Clinical characteristics and genetic analysis of four patients with central hypothyroidism due to IGSF1 gene variants / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical manifestations and genetic characteristics of patients with congenital central hypothyroidism due to variants of IGSF1 gene.@*METHODS@#Clinical data, results of genetic testing, and follow-up of four patients admitted to Children's Hospital of Soochow University during 2017 to 2021 were retrospectively analyzed.@*RESULTS@#All of the four patients were males. Patient 1 had presented neonatal jaundice, patients 2 and 3 were admitted for growth retardation during childhood, and thyroid function test indicated slightly low free thyroxine (FT4), patient 4 was found to have reduced FT4 in the neonatal period. Genetic testing revealed that all of the four patients have harbored pathogenic variants of the IGSF1 gene, which were all inherited from their mothers. The thyroid functions in all patients were well controlled with oral levothyroxine and regular follow-up.@*CONCLUSION@#Pathogenic variants of the IGSF1 gene probably underlay the congenital central hypothyroidism with a variety of clinical manifestations, and genetic testing can facilitate the diagnosis at an early stage.

MELAS syndrome caused by A3252G mutation in MT-TL1 gene: One case report and literature review / 中华内分泌代谢杂志

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS) is one of the most common inherited mitochondrial diseases. This paper reports a rare mutation associated with MELAS syndrome, the m. 3252 A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNALeu(UUR). The 6-year-old girl suffered from recurrent convulsion and lactic acidemia. The mtDNA sequencing detected a variant m. 3252A>G(MT-TL1 gene) in the proband and her maternal relatives. The heteroplasmic levels in peripheral blood and urine sediment were 66.53% and 97.42%, respectively, which were obviously higher than those of her maternal relatives. Together with 3 previously reported cases, the variant m. 3252A>G could be classified pathogenic. All the reported pathogenic variants in MT-TL1 gene were reviewed to explore the genotype-phenotype correlations of pathogenic variants in MT-TL1 gene.

Whole-exome sequencing in diagnosing 2 cases of Gitelman syndrome / 中南大学学报(医学版)

Two patients with Gitelman syndrome were admitted to the Department of Endocrinology, Third Xiangya Hospital of Central South University. The genomic DNA from the patients' peripheral blood was extracted and the whole-exome sequencing was performed to detect the possible mutations. The function of the mutation sites was analyzed by bioinformatics software. Through whole-exome sequencing and Sanger sequencing, we have found that 2 patients with Gitelman syndrome carried compound heterozygous mutations of SLC12A3 gene, which were c.486_490delTACGGinsA, p.R943W, p.D486N, and p.R928C. Among them, c.486_490delTACGGinsA insertion deletion mutation causes frame shift and protein truncation. The p.R943W, p.D486N, and p.R928C of SLC12A3 gene were predicted to be pathogenic mutations by SIFT, PolyPhen2, and Mutation Taster. These 4 mutations were all reported, but p.R943W was first reported in Chinese population. Gitelman syndrome is rare in clinic and the rate of missed diagnosis is high. Early genetic analysis in patients with Gitelman syndrome is helpful to determine the etiology and guide the treatment.

Value of serum insulin-like growth factor-1, dehydroepiandrosterone sulphate, anti-Müllerian hormone and bone morphogenetic protein 6 in prediction of rapidly progressive puberty in girls / 中华实用儿科临床杂志

