One family with osteosclerosis caused by D111Y mutation in the low-density lipoprotein receptor-related protein 5 gene / 中华内分泌代谢杂志

Objective:To investigate the clinical features and pathogenic genes of a family with osteosclerosis.Methods:Six patients and six family members from a family in Jiangsu were tested for biochemical parameters, bone metabolic markers, bone mineral density, thoracolumbar anterior lateral slices, skull positive lateral radiographs, and pelvic plain films. Meanwhile, Sanger sequencing was performed to detect gene mutations of the proband and five other family members with high bone mass. The conformation of the mutational low-density lipoprotein receptor-related protein 5 (LRP5) protein was predicted by SWISS-MODEL.Results:Four adult patients (one male and three females) were tall, with mandibular enlargement and kyphosis in the center of the lower jaw, and none of the four had fractures. Their X ray examination revealed that the skull and long bone cortex was thickened, while the sella and mandible was enlarged. In addition, the absolute values of bone mineral density at each site of all patients were significantly higher as compared with the standard age- and sex-matched adults or adolescent mean reference values, with Z scores of L2-4, femoral neck and total hip being (6.31±4.03) SD, (6.56±2.36) SD, and (7.19±2.03) SD, respectively. The results of genetic sequencing revealed that all six patients carried a heterozygous mutation (c.331G>T; D111Y) in exon 2 of LRP5 gene, while other family members showed wild type (c.331G>G; D111D). Functional prediction indicated that this mutation was located at the amino acid terminal of exon 2 of LRP5 gene, which encodes the first β-helix-generating region of LRP5 protein.Conclusion:The D111Y mutation in LRP5 gene leads to a clinical phenotype characterized by benign increased bone mineral density without increasing the risk of fracture. This mutation may further affect the downstream Wnt signaling pathway by altering the spatial structure of LRP5 protein, thereby promoting maturation and differentiation of osteoblasts and resulting in osteosclerosis.

One family with osteosclerosis caused by D111Y mutation in the low-density lipoprotein receptor-related protein 5 gene / 中华内分泌代谢杂志

Objective@#To investigate the clinical features and pathogenic genes of a family with osteosclerosis.@*Methods@#Six patients and six family members from a family in Jiangsu were tested for biochemical parameters, bone metabolic markers, bone mineral density, thoracolumbar anterior lateral slices, skull positive lateral radiographs, and pelvic plain films. Meanwhile, Sanger sequencing was performed to detect gene mutations of the proband and five other family members with high bone mass. The conformation of the mutational low-density lipoprotein receptor-related protein 5 (LRP5) protein was predicted by SWISS-MODEL.@*Results@#Four adult patients (one male and three females) were tall, with mandibular enlargement and kyphosis in the center of the lower jaw, and none of the four had fractures. Their X ray examination revealed that the skull and long bone cortex was thickened, while the sella and mandible was enlarged. In addition, the absolute values of bone mineral density at each site of all patients were significantly higher as compared with the standard age- and sex-matched adults or adolescent mean reference values, with Z scores of L2-4, femoral neck and total hip being (6.31±4.03) SD, (6.56±2.36) SD, and (7.19±2.03) SD, respectively. The results of genetic sequencing revealed that all six patients carried a heterozygous mutation (c.331G>T; D111Y) in exon 2 of LRP5 gene, while other family members showed wild type (c.331G>G; D111D). Functional prediction indicated that this mutation was located at the amino acid terminal of exon 2 of LRP5 gene, which encodes the first β-helix-generating region of LRP5 protein.@*Conclusion@#The D111Y mutation in LRP5 gene leads to a clinical phenotype characterized by benign increased bone mineral density without increasing the risk of fracture. This mutation may further affect the downstream Wnt signaling pathway by altering the spatial structure of LRP5 protein, thereby promoting maturation and differentiation of osteoblasts and resulting in osteosclerosis.

Expression of Th17 cells and related cytokines in peripheral blood of patients with Graves′disease / 中国免疫学杂志

