Auditory Effects of Acoustic Noise From 3-T Brain MRI in Neonates With Hearing Protection.

BACKGROUND: Neonates with immature auditory function (eg, weak/absent middle ear muscle reflex) could conceivably be vulnerable to noise-induced hearing loss; however, it is unclear if neonates show evidence of hearing loss following MRI acoustic noise exposure. PURPOSE: To explore the auditory effects of MRI acoustic noise in neonates. STUDY TYPE: Prospective. SUBJECTS: Two independent cohorts of neonates (N = 19 and N = 18; mean gestational-age, 38.75 ± 2.18 and 39.01 ± 1.83 weeks). FIELD STRENGTH/SEQUENCE: T1-weighted three-dimensional gradient-echo sequence, T2-weighted fast spin-echo sequence, single-shot echo-planar imaging-based diffusion-tensor imaging, single-shot echo-planar imaging-based diffusion-kurtosis imaging and T2-weighted fluid-attenuated inversion recovery sequence at 3.0 T. ASSESSMENT: All neonates wore ear protection during scan protocols lasted ~40 minutes. Equivalent sound pressure levels (SPLs) were measured for both cohorts. In cohort1, left- and right-ear auditory brainstem response (ABR) was measured before (baseline) and after (follow-up) MRI, included assessment of ABR threshold, wave I, III and V latencies and interpeak interval to determine the functional status of auditory nerve and brainstem. In cohort2, baseline and follow-up left- and right-ear distortion product otoacoustic emission (DPOAE) amplitudes were assessed at 1.2 to 7.0 kHz to determine cochlear function. STATISTICAL TEST: Wilcoxon signed-rank or paired t-tests with Bonferroni's correction were used to compare the differences between baseline and follow-up ABR and DPOAE measures. RESULTS: Equivalent SPLs ranged from 103.5 to 113.6 dBA. No significant differences between baseline and follow-up were detected in left- or right-ear ABR measures (P > 0.999, Bonferroni corrected) in cohort1, or in DPOAE levels at 1.2 to 7.0 kHz in cohort2 (all P > 0.999 Bonferroni corrected except for left-ear levels at 3.5 and 7.0 kHz with corrected P = 0.138 and P = 0.533). DATA CONCLUSION: A single 40-minute 3-T MRI with equivalent SPLs of 103.5-113.6 dBA did not result in significant transient disruption of auditory function, as measured by ABR and DPOAE, in neonates with adequate hearing protection. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 5.

Convalescent plasma is of limited clinical benefit in critically ill patients with coronavirus disease-2019: a cohort study.

BACKGROUND: Recently, convalescent plasma (CP) transfusion was employed for severe or critically ill patients with coronavirus disease-2019. However, the benefits of CP for patients with different conditions are still in debate. To contribute clinical evidence of CP on critically ill patients, we analyze the characteristics and outcomes of patients with or without CP transfusion. METHODS: In this cohort study, 14 patients received CP transfusion based on the standard treatments, whereas the other 10 patients received standard treatments as control. Clinical characteristics and outcomes were analyzed. The cumulative survival rate was calculated by Kaplan-Meier survival analysis. RESULTS: Data analysis was performed on 24 patients (male/female: 15/9) with a median age of 64.0 (44.5-74.5) years. Transient fever was reported in one patient. The cumulative mortality was 21% (3/14) in patients receiving CP transfusion during a 28-day observation, whereas one dead case (1/10) was reported in the control group. No significant difference was detected between groups in 28-day mortality (P = 0.615) and radiological alleviation of lung lesions (P = 0.085). CONCLUSION: In our current study, CP transfusion was clinically safe based on the safety profile; however, the clinical benefit was not significant in critically ill patients with more comorbidities at the late stage of disease during a 28-day observation.

Clinical and epidemiological characteristics of pediatric SARS-CoV-2 infections in China: A multicenter case series.

