Objective To evaluate the efficacy of prevention of recurrent femur fracture in children with osteogenesis imperfecta.Methods Data of 35 patients (19 boys,16 girls) who were treated for femur deformity due to osteogenesis imperfecta at our hospital from Jun 2009 to Jun 2013 were retrospectively analyzed.The average age of the patients was 9 years 3 months,ranging from 3 years 6 months to 13 years 1 month.All the patients had suffered from recurrent femur fractures before which led to femoral deformity.The mean angulation angle was 55° (range,10°-90°).10 patients were operated at one side;the other 25 patients were treated bilaterally.None of them received operation before for fractures.The average incidence of femur fracture before operation was 2.4/year (range,2-4).According to the modified Sillence classification system,9 were type Ⅲ OI,14 type Ⅳ,and 12 type I.The curved deformity of the femurs were corrected by osteotomy and stabilized by telescopic intramedullary rods in 35 patients.Results All the 35 patients were followed up for a mean period of 62 months (range,36-72).The average healing time of the osteotomy site of the femur was 8.5 weeks (range,7-12).The patient was encouraged to begin weightbearing and walking when the Xray film showed healing of the osteotomy site.By the latest follow up,80％ of the patients could stand and walk independently.The incidence of femur fracture decreased significantly to the level of 0.3±0.1/year,compared with the level of 2.4± 1.3/year before operation.All the parents of the children were satisfied with the result of deformity correction.At the latest follow up,the Barthel index score increased from 71.82 (range,51-92) before operation to 92.32 (range,82-100) postoperatively,while the WeeFIM score increased from 53.32 (range,42-72) before operation to 78 (range,70-86) postoperatively.The difference of Barthel index score and WeeFIM score between that before and post operation was significant.The children's selfcare and motion ability improved obviously after operation.During follow up,22 patients suffered from recurrent fracture of the femur by various degree,7 of them were treated by open reduction and telescopic rodding surgery,while the other 15 patients were treated conservatively because the fracture displaced or angulated minimally and the fracture healed uneventfully.Conclusion The telescopic intramedullary rod can maintain the correction of the femur deformity and improve the quality of the bone,thus prevent the recurrent fracture of the femur in children with osteogenesis imperfecta effectively.

ObjectiveTo evaluate the safety,therapeutic effect and complications of the operation of multi-section osteotomy and intramedullary fixation for children with osteogenesis impeffecta.Methods One hundred and twenty-three children with osteogenesis imperfecta,including 85 males and 39 females,were selected from August 2005 to August 2008.According to the modified Sillence classification,45 cases was in type Ⅲ,74 in type Ⅳ,and 5 in type Ⅴ.Patients' age was ranging from 2 years and 1 month to 15 years and 7 months (mean,8 years and 3 months).The location of osteotomy was established according to the pre-operative measurement of X-ray image,and all the procedures of osteotomy were completed under direct vision.Then we chose the intramedullary pin with suitable size and insert the pin into femur from greater trochanter,and tibia from pelma.After the surgery,external fixation (spica cast for the femur,long leg plaster cast for the tibia) was made for further stabilization.Plaster supporters were removed 6 weeks later and all children began to stand and walk under the protection of orthoses.In addition,all patients received the treatment of pamidronate disodium periodically.ResultsAll 123 children were followed up for an average of 38months (range,13-64 months).Parents of all children were satisfied with the result of surgical operation,and the children's self-care and motion ability improved obviously.Fourteen children were performed the second operation due to the translocation of Rush pin,and 25 children changed the internal fixation because of the shorter Rush pin 2 years postoperatively.Bone delayed union was not found in all patients.Conclusion Multi-section osteotomy and intramedullary fixation for children with osteogenesis imperfecta could correct skeletal deformity,improve motion ability and avoid second fracture efficiently.However,such complications as translocation of intramedullary pin and changing the internal fixation with the growth of child need to pay more attention.

