Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review

SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study / 生物医学与环境科学（英文）

Objective@#The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.@*Methods@#The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.@*Results@#A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).@*Conclusion@#An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

miR-214 inhibits the osteogenic differentiation of dental follicle cells in vitro / 口腔疾病防治

Objective @# To investigate the effect of miR-214 on the osteogenic differentiation of dental follicle cells (DFCs).@*Methods@#Purified DFCs were cultured in vitro by bidirectional differential passage, with the untransfected DFCs as the control group (DFCs group). The expression of miR-214-3p in DFCs was upregulated and downregulated by transfection of miR-214-3p(miR-214 mimics group) or miR-214-3p inhibitors(miR-214 inhibitor group) into DFCs. The expression levels of miR-214, alkaline phosphatase (ALP), osteonectin (OSN) and runt-related transcription factor-2(RUNX-2) were detected by qRT-PCR after 7 days of osteogenesis induction, the protein expression levels of RUNX-2 and β-catenin were detected by western blot, and the formation of mineralized nodules was observed with alizarin red staining after 14 days of osteogenesis induction. @*Results @# Compared with the DFCs group, in the miR-214 mimics group, the expression of miR-214 was upregulated after 7 days of osteogenesis induction. The mRNA expression of ALP, OSN and RUNX-2 in the miR-214 mimics group was lower than that in the DFCs group, but only ALP in the two groups was statistically significant (P > 0.05); the mRNA expression of ALP, OSN and RUNX-2 in the miR-214 inhibitor group was higher than that in the DFCs group, and the difference was statistically significant (P < 0.05). The protein expression of RUNX-2 and β-catenin in the miR-214 mimics group was lower than that in the miR-214 inhibitor group. The number of calcified nodules in the miR-214 mimics group was significantly less than that in the DFCs group, while that in the miR-214 inhibitor group was significantly higher than that in the DFCs group. @*Conclusion@#The upregulation of miR-214 can downregulate the expression of β-catenin, can inhibit the expression of ALP, OSN and RUNX-2 related to osteogenesis, and can inhibit osteogenic differentiation. The downregulation of miR-214 demonstrated the opposite results; miR-214 may downregulate the expression of β-catenin and inhibit the osteogenic differentiation of DFCs.

A prospective cohort study on the risk of HBV infection in preschool children without immune response to hepatitis B vaccine / 中华疾病控制杂志

@# Objective To evaluate the risk of hepatitis B virus(HBV) infection among preschool children who were the non-responders to hepatitis B vaccine in future. Methods A prospective cohort study was conducted. Children aged 2 to 5 years were selected from 64 kindergartens.These children were inoculated three doses of hepatitis b vaccine at 0, 1 and 6 months after birth. Hepatitis B surface antigen (HBsAg)and Hepatitis B surface antibody (anti-HBs)were detected during the period from March to May 2015. The children who were HBsAg negative were enrolled in the study. The subjects were divided into exposure group (anti-HBs negative) and control group (anti-HBs positive) . The follow-up began on June 1, 2015 and ended on June 1, 2016. Serum HBsAg of children in the cohort was then collected and detected from June 1 to 30, 2016. At the end of the study, the HBsAg positive rates between two groups were compared. Results 83 children who received hepatitis B vaccine again during the follow-up period were excluded from 1 907 non-responders. The actual number in non-responders group was 1 824. 151 children were lost at the end of the study. The actual number of follow-up was 1 673 and 5 children were found to be positive for HBsAg and the infection rate was 0.30% (5/1673). In the respondent goup, 2 054 were enrolled and followed. Finally, 140 children were lost and none of the remaining 1 914 people were HBsAg positive at the end of the study. HBsAg positive rate was higher in the non-responder group than in the responder group (P=0.023). Conclusion There is a risk of HBV infection in the children who are non-responders to hepatitis B vaccine in future.

Efficacy and safety of orthokeratology to control myopia in Asia children: A Meta-analysis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To assess the efficacy and safety of orthokeratology for reducing the progression of myopia in Asia children.?METHODS: Seven databases, including the Cochrane Library, Medline, EMbase, CBM, CNKI, VIP, and WanFang Data, were searched. The published languages were limited to English and Chinese. The risk bias tool provided by Cochrance cooperation and methodological index for non-randomized studies ( MINORS) scale were used to assess the risk bias of included studies (randomized controlled trials and controlled trials). The published biases of included studies were assessed with funnel plot. Meta-analysis was performed with Review Manager 5. 3.? RESULTS: Seven eligible studies, including 478 children, were included, 250 cases in ortho-k group, 228 cases in control group. The Meta-analysis indicated that change in axial length of ortho-k group was significantly less than the control group [WMD=-0. 31, 95％CI(-0. 35,-0. 26), P<0. 001]. Five studies observed adverse effects which all included the effect of positive staining of corneal fluorescein. One study reported chalazion in one child. None of the studies reported severe adverse events.? CONCLUSION: The overall findings suggested that orthokeratology might slow the progression of myopia in children of Asia.

