Publications by authors named "Weibin Zhang"

91 Publications

Clinical and Objective Cognitive Measures for the Diagnosis of Cognitive Frailty Subtypes: A Comparative Study.

Front Psychol 2021 24;12:603974. Epub 2021 May 24.

Shanghai Institute of Geriatrics and Gerontology, Shanghai Key Laboratory of Clinical Geriatrics, Huadong Hospital, Research Center of Aging and Medicine, Shanghai Institute of Geriatrics and Gerontology, Shanghai Medical College, Fudan University, Shanghai, China.

Background: Cognitive frailty (CF) includes reversible and potentially reversible subtypes; the former is known as concurrent physical frailty (PF) and pre-mild cognitive impairment subjective cognitive decline (pre-MCI SCD), whereas the latter is known as concurrent PF and MCI. The diagnoses of pre-MCI SCD and MCI are based on clinical criteria and various subjective cognitive decline questionnaires. Heterogeneous assessment of cognitive impairment (CI) results in significant variability of CI, CF, and their subtype prevalence in various population-based studies.

Objective: This study aimed to compare the classification differences in CI and CF subtypes from PF and normal cognition by applying clinical and objective cognitive criteria. Clinical criteria comprised Fried PF and clinical MCI criteria combined with the SCD questionnaire, whereas objective criteria comprised Fried PF and objective cognitive criteria based on the norm-adjusted six neuropsychological test scores.

Methods: Of the 335 volunteers (age ≥ 60 years) in this study, 191 were diagnosed with CI based on clinical cognitive diagnosis criteria, and 144 were identified as robust normal based on objective cognitive assessment from the community-dwelling older adult cohort. Individuals with clinical CI, including 94 with MCI and 97 with pre-MCI SCD, were reclassified into different -score-derived MCI, pre-MCI SCD, and normal subgroups based on objective cognitive criteria. The classification diagnostic accuracy of normal cognition, PF, pre-MCI, MCI, CF, and CF subtypes based on clinical and objective criteria was compared before and after adjusting for age, sex, and education level.

Results: The reclassification of objective assessments indicated better performance than that of clinical assessments in terms of discerning CI severity among different subgroups before adjusting for demographic factors. After covariate adjustment, clinical assessments significantly improved the ability to cognitively discriminate normal individuals from those with pre-MCI SCD and MCI but not the -score-derived pre-MCI SCD and MCI groups from the robust normal group. Furthermore, the adjustment did not improve the ability to discriminate among individuals with reversible CF from those with potentially reversible CF and pre-MCI only SCD from MCI only SCD.

Conclusions: Objective criteria showed better performance than clinical criteria in the diagnosis of individuals with CI or CF subtypes. Rapid clinical cognitive screening in combination with normative -scores criteria is cost effective and sustainable in clinical practice.
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http://dx.doi.org/10.3389/fpsyg.2021.603974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182758PMC
May 2021

pH-Controlled Release of Antigens Using Mesoporous Silica Nanoparticles Delivery System for Developing a Fish Oral Vaccine.

Front Immunol 2021 19;12:644396. Epub 2021 Apr 19.

Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Science, Fujian Normal University, Fuzhou, China.

The development of effective vaccines and delivery systems in aquaculture is a long-term challenge for controlling emerging and reemerging infections. Cost-efficient and advanced nanoparticle vaccines are of tremendous applicability in prevention of infectious diseases of fish. In this study, dihydrolipoamide dehydrogenase (DLDH) antigens of were loaded into mesoporous silica nanoparticles (MSN) to compose the vaccine delivery system. Hydroxypropyl methylcellulose phthalate (HP55) was coated to provide protection of immunogen. The morphology, loading capacity, acid-base triggered release were characterized and the toxicity of nanoparticle vaccine was determined . Further, the vaccine immune effects were evaluated in large yellow croaker oral administration. studies confirmed that the antigen could be stable in enzymes-rich artificial gastric fluid and released under artificial intestinal fluid environment. cytotoxicity assessment demonstrated the vaccines within 120 μg/ml have good biocompatibility for large yellow croaker kidney cells. Our data confirmed that the nanoparticle vaccine could elicit innate and adaptive immune response, and provide good protection against challenge. The MSN delivery system prepared may be a potential candidate carrier for fish vaccine oral administration feeding. Further, we provide theoretical basis for developing convenient, high-performance, and cost-efficient vaccine against infectious diseases in aquaculture.
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http://dx.doi.org/10.3389/fimmu.2021.644396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089398PMC
April 2021

Application of double layered end-to-end anastomosis with continuous manual suture for completing digestive tract reconstruction in totally laparoscopic distal gastrectomy.

