Mitochondria Targeted Peptide Attenuates Mitochondrial Dysfunction, Controls Inflammation and Protects Against Spinal Cord Injury-Induced Lung Injury.

BACKGROUND/AIMS: Spinal cord injury (SCI) is a common and devastating disease, which results in systemic inflammatory response syndrome and secondary lung injury. Mitochondrial dysfunction and inflammation are closely related to lung injury in diverse disease models. No studies have demonstrated the effects of mitochondrial targeted peptide SS-31 in a mouse model of SCI-induced lung injury. METHODS: Immediately after injury, mice in the treatment groups received a daily, single-dose intraperitoneal injection of SS-31 and for the next 2 days. The sham and SCI groups also received a daily single dose of vehicle (DMSO and 0.9% NaCl, 1: 3). The lung tissue of mice was examined after SCI, and tissue damage, apoptosis, inflammation, and mitochondrial dysfunction were recorded. RESULTS: SS-31 treatment attenuated lung edema and tissue damage. Furthermore, SS-31 treatment reduced apoptosis of alveolar type II cells, the number of total macrophages and M1 macrophages, and neutrophil infiltration. Moreover, SS-31 treatment attenuated reactive oxygen species levels, reversed mitochondrial dysfunction and inhibited NLRP3 inflammasome activation. CONCLUSIONS: Collectively, our results demonstrate that SS-31 attenuates mitochondrial dysfunction, controls inflammatory responses, and alleviates the severity of lung damage in a mouse model of SCI-induced lung injury.

Fibroblast growth factor-21 concentration in serum and synovial fluid is associated with radiographic bone loss of knee osteoarthritis.

We aimed to evaluate whether FGF-21 concentration in serum and synovial fluid (SF) is associated with radiographic bone loss of knee osteoarthritis (OA). A total of 186 OA patients and 108 controls were recruited. The radiographic bone loss of knee OA was assessed by the Ahlbäck grading scale. FGF-21 concentration in serum and SF was measured by enzyme-linked immunosorbent assay (ELISA). We demonstrated that OA patients had significantly higher serum FGF-21 concentration compared with controls (204.30 [range 158.25-279.16] ng/L vs. 130.72 [range 94.93-218.03] ng/L, p < 0.01). FGF-21 concentration in serum was well correlated with that in paired SF samples (r = 0.668, p < 0.001). In OA patients, those with a higher Ahlbäck grade had significantly higher serum and SF FGF-21 concentration (p < 0.001 for both). FGF-21 concentration in serum and SF was significantly and independently associated with the Ahlbäck grade (r = 0.403, p < 0.001 and r = 0.410, p < 0.001; respectively). These findings indicated that FGF-21 might be a potential biomarker for predicting bone loss of OA. Therapeutic interventions by blocking FGF-21 signaling pathways to delay the degenerative process of OA warrants further investigations.

Serum fetuin-A levels are inversely associated with clinical severity in patients with primary knee osteoarthritis.

The present study aimed to detect serum fetuin-A levels in knee osteoarthritis (OA) patients and to investigate their correlation with clinical severity. We enrolled 215 knee OA patients and 76 healthy controls. We measured serum fetuin-A levels by enzyme-linked immunosorbent assay and assessed the correlation between serum fetuin-A levels and Kellgren-Lawrence grades as well as Western Ontario and McMaster Universities Arthritis Index scores in OA patients. Our results demonstrated that serum fetuin-A levels were independently and negatively correlated with greater clinical severity in OA patients.

Calcineurin/NFAT pathway mediates wear particle-induced TNF-α release and osteoclastogenesis from mice bone marrow macrophages in vitro.