BACKGROUND: As of April 18, 2020, over 2,000,000 patients had been diagnosed with coronavirus disease-2019 (COVID-19) globally, and more than 140,000 deaths had been reported. The clinical and epidemiological characteristics of adult patients have been documented recently. However, information on pediatric patients is limited. We describe the clinical and epidemiological characteristics of pediatric patients to provide valuable insight into the early diagnosis and assessment of COVID-19 in children. METHODS AND FINDINGS: This retrospective, observational study involves a case series performed at 4 hospitals in West China. Thirty-four pediatric patients with COVID-19 were included from January 27 to February 23, 2020. The final follow-up visit was completed by March 16, 2020. Clinical and epidemiological characteristics were analyzed on the basis of demographic data, medical history, laboratory tests, radiological findings, and treatment information. Data analysis was performed for 34 pediatrics patients with COVID-19 aged from 1 to 144 months (median 33.00, interquartile range 10.00-94.25), among whom 14 males (41%) were included. All the patients in the current study presented mild (18%) or moderate (82%) forms of COVID-19. A total of 48% of patients were noted to be without a history of exposure to an identified source. Mixed infections of other respiratory pathogens were reported in 16 patients (47%). Comorbidities were reported in 6 patients (18%). The most common initial symptoms were fever (76%) and cough (62%). Expectoration (21%), vomiting (12%), and diarrhea (12%) were also reported in a considerable portion of cases. A substantial increase was detected in serum amyloid A for 17 patients (among 20 patients with available data; 85%) and in high-sensitivity C-reactive protein for 17 patients (among 29 patients with available data; 59%), whereas a decrease in prealbumin was noticed in 25 patients (among 32 patients with available data; 78%). In addition, significant increases in the levels of lactate dehydrogenase and α-hydroxybutyrate dehydrogenase were detected in 28 patients (among 34 patients with available data; 82%) and 25 patients (among 34 patients with available data; 74%), respectively. Patchy lesions in lobules were detected by chest computed tomographic scans in 28 patients (82%). Ground-glass opacities, which were a typical feature in adults, were rare in pediatric patients (3%). Rapid radiologic progression and a late-onset pattern of lesions in the lobules were also noticed. Lesions in lobules still existed in 24 (among 32 patients with lesions; 75%) patients that were discharged, although the main symptoms disappeared a few days after treatment. All patients were discharged, and the median duration of hospitalization was 10.00 (8.00-14.25) days. The current study was limited by the small sample size and a lack of dynamic detection of inflammatory markers. CONCLUSIONS: Our data systemically presented the clinical and epidemiological features, as well as the outcomes, of pediatric patients with COVID-19. Stratified analysis was performed between mild and moderate cases. The findings offer new insight into early identification and intervention in pediatric patients with COVID-19.

[A comparative analysis of the efficacy of two vitamin D supplementation regimens in preterm infants: a prospective randomized controlled study].

OBJECTIVE: To study the effect of different vitamin D supplementation regimens on the nutritional status of vitamin D on day 28 after birth in preterm infants with a gestational age of <34 weeks. METHODS: A total of 59 preterm infants with a gestational age of <34 weeks who were born from October 2018 to October 2019 were enrolled and divided into an observation group with 30 infants and a control group with 29 infants. The infants in the observation group received a single-dose intramuscular injection of vitamin D3 (10 000 IU/kg), while those in the control group received oral vitamin D3 drops (900 IU/d) for 25 days. Venous blood samples were collected within 48 hours after birth (before vitamin D3 supplementation) and on day 28 after birth to measure the serum 25-hydroxyvitamin D [25(OH)D] level. RESULTS: Within 48 hours after birth, the prevalence rate of vitamin D deficiency (≤15 ng/mL) was 78% among the 59 preterm infants. There were no significant differences in the serum 25(OH)D level and the prevalence rate of vitamin D deficiency between the two groups (P>0.05). Compared with the control group on day 28 after birth, the observation group had a significantly higher serum 25(OH)D level (P<0.05) and a significantly lower prevalence rate of vitamin D deficiency (P<0.05). There were no cases of vitamin D overdose or poisoning. CONCLUSIONS: In preterm infants with a gestational age of <34 weeks, single-dose intramuscular injection of 10 000 IU/kg vitamin D3 can significantly increase serum 25(OH)D level on day 28 after birth and safely and effectively reduce the prevalence rate of vitamin D deficiency.

