OBJECTIVE To study the effects of methimazole on the urinary metabolomics of hyperthyroidism rats， and to preliminarily investigate its possible mechanism. METHODS Thirty SD rats were randomly divided into control group， model group and methimazole group， with 10 rats in each group. Except for the control group， the rats in the other two groups were given Levothyroxine sodium tablets 160 mg/kg by intragastric administration for 15 days； at the same time， methimazole group was additionally given methimazole 3.6 mg/kg daily by intragastric administration every day. The basic condition of the rats was observed， and the body weight and anal temperature were measured. After the last medication， the serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， free triiodothyronine （FT3）， free tetraiodothyronine （FT4）， and thyroid stimulating hormone （TSH） were determined； 24-hour urine was collected on the 15th day after administration. UPLC-TOF-MS was used to analyze the urine metabolomics of rats. Principal component analysis and orthogonal partial least squares-discriminant analysis were used to screen out related differential metabolites， and potential metabolic pathways were analyzed by using HMDB and KEGG. RESULTS Compared with the control group， the rectal temperature， serum levels of T3， T4， FT3 and FT4， the expressions of differential metabolites sebacic acid， cholic acid 3-O-glucuronic acid and N6， N6， N6-trimethyl-L-lysine in urine were significantly up-regulated， while body weight， serum level of TSH， the expressions of deoxycytidine and 2-oxo-4-methylthiobutanoic acid in urine were significantly down-regulated （P＜0.01）. Compared with model group， above indexes of rats were reversed significantly in methimazole group （P＜0.01 or P＜0.05）. Above five differential metabolites were mainly involved in four signaling pathways: pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism. CONCLUSIONS Methimazole might improve hyperthyroidism by modulating the four pathways of pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism.

Objective:To explore teaching methods to improve the teaching effect in view of many difficulties in learning medical statistics for clinical medical students.Methods:Taking the clinical medical students of the same grade as the research objects, the students were randomly divided into two groups by cluster sampling in class, i.e. control group and experimental group. The traditional teaching methods and the scenario-based interactive learning software teaching methods were used respectively. The scores of medical statistics courses examinations and the statistical errors in responding to projects of extracurricular research activities were compared between the two groups. SPSS 19.0 was performed for statistical analysis.Results:The results of subject achievements of the students in the experimental group (74.08±11.19) were higher than those in the control group (63.82±10.10) ( t=3.926, P<0.001), especially the comprehensive capabilities of the innovative analysis questions and the multiple-choice questions. The statistical errors of the students in the experimental group was less than those in the control group. There were significant differences between the two groups in the estimation of sample size ( χ2=4.189, P=0.041), statistical design ( χ2=5.558, P=0.018) and data analysis ( χ2=3.971, P=0.046). Conclusion:The results suggest that scenario-based interactive learning software is helpful to improve teaching efficiency, and enhance students' ability to analyze and solve practical problems by using medical statistics knowledge.

OBJECTIVE: To explore the clinical characteristics of congenital neutropenia caused by ELANE gene mutations. METHODS: Clinical manifestations, absolute blood neutrophil count, high-throughput exome sequencing for mutation screening, suspected locus Sanger sequencing verification, processes of diagnosis and treatment of two patients with congenital neutropenia caused by ELANE gene mutation were retrospectively analyzed. RESULTS: High-throughput sequencing has found that proband 1 has carried a heterozygous c.170C>T (p.Ala57Val) missense mutation in exon 2 of the ELANE gene, which was known to be pathological, and a heterozygous c.251T>G (p.Leu84Arg) mutation in exon 3 of proband 2, which was unreported previously. Sanger sequencing confirmed that neither mutation was inherited from their parents. CONCLUSION ELANE mutation is an important cause for congenital neutropenia. Detection of new pathogenic variants has enriched the mutation spectrum of the ELANE gene.