AIM: To investigate the roles of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in regulation of wear particles-induced cytokine release and osteoclastogenesis from mouse bone marrow macrophages in vitro. METHODS: Osteoclasts were induced from mouse bone marrow macrophages (BMMs) in the presence of 100 ng/mL receptor activator of NF-κB ligand (RANKL). Acridine orange staining and MTT assay were used to detect the cell viability. Osteoclastogenesis was determined using TRAP staining and RT-PCR. Bone pit resorption assay was used to examine osteoclast phenotype. The expression and cellular localization of NFATc1 were examined using RT-PCR and immunofluorescent staining. The production of TNFα was analyzed with ELISA. RESULTS: Titanium (Ti) or polymethylmethacrylate (PMMA) particles (0.1 mg/mL) did not significantly change the viability of BMMs, but twice increased the differentiation of BMMs into mature osteoclasts, and markedly increased TNF-α production. The TNF-α level in the PMMA group was significantly higher than in the Ti group (96 h). The expression of NFATc1 was found in BMMs in the presence of the wear particles and RANKL. In bone pit resorption assay, the wear particles significantly increased the resorption area and total number of resorption pits in BMMs-seeded ivory slices. Addition of 11R-VIVIT peptide (a specific inhibitor of calcineurin-mediated NFAT activation, 2.0 µmol/L) did not significantly affect the viability of BMMs, but abolished almost all the wear particle-induced alterations in BMMs. Furthermore, VIVIT reduced TNF-α production much more efficiently in the PMMA group than in the Ti group (96 h). CONCLUSION: Calcineurin/NFAT pathway mediates wear particles-induced TNF-α release and osteoclastogenesis from BMMs. Blockade of this signaling pathway with VIVIT may provide a promising therapeutic modality for the treatment of periprosthetic osteolysis.

Correlation of synovial fluid HMGB-1 levels with radiographic severity of knee osteoarthritis.

PURPOSE: This study measured high-mobility group box 1 (HMGB-1) levels in serum and synovial fluid (SF) in patients with primary knee osteoarthritis (OA) and correlated these levels with radiographic disease severity. METHODS: Seventy-eight OA patients and 30 controls were enrolled in this study. All OA patients were scored according to the Kellgren-Lawrence (KL) grading system. HMGB-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: SF HMGB-1 levels were significantly higher in knee OA patients, compared with controls (P < 0.01). Moreover, SF HMGB-1 levels were positively associated with KL scores (P < 0.01). Multinomial logistic regression demonstrated that the SF HMGB-1 level was an independent factor for radiographic severity of OA (P=0.002); however, serum HMGB-1 levels did not differ significantly between OA patients and controls and did not correlate with KL scores (P > 0.05). CONCLUSION: These results demonstrate that HMGB-1 levels in SF of knee OA patients are independently associated with radiographic disease severity.

The utility of digital templating in Total Hip Arthroplasty with Crowe type II and III dysplastic hips.

With the superiority of digital imaging, conventional preoperative acetate templating is gradually being replaced by digital templating in total hip arthroplasty (THA). The purpose of this study was to assess the utility of digital templating for patients with Crowe type II and III dysplastic hips. In this study, 41 THA patients with Crowe type II or III dysplastic hips and 48 THA patients with other primary diseases were retrospectively reviewed. All patients were fitted with cementless prostheses in 2008. For the THA patients with dysplastic hips, we attempted to restore their hip centres to the position of the true acetabulum. Digital templating was the method chosen to achieve hip centre restoration. The prosthesis prediction accuracy (within ± one size using digital templating) was 20 (48.8%) for the cup size and 30 (73.2%) for the stem size. Meanwhile, for patients with other primary diseases, the accuracy for the cup size within ± one size was 34 (70.8%) and for the stem size accuracy was within ± one size in 38 (79.2%). Between the two patient groups, there was a significant difference in the predicted cup size. In patients with dysplastic hips, the low accuracy of the predicted cup size may have resulted from difficulty in predicting the vertical location of the hip centre. Despite this limitation, preoperative planning using digital templating is a convenient technique for THA patients with Crowe type II and III dysplastic hips.

Loss of Reduction after Cephalomedullary Nail Fixation of Intertrochanteric Femoral Fracture: A Brief Report.

