Multivariable analysis of anatomic risk factors for anterior cruciate ligament injury in active individuals.

OBJECTIVE: The aim of the present study was to compare the morphometric differences between patients with or without anterior cruciate ligament (ACL) injury, and identify the anatomic risk factors associated with ACL injury in active individuals. METHODS: The knee joint magnetic resonance images (MRI) of 100 subjects were included in this study. Data from the ACL-injured group (50 patients) and matched controls (50 subjects) were obtained from the same hospital. These data were analyzed by univariable analysis or multivariable conditional logistic regression analysis to examine the effects of the following variables on the risk of suffering ACL injury for the first time: TT-TG distance, medial and lateral tibial slope, intercondylar notch width and depth, femur condylar width, lateral femoral condylar depth, notch width index (NWI), notch shape index (NSI), notch depth index (NDI), and cross-sectional area (CSA). RESULTS: In the univariable analysis, the ACL-injured group had a larger TT-TG distance, increased medial and lateral tibial slope, narrower intercondylar notch width, deeper lateral femoral condylar depth, lesser NWI and NSI, and CSA when compared with the control group (P < 0.05). However, there were no significant between-group differences in intercondylar notch depth (P = 0.174), femur condylar width (P = 0.797), and NDI (P = 0.436). The multivariable analysis revealed that TT-TG distance [odds ratio (OR) = 1.37, 95% CI = 1.04-1.81, P = 0.028], medial tibial slope (OR = 1.30, 95% CI = 1.02-1.66, P = 0.036) and NWI (OR = 0.46, 95% CI = 0.24-0.91, P = 0.025) had significant multivariable associations with the sole independent risk of ACL injury. CONCLUSION: Larger TT-TG distance, increased MTS, and lesser NWI are independent anatomic risk factors for active individuals with ACL injury. LEVEL OF EVIDENCE: Case-control study; Level of Evidence, III.

Long non-coding RNA ASBEL promotes osteosarcoma cell proliferation, migration, and invasion by regulating microRNA-21.

Osteosarcoma is the most common malignant bone tumor in children and adolescents with high rate of incidence, high frequency of recurrence, and high degree of metastasis. This study aimed to investigate the effects of long noncoding RNA antisense ncRNA in the abundant in neuroepithelium area (ANA)/B-cell translocation gene 3 (BTG3) locus (lncRNA ASBEL) on the pathogenesis of osteosarcoma. The expression levels of ASBEL in human osteoblast cells and human osteosarcoma cells were evaluated using qRT-PCR. Effects of ASBEL knockdown on cell viability, migration, and invasion were detected using trypan blue exclusion assay, cell migration, and cell invasion assay, respectively. The regulatory effects of ASBEL on microRNA-21 (miR-21) were analyzed using qRT-PCR. The roles of miR-21 and protein phosphatase 2A (PP2A), the possible downstream factor of miR-21, in osteosarcoma cell proliferation, migration, and invasion were also explored. The results showed that ASBEL was highly expressed in osteosarcoma cells. Knockdown of ASBEL inhibited osteosarcoma cell viability, migration, and invasion, as well as the expression level of miR-21. PP2A was a direct target of miR-21, which participated in the effects of ASBEL and miR-21 on the activation of phosphatidylinositol 3-kinase/protein kinase 3/glycogen synthase kinase-3ß (PI3K/AKT/GSK3ß) and mitogen-activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathways as well as the enhancement of osteosarcoma cell proliferation, migration, and invasion. In conclusion, we verified that ASBEL-miR-21-PP2A pathway might play critical regulatory effects on the pathogenesis of osteosarcoma and could be as the potential therapeutic target and biomarker for osteosarcoma treatment.

Glenoid morphology and the safe zone for protecting the suprascapular nerve during baseplate fixation in reverse shoulder arthroplasty.

