Lethal mitochondrial trifunctional protein deficiency caused by HADHB gene variation: a case report / 中华围产医学杂志

This article reported a male neonate with lethal mitochondrial trifunctional protein deficiency (MTPD) caused by compound heterozygous variations in the HADHB gene. The patient presented with poor milk intake complicated by abnormal myocardial enzymes within 24 h after birth and was transferred to the Children's Hospital of Nanjing Medical University on day 4. Physical examination revealed no obvious abnormalities on admission. Laboratory examination showed increased creatine kinase isoenzyme and cardiac troponin levels, and electrocardiogram suggested sinus tachycardia and low QRS voltage in limb leads. Blood screening for metabolic abnormalities showed high levels of tetradecenyl carnitine and various 3-hydroxycarnitines. Heterozygous mutations of c.739C>T(p.Arg247Cys) and c.607C>T(p.Arg203Ter,272) were detected in the HADHB gene in the boy, which were pathogenic variants included in the Human Gene Mutation Database. Followed up to three months of age, the boy was readmitted to hospital due to poor milk intake for one week and poor response for 2 d after catching a cold. After admission, he quickly developed multiple organs dysfunction such as heart failure and respiratory failure, and then died. Lethal MTPD is rare with no effective treatment and poor prognosis. Lethal MTPD should be highly suspected when unexplained cardiomyopathy, hypoglycemia, acidosis and other metabolic abnormalities appear in the neonatal period, and an early diagnosis could be confirmed with genetic testing in the neonatal period.

Predictive value of ultrasonic cardiac output monitor in premature infants with hemodynamic significant patent ductus arteriosus / 中华实用儿科临床杂志

Objective:To evaluate the diagnostic and predictive value of ultrasonic cardiac output monitor (USCOM) in premature infants with hemodynamic significant patent ductus arteriosus (hsPDA).Methods:A total of 165 preterm infants with gestational age less than 34 weeks and within 72 hours after birth in the Neonatal Medical Center of Children′s Hospital of Nanjing Medical University from January 2018 to June 2020 were retrospectively analyzed.According to the echocardiograph (ECHO) results within 72 hours after birth, clinical manifestations and oral administration of Ibuprofen, premature infants were divided into non-patent ductus arteriosus (non-PDA group, 77 cases), non-hsPDA group (59 cases), and hsPDA group (29 cases). USCOM was performed within half of an hour after ECHO.During the course of oral medication of Ibuprofen in the hsPDA group, USCOM was repeatedly examined every 24 hours.ECHO and USCOM were re-examined within 24 hours after the course of oral medication of ibuprofen.Results:Compared with non-hsPDA group and non-PDA group, the gestational age [(31.51±1.62) weeks, (32.09±1.27) weeks vs.(30.82±1.61) weeks, F=8.425, P<0.001], birth weight [(1 154.49±192.55) g, (1 195.58±182.02) g vs.(1 094.66±153.69) g, F=3.366, P=0.037] and the mean blood pressure [(38.37±2.20) mmHg, (38.53±2.37) mmHg vs.(30.52±2.31) mmHg, 1 mmHg=0.133 kPa, F=142.860, P<0.001]were significantly lower in hsPDA group.On the contrary, the heart rate[(129.68±7.11) times/min, (130.34±7.27) times/min vs.(164.76±7.65) times/min, F=271.790, P<0.001], B-type natriuretic peptide[(203.76±108.68) ng/L, (152.43±54.24) ng/L vs.(3 385.31±856.26) ng/L, F=931.30, P<0.001] and left artrium/aorta (1.32±0.12, 1.29±0.09 vs.1.60±0.12, F=84.970, P<0.001)were significantly higher.Among the USCOM parameters, left ventricular cardiac output [(0.40±0.08) L/min, (0.40±0.08) L/min vs.(0.51±0.04) L/min, F=26.760, P<0.001], cardiac index (CI) [(3.76±0.48) L/(min·m 2), (3.54±0.30) L/(min·m 2) vs.(4.43±0.36) L/(min·m 2), F=56.060, P<0.001], stroke volume[(3.75±0.28) mL, (3.70±0.23) mL vs.(4.22±0.36)mL, F=40.170, P<0.001], stroke volume index [(34.42±2.66) mL/m 2, (34.47±3.29) mL/m 2vs.(38.45±3.32) mL/m 2, F=20.080, P<0.001], peak ejection velocity [(1.12±0.12) m/s, (1.11±0.10) m/s vs.(1.23±0.09) m/s, F=14.890, P<0.001] and corrected flow time [(379.02±22.69) ms, (376.51±27.95) ms vs.(403.69±39.04) ms, F=10.120, P<0.001]were significantly higher in hsPDA group, while systemic vascular resistance index (SVRI) [(1 109.49±115.67) ds·cm -5·m 2, (1 070.01±133.55) ds·cm -5·m 2vs.(861.31±115.22) ds cm -5m 2, F=41.130, P<0.001]was significantly lower than that of non-hsPDA and non-PDA group.The area under the receiver operating characteristic curve of CI and SVRI for predicting hsPDA were 0.916 and 0.905, respectively.The sensitivity and specificity of CI>4.05 L/(min·m 2) for predicting hsPDA was 0.828 and 0.860, respectively, which was 0.660 and 1.000 for SVRI<1 002.5 ds·cm -5·m 2.The sensitivity and specificity of combining CI and SVRI for predicting hsPDA was 0.966 and 0.949, respectively. Conclusions:USCOM has a good diagnostic and predictive value for hsPDA in premature infants.The combined application of CI and SVRI can improve the predictive value, and help formulate the early diagnostic and treatment strategy for PDA in premature infants