Study on association of CTLA4 gene polymorphism with Grave's disease in Guangxi Zhuang nationality population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the polymorphic (AT)n repeats in 3ountranslated region of exon 4 of CTLA4 gene [CTLA4(AT)n] and Graveso disease (GD) in Zhuang nationality population of Guangxi province.</p><p><b>METHODS</b>The studied groups comprised 48 patients with GD and 44 normal controls. Amplification of target DNA was carried out by polymerase chain reaction (PCR). The amplified products were run by 8% polyacrylamide gel electrophoresis, and then followed by 0.1% silver staining. Some of amplified products were sequenced directly.</p><p><b>RESULTS</b>Nineteen alleles of CTLA4 gene microsatellite polymorphism were found in Guangxi Zhuang nationality individuals. The 106 bp long allele was apparently increased in patients with GD of Zhuang nationality but not in healthy controls (P< 0.05).</p><p><b>CONCLUSION</b>CTLA4 gene microsatellite polymorphism is strongly associated with Graveso disease in Zhuang nationality population of Guangxi province. CTLA4(AT)n 106 bp may be the susceptible gene in GD patients of Zhuang nationality in Guangxi; 19 alleles of CTLA4 gene microsatellite polymorphism were found in Guangxi Zhuang nationality individuals.</p>

Clinical study on the postburn change in the hypothalamus-pituitary-adrenal hormones in severely burned patients / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the postburn dynamic changes in the hypothalamus-pituitary-adrenal hormones in severely burned patients.</p><p><b>METHODS</b>Fifty burn patients were enrolled in the study. The plasma contents of total GC (cortisol), ACTH and aldosterone (ALDO) and urinary contents of 17-OHO and 17-KS were determined with radio-immunological assay (RIA) method after burn injury to compare with the normal values which were well established clinically.</p><p><b>RESULTS</b>The postburn plasma and urinary contents of the above indices were increased evidently with two peak values in shock and infectious stages, whilst the majority of he indices were lower than the normal values after 6 postburn weeks (PBWs). The values of these hormones were the lowest in dying patients. On the other hand, the values approached normal levels in those patients whose burn wounds were healing.</p><p><b>CONCLUSION</b>Increases of the plasma and urinary levels of hypothalamus-pituitary -adrenal hormones in severely burned patients were constantly seen. Burn shock and infection seemed to be the two major factors in inducing postburn stress reaction in burn victims. Abrupt decrease of the hormone levels in plasma and or urine indicated adrenal failure predicting a poor prognosis of the burn patients.</p>

The prevalence of metabolic syndrome in Han and Zhuang Chinese in Guangxi / 中华内分泌代谢杂志

Objective To investigate the prevalence of metabolic syndrome(MS)and its components among people aged over 15 years in Guangxi Zhuang Autonomous Region and to compare the difference between Zhuang and Han populations.Methods Adopting cluster sampling,a survey of diabetes mellitus was conducted in Guangxi from 2003 to 2005.A total of 27 240 subjects aged over 15 years with complete data,including background information of each individual,blood pressure,lipid profile,plasma glucose,blood uric acid and fasting insulin were analyzed in this study.The prevalence of MS and its components were analysed in Han and Zhuang Chinese in Guangxi.The criteria of International Diabetes Federation(IDF)in 2005 and the China Diabetes Society(CDS)in 2004 were applied for diagnosis.Results(1)The crude prevalence rates of MS according to IDF definition were 13.15%in total,12.41%in male and 14.11%in female respectively.The age- standardized prevalence rates of MS(according to the population composition in China in 2000)were 7.66%in total,7.26%in male and 8.81%in female.The crude prevalence rates of MS according to CDS definition were 10.75%in total,13.45%in male and 7.28%in female respectively and the age-standar-dized prevalence rates of MS were 5.9%in total,7.21%in male and 4.31%in female.The prevalence of MS in total,male and female was increasing with age(P

Expressions and significance of human telomerase reverse transcriptase mRNA and protein in pheochromocytoma / 中华内分泌代谢杂志

Objective To investigate the expressions of human telomerase reverse transcriptase(hTERT) mRNA and protein in pheochromocytoma and paraganglioma and their significance as diagnostic markers in predicting the biological behaviour of these tumours.Methods Expression of hTERT mRNA was determined by in situ hybridization in 45 pheochromocytomas/paragangliomas(31 benign,7 suspected malignant and 7 malignant) and 9 normal adrenal medulla samples,hTERT protein was determined by immunohistoebemistry.Results hTERT mRNA was expressed in 5/7 malignant turnouts and 5/7 suspected malignant tumours as compared with 3/31 benign tumours(P