Effective axon regeneration is essential for the successful restoration of nerve functions in patients suffering from axon injury-associated neurological diseases. Certain self-regeneration occurs in injured peripheral axonal branches of dorsal root ganglion (DRG) neurons but does not occur in their central axonal branches. By performing rat sciatic nerve or dorsal root axotomy, we determined the expression of the dysbindin domain containing 2 (DBNDD2) in the DRGs after the regenerative peripheral axon injury or the non-regenerative central axon injury, respectively, and found that DBNDD2 is down-regulated in the DRGs after peripheral axon injury but up-regulated after central axon injury. Furthermore, we found that DBNDD2 expression differs in neonatal and adult rat DRGs and is gradually increased during development. Functional analysis through DBNDD2 knockdown revealed that silencing DBNDD2 promotes the outgrowth of neurites in both neonatal and adult rat DRG neurons and stimulates robust axon regeneration in adult rats after sciatic nerve crush injury. Bioinformatic analysis data showed that transcription factor estrogen receptor 1 (ESR1) interacts with DBNDD2, exhibits a similar expression trend as DBNDD2 after axon injury, and may targets DBDNN2. These studies indicate that reduced level of DBNDD2 after peripheral axon injury and low abundance of DBNDD2 in neonates contribute to axon regeneration and thus suggest the manipulation of DBNDD2 expression as a promising therapeutic approach for improving recovery after axon damage.
Animals ; Ganglia, Spinal/metabolism* ; Nerve Regeneration/genetics* ; Rats ; Axons/metabolism* ; Sciatic Nerve/injuries* ; Rats, Sprague-Dawley ; Male

Objective:To explore the genetic basis for a fetus featuring oligodactyly.Methods:A fetus with hand deformity identified by ultrasound at the Maternal and Child Health Care Hospital of Hubei Province on October 20, 2018 was selected as the study subject. Clinical information and ultrasonographic finding of the pregnant woman were collected. Following elected abortion, umbilical cord and peripheral venous blood samples of the couple were collected for the extraction of genomic DNA. Copy number variation sequencing (CNV-seq) and trio-whole exome sequencing (trio-WES) were carried out. Candidate variants were verified by Sanger sequencing.Results:Ultrasonographic examination at 30 + 2 weeks of gestation revealed that the fetus had small right hand with absence of 2nd ~ 5th fingers, whilst its left hand had appeared to be normal. By CNV-seq, no pathogenic or likely pathogenic copy number variation (CNV) (> 100 kb) was detected in the fetus. Trio-WES revealed that the fetus had harbored a novel heterozygous c.3298G>A (p.Val1100Met) variant of the SMC3 gene. The variant has not been recorded in the population databases, and was predicted to be deleterious by several bioinformatics software and evolutionarily conserved based on multiple sequence alignment analysis. Sanger sequencing showed that neither parent has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3). Conclusion:The fetus was diagnosed with Cornelia de Lange syndrome, for which the novel heterozygous c.3298G>A variant of the SMC3 gene may be accountable.

Purpose To explore the feasibility of prenatal MRI as a supplementary imaging examination of fetal multicystic dysplastic kidney(MCDK),and to improve the accuracy of imaging diagnosis.Materials and Methods The MR images of 104 fetuses diagnosed as MCDK by prenatal fetal MRI in Hubei Maternal and Children's Hospital from January 2018 to December 2021 were retrospectively analyzed.The results of fetal MRI were compared with those of autopsy or postnatal surgery,ultrasound and MRI,and the diagnostic accuracy of MRI and ultrasound was compared,respectively,the advantages of MRI combined with ultrasound in the diagnosis of MCDK was also analyzed.Results Among 104 fetuses diagnosed as MCDK by MRI,there were 102 cases with MCDK and 2 cases with misdiagnoses.Amniotic fluid was obviously reduced or absent in 4 cases.Among the 102 cases of MCDK,58 cases(56.9％)were correctly diagnosed as MCDK by ultrasound,40 cases(39.1％)were identified with polycystic alterations,without diagnosed as MCDK,and 4 cases(3.9％)were misdiagnosed as other diseases(1 case with adult polycystic kidney,1 case with multiple renal cyst and 2 cases with renal absence).Conclusion Compared with prenatal ultrasound,prenatal MRI can obtain more information,especially in oligohydramnios and maternal obesity affecting the quality of ultrasound image.MRI can be used as a reliable supplementary method of prenatal ultrasound.

