Oleanolic acid prevents cartilage degeneration in diabetic mice via PPARγ associated mitochondrial stabilization.

Hyperglycemia-induced cartilage degeneration induces osteoarthritis (OA). Since oleanolic acid (OLA) have several pharmacological effects such as anti-inflammatory, anti-oxidant, we hypothesized it possesses protection against high glucose injured cartilage. We now report that OLA decreased type X collagen and reversed the cartilage degeneration in growth plate from db/db mice. OLA increased type Ⅱ collagen expression in a concentration-dependent manner (10-50 µΜ) in high glucose-treated chondrocytes. OLA prevented the high glucose induced cell injury and decreased the level of MMP-13, PGE2 and IL-6 due to decreasing mitochondrial membrane potential and stimulated the ATP production. Moreover, OLA treatment inhibited apoptosis. And the reversed SOD2 expression and activity may be ascribed to decreased SOD2 protein degradation by OLA treatment, via PPPAγ. In conclusion, OLA protected against the high-glucose-induced cartilage injury via PPARγ/SOD2 pathway.

Cross-cultural translation of the Western Ontario Cuff Index in Chinese and its validation in patients with rotator cuff disorders.

BACKGROUND: The Western Ontario Rotator Cuff Index (WORC) is a scale designed to evaluate the impact of rotator cuff (RC) disorders on patients' general quality of life. Our study aims to adapt the WORC for Chinese patients and to assess its reliability, validity, and responsiveness in Chinese patients with RC disorders. METHODS: First, we developed the Chinese version of the WORC (C-WORC) in a five-step procedure of translation and cross-cultural adaptation. Next, the recruiting patients finished all three rounds of scales of the C-WORC, the Medical Outcomes Study Short-Form 36 (SF-36), and the Oxford Shoulder score (OSS). Then we calculated Cronbach's alpha, the intra-class correlation coefficient (ICC), Pearson's or Spearman's correlation coefficient (r or r s), the effect size (ES), and the standardized response mean (SRM) to evaluate the reliability, validity and responsiveness of the C-WORC, respectively. RESULTS: Overall, 124 patients with RC disorders successfully completed the first two rounds of the scales, and 108 patients completed the last round of the scales. Good or excellent internal consistency (Cronbach's alpha = 0.872-0.954) was found in the overall scale and subscales of C-WORC, as well as good or excellent test-retest reliability (ICC = 0.828-0.961). Moderate or good correlations (r/r s = 0.472-0.787) were obtained between the physical subscales of the C-WORC and the OSS and the physical subscales of SF-36; the results were also obtained for the emotions subscale of the C-WORC and the mental subscales of SF-36 (r/r s = 0.520-0.713), which, adequately illustrated that good validity was included in the C-WORC. In addition, good responsiveness was also observed in the overall scale and subscales of the C-WORC (ES = 1.57-2.27, SRM = 1.52-2.28). CONCLUSIONS: The C-WORC scale is reliable, valid and responsible for the evaluation of Chinese-speaking patients with RC disorders and would be an effective instrument.

Reactive oxygen species induce cell death via Akt signaling in rat osteoblast-like cell line ROS 17/2.8.

In bones, osteoblasts are responsible for bone formation. The cell death of osteoblasts may cause a series of bone diseases and lead to bone loss, such as osteoarthrosis, hyperparathyroidism, and Paget's disease. Reactive oxygen species (ROS) are reported as a main factor for osteoblast cell death and further several bone diseases. However, the detailed mechanism is still largely unknown. Here, we found that ROS could induce cell death of rat osteoblast-like cell line ROS 17/2.8 via Akt (protein kinase B). Also, the mammalian target of rapamycin signaling was involved in this process. Our findings could help to reveal the cellular mechanism of osteoblast cell death, which is served for the pursuit of clinical treatment targets of relative bone diseases.

Comparison of 2 kinds of pedicle screws in primary spinal instrumentation: biomechanical and interfacial evaluations in sheep vertebrae in vitro.

