Evaluation of Accuracy of Clinical Examination and MRI on Diagnosing Anterior Cruciate Ligament and Meniscal Tears in Comparison to Diagnostic Arthroscopy among Patients Attending at Muhimbili Orthopedic Institute

Routine use of Magnetic Resonance Imaging (MRI) as screening test after clinical diagnosis for meniscal and/or anterior cruciate ligament (ACL) has a detrimental effect on patients in limited resourced countries. This study was done to compare accuracy of clinical examination and that of (MRI) on diagnosing meniscal and or (ACL) tears. Methodology: A cross-sectional-descriptive study was done on 57 knees of patients. Clinical examination, MRI and then diagnostic arthroscopy, as the gold standard, were done to all the cases. Results were recorded;the accuracies of MRI and clinical examination were evaluated and their results were compared. Results: Median age of patients was 40 years. Clinical examination had sensitivity of 93.62% and specificity of 40% for diagnosing meniscal tears;and sensitivity of 100%;and specificity of 97.67% for diagnosing ACL tear. MRI had sensitivity of 85.11%, and specificity of 40% for meniscal tear diagnosis and 71% and 100% respectively for ACL tear diagnosis. Diagnostic accuracy was 84.21% for meniscal and 98.24% for ACL tears by clinical examination and by MRI was 77.19% and 92.98% respectively. Conclusion: Clinical examination has higher accuracy than MRI on diagnosing both ACL and meniscal tear. Thus patients may be scheduled for diagnostic and interventional arthroscopy if clinical examination reveals meniscal and or ACL injuries. MRI use should be reserved when clinical evaluation is inconclusive or cannot be done.

Single-cell RNA sequencing in orthopedic research

Although previous RNA sequencing methods have been widely used in orthopedic research and have provided ideas for therapeutic strategies,the specific mechanisms of some orthopedic disorders,including osteoarthritis,lumbar disc herniation,rheumatoid arthritis,fractures,tendon injuries,spinal cord injury,heterotopic ossification,and osteosarcoma,require further elucidation.The emergence of the single-cell RNA sequencing(sc RNA-seq)technique has introduced a new era of research on these topics,as this method provides information regarding cellular heterogeneity,new cell subtypes,functions of novel subclusters,potential molecular mechanisms,cell-fate transitions,and cell-cell interactions that are involved in the development of orthopedic diseases.Here,we summarize the cell subpopulations,genes,and underlying mechanisms involved in the development of orthopedic diseases identified by sc RNA-seq,improving our understanding of the pathology of these diseases and providing new insights into therapeutic approaches.

A new perspective on intervertebral disc calcification—from bench to bedside

Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

Sema3A secreted by sensory nerve induces bone formation under mechanical loads

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 hours.Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.

Skeletal interoception in osteoarthritis

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the organism.Among its various forms,skeletal interoception specifically regulates the metabolic homeostasis of bones.Osteoarthritis(OA)is a complex joint disorder involving cartilage,subchondral bone,and synovium.The subchondral bone undergoes continuous remodeling to adapt to dynamic joint loads.Recent findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone,resulting in subchondral bone sclerosis in OA.The skeletal interoception is also a potential mechanism for chronic synovial inflammation in OA.In this review,we offer a general overview of interoception,specifically skeletal interoception,subchondral bone microenviroment and the aberrant subchondral remedeling.We also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA,as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

Metabolic reprogramming: a new option for the treatment of spinal cord injury

Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.

Mazabraud’s syndrome in female patients:Two case reports

BACKGROUND Mazabraud’s syndrome(MS)is a rare and slowly progressive benign disease characterized by the concurrent presence of fibrous dysplasia of bone and intramuscular myxoma,and is thought to be associated with mutations of the GNAS gene.To date,only about 100 cases of MS have been reported in the literature,but its standard treatment strategy remains unclear.CASE SUMMARY We report two cases of MS in young women who underwent different treatments based on their symptoms and disease manifestations.The first patient,aged 37,received internal fixation and intravenous bisphosphonate for a pathological fracture of the right femoral neck,excision of a right vastus medialis myxoma was subsequently performed for pain control,and asymptomatic psoas myxomas were monitored without surgery.Genetic testing confirmed a GNAS gene mutation in this patient.The second patient,aged 24,underwent right vastus intermedius muscle myxoma resection,and conservative treatment for fibrous dysplasia of the ilium.These patients were followed-up for 17 months and 3 years,respectively,and are now in a stable condition.CONCLUSION Various treatments have been selected for MS patients who suffer different symptoms.The main treatment for myxomas is surgical resection,while fibrous dysplasia is selectively treated if the patient experiences pathological fracture or severe pain.However,given the documented instances of malignant transformation of fibrous dysplasia in individuals with MS,close follow-up is necessary.