ObjectiveTo evaluate and compare the outcomes of missed Monteggia fractures in children treated with ulnar angulation-distraction osteotomy and plate fixation or external fixation.Methods Nineteen patients,including 11 boys and 8 girls who presented with missed Monteggia fracture,were reviewed from July 2005 to June 2011.Twelve children (Group A) were treated with ulna angulation osteotomy and plate fixation,and 7 eases(Group B) with ulna angulation-distraction osteotomy and external fixator.Thirteen patients were classified as type Bado Ⅰ,and six as type Bado Ⅲ.The age,the delay from injury to surgery,complications,elbow and forearm function,and the healing time of the osteotomy were compared.ResultsAll 19 patients were followed up.The duration of missed dislocation was from 6 to 36 months (mean,10 months).Redislocation of the radiocapitellar joint occurred after surgery in one case in group A.Forearm compartment syndrome occurred in one case after surgery in group B.All patients,except one,regained full elbow flexion in group A and B,various forearm pronation limitation were noted in all patients (mean,15°).The average healing of osteotomy of group A and B was 8 weeks(6-15 weeks) and 22 weeks (10-44 weeks).ConclusionThe ulnar angulation-distraction osteotomy could correct the ulnar deformity in children of missed Monteggia fractures,which is the key issue to be corrected.Both of the fixation strategies can obtain the same treatment results.Preoperative assessment is most important,plate internal fixation was recommended for young age and short delay cases,on the contrary,we prefer to choose external fixator.

Objective To study on the endoscopic resection of submucosal tumors (SMT) in gastro-intestinal tract with especial regards to the effectiveness and safety, and the value of endoscopic ultrasonogra phy ( EUS) in SMT before endoscopic resection. Methods Endoscopic therapy was performed in 71 patients with gastrointestinal SMT diagnosed by endoscopy, and of them 64 patients (90. 1 % ) were examined by EUS before the procedure. The SMT located in the esophagus 36 cases, stomach 29 cases, duodenum 3 cases and rectum 3 cases. The median tumor diameter was 14. 2 mm ( ranged 6-20 mm). Endoscopic mucosal resection was performed using a two-channel endoscope after submucosal injection of saline solution in 55 cases, then the SMT resected. In 16 patients, the SMT was resected completely with one-step standard procedure using cap-fitted endoscope ( 10 cases, the SMT less than 10 mm in diameter) or two-channel endoscope (6 cases). Results Sixty-eight of seventy-one solid SMT were removed completely under endoscopy and 2 SMT (one ectopic pancreas and one gastric leiomyoma) were resected incompletely; the findings were showed at 4th week by repeated endoscopy. One patient with rectal leiomyoma required surgical resection after unsuccessful endoscopic resection. The follow up period was 18. 7 months on average, no recurrences were found in 67 cases. Histological results showed 51 (71. 8% ) leiomyomas, one granular cell tumor, 4 fibromas, 3 ectopic pancreas, 3 lipomas, 2 stromal tumors and 2 carcinoids in the SMT. Five tumors of mesenchymal tissue , their histological origin cannot be firmly defined due to lack of immunoassayed specimen. Bleeding occurred in only 9 of 71 cases and was easily managed with endoscopic haemostatic measures. One patient with stromal tumor suffered from gastric perforation after the procedure. Conclusions Endoscopic resection of gastrointestinal SMT is a safe and effective procedure and obtains the histological diagnosis simultaneously. EUS is helpful in selecting indicated cases for endoscopic resection.

Objective To understand the feeling of mothers of children with osteogenesis imperfecta during the accompany of children's diagnosis and treatment.Methods A total of 20 mothers of children with osteogenesis imperfecta participated the semi-structured interview.The data were analyzed by Colaizzi's method of phenomenology.Results Three themes were acquired including heavy psychological burden,facing multiple pressure and mother's support through analysis,reorganization and extraction of the subjects.Conclusions Mothers of children with osteogenesis imperfecta needed humanistic concern and emotional support.Nursers should adopted personalized care measures to improve their quality of life.

Objective To evaluate the therapeutic effect of extendable intramedullary nail on children with femoral deformity due to osteogenesis imperfecta.Methods From June 2009 to June 2012,21 patients with femoral deformity due to osteogenesis imperfecta were treated with extendable intramedullary nail.There were 13 males and 8 females,aged from 9 years and 6 months to 15 years and 7 months (average,12 years and 3 months).All children had been performed osteotomy on the shaft of femur and implanted with non-extendable nail before 2-4 years (average,3 years).All children had suffered refracture and deformity,including 9 children with femoral bending deformity and 12 with refracture.The deformity angle ranged from 10°to 30°,with an average of 15°.According to revised Sillence classifications,there were 6 cases with type Ⅲ and 14 with type Ⅳ and 1 case with type Ⅴ.Twenty-one patients were operated with extendable nail for fixing fracture and correcting deformity and incisions were 2-3 cm long and located on the great trochanter and distal osteotomy point.Results All of 21 children were followed up for 6-30 months (average,18 months).The bone healing time was 7-12 weeks (average,8.5 weeks).Patients started to walk after X-ray showing bone union.Parents of 21 children were satisfied with surgical operation effect and deformity correction.The Barthel index score improved from 72.85 (range,50-90 points) preoperatively to 91.42 (range,80-100 points) postoperatively at the latest follow-up of patients.WeeFIM index score increased from preoperative average of 55.42 points (range,40-70points) to postoperative average 79.00 points (range,70-86 points).Ten of all children with stick aid preoperative could walk independently after small incision repairing,and 6 of all children in sickbed preoperative,4 of 6 children could walk independently,2 of 6 children could walk with stick aid.Conclusion Small incision repair with extended intramedullary nail operation therapy is advantaged.It gets less bloody,less damages,less pain,less healing time and walking after removing plaster.

