Cepharanthine Ameliorates Chondrocytic Inflammation and Osteoarthritis via Regulating the MAPK/NF-κB-Autophagy Pathway.

Osteoarthritis is a worldwide joint disease caused by abnormal chondrocytic metabolism. However, traditional therapeutic methods aimed at anti-inflammation for early-stage disease are palliative. In the present study, we demonstrated that cepharanthine (CEP), extracted from the plant Stephania cepharantha, exerted protective medicinal efficacy on osteoarthritis for the first time. In our in vitro study, CEP suppressed the elevated expression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and inducible nitric oxide synthase (iNOS) stimulated by IL-1ß or TNF-α by inhibiting the activation of MAPK and NF-κB signaling pathways, and upregulated the protein expression of aggrecan, collagen II, and Sox9. Also, CEP could reverse the reduced level of cellular autophagy in IL-1ß or TNF-α-induced chondrocytes, indicating that the protective effect of CEP on osteoarthritis was achieved by restoring MAPK/NF-κB-mediated autophagy. Furthermore, in a murine OA model, CEP mitigated cartilage degradation and prevented osteoarthritis in the CEP-treated groups versus the OA group. Hence, our results revealed the therapeutic prospect of CEP for anti-osteoarthritic treatment.

MAKO robotic assisted total hip replacement (THR) for patients with fused hips.

BACKGROUND: Previous articles about MAKO robotic-assisted total hip replacement (THR) were mainly in patients with comparatively normal anatomy. METHODS: From July 2020 to June 2021, we performed MAKO robotic-assisted THR in three hip-fused patients. We assessed the accuracy of prostheses implantation, collected clinical data, and discussed the value of this technique in this kind of patients. RESULT: All three patients achieved good leg length and prostheses position. A patient got femoral artery injury during the surgery. Moreover, she developed a thrombus. All three patients got acceptable Visual Analogue Scale scores and function recovery 6 months later. CONCLUSION: MAKO robotic-assisted THR achieved excellent prosthesis position in hip fused patients. More cases are needed to confirm this advantage. The function recovery was acceptable. Caution should be paid to protect the surrounding abnormal arteries, especially in a limited surgical field.

The combination of PLLA/PLGA/PCL composite scaffolds integrated with BMP-2-loaded microspheres and low-intensity pulsed ultrasound alleviates steroid-induced osteonecrosis of the femoral head.

Low-intensity pulsed ultrasound (LIPUS), which has been previously reported to promote bone repair, is proposed to be a noninvasive form of therapy for the treatment of osteonecrosis. Bone fillers made from composite scaffolds have been demonstrated to be effective for preventing bone defects such as osteonecrosis. The present study aimed to investigate whether the application of LIPUS combined with bone morphogenetic protein-2 (BMP-2)-loaded poly-L-lactic acid/polylactic-co-glycolic acid/poly-ε-caprolactone (PLLA/PLGA/PCL) composite scaffolds can improve recovery in a rat model of steroid-induced osteonecrosis of the femoral head (ONFH). BMP-2-loaded PLGA microspheres incorporated into PLLA/PLGA/PCL composite scaffolds were constructed. Bilateral femoral head LIPUS intervention was conducted in rats with steroid-induced ONFH. LIPUS intervention alone contributed to the alleviation of osteonecrosis, in addition to improving load-carrying capacity and accelerated bone formation, angiogenesis and differentiation. Subsequently, femoral head parameters and assessment of load-carrying capacity, bone formation-related factors, and angiogenesis- and differentiation-related factors were measured in rats with or without implanted BMP-2-loaded PLLA/PLGA/PCL composite scaffolds. LIPUS combined with the implantation of PLLA/PLGA/PCL composite scaffolds loaded with BMP-2 microspheres protected rats against steroid-induced ONFH and improved load-carrying capacity, bone formation, angiogenesis and differentiation. Together, these data support the use of BMP-2-loaded PLLA/PLGA/PCL composite scaffolds combined with LIPUS for ONFH as a potential alternative curative solution for treating bone diseases.

Debridement, antibiotics, and implant retention for periprosthetic knee infections: a pooling analysis of 1266 cases.