Objective:To investigate the value of serum insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone sulphate (DHEAS), anti-Müllerian hormone (AMH) and bone morphogenetic protein 6 (BMP-6) in prediction of rapidly progressive puberty(RPP) in girls.Methods:The data of 750 girls who visited the Department of Endocrinology, Metabolism and Genetic Disorders, Children′s Hospital of Soochow University from August 2017 to October 2018 because of breast development were retrospectively analyzed.After following up these girls for 6 months to 1 year, those who were lost to follow up, received early treatment and failed to meet the inclusion criteria were excluded.The remaining 138 girls were divided into the central precocious puberty group (CPP, 32 cases), the early puberty with RPP group (EP-RPP, 33 cases), the early puberty with slow progression puberty group (EP-SPP, 32 cases) and RPP group (41 cases) according to the inclusion criteria.The healthy control group consisted of 33 undeveloped girls aged 8 to 9 who underwent physical examination in the same hospital over the same period.The serum concentrations of IGF-1, DHEAS, AMH and BMP-6 were measured.The general information, clinical manifestations, laboratory examination results and radiological features were compared among different groups.Statistical analysis was performed by using SPSS 22.0, and the receiver operating characteristic curve (ROC) was drawn to investigate the value of IGF-1, DHEAS, AMH and BMP-6 in prediction of RPP.Results:(1)The serum follicle stimulating hormone(FSH) peak value was 15.10(13.86-19.80) IU/L in the EP-SPP group, 11.99(9.18-16.16) IU/L in the EP-RPP group and 11.43(9.37-15.63) IU/L in the RPP group.The ratio of serum FSH/luteinizing hormone(LH) peak values was 3.20(2.44-4.58) in the EP-SPP group, 1.86(1.05-3.16) in the EP-RPP group and 0.76(0.49-0.99) in the RPP group.The serum FSH peak value and the ratio of serum FSH/LH peak values in the EP-SPP group were significant higher than those in the EP-RPP group(all P<0.05). There was no significant difference in the serum FSH peak value between the EP-RPP group and the RPP group( P>0.05). (2)The serum IGF-1 levels of the healthy control group, EP-SPP group, EP-RPP group, CPP group and RPP group were 166.00(126.50-188.00) μg/L, 199.00(170.50-262.50) μg/L, 252.00(233.00-291.50) μg/L, 288.00(252.00-376.00) μg/L and 382.00(264.0-499.50) μg/L, respectively.The serum IGF-1 levels of the EP-SPP group, EP-RPP group, CPP group and RPP group were all significantly higher than those in the healthy control group (all P<0.05). The serum IGF-1 levels in the EP-RPP group were higher than those in the EP-SPP group( P<0.01). As the puberty rapidly progressed, the serum IGF-1 levels gradually increased.The RPP group had the highest IGF-1 levels, and the difference in IGF-1 levels between the RPP group and EP-RPP group was statistically significant( P<0.01). (3)The serum DHEAS levels were 41.65(14.80-59.88) μg/L in the healthy control group, 42.50(30.15-79.83) μg/L in the EP-SPP group, 52.32(43.08-98.54) μg/L in the CPP group, 63.30(34.00-81.55) μg/L in the EP-RPP group and 70.89(51.85-100.02) μg/L in the RPP group.The DHEAS levels of the healthy control group, EP-RPP group and RPP group gradually increased.The RPP group had the highest DHEAS levels.There was significant difference in DHEAS levels among the healthy control group, EP-RPP group and RPP group ( P<0.05). There was no significant difference in DHEAS levels among the EP-SPP group, CPP group and EP-RPP group( P>0.05). (4)The serum AMH and BMP-6 levels in the EP-RPP group, EP-SPP group, RPP group, CPP group and healthy control group were not significantly different( P>0.05). (5)The area under the ROC curve of serum IGF-1 levels was 0.765, the cut-off value was 232.5 μg/L, the specificity for the cut-off value was 83.30%, and the sensitivity was 75.00%.The combined area under the ROC curve of the serum FSH peak value and the ratio of serum FSH/LH peak values was 0.795. Conclusions:Serum IGF-1 levels and the combination of the serum FSH peak value and the ratio of serum FSH/LH peak values can be used as effective indicators of slowly and rapidly progressive puberty in early adolescent girls.Serum DHEAS cannot be used as an early warning index of RPP, but it plays a critical role in the regulation of puberty initiation and process.Serum DHEAS levels may be related to the Tanner stage.

Clinical and genetic analysis of five Chinese pedigrees affected with short stature due to variants of ACAN gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and genetic characteristics of five Chinese pedigrees affected with short stature.@*METHODS@#A retrospective analysis was carried out for the clinical data and results of genetic testing for the probands. A literature search was also conducted.@*RESULTS@#The five probands have all featured short stature with a family history. Genetic testing has revealed that they have harbored variants of the ACAN gene, including p.Val2042Argfs*6, p.Val1597del, c.630-1G>A, c.23delT and c.2026+1G>A(previously reported).@*CONCLUSION@#Except for short stature, children harboring heterozygous variants of the ACAN gene may have no involvement of other systems. Some of these children may response to short-term growth hormone treatment.