Objective To validate the analytical performance of three Cys C reagents with particle-enhanced turbidimetric immunoassay(PETIA) method used on the automatic biochemistry analyzer for preliminary clinical application.Methods The performance of three Cys C reagents (labeled as A, B, C) with PETIA method from Shanghai Jing Yuan Co., Beijing Leadman Co. and Beijing Jiuqiang Co. on OlympusAU2700 automatic biochemistry analyzer were assessed.According to the standard of CLSI EP6-A, EP15-A and EP7-P, the precision, linearity range, disturbance (bilirubin, hemoglobin, chyle) were assessed, and compared with those of Cys C reagent based on particle-enhanced nephelometric immunoassay(PENIA) from Dade Behring Co.. The reference ranges for Cys C in serum of 120 healthy individual were evaluated.Results The within-run CVs of the three reagents (A, B and C) were 3.08%-3.2%, 2.3%-4.15% and 1.38%-1.53% respectively.The total CV in A, B and C were 3.29%-3.44%, 2.65%-5.18% and 1.67%-1.69% respectively, lower than the stated.Limits of quantitative determination (LOQ) of the three reagents were 0.41, 0.23 and 0.07 mg/L, basically meeting the testing requirement.The linearity range was 0.22-7.26 mg/L(r=0.996), 0.20-7.72 mg/L(r=0.999)and 0.20-7.62 mg/L(r=0.997)in the three reagents, which demonstrated a sound linear correlation. For interference tests, no remarkable interference (<±10%) of reagent C was detected when bilirubin≤684 μmol/L, hemoglobin≤9.7 g/L and Chyle turbidity≤6 200 FTU; and no significant interference of reagent B was found when bilirubin≤684 μmol/L, hemoglobin≤6.79 g/L and Chyle turbidity≤6 200 FTU; when bilirubin≤684 μmol/L, hemoglobin≤4.85 g/L and Chyle turbidity≤1 240 FTU reagent A was not interfered significantly. The comparison afte and before the high-speed centrifugation reveals that the average percentage of bias for reagents A, B, C measured Cys C in chylous serum samples of patients was -8.31%, 1.52%, 1.32%, respectively.In method comparison tests, the regression equations of the three reagents compared with Dade Behring PENIA Cys C reagent were as follows:Y=0.787X+0.492 (R2=0.976), Y=1.098X+0.137 (R2=0.982) and Y=1.037X+0.249 (R2=0.996), respectively. Agreement rates of the high Cys C in reagent A, B, C and Dade Behring Cys C reagent were 80% (Kappa=0.615,P=0.000), 100% (Kappa=1.000,P=0.000), 91.2% (Kappa=0.824,P=0.000); While for reference range of preliminary clinical assessment, diagnosis coincidence rate of reagent A increased to 98.8% (Kappa=0.974,P=0.000). Conclusions When used in automatic biochemical analyzer, the three Cys C reagent with PETIA showed high precision,sensitivity, and sound correlation with Dade Behring PENIA reagents.The three reagents are all able to meet clinical test requirements, nevertheless, anti-interference capability were diffierent and the reference range should be further validated.

