Publications by authors named "Qirong Qian"

36 Publications

Hsa_circ_0066523 promotes the proliferation and osteogenic differentiation of bone mesenchymal stem cells by repressing PTEN.

Bone Joint Res 2021 Aug;10(8):526-535

Department of Orthopedics, Changzheng Hospital, Shanghai, China.

Aims: Circular RNAs (circRNAs) are a novel type of non-coding RNA that plays major roles in the development of diverse diseases including osteonecrosis of the femoral head (ONFH). Here, we explored the impact of hsa_circ_0066523 derived from forkhead box P1 (FOXP1) (also called circFOXP1) on bone mesenchymal stem cells (BMSCs), which is important for ONFH development.

Methods: RNA or protein expression in BMSCs was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot, respectively. Cell Counting Kit 8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) were used to analyze cell proliferation. Alkaline phosphatase (ALP) activity, ALP staining, and Alizarin Red S staining were employed to evaluate the osteoblastic differentiation. Chromatin immunoprecipitation (ChIP), luciferase reporter, RNA pull down, and RNA immunoprecipitation (RIP) assays were combined for exploring molecular associations.

Results: Circ_0066523 was upregulated in osteogenic induction process of BMSCs. Silencing circ_0066523 restrained the proliferation and osteogenic differentiation of BMSCs. Mechanistically, circ_0066523 activated phosphatidylinositol-4,5-bisphosphate 3-kinase / AKT serine/threonine kinase 1 (PI3K/AKT) pathway via recruiting lysine demethylase 5B (KDM5B) to epigenetically repress the transcription of phosphatase and tensin homolog (PTEN). Functionally, AKT signalling pathway agonist or PTEN knockdown counteracted the effects of silenced circ_0066523 on BMSC proliferation and differentiation.

Conclusion: Circ_0066523 promotes the proliferation and differentiation of BMSCs by epigenetically repressing PTEN and therefore activating AKT pathway. This finding might open new avenues for the identification of therapeutic targets for osteoblast differentiation related diseases such as ONFH. Cite this article:  2021;10(8):526-535.
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http://dx.doi.org/10.1302/2046-3758.108.BJR-2020-0127.R2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414438PMC
August 2021

Comparison between Intra-Articular Injection of Infrapatellar Fat Pad (IPFP) Cell Concentrates and IPFP-Mesenchymal Stem Cells (MSCs) for Cartilage Defect Repair of the Knee Joint in Rabbits.

Stem Cells Int 2021 27;2021:9966966. Epub 2021 Jul 27.

Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic method in regenerative medicine. Our previous research adopted a simple nonenzymatic strategy for the preparation of a new type of ready-to-use infrapatellar fat pad (IPFP) cell concentrates. The aim of this study was to compare the therapeutic efficacy of intra-articular (IA) injection of autologous IPFP cell concentrates and allogeneic IPFP-MSCs obtained from these concentrates in a rabbit articular cartilage defect model. IPFP-MSCs sprouting from the IPFP cell concentrates were characterized via flow cytometry as well as based on their potential for differentiation into adipocytes, osteoblasts, and chondrocytes. In the rabbit model, cartilage defects were created on the trochlear groove, followed by treatment with IPFP cell concentrates, IPFP-MSCs, or normal saline IA injection. Distal femur samples were evaluated at 6 and 12 weeks posttreatment via macroscopic observation and histological assessment based on the International Cartilage Repair Society (ICRS) macroscopic scoring system as well as the ICRS visual histological assessment scale. The macroscopic score and histological score were significantly higher in the IPFP-MSC group compared to the IPFP cell concentrate group at 12 weeks. Further, both treatment groups had higher scores compared to the normal saline group. In comparison to the latter, the groups treated with IPFP-MSCs and IPFP cell concentrates showed considerably better cartilage regeneration. Overall, IPFP-MSCs represent an effective therapeutic strategy for stimulating articular cartilage regeneration. Further, due to the simple, cost-effective, nonenzymatic, and safe preparation process, IPFP cell concentrates may represent an effective alternative to stem cell-based therapy in the clinic.
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http://dx.doi.org/10.1155/2021/9966966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8337123PMC
July 2021

Fibrin Glue-Kartogenin Complex Promotes the Regeneration of the Tendon-Bone Interface in Rotator Cuff Injury.

Stem Cells Int 2021 26;2021:6640424. Epub 2021 Mar 26.

Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.

Objective: Rotator cuff injury healing is problematic because the tendon-bone junction often forms cicatricial tissues, rather than fibrocartilage, which leads to mechanical impairment and is prone to redamage. Kartogenin (KGN) is a newly discovered small molecule compound which can induce cartilage formation through chondrogenesis of endogenous mesenchymal stem cells.

Methods: In this study, we used KGN with fibrin glue (FG) to repair the rotator cuff injury by promoting the formation of fibrocartilage at the tendon to bone interface. Firstly, we assessed the release rate of KGN from the FG-KGN complex and then created a rabbit rotator cuff tendon graft-bone tunnel model. The rabbits received saline, FG-KGN, or FG injections onto the tendon to bone interface after injury. Shoulder tissues were harvested at 6 and 12 weeks, and the sections were stained with HE and Safranin O/Fast green. The samples were assessed by histologic evaluation and biomechanical testing. Synovial mesenchymal stem cells derived from the synovial tissue around the rotator cuff were harvested for western blotting and qRT-PCR analysis.

Results: KGN was released rapidly from the FG-KGN complex during first 4 hrs and followed by a slow release until 7 days. The tendon graft-bone interface in the control (saline) group and the FG group was filled with scar tissue, rather than cartilage-like tissue, and only a small number of chondrocytes were found at the adjacent bone surface. In the FG-KGN group, the tendon to bone interface was fully integrated and populated by chondrocytes with proteoglycan deposition, indicating the formation of fibrocartilage-like tissues. At 12 weeks, the maximum tensile strength of the FG-KGN group was significantly higher than that of the FG and control groups ( < 0.01). The RNA expression levels of tendinous genes such as Tenascin C and the chondrogenic gene Sox-9 were substantially elevated in SMSCs treated with the FG-KGN complex compared to the other two groups.

Conclusion: These results indicated that fibrin glue is an effective carrier for KGN, allowing for the sustained release of KGN. The FG-KGN complex could effectively promote the regeneration and formation of fibrocartilage tissue of the tendon-bone interface in the rabbit rotator cuff tendon graft-bone tunnel model.
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http://dx.doi.org/10.1155/2021/6640424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019366PMC
March 2021

Exosomes from Kartogenin-Pretreated Infrapatellar Fat Pad Mesenchymal Stem Cells Enhance Chondrocyte Anabolism and Articular Cartilage Regeneration.

Stem Cells Int 2021 9;2021:6624874. Epub 2021 Mar 9.

Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.

Objective: To evaluate the effect of Kartogenin-pretreated exosomes derived from infrapatellar fat pad mesenchymal stem cells on chondrocyte in vitro and articular cartilage regeneration in vivo.

