Is intraoperative corticosteroid a good choice for postoperative pain relief in total joint arthroplasty? A meta-analysis of 11 randomized controlled trials.

BACKGROUND: Effective postoperative analgesia is of great significance for postoperative rehabilitation. This meta-analysis aimed to investigate the efficacy of corticosteroid on pain following total joint arthroplasty. METHOD: PubMed (1996-December 2020), Embase (1996-December 2020), and the Cochrane Library (CENTRAL, December 2020) were searched and a total of 11 randomized controlled trials met our inclusion criteria. RESULTS: Eleven randomized controlled trials met the inclusion criteria. Pooled data indicated the corticosteroid group was effective compared to the control group in terms of the visual analogue scale at rest (P < .05) and movement (P < .05), the total morphine equivalent consumption (P < .05), and the length of stay (P < .05), without increasing the risk of periprosthetic joint infection (P = .74) and the length of stay (P = .32). CONCLUSIONS: Compared to the control group, intraoperative corticosteroid was benefit to the pain management in total joint arthroplasty.

[Progress on prevention and treatment of heterotopic ossification].

Heterotopic ossification is the formation of pathological bone in non-skeletal tissues (including muscles, tendons or other soft tissues), and the pathogenesis is not completely clear. It is often caused by musculoskeletal trauma, postoperative bone and joint surgery, or damage of the nervous system, the clinical manifestations are joint swelling, pain, and movement disorders, which often occur around the hips, knees, and elbows. At present, the prevention of heterotopic ossification mainly includes drugs, radiotherapy, molecular biological mechanism intervention, and Chinese medicine-related measures. Among them, drugs and radiotherapy are more effective methods to prevent heterotopic ossification. The intervention of molecular biology mechanism to prevent heterotopic ossification has become a new research direction and focus of attention inrecent years, and is basically at the experimental research stage. The treatment of heterotopic ossification includes various methods such as drugs, physical therapy, and surgery. Among them, surgery is recognized as the most effective treatment, however there are still some controversies and disagreements about the choice of operation time and surgical methods.

Comparison of adductor canal block with periarticular infiltration analgesia in total knee arthroplasty: A meta-analysis of randomized controlled trials.

BACKGROUND: Total knee arthroplasty (TKA) is accompanied by moderate to severe postoperative pain. Multimodal analgesia, such as femoral nerve block, periarticular infiltration analgesia (PIA), and patient-controlled intravenous analgesia, have been used for postoperative analgesia. Recently, randomized controlled trials have compared the efficacy of the adductor canal block (ACB) and the PIA in patients undergoing TKA. However, there is no definite answer as to the efficacy and safety of the ACB compared with the PIA. METHOD: Randomized controlled trials about relevant studies were searched from PubMed (1996 to May 2019), Embase (1980 to May 2019), and Cochrane Library (CENTRAL, May 2019). Five studies which compared the ACB with the PIA methods were included in our meta-analysis. RESULTS: Five studies containing 413 patients met the inclusion criteria. There were no significant differences between the ACB and the PIA group in visual analog scale (VAS) score at rest (P = .14) and movement (P = .18), quadriceps muscle strength (P = .95), complications (P = .78), length of stay (LOS) (P = .54), and time up and go (TUG) test (P = .09), While patients in the ACB group had less equivalent morphine consumption (P < .05) compared with the PIA group. CONCLUSIONS: Our pooled data indicated the ACB group reduced the equivalent morphine consumption compared with the PIA group, with no statistically significant differences in the VAS score, quadriceps muscle strength, TUG test, complications, and LOS.

[Methylation Status and mRNA Expression of DKK-3 and WIF-1 in Acute Myeloid Leukemia Patients].