BMC Surg 2021 Apr 26;21(1):213. Epub 2021 Apr 26.

Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Zhongshan Road 467, Shahekou District, Dalian, Liaoning, China.

Background: We retrospectively reviewed and consecutively collected the clinical data of distal gastric cancer patients who received surgical treatment, and we discuss the safety and feasibility of double layered end-to-end anastomosis with continuous manual suture to complete digestive tract reconstruction in totally laparoscopic distal gastrectomy.

Methods: We reviewed the clinical data of 41 patients with distal gastric cancer from the gastroenterology department of the Second Affiliated Hospital of Dalian Medical University, from September 2018 to August 2019, who underwent totally laparoscopic distal gastrectomy. During the operation, the method of double layered end-to-end anastomosis with continuous manual suture was used for Billroth type I anastomosis to complete digestive tract reconstruction. All patients have been given a follow-up visit and gastroscopy three months after the operation. The peri-operative clinical information and postoperative follow-up information were collected for analysis, and the clinical application value was evaluated.

Results: General information: male(n = 27), female(n = 14), age = 65.02(SD 9.94) years, and BMI = 23.52(SD 2.56) kg/m, Tumor location: antrum(32,78.0%), angle (6,14.6%), and body (3,7.3%). Clinical stage: I (27, 65.9%), II (7, 17.1%), and III (7, 17.1%). Operative information: operation time = 154.51(SD 33.37) min, anastomosis time = 26.88(SD 5.11) min; intraoperative bleeding = 66.34(SD 48.81) ml; first postoperative ambulation Median = 1(IQR 0) d, first postoperative flatus Median = 3(IQR 2) d, first postoperative diet Median = 3(IQR 1) d, postoperative hospital stay Median = 7(IQR 2) d, and total hospitalization cost = 10,935.00(SD 2205.72)USD. Differentiation degree: high and high-moderate (3,7.32%), moderate and poor-moderate (24, 58.54%), poor differentiation (14, 34.15%), dissected lymph nodes Median = 31(IQR 17), and positive lymph nodes Median = 0(IQR 1). Pathological stage: IA (20, 48.78%), IB (3, 7.32%), IIA (4, 9.76%), IIB (5, 12.20%), IIIA (1, 2.44%), IIIB (3, 7.32%), and IIIC (5, 12.20%). Complications (n = 4): lung infection (1, 2.44%), anastomotic leakage (1, 2.44%), and gastroparesis (2, 4.88%).

Conclusion: It is safe and feasible in clinical treatment to apply the method of double layered end-to-end anastomosis with continuous manual suture to complete digestive tract reconstruction in totally laparoscopic distal gastrectomy.
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http://dx.doi.org/10.1186/s12893-021-01207-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077891PMC
April 2021

Development and Validation of a Hypoxia-Associated Prognostic Signature Related to Osteosarcoma Metastasis and Immune Infiltration.

Front Cell Dev Biol 2021 18;9:633607. Epub 2021 Mar 18.

Department of Orthopedics, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Increasing evidence has shown that hypoxia microenvironment relates to tumor initiation and progression. However, no studies focus on the application of hypoxia-associated genes in predicting osteosarcoma patients' prognosis. This research aims to identify the hypoxia-associated genes related to osteosarcoma metastasis and construct a gene signature to predict osteosarcoma prognosis.

Methods: The differentially expressed messenger RNAs (DEmRNAs) related to osteosarcoma metastasis were identified from Therapeutically Applicable Research to Generate Effective Treatments (Target) database. Univariate and multivariate cox regression analyses were performed to develop the hypoxia-associated prognostic signature. The Kaplan-Meier (KM) survival analyses of patients with high and low hypoxia risk scores were conducted. The nomogram was constructed and the gene signature was validated in the external Gene Expression Omnibus (GEO) cohort. Single-sample gene set enrichment analysis (ssGSEA) was conducted to investigate the relationships between immune infiltration and gene signature.

Results: Two genes, including decorin (DCN) and prolyl 4-hydroxylase subunit alpha 1 (P4HA1), were involved in the hypoxia-associated gene signature. In training and testing datasets, patients with high-risk scores showed lower survival rates and the gene signature was identified as the independent prognostic factor. Receiver operating characteristic (ROC) curves demonstrated the robustness of signature. Functional analyses of DEmRNAs among high- and low-risk groups revealed that immune-associated functions and pathways were significantly enriched. Furthermore, ssGSEA showed that five immune cells (DCs, macrophages, neutrophils, pDCs, and TIL) and three immune features (CCR, APC co inhibition, and Check-point) were down-regulated in the high-risk group.