The clinical value of video-electroencephalogram on the diagnosis and prognosis of neonatal seizure / 中国新生儿科杂志

Objective To study the clinical value of video-electroencephalogram (VEEG) on the diagnosis and prognosis of neonatal seizure.Method From January 2016 to December 2017,the medical records of 118 neonates who had seizure and received VEEG in our hospital were collected.The results of VEEG and medical records were analyzed using x2 test,Fisher's exact test or rank sum test.Result Among the 118 neonates,94 cases(79.6％) had abnormal VEEG results,including 59 mildly abnormal cases,21 moderately abnormal cases,and 14 severely abnormal cases.The characteristics of mildly abnormal VEEG was delayed mature,and moderately and severely abnormal VEEG were paroxysmal abnormal activities.All of the severely abnormal VEEGs showed abnormal background activities.The incidence of abnormal background activities of severely abnormal group was higher than mildly and moderately abnormal group,the difference was significant (P＜0.001).Neonates with abnormal background activities had higher rates of epileptic seizure and delayed maturation than those with normal background,and the differences were significant (P＜0.001).Among 32 neonates with paroxysmal events,17 cases had non-epileptic events including subtle seizures,myoclonus seizures,and symmnetrical tonic seizures;15 cases had epileptic electrographic seizures and electro-clinical seizures,12 cases had focal seizures.The degree of abnormal VEEG had positive correlations with the incidences of epileptic seizures and delayed maturation (P＜0.001).Conclusion Neonates with seizure has higher rate of abnormal VEEG.Non-epileptic events presents as subtle seizures and myoclonus seizures,and epileptic seizures as focal seizures.The background activities of neonatal VEEG has important predictive value for prognosis.The worse the VEEG is,the higher the possibility of epileptic seizure and delayed maturation.