OBJECTIVE: To analyze the promoter methylation status, mRNA expression and clinical significance of DKK-3 and WIF-1 genes in patients with acute myeloid leukemia(AML). METHODS: Methylation specific polymerase chain reaction (MS-PCR) mothod was carried out to detect DKK-3 and WIF-1 gene promoter methylation status in bone marrow specimen from 56 patients with AML and 20 patients with iron deficiency anaemia(IDA) as control; then the real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect mRNA expression of DKK-3, WIF-1 gene and ß -catenin in the above-mentioned specinens, and their relationship with the clinical features and survival time was analyzed. RESULTS: The promoter methylation rate of DKK-3 and WIF-1 gene in AML patients were significantly higher than that in control group(χ2=15.330,P<0.001; χ2=17.371,P<0.001). There was no relationship between DKK-3 and WIF-1 gene promoter methylation rate and AML patient's sex, age, clinical typing. The relative expression of DKK-3 and WIF-1 gene mRNA in AML group were 0.840±0.320 and 0.792±0.313, which were lower than those in control group (1.134±0.392 and 1.047±0.334) respectively, the difference was statistically significant (t=3.415,P=0.000; t=3.070, P=0.003). The relative expression of ß-catenin mRNA in AML bone marrow specimens in AML group was 0.756±0.304, which was higher than that in control group(0.342±0.105), the difference was statistically significant (t=5.943, P=0.001). The expression of DKK-3 and WIF-1 gene mRNA negatively correlated with ß-catenin mRNA(r=-0.543; r=-0.562). Kaplan Meier survival curve analysis showed that overall survival time in AML patients with DKK-3 gene methylation was shorter than that in the AML patients with DKK-3 gene unmethylation(χ2=3.957, P=0.042). Futhermore, the orerall survival time in AML patients with WIF-1 gene methylation was also shorter than that in AML patients with WIF-1 gene unmethylation (χ2=4.520, P=0.029). CONCLUSION: Wnt/ß-catenin signaling pathway is abnormally activated in AML patients, the DKK-3 and WIF-1 gene promoter methylation may be involved in Wnt pathways activation and the pathogenesis of AML.

[Analysis of Relationship between Serum Total Light Chain κ/λ Ratio and Proportion of Bone Marrow Plasma Cells in Patients with IgG type and IgA type Multiple Myeloma].

OBJECTIVE: To explore the relationship between serum total light chain κ/λ ratio (sTLC-κ/λ) and proportion of bone marrow plasma cells (BMPC) in patients with IgG type and IgA type multiple myeloma (MM) and its clinical significance. METHODS: The levels of serum IgG, IgA, κ type and λ type total light chain were detected in 79 newly diagnosed patients with IgG type (n=52) and IgA type (n=27) MM by immuno-nephelometric assay and the sTLC-κ/λ ratio was calculated. The proportion of BMPC was determined by bone marrow smears in the corresponding period, and the changes in sTLC-κ/λ ratio and the proportion of BMPC were observed in 19 patients with IgG type(n=16) and IgA type (n=3) MM undergoing treatment, 26 cases of non-phasmocytic proliferative diseases were enrolled in control group. RESULTS: In MM patients with IgGκ type and IgAκ type, the sTLC-κ/λ ratio was significantly higher than that in the control group (P<0.01), while in MM patients with IgGλ type and IgAλ type, the sTLC-κ/λ ratio was significantly lower than that in the control group (P<0.01). In MM patients with IgGκ, the sTLC-κ/λ ratio was significantly higher than that in MM patients with IgAκ(P<0.01), while the sTLC-κ/λ ratio in MM patients with IgGλ was significantly lower than that in MM patients with IgAλ. The sTLC-κ/λ ratios in MM patients with IgGκ and IgAκ were positively correlated with the concentrations of IgG (r=0.778,P=0.000) and IgA (r=0.601,P=0.039), while the sTLC-κ/λ ratios of patients with IgGλ and IgAλ were negativily correlated with the IgG(r=-0.586,P=0.01) and IgA level(r=-0.718,P=0.003). In addition, a correlation between each type MM was not found except the IgGκ type MM which had a positive correlation between the sTLC-κ/λ ratio and proportion of BMPC (r=0.579,P=0.002). Nonetheless, 18 of 19 patients with IgG type and IgA type MM undergoing treatment showed concordance between the sTLC-κ/λ ratio and proportion of BMPC change. CONCLUSION: There is a lower correlation between the sTLC-κ/λ ratio and the proportion of BMPC in MM patients with IgG type and IgA type, but there is a high concordance between the sTLC-κ/λ ratio and the proportion of BMPC change in the same patient and it suggests that the sTLC-κ/λ ratio plays an important role in the diagnosis and monitoring of IgG type and IgA type MM.