PURPOSE: The purpose of this study was to investigate glenoid morphology and define the safe zone for protecting the suprascapular nerve baseplate screw during baseplate fixation in reverse shoulder arthroplasty (RSA) in a Chinese population. METHODS: Shoulder computed tomography (CT) scans from 56 subjects were retrospectively reviewed. Three-dimensional (3D) reconstruction was performed using Mimics software, and corresponding bony references were used to evaluate glenoid morphology. To standardize evaluation, the coronal scapular plane was defined. Safe fixation distances and screw placements were investigated by constructing a simulated cutting plane of the baseplate during RSA. RESULTS: Mean glenoid height was 35.83 ± 2.95 mm, and width was 27.32 ± 2.78 mm, with significant sexual dimorphism (p < 0.01). According to the cutting plane morphology, the average baseplate radius was 13.84 ± 1.34 mm. The distances from the suprascapular notch and from two bony reference points at the base of the scapular spine to the cutting plane were 30.27 ± 2.77 mm, 18.39 ± 1.67 mm and 16.52 ± 1.52 mm, respectively, with a gender-related difference. Based on the clock face indication system, the danger zone caused by the suprascapular nerve projection was oriented between the two o'clock and eight o'clock positions in reference to the right shoulder. CONCLUSIONS: Glenoid size and the safe zone for screw fixation during RSA were characterized in a Chinese population. Careful consideration of baseplate fixation and avoidance of suprascapular nerve injury are important for improved clinical outcome.

Preoperative T1 Slope as a Predictor of Change in Cervical Alignment and Range of Motion After Cervical Disc Arthroplasty.

BACKGROUND This study analyzed the effect of preoperative T1 slope on cervical alignment and range of motion (ROM) after cervical disc arthroplasty (CDA) in patients with cervical degenerative disease. MATERIAL AND METHODS This retrospective study included 32 patients with single-level symptomatic cervical disc disease who underwent CDA with the Mobi-C cervical disc prosthesis and had a mean follow-up of 26.8±6.4 months. Standing lateral, flexion, and extension X-rays of the cervical spine were obtained preoperatively and postoperatively at 24-month follow-up. Simple linear regression analysis was used to assess the impact of preoperative T1 slope on changes from preoperative values in radiologic parameters. RESULTS Compared to preoperative values, at 24-month follow-up, there was a significant increase in mean functional spinal unit (FSU) angle (+7.4°), upper adjacent segment (UAS) angle (+3.1°), and overall cervical alignment (C2-C7 angle) (+6.3°), and a significant decrease in mean lower adjacent segment (LAS) angle (-2.4°). Mean ROM of the FSU (-3.6°), LAS (-3.0°), and overall cervical spine (-11.5°) significantly decreased, and mean ROM of the UAS (+1.6°) significantly increased. There were significant correlations between preoperative T1 slope and mean change from preoperative value in FSU angle, C2-C7 angle, and ROM of the overall cervical spine (C2-C7). CONCLUSIONS T1 slope is useful for evaluating changes in the FSU angle, C2-C7 angle, and ROM of the overall cervical spine following CDA with the Mobi-C disc. Patients with a large preoperative T1 slope may be good candidates for CDA with the Mobi-C prosthesis due its motion maintenance and the fact that it has little adverse impact on sagittal alignment. It also could be a good option in terms of sagittal alignment improvement or motion maintenance for patients with kyphosis.

Study of three-dimensional morphology of the proximal femur in developmental adult dysplasia of the hip suggests that the on-shelf modular prosthesis may not be an ideal choice for patients with Crowe type IV hips.