BACKGROUND: The debridement, antibiotics, and implant retention (DAIR) procedure is an established therapeutic option for periprosthetic knee infections (PKI). However, the efficacy and the indication for this procedure are still controversial. METHODS: All the relevant literatures were systematically reviewed and analyzed. The present study aimed to assess the success rate of DAIR in the management of PKI, identify the factors associated with prognosis of DAIR, and establish a simple algorithm for predicting a high success rate of DAIR. RESULTS: Totally, 33 studies with 1266 cases were included. The overall success rate following DAIR in the management of PKI was 57.11%. In the subgroup analyses, the factors of "the time from symptoms to debridement was < 3 weeks" and "the bacterial species other than methicillin-resistant Staphylococcus aureus" significantly improved the success rate of DAIR and thus were defined as the major criteria. The statistically insignificant factors of "the open debridement and liner exchange" and "the comorbidity of rheumatoid arthritis" were set as the minor criteria. The success rate of DAIR for PKI meeting all the major criteria and no less than one minor criterion was 80.98%, which was significantly higher than the overall success rate of DAIR (p < 0.05). CONCLUSION: PKI cases meeting two major criteria and no less than one minor criterion may confer a high success rate of DAIR. This simple algorithm may contribute to identifying the appropriate PKI patient for DAIR treatment and predicting the prognosis of DAIR.

Effects of sequential treatment with intermittent parathyroid hormone and zoledronic acid on particle-induced implant loosening: Evidence from a rat model.

Particle-induced implant loosening is a major challenge to long-term survival of joint prostheses. Administration of intermittent parathyroid hormone (PTH) has shown potential in the treatment of cases of early-stage periprosthetic osteolysis, while sequential administration of intermittent PTH (iPTH) and bisphosphonates (Bps) has achieved significant effects on treatment of postmenopausal osteoporosis. The objective of this study was to determine whether sequential treatment could preserve bone mass and implant fixation during a pathological course of peri-implant osteolysis in a rat model. Ninety male Sprague Dawley rats were randomly divided into nine groups, four of which were used for confirmation of establishment of the peri-implant osteolysis model at two time points, while the other five were used to determine the efficiency of the sequential treatment on peri-implant osteolysis. Implant fixation and peri-implant bone mass were evaluated using biomechanical testing, micro-CT analysis, and histology at 6 and 12 weeks postoperative. The biomechanical test demonstrated that the maximum loading force during a push-out test was significantly elevated in the sequential treatment group compared to the osteolysis group and iPTH withdrawal group at 12 weeks. Peri-implant bone morphology also indicated a robust increase in bone volume in the sequential treatment group. Sequential administration of iPTH and Bps was effective in preventing experimental peri-implant osteolysis, resulting in improved implant fixation and increased peri-implant bone volume. Clinical significance: The innovative application of sequential treatment in peri-implant osteolysis could be used clinically to improve the prognosis of patients with early-stage periprosthetic osteolysis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1489-1497, 2019.

Tomatidine suppresses osteoclastogenesis and mitigates estrogen deficiency-induced bone mass loss by modulating TRAF6-mediated signaling.

Postmenopausal osteoporosis is initiated by estrogen withdrawal and is characterized mainly by overactivated osteoclastic bone resorption. Targeting TNF receptor-associated factor 6 (TRAF6) or its downstream signaling pathways to modulate osteoclast formation and function is an appealing strategy for osteoclast-related disorders. In the present study, we determined the effect of tomatidine, a steroidal alkaloid derived from Solanaceae, on the formation and function of receptor activator of NF-κB (RANK) ligand-induced osteoclasts and the underlying mechanism. Tomatidine inhibited osteoclast formation in a dose-dependent manner and decreased the expression of osteoclast marker genes. Actin ring formation and osteoclastic bone resorption were attenuated in the presence of tomatidine in vitro. Eight weeks after ovariectomy, tomatidine prevented estrogen deficiency-induced bone loss and restored the mechanical properties of the femur. At the molecular level, tomatidine abrogated phosphorylation of c-Jun N-terminal kinase (JNK)/p38, NF-κB, and protein kinase B (Akt) pathway proteins by suppressing RANK expression, inhibiting the binding of TRAF6 to RANK, and downregulating the osteoclastogenesis marker-related protein expression. In summary, these data demonstrated that tomatidine attenuated osteoclast formation and function by modulating multiple TRAF6-mediated pathways. Therefore, tomatidine could be a novel candidate for the treatment of osteoclast-related disorders, including osteoporosis.-Hu, B., Sun, X., Yang, Y., Ying, Z., Meng, J., Zhou, C., Jiang, G., Li, S., Wu, F., Zhao, X., Zhu, H., Wu, H., Cai, X., Shi, Z., Yan, S. Tomatidine suppresses osteoclastogenesis and mitigates estrogen deficiency-induced bone mass loss by modulating TRAF6-mediated signaling.