Local influence of high molecular polyethylene particles on heterotopic ossification.

We studied the effect of molecular polyethylene particles on local heterotopic ossification. A total of 36 healthy Sprague-Dawley rats were randomly divided into the control group (n=18) and the observation group (n=18). High molecular polyethylene particles were injected to rupture Achilles tendon position in the observation group, and normal saline was injected in the control group. X-ray examinations were conducted on Achilles tendon in the 4th, 8th and 12th week after operation. The incidence rate of heterotopic ossification was evaluated, and bone trabecula morphological structure was studied under optical microscope after hematoxylin and eosin staining. Bone morphogenetic protein 2 (BMP-2), transforming growth factor-ß (TGF-ß), interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), runt-related transcription factor 2 (Runx2) and matrix metalloproteinase-9 (MMP-9) expression levels were also measured. Our results showed that heterotopic ossification incidence in the observation group was significantly lower than that in the control group. Achilles tendon structure in the control group increased in volume, and its texture was harder and cartilage-like. In the observation group, trabecular bone volume, thickness and quantity were more than those observed in the control group. BMP-2, TGF-ß, IL-1, TNF-α, Runx2 and MMP-9 levels in the observation group were significantly lower than those in the control group. We concluded that, high molecular polyethylene particles had a significant inhibiting effect on local heterotopic ossification.

Mechanisms underlying the antiapoptotic and anti-inflammatory effects of monotropein in hydrogen peroxide-treated osteoblasts.

Monotropein, the primary iridoid glycoside isolated from Morindacitrifolia, has been previously reported to possess potent antioxidant and antiosteoporotic properties. However, there is no direct evidence correlating the antiosteoporotic effect of monotropein with its observed antioxidant capacity, and the molecular mechanisms involved in mediating these processes remain unclear. Therefore, the aim of the present study was to investigate the protective effects of monotropein against oxidative stress in osteoblasts and the mechanisms involved in mediating this process. Osteoblast viability was evaluated using the MTT assay. The mitochondrial membrane potential and reactive oxygen species were detected by flow cytometry analyses. Western blotting and enzyme­linked immunosorbent assays were performed to detect protein expression levels. A significant reduction in osteoblast viability was observed at 24 h following exposure to various concentrations (100­1,000 µM) of H2O2 compared with untreated osteoblasts. The cytotoxic effect of H2O2 was notably reversed when osteoblasts were pretreated with 1­10 µg/ml monotropein. Pretreatment with 1-10 µg/ml monotropein increased the mitochondrial membrane potential and reduced the generation of reactive oxygen species in osteoblasts following exposure to H2O2. In addition, the H2O2­induced increase in apoptotic markers (caspase-3 and caspase-9) and H2O2-induced reduction in sirtuin 1 levels were significantly reversed following pretreatment of cells with monotropein. Furthermore, monotropein significantly reduced H2O2­induced stimulation of NF­κB expression, in addition to the expression of a number of proinflammatory mediators. These results indicate that monotropein suppresses apoptosis and the inflammatory response in H2O2­induced osteoblasts through the activation of the mitochondrial apoptotic signaling pathway and inhibition of the NF­κB signaling pathway.

4­Phenylbutyrate protects rat skin flaps against ischemia­reperfusion injury and apoptosis by inhibiting endoplasmic reticulum stress.

4­phenylbutyrate (4­PBA) is a low molecular weight fatty acid, which has been demonstrated to regulate endoplasmic reticulum (ER) stress. ER stress­induced cell apoptosis has an important role in skin flap ischemia; however, a pharmacological approach for treating ischemia­induced ER dysfunction has yet to be reported. In the present study, the effects of 4­PBA­induced ER stress inhibition on ischemia­reperfusion injury were investigated in the skin flap of rats, and transcriptional regulation was examined. 4­PBA attenuated ischemia­reperfusion injury and inhibited cell apoptosis in the skin flap. Furthermore, 4­PBA reversed the increased expression levels of two ER stress markers: CCAAT/enhancer-binding protein­homologous protein and glucose­regulated protein 78. These results suggested that 4­PBA was able to protect rat skin flaps against ischemia­reperfusion injury and apoptosis by inhibiting ER stress marker expression and ER stress­mediated apoptosis. The beneficial effects of 4­PBA may prove useful in the treatment of skin flap ischemia­reperfusion injury.