Objective To investigate the situation and the causes of neonatal death in Henan Province.Methods This study retrospectively analyzed the clinical data of 277 neonates who died at 18 hospitals in Henan Province in 2017.Distribution and causes of neonatal deaths,differences between perinatal conditions of premature and term/post-term infants,causes of early (＜ 7 d) and late (7-28 d) neonatal deaths and the differences in neonatal death cases between Maternal and Child Health Care Hospitals and General/Children's Hospitals were analyzed.We used t,rank-sum and Chi-square test (or corrected Chi-square test,or Fisher's exact test) for statistical analysis.Results (1) A total of 50 993 newboms were admitted to the 18 hospitals in 2017,297 of which died with a mortality of 5.82‰.After excluding 20 cases with uncertain birth or maternal pregnancy history or clinical data,277 cases with complete data were analyzed.Among them,168 (60.6％) were preterm neonates and 109 (39.4％) were term/post-term ones.Early and late neonatal deaths accounted for 74.0％ (205 cases) and 26.0％ (72 cases),respectively.(2) The top five causes of neonatal deaths were infection (78 cases,28.2％),asphyxia (54 cases,19.5％),neonatal respiratory distress syndrome (NRDS,33 cases,11.9％),severe congenital malformations (26 cases,9.4％) including cyanotic congenital heart diseases,digestive malformations,airway malformations and neural tube defects and pulmonary hemorrhage (23 cases,8.3％).Among them,the top three causes of early neonatal deaths were asphyxia (48 cases,23.4％),infection (43 cases,21.0％) and NRDS (33 cases,16.1％),while the main causes of late neonatal deaths were infection (35 cases,48.6％),major congenital malformations (9 cases,12.5％) and chromosome abnormities/inherited metabolic diseases (7 cases,9.7％).(3) Maternal complications during pregnancy accounted for 79.1％ (219 cases) and the predominant types were pregnancy-induced hypertension (43 cases,19.6％),followed by infection (36 cases,16.4％),placental-related conditions (32 cases,14.6％),gestational diabetes mellitus (23 cases,10.5％),hypothyroidism (20 cases,9.1％),fetal distress (18,8.2％),twin-twin transfusion syndrome (10 cases,4.6％) and cholestasis syndrome (9 cases,4.1％).(4) Compared with the term/post-term cases,the preterm cases had higher proportions of multiple births [27.4％ (46/168) vs 6.4％ (9/109),x2=14.016,P ＜ 0.05],assisted reproduction [7.1％ (12/168) vs 0.9％ (1/109),x2=4.421,P ＜ 0.05] and maternal hypertensive disorders of pregnancy [21.4％ (36/1 68) vs 6.4％ (7/109),x2=11.353,P ＜ 0.05],infection [16.7％ (28/168) vs 7.3％ (8/109),x2=4.295,P ＜ 0.05] and twin-to-twin transfusion syndrome [6.0％ (10/168) vs 0.0％ (0/109),x2=6.707,P ＜ 0.05].(5) Among all the early neonatal deaths,preterm cases had a higher incidence of NRDS than term/post-term neonates [20.3％ (27/133) vs 8.3％ (6/72),x2=1 1.937,P ＜ 0.05],but lower incidence of meconium aspiration syndrome (MAS),severe congenital malformations and chromosome abnormalities/inherited metabolic diseases [0.8％ (1/133) vs 5.6％ (4/72),x2=4.508;3.8％ (5/133) vs 16.7％ (12/72),x2=10.233;1.5％ (2/133) vs 6.9％ (5/72),~=4.172;all P ＜ 0.05].Among the late neonatal deaths,the incidence of severe intracranial hemorrhage in preterm infants was higher than that in term/post-term neonates [7.1％ (3/42) vs 0.0％ (0/30),x2=2.205,P ＜ 0.05].(6) Compared with the cases in General/Children's Hospitals,those in Maternal and Child Health Care Hospitals showed a higher proportion of preterm neonatal deaths [67.3％ (105/156) vs 52.1％ (63/121),x2=6.010,P ＜ 0.05],younger gestational age [(32.8±5.3) weeks vs (34.6±4.9) weeks,t=3.072,P ＜ 0.05],lower birth weight [(2 132.6± 1 014.5) g vs (2 409.4±987.3) g,t=-2.513,P ＜ 0.05],and higher average age of death [M(P25-P75),3 (1-8) d vs 2 (1-4) d,Z=3.710,P ＜ 0.05].Conclusions Neonatal death occurs mainly within one week after birth in those with maternal complications.Late preterm deaths and term/post-term cases account for nearly half of total neonatal deaths.The causes of death for preterm and term/post-term newborns vary with postnatal age.Infection,asphyxia and severe congenital malformations are important causes of neonatal deaths.

