Trimethylamine-N-oxide (TMAO),metabolites of the intestinal microflora,is a newly discovered risk factor for cardiovascular disease.The intestinal flora converted choline and L-carnitine into trimethylamine in the food.Trimethylamine is oxidized to TMAO in liver enzymes.Lowering TMA can stimulate macrophages to reverse cholesterol transport and inhibit atherogenesis.TMAO poietin-monooxygenase 3 (FMO3) is a tool for cholesterol metabolism and reverse cholesterol transpor,lowering FMO3 can slow the gallbladder's secretion of bile,delay intestinal absorption of cholesterol,and limit the synthesis of oxidized cholesterol and cholesterol esters.TMAO in the blood can up regulate scavenger receptors in macrophages,and promote accumulation of cholesterol and formation of foam cells in macrophages,thereby promoting vascular plaque formation and promote the inflammatory response by MAPK and nuclear factor kappa B pathway.TMAO concentrates on affecting cholesterol metabolism,increasing insulin resistance,promoting platelet aggregation,increasing thrombosis,promoting vascular inflammatory response and directly leading to the formation of atherosclerotic plaques.Lowering TMAO levels can potentially prevent or treat atherosclerotic related diseases and reduce the incidence of cardiovascular and cerebrovascular diseases.The intestinal flora of the TMA/FMO3/TMAO pathway is the major pathway regulating lipid metabolism and inflammation.

BACKGROUND: Ghildren refractory clubfoot includes idiopathic multiple contracture, untreated idiopathic clubfoot in older children and failure cases of repeated operations. It is very difficult to treat this type of children patients. It has important significance in the exploration of new therapeutic methods.OBJECTIVE: To improve the therapeutic effectiveness of refractory clubfoot in children with Ilizarov method.DESIGN: a self-controlled study.SETTING: Department of Orthopedics, Nanjing Children' s Hospital, Nanjing Medical University.PARTICIPANTS: Totally 3 cases of children idiopathic multiple contracture, 2 cases of idiopathic clubfoot in children aged more than 10 years old without treatment and 6 cases of postoperative recurrent idiopathic clubfoot were admitted by the Department of Orthopedics of Nanjing Children' s Hospital Affiliated to Nanjing Medical University during 1999 to 2000. All cases manifested abnormal ankylosis and shortening deformity in foot.METHODS: Twelve refractory clubfeet in eleven patients were treated with the Ilizarov method. After achilles tendon lengthening and posterior release,kieschner' wires or olive wires with tension were penetrated through multiple planes of the middle lower 1/3 of tibia, calcaneus and the 1st to the 5th metatarsals, which were fixed respectively to external bone fixer of a ring,half-ring or horseshoe shape and connected with each other by multiple screw bars into a three-dimensional external bone fixing set. Plantarflexion, inversion, adduction and shortening deformities were corrected by the adjustment of the distance between each part of the external bone fixing set through extension, compression, and rotation, etc., and navicular and cuboid osteotomy.MAIN OUTCOME MEASURES: All 11 cases were followed up for 2 to 10 years with an average period of 4. 5 years. Indices like foot morphology,talocrural articualr activity range and deformity correction were observed during the follow up.RESULTS: The results were excellent in 5 cases (6 feet), good in 4 cases (4 feet), fair 2 cases(2 feet) according to the Garceau standard scale. The rate of excellent and good clinical results was 83.3%. Mild forefoot adduction was left in 2 feet of 2 cases and quite obvious tarsal articular ankylosis was found in 4 feet of 4 cases; however, there were no significant differences of gait and load bearing between these patients and normal children.CONCLUSION: The Ilizarov technique is a safe and effective method for the treatment of refractory children clubfoot while its indications should be controlled strictly.

