Clinical feature and genetic analysis of a patient with Idiopathic hypogonadotropic hypogonadism due to a novel variant of CHD7 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical feature and genetic etiology of a patient with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) due to variant of CHD7 gene.@*METHODS@#A patient who had presented at Anhui Provincial Children's Hospital in October 2022 was selected as the study subject. Clinical data of the patient was collected. The patient and his parents were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The patient had featured delayed development of secondary sexual characteristics but normal olfactory function. Genetic testing revealed that he has harbored a c.3052C>T (p.Pro1018Ser) missense variant of the CHD7 gene, for which both of his parents were of the wild type. The variant has not been recorded in the PubMed and HGMD databases. Analysis of amino acid sequences suggested that the variant site is highly conserved, and the variant may affect the stability of protein structure. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.3032C>T variant was classified as a likely pathogenic (PS2+PM2_Supporting+PP2+PP3+PP4).@*CONCLUSION@#The delayed development of secondary sexual characteristics of the patient may be attributed to the c.3052C>T (p.Pro1018Ser) variant of the CHD7 gene. Above finding has expanded the variation spectrum of the CHD7 gene.

Clinical characteristics and genetic analysis of an ethnic Han Chinese child with Keppen-Lubinsky syndrome due to a de novo KCNJ6 mutation / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical characteristics and genetic basis for a child with Keppen-Lubinsky syndrome (KPLBS).@*METHODS@#Trio-whole exome sequencing (Trio-WES) was carried out for the proband and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child has featured peculiar facies including large eyes, alar hypoplasia, microretrognathia, premature aging appearance in addition with growth delay and mental retardation. Trio-WES has identified that she has carried a de novo variant of the KCNJ6 gene, namely c.460G>C (p.Gly154Arg). The variant has not been recorded in the database. Prediction of protein structure indicated that the variant may affect the potassium ion selective filtration structure channel in the transmembrane region of KCNJ6 protein, which may result in up regulation of the function of the channel.@*CONCLUSION@#The de novo c.460G>C (p.Gly154Arg) variant of the KCNJ6 gene probably underlay the KPLBS in this child. Above finding has enriched the genotypic and phenotype spectrum of this syndrome.

Expressions of miRNA-146a in peripheral mononuclear cells of children with systemic juvenile idiopathic arthritis and its clinical significance / 中华实用儿科临床杂志

Objective:To investigate the role of miR-146a in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA) and its clinical significance.Methods:This article is a prospective clinical cohort study.Twenty-six patients with sJIA (14 cases of initial active group and 12 cases of stable group), 15 patients with multijoint juvenile idiopathic arthritis (JIA) and 15 patients with oligojoint JIA diagnosed in the Department of Rheumatology and Immunology of Anhui Provincial Children′s Hospital from June 2018 to December 2020 were enrolled.Twenty healthy controls from the out-patient clinic were also recruited.The expression level of miR-146a in peripheral blood mononuclear cells (PBMCs) of research objects was detected by real-time fluorescence quantitative polymerase reaction (qPCR), and the serum levels of interleukin (IL) - 6, tumor necrosis factor (TNF) - α and IL-1β in sJIA patients and healthy controls were detected by enzyme-linked immunosorbent assay.The expression levels of miR-146a in PBMCs and cytokines among different groups were compared by analysis of variance. Pearson correlation analysis was used to analyze the correlation of the relative expression level of miR-146a in PBMCs with clinical inflammatory indexes and serum cytokines in sJIA patients. Results:(1) The expression level of miR-146a in PBMCs of early sJIA patients was significantly higher than that in the multijoint JIA group and oligojoint JIA group (8.77±3.15 vs.4.40±1.59, 2.55±1.15, t=6.27, 14.23; all P<0.05). The expression level of miR-146a in PBMCs of sJIA active patients was significantly higher than that in sJIA stable patients (8.77±3.15 vs.3.63±1.37, t=10.27, P<0.05). There was no significant difference in the expression level of miR-146a between the sJIA stable group and healthy control group ( P>0.05). (2) The expression levels of IL-1β, IL-6 and TNF-α were significantly higher in sJIA active patients group than those in sJIA stable group[(58.56±17.47) ng/L vs.(26.32±10.54) ng/L, (73.72±11.16) ng/L vs.(23.20±9.12) ng/L, (70.93±19.97) ng/L vs.(24.25±9.49) ng/L, all P<0.05]. There was no significant difference in the expression levels of IL-1β, IL-6 and TNF-α between the sJIA stable group and healthy control group(all P>0.05). (3)The expression of miR-146a in PBMCs of sJIA patients was positively correlated with serum ferritin levels, platelets, erythrocyte sedimentation rates, C-reactive proteins, IL-1β, IL-6 and TNF-α( r=0.542, 0.433, 0.329, 0.306, 0.333, 0.342, 0.319, all P<0.05). Conclusions:miR-146a may be involved in the inflammatory process of sJIA disease.miR-146a can well distinguish sJIA from multijoint JIA and oligojoint JIA.TNF-α, IL-1β and IL-6 are involved in sJIA inflammatory responses.

