ZIF-8-Encapsulated Pexidartinib Delivery via Targeted Peptide-Modified M1 Macrophages Attenuates MDSC-Mediated Immunosuppression in Osteosarcoma.

Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF-8 and are named P@ZIF/M1-KTP. The tumor volumes in the P@ZIF/M1-KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1-KTP exhibited enhanced anti-tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1-KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA-seq further confirms the enhanced immune cell function. Consequently, P@ZIF/M1-KTP has great potential as a novel adoptive cellular therapeutic strategy for tumors.

Investigating the synergy of Shikonin and Valproic acid in inducing apoptosis of osteosarcoma cells via ROS-mediated EGR1 expression.

BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumour with a poor prognosis. Shikonin (SHK) is derived from the traditional Chinese medicine Lithospermum that has been extensively studied for its notable anti-tumour effects, including for osteosarcoma. However, its application has certain limitations. Valproic acid (VPA) is a histone deacetylase inhibitor (HDACI) that has recently been employed as an adjunctive therapeutic agent that allows chromatin to assume a more relaxed state, thereby enhancing anti-tumour efficacy. PURPOSE: This study was aimed to investigate the synergistic anti-tumour efficacy of SHK in combination with VPA and elucidate its underlying mechanism. METHODS/STUDY DESIGN: CCK-8 assays were utilized to calculate the combination index. Additional assays, including colony formation, acridine orange/ethidium bromide double fluorescent staining, and flow cytometry, were employed to evaluate the effects on osteosarcoma cells. Wound healing and transwell assays were utilized to assess cell mobility. RNA sequencing, PCR, and Western blot analyses were conducted to uncover the underlying mechanism. Rescue experiments were performed to validate the mechanism of apoptotic induction. The impact of SHK and VPA combination treatment on primary osteosarcoma cells was also assessed. Finally, in vivo experiments were conducted to validate its anti-tumour effects and mechanism. RESULTS: The combination of SHK and VPA synergistically inhibited the proliferation and migration of osteosarcoma cells in vitro and induced apoptosis in these cells. Through a comprehensive analysis involving RNA sequencing, PCR, Western blot, and rescue experiments, we have substantiated our hypothesis that the combination of SHK and VPA induced apoptosis via the ROS-EGR1-Bax axis. Importantly, our in vivo experiments corroborated these findings, demonstrating the potential of the SHK and VPA combination as a promising therapeutic approach for osteosarcoma. CONCLUSION: The combination of SHK and VPA exerted an anti-tumour effect by inducing apoptosis through the ROS-EGR1-Bax pathway. Repurposing the old drug VPA demonstrated its effectiveness as an adjunctive therapeutic agent for SHK, enhancing its anti-tumour efficacy and revealing its potential value. Furthermore, our study expanded the application of natural compounds in the anti-tumour field and overcame some of their limitations through combination therapy. Finally, we enhanced the understanding of the mechanistic pathways linking reactive oxygen species (ROS) accumulation and apoptosis in osteosarcoma cells. Additionally, we elucidated the role of EGR1 in osteosarcoma cells, offering novel strategies and concepts for the treatment of osteosarcoma.

Umbilical cord mesenchymal stem cells relieve osteoarthritis in rats through immunoregulation and inhibition of chondrocyte apoptosis.