PURPOSE: The purpose of this study was to investigate the three-dimensional morphological features of the proximal femur of developmental dysplasia of the hip (DDH). METHODS: From January 2012 to December 2014, 38 patients (47 hips) of DDH were admitted and 30 normal hips were selected as controls. All hips from both groups were examined by CT scan. CT data were imported into Mimics 17.0. Three-dimensional models of the proximal femur were then reconstructed, and the following parameters were measured: neck-shaft angle, neck length, offset, height of the centre of femoral head, level of isthmus, height of the tip of greater trochanter, the medullary canal diameter of isthmus(Di), the medullary canal diameter 10 mm above the apex of the lesser trochanter(DT + 10), the medullary canal diameter 20 mm below the apex of the lesser trochanter(DT-20), and then DT + 10/Di, DT-20/Di and DT + 10/DT-20 were calculated. RESULTS: There was no significant difference in neck-shaft angle between Crowe I, Crowe II-III DDH and the control group, while the neck-shaft angle was much smaller in Crowe IV DDH. The neck length of Crowe IV DDH was also much smaller than those of Crowe I and Crowe II-III DDH. Height of the tip greater trochanter in Crowe IV was greater than that in Crowe I, Crowe II-III DDH and the control group. The centre of femoral head in Crowe IV DDH was lower than those in Crowe I, Crowe II-III DDH and the control group. The level of isthmus in Crowe IV was much higher than those in Crowe I, Crowe II-III DDH and the control group. DT + 10, DT-20, DT + 10/Di and DT-20/Di were much smaller in Crowe IV DDH than those in Crowe I, Crowe II-III and the control group. CONCLUSIONS: Neck-shaft angle in the DDH groups was not larger than that in the control group. Comparing to Crowe I, Crowe II-III DDH and the control group, Crowe IV DDH had a dramatic change in the intramedullary and extramedullary parameters, especially the dramatic narrowing of medullary canal around the level of the lesser trochanter. The on-shelf modular prosthesis may not be an ideal choice for the Chinese patients with Crowe IV hips.

Expression of CD44 standard form and variant isoforms in human bone marrow stromal cells.

Human Bone Marrow Stromal Cells (hBMSCs) can migrate from bone marrow to injured tissues, where they may differentiate into different types of new cells for replacement of dysfunctional cells. CD44 plays an important role in stem cell movement. The expression distribution of CD44 standard form (CD44S) and CD44 variants (CD44V) is closely related to cell movement and tissue migration. The aim of this study was to evaluate the expressions of CD44S and CD44V in hBMSCs. The hBMSCs from four human subjects were cultured in vitro. Phenotypic properties were analyzed by flow cytometry, and adipocyte and osteoblast differentiations were evaluated at passage 4. The expressions of CD44S and CD44V were examined using quantitative real-time polymerase chain reaction (q-PCR). Results showed that hBMSCs were successfully cultured, with positive expressions of markers of mesenchymal cells (CD90, CD73, CD105), and negative expressions of markers of hematopoietic cells (CD34, CD45). The cultured hBMSCs can be induced to differentiate into adipocytes and osteoblasts. Q-PCR results showed that the expression of CD44S was significantly higher than the expressions of different CD44V isoforms in different samples. These results revealed significant differences in the distributions of CD44S and CD44V gene expressions, demonstrating a dominant CD44S expression in hBMCSs.

[Three dimensional reconstruction and measurement of the proximal femur in adult developmental dysplasia of the hip].