Advances on researches of clinical pathology and pathogenesis in patients with acute alcoholic hepatitis / 中国中西医结合急救杂志

Alcoholic hepatitis (AH) is an acute severe decompensated alcoholic liver disease (ALD), commonly occurring in heavy drinkers. The pathogenesis of AH is still not fully understood, which may be related to the interactions of multiple complex factors such as alcohol metabolism, inflammation and heredity, etc. Under the background of continuous alcoholic exposure, the pathological changes include hepatocyte steatosis, liver inflammation and fibrosis occurring in the body. This paper summarizes the recent research literatures related to the clinicopathological features, pathogenesis and prognosis evaluation of ALD to comprehensively understand the pathogenesis and pathophysiological characteristics of AH in order to provide theoretical basis for clinical diagnosis and treatment of this disease.

Clinicopathological features analysis of common complications in pediatric liver transplantation / 中华器官移植杂志

Objective The purpose of this study was to explore common complications and their clinicopathological features in pediatric liver transplantation.Methods Clinical and pathological data of 240 liver biopsies from 168 children that conducted liver puncture from January 2015 to May 2018 in Tianjin First Central Hospital was retrospectively analyzed.We comprehensively analyzed incidence rate and pathological features of various complications,and correlations between acute rejection and C4d staining result or Banff score.Results A total of 86.67％ (208/240) liver biopsies could be definitely diagnosed with incidence rate of main complications in descending order as follows:T cell mediated rejection (TCMR) 60.57％ (126/208),drug-induced liver injury (DILI) 17.31％ (36/208),biliary complication 8.17％ (17/208),vascular complication 3.37％ (7/208),ischemia/reperfusion injury (IRI) 2.88％ (6/208),antibody mediated acute rejection (AMR) 1.92％ (4/208),HBV infection 1.92％ (4/208),non-alcoholic fatty liver disease (NAFLD) 1.44％ (3/208),chronic rejection (CR) 0.96 ％ (2/208) and HCV infection 0.48 ％ (1/208).TCMR and AMR in acute rejection (AR) accounted for 96.92％ (126/130) and 3.08％ (4/160),and into(portal-based,PB)type TCMR accounted for 96.03％(121/126) with the detectable rate of BP type subtype TCMR of 26.45％(32/121)within 30 d.There were 65.87％ (83/126)、25.40％ (32/126) 和4.76％ (6/126) of BP TCMR samples with "Banff ACR RAI" score within 3-5,6-7 and 8-9,and RAI score was negatively correlated with postoperative time (r =0.127,P =0.084).The incidence rate of central perivenulitis (CP) and portal eosinophils infiltration (PEI) in BP TCMR was 63.63％ (77/121) 和43.80％ (53/ 121),respectively,additionally,the PEI level was positively correlate with RAI score (P＜0.05).CP TCMR and AMR occurred within 30d-365 d and 8 d-180 d,respectively postoperative,while,the two CR occurred at 1095 d and 1335 d postoperative,and significant correlation was strikingly observed between rejection subtype and postoperative time (Z =9.231,P =0.026).C4d positive rate was 10％ (24/240),which was associated with Banff score and postoperative time,besides,C4d score was also correlated with rejection subtype and RAI score.The occurrence of DILI was mainly at time of ＜90 d or ＞180 d postoperative,and the detectable rate of biliary complication within 180 d postoperative was 82.35％ (14/17),IRI Appear in ＜30d.Hepatic artery complication account for nearly 57.14％ (4/7),occurrence time is ≤90 d.Occurrence of HBV infection,CMV infection and NAFLD were mainly at ＞365 d,＜90 d and ＜365 d,respectively.Conclusion There were lots of differences in clinical and pathological features among multi pediatric liver transplantation complications.Liver puncture plays an important role in rejection subtype classification and grading,as well as in non-rejection complications identification.

