A novel compound heterozygous variation in the FKBP10 gene causes Bruck syndrome without congenital contractures: A case report.

Background: Bruck syndrome (BS) is an extremely rare autosomal-recessive connective tissue disorder mainly characterized by bone fragility, congenital joint contracture, and spinal deformity. It is also considered as a rare form of osteogenesis imperfecta (OI) due to features of osteopenia and fragility fractures. Its two forms, BS1 and BS2, are caused by pathogenic variations in FKBP10 and PLOD2, respectively. Objective: We aimed to improve the clinical understanding of BS by presenting a case from China and to identify the genetic variants that led to this case. Methods: OI was suspected in a Chinese boy with a history of recurrent long bone fractures, lumbar kyphosis, and dentinogenesis imperfecta (DI). Whole-exome sequencing (WES) was performed to identify pathogenic variations. Sanger sequencing was used to confirm the results of the WES. In silico analysis was used to predict the pathogenicity of genetic variants. Results: WES and Sanger sequencing revealed a compound heterozygous variation in the FKBP10 gene (NM_021939, c.23dupG in exon 1, and c.825dupC in exon 5). Both variants resulted in a frameshift and premature stop codon. Of these two variants, c.23dupG has not been previously reported. The patient's parents were heterozygous carriers of one variant. In addition, zoledronic acid treatment improved the vertebral deformity and bone mineral density (BMD) significantly in this patient. Conclusions: A novel compound heterozygous variation of FKBP10, c.23dupG/c.825dupC, was identified in a patient with moderately severe OI. Based on these findings, the patient was diagnosed with BS1 without congenital joint contractures or OI type XI. This study expands the spectrum of FKBP10 genetic variants that cause BS and OI.

Carpaine alleviates tendinopathy in mice by promoting the ubiquitin-proteasomal degradation of p65 via targeting the E3 ubiquitin ligase LRSAM1.

BACKGROUND: Currently, there are no specific drugs or targets available for the treatment of tendinopathy. However, inflammation has recently been found to play a pivotal role in tendinopathy progression, thereby identifying it as a potential therapeutic target. Carpaine (CA) exhibits potential anti-inflammatory pharmacological properties and may offer a therapeutic option for tendinopathy. PURPOSE: This study aimed to investigate the effectiveness of CA in addressing tendinopathy and uncovering its underlying mechanisms. METHODS: Herein, the efficacy of CA by local administration in vivo in comparison to the first-line drug indomethacin was evaluated in a mouse collagenase-induced tendinopathy (CIT) model. Furthermore, IL-1ß induced a simulated pathological inflammatory microenvironment in tenocytes to investigate its underlying mechanisms in vitro. Further confirmation experiments were performed by overexpressing or knocking down the selective targets of CA in vivo. RESULTS: The findings demonstrated that CA was dose-dependent in treating tendinopathy and that the high-dose group outperformed the first-line drug indomethacin. Mechanistically, CA selectively bound to and enhanced the activity of the E3 ubiquitin ligase LRSAM1 in tendinopathy. This effect mediated the ubiquitination of p65 at lysine 93, subsequently promoting its proteasomal degradation. As a result, the NF-κB pathway was inactivated, leading to a reduction in inflammation of tendinopathy. Consequently, CA effectively mitigated the progression of tendinopathy. Moreover, the LRSAM1 overexpression demonstrated effectiveness in mitigating the tendinopathy progression and its knockdown abolished the therapeutic effects of CA. CONCLUSION: CA attenuates the progression of tendinopathy by promoting the ubiquitin-proteasomal degradation of p65 via increasing the enzyme activity of LRSAM1. The exploration of LRSAM1 has also unveiled a new potential target for treating tendinopathy based on the ubiquitin-proteasomal pathway.

[Analysis of a case of Multiple pterygium syndrome due to a novel variant of CHRNG gene].