OBJECTIVE: To investigate characteristics and the differences of the anatomical parameters of the proximal femur of the developmental dysplasia of the hip (DDH). METHODS: A total of 38 patients(47 hips) diagnosed as DDH with CT scan data and the pelvis radiograph from January 2012 to December 2014 in China-Japan Union Hospital of Jilin University were retrospectively analyzed. All the hips were divided into 3 groups according to Crowe classification method. Thirty normal hips were selected as controls who admitted at the same time. CT data of the patients were imported into Mimics 17.0. The three-dimensional models of the proximal femur were then reconstructed, and the following parameters were measured: neck-shaft angle, neck length, offset, height of the centre of femoral head, height of the isthmus, height of greater trochanter, the medullary canal diameter of isthmus (Di), the medullary canal diameter 10 mm above the apex of the lesser trochanter (DT+ 10), the medullary canal diameter 20 mm below the apex of the lesser trochanter (DT-20), and then DT+ 10/Di, DT-20/Di and DT+ 10/DT-20 were calculated.Variance discrepancy analysis was used to compare the difference among the four groups, and LSD method was used to compare the difference between either two groups. RESULTS: The parameters of neck-shaft angle of DDH with Crowe I, Crowe II-III, Crowe IV and the control group were (131.8°±7.1°), (131.7°±6.5°), (122.8°±11.4°) and (131.8°±5.9°), respectively; the parameters of neck-shaft angle of DDH with Crowe IV was smaller than that of DDH with Crowe I, Crowe II-III and control group (all P<0.05). The parameters of the neck length of DDH with Crowe IV ((44.6±6.6) mm) was smaller than that of DDH with Crowe I ((48.6±6.7) mm), Crowe II-III ((50.4±4.7) mm) (all P<0.05). There is no statistic difference in the offset among the groups (F=2.392, P>0.05). The parameters of the height of greater trochanter of DDH with Crowe IV ((12.1±6.1) mm) was bigger than that of DDH with Crowe I ((8.9±7.2) mm), Crowe II-III ((7.5±3.3) mm) and control group ((6.1±3.9) mm) (all P<0.05). The parameters of the height of the centre of femoral head of DDH with Crowe I, Crowe II-III, Crowe IV were (39.6±6.5) mm, (39.1±4.2) mm, (38.8±8.6) mm, which were smaller than that of the control group ((46.5±6.2) mm) (all P<0.05). The parameters of Di of DDH with Crowe I, Crowe II-III, Crowe IV and the control group were (9.9±2.2) mm, (8.3±1.8) mm, (8.7±1.7) mm and (10.1±1.4) mm; the parameters of Di of DDH with Crowe II-III and Crowe IV were smaller than that of the control group (all P<0.05). The parameters of DT+ 10 ((17.2±5.3) mm) and DT-20 ((12.2±3.0) mm) of DDH with Crowe IV were smaller than that of DDH with Crowe I ((25.2±3.4) mm, (17.1±2.3) mm) and Crowe II-III ((21.9±4.2) mm, (16.3±3.2) mm) (all P<0.05). The parameter of the height of the isthmus of DDH with Crowe IV ((94.1±19.7) mm) was smaller than that of DDH with Crowe I ((106.2±13.8) mm), Crowe II-III ((108.8±10.5) mm) and control group ((116.5±10.6) mm), respectively (P=0.010, 0.008, 0.000). The parameters of DT+ 10/Di (2.0±0.4) and DT-20/Di (1.4±0.2) of DDH with Crowe IV were smaller than that of DDH with Crowe I (2.6±0.5, 1.8±0.3), Crowe II-III (2.7±0.60, 1.9±0.3) (all P<0.05). CONCLUSIONS: Comparing to DDH with Crowe I-III and control group, DDH with Crowe IV has a dramatic change in the intramedullary and extramedullary parameters. The isthmus and the great trochanter are higher and there is apparent narrowing of the medullary canal around the level of the lesser trochanter.

Design and synthesis of a novel series of histamine H3 receptor antagonists through a scaffold hopping strategy.

Lead compounds 5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenyl]-benzamide (1), tetrahydro-pyran-4-carboxylic acid [((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenyl]-amide (2), and 3,5-dimethyl-isoxazole-4-carboxylic acid [((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenyl]-amide (3) discovered in our laboratory, displayed high histamine H3 receptor (H3R) affinity, good selectivity and weak human Ether-à-go-go-Related Gene (hERG) channel affinity with desirable overall physico-chemical and pharmacokinetic (PK) profiles. Herein, we describe the design and synthesis of a novel series of H3R antagonists utilizing a scaffold hopping strategy. Further structure-activity relationship (SAR) studies of the series culminated in the identification of ((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-naphthalene-2-carboxylic acid (tetrahydro-pyran-4-yl)-amide (4c) and -[4-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenyl]-N-(tetrahydro-pyran-4-yl)-acetamide (4d), which exhibited good H3R affinity in vitro, good selectivity, and desirable PK properties. Compounds 4c and 4d were also assessed in cardiac safety experiments. In particular, the effects of the compounds on action potentials recorded from ventricular myocytes isolated from guinea pigs were used to screen compounds that not only displayed a low affinity towards hERG channel, but also had lower interference with other cardiac ion channels. Compound 4c did not alter the major parameters in this model system at ⩽10 µM, and no significant induction of any major haemodynamic effect when intravenously administered at 3mg/kg dose to anaesthetized mongrel dogs. Compound 4c is a new promising lead as orally potent and selective H3R antagonist belonging to a distinct structural class.

Versican 3'-untranslated region (3'-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity.

