Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3

Extracellular matrix(ECM)stiffening is a typical characteristic of cartilage aging,which is a quintessential feature of knee osteoarthritis(KOA).However,little is known about how ECM stiffening affects chondrocytes and other molecules downstream.This study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane(PDMS)substrates.It demonstrated that epigenetic Parkin regulation by histone deacetylase 3(HDAC3)represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte physiology.We found that ECM stiffening accelerated cultured chondrocyte senescence in vitro,while the stiffness ECM downregulated HDAC3,prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis(OA)in mice.Contrarily,intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in mice.The findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals,promoted the Parkin acetylation and hyperactivated mitophagy,and damaged chondrocyte health.These results may provide new insights into chondrocyte regulation by the mechanical properties of ECM,suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.

CLINICAL APPLICATION OF THE TONIFICATION METHOD IN ORTHOPEDICS AND TRAUMATOLOGY

Traumatological and orthopedical diseases with obstruction and blockage are in most cases treated by the reducing method like promoting qi flow and activating blood circulation, dispersing and removing obstruction. However, the therapeutic

Primary Total Hip Arthroplasty on Complex Hips Conditions in a Low-Resource Setting

Introduction: Total hip arthroplasty of complex morphology is a challenge for the orthopaedic surgeon. Careful analysis of the hip’s anatomy helps to unravel the difficulties and anticipate the procedures to be performed and the implants to be planned. The aim was to identify the types of hip that make first-line THR difficult, specify the technical procedures to be used on these sites, and assess the functional results of the series. Material and Methods: This was a retrospective study that concerned patients operated on for total hip arthroplasty between January 2015 and December 2022 at the medical center “La Grâce” in Bobo-Dioulasso, Burkina Faso. Patients with coxarthrosis (on hip dysplasia, acetabular protrusio, acetabular malunion or neurological hip) and those with ankylosis of the hip, osteonecrosis secondary to neglected dislocation of the hip or hemoglobinopathy were included. Results: A total of 31 total hip replacements were performed in 30 patients. The mean age of patients at the surgery time was 36.2 years with extremes of 17 and 61 years. The male-to-female sex ratio was 1. The main indications for THA were the dysplasic hip osteoarthritis (11 cases) and the neglected hip dislocations (7 cases). In situ femoral neck osteotomy before hip dislocation was performed in seven cases. The acetabulum reconstruction techniques varied from the structural iliac bone graft (n = 3) and cancellous bone graft (n = 4) to the Kerboull plate (n = 1). After 45 months of mean follow-up, all hips were evaluated. The mean PMA score increased from 7.1 [4 - 8] before the surgery to 13.2 [13 - 17]. Conclusion: The large spectrum of challenges in complex hip management requires effective preoperative planning. Preoperative planning minimizes complications and ensures a better outcome.

Traumatic Neglected Antero-Medial Knee Dislocation: Case Report

Introduction: Neglected knee dislocation is an unusual injury, only a few cases have been reported in the literature. The circumstances of onset are generally an unnoticed knee dislocation in a polytrauma context or a delay in consultation after the initial trauma. Presentation of case: We report the case of a 48-year-old female patient who sustained a knee injury during a domestic accident. Initial treatment was traditional and was followed for 3 years. She then consulted hospital, where a neglected knee dislocation was identified and treated with femorotibial arthrodesis. Discussion and conclusion: The treatment options of neglected knee dislocation include open reduction and fixation, arthrodesis and total knee arthroplasty. That the choice depends on the old unreduced of dislocation.

Functional outcomes of traumatic and non-traumatic rotator cuff tears after arthroscopic repair

AIM To compare the functional outcomes of traumatic and non-traumatic rotator cuff tears after arthroscopic repair. METHODS Eighty-seven patients with rotator cuff tears following arthroscopic treatment were divided into traumatic and non-traumatic tear groups. Postoperative muscle strength and outcomes using the modified University of California, Los Angeles score were evaluated. Sex, age, affected limb and dominant limb were correlated between groups. Muscle strength of the repaired and unaffected shoulders was compared. Rotator cuff injury size was measured. RESULTS Of the 87 patients who underwent rotator cuff repairs, 35 had traumatic tears and 52 had non-traumatic tears. In patients with non-traumatic tears, the average age was 59 years, 74.5% were female, 96.1% were righthand dominant and 92.3% had their dominant shoulder affected. Patients with traumatic tears were 59.5 yearsold on average, 51.4% were female, 91.4% were righthand dominant and 88.5% had their dominant shoulder affected. No difference existed in the mean modified University of California, Los Angeles score between patients with traumatic tears(33.7) compared with those with non-traumatic tears(32.8). No strength differences were observed between groups: The strength difference between the non-affected and affected sides was 1.21 kg in the non-traumatic group and 1.39 kg in the traumatic group(P = 0.576), while the strength ratio between the non-affected/affected sides was 0.805 in the nontraumatic group and 0.729 in the traumatic group(P = 0.224). CONCLUSION The functional results of traumatic rotator cuff repairs are similar to non-traumatic tears. Both outcomes are satisfactory.