Objective To assess the value of transesophageal echocardiography (TEE) in left atrial appendage (LAA) closer with Amplatzer Cardiac Plug (ACP).Methods Consecutive 32 atrial fibrillation patients (CHADS2≥1) with high risk bleeding underwent LAA occlusion with ACP LAA occlusion device under the guidance of TEE.Measurements of LAA anchoring area diameter (AAD) and LAA anatomical orifice diameter (AOD) including maximum,minimum values,and LAA depth on 2 dimentional TEE (2D TEE) were conducted before closer device implantation.The outcomes of LAA occlusion were analyzed.Results Among 32 patients,27 cases achieved successful LAA occlusion,including 2 cases with peripheral leakage ≤5 mm,and 5 cases failed occlusion.Among 5 failed closed patients,3 cases with LAA AAD≥ 30 mm,1 case with LAA of short depth,and 1 case with anatomical variation of LAA of low position that access sheath could not be positioned in the LAA.LAA AAD maximum,minimum and LAA depth were (25.9±4.9)mm,(20.0±3.8)mm,(31.0±5.6)mm,respectively,and LAA AOD maximum,minimum diameters were (26.2±6.2)mm,(19.4±4.3)mm,respectively.Among 10 cases with LAA AAD≥30 mm,7 cases achieved successful LAA occlusion,but 3 cases failed.The implanted device diameter was (26.4±3.8)mm,and device compression rate was (7.6±5.5)%.The coefficient of correlation between device diameter and large LAA AAD and AOD is 0.770 and 0.717,respectively.There was no complication but 1 case with pericardial effusion.Conclusions Two dimentional TEE measurements of LAA have clinical guiding significance in the selection of proper size of ACP LAA occluder.The AAD of 2D TEE has the good correlation with ACP occluder′s size,the AADs are important factors which affect the success of LAA occlusion.

Objective To evaluate right ventricular (RV)systolic function in type-2 diabetes mellitus (T2DM)patients.Methods Fifty T2DM patients and fifty normal controls were included in the study and underwent echocardiographic examinations.The following parameters were measured:1 ) Right heart dimensions,pulmonary artery (PA)diameter,pulmonary acceleration time (AT)and PA systolic pressure (PASP);2)RV systolic function:RV fractional area change (RVFAC),tissue Doppler-derived tricuspid lateral annular systolic velocity (S'),tricuspid annular plane systolic excursion (TAPSE),longitudinal strain of six RV segments by 2-dimensional speckle tracking imaging (2D-STI);3 )RV diastolic function:E,A ratio of the tricuspid inflow spectrum (E/A),E,E'(peak early diastolic velocity of the tricuspid annulus) ratio (E/E');4)RV Tei index.Results Statistic analysis showed that T2DM patients had thicker RV walls,wider PAs and shorter AT than the control group (P =0.000,0.001 and 0.000),while their right heart chamber sizes and PASP remained unchanged.Among systolic parameters,absolute values of RV longitudinal strain at the lateral wall-mid (lat-m),septum-mid (sep-m)and septum-basal (sep-b)segments were significantly lower in the diabetic group than the control group (P =0.001 ,0.000 and 0.005),whereas strain of the other three RV segments and RVFAC,TAPSE.S'were not significantly different.Moreover, E/A,E/E'and Tei index were all significantly different between the two groups (P = 0.000,0.000 and 0.006),indicating declined diastolic and general function of RV in the T2DM group.Conclusions RV myocardial strain by 2D-STI is more sensitive in detecting RV systolic dysfunction than TAPSE,S' and RVFAC.Among the six segments of RV walls,lat-m,sep-m and sep-b are better locations for 2D-STI than the other three.

Objective To evaluate the role of real-time three-dimensional transesophageal echocardiography(RT-3D TEE)in left atrial appendage (LAA)occlusion.Methods Consecutive 10 atrial fibrillation (AF)patients (CHADS2 ≥ 2 )with high risk bleeding underwent LAA occlusion under the guidance of TEE.The LAA orifice shape and characteristics of lobes were assessed,the size of LAA with RT-3D TEE wee measured before closer implanation,and the position of the LAA occlusion device were evaluated by RT-3D TEE.The correlational analysis between LAA diameter and occluder size was conducted.Results Among 10 patients,the test results revealed 8 cases with complete LAA occlusion and 1 case with incomplete occlusion,and 1 case with failed occlusion.Five cases showed approximate round LAA ostium,and the other 5 showed approximate oval ostium.The average number of LAA lobes were 2.2±0.7. LAA ostium long diameter were larger by 3D TEE compared with 2D TEE[(21 .8±5.1)mm vs (20.8±4.1) mm],and ostium short diameter were smaller by 3D TEE compared with 2D TEE [(16.1 ± 3.0 )mm vs (1 7.0±2.6)mm],however there were no significant differences between 2D and 3D TEE measurements,and the mean ostium diameter and LAA depth were comparable between two methods.LAA ostium long diameter,short diameter,average diameter and LAA depth assessed by 3D TEE and 2D TEE showed good correlation with occluder diameter (3D TEE:r =0.719,0.690,0.791 ,0.71 1 ,and P =0.029,0.040,0.01 1 , 0.032,respectively;2D TEE:r = 0.887,0.894,0.932,0.896,and P = 0.001 ,0.001 ,0.000,0.000, respectively).LAA occlusion device position assessed by RT-3D:6 cases with appropriate position, acceptable position with 2 cases,and 1 case with malposition.Conclusions RT-3D TEE can play important role in evaluating the morphology of LAA,accurately judging LAA ostium shape and size and position of the occlusion device.

