Objective:To explore the potential genetic causes of unexplained neonatal encephalopathy.Methods:This retrospective study enrolled 113 infants diagnosed with unexplained neonatal encephalopathy and underwent genetic testing in the Children's Hospital of Hunan Province from January 2019 to May 2021. Perinatal data, clinical manifestations, electroencephalograph, brain MRI findings, genetic information, and prognosis of those patients were analyzed. T-test or Chi-square test were used for data analysis. Results:Of the 113 infants enrolled, 74 (65.5%) were males. The gestational age at birth was (38.6±1.5) weeks, and the birth weight was (2 957±561) g. The most common clinical manifestation was the disturbance of consciousness (83/113, 73.5%), followed by seizures (39/113, 34.5%). There were 38.2% (34/89) of the patients with abnormal brain MRI, and 80.4% (74/92) presented abnormal electroencephalography. Among the 113 infants, 60 (53.1%) had genetic abnormalities, including 48 with single nucleotide variations, eight with copy number variations, and four with chromosome abnormalities. Single nucleotide variations in the 48 patients were classified into syndromic ( n=18, 37.5%), metabolic ( n=16, 33.3%), epileptic ( n=11, 22.9%) and mitochondrial-related genes ( n=3, 6.3%), of which 14 were not included in any database. Among the 103 cases which were successfully followed up until December 31, 2021, 75 (72.8%) had a poor prognosis, including 52 (50.5%) death cases and 23 (22.3%) cases of development retardation. Birth weight and the incidence of seizures in the poor prognosis group were both lower than those in the non-poor prognosis group [(2 876±536) vs (3 254±554) g, t=3.15; 29.3% (22/75) vs 53.6% (15/28), χ2=5.20; both P<0.05], while the incidence of disturbance of consciousness was higher [80.0% (60/75) vs 53.6% (15/28), χ2=7.19, P<0.05]. The proportion of infants with genetic abnormalities in the poor prognosis group was higher than that in the non-poor prognosis group, but the difference was not statistically significant [53.3% (40/75) vs 46.4% (13/28), χ2=0.39, P=0.533]. Conclusions:Genetic abnormality is one of the leading causes of unexplained neonatal encephalopathy. Nucleotide variation is the most common genetic type. Syndromic, metabolic, and epileptic variants are frequently detected in these patients.

Objective:To study the clinical characteristics and differences of severe hyperbilirubinemia caused by hemolytic disease of the newborn (HDN) and glucose-6-phosphate dehydrogenase (G6PD) deficiency.Methods:From January 2014 to December 2021, newborns (gestational age ≥ 35 weeks and postnatal age ≤ 28 d) admitted to the Department of Neonatology of Hunan Children's Hospital with severe hyperbilirubinemia caused by HDN or G6PD deficiency were retrospectively analyzed. According to the etiology of hyperbilirubinemia, they were assigned into HDN group and G6PD deficiency group. The general conditions, clinical manifestations, laboratory results, treatment and prognosis of the two groups were compared using SPSS 26.0 software.Results:A total of 532 cases were in the HDN group and 413 cases in the G6PD deficiency group. The HDN group reached peak hyperbilirubinemia earlier than the G6PD deficiency group [3(2,5) d vs. 6(4,8)d, P<0.05]. The HDN group had lower peak value of total serum bilirubin [379.5(345.6,426.7) μmol/L vs. 486.4 (413.5,577.4) μmol/L] and lower incidence of anemia [37.4% (199/532) vs. 55.0% (227/413)]than the G6PD deficiency group.The incidence of anemia with elevated reticulocyte percent(Ret%) in the HDN group was higher than the G6PD deficiency group[66.3%(132/199) vs. 5.7%(13/227), P<0.05]. Compared with the G6PD deficiency group, the incidences of exchange transfusion and repeated (≥2 times) exchange transfusion, acute bilirubin encephalopathy(ABE) and the mortality rate after withdrawal of treatment in the HDN group were significantly lower ( P<0.05). Conclusions:Neonatal severe hyperbilirubinemia caused by HDN has early onset. G6PD deficiency caused hyperbilirubinemia has higher incidences of anemia, more severe jaundice and ABE, without increased Ret%.

Objective:To study the risk factors and prognosis of pulmonary hypertension(PH) associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants(EPIs).Methods:From January 2020 to December 2021, EPIs [gestational age (GA) <32 w] with BPD admitted to NICU of our hospital were retrospectively assigned into two groups: BPD with late-onset PH(PH group) and BPD without late-onset PH(non-PH group). Their general condition, treatment and prognosis were compared and the risk factors of late-onset PH were analyzed.Results:A total of 229 EPIs with BPD were enrolled, including 24(10.5%) in the PH group and 205(89.5%) in the non-PH group. The PH group had significantly smaller GA [(27.9±2.3) w vs. (28.7±1.8) w], longer mechanical ventilation [42.0(16.0, 84.0) d vs. 9.0(2.0, 23.0) d], longer hospital stay [100.5(86.3, 142.0) d vs. 77.0(56.5, 96.5)d],higher incidence of early-onset PH(54.2% vs. 9.3%) and higher mortality rate(33.3% vs. 9.8%) than the non-PH group ( P<0.05). Multivariate logistic regression analysis showed prolonged mechanical ventilation ( OR=1.046, 95% CI 1.011~1.064), early-onset PH ( OR=5.414, 95% CI 1.796~16.323) were independent risk factors for BPD with late-onset PH. 8(33.3%) patients in the PH group died, including 2 with grade Ⅱ BPD and 6 grade Ⅲ BPD. Conclusions:Prolonged mechanical ventilation and early-onset PH are independent risk factors for late-onset PH in BPD infants. BPD infants with late-onset PH have longer hospital stay, higher mortality and worse prognosis.