This study aims to investigate the effectiveness of umbilical cord mesenchymal stem cells (UCMSCs) in treating osteoarthritis (OA). Sprague-Dawley rats were used in in vivo experiments and divided into four groups: normal, OA model, saline, and UCMSC-treated groups (n = 6). An OA model was established by injecting iodoacetic acid into the joint cavity. The results indicate that UCMSC transplantation significantly reduced joint surface and articular cartilage damage, and the levels of IL-1ß, TNF-α, and MMP13 in the joint fluid were significantly reduced after UCMSC treatment. In vitro experiments showed that co-culturing UCMSCs and chondrocytes promoted the expression of aggrecan, COL2, SOX9, and BCL-2; downregulated the expression of BAX and BAD in chondrocytes; and promoted the expression of IL-10 and TGF-ß1 in UCMSCs. Additionally, the supernatant of UCMSCs inhibited the expression of IL-1ß and TNF-α in the articular cavity and promoted the expression of COL2 and aggrecan in vivo. These effects were impaired when IL-10 and TGF-ß1 were removed. Collectively, UCMSC transplantation appears to improve joint pathology, reduce inflammatory factors, and decrease chondrocyte apoptosis, likely through the involvement of IL-10 and TGF-ß1, thus providing a potential therapeutic option for patients with OA.

Strategy insight: Mechanical properties of biomaterials' influence on hydrogel-mesenchymal stromal cell combination for osteoarthritis therapy.

Osteoarthritis (OA) is a kind of degenerative joint disease usually found in older adults and those who have received meniscal surgery, bringing great suffering to a number of patients worldwide. One of the major pathological features of OA is retrograde changes in the articular cartilage. Mesenchymal stromal cells (MSCs) can differentiate into chondrocytes and promote cartilage regeneration, thus having great potential for the treatment of osteoarthritis. However, improving the therapeutic effect of MSCs in the joint cavity is still an open problem. Hydrogel made of different biomaterials has been recognized as an ideal carrier for MSCs in recent years. This review focuses on the influence of the mechanical properties of hydrogels on the efficacy of MSCs in OA treatment and compares artificial materials with articular cartilage, hoping to provide a reference for further development of modified hydrogels to improve the therapeutic effect of MSCs.

Silencing eL31 suppresses the progression of colorectal cancer via targeting DEPDC1.

BACKGROUND: Colorectal cancer (CRC) is one of the most commonly diagnosed human malignancies. Ribosomal protein L31 (RPL31, aka eL31) is a component of the 60S large ribosomal subunit, and its expression pattern and functional role in CRC have not been reported. METHODS: Herein, we identified that eL31 protein level was dramatically increased in CRC tissues through using IHC analysis. More notably, elevated eL31 was associated with larger tumor size and shorter overall survival. Besides, we evaluated the effects of eL31 depletion on CRC cell phenotypes in vitro. RESULTS: The data indicated that eL31 knockdown restricted CRC cell proliferation, migration and colony formation whilst enhancing cell apoptosis. Importantly, eL31 was also essential for CRC tumor growth in vivo, as demonstrated by impaired tumor growth markers and reduced Ki67 levels in xenografts from eL31-depleted cells. In addition, our evidence indicated that DEP domain containing 1 (DEPDC1) was a potential downstream target of eL31 in regulating CRC. Consistently, DEPDC1 depletion restrained CRC cell proliferation and migration, as well as facilitated cell apoptosis. More interestingly, DEPDC1 depletion could reverse the promotion effects of eL31 elevation on CRC cells. CONCLUSIONS: Identification of eL31's function in CRC may pave the way for future development of more specific and more effective targeted therapy strategies against CRC.

Establishment and evaluation of a specific antibiotic-induced inflammatory bowel disease model in rats.

