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Background@#The transcription factor paired box 8 (PAX8) was associated with type 2 congenital non-goitrous hypothyroidism (CHNG2), a clinical phenotype of congenital hypothyroidism (CH). Though studied in a few regions with different ethnicities, the incidence of PAX8 mutations varied, even among Chinese cohorts in different regions. This study aimed to identify and characterize PAX8 mutations and explore the prevalence of its mutations in another cohort of CH.@*Methods@#The 105 unrelated Chinese patients with CH were collected from four major hospitals. Exomes of the 105 samples were sequenced by Hiseq 2000 platform to identify mutations of PAX8 on genomic DNAs extracted from peripheral blood samples. Luciferase reporter assays were used to assess the effects of mutations on the transcription of thyroid peroxidase (TPO).@*Results@#Three PAX8 mutations in four subjects were identified in 105 samples. One variant, rs189229644, was detected in two subjects, and categorized as uncertain significance. The other two missense mutations (275T>C/Ile92Thr and 398G>A/Arg133Gln) were not detected in three large-scale genotyping projects, namely 1000 Genome Project, Exome Aggregation Consortium and GO Exome Sequencing Project. Functional studies for the two mutations revealed that they could impair the transcription ability of PAX8 on one of its target genes, TPO. Therefore, the two mutations were causative for the pathogenesis of CHNG2. After combining the studies of PAX8 mutations, an average frequency of 1.74% (21/1209) could be obtained in Chinese patients with CH.@*Conclusion@#The study specifically demonstrates the role of two mutations in impairing the transcription ability of PAX8, which should be considered as pathogenic variants for CH.
ABSTRACT
BACKGROUND@#The transcription factor paired box 8 (PAX8) was associated with type 2 congenital non-goitrous hypothyroidism (CHNG2), a clinical phenotype of congenital hypothyroidism (CH). Though studied in a few regions with different ethnicities, the incidence of PAX8 mutations varied, even among Chinese cohorts in different regions. This study aimed to identify and characterize PAX8 mutations and explore the prevalence of its mutations in another cohort of CH.@*METHODS@#The 105 unrelated Chinese patients with CH were collected from four major hospitals. Exomes of the 105 samples were sequenced by Hiseq 2000 platform to identify mutations of PAX8 on genomic DNAs extracted from peripheral blood samples. Luciferase reporter assays were used to assess the effects of mutations on the transcription of thyroid peroxidase (TPO).@*RESULTS@#Three PAX8 mutations in four subjects were identified in 105 samples. One variant, rs189229644, was detected in two subjects, and categorized as uncertain significance. The other two missense mutations (275T>C/Ile92Thr and 398G>A/Arg133Gln) were not detected in three large-scale genotyping projects, namely 1000 Genome Project, Exome Aggregation Consortium and GO Exome Sequencing Project. Functional studies for the two mutations revealed that they could impair the transcription ability of PAX8 on one of its target genes, TPO. Therefore, the two mutations were causative for the pathogenesis of CHNG2. After combining the studies of PAX8 mutations, an average frequency of 1.74% (21/1209) could be obtained in Chinese patients with CH.@*CONCLUSION@#The study specifically demonstrates the role of two mutations in impairing the transcription ability of PAX8, which should be considered as pathogenic variants for CH.
