BACKGROUND:Early complications after arthroplasty for geriatric femoral neck fractures are known to negatively affect postoperative recovery and increase postoperative mortality. Identifying risk factors associated with early complications after arthroplasty may offer an opportunity to address and prevent these complications in many patients.OBJECTIVE:To evaluate preoperative risk factors for early complications after arthroplasty in elderly patients with a femoral neck fracture.METHODS:119 elderly patients with femoral neck fractures who had been treated with arthroplasty (hemiarthroplasty or total hip arthroplasty) between December 2015 and December 2018 were retrospectively analysed. Early complications were defined as any complications that did not exist preoperatively, and occurred during hospital stay after arthroplasty Preoperative clinical, epidemiological and laboratory data were collected. Binary univariable and multivariable logistic regression analysis were applied to identify predictors of early complications after arthroplasty for geriatric femoral neck fractures.RESULTS:Median age of all patients was 80.0 (IQR 74.0-84.0) years. We identified 28 (23.5%) early complications after arthroplasty. Univariable logistic regression analysis found that preoperative body mass index (BMI p= 0.031), C-reactive protein (CRP p= 0.017) and serum Albumin (p= 0.006) were potential risk factors for early complications. Then preoperative BMI, CRP and serum Albumin were stratified and used for multivariable logistic regression analysis The multivariate logistic regression analysis showed that preoperative higher BMI (⩾ 28 kg/m2; OR 10.440; 95% CI 2.674-41.170; p= 0.001) and lower serum Albumin (⩽ 35 g/L; OR 3.933; 95% CI 1.509-10.800; p= 0.006) were independent risk factors for early complications after arthroplasty in geriatric femoral neck fractures. However, preoperative higher CRP levels (> 10 mg/L; OR 1.139; 95% CI 1034-1428; p= 0.833) was found to be not an independent risk factor for early complications.CONCLUSION:Our results demonstrate that obesity and hypoalbuminemia are independent predictors for early complications during hospital stay after arthroplasty, which should be meticulously noted to minimize these risk factors in geriatric femoral neck fractures.

Objective Three-dimensionally (3D) printed patient-specific instrumentation (PSI) might help in this regard with individual design and more accurate osteotomy, but whether the utility of such instrumentations minimizes the variability of patellar height in total knee arthroplasty (TKA) and the reasons for this effect are unknown. Our aim is to compare and analyze the variability of patellar height with PSI and conventional instrumentation (CI) in TKA. Methods Between March 2018 and November 2021, 215 patients with severe knee osteoarthritis who were treated with primary unilateral TKA were identified for this observational study. The patients were divided into the CI-TKA group and PSI-TKA group according to the osteotomy tools used in TKA. Preoperative and postoperative radiographic parameters including hip–knee–ankle angle (HKA), posterior tibial slope (PTS), Insall–Salvati ratio, modified Caton–Deschamps (mCD) ratio, anterior condylar offset (ACO), and posterior condylar offset (PCO) were evaluated. Results The groups were similar in patients' demographic data, clinical scores, and radiographic parameters preoperatively. Overall, according to the results of the Insall–Salvati ratio, postoperative patellar height reduction was noted in 140 patients (65.1%). Interestingly, the variability of patellar height was smaller in the PSI-TKA group. Radiographic evaluation revealed that the Insall–Salvati ratio after TKA had a minor change in the PSI-TKA group ( p = 0.005). Similarly, the mCD ratio after TKA also had a minor change in the PSI-TKA group ( p < 0.001). Compared to those in the CI-TKA group, the ACO ( p < 0.001) and PCO ( p = 0.011) after TKA had a minor change in the PSI-TKA group, but no minor PTS change ( p = 0.951) was achieved in the PSI-TKA group after TKA. However, even with 3D-printed patient-specific instrumentation, there were still significant reductions in patellar height, ACO, PCO, and PTS after TKA ( p < 0.001). Conclusion The variability of patellar height was sufficiently minimized with more accurate anterior and posterior femoral condyle osteotomy when 3D printed PSI was used. Furthermore, there was a trend in over-resection of the femoral anterior and posterior condyle and a marked reduction in PTS during TKA, which could lead to a change in patellar height and might result in more patellofemoral complications following TKA. Level of evidence Level II.