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with multiple pterygium syndrome (MPS). METHODS: A child with MPS who was treated at the Orthopedics Department of Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University on August 19, 2020 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were also collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing of her parents and bioinformatic analysis. RESULTS: The child, an 11-year-old female, had a complain of "scoliosis found 8 years before and aggravated with unequal shoulder height for 1 year". WES results revealed that she has carried a homozygous c.55+1G>C splice variant of the CHRNG gene, for which both of her parents were heterozygous carriers. By bioinformatic analysis, the c.55+1G>C variant has not been recorded by the CNKI, Wanfang data knowledge service platform and HGMG databases. Analysis with Multain online software suggested that the amino acid encoded by this site is highly conserved among various species. As predicted with the CRYP-SKIP online software, the probability of activation and skipping of the potential splice site in exon 1 caused by this variant is 0.30 and 0.70, respectively. The child was diagnosed with MPS. CONCLUSION: The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient.

Ulnar osteotomy and monolateral external fixator for the treatment of chronic Monteggia fractures in children: comparison between gradual and acute radial head reduction.

This study evaluated the outcomes of chronic Monteggia fractures (CMFs) treated by ulnar osteotomy and monolateral external fixator (MEF), and compare the outcome of gradual versus acute radial head reduction. Two groups of patients were identified. Group 1: gradual reduction of the radial head ( n = 13); group 2: acute reduction ( n = 6). Clinical outcome was evaluated by Kim Elbow Score, whereas radiographic outcome was assessed on plain radiographs. The effect of age, side, time from initial trauma to surgery, rate of unplanned surgery, amount of angulation and lengthening, and final outcome were evaluated. Univariate analysis was performed to identify factors associated with good radiographic outcome. Thirteen patients underwent gradual correction of the ulna. The mean duration of correction was 43.4 days (range, 21-82); the mean angulation and lengthening of the ulna were 22.8° (range, 0°-35°) and 22.2 mm (range, 12.2-40.9), respectively. Six patients underwent acute reduction intraoperatively, the mean angulation and lengthening of the ulna were 17.2° (range, 4°-33.9°) and 5.2 mm (range, 2.5-12.2), respectively. CMF treated by ulnar osteotomy and gradual distraction had better radiological outcome (Group 1; 92.3% 12/13) than those treated by acute reduction of the radial head (Group 2; 3/6, 50%) ( P = 0.071). Reoperation rate was found to be significantly correlated with a fair or poor radiographic results ( P = 0.016). Good clinical and radiological outcomes should be expected in CMF patients treated by gradual lengthening and angulation of the ulna with a MEF.

Radiographic features of congenital thumb duplication type C2 of Wu et al. classification: new subtypes and surgical strategies.

Objective: This study aimed (i) to evaluate the radiographic characteristics of patients with congenital thumb duplication (CTD) type C2 according to the classification of Wu et al., (ii) to describe the various subtypes of type C2 CTD, and (iii) to propose a classification system that allows the identification of different surgical strategies based on the radiographic anatomy of this specific subtype of duplication. Methods: We retrospectively reviewed 92 patients (92 thumbs) with type C2 CTD according to the Wu et al. classification in our institution between August 2015 and April 2021. All CTDs were classified according to the interphalangeal joint alignment of the main thumb at the posteroanterior radiograph of the thumb before operation: type I (no deviation), type II (ulnar deviation), and type III (radial deviation). Results: All CTDs (n = 92) could be classified according to the proposed classification system: 76 (82.6%) were type I, 10 (10.9%) were type II, and six were type III (6.5%). According to the Kim system of subtype classification, there were 55 (59.8%) type 1, 24 (26.1%) type 2, and 13 (14.1%) type 3 cases. Conclusions: The suggested classification completes the Wu et al. system and has the potential to guide surgical treatment in children with type C2 CTD. Level of evidence: III.

Epidemiological characteristics and distribution of congenital thumb duplication in south China: An analysis of 2,300 thumbs in 2,108 children.