Objective:To explore the relationship between the neural development of preterm infants and gut microbiota.Methods:66 premature infants who were hospitalized in the Neonatology Department of Hunan Children′s Hospital from September 2018 to September 2019 were included in the study. Their fecal samples and clinical data from the first admission were collected. According to the neurodevelopment, the patients were divided into normal neurodevelopment group and neurodysplasia group. The bacterial DNA of fecal samples was extracted by 16S rDNA high-throughput sequencing technology and bioinformatics analysis was conducted to compare the composition and diversity of gut microbiota between the two groups.Results:(1) The Shannon index of gut microbiota in normal neurodevelopmental group and neurodysplastic group was 0.89(0.41, 1.51) and 1.01(0.47, 1.31), respectively. There was no significant difference in diversity index between the two groups ( P>0.05). (2) Bifidobacterium, veronica and negativites in the gut microbiota of the normal neurodevelopmental group were significantly higher (all P<0.05), and streptococcus in the gut microbiota of the dysplastic group were significantly higher ( P<0.05). The gut microbiota of the two groups were mainly enterococcus and escherichia shigella. Conclusions:At the genus level, enterococcus and escherichia are the dominant flora of early gut microbiota in preterm infants. Gut microbiota is related to the neural development of preterm infants. The increased abundance of streptococcus, and the decreased abundance of bifidobacterium, veronicus, and negativites may be risk factors for neurodysplasia of preterm infants. The diversity of gut microbiota in early preterm infants may not be significantly related to neural development.

Objective:To explore the clinical significance of different metabolic parameters measured by 18F-fluorodeoxyglucose (FDG) PET/CT in predicting the effectiveness of chemotherapy in advanced lung adenocarcinoma patients. Methods:A set of metabolic parameters of PET/CT and clinical characteristics which were detected from 127 patients (70 males, 57 females, age (56.8±10.1) years) with advanced lung adenocarcinoma treated with at least two cycles of chemotherapy in Hainan Cancer Hospital between August 2017 and June 2019 were retrospectively analyzed. The effects of those parameters on patients′ survival were analyzed by receiver operating characteristic (ROC) curve, Kaplan-Meier method (log-rank test) and Cox proportional hazards model.Results:Maximum standardized uptake value (SUV max), metabolic tumor volume 30% (MTV 30), and total lesion glycolysis 30% (TLG 30) had larger areas under the curve (0.581, 0.606 and 0.693 respectively) compared with other imaging parameters, and the optimal cut-off values were 10.12, 20.21 cm 3 and 81.25 g respectively. Kaplan-Meier univariate and Cox analyses synergistically showed that clinical stage (hazard ratio ( HR)=0.293(95% CI: 0.190-0.451), P<0.001), smoking ( HR=0.732(95% CI: 0.605-0.885), P=0.001), and MTV 30 ( HR=1.555(95% CI: 1.078-2.242), P=0.018) had significant predictive value for progression-free survival (PFS). Stratified analysis showed that smoking and MTV 30>20.21 cm 3 were independent prognostic factors for poor PFS in patients with advanced lung adenocarcinoma receiving chemotherapy ( HR=0.738(95% CI: 0.611-0.893), P=0.002; HR=1.502(95% CI: 1.037-2.177), P=0.032). Conclusions:Clinical stage, smoking and MTV 30 are independent prognostic factors of PFS in patients with advanced lung adenocarcinoma receiving chemotherapy. MTV 30≤20.21 cm 3 is expected to be an image biomarker for predicting survival and selecting patients with advanced lung adenocarcinoma who are more likely to benefit from chemotherapy.

Objective To explore the genetic basis for a Chinese neonate with lipoprotein lipase deficiency.Methods Targeted capture and next-generation sequencing (NGS) were carried out to detect variants of genes associated with inborn errors of metabolism.Suspected variants were validated by Sanger sequencing.Results Genetic testing revealed novel complex heterozygous variants,namely c.347G＞ C (p.Arg116Pro) and c.472T＞G(p.Tyr158Asp),of the LPL gene,which were respectively inherited from his father and mother.Conclusion Compound heterozygous variants c.347G＞C and c.472T＞G of the LPL gene probably underlie the lipoprotein lipase deficiency in this child.