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b.Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases.It is involved in regulating the pathological process of myocardial infarction,myocardial ischemia/reperfusion injury,cardiac hypertrophy,atrial fibrillation,diabetic cardiomyopathy,atherosclerosis,pulmonary hyperten-sion,cerebral ischemia/reperfusion injury,Parkinson's disease,and Alzheimer's disease.Obviously,miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases.However,the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed.Therefore,in this review,we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases.Drugs targeting miR-135b for the treatment of diseases and related patents,highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases,have been discussed.

Objective To investigate the diagnostic effect of 64-slice spiral CT in patients with traumatic brain injury(TBI),and to evaluate the correlation between CT scores and cognitive function.Methods A total of 138 cases of TBI patients underwent surgical treatment were selected.The surgical pathological examination results were regarded as the gold standard.The prognosis was assessed by Glasgow outcome scale(GOS).The CT scores of all patients were compared by Montreal cognitive assessment(MoCA)and mini-mental state examination(MMSE)scores,and correlation between CT scores and cognitive-related scores was analyzed.Results The sensitivity of 64-slice spiral CT was 74.64%,82.61%and 98.55%within 3 hours,1 day and 2-3 days after admission,respectively.The MoCA and MMSE scores of severe patients were significantly higher than those of moderate and mild patients,and the MoCA and MMSE scores of moderate patients were significantly higher than those of mild patients(P<0.05).CT score was positively correlated with both MoCA and MMSE scores(P<0.05).The GOS of severe patients was significantly higher than that of moderate and mild patients,and the GOS of moderate patients was significantly higher than that of mild patients(P<0.05).Conclusion TBI can be detected with high sensitivity via 64-slice spiral CT.CT score has a significant positive correlation with the cognitive function,and is closely related to the prognosis.It can provide an effective basis for the clinical diagnosis and treatment.

BackgroundMental illness during pregnancy has become a major public health problem in China over the recent years， and depression is the most common psychological symptom during pregnancy. Current research efforts are directed towards the therapy on prenatal depression， whereas the construction of prediction model for prenatal depression risk has been little studied. ObjectiveTo construct a simple model for predicting the risk of prenatal depression， thus providing a valuable reference for the prevention of maternal depression during pregnancy. MethodsA total of 803 pregnant women attending three hospitals in Nanchong city were consecutively recruited from May 2021 to February 2022. A self-administered questionnaire was developed for the assessment of social demographic variables， obstetrical and general medical indexes and psychological status of all participants， and Self-rating Depression Scale （SDS） was utilized to screen for the presence of maternal depression. Subjects were randomly assigned into modelling group （n=635） and validation group （n=168） at the ratio of 8∶2 under simple random sampling with replacement. The candidate risk factors of maternal depression during pregnancy were screened using binary Logistic regression analysis， and the predictive model was constructed. Then the performance of the predictive model was validated using receiver operating characteristics （ROC） curve. Results① Lack of companionship （β=-0.692， OR=0.501， 95% CI： 0.289~0.868）， low mood during the last menstrual period （β=-1.510， OR=0.221， 95% CI： 0.074~0.656）， emotional stress during the last menstrual period （β=-1.082， OR=0.339， 95% CI： 0.135~0.853）， unsatisfactory relationship between mother-in-law and daughter-in-law （β=-1.228， OR=0.293， 95% CI： 0.141~0.609）， and indifferent generally relationship between mother-in-law and daughter-in-law （β=-0.831， OR=0.436， 95% CI： 0.260~0.730） were risk factors for prenatal depression in pregnant women （P<0.05 or 0.01）. ② Model for predicting the prenatal depression risk yielded an area under curve （AUC） of 0.698 （95% CI： 0.646~0.749）， the maximum Youden index was 0.357 in modelling group with the sensitivity and specificity was 0.606 and 0.751， and an AUC of 0.672 （95% CI： 0.576~0.767） and maximum Youden index of 0.263 in validation group with the sensitivity and specificity of 0.556 and 0.707. ConclusionThe simple model constructed in this study has good discriminant validity in predicting of the risk of prenatal depression. ［Funded by Nanchong Social Science Research Project of the 14th Five-Year Plan （number， NC21B165）］