Objective: The objective of this study was to evaluate epidemiological and anatomical characteristics of children with congenital thumb duplication (CTD). Methods: We retrospectively reviewed 2108 children with CTD. Data regarding sex, age at the surgery, laterality, uni- or bilateral involvement, and dominant side were retrieved from the medical charts. Plain radiographs were used to classify all CTD according to Wassel-Flatt, Rotterdam and Chung classification systems and to evaluate the patho-anatomy of the duplication as well as the presence of associated anomaly. Results: A total of 796 girls and 1,312 boys with CTD (n = 2,300 thumbs) met the inclusion criteria. The male to female and unilateral to bilateral ratio were 1.6:1 and 10:1, respectively. Associated anomaly was found in 238/2108 patients (11.3%), and the middle phalanx deformity of the 5th finger was the most common one. A dominant thumb, larger and more developed, was on the ulnar side in 2270/2,300 cases (98.7%).According to the Wassel-Flatt classification, type IV (40.2%) was the most common deformity and the extra thumb was connected to the main thumb by a joint in most cases (437/780); overall, 15.7% of thumbs (n = 360) did not fit the Wassel-Flatt classification.According to the Rotterdam classification, type IV (51.3%) was the most common form; in most cases (363/1180) the thumb was hypoplastic or floating. Overall, 3/2,300 thumbs (0.1%) could not be classified according to Rotterdam classification.According to the Chung classification, type A was the most common subtype (44.1%); in most cases (716/1015) the duplication was at the level of the metacarpal bone. Overall, 2/2,300 thumbs (0.1%) did not fit the Chung classification. Conclusions: In patients from southern China, CTD shows male and right-sided predominance with ulnar-dominant thumb. Abnormalities of the middle phalanx of the 5th finger are more frequent in patients with associated anomaly. The development of a simple and comprehensive classification system is needed to guide treatment and to adequately assess the epidemiological characteristics of patients with CTD in order to facilitate comparison between different patients' populations. Level of evidence: III.

To Angulate or Not to Angulate the Ulna during the Progressive Distraction Period Performed with a Monolateral External Fixator in Paediatric Patients with a Chronic Monteggia Fracture?

Background and Objectives: The purpose of this study was to compare the clinical and radiographic evolution of chronic Monteggia fractures (CMFs) treated by ulnar osteotomy and monolateral external fixators (MEFs) with or without angulation of the ulna during the distraction period. Materials and Methods: This retrospective study evaluated 20 children (14 boys and 6 girls) with CMFs. According to the strategy of ulnar lengthening, two groups of patients were identified: patients undergoing gradual lengthening with (Group A, n = 11) or without ulna angulation (Group B, n = 9). The mean age at the time of surgery was 7.7 years old (range, 5.4−12.9). The mean time from initial trauma to surgery was 26.3 months (range, 1−96), and the mean follow-up was 24.6 months (range, 5.5−45.4). Clinical outcomes were evaluated by Kim et al.'s Elbow Performance Score, while radiographic outcomes were assessed on plain radiographs. Results: Age at surgery, sex, laterality, time between trauma and surgery, and time of follow up in the two groups of patients showed no significant differences. The radial head was successfully reduced in 9 of 9 and 10 of 11 patients in Groups B and A, respectively (p = 1.00). The mean time to achieve radial head reduction was shorter in Group B (18.1 ± 5.3 days) than in Group A (39.2 ± 18.7 days; p = 0.004). The mean angulation of the ulna at the end of treatment was significantly lower in Group B (0.6° ± 1.1°) than in Group A (25.9° ± 6.3°; p < 0.0001). The average ulnar lengthening at the end of treatment in Group B (14.1 ± 5.8 mm) was, on average, 7.7 mm less than that in Group A (21.8 ± 9.7 mm; p = 0.05). The Kim et al. Elbow Performance Score at the last follow-up visit was comparable between the two groups of patients (p = 1.00). Conclusions: A shorter time to achieve radial head reduction and less deformity of the ulna can be expected in paediatric patients with CMFs undergoing intraoperative restoration of ulnar alignment and gradual lengthening without angulation postoperatively.