Hyperoside enhances the suppressive effects of arsenic trioxide on acute myeloid leukemia cells.

Hyperoside (Hyp) is the chief component of some Chinese herbs which has anticancer effect and the present study is to identify whether it could enhance the anti leukemic properties of arsenic trioxide (As2O3) in acute myeloid leukemia (AML). We provide evidence on the concomitant treatment of HL-60 human AML cells with hyperoside potentiates As2O3-dependent induction of apoptosis. The activation of caspase-9, Bcl-2-associated agonist of cell death (BAD), p-BAD, p27 was assessed by Western blot. Results showed that hyperoside inhibited BAD from phosphorylating, reactivated caspase-9, and increased p27 levels. Importantly, hyperoside demonstrated its induction of autophagy effect by upregulation of LC-II in HL-60 AML cell line. Taken together, hyperoside may serve as a great candidate of concomitant treatment for leukemia; these effects were probably related to induction of autophagy and enhancing apoptosis-inducing action of As2O3.

Curculigoside regulates proliferation, differentiation, and pro-inflammatory cytokines levels in dexamethasone-induced rat calvarial osteoblasts.

BACKGROUND: Curculigoside (CCG), one of the main bioactive phenolic compounds isolated from the rhizome of Curculigo orchioides Gaertn., is reported to prevent bone loss in ovariectomized rats. However, the underlying molecular mechanisms are largely unknown. Therefore, we investigated the effects of CCG on proliferation and differentiation of calvarial osteoblasts and discussed the related mechanisms. MATERIALS AND METHODS: Osteoblasts were incubated with dexamethasone (DEX) in the absence or presence of CCG concentrations for 24-72 h. Cell proliferation was evaluated by Cell Counting Kit-8 assay. Mitochondria membrane potential (MMP) and reactive oxygen species (ROS) were assessed by flow cytometry. We assessed the anti-inflammatory responses of CCG on DEX-induced osteoblasts by an enzyme-linked immunosorbent assay (ELISA). Relative protein expression of BMP-2, b-catenin, RANKL, OPG and RANK was measured using Western blotting. RESULTS: It was found that osteoblasts proliferation decreased significantly after treated with 1 µM of dexamethasone (DEX), compared with untreated osteoblasts and the cytotoxic effect of DEX was reversed remarkably when pretreatment with 25-100 µg/ml of CCG. Pretreatment with 25-100 µg/ml of CCG increased MMP level and decreased ROS production in osteoblasts induced by DEX. In addition, DEX-induced inhibition of differentiation markers such as alkaline phosphatase (ALP), OPG, BMP-2, ß-catenin, IGF-1 and M-CSF level, and promotion of differentiation markers such as RANKL and RANK was significantly reversed in the presence of CCG. CCG also reversed DEX-induced production of pro-inflammatory cytokines. CONCLUSIONS: These results provide new insights into the osteoblast-protective mechanisms of CCG through inducing proliferation and differentiation and reducing the inflammatory responses, indicating that CCG may be developed as an agent for the prevention and treatment of osteoporosis.

[Total hip arthroplasty for crowe type IV developmental dysplasia of the hip with S-ROM prosthesis].

