Jingsheng Shi

Bio: Jingsheng Shi is an academic researcher from Fudan University. The author has contributed to research in topics: Femoral head & Medicine. The author has an hindex of 8, co-authored 26 publications receiving 188 citations.

CXCL12–CXCR4 contributes to the implication of bone marrow in cancer metastasis

Abstract: The CXCL12-CXCR4 axis is postulated to be a key pathway in the interaction between (cancer) stem cells and their surrounding supportive cells in the (cancer) stem cell niche. As the bone marrow constitutes a unique microenvironment for cancer cells, the CXCL12-CXCR4 axis assists the bone marrow in regulating cancer progression. This interaction can be disrupted by CXCR4 antagonists, and this concept is being used clinically to harvest hematopoietic stem/progenitor cells from the bone marrow. The functions of CXCL12-CXCR4 axis in cancer cell-tumor microenvironment interaction and angiogenesis have been recently studied. This review focuses on how CXCL12-CXCR4 helps the bone marrow in creating a tumor mircoenvironment that results in the cancer metastasis. It also discusses ongoing research regarding the clinical feasibility of CXCR4 inhibitors.

Computer Navigation and Total Knee Arthroplasty

Abstract: Research has added evidence in favor of computer-navigated techniques over conventional surgery for total knee arthroplasty (TKA). The goal of the current meta-analysis was to compare the outcome of outliers in mechanical axis and postoperative complications in patients undergoing conventional vs computer-navigated techniques for TKA. English literature searches were performed in PubMed, EMBASE, Web of Science, and the Cochrane Library for studies published between January 2002 and August 2012. Randomized, controlled trials comparing computer navigation with conventional surgery for the measurement of mechanical axes in patients with primary osteoarthritis were considered eligible. Fifteen trials were eligible for inclusion. The baseline demographics of 2089 patients (computer-navigated=1111; conventional=978) were well matched. Publication bias was eliminated using the funnel plot. A mechanical axis of more than 30° was considered to be malalignment and an outlier in limb alignment. A significant increase of 16.9 minutes in mean operative time for computer-navigated TKA was observed (P=.046). Although patients undergoing computer-navigated TKA had fewer outliers in mechanical axis (13.4%) compared with the conventional technique (27.4%), the results did not achieve statistical significance (I2=0.0%; P=1.000). Fewer complications were observed in patients undergoing computer-navigated TKA (4%) compared with conventional TKA (6.5%).

HDAC5 promotes osteosarcoma progression by upregulation of Twist 1 expression.

Abstract: Histone deacetylases (HDACs) form a family of enzymes, which have fundamental roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation, and apoptosis of cancer cells. In this study, we firstly investigated the biological function of HDAC5 in osteosarcoma cells. We found that mRNA and protein levels of HDAC5 were upregulated in osteosarcoma tissues and cell lines. Furthermore, overexpression of HDAC5 could promote cell proliferation in osteosarcoma cell lines. In contrast, HDAC5 knockdown using small interfering RNA inhibited cell proliferation. At the molecular level, we demonstrated that HDAC5 promoted mRNA expression of twist 1, which has been reported as an oncogene. Together, these results highlighted for the first time an unrecognized link between HDAC5 and osteosarcoma progression and demonstrated that its specific inhibition might contribute to the treatment of tumorigenesis.

Predictive values of the postoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio for the diagnosis of early periprosthetic joint infections: a preliminary study