Objective To investigate the effect of autophagy expression levels of different weight‐bearing states and different stages of osteoarthritis in animal models, as well as the corresponding mechanisms. Methods We used the male Sprague–Dawley (SD) rats (12‐week‐old, SPF) to establish the OA animal models by modified Hulth method, and grouped animal models according to the length of time after surgery and different weight‐bearing areas. RT‐qPCR was carried out for detection of autophagy‐related genes such as Atg7, Atg12, P62, etc. Western blot analysis was used to detect the expression levels of corresponding autophagy‐related proteins such as LC3B, P62, etc. T test was performed for statistical analysis to compare different groups, while the differences were deemed statistically significant with P < 0.05. Transmission electron microscopy was used to observe the autophagosome to demonstrate the level of autophagy expression and the status of the chondrocytes. Results The results of the RT‐qPCR testing showed that when the weight‐bearing cartilage of the 4‐week group (relatively mild) was compared with that of the 10‐week group (relatively severe), there were statistically significant differences in all the genes tested, in detail: Atg3 (P < 0.01), Atg7 (P < 0.01), Atg12 (P < 0.01), P62 (P < 0.0001). The expression of autophagy‐related mRNA in the 4‐week group is increased compared with that of the 10‐week group. As for the expression of proteins, Western blotting showed that in the comparison between the 4‐ and the 10‐week groups, statistically significant results include Atg12 (P < 0.01) in the non‐weight‐bearing area, with decreased autophagy in the 10‐week group compared with that of the 4‐week group, while expression of LC3B (P < 0.05) protein was significantly higher in the 4‐week group than in the control in the non‐weight‐bearing area. The expression of LC3B (P < 0.0001) and P62 (P < 0.05) in the 10‐week group were higher than that of the control. Transmission electron microscope showed that autophagy in the weight‐bearing area is stronger than that in the non‐weight‐bearing area, and autophagy in the 4‐week group is stronger than in the 10‐week group for the weight‐bearing area. Conclusions The expression of autophagy varies during different stages of osteoarthritis, in which the autophagy is stronger in the early stage of osteoarthritis, and gradually decreases with the progression of the disease. Autophagy in different weight‐bearing areas may also be different.

Abstract Background The aim of this study was to investigate the role of Vaspin on the chondrogenic differentiation of bone mesenchymal stem cells (BMSCs), and its effect on chondrocyte survival and ECM secretion. We also assessed whether the Akt activation participates in these processes. Methods In vivo, immunohistochemistry was used to examine the positive rate of the protein expressions of Akt in Wistar rat articular cartilage and subchondral bone after Vaspin intraperitoneal injection for 14 days. In vitro, we isolated and expanded BMSCs from Wistar rats, and further cultured BMSCs as pellets in a chondrogenic-differentiation medium supplemented with different concentrations of Vaspin. After 21 days, the pellets were processed for cell counting kit assay. The mRNA level of Akt, SOX9 and COL2A1 in the pellets were investigated using quantitative Real-Time polymerase chain reaction, and the protein level of COMP was detected using western blot. Results During the chondrogenic differentiation of BMSCs, Vaspin promoted the chondrogenic differentiation of BMSCs and chondrocyte survival by activating the Akt pathway. These effects were significantly reduced by treatment with an Akt inhibitor. Moreover, Vaspin promoted chondrogenic differentiation of BMSCs by increasing the expression of markers in cartilage formation and extracellular matrix secretion. Furthermore, our study also found that Vaspin could increase Akt expression in cartilage cavities and subchondral bone in vivo. Conclusion These findings demonstrate that Vaspin can promote the chondrogenic differentiation of BMSCs and chondrocyte survival via Akt activation. Our study provides new insights into the potential ability of Vaspin to ameliorate the chondrogenic differentiation of BMSCs and chondrocyte survival in OA.