Mechanical Properties and Porosity of Acrylic Cement Bone Loaded with Alendronate Powder.

Aseptic loosening is the most common complication of joint replacement. Previous studies showed that acrylic bone cement loaded with a commercially-available alendronate powder (APAC) had good promise against wear debris-mediated osteolysis for prevention of aseptic loosening. The purpose of the present study was to investigate the effect of adding alendronate powder to an acrylic bone cement on quasi-static mechanical properties (namely, compressive strength, compressive modulus, tensile strength, and flexural strength), fatigue life, porosity, and microstructure of the cement. The results showed that adding up to 1 wt./wt.% alendronate powder exerted no detrimental effect on any of the quasi-static mechanical properties. However, the fatigue life of APAC decreased by between ~17% and ~27 % and its porosity increased by between ~ 5-7 times compared with corresponding values for the control cement (no alendronate powder added). Fatigue life was negatively and significantly correlated with porosity. Considering that fatigue life of the cement plays a significant role in joint replacement survival, clinical use of APAC cannot be recommended.

Microbubble-Mediated Ultrasound Outweighs Low-Intensity Pulsed Ultrasound on Osteogenesis and Neovascularization in a Rabbit Model of Steroid-Associated Osteonecrosis.

Microbubbles magnify the acoustic pressure of low-intensity pulsed ultrasound (LIPUS) and may enhance its bioeffect for diagnostic and therapeutic purposes. This study compared the effect of this novel microbubble-mediated ultrasound (MUS) with that of the traditional LIPUS on osteogenesis and neovascularization in a rabbit model of steroid-associated osteonecrosis. We hypothesized that MUS might outweigh LIPUS on promoting osteogenesis and neovascularization in steroid-associated osteonecrosis. The bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in the rabbits. The indices of bone mineral density (BMD), trabecular number, maximal loading strength, and mineral apposition rate were analyzed, demonstrating that the animal model of steroid-associated osteonecrosis was successfully established. Both the MUS group (GM) and the LIPUS group (GL) were insonated 20 min daily for six weeks. GM received an extra intracapsular injection of microbubbles before insonation every other day. Fluorescence bone labeling, Micro-CT Analysis, biomechanical test, quantitative real-time PCR, Western blot analysis, and histological evaluation were performed for comparing GM with GL. The results demonstrated a 39% higher mineral apposition rate in GM compared with GL. The BMD and the maximal loading strength of femoral head of GM increased by 4.3% and 27.8% compared to those of GL, respectively. The mRNA and protein expression of BMP-2 and VEGF were also significantly higher in GM. The number of blood vessels of GM was 65% greater than that of GL. MUS is more potent than LIPUS in enhancing osteogenesis, neovascularization, and biomechanical strength of femoral head in the animal model of steroid-associated osteonecrosis. Without increasing the intensity of insonation or the risk of tissue damage, MUS is better for inhibiting the process of steroid-associated osteonecrosis.

Low-intensity pulsed ultrasound inhibits RANKL-induced osteoclast formation via modulating ERK-c-Fos-NFATc1 signaling cascades.

Low-intensity pulsed ultrasound (LIPUS), which is a noninvasive form of mechanical energy, has been utilized as a clinical therapy for bone fracture healing. However, the mechanism how LIPUS affects osteoclast formation and osteoclast activity, has not been fully detailed. Here we found that LIPUS inhibited RANKL-induced osteoclast differentiation in vitro, characterized by decreased number and area of tartrate-resistant acid phosphatase (TRAP) positive cells. Moreover, the expression levels of osteoclast-specific gene were also suppressed by LIPUS treatment. Interestingly, F-actin staining and resorption pit assay showed that LIPUS did not affect the bone resorptive activity of mature osteoclasts. Mechanistically, LIPUS achieved these inhibitory effects by disrupting the phosphorylation of ERK and subsequent activation of the osteoclastic transcription factors, c-Fos and NFATc1. Collectively, our results demonstrated that LIPUS effectively suppresses osteoclast differentiation and osteoclast-specific gene expression through the inhibition of ERK-c-Fos-NFATC1 cascades.