Objective:To investigate the impact of short-term variability in fasting blood glucose (FPG) on the recent major cardiovascular adverse events (MACE) in patients with ST segment elevation myocardial infarction (STEMI) with different levels of glycated hemoglobin (HbA 1c) . Methods:Retrospective analysis was made on the patients with type 2 diabetes mellitus who underwent emergency percutaneous coronary intervention (PCI) due to STEMI from January 2016 to March 2020 in Shenzhen Hospital, Fuwai Hospital, Chinese Academy of Medical Sciences. The patients were divided into HbA 1c compliant group (<6.5%) and non-compliant group (≥6.5%). The blood glucose variability indexes defined included FPG variability score (FPG-VS), variability index independent of FPG mean (VIM) and mean fast plasma glucose (FPG-M). The logistic regression model was used to evaluate the relationship between different HbA 1c levels, blood glucose variability risk indicators, and MACE. Results:A total of 612 patients were ultimately included in the analysis. The blood glucose variability indicators (FPG-VS, VIM) of the HbA 1c non-compliant group (302 cases) were higher than those of the compliant group (310 cases): [FPG-VS: (0.7±0.3) vs (0.4±0.4), P<0.001, VIM: (0.4±0.2) vs (0.3±0.2), P<0.001], while there was no statistically significant difference in FPG-M between the two groups [(7.9±3.2) vs (8.0±3.9), P=0.221]. In the HbA 1c non-compliant group, the correlation between FPG-VS, VIM, and FPG-M and the risk of MACE within 30 days was 0.89(95% CI: 0.69-1.15), 1.21(95% CI: 0.65-2.25), and 1.06(95% CI: 0.97-1.16), respectively (all P>0.05). In the HbA 1c compliant group, FPG-VS was associated with an increase in MACE risk within 30 days ( P=0.04): for each increase in FPG variation ≥1 mmol/L, after multiple factor adjustment, the risk of MACE increased by 8% within 30 days ( OR=1.08, 95% CI: 0.71-1.65); Compared with FPG-VS<20%, FPG-VS≥80% increased the risk of MACE within 30 days by 33% ( OR=1.33, 95% CI: 0.21-8.25, P<0.01), while the correlation between VIM and FPG-M and the risk of MACE within 30 days was 1.65(95% CI: 0.96-2.83) and 1.15(95% CI: 0.98-1.35), respectively (all P>0.05). Conclusions:High FPG-VS is associated with the recent MACE risk in STEMI patients who do not meet HbA 1c standards. After reaching HbA 1c standards, FPG-VS remains an independent MACE risk factor.

We report a fetus with recurrent intraparenchymal hemorrhage and cystic leukomalacia during pregnancy who was postnatally detected with a de novo mutation in the COL4A1 gene by genetic testing of umbilical cord blood. Multiple fresh hemorrhagic foci were detected in the fetal brain parenchyma and cerebellar hemisphere by ultrasound at 25 gestational weeks. Regular re-examination of the nervous system's ultrasound and magnetic resonance imaging (MRI) indicated recurrent multiple intraparenchymal hemorrhages followed by cystic leukomalacia. However, karyotyping and chromosomal microarray analysis of amniotic fluid showed no abnormality. The newborn was born by cesarean section at 37 +3 gestational weeks with an Apgar score of 10 at 1 and 5 min. Repeated apnea occurred after birth. MRI detected new intraparenchymal hemorrhage and cystic leukomalacia on the six-day of life. The infant's limb muscle tone remained low on the 90-day follow-up. The patient was lost to follow up. Whole-exome sequencing of the cord blood identified a de novo heterozygous mutation- c.4738G>A in the COL4A1 gene (NM_001845.4; p.G1580S) neither parent carried. It suggests that the genetic test of the COL4A1 mutation should be considered for fetuses with intracranial hemorrhage in the prenatal diagnosis, especially those with recurrent fetal intraparenchymal hemorrhage followed by cystic leukomalacia. Genetic tests could help analyze the fetal prognosis, and guide the delivery mode.