CASE We report a patient with rheumatoid arthritis (RA) who developed hemophagocytic syndrome (HPS). The HPS was attributed to sepsis, itself a consequence of methotrexate (MTX) overdose. The discovery of MTX overdose was facilitated by the presence of epidermolysis bullosa, multiple ulcers of the whole digestive tract, and additional history from the patient's family. CONCLUSION For arthroplasty patients with underlying inflammatory disorders such as RA, drug history should be thoroughly inquired. Correct diagnosis results from careful history review, detailed physical examination, and necessary laboratory tests.

OBJECTIVE:The aim of this study was to estimate the possible role of vaspin in the proliferation of bone mesenchymal stem cells (BMSCs) and its molecular mechanisms in the bone marrow microenvironment of osteoarthritis (OA).METHODS:This study included 15 non-obese elderly patients with severe knee OA and 15 non-obese controls with femoral neck fracture. Patients all underwent hip or knee arthroplasty surgery to restore joint shape and function. Bone marrow samples were taken during surgery to estimate vaspin and transforming growth factor (TGF)-β1 levels by enzyme-linked immunosorbent assay and to observe the effect of vaspin on BMSCs proliferation by Cell Counting Kit-8. Real-time polymerase chain reaction and western blot were performed to evaluate the effect of vaspin on the genes and proteins of Akt involved in the PI3K/AKT signaling pathway.RESULTS:Bone marrow vaspin levels were significantly lower in OA patients compared to controls (P = .03). Furthermore, we found a significant correlation between vaspin and TGF-β1 concentrations in bone marrow (r = .60, P < .01). In addition, the in vitro studies indicated the proliferation of BMSCs was significantly promoted when the vaspin treatment concentration was 150 ng/mL (P < .01). Meanwhile, we found that the Akt messenger RNA and pAkt protein levels in BMSCs were increased after vaspin treatment (P < .05).CONCLUSION:The findings of this study suggest there was abnormal expression of vaspin in OA bone marrow microenvironment, and vaspin likely had a mediator role in the proliferation of BMSCs, which may work by promoting the activation of the PI3K/AKT signaling pathway.

To investigate the effect of tumor necrosis factor alpha (TNF-α) on the proliferation of fibroblast-like synoviocytes (FLS) and the expression of programmed cell death factor 5 (PDCD5) in an inflammatory microenvironment, for the further understanding of the mechanism of action of TNF-α in promoting the proliferation of synovial cells and the apoptosis of the chondrocytes. Articular carriage specimens were obtained from 21 cases with osteoarthritis and 12 cases with femoral neck fractures as healthy controls during arthroplasties. The expression of PDCD5 was evaluated by immunofluorescence analyzed by mean option density (MOD) detected using the software ImagePro Plus. Real-time PCR was performed to evaluate the transcriptions of PDCD5 and TNF-α in synovium. FLS cells derived from rheumatoid arthritis patients were cultured in vitro and incubated with different concentrations of TNF-α. The effects of TNF-α at different concentrations on the proliferation of FLS cells were detected by Cell Counting Kit-8 (CCK-8) assay to evaluate the cell proliferation rate. After incubation with the absence or presence of recombinant human TNF-α at different concentrations, the FLS cells were isolated for detection of PDCD5 protein and PDCD5 gene. The expression of PDCD5 protein was detected by western-blot and the transcription of PDCD5 gene from the cells was detected by real-time quantitative PCR. The MOD of PDCD5 as well as TNF-α of osteoarthritis cartilage sections were significantly increased compared with those of the controls, and in synovium there was a positive correlation between transcriptions of their mRNA. When the concentration of TNF-α was 1 ng/mL, the cell proliferation rate was not significantly different from that of the control group ( P = 0.592), while the proliferation of FLS cells was significantly promoted when the concentration of TNF-α was 5, 10, 15, or 20 ng/mL, and the proliferation-promoting rates were 35.64% ± 6.96%, 48.72% ± 7.69%, 45.60% ± 8.85%, and 39.32% ± 6.18%, respectively ( P < 0.01). The transcription of PDCD5 gene was significantly downregulated, which was 80.44% ± 4.07% and 84.30% ± 5.48%, respectively ( P < 0.05), in the FLS cells incubated with TNF-α at the concentration of 10 and 15 ng/mL for 24 h. When the concentration of TNF-α was 1, 5, or 20 ng/mL, the transcription of PDCD5 mRNA in FLS cells was not significantly different from that in the control group ( P > 0.05). The expression of PDCD5 protein was only significantly downregulated when the concentration of TNF-α was 10 ng/mL ( P < 0.01), while the expression of PDCD5 protein in FLS cells was not significantly different from that in the control group ( P > 0.05). The expression of PDCD5 as well as TNF-α in osteoarthritis cartilage and synovium was significantly higher than in healthy tissues, and TNF-α can promote the proliferation of FLS cells in patients with rheumatoid arthritis, and inhibit the expression of PDCD5. PDCD5 may be involved in the abnormal proliferation of synoviocytes and the degeneration of chondrocytes stimulated by TNF-α.