STUDY DESIGN: Expansive pedicle screw (EPS) and polymethylmethacrylate-augmented pedicle screw (PMMA-PS) were inserted in sheep vertebrae in vitro and were evaluated by performing biomechanical tests, radiographic examinations and histological observations. OBJECTIVE: The objective of the study was to compare the biomechanical and interfacial performances of EPS and PMMA-PS in sheep lumbar vertebrae in vitro. SUMMARY OF BACKGROUND DATA: It is a great challenge for orthopedic surgeons performing transpedicular fixation in the osteoporotic spine. It was reported that either the EPS or PMMA-PS could increase the screw stability. However, there are no studies comparing the 2 kinds of screws especially in primary spinal instrumentation. METHODS: A total of 60 sheep lumbar vertebrae were randomly divided into 3 groups. A pilot hole was made in advance in all samples using the same method. Thereafter, the conventional pedicle screw (CPS) was inserted directly into the pilot hole in the CPS group; the hole in PMMA-PS group was first filled with polymethylmethacrylate (PMMA; 1.0 mL) and then inserted with CPS; and the EPS was inserted directly into the vertebrae in EPS group. After a period of 24 hours, biomechanical tests were performed to evaluate screw stability, and x-ray examination, micro-computerized tomography analysis, and histologic observation were performed to evaluate the interface between screw and bone. RESULTS: Compared with the stability of CPS, those of EPS and PMMA-PS were significantly enhanced. However, no significant differences were detected between the stabilities of EPS and PMMA-PS. The PMMA surrounding the screw blocked direct contact between bone and screw and formed a "screw-PMMA-bone" interface in the PMMA-PS group. There was a "screw-bone" interface in both CPS and EPS groups. Nevertheless, the expanded anterior part of EPS formed a claw-like structure pressing the surrounding bone trabeculae, which made the local bone tissue more compacted and denser than that in the CPS group. CONCLUSIONS: EPS can enhance the screw stability as markedly as the traditional PMMA-PS in primary surgery, and EPS can form a better immediate interface between screw and bone compared with PMMA-PS. EPS also can effectively avoid thermal injury, leakage, and compression caused by PMMA. A great feasibility was proved in this study to perform comparisons between the 2 kinds of pedicle screws in osteoporotic sheep vertebrae in vivo in the further research. In conclusion, we propose that EPS has a great application potential in augmentation of screw stability in the clinic.

Laparoscopic or open liver resection for intrahepatic cholangiocarcinoma: A meta-analysis and systematic review.

Background: Although laparoscopic hepatectomy has been widely used in the treatment of benign and malignant liver diseases, its applicability in intrahepatic cholangiocarcinoma (ICC) is controversial. We conducted a meta-analysis to compare the short-term and long-term outcomes of laparoscopic hepatectomy (Lap-ICC) and open hepatectomy (Open-ICC) in ICC patients. Methods: The PubMed, Web of science, Cochrane Library, China National Knowledge Infrastructure and other databases were searched for the relevant literature. The research data were extracted according to the inclusion and exclusion criteria. Results: Seventeen studies, including 3975 ICC patients, were selected for the meta-analysis. Compared to Open-ICC, Lap-ICC had lower rates of lymph node dissection (OR=0.44, P=0.01) and metastasis (OR=0.58, P=0.03), along with less intraoperative bleeding (MD=-128.43 ml, P<0.01) lower blood transfusion rate (OR=0.43, P<0.01), shorter hospital stay (MD=-2.75 day, P<0.01), higher R0 resection rate (OR=1.60, P<0.01), and lower tumor recurrence rate (OR=0.67, P=0.01). However, there was no difference between the two groups in terms of operation time, number of lymph node dissection, incision margin distance, overall complications rate, severe complications rate, and the 1-, 3- and 5-year DFS and OS rates. Conclusion: Laparoscopic hepatectomy is partially superior to open hepatectomy in terms of less bleeding, shorter hospital stay and higher R0 resection rate, while the long-term efficacy of the two approaches is similar.

Analysis of risk factors for acute pancreatitis complicated with pancreatic sinistral portal hypertension and construction of predictive model.

