Objective:To report the clinical characteristics, diagnosis, and treatment of 2 cases of X-linked acrogigantism(X-LAG).Methods:The clinical information of two patients were retrospectively reported, and peripheral blood DNA was collected for copy number variations detection.Results:Both patients had onset at age of two, with common clinical characteristics including linear growth acceleration, mild facial coarsening, enlargement of hands and feet, increased appetite, and snoring, etc. The heights Z scores of the two patients before treatment were + 6.86 and + 6.53, respectively. Growth hormone(GH) glucose inhibition test showed that GH nadir values were over 1 ng/mL and insulin-like growth factor-Ⅰ(IGF-Ⅰ) were 586.0 ng/mL and 1 042.0 ng/mL, respectively. Patient 1 received three cycles of octreotide microspheres therapy followed by surgery, and achieved clinical and biochemical remission. Patient 2 had lanreotide for 5.5 years but failed biochemical remission. Microduplication of Xq26.3, which contained pathogenic gene G-protein coupled receptor 101(GPR101), was found in germline DNA of two patients through copy number variation detection, leading to the diagnosis of X-LAG.Conclusion:It should be cautious of X-LAG when children below 2 years old presents symptoms such as overgrowth and so on. Medication combined with surgery is effective.

Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.

Objective:To explore the value of octreotide suppression test(OST) in predicting the efficacy of somatostatin receptor ligands(SRLs) in the treatment of active acromegaly.Methods:The clinical data of 76 patients with active acromegaly from 2011 to 2020 was retrospectively analyzed. OST was carried out as follows: After an overnight fasting and baseline sampling of growth hormone(GH), 100 μg octreotide was subcutaneously injected, and sampling for GH was obtained every 2 hours for 8 hours. All patients were treated with SRLs for at least 3 months. A good GH response is defined as a post-treatment random GH<1 μg/L or >80% fall compared with the baseline GH. A good insulin-like growth factor Ⅰ(IGF-Ⅰ) response is defined as IGF-Ⅰ<1.3 upper limit of normal(ULN) or >50% reduction compared with the baseline. If both GH and IGF-Ⅰ fulfill the criteria of a good response, it is defined as a good GH and IGF-Ⅰ response.Results:The baseline level of GH during OST was 15.00(6.38, 34.20) μg/L, the median time to reach the nadir GH was(3.65±1.65) hours, and the nadir GH level was 1.47(0.50, 4.19) μg/L. The median GH suppression rate was 89.12%(72.71%, 95.09%). When the cutoff value of GH suppression rate in predicting a good GH response was 89.32%, the area under the curve(AUC) was 0.74, with a sensitivity of 81.80% and specificity of 66.00%. When the cutoff value of GH suppression rate in predicting a good IGF-Ⅰ response was 93.14%, the AUC was 0.64, with a sensitivity of 50.00% and specificity of 75.60%. When the GH suppression rate was 90.71%, the AUC was 0.78, with the sensitivity of 83.30% and specificity of 70.00% in predicting a good GH and IGF-Ⅰ response. Compared with GH/IGF-Ⅰ non-responders, GH/IGF-Ⅰ responders displayed lower nadir GH during OST, higher GH suppression rate and IGF-Ⅰ reduction rate, and lower ratio of IGF-1 to ULN( P<0.05). Conclusion:GH suppression rate during the OST is a valuable predictor to evaluate the efficacy of SRLs in patients with acromegaly, with the highest sensitivity and specificity when the cutoff value is 90.71%.

To compare changes in platelet related parameters in obese patients before and after sleeve gastrectomy (SG), we retrospectively analyzed the clinical data of 31 obese patients who underwent SG in Peking Union Medical College Hospital from December 2012 to September 2020. Results showed that compared with those before surgery, platelet count (PLT) decreased significantly at 2-12 weeks of follow-up ( P=0.009), while platelet distribution width (PDW), mean platelet volume (MPV), and large platelet ratio (P-LCR) increased significantly at the same periods of follow-up after operation ( P<0.001). However, the levels of PDW, MPV, and P-LCR began to decrease at 16-55 weeks when compared with those at 2-12 weeks of follow-up ( P<0.01). PLT was positively correlated with white blood cells and neutrophils at 2-12 weeks of follow-up and positively correlated with high sensitivity C-reactive protein at 16-55 weeks of follow-up after operation ( P<0.05).