Squeaking in fourth-generation ceramic-on-ceramic total hip replacement and the relationship with prosthesis brands: meta-analysis and systematic review.

BACKGROUND: Postoperative squeaking in patients who applied the fourth-generation ceramic bearing in primary hip replacement has not been reported systematically; we aim to study the squeaking incidence in the fourth-generation ceramic bearing and related risk factors for squeaking, and we also attempt to explore the relationship between squeaking and prosthetic brands. METHODS: The PubMed, Embase, and Cochrane library were searched, and 14 articles were finally included. Patients' demographic data, surgical-related information, and prosthesis data were extracted. The occurrence rate of squeaking was calculated by meta-analysis, and subgroup analysis was performed based on prosthetic brands and follow-up time. Regression analysis was further applied to investigate the relationship between various risk factors and squeaking. RESULTS: The squeaking incidence in patients with the fourth-generation ceramic bearing was 3%. Age, gender, body mass index, and abduction and anteversion angles of acetabular cup might have no influence on squeaking. The squeaking incidence was significantly high with the presence of Delta Motion cup (DePuy, Warsaw, Indiana) and Secure-Fit stem (Stryker, Kalamazoo, MI), and the overall incidence of DePuy femoral stem was relatively small except for the Summit femoral stem. And there was no significant difference of squeaking incidence between less than 5-year and more than or equal to 5-year follow-up subgroups. CONCLUSIONS: In our study, squeaking in the fourth-generation ceramic bearing occurred at a rate of 3%; occurrence rate was high when the Delta Motion cup was applied. We hope for more relevant researches to focus on this issue.

Effectiveness of corticosteroid injections in adhesive capsulitis of shoulder: A meta-analysis.

BACKGROUND: Primary adhesive capsulitis is mainly characterized by spontaneous chronic shoulder pain and the gradual loss of shoulder motion. The main treatment for adhesive capsulitis is a trial of conservative therapies, including analgesia, exercise, physiotherapy, oral nonsteroidal anti-inflammation drugs, and intra-articular corticosteroid injections. Previously, it was reported that intra-articular corticosteroid lead to fast pain relief and improvement of range of motion (ROM). The objective of this study was to determine whether corticosteroid injections would lead to better pain relief and greater improvement in ROM. METHODS: We searched PubMed, Medline, and the Cochrane library. We included 5 articles of the 1166 articles identified. Totally injection group included 115 patients and placebo group included 110 patients. We calculated the weighted mean differences to evaluate the pain relief as the primary outcome. We determined the ROM as the secondary outcome. Study quality was evaluated using the 12-item scale. We also used the criteria of the Grading of Recommendations Assessment, Development and Evaluation to evaluate the quality of evidence. RESULTS: In total, 5 studies were included, 4 of which were randomized clinical trials, with a sample size of 225 patients with adhesive capsulitis of the shoulders. The overall pooled data demonstrated that, compared with placebo as control treatment, intra-articular corticosteroid injections were more effective in reducing the pain score at 0 to 8 weeks, but there was no difference between the injection group and the control group at 9 to 24 weeks. Improvement of ROM in the injection group was greater than that of the control group both at 0 to 8 and 9 to 24 weeks. CONCLUSIONS: Intra-articular corticosteroid injections were more effective in pain relief in the short term, but this pain relief did not sustain in the long term. Intra-articular corticosteroid injection resulted in greater improvement in passive ROM both in the short and the long terms.

A systematic review of undisplaced femoral neck fracture treatments for patients over 65 years of age, with a focus on union rates and avascular necrosis.