Identification of a novel TBX5 mutation in a Chinese family with rare symptoms of Holt-Oram syndrome.

Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder characterized by skeletal abnormalities of the upper limbs and often cardiac malformations. We investigated a Chinese family with clinical features suggestive of HOS. Clinical examinations revealed that both the proband and his father had anomalies in the upper limbs and heart. The proband had a rare common atrium. Whole exome sequencing detected a novel small-insertion mutation (c.680_681insCTGAGAATAAT; p.Ile227fs∗) in TBX5 gene, the known disease gene for HOS. The mutation cosegregated with HOS phenotypes in the family and was predicted to cause frameshift, resulting in a truncated protein. In this study, we described a rare HOS case with common atrium. A novel small-insertion in TBX5 coding sequence was identified and speculated to be the disease-causing genetic variant in the family. Our finding expands the clinical feature spectrum and genetic aetiology spectrum of HOS.

Modified Radiographic Classification System for Congenital Thumb Duplication: An Analysis of 2,300 Thumbs in 2,108 Children.

PURPOSE: The objectives of this study were to (1) evaluate the radiographic characteristics of children with congenital thumb duplication (CTD) seen in our institution between August 2015 and April 2021; (2) introduce a modified radiographic classification system (MCS) capable of including all cases of CTD based on their radiographic pathoanatomy; and (3) evaluate the inter- and intrarater reliability of the new classification system. METHODS: We retrospectively reviewed 2,108 patients with 2,300 CTDs. The MCS is based on the Wassel-Flatt and Chung et al classification systems and includes specific subtypes from the Rotterdam and modified Wassel-Flatt classifications. The MCS is characterized by 4 groups according to the anatomical morphology of the duplication: A (joint), B (epiphysis), C (bone), and D (soft tissues). Each group includes 4 subtypes according to the location of the CTD, with subtypes 1-3 extending from the distal phalanx to the metacarpal or interphalangeal joints, then to the carpometacarpal joint, and with subtype 4 only including the triphalangia of the main thumb. RESULTS: Among the 2,300 fingers, 360 (15.7%), 2 (0.1%), and 3 (0.1%) CTDs could not be classified according to the Wassel-Flatt, Chung et al, and Rotterdam classifications, respectively. According to the MCS, the 2 most common forms of CTD were A2 (680/2,300; 29.6%) and D2 (308/2,300; 13.4%). All cases could be classified according to this classification system. The MCS showed excellent intrarater (0.875) and interrater (0.851) reliability relative to the Wassel-Flatt (0.863 and 0.820, respectively), Chung et al (0.793 and 0.822, respectively), and Rotterdam (0.873 and 0.836, respectively) systems. CONCLUSIONS: The MCS is a potential radiographic classification for CTD that enables the classification of all patients and has excellent inter- and intrarater reliability. CLINICAL RELEVANCE: Existing classification systems do not allow classification of the full spectrum of CTD and are not always related to surgery, and some existing systems are complex, with many categories that are rarely encountered, or are difficult to use widely in clinical practice.

Closed reduction and percutaneous pinning versus open reduction and internal fixation for Jakob type 3 lateral condyle fractures in children.