Objective: Pancreatic sinistral portal hypertension (PSPH) is a common complication of acute pancreatitis (AP) and can cause massive gastrointestinal bleeding, which is one of the causes of AP-related mortality. However, there is currently no predictive model for AP concurrent with PSPH. This study aimed to identify the risk factors for AP concurrent with PSPH and use these factors to build a related predictive model. Materials and methods: We collected clinical data from 282 patients with AP. 192 patients were used as a training group and 90 patients as a validation group. Univariate and multivariate analyses were used to identify independent risk factors for AP complicated with PSPH, and then a nomogram was established. The models are cross verification and Internal verification. The predictive ability and accuracy of the model were evaluated based on the working curve of the subjects and the calibration curve, respectively. The clinical value of the model was evaluated using decision curve analysis (DCA). Results: The univariate analysis revealed significant differences in the occurrence of PSPH with respect to sex, recurrent AP, history of hypertension, smoking history, patency of the splenic vein, pancreatic necrosis or pancreatic pseudocyst formation, the most significant site of pancreatic swelling, presence of a Dmure D polymer, MCTSI, and involvement of lipase and amylase. The logistic multivariate regression analysis showed that male sex, splenic-vein stenosis or occlusion and swelling were located in the body-tail, and MCTSI was an independent risk factor for PSPH. The nomogram and ROC curve were constructed. The area under the working curve of the subjects was 0.91, and the sensitivity and specificity were 82.5% and 89.1%, respectively. In the validation group, the C-index is 0.826. The nomogram was internally validated using 1,000 bootstrap samples, and the c-index was 0.898. The calibration curve demonstrated that the predicted probability was concordant with the observed probability, and the DCA confirmed that the model had robust clinical utility. Conclusion: Male sex, splenic-vein stenosis or occlusion, recurrent AP, and swelling are located in the body-tail, and MCTSI is an independent risk factor for the occurrence of PSPH. The predictive model developed for AP complicated with PSPH may serve toward developing preventive and therapeutic approaches for PSPH.

Efficacy of lenvatinib combined with sequential transarterial chemoembolization for primary hepatocellular carcinoma and the effects on serum basic fibroblast growth factor and vascular endothelial growth factor.

Objective: The aim of this research was to investigate the therapeutic efficacy of lenvatinib combined with sequential transarterial chemoembolization (TACE) on primary hepatocellular carcinoma (HCC) and the effects on serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Method: A total of 104 patients with primary HCC, admitted to People's Hospital of Leshan from April 2018 to January 2021, were selected as the study subjects and were divided into the TACE-LEN group (n = 53) who were treated with lenvatinib combined with sequential TACE and the TACE group (n = 51) who were treated with TACE alone, according to the appropriate treatment modalities. The clinical efficacy 8 weeks after treatment; the serum levels of total bilirubin, conjugated bilirubin, and alanine aminotransferase (ALT); the prothrombin time (PT); the indocyanine green retention rate at 15 min (ICGR15); and the serum bFGF and VEGF levels before treatment and at 8 weeks after treatment were compared between the two groups. The incidence of adverse events and the survival rates at 18 months were also recorded for both groups. COX regression analysis was used to analyze the risk factors affecting the survival of patients. Results: Eight weeks after treatment, the objective response rate was higher in the TACE-LEN group than in the TACE group (77.36% vs. 56.36%, p < 0.05), but there were no statistically significant differences in the bilirubin and ALT levels, the PT, and the ICGR15 between the two groups (p > 0.05). The serum bFGF and VEGF levels post-therapeutic were lower in the TACE-LEN group than in the TACE group (p < 0.05). The differences in the incidence of postoperative adverse events and the survival rate within 6 months were not statistically significant between the two groups (p > 0.05). In addition, the survival rates within 12 and 18 months after treatment were higher in the TACE-LEN group than in the TACE group than in the TACE group (81.1% vs. 64.7%, 69.8% vs. 49.1%, p < 0.05). ICG-R15 and treatment regimen are risk factors for survival. Conclusion: The worse the liver reserve is, the worse the prognosis is. The combination of TACE and lenvatinib showed better efficacy and longer survival than TACE monotherapy for HCC patients and reduced the levels of bFGF and VEGF.

Exploring the Application of a Multi-Targeted Nursing Group for Enhanced Recovery After Surgery Using the LEER ("Less Pain", "Early Movement", "Early Return to a Normal Diet" and "Reassurance") Model.