[Sedative effect of intranasal midazolam in neonates undergoing magnetic resonance imaging: a prospective single-blind randomized controlled study].

OBJECTIVE: To compare intranasal midazolam and intramuscular phenobarbital sodium for their sedative effect in neonates undergoing magnetic resonance imaging (MRI). METHODS: A total of 70 neonates who underwent cranial MRI from September 2017 to March 2019 were randomized into an observation group and a control group, with 35 cases in each group. The observation group received intranasal drops of midazolam (0.3 mg/kg), and the control group received intramuscular injection of phenobarbital sodium (10 mg/kg). The sedation status of the neonates was evaluated using the Ramsay Sedation Scale. Meanwhile, the two groups were compared for the success rate of MRI procedure and incidence of adverse reactions. RESULTS: In the observation group, the sedation score was the highest at 20 minutes post administration, then was gradually decreasing, and decreased to the lowest level at 70 minutes post administration. In the control group, the sedation score was the lowest at 10 minutes post administration, then was gradually increasing, and increased to the highest level at 40 minutes and 50 minutes post administration, followed by a gradual decrease. Comparison of the sedation score at each time period suggested that the sedation score was significantly higher in the observation group than in the control group within 40 minutes post administration (P<0.05), while there were no significant differences between the two groups in the sedation score after 40 minutes post administration (P>0.05). The success rate of MRI procedure was significantly higher in the observation group than in the control group (89% vs 69%, P<0.05). There was no significant difference between the two groups in the incidence of adverse reactions (P>0.05). CONCLUSIONS: Intranasal midazolam is superior to intramuscular phenobarbital sodium in the sedative effect in neonates undergoing MRI, with the benefits of being fast, convenient, safe, and effective.

Proper timing for the evaluation of neonatal brain white matter development: a diffusion tensor imaging study.

OBJECTIVE: We aimed to determine the timing for assessing birth status of the developing brain (i.e. brain maturity at birth) by exploring the postnatal age-related changes in neonatal brain white matter (WM). METHODS: The institutional review board approved this study and all informed parental consents were obtained. 133 neonates (gestational age, 30-42 weeks) without abnormalities on MRI were studied with regard to WM development by diffusion tensor imaging-derived fractional anisotropy (FA). Tract-based spatial statistics (TBSS), locally-weighted scatterplot smoothing (LOESS) and piecewise linear-fitting were used to investigate the relationship between FA and postnatal age. FA along corticospinal tract (CST), optic radiation (OR), auditory radiation (AR) and thalamus-primary somatosensory cortex (thal-PSC) were extracted by automated fibre-tract quantification; their differences and associations with neonatal neurobehavioural scores at various postnatal age ranges were analysed by Wilcoxon's rank-sum test and Pearson's correlation. RESULTS: Using TBSS, postnatal age (days 1-28) positively correlated with FA in multiple WMs, including CST, OR, AR and thal-PSC (p<0.05). On the other hand, when narrowing the postnatal age window to days 1-14, no significant correlation was found, suggesting a biphasic WM development. LOESS and piecewise linear-fitting indicated that FA increased mildly before day 14 and its growth accelerated thereafter. Both FA and correlations with neurobehavioural scores in postnatal age range 2 (days 15-28) were significantly higher than in range 1 (days 1-14) (FA comparison: p<0.05; maximal correlation-coefficient: 0.693 vs. 0.169). CONCLUSION: Brain WM development during the neonatal stage includes two phases, i.e. a close-to-birth period within the first 14 days and a following accelerated maturation period. Therefore, evaluations of birth status should preferably be performed during the first period. KEY POINTS: • Brain white matter development within the first two postnatal weeks resembles a close-to-birth maturation. • Brain white matter development in the audio-visual, sensorimotor regions accelerates after two postnatal weeks. • Postnatal age-related effects should be considered in comparing preterm and term neonates.

[The Function of Potassium Channel in KCNQ2 G271V Mutants of Benign Familial Neonatal Convulsions].