Recent progress in Mg-based alloys as a novel bioabsorbable biomaterials for orthopedic applications

Traditional orthopedic metal implants,such as titanium(Ti),Ti alloys,and cobalt-chromium(Co-Cr)alloys,cannot be degraded in vivo.Fracture patients is must always suffer a second operation to remove the implants.Moreover,stress shielding,or stress protection occurs when traditional orthopedic metal implants are applied in fractures surgery.The mechanical shunt produced by traditional orthopedic metal implants can cause bone loss over time,resulting in decreased bone strength and delayed fracture healing.Biodegradable metals that‘biocorrode’are currently attracting significant interest in the orthopedics field due to their suitability as temporary implants.As one of the biodegradable metals,magnesium(Mg)and Mg alloys have gained interest in the field of medicine due to their low density,excellent biocompatibility,high bioresorbability,and proper mechanical properties.Additionally,Mg ions released from the metal implants can promote osteogenesis and angiogenesis during the degradation process in vivo,which is substantially better for orthopedic fixation than other bioinert metal materials.Therefore,this review focuses on the properties,fabrication,biological functions,and surface modification of Mg-based alloys as novel bioabsorbable biomaterials for orthopedic applications.

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Inhibiting tau protein improves the recovery of spinal cord injury in rats by alleviating neuroinflammation and oxidative stress

After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for many central nervous system diseases,including traumatic brain injury and Alzheimer's disease.However,whether it can play a role in the treatment of spinal cord injury remains unclear.In this study,the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression.We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators,including tumor necrosis factor-α,interleukin-6 and interleukin-1β.It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype,and reduced the amount of reactive oxygen species in the acute phase.Furthermore,the survival of residual neural cells around the injury epicenter,and neuronal and axonal regeneration were also markedly enhanced,which promoted locomotor recovery in the model rats.Collectively,our findings support the conclusion that tau inhibition can attenuate neuroinflammation,alleviate oxidative stress,protect residual cells,facilitate neurogenesis,and improve the functional recovery after spinal cord injury,and thus suggest that tau could be a good molecular target for spinal cord injury therapy.

Benidipine-loaded nanoflower-likemagnesium silicate improves bone regeneration

Regeneration and reconstruction of bone tissue is always a challenge for clinicians due to the uncertainty of bone repair materials in terms of long-term and efficient effects on osteoblasts.Here,we propose a novel strategy combining benidipine,an antihypertensive drug and nanoparticles to synergistically promote the healing of bone defects.Loose and porous benidipine-loaded magnesium silicate nanoparticles were prepared and validated for their biosafety.The nanoparticles were efficiently taken up by preosteoblasts and uniformly distributed around the nucleus.After internalization into cells,the nanosystem is degraded by lysosomes,and the effect of promoting osteogenic differentiation is reflected by the continuous release of benidipine,silicon and magnesium ions.Our results clearly evaluated that the nanoflower-like magnesium silicate delivering benidipine tends to be more appropriate for the bone regeneration in preosteoblasts,indicating that it might be a potential approach in guiding bone repair in clinical applications.

Exercise combined with administration of adipose-derived stem cells ameliorates neuropathic pain after spinal cord injury

Experimental studies have shown that exercise and human adipose-derived stem cells(ADSCs)play positive roles in spinal cord injury(SCI).However,whether ADSCs and/or exercise have a positive effect on SCI-induced neuropathic pain is still unclear.Thus,there is a need to explore the effects of exercise combined with administration of ADSCs on neuropathic pain after SCI.In this study,a thoracic 11(T11)SCI contusion model was established in adult C57BL/6 mice.Exercise was initiated from 7 days post-injury and continued to 28 days post-injury,and approximately 1×105 ADSCs were transplanted into the T11 spinal cord lesion site immediately after SCI.Motor function and neuropathic pain-related behaviors were assessed weekly using the Basso Mouse Scale,von Frey filament test,Hargreaves method,and cold plate test.Histological studies(Eriochrome cyanine staining and immunohistochemistry)were performed at the end of the experiment(28 days post-injury).Exercise combined with administration of ADSCs partially improved early motor function(7,14,and 21 days postinjury),mechanical allodynia,mechanical hypoalgesia,thermal hyperalgesia,and thermal hypoalgesia.Administration of ADSCs reduced white and gray matter loss at the lesion site.In addition,fewer microglia and astrocytes(as identified by expression of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein,respectively)were present in the lumbar dorsal horn in the SCI+ADSCs and SCI+exercise+ADSCs groups compared with the sham group.Our findings suggest that exercise combined with administration of ADSCs is beneficial for the early recovery of motor function and could partially ameliorate SCIinduced neuropathic pain.