Objective To study the clinical features of acute limited neck motion in children and its differential diagnosis, and to improve doctors' awareness and the early diagnosis of the disease.Methods A total of 420 patients with acute limited neck motion as the chief complaint and atlantoaxial rotary subluxation as the first diagnosis between January 2005 and January 2014 in Nanjing Children's Hospital Affiliated to Nanjing Medical University were enrolled.The clinical manifestations, imaging and consultation data of the 420 patients were retrospectively analyzed.Results There were totally 248 male patients and 172 female patients.The ages ranged from 2 to 14 years old(the mean age was 7.2 years old) ,the course ranged from 2 hours to 2 days.Among 420 patients,353 patients were diagnosed as atlantoaxial rotatory subluxation.Forty-two patients were diagnosed as cervical intervertebral disc calcification.Seven patients were diagnosed as Tourette syndrome.Four patients were diagnosed as intracranial tumors.Three patients were diagnosed as cervical eosinophilic granuloma.Two patients were diagnosed as cervical spinal tuberculosis.Two patients were diagnosed as viral encephalitis.Two patients were diagnosed as benign paroxysmal torticollis.Two patients were diagnosed as Kawasaki disease.One patient was diagnosed as neuroblastoma.One patient was diagnosed as hemophilia A.One patient was diagnosed as drug adverse reaction of metoclopramide.According to Fielding clinical classification,204 patients were type Ⅰ, 122 patients were type Ⅱ,21 patients were type Ⅲ, and 6 patients were type Ⅳ.Conclusions Based on disease distribution of acute limited neck motion in children, atlantoaxial rotatory subluxation seems to be the predominant while non-atlantoaxial rotatory subluxation is not uncommon.Differential diagnoses should be considered to avoid misdiagnosis.For atlantoaxial rotatory subluxation, conservative treatment including continuous mandible occipital belt traction and brace has been proved to be very effective methods.

Objective To investigate the curative effect and feasibility of closed reduction with elastic intramedullary nailing and open reduction with Kirschner wire fixation in treatment of obviously displaced radial neck fractures in children. Methods From July 2006 to December 2007, 18 children with types Ⅱ and Ⅲ O' Brien radical neck fractures were admitted to Nanjing Children' s Hospital. Of all, six children received open reduction and fixation with Kirschner wire and six weeks of cast immobilization; the other 12 children received closed reduction and fixation with elastic intramedullary nail and three weeks of cast immobilization. The children were followed up for mean 12 months to investigate postoperative functional recovery of the elbow joint and presence of complications. Results All children achieved excellent clinical outcomes, without excessive radial bone growth, early closure of radial bone marrow, bone bridge formation or ectopic calcification around the joint. According to Tibone and Stoltz' s clinical evaluation methods, closed reduction with elastic intramedullary nailing had less trauma, faster recovery, fewer complications and better cosmesis than traditional open reduction with Kirschner wire fixation for children with obviously displaced radial neck fractures. Conclusion Closed reduction with elastic intramedullary nailing is a better option for obviously displaced radial neck fractures in children.

Objective:To evaluate the clinical efficacy of multi-disciplinary single center's CCCG-HB-2016 regimen in the treatment of hepatoblastoma (HB) in children.Methods:Clinical data of 36 HB patients treated with CCCG-HB-2016 program from Aug 2016 to March 2020 were analyzed.Results:These 36 patients included 20 boys and 16 girls. The serum AFP was all higher than 2 792 ng/ml,there was a correlation between AFP and tumor risk stratification ( H=14.973, P<0.05). Twenty eight cases (77.78%) were epithelial type and 8 cases (22.22%) were mixed epithelial mesenchymal type.All children were treated by tumor resection combined with chemotherapy, and there was a correlation between tumor risk stratification and surgical resection of liver lobe ( H=8.847, P<0.05). The probability of bone marrow suppression in the low-risk group was 58.33% (35/60),that in the intermediate-risk group was 73.49% (61/83) and in the high-risk group was 80.23% (69/86).All 36 cases were followed up to March 31, 2020,with an average follow-up of 21.9 months and the median survival was 22.5 months.The overall survival rate (OS) and event-free survival rate (EFS) were 97.2% and 83.3% respectively. Conclusions:The multidisciplinary CCCG-HB-2016 regimen was with a high success rate and along with a high incidence of bone marrow suppression.