Physical and chemical methods for generating rat models of enteritis have been established; however, antibiotic induction has rarely been used for this purpose. The present study aimed to establish and evaluate a rat model of inflammatory bowel disease (IBD) using antibiotics. A total of 84 Sprague-Dawley (SD) rats were divided into the following groups, according to the dosage and method of administration of the antibiotics: A, control; B, low-dose clindamycin; C, medium-dose clindamycin; D, high-dose clindamycin; E, low-dose clindamycin, ampicillin and streptomycin; F, medium-dose clindamycin, ampicillin and streptomycin; and G, high-dose clindamycin, ampicillin and streptomycin. Antibiotic administration was stopped on day 7; the modeling period covered days 1-7, and the recovery period covered days 8-15. Half of the animals were dissected on day 11, with the remaining animals dissected on day 15. Food and water intake, body weight and fecal weight were recorded. Intestinal flora was analyzed via microbial culture and quantitative PCR. The content of TNF-α, IL1-ß, IL-6 and C-reactive protein (CRP) was assessed in abdominal aorta blood. Colonic and rectal tissues were examined pathologically via hematoxylin-eosin staining to assess leukocyte infiltration and intestinal mucosal changes as indicators of inflammation. Rat weight, food intake, water intake and 2-h fecal weight were significantly different across the experimental groups (P = 0.040, P = 0.016, P<0.001 and P = 0.009, respectively). Microbial cultures revealed no significant differences between group A and B,C (P = 0.546,0.872) but significant differences betwenn group A and the other experimental groups (all P<0.001). Furthermore, significant differences in the levels of Bacteroides, Faecalibacterium prausnitzii and Dialister invisus on day 4 between groups A, C and F (P = 0.033, P = 0.025 and P = 0.034, respectively). Significant differences were detected in the levels of TNF-α, IL1-ß, IL-6 and CRP between the groups (all P<0.001). The colonic and rectal pathological inflammation scores of the experimental groups were significantly different compared with group A (B vs. A, P = 0.002; others, all P<0.001). These findings indicated that an antibiotic-induced IBD model was successfully established in SD rats; this animal model may serve as a useful model for clinical IBD research.

Molecular mechanisms of mechanical load-induced osteoarthritis.

INTRODUCTION: Mechanical loading enhances the progression of osteoarthritis. However, its molecular mechanisms have not been established. OBJECTIVE: The aim of this review was to summarize the probable mechanisms of mechanical load-induced osteoarthritis. METHODS: A comprehensive search strategy was used to search PubMed and EMBASE databases (from the 15th of January 2015 to the 20th of October 2020). Search terms included "osteoarthritis", "mechanical load", and "mechanism". RESULTS: Abnormal mechanical loading activates the interleukin-1ß, tumour necrosis factor-α, nuclear factor kappa-B, Wnt, transforming growth factor-ß, microRNAs pathways, and the oxidative stress pathway. These pathways induce the pathological progression of osteoarthritis. Mechanical stress signal receptors such as integrin, ion channel receptors, hydrogen peroxide-inducible clone-5, Gremlin-1, and transient receptor potential channel 4 are present in the articular cartilages. CONCLUSION: This review highlights the molecular mechanisms of mechanical loading in inducing chondrocyte apoptosis and extracellular matrix degradation. These mechanisms provide potential targets for osteoarthritis prevention and treatment.

Development and Verification of a Hypoxic Gene Signature for Predicting Prognosis, Immune Microenvironment, and Chemosensitivity for Osteosarcoma.

Objective: Hypoxic tumors contribute to local failure and distant metastases. Nevertheless, the molecular hallmarks of hypoxia remain ill-defined in osteosarcoma. Here, we developed a hypoxic gene signature in osteosarcoma prognoses. Methods: With the random survival forest algorithm, a prognostic hypoxia-related gene signature was constructed for osteosarcoma in the TARGET cohort. Overall survival (OS) analysis, receiver operating characteristic (ROC) curve, multivariate cox regression analysis, and subgroup analysis were utilized for assessing the predictive efficacy of this signature. Also, external validation was presented in the GSE21257 cohort. GSEA was applied for signaling pathways involved in the high- and low-risk samples. Correlation analyses between risk score and immune cells, stromal/immune score, immune checkpoints, and sensitivity of chemotherapy drugs were performed in osteosarcoma. Then, a nomogram was built by integrating risk score, age, and gender. Results: A five-hypoxic gene signature was developed for predicting survival outcomes of osteosarcoma patients. ROC curves confirmed that this signature possessed the well predictive performance on osteosarcoma prognosis. Furthermore, it could be independently predictive of prognosis. Metabolism of xenobiotics by cytochrome P450 and nitrogen metabolism were activated in the high-risk samples while cell adhesion molecules cams and intestinal immune network for IgA production were enriched in the low-risk samples. The low-risk samples were characterized by elevated immune cell infiltrations, stromal/immune scores, TNFRSF4 expression, and sensitivity to cisplatin. The nomogram accurately predicted 1-, 3-, and 5-years survival duration. Conclusion: These findings might offer an insight into the optimization of prognosis risk stratification and individualized therapy for osteosarcoma patients.

