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OBJECTIVE@#To improve the recognition of Familial glucocorticoid deficiency type 1 (FGD1) due to variants of melanocortin 2 receptor (MC2R) gene.@*METHODS@#Two children with FGD1 diagnosed at the Henan Children's Hospital respectively in 2019 and 2021 were selected as the study subjects. Clinical data, treatment, follow-up and results of genetic testing were collected and retrospectively analyzed.@*RESULTS@#Whole exome sequencing revealed that both children had harbored compound heterozygous variants of the MC2R gene, including c.433C>T (p.R145C) and c.710T>C (p.L237P) in child 1, and c.145delG (p.V49Cfs*35) and c.307G>A (p.D103N) in child 2, among which c.710T>C (p.L237P) and c.145delG (p.V49Cfs*35) were unreported previously.@*CONCLUSION@#FGD1 is clinically rare, and genetic sequencing is crucial for the definite diagnosis. Discovery of the and novel variants has enriched the mutational spectrum of the FGD1 gene.
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Humans , Child , Glucocorticoids/therapeutic use , Receptor, Melanocortin, Type 2/genetics , Retrospective Studies , Adrenal Insufficiency/genetics , MutationABSTRACT
Blood glucose monitoring is a tool to guide medical nutrition therapy,exercise intensity and time,and helps to effectively prevent hypoglycemia and adjust insulin treatment programs.It is an important part of comprehensive treatment of diabetes mellitus.Continuous glucose monitoring (CGM),as a supplement to self-monitoring blood glucose,helps to reduce the incidence of hypoglycemia and the duration of hypoglycemia in diabetic children.In addition,parents and children are satisfied with CGM,so it is increasingly used in children with diabetes mellitus.However,current research and clinical experience have shown that it is not entirely possible to rely on CGM values for treatment adjustment in children.Success with CGM requires detailed education and training in diabetes management coupled with extensive training in the use of CGM.
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Blood glucose monitoring is a tool to guide medical nutrition therapy, exercise intensity and time, and helps to effectively prevent hypoglycemia and adjust insulin treatment programs.It is an important part of comprehensive treatment of diabetes mellitus.Continuous glucose monitoring (CGM), as a supplement to self-monitoring blood glucose, helps to reduce the incidence of hypoglycemia and the duration of hypoglycemia in diabetic children.In addition, parents and children are satisfied with CGM, so it is increasingly used in children with diabetes mellitus.However, current research and clinical experience have shown that it is not entirely possible to rely on CGM values for treatment adjustment in children.Success with CGM requires detailed education and training in diabetes management coupled with extensive training in the use of CGM.
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Objective To research the effect of alkylation of glycerol phosphate synthase (AGPS) in isoproterenol (ISO) induced rat cardiac hypertrophy. Methods The pathological cardiac hypertrophy rat model was constructed by ISO intraperitoneal injection. Twelve healthy Sprague-Dawley rats (120～150 g) were divided into ISO group and control group randomly. In the ISO group, rats were injected with ISO (3 mg/kg) per day for two consecutive weeks. In the control group, rats were injected with normal saline (3 mg/kg) per day for two consecutive weeks. Changes of left ventricular diastolic diameter, left ventricular posterior wall thickness, left ventricular ejection fraction, left ventricular short-axis shortening rate and left ventricular mass were detected by echocardiography. The cross-sectional area of myocardial cells in rats was measured by hematoxylin-eosin staining. The expression of hypertrophic factors [atrial natriuretic peptide (ANP), myosin light chain-2V (MLC-2V), α-myosin heavy chain (α-MHC)] and AGPS were detected by Western Blot and real-time quantitative PCR (qPCR). Results The results of echocardiography showed that the cardiac hypertrophy rat model was successfully constructed. The results of hematoxylin-eosin staining showed that the myocardial cross-sectional area in the ISO group was significantly larger than that of the control group. The Western Blot and qPCR results indicated that the relative expression of protein and mRNA of hypertrophic factor and AGPS in the ISO group were both up-regulated comparing with that of the control group, and the differences were statistical significance (all P<0.05). Conclusions The rat model of pathological cardiac hypertrophy with up-regulated AGPS expression was successfully constructed providing a theoretical basis for further study on the role of AGPS in pathogenesis of pathological cardiac hypertrophy.