The aim of this study was to assess the effects of orlistat or metformin treatment on lipid and glucose metabolism, and gonadal function in obese/overweight women with polycystic ovary syndrome (PCOS). A total of 39 patients diagnosed with PCOS were randomly (digital table method) divided into orlistat treatment group (20 cases) and metformin treatment group (19 cases). Compared with those before, treatment with either orlistat or metformin significantly reduced body weight, body mass index (BMI), hip circumferences, and serum insulin levels of the PCOS patients both at the end of 3 months and 6 months ( P<0.05). No significant differences could be viewed between orlistat and metformin treated subjects. Moreover, orlistat treatment significantly lowered the levels of low-density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and homeostasis model assessment-insulin resistance (HOMA-IR) ( P<0.05), while there were no significant changes in above parameters with metformin treatment. The improvement of menstrual cycle was observed after 6-month treatment in both groups ( P<0.05). However, changes in polycystic ovarian morphology by ultrasound were only observed in orlistat treated group. In conclusion, orlistat is comparable with metformin in weight loss and improvement of insulin resistance and menstrual cycle, and is superior to metformin in improvement of lipid metabolism in overweight/obese PCOS patients.

Objective: This article reported the clinical characteristics and gene mutations of two pseudoachondroplasia cases, and made a literature review in order to improve clinicians′ understanding of the disease. Methods: Clinical features of two patients who were short stature accompanied with skeletal deformities were summarized, and they accepted whole exome sequencing. We also reviewed literature to summarize the clinical characteristics and known gene research progress of all reported Chinese pseudoachondroplasia cases. Results: The two patients′ clinical characteristics were short limbdwarfism with skeletal deformity. Genetic results showed that there were two heterozygous mutations in the cartilage oligomeric matrix protein (COMP) gene of the two patients, c. 1417_1419delGAC and c. 1552G>A, respectively. Up to March 2019, a total of 58 cases of pseudoachondroplasia have been reported in China. The median height of these patients is -5.03 SDS. The clinical features include abnormal gait, short limbs, short fingers/toes, scoliosis, bracelet sign, ankle sign and other skeletal deformities. COMP is the pathogenic gene and mutations mainly located in calmodulin-like domains. The hotspot mutation is c. 1417_1419delGAC. Conclusions Pseudoachondroplasia is a kind of rare genetic disease characterized by short stature and skeletal deformities. The clinical and genetic characteristics of the disease were summarized, which may improve the early diagnosis rate.

Objective? To design a Seminar curriculum model for graduate nursing students based on the discussion of SCI papers and evaluate its effect on students' scientific research ability. Methods? Using the cluster sampling method, 57 graduate nursing students from a medical university were selected as the control group, and 58 graduate nursing students were selected as the experimental group. Using SCI nursing papers as the subject of discussion, the control group implemented the empirical Seminar curriculum model. The experimental group constructed and implemented the curriculum model based on the research capability structure model and the Seminar learning objectives. The effects of the intervention were evaluated using the Research Motivation Scale (RMS), the Nursing Research Self-Efficacy Scale (NURSES), the Nursing Staff Scientific Research Self-Assessment Scale (SRASES), and the Seminar Survey Questionnaire. Results? After the course, the scores of RMS total score, intrinsic motivation and extrinsic motivation of the nursing students in the experimental group were higher than those in the control group, and the differences were statistically significant (P＜0.05). At the end of the course, the scores of the NURSES total scores, scientific knowledge resources of the nursing students and "effect of collective research" in the experimental group were higher than those in the control group, and the differences were statistically significant (P＜0.05). At the end of the course, the scores of the total scores and dimensions of the SRASES in the experimental group were higher than those in the control group, and the differences were statistically significant (P＜0.05). Conclusions? The Seminar curriculum model based on SCI papers can improve the motivation, scientific research efficacy and scientific research ability of graduate nursing students to a certain extent. However, it is still necessary to further explore the curriculum model to help students avoid the motivation of scientific research failure and the understanding and application of theory.