PURPOSE: The management of type 3 lateral condyle fractures (LCFs) remains controversial. The main goal of this study was to evaluate the feasibility of closed reduction and percutaneous pinning (CRPP) in patients with type 3 LCFs and to assess the outcome of such injuries according to the type of treatment, CRPP, or open reduction and internal fixation (ORIF). METHODS: This is a retrospective review of prospectively enrolled children with type 3 LCF managed by CRPP or ORIF between 2018 and 2021. All patients were followed for at least 12 months. Patients were divided into two groups according to the type of treatment, CRPP or ORIF. Demographic characteristics were recorded for all patients. Standard radiographs were used to identify, evaluate, and classify each fracture and to detect the presence of other concomitant bone lesions. The clinical outcome was assessed according to the Hardacre et al. criteria. RESULTS: Seventy-eight children with type 3 LCF were included; 42 were treated by CRPP (53.8%) and 36 by ORIF (46.2%); the mean follow-up time was 17.7 months (range, 12.3-40.9). The baseline characteristics did not differ between the two groups of patients. Overall, successful CRPP could be achieved in 39 out of 42 patients (92.9%). The mean surgical time was 63.4 and 84.5 min in patients treated by CRPP and ORIF, respectively (p = 0.01). Fluoroscopy time was significantly shorter in patients managed by ORIF than in those treated by CRPP (12 versus 40 s, respectively; p < 0.001). Clinical outcome according to the Hardacre et al. criteria was excellent in 37 out of 39 (94.4%) and in 35 out of 36 patients (97.2%) treated by CRPP and ORIF, respectively (p = 0.09). CONCLUSIONS: CRPP management of paediatric type 3 LCF has clinical and radiographic outcomes similar to ORIF; if satisfactory reduction cannot be achieved by CRPP, conversion to ORIF should be considered.

Effects of posterior hemivertebra resection and short segment fusion on the evolution of sagittal balance in children with congenital scoliosis.

There is a paucity of data describing sagittal alignment changes in children with congenital scoliosis (CS) treated by hemivertebra (HV) resection. This study aimed to evaluate the effects of posterior HV resection on spine sagittal alignment in children with CS. This is a retrospective analysis of 31 children with CS (mean age at surgery: 49.61 ± 10.21 months; range, 39-72; mean follow-up time: 5.16 ± 1.21 years; range: 3-7) treated at our Institution. Only patients with single thoracic or single lumbar, fully segmented HV managed by posterior HV resection and two segments fusion with four screws and two robs were included. According to the anatomical location of the HV, patients were divided into two groups: thoracic (group A) and lumbar (group B). Thoracic kyphosis (T1-T12; TK) and lumbar lordosis (L1-S1; LL) were measured pre- and postoperatively at 6 months interval. Postoperative TK and LL were 30.3 ± 11.47 and 28.8 ± 9.47, and were 31.98 ± 9.66 and 46.7 ± 11.37 at the last follow-up visit, respectively. The incidence of thoracic hypokyphosis in group B was 53.3%, and it was significantly higher compared to group A (12.5%, P = 0.04). During follow-up, TK changes were comparable between the two groups of patients while LL improved in all patients 6 months after surgery, and continued to improve thereafter. Posterior HV resection and short segment fusion have limited impact on the evolution of TK; in particular, children with lumbar HV were more likely to be hypokyphotic preoperatively, but less likely postoperatively with an increase in LL and a stabilization of TK.

A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate.

Hereditary multiple exostoses (HME) is a rare skeletal disorder characterized by the formation of multiple benign cartilage-capped tumors, usually in the metaphyseal region of the long bones. Over 70% of HME cases arise from monoallelic mutations in either of the two genes encoding the heparan sulfate (HS) synthesis enzymes, ext1 and ext2. To identify more HME-associated mutations, genomic DNA from members of five independent consanguineous families with HME was sequenced with whole exome sequencing (WES). A novel heterozygous splice site mutation (c.1173+2T>A) in ext2 was detected in all three affected members of family V. Further study showed that the novel mutation caused exon 7 of ext2 mRNA to be skipped during splicing and caused a frameshift after the codon for Arg360, which results in the appearance of new 43 codons, followed by a termination codon. Although the resulting truncated protein was still localized to the Golgi, similar to the full-length EXT2, its HS synthesis activity decreased by 40%. In this study, a novel splice site mutation in ext2 was identified and suggested to be a pathogenic mutation of HME, which may expand the genetic etiology spectrum of HME and may be helpful for clinical genetic counseling and prenatal diagnosis.

