Comprehensive analysis of anoikis-related genes in diagnosis osteoarthritis: based on machine learning and single-cell RNA sequencing data.

Osteoarthritis (OA) is a degenerative disease closely associated with Anoikis. The objective of this work was to discover novel transcriptome-based anoikis-related biomarkers and pathways for OA progression.The microarray datasets GSE114007 and GSE89408 were downloaded using the Gene Expression Omnibus (GEO) database. A collection of genes linked to anoikis has been collected from the GeneCards database. The intersection genes of the differential anoikis-related genes (DEARGs) were identified using a Venn diagram. Infiltration analyses were used to identify and study the differentially expressed genes (DEGs). Anoikis clustering was used to identify the DEGs. By using gene clustering, two OA subgroups were formed using the DEGs. GSE152805 was used to analyse OA cartilage on a single cell level. 10 DEARGs were identified by lasso analysis, and two Anoikis subtypes were constructed. MEgreen module was found in disease WGCNA analysis, and MEturquoise module was most significant in gene clusters WGCNA. The XGB, SVM, RF, and GLM models identified five hub genes (CDH2, SHCBP1, SCG2, C10orf10, P FKFB3), and the diagnostic model built using these five genes performed well in the training and validation cohorts. analysing single-cell RNA sequencing data from GSE152805, including 25,852 cells of 6 OA cartilage.

An inflammation-associated ferroptosis signature optimizes the diagnosis, prognosis evaluation and immunotherapy options in hepatocellular carcinoma.

Inflammation and ferroptosis crosstalk complexly with immune microenvironment of hepatocellular carcinoma (HCC), thus affecting the efficacy of immunotherapy. Herein, our aim was to identify the inflammation-associated ferroptosis (IAF) biomarkers for contributing HCC. A total of 224 intersecting DEGs identified from different inflammation- and ferroptosis-subtypes were set as IAF genes. Seven of them including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 were used for construction of a risk model which classified HCC patients into two groups (high and low risk). HCC patients in the high-risk group exhibited shorter survival rate and higher immune score, and were predicted to have higher respond rate in immune checkpoint inhibition (ICI) therapy. Levels of the seven genes were significantly changed in HCC tissues in comparison to adjacent tissues. After inserting the gene expression into the risk model, we found that the risk model exhibited the higher diagnostic value for distinguish HCC tissues compared each single gene. Furthermore, HCC tissues from our research group with high-risk score exhibited more cases of microsatellite instability (MSI), heavier tumour mutational burden (TMB), higher expression level of PDL1 and cells with CD8. Knockdown of APOA5 reduced HCC cell proliferation combining with elevating inflammation and ferroptosis levels. In conclusion, we considered APOA5 maybe a novel target for suppressing HCC via simultaneously elevating inflammation and ferroptosis levels, and signature constructed by seven IAF genes including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 can act as a biomarker for optimising the diagnosis, prognosis evaluation and immunotherapy options in HCC patients.

LncAABR07053481 inhibits bone marrow mesenchymal stem cell apoptosis and promotes repair following steroid-induced avascular necrosis.

The osteonecrotic area of steroid-induced avascular necrosis of the femoral head (SANFH) is a hypoxic microenvironment that leads to apoptosis of transplanted bone marrow mesenchymal stem cells (BMSCs). However, the underlying mechanism remains unclear. Here, we explore the mechanism of hypoxic-induced apoptosis of BMSCs, and use the mechanism to improve the transplantation efficacy of BMSCs. Our results show that the long non-coding RNA AABR07053481 (LncAABR07053481) is downregulated in BMSCs and closely related to the degree of hypoxia. Overexpression of LncAABR07053481 could increase the survival rate of BMSCs. Further exploration of the downstream target gene indicates that LncAABR07053481 acts as a molecular "sponge" of miR-664-2-5p to relieve the silencing effect of miR-664-2-5p on the target gene Notch1. Importantly, the survival rate of BMSCs overexpressing LncAABR07053481 is significantly improved after transplantation, and the repair effect of BMSCs in the osteonecrotic area is also improved. This study reveal the mechanism by which LncAABR07053481 inhibits hypoxia-induced apoptosis of BMSCs by regulating the miR-664-2-5p/Notch1 pathway and its therapeutic effect on SANFH.