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Congenital hyperinsulinism (CHI) is the most frequent cause of persistent hypoglycemia in infancy,and it is a rare genetic disorder characterized by severe hypoglycemia caused by inappropriate insulin secretion by pancreatic β-cells.The clinical presentation,histology,genetics and response to medical treatment are of genetic heterogeneity.Appropriate treatment is critically important as profound and repeated episodes of hypoglycemia often cause severe brain damage.Based on the biochemical profiles,clinical diagnosis is relative easier to be established,however,the genetic basis is only found in approximately 45％-55％ of patients.In terms of treatment,Diazoxide is recommended as first-line treatment for all patients [5-20 mg/(kg · d)].In patients unresponsive to Diazoxide,if genetic result confirms a monoallelic,recessive paternally-inherited mutation in ABCC8 or KCNJ11,and 18F-fluorodihydroxyphenylalanine-positron emission tomography-computed tomography scan indicates the lesion is located in the body or tail of the pancreas,surgical treatment is recommended.And for the other patients,subcutaneous octreotide,intravenous glucagon,or oral calcium antagonist should be sequentially attempted in order to minimize the need for near-total/subtotal pancreatectomy.
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Objective To construct rat lysine-specific histone demethylase 1 (LSD1) overexpression plasmids and LSD 1 demethylation fragment disfunction plasmids,and to evaluate their expression levels in HEK293T cells.Methods LSD1 fragments were amplified by PCR,and LSD1 demethylation disfunction fragments were amplified by overlap PCR.Rat-specific LSD1 overexpression plasmids and LSD1 demethylation disfunction plasmids were constructed and verified by agarose gel electrophoresis and sequencing.HEK293T cells were infected using the validated recombinant plasmids and blank vectors,and the stably expressed cells were selected by puromycin.The expression of LSD1 in the stably expressed HEK293T was detected by Western Blot and real-time quantitative PCR.Results The results of agarose gel electrophoresis and sequencing showed that LSD1 overexpression plasmids and LSD1 demethylation disfunction plasmids were successfully constructed.The Western Blot and real-time quantitative PCR results showed that compared with the blank group,the relative expression of LSD1 and mRNA in the LSD1 overexpression group and the LSD1 demethylation disfunction group were up-regulated,and the differences were statistically significant(all P＜0.01).Conclusions The constructed LSD1 overexpression plasmids and LSD1 demethylationi disfunction plasmids can achieve overexpression of LSD1 gene in HEK293T cells.This paper lays a foundation for further study of the relationship between LSD 1 gene and related diseases and demethylation of LSD 1.
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According to:, the indications of twelve meridians were divided into two parts, the "" diseases and "" diseases. Traditional Chinese medicine practitioners of later generation provided several assumptions to differentiate them, but a general conclusion was still not drawn. In this paper, the opinions of previous researches were summarized; based on this, the viewpoints of each opinion were reviewed, and the authors' opinion on method to differentiate "" diseases and "" disease was proposed. It was concluded the differences of "" diseases and "" disease inwas only based on style of the composing, not involving medical principles. The role of two parts on diagnosis and treatment was similar.
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Back-shu points were firstly discussed in(the), and various location methods of back-points had been proposed by acupuncturists until conclusive method was made indynasty. In this paper, the different location methods of back-points were reviewed; based on this, the reasons of divergences among each theory on location methods were discussed, and the theoretical background and reference of the original establishment of back-points were further explored. Therefore, it was proposed that the standardized location of back-points should be just considered as the center of possible distribution range, and adjustment should be made during clinical application according to the variability of individual combined with finger pressing.
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<p><b>OBJECTIVE</b>To observe the effects of electroacupuncture(EA) at different acupoints for fasting blood glucose(FBG) and oral glucose tolerance in type 2 diabetes rats so as to verify the glucose-lowering effects of EA.</p><p><b>METHODS</b>Total 100 SD male rats were seen as experimental objects,among which 13 were randomly assigned into a blank group. Other rats were fed with high fat and high sugar diet combined with intraperitoneal injection of small dose streptozotocin (STZ) to establish type 2 diabetes model. Sixty diabetic rats were randomly assigned into a model group,a Weiwanxiashu group,a Xinshu group,a Shenshu group and a Housanli group,12 cases in each one. Combined with the improved diet habits and routines,EA (2 Hz and 2 mA) was used at "Weiwanxiashu" (EX-B 3),"Xinshu" (BL 15),"Shenshu" (BL 23) and "Housanli" (ST 36) in the corresponding groups,6 times a week for 4 weeks. There was no treatment in the blank group and in the model group. The observation indexes were the FBG on the 7th,14th,21st,and 28th day of intervention,the instant glucose-lowering effect on the 21st day during treatment,and the area under the curve of oral glucose tolerance test (OGTT) after intervention. Also,the glucose regulation condition was observed.