Objective To investigate COL1A1 gene mutation by PCR-high resolution melting (PCR-HRM) and an-alyze the correlation between genotype and clinical phenotype in a child (proband) with osteogenesis imperfecta (OI). Methods The family history of OI pedigree along with the clinical data was collected. Blood samples from the proband and his family members, as well as 50 normal controls, were collected. The mutation of COL1A1 gene was screened using PCR-HRM and validated by the gene sequence. Results The detection of PCR-HRM showed the abnormal result of COL1A1 17 exon in proband with a lower melting temperature (Tm) value than that of normal controls by 0.4℃. There were signifi-cant differences in the standardization melting curve and the different melting curve between the proband and the normal controls. The sequencing result was c.1138G>A, which meant that cDNA of 1138 base G mutation into A. The mutations transformed the amino acid glycine into a serine at amino acid 380(P. Gly 380 Ser), which resulted in missense mutations. The proband’s father and grandmother had the same mutation of COL1A1 gene. The mutation was not found in the proband’s mother and normal controls. There was no report for such mutation in Chinese population. Pedigree analysis showed the fami-ly genetic characteristics of autosomal dominant inheritance. The proband was clinically diagnosed as OI type Ⅳwith more severe clinical phenotype. Conclusion PCR-HRM analysis is a new effective method for genetic screening of OI. COL1A1 mutation of c.1138G>A is a newly discovered mutation in Chinese population. Gly replaced inαhelical domain may lead to a more severe clinical phenotype.

Objective To evaluate specific clinical and imaging features of osteogenesis imperfecta V and to improve diagnostic accuracy of this disease. Methods Data of 15 patients with osteogenesis imperfecta type V were retrospectively analyzed for their clinical and imaging features. There were 10 males and 5 females, aged from 1 year and 30 years old (median age,12.5 years ). All 15 patients had plain X-ray, and 4 of 15 had CT. All data were analyzed by 3 experienced deputy chief doctors in OI according to OI V standard. Results X-ray:calcification of the interosseous membrane between radius-ulna was detected in all patients and calcification of the interosseous membrane between tibia-fibula was detected in 2 of 15 patients. Dislocation of the radial head was seen in 13 of 15 patients,bilateral in 9 and utilateral in 4.All patients showed restriction in the pronation and supination of the forearm and restricton in the flexion and extention of the elbow joint. Patients with dislocation of raidal head were associated with large coronoid process and olecranon of the ulna. Hyperplastic callus of the extremities were detected in 7 of 15 patients (7 at femur , 3 at humerus, 1 at tibia.In early stage, hyperplastic callus showed thin cortice, and clear boundares with the diaphysis showing and low density, irregular, mesh-like lamellation inside. In the later stage, there were dense calcification inside hyperplastic callus, and no difference in density with the diaphysis. Diaphysis surrounded by hyperplastic callus had clear boundaries with the hyperplastic callus. No cortical destruction was detected. CT:there were sparse needle-dot calcification inside hyperplastic callus, with the patterns of granular, ring-and-arch,irregular streaky mineralization. The cross section of proximal femoral shaft showed irregular shape , flat square shape and tiny medullary cavity, with no calcification on the edge of hyperplastic callus. CT value:-91 HU inside hyperplastic callus; 283 HU in femoral shaft. Conclusions Interosseous membrane between radius-ulna or tibia-fibula, hyperplastic callus ,dislocation of the radial head are specific features in osteogenesis imperfecta V. X-ray can make a definitive diagnosis of osteogenesis imperfecta V. CT scan is helpful in the differential diagnosis of osteogenesis imperfecta V from osteosarcoma.

OBJECTIVETo detect potential mutations of COL1A1 and COL1A2 genes with polymerase chain reaction-high-resolution melting analysis(PCR-HRMA) in a proband diagnosed with osteogenesis imperfecta (OI).

METHODSPeripheral blood samples were collected from the proband and members of his family as well as healthy controls. The mutations were detected by PCR-HRMA and confirmed by direct sequencing. Potential effects of the mutations were predicted using softwares including PolyPhen, SIFT and Align GVGD.

RESULTSThe PCR-HRMA has indicated mutations in exon 45 of the COL1A1 gene in the proband as well as his parents, which were presented as the difference in the melting curves between the patients and the control samples. Sequencing analysis confirmed that the proband has carried two heterozygous mutations (c.3235G>A, p.Gly1079Ser and c.3247G>A, p.Ala1083Thr) in exon 45 of the COL1A1 gene. Among them, c.3235G>A was predicted to have impeded alpha helix structure domain, which was inherited from the father who also had OI. c.3247G>A was inherited from mother who had a normal phenotype. All three softwares predicted that the c.3235G>A mutation can interfere with the function of the protein, while the c.3247G>A may have a benign effect by PolyPhen analysis.

CONCLUSIONThe study identified two mutations (c.3235G>A and c.3247G>A) occurred simultaneously in COL1A1 gene in a case. The case is the first reported in human collagen mutation database. As identified,mutation of c.3235G>A may be the major cause of the disease in the proband.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; Child ; Child, Preschool ; China ; Collagen Type I ; genetics ; Exons ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Osteogenesis Imperfecta ; genetics ; Pedigree ; Point Mutation