Identification and validation of an anoikis-related lncRNA signature to predict prognosis and immune landscape in osteosarcoma.

Background: Anoikis is a specialized form of programmed apoptosis that occurs in two model epithelial cell lines and plays an important role in tumors. However, the prognostic value of anoikis-related lncRNA (ARLncs) in osteosarcoma (OS) has not been reported. Methods: Based on GTEx and TARGET RNA sequencing data, we carried out a thorough bioinformatics analysis. The 27 anoikis-related genes were obtained from the Gene Set Enrichment Analysis (GSEA). Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis were successively used to screen for prognostic-related ARLncs. To create the prognostic signature of ARLncs, we performed multivariate Cox regression analysis. We calculated the risk score based on the risk coefficient, dividing OS patients into high- and low-risk subgroups. Additionally, the relationship between the OS immune microenvironment and risk prognostic models was investigated using function enrichment, including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), single-sample gene set enrichment analysis (ssGSEA), and GSEA analysis. Finally, the potential effective drugs in OS were found by immune checkpoint and drug sensitivity screening. Results: A prognostic signature consisting of four ARLncs (AC079612.1, MEF2C-AS1, SNHG6, and TBX2-AS1) was constructed. To assess the regulation patterns of anoikis-related lncRNA genes, we created a risk score model. According to a survival analysis, high-risk patients have a poor prognosis as they progress. By using immune functional analysis, the lower-risk group demonstrated the opposite effects compared with the higher-risk group. GO and KEGG analysis showed that the ARLncs pathways and immune-related pathways were enriched. Immune checkpoints and drug sensitivity analysis might be used to determine the better effects of the higher group. Conclusion: We identified a novel prognostic model based on a four-ARLncs signature that might serve as potential prognostic indicators that can be used to predict the prognosis of OS patients, and immunotherapy and drugs that may contribute to improving the overall survival of OS patients and advance our understanding of OS.

Direct Anterior Approach Versus Posterolateral Approach in Total Hip Arthroplasty: A Systematic Review and Meta-analysis of Randomized Controlled Studies.

OBJECTIVE: To compare the early rehabilitation effects of total hip arthroplasty (THA) with the direct anterior approach (DAA) versus the posterior approach (PA). METHODS: We searched PubMed, Embase, Web of Science, the Cochrane Library, and Google databases from inception to June 2019 to select studies that compared the DAA and PA for THA. Only randomized controlled trials (RCT) were included. Two researchers independently screened studies for inclusion, extracted data, and assessed the methodological quality. A meta-analysis was conducted using RevMan 5.3 software provided by Cochrane Assisted Network. RESULTS: A total of 932 patients underwent THA. There were 467 cases in group DAA and 465 cases in group PA. There was a significant difference in the incidence of lateral femoral cutaneous nerve injury between DAA and PA groups (RR = 38.97, 95% CI: 7.89-192.57, P < 0.05). DAA was associated with less pain compared with PA [WMD = -0.65, 95% CI (-0.91-0.38), P < 0.05]. There was no significant difference in operation time, hospitalization stay, and intraoperative bleeding volume. Moreover, in supplementary data, the number of acetabular prostheses in Lewinnek's safety zones in DAA was more than that in the PA group (RR = 1.20, 95% CI [1.04-1.39], P < 0.05), and the time of discontinuation of walking aids in the DAA group was earlier than that in the PA group (WMD = -11.05, 95% CI [-17.79-4.31], P < 0.05). CONCLUSION: The DAA total hip arthroplasty has comparable results with PA, with earlier postoperative functional recovery, less postoperative pain scores, and higher incidence of lateral femoral cutaneous nerve injury. The results need to be validated by large-sample, high-quality RCT studies, and long-term follow-up of complications.

