The etiology of peripheral precocious puberty(PPP) is complex and varied,which is mainly categorized into either genetic or acquired disorders.Albright-McCune syndrome and familial male-limited precocious puberty are the 2 most important genetic PPPs.The purposes of therapy are to halt pubertal development and restore sex steroids to prepubertal values and delayed rate of skeletal maturation in order to maximize height potential.The several major categories of clinical drugs for PPP include anti estrogen/androgen,estrogen receptor blocker,aromatase inhibitors and cytochrome P450 inhibitors and so on.

It is found in clinical practice that decisions made by agents on hehalf of the patients without capability of independent choice may sometimes conflict interests of the patient in question. The author summarized by categories common dilemmas faced by clinicians, and came up with the ethical principles to resolve the problems, as proven in case studies. Doctors should fully respect reasonable decisions of agents of such patients. Furthermore, to make a reasonable decision on their behalf, the agent is expected to make medical decisions in the interests of the life and health of the patient, with adequate knowledge of the disease, therapeutic measures and outcomes, and without any damage to interests of the patient they represent. Such a reasonable decision should neither violate laws of the state, nor infringe on interests of other individuals, collectives and the society at large for benefits of the patient in question. In addition, it should conform to the medical ethics of fair distribution of health resources.

Thermophilic and alkalophilic xylanases have great potential in the pulp bleaching industry. In order to improve the thermal stability of an alkaline family 11 xylanase Xyn11A-LC, aromatic residues were introduced into the N-terminus of the enzyme by rational design. The mutant increased the optimum temperature by 5 degrees C. The wild type had a half-time of 22 min at 65 degrees C and pH 8.0 (Tris-HCl buffer). Under the same condition, the mutant had the half-time of 106 min. CD spectroscopy revealed that the melting temperature (T(m)) values of the wild type and mutant were 55.3 degrees C and 67.9 degrees C, respectively. These results showed that the introduction of aromatic residues could enhance the thermal stability of Xyn11A-LC.
Endo-1,4-beta Xylanases ; chemistry ; Enzyme Stability ; Hydrogen-Ion Concentration ; Protein Engineering ; Temperature

BACKGROUND: Panel reaction antibody (PRA) plays an important role in rejection of recipients undergoing solid organ transplantation, which has a positive effect on nonfunction of implant. OBJECTIVE: To evaluate the effect of thalassemic serum-specific PRA on the proliferation and differentiation of umbilical cord blood hernatopoetic stem/progenitor cells (HSC/HPCs) in children patients with thalassemia. DESIGN, TIME AND SETTING: The in vitro cytology experiment was performed at the Experimental Research Center, Second Affiliated Hospital, Zhongshan University from January 2006 to August 2007. MATERIALS: Five samples of umbilical cord blood from healthy full-term birth puerperants (each 80 100 mL) were used in this study. PRA serum samples of children patients with thalassemia after repetitive blood transfusion, five samples of AB blood grouping serum, and six samples of positive anticoagulation vein blood (10 mL) were used in the study. METHODS: Mononuclear cells were harvested from umbilical cord blood by Ficoll-Hypaque gradient centrifugation. 1 × 105 rnononuclear cells from umbilical cord blood were incubated with different levels of experimental or AB control serum (0, 50, 100 μ L) from healthy children. The mixture mentioned above was incubated with rabbit complement for semisolid colony culture.MAIN OUTCOME MEASURES: Colony-forming units (CFU) were counted and observed after 7 days and 14 days of culture under an inverted microscope.RESULTS: After incubation with HSC/HPCs PRA serum, total number of CFUs and varied CFUs decreased to different extents, of which the total number of CFUs and CFU- granulocyte-rnacrophages (CFU-GM) had significant differences (P < 0.01). Moreover, there were negative correlations between different levels of serum PRA and the followings: number of total colonies, CFU- GM, CFU- granulocyte-erythrocyte-monocyte-megakaryocytes, CFU-erythroids, burst forming unit-megakaryocytes, and CFU-megakaryocytes (P < 0.05).CONCLUSION: The thalassemic serum PRA has an apparent inhibitory effect on the proliferation and differentiation of cord blood HSC/HPCs in vitro, an effect that may be pronounced with increasing serum PRA.