Clinical and genetic analysis of Ulnar-Mammary syndrome caused by TBX3 de novo mutation in a boy and literature review / 中华内分泌代谢杂志

Objective:To investigate the clinical and genetic characteristics of a boy with Ulnar-Mammary syndrome(UMS), and to review the literature.Methods:The clinical and genetic data of a boy with UMS, who was admitted to the Department of Endocrinology, Genetics and Metabolism, Children′s Hospital of Soochow University in May 2018 were analyzed. Original papers on UMS published up to July 2019 were retrieved.Results:A male patient at the age of 12 years and 8 months visited us for growth retardation. He presented with high forehead, epicanthic folds, broad nasal tip, anteverted nostrils, high palate, dental crowding, mammary gland hypoplasia, and absence of axillary hairs, with height 148.9 cm(<-1 SD). Growth hormone stimulation test indicated growth hormone deficiency(growth hormone peak <5 ng/ml). After one year of treatment with recombinant human growth hormone, his height was improved. Gene sequencing identified a de novo heterozygous mutation of TBX3 c. 711DelC(p.N238Mfs* 4). According to ACMG guidelines in 2015, the mutation is pathogenic and has not been reported in the above databases.However, this mutation was not detected in his parents.Conclusion:UMS should be considered in dwarfism with special face, dysplasia of external genitalia, sweat glands, and mammary glands, and TBX3 is a pathogenic gene.

Clinical characteristics of thyroid hormone resistance syndrome in two cases with different subtypes / 中华儿科杂志

Objective@#To analyze the clinical characteristics of children with two types of thyroid hormone resistance (RTH) syndrome, and to detect the variants of thyroid hormone receptor alpha(TRα) and TRβ gene in children.@*Method@#Two children with RTH were reported in regard to clinical manifestation, laboratory examination and genetic variants. Some related reports in literature were reviewed.@*Result@#Case 1 was a girl, 10 years old, with thyroid enlargement for several days and without thyrotoxicosis. Laboratory work-up revealed that free thyroxine (FT4) was 65.77 pmol/L (reference 12-22) , free triiodothyronine (FT3) was 15.36 pmol/L (reference 3.1-6.8) and thyroid stimulating hormone (TSH) level was normal. There was a likely pathogenic missense variant detected in TRβ gene and this patient was diagnosed with RTHβ. Case 2 was a boy, 3 years old, with classic features of hypothyroidism(growth retardation, developmental retardation, skeletal dysplasia) but had only borderline-abnormal thyroid hormone levels. Targeted sequencing showed a de novo heterozygous nonsense variant in TRα gene which is a pathogenic variant and this patient been diagnosed with RTHα.@*Conclusion@#Thyroid enlargement is a common clinical manifestation of RTHβ, with laboratory work-up reveals elevated FT4 and FT3 levels but TSH level is normal. The clinical manifestations of RTHα are similar to those of hypothyroidism, but the thyroid hormone levels are almost normal. The gene sequence and the pathogenicity analysis for TRα and TRβ will help to make a definitive diagnosis.

Effect of exposure to different doses of Bisphenol A during neonate on hypothalamic -pituitary -testis axis in male rats / 中华实用儿科临床杂志