OBJECTIVE: To develop the techniques of total hip arthroplasty(THA) for Crowe type IV developmental dysplasia of the hip (DDH) with S-ROM prosthesis,and to assess its clinical results. METHODS: From October 2000 to October 2011,30 patients (36 hips) with Crowe type IV DDH underwent THA,including 6 patients with bilateral hip involved and 24 patients with unilateral. S-ROM prosthesis was adopted together with subtrochanteric transverse osteotomy. All the cementless acetabular cups were placed at the original anatomic location. The threaded cups were put in or near the level of the true acetabulum in all patients. Full coating stems were used in femoral side. All the patients were evaluated by using the Modified Harris Hip Score. Radiographic evaluations were made preoperatively and during follow-up. RESULTS: Two patients lost of follow-up. Twenty-seven patients with 32 hips were followed up,and the average duration was 48 months (ranging from 7 to 84 months). There was 1 patient with bilateral THA died from hemorrhagic shock. Two patients could walk freely with the visible fracture lines at 12th and 18th months postoperatively. There were no complications such as infection or nerve injuries. Modified Harris Hip Score improved from preoperative 41.7+/-3.7 to postoperative 89.1+/-2.9. There was no acetabular or femoral component revision because of mal-position or loosening of the prostheses in all patients. Postoperative X-ray showed that all the prostheses in place,good integration between acetabular cups,femoral prosthesis and host bone without loosening. All bone grafts were integrated. All the hips acquired union of osteotomy and bone in-growth. None of the patients had radiographic evidence of aseptic loosening of prosthesis. CONCLUSION: For the complex DDH, follow methods should be used to improve therapeutic effects:good exposure of the true acetabulum,deepen acetabulum, femoral shortening, oblique osteotomy, using the S-ROM prosthesis.

Low-intensity pulsed ultrasound (LIPUS) may prevent polyethylene induced periprosthetic osteolysis in vivo.

We investigated the effect of local low-intensity pulsed ultrasound (LIPUS) on polyethylene debris induced periprosthetic osteolysis. The periprosthetic osteolysis model was made by injecting endotoxin-free pure polyethylene particles into the distal part of the femur canal and inserting a stainless steel plug into this femur. The effects of polyethylene and LIPUS were assessed histologically and by the shear strength test and periprosthetic bone mineral density (BMD) test. Sixteen rabbits received a stainless steel plug on one side and both polyethylene and a stainless steel plug on the other side. Three months later, the side that received polyethylene showed periprosthetic osteolysis. Subsequently, another 16 rabbits received polyethylene plus local LIPUS (200 mW/cm(2) for 20 min daily) on one side and polyethylene alone on the other side. Three months later, LIPUS effectively prevented the periprosthetic osteolysis caused by polyethylene in this rabbit model.

The effects of local and systemic alendronate delivery on wear debris-induced osteolysis in vivo.

We investigated the effects of locally and systemically administered alendronate on wear debris-induced osteolysis in vivo. Endotoxin-free titanium particles were injected into rabbit femurs, prior to insertion of a nonweight-bearing polymethylmethacrylate plug into the distal femur canal. Then the particles were repeatedly injected into the knee 2, 4, and 6 weeks after the implantation. Alendronate was incorporated at three different concentrations (0.1, 0.5, and 1.0 wt %) into bone cement for local delivery. For systemic delivery, alendronate was subcutaneously injected (1.0 mg/kg/week) 1 week after the implantation and then once a week until sacrifice. Eight weeks postoperatively, there was significant evidence of osteolysis surrounding the plug in the control group compared with markedly blocked osteolysis in the 0.5 wt % and the 1.0 wt % groups, and the systemic group. There was a concentration-dependent effect of alendronate-loaded bone cement on the improvement of peri-prosthetic bone stock. Notably, no significant differences were found between the 0.5 wt % and the systemic group in peri-prosthetic bone stock and implant fixation. Collectively, although the biological efficacy after the systemic delivery of alendronate was slightly higher than that in the local treatment groups, alendronate-loaded bone cement may be therapeutically effective in inhibiting titanium particle-induced osteolysis in vivo.

[Down-regulation of expression of survivin and induction of apoptosis in the human Burkitt lymphomas cells by ligation of CD40-CD40L].