Objective:To retrospectively analyze the classification of twin reversed arterial perfusion(TRAP) by prenatal ultrasound diagnosis, and to explore the clinical significance of this classification method.Methods:One hundred and fourteen TRAP cases were selected for prenatal ultrasound examination from January 2001 to January 2020 in Maternal and Child Health Hospital of Hubei Province, and were studied following the classification: hemiacardius(type Ⅰ), anceps trunk(type Ⅱ), acephalus trunk(type Ⅲ), acephalus acormus(type Ⅳ), acardius amorphous(type Ⅴ). Natural pregnancy outcomes were analyzed between group A(type Ⅰ, type Ⅱ, type Ⅲ) and group B(type Ⅳ, type Ⅴ).Results:Among 114 cases of TRAP, 27 cases (23.7%) were live birth, 33 cases (29.0%) were intrauterine death, 7 cases (6.1%) were perinatal death, 22 cases (19.3%) were induced labor complicated with heart failure, 4 cases (3.5%) were induced labor with malformation of pump twin, 21 cases (18.4%) were induced without heart failure of pump twim. Among 114 cases of TRAP, 20 cases (17.5%) were type Ⅰ, 27 cases (23.7%) were type Ⅱ, 48 cases (42.1%) were type Ⅲ, 8 cases (7.0%) were type Ⅳ and 11 cases (9.7%) were type Ⅴ. The prognosis of group B was better than group A during natural pregnancy ( P=0.007). Conclusions:Based on the diagnosis of prenatal ultrasound, the prognosis of type Ⅳ and type Ⅴ TRAP is better than that of type Ⅰ, type Ⅱ and type Ⅲ. The classification by prenatal ultrasound has positive significance for the clinical prognosis of pump twin.

Objective:To investigate the neonatal outcomes and prognosis of fetuses who were prenatally diagnosed with intraventricular hemorrhage(IVH) to provide evidence for clinical consultation and management.Methods:Clinical data of fetal IVH cases ( n=89) diagnosed by fetal neurosonogram (NSG) in Peking University First Hospital from January 2012 to April 2020 were retrospectively collected, and neonatal outcomes were analyzed, involving fetuses with different grades of IVH and coexisting abnormalities. These patients were followed up for more than three months after birth. Two child development screening systems, Ages & Stages Questionnaires (Third Edition) (ASQ-3) and Ages & Stages Questionnaires: Social-Emotional (ASQ-SE), were used to assess the development of the patients from several aspects including physical growth, oral communication, motor ability and social emotions. Descriptive statistical analysis was used in this study. Results:(1) A total of 89 fetuses were enrolled and 66.3% (59/89) of them underwent fetal cranial MRI examination after ultrasound diagnosis. Among these 59 cases, 32(54.2%) had the same results with fetal NSG; 20(33.9%) with the diagnosis of remote ventricular cystic hemorrhage by fetal NSG, but misdiagnosed by MRI, were all confirmed by neonatal craniocerebral ultrasound; 7(11.9%) were lost to follow-up or terminated. In addition to IVH that was consistent with the ultrasound diagnosis, MRI also found three cases of cortical malformation, three cases of subdural hemorrhage and two cases of cerebral parenchymal hemorrhage. (2) Among the 89 cases, 37 (41.6%) underwent neonatal craniocerebral ultrasound examination after birth showing small amount of remote IVH, which was consistent with previous fetal NSG diagnosis. (3) There were 38 cases complicated by lateral ventricular widening (three lost to follow-up, 18 were terminated , one died in uterus, 15 with good and one with poor outcome), 10 cases by severe IVH sequelae (one lost to follow-up and nine were terminated) and 10 by craniocerebral malformation (one lost to follow-up, eight were terminated and one with poor neonatal prognosis). Two cases with extracranial malformation (ureteropelvic junction obstruction) were healthy after birth. (4) There were 29, 30, 16 and 14 cases of gradeⅠ,Ⅱ,Ⅲ andⅣ of fetal IVH, respectively. Among all cases, 12 were lost to follow-up; three died in uterus (all with gradeⅣ IVH); 31 were terminated and 43 were born and followed up. During the follow-up of the 43 cases, two (one grade Ⅰ case with corpus callosum dysplasia and one grade Ⅲ case with fetal cytomegalovirus infection) had poor prognosis, while the other 41 (one gradeⅢ, 17 gradeⅡ and 23 gradeⅠcases) showed no severe abnormalities.Conclusions:Fetal NSG is the first choice in screening fetal IVH and MRI can be a valuable aid. The neonatal prognosis may be associated with the grade of hemorrhage and coexisting abnormalities. Fetuses with isolated grade Ⅰ or Ⅱ IVH usually have a relatively good prognosis.