Objective To explore the effect of neonatal exposure to different doses of Bisphenol A (BPA)on the hypothalamic -pituitary -testis axis in toddler and adolescent male rats.Methods Neonatal male Sprague -Daw-ley rats were randomly divided into 5 groups through random digital table method:control group,vehicle group,low -dose BPA [25 μg/(kg · d)]group,medium -dose BPA [50 μg/(kg · d)]group and high -dose BPA [250μg/(kg·d)]group.The rats were subcutaneously injected with respective agents on postnatal days 1 -7 (PND 1 -7).Pups were sacrificed on PND 22 and PND 50.The hypothalamus and testis were taken and weighed.The hypotha-lamic Kiss -1 mRNA and the testis androgen receptor (AR)mRNA were tested by using real -time fluorescence quan-titative and the levels of serum luteinizing hormone (LH),follicle stimulating hormone (FSH),testosterone (T)were tested by using radio immunity method,and inhibin B was measured by using enzyme linked immunosorbent assay. Results Compared with the controls,the level of serum FSH [(1 .610 0 ±0.693 2)IU /L,(1 .574 3 ±0.675 0)IU /L vs (2.362 9 ±0.580 3)IU /L](F =3.314,P =0.026),LH [(3.876 3 ±0.908 0)IU /L,(3.603 8 ±1 .350 2)IU /L vs (5.302 5 ±0.768 4)IU /L](F =3.1 39,P =0.027)and T [(0.383 8 ±0.1 77 8)μg/L,(0.442 5 ±0.21 4 1 )μg/L vs (0.782 5 ±0.282 1 )μg/L](F =5.1 06,P <0.01 )of medium and high -dose BPA groups,were decreased in PND 22,and the organ coefficient of testis [(0.952 90 ±0.049 1 5)%,(0.969 20 ±0.045 82)% vs (1 .022 80 ± 0.01 1 08)%](F =1 0.326,P <0.01 )and serum T [(1 .758 6 ±0.369 6)μg/L,(1 .71 8 8 ±0.395 7)μg/L vs (3.357 5 ±0.749 8)μg/L](F =1 3.799,P =0.01 2)were significantly decreased in PND 50.In high -dose BPA group of PND 22,the expression of hypothalamic Kiss -1 mRNA (0.068 80 ±0.01 1 79)was increased compared with the other groups (F =272.1 25,P <0.01 ),while in PND 50,compared with control group,the Kiss -1 mRNA (0.002 00 ±0.000 25,0.001 90 ±0.000 48 vs 0.001 40 ±0.000 1 7)of medium -and high -dose BPA groups was decreased(F =1 91 .826,P <0.01 ).Conclusions Neonatal exposure to the medium and high -dose BPA may impair the function of testis in toddler and adolescent male rats,and affect the hypothalamus -pituitary -testis axis.Neonatal exposure to the low -dose BPA does not have a significant influence on the hypothalamus -pituitary -testis axis.

Investigation and analysis of macular thickness in natural population and diabetes patients in Changping district of Beijing / 国际生物医学工程杂志

Objective To measure the macular thickness of natural population in Changping district of Beijing by optical coherence tomography (OCT), and to analyze whether there is an increased thickness in diabetic patients.Methods In a cross-sectional population-based study, OCT was performed on 521 subjects (233 with normal glucose homeostasis, 174 with pre-diabetes and 114 with type 2 diabetes (T2D) according to 2011 Health Examination Survey of Changping.The subjects also received physical examination and laboratory measurements including fasting plasma glucose (FPG), oral glucose tolerance test (OGTT)-2 h plasma glucose and hemoglobin A1c (HbA1c).Results The results showed that central subfield thickness (CST) of the retina of men ((246±22) μm) was significantly greater than that of women ((235±26) μm) (P＜0.001).Meanwhile, no significant difference was found in the CST in subjects of different age, HbAlc and body mass index (BMI) (P＞0.05).Difference in thickness of different glucose groups was not seen in central subfield, inner subfields and outer subfields(P＞0.05).Conclusions Retina CST of men was significantly greater than that of women.No significant difference was found in the CST in subjects of different age, HbA1c and BMI.