OBJECTIVE: To explore the effects and value of establishing a multi-target nursing group (MTNG) for facilitating goal-oriented enhanced recovery after surgery (ERAS) using the LEER ("less pain", "early movement", "early return to a normal diet" and "reassurance") model. METHODS: The clinical data of 198 patients with hepatobiliary and pancreatic malignancies were retrospectively analyzed. The patients were divided into two groups: 91 cases were collected in a traditional group, which adopted traditional perioperative care, and 107 cases were collected in an MTNG group, which adopted MTNG measures. The differences in the clinical data including postoperative recovery, unplanned readmission rate, the implementation rate of nursing measures, the degree of a patient's understanding of the disease, and patient compliance and satisfaction with nursing care during hospitalization were compared and analyzed between the two groups. RESULTS: The MTNG group reflected a lower pain degree and hospitalization expenses (P < 0.05), earlier postoperative flatulence, earlier recommencing of a normal diet, and earlier postoperative ambulation (P < 0.05), together with a shorter postoperative indwelling catheter duration and length of hospital stay (P < 0.05). There were no significant differences in the incidence of postoperative complications and unplanned postoperative readmission rates between the two groups (P > 0.05). The implementation rate of nursing measures and the degree of patients understanding the disease, and patient compliance and satisfaction with nursing care were higher in the MTNG group (P < 0.05). CONCLUSION: The MTNG approach, based on ERAS with the LEER model, was conducive to the safe and rapid postoperative recovery of patients, the precise and efficient implementation of ERAS measures, the improvement of medical treatment satisfaction among patients.

Reliability, validity and responsiveness of the Chinese version of the Rotator Cuff Quality of Life Index (RC-QOL) in patients with rotator cuff disorders.

BACKGROUND: The Rotator Cuff Quality of Life Index (RC-QOL) is a scale designed to evaluate the impact of rotator cuff (RC) disorders on the general quality of life of patients. Our study aims to adapt the RC-QOL into Chinese and to assess its reliability, validity and responsiveness in Chinese patients with RC disorders. METHODS: First, we developed the Chinese version of RC-QOL (C-RC-QOL) through a five-step procedure. Next, the recruited patients gave three rounds of responses to the C-RC-QOL, Medical Outcomes Study Short Form 36 (SF-36) and Oxford Shoulder Score scales (OSS). Then, we calculated the Cronbach's alpha, standard error of measurement (SEM), minimally detectable change (MDC), intra-class correlation coefficient (ICC), Pearson's correlation coefficient (r), effect size (ES) and standardized response mean (SRM) to evaluate the reliability, validity and responsiveness of the C-RC-QOL respectively. The unidimensionality of each subscale was assessed by principal component analysis (PCA) of the residuals. RESULTS: Overall, 124 patients with RC disorders successfully completed the first two rounds of the scales, and 108 patients completed the last round of the scales. Good or excellent internal consistency (Cronbach's alpha = 0.953) was found in the overall scale and subscales of the C-RC-QOL, and good or excellent test-retest reliability (ICC = 0.854) was found as well. The SEM and MDC values of the C-RC-QOL were 4.6 and 12.8 respectively. Moderate, good or excellent correlations (r = 0.452-0.839) were obtained between the physical subscales of the C-RC-QOL and the OSS, as well as the physical subscales of the SF-36; similar results were obtained between the emotion subscale of the C-RC-QOL and the mental subscales of the SF-36 (r = 0.490-0.733), which, illustrated the good validity of the C-RC-QOL. In addition, high responsiveness was observed in the overall scale and subscales of the C-RC-QOL (ES = 1.77, SRM = 1.98). The unidimensionality of five subscales was respected according to PCA of the residuals. CONCLUSIONS: The C-RC-QOL scale is reliable, valid and responsive for the evaluation of Chinese-speaking patients with RC disorders and it would be an effective instrument.

Cross-cultural adaptation and validation of the Chinese version of the shoulder pain and disability index in patients with symptomatic shoulder pain: A prospective case series.