Methods: Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) were isolated from rabbits to harvest exosomes. After identification of mesenchymal stem cells and exosomes, rabbit chondrocytes were divided into three groups for further treatment: the EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells), KGN-EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells pretreated with KGN), and control group. After processing and proliferation, phenotypic changes of chondrocytes were measured. In the in vivo study, 4 groups of rabbits with articular cartilage injury were treated with KGN-EXO, EXO, IPFP-MSCs, and control. Macroscopic evaluation and histological evaluation were made to figure out the different effects of the 4 groups on cartilage regeneration in vivo.

Results: The proliferation rate of chondrocytes in the EXO or KGN-EXO group was significantly higher than that in the control group ( < 0.05). The qRT-PCR results showed that the expression of Sox-9, Aggrecan, and Col II was the highest in the KGN-EXO group compared with the EXO group and the control group ( < 0.05). The results of Western blot were consistent with the results of qRT-PCR. In vivo, the cartilage defects in the KGN-EXO group showed better gross appearance and improved histological score than those in IPFP-MSC groups, EXO groups, and control groups ( < 0.05). At 12 weeks, the defect site in the KGN-EXO group was almost completely repaired with a flat and smooth surface, while a large amount of hyaline cartilage-like structures and no obvious cracks were observed.

Conclusion: Our study demonstrates that the exosomes isolated from infrapatellar fat pad mesenchymal stem cells pretreated with KGN have potent ability to induce chondrogenic differentiation of stem cells, effectively promoting the proliferation and the expression of chondrogenic proteins and genes of chondrocytes. The KGN-EXO can also promote the repair of articular cartilage defects more effectively, which can be used as a potential therapeutic method in the future.
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http://dx.doi.org/10.1155/2021/6624874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7964125PMC
March 2021

Regulating effect of Circ_ATRNL1 on the promotion of SOX9 expression to promote chondrogenic differentiation of hAMSCs mediated by MiR-145-5p.

J Tissue Eng Regen Med 2021 05 7;15(5):487-502. Epub 2021 Apr 7.

Department of Joint Surgery and Orthopedic Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.

Circ_ATRNL1 is significantly highly expressed in cartilage tissues of patients with osteoarthritis. This study explored the role and mechanism of circ_ATRNL1 in cartilage differentiation of human adipose-derived mesenchymal stem cells (hAMSCs). hAMSCs were isolated and identified by flow cytometry. The degree of chondrocyte and adipogenic differentiation was assessed using Alcian blue staining and Oil Red O staining, respectively. The expressions of cartilage- and adipogenic-related genes, circ_ATRNL1, and SOX9 were detected by reverse transcription quantitative polymerase chain reaction. The correlation between SOX9 and circ_ATRNL1 was analyzed using Pearson test. Bioinformatics and luciferase analysis were used to detect the overlapped target miRNAs of circ_ATRNL1 and SOX9. The role of circ_ATRNL1/miRNA/SOX9 was examined using functional rescue assays. hAMSCs were identified as CD90-, CD105-, and CD44-positive. The degree of cartilage differentiation of hAMSCs was significantly enhanced after 2 weeks. Cartilage-related genes, circ_ATRNL1 and SOX9, were significantly upregulated, and positively correlated with each other. Circ_ATRNL1 overexpression enhanced hAMSC proliferation and differentiation into chondrogenesis, and promoted the expressions of COL2, Aggrecan, and SOX9. Overexpression of circ_ATRNL1 inhibited the adipogenic differentiation of hAMSCs and the expressions of adipogenic-related genes. miR-145-5p was a target miRNA for circ_ATRNL1 and SOX9. miR-145-5p mimic inhibited hAMSC differentiation toward cartilage, and inhibited the expression of cartilage-related factors. miR-145-5p mimic effectively reversed the regulating effect of circ_ATRNL1 on hAMSCs. Circ_ATRNL1 regulates the promotion of SOX9 expression to promote chondrogenic differentiation of hAMSCs mediated by miR-145-5p.
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http://dx.doi.org/10.1002/term.3189DOI Listing
May 2021

RNA Sequencing Reveals LINC00167 as a Potential Diagnosis Biomarker for Primary Osteoarthritis: A Multi-Stage Study.

Front Genet 2020 14;11:539489. Epub 2021 Jan 14.

Department of Orthopedics, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.

Objectives: Given the roles played by lncRNA in human diseases and the high incidence of OA, this study investigated the pivotal pathways involved in the disease and identified potential biomarkers for OA diagnosis.

Methods: We first performed an exploration of RNA-sequencing in peripheral blood leukocytes from six subjects (3 OA and 3 healthy controls). Promising candidate lncRNAs were evaluated in first stage validation using a GEO dataset (GSE114007) of 38 subjects (20 OA and 18 healthy controls), followed by a second stage validation using quantitative PCR analysis with 101 subjects (67 OA and 34 controls). The third stage investigated the potential value of validated lncRNA in the early diagnosis of OA in peripheral blood leukocytes from a total of 120 participants (60 cases and 60 controls).

Results: The dataset identified a total of 1,380 up-regulated and 719 down-regulated mRNAs and 5,743 up-regulated and 7,384 down-regulated lncRNAs. The up-regulated DEGs were mainly enriched in the extracellular matrix, while the down-regulated DEGs were mainly enriched in the IL-17 and wnt signaling pathways. 18 overlapping candidate lncRNAs survived after first-stage validation. 3 hub lncRNAs were selected for the second validation stage and qualified in an external sample, and lncRNA was further confirmed with a similar result (down-expressed in both stages). Receiver operating characteristic analysis showed that can distinguish OA cases from healthy controls with a high area under the curve of 0.879 (95%CI: 0.819, 0.938; < 0.001), with a sensitivity of 80.7% and specificity of 83.5%.

Conclusion: The expression profile of OA was identified and critical pathways were elucidated by an integrated approach to RNA-seq from easily accessible blood. may serve as a potential early diagnosis marker for OA in clinical practice. The detailed mechanism of action of this lncRNA requires further elucidation in future studies.
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http://dx.doi.org/10.3389/fgene.2020.539489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841430PMC
January 2021

The clinical efficacy of arthroscopic therapy with knee infrapatellar fat pad cell concentrates in treating knee cartilage lesion: a prospective, randomized, and controlled study.

J Orthop Surg Res 2021 Jan 28;16(1):87. Epub 2021 Jan 28.

Department of Joint Surgery and Sports Medicine, Shanghai Changzheng Hospital, Naval Medical University, No.415 Fengyang Road, Shanghai, 200003, China.

Introduction: To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method.

Methods: Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention.

Results: Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups.

Conclusions: The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions.

Trial Registration: ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901 .
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http://dx.doi.org/10.1186/s13018-021-02224-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841893PMC
January 2021

Combination Therapy Using Kartogenin-Based Chondrogenesis and Complex Polymer Scaffold for Cartilage Defect Regeneration.

