impaired pulmonary function,characterized by obstruction in small airway,and increases the risk of bronchitis and wheezing during the first three year of life.

Objective To explore the clinical characteristics,treatment and prognosis of neonatal group B streptococcus (GBS) sepsis.Methods According to the onset time and clinical features of the patients,30 cases of neonatal GBS sepsis in Department of Noonatology,Zhuhai People's Hospital and ICU of Newborn of Maternity and Child Care Health Hospital of Guangxi from January 2013 to February 2015 were divided into the early-onset group (onset day of the patients ≤7 days) and late-onset group (onset day of the patients ＞7 days).The clinical manifestations,the examination results of laboratory,imaging examination,treatment and prognosis were retrospectively analyzed.Results Among the newborns diagnosed as neonatal GBS sepsis,there were 19 cases of early-onset sepsis and 11 cases of late-onset sepsis,including 17 males and 13 females,consisting of 24 term infants and 6 premature infants.The early-onset newborns were mainly diagnosed with respiratory symptoms like anhelation,groaning (73.7％,14/19 cases),late-onset GBS sepsis with high fever (81.8％,9/11 cases),high frequency of early-onset intrauterine infection pneumonia (89.5％,17/19 cases) and late-onset intracranial infection (63.6％,7/11 cases).The differences between the 2 groups were statistically significant (all P ＜ 0.05).Laboratory tests of GBS sepsis showed that the early value of procalcitonin (PCT) increased,while the number of white blood cells,platelet decreased and C-reactive protein (CRP) increased relatively late.Chest X-ray examination showed 16 cases of pneumonia in children,1 case of pulmonary hemorrhage,1 case of bilateral pneumothorax.Head CT,B ultrasound,and magnetic resonance imaging discover 1 case of ventricular perivascular hemorrhnge,2 cases of intraventricular hemorrhage with ventricular dilatation and 1 case of subdural effusion.Drug sensitivity test showed that 30 cases of children were sensitive to Penicillin,Vanoomycin among which 17 cases (56.66％) were cured,4 cases (23.33％) were improved,9 cases died,6 cases died of abandoning treatment,and the total mortality was 30.00％ (9/30 cases).The 6-month follow-up of 9 cases of purulent meningitis newborns showed that there were 2 cases of mild mental retardation and motor dysfunction,1 case of mild ventricular dilatation with no progressive increase,and 6 cases with no significant sequelae.Conclusion The clinical manifestations of neonatal GBS sepsis are typical.Dynamically monitoring the changes of PCT,CRP,white blood cells and platelet helps to early identify GBS sepsis infection and use sensitive antibiotics to cure the newborns.