ABSTRACT
Postpartum hemorrhage (PPH) is one of the most adverse obstetric outcomes.Our aim is to detect the risks of multilevel PPH in different cesarean section (CS) groups [including nulliparous CS with indications,nulliparous CS without indications,repeat cesarean (RC),vaginal birth after cesarean (VBAC),cesarean after vaginal birth (CAVB)].We conducted a retrospective cohort study,and the data on 127 145 women collected from January 2014 to May 2016 and from 35 tertiary hospitals in Shanxi province,China,were reviewed.Based on the measuring results of PPH,an ordered logistic regression model was used to analyze the adjusted PPH risks for each of the CS groups,and comparisons were drawn between them.Finally,a total of 99 066 nulliparous (77.92％) and 28 079 multiparous (22.08％) women were observed.The number of CS cases was 61 117,and the rate for CS was 48.07％.A total of 10 029 women did not show indications for CS and accounted for 16.41％ of the CS parturient,whereas 9103 women underwent a repeated cesarean,with a CS frequency of 14.89％.The number of VBAC cases was 989,whose rate was 9.88％ in prior CS women.The number (proportions) of PPH was 3658 (2.88％) in LI (PPH volume:≥900 and ＜1500 mL),520 (0.41％) in L2 (PPH volume:≥1500 and＜2100 mL),and 201 (0.16％) in L3 (PPH volume:≥2100 mL).The Ln (n=1,2,3,etc.) represented the increasing order of PPH severity.In the adjusted results,compared with spontaneous vaginal delivery (SVD) as the reference group,in the adjusted result for nulliparous,there was a decreased PPH risk in CS with indications (OR:2.32;CI:2.04-2.62),which was lower than that of CS without indications (OR:2.50;CI:2.01-2.96).The highest PPH risk in all subgroups (i.e.nulliparous and multiparous groups) was observed in the RC (OR:3.61;CI:3.16-4.17),which was nearly twice higher than that of the VBAC (OR:1.82;CI:1.33-2.52).CAVB (OR:1.03;CI:0.65-1.62) showed no significant difference with the reference group.Thus,we deemed that CS should be avoided in nulliparous pregnancies unless indicated,to prevent or reduce the rates for the use of RC or VBAC which are high risks of severe PPH to the parturient women.
ABSTRACT
Postpartum hemorrhage (PPH) is one of the most adverse obstetric outcomes.Our aim is to detect the risks of multilevel PPH in different cesarean section (CS) groups [including nulliparous CS with indications,nulliparous CS without indications,repeat cesarean (RC),vaginal birth after cesarean (VBAC),cesarean after vaginal birth (CAVB)].We conducted a retrospective cohort study,and the data on 127 145 women collected from January 2014 to May 2016 and from 35 tertiary hospitals in Shanxi province,China,were reviewed.Based on the measuring results of PPH,an ordered logistic regression model was used to analyze the adjusted PPH risks for each of the CS groups,and comparisons were drawn between them.Finally,a total of 99 066 nulliparous (77.92％) and 28 079 multiparous (22.08％) women were observed.The number of CS cases was 61 117,and the rate for CS was 48.07％.A total of 10 029 women did not show indications for CS and accounted for 16.41％ of the CS parturient,whereas 9103 women underwent a repeated cesarean,with a CS frequency of 14.89％.The number of VBAC cases was 989,whose rate was 9.88％ in prior CS women.The number (proportions) of PPH was 3658 (2.88％) in LI (PPH volume:≥900 and ＜1500 mL),520 (0.41％) in L2 (PPH volume:≥1500 and＜2100 mL),and 201 (0.16％) in L3 (PPH volume:≥2100 mL).The Ln (n=1,2,3,etc.) represented the increasing order of PPH severity.In the adjusted results,compared with spontaneous vaginal delivery (SVD) as the reference group,in the adjusted result for nulliparous,there was a decreased PPH risk in CS with indications (OR:2.32;CI:2.04-2.62),which was lower than that of CS without indications (OR:2.50;CI:2.01-2.96).The highest PPH risk in all subgroups (i.e.nulliparous and multiparous groups) was observed in the RC (OR:3.61;CI:3.16-4.17),which was nearly twice higher than that of the VBAC (OR:1.82;CI:1.33-2.52).CAVB (OR:1.03;CI:0.65-1.62) showed no significant difference with the reference group.Thus,we deemed that CS should be avoided in nulliparous pregnancies unless indicated,to prevent or reduce the rates for the use of RC or VBAC which are high risks of severe PPH to the parturient women.