Objective:To explore the outcomes of T?nnis triple osteotomy for developmental dysplasia of the hip (DDH) in older children.Methods:Clinical data of 21 children (22 hips, 12 left and 10 right hips) treated by T?nnis triple osteotomy from October 2016 to June 2019 were retrospectively analyzed.There were 8 males and 13 females with a mean age of operation at 13.5 (8.6-16.8) years.Based on the T?nnis classification, all the cases were in Grade Ⅰ.Statistical analysis was performed using the SPSS 22.0 statistical software.Results:All recruited patients were followed up for 1.5-3.5 years.Compared with preoperative values and those at the last follow-up visit, the mean Sharp acetabular angle of the affected side recovered from 53.5°±5.2° to 40.8°±2.3°.The mean center-edge angle increased from 10.5°±2.9° to 35.4°±5.6°.The mean acetabular roof angle decreased from 38.6°±2.8° to 6.7°±1.3°.The mean acetabular head index enhanced from (54.3±5.2)% to (86.2±2.7)%.The differences between the preoperative and postoperative values were statistically significant ( t=24.3, 17.6, 50.1, 27.5; all P<0.05). According to the Harris classification, there were 17, 3 and 2 hips achieved excellent, good and fair outcomes at the last follow-up visit, respectively, with the percentage of excellent and good outcomes up to 90.9%(20/22 hips). Accor-ding to the Severin radiographic classification, 8, 12 and 2 hips were in grade Ⅰ, Ⅱ, and Ⅲ, respectively, with the percentage of excellent and good hips at 90.9%(20/22 hips). At the last follow-up visit, the bone healing of iliac and pubic bones was well, and the nonunion of ischial bones were reported in 3 cases (13.6%). Conclusion:The outcome of the T?nnis triple osteotomy is satisfactory for DDH in older children.

Objective:To analyze the curative effect of locking compression pediatric hip plate (LCH-PHP) in the treatment tumor-like lesions of femoral neck in children.Methods:From January 2012 to June 2019, 45 children with Erol type Ⅱ-Ⅳ tumor-like lesions of femoral neck were retrospectively analyzed, involving 32 males and 13 females, aged 2-14 years.Among them, 27 cases were simple bone cyst, 15 cases were fibrous dysplasia, 3 cases were Langerhans histiocytosis, and 17 cases were accompanied with pathological fracture.Patients without pathological fracture were divided into 2 groups according to different surgical methods: lesion removal and bone grafting+ LCH-PHP preventive fixation group (group A) and lesion removal and bone grafting group (group B). Patients with pathological fracture were divided into 2 groups according to the different surgical methods: lesion removal and bone grafting+ LCH-PHP fixation and reduction group (group C) and lesion removal and bone grafting group (group D). The loss of femoral neck-stem angle, healing time and Musculoskeletal Tumor Society (MSTS) scores were compared between group A and group B. Changes of femoral neck-stem angle were compared between group C and group D at postoperative 1 day and the last follow-up.Results:Forty-five patients were followed up for an average of 2.6 (1-4) years.The loss of femoral neck-stem angle in group A and group B were (0.50 ± 0.45)°, and (2.26 ± 1.64)°, which was significantly different ( t=-3.193, P<0.05). There were no significant differences in the healing condition, healing time and MSTS scores at the last follow-up between group A and group B(all P>0.05). In group C, the ipsilateral femoral neck-stem angle at the postoperative 1 day and the last follow-up were (133.67±4.53)°and (133.00±4.32)°, respectively, which was comparable ( P>0.05). In group D, the ipsilateral femoral neck-stem angle at the postoperative 1 day and the last follow-up were (133.36±7.82)°and (130.63±8.24)°, respectively, which was significantly different ( t=7.11, P<0.05). Conclusions:LCH-PHP fixation can effectively maintain the femoral neck-stem angle and prevent the occurrence of pathological fracture children with Erol Ⅱ-Ⅳ tumor-like lesions of femoral neck.

Objective: To summarize the clinical data of elastic stable intramedullary nailing(ESIN) in the treatment of long bone fracture of children in a single medical center, and to analyze the problems occurred after the ESIN surgery and corresponding solutions. Methods: A retrospective analysis was conducted regarding the clinical data of 2 133 pediatric long bone fractures conforming to inclusion and exclusion criteria from June, 2005 to December, 2017 in Department of Orthopedics, Children′s Hospital of Nanjing Medical University.There were 1 191 boys and 942 girls, aged from 23 months to 14 years with mean age of (5.7 ± 3.1)years.There were 1 866 cases treated with closed reduction with ESIN, while 267 cases were treated with small incision assisted reduction with ESIN.Postoperative problems have been statistically analyzed. Results: There were altogether 2 133 children, including 603 cases of femur, 311 cases of tibia, 8 cases of fibula, 219 cases of humerus, and 992 cases of ulna/radius.The postoperative complications mainly consist of 62 cases of needle tail irritation reaction, 21 cases of misalignments of fracture alignment, 11 cases of intramedullary nail deformity or angular deformity, 7 cases of limb shortening, 14 cases of limited joint activity, 4 cases of nerve injury, 2 cases of tendon injury, 14 cases of difficult nail removal, 4 cases of cortical cleavage, 8 cases of delayed union, 1 case of nonunion, 6 cases of varus/valgus deformity, 5 cases of epiphyseal injury, 6 cases of ESIN exposure, and 2 cases of metal debris of ESIN′ end. Conclusions The complications of treatment for children with long bone fractures by ESIN cannot be ignored.To master the important biomechanical properties, to get familiar with the local anatomy and to avoid obvious technical errors can reduce the occurrence of postoperative complications.