OBJECTIVE: To determine the function of potassium channel in KCNQ2 G271V mutants of benign familial neonatal convulsions. METHODS: HEK293 cells were transfected with pcDNA3-WT-KCNQ2 and / or pcDNA3-G271V-KCNQ2 and pcDNA3-WT-KCNQ3. The potassium channel function of G271V mutants was assessed using the whole cell patch clamp technique. RESULTS: G271V mutants did not show currents in the transfected HEK cells, inducing large depolarizing shift of the conductance voltage relationship and slowing down the current activation kinetics. The required current density was (2.47±0.41) pA/pF (n=12) for the expression of G271V, and whereas (20.53±2.51) pA/pF (n=10,P<0.001) for Kv7.2. G271V mutants abolished currents in the homomeric channel. Kv7.2/Kv7.3 induced robust current was (123.68±15.21) pA/pF (n=15) and Kv7.2/G271V/Kv7.3 (42.71±6.27) pA/pF (n=10), G271V/Kv7.3 induced almost no current (3.74±0.76) pA/pF (n=10,P<0.05), resulting in about 50% reduction of currents in Kv7.2/G271V/Kv7.3 in the heteromultimeric condition. CONCLUSIONS: The G271V channel fails to open potassium currents in response to depolarization, indicating a more severe functional defect of the Kv7 potassium channel.

[Influence of acute pancreatitis in pregnancy on pregnancy outcomes and neonates].

OBJECTIVE: To study the influence of acute pancreatitis in pregnancy (APIP) on pregnancy outcomes and neonates. METHODS: A retrospective analysis was performed for 33 APIP patients and 31 neonates born alive. RESULTS: Of the 33 APIP patients, 26 (79%) developed APIP in the late pregnancy. Fourteen (45%) patients had hyperlipidemic APIP, 13 (42%) had biliary APIP, and 4 (13%) had other types of APIP. According to the severity, 22 (67%) were mild APIP, 5 (15%) were moderate APIP, and 6 were severe APIP. None of the 33 APIP patients died. Among the 20 patients with term delivery, 11 underwent termination of pregnancy; among the 10 patients with preterm delivery, 9 underwent termination of pregnancy; two patients experienced intrauterine fetal death, and one experienced abortion during the second trimester. Among the 31 neonates born alive (two of them were twins), 1 (3%) died, 12 (39%) experienced neonatal hyperbilirubinemia, 8 (26%) had neonatal hypoglycemia, 6 (19%) had neonatal respiratory distress syndrome, 5 (16%) experienced infectious diseases, and 2 (6%) experienced intracranial hemorrhage. The hyperlipidemic APIP group had a higher percentage of patients undergoing termination of pregnancy than the biliary APIP and other types of APIP groups (P<0.05). The incidence rate of preterm infants in the moderate APIP was higher than in the mild and severe APIP groups (P<0.05). The mean birth weights of neonates were the lowest in the moderate APIP group. The incidence rates of neonatal respiratory distress syndrome, intracranial hemorrhage, and infectious disease were the lowest in the mild APIP group (P<0.05). CONCLUSIONS: APIP can lead to adverse pregnancy outcomes and neonatal diseases, which are associated with the severity of pancreatitis.

[Site-directed mutagenesis and protein expression of ABCA3 gene in A549 cells].

OBJECTIVE: To study the protocol of construction of the mutation E292V and M723I of hABCA3 gene associated with neonatal respiratory distress syndrome, as well as their eukaryotic green fluorescent protein expression rectors, and to examine the expression of mutation proteins in human lung carcinoma epithelial cells (A549). METHODS: Site-directed mutagenesis method based on overlap extension PCR was used to introduce mutations in the two sites which were E292V and M723I in the ABCA3. The PCR fragments were subcloned to PEGFP-C2 vectors to construct the eukaryotic green fluorescent protein expression rectors. A549 cells were transiently transfected with the recombinants using Lipofectamine 2000 and the transfection efficiency was confirmed through GFP signal. The expression and location of recombinants were detected by FV1000 laser scanning microscope. RESULTS: Direct sequence analysis confirmed an A to T transition at position 875 in E292V and a G to A transition at position 2169 in M723I. Recombinants were transfected to A549 cells and both wild type and mutant ABCA3 proteins were expressed in the cytoplasm. CONCLUSIONS: The eukaryotic green fluorescent protein expression rectors of wild type and mutant ABCA3 gene were constructed and they were successfully expressed in A549 cells. This experiment provides a basis for subsequent research.

