A Rabbit Model of Hormone-induced Early Avascular Necrosis of the Femoral Head

Objective To establish an experimental model of early stage avascular necrosis of the femoral head （ANFH） caused by corticosteroid in adult rabbits and to observe the pathological changes with various imaging techniques. Methods ANFH was induced by a combination of hypersensitivity vasculitis caused by injection of horse serum and subsequent administration of a high dose of corticosteroid. The pathological changes were detected with digital radiography （DR）, computed tomography （CT）, magnetic resonance imaging （MRI）, ink artery infusion angiography, hematoxylin-eosin staining, and immunohistochemistry. Results The imageological and pathological changes corresponded to the clinical characteristics of early stage ANFH. DR showed bilaterally increased bone density, an unclear epiphyseal line, and blurred texture of cancellous bone. CT showed spot-like low-density imaging of cancellous bone, thinner cortical bone, osteoporosis, and an unclear epiphyseal line. MR! showed bone marrow edema and spot-like high signals in T2-weighted imaging in cancellous bone. Ink artery infusion angiography showed fewer obstructed blood vessels in the femoral head. HE staining of pathological sections showed fewer trabeculae and thin bone, an increased proportion of empty osteocyte lacunae, decreased hematopoiesis, thrombosis, and fat cell hypertrophy. Immunohistochemistry showed attenuated expression of vascular endothelial growth factor in osteoblasts and chondrocytes, and on the inner membrane of blood vessels. Conclusion Experimental rabbit model of early stage ANFH caused by corticosteroid can be successfully established and provide the foundation for developing effective methods to treat early stage ANFH.

Experimental Study of Vascular Endothelial Growth Factor Gene Therapy for Avascular Necrosis of the Femoral Head

To explore a new method for the therapy of the avascular necrosis of the femoral head, the recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head The expression of vascular endothelial growth factor (VEGF) was detected by RNA dot hybridization and immunohistochemical method The repair of the femoral head was observed by histological method The results showed that the expression of VEGF was detectable in the femoral head treated with VEGF gene Angiogenesis in these femoral heads was more abundant than the control Bone repairing was augmented in the femoral head treated with VEGF gene The results suggest that angiogenesis in bone tissue could be augmented by gene transfection of VEGF and bone repairing would be accelerated accordingly

Regulation of Quan Du Zhong capsule on VEGF/bFGF and expression of Bcl‑2/Bax and Caspase‑3 protein in the repairing process of canine femoral head necrosis

Objective:To explore the repair and treatment effect of Quan Du Zhong capsule on necrosis of femoral head in dogs.Methods:Totally 12 beagles were randomly divided into normal group,model group,Quan Du Zhong capsule group and Xianlinggubao capsule group,with three in each group.In addition to the normal group,the other groups established the femoral head necrosis model by liquid nitrogen alternative freezing.The normal group and the model group did not have any intervention during the modeling period,and the Quan Du Zhong group began to receive the Quan Du Zhong by gavage on the day of modeling;Xianlinggubao capsule group was given Xianlinggubao capsule by gavage once a day for 12 consecutive weeks on the day of modeling.The levels of VEGF and bFGF in the blood vessels of each group at the 12th week were compared,and the ratios of BMD,BS/BV,BV/TV,Tb.Th,Tb.N were measured by Micro CT,and the expressions of Bcl-2,Bax,Caspase-3 proteins were detected by immune reaction.Results:1.Compared with the normal group,the level of serum VEGF and bFGF in the model group decreased after 12 weeks of modeling(P<0.05);Compared with the model group,the levels of serum VEGF and bFGF water in the Xianlinggubao capsule group and the Quan Du Zhong capsule group increased on average at the 12th week of modeling,with statistical difference(P<0.05).The level of the Quan Du Zhong capsule group was the highest,followed by the Xianlinggubao capsule group.2.Compared with the normal group,BMD,BS/BV,BV/TV,Tb.Th and Tb.N in the model group were lower,and Tb.SP were higher,the results were statistically significant(P<0.05).Compared with the model group,the BMD,BV/TV,Tb.Th and Tb.N of Xianlinggubao capsule group and the total eucommia capsule group increased,while the BS/BV and Tb.SP decreased(P<0.05).3.The Quan Du Zhong capsule group and Xianlinggubao capsule group could significantly increase the expression of bcl-2 protein in the femoral head of dogs,which was significantly different from the model group(P<0.05).The expression of bax protein in the femoral head of dogs in the Quan Du Zhong capsule group and the Xianlinggubao capsule group was significantly reduced compared with the model group(P<0.05).The expression of caspase-3 protein in the femoral head of dogs was significantly reduced in the Quan Du Zhong capsule group and Xianlinggubao capsule group,which was significantly different from the model group(P<0.05).Conclusion:Quan Du Zhong capsule can increase the expression of VEGF and bFGF in serum,increase the expression of bcl-2,inhibit the expression of bax,and reduce the expression of caspase-3,which plays a synergistic role in the treatment of avascular necrosis of the femoral head,and has potential targets.