OBJECTIVETo analyze the association of preoperative C-reactive protein (CRP) level with postoperative complications in elderly patients undergoing surgeries for femoral neck fracture.METHODSWe retrospectively analyzed the data of 147 elderly patients (median age 80 years; 73.5% of the patients were female) undergoing surgeries for femoral neck fracture. According to preoperative CRP level, the patients were divided into normal CRP (< 10 mg/L) group (31 patients), mild elevation group (CRP level of 10-40 mg/L; 51 patients), and severe elevation group (CRP ≥40 mg/L; 65 patients). The association of preoperative CRP levels with postoperative complications was analyzed.RESULTSPreoperative CRP level was significantly correlated with the occurrence of postoperative complications (P=0.003). Compared with that in normal CRP group, the unadjusted ORs in mild and severe elevation groups were 0.97 (95%CI: 0.29-3.27) and 3.04 (95%CI: 1.03-8.98) with the adjusted ORs of 1.13 (95%CI: 0.33-3.90) and 4.89 (95%CI: 1.47-16.26), respectively.CONCLUSIONSPreoperative CRP level has a dose-response relationship with complications in elderly patients following arthroplasty for femoral neck fracture, and the patients with a preoperative CRP level ≥40 mg/L are exposed to a significantly increased risk for postoperative complications by 3.89 folds compared with the patients with a normal CRP level.

BACKGROUND:Programmed cell death 5 (PDCD5) is an apoptosis-related gene cloned from TF-1 cells whose primary biological functions are to promote apoptosis and immune regulation. The effects and mechanisms exerted by key mediators of arthritic inflammation remain unclear in PDCD5 transgenic (PDCD5 tg) mice.RESULTS:In the current study, PDCD5 tg mice inhibited the progression of adjuvant-induced arthritis, specifically decreasing clinical signs and histological damage, compared with arthritis control mice. Additionally, the ratio of CD4+IFN-γ+ cells (Th1) and CD4+IL-17A+ cells (Th17), as well as the mRNA expression of the pro-inflammatory mediators IFN-γ, IL-6, IL-17A and TNF-α, were decreased in PDCD5 tg mice, while CD4+CD25+Foxp3+ regulatory T (Treg) cells and the anti-inflammatory mediators IL-4 and IL-10 were increased. Furthermore, PDCD5 tg mice demonstrated reduced serum levels of IFN-γ, IL-6, IL-17A and TNF-α and increased levels of IL-4.CONCLUSIONS:Based on our data, PDCD5 exerts anti-inflammatory effects by modifying the T lymphocytes balance, inhibiting the production of pro-inflammatory mediators and promoting the secretion of anti-inflammatory cytokines, validating PDCD5 protein as a possible treatment for RA.