BACKGROUND: It remains unclear whether conservative treatment should be used to treat the common undisplaced femoral neck fractures that develop in the elderly. Herein, we systematically review the rates of union and avascular necrosis after conservative and surgical treatment of undisplaced femoral neck fractures. METHODS: We searched the EMBASE, PubMed, OVID, Cochrane Library, Web of Science, and Scopus databases for randomized controlled trials or observational studies that assessed the outcomes of conservative or surgical treatments of undisplaced femoral neck fractures. No language or publication year limitation was imposed. Statistical analyses were performed with the aid of the chi-squared test. We evaluated the quality of each publication and the risk of bias. RESULTS: Twenty-nine studies involving 5071 patients were ultimately included; 1120 patients were treated conservatively and 3951 surgically. The union rates were 68.8% (642/933) and 92.6% (635/686) in the former and latter groups, respectively (p < 0.001). The avascular necrosis rate in the conservatively treated group was 10.3% (39/380), while it was 7.7% (159/2074) in the surgically treated group (p = 0.09). CONCLUSIONS: Surgery to treat undisplaced femoral neck fractures was associated with a higher union rate and a tendency toward less avascular necrosis than conservative treatment.

Low-intensity pulsed ultrasound enhances bone repair in a rabbit model of steroid-associated osteonecrosis.

BACKGROUND: Steroids are a leading cause of femoral head osteonecrosis. Currently there are no medications available to prevent and/or treat steroid-associated osteonecrosis. Low-intensity pulsed ultrasound (LIPUS) was approved by the FDA for treating delayed union of bone fractures. Some studies have reported that LIPUS can enhance bone formation and local blood flow in an animal model of fracture healing. However, whether the effect of osteogenesis and neovascularization by LIPUS can enhance the repair progress in steroid-associated osteonecrosis is unknown. QUESTIONS/PURPOSES: We hypothesized that LIPUS may facilitate osteogenesis and neovascularization in the reparative processes of steroid-associated osteonecrosis. Using a rabbit animal model, we asked whether LIPUS affects (1) bone strength and trabecular architecture; (2) blood vessel number and diameter; and (3) BMP-2 and VEGF expression. METHODS: Bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in 24 rabbits. The left femoral heads of rabbits received LIPUS therapy (200 mW/cm(2)) for 20 minutes daily and were classified as the LIPUS group. The right femoral heads of the same rabbits did not receive therapy and were classified as the control group. All rabbits were euthanized 12 weeks after LIPUS therapy. Micro-CT, biomechanical testing, histologic evaluation, immunohistochemistry, quantitative real-time PCR, and Western blot were used for examination of the effects of LIPUS. RESULTS: Twelve weeks after LIPUS treatment, the loading strength in the control group was 355 ± 38 N (95% CI, 315-394 N), which was lower (p = 0.028) than that in the LIPUS group (441 ± 78 N; 95% CI, 359-524 N). The bone tissue volume density (bone volume/total volume) in the LIPUS group (49.29% ± 12.37%; 95 % CI, 36.31%-62.27%) was higher (p = 0.022) than that in the control group (37.93% ± 8.37%; 95 % CI, 29.15%-46.72%). The percentage of empty osteocyte lacunae in the LIPUS group (17% ± 4%; 95% CI, 15%-20%) was lower (p = 0.002) than that in the control group (26% ± 9%; 95% CI, 21%-32%). The mineral apposition rate (µm/day) in the LIPUS group (2.3 ± 0.8 µm/day; 95% CI, 1.8 2.8 µm/day) was higher (p = 0.001) than that in the control group (1.6 ± 0.3 µm/day; 95% CL, 1.4-1.8 µm/day). The number of blood vessels in the LIPUS group (7.8 ± 3.6/mm(2); 95% CI, 5.5-10.1 mm(2)) was greater (p = 0.025) than the number in the control group (5.7 ± 2.6/mm(2); 95% CI, 4.0-7.3 mm(2)). Messenger RNA (mRNA) and protein expression of BMP-2 in the LIPUS group (75 ± 7, 95% CI, 70-79; and 30 ± 3, 95% CI, 28-31) were higher (both p < 0.001) than those in the control groups (46 ± 5, 95% CI, 43-49; and 15 ± 2, 95% CI, 14-16). However, there were no differences (p = 0.114 and 0.124) in mRNA and protein expression of vascular endothelial growth factor between the control (26 ± 3, 95% CI, 24-28; and 22 ± 6, 95% CI, 18-26) and LIPUS groups (28 ± 2, 95% CI, 26-29; and 23 ± 6, 95% CI, 19-27). CONCLUSIONS: The results of this study indicate that LIPUS promotes osteogenesis and neovascularization, thus promoting bone repair in this steroid-associated osteonecrosis model. CLINICAL RELEVANCE: LIPUS may be a promising modality for the treatment of early-stage steroid-associated osteonecrosis. Further research, including clinical trials to determine whether LIPUS has a therapeutic effect on patients with early-onset steroid-associated osteonecrosis may be warranted.