ACS Biomater Sci Eng 2020 11 13;6(11):6276-6284. Epub 2020 Oct 13.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

Articular cartilage has a highly organized structure, responsible for supporting tremendous mechanical loads. How to repair defected articular cartilage has become a great challenge as the avascular nature of cartilage limits its regenerative ability. Aiming to facilitate chondrogenic differentiation and cartilage regeneration, we recently explored a novel combination therapy using soluble poly-l-lysine/Kartogenin (L-K) nanoparticles and a poly(lactic--glycolic acid) PLGA/methacrylated hyaluronic acid (PLHA) complex scaffold. The potential use for joint cartilage reconstruction was investigated through L-K nanoparticles stimulating adipose-derived stem cells (ADSCs) on PLHA scaffolding, which ultimately differentiated into cartilage . In this study, on one hand, an effective method was established for obtaining uniform L-K nanoparticles by self-assembly. They were further proved to be biocompatible to ADSCs cytotoxicity assays and to accelerate ADSCs secreting type 2 collagen in a dose-dependent manner by immunofluorescence. On the other hand, the porous PLHA scaffold was manufactured by the combination of coprecipitation and ultraviolet (UV) cross-linking. Nanoindentation technology-verified PLHA had an appropriate stiffness close to actual cartilage tissue. Additional microscopic observation confirmed that the PLHA platform supported proliferation and chondrogenesis for ADSCs . In the presence of ADSCs, a 12-week osteochondral defect regeneration by the combination therapy showed that smooth and intact cartilage tissue successfully regenerated. Furthermore, the results of combination therapy were superior to those of phosphate-buffered saline (PBS) only, KGN, or KGN/PLHA treatment. The results of magnetic resonance imaging (MRI) and histological assessment indicated that the renascent tissue gradually regenerated while the PLHA scaffold degraded. In conclusion, we have developed a novel multidimensional combination therapy of cartilage defect repair that facilitated cartilage regeneration. This strategy has a great clinical translational potential for articular cartilage repair in the near future.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00724DOI Listing
November 2020

Over-expression of MEG3 promotes differentiation of bone marrow mesenchymal stem cells into chondrocytes by regulating miR-129-5p/RUNX1 axis.

Cell Cycle 2021 01 7;20(1):96-111. Epub 2021 Jan 7.

Department of Joint Surgery and Orthopedic Medicine, Shanghai Changzheng Hospital, Second Military Medical University , Shanghai, China.

This study explored the role of MEG3 in the cartilage differentiation of bone marrow mesenchymal stem cells (BMSCs). We investigated the effects of over-expression and knockdown of MEG3 on cell viability, cell differentiation, and the expressions of MEG3, miR-129-5p, COL2, chondrocyte differentiation-related genes (sry-type high-mobility-group box 9 (SOX9), SOX5, Aggrecan, silent information regulator 1 (SIRT1), and Cartilage oligomeric matrix protein (COMP)). The targeting relationship between MEG3 and miR-129-5p and the target gene of miR-129-5p was confirmed through Starbase, TargetScan and luciferase experiments. Finally, a series of rescue experiments were conducted to study the regulatory effects of MEG3 and miR-129-5p. BMSCs were identified as CD29 and CD44 positive, and their differentiation was time-dependent. As BMSCs differentiated, MEG3 expression was up-regulated, but miR-129-5p was down-regulated. Over-expressed MEG3 promoted the viability and differentiation of BMSCs, up-regulated the expressions of COL2 and chondrocyte differentiation-related genes, and inhibited miR-129-5p. Runt-related transcription factor 1 (RUNX1) was negatively regulated as a target gene of miR-129-5p. Results of rescue experiments showed that the inhibitory effect of miR-129-5p mimic on BMSCs could be partially reversed by MEG3. Over-expression of MEG3 regulated the miR-129-5p/RUNX1 axis to promote the differentiation of BMSCs into chondrocytes. This study provides a reliable basis for the application of lncRNA in articular cartilage injury.
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http://dx.doi.org/10.1080/15384101.2020.1863043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849720PMC
January 2021

Natural outcome of hemoglobin and functional recovery after the direct anterior versus the posterolateral approach for total hip arthroplasty: a randomized study.

J Orthop Surg Res 2020 Jun 1;15(1):200. Epub 2020 Jun 1.

Department of Joint Surgery and Sports Medicine, Shanghai Changzheng Hospital, Second Military Medical University, No.415, Fengyang Road, Shanghai, 200003, China.

Background: Total hip arthroplasty (THA) is one of the most successful orthopedic surgeries. There are many common surgical approaches for THA. The direct anterior approach (DAA) and posterolateral approach (PLA) were compared, leading to controversial results.

Methods: We report on a prospective randomized study which compared the changes of perioperative hemoglobin (Hb), the Harris hip score (HHS) and a visual analog scale (VAS) pain score following THA using DAA or PLA. A total of 130 participants were randomly divided into two groups (65 DAA versus 65 PLA). Perioperative ΔHb and other clinical outcomes were recorded.

Results: A total of 130 participants completed follow-up, while 14 patients were not recorded in blood outcomes due to blood transfusions and complications. The average Hb decrease immediately after surgery in the DAA group was greater than that in the PLA group (21.1 versus 15.8 g/L, P < .001). However, post-operative Hb descent velocity was slower in the DAA group, and the lowest point was reached earlier. No significant differences in ΔHb levels could be observed after 1 month in the two groups. When compared with the PLA group, the DAA group had a shorter incision (9.1 versus 13.5 cm, P < .001) and shorter hospital stay (4.2 versus 4.7 days, P = .004). However, the operation time of the DAA group was longer (88.0 versus 66.8 min, P < .001). The DAA group had a better HHS and VAS pain score at 6 weeks post-surgery. However, no significant differences were observed at later time points.

Conclusion: We concluded that DAA performed better on enhanced recovery after surgery (ERAS) than PLA in THA, while both DAA and PLA could result in a positive, similar result after 3 months.

Trial Registration: The study was registered by the Chinese Clinical Trial Registry (ChiCTR1900020770, 19 January 2019).
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http://dx.doi.org/10.1186/s13018-020-01716-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268999PMC
June 2020

Corrigendum to "Improved accumulation of TGF-β by photopolymerized chitosan/silk protein bio-hydrogel matrix to improve differentiations of mesenchymal stem cells in articular cartilage tissue regeneration" [Journal of Photochemistry & Photobiology, B: Biology 203 (2020) 1-10/111744].

J Photochem Photobiol B 2020 06 5;207:111884. Epub 2020 May 5.

Department of Joint Surgery and Orthopedic Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200,003, China. Electronic address:

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http://dx.doi.org/10.1016/j.jphotobiol.2020.111884DOI Listing
June 2020

Chitosan modified FeO/KGN self-assembled nanoprobes for osteochondral MR diagnose and regeneration.

Theranostics 2020 15;10(12):5565-5577. Epub 2020 Apr 15.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, PR China.