This study was designed to explore the role of versican in the development of hepatocellular carcinoma (HCC). Ectopic expression of the versican 3'-untranslated region (3'-UTR) was studied as a competitive endogenous RNA for regulating miRNA functions. We used this approach to modulate the expression of versican and its related proteins in 3'-UTR transgenic mice and in the liver cancer cell line HepG2, stably transfected with the 3'-UTR or a control vector. We demonstrated that transgenic mice expressing the versican 3'-UTR developed HCC and increased expression of versican isoforms V0 and V1. HepG2 cells transfected with versican 3'-UTR displayed increased proliferation, survival, migration, invasion, colony formation, and enhanced endothelial cell growth, but decreased apoptosis. We found that versican 3'-UTR could bind to miRNAs miR-133a, miR-199a*, miR-144, and miR-431 and also interacted with CD34 and fibronectin. As a consequence, expression of versican, CD34, and fibronectin was up-regulated by ectopic transfection of the versican 3'-UTR, which was confirmed in HepG2 cells and in transgenic mice as compared with wild-type controls. Transfection with siRNAs targeting the versican 3'-UTR abolished the effects of the 3'-UTR. Taken together, these results demonstrate that versican V0 and V1 isoforms play important roles in HCC development and that versican mRNAs compete with endogenous RNAs in regulating miRNA functions.

Design and synthesis of D1 agonist/D2 antagonist for treatment of schizophrenia.

A series of tetrahydroisoquinolines were designed, synthesized and evaluated as the first non-natural product type of compounds with dual D(1) receptor (D(1)R) agonism and D(2) receptor (D(2)R) antagonism properties for treatment of schizophrenia. The initial SAR of the series was explored. The lead in the series, 3g, exhibited high affinity and good potency. Compound 3g displayed 95% of D(1)R occupancy (10 mg/kg, sc) and 75% of D(2)R occupancy (10 mg/kg, sc) in the striatum of male CD-1 mice. The series exhibited unique pharmacology and merit as tool compounds for target validation and future optimizations.

Identification and profiling of 3,5-dimethyl-isoxazole-4-carboxylic acid [2-methyl-4-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)phenyl] amide as histamine H(3) receptor antagonist for the treatment of depression.

Lead optimization guided by histamine H3 receptor (H3R) affinity and calculated physico-chemical properties enabled simultaneous improvement in potency and PK properties leading to the identification of a potent, selective, devoid of hERG issues, orally bioavailable, and CNS penetrable H3R antagonist/inverse agonist 3h. The compound was active in forced-swimming tests suggesting its potential therapeutic utility as an anti-depressive agent. This Letter further includes its cardiovascular and neuropsychological/behavioral safety assessments.

Synthesis, characterization, and biological assessment of the four stereoisomers of the H(3) receptor antagonist 5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl[1,3']bipyrrolidinyl-1'-yl)phenyl]benzamide.

This Letter describes the asymmetric synthesis of the four stereoisomers (8a-8d) of a potent and highly selective histamine H3 receptor (H3R) antagonist, 5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl[1,3']bipyrrolidinyl-1'-yl) phenyl]benzamide (1). The physico-chemical properties, in vitro H3R affinities and ADME of 8a-8d were determined. Stereoisomer 8c (2S,3'S) displayed superior in vitro H3R affinity over other three stereoisomers and was selected for further profiling in in vivo PK and drug safety. Compound 8c exhibited excellent PK properties with high exposure, desired brain to plasma ratio and reasonable brain half life. However, all stereoisomers showed similar unwanted hERG affinities.

Discovery of aryl ureas and aryl amides as potent and selective histamine H3 receptor antagonists for the treatment of obesity (part I).

A series of structurally novel aryl ureas was derived from optimization of the HTS lead as selective histamine H3 receptor (H3R) antagonists. The SAR was explored and the data obtained set up the starting point and foundation for further optimization. The most potent tool compounds, as exemplified by compounds 2l, 5b, 5d, and 5e, displayed antagonism potencies in the subnanomolar range in in vitro human-H3R FLIPR assays and rhesus monkey H3R binding assays.

Discovery of aryl ureas and aryl amides as potent and selective histamine H3 receptor antagonists for the treatment of obesity (part II).