Individualized Drug Repositioning For Rheumatoid Arthritis Using Weighted Kolmogorov-Smirnov Algorithm.

BACKGROUND: Existing drugs are far from enough for investigators and patients to administrate the therapy of rheumatoid arthritis. Drug repositioning has drawn broad attention by reusing marketed drugs and clinical candidates for new uses. PURPOSE: This study attempted to predict candidate drugs for rheumatoid arthritis treatment by mining the similarities of pathway aberrance induced by disease and various drugs, on a personalized or customized basis. METHODS: We firstly measured the individualized pathway aberrance induced by rheumatoid arthritis based on the microarray data and various drugs from CMap database, respectively. Then, the similarities of pathway aberrances between RA and various drugs were calculated using a Kolmogorov-Smirnov weighted enrichment score algorithm. RESULTS: Using this method, we identified 4 crucial pathways involved in rheumatoid arthritis development and predicted 9 underlying candidate drugs for rheumatoid arthritis treatment. Some candidates with current indications to treat other diseases might be repurposed to treat rheumatoid arthritis and complement the drug group for rheumatoid arthritis. CONCLUSION: This study predicts candidate drugs for rheumatoid arthritis treatment through mining the similarities of pathway aberrance induced by disease and various drugs, on a personalized or customized basis. Our framework will provide novel insights in personalized drug discovery for rheumatoid arthritis and contribute to the future application of custom therapeutic decisions.

Construction of Anti-hPD-L1 HCAb Nb6 and in Situ 124I Labeling for Noninvasive Detection of PD-L1 Expression in Human Bone Sarcoma.

Immunotherapy is considered the fourth major treatment mode for cancer following surgery, chemotherapy, and radiotherapy. In recent years, tumor immunotherapy has achieved breakthrough progress; therefore, it is important to screen patients to identify those who will respond to tumor immunotherapy. Here, we report the construction of a novel heavy chain-only antibody (HCAb) and its corresponding 124I-labeled probe. Using phage display technology, we generated a novel anti-hPD-L1-specific HCAb named Nb6 (selected from 95 monoclones) with high affinity for hPD-L1. The positron-emitting 124I-labeled hPD-L1-targeted HCAb probe was prepared for further evaluation, and nonradioactive natural iodine (natI)-labeled anti-hPD-L1 Nb6 was synthesized as a reference compound. 125I-anti-hPD-L1 Nb6 uptake in OS-732 cells in vitro can be blocked by the precursor. The binding affinity of 125I-anti-hPD-L1 Nb6 to OS-732 cell lines was 2.19 nM. For in vivo studies, an osteosarcoma OS-732 tumor-bearing mouse model was successfully constructed. Polymerase chain reaction (PCR) and Western blot analyses were performed to confirm the presence of the hPD-L1 gene and antigen in the tumor tissue of the OS-732 mouse model. Biodistribution showed that uptake of 124I-anti-hPD-L1 Nb6 probes at 24 h was 4.43 ± 0.33% ID/g in OS-732 tumor tissues. Tumor lesions can be clearly delineated on micro-PET (positron emission tomography)/CT (computed tomography) imaging 24 h after injection of 124I-anti-hPD-L1 Nb6, while the blocking group shows substantially decreased uptake on imaging. Pathological staining validated hPD-L1 expression on the surface of the tumor cell membrane; thus, 124I-anti-hPD-L1 Nb6 can be used for in vivo noninvasive PET imaging. When administered in tandem, Nb6 and 124I-anti-hPD-L1 Nb6 may provide a novel strategy to clinically screen patients for hPD-L1 to identify those who would benefit from immunotherapy of malignant tumors such as osteosarcoma.

The effect of anticoagulants on venous thrombosis prevention after knee arthroscopy: a systematic review.