Chondral and osteochondral defects caused by trauma or pathological changes, commonly progress into total joint degradation, even resulting in disability. The cartilage restoration is a great challenge because of its avascularity and limited proliferative ability. Additionally, precise diagnosis using non-invasive detection techniques is challenging, which increases problems associated with chondral disease treatment. To achieve a theranostic goal, we used an integrated strategy that relies on exploiting a multifunctional nanoprobe based on chitosan-modified Fe3O4 nanoparticles, which spontaneously self-assemble with the oppositely charged small molecule growth factor, kartogenin (KGN). This nanoprobe was used to obtain distinctively brighter T-weighted magnetic resonance (MR) imaging, allowing its use as a positive contrast agent, and could be applied to obtain accurate diagnosis and osteochondral regeneration therapy. This nanoprobe was first investigated using adipose tissue-derived stem cells (ADSCs), and was found to be a novel positive contrast agent that also plays a significant role in stimulating ADSCs differentiation into chondrocytes. This self-assembled probe was not only biocompatible both and , contributing to cellular internalization, but was also used to successfully make distinction of normal/damaged tissue in T-weighted MR imaging. This novel combination was systematically shown to be biosafe via the decrement of apparent MR signals and elimination of ferroferric oxide over a 12-week regeneration period. Here, we established a novel method for osteochondral disease diagnosis and reconstruction. Using the FeO-CS/KGN nanoprobe, it is easy to distinguish the defect position, and it could act as a tool for dynamic observation as well as a stem cell-based therapy for directionally chondral differentiation.
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http://dx.doi.org/10.7150/thno.43569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196312PMC
May 2021

MiR-146a-5p promotes IL-1β-induced chondrocyte apoptosis through the TRAF6-mediated NF-kB pathway.

Inflamm Res 2020 Jun 23;69(6):619-630. Epub 2020 Apr 23.

Department of Joint Surgery and Orthopedic Medicine, Shanghai Changzheng Hospital, Second Military Medical University, No. 415 FengYang Road, Shanghai, 200003, China.

Objective: This study aimed to explore the role of the miR-146a-5p/TRAF6/NF-KB axis in chondrocyte apoptosis.

Methods: Transcriptome sequencing for microRNA expression in control and osteoarthritic cartilage was performed. Bioinformatic analysis was performed to identify the target genes of miR-146a-5p, and subsequently, Gene Ontology (GO) terms and KEGG pathways were identified. Furthermore, protein-protein interactions were analyzed to identify the hub regulatory gene of miR-146a-5p. MiR-146a-5p mimic, inhibitor and the corresponding negative control were constructed, and the apoptosis rates were measured in the transfected groups by flow cytometry, TUNEL staining and Western blot. Potential miRNA-target interactions were identified by dual-luciferase reporter assay.

Results: The microRNA array demonstrated that miR-146a-5p was significantly upregulated in osteoarthritic tissues, which was further confirmed by PCR analysis. Compared with the control group, IL-1β significantly decreased the viability of chondrocytes, while coculture with miR-146a-5p inhibitor rescued the IL-1β-induced inhibition of chondrocyte viability. Western blot results also identified the proapoptotic effects of miR-146a-5p. Bioinformatic analysis results revealed that miR-146a-5p targeted 159 potential genes, and TRAF6 was the hub gene among the 159 genes. The relative expression of TRAF6 was significantly decreased in the IL-1β-induced group. When siTRAF6 was added, apoptosis was significantly increased. Luciferase reporter assays showed that luciferase activity of the TRAF6 3'-UTR reporter was decreased in chondrocytes after transfection with the miR-146a-5p mimic.

Conclusions: This work showed that miR-146 induces chondrocyte apoptosis by targeting the TRAF6-mediated NF-KB signaling pathway, and miR-146 may be a potential target for OA treatment.
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http://dx.doi.org/10.1007/s00011-020-01346-wDOI Listing
June 2020

Improved accumulation of TGF-β by photopolymerized chitosan/silk protein bio-hydrogel matrix to improve differentiations of mesenchymal stem cells in articular cartilage tissue regeneration.

J Photochem Photobiol B 2020 Jan 14;203:111744. Epub 2019 Dec 14.

Department of Joint Surgery and Orthopedic Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address:

Articular cartilage regeneration is a challenging process due to its inadequate ability of self-recovering biological mechanisms. The progresses of cartilage tissue engineering is supported to overwhelmed the repairing difficulties and degenerative diseases. The main goal of the present study is to design biomaterials with suitable physico-chemical, mechanical and biological properties for the carrier of growth factor and improving differentiation of mesenchymal stem cell into damaged cartilage tissues. Herein, TGF-β loaded hydrogel network was prepared through the chemical interactions between vinyl group of natural polymers. Fourier-transform infrared spectroscopy results show the characteristic peaks at 3074 cm, 1713 cm, and 810 cm, which confirm the existence of the vinyl group and successful formation of maleoyl functionalized Chitosan (MCh). The obtained MCh was freely dissolved in the distilled water up to 8% (w/v). X-ray photoelectron spectroscopy survey spectral results show a peak at 289.0 eV which revealed that the OCO and DS were 1.2% and also evidenced the methacryl substitution of Silk fibroin (SF) nanoformulations. The weight loss and mechanical test were analyzed and the results showed that MSF acts as a foremost crosslinking point with MCh through the reaction between the methacrylate groups of MSF and maleoyl groups of MCh which led to enhancing the density and improved the compressive strength. The maximum drug release activity was recorded in the TGF-β loaded [email protected] hydrogel compared to bare MCh hydrogel. Further, the TGF-β loaded [email protected] MSF hydrogel exhibited the cell viability percentage nearly at 79-102% for MC3T3-E1 and 88-104% for BMDSCs. Similarly, the TGF-β loaded [email protected] exhibited the highest inhibitory activity against E. coli (83%) than S. aureus (67%). Overall, this study concluded the TGF-β loaded [email protected] showed better biocompatibility and could be utilized in the field of cartilage tissue engineering.
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http://dx.doi.org/10.1016/j.jphotobiol.2019.111744DOI Listing
January 2020

Reliability and validity of Simplified Chinese version of Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire: cross-cultural adaptation and validation.

Clin Rheumatol 2019 Nov 3;38(11):3281-3287. Epub 2019 Jul 3.

Department of Rehabilitation, Minimally Invasive Spine Center, 6th Medical Center, PLA General Hospital, No. 6, Fucheng Road, Haidian District, Beijing, 100048, People's Republic of China.

Objective: To translate and cross-culturally adapt Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) Questionnaire into a Simplified Chinese version (QuickDASH-C), and evaluate the reliability and validity of the QuickDASH-C in patients with upper limb disorders.

Methods: Cross-cultural adaptation was performed according to the internationally recognized guidelines of American Academy of Orthopedic Surgeons Outcome Committee. A total of 150 participants were recruited in this study. Internal consistency was estimated using Cronbach's alpha. Intra-class correlation coefficient (ICC) was used to determine test-retest reliability. Construct validity was analyzed by evaluating the correlations between QuickDASH-C and Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and visual analogue scale (VAS) as well as the short form (36) health survey (SF-36).

Results: The original version of the QuickDASH was well cross-culturally adapted and translated into Simplified Chinese. QuickDASH-C was indicated to have excellent reliability (Cronbach's alpha = 0.818, ICC = 0.907). QuickDASH-C correlated almost perfectly to DASH (r = 0.820, p < 0.001). Moderate to substantial correlations between QuickDASH-C and VAS (r = 0.463, p < 0.001), as well as physical function (r = - 0.630, p < 0.001), role physical (r = - 0.471, p < 0.001), bodily pain (r = - 0.563, p < 0.001) and general health (r = - 0.414, p < 0.001) subscales of SF-36, were observed.