A study of bisphenol A and precocious puberty in 6-8 years old girls / 临床儿科杂志

Objective To study the relationship between bisphenol A and precocious puberty in 6-8 years girls. Meth-ods Atotal of 103 girls aged 6-8 years with precocious puberty in our Endocrine clinic from August to December 2012 were se-lected. According to the classiifcation standard of precocious puberty, girls are divided into idiopathic central precocious puberty (ICPP) group (n=47) and permature thelarche (PT) group (n=56), 53 girls with no puberty development were chosen as control group. BPA concentrations were determined with HPLC-MS-MS, sex hormones were determined with chemiluminescence meth-od and Kisspeptin concentrations were determined with ELISA, then the differences among the three groups were compared and the relationships between bisphenol A and sex hormones and Kisspeptin were analyzed. Results The BPA relevance ratio and concentration in ICPP group were higher than those of PT group and control group (P0.05). There were correlations between the concentrations of BPA and E2 and LH peak concentration and LH/FSH (P<0.05). Conclusions There is a certain correlation between the concentrations of BPA and ICPP.

The relationship between subclinical hypothyroidism and diabetic retinopathy in elderly type 2 diabetic patients / 中华老年医学杂志

Objective To investigate the relationship between subclinical hypothyroidism (SCH) and diabetic retinopathy (DR) in elderly type 2 diabetic patients.Methods 1170 hospitalized patients with type 2 diabetes mellitus were enrolled in our study.After identified by systematic sampling,all the elderly patients received examinations of thyroid function,biochemical indexes,steamed bread meal test and C-peptide releasing test.The serious degree of DR was observed through digital fundus photography and ophthalmofundoscope.The relationship between SCH and DR was analyzed.Results All the subjects were divided into two subgroups:euthyroid group(TSH≤4mU/L)and subclinical hypothyroidism (SCH) group (mild SCH group,TSH ＞4～10 mU/L; serious SCH group,TSH＞10 mU/L).Free thyroxine (FT4) was significantly lower in SCH group than in euthyroid group[(13.91±2.17) pmol/L vs.(16.55±2.81)pmol/L,P＜0.001].The levels of basal (CP0) and post glucose-challenge (CP1-3) C-peptide were significantly higher in SCH group than in euthyroid group (P0-3 value:0.001,0.012,0.004,0.001).There were significant differences in the progress of diabetic retinopathy between SCH and euthyroid groups (retinopathy-L,P=0.018; retinopathy-R P=0.013).Conclusions Elderly type 2 diabetic patients with SCH have a higher incidence of diabetic retinopathy (DR).The elevated FT4 level and decreased basal C-peptide level are probably the main reasons.

Effect ofTangshen-Huazhuorecipe on the levels of serum transforming growth factorβ1 and platelet derived growth factor in patients with IV stage of diabetic nephropathy / 国际中医中药杂志

Objective To investigate the effect of extract ofTangshen-HuazhuoRecipe(TSHZR) on the serum concentrations of transforming growth factorβ1(TGF-β1) and platelet derived growth factor(PDGF) in patients withⅣ stage of diabetic nephropathy(DN).Methods From June 2012 to December 2012, 98 patients ofⅣstage DN in our hospital outpatient were enrolled and randomly divided into treatment group(n=48) and control group(n=50) using random number table. All patients received conventional therapies of controlling blood sugar, lipid, blood pressure and anticoagulant therapy. On such basis, the control group was treated by irbesartan, 150 mg/d, and the treated group treated by TSHZR combined with irbesartan,150 mg/d, for 6 months. Serum TGF-β1 and PDGF were determined with ELISA before and after treatment,and urinary albumin excretion rate,HbA1c,serum creatinine,blood urea nitrogen and lipid profiles were examined as well. ResultsIn the treated group, the TGF-β1 was(172.5±31.3), (123.6±21.2)pg/ml, the PDGF was(860.9± 131.2), (500.6±130.2)pg/ml before the treatment and after the treatment, respectively. The TGF-β1 and PDGF after the treatment were significantly decreased than those before the treatment(P<0.01). After the treatment, TGF-β1 and PDGF in the treated group were statistically significant compared to the control group[TGF-β1 is(157.4±39.6)pg/ml, PDGF is(765.7±161.8)]pg/ml,P<0.01). After the treatment, the treatment group was superior to the control group in TG(1.72±0.25)mmol/L,(2.09±0.27)mmol/L,(P<0.01), TC(4.56± 0.64)mmol/L,(6.11±0.93)mmol/L, (P<0.01), HDL-C(1.56±0.50)mmol/L,(1.36±0.44)mmol/L, (P<0.01), LDL-C(2.46±1.08)mmol/L(3.32±0.87)mmol/L,(P<0.05)and UAER(100.73±204.24)μg/min, (226.24±396.38)μg/min, (P<0.01).Conclusion TSHZR can inhibit the progressive of IV stage of diabetic nephropathy by suppressing TGF-β1 and PDGF expression level.