Predicting recurrence in osteosarcoma via a quantitative histological image classifier derived from tumour nuclear morphological features

Recurrence is the key factor affecting the prognosis of osteosarcoma.Currently,there is a lack of clinically useful tools to predict osteosarcoma recurrence.The application of pathological images for artificial intelligence‐assisted accurate prediction of tumour out-comes is increasing.Thus,the present study constructed a quantitative histological image classifier with tumour nuclear features to predict osteosarcoma outcomes using haema-toxylin and eosin(H&E)‐stained whole‐slide images(WSIs)from 150 osteosarcoma patients.We first segmented eight distinct tissues in osteosarcoma H&E‐stained WSIs,with an average accuracy of 90.63%on the testing set.The tumour areas were auto-matically and accurately acquired,facilitating the tumour cell nuclear feature extraction process.Based on six selected tumour nuclear features,we developed an osteosarcoma histological image classifier(OSHIC)to predict the recurrence and survival of osteo-sarcoma following standard treatment.The quantitative OSHIC derived from tumour nuclear features independently predicted the recurrence and survival of osteosarcoma patients,thereby contributing to precision oncology.Moreover,we developed a fully automated workflow to extract quantitative image features,evaluate the diagnostic values of feature sets and build classifiers to predict osteosarcoma outcomes.Thus,the present study provides a novel tool for predicting osteosarcoma outcomes,which has a broad application prospect in clinical practice.

细胞流变学研究Ⅰ 肺癌患者红细胞粘弹性特性分析

本文采用平面流动腔技术设计了狭缝流动测试系统，用于评价单个细胞的粘弹性特性，从而提供了一种能直接、定量地测定单个细胞变形能力等参数的方法。通过对１５例肺癌患者手术前、后及放疗前红细胞变形性等参数的测量，并同正常对照组比较，验证了该技术和方法。最后，对平面流动腔内的Ｈｅｌｅ—Ｓｈａｗ流动进行了讨论。

Speckle tracking echocardiography:A new approach to myocardial function

Echocardiography is the most common diagnostic method for assessing cardiac function but some limitations affect this technique.Until now,visual assessment of wall motion and thickening has allowed only a subjective evaluation of myocardial function and requires long-term training.Recently,new echocardiographic techniques have been introduced to evaluate myocardial mechanics.Tissue Doppler imaging(TDI)technique is limited by angle-dependency such that only deformation along the ultrasound beam can be derived from velocities,while myocardium deforms simultaneously in three dimensions.Speckle tracking echocardiography (STE)is a more recent technique that provides a global approach to left ventricular myocardial mechanics,giving information about the three spatial dimensions of cardiac deformation.In this editorial,we describe the physical and pathophysiological concepts of STE,discussing the differences compared to TDI and underlining the pitfalls of this new technique.

The effect of the fibre orientation of electrospun scaffolds on the matrix production of rabbit annulus fibrosus-derived stem cells

Annulus fibrosus （AF） tissue engineering has recently received increasing attention as a treatment for intervertebral disc 0VD） degeneration; however, such engineering remains challenging because of the remarkable complexity of AF tissue. In order to engineer a functional AF replacement, the fabrication of cell-scaffold constructs that mimic the cellular, biochemical and structural features of native AF tissue is critical. In this study, we fabricated aligned fibroua polyurethane scaffolds using an electrospinning technique and used them for culturing AF-derived-stem/progenitor cells （AFSCs）. Random fibrous scaffolds, also prepared via electrospinningy were used as a control. We compared the morphology, proliferation, gene expression and matrix production of AFSCs on aligned scaffolds and random scaffolds. There was no apparent difference in the attachment or proliferation of cells cultured on aligned scaffolds and random scaffolds. However, compared to cells on random scaffolds, the AFSCs on aligned scaffolds were more elongated and better aligned, and they exhibited higher gene expression and matrix production of coUagen-I and aggrecan. The gene expression and protein production of coUagen-II did not appear to differ between the two groups. Together, these findings indicate that aligned fibrous scaffolds may provide a favourable microenvironment for the differentiation of AFSCs into cells similar to outer AF cells, which predominantly produce collagen-I matrix.