PURPOSE: Knee arthroscopy, with its unique advantages, has become a routine surgery and is widely carried out around the world. Venous thromboembolism (VTE) after knee arthroscopy is a potentially serious complication. This article analyzes the effects of anticoagulant therapy after knee arthroscopy. METHODS: We used key words or entry terms without any limitations to search the PubMed, Embase, and Cochrane Library databases. Randomized controlled trials (RCTs) of drug prophylaxis for VTE after knee arthroscopy until November 2017 were included in our review. RESULTS: This systematic review identified nine RCTs, consisting of 4290 patients, investigating drug prophylaxis in knee arthroscopy. There are three main drugs for preventing thrombosis after arthroscopic knee surgery: low-molecular-weight heparin (LMWH), rivaroxaban, and aspirin. Our study concluded that there is no difference in symptomatic VTE (excluding symptomatic distal DVT) risk during anticoagulant prophylaxis (RR, 0.98; 95% CI, 0.44-2.19; I2 value = 0%; P = 0.97). Moreover, there was a lower incidence of symptomatic distal DVT (RR, 0.16; 95% CI, 0.06-0.45; I2 value = 0%; P = 0.0005) in the anticoagulant group than in the control group. CONCLUSIONS: In our study, anticoagulant therapy after knee arthroscopy was ineffective. We recommend that anticoagulants not be provided routinely after knee arthroscopy.

Rivaroxaban versus enoxaparin for the prevention of venous thromboembolism after total knee arthroplasty: A meta-analysis.

OBJECTIVE: This article analyzed the clinical efficacy and tolerability of rivaroxaban and enoxaparin in patients undergoing total knee arthroplasty (TKA) surgery. METHODS: Five randomized, controlled clinical trials on rivaroxaban versus enoxaparin in patients who underwent TKA were identified and included in this meta-analysis. RESULTS: The meta-analysis indicated that rivaroxaban prophylaxis was associated with lower rates of symptomatic venous thromboembolism (VTE) (relative risk[RR]:0.55; 95% confidence interval [CI]: 0.35-0.86; P = .009), symptomatic deep vein thrombosis (DVT) (RR 0.44, 95% CI 0.25-0.80, P = .007), asymptomatic DVT (RR: 0.57; 95% CI: 0.37-0.89; P = .01), distal DVT (RR: 0.62; 95% CI: 0.45-0.85; P = .003) and proximal DVT (RR: 0.42; 95% CI: 0.24-0.75; P = .004). Compared with the enoxaparin group, the incidence of symptomatic pulmonary embolism (PE) (RR: 0.48; 95% CI: 0.19-1.24; P = .13) in the rivaroxaban group was not significantly different. A nonsignificant trend towards all-cause death (RR: 0.38; 95% CI: 0.03-4.92; P = .46) or major bleeding (RR: 1.59; 95% CI: 0.77-3.27; P = .21) risk between rivaroxaban and enoxaparin prophylaxis was found. CONCLUSION: Compared with the enoxaparin group, the group using rivaroxaban after TKA had a significantly lower rate of symptomatic VTE, symptomatic DVT, asymptomatic DVT, distal DVT, and proximal DVT. Our study shows that rivaroxaban after TKA is more effective than enoxaparin and did not increase major bleeding or all-cause mortality.

miR-1307-3p suppresses the chondrogenic differentiation of human adipose-derived stem cells by targeting BMPR2.

MicroRNAs (miRs) are involved in several physiological processes, including chondrogenic differentiation, however, their expression and roles in the chondrogenic differentiation of human adipose­derived stem cells (hADSCs) remain to be fully elucidated to date. Our previous study showed that miR­1307­3p was significantly downregulated during chondrogenic differentiation by microarray and northern blot analysis. The present study aimed to investigate the effects of miR­1307­3p on chondrogenic differentiation and the underlying mechanisms. First, the decreased expression of miR­1307­3p was confirmed by reverse transcription­quantitative polymerase chain reaction analysis. Subsequently, gain­ and loss­of­function of miR­1307­3p experiments showed that the overexpression of miR­1307­3p suppressed the deposition of cartilage matrix proteoglycans and decreased the expression of cartilage­related markers, including sex determining region Y­box 9, collagen type II α1 chain and aggrecan, whereas the knockdown of miR­1307­3p had the opposite effect. In addition, bone morphogenetic protein receptor type 2 (BMPR2) was identified as a target of miR­1307­3p. Further mechanistic investigations showed that miR­1307­3p attenuated the chondrogenic differentiation of hADSCs at least partly by inhibiting BMPR2­mothers against decapentaplegic signaling pathways. In conclusion, the findings revealed that miR­1307­3p inhibited the chondrogenic differentiation of hADSCs by targeting BMPR2 and its downstream signaling pathway, which may provide novel therapeutic clues for the treatment of cartilage injury.