Objective:To assess the clinical effect of retrograde elastic stable intramedullary nailing(ESIN) in distal humerus metaphysis-diaphyseal junction fractures in children.Methods:A total of 14 cases of children with distal humerus metaphysis-diaphyseal junction fractures treated by retrograde ESIN in Children′s Hospital of Nanjing Medical University from January 2016 to December 2018 were retrospectively analyzed.There were 9 males and 5 females, aged 3.0-13.2 years old(median: 6.4 years old). Nine cases had fractures on the left side and 5 cases on the right side.Two prebent ESINs were inserted into the proximal humerus metaphysis through the humerus marrow cavity from medial and lateral sides of the distal humerus respectively after the closed/open reduction of fractures.After surgery, the shoulder abductor stent or long arm plaster was used for fixation post-operatively.X - ray examination was performed at regular post-operative follow-up.The stability of internal fixation was analyzed by measuring the Baumann angle and checking whether humeral anterior lines passed through capitulum humeri in lateral radiographs immediately after the surgery and at the last follow-up.Meanwhile, efficacy was evaluated according to Flynn functional evaluation criteria.Results:All the 14 patients in this group were followed up for 10-27 months after the operation, with an average of 18.4 months.The Baumann angle was within the normal range at both the end of the operation and the last follow-up, and no significant difference was observed.Lateral radiographs showed humeral anterior lines passed through the capitulum humeri.According to Flynn functional scores, there were 13 excellent cases and 1 good case.No wound infection, intramedullary nailing displacement, Volkmann contracture, cubital varus deformity, or iatrogenic nerve injury occurred in any of the children.Conclusion:Retrograde ESIN technique is a safe and reliable treatment for children with distal humerus metaphysis-diaphyseal junction fractures.

Objective To compare the clinical efficacy of three internal fixation techniques,namely K-wire,hollow screw and pediatric hip locking compression plate (LCP),for treating displaced femoral neck fractures in children.Methods The clinical data of 56 patients treated from January 2010 to August 2015 were retrospectively analyzed by case-control study.All the patients received open reduction after unsuccessful closed reduction.According to the methods of internal fixation,the patients were divided into K-wire group (18 cases),hollow screw group (21 cases) and LCP group (17 cases).Operation time,intraoperative blood loss,neck-shaft reduction,bone union time,and complications after surgery were recorded.Ratliff and Harris scores at final follow-up visit were evaluated.Results In K-wire group,hollow screw group and LCP group,the operation times were respective(74.2 ± 12.9) min,(90.2 ± 18.9) min and (125.1 ± 20.6) min,the intraoperative blood loss of the three groups were respective (27.3 ± 15.4) ml,(32.4 ± 18.7) ml and (57.7 ± 22.1) ml,and the neck shaft reduction of the three groups were respective (3.74 ± 0.80) °,(2.96 ± 0.74) ° and (1.22 ± 0.39) °.K-wire group were superior to other two groups in operation time and intraoperative blood loss,and PHP group were better than the other two groups in prevention of neck-shaft reduction(P ＜ 0.05).There was one case in K-wire group with bone nonunion combined with hip varus.In K-wire group,hollow screw group and LCP group,the avascular necrosis were 11％,14％ and 12％,respectively (P ＞ 0.05).There were no statistically significant differences in follow-up time,bone union time,and Ratliff as well as Harris scores among the three groups (P ＞ 0.05).The case of epiphyseal premature closure,iatrogenic injury of blood vessel and nerve as well as osteo-fascial compartment syndrome was not observed after surgery.None of the patients had epiphyseal close,neurovascular injury and osteofacial compartment syndrome.Conclusions All three internal fixation techniques can have good clinical results in children with displaced femoral neck fractures after unsuccessful closed reduction.K-wire has advantages of less blood loss,shorter operation time and easier handling.Hollow screw has no obvious advantages or disadvantages in intraoperative situation and postoperative complications.Pediatric hip LCP can reduce the loss of neck-shaft angle and decrease the occurrence of hip varus.