OBJECTIVE: To study the biological effects of ligation of CD40 mediated by soluble recombinant human CD40 ligand (srhCD40L) on the human malignant hematogenous cells and to explore the molecular mechanism thereof. METHODS: Human Burkitt lymphoma cells of the line CA46 were cultured. Flow cytometry was used to detect the expression of CD40 molecule on the cell surface. CA46 cells were put into 96-well plate and added with solutions of srhCD40L of the terminal concentrations of 0.04 microg/ml, 0.2 microg/ml, 1.0 microg/ml, and 5.0 microg/ml respectively, and 24, 28, 72, 96, and 120 hours later cell growth curve was drawn. MTT assay was used to other CA46 cells co-incubated with srhCD40L of the terminal concentrations of 0.04 microg/ml, 0.2 microg/ml, 1.0 microg/ml, and 5.0 microg/ml respectively so as to calculate the proliferation inhibition rate. CA46 cells were treated with srhCD40L of the concentrations of 1.0 microg/ml for 24, 48, and 72 hours respectively, FCM was used to analyze the DNA cycle and TUNEL was used to calculate the apoptotic rate. Annexin-V labeling method was used to detect the positive rate of apoptotic cells. CA46 cells were treated with srhCD40L of the concentration of 1 microg/ml for 24, 48, 72, or 96 hours, semi-quantitative RT-PCR was used to detect the mRNA expression of survivin, an anti-apoptosis protein, and the protein expression of survivin was detected by Western blotting. RESULTS: The expression rate of CD40 in the human Burkitt CA46 cells was 99%. srhCD40L dose-dependently inhibited the proliferation of the CD46 cells. Treated by srhCD40L, the progress of cells at S stage into G(2)/M stage was inhibited. TUNEL showed that treated by srhCD40L (1.0 microg/ml) for 24, 48, and 72 hours the apoptotic rates of the cells were 9%, 18%, and 35% respectively. Annexin-V showed that after incubation with srhCD40L (1.0 microg/ml) for 24 h the apoptotic rate was 10.04%. Two apoptotic peaks appeared 48 and 72 hours later. Semi-quantitative RT-PCR and Western blotting showed that the survivin mRNA expression and protein expression were both down-regulated. CONCLUSION: Ligation of CD40 by srhCD40L inhibits the proliferation of malignant hematogenous cells and induces their apoptosis. Expression of survivin mRNA and protein may be related to cell growth inhibition and to the apoptosis mediated by Ligation of CD40 by srhCD40L.

[Expression of antigen CD40 and survivin gene and their clinical implications in acute myeloid leukemia].

OBJECTIVE: To evaluate the expressions of CD40 antigen and anti-apoptosis gene survivin in acute myeloid leukemia (AML) and their clinical significance. METHODS: By using flow cytometry (FCM) and reverse transcriptase polymerase chain reaction (RT-PCR), CD40 antigen and anti-apoptosis gene survivin mRNA were studied in 48 AML cases and their association with the clinical features of AML was analysed. RESULTS: (1) In the 48 AML cases, positive expression of CD40 antigen was found in 25 cases (52.1%) and positive expression of anti-apoptosis gene survivin mRNA in 35 cases (72.9%). (2) The incidence of splenomegaly, thrombocytopenia and hyperleukocytosis in CD40+ AML cases was significantly higher than those in CD40- AML ones (36.0% vs 8.7%), P=0.025; (72.0% vs 43.5%), P=0.045; (32.0% vs 4.4%), P=0.024. (3) There was no difference in the number of the expression of survivin mRNA between CD40+ AML cases and CD40- AML ones (20/25 vs 15/23) P=0.25, but the expression of survivin mRNA of both the groups was high than those of normal controls (20/25 vs 6/20), P=0.001; (15/23 vs 6/20), P=0.021. In the 48 AML cases the rate of the expression of CD40 antigen was less than those of anti-apoptosis gene survivin mRNA (52.1% vs 72.9%), P=0.041. (4) The complete remission (CR) rate in the survivin+ AML cases receiving chemotherapy was significantly less than that in the survivin- AML ones (31.4% vs 69.2%), P=0.018. CONCLUSIONS: The expression of CD40 antigen might be associated with some unfavorable clinical features of AML. The expression of anti-apoptosis gene survivin might be one of the reasons that AML have a lower CR rate, and it is one of the prognostic factors in AML.