Abstract: Several studies have been conducted to report diagnostic values of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in the many diseases, such as oncological, inflammatory, and some infectious diseases. However, the predictive value of these laboratory parameters for early periprosthetic joint infections (PJIs) has not yet been reported. The aim of this study was to determine predictive values of the postoperative NLR, PLR, and LMR for the diagnosis of PJIs. In this retrospective study, 104 patients (26 early PJI cases and 78 non-PJI cases) who underwent total joint arthroplasty were enrolled in this study. All the patients were then categorized into two groups: PJI group, patients with the diagnosis of PJI (26 patients; 14 males, 12 females; mean age = 65.47 ± 10.23 age range = 51–81 ) and non-PJI group, patients without PJI (78 patients; 40 males, 38 females; mean age = 62.15 ± 9.33, age range = 41–92). We defined “suspected time” as the time that any abnormal symptoms or signs occurred, including fever, local swelling, or redness around the surgical site between 2 and 4 weeks after surgery and before the diagnosis. Suspected time and laboratory parameters, including NLR, PLR, LMR, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), were compared between both groups. The trends of postoperative NLR, LMR, PLR, CRP, and ESR were also reviewed. The predictive ability of these parameters at the suspected time for early PJI was evaluated by multivariate analysis and receiver operating characteristic (ROC) curve analysis. NLR, PLR, and LMR returned to preoperative levels within 2 weeks after surgery in the two groups. In the PJI group, NLR and PLR were significantly increased during the incubation period of infection or infection, and LMR was significantly reduced, although 61.5% (16/26) of the patients had normal white blood cells. Interestingly, ESR and CRP were still relatively high 2 weeks after surgery and were not different between the two groups before infection started (p = 0.12 and 0.4, respectively). NLR and PLR were significantly correlated with early PJI (Odds ratios for NLR and PLR = 88.36 and 1.12, respectively; p values for NLR and PLR = 0.005 and 0.01, respectively). NLR had great predictive ability for the diagnosis of early PJI, with a cut-off value of 2.77 (sensitivity = 84.6%, specificity = 89.7%, 95% CI = 0.86–0.97). ESR and CRP seem not to be sensitive for the diagnosis of early PJI due to their persistently high levels after arthroplasty. The postoperative NLR at the suspected time may have a great ability to predict early PJI.

Current state of computer navigation and robotics in unicompartmental and total knee arthroplasty: a systematic review with meta-analysis.

Abstract: Recently, there is a growing interest in surgical variables that are intraoperatively controlled by orthopaedic surgeons, including lower leg alignment, component positioning and soft tissues balancing. Since more tight control over these factors is associated with improved outcomes of unicompartmental knee arthroplasty and total knee arthroplasty (TKA), several computer navigation and robotic-assisted systems have been developed. Although mechanical axis accuracy and component positioning have been shown to improve with computer navigation, no superiority in functional outcomes has yet been shown. This could be explained by the fact that many differences exist between the number and type of surgical variables these systems control. Most systems control lower leg alignment and component positioning, while some in addition control soft tissue balancing. Finally, robotic-assisted systems have the additional advantage of improving surgical precision. A systematic search in PubMed, Embase and Cochrane Library resulted in 40 comparative studies and three registries on computer navigation reporting outcomes of 474,197 patients, and 21 basic science and clinical studies on robotic-assisted knee arthroplasty. Twenty-eight of these comparative computer navigation studies reported Knee Society Total scores in 3504 patients. Stratifying by type of surgical variables, no significant differences were noted in outcomes between surgery with computer-navigated TKA controlling for alignment and component positioning versus conventional TKA (p = 0.63). However, significantly better outcomes were noted following computer-navigated TKA that also controlled for soft tissue balancing versus conventional TKA (mean difference 4.84, 95 % Confidence Interval 1.61, 8.07, p = 0.003). A literature review of robotic systems showed that these systems can, similarly to computer navigation, reliably improve lower leg alignment, component positioning and soft tissues balancing. Furthermore, two studies comparing robotic-assisted with computer-navigated surgery reported superiority of robotic-assisted surgery in controlling these factors. Manually controlling all these surgical variables can be difficult for the orthopaedic surgeon. Findings in this study suggest that computer navigation or robotic assistance may help managing these multiple variables and could improve outcomes. Future studies assessing the role of soft tissue balancing in knee arthroplasty and long-term follow-up studies assessing the role of computer-navigated and robotic-assisted knee arthroplasty are needed.

A review of translational medicine. The future paradigm: how can we connect the orthopedic dots better?