The aim of this study is to cross-culturally adapt and translate the original version of SPADI into Chinese (C-SPADI), and to test the reliability, validity, and responsiveness of the C-SPADI.This research was a test of previously developed diagnostic criteria in a series of consecutive patients with universally applied gold standard. The original version was translated into Chinese according to international recognized standards. Patients who were diagnosed with a shoulder disorder and underwent shoulder arthroscopic treatments from 2014 to 2015 were enrolled in our study. Each participant was asked to finish the C-SPADI, the Short-Form 36 (SF-36), and the Oxford Shoulder score (OSS) at first visit. The C-SPADI was completed a second time with an interval of 7 days. Six months after arthroscopic treatments, the C-SPADI was completed a third time for responsiveness evaluation. The Cronbach alpha, intraclass correlation coefficient (ICC), standard error of measurement (SEM), minimally detectable change (MDC), Pearson correlation coefficient (r), effect size (ES), and standardized response mean (SRM) were calculated to evaluate the reliability, validity, and responsiveness of C-SPADI respectively.The original version of the SPADI was well adapted and translated into Chinese. The Cronbach alpha ranged from 0.812 to 0.912 in all subscales and total scale of the C-SPADI, indicating good or excellent internal consistency. The test-retest reliability (ICC = 0.887-0.915, SEM = 5.47, MDC = 15.16) was proved to be good or excellent. Moderate or good correlations (r = 0.556-0.672) were obtained between the C-SPADI and the OSS, physical subscales of SF-36; and poor, fair, or moderate correlations (r = 0.038-0.492) were obtained between the C-SPADI and mental subscales of SF-36, which, adequately illustrated good discriminant validity in the C-SPADI. Additionally, the responsiveness was considered good in the C-SPADI (SRM = 1.58-2.44, ES = 1.79-2.17).The C-SPADI was documented to be a reliable, valid, and responsible instrument for self-assessment of patients with shoulder disorders in China. LEVEL OF EVIDENCE: Level II.

Biomechanical study of injectable hollow pedicle screws for PMMA augmentation in severely osteoporotic lumbar vertebrae: effect of PMMA distribution and volume on screw stability.

OBJECTIVEThe purpose of this study was to compare stability of injectable hollow pedicle screws with different numbers of holes using different volumes of polymethylmethacrylate (PMMA) in severely osteoporotic lumbar vertebrae and analyze the relationship between screw stability and distribution and volume of PMMA.METHODSForty-eight severely osteoporotic cadaveric lumbar vertebrae were randomly divided into 3 groups-groups A, B, and C (16 vertebrae per group). The screws used in group A had 4 holes (2 pairs of holes, with the second hole of each pair placed 180° further along the thread than the first). The screws used in group B had 6 holes (3 pairs of holes, placed with the same 180° difference in position). Unmodified conventional screws were used in group C. Each group was randomly divided into subgroups 0, 1, 2, and 3, with different volumes of PMMA used in each subgroup. Type A and B pedicle screws were directly inserted into the vertebrae in groups A and B, respectively, and then different volumes of PMMA were injected through the screws into the vertebrae in subgroups 0, 1, 2, and 3. The pilot hole was filled with different volumes of PMMA followed by insertion of screws in groups C0, C1, C2, and C3. Distributions of PMMA were evaluated radiographically, and axial pull-out tests were performed to measure the maximum axial pullout strength (Fmax).RESULTSRadiographic examination revealed that PMMA surrounded the anterior third of the screws in the vertebral bodies (VBs) in groups A1, A2, and A3; the middle third of screws in the junction area of the vertebral body (VB) and pedicle in groups B1, B2, and B3; and the full length of screws evenly in both VB and pedicle in groups C1, C2, and C3. In addition, in groups A3 and B3, PMMA from each of the screws (left and right) was in contact with PMMA from the other screw and the PMMA was closer to the posterior wall and pedicle than in groups A1, A2, B1, and B2. One instance of PMMA leakage was found (in group B3). Two-way analysis of variance revealed that 2 factors-distribution and volume of PMMA-significantly influenced Fmax (p < 0.05) but that they were not significantly correlated (p = 0.078). The Fmax values in groups in which screws were augmented with PMMA were significantly better than those in groups in which no PMMA was used (p < 0.05).CONCLUSIONSPMMA can significantly improve stability of different injectable pedicle screws in severely osteoporotic lumbar vertebrae, and screw stability is significantly correlated with distribution and volume of PMMA. The closer the PMMA is to the pedicle and the greater the quantity of injected PMMA used, the greater the pedicle screw stability is. Injection of 3.0 mL PMMA through screws with 4 holes (2 pair of holes, with the screws in each pair placed on opposite sides of the screw) produces optimal stability in severely osteoporotic lumbar vertebrae.