mTOR signaling in skeletal development and disease

The mammalian/mechanistic target of rapamycin(m TOR) is a serine/threonine protein kinase that integrates inputs from nutrients and growth factors to control many fundamental cellular processes through two distinct protein complexes m TORC1 and m TORC2.Recent mouse genetic studies have established that m TOR pathways play important roles in regulating multiple aspects of skeletal development and homeostasis. In addition, m TORC1 has emerged as a common effector mediating the bone anabolic effect of Igf1,Wnt and Bmp. Dysregulation of m TORC1 could contribute to various skeletal diseases including osteoarthritis and osteoporosis.Here we review the current understanding of m TOR signaling in skeletal development and bone homeostasis, as well as in the maintenance of articular cartilage. We speculate that targeting m TOR signaling may be a valuable approach for treating skeletal diseases.

Optimal time for subarachnoid transplantation of neural progenitor cells in the treatment of contusive spinal cord injury

This study aimed to identify the optimal neural progenitor cell transplantation time for spinal cord injury in rats via the subarachnoid space. Cultured neural progenitor cells from 14-day embryonic rats, constitutively expressing enhanced green fluorescence protein, or media alone, were injected into the subarachnoid space of adult rats at 1 hour （acute stage）, 7 days （subacute stage） and 28 days （chronic stage） after contusive spinal cord injury. Results showed that grafted neural progenitor cells migrated and aggregated around the blood vessels of the injured region, and infiltrated the spinal cord parenchyma along the tissue spaces in the acute stage transplantation group. However, this was not observed in subacute and chronic stage transplantation groups. 04- and glial fibrillary acidic protein-positive cells, representing oligodendrocytes and astrocytes respectively, were detected in the core of the grafted cluster attached to the cauda equina pia surface in the chronic stage transplantation group 8 weeks after transplantation. Both acute and subacute stage transplantation groups were negative for 04 and glial fibrillary acidic protein cells. Basso, Beattie and Bresnahan scale score comparisons indicated that rat hind limb locomotor activity showed better recovery after acute stage transplantation than after subacute and chronic transplantation. Our experimental findings suggest that the subarachnoid route could be useful for transplantation of neural progenitor cells at the acute stage of spinal cord injury. Although grafted cells survived only for a short time and did not differentiate into astrocytes or neurons, they were able to reach the parenchyma of the injured spinal cord and improve neurological function in rats. Transplantation efficacy was enhanced at the acute stage in comparison with subacute and chronic stages.

Season of the year influences infection rates following total hip arthroplasty

AIM To research the influence of season of the year on periprosthetic joint infections.METHODS We conducted a retrospective review of the entire Medicare files from 2005 to 2014. Seasons were classified as spring, summer, fall or winter. Regional variations were accounted for by dividing patients into four geographic regions as per the United States Census Bureau(Northeast, Midwest, West and South). Acute postoperative infection and deep periprosthetic infections within 90 d after surgery were tracked. RESULTS In all regions, winter had the highest incidence of periprosthetic infections(mean 0.98%, SD 0.1%) and was significantly higher than other seasons in the Midwest, South and West(P < 0.05 for all) but not the Northeast(P = 0.358). Acute postoperative infection rates were more frequent in the summer and were significantly affected by season of the year in the West.CONCLUSION Season of the year is a risk factor for periprosthetic joint infection following total hip arthroplasty(THA). Understanding the influence of season on outcomes following THA is essential when risk-stratifying patients to optimize outcomes and reduce episode of care costs.

Mechanical properties of nerve roots and rami radiculares isolated from fresh pig spinal cords

No reports have described experiments designed to determine the strength characteristics of spinal nerve roots and rami radiculares for the purpose of explaining the complexity of symptoms of medullary cone lesions and cauda equina syndrome. In this study, to explain the pathogenesis of cauda equina syndrome, monoaxial tensile tests were performed to determine the strength characteristics of spinal nerve roots and rami radiculares, and analysis was conducted to evaluate the stress-strain relationship and strength characteristics. Using the same tensile test device, the nerve root and ramus radiculares isolated from the spinal cords of pigs were subjected to the tensile test and stress relaxation test at load strain rates of 0.1, 1, 10, and 100 s-1 under identical settings. The tensile strength of the nerve root was not rate dependent, while the ramus radiculares tensile strength tended to decrease as the strain rate increased. These findings provide important insights into cauda equina symptoms, radiculopathy, and clinical symptoms of the medullary cone.