OBJECTIVE: At present, cephalomedullary nail is the most frequently used implant in the management of intertrochanteric fractures around the world. The implant design and fixation techniques of the cephalomedullary nail have been continuously improved to ensure uncomplicated bone union during the past decade. However, a degree of reduction loss during bone healing is still not rare in clinical work. Many attributed this complication to misoperation during the surgery and hold that a series of techniques and tips could help to avoid the loss of reduction. However, until now there has been no research to explore whether the reduction loss after the operation can be fully prevented in the best cases. The purposes of the study are as follows: (i) to evaluate the efficiency of the current established CMN techniques; (ii) to quantify the loss of reduction under an appropriately implanted CMN to anatomically realigned intertrochanteric fractures; and (iii) to explore the possible underlying causes for the inevitable loss of reduction. METHODS: In the retrospective study, 163 consecutive cases with the intertrochanteric fractures fixed with standard cephalomedullary nail technique were reviewed. The anatomical reduction and optimal positioning of the nail were confirmed by postoperative imaging. The fracture types ranged from 31-A1.1-2.3 according to the OTA/AO fracture classification. One hundred and fifteen cases with stable fracture types (31A1.1-2.1) were allocated to Group A, and 48 cases with unstable 31A2.2-2.3 fracture types were allocated to Group B. The radiological measurements included femoral neck shortening, loss of the neck-shaft angle, cutout, and cut-through of the blade. The outcomes between postoperative and 1 year after the operation were evaluated and compared. RESULTS: The patients consisted of 66 males and 97 females with an average age of 69.4 (range: 46-78, SD: 14.6) years. At the 1-year follow-up, no fixation failure or nonunion was observed in each group. The mean femoral neck shortening and loss of the neck-shaft angle were 4.47 mm (range: 0.43-17.68, SD: 3.71) and 5.4° (range: 0.51-19.10, SD: 3.58) separately. The mean cutout and cut-through were 1.84 mm (range: 0.24-11.30, SD: 2.33) and 1.25 mm (range: 0.51-10.29, SD: 1.74). The average femoral neck shortening and loss of the neck-shaft angle were higher in Group B than Group A. Among the 23 cases with the femoral neck shortening more than 10 mm, 19 cases (16.5%) were from Group A and four cases (8.3%) were from Group B. There were nine (7.8%) cases with the loss of the neck-shaft angle more than 10° in Group A and six (12.5%) cases in Group B. CONCLUSIONS: Current established CMN techniques are efficient in treating intertrochanteric femoral fracture. However, even with currently consensual techniques of cephalomedullary nail, the process of fracture healing still risks the loss of reduction, although the migration of the blade could be minimized. This situation may associate with the intrinsic design of the CMN and further improvement is still needed.

Interleukin-34 Synovial Fluid Was Associated with Knee Osteoarthritis Severity: A Cross-Sectional Study in Knee Osteoarthritis Patients in Different Radiographic Stages.

BACKGROUND: Inflammation might play a crucial role in the pathogenesis of osteoarthritis (OA). Interleukin-34 (IL-34) is a well-known proinflammatory cytokine. OBJECTIVE: The objective of this study was to detect IL-34 levels in serum and synovial fluid (SF) of patients with OA and to investigate their correlation with radiographic and symptomatic severity. METHODS: One hundred and eighty-two OA patients and 69 controls were recruited. IL-34 levels were measured by enzyme-linked immunosorbent assay (ELISA). Radiographic and symptomatic severity of OA was reflected by Kellgren-Lawrence (KL) grades and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores, respectively. RESULTS: SF IL-34 levels were independently associated with the KL grade (B = 0.273, 95% CI: 0.150-0.395; P < 0.001). SF IL-34 levels were significantly correlated with WOMAC scores (r = 0.265, 95% CI: 0.123-0.399; P < 0.001). The correlation between SF IL-34 levels and WOMAC scores was still significant after adjusting for confounding factors (B = 0.020, 95% CI: 0.001-0.038; P = 0.035) in OA patients. CONCLUSIONS: We found that IL-34 levels in SF were significantly associated with the radiographic and symptomatic severity of knee OA.

[Clinical treatment of small bowel diverticula: review of 32 cases].

OBJECTIVE AND METHOD: To retrospectively summarize the pathological features and management of small bowel diverticula of in 32 cases. RESULTS: Complications of small bowel diverticula were effectively treated surgically with good short-term and long-term clinical outcomes. The diverticulum found during the abdominal operation should be treated in time. The complications from the small intestine diverticulum included inflammation, bleeding, stone, perforation and bowel obstruction which arised from the stagnation, impaction, and friction of the contents in the diverticulum or from adhesion zone of long diveritculum. The complications were closely related to the histology of diverticular wall, the type of heterotopic tissue of diverticular mucosa, morphology of the diverticulum and contents in the diverticulum. CONCLUSION: The complications of small bowel diverticulum are the rare cause of acute abdomen which would be surgically treated effectively.