Preparation of lithium-doped poly-glycerol sebacate scaffold and its properties / 吉林大学学报(医学版)

Objective:To prepare the lithium-doped poly-glycerol sebacate (PGS-Li) scaffold using the specific effects of lithium ions and the excellent performance of PGS, and to provide the basis for its application prospects in cementation tissue engineering scaffold.Methods:The scaffolds were divided into two groups.The PGS-Li scaffolds prepared by adding lithium phosphate during the PGS cross-linking process were used as PGS-Li group, and the PGS scaffolds synthesized by the equal-purification of sebacic acid and glycerol were used as PGS group.The molecular weights of the scaffolds in two groups were determined by gel permeation chromatography.The structures of the scaffolds in two groups were analyzed by fourier transform infrared spectroscope.The surface morphology and the porosities and the pore sizes of the scaffolds in two groups were observed by scanning electron microscope.X-ray photoelectron (XPS) spectroscope and inductively coupled plasma optical emission spectrometer were used to determine the Li ion contents in the scaffolds in two groups.Thermogravimetric analyzer was used to analyze the thermal stabilities of the scaffolds in two groups.Contact angle measuring instrument was used to compare the hydrophilicities of the scaffolds in two groups.In vitro weight loss test was used to determine the degradation rates of the scaffolds in two groups.The OCCM-30cells were divided into experimental group (added with PGS-Li scaffold extract) , PGS group (added with PGS scaffold extract) and blank control group (added with DMEM culture medium) .MTT assay was used to detect the proliferation activities of cells in various groups at different time (24, 48and 72h) ;the cell morphology was observed by calcein-AM staining.Results:The gel permeation chromatography results showed that the molecular weight of the PGS-Li scaffold was slightly larger than that of the PGS scaffold.The specific absorption peak of phosphate was detected in the fourier infrared spectrum of the PGS-Li scaffold.The scaffolds in two groups had irregular three-dimensional network structures under scanning electron microscope, and the pore size was 20-160μm, the porosity of PGS scaffold was (53.92±2.18) ％, and the porosity of PGS-Li scaffold was (53.58±1.73) ％, there was no statistical difference between two groups (P＞0.05) .The XPS results showed that a peak appeared at 54.9eV in PGS-Li group, which coincided with the Li 1s binding energy, while the inductively coupled plasma emission spectrometer results showed that the Li ion content in the PGS-Li scaffold was 0.084％.The thermogravimetric analysis results showed that PGS-Li scaffolds began to degrade at a higher temperature and ceased at a lower temperature compared with PGS scaffolds.The contact angle measurement results indicated that both the materials were hydrophilic materials;the contact angle of PGS scaffold meterial was 78.26°±2.00°, and the contact angle of the PGS-Li scaffold material was 69.78°±1.15°;there was statistical difference between two groups (P＜0.05) .The in vitro degradation experiments showed that the degradation rate of PGS-Li scaffolds was faster than that of PGS scaffolds.The proliferation activity of OCCM-30cells in PGS-Li group had no significant difference compared with PGS group and blank control group (P＞0.05) .The calcein-AM staining results showed the green fluorescence in the OCCM-30cells in PGS and PGS-Li groups, and there were no significant changes in the morphology of cementoblasts.Conclusion:PGS-Li scaffolds have similar composition and structure to PGS scaffolds, and have better performance in hydrophilicity and thermal stability.PGS-Li scaffolds have no effect on the proliferation of cementoblasts and have broad application prospects in cementum tissue engineering.

Preparation of lithium-doped poly-glycerol sebacate scaffold and its properties / 吉林大学学报(医学版)