</p><p><b>RESULTS</b>Type 2 diabetes model could be established by high fat and high sugar diet combined with intraperitoneal injection of small dose STZ. Glucose decreased apparently at the end of the 1st week or the 2nd week compared with that before treatment in the Weiwanxiashu,Xinshu and Shenshu groups(<0.05,<0.01). The instant FBG of the Weiwanxiashu and Xinshu groups was obviously lower than that of the model and Housanli groups at the end of the 3rd week(all<0.01). The area under the curve of OGTT of the Weiwanxiashu group was apparently smaller than that of the model group (<0.05),and the results of the index in the other groups were not significantly different from that of the model group(all>0.05).</p><p><b>CONCLUSIONS</b>Low frequency EA at "Weiwanxiashu"(EX-B 3),"Xinshu"(BL 15) and "Shenshu"(BL 23) can reduce glucose with different onset times,effects,and durations. And "Weiwanxiashu"(EX-B 3) is more effective.</p>
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Neonatal diabetes mellitus(NDM)occurs within the first 6 months of life. Depending on clinical outcomes,it is classified into transient neonatal diabetes mellitus(TNDM)and permanent neonatal diabetes mellitus (PNDM). TNDM,which accounts for 50% of NDM goes into remission after treatment for an average period of 12 weeks,but relapse in puberty and early adulthood. PNDM,on the other hand,is a lifelong disease without remission. The clinical features of TNDM and PNDM overlap,and the typing is based on clinical remission on follow - up. More than 20 pathogenic genes have been identified in PNDM,of which the most common are KCNJII and ABCC8 encoding the Kir6. 2 and SUR1 subunits of KATP channel accounting for 50% . TNDM is caused by defects associated with overexpres-sion of paternally expressed genes in the imprinted region of chromosome 6q24 in 70% cases. About 26% of the defects contain mutations in KCNJII,ABCC8,INS or HNFIB. In vitro and clinical studies suggest that treatment with oral sul-fonylurea can close KATP channel and improve glycemic control and neuropsychological development. However,10% of patients with KCNJII and 15% ABCC8 mutations fail to achieve glycemic control when insulin therapy is switched to o-ral sulfonylureas. Therefore,molecular diagnosis is vital not only in accurate typing but also for better prognostication.
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<p><b>OBJECTIVE</b>To summarize the clinical features of idiopathic hypogonadotropic hypogonadism (IHH) diagnosed during childhood, and detect mutations in KAL1 and FGFR1, acting as key clues for diagnoses.</p><p><b>METHOD</b>We collected and analyzed clinical data of 21 cases (including demographic data, chief complaint, history of present illness, family history, physical examination, laboratory tests and imaging studies, etc.) diagnosed with IHH from December 2008 to February 2013. Polymerase chain reaction and gene sequencing was applied to detect mutations on KAL1 and FGFR1. Fifty healthy unrelated individuals were choosen as controls.</p><p><b>RESULT</b>Of 21 patients with IHH, 19 were males and 2 females, they visited us initially from 8-17 years old, with an average of (13.58 ± 2.38) years old. Sixteen cases were KS patients (76%). One boy reported abnormal sense of smelling but having olfactory perfect picture on MRI; 2/19 male cases had no puberty when they were over 13-14 years old without abnormal external genitalia. 8/19 cases only had small penis, 8/19 had both of cryptorchidism and small penis, and the Case 2 also had hypospadias. One boy had cryptorchidism combined with a normal penis. Only 2 girls diagnosed as IHH who visited us because of no puberty signs when they were 13 and 16 years old, respectively. Other clinical manifestations included: one with gynecomastia, 2 had mental retardation, and one was deaf; one with high palatal arch; one with mirror-movement and one with left renal agenesis but normal renal function respectively. Laboratory tests showed that the basic testosterone (T) is low and with inappropriately low or normal gonadotropin hormones. The results of cases of standard human chorionic gonadotropin (HCG) test of 7 cases out of 19 male children's were normal (testosterone>1 100 ng/L), and another nine cases continued to complete the extended HCG test, and the testosterone levels of two of them (cases 6, 8) were still lower than 1 000 ng/L. Family history: the parents in 9/21 family had delayed puberty, involving only one parent in 6 families, involving both in 2 families and the other one was an uncle having micropenis with a child. Among these 21 cases, only one boy's father had hyposmia and his first emission age was 14-15 years. Eleven patients accompanied abnormal sense of smelling and the olfactory organ abnormalities on MRI, 4 had olfactory organ abnormalities on MRI while they had good smelling function self-reportedly. We got 15 samples (12 KS and 3 nIHH cases) to screen the mutation of KAL1 (14 exons) and FGFR1 (18 exons). A splicing mutation c.1062+1G>A in KAL1 is identified in case 17 with IHH. One novel heterozygous FGFR1 mutation, a single base deletion mutation on the exon 1 c.27delC is identified in case 14. This mutation causes the premature termination codons.</p><p><b>CONCLUSION</b>This pilot research showed that IHH/KS diagnosis in children depends on clinical manifestation rather than gene analysis. Small penis or cryptorchidism, smelling abnormality and positive familial history may contribute to the KS/HH diagnosis. MRI of olfactory bulb acts as important proof for diagnosis of KS. Mutations in KAL1 and FGFR1 gene are not main causes of Kallmann syndrome.</p>