Efficacy and safety of low-molecular-weight heparin after knee arthroscopy: A meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is considered a potentially serious complication of knee arthroscopy and leads to conditions such as deep venous thrombosis (DVT) and pulmonary embolism (PE). Low-molecular-weight heparin (LMWH) is widely employed in knee arthroscopy to reduce perioperative thromboembolic complications. However, the efficacy and safety of LMWH in knee arthroscopy remains unclear. METHODS: Seven randomized controlled clinical trials on LMWH in knee arthroscopy were identified and included in this meta-analysis. The main outcomes of the effectiveness (prevention of DVT and PE) and complications (death, major bleeding, and minor bleeding) of LMWH in knee arthroscopic surgery were assessed using Review Manager 5.3 software. RESULTS: The meta-analysis indicated that LMWH prophylaxis comprised 79% of asymptomatic DVT. No association was found in symptomatic VTE (RR: 0.90; 95% confidence interval [CI]: 0.39-2.08; P = 0.80), symptomatic DVT (RR: 0.79; 95% CI: 0.28-2.23; P = 0.66), symptomatic PE (RR: 1.36; 95% CI: 0.37-4.97; P = 0.64) and major bleeding (RR: 0.70; 95% CI: 0.12-3.95; P = 0.68) risk during LMWH prophylaxis were identified. Death was not reported in these studies. Moreover, there was a lower incidence of minor bleeding (RR: 0.64; 95% CI: 0.49 to 0.83; P = 0.001) in the control group than in the LMWH group. CONCLUSION: Compared with the control group, the group treated with LMWH after knee arthroscopy was no association in reducing the symptomatic VTE rate, symptomatic DVT rate or symptomatic PE rate. The symptomatic VTE rate was 0.5% (11/2,166) in the LMWH group versus 0.6% (10/1,713) in the control group. Although the limitations of this meta-analysis cannot be ignored, the results of our study show that LMWH after knee arthroscopy is ineffective. We recommend that LMWH should not be routinely provided for knee arthroscopy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03164746.

Short-term Follow-up of Antibiotic-loaded Articulating Cement Spacers in Two-stage Revision of Infected Total Knee Arthroplasty: A Case Series.

OBJECTIVE: Infection of total knee arthroplasty (TKA) is a rare but devastating complication. Two-stage revision is an effective treatment for late infected TKA. This study aimed to assess the short-term results of two-stage revision using articulating antibiotic-loaded spacers. METHODS: Twenty-five patients (10 men and 15 women) were diagnosed with late infections after TKA and treated with two-stage revision from April 2006 to August 2010; 19 of these patients had TKA for osteoarthritis and 6 for rheumatoid arthritis. Median age was 64.9 (range, 56-83) years. In the first-stage surgery, the prosthesis and all bone cement was removed. After thorough debridement, bone cement with vancomycin and tobramycin was put into a die cavity and made into temporary femoral and tibial spacers, respectively. In the cases of good knee range of motion, the temporary spacers were affixed to the bone surface using the same antibiotic bone cement. In the second surgery, gentamycin Refobacin Bone Cement with vancomycin was used to fix the prosthesis. After two-stage revision, patients were followed up clinically and radiologically at 1, 3, and 6 months, and then annually. Knee Society Score (KSS), knee function score, knee pain score, and knee range of motion (ROM) were assessed. RESULTS: Among the group, all spacers were easily removed, and bone defect degree showed no obvious change compared with pre-implant, 24 (96%) patients had been debrided once, and 1 patient had been debrided twice before reimplant prosthesis. Mean follow-up was 64.2 (range, 52-89) months. There was no infection recurrence at final follow-up. Compared with preoperative data, the KSS (66 [59, 71], 83 [80, 88] vs 46 [43, 57], P < 0.01), knee function score (43 [42, 49], 78 [73, 82] vs 32 [25, 37], P < 0.01), knee pain score (34 [33, 37], 42 [40, 45] vs 18 [16, 23], P < 0.01), and knee ROM (92° [86°, 96°], 94° [90°, 98°] vs 78° [67°, 86°], P < 0.01) were all improved during follow-up and at final visit. Three patients experienced complications in the interval period: one case had knee dislocation, one had knee instability, and one had a chip in the femoral component of the spacer. CONCLUSION: Using articulating antibiotic-loaded spacers showed benefits for treating infected TKA in selected patients. No infection recurrence was observed during follow-up.