Frequency of Comorbid Musculoskeletal Problems in Patients with Parkinson’s Disease: What and When?

Background: Musculoskeletal problems, deteriorating posture and pain are common complaints/comorbidities in Parkinson’s disease (PD). The aim of this study was to investigate the frequency of comorbid musculoskeletal problems in PD, and their relationship with disease stage and severity. Methods: The study was approved by the local ethical committee of Duzce University numbered with 2018/52 on date 26.03.2018. Patients with PD (pwPD) underwent a detailed examination to investigate the possible comorbidity of musculoskeletal findings in the orthopedics and traumatology clinic. Socio-demographic features, disease characteristics, motor and non-motor scores were recorded. Results: Thirty-seven pwPD were enrolled in the study. Mean age was 68.75 ± 10.75 years. Comorbid musculoskeletal problems were rotator cuff syndrome (27%), knee osteoarthritis (24.3%), meniscus (13.5%), lumber disc herniation (10.8%), kyphosis (8.1%), myotendinous diseases (16.3%). Rotator-cuff disease and knee osteoarthritis were most common comorbidities, especially in the “mild” and “moderate” stages of pwPD. Conclusion: Since most of the pwPD, especially the ones that have musculoskeletal complaints prior to the diagnosis of PD, present to the orthopedics and traumatology clinics or physiotherapists, it is mandatory to enhance the awareness of the orthopedic surgeons, and physiotherapy specialist in order to keep PD in mind.

Comparing shoulder maneuvers to magnetic resonance imaging and arthroscopic findings in patients with supraspinatus tears

BACKGROUND Shoulder maneuvers and magnetic resonance imaging(MRI)are performed to diagnose supraspinatus tendon tears regardless of arthroscopy exam.Although there are many studies on this subject,there is a lack of studies comparing the sensitivity(Se)and specificity(Sp)of shoulder maneuvers and MRI to arthroscopic findings(intact,partial,or full thickness supraspinatus tendon tear).AIM To compare the diagnostic values of shoulder maneuvers with MRI for supraspinatus tendon tears in patients undergoing shoulder arthroscopy.METHODS A total of 199 consecutive patients from four orthopedic centers met the eligibility criteria of shoulder pain persisting for at least four weeks.They were prospectively enrolled in this study from April 2017 to April 2019.Seven clinical tests(full can,empty can,drop arm,Hawkins’,painful arc,Neer’s sign and resisted external rotation)and MRI were performed,and all were compared with surgical findings.Full can,empty can and resisted external rotation tests were interpreted as positive in the case of pain and/or weakness.We assessed the Se,Sp,accuracy,positive predictive value(PPV)and negative predictive value(NPV),positive and negative likelihood ratio and diagnostic odds ratio for overall,partial and fullthickness supraspinatus tears.RESULTS MRI had the highest Se for overall(0.97),partial(0.91)and full-thickness(0.99)tears;moreover,MRI had the highest NPV:0.90,0.88 and 0.98 for overall,partial and full-thickness tears,respectively.For overall supraspinatus tears,the Se and PPV were:Painful arc(Se=0.85/PPV=0.91),empty can(pain)(Se=0.80/PPV=0.89),full can(pain)(Se=0.78/PPV=0.90),resisted external rotation(pain)(Se=0.48/PPV=0.87),drop arm(Se=0.19/PPV=0.97),Neer’s sign(Se=0.78/PPV=0.93)and Hawkins’(Se=0.80/PPV=0.88).MRI had the highest PPV(0.99).The Hawkin’s test had the highest false positive rate in patients with intact tendons(0.36).The Sp of the empty can and full can(both tests positive for pain and weakness),drop arm and MRI were:0.93,0.91,0.98 and 0.96,respectively.For partial and full-thickness tears,the empty can test(positive for pain and weakness)had a Sp of 0.93,and the drop arm and MRI had the same Sp(0.98).CONCLUSION Physical examination demonstrated good diagnostic value,the drop arm test had a Sp as good as MRI for supraspinatus tears;however,MRI was more accurate in ruling out tears.The Hawkins’test had high false-positive findings in patients with intact tendons.