Objective:To explore the proportions of Th17 cells in the peripheral blood and levels of IL-17,IL-23 in the serum of patients with Graves′disease ( GD ) and their clinical significance.Methods: We studied 29 patients with GD ( GD group ) , and reevaluated the GD group after therapy ( euthyroid GD group ).29 gender-and age-matched volunteers were selected as the normal control ( NC group).The proportions of Th17 cells were investigated by flow cytometry.The levels of IL-23,IL-17 in the serums were measured by ELISA.The levels of FT3,FT4,TSH were determined by ECLIA and the levels of TrAb were tested by RRA.Results:There were no significant difference among 3 study groups in sex and age match ( F=0.0075 , P>0.05;χ2=0.4213 , P>0.05 ).The proportions of Th17 cells and the levels of IL-17 , IL-23 were increased in the GD and euthyroid GD patients compared with the control group (respectively,P0.05).Correlation analysis revealed that the proportions of Th17 cells ,and the levels of IL-17,IL-23 were positively correlated with the levels of FT3,FT4,TrAb(r=0.588 2,0.337 2,0.371 0;0.549 6,0.287 5,0.342 7;0.361 0,0.420 8, 0.330 8;P<0.05 ,for all parameters ) ,and were negatively correlated with the levels of TSH ( r=-0.319 7 ,-0.472 8 ,-0.428 2;P<0.05,for all parameters).Conclusion:Th17 cells and their related cytokines IL-17,IL-23 are highly expressed in the serum of patients with GD.Th17 cells and their relative cytokines have certain relevance with 4 thyroid function parameters of the patients with GD , which can be used as biological markers for GD.

Study on levels of IFN-γ,IL-6,IL-17 and TGF-β1 in patients with Graves′disease / 中国免疫学杂志

Objective:To explore the role of cytokines in the pathogenesis of Graves′disease(GD),by detecting the levels of IFN-γ,IL-6,IL-17 and TGF-β1 in GD patients who were newly diagnosed.Methods:A total of 23 patients with new onset GD and 23 gender-and age-matched healthy controls were examined.The levels of serum IFN-γ, IL-6, IL-17 and TGF-β1 were measured by ELISA,FT3,FT4 and TSH levels were determined by ECL IA;TrAb levels were tested by RRA.Results: There were no significant difference among GD and NC group in sex and age match ( t=0.334 8 ,P>0.05;χ2=0.410 7 ,P>0.05 ).The levels of serum IFN-γ,IL-6,IL-17 and TGF-β1 in the GD group were significantly higher than the control group ( P<0.05 ) .Correlation analysis revealed that IFN-γ,IL-6,IL-17 and TGF-β1 were positively correlated with FT3,FT4(r=0.324 6,0.453 2,0.431 0,0.463 8;0.413 2,0.441 5, 0.436 2,0.467 1;P<0.05 ).Conclusion: IFN-γ, IL-6, IL-17 and TGF-β1 are highly expressed in the newly diagnosed GD patients.They play an important role in the pathogenesis of GD ,and provide helpful evaluation indices of immune dysfunction to Graves disease.

The effects of new volume-removing drugs on refractory heart failure / 重庆医学

Objective To investigate the effect of diuretics combined with the new class volume-removing drugs nesiritide and tolvaptan on refractory heart failure (RHF).Methods We collected 78 patients with RHF from cardiovascular ICU in our hos-pital,and patients were divided into combined volume-removing drugs treatment group (CVR group)and traditional diuretics com-bined with inotropic treatment group (control group).We observed the differences in the heart failure symptoms control rate and the average hospitalization days between the two groups.The difference in average urine volume and weight loss during hospitaliza-tion was observed.Results The heart failure symptoms were controlled and successful discharge in 89.7% of patients in CVR group,which was better than that in control group(71.8%).The corresponding rates of death or abandonment was decreased sig-nificantly in CVR group,and the average number of hospitalization days in CVR group was significantly shorter than that in control group(P <0.05).Meanwhile,the average daily urine volume and the weight loss decreased significantly in CVR group than those in control group(P <0.05).Conclusion The therapy strategy of combined volume-removing drugs can significantly improve the vol-ume removing and control rate of heart failure symptoms.

Effect of Qingdu Granules on Breast Cancer in Rats via Suppressing Immune Escape / 中国药师

To study the effect and mechanism of Qingdu granules on the tumor growth of 7, 12-dimethyl-benz[ a] an-thracene ( DMBA)-induced breast cancer in Sprague-Dawley rats. Methods: DMBA was used to induce breast cancer in rats. The tumor inhibition of Qingdu granules was observed. Pathological features were observed after hematoxylin-eosin staining, the distribution and content of Ki-67 in tumor were tested by IHC and the content of IL-12, IFN-γ, IL-4 and IL-10 in serum was determined by ELISA. Results:The inhibitory rate of Qingdu granules at low, middle and high dose and saikosaponin a was 30. 93%,43. 84% and 44. 17% and 43. 48%, respectively. The expression of Ki-67 was reduced in Qingdu granules groups and saikosaponin a group, the content of IL-12 and IFN-γ in serum was increased and the level of IL-4 and IL-10 was reduced in the above groups. Conclusion:Qingdu granules can inhibit breast cancer obviously, and the mechanism is probably related to the ability of immune system adjustment, which can enhance the antitumor effect.