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The current situation of medical staff's awareness about high alert medication was investigated in order to promote safe medication and standardized management of the high alert medication in China. Twenty questions were designed concerning elementary knowledge of high alert medications, storage management, medication issues and risks. In order to understand the knowledge level and education status of high alert medication, a convenient survey was conducted among 300 medical staffs in Tianjin. Medical staff's average score of high alert medication knowledge was 12.43±0.27, and the average scores of elementary knowledge of high alert medication, storage management, medication issues and risks were 3.38±0.11, 2.46±0.14, 3.17±0.11 and 3.41±0.12 respectively. Occupation (F=4.86, P=0.003), education background (F=5.57, P=0.019) and professional titles (F=13.44, P≤0.001) contributed to the high alert medications knowledge scores. Currently, the most important channel to obtain high alert medication knowledge was hospital files or administrative rules, and clinical pharmacist seminars were the most popular education form. It was suggested that the high alert medication knowledge level of the medical staff needs to increase, and it might benefit from targeted, systematic and diverse training to the medical staff working in the different circulation nodes of the medications. Further research to develop and validate the instrument is needed.
ABSTRACT
The current situation of medical staff's awareness about high alert medication was investigated in order to promote safe medication and standardized management of the high alert medication in China. Twenty questions were designed concerning elementary knowledge of high alert medications, storage management, medication issues and risks. In order to understand the knowledge level and education status of high alert medication, a convenient survey was conducted among 300 medical staffs in Tianjin. Medical staff's average score of high alert medication knowledge was 12.43±0.27, and the average scores of elementary knowledge of high alert medication, storage management, medication issues and risks were 3.38±0.11, 2.46±0.14, 3.17±0.11 and 3.41±0.12 respectively. Occupation (F=4.86, P=0.003), education background (F=5.57, P=0.019) and professional titles (F=13.44, P≤0.001) contributed to the high alert medications knowledge scores. Currently, the most important channel to obtain high alert medication knowledge was hospital files or administrative rules, and clinical pharmacist seminars were the most popular education form. It was suggested that the high alert medication knowledge level of the medical staff needs to increase, and it might benefit from targeted, systematic and diverse training to the medical staff working in the different circulation nodes of the medications. Further research to develop and validate the instrument is needed.
Subject(s)
Humans , China , Drug Prescriptions , Knowledge , Medical Staff , PsychologyABSTRACT
Objective To evaluate the value of ultrasound elastography score and strain ratio index in the differential diagnosis of thyroid solid nodules. Methods Eighty-six thyroid solid nodules of 69 patients were divided into 2 groups based on their pathologic results: benign nodules group and malignant nodules group.Compared with pathological results, each thyroid solid nodules' elastographic scores and strain ratio index were respectively analyzed. The sensitivity, specificity and accuracy of elasticity score and strain ratio index were calctlated.The receiver operator characteristic (ROC) curves were drawn according to the results, to choose the best cut-off value.Results There were 67 nodules in benign nodules group and 19 nodules in malignant nodules group. The diameter of benign nodules was (2.05 ± 0.21)cm, malignant nodules was (1.62 ± 0.12)cm. There were no significant differences in the elasticity score and strain ratio index between benign and malignant nodules(t= - 1.736, P ＞ 0.05). Malignant lesions had a higher score and strain ratio index(median 3, 3.97, respectively) than benign ones(median 2, 1.66,respectively, Z = - 5.290, - 5.450, all P ＜ 0.05). If the cut-off value of the elastographic scores was equal or more than 3, the sensitivity, specificity and accuracy were 84.2%(16/19) ,86.6%(58/67) and 86.0%(74/86), respectively,with an area under ROC curve of 0.854. If the cut-off value of the strain ratio index was equal or more than 2.50,the sensitivity, specificity and accuracy were 89.4%(17/19),86.6%(58/67) and 87.2%(75/86), respectively, with an area under ROC curve of 0.911. Conclusion Elasticity score and strain ratio index are helpful in differentiating benign and malignant lesions of thyroid with high clinical value.