Background Programmed cell death 5 (PDCD5) is a novel apoptotic regulatory gene that promotes apoptosis in various tumor cells. Studies have shown that PDCD5 accelerates the apoptosis of synoviocytes in vitro, implying a potential role in rheumatoid arthritis (RA) pathogenesis. This study examined the expression of PDCD5 in serum and synovial fluid of RA patients, its effect on the expression of inflammatory cytokine, interleukin-17 (IL-17), and the assessment of disease activity in RA.Methods PDCD5 and IL-17 levels in serum and synovial fluid from 18 patients with RA and 22 patients with osteoarthritis (OA) were detected using enzyme-linked immunosorbent assay (ELISA). Concentrations of serum PDCD5 in 40 healthy people were also detected as controls. As disease activity indices, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and X-ray grading scale were also evaluated.Results Serum and synovial fluid PDCD5 levels in RA patients were significantly higher than those in OA and healthy controls. Serum PDCD5 level was inversely correlated to CRP and ESR, and was significantly higher in the RF negative group than in the positive group. PDCD5 level was also negatively correlated with IL-17 levels both in serum and synovial fluid of RA patients. However, differences in synovial fluid PDCD5 level from RA patients at different Larsen stages were not detectable.Conclusions PDCD5 affects RA pathogenesis. Insufficient apoptosis of fibroblast-like synoviocytes and inflammatory cells in RA could increase the expression of PDCD5 protein. As PDCD5 levels correlated negatively with disease activity indices and IL-17 level, PDCD5 could become a target in the diagnosis and treatment of RA.

Context: Programmed cell death 5 (PDCD5), a novel apoptotic regulatory gene, has been reported to be associated with rheumatoid arthritis (RA) and osteoarthritis (OA), which can regulate the apoptosis of synoviocytes and chondrocytes cultured in vitro.Objective: To study expression characteristic of PDCD5 in plasma and synovial fluid of RA patients, and analyze its correlation with tumor necrosis factor alpha (TNF-α) and disease activity in RA.Methods: A total of 135 subjects were recruited into this study (44 RA patients, 46 OA patients and 45 healthy controls). PDCD5 and TNF-α concentrations in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay.Results: Plasma and synovial fluid PDCD5 concentrations were significantly elevated in RA patients. Pearson correlation analysis indicated that plasma and synovial fluid PDCD5 levels were inversely correlated with TNF-α. Moreover, plasma PDCD5 levels were also inversely correlated with C-reactive protein and erythrocyte sedimentation rate.Conclusion: Plasma and synovial fluid PDCD5 could be useful for monitoring the activity and progression of RA, and its abnormal expression and dysfunction may be correlated to TNF-α in RA patients.

BACKGROUND:Multiple drug resistance (MDR) greatly limits the efficacy of chemotherapy for colon cancer. An adenovirus armed with Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24; abbreviated to 'IL-24' here) was shown to reverse the MDR of colon cancer cells to oxaliplatin and doxorubicin. However, the relatively low expression level of IL-24 mediated by a replication-deficient adenoviral vector hindered its clinical application.METHODS:To enhance IL-24-dependentreversion of the MDR phenotype, we utilized a conditionally replicative adenoviral vector, AdBB-IL24, to express IL-24 at a high level for more efficient MDR reversion.RESULTS:An enzyme-linked immunosorbent assay (ELISA) suggested conditionally replicative adenoviral vector-mediated IL-24 expression was elevated in comparison with that of a replication-deficient adenoviral vector, Ad-IL24. AdBB-IL24 was shown to reverse MDR in colon cancer cells more potently than Ad-IL24. The AdBB-IL24-induced MDR reversion was linked to reduced P-glycoprotein (Pgp) and breast cancer resistance protein 1 (BCRP1) expression. Consistently, 5-fluorouracil and doxorubicin induced more apoptosis in AdBB-IL24-infected colon cancer cells compared with that in the Ad-IL24-infected cells. A cell viability assay showed that AdBB-IL24 could enhance the growth-inhibitory effect of 5-fluorouracil and doxorubicin on colon cancer cells more effectively than Ad-IL24 in vitro. In a mouse model, we also found that the combination of 5-fluorouracil and doxorubicin with AdBB-IL24 completely inhibited the growth of colon cancer cells.CONCLUSION:We here provide evidence supporting conditionally replicative adenoviral vector-based gene therapy as a powerful strategy to enhance mda7/IL-24-dependent MDR reversion of colon cancer cells.