Correlation of Cup Inclination Angle with Liner Wear for Metal-on-polyethylene in Hip Primary Arthroplasty.

OBJECTIVES: The relationship between cup inclination angle and liner wear is controversial. Most authors in the published literature agree that the ideal cup inclination is associated with lower inner wear; however, some disagree. All previous studies did not control for femoral head diameter and inclination, so it is difficult to assess the relative or synergistic effects of cup angle on outcomes. METHODS: We retrospectively reviewed 154 patients (171 hips) with primary total hip arthroplasties performed from 2001 to 2004. All surgeries had been performed by the same physician team. A posterior approach was applied in all patients. All prostheses were non-cemented cups with a 28-mm metal head. Inclusion criteria included that the radiographic material was not completed or lost for primary or last follow up. Patients were divided into four groups according to different cup inclination angle. There were 108 hips with inclination angles below 50°; 35 hips with angles between 50° and 55°; 17 hips with angles between 55° and 60°; and 11 hips with angles greater than 60°. An immediate postoperative radiograph was compared with a follow-up radiograph. Clinical and radiographic data were collected on standardized hip evaluation forms preoperatively, 6 months after surgery and at yearly follow-up visits. Radiographs were digitized and enlarged 100%. After the radiographs were digitized, polyethylene wear rates and acetabular cup abduction were measured on all patients with Cavas 15.0 software. The results were analyzed using Student's two-tailed paired t-test with SPSS 11.5. RESULTS: The preoperative mean Harris hip score improved from 45.36 to 93.5 points 10 years after surgery. No acetabular component was revised for aseptic loosening. Three patients (three hips) had to undergo bone grafting and a lined arthroplasty for severe osteolysis around the acetabular component. The rate of implant survival at 10 years with respect to loosening was 100%. The mean liner wear rate was 0.135 mm/year in cups with inclination angles below 50°, 0.144 mm/year between 50° and 55°, 0.260 mm/year between 55° and 60°, and 0.403 mm/year when the angle was greater than 60°. Liner wear increased when the cup angle was larger than 55° (P < 0.05). CONCLUSIONS: For metal-on-polyethylene prostheses, liner wear correlates with cup inclination angle larger than 55°. The ideal abduction angle for metal-on-polyethylene prostheses is less than 55°.

Osteogenic Ability Detection of Human Bone Morphogenetic Protein-2 Gene-activated Nano Bone Putty by Reusable Double-Cavity Bone Harvest Chamber.