Conclusion: The current study established and validated a novel hypoxia-associated gene signature in osteosarcoma. It could act as a prognostic biomarker and serve as therapeutic guidance in clinical applications.
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http://dx.doi.org/10.3389/fcell.2021.633607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012854PMC
March 2021

Heterogeneous Influence of Frailty Phenotypes in Age-Related Hearing Loss and Tinnitus in Chinese Older Adults: An Explorative Study.

Front Psychol 2020 16;11:617610. Epub 2021 Feb 16.

Shanghai Institute of Geriatrics and Gerontology, Shanghai Key Laboratory of Clinical Geriatrics, Huadong Hospital, Research Center of Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai, China.

Background: Fried physical frailty, with mobility frailty and non-motor frailty phenotypes, is a heterogeneous syndrome. The coexistence of the two phenotypes and cognitive impairment is referred to as cognitive frailty (CF). It remains unknown whether frailty phenotype has a different association with hearing loss (HL) and tinnitus.

Methods: Of the 5,328 community-dwelling older adults, 429 participants aged ≥58 years were enrolled in the study. The participants were divided into robust, mobility, and non-mobility frailty, mobility and non-mobility CF (subdivided into reversible and potentially reversible CF, RCF, and PRCF), and cognitive decline [subdivided into mild cognitive impairment (MCI) and pre-MCI] groups. The severity and presentations of HL and/or tinnitus were used as dependent variables in the multivariate logistic or nominal regression analyses with forward elimination adjusted for frailty phenotype stratifications and other covariates.

Results: Patients with physical frailty (mobility frailty) or who are robust were found to have lower probability of developing severe HL and tinnitus, and presented HL and/or tinnitus than those with only cognitive decline, or CF. Patients with RCF and non-mobility RCF had higher probability with less HL and tinnitus, and the presentation of HL and/or tinnitus than those with PRCF and mobility RCF. Other confounders, age, cognitive and social function, cardiovascular disease, depression, and body mass index, independently mediated the severity of HL and tinnitus, and presented HL and/or tinnitus.

Conclusion: Frailty phenotypes have divergent association with HL and tinnitus. Further research is required to understand the differential mechanisms and the personalized intervention of HL and tinnitus.

Clinical Trial Registration: ClinicalTrials.gov identifier, NCT2017K020.
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http://dx.doi.org/10.3389/fpsyg.2020.617610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921692PMC
February 2021

Early immune response in large yellow croaker (Larimichthys crocea) after immunization with oral vaccine.

Mol Cell Probes 2021 04 24;56:101708. Epub 2021 Feb 24.

Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou, 350117, China. Electronic address:

Mesoporous silica nanoparticles (MSNs) have been used in the field of biomedicine as antigen carriers and adjuvants for protective antigens. In the present study, an oral nanovaccine against Vibrio alginolyticus was prepared employing MSNs as carriers. The uptake of the dihydrolipoamide dehydrogenase (DLDH) antigens in the intestine of large yellow croaker was evaluated using an immunohistochemistry assay. Additionally, the effects of the nanovaccine on the early immune response in large yellow croaker were investigated via oral vaccination. The presence of the antigens was detected in the mucosa and lamina propria of the foregut, midgut, and hindgut of large yellow croaker at 3 h following oral immunization. The expression levels of cytokines (i.e., lysozyme, IFN-γ, IFITM, TNF-α, IL-1β, IL-2, IL-4, IL-10, and IL-13) in the intestine, spleen, and head kidney tissues of large yellow croaker before and after the immune challenge were determined via RT-qPCR assay. The obtained results revealed that the expression levels of lysozyme, IFN-γ, IFITM, TNF-α, IL-1β, IL-2, IL-4, IL-10, and IL-13 in the intestine and head kidney of the vaccinated large yellow croaker, as well as the expression of lysozyme, IL-1β, and IL-10 in the spleen, exhibited time-dependent oscillation regulation patterns. Notably, the nanovaccine immunization could induce early (6 h) and high expression of IFN-γ in the spleen and kidney tissues after the bacterial infection. The current study supplements the available data on the early immune response to fish nanovaccines. It also provides a valuable theoretical basis for the future development of large yellow croaker oral vaccines.
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http://dx.doi.org/10.1016/j.mcp.2021.101708DOI Listing
April 2021

Impaired Limb Functional Outcome of Peripheral Nerve Regeneration Is Marked by Incomplete Recovery of Paw Muscle Atrophy and Brain Functional Connectivity in a Rat Forearm Nerve Repair Model.

Neural Plast 2021 11;2021:6689476. Epub 2021 Feb 11.