Expression and significance of related genes in the early stage of post-traumatic heterotopic ossification in a rat model of Achilles tenotomy.

OBJECTIVE: This study aims to determine expression profiles of relevant genes in the early stages of post-traumatic heterotopic ossification (HO) in a rat model of Achilles tenotomy. METHODS: A total of 80 male Sprague-Dawley rats were randomly assigned to two groups: the HO group and the control group. Tenotomy was performed in the Achilles tendon of the rats in the HO group, and no intervention was conducted in the control group. On the 3rd, 5th, 8th, and 14th days after the operation, 8 rats were taken from each group at each time point, and the Achilles tendon and surrounding tissue specimens were collected. Gene expressions of TGF-ß, BMP, GDF, IL, and MMP families as well as TNF-α, HIF-1α chordin, gremlin, noggin, and NODAL were analyzed by qRT-PCR. The relevant genes that were highly expressed at different time points were screened, and immunohistochemical staining was then used to verify their expression. At the 10th week, HO formation was explored by radiographic and histological examination in the remaining 8 rats of each group. RESULTS: Both the radiographic and histological analyses indicated that all the rats developed HO in the HO group (100%), whereas no HO occurred in the control group. Surrounding tissues obtained from the HO group showed significantly higher gene expressions of TGF-ß1, BMP-1, IL1ß, HIF-1α, and MMP-2 but lower expressions of BMP-4, GDF-8, and TNF-α compared with the control group. In addition, immunohistochemical staining confirmed the higher protein expression levels of relevant genes in the HO group. CONCLUSION: TGF-ß1, BMP-1, IL-1ß, HIF-1α, MMP-2, BMP4, GDF-8, and TNF-α may be associated with the formation of traumatic HO; and BMP4, GDF-8, and TNF-α may play a protective role in the early stage of HO. In this study, we investigated the expression levels of the related cytokines in the early stages of traumatic HO in the Achilles tendon tenotomy rat model to better understand the pathogenesis of HO.

Inhibition of Nf-ҝb prevents trauma-induced heterotopic ossification in rat model.

PURPOSE: To investigate the pathogenesis and find a better prophylactic method of acquired heterotopic ossification (HO). MATERIALS AND METHODS: In the first part, we designed the brain-traumatic/burn/tenotomy rat model and testified its efficacy as HO model. 44 rats were randomly divided into experimental group and control group. After operation, the bilateral tendons of 2 rats were collected at the 2nd, 3rd, 4th, 6th, 8th, and 10th weeks to determine the expression levels of p65. Additionally, the remaining rats were exposed to X-Ray examination at the 10th week. In the second part, 124 rats were randomly divided into four groups based on the administration dosage of Ammonium pyrrolidinedithiocarbamate (PDTC). Then, three rats of each group were euthanized every week in the first seven weeks to collect tendon to detect the expression levels of p65 by qRT-PCR and Western Blot. The remaining rats were exposed to X-Ray examination at the 10th week to assess the size of HO before being euthanized for HE staining. RESULTS: The success rate of Brain-traumatic/Burn/Tenotomy model was 100%. Pharmacologic inhibition of Nf-ҝb signaling pathway by PDTC could significantly reduce the expression levels of p53 and the size of HO, and the reduction was most significant in the 0.6mg dosage group. CONCLUSIONS: Brain-traumatic/Burn/Tenotomy model was highly reliable HO model. Inhibition of Nf-ҝb signaling pathway by PDTC could significantly reduce HO formation, and the most effective concentration was 6 mg/ml for local injection.

Dynamics of MMP­9, MMP­2 and TIMP­1 in a rat model of brain injury combined with traumatic heterotopic ossification.

The present study aimed to detect early changes in the concentration of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase­2 (MMP­2) and tissue inhibitor of metalloproteinase­1 (TIMP­1) in a rat model of brain injury combined with traumatic heterotopic ossification (HO). A total of 132 male Sprague­Dawley rats were used to establish the experimental and control groups. Anatomy and sample collection were conducted on postoperative days 1, 2, 3, 4, 5, 6 and 7. Hematoxylin and eosin and immunohistochemical staining were performed for local tissues. MMP­9, MMP­2 and TIMP­1 levels and gene expression level were measured by ELISA and reverse transcription­quantitative polymerase chain reaction. Radiological investigation of the rat lower limbs was conducted at weeks 5 and 10 following modeling to observe the occurrence of HO. The incidence of HO for rats in the experimental group was higher compared with the control group. The serum MMP­9 levels of the experimental group were notably higher on postoperative days 5­7 compared with the control group. The MMP­9 gene expression of the experimental group was higher on postoperative days 3­7 compared with the control group. The TIMP­1 gene expression levels were markedly higher compared with the control group at each time point. Thus, an increase in inflammatory response is closely associated with brain injury, in addition to an increase in the number of inflammatory cells with the incidence of HO. The pathological elevation of MMP­9 and the altered dynamic equilibrium between MMP­9 and TIMP­1 contributed to the degradation, remodeling and calcification of the extracellular matrix, resulting in the induction of osteoblast precursor cells in HO. MMP­9 is a predictive marker of HO.

[EFFECTIVENESS OF SURGICAL TREATMENT FOR SENILE CHRONIC SHOULDER DISLOCATION].

OBJECTIVE: To investigate the surgical treatment and effectiveness of senile chronic shoulder dislocation. METHODS: Between October 2011 and April 2014, 7 elderly patients with chronic shoulder dislocation were treated. There were 2 males and 5 females with an average age of 74 years (range, 61-83 years). The causes of injuries were falling injury in 6 patients and traffic accident injury in 1 patient. The interval between injury and confirmed diagnosis was 4-12 weeks (mean, 6.7 weeks). Preoperative apprehension test and Dugas sign of the shoulder joint were positive. Before operation, the forward elevation, abduction, and external rotation were (50.7±8.4), (44.5±3.3), and (35.8±4.8), respectively; and internal rotation reached T6, T11, L4 in 1 case and reached T10, T12 in 2 cases separately. The Constant-Murley score and Neer score were 51.2±8.3 and 45.4±7.3, respectively. RESULTS: All the incisions healed by first intention, and no complication of fracture or neurovascular injuries occurred. Seven patients were followed up 12-18 months (mean, 16 months), and no re-dislocation happened. At last follow-up, apprehension test and Dugas sign of the shoulder joint were negative. The forward elevation, abduction, and external rotation were significantly improved to (117.5±13.1), (72.0±4.6), and (39.0±3.4)° (t= -33.746, P=0.000; t= -30.614, P=0.000; t= -2.802, P=0.031); and internal rotation reached T6, T10, T12, and L3 in 1 case respectively, and L3 in 3 cases, showing no significant difference when compared with preoperative values (Z= -1.732, P=0.083). The Constant-Murley score and Neer score were significantly improved to 85.4±4.3 and 84.0±4.8 when compared with preoperative score (t= -21.016, P=0.000; t= -29.518, P=0.000). CONCLUSION: Surgical treatment of senile chronic shoulder dislocation can improve the range of motion and function of the shoulder joint obviously.

[Dynamic changes of matrix metalloproteinase 9 in heterotopic ossification of rat model].

OBJECTIVE: To explore the value of matrix metalloproteinase 9 (MMP-9) in predicting the occurrence of heterotopic ossification by observing the expression of MMP-9 in heterotopic ossification of the early trauma rat model. METHODS: A total of 132 male Sprague Dawley rats, aged 4-5 weeks, weighing (135.0 ± 6.5) g, were randomly divided into experimental group and control group (n = 66). In experimental group, the Achilles tendon was cut off and clamped to prepare heterotopic ossification model; in control group, only Achilles tendon was exposed by making a incision. The general condition of the rats was observed after operation; at 2, 3, 4, 5, 6, 7, and 8 days after operation, the Achilles tendon tissue was harvested for gross observation, histological observation, and immunohistochemical staining observation; the serum and Achilles tendon tissue were harvested to detect the expressions of MMP-9 protein and mRNA by ELISA and RT-PCR. The X-ray films at 5 and 10 weeks and histological examination at 10 weeks after operation were used to observe heterotopic ossification. RESULTS: All rats survived to the end of the experiment. The Achilles tendon had no significant change in control group at each time point, showing normal tendon structure. In experimental group, the hardness of Achilles tendon tissue gradually increased with the time; there were a large number of irregular connective tissue and cartilage cells; and immunohistochemical staining for MMP-9 was positive results. The MMP-9 protein and mRNA expression levels of experimental group were significantly higher than those of the control group at each time point (P < 0.05). MMP-9 protein and mRNA expression levels of experimental group showed an increasing tendency (P < 0.05). According to the results of X-ray films and histological observation, heterotopic ossification occurred at 10 weeks after operation in experimental group, but no heterotopic ossification was observed in control group. CONCLUSION: In early heterotopic ossification of rat Achilles tendon, the expression of MMP-9 increases significantly, indicating that it has reference significance in predicting heterotopic ossification.

[Effects of selective and non-selective cyclooxygenase 2 inhibitors on heterotopic ossification in rat model with Achilles tenotomy].

OBJECTIVE: To compare the efficacy of selective cyclooxygenase 2 (COX2) inhibitor and non-selective COX2 inhibitor drugs in prevention of heterotopic ossification in rats model so as to provide reference for clinical drugs selection of heterotopic ossification prevention. METHODS: Fifty male Sprague Dawley rats, 6 to 8 weeks old, weight (190.0 +/- 8.5) g, were selected; the right Achilles tendon was cut off to induce ectopic bone formation. The rats were randomly divided into 5 groups (n = 10): on the 1st day after modeling, celecoxib was given in groups A [2 mg/(kg x d)] and B [10 mg/(kg x d)], indomethacin in groups C [(2 mg/(kg x d) and D [10 mg/(kg x d)], and 2 mL of saline in group E for 10 weeks. The general condition of rats was observed after operation. At 5 and 10 weeks after operation, X-ray films of the right lower limb were taken to observe new bone formation. At 10 weeks after operation, the right Achilles tendon tissue was harvested for histological observation. Based on X-ray and histological results, heterotopic ossification was assessed. Immunohistochemical staining was used to evaluate COX2 and bone morphogenetic protein 2 (BMP-2) expression levels in local Achilles tendon. RESULTS: During the experiment, 5 rats died (2 in group B, 1 in group C, and 2 in group D), the other rats survived to the end of the experiment. General observation of Achilles tendon tissue showed that the tendon tissue volume of group B was the smallest, with soft texture and no cartilage-like tissue; the tendon tissue volume of group E was the biggest, with hard texture and cartilage-like tissue. The incidence of heterotopic ossification was 80.0% (8/10), 25.0% (2/8), 88.9% (8/9), 50.0% (4/8), and 100% (10/10) in groups A-E respectively at 10 weeks after operation; significant differences were found between groups B, D and group E (P = 0.002, P = 0.023) and between groups B and C (P = 0.015), but no significant difference was found among the other groups (P > 0.05). COX2 expression level in groups B and D was significantly lower than that in group E (P < 0.05 ), but no significant difference was found among the other groups (P > 0.05); BMP-2 expression level in group B was significantly lower than that in groups A, C, and E (P < 0.05), but no significant difference was found among the other groups (P > 0.05). CONCLUSION: Celecoxib at a dose of 10 mg/(kg x d) can effectively reduce the incidence of heterotopic ossification in rats.