Objective To investigate the etiological factors fc,r abnormal vaginal bleeding in girls.Methods Data of 65 female children aged from 3 months and 10 years old with abnormal vaginal bleeding,who were treated in Department of Endocrinology,Wnhan Children's Hospital from March 2009 to October 2013 were collected by using medical records and follow-ups.By means of pelvic ultrasound,bone age assessment,hysteroscope,hormone level and genetic testing,the causes of the disease were analyzed.Results Of 65 patients,37 cases had breast developed,21 ca-ses had nipple,areola and vulva pigmentation increased,16 cases with genital secretions increasing and odor,the height growth in 21 cases accelerated,abdominal pain was presented in 5 cases,and 6 cases had skin milk coffee spots.The leading etiological factors for vaginal hemorrhage in these girls were sexual precocity.The peripheral precocious puberty accounted for the first place (30/65 cases,46.2％),and followed by the central precocious puberty (20/65 cases,30.8 ％).Hyperphlogosis accounted for 12.3 ％ (8/65 cases),vaginal foreign body accounted for 6.2 ％ (6/65 cases),and genital tract tumors accounted for 4.6％ (3/65 cases).In the 30 peripheral precocious puberty cases,exogenous precocious puberty accounted for 16.9％ (11 cases),8 cases(12.3％) were of solitary ovarian cyst,8 cases(12.3％) of McCune-Albright syndrome,and 3 cases of ovarian tumors.In the 20 central precocious puberty cases,idiopathic central precocious puberty accounted for 18.5％ (12 cases),4 cases(6.2％) were of organic disease of central nervous system,and 4 cases (6.2％) of hypothyroidism.Of 65 children,12 cases lost follow-up and 1 case abandoned treatment.The rests received appropriate treatment according to different causes,and the vaginal bleeding were effectively controlled after 3 months to 2.5 years of follow-ups without recurrence of bleeding.But there were 2 cases of isolated ovarian cyst and 3 cases of McCune-Albright syndrome turned into central precocious puberty.Conclusions Endocrine diseases are the common factors for children's vaginal bleeding.Neoplasm is not rare in girl's abnormal vaginal hemorrhage.

Objective To explore the clinical feature and gene mutation in steroid 5α-reductase 2 deficiency (SRD5A2). Method The clinical data of SRD5A2 in a child with vulva abnormality as the first manifestation was retrospectively analyzed. Results This was a 29-month-old child, whose social gender was female. The level of her basic luteinizing hormone (LH) was 0.07 mIU/mL, and follicle-stimulating hormone was (FSH) 0.39 mIU/mL. The baseline levels of testosterone (T), dihydrotestosterone (DHT), 17-hydroxyprogesterone (17-OHP) and androstendione (A2) were 0.06 ng/mL, 19.67 pg/mL, 1.20 ng/mL, and 0.07 ng/mL respectively. Those levels were 3.65 ng/mL, 68.25 pg/mL, 51.72 ng/mL, and 14.70 ng/mL respectively after Human chorionic gonadotropin (HCG) stimulation. The levels of her anti-mullerian hormone (AMH) was 22.97 ng/mL, and inhibin B (INH-B) was 274.4 pg/mL. The uterus and ovaries were not detected by Pelvic ultrasound and MRI. The chromosome showed 46, XY. Sex determination (SRY) gene detection showed normal. Androgen receptor (AR) gene detection showed negative. There was pathogenic mutation of 5α-reductase 2 (SRD5A2) gene in peripheral blood of the child and her parents. The penis grows 2 cm after 4 months of treatment with 2.5% DHT gel. Conclusion SRD5A2 is diagnosed mainly based on the increase of T/DHT after HCG stimulation experiment and it can be confirmed by detection of pathogenic SRD5A2 mutation.

OBJECTIVE: To investigate the impact of renal denervation on the blood pressure, plasma renalase content and expression of renalase and tyrosine hydroxylase (TH) in the idney of spontaneous hypertensive (SH) rats and to explore the role of renal denervation in lowering the blood pressure. METHODS: SH rats were randomly assigned into a baseline group, a surgery (renal denervation) group, a sham group and a control group (n=48). WKY rats matched in age (n=12) served as a baseline control group. All rats were housed until 12 weeks old. Then, the rats in the baseline group and the WKY group were sacrificed whose blood and kidney were collected for examination. In the renal denervation group, the sham group and the control group, the blood pressure was monitored continuously. One week and 6 weeks after the renal denervation, 6 rats in each group were sacrificed whose blood and kidney were collected. ELISA was employed to measure the plasma renalase and Western blot assay done to detect the expression of TH and renalase in the kidney. RESULTS: Compared with WKY rats, blood pressure significantly increased and TH protein expression markedly elevated (P<0.05) in SH rats in the baseline group, but plasma renalase content and protein expression of renalase in the kidney dramatically reduced (P<0.05). One week after the surgery, the mean arterial pressure and TH protein expression in the surgery group were lowered compared with the baseline group and dramatically reduced compared with the sham group and the control group (P<0.05). In the surgery group, the renalase level was markedly increased compared with the baseline group, the sham group, and the control group (P<0.05). Six weeks after the renal denervation, the mean arterial pressure and TH level in the surgery group were significantly increased but the renalase content and expression markedly reduced compared with those 1 week, but there were no marked differences among the surgery group, the sham group, and the control group (P>0.05). No pronounced differences in the above variables were found between the sham group and the control group at any time point (P>0.05). CONCLUSION Renal denervation can lower the blood pressure, which may attribute to the suppression of sympathetic nerves, increase in plasma renalase content and renalase expression in the kidney.
Animals ; Blood Pressure ; physiology ; Hypertension ; surgery ; Kidney ; enzymology ; innervation ; Male ; Monoamine Oxidase ; blood ; metabolism ; Rats ; Rats, Inbred SHR ; Sympathectomy ; methods ; Sympathetic Nervous System ; physiopathology ; Tyrosine 3-Monooxygenase ; metabolism