A novel series of histamine H3 receptor (H3R) antagonists was derived from an arylurea lead series (1) via bioisosteric replacement of the urea functionality by an amide linkage. The arylamide series was optimized through SAR studies by a broad variation of substituents in the left-hand side benzoyl residue (analogs 2a-2ag) or replacement of the benzoyl moiety by heteroarylcarbonyl residues (analogs 5a-5n). Compounds 2p and 2q were identified within the series as potent and selective H3R antagonists/inverse agonists with acceptable overall profile. Compound 2q was orally active in food intake inhibition in diet-induced obese (DIO) mice. Compound 2q represents a novel H3R antagonist template with improved in vitro potency and oral efficacy and has its merits as a new lead for further optimization.

Discovery of a potent, selective, and orally bioavailable histamine H3 receptor antagonist SAR110068 for the treatment of sleep-wake disorders.

Previous studies have shown that compound 1 displayed high affinity towards histamine H3 receptor (H3R), (human (h-H3R), K(i)=8.6 nM, rhesus monkey (rh-H3R), K(i)=1.2 nM, and rat (r-H3R), K(i)=16.5 nM), but exhibited high affinity for hERG channel. Herein, we report the discovery of a novel, potent, and highly selective H3R antagonist/inverse agonist 5a(SS) (SAR110068) with acceptable hERG channel selectivity and desirable pharmacological and pharmacokinetic properties through lead optimization sequence. The significant awakening effects of 5a(SS) on sleep-wake cycles studied by using EEG recording in rats during their light phase support its potential therapeutic utility in human sleep-wake disorders.

Zinc finger X-chromosomal protein promotes growth and tumorigenesis in human osteosarcoma cells.

OBJECTIVE: To investigate the role of Zinc finger X-chromosomal protein (ZFX) in oncogenesis of Osteosarcoma tumor. METHODS: Here, we first conducted an expression analysis of ZFX in Osteosarcoma cell lines. Then, we constructed ZFX-specific small interfering RNA (siRNA)-lentiviral vector that is capable of effectively inhibiting the expression of ZFX gene in human Osteosarcoma Saos-2 cells, and investigated systemically the impacts of ZFX silence on the growth and invasive ability of the cancer cells in vitro. Furthermore, we determined the effects of ZFX knockdown on the cell cycle distribution and apoptosis of Saos-2 cells. RESULTS: We found that ZFX inhibition resulted in significantly impaired proliferation and colony formation as well as mitigated invasiveness of Saos-2 cells. Importantly, si-ZFX infected cells exhibited a greater portion of cells at G1 phase, but a minor portion of S and G2/M phase cells. Moreover, a greater portion of sub-G1 apoptotic cells was observed in si-ZFX infected cells. CONCLUSIONS: These results strongly suggest that ZFX is a novel proliferation regulator that promotes growth of Osteosarcoma cells, and downregulation of ZFX expression induces growth suppression of Saos-2 cells via arrested G0/G1 phase cell cycle and apoptosis pathways, thereby indicating that ZFX may serve as a new molecular target for Osteosarcoma tumor therapy.

BAP1 is a good prognostic factor in advanced non-small cell lung cancer.

PURPOSE: Non-small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting epidermal growth factor receptor (EGFR) mutations have been developed, most advanced NSCLC is still incurable and new targets for anticancer drugs are in demand. BRCA1-associated protein-1 (BAP1) is a component of the ubiquitin proteasome system (UPS). UPS has emerged as a potential target for anticancer drugs. The aim of the present study was to investigate the expression of BAP1 protein in patients with NSCLC. METHODS: BAP1 expression was measured using Western blot analysis in 103 cases patients with advanced NSCLC. RESULTS: Results revealed 49 (47.5%) patients were classified with high expression of BAP1. Squamous cell carcinomas were more likely to be observed in BAP1 high expressers compared with adenocarcinomas (55.8% vs. 32.3%, p = 0.001). High BAP1 expression was associated with no lymph node metastasis (p = 0.002). There was also a significant association between BAP1 expression and histological type (p = 0.014), while expression of BAP1 was not correlated with other clinical or pathological characteristics. Kaplan-Meier survival analysis showed that patients with high BAP1 expression had a longer median survival compared with patients with low BAP1 expression (23.2 vs. 14.7 months, p = 0.021). Multivariate analysis revealed that high BAP1 expression was an independent lower risk for all 103 patients (HR = 0.61, 95% CI 0.32-0.71, p = 0.003). CONCLUSIONS: BAP1 may be a useful prognostic factor of NSCLC patients and potential target for anticancer drugs.