Review on the application of imaging examination for brain injury in premature infants.

Brain injury is the main factor leading to the decline of the quality of life in premature infants. The clinical manifestations of such diseases are often diverse and complex, lacking obvious neurological symptoms and signs, and the disease progresses rapidly. Due to missed diagnosis, it is easy to miss the best treatment opportunity. Brain ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and other imaging methods can help clinicians diagnose and assess the type and extent of brain injury in premature infants to some extent, but the three methods have their own characteristics. This article briefly reviews the diagnostic value of these three methods for brain injury in premature infants.

Measurement of the burdens of neonatal disorders in 204 countries, 1990-2019: a global burden of disease-based study.

Background: Neonatal disorders are facing serious public health challenges. Previous studies were based on limited data sources and had a narrow geographical scope. We aim to understand the trends of alteration in the burden of neonatal disorders from 1990 to 2019 in 204 countries and territories. Methods: Data were investigated from the Global Burden of Disease Study 2019. First, we visualized the burden of neonatal disorders using the number of cases and the age-standardized incidence rate (ASIR), death rate (ASDR), and disability-adjusted life years (ASR-DALYs) from 1990 to 2019. Second, estimated annual percentage changes (EAPCs) were used to evaluate the temporal trends of disease burden during different periods. Finally, the sociodemographic index (SDI) and human development index (HDI) were used to determine whether there exists a correlation between socioeconomic development level, human development level, and potential burden consequences. Results: Overall, in the past 30 years, the ASIR trends have remained relatively steady, whereas the ASDR and ASR-DALYs have declined. However, the burden of neonatal disorders varied greatly in various regions and countries. Among 21 regions, the ASIR trend had the largest increase in Central Latin America (EAPC = 0.42, 95%CI = 0.33-0.50). Conversely, the ASDR and ASR-DALYs experienced the largest decrease in Central Europe (EAPC = -5.10, 95%CI = -5.28 to 4.93) and East Asia (EAPC = -4.07, 95%CI = -4.41 to 3.73), respectively. Among 204 countries, the ASIR (EAPC = 3.35, 95%CI = 3.13-3.56) trend in Greece displayed the most significant increase, while the ASDR (EAPC = 1.26, 95%CI = 1.01-1.50) and ASR-DALYs (EAPC = 1.26, 95%CI = 1.03-1.49) trends in Dominica experienced the most substantial increase. Furthermore, there was a strong correlation between the EAPCs in ASIR, ASDR, ASR-DALYs, and SDI or HDI in 2019, with some exceptions. In addition, countries with elevated levels of HDI experienced a faster increase in ASDR and ASR-DALYs for neonatal disorders. Conclusion: Although the burden of neonatal disorders shows a downward trend from 1990 to 2019, it is still not optimistic. It is necessary to implement a multi-pronged approach to reduce the increasing burden of neonatal disorders.

Primary repair of esophageal atresia gross type C via thoracoscopic magnetic compression anastomosis: A case report.

BACKGROUND: Esophageal atresia (EA) is a life-threatening congenital malformation in newborns, and the traditional repair approaches pose technical challenges and are extremely invasive. Therefore, surgeons have been actively investigating new minimally invasive techniques to address this issue. Magnetic compression anastomosis has been reported in several studies for its potential in repairing EA. In this paper, the primary repair of EA with magnetic compression anastomosis under thoracoscopy was reported. CASE SUMMARY: A full-term male weighing 3500 g was diagnosed with EA gross type C. The magnetic devices used in this procedure consisted of two magnetic rings and several catheters. Tracheoesophageal fistula ligation and two purse strings were performed. The magnetic compression anastomosis was then completed thoracoscopically. After the primary repair, no additional operation was conducted. A patent anastomosis was observed on the 15th day postoperatively, and the magnets were removed on the 23rd day. No leakage existed when the transoral feeding started. CONCLUSION: Thoracoscopic magnetic compression anastomosis may be a promising minimally invasive approach for repairing EA.