OBJECTIVE: To explore the feasibility of implanting a self-designed reusable double-cavity bone harvest chamber into Guizhou mini-pigs for observation of the osteogenic effect of human bone morphogenetic protein-2 (hBMP-2) gene-activated nano bone putty on bone in growth. METHODS: Eight healthy 12-month-old female Guizhou mini-pigs were used for the present experiment. In the first operation, empty double-cavity bone harvest chambers (n = 8) were implanted into the femoral metaphysis of the animals as a blank control group. In the second operation, the femoral metaphyses were implanted with the chambers filled by the nano bone putty+hBMP-2 plasmid in one cavity and nothing in the other cavity, respectively (experiment group, n = 8). The time interval between every operation was 3 months. The cavity materials were retrieved and replaced for assessment by gross observation, histological examination, and bone morphology metrology analysis to compare osteogenesis ability and alkaline phosphatase. RESULTS: Three months after surgery, the nano bone putty+hBMP-2 plasmid in one cavity of the chambers had hard gray and white tissues inside, while the cavities pre-installed with nothing were filled with soft brown tissues. Light microscopy showed new generated bone tissue around the filled material, but only fibrous tissues in the empty cavities. Osteogenesis ability and alkaline phosphatase of the nano bone putty+hBMP-2 plasmid group were significantly higher than those of the blank control group (P < 0.05). CONCLUSION: The reusable double-cavity bone harvest chamber can be used to observe the osteogenic potential of the hBMP-2 gene-activated nano bone putty.

[Plasma from patients with systemic lupus erythematosus inhibits suppressive activity of mesenchymal stem cells against lupus B lymphocytes].

OBJECTIVE: To investigate whether plasma from patients with systemic lupus erythematosus (SLE) inhibits the suppressive effects of mesenchymal stem cells (MSCs) on lupus B lymphocytes. METHODS: MSCs isolated and expanded from the bone marrow of healthy donors were co-cultured with B cells purified from the peripheral blood of SLE patients in the presence of fetal bovine serum or pooled plasma from SLE patients, and the proliferation and maturation of the B lymphocytes were analyzed. RESULTS: s Co-culture with normal MSCs obviously inhibited the proliferation of lupus B cells and suppressed the maturation of B lymphocytes, which showed lowered expressions of CD27 and CD38. The pooled plasma from SLE patients significantly inhibited the suppressive effects of normal MSCs on B cell proliferation and maturation. CONCLUSION: Plasma from SLE patients negatively modulates the effects of normal MSCs in suppressing lupus B cell proliferation and maturation to affect the therapeutic effect of MSC transplantation for treatment of SLE. Double filtration plasmapheresis may therefore prove beneficial to enhance the therapeutic effects of MSC transplantation for SLE.

Potential role of andrographolide in the proliferation of osteoblasts mediated by the ERK signaling pathway.

The aim of the present study was to explore the effects of andrographolide (AG) and the ERK signaling pathway on the proliferation of osteoblasts (OBs) in vitro. The calvarial OBs from Sprague Dawley (SD) rats were collected and treated at different concentrations of AG and U0126. The concentrations of AG were measured by colorimetry. Based on different treatment methods, the cells were separated into four groups: control group, U0126 group, AG group, and AG+U0126 group. The cells were cultured for 24h, 48h and 72h. An inverted phase contrast microscope was used to observe the morphologies of treated OBs. The MTT assay was performed to plot OB proliferation curves, and to measure the changes in alkaline phosphatase and hydroxyproline contents after U0126 treatments. The expressions of proliferating cell nuclear antigen (PCNA), Ki67, core binding factor alpha-1 (Cbfa1), type I collagen (Col I), osterix (OSX), p38, extracellular signal regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) were measured by fluorescent quantitative polymerase chain reaction (PCR) and Western blotting. In different cell groups, the in vitro proliferation rates of OBs reached the highest at an AG concentration of 20µmol/L, and the amounts of alkaline phosphatase, hydroxyproline, PCNA, Ki67, Cbfa1, Col I, OSX, and ERK were significantly higher than at other concentrations (all P<0.05). U0126 intervention significantly decreased the expressions of these factors (all P<0.05). At the meantime, p38 and JNK were not affected by AG and were only inhibited by U0126. In conclusion, ERK played an important role in mediating the functions of AG in the proliferation of OBs, indicating that the ERK signaling pathway may be the main pathway through which AG exerts its effects.

Establishing a Customized Guide Plate for Osteotomy in Total Knee Arthroplasty Using Lower-extremity X-ray and Knee Computed Tomography Images.