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Schaaf-Yang syndrome (SYS). METHODS: Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Sanger sequencing was used for family constellation verification, and bioinformatic analysis was performed for the candidate variant. RESULTS: The child, a 1-year-and-9-month-old boy, had clinical manifestations of retarded growth, small penis, and unusual facies. Genetic testing revealed that the child has harbored a novel heterozygous variant of c.3078dupG (p.Leu1027Valfs*28) of the MAGEL2 gene. Sanger sequencing showed that neither parent of the child carried the same variant. The c.3078dupG(p.Leu1027Valfs*28) variant of the MAGEL2 gene has not been included in the databases of ESP, 1000 Genomes and ExAC. According to the Standards and Guidelines for the Interpretation of Sequence Variants of the American College of Medical Genetics and Genomics (ACMG), the variant was judged to be pathogenic. CONCLUSION The c.3078dupG (p.Leu1027Valfs*28) variant of the MAGEL2 gene probably underlay the SYS in this child, which has further expanded the spectrum of the MAGEL2 gene variants.
Child ; Humans ; Infant ; Male ; Exome Sequencing ; Genetic Testing ; Heterozygote ; Mutation ; Proteins/genetics* ; Developmental Disabilities/genetics*

Studies have shown that targeting xanthine oxidase (XO) can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia. This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato (diacylated AF-PSPs) on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet. The body weight, organ index, serum biochemical indexes, and liver antioxidant indexes of mice were measured, and the kidneys were observed in pathological sections. The relative expression levels of messenger RNAs (mRNAs) of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain (qPCR) reaction technique, and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry (IHC) technique. Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice, and that this effect might be related to the regulation of liver XO activity, lipid accumulation, and relevant renal transporters. Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder, liver lipid accumulation, and liver oxidative stress, thereby enhancing insulin utilization and sensitivity, lowering blood sugar, and reducing hyperglycemia in mice. Also, diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism, and reduced kidney injury and inflammation. This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid (UA) by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.
Mice ; Animals ; Hyperuricemia/drug therapy* ; Diet, High-Fat/adverse effects* ; Anthocyanins/chemistry* ; Ipomoea batatas/chemistry* ; Fructose/adverse effects* ; Hyperglycemia/drug therapy* ; Lipids

Objective To investigate the clinical features of hypopituitarism with nonalcoholic fatty liver disease (NAFLD) in children after sellar tumor surgery and the association between hypopitarism and NAFLD in children. Methods A retrospective analysis was performed for the clinical data of children with hypopituitarism and NAFLD after sellar tumor surgery who were followed up regularly in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2017 to December 2021, and their clinical features were analyzed. Results There were 32 children with regular follow-up and complete clinical data after sellar tumor surgery, and 10 children (31.25%) developed NAFLD, among whom there were 5 boys and 5 girls. Among these 10 children, 9 had craniopharyngioma and underwent surgical treatment, and 1 had germinoma and underwent local radiotherapy. The 10 children had a median age of 8.4(6.29.8) years at the diagnosis of hypopituitarism and a median age of 11.9(8.7-12.6) years at the diagnosis of NAFLD. The median number of years from the diagnosis of hypopituitarism to the diagnosis of NAFLD was 2.0(1.4-4.0) years. At the diagnosis of NAFLD, all 10 children had obesity, and body mass index (BMI) was increased by 7.26±4.25 kg/m 2 on average since the diagnosis of hypopituitarism; the 10 children had a mean fasting blood glucose level of 4.67±0.55 mmol/L, a mean fasting insulin level of 25.40±5.93 μIU/ml, and a mean HOMA-IR index of 5.26±1.29. Among these 10 children, 9 had hypertriglyceridemia, and 1 had elevated triglyceride, with a mean level of 3.08±1.09 mmol/L; 6 children had hypercholesterolemia, with a mean level of 5.67±1.25 mmol/L; 8 children had high-density lipoprotein cholesterolemia, with a mean level of 3.97±1.27 mmol/L. After the diagnosis of NAFLD, 2 children were treated with recombinant human growth hormone and metformin and achieved reductions in BMI, HOMA-IR, and triglyceride after treatment, and total cholesterol and low-density lipoprotein cholesterol were reduced to the normal range. Conclusion Children may experience weight gain, hypopituitarism, insulin resistance, and dyslipidemia after sellar tumor surgery, which may lead to the onset of NAFLD. Weight management and active pituitary hormone replacement therapy are recommended for such children, as well as routine screening and management of fatty liver disease.