Comparison of Periarticular Multimodal Drug Injection and Femoral Nerve Block for Postoperative Pain Management in Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

The analgesic efficacy and safety of periarticular multimodal drug injection (PMDI) compared with femoral nerve block (FNB) for postoperative pain management in total knee arthroplasty (TKA) still remains controversial. We therefore conducted a meta-analysis to quantitatively compare PMDI to FNB in TKA. 10 randomized controlled trials (RCTs) with 744 TKAs in 728 patients were included in this study. The meta-analysis showed that single shot FNB may have better pain relief in the early postoperative period compared with single shot PMDI, and continuous PMDI provided postoperative analgesia comparable to that of continuous FNB. No significant difference was seen in regard to the complications between the two groups. However, due to the variation of the included studies, no firm conclusions can be drawn.

In vitro and in vivo evaluation of vancomycin-loaded PMMA cement in combination with ultrasound and microbubbles-mediated ultrasound.

Ultrasound (US) has been used to increase elution of antibiotic from an antibiotic-loaded poly(methyl methacrylate) (PMMA) bone cement (ALBC). We aimed to further investigate whether microbubbles-mediated US (US + MB) facilitate elution of vancomycin (VAN) from cylindrical specimens and enhance the activity of the eluted antibiotic against Staphylococcus aureus (S. aureus) in vitro. The study groups comprised cylindrical bone cement fabricated with VAN (VAN), ALBC using US (VAN + US), and ALBC using MB-mediated US (VAN + US + MB). We also carried out an in vivo study involving the activity of VAN from cylindrical cement implanted in tibiae of New Zealand white rabbits inoculated with S. aureus. We found that (1) in vitro, elution from VAN + US + MB cylinders was significantly higher than from either the VAN or VAN + US specimens; (2) the activity of the eluted VAN from the VAN + US + MB cylinders against planktonic S. aureus was significantly higher than from either the control or VAN or VAN + US specimens; and (3) in the rabbits, the activity of the eluted VAN from the VAN + US + MB cylinders against S. aureus was significantly higher than from either the control or VAN or VAN + US specimens. The present results suggest that VAN-loaded PMMA cement irradiated with MB-mediated US may have a role in controlling prosthetic joint infection.

Microbubble injection enhances inhibition of low-intensity pulsed ultrasound on debris-induced periprosthetic osteolysis in rabbit model.

We determined whether the addition of microbubbles enhances the effect of low-intensity pulsed ultrasound (LIPUS) on bone-implant integration in an early-stage osteolysis model. The bone canals were injected with titanium particles before implantation to establish the periprosthetic osteolysis model. Before ultrasonic therapy, the microbubble-enhanced LIPUS group (GTi-Us-Mb) received an intra-articular injection of microbubbles. Biomechanical testing revealed that GTi-Us-Mb had significantly greater fixation strength than the LIPUS group (GTi-Us). Distal periprosthetic bone mineral density was also higher in GTi-Us than in the Ti group (GTi), but no significant increase was detected after administration of microbubbles. Histomorphometric analyses revealed that bone formation around the implant in GTi-Us was enhanced by the addition of microbubbles in GTi-Us-Mb. Taken together, our data indicate that microbubble injection enhances the inhibitory effect of LIPUS on debris-induced osteolysis and further strengthens the mechanical fixation of implants in an early-stage osteolysis model in vivo.

Microbubble-mediated ultrasound enhances the lethal effect of gentamicin on planktonic Escherichia coli.