Analysis of cranial ultrasound images for newborn.

Introduction: Neonatal cranial ultrasound plays an important role in the evaluation of neonatal brain development and related diseases. Methods: This paper preliminarily explored the analysis and interpretation methods of neonatal brain ultrasound images, and applied the relevant medical image analysis methods to analyze the relevant neonatal brain ultrasound images in more detail. Results: Compared with other types of imaging methods, ultrasound has its unique advantages and characteristics in such applications as neonatal head imaging. Discussion: The analysis steps and schemes adopted in this paper have certain reference significance for the analysis of other neonatal brain pictures.

Clinical features and antibiotic treatment of early-onset neonatal listeriosis.

OBJECTIVE: To analyze the clinical features, efficacy of antibiotic treatment, and outcome of neonatal listeriosis. METHODS: This was a retrospective study that included all neonates diagnosed with listeriosis between January 2010 and December 2021. RESULTS: Nine male patients and five female patients were analyzed, including 11 preterm and 3 term infants. The mean gestational age was 34 ± 2.6 weeks (29 + 2-40 + 2 weeks), and the mean birth weight was 2392 ± 603 g (1370-3580 g). The maternal clinical manifestations included fever (13/14 [92.9%]), meconium-stained amniotic fluid (12/14 [85.7%]), and intrauterine fetal distress (11/14 [78.6%]). The neonates presented with fever (14/14 [100%]), generalized maculopapular rash (7/14 [50%]), and convulsions (8/14 [57.1%]). Laboratory tests showed leukocytosis (11/14 [78.6%]), monocytosis (9/14 [64.3%]), elevated C-reactive protein levels (13/14 [92.9%]), and thrombocytopenia (6/14 [42.9%]). Eight patients had central nervous system involvement, and Listeria monocytogenes was isolated from the blood in all cases. Empiric antibiotic therapy consisted of a combination of third-generation cephalosporins and penicillin or vancomycin. Four patients died, and 10 patients were cured. CONCLUSIONS: Preterm infants were more susceptible to listeria infection than term infants, with most having multiple organ injuries. Combined antibiotic application improved the effectiveness of treatment.

Topical and intravenous administration of human umbilical cord mesenchymal stem cells in patients with diabetic foot ulcer and peripheral arterial disease: a phase I pilot study with a 3-year follow-up.

BACKGROUND: Diabetic foot ulcer (DFU) is a serious chronic complication of diabetes mellitus that contributes to 85% of nontraumatic lower extremity amputations in diabetic patients. Preliminary clinical benefits have been shown in treatments based on mesenchymal stem cells for patients with DFU or peripheral arterial disease (PAD). However, the long-term safety and benefits are unclear for patients with both DFU and PAD who are not amenable to surgical revascularization. METHODS: In this phase I pilot study, 14 patients with PAD and incurable DFU were enrolled to assess the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) administration based on conservative treatments. All patients received topical and intravenous administrations of hUC-MSCs at a dosage of 2 × 105 cells/kg with an upper limit of 1 × 107 cells for each dose. The adverse events during treatment and follow-up were documented for safety assessments. The therapeutic efficacy was assessed by ulcer healing status, recurrence rate, and 3-year amputation-free rate in the follow-up phase. RESULTS: The safety profiles were favorable. Only 2 cases of transient fever were observed within 3 days after transfusion and considered possibly related to hUC-MSC administration intravenously. Ulcer disclosure was achieved for more than 95% of the lesion area for all patients within 1.5 months after treatment. The symptoms of chronic limb ischaemia were alleviated along with a decrease in Wagner scores, Rutherford grades, and visual analogue scale scores. No direct evidence was observed to indicate the alleviation of the obstruction in the main vessels of target limbs based on computed tomography angiography. The duration of rehospitalization for DFU was 2.0 ± 0.6 years. All of the patients survived without amputation due to the recurrence of DFU within 3 years after treatments. CONCLUSIONS: Based on the current pilot study, the preliminary clinical benefits of hUC-MSCs on DFU healing were shown, including good tolerance, a shortened healing time to 1.5 months and a favorable 3-year amputation-free survival rate. The clinical evidence in the current study suggested a further phase I/II study with a larger patient population and a more rigorous design to explore the efficacy and mechanism of hUC-MSCs on DFU healing. TRIAL REGISTRATION: The current study was registered retrospectively on 22 Jan 2022 with the Chinese Clinical Trial Registry (ChiCTR2200055885), http://www.chictr.org.cn/showproj.aspx?proj=135888.