Effect of Yang-Warming and Kidney-Tonifying Prescription on Expression of Osteogenic and Angiogenic Factors and H-Type Vascular Markers in Steroid-Induced Avascular Necrosis of Femoral Head in Rabbits

Objective: To investigate the effect of Yang-warming and Kidney-tonifying Prescription (YKP) on the treatment of steroid-induced avascular necrosis of the femoral head (SANFH) in rabbits. And to further explore whether its therapeutic mechanism is related to the expression of HIF-1α and VEGF (angiogenic factors), BMP2 and Osterix (osteogenic factor), CD31 (type H vascular marker) and MMP13 (bone destruction-related factor). Methods: Twenty-seven healthy male New Zealand white rabbits were divided into a normal group, model group, traditional Chinese medcine (TCM) group (clinical equivalent dose group of YKP), miR-130a inhibitor group and TCM + inhibitor group. The SANFH model was established by combining horse serum with methylprednisolone. After the model is successfully established, TCM group was given 6.44 g/kg·d YKP by gavage, and the miR-130a gene inhibitor group was intraperitoneally injected with 25 mg/kg miR-130a inhibitor, locked nucleic acid (LNA)-anti-miR-130a. TCM + inhibitor group was treated with YKP intragastrically and miR-130a inhibitor intraperitoneally. The rabbits in the normal group and the model group were intragastrically administered with normal saline 10 ml/d. Once a day for 4 weeks. The avascular necrosis was detected by HE staining. The contents of HIF-1α, VEGF, BMP2 and Osterix in rabbit tissues were detected by qRT-PCR kit, and the expression of CD31 and MMP13 was detected by immunofluorescence staining. Results: In the normal group, the surface of the cartilage layer of the femoral head was smooth, the bone trabeculae were intact and densely arranged, the cells of each layer were neatly arranged, the morphology of the bone cells, the chondrocytes and the adipocytes were normal. In the model group, cartilage surfaces of the femoral head showed exfoliative cracks. The bone trabecular structure was loose and incomplete, chondrocytes, osteoblasts and bone marrow cells were significantly reduced, and the number of empty bone traps was significantly increased. In the TCM-treated group, more chondrocytes, thicker cartilage layer, and more regular bone trabeculae were detected as compared to model rabbits. In contrast, the cartilage layer was thinner, the destruction and fracture of bone trabeculae was more serious, chondrocytes and osteocytes were decreased as compared to model group. The expression of HIF-1α, VEGF, BMP2, and Osterix in the model group decreased significantly as compared to the normal group (P Conclusion: YKP can regulate the expression of angiogenic-related factors (VEGF and HIF-α), osteogenic-related factors (BMP2 and Osterix), and H-type vascular marker CD31, resulting in increased expressions of VEGF, HIF-α, BMP2, and Osterix, which promote intra-femoral head revascularization. Meanwhile, YKP decreased the expression of bone-destruction-related factor MMP13, thus enhancing the ability of bone tissue to repair itself. Regulation of these molecules’ expression may be one of the mechanisms of YKP in the treatment of hormonal femoral head necrosis.

Efficacy and risk factors for anxiety and depression after miniincision hip arthroplasty for femoral head osteonecrosis

BACKGROUND Osteonecrosis of the femoral head(ONFH)is a prevalent orthopedic issue,leading to the collapse and fragmentation of the femoral head in its advanced stages,which can severely impair patients'quality of life.Total hip arthroplasty(THA)is a clinical intervention frequently used to alleviate ONFH symptoms and reinstate hip functionality.The conventional surgical technique is invasive and comes with an extended recuperation period,posing significant challenges for patients.With the progression of medical technology,the use of the mini-incision technique in minimally invasive THA(MITHA)has become more prevalent.However,comparative studies examining the effectiveness of these two surgical procedures in treating ONFH remain scarce.Furthermore,understanding patients'psychological well-being is crucial given its profound influence on postoperative recuperation.AIM To evaluate the impact of mini-incision MITHA on ONFH treatment and to identify the risk factors associated with postoperative anxiety and depression.METHODS A retrospective study was conducted on 125 patients treated for ONFH at Xi’an Hong Hui Hospital between February 2020 and January 2022,with the term"consecutive"indicating that these patients were treated in an unbroken sequence without any selection.Among these,60 patients(control group)underwent traditional THA,while 65 patients(observation group)were treated with miniincision MITHA.Variations in the visual analog scale(VAS)score and the Harris hip score were monitored.Additionally,shifts in pre-and posttreatment Hamilton anxiety(HAMA)and Hamilton depression(HAMD)scale scores were recorded.Patients with both postoperative HAMA and HAMD scores of≥8 were identified as those experiencing negative emotions.Logistic regression was utilized to analyze the determinants influencing these negative emotional outcomes.Comparative analyses of surgical and postoperative metrics between the two groups were also conducted.RESULTS Posttreatment results indicated a significantly higher VAS score in the control group than in the observation group,while the Harris score was considerably lower(P<0.0001).The observation group benefited from a notably shorter operation duration,reduced blood loss,diminished incision size,and a decreased postoperative drainage time(P<0.0001),accompanied by a reduced hospital stay and lower treatment costs(P<0.0001).The control group had elevated posttreatment HAMA and HAMD scores in comparison to the observation group(P<0.0001).Multivariate logistic regression revealed that being female[odds ratio(OR):4.394,95%CI:1.689-11.433,P=0.002],having a higher postoperative VAS score(OR:5.533,95%CI:2.210-13.848,P<0.0001),and having higher treatment costs(OR:7.306,95%CI:2.801-19.057,P<0.0001)were significant independent determinants influencing postoperative mood disturbances.CONCLUSION Compared to conventional THA,mini-incision MITHA offers advantages such as reduced operation time,minimal bleeding,and a shorter incision in ONFH patients.Moreover,factors such as sex,postoperative pain(reflected in the VAS score),and treatment costs significantly impact postoperative anxiety and depression.

Microstructures and properties of cancellous bone of avascular necrosis of femoral heads

The aim of this study is to investigate microscopic structure and characterize cancellous bone of avascular necrosis of the femoral head （ANFH）. The rabbit model of the ANFH is established. The histopathologic features are studied successfully. The differences between the steroidinjection group （S.G.） and the controlled group （C.G.） are examined, including the weight of rabbits, the hematological examination and the three-dimensional stnactures. It is found that the plasma levels of cholesterol （CHO）, high-density lipoprotein （HDL） and low-density lipoprotein （LDL） in S.G. are lower than those in C.G. when the triglyceride （TG） increased in the S.G.; but the bone mineral content （BMC） and the structural model index （SMI） of the organ and tissue decreased significantly in S.G. Three-dimensional structures of the femoral head are obtained using micro-computed tomography （CT） scanning and the mechanical model is established to analyze the influences of these structural changes on the mechanical properties of the cancellous bone.

Clinical Value of ABCB1 and PAI-1 Gene Polymorphisms in Predicting Glucocorticoid-induced Adverse Reactions in Nephrotic Syndrome Patients

Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.

A Study on the Correlativity of MRI Signal Classifications with TCM Syndromes in Femoral Head Necrosis Patients

Objective:To probe into the relation between magnetic resonance imaging(MRI) signal classifications and TCM syndromes in femoral head necrosis patients,so as to provide reference for TCM diagnosis of this disease.Methods:Refering to the criteria for TCM syndrome types of necrosis of the femoral head described in "The Guiding Principles of Clinical Studies of New Chinese Drugs" and Shimizu and Mitchell's MRI signal classifications,MRI signal classifications between different TCM syndrome types were compared.Results:The Shimizu signal classification of different TCM syndrome types had statistically significant difference(P=0.04);Both T2WI+fs and Mitchell signal classifications of different TCM syndrome types had no statistical by significant differences(P=0.42 or P=0.15).Conclusion:There is a certain correlativity of TCM syndrome types of necrosis of the femoral head with T1WI signal classification of MRI.MRI signal classification may contribute to objectivity in TCM syndrome typing of this disease.

Reconstructing avascular necrotic femoral head through a bioactiveβ-TCP system:From design to application

A variety of techniques have been used for treating avascular necrosis of the femoral head(ANFH),but have frequently failed.In this study,we proposed aβ-TCP system for the treatment of ANFH by boosting revascularization and bone regeneration.The angio-conductive properties and concurrent osteogenesis of the highly interconnected porousβ-TCP scaffold were revealed and quantified through an in vivo model that simulated the ischemic environment of ANFH.Mechanical test and finite element analysis showed that the mechanical loss caused by tissue necrosis and surgery was immediately partially compensated after implantation,and the strength of the operated femoral head was adaptively increased and eventually returned to normal bone,along with continuous material degradation and bone regeneration.For translational application,we further conducted a multi-center open-label clinical trial to assess the efficacy of theβ-TCP system in treating ANFH.Two hundred fourteen patients with 246 hips were enrolled for evaluation,and 82.1%of the operated hips survived at a 42.79-month median follow-up.The imaging results,hip function,and pain scores were dramatically improved compared to preoperative levels.ARCO stage II disease outperformed stage III in terms of clinical effectiveness.Thus,bio-adaptive reconstruction using theβ-TCP system is a promising hip-preserving strategy for the treatment of ANFH.

Diagnosis with Multiple Epiphyseal Dysplasia Using Whole-exome Sequencing in a Chinese Family

Multiple epiphyseal dysplasia （MED; EDMI, OMIM 132400; EDM2, OMIM 600204; EDM3, OMIM 600969; EDM4, OMIM 226900; EDM5~ OMIM 607078; EDM6, OMIM 614135） is an autosomal dominant inherited disease of the skeletal system, characterized by mild short stature and early-onset degenerative joint disease, caused by heterogeneous genotypes involving more than six genes （COMP, COL9A 1, COL9A2, COL9A3, MATN3, DTDST）.However, in approximately 10-20% of all samples analyzed, a mutation cannot be identified in any of the six genes mentioned above, suggesting that the presence of other unidentified causative genes is also involved in the pathogenesis of MED.