Clinical study of growth development and endocrine function of long-survived children with acute lymphoblastic leukemia / 中国基层医药

ObjectiveTo study the effects of chemotherapy on growth development and endocrine function of long-survived children with acute lymphoblastic leukemia (ALL). Methods30 ALL patients who were received standard chemotherapy and survived more than five years were enrolled in this study. Their growth and development data and endocrine function examination were investigated. ResultsThrough testing,except two cases of height more than two standard deviation above,the others were all within the normal range; BMI exceeded bid in 1, and the rest were in the normal range;The results of sex hormones examination were consistent with age and Tanner installment, the girls appeared secondary sex characteristics in 9 years old or so,menstruation in 13 years old. Boys appeared sec-ondary sex characteristics around 10 years old;Cortisol and promote adrenal cortical hormone with 2 cases of obese children were in the normal range,but c-peptide and insulin were elevatory;The results of IGF-1 were in the normal range. ConclusionChemotherapy had no significant effect on growth development and endocrine function for patients with ALL.

Study on Reform Mode for Township Hospitals in Zhangjiagang / 中国药房

OBJECTIVE:To provide reference for systematic reform in national state-owned hospital.METHODS:System reforms of township hospitals in Zhangjiagang were analyzed.Then three kinds of reform modes were summarized including privatization,town-owned-town-management and sino-foreign joint venture.Reform effects were also discussed.RESULTS & CONCLUSIONS:The achievement that the reformed township hospitals have made in Zhangjiagang in improving the medical insurance and pharmaceutical management system,reforming hospital management system and operation mechanism and creating a harmonious relationship between doctor and patient can provide a reference for domestic state-owned hospital reform.

MR Imaging Diagnosis of Pituitary Stalk Interruption Syndrome / 实用放射学杂志

Objective To study MRI features of pituitary stalk interruption syndrome(PSIS).Methods 10 cases in 42 with growth retardation patients diagnosed as PSIS by MRI,all of them were male,age ranged from 5 to 18 with average 13.6 years.Results The anterior-pituitary superior border was depressed,anterior-pituitary volume decreased(average height 2.1 mm,average width 7.8 mm),ectopic posterior-pituitary lobe located at infundibulum stem and pituitary stalk was absent in all cases.The blood hormorne test showed the growth hormone deficiency and multiple growth hormone deficienty.Conclusion PSIS often see in men,MRI findings of PSIS are characteristic.

Chemical constituents of Wedelia trilobata / 中草药

Objective To investigate the chemical constituents of Wedelia trilobata.Methods The chemical constituents were separated by chromatography and their structures were determined by physico-chemical constants and spectral analyses.Results Eleven compounds were isolated and identified as grandiflorenic acid(1),1?-acetoxy-6?,9?-dihydroxy-4,10?-dimethyl-5?H,7?H,8?H-endesm-3-en-8,12-olide(2),1?-acetoxy-4?-hydroxy-6?-isobutyryloxy-9?-isovaleryloxyprostatolide(3),16?-hydroxy-ent-kauran-19-oic acid(4),(3R,4R,6R)-3,4-dihydroxy-1-menthene(5),trilobolide-6-O-isobutyrate(6),1?-acetoxy-4?,9?-dihydroxy-6?-isobutyroxyprostatolide(7),16?,17-dihydroxy-ent-kauran-19-oic acid(8),daucosterol(9),protocatechualdehyde(10),and caffeic acid(11).Conclusion All the compounds are isolated from W.trilobata for the first time except compounds 6 and 7.Compounds 2 and 3 are new sesquiterpene lactones,named as trilobolide A and 1?-acetoxy-4?-hydroxy-6?-isobutyryloxy-9?-isovaleryloxyprostatolide,respectively.