[Site-directed mutagenesis and protein expression of KCNQ2 gene associated with neonatal convulsions].

OBJECTIVE: To study the protocol of construction of a KCNQ2-c.812G>T mutant and it's eukaryotic expression vector, the c.812G>T (p.G271V) mutation which was detected in a Chinese pedigree of benign familial infantile convulsions, and to examine the expression of mutant protein in human embyonic kidney (HEK) 293 cells. METHODS: A KCNQ2 mutation c.812G>T was engineered on KCNQ2 cDNAs cloned into pcDNA3.0 by sequence overlap extension PCR and restriction enzymes. HEK293 cells were co-transfected with pRK5-GFP and KCNQ2 plasmid (the wild type or mutant) using lipofectamine and then subjected to confocal microscopy. The transfected cells were immunostained to visualize the intracellular expression of the mutant molecules. RESULTS: Direct sequence analysis revealed a G to T transition at position 812. The c.812G>T mutation was correctly combined to eukaryotic expressive vector pcDNA3.0 and expressed in HEK293 cells. Immunostaining of transfected cells showed the expression of both the wild type and mutant molecules on the plasma membrane, which suggested that the c.812G>T mutation at the pore forming region of KCNQ2 channel did not impair normal protein expression in HEK293 cells. CONCLUSIONS: Successful construction of mutant KCNQ2 eukaryotic expression vector and expression of KCNQ2 protein in HEK293 cells provide a basis for further study on the functional effects of convulsion-causing KCNQ2 mutations and for understanding the molecular pathogenesis of epilepsy.

Neonatal isovaleric acidemia in China: A case report and review of literature.

BACKGROUND: Isovaleric acidemia (IVA) is a rare autosomal recessive inherited organic acidemia caused by a genetic deficiency of isovaleryl-CoA dehydrogenase (IVD). Its morbidity is low, but mortality is high. There is no effective cure for this disease. Early identification of IVA using clinical features can significantly slow disease progression and reduce mortality. Here we report a Chinese neonate with two mutations of IVD and share valuable information on this disease. CASE SUMMARY: A 12-day-old male neonate with "poor response for 1 d and repeated convulsions accompanied by high muscle tension for 6 h" was hospitalized. The patient was the first child of nonconsanguineous ethnic Chinese parents. He was delivered by cesarean section due to breech position at 39 + 1 wk of gestation with a birth weight of 3.27 kg. Initially, he suffered from dyspnea and rhinobyon, and at 10 d after birth the patient suddenly developed poor feeding, low response, lethargy and seizures. Organic acid analysis of blood and urine by tandem mass spectrometry and gas chromatography mass spectrometry showed extremely high concentrations of isovaleryl glycine. The patient had an acute episode of IVA causing severe metabolic stress and eventually died. CONCLUSION: A new case of an IVA patient carrying c.1193G>A (p.Arg398Gln) and c.1208A>G (p.Try403Cys) mutations is reported in China.

Clinical Recognition of Sensory Ataxia and Cerebellar Ataxia.

Ataxia is a kind of external characteristics when the human body has poor coordination and balance disorder, it often indicates diseases in certain parts of the body. Many internal factors may causing ataxia; currently, observed external characteristics, combined with Doctor's personal clinical experience play main roles in diagnosing ataxia. In this situation, different kinds of diseases may be confused, leading to the delay in treatment and recovery. Modern high precision medical instruments would provide better accuracy but the economic cost is a non-negligible factor. In this paper, novel non-contact sensing technique is used to detect and distinguish sensory ataxia and cerebellar ataxia. Firstly, Romberg's test and gait analysis data are collected by the microwave sensing platform; then, after some preprocessing, some machine learning approaches have been applied to train the models. For Romberg's test, time domain features are considered, the accuracy of all the three algorithms are higher than 96%; for gait detection, Principal Component Analysis (PCA) is used for dimensionality reduction, and the accuracies of Back Propagation (BP) neural Network, Support Vector Machine (SVM), and Random Forest (RF) are 97.8, 98.9, and 91.1%, respectively.