Conclusion: QuickDASH-C was demonstrated to have excellent acceptability, reliability, and validity in patients with upper limb disorders, which could be recommended for patients in mainland China.

Key Points: • This study translated and cross-culturally adapted Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire into a Simplified Chinese version. • The reliability and validity of Simplified Chinese version of QuickDASH were good in evaluating patients with upper limb disorders.
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http://dx.doi.org/10.1007/s10067-019-04661-8DOI Listing
November 2019

Ubiquitin-specific protease 3 targets TRAF6 for deubiquitination and suppresses IL-1β induced chondrocyte apoptosis.

Biochem Biophys Res Commun 2019 06 2;514(2):482-489. Epub 2019 May 2.

Center of Joint Surgery and Sports Medicine, Department of Orthopedics, Changzheng Hospital, Second Military Medical University, China. Electronic address:

Traditionally, the development of osteoarthritis (OA) is associated with factors such as aging and injure, but more and more epidemiological and biological evidence suggests that the disease is closely related to metabolic syndrome and metabolic components. Ubiquitin-specific protease 3(USP3), a member of the USPs family, is a specific protease capable of cleavage of ubiquitin chains linked by proline residues. In our presented study, we firstly found that USP3 expression level was decreased in OA. USP3 overexpression inhibited IL-1β induced chondrocytes apoptosis and nuclear factor κB (NF-κB) activation. USP3 knockdown induced chondrocytes apoptosis and activated NF-κB pathway. USP3 interacts with TRAF6 (tumor necrosis factor-receptor-associated factor 6), which is an essential adaptor protein for the NF-κB (nuclear factor κB) signaling pathway and plays important roles in inflammation and immune response. IL-1β treatment up-regulated the polyubiquitination of TRAF6 in chondrocytes, which was attenuated when USP3 was forced expression. Our study mechanistically links USP3 to TRAF6 in osteoarthritis development. Moreover, these data support the pursuit of USP3 and TRAF6 as potential targets for osteoarthritis therapies.
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http://dx.doi.org/10.1016/j.bbrc.2019.04.163DOI Listing
June 2019

Cross-cultural adaptation and validation of the Simplified Chinese version of Copenhagen Hip and Groin Outcome Score (HAGOS) for total hip arthroplasty.

J Orthop Surg Res 2018 Nov 6;13(1):278. Epub 2018 Nov 6.

Department of Rehabilitation, Minimally Invasive Spine Center, Navy General Hospital, No. 6, Fucheng Road, Haidian District, Beijing, 100048, People's Republic of China.

Background: To translate and cross-culturally adapt the Copenhagen Hip and Groin Outcome Score (HAGOS) into a Simplified Chinese version (HAGOS-C) and evaluate the reliability, validity, and responsiveness of the HAGOS-C in total hip arthroplasty (THA) patients.

Methods: The cross-cultural adaptation was performed according to the internationally recognized guidelines of the American Academy of Orthopaedic Surgeons Outcome Committee. A total of 192 participants were recruited in this study. The intra-class correlation coefficient (ICC) was used to determine reliability. Construct validity was analyzed by evaluating the correlations between HAGOS-C and EuroQoL 5-dimension (EQ-5D), as well as the short form (36) health survey (SF-36). Responsiveness of HAGOS-C was evaluated according to standard response means (SRM) and standard effect size (ES) between the first test and the third test (6 months after primary THA).

Results: The original version of the HAGOS was well cross-culturally adapted and translated into Simplified Chinese. HAGOS-C was indicated to have excellent reliability (ICC = 0.748-0.936, Cronbach's alpha = 0.787-0.886). Moderate to substantial correlations between subscales of HAGOS-C and EQ-5D (r = 0.544-0.751, p < 0.001), as well as physical function (r = 0.567-0.640, p < 0.001), role physical (r = 0.570-0.613, p < 0.001), bodily pain (r = 0.467-0.604, p < 0.001), and general health (r = 0.387-0.432, p < 0.001) subscales of SF-36, were observed. The ES of 0.805-1.100 and SRM of 1.408-2.067 revealed high responsiveness of HAGOS-C.

Conclusions: HAGOS-C was demonstrated to have excellent acceptability, reliability, validity, and responsiveness in THA, which could be recommended for patients in mainland China.
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http://dx.doi.org/10.1186/s13018-018-0971-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219004PMC
November 2018

Arthroscopic lateral retinacular release, medial retinacular plication and partial medial tibial tubercle transfer for recurrent patellar dislocation.

Int J Surg 2017 Aug 15;44:43-48. Epub 2017 Jun 15.

Joint Surgery and Sports Medicine Department, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Huangpu District, Shanghai, China. Electronic address:

Objective: To assess the efficacy of a therapeutic protocol composed of arthroscopic lateral retinacular release, medial retinacular plication, and partial medial tibial tuberosity transfer for patients with recurrent patellar dislocation.

Method: 71 patients, 11 males and 60 females and a total of 77 knees, with recurrent dislocation of the patella were enrolled between 1998 and 2012. The average age of the patients was 19.5 years and 67 of them had previous knee trauma history. Tibial tubercle avulsion fractures were all surgically treated without complications like dysplasia in the femoral trochlear groove or valgus deformity. The Q angle, sulcus angle, patella-femoral trochlear congruence angle and lateral patellofemoral angle were measured on X-ray, while tibial tubercle-trochlear groove (TT-TG) distance was measure on CT scans, before the arthroscopic operation.

Result: 69 patients were followed-up for 2-16 years (average of 7.2 years), while 2 patients were lost during follow-up. Among the patients with follow-up, one patient had recurrent patella dislocation two months after the operation. Q angle decreased from 13.2° to 9.2° in male patients (P < 0.05) and from 21.0° to 15.4° in female patients (P < 0.05). On average, the patella-femoral trochlear congruence angle decreased from 24.2 ± 6.8° to -2.1 ± 5.8° (P < 0.05) and the lateral patellofemoral angle increased from -2.0 ± 5.2° to 10.9 ± 4.0° (P < 0.05). TT-TG distance decreased from 19.8 ± 2.1 mm to 13.6 ± 1.8 mm (P < 0.01). Mean Lysholm score increased from 45.6 ± 4.8 to 92.3 ± 10.8 (P < 0.05) and, IKDC score increased from 48.3 ± 6.8 to 94.3 ± 8.4 (P < 0.05).

Conclusion: As evidenced by minimal trauma and markedly improved knee joint function, the proposed therapeutic protocol demonstrated clear benefits for patients with recurrent patella dislocation.
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http://dx.doi.org/10.1016/j.ijsu.2017.06.027DOI Listing
August 2017

Is soft tissue repair a right choice to avoid early dislocation after THA in posterior approach?

BMC Surg 2017 May 19;17(1):60. Epub 2017 May 19.

Joint Surgery and Sports Medicine Department, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.

Background: Dislocation is the second most common complication after total hip arthroplasty (THA). The effectiveness of soft tissue repair to reduce dislocation rate is still debated and thus a meta-analysis was conducted.

Methods: A systematic search in PubMed, Embase, and Cochrane databases was conducted for this meta-analysis.