Objective To evaluate the effects of a traditional Chinese medicine Rubia cordifolia L.aqueous extract (RCAE) on body weight, fat mass and parameters of glucose and lipid metabolism in high fat diet (HFD)-induced obese rats and its mechanism.Methods pGL3-Enhancer-PPARγ2 (625 bp)-Luc plasmid, a luciferase reportergene expression plasmid containing PPARγ2 promoter was constructed and stably transfected 3T3-L1 preadipocytes were established.PPARγ2 promoter`s activities in these cells were detected after administration with different concentration (0.1 mg/L~1 000 mg/L) of RCAE or with 100 mg/L RCAE for different action time.PPARγ2 mRNA expression in human adipocytes were detected after administration with 100 mg/L RCAE.Meanwhile, HFD-induced obese rats were administrated with low or high dose RCAE to investigate the effects of RCAE on serum glucose, lipid and insulin levels, body weight, visceral fat mass and so on.Results 10 mg/L RCAE could increase luciferase expression in 3T3-L1 cells to 1.43 folds of that in control group (P<0.01) and it reached 3.24 folds of that in control group when the concentration of RCAE was 1000 mg/L (P<0.01).With the administration with 100 mg/L RCAE, the luciferase activity of 3T3-L1 cells peaked at 28 h where it was 2.72 folds of that in control group (P<0.01), and the expression of PPARγ2 mRNA in human adipocytes increased to 2.27 folds of that in control group (P<0.01).Compared with HFD group, low dose RCAE significantly reduced the fasting insulin level, HOMA-IR and visceral fat mass (P<0.05).Conclusions Low dose RCAE significantly reduces the visceral fat mass and ameliorates insulin resistance in HFD-induced obese rats.The potential mechanism may be explained by the stimulation of PPARγ2 promoter activities and the increased expression of PPARγ2 gene.

Objective To study the clinical diagnosis and treatment of malignant gastrointestinal stromal tumor. Methods To retrospectively analyze the clinical data of 28 cases with malignant gastrointestinal stromal tumors underweat surgical treatment . Results The malignant gastrointestinal stromal tumor in adults were more than 50 years old,71.4%(20/28) ,and common clinical symptoms were gastrointestinal bleeding,anemia,and pain. The lesion site: 19 cases of gastric bowel, 8 cases of small intestine, 1 case of colon, radical excision in 22 cases, local excision palliative resection in 5 cases, three cases were multi-visceral resection. Conclusion Malignant gastrointestinal stromal tumor could be diagnosed by the means of endoscopic imaging and clear,and preoperative diagnosis was difficult. Surgical resection was the pathology diagnosis and treatment of primary method,if necessary,to ensure multi-visceral resection of the tumor to prevent recurrence of thoroughness, had important significance.

Objective To clarify the possible gene mutations in luteinizing hormone(LH) receptor gene in a boy with LH independent precocious puberty and probe the mechanism the of diseases caused by LH receptor activating mutations. Methods ( 1 ) Describe the clinical manifestations and laboratory data in a 5-year-old boy with LH independent precocious puberty. (2) Peripheral leukocytes were collected from the proband, his parents and other 20 normal puberty developed males. PCR and direct DNA sequence of 11 exons in LH receptors gene were conducted. Results (1) The proband was diagnosed to have LH independent precocious puberty according to the clinical symptoms and the laboratory tests. (2) A germ-line heterozygous point mutation in the 11 exon of LH receptor gene was found in the proband and his mother:c1193 T→C leading to amino acid change with M398T, which causes consecutively an activation of the LH receptor. (3) Other nucleotide changes in the proband and other normal males include c935 A→ G (N312S) and c1065 T→C(same sense mutation). Conclusions (1) A germ-line heterozygous point mutation in the LH receptor gene with M398T leads to consecutively activation of the LH receptor and LH independent precocious puberty. (2) The same point mutation does not have any influence on the puberty development, menstruation and productive functions of the proband's mother. (3) The LH receptor gene has possible polymorphism in the Han ethnic population.