BACKGROUND: The conventional method cannot guarantee the precise osteotomies required for a perfect realignment and a better prognosis after total knee arthroplasty (TKA). This study investigated a customized guide plate for osteotomy placement in TKAs with the aid of the statistical shape model technique using weight-bearing lower-extremity X-rays and computed tomography (CT) images of the knee. METHODS: From October 2014 to June 2015, 42 patients who underwent a TKA in Guizhou Provincial People's Hospital were divided into a guide plate group (GPG, 21 cases) and a traditional surgery group (TSG, 21 cases) using a random number table method. In the GPG group, a guide plate was designed and printed using preoperative three-dimensional measurements to plan and digitally simulate the operation. TSG cases were treated with the conventional method. Outcomes were obtained from the postoperative image examination and short-term follow-up. RESULTS: Operative time was 49.0 ± 10.5 min for GPG, and 62.0 ± 9.7 min in TSG. The coronal femoral angle, coronal tibial angle, posterior tibial slope, and the angle between the posterior condylar osteotomy surface and the surgical transepicondylar axis were 89.2 ± 1.7°, 89.0 ± 1.1°, 6.6 ± 1.4°, and 0.9 ± 0.3° in GPG, and 86.7 ± 2.9°, 87.6 ± 2.1°, 8.9 ± 2.8°, and 1.7 ± 0.8° in TSG, respectively. The Hospital for Special Surgery scores 3 months after surgery were 83.7 ± 18.4 in GPG and 71.5 ± 15.2 in TSG. Statistically significant differences were found between GPG and TSG in all measurements. CONCLUSIONS: A customized guide plate to create an accurate osteotomy in TKAs may be created using lower-extremity X-ray and knee CT images. This allows for shorter operative times and better postoperative alignment than the traditional surgery. Application of the digital guide plate may also result in better short-term outcomes.

Effect of daily milk supplementation on serum and umbilical cord blood folic acid concentrations in pregnant Han and Mongolian women and birth characteristics in China.

Many studies have demonstrated the efficacy of folic acid (FA) supplementation in prevention of neural tube defects (NTDs), although the extent of NTDs varies among individuals of different races and ethnic origin. China is a multi-ethnic country with no standard practice for FA-fortified food. Milk is consumed by women, but little is known about the effects of milk on folate concentration in maternal blood and neonatal umbilical cord blood in Han and Mongolian women after stopping taking the supplement for a month and five month, respectively. The objective of this study was to determine whether only daily consumption of liquid milk can increase the blood folate concentration in pregnant women and whether there are differences in blood folate concentrations between Han and Mongolian women after cessation of FA supplementation. Of the 4052 women enrolled in the parallel group design study. Three thousand five hundred and twenty-six women had confirmed pregnancies and were randomized to receive liquid milk or not until delivery. Women who consumed the liquid milk had significantly increased serum folate concentrations at 16 and 32 weeks of gestation as well as cord blood at birth compared to control groups in both ethnic groups. Infants born to women drinking milk also had better the term birth weight and height, which may be related to the increased concentration of folate. In conclusion, daily consumption of milk can increase the serum folate concentration in pregnant Han and Mongolian women in China (differences in the efficacy of FA and milk supplementation) and may enhance birth outcomes.

Cementless total hip arthroplasty with structural allograft for massive acetabular defect in hip revision.

OBJECTIVE: To study retrospectively 20 hip revison patients treated by cementless total hip arthroplasty with structural allograft. METHODS: Twenty patients suffering from aseptic loosening of an uncemented cup complicated by a large defect underwent cementless total hip arthroplasty with structural allograft and were followed up for at least 5 years. Clinical results were evaluated by Harris score and leg length measurements. Radiographic analysis included implants migration, graft absorbance, osteolysis and liner wear. RESULTS: No cup loosening or graft reabsorption was found at final follow-up. Clinical improvements in pain and functional status were demonstrated during the follow-up period. The mean Harris hip scores improved from 29 preoperatively (range 20-41) to 81 postoperatively (range 73-89). CONCLUSION: Our study shows that cementless total hip arthroplasty with allograft is a good way for massive defect in acetabular bone stock.