Expression and significance of Nanog and Oct4 in endometriosis and adenomyosis / 实用医学杂志

Objective To investigate the expressions of Nanog and Oct4 (stem cell transcription factors) in endometriosis and adenomyosis, and to explore their potential functions in the development of endometriosis and adenomyosis. Methods The expressions of Nanog and Oct4 in the ectopic and eutopic endometrium of 50 patients with endometriosis and/or adenomyosis (ectopic endometrium group and eutopic endometrium group), and 21 patients free from endometriosis and adenomyosis (control group) were detected by immunohistochemical SABC methods. Statistical analysis was conducted for the correlation between the expressions of Nanog and Oct4 based on patients′ clinical pathological parameters. Results Nanog and Oct4 protein expressions in ectopic endometrium group were higher than that in control group (P 0.05); there was positive correlation between the expressions of Nanog and Oct4 in ectopic endometrium group (r = 0.590, P < 0.01). Conclusion Nanog and Oct4 present high expression in eutopic and ectopic endometrium , which may play a important role in the development of endometriosis and adenomyosis.

Value of color Doppler ultrasonography in the diagnosis of precocious puberty in girls / 中华超声影像学杂志

Objective To assess the role of pelvic ultrasound examination in discriminating between normal girls,isolated premature thelarche/pubarche /menarche and central precocious puberty (CPP).Methods Eighty-four isolated premature thelarche/pubarche /menarche cases,47 CPP cases,and 177 normal girls aged 0-10 years were recruited.All diagnoses were confirmed by the gonadotropin-releasing hormone-stimulation test.All subjects underwent pelvic ultrasound examination for the measurement of length,width,thickness,and volume of the uterine body,uterine cervix,and ovary,and the number of follicles with diameter≥ 4 mm.The groups were subdivided by age intervals when the difference in ultrasound measurements between CPP,isolated premature thelarche/pubarche/menarche,and normal girls were analyzed.Results 1) Differentiation between CPP and normal girls:for the 6-8 years,there were 11 variables elevated in CPP as compared to the normal girls.Uterine cervix thickness was the most efficient parameter as judged by the largest value of area under the ROC curve (0.958).The best cut-off,sensitivity,and specificity was 0.73 cm,93.30％,and 85.70％ respectively;for the 8-10 years,uterine body volume was the best parameter among the 10 elevated variables as judged by the largest area under the ROC curve (0.869),3.23 cm3 was the best cut-off limit with a sensitivity of 84.21％ and a specificity of 52.11％.2) Differentiation between isolated premature thelarche/pubarche/menarche and normal girls:for the 0-6 years,ovary thickness was the best variable as judged by the largest area under the ROC curve (0.806),0.98cm was the best cut-off limit with a sensitivity of 76.46％ and a specificity of 84.85 ％ ;for the 6-8 years,ovary width was the best variable among the 8 valuable variables for its largest area under the ROC curve (0.843),1.39 cm was the best cut-off limit with a sensitivity of 85.71％ and a specificity of 73.81％ respectively;for the 8-10 years,uterine cervix thickness was the best variable among the 5 valuable variables for its largest area under ROC curve (0.841),0.75 cm was the best cut-off limit with a sensitivity of 90.48％ and a specificity of 64.21％.3) Differentiation between CPP and isolated premature thelarche/ pubarche/menarche cases:for the 6-8 years,uterine cervix length and width were potential parameters.Uterine cervix length was the best variable for its largest area under the ROC curve(0.764),and 1.49 cm was the best cut-off limit,the corresponding sensitivity and specificity was 93.33％ and 55.17％ respectively;for the 8-10 years,3 variables could be used,among which uterine cervix length was the best variable for its largest area under the ROC curve (0.893),1.88 cm was the best cut-off limit with a sensitivity of 100％ and a specificity of 71.43％.Condusions Pelvic ultrasound examination is a valuable tool for the diagnosis and differentiation between CPP,isolated premature thelarche/pubarche /menarche and normal girls.

An integrated segmentation method for 3D ultrasound carotid artery / 中国医疗器械杂志

An integrated segmentation method for 3D ultrasound carotid artery was proposed. 3D ultrasound image was sliced into transverse, coronal and sagittal 2D images on the carotid bifurcation point. Then, the three images were processed respectively, and the carotid artery contours and thickness were obtained finally. This paper tries to overcome the disadvantages of current computer aided diagnosis method, such as high computational complexity, easily introduced subjective errors et al. The proposed method could get the carotid artery overall information rapidly, accurately and completely. It could be transplanted into clinical usage for atherosclerosis diagnosis and prevention.