Acetabular Revision Arthroplasty Based on 3-Dimensional Reconstruction Technology Using Jumbo Cups.

Background: This study was aimed at evaluating the changes in cup coverage (CC) and hip center of rotation (HCOR) in acetabular defects of various severities treated with acetabular revision using jumbo cups. Methods: A total of 86 hips were included. The American Academy of Orthopedic Surgeons (AAOS) classification of these patients was as follows: 16 patients, AAOS I; 16 patients, AAOS II; and 16 patients, AAOS III. A three-dimensional (3D) implant simulation technique was used to visualize the placement of jumbo cups during revision arthroplasty. The acetabular anteversion, inclination, CC, and the HCOR were measured. Results: The inclination and anteversion of simulated acetabular cups in AAOS I-III groups were consistent with the normal acetabular anatomy. Compared with the controls, in AAOS I-III groups, the HCOR was significantly increased and CC was significantly decreased. The HCOR elevation was significantly higher in AAOS III patients than in AAOS I (p = 0.001) and AAOS II patients (p < 0.001). The use of the jumbo cup technology for acetabular revision would decrease the CC in AAOS I-III patients to 86.47, 84.78, and 74.51%, respectively. Conclusion: Our study demonstrated that in patients with acetabular defects, acetabular revision arthroplasty using jumbo cups will lead to decreased CC and HCOR upshift. Upon classifying these patients according to the AAOS classification, CC decreased with the severity of acetabular defects, and the elevation of the HCOR in AAOS III patients exceeded 10 mm and was significantly higher than in other patients.

[Research status of acetabular reconstruction in Crowe type â ¡ and â ¢ developmental dysplasia of the hip].

Developmental dysplasia of the hip (DDH) is a major cause of hip arthritis and ultimately total hip arthroplasty. Due to the dysplastic acetabulum, how to place the acetabular cup becomes a challenge in acetabular reconstruction for such patients. Especially in the acetabula classified as Crowe typeⅡand type Ⅲ, the dislocation of the femoral head causes bone defects above the true acetabulum, which will affect the stability of the acetabular cup when the acetabular reconstruction is performed at the true acetabulum. Many acetabular reconstruction methods such as bone grafting, the use of small acetabular cups, socket medialization technique, and high hip center technique are used to increase the host bone coverage of the cup. However, each method has its own shortcomings that can not be ignored so that there is no unified conclusion on the acetabular reconstruction methods for Crowe typeⅡand type Ⅲ hip dysplasia. This article summarized and evaluated various reconstruction methods in combination with the acetabular morphology of DDH, and put forward the research direction in the future.

Overexpression of LIMK1 promotes migration ability of multidrug-resistant osteosarcoma cells.

Multidrug resistance (MDR) to chemotherapy is a major obstacle in the treatment of cancer and the resistance process is multifactorial. Studies on multidrug resistance mechanisms relied on the availability of cancer multidrug resistance cell lines that have been established. In this study we successfully established a multidrug resistance cell line MG63/VCR derived from human osteosarcoma cell line MG63 based on the induction by vincristine. MG63/VCR cells exhibited high resistance to vincristine and other anticancer drugs, accompanied by upregulated expression of MDR-associated genes MDR1, MRP1, and Bcl-2. Notably, we found that MG63/VCR cells exhibited higher migration ability compared to parental MG63 cells. Moreover, we demonstrated that LIMK1, a key regulator of actin cytoskeleton, was overexpressed at both mRNA and protein levels in MG63/VCR cells and the higher LIMK1 protein level was correlated with higher level of phosphorylated cofilin. In addition, knockdown of LIMK1 abolished the higher migration ability of MG63/ VCR cells. These results suggest that LIMK1 overexpression contributes to the invasion and metastasis of drug-resistant osteosarcoma and reveal LIMK as a novel therapeutic target for drug resistant osteosarcoma.