Preliminary Results of Double-Bundle Anterior Cruciate Ligament Reconstruction and Technique-Specific Problems

Background: In this study, we determined the efficiency of anterior cruciate ligament (ACL) reconstruction using the double-bundle technique and addressed technique-specific problems. Patients and Methods: Twenty-nine patients who underwent ACL reconstruction due to ACL rupture with the arthroscopic double-bundle ENDOBUTTON CL method using autogenous hamstring tendons were evaluated. All patients were males and the mean age was 24.3 years (range 20 - 41 years). The mean follow-up period was 36.4 months (minimum 16 and maximum 53 months). Diagnosis was based on medical history and physical examination. Lachman, anterior drawer and pivot shift tests were performed. The patient diagnosis was verified with X-ray roentgenogram and magnetic resonance imaging (MRI). Tunnel mergence and graft hanging problems were discussed. Results: Pre- and postoperative clinical assessments of the patients showed the mean Lysholm score increased from 60.2 (48 - 72) preoperatively to 91.5 (85 - 98) at the final visit, whereas the mean Tegner score increased from 5.58 (3 - 9) preoperatively to 6.03 (4 - 9) at the final visit. According to the International Knee Documentation Committee (IKDC) knee ligament standard evaluation system, five patients were classified as B (17%);11 patients were classified as C (38%);and 13 patients were classified as D (45%) before the surgery. At the postoperative evaluation, 17 (59%) patients were classified as A;11 (38%) patients were classified as B;and 1 (3%) patient was classified as C. Conclusion: The double-bundle technique using hamstring tendons and femoral braces is an efficient and satisfactory method for ACL reconstruction.

Ankle Fractures, Short Term Operative Outcome: A Retrospective Case Series

Introduction and Background: Ankle injury is one of the most frequent presenting injuries to the emergency room and ankle fractures are common fracture in the lower limbs injuries that may require operative treatment with variable outcomes. Materials and Methods: Sixty-three patients were included in my retrospective study, and all with a displaced fracture of the ankle caused by high energy trauma were treated by open reduction and rigid internal fixation. Results: After follow-up at six weeks and twelve weeks, the results were satisfactory in fifty-five percent out of all the sixty-three patients. Conclusions and Recommendations: Ankle fractures occur mainly in young males of the age group between 26 and 35 years, mostly caused by fall down and motor vehicle accident.

Corrective osteotomies of the radius:Grafting or not?

AIM:To review the current literature regarding corrective osteotomies to provide the best evidence of the rule of bone grafting.METHODS:Our MEDLINE literature search included 280 studies using the following key words "Malunited distal radius fracture" and 150 studies using key words "Corrective osteotomy of the distal radius".Inclusion criteria were:Malunited distal radial,extra articular fracture,volar locking plate,use of iliac bone graft(cancellous or corticocancellous),non-use of bone graft.Twelve studies met the inclusion criteria.RESULTS:Seven of the 12 studies considered,described the use of a graft;the remaining five studies didn't use any graft.Type of malunion was dorsal in most of the studies.The healing time was comparable using the graft or not(mean 12.5 wk),ranging from 7.5 to 16 wk.The mean disabilities of the arm,shoulder and hand score improvement was 23 points both in the studies that used the graft and in those not using the graft.CONCLUSION:This review demonstrated that corrective osteotomy of extra-articular malunited fractures of the distal radius treated by volar locking plate does not necessarily require bone graft.

Ciliary parathyroid hormone signaling activates transforming growth factor-βto maintain intervertebral disc homeostasis during aging

Degenerative disc disease(DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus(NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor(PTH1 R) to the cilia and enhances parathyroid hormone(PTH) signaling in NP cells. PTH induces transcription of integrin α_vβ_6 to activate the transforming growth factor(TGF)-β-connective tissue growth factor(CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH(iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1 R is expressed in both mouse and human NP cells. Importantly,knockout PTH1 R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1 R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD.

白及对小儿前臂骨骺骨折闭合复位术后机体炎症应激反应的影响

目的研究白及治疗对小儿前臂骨骺骨折闭合复位术后机体炎症应激反应的影响。方法将2012年4月至2014年4月期间我院收治的100例小儿前臂骨骺骨折患者纳入研究,采用随机数表将入组者分为两组,观察组患者接受手法复位夹板外固定联合白及内服治疗,对照组患者接受手法复位夹板外固定联合常规支持治疗,比较两组患者炎症反应和应激反应程度。结果治疗后1周时,观察组患者的IL-6、IL-8、TNF-α以及皮质醇、肾上腺素、去甲肾上腺素水平低于对照组,差异有统计学意义(P驥0.05)。结论白及治疗有助于缓解机体的炎症和应激反应,是小儿前臂骨骺骨折闭合复位术后理想的治疗方法。

Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling

Mutation of the MAPK7 gene was related to human scoliosis.Mapk7 regulated the development of limb bones and skulls in mice.However,the role of MAPK7 in vertebral development is still unclear.In this study,we constructed Col2a1-cre;Mapk7 f/f transgenic mouse model to delete Mapk7 in cartilage,which displayed kyphosis and osteopenia.Mechanistically,Mapk7 loss decreased MEF2C expression and thus activated PTEN to oppose PI3K/AKT signaling in vertebral growth plate chondrocytes,which impaired chondrocyte hypertrophy and attenuated vertebral ossification.In vivo,systemic pharmacological activation of AKT rescued impaired chondrocyte hypertrophy and alleviated mouse vertebral defects caused by Mapk7 deficiency.Our study firstly clarified the mechanism by which MAPK7 was involved in vertebral development,which might contribute to understanding the pathology of spinal deformity and provide a basis for the treatment of developmental disorders of the spine.

Pilon fractures： a new classification and therapeutic strategies

Background Operative decision-making of Pilon fractures are of great challenges until now. The aim of this study was to investigate the guidance of the four-column theory in decision-making therapeutic strategies for Pilon fractures and its result. Methods One hundred and ten cases （107 patients） of Pilon fractures classified by the four-column theory and treated by ORIF, were reviewed. According to the four-column classification scheme, lateral column of 85 cases, posterior column of 66 cases, medial column of 77 cases, and anterior column of 61 cases are involved. Among all the 110 cases, single column of 14 cases, two columns of 46 cases, three columns of 17 cases, and all of four columns of 33 cases are involved. Results One hundred and eight cases have been followed up. The average follow up time is 14.7 months, varying between 7 and 52 months. The average healing time is 3.6 months, ranging from 2.5 to 8.0 months. Reduction of 86.1% reviewed Pilon cases are good or acceptable according to Burwell and Charley＇s Radiology Evaluation System. Ankle function of 87.1% cases are excellent or good according to the AOFAS evaluation system. Conclusion As a simple and comprehensive classification, the four-column classification can contribute to reasonable operation decision-making and good prognosis of Pilon fracture.

Electroacupuncture at jiājǐ(夹脊 EX-B2) for lumbar intervertebral disc herniation:A randomized controlled trial

Objective： To compare the effect differences of electroacupuncture（EA） at Jiajǐ（夹脊 EX-B2） and conventional acupoints for lumbar intervertebral disc herniation（LIDH） and the factors influenced the effect during the way of data mining.Methods： A total of 160 patients of LIDH were randomly assigned into the EX-B2 group and the conventional acupoints group, 80 cases in each one. The patients in the EX-B2 group received EA at the symmetrical 2 acupoints of the bilateral EX-B2 on the lesion part. The patients in the conventional acupoints group received EA at the tender point of the lesion part, Zhibian（ 秩边BL54）, Huantiao（环跳 GB30）,weǐzhōng（委中BL40）, Chéngshān（承山BL57） and Fúyáng（跗阳BL59） on the affected side. The retain time of the needles is both 45 min. The treatment of the two groups is 3 times a week and for a connective 20 times. The modified Assessment Criteria for Low Lumbar Pain of Japanese Orthopedic Association（JOA）,Visual Analogue Scale（VAS） were evaluated before and after the treatment and at the 6-month follow up.Results：（1） Effective outcomes. JOA score： The JOA score of the patients in the EX-B2 group after treatment was（20.89 士 3.43）, and was（19.35 ±4.02） on the follow-up. Compared with the JOA score（12.35 ±4.42） in the same group before the treatment, there were statistical significant higher（both P0.05）. The JOA score in the EX-B2 group after treatment and on the follow-up were both higher than that of the conventional acupoints group at the same time point（both P0.05）. VAS score： The VAS score of the patients in the EX-B2 group on the 24 h after the first treatment was（4.09 ± 1.81）, and was（2.11 ± 1.30） after the treatment. Compared with the VAS score（4.09 ± 1.81） in the same group before the treatment, there were statistical significant lower（both P0.05）. The VAS score in the EX-B2 group on the 24 h after the first treatment and after treatment showed no statistical differences than that of the conventional acupoints group at the same time point（both P0.05）.（2）Related results from data mining： The middle-aged people and disease duration less than six months, their effect of the immediate treatment was the best. According to JOA score, EA at EX-B2 was better than EA conventional acupoints,either in the process of treatment effect, or in pertinence of the treatment, which were superior to EA conventional acupoints therapy; The best curative effect time of EA at EX-B2 was the first treatment after24 h, and the best curative effect of the conventional acupoints was after the first treatment. The age and disease duration also affected curative effect.Conclusion： The effect of EA at EX-B2 was superior to the conventional acupoints in treating LIDH.