Previous research has found that low-intensity ultrasound enhanced the lethal effect of gentamicin on planktonic E. coli. We aimed to further investigate whether microbubble-mediated low-intensity ultrasound could further enhance the antimicrobial efficacy of gentamicin. The planktonic E. coli (ATCC 25922) was distributed to four different interventions: control (GCON), microbubble only (GMB), ultrasound only (GUS), and microbubble-mediated ultrasound (GMUS). Ultrasound was applied with 100 mW/cm(2) (average intensity) and 46.5 KHz, which presented no bactericidal activity. After 12 h, plate counting was used to estimate the number of bacteria, and bacterial micromorphology was observed with transmission electron microscope. The results showed that the viable counts of E. coli in GMUS were decreased by 1.01 to 1.42 log10 CFU/mL compared with GUS (P < 0.01). The minimal inhibitory concentration (MIC) of gentamicin against E. coli was 1 µ g/mL in the GMUS and GUS groups, lower than that in the GCON and GMB groups (2 µ g/mL). Transmission electron microscopy (TEM) images exhibited more destruction and higher thickness of bacterial cell membranes in the GMUS than those in other groups. The reason might be the increased permeability of cell membranes for gentamicin caused by acoustic cavitation.

Alendronate versus Raloxifene for Postmenopausal Women: A Meta-Analysis of Seven Head-to-Head Randomized Controlled Trials.

Purpose. The aim of this study was to directly compare the efficacy and the safety of the two agents for postmenopausal women. Methods/Principal Findings. Electronic databases were searched for relevant articles that met our predefined inclusion criteria. Seven randomized controlled trials (RCTs) involving 4054 women were identified and included. Although Aln was more effective than Rlx in increasing bone mineral density (BMD), no statistical differences were observed in reducing the risk of neither vertebral fractures (P = 0.45) nor nonvertebral fractures (P = 0.87) up to two-year followup. Aln reduced the risk of vasomotor (P = 0.006) but increased the risk of diarrhea compared to Rlx (P = 0.01). Our subgroup analysis further indicated the difference between Aln and Rlx in fracture risk and was not materially altered by the administration pattern, the age. The weekly strategy of Aln would further reduce the upper gastrointestinal (GI) disorders and might gain more bone mass increment at lumbar spine compared to its daily treatment. Conclusion. There was no evidence of difference of fracture risk reduction between Aln and Rlx. In addition, age did not obviously influence their relative antifracture efficacy. For Aln the weekly strategy would further reduce the upper GI disorders and gain more bone mass increment compared to the daily treatment. During clinical decision making, the patients' adherence and the related side-effects associated with both drugs should also be taken into account.

Intramedullary nailing versus plating for extra-articular distal tibial metaphyseal fracture: a systematic review and meta-analysis.

INTRODUCTION: With development in the techniques of reduction and fixation, there has been a controversy in comparison between intramedullary nailing (IMN) and plating for the treatment of distal tibial metaphyseal fracture (DTF). The study aimed to investigate: (1) which fixation, IMN or plating, was better in the clinical outcomes and in the complications for the treatment of DTF and (2) which modifying variables affected the comparative results between the two modalities. METHODS: PubMed, EMBASE, OVID, Scopus, ISI Web of Science, the Cochrane Library, Google Scholar and specific orthopaedic journals were searched from inception to July 2013, using the search strategy of '('Fracture Fixation, Intramedullary' [MeSH]) AND ('Tibial Fractures' [MeSH]) AND (plate OR plating)'. All prospective and retrospective controlled trials comparing function, pain, bone union and complications between IMN and plating for DTF were identified. Our analysis had no limitation of the language or the publication year. The primary outcome measurements were complication rate, union time, operation time and hospital stays, while the secondary outcome measurements were functional score and pain score. RESULT: Fourteen of 6620 studies with 842 patients were included. IMN was probably preferential to plating for DTF given its higher functional score (p=0.01), lower risk of infection (p=0.02) and comparable pain score (p=0.33), total complication rate (p=0.53) and time to union (p=0.86). However, plating had a lower malunion rate than IMN (p<0.0001). All the results were based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence of moderate quality. CONCLUSIONS: With a satisfying alignment obtained, IMN may be preferential to plating for fixation of DTF with better function and lower risk of infection. However, IMN showed higher malunion rate for fixation of DTF. With the biases in our meta-analysis, it will ultimately require a rigorous and adequately powered randomised controlled trial (RCT) to prove. LEVEL OF EVIDENCE: Level III, therapeutic study (systematic review).