Endogenus chondrocytes immobilized by G-CSF in nanoporous gels enable repair of critical-size osteochondral defects.

Injured articular cartilage is a leading cause for osteoarthritis. We recently discovered that endogenous stem/progenitor cells not only reside in the superficial zone of mouse articular cartilage, but also regenerated heterotopic bone and cartilage in vivo. However, whether critical-size osteochondral defects can be repaired by pure induced chemotatic cell homing of these endogenous stem/progenitor cells remains elusive. Here, we first found that cells in the superficial zone of articular cartilage surrounding surgically created 3 × 1 mm defects in explant culture of adult goat and rabbit knee joints migrated into defect-filled fibrin/hylaro1nate gel, and this migration was significantly more robust upon delivery of exogenous granulocyte-colony stimulating factor (G-CSF). Remarkably, G-CSF-recruited chondrogenic progenitor cells (CPCs) showed significantly stronger migration ability than donor-matched chondrocytes and osteoblasts. G-CSF-recruited CPCs robustly differentiated into chondrocytes, modestly into osteoblasts, and barely into adipocytes. In vivo, critical-size osteochondral defects were repaired by G-CSF-recruited endogenous cells postoperatively at 6 and 12 weeks in comparison to poor healing by gel-only group or defect-only group. ICRS and O'Driscoll scores of articular cartilage were significantly higher for both 6- and 12-week G-CSF samples than corresponding gel-only and defect-only groups. Thus, endogenous stem/progenitor cells may be activated by G-CSF, a Food and Drug Administration (FDA)-cleared bone-marrow stimulating factor, to repair osteochondral defects.

The value of different imaging methods in the diagnosis of breast cancer: A protocol for network meta-analysis of diagnostic test accuracy.

BACKGROUND: : Breast cancer (BC) is the most common cancer in women all over the world and the second most common cause of cancer-related mortality. Imaging examination plays an important role in the diagnosis of early breast cancer. Due to different imaging principles and methods, all kinds of examinations have their advantages and disadvantages. It is particularly important for clinicians to choose these examination methods reasonably to achieve the best diagnostic effect. The objectives of this systematic review and NMA are to determine the diagnostic accuracy of imaging technologies for breast cancer and to compare the diagnostic accuracy of different index tests and to support guidelines development and clinical practice. METHODS: : PubMed, Embase.com, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and SinoMed will be searched to identify relevant studies up to August 31, 2021. We will include random controlled trials, cross-sectional studies, case-control studies, and cohort studies that evaluate the diagnostic accuracy of different imaging diagnostic methods for breast cancer. The Quality Assessment of Diagnostic Accuracy Studies 2 quality assessment tool will be used to assess the risk of bias in each study. Standard pairwise meta-analysis and NMA will be performed using STATA V.12.0, MetaDiSc 1.40, and R 3.4.1 software to compare the diagnostic efficacy of different imaging diagnostic methods. Subgroup analyses and sensitivity analyses will be conducted to investigate the sources of heterogeneity. RESULTS: : The results of this study will be published in a peer-reviewed journal. CONCLUSION: : This study will comprehensively evaluate the accuracy of different imaging diagnostic methods in the diagnosis of breast cancer. The results of this study will provide high-quality evidence to support clinical practice and guidelines development.

Characteristics of systematic reviews evaluating treatments for COVID-19 registered in PROSPERO.

Characteristics and research collaboration of registered systematic reviews (SRs) on treatment modalities for coronavirus disease-2019 (COVID-19) remain unclear. This study analysed research collaboration, interventions and outcome measures in registered SRs on COVID-19 treatments and pointed out the relevant problems. PROSPERO (international prospective register of systematic reviews) was searched for SRs on COVID-19 treatments as of 2 June 2020. Excel 2016 was used for descriptive analyses of the extracted data. VOSviewer 1.6.14 software was used to generate network maps for collaborations between countries and institutions. A total of 189 SRs were included, which were registered by 301 institutions from 39 countries. China (69, 36.50%) exhibited the highest output. Cooperation between countries was not close enough. As an institution, the Chengdu University of Traditional Chinese Medicine (7, 3.70%) had the highest output. There was close cooperation between institutions. Interventions included antiviral therapy (81, 42.86%), respiratory support (16, 8.47%), circulatory support (11, 5.82%), plasma therapy for convalescent patients (11, 5.82%), immunotherapy (9, 4.76%), TCM (traditional Chinese medicine) treatment (9, 4.76%), rehabilitation treatment (5, 2.65%), anti-inflammatory treatment (16, 8.47%) and other treatments (31, 16.40%). Concerning antiviral therapy (81, 42.86%), the most commonly used antiviral agents were chloroquine/hydroxychloroquine (26, 13.76%), followed by remdesivir (12, 6.35%), lobinavir/ritonavir (11, 5.82%), favipiravir (5, 2.65%), ribavirin (5, 2.65%), interferon (5, 2.65%), abiron (4, 2.12%) and abidor (4, 2.12%). The most frequently used primary and secondary outcomes were the mortality rate (92, 48.68%) and hospital stay length (48, 25.40%), respectively. The expression of the outcomes was not standardised. Many COVID-19 SRs on treatment modalities have been registered, with a low completion rate. Although there was some collaboration between countries and institutions in the currently registered SRs on treatment modalities for COVID-19 on PROSPERO, cooperation between countries should be further enhanced. More attention should be directed towards identifying deficiencies of outcome measures, and the standardisation of results should be maximised.