Inclusion Criteria: clinical comparative trials on the use of soft tissue repair including rotators and capsule repair in primary THA. The main data outcome were the incidences of early hip dislocation after primary THA. HSS score, incidence of other complications was also included in the outcomes.

Results: A total of 4816 cases were included for the analysis from ten studies (3 RCTs/7 Retrospective trials). Overall, the soft tissue repair group showed a significant lower early dislocation rate and higher HSS score compared to the no repair group; but no significant difference was observed between the two groups in regards to the early dislocation rate in RCT studies only. The capsule repair group showed a significant lower early dislocation rate than no capsule repair group while no significant difference was observed between the rotators repair group and no rotators repair group. In all included studies, 4 greater trochanter fractures, 2 sciatic nerve palsies and 1 infection were reported in soft tissue repair group while no cases were observed in the no repair group.

Conclusions: The efficacy of soft tissue repair is positive but still not conclusive to reduce the early dislocation rate after primary THA while soft tissue repair may bring more other complications. Capsule repair seems more effective than rotators repair only.
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http://dx.doi.org/10.1186/s12893-017-0212-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438560PMC
May 2017

Simplified Chinese Version of University of California at Los Angeles Activity Score for Arthroplasty and Arthroscopy: Cross-Cultural Adaptation and Validation.

J Arthroplasty 2017 09 13;32(9):2706-2711. Epub 2017 Apr 13.

Joint Surgery and Sports Medicine Department, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.

Background: To translate and cross-culturally adapt the University of California at Los Angeles (UCLA) activity score into a simplified Chinese version (UCLA-C) and evaluate the reliability and validity of the UCLA-C for patients with both knee arthroscopy and total knee arthroplasty.

Methods: Cross-cultural adaptation was performed according to the internationally recognized guidelines of the American Academy of Orthopaedic Surgeons Outcome Committee. A total of 200 participants (100 arthroscopy and 100 total knee arthroplasty) were recruited in this study. An intraclass correlation coefficient (ICC) was used to determine reliability. Construct validity was analyzed by evaluating the correlations between UCLA-C and the Tegner activity score, Knee Injury and Osteoarthritis Outcome Score, and the short-form (36) health survey.

Results: The original version of the UCLA activity score was cross-culturally well adapted and translated into simplified Chinese. UCLA-C was found to have excellent reliability in both arthroscopy (ICC = 0.984, 95% confidence interval 0.976-0.989) and arthroplasty (ICC = 0.946, 95% confidence interval 0.920-0.964). Absolute reliability as evaluated by minimal detectable change was 0.789 and 0.837 for both arthroscopy and arthroplasty groups. Moderate to high correlations between UCLA-C and Tegner activity score (0.799, P < .001); Knee Injury and Osteoarthritis Outcome Score (0.449-0.715, P < .001); and Physical Functioning, Pain, General Health, and Social Functioning (0.549-0.746, P < .001) subdomains of short-form (36) health survey were observed.

Conclusion: UCLA-C was demonstrated to have excellent acceptability, reliability, and validity in both arthroscopy and arthroplasty, and could be recommended for patients in mainland China.
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http://dx.doi.org/10.1016/j.arth.2017.03.057DOI Listing
September 2017

Simplified Chinese version of the Forgotten Joint Score (FJS) for patients who underwent joint arthroplasty: cross-cultural adaptation and validation.

J Orthop Surg Res 2017 Jan 14;12(1). Epub 2017 Jan 14.

Joint Surgery and Sports Medicine Department, Changzheng Hospital, Second Military Medical University, No. 415, Fengyang Road, Huangpu District, Shanghai, 200003, People's Republic of China.

Background: The Forgotten Joint Score (FJS) is a newly developed health-related quality of life (HRQoL) questionnaire designed to evaluate the awareness after total knee arthroplasty (TKA). This study cross-culturally adapted and psychometrically validated a simplified Chinese version of the FJS (SC-FJS).

Methods: Cross-cultural adaptation was performed according to the internationally recognized guidelines. One-hundred and fifty participants who underwent primary TKA were recruited in this study. Cronbach's α and intra-class correlations were used to determine reliability. Construct validity was analyzed by evaluating the correlations between SC-FJS and the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the short form (36) health survey (SF-36).

Results: Each of the 12 items was properly responded and correlated with the total items. SC-FJS had excellent reliability [Cronbach's α = 0.907, intra-class correlation coefficient (ICC) = 0.970, 95% CI 0.959-0.978). Elimination of any one item in all did not result in a value of Cronbach's α of <0.80. SC-FJS had a high correlation with symptoms (0.67, p < 0.001) and pain (0.60, p < 0.001) domains of KOOS and social functioning (0.66, p < 0.001) domain of SF-36, and it also moderately correlated with function in daily living (0.53, p < 0.001) and function in sport and recreation (0.40, p < 0.001) domains of KOOS, and physical subscale of SF-36 (0.49-0.53, p < 0.001) but had a low (r = 0.20) or not significant (p > 0.05) correlation with mental subscale of SF-36.

Conclusions: SC-FJS demonstrated excellent acceptability, internal consistency, reliability, and construct validity, which can be recommended for patients who underwent joint arthroplasty in Mainland China.
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http://dx.doi.org/10.1186/s13018-016-0508-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237477PMC
January 2017

Opposing Roles of Wnt Inhibitors IGFBP-4 and Dkk1 in Cardiac Ischemia by Differential Targeting of LRP5/6 and β-catenin.

Circulation 2016 Dec 1;134(24):1991-2007. Epub 2016 Nov 1.

From Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, China (D.W., Jinhui Peng, D.-n.R., J.C., Y. Zhu, Y.Y., H.Y., E.M., Y.C., Zhongmin Liu, S.L., L.A., W.Z.); Department of Orthopedics, Changzheng Hospital, Shanghai, China (Jinhui Peng, Q.Q.); Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China (L.Q., Jun Peng); Shanghai Key Laboratory of Signaling and Disease Research, The School of Life Sciences and Technology, Tongji University, China (Zhenping Liu, C.J.); State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai, China (Y.Y., T.Z.); and Institutes of Biomedical Sciences, Fudan University, Shanghai, China (J.W., Y. Zou).

Background: Myocardial infarction is one of the leading causes of morbidity and mortality worldwide, triggering irreversible myocardial cell damage and heart failure. The role of low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) as coreceptors of the Wnt/β-catenin pathway in the adult heart remain unknown. Insulin-like growth factor binding protein 4 and dickkopf-related protein 1 (Dkk1) are 2 secreted LRP5/6 binding proteins that play a crucial role in heart development through preventing Wnt/β-catenin pathway activation. However, their roles in the adult heart remain unexplored.

Methods: To understand the role of LRP5/6 and β-catenin in the adult heart, we constructed conditional cardiomyocyte-specific LRP5/6 and β-catenin knockout mice and induced surgical myocardial infarction. We also directly injected recombinant proteins of insulin-like growth factor binding protein 4 and Dkk1 into the heart immediately following myocardial infarction to further examine the mechanisms through which these proteins regulate LRP5/6 and β-catenin.