Bone marrow adipoq+ cell population controls bone mass via sclerostin in mice

Dear editor,The comorbidity of obesity and osteoporosis illustrates the communication and coordination of adipose and bone tissues.Leptin and adiponectin derived from adipocytes regulate osteoblast formation and function to impact bone mass through direct and indirect mechanisms.1 It is known that bone marrow adipocytes(BMA)can control bone mass by modulating the bone morphogenetic protein(BMP)and other signaling pathways.BMAs can secret soluble factors,which impact osteoblasts,osteoclasts,and osteocytes.2 Sclerostin is a potent inhibitor of bone acquisition that antagonizes Wnt/β-catenin signaling.

Biomembrane-inspired design of medical micro/nanorobots:From cytomembrane stealth cloaks to cellularized Trojan horses

Micro/nanorobots are promising for a wide range of biomedical applications(such as targeted tumor,thrombus,and infection therapies in hard-to-reach body sites)because of their tiny size and high maneuverability through the actuation of external fields(e.g.,magnetic field,light,ultrasound,electric field,and/or heat).However,fully synthetic micro/nanorobots as foreign objects are susceptible to phagocytosis and clearance by diverse phagocytes.To address this issue,researchers have attempted to develop various cytomembrane-camouflaged micro/nanorobots by two means:(1)direct coating of micro/nanorobots with cytomembranes derived from living cells and(2)the swallowing of micro/nanorobots by living immunocytes via phagocytosis.The camouflaging with cytomembranes or living immunocytes not only protects micro/nanorobots from phagocytosis,but also endows them with new characteristics or functionalities,such as prolonging propulsion in biofluids,targeting diseased areas,or neutralizing bacterial toxins.In this review,we comprehensively summarize the recent advances and developments of cytomembrane-camouflaged medical micro/nanorobots.We first discuss how cytomembrane coating nanotechnology has been employed to engineer synthetic nanomaterials,and then we review in detail how cytomembrane camouflage tactic can be exploited to functionalize micro/nanorobots.We aim to bridge the gap between cytomembrane-cloaked micro/nanorobots and nanomaterials and to provide design guidance for developing cytomembrane-camouflaged micro/nanorobots.

Observation on Clinical Effects of Acupotomy plus Cupping for Knee Osteoarthritis

Objective: To observe the clinical effect of acupotomy plus cupping for knee osteoarthritis(KOA). Methods: Sixty cases with KOA were randomly divided into a treatment group and a control group, 30 cases in each group. The patients in the treatment group were given acupotomy and cupping, while the patients in the control group were given injection of Sodium Hyaluronate. The index of severity for osteoarthritis(ISOA), the change of the effusion of knee joint and clinical effects were observed after treatment. Results: The total effective rate was respectively 96.7% in the treatment group and 66.7% in the control group. The difference in the clinical effects between the two groups was statistically significant(P<0.05). After treatment, ISOA scores and scores of knee effusion in the two groups were remarkably reduced than those before treatment(P<0.05). The changes of the scores of the two indexes were statistically significant(both P<0.05). Conclusion: Acupotomy plus cupping is better than injection of Sodium Hyaluronate in treatment of KOA.

Influence of Needling Point Hegu(LI4)on Colonoscopy

Purpose： To investigate the influence of needling bilateral points Hegu （LI 4） before colonoscopy on the examined patients and the time of inserting colonoscope. Methods： 185 patients to receive colonoscopy were randomly divided into an acupuncture group （93 cases） and a control group （92 cases） in order of examination. Bilateral points Hegu （LI 4） were needled before colonoscopy in the acupuncture group. No preventive measures were taken in the control group. Pain grades during the period that colonoscope passes the sigmoid and transverse colons were observed and the time of inserting colonoscope was recorded. Results.. One hundred and sixty-five patients underwent colonoscopic insertion successfully, which were taken as the effective cases. Of them, 84 cases were in the acupuncture group and 81 cases in the control group. Statistics indicated that pain grades during colonoscope＇s passing the sigmoid and transverse colons were significantly lower in the acupuncture group than in the control group （P 〈 0.01）; the time of inserting colonoscope was significantly shorter in the acupuncture group than in the control group （P〈 0.05）. Conclusion. Needling bilateral points Hegu（LI 4） before colonoscopy can effectively relieve the patients＇discomfort and shorten the colonoseopic time during the examination.