The Influence of Cell Proliferation and Microvessel Density on the Recurrence of Synovial Sarcoma / 中国肿瘤临床

Objective: To study the prognostic significance of cell proliferation and apoptosis, MVD and clinicopathologi-cal parameters for the recurrence of synovial sarcoma. Methods: We analyzed the clinical and follow-up data of 56 synovial sarcoma patients without metastasis. RT-PCR was used to detect the subtype of SYT-SSX fusion gene. The expression of Ki67 and MVD was detected by immunohistochemistry. Univariate analysis was employed to analyze the influence of the above factors and clinicopathological parameters on the recurrence free survival and to explore the influencing factors for the recurrence of synovial sarcoma. Results: Of all the patients, 73.2% (41/56) had recurrence during the follow-up. The median recurrence free survival was 19.5 months. The recurrence free 1-, 2-, 3-, 4-, and 5-year survival rates after surgery were 45.0%, 41.0%, 34.0%, 28.0%, and 28.0%, respectively. Ki-67 labeling index (LI) was 19.98%±11.64% and MVD was 51.83±21.92 per ×400. There was no significant difference in apoptotic index (AI) between the two groups (P=0.607). Χ~2 analysis showed that histological type (P=0.000) and MVD (P=0.045) were significantly correlated with the recurrence of sy-novial sarcoma. Univariate analysis showed that Ki67 LI (P=0.009), histological type (P=0.012) and radiotherapy (P= 0.014) were significantly correlated with the recurrence free survival of synovial sarcoma patients. Sex (P=0.015), tumor lo-cation (P=0.411), tumor size (P=0.801), necrosis (P=0.486), MVD (P=0.454), chemotherapy (P=0.272), and apoptotic grade (P=0.899) were not correlated with the recurrence free survival of synovial sarcoma patients. Multivariate analysis re-vealed that higher expression of Ki67 (RR=1.944, P=0.045), radiotherapy (RR=0.482, P=0.04), and histological type (RR= 0.207, P=0.031) were independent risk factors for the recurrence of synovial sarcoma. Conclusion: The expression of Ki67, radiotherapy and histological type are important factors for evaluating the recurrence and prognosis of synovial sarcoma.

The Influence of SYT-SSX Fusion Gene, E-cadherin and β-Catenin on the Metastasis of Synovial Sarcoma / 中国肿瘤临床

Objective: To study the prognostic significance of the subtype of SYT-SSX fusion gene, E-cadherin, β-Catenin and clinicopathologicel parameters for the metastasis of synovial sarcomas. Methods: A total of 98 synovial sar-coma patients with complete clinical and follow-up data were reviewed. RT-PCR was used to detect the subtype of SYT-SSX fusion geneo The expression of E-cadherin and β-catenin was detected by immunohistochemistry. Univariate and multivariate analyses were performed to analyze the influence of the above factors and clinicopathological parameters on the metastasis free survival to explore the factors affecting the metastasis of synovial sarcoma. Results: Of all the pa-tients, 69.4% (68/98) had metastasis during follow-up. The median metastasis free survival was 48 months. The metastasis free 1-, 2-, 3-, 4-, and 5-year survival rate after surgery was 97.5%, 75.5%, 63.5%, 54.0%, and 48.5%, respectively; 31.6% (31/98) patients were found with SYT-SSX1 and 68.4% (67/98) patients with SYI-SSX2. The positive rate of E-cadherin ex-pression was 38.8% (38/98), the positive rate of β-catenin expression was 39.8% (39198) on cellular membrane and 53.1% (52/98) in cellular nucleus/cytoplasm. Univariate analysis showed that age (P=0.003), mitotic figure (P=0.002), histological grade (P=0.001), the subtype fusion gene of SYT-SSX (P=0.014), E-cadherin expression (P=0.015) and β-catenin expres-sion on cellular membrane (P=0.020) were significantly correlated with metastasis free survival of synovial sarcoma pa-tients. Sex (P=0.190), tumor location (P=0.105), tumor size (P=0.180), histological type (P=0.354), necrosis (P=0.451), β-catenin expression in cell nucleus/cytoplasm (P=0.911), radiotherapy (P=0.193), and chemotherapy (P=0.249) had no sig-nificant correlation with metastasis free survival of synovial sarcoma patients. Multivariate analysis revealed that the sub-type of SYT-SSX1 fusion gene (RR=2.505, P=0.003), negative expression of E-cadherin (RR=3.282, P=0.000), patient age (RR=2.157, P=0.004), and grade Ⅲ (RR=1.784, P=0.030) were independent risk factors for metastasis of synovial sarco-ma. Conclusion: The subtype of SYT-SSX, expression of E-cadherin, histological grade and the age of patients are impor-tant factors for evaluating the metastasis and prognosis of synovial sarcoma.