Objective: To prepare the lithium-doped poly-glycerol sebacate (PGS-Li) scaffold using the specific effects of lithium ions and the excellent performance of PCS, and to provide the basis for its application prospects in cementation tissue engineering scaffold. Methods: The scaffolds were divided into two groups. The PGS-Li scaffolds prepared by adding lithium phosphate during the PGS cross-linking process were used as PGS-Li group, and the PGS scaffolds synthesized by the equal-purification of sebacic acid and glycerol were used as PGS group. The molecular weights of the scaffolds in two groups were determined by gel permeation chromatography. The structures of the scaffolds in two groups were analyzed by fourier transform infrared spectroscope. The surface morphology and the porosities and the pore sizes of the scaffolds in two groups were observed by scanning electron microscope. X-ray photoelectron (XPS) spectroscope and inductively coupled plasma optical emission spectrometer were used to determine the Li ion contents in the scaffolds in two groups. Thermogravimetric analyzer was used to analyze the thermal stabilities of the scaffolds in two groups. Contact angle measuring instrument was used to compare the hydrophilicities of the scaffolds in two groups. In vitro weight loss test was used to determine the degradation rates of the scaffolds in two groups. The OCCM-30 cells were divided into experimental group (added with PGS-Li scaffold extract), PGS group (added with PGS scaffold extract) and blank control group (added with DMEM culture medium). MTT assay was used to detect the proliferation activities of cells in various groups at different time (24, 48 and 72 h); the cell morphology was observed by calcein-AM staining. Results: The gel permeation chromatography results showed that the molecular weight of the PGS-Li scaffold was slightly larger than that of the PGS scaffold. The specific absorption peak of phosphate was detected in the fourier infrared spectrum of the PGS-Li scaffold. The scaffolds in two groups had irregular three-dimensional network structures under scanning electron microscope∗ and the pore size was 20- 160 /im, the porosity of PGS scaffold was (53. 92 ±2. 18) %∗ and the porosity of PGS-Li scaffold was (53. 58± 1. 73)% ? there was no statistical difference between two groups ( P> 0.05). The XPS results showed that a peak appeared at 54. 9 eV in PGS-Li group, which coincided with the Li Is binding energy, while the inductively coupled plasma emission spectrometer results showed that the Li ion content in the PGS-Li scaffold was 0.084%. The thermogravimetric analysis results showed that PGS-Li scaffolds began to degrade at a higher temperature and ceased at a lower temperature compared with PGS scaffolds. The contact angle measurement results indicated that both the materials were hydrophilic materials; the contact angle of PGS scaffold meterial was 78. 26 ±2. 00 , and the contact angle of the PGS-Li scaffold material was 69. 78 ±1.15 ; there was statistical difference between two groups (P0. 05). The calcein-AM staining results showed the green fluorescence in the OCCM-30 cells in PGS and PGS-Li groups, and there were no significant changes in the morphology of cementoblasts. Conclusion: PGS-Li scaffolds have similar composition and structure to PGS scaffolds, and have better performance in hydrophilicity and thermal stability. PGS-Li scaffolds have no effect on the proliferation of cementoblasts and have broad application prospects in cementum tissue engineering.

The analysis of lung adenocarcinoma transcript 1 expression in non-small cell lung cancer / 中国综合临床

Objective To investigate the significance of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in the occurrence and development of non-small cell lung cancer(NSCLC).Methods Eighty-six NSCLC lung tissue samples and 86 corresponding adjacent tissues were collected.Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect MALAT1 mRNA expression.The correlation analysis of the gender,age,carcinoma embryonic antigen (CEA),clinical stage,and the degree of differentiation was performed.Results MALAT1 expression levels showed an average 2.16-fold increase in NSCLC lung tissues(87.23 ±9.72) when compared with adjacent tissues(40.38 ± 5.49),the difference was statistically significant (t =7.894,P ＜ 0.01).There was no significant difference between gender,age,histological type,tumor diameter,CEA level in terms of MALAT1 expression (P ＞ 0.05).There was significant differences between pathological stage (Ⅰ stage =52.38％ (11/21),Ⅱ stage =76.00％ (19/25),Ⅲ stage =97.50％ (39/40),x2 =11.839,P =0.042),tumor differentiation (High differentiated =39.13％ (9/23),moderately differentiated =74.47％ (35/47),low differentiated =100％ (16/16),x2 =15.383,P =0.032)and lymph node metastasis (with =97.22％ (35/36),no =46.00％ (23/50),x2 =23.947,P =0.030).Conclusion MALAT1 might be involved in the development of NSCLC,and could be an auxiliary diagnosis marker.