Subject(s)
Adolescent , Child , Female , Humans , Male , DNA Mutational Analysis , Exons , Genetics , Extracellular Matrix Proteins , Genetics , Heterozygote , Hypogonadism , Diagnosis , Genetics , Kallmann Syndrome , Genetics , Mutation , Genetics , Nerve Tissue Proteins , Genetics , Olfaction Disorders , Receptor, Fibroblast Growth Factor, Type 1 , Genetics , Sexual MaturationABSTRACT
Objective To analyze the clinical features of 35 patients with Silver-Russell syndrome (SRS) in Beijing Children's Hospital in recent 6 years,and to recognize the clinical manifestations and improve the diagnosis of the disease.Methods The diagnostic criteria of SRS were studied retrospectively,the differences among 3 different diagnostic criteria were compared.Results Thirty-five SRS patients were diagnosed by means of 3 criteria,over a period from 2006 to 2012.There were 23 males and 12 females,with age range 0.08 ～ 12.15 yr.77 ％ of cases met the three criteria,97％ met two of the three criteria.There were dwarfism in 33 cases (94.2％),genital abnormalities in 1 case (2.9％),and asymmetry of limbs in 1 case (2.9％).The clinical characteristics with the frequencies accounting for over 80％ included short stature (average height-3.61 SDS),leanness (body mass index ＜-2.11SDS),bone dysmorphism including triangular face,irregular teeth,asymmetry of limbs,clinodactyly of fifth finger,and bone age obviously lagged behind.60％ of the cases showed bone age lagging behind more than 1 year.Height lagging behind was more obviously then bone age.Conclusions The diagnosis of SRS is mainly based on Clinical manifestation,laboratory and biochemical examinations are of no avail.There is a high coincidence with the 3 different diagnostic criteria.Clinical features in more than 80％ patients with SRS are short stature,craniofacial triangular dysmorphism,irregular teeth,limbs asymmetry and fifth finger clinodactyly,and mild lagging behind of bone age.
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Objective The report was focused on polycystic ovary syndrome(PCOS) in female adolescents related to homosexual precocious puberty,and the new awareness of its influence on long-term health of homosexual precocious girls.Methods A girl with idiopathic central precocious puberty (ICPP) but diagnosed as PCOS in adolescence was reported and the data were reviewed.Results A girl was diagnosed as ICPP when she was near 8 years old with obesity,but without hyperinsulinemia,then she received the treatment of a 3.75 mg dose gonadotropin hormone analogues (GnRHa) every 28 days.Her gonads development was under control while her growth was arrested.Growth hormone(GH) injection started at 13 months.She stopped all medications when finished GH and GnRHa treatment for 12 months and 25 months.She went to see doctors again because of no menarche after discontinuing medication for nearly 2 years.She appeared obese and acne,hirsutism,athanens negricans and purple purple striae on the skin.Hyperinsulinemia and hypertestosterone were demonstrated.Pelvic B ultrasonography showed polycystic ovary,and she was diagnosed as PCOS.She was ordered to lose weight and to take metformin.And adrenocorticotropic hormone stimulating test was done,and B ultrasonography again ruled out atypical congenital adrenal hyperplasia and tumor of adrenal gland.She got her menarche 1 month later.Twelve months after the PCOS diagnosis and treatment,she had 4 menses,her insulin level decreased,glucose tolerance and her serum testosterone level turned normal.At the same time,the form of ovarian and follicular was significantly reduced.After taking mefformin for 20 months,her height and weight did not change,her menstrual was regular every 35-40 days,each time lasting about 7 days.She was followed up.We also reviewed literatures and learnt that precocious puberty might not be a benign situation and it might have an intrinsic relation to obesity,precocious puberty and PCOS.It might be the cofactors for causing PP and PCOS that accessed luteinizing hormone(LH) secretion and disorder of hypothalamus pituitary gonad(HPG) axis except obesity with hyperinsulinemia.Reported pubertas praecox in childhood developed to PCOS at 30％ with high prevalence of obesity.GnRHa suppressive therapy might relate to PCOS and had disputation for improving final height.There were fewer investigations on adolescent PCOS,and no consensus guideline on it in China.Conclusions Girls with ICPP may develop to PCOS some time later.The clinical features of the reported girl and the knowledge from literatures support the hypothesis that inner relationship between the CPP and the PCOS.The LH high secretion and disorder of HPG axis may be the causes of them; LH treatment on suppressing obesity should be cautious during treatment.The benefit and risk from GnRHa treatment should be evaluated thoroughly.Further clinical research should be conducted on adolescent PCOS.