Objective To explore the imaging features of papillary thyroid microcarcinoma(PTMC) with real time contrast-enhanced ultrasound.Methods One hundredand forty-three cases with 149 thyroid nodules(no diffuse lession) were divided into two groups according to the diameter size(group 1,＜0.5 cm;group 2,0.5-1.0 cm) and examined by contrast-enhanced ultrasound during preoperation.Pathology was followed up as golden diagnosis criteria.Results Seventy-five benign tumors and 74 PTMC were confirmed by pathology.There were significant differences in echoes homogeneity between benign and malignant tumors in group 2(W =1 029.5,Z =-5.524,P =0.000) but no in group 1(W =933.0,Z =-1.738,P =0.082).And nonhomogeneous enhancement were showed in most PTMC in group 2.But most PTMC showed homogeneous enhancement in group 1.Conclusions Contrast-enhanced ultrasound is valuable in diagnosis of PTMC with the diameter size of 0.5-1.0 cm.

Objective To discuss the feasibility and accuracy of left atrial appendage (LAA)ejection fraction by real-time 3 dimensional imaging (3D-EF),and tissue velocity of the LAA wall by tissue Doppler imaging (TDI)via transesophageal echocardiography (TEE)in assessing LAA functions.Methods A total number of 76 patients with atrial fibrillation (AF)were included in the study consecutively and underwent TEE for LAA investigations.3D-EF,fractional area change by 2 dimensional imaging (2D-FAC),peak emptying velocity (PEV),LAA tissue velocity by TDI at the mid-portion of lateral wall (TDI-L),mid-portion of septal wall (TDI-S)and the apical tip (TDI-A)were calculated.Results Statistic analysis showed the following results:1 )2D-FAC,3D-EF,PEV,TDI-L,TDI-S and TDI-A were all significantly higher in patients with sinus rhythm than those with AF during the TEE examinations (all P <0.05),and significantly higher in patients without spontaneous echo contrast (SEC)than those who had SEC (all P <0.05);2)The results of 3D-EF showed a good correlation with 2D-FAC (r=0.727,P =0.000),and their correlations with PEV were similar (2D-FAC and PEV:r =0.685;3D-EF and PEV:r =0.632,both P =0.000);3)TDI-A [(14.95±4.63)cm/s]were significantly higher than TDI-L [(12.62±3.96)cm/s]and TDI-S [(12.68±3.59)cm/s](both P =0.000).The correlations of TDI-A with PEV,2D-FAC and 3D-EF were all marked higher than those of TDI-L and TDI-S (with PEV:r=0.840 vs r=0.564,r=0.524;with 2D-FAC:r=0.701 vs r=0.486,r=0.504;with 3D-EF:r=0.753 vs r=0.493,r=0.522,all P <0.05). Conclusions 3D TEE is feasible and reliable in assessing LAA emptying function.The best location for LAA tissue velocity evaluation is the apical tip.

Objective To apply the binary Logistic regression model and evaluate the value of grey scale ultrasonography(US),ultrasond elastography(UE) and contrast-enhanced ultrasound(CEUS).Methods US,UE and CEUS were performed in 130 patients with 142 solid thyroid micronodules (the largest diameter less than 10 mm).Pathology was followed up as golden diagnosis criteria.A Logistic model on the basis of ultrasonographic features was obtained.A receiver operating characteristic(ROC) curve was used to assess the performance of Logistic model.Results Four ultrasonic indexes were finally entered into the Logistic regression model including microcalcification,acpect ratio,advanced CEUS mode and elasticity score.The percentage correction of prediction was 92.1％ (129/142),the area under the ROC curve was 0.944.Conclusions The multivariate analysis model of binary Logistic regression can describe and analyze the process of differential diagnosis of malignant and benign solid thyroid micronodules by ultrasonography,and select out the valuable indexes for differential diagnosis.