Department of Orthopaedics, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Skilled sensorimotor deficit is an unsolved problem of peripheral nerve injury (PNI) led by limb trauma or malignancies, despite the improvements in surgical techniques of peripheral nerve anastomosis. It is now accepted that successful functional recovery of PNI relies tremendously on the multilevel neural plasticity from the muscle to the brain. However, animal models that recapitulate these processes are still lacking. In this report, we developed a rat model of PNI to longitudinally assess peripheral muscle reinnervation and brain functional reorganization using noninvasive imaging technology. Based on such model, we compared the longitudinal changes of the rat forepaw intrinsic muscle volume and the seed-based functional connectivity of the sensorimotor cortex after nerve repair. We found that the improvement of skilled limb function and the recovery of paw intrinsic muscle following nerve regeneration are incomplete, which correlated with the functional connectivity between the primary motor cortex and dorsal striatum. Our results were highly relevant to the clinical observations and provided a framework for future investigations that aim to study the peripheral central sensorimotor circuitry underlying skilled limb function recovery after PNI.
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http://dx.doi.org/10.1155/2021/6689476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892249PMC
February 2021

Development and analysis of long non-coding RNA-associated competing endogenous RNA network for osteosarcoma metastasis.

Hereditas 2021 Feb 16;158(1). Epub 2021 Feb 16.

Department of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, PR China.

Background: Osteosarcoma is the primary bone malignant neoplasm that often develops metastasis. Increasing evidences have shown that non-coding RNAs (ncRNAs) relate to the progression of osteosarcoma. However, the ncRNAs' roles in osteosarcoma metastasis are still unknown.

Methods: Differentially expressed (DE) RNAs were identified from Gene Expression Omnibus (GEO) database. Protein-protein interaction (PPI) of DE messenger RNAs (DEmRNAs) was built through STRING database. The target mRNAs and long ncRNAs (lncRNAs) of microRNAs (miRNA) were predicted through miRDB, Targetscan and Genecode databases, which then cross-checked with previously obtained DERNAs to construct competing endogenous RNA (ceRNA) network. All networks were visualized via Cytoscape and the hub RNAs were screened out through Cytoscape plug-in Cytohubba. The gene functional and pathway analyses were performed through DAVID and MirPath databases. The survival analyses of hub RNAs were obtained through Kaplan-Meier (KM) survival curves.

Results: Five hundred sixty-four DEmRNAs, 16 DElncRNAs and 22 DEmiRNAs were screened out. GO functional and KEGG pathway analyses showed that DERNAs were significantly associated with tumor metastasis. The ceRNA network including 6 lncRNAs, 55 mRNAs and 20 miRNAs were constructed and the top 10 hub RNAs were obtained. Above all, PI3K/AKT signaling pathway was identified as the most important osteosarcoma metastasis-associated pathway and its hub ceRNA module was constructed. The survival analyses showed that the RNAs in hub ceRNA module closely related to osteosarcoma patients' prognosis.

Conclusions: The current study provided a new perspective on osteosarcoma metastasis. More importantly, the RNAs in hub ceRNA module might act as the novel therapeutic targets and prognostic factors for osteosarcoma patients.
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http://dx.doi.org/10.1186/s41065-021-00174-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887822PMC
February 2021

New Insights into Cd/Fe Co-Doped BiOBr for Enhancing the Photocatalysis Efficiency of Dye Decomposition under Visible-Light.

Nanomaterials (Basel) 2021 Feb 7;11(2). Epub 2021 Feb 7.

School of Physics and Optoelectronic Engineering, Yangtze University, Jingzhou 434023, China.

Uniform flowerlike microspheres Cd/Fe co-doped BiOBr were prepared with the aid of the microwave hydrothermal process. The results indicate that the degradation performance of BiCdOBr and BiFeOBr are 1.31 and 2.05 times that of BiOBr for RhB, respectively. Moreover, the novel Cd/Fe co-doped BiOBr photocatalysts with ~0.42 eV impurity bands presented remarkably enhanced photocatalytic activities with being 3.10 times that of pure BiOBr, by achieving e/h efficient separation and narrowed bandgap with the ions synergistic effect of Cd and Fe. Based on DFT insights, the photodegradation mechanism was systematically studied that the conversion of multivalent Fe ions promoted the production of •O, and Cd ions worked as electron transfer mediators, which elucidated that the •O and h mainly participated in the catalytic reaction. The experimental and theoretical results show that the synergistic effects of multi-ion doping have great potential in the field of photocatalysis.
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http://dx.doi.org/10.3390/nano11020423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914912PMC
February 2021

Targeting autophagy enhances atezolizumab-induced mitochondria-related apoptosis in osteