Exploration Of Surgical Treatment Of Developmental Dysplasia Of Hip Joint And Study On The Mechanism Of Hip Joint Capsule Lesion

Objective(s):Developmental hip dysplasia(Developmental Dysplasia of Hip,DDH)is a common hip disease with an incidence of 1-3 ‰.It is a common disease in newborns and one of the important pathogenic factors of adult hip osteoarthritis.The late disability rate is high,so it needs repair and reconstruction surgery such as total hip arthroplasty and other repair and reconstruction surgery.The corresponding treatment methods of DDH change with different deformity degree and onset stage,and with the increase of age,the complexity and cost of treatment are also rising,which not only brings pain and economic pressure to patients,but also brings great confusion and challenge to surgeons.At present,there are some problems in clinical practice,such as incomplete cognition of DDH disease,weak mastery of surgical methods,and difficulty in revealing the pathogenesis.In this paper,we reviewed the current relevant knowledge of the etiology and pathological changes of DDH disease,especially summarized its treatment schemes,and reviewed the indications and challenges of different treatment schemes.In response to the problems we found earlier,we conducted a follow-up study on Periacetabular Osteotomy(PAO),the most difficult of many osteotomy treatments for DDH.First,the risk of injury to important Periacetabular vessels and nerves was assessed by simulating surgical procedures in cadaveric specimens,and methods to avoid injury were summarized.Then the ischial branch osteotomy was performed through an auxiliary posterior incision on the cadaver,and this operation was compared with a single incision PAO to find out the difference between them.On this basis,by improving this method and introducing in detail the operation experience and details of Berne Periacetabular osteotomy assisted by posterolateral small incision,we strive to reduce the technical difficulty of PAO operation and shorten the learning curve,so as to provide some references for doctors engaged in hip orthopaedic surgery in their cognition and mastery of this operation.As a progressive disease,the significance of early detection and intervention of DDH is much greater than that of subsequent treatment.How to determine the etiology of DDH and the causes of disease progression and targeted intervention in order to reduce the occurrence of disease,delay or even block the progress of the disease has become an important direction of DDH research.Although many studies have tried to reveal the causes of the occurrence and development of DDH,unfortunately,the relevant studies have not come to a widely accepted conclusion that DDH is still considered to be a multietiological disease.With the completion of the Human Genome Project,more and more diseases have been found to be genetically related,and studies have been conducted to analyze the role of genes in DDH.These studies mainly focus on cartilage development and subsequent development of osteoarthritis,but there are no studies related to maintaining the stability of the hip joint-joint capsule.Therefore,in our follow-up study,we selected the joint capsule as the research object,compared the pathological and molecular changes of hip joint capsule in patients with DDH with the control group,and through high-throughput sequencing to understand the changes of gene expression in hip joint capsule in patients with DDH,analyzed and summarized the gene expression changes of the hip capsule in DDH patients by high-throughput sequencing,in order to lay the foundation for revealing the pathogenesis of DDH.On this basis,we screened the possible differential genes,and selected some factors that may be related to the occurrence and development of the disease for preliminary exploration,to guide the subsequent research.Methods:Part I:Through the interpretation and summary of the relevant guidelines and standards and classical literature in recent years,combined with our understanding of the experience of DDH treatment in different periods from children to adults,we summarize and analyze the etiology,pathology and treatment of DDH respectively.Through surgical simulation and dissection of cadavers,the relationship between PAO operation and the surrounding structure of the hip joint was further explored.An auxiliary posterolateral small incision was used to complete the ischiotomy under direct vision,and the two surgical approaches were compared to explore a safer and simpler surgical approach.Part II:Berne PAO osteotomy is the most difficult method in DDH osteotomy.In order to simplify the operation and make it more universal.After improving the operation method according to the operator’s experience,the operation procedure and operation details of the improved operation were introduced in detail by the combination of picture and text.Then,through a retrospective study,58 DDH patients(65 hips)who underwent Berne PAO osteotomy with modified Smith-Peterson or Bikini approach combined with posterolateral small incision approach,The clinical data of these patients were analyzed statistically.The degree of hip dysplasia was evaluated by Tonnis hip osteoarthritis classification and Hartofilakidis classification system.All patients were retrospectively analyzed and evaluated according to the standard and evaluation index(including follow-up cases in the learning curve period).There were 52 females and 6 males with an average age of 28.1 years at the time of surgery.Part III:In this study,15 patients with DDH were included in the study group and 12 patients with normal hip joint development were selected as the control group.In 2019,the 920th Hospital of the Joint Logistics Support Force obtained the hip joint capsule tissues of DDH patients and control groups from Colonna arthroplasty and open reduction of fractures.The differentially expressed genes in the hip joint capsule of healthy controls and DDH patients were identified by high-throughput sequencing.The role of differentially expressed genes in DDH pathology was determined by biological identification such as cell cycle,cell viability,apoptosis,immunofluorescence,RT-PCR and Western blotting.Then,according to the previous basis,the animal model of DDH was reproduced,and the possible susceptible genes were screened from the early differential gene bank,and preliminary verification was carried out in the animal model.Finally,by summarizing the research on DDH genes in recent years,the role of these genes is analyzed and discussed.We will look for potential diagnostic and therapeutic targets for the disease in the future.Results:Part I:Through the combination of picture and text,this paper shows a summary of the etiology,pathology and treatment of DDH,and finally summarizes the diagnosis and treatment route of DDH.On this basis,the advantages and disadvantages of current treatment options for DDH are discussed subsequent research.In the surgical simulation and anatomy of 8 cadavers(16 hips),it was found that the risk of nerve and vascular injury could be reduced by changing the posture during the operation.At the same time,by assisting the posterolateral small incision,the operation time and ischial osteotomy time can be shortened,and the number of effective intraoperative fluoroscopies could be reduced.Part II:The mean follow-up period was 35.2 months.No patient was converted to total hip arthroplasty.Complications included neurosensory disorders in 6 hips(9.2%)and delayed wound healing in 1 hip(1.5%).The average operation time was 88.6 minutes,and the intraoperative blood loss was 402.8 ml.The mean modified Harris hip score improved from 72.2 preoperatively to 91.3 at final follow-up.Fifty-five patients(62 hips,95.4%)were satisfied with the outcome.A good preoperative functional score was associated with a satisfactory outcome.In addition,the average lateral CE angle,anterior CE and acetabular index angle were well corrected after operation.Part III:It was found that more than 1000 differentially expressed genes were found in the hip capsule between the healthy control group and the DDH group.Gene ontology(GO)and Kyoto Encyclopedia of Gene and Genome(KEGG)analysis showed that extracellular matrix(ECM)modification,muscle system process and cell proliferation were significantly affected by differentially expressed genes.In DDH group,the expression of COL1A1,COL3A1,MMP1,MMP3,MMP9 and MMP13 was down-regulated,accompanied by loss of collagen fibers in the articular capsule.The expression of TGF-β1 was down-regulated,while the expression of TGF-β2,SMAD3 and WNT11 was up-regulated in DDH group,and a-SMA was a key myofibroblast marker,showing a slight increase.In vitro studies showed that the proliferation of fibroblasts was inhibited in DDH group,which was related to cell cycle arrest in GO/G1 and G2/M phases.The expression of cell cycle regulators including CCNB1,CCNE2,CCNA2,CDK1,E2F1,CDC6 and CDC7 was downregulated in DDH group.The animal model of DDH was reproduced by swaddling newborn rat cubs,and verified by subsequent imaging and morphology.The animal model showed manifestations of hip dislocation,femoral head and acetabular dysplasia,joint capsule and round ligament distention similar to human DDH.In the preliminary immunological screening,it was found that compared with the control group,the mechanical force-related Piezo 1 gene and its downstream genes(COL1A1,a SMA,ECM1)were overexpressed in the hip joint capsule of the DDH experimental group.The current gene research related to DDH is summarized to guide the followup research direction.Conclusion(s):1.The pathological changes of different types of DDH vary in different periods,and each of these treatment schemes has corresponding indications and accompanying complications and risks.orthopedic surgeons must be aware of these complications and risks,and understand and re-recognize DDH in all aspects in order to maximize the health benefits of patients.It is necessary for us to continue our research on DDH to find new treatment options and early diagnosis methods,and to further clarify the indications of different treatment schemes,to prevent the occurrence of avascular necrosis of the femoral head(Avascular Necrosis,AVN)in the early stage,and to reduce the hip replacement rate caused by DDH in adulthood,so as to better face this global health challenge.As an effective surgical treatment for young and adult DDH patients,PAO is difficult to operate and has a long learning curve.By assisting the posterolateral small incision,the ischial osteotomy under fluoroscopy can be changed to the operation under direct vision,which can effectively reduce the difficulty of operation and shorten the learning curve.2.The modified S-P or Bikini combined approach assisted by posterolateral small incision is safe and effective for Periacetabular osteotomy.In addition,this technique shortens the learning curve and reduces the complexity of operation(especially for beginners).3.Compared with the control group,the loss of collagen fibers and fibroblasts in the DDH joint capsule may lead to the loosening of the joint capsule,increase the instability of the hip joint,and become an important factor in the occurrence and progression of the disease.In animal experiments,we found that mechanical traction can change the expression of related proteins,but this change was not found in the articular capsule of patients with DDH.Whether this difference is the reason for the progression of DDH disease,the role of related factors remains to be further studied.