Results: Deletion of LRP5/6 promoted cardiac ischemic insults. Conversely, deficiency of β-catenin, a downstream target of LRP5/6, was beneficial in ischemic injury. It is interesting to note that although both insulin-like growth factor binding protein 4 and Dkk1 are secreted Wnt/β-catenin pathway inhibitors, insulin-like growth factor binding protein 4 protected the ischemic heart by inhibiting β-catenin, whereas Dkk1 enhanced the injury response mainly through inducing LRP5/6 endocytosis and degradation.

Conclusions: Our findings reveal previously unidentified dual roles of LRP5/6 involved in the cardiomyocyte response to ischemic injury. These findings suggest new therapeutic strategies in ischemic heart disease by fine-tuning LRP5/6 and β-catenin signaling within the Wnt/β-catenin pathway.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024441DOI Listing
December 2016

Human CIK Cells Loaded with Au Nanorods as a Theranostic Platform for Targeted Photoacoustic Imaging and Enhanced Immunotherapy and Photothermal Therapy.

Nanoscale Res Lett 2016 Dec 6;11(1):285. Epub 2016 Jun 6.

Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, PR China.

How to realize targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer has become a great challenge. Herein, we reported for the first time that human cytokine-induced killer cells (CIK) loaded with gold nanorods were used for targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer. Silica-modified gold nanorods were prepared; then incubated with human cytokine-induced killer cells (CIK), resultant human CIK cells loaded with Au nanorods were evaluated for their cytotoxicity, targeted ability of gastric cancer in vitro and in vivo, immunotherapy, and photothermal therapy efficacy. In vitro cell experiment shows that human CIK cells labeled with gold nanorods actively target gastric cancer MGC803 cells, inhibit growth of MGC803 cells by inducing cell apoptosis, and kill MGC803 cells under low power density near-infrared (NIR) laser treatment (808-nm continuous wave laser, 1.5 W/cm(2), 3 min). In vivo experiment results showed that human CIK cells labeled with gold nanorods could target actively and image subcutaneous gastric cancer vessels via photoacoustic imaging at 4 h post-injection, could enhance immunotherapy efficacy by up-regulating cytokines such as IL-1, IL-12, IL-2, IL-4, IL-17, and IFN-γ, and kill gastric cancer tissues by photothermal therapy via direct injection into tumor site under near-infrared (NIR) laser irradiation. High-performance human CIK cells labeled with Au nanorods are a good novel theranostic platform to exhibit great potential in applications such as tumor-targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy in the near future.
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http://dx.doi.org/10.1186/s11671-016-1468-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894853PMC
December 2016

Association of PPARγ gene polymorphisms with osteoarthritis in a southeast Chinese population.

J Genet 2014 Dec;93(3):719-23

Joint Department, Changzheng Hospital, Fengyang Road 415, Huangpu District, Shanghai 20003, People's Republic of China.

Primary osteoarthritis (OA) is a leading cause of disability in developed countries. Currently no satisfactory treatment to stop disease progression exists. Recent studies suggest that activation of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) is an interesting therapeutic target for this disease. PPARγ is a transcription factor important for adipogenesis and adipocyte differentiation. Agonists of PPARγ inhibit inflammation and reduce generation of cartilage degradation products both in vitro and in vivo, and reduce the development/progression of cartilage lesions in OA animal models. However, there are no studies to assess the role of PPARγ in OA susceptibility of human peripheral joints in a Chinese population. We conducted a case-control study in a southeast Chinese population to determine the association of PPARγ gene polymorphisms (rs1801282, rs12629751, rs2292101, rs4135275 and rs1175543) with OA. One-hundred knee OA cases and 100 controls were studied. Statistically significant differences were detected in genotype and allele frequencies between OA and control groups in this population. For knee OA, the highest risk was associated with the variant allele T of the single nucleotide polymorphism rs12629751 (odds ratio (OR): 0.341, 95% confidence interval (CI):0.173-0.673, P = 0.002), and allele T of SNP rs12629751 (chi-square: 9.546, P = 0.002) could be considered as a risk factor of knee OA. Therefore, PPARγ mutation could be associated with the incidence of OA in a Chinese population. There is a significant association between the PPARγ polymorphism rs12629751 and susceptibility to knee OA in a southeast Chinese population.
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http://dx.doi.org/10.1007/s12041-014-0444-2DOI Listing
December 2014

Changes of hemoglobin and hematocrit in elderly patients receiving lower joint arthroplasty without allogeneic blood transfusion.

Chin Med J (Engl) 2015 Jan;128(1):75-8

Joint Division of Orthopedics Department, Orthopaedic Institute of People's Liberation Army, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.

Background: It has rarely been reported about the changes of hemoglobin (Hb) and hematocrit (Hct) in elderly patients receiving total knee arthroplasty (TKA) or total hip arthroplasty (THA). This study aimed to evaluate the changes of Hb and Hct after TKA or THA in elderly patients, and analyze its relationship with sex and type of arthroplasty.

Methods: This is a prospective cohort study, including 107 patients receiving TKA or THA without allogeneic blood transfusion. There were 54 males and 53 females, with a mean age of 69.42 years. Levels of Hb and Hct were examined preoperatively and during the 6 months follow-up after operation.

Results: Levels of Hb and Hct decreased postoperatively and reached their minimum points on postoperative day 4. Thereafter, Hb and Hct recovered to their preoperative levels within 6-12 weeks. No significant differences in the levels of Hb and Hct were noticed between different sexes. THA patients showed significantly greater drop in Hb and Hct than TKA patients in the first 4 days postoperatively (P < 0.05).

Conclusions: Levels of Hb and Hct decreased during the first 4 days after arthroplasty and gradually returned to their normal levels within 6-12 weeks postoperatively. THA may be associated with higher postoperative blood loss than TKA.
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http://dx.doi.org/10.4103/0366-6999.147817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837824PMC
January 2015

Does intramedullary canal irrigation reduce fat emboli? A randomized clinical trial with transesophageal echocardiography.

J Arthroplasty 2015 Mar 14;30(3):451-5. Epub 2014 Oct 14.

Department of Computer Science, Institute of Information Engineering, Shanghai, Maritime University, Shanghai, China. Electronic address:

The effect of medullary cavity irrigation on fat emboli during total knee arthroplasty (TKA) was evaluated. Thirty female patients with osteoarthritis were randomly assigned to undergo conventional TKA without irrigation (conventional group) or with medullary canal saline irrigation (irrigation group). The four-chamber view was monitored by transesophageal echocardiography (TEE) and echogenic reflections of fat emboli were observed. The grey-scale score and area ratio of fat emboli were calculated during TKA. Hemodynamic parameters were simultaneously monitored and showed no obvious change between two groups (P>0.05). The average grey-scale score (P=0.016) and area ratio (P=0.033) of emboli were significantly decreased in irrigation group. Removal of medullary contents by irrigation could significantly reduce the formation of fat emboli during TKA.
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http://dx.doi.org/10.1016/j.arth.2014.10.006DOI Listing
March 2015

Glutathione-capped fluorescent gold nanoclusters for dual-modal fluorescence/X-ray computed tomography imaging.

J Mater Chem B 2013 Oct 21;1(38):5045-5053. Epub 2013 Aug 21.

Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, Shanghai 200240, PR China.

The development of efficient multifunctional nanoprobes for tumour imaging has become a great challenge. Herein, we report for the first time the synthesis of folic acid (FA)-conjugated glutathione (GSH)-capped gold nanoclusters (Au NCs) for dual mode fluorescence/X-ray computed tomography imaging of gastric cancer. Water-soluble GSH-capped Au NCs were synthesized by using tetrabutylammonium borohydride (TBAB) as the reducing agent, and was characterized by transmission electron microscopy, UV-vis absorption spectroscopy, fluorescence spectroscopy, and X-ray photoelectron spectroscopy. The [email protected] showed excellent photoluminescence properties and negligible cytotoxicity at a concentration as high as 200 μg mL. Folic acid was covalently anchored to the [email protected]; the nanoprobe showed highly selective targeting of the gastric cancer MGC-803 cells revealed by laser scanning confocal microscopy (LSCM). Hematoxylin and eosin (HE) staining results showed that [email protected] displayed no toxicity to important organs. In conclusion, the FA-conjugated [email protected] nanoprobe can be used for gastric cancer fluorescence imaging and X-ray computed tomography (CT) imaging. Therefore, the applications of [email protected] could be extended and bring more benefits to nanotechnology as an ideal biomedical platform.
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http://dx.doi.org/10.1039/c3tb20784fDOI Listing
October 2013

Folic acid-conjugated silica capped gold nanoclusters for targeted fluorescence/X-ray computed tomography imaging.

J Nanobiotechnology 2013 May 29;11:17. Epub 2013 May 29.

Background: Gastric cancer is 2th most common cancer in China, and is still the second most common cause of cancer-related death in the world. Successful development of safe and effective nanoprobes for in vivo gastric cancer targeting imaging is a big challenge. This study is aimed to develop folic acid (FA)-conjugated silica coated gold nanoclusters (AuNCs) for targeted dual-modal fluorescent and X-ray computed tomography imaging (CT) of in vivo gastric cancer cells.

Method: AuNCs were prepared, silica was coated on the surface of AuNCs, then folic acid was covalently anchored on the surface of AuNCs, resultant FA-conjugated [email protected] nanoprobes were investigated their cytotoxicity by MTT method, and their targeted ability to FR(+) MGC803 cells and FR(-) GES-1 cells. Nude mice model loaded with MGC803 cells were prepared, prepared nanoprobes were injected into nude mice via tail vein, and then were imaged by fluorescent and X-ray computed tomography (CT) imaging.

Results: FA-conjugated [email protected] nanoprobes exhibited good biocompatibility, and could target actively the FR(+) MGC-803 cells and in vivo gastric cancer tissues with 5 mm in diameter in nude mice models, exhibited excellent red emitting fluorescence imaging and CT imaging.

Conclusion: The high-performance FA-conjugated [email protected] nanoprobes can target in vivo gastric cancer cells, can be used for fluorescent and CT dual-mode imaging, and may own great potential in applications such as targeted dual-mode imaging of in vivo early gastric cancer and other tumors with FR positive expression in near future.
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http://dx.doi.org/10.1186/1477-3155-11-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669628PMC
May 2013

Differential expression of phospholipase C epsilon 1 is associated with chronic atrophic gastritis and gastric cancer.

PLoS One 2012 15;7(10):e47563. Epub 2012 Oct 15.

Department of Bio-Nano Science and Engineering, Key Lab of Thin Film and Microfabrication Technology of Department of Education, Institute of Micro/Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

Background: Chronic inflammation plays a causal role in gastric tumor initiation. The identification of predictive biomarkers from gastric inflammation to tumorigenesis will help us to distinguish gastric cancer from atrophic gastritis and establish the diagnosis of early-stage gastric cancer. Phospholipase C epsilon 1 (PLCε1) is reported to play a vital role in inflammation and tumorigenesis. This study was aimed to investigate the clinical significance of PLCε1 in the initiation and progression of gastric cancer.

Methodology/principal Findings: Firstly, the mRNA and protein expression of PLCε1 were analyzed by reverse transcription-PCR and Western blotting in normal gastric mucous epithelial cell line GES-1 and gastric cancer cell lines AGS, SGC7901, and MGC803. The results showed both mRNA and protein levels of PLCε1 were up-regulated in gastric cancer cells compared with normal gastric mucous epithelial cells. Secondly, this result was confirmed by immunohistochemical detection in a tissue microarray including 74 paired gastric cancer and adjacent normal tissues. Thirdly, an independence immunohistochemical analysis of 799 chronic atrophic gastritis tissue specimens demonstrated that PLCε1 expression in atrophic gastritis tissues were down-regulated since PLCε1 expression was negative in 524 (65.6%) atrophic gastritis. In addition, matched clinical tissues from atrophic severe gastritis and gastric cancer patients were used to further confirm the previous results by analyzing mRNA and protein levels expression of PLCε1 in clinical samples.

Conclusions/significances: Our results suggested that PLCε1 protein may be a potential biomarker to distinguish gastric cancer from inflammation lesion, and could have great potential in applications such as diagnosis and pre-warning of early-stage gastric cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0047563PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471869PMC
April 2013

Chloroplasts-mediated biosynthesis of nanoscale Au-Ag alloy for 2-butanone assay based on electrochemical sensor.

Nanoscale Res Lett 2012 Aug 23;7(1):475. Epub 2012 Aug 23.

Department of Bio-Nano-Science and Engineering, National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People's Republic of China.

We reported a one-pot, environmentally friendly method for biosynthesizing nanoscale Au-Ag alloy using chloroplasts as reducers and stabilizers. The prepared nanoscale Au-Ag alloy was characterized by UV-visible spectroscopy, X-ray diffraction (XRD) and high resolution transmission electron microscopy (HR-TEM). Fourier transform infrared spectroscopy (FTIR) analysis was further used to identify the possible biomolecules from chloroplasts that are responsible for the formation and stabilization of Au-Ag alloy. The FTIR results showed that chloroplast proteins bound to the nanoscale Au-Ag alloy through free amino groups. The bimetallic Au-Ag nanoparticles have only one plasmon band, indicating the formation of an alloy structure. HR-TEM images showed that the prepared Au-Ag alloy was spherical and 15 to 20 nm in diameter. The high crystallinity of the Au-Ag alloy was confirmed by SAED and XRD patterns. The prepared Au-Ag alloy was dispersed into multiwalled carbon nanotubes (MWNTs) to form a nanosensing film. The nanosensing film exhibited high electrocatalytic activity for 2-butanone oxidation at room temperature. The anodic peak current (Ip) has a linear relationship with the concentrations of 2-butanone over the range of 0.01% to 0.075% (v/v), when analyzed by cyclic voltammetry. The excellent electronic catalytic characteristics might be attributed to the synergistic electron transfer effects of Au-Ag alloy and MWNTs. It can reasonably be expected that this electrochemical biosensor provided a promising platform for developing a breath sensor to screen and pre-warn of early cancer, especially gastric cancer.
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http://dx.doi.org/10.1186/1556-276X-7-475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506472PMC
August 2012
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