Effect of Taijiquan assisted rehabilitation for breast cancer patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Taijiquan, as a supplementary and alternative method, has attracted more and more attention in the treatment of breast cancer. But up to now, no systematic review has been performed to evaluate the efficacy of Taijiquan in the treatment of breast cancer. In this study, Cochrane systematic review method will be used to evaluate the effect of Taijiquan in the rehabilitation process of breast cancer patients after treatment. METHODS: PubMed, Embase. com, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and SinoMed will be searched to identify relevant studies up to May 31, 2021. We will include randomized controlled trials (RCTs) of the application of Taijiquan in post-treatment breast cancer patients. We will use the Cochrane bias risk assessment tool to assess the quality of included RCTs. We will use Stata 13.0 to perform pairwise meta-analyses using the inverse variance method. Subgroup analyses and sensitivity analyses will be conducted to investigate the sources of heterogeneity. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will comprehensively evaluate the efficacy of Taijiquan in the rehabilitation treatment of breast cancer. The results of this study will provide high-quality evidence to support clinical practice and guidelines development.

Relationship between digestive diseases and COVID-19 severity and mortality: A protocol for systematic review and meta-analysis.

BACKGROUND: Digestive diseases have been often reported in COVID-19 patients, but whether COVID-19 patients with existing digestive comorbidities are at an increased risk of serious disease and death remains unclear. This study aims to evaluate the association between digestive diseases and COVID-19 severity and mortality. METHODS: PubMed, Embase.com, the Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure, Wanfang, and SinoMed will be searched to identify relevant studies up to October 1, 2020. We will use the Newcastle-Ottawa quality assessment scale to assess the quality of included studies. We will use Stata to perform pairwise meta-analyses using the random-effects model with the inverse variance method to estimate the association between digestive diseases and the mortality and severity of COVID-19. Subgroup analyses and sensitivity analyses will be conducted to investigate the sources of heterogeneity. We will create a "Summary of findings' table presenting our primary and secondary outcomes using the GRADEpro Guideline Development Tool software. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSIONS: This study will comprehensively evaluate the association between digestive diseases and the severity and mortality of patients with COVID-19. The results of this study will provide high-quality evidence to support clinical practice and guidelines development.

Impact of cancer on mortality and severity of corona virus disease 2019: A protocol for systematic review and meta-analysis.

BACKGROUND: Cancer patients are in a state of systemic immunosuppression and are considered a highly vulnerable population in the Corona Virus Disease 2019 (COVID-19) epidemic. However, the relationship between cancer and the severity and mortality of patients with COVID-19 remains unclear. This study aims to evaluate whether cancer patients with COVID-19 may be at an increased risk of severe illness and mortality. METHODS: We will perform comprehensive searches in PubMed, EMBASE.com, Web of Science, and the Cochrane Central Register of Controlled Trials to identify studies providing prevalence of cancer between patients with severe and non-severe illness or between non-survivors and survivors. We will use the Newcastle-Ottawa quality assessment scale to assess the quality of included studies. We will conduct pairwise meta-analyses to compute the odds ratio and 95% confidence interval using the Mantel Haenszel method with the random-effects model. The statistical heterogeneity will be assessed using the I statistic. Subgroup analyses, sensitivity analyses, and meta-regression analyses will be performed to explore the sources of heterogeneity. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: Our meta-analysis will systematically evaluate the association between cancer and the severity and mortality of patients with COVID-19. This study will provide evidence to help determine whether cancer patients should be provided with special precautions and advised to use stronger personal protection. INPLASY REGISTRATION NUMBER: INPLASY202090093.

Design of pH/reduction dual-responsive nanoparticles as drug delivery system for DOX: Modulating controlled release behavior with bimodal drug-loading.

pH/Reduction dual-responsive P(FPA-co-PEGMA-co-MAA) (PFPM) nanoparticles were designed for tumor-specific intracellular triggered release of anticancer drug DOX by emulsion copolymerization of 4-formylphenyl acrylate (FPA), methacrylic acid (MAA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA), with N,N-bis(acryloyl)cystamine (BACy) as crosslinker. Then three drug delivery systems (DDSs) with average hydrodynamic diameter around 200nm and drug-loading capacity (DLC) of >35% were obtained via the noncovalent interaction of DOX with the carboxyl and aldehyde groups in MAA and FPA units, covalently conjugating DOX onto the FPA units via acid-labile imine bond, or both the two modes. The in vitro release profiles showed that all the three DDSs exhibited good tumor intracellular triggered release characteristic whitout burst release. And the bimodal drug-loaded one (DOX/PFPMC+N), which had the highest DLC of >54%, possessed the middle drug release rate, faster than the one via covalent conjugation (DOX/PFPMC) but slower than the one via noncovalent interaction (DOX/PFPMN). The results demonstrated that the controlled release behavior of such functional nanoparticles could be tailored with drug-loading modes.

Fluorescent Copolymer-Based Prodrug for pH-Triggered Intracellular Release of DOX.

A novel water-soluble pH stimuli-responsive fluorescent copolymer of P(PEGMA-b-(MAH-co-Rh6GEAm)) was synthesized by two-step sequential RAFT polymerization. The prodrug with drug content of 0.1560 mg/mg was prepared by coupling doxorubicin (DOX) onto the copolymer via acid-cleavable hydrazone bond, formed between the carbonyl group of DOX and abundant hydrazide functional groups in the copolymer. The amphiphilic DOX-conjugated prodrug (P(PEGMA-b-(MAH-DOX-co-Rh6GEAm))) could easily form a micelle in water with Dh of less than 100 nm. It could be transported into HepG2 cells and release DOX without burst release, while the leakage of DOX can be avoided in the simulated normal physiological media. Furthermore, its fluorescence intensity experienced a reversible change with the transformation of the media pH. The better biocompatibility, pH stimuli-responsiveness, and the strong fluorescence at low pH media make the nanoparticles a potential platform for the controlled release of anticarcinogens and real-time fluorescent imaging of tumor tissues.