Composite Coating of Graphene Oxide/TiO2 Nanotubes/HHC-36 Antibacterial Peptide Construction and an Exploration of Its Bacteriostat and Osteogenesis Effects.

Graphene oxide (GO), a kind of polymer, is often selected as a controlled released agent, whereas titanium dioxide (TiO2) nanotubes are commonly used as a drug-coated carrier. This study was conducted to develop methods for manufacturing the GO/TiO2/HHC-36 composite coating and exploring its bacteriostat and osteogenesis properties. The GO/TiO2 nanotubes were prepared by electrochemical methods and HHC-36 was then adsorbed to GO/TiO2to obtain GO/TiO2/HHC-36. Sustained release of HHC-36 was analyzed and the antibacterial effect was examined by the inhibition zone test. The biocompatibility and osteogenesis in vitro of GO/TiO2/HHC-36 were explored. Finally, the osteogenesic property of the composite coating was investigated in a rat femoral defect model in vivo. GO/TiO2/HHC-36 was successfully prepared and had good controlled released performance in vitro. The inhibit zone size of S. aureus was 2.1 mm and that of E. coli was 3.0 mm. GO/TiO2/HHC-36 showed good biocompatibility with mesenchymal stem cells (MSCs) and promoted their adhesion, migration, and differentiation. In addition, the secretion of alkaline phosphatase, collagen, mineralized matrix and osteoblast-related nutrient factors of MSCs was increased after treatment with GO/TiO2/HHC-36. Furthermore, GO/TiO2/HHC-36 also stimulated endotheliocytes to secrete VEGF, leading to angiogenesis. Finally, implantation of GO/TiO2/HHC-36 in the rat femur defect model resulted in MSC migration and increased expression of osteoblast related proteins. The composite coating with controlled released of HHC-36 showed distinct antibacterial properties and promoted osteogenesis in vitro and in vivo.

The impact of miR-9 in osteosarcoma: A study based on meta-analysis, TCGA data, and bioinformatics analysis.

The function of miR-9 in osteosarcoma is not well-investigated and controversial. Therefore, we conducted meta-analysis to explore the role of miR-9 in osteosarcoma, and collected relevant TCGA data to further testify the result. In addition, bioinformatics analysis was conducted to investigate the mechanism and related pathways of miR-9-3p in osteosarcoma.Literature search was operated on databases up to February 19, 2020, including PubMed, Web of Science, Science Direct, Cochrane Central Register of Controlled Trials, and Wiley Online Library, China National Knowledge Infrastructure, China Biology Medicine disc, Chongqing VIP, and Wan Fang Data. The relation of miR-9 expression with survival outcome was estimated by hazard ratio (HRs) and 95% CIs. Meta-analysis was conducted on the Stata 12.0 (Stata Corporation, TX). To further assess the function of miR-9 in osteosarcoma, relevant data from the TCGA database was collected. Three databases, miRDB, miRPathDB 2.0, and Targetscan 7.2, were used for prediction of target genes. Genes present in these 3 databases were considered as predicted target genes of miR-9-3p. Venny 2.1 were used for intersection analysis. Subsequently, GO, KEGG, and PPI network analysis were conducted based on the overlapping target genes of miR-9-3p to explore the possible molecular mechanism in osteosarcoma.Meta-analysis shown that overexpression of miR-9 was associated with worse overall survival (OS) (HR = 4.180, 95% CI: 2.880-6.066, P < .001, I = 23.5%). Based on TCGA data, osteosarcoma patients with overexpression of miR-9-3p (HR = 1.603, 95% CI: 1.028-2.499, P = .037) and miR-9-5p (HR = 1.698, 95% CI: 1.133-2.545, P = .01) also suffered poor OS. In bioinformatics analysis, 2 significant and important pathways were enriched: Wnt signaling pathway from gene ontology analysis (gene ontology:0016055, P-adjust = .008); hippo signaling pathway from Kyoto Encyclopedia of Genes and Genomes analysis (P-adjust = .007). Moreover, network analysis relevant protein-protein interaction was visualized, revealing 117 nodes and 161 edges.High miR-9 expression was associated with poor prognosis. Based on bioinformatics analysis, this study enhanced the understanding of the mechanism and related pathways of miR-9 in osteosarcoma.