Abstract: Introduction: Patients with complex medical and surgical problems often travel great distances to prestigious university medical centers in search of solutions and in some cases for nothing more th

BMSC-derived exosomes carrying microRNA-122-5p promote proliferation of osteoblasts in osteonecrosis of the femoral head

Abstract: Mesenchymal stem cells (MSCs) with multipotential differentiation capacity can differentiate into bone cells under specific conditions and can be used to treat osteonecrosis (ON) of the femoral head (ONFH) through cell transplantation. The current study aims to explore the role of bone marrow (BM) MSCs (BMSCs)-derived exosomes carrying microRNA-122-5p (miR-122-5p) in ONFH rabbit models.First, rabbit models with ONFH were established. ONFH-related miRNAs were screened using the Gene Expression Omnibus (GEO) database. A gain-of-function study was performed to investigate the effect of miR-122-5p on osteoblasts and BMSCs and effects of exosomes carrying miR-122-5p on ONFH. Co-culture experiments for osteoblasts and BMSCs were performed to examine the role of exosomal miR-122-5p in osteoblast proliferation and osteogenesis. The target relationship between miR-122-5p and Sprouty2 (SPRY2) was tested.MiR-122, significantly decreased in ONFH in the GSE89587 expression profile, was screened. MiR-122-5p negatively regulated SPRY2 and elevated the activity of receptor tyrosine kinase (RTK), thereby promoting the proliferation and differentiation of osteoblasts. In vivo experiments indicated that bone mineral density (BMD), trabecular bone volume (TBV), and mean trabecular plate thickness (MTPT) of femoral head were increased after over-expressing miR-122-5p in exosomes. Significant healing of necrotic femoral head was also observed.Exosomes carrying over-expressed miR-122-5p attenuated ONFH development by down-regulating SPRY2 via the RTK/Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Findings in the present study may provide miR-122-5p as a novel biomarker for ONFH treatment.

Have the Causes of Revision for Total and Unicompartmental Knee Arthroplasties Changed During the Past Two Decades

Abstract: Revisions after knee arthroplasty are expected to increase, and the epidemiology of failure mechanisms is changing as new implants, technology, and surgical techniques evolve. (1) Was there improvement in survival for TKA and unicompartmental knee arthroplasty (UKA) when comparing two consecutive 11-year periods with similar followups in a national registry? (2) Were there changes in the causes of revision during the two times? (3) Could the changes in revision causes be attributed to patient or implant characteristics? A total of 60,623 TKAs (2426 revisions) and 7648 UKAs (725 revisions) were selected from the Norwegian Arthroplasty Register and analyzed based on year of primary surgery: 1994 to 2004 (Period 1) and 2005 to 2015 (Period 2). TKAs had median followup of 3.5 years in Period 1 and 4.2 years in Period 2. Median followup for UKAs was 2.7 years in Period 1 and 4.6 years in Period 2. Of the patients included in the registry, 99.6% were accounted for at the time of analysis, whereas 0.4% had moved abroad. We used Kaplan-Meier analyses and log-rank test to investigate changes in survival. Relative risk of revision in Period 2 relative to Period 1 was calculated for each registered revision cause in a Cox regression model adjusted for age, sex, diagnosis, fixation, and patella resurfacing. For TKAs, the 10-year Kaplan-Meier survival free from revision improved from Period 1 to Period 2 from 91% (95% CI, 90%–92%) to 94% (95% CI, 94%–95%; p < 0.001). Revisions resulting from aseptic loosening of the femoral component, polyethylene wear/breakage, patellar dislocation, and unexplained pain decreased, whereas revisions resulting from early infection increased. Patients in Period 2 were younger and more often men compared with patients in Period 1. A higher risk of revision was found for male sex (relative risk [RR], 1.1; 95% CI, 1.0–1.2; p = 0.048) and age younger than 65 years (RR, 1.7; 95% CI, 1.6–1.9; p < 0.001). With UKAs, the 10-year survival free from revision was 80% (95% CI, 76%–84%) in Period 1 and 81% (95% CI, 79%–83%; p = 0.261) in Period 2. Revisions resulting from tibial aseptic loosening, polyethylene wear/breakage, and periprosthetic fractures decreased, but there were more revisions resulting from progression of osteoarthritis. In Period 2, there were more men and the average age was younger than for patients in Period 1. For UKAs, age younger than 65 years had a higher risk of revision (RR, 1.7; 95% CI, 1.5–2.0; p < 0.001), whereas sex did not affect the risk of revision. We found an improvement in survival free from revision for TKA in the last period, but no similar improvement for UKA, and the survivorship for UKAs remains rather dramatically lower than that observed for TKAs. The decision to perform a UKA should be made with the explicit awareness that its survivorship is substantially inferior to that of TKA; any perceived advantages of UKA should be balanced against this issue of its decreased durability. Level III, therapeutic study.