Biomechanical comparison of pedicle screw augmented with different volumes of polymethylmethacrylate in osteoporotic and severely osteoporotic cadaveric lumbar vertebrae: an experimental study.

BACKGROUND CONTEXT: Polymethylmethacrylate (PMMA) is widely used for pedicle screw augmentation in osteoporosis. Intriguingly, there have been no biomechanical comparisons of the stability of pedicle screws augmented with different volumes of PMMA or studies of the relationship between screw stability and volume of PMMA, especially in different degrees of osteoporosis. PURPOSE: The purposes of the study reported here were to compare screw stability by different volumes of PMMA augmentation, to analyze the relationship between screw stability and PMMA volume, and to make a preliminary determination of the optimum volume of PMMA augmentation for different degrees of osteoporosis. STUDY DESIGN: This study is a biomechanical comparison of pedicle screws augmented with various volumes of PMMA in cadaveric lumbar vertebrae. METHODS: Thirty-six pedicles from 18 osteoporotic lumbar vertebrae were randomly divided into groups A0 through A5, and 36 pedicles from 18 severely osteoporotic lumbar vertebrae were randomly divided into groups B0 through B5. A different volume of PMMA was injected into each one of groups A0 through A5 (0, 0.5, 1.0, 1.5, 2.0, and 2.5 mL, respectively) and into each one of groups B0 through B5 (0, 1.0, 1.5, 2.0, 2.5, and 3.0 mL, respectively), and then pedicle screws were inserted in all vertebrae. After complete solidification of the PMMA, we examined pedicle X-rays, performed axial pullout tests, and determined the maximum axial pullout strength (Fmax) for all samples. RESULTS: No PMMA was found around the screws in groups A0 and B0. In groups A1 to A5 and B1 to B5, screws were wrapped by gradually increasing amounts of PMMA. There was no PMMA leakage or screw malpositioning in any samples. The Fmax in groups A1 through A5 increased by 32.40%, 64.42%, 116.02%, 174.07%, and 207.42%, respectively, compared with that in group A0. There were no significant differences in Fmax between groups A0 and A1, A1 and A2, A2 and A3, A3 and A4, and A4 and A5 (p>.05), but there were significant differences in Fmax between any other two groups (p<.05). The Fmax in groups B1 through B5 increased by 23.48%, 48.40%, 106.60%, 134.73%, and 210.04%, respectively, compared with that in group B0. There were no significant differences in Fmax between groups B0 and B1, B0 and B2, B1 and B2, B2 and B3, B3 and B4 (p>.05), but there were significant differences in Fmax between any other two groups (p<.05). There was a significant positive correlation between Fmax and volume of PMMA in both osteoporotic and severely osteoporotic lumbar vertebrae (p<.05). CONCLUSIONS: Polymethylmethacrylate can significantly enhance stability of pedicle screws in both osteoporotic and severely osteoporotic lumbar vertebrae. There is a significant positive correlation between screw stability and volume of PMMA. Within a certain range, nevertheless, increasing the volume of PMMA does not significantly improve screw stability. We suggest that 1.5 and 3 mL, respectively, are the volumes of injected PMMA that will optimize pedicle screw stability in osteoporotic and severely osteoporotic lumbar vertebrae.

Local Treatment of Osteoporotic Sheep Vertebral Body With Calcium Sulfate for Decreasing the Potential Fracture Risk: Microstructural and Biomechanical Evaluations.