Role of the PGE2 receptor in ischemia-reperfusion injury of the rat retina.

Purpose: To investigate the function and expression of the PGE2 receptors EP1-4 in rat retinal ischemia-reperfusion (I/R) injury and to determine the regulatory role of resveratrol (RES) in this process. Methods: In vitro, we stimulated primary astrocytes extracted from the optic disc of rats with epidermal growth factor (EGF) and RES, and detected the location of EP1-4 expression with immunofluorescence. The expression of antiglial fibrillary acidic protein (GFAP), EGF receptor (EGFR), inducible NOS (iNOS), and EP1-4 in astrocytes was detected with western blotting. In vivo, we established an I/R injury model and RES treatment model with Sprague-Dawley rats. Changes in the thickness of the inner retina were observed with hematoxylin and eosin (H&E) staining. EP1-4 localization in the retina was observed with immunohistochemistry. The expression of COX-2, iNOS, and EP1-4 in the control and model groups was detected with western blotting. Results: In this study, immunofluorescence and immunohistochemistry showed that EP1-4 are expressed in astrocytes and the rat retina. EGF stimulation increased the expression of EGFR, iNOS, EP1, EP2, and EP4 in astrocytes. The expression of EP1-4 was statistically significantly increased on the third day after model induction, and EP1-4 expression decreased to normal levels on day 7. EGF and RES mediated the decrease in the expression of EP2. RES treatment significantly reduced retinal damage and RGC loss, as demonstrated by the relatively intact tissue structure on day 7 observed with H&E staining. Moreover, inflammation was associated with this I/R injury model, as demonstrated by the early induction of proinflammatory mediators, and this inflammation was significantly attenuated after RES treatment. Conclusions: These results indicate that the COX-2/PGE2/EPs pathway is involved in retinal damage and astrocyte inflammation. In addition, the results suggest that the neuroprotective effects of RES may be associated with decreased production of inflammatory mediators. These results suggest that the PGE2 receptor may be a key factor in the treatment of neurodegenerative diseases, and that RES may be used as a possible therapeutic strategy for glaucoma.

Doxycycline Attenuates Atrial Remodeling by Interfering with MicroRNA-21 and Downstream Phosphatase and Tensin Homolog (PTEN)/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway.

BACKGROUND Atrial remodeling especially in the form of fibrosis is the most important substrate of atrial fibrillation (AF). The aim of this study was to investigate the effects of doxycycline on chronic intermittent hypoxia (CIH)-induced atrial remodeling and the pathophysiological mechanisms underlying such changes. MATERIAL AND METHODS A total of 30 Sprague-Dawley rats were randomized into 3 groups: Control group, CIH group, and CIH with doxycycline treatment group. CIH rats were subjected to CIH 6 h/d for 30 days and treatment rats were administrated doxycycline while they received CIH. After the echocardiography examination, rats were sacrificed at 31 days. The tissues of atria were collected for histological and molecular biological experiments, Masson staining was used to evaluate the extent of atrial fibrosis, microRNA-21, and its downstream target phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K) were assessed. RESULTS Compared to the control group, the CIH rats showed higher atrial interstitial collagen fraction, increased microRNA-21, PI3K levels, and decreased PTEN levels. Doxycycline treatment attenuated CIH-induced atrial fibrosis, reduced microRNA-21 and PI3K, and increased PTEN. CONCLUSIONS CIH induced significant atrial remodeling, which was attenuated by doxycycline in our rat model. These changes may be explained due to alterations in the microRNA-21-related signaling pathways by doxycycline.