[Linkage analysis and gene mapping of one Chinese family with benign familial infantile convulsions].

OBJECTIVE: The present study performed linkage analysis and gene mapping to find the possible chromosome locus harboring in one family with benign familial infantile convulsions (BFIC) and investigate the possible molecular pathogenesis of BFIC. METHODS: A four-generation family with BFIC was investigated. The family was genotyped using eight hypervariable microsatellite markers covering four loci: D19S245 and D19S250 for the 19q12-13.1 region, D16S3131 and D16S3133 for the 16p12-q12 region, D2S156 and D2S286 for the 2q24 region, and D20S480 and D20S481 for the 20q13.3 region. Polymorphism fragments were amplified using polymerase chain reaction (PCR) method. PCR products for the markers were subjected to electrophoresis on 8% denatured polyacrylamide gel and silver staining for length judgment of amplification fragment. Linkage analysis was performed by use of MLINK in the LINKAGE computer package. Two-point LOD scores were calculated to estimate the linkage relationship. RESULTS: The two-point LOD scores were less than -2.0 for the genetic markers at chromosomes 19q12-13.1, 16p12-q12 and 2q24 at the recombination rate between 0.000 and 0.01. The two-point LOD scores for D20S481 at the 20q13.3 region were 0.3 and 0.25 at the recombination rate of 0.000 and 0.01, respectively. CONCLUSIONS: There is no evidence that this family with BFIC is linked to one of the following loci: 19q12-13.1, 16p12-q12 and 2q24, but a possible linkage with 20q13.3 region cannot be excluded.

Therapeutic evidence of umbilical cord-derived mesenchymal stem cell transplantation for cerebral palsy: a randomized, controlled trial.

BACKGROUND: Cerebral palsy (CP) is a syndrome of childhood movement and posture disorders. Clinical evidence is still limited and sometimes inconclusive about the benefits of human umbilical cord mesenchymal stem cells (hUC-MSCs) for CP. We conducted a randomized trial to evaluate the safety and efficacy of hUC-MSC transplantation concomitant with rehabilitation in patients with CP. METHODS: Eligible patients were allocated into the hUC-MSC group and control group. In addition to rehabilitation, the patients in the hUC-MSC group received four transfusions of hUC-MSCs intravenously, while the control group received a placebo. Adverse events (AEs) were collected for safety evaluation in the 12-month follow-up phase. Primary endpoints were assessed as activities of daily living (ADL), comprehensive function assessment (CFA), and gross motor function measure (GMFM) scales. In addition, cerebral metabolic activity was detected by 18F-FDG-PET/CT to explore the possible mechanism of the therapeutic effects. Primary endpoint data were analyzed by ANOVA using SPSS version 20.0. RESULTS: Forty patients were enrolled, and 1 patient withdrew informed consent. Therefore, 39 patients received treatments and completed the scheduled assessments. No significant difference was shown between the 2 groups in AE incidence. Additionally, significant improvements in ADL, CFA, and GMFM were observed in the hUC-MSC group compared with the control group. In addition, the standard uptake value of 18F-FDG was markedly increased in 3 out of 5 patients from the hUC-MSC group at 12 months after transplantation. CONCLUSIONS: Our clinical data showed that hUC-MSC transplantation was safe and effective at improving the gross motor and comprehensive function of children with CP when combined with rehabilitation. Recovery of cerebral metabolic activity might play an essential role in the improvements in brain function in patients with CP. The therapeutic window, transfusion route, and dosage in our study were considerable for reference in clinical application. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1800016554. Registered 08 June 2018-retrospectively registered. The public title was "Randomized trial of umbilical cord-derived mesenchymal stem cells for cerebral palsy."