The post-stroke depression (PSD) is one of the common complications of stroke.It can not only delay the recovery of the neurological function in patients, seriously affect the quality of life of patients, but also increase the mortality and morbidity.More and more attention has been paid to the pathogenesis of PSD.Recent studies have confirmed that brain small vessel disease is closely related to the occurrence of PSD.This article reviews relationship between brain small vessel diseases and PSD.

OBJECTIVETo detect potential mutation of the UGT1A1 gene in a child affected with Crigler-Najjar syndrome type II.

METHODSBlood samples were collected from the patient and his parents for the extraction of genomic DNA. Potential mutation of the UGT1A1 gene was detected with polymerase chain reaction (PCR) and direct sequencing. The child was followed up until the age of 3 years and 6 months.

RESULTSThe patient showed persistent unconjugated hyperbilirubinemia. Sequencing of the UGT1A1 gene has detected a rare heterozygous c.610 A>G (p.Met204Val) mutation in the exon 1, in addition with a heterozygous c.1091 C>T (p.Pro364Leu) mutation in exon 4. The two mutations were inherited from his father and mother, respectively. The patient was diagnosed with Crigler-Najjar syndrome type II and received oral phenobarbital treatment.

CONCLUSIONThe compound UGT1A1 gene mutation probably accounts for the disease in the patient manifesting persistent mild unconjugated hyperbilirubinemia. Genetic counseling and prenatal diagnosis should be provided for his family.

Objective To investigate the relationship between the severity of coronary artery disease and malignant arrhythmia in the acute ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), and guide clinical prevention and treatment .Methods By retrospective analysis method , 418 cases of hospitalized patients with a diagno-sis of STEMI undergoing direct PCI were continuously collected in the Department of Cardiology , the First Affiliated Hospital of China Medical University, from 2008 January to 2010 December.Electrocardiography (ECG) was given after admission.Those patients were divided into two groups according to whether the occurrence of malignant ventricular arrhythmias that was defined as sustained ventricu -lar tachycardia (sVT) or ventricular fibrillation (VF)].In sVT/VF patients, the preoperative and postoperative groups were divided according to sVT/VF time.The degree of coronary artery lesions was calculated in patients with STEMI .The incidence of sVT/VF was counted in each group with Gensini scores <60,≥60 and<120, and ≥120.The relationship between the severity of coronary le-sions and malignant arrhythmia was observed in STEMI undergoing direct PCI patients .Results ⑴In this study , a total of 47 cases ( 11.2%) occurred with sVT/VF in patients;Killip grade >I, fast heart rate , low blood pressure , and low ejection fraction were risk factors of sVT/VF( P <0.05).The occurrence of sVT/VF among the Gensini groups were significant difference (7.1%vs 10.8%vs 20.5%, P =0.012 ) .⑵The occurrence of sVT/VF was 44.8% ( 22 patients ) with direct PCI before operation; the preoperative sVT/VF rate among the Gensini groups had significant difference (2.1%vs 5.9%vs 9.6%, P =0.045).⑶The occurrence of sVT/VF is 53.3%(25 patients) with direct PCI after operation; the postoperative sVT/VF rate among Gensini groups had no significant difference(5.0%vs 4.9%vs 11.0%, P =0.142);⑷Paired with age ( x±2), gender, hypertension, and diabetes 1, Logistic re-gression analysis showed that the heart rate greater than 80 beats /min ( P =0.04 , OR:2.667 , 95%CI:1.043~6.815 ) was an independent risk factor of preoperative sVT/VF, that Gensini score was not an independent risk factor of preoperative malignant ar -rhythmia.Conclusions For STEMI PCI patients, the more serious the degree of coronary artery is , the higher may be preoperative malignant arrhythmia , while the postoperative malignant arrhythmia rate has no significant difference .

Objective To investigate the significance and mechanism of intracerebroventricular injection viper venom nerve growth factor (Vngf) in rat neural plasticity after cerebral ischemia reperfusion injury.Methods Ninety Wistar male rats were randomly assigned into Vngf-25 U group (n = 18), Vngf-50 U group (n = 18), Vngf-100 U group (n = 18), ischemia reperfusion group (n = 18) and sham operated group.The expression of candidate plasticity-related gene 15(cpg-15) Mrna and nuclear factor of kappa B ( NF-Κb ) Mrna in rat brain tissues which were collection at 2,7,14 days after surgery were evaluated by the real time PCR.Results The expression of cpg-15 Mrna and NF-Κb Mrna began to increase after surgery( the F value of cpg-15:70.43, 34.11, 31.89, the F value of NF-Κb: 27.47, 34.56, 31.89,P＜0.01).At the same time, expression of cpg-15 Mrna and NF-Κb Mrna in the Vngf groups was significantly different from the I/R group and the sham operated group (the F value of cpg-15:48.18, 55.93, 78.43, the F value of NF-Κb: 45.92, 55.72, 50.49, P ＜0.01).The more Vngf were injected, the more cpg-15 Mrna and NF-Κb Mrna were expressed in Vngf groups.Conclusions The Vngf could accelerate neural plasticity and restore neurofunctional defect through up-regulated the expression of cpg-15 and NF-Κb.