Overexpression of miR-92a promotes the tumor growth of osteosarcoma by suppressing F-box and WD repeat-containing protein 7.

MicroRNAs (miRNAs) have been reported to be critical players in osteosarcoma (OS). Among numerous cancer-related miRNAs, the expression level of miR-92a and its potential role in OS has not been investigated. Here, We showed that overexpression of miR-92a was identified in OS specimens and cells compared to normal bone tissues. The high level of miR-92a was correlated with high T classification and advanced clinical stages of OS patients. Notably, miR-92a highly expressing OS patients showed a notably reduced survival rate. In vitro experiments showed that loss of miR-92a inhibited U2OS cell proliferation and cell-cycle progression while induced apoptosis. In turn, its restoration facilitated MG-63 cell growth and suppressed apoptosis. Experimental nude mice showed that miR-92a silencing prohibited the in vivo growth of OS cells. Furthermore, bioinformatics software predicted that F-box and WD repeat-containing protein 7 (FBXW7) was a direct target of miR-92a. We then observed the negative regulation of miR-92a on FBXW7 expression and the direct binding between them was further verified by dual-luciferase assays in OS cells. Forced expression of FBXW7 resulted in reduced proliferation, cell cycle arrest at G1 phase and increased apoptosis in miR-92a overexpressing MG-63 cells. In summary, this study demonstrates miR-92a probably functions as a driver of tumor progression by targeting FBXW7, and highlights the potential effects of miR-92a on prognosis and treatment of OS.

HSP90B1 overexpression predicts poor prognosis in NSCLC patients.

Non-small cell lung cancer (NSCLC) accounts for 85 % of lung cancer-related mortality worldwide. The heat shock protein 90B1 (HSP90B1) and DNA damage-inducible transcript 3 (DDIT3) are endoplasmic reticulum stress-related proteins that are associated with many malignancies. However, the roles of two proteins on NSCLC remain uncovered. To investigate the correlation between the expressions of HSP90B1 and DDIT3 and clinicopathological parameters of NSCLC as well as the significance of prognosis in NSCLC, a total of 143 NSCLC tissue samples and 45 control tissues samples were assessed. NSCLC patients were followed up from the day of surgery and ended by March 2014. The expressions of HSP90B1 and DDIT3 proteins were detected in all paraffin-embedded biopsy samples by immunochemistry. The HSP90B1 was highly expressed (65.2 %) in the 143 NSCLC patients, and its high expression was correlated with clinical stages (P = 0.001) and lymph node metastasis (P = 0.016). Similarly, DDIT3 was highly expressed in 43 (30.1 %) of 143 NSCLC patients, but only correlated with lymph node metastasis. Furthermore, Log-rank test suggested that high HSP90B1 expression may predict shorter survival (overall survival (OS)) and disease-free survival (DFS) for NSCLC patients. Cox model multivariate analyses indicated that HSP90B1 overexpression was an independent poor prognostic factor for both of OS and DFS. Therefore, HSP90B1 and DDIT3 may the potential biomarker to predict the NSCLC clinicopathological progress. Meanwhile, high HSP90B1 expression means poor prognosis, and HSP90B1 can be a promising prognosis factor for NSCLC.

[Reconstruction of hip center in total hip arthroplasty for developmental dysplasia of hip].