STUDY DESIGN: In this study, calcium sulfate (CS) was injected through pedicle into the osteoporotic vertebral body in vivo in sheep, and micro-computed tomography analysis, histologic observation, and biomechanical test were performed. OBJECTIVE: To investigate the improvement on microstructure and biomechanical performance of lumbar vertebrae augmented with CS in osteoporotic sheep. SUMMARY OF BACKGROUND DATA: The present treatments for osteoporosis relies on systemic medications intended to increase the bone mineral density (BMD). Although effective, these time-consuming medications provide little protection from fracture in the "early period" after initiation of therapy. In this regard, the strategy of local treatment is to target specific areas of the skeletal system that are prone to osteoporotic fractures. However, there is little or no research focused on local treatment of osteoporotic vertebrae with CS. METHODS: Eight female sheep were induced to osteoporosis with bilateral ovariectomy and methylprednisolone administration for 12 months. After successful establishment of an osteoporotic model, lumbar vertebrae (L1-L4) in every sheep were randomly divided into 2 groups: CS group and control group (2 vertebrae in each group in every sheep). CS was injected into the vertebral body transpedicularly in the CS group and no treatments were performed in the control group. Three months later, all sheep were killed and all L1-L4 vertebrae were harvested. Thereafter, microstructure and biomechanical performance of the cancellous bone of the vertebral body were assessed through micro-computed tomography analysis, histologic observation, and biomechanical test, respectively. RESULTS: After a 12-month induction with ovariectomy and methylprednisolone administration, the mean BMD of the sheep lumbar vertebrae significantly decreased (>25%) compared with the value before induction, which demonstrated successful establishment of osteoporosis. Three months after injection of CS, CS was completely degraded without any remains in bone tissue and the quality of bone tissue (amount and density of the bone tissue) in the CS group was significantly higher than that in the control group. The ultimate load, stiffness, and energy absorption in the CS group were all significantly higher than those in the control group. CONCLUSIONS: The preliminary data suggest that local injection of CS can significantly improve the amount, density, and biomechanical performance of the bone trabeculae in osteoporotic vertebra. The local injection of CS could also be used as a new method to improve the physical microstructure and augment the mechanical properties in "high-risk" vertebral bodies, decreasing the potential fracture risk of patients with osteoporosis. The strict inclusion and exclusion criteria should be performed before treatment.

C/EBP-α, involvement of a novel transcription factor in leptin-induced VCAM-1 production in mouse chondrocytes.

Leptin and vascular cell adhesion molecules-1 (VCAM-1) are two important mediators in obesity-related osteoarthritis, while the molecular mechanism linking leptin to VCAM-1 production is still obscure. Here we show that leptin upregulates VCAM-1 mRNA and protein levels in a time- and dose-dependent manner. Mechanistically, leptin induces VCAM-1 promoter activity by increasing the expression of C/EBP-α and facilitating its binding to a newly identified element in the VCAM-1 gene. Gain or loss of function studies reveal a regulatory role of C/EBP-α on VCAM-1 expression. Finally, elevated plasma leptin level correlates to increased C/EBP-α and VCAM-1 production in chondrocytes from obese mice.

Comparison of expansive pedicle screw and polymethylmethacrylate-augmented pedicle screw in osteoporotic sheep lumbar vertebrae: biomechanical and interfacial evaluations.

BACKGROUND: It was reported that expansive pedicle screw (EPS) and polymethylmethacrylate-augmented pedicle screw (PMMA-PS) could be used to increase screw stability in osteoporosis. However, there are no studies comparing the two kinds of screws in vivo. Thus, we aimed to compare biomechanical and interfacial performances of EPS and PMMA-PS in osteoporotic sheep spine. METHODOLOGY/PRINCIPAL FINDINGS: After successful induction of osteoporotic sheep, lumbar vertebrae in each sheep were randomly divided into three groups. The conventional pedicle screw (CPS) was inserted directly into vertebrae in CPS group; PMMA was injected prior to insertion of CPS in PMMA-PS group; and the EPS was inserted in EPS group. Sheep were killed and biomechanical tests, micro-CT analysis and histological observation were performed at both 6 and 12 weeks post-operation. At 6-week and 12-week, screw stabilities in EPS and PMMA-PS groups were significantly higher than that in CPS group, but there were no significant differences between EPS and PMMA-PS groups at two study periods. The screw stability in EPS group at 12-week was significantly higher than that at 6-week. The bone trabeculae around the expanding anterior part of EPS were more and denser than that in CPS group at 6-week and 12-week. PMMA was found without any degradation and absorption forming non-biological "screw-PMMA-bone" interface in PMMA-PS group, however, more and more bone trabeculae surrounded anterior part of EPS improving local bone quality and formed biological "screw-bone" interface. CONCLUSIONS/SIGNIFICANCE: EPS can markedly enhance screw stability with a similar effect to the traditional method of screw augmentation with PMMA in initial surgery in osteoporosis. EPS can form better biological interface between screw and bone than PMMA-PS. In addition, EPS have no risk of thermal injury, leakage and compression caused by PMMA. We propose EPS has a great application potential in augmentation of screw stability in osteoporosis in clinic.