OBJECTIVE: To explore the surgical technique and the effectiveness of reconstructing the hip center in total hip arthroplasty (THA) for developmental dysplasia of hip (DDH). METHODS: Between January 2004 and January 2010, 29 patients (32 hips) with DDH underwent THA. There were 6 males (6 hips) and 23 females (26 hips), aged 45-67 years (mean, 50.6 years). The locations were left side in 22 hips and right side in 10 hips. According to Crowe classification, 12 hips were rated as Crowe I and 20 hips as Crowe II. The patients had limb length discrepancy of 1.9-4.4 cm. The Harris score was 50.7 +/- 8.6. RESULTS: All incisions healed by first intension. Posterior hip dislocation occurred in 1 case (1 hip) after operation. All patients were followed up 2 years-4 years and 6 months (mean, 2.3 years). The lower limbs were lengthened by 0.5-5.8 cm (mean, 2.5 cm). The Harris score was 87.7 +/- 5.9 at 1 year after operation, showing significant difference when compared with preoperative score (t = 21.77, P = 0.00). X-ray films showed loosening of acetabular component in 1 case (1 hip) and displacement of acetabular component with too large abduction angle in 1 case (1 hip); no loosening and subsidence of acetabular or femoral components occurred in the other patients during follow-up. The horizontal location of hip center, the vertical distance between teardrop and the hip center, the vertical acetabular abduction angle, and the femoral offset were better than those before operation (P < 0.05). CONCLUSION: For DDH patients, reconstructing the hip center in THA can lengthen the limb, improve the joint function, and reduce the failure rate of joint replacement.

[Analysis of perioperation complications of total hip arthroplasty in treating Crowe type IV developmental dysplasia of the hip].

OBJECTIVE: To evaluate the clinical effects of total hip arthroplasty (THA) for Crowe type IV developmental dysplasia of the hip (DDH) and analyze perioperative complications. METHODS: From March 2000 to March 2010, 19 patients (23 hips, of them, 4 patients with bilateral hips) with Crowe type IV DDH underwent THA. There were 5 males and 14 females, with average age of 61.3 years (ranged, 41 to 72 years). All hips were treated with small acetabular components combined with medial protrusion technique in acetabular reconstruction, as well as subtrochanteric shortening osteotomy in femur. Joint function of hips were evaluated according to Harris scoring. RESULTS: All patients were followed up with an average of 4.2 years (ranged, 1 to 8 years). Postoperative X-ray films showed all acetabular prosthesis were in true acetabulum. No loosening and nonunion were found in all patients. Harris scoring improved from preoperative 34.0 +/- 6.9 to postoperative 85.0 +/- 7.5. Complications occurred in 11 cases in the patients, including femoral split fracture in 3 cases, nerve injury in 3 cases, delayed union in 2 cases, dislocation in 3 cases. CONCLUSION: Total hip arthroplasty using small acetabular component, medial protrusion, femoral subtrochanteric shortening osteotomy technique for the Crowe type IV DDH can effectively restore hip function and leg length. But incidence of complications is high. The long-term follow-up is necessary for further study.

Effects of human midkine on spontaneous resorption of herniated intervertebral discs.

This study was performed in 36 rabbits to investigate the role of midkine (MK) in the resorption of herniated intervertebral discs. The L(1-2) disc was excised and immersed in one of three kinds of solution for two hours before relocation into the L4 epidural space. In the MK-treated group, the weight of relocated intervertebral discs decreased more over time than in the control group. Newly formed vessels and inflammatory cells were more frequently observed in the MK-treated group than in the control group two weeks after surgery. The degradation of matrix was more significant in the MK-treated group than in the control group four weeks after surgery. Larger areas were replaced by fibrous tissues in the MK-treated group eight weeks after surgery. Thus, MK can accelerate the resorption of the intervertebral disc relocation to the epidural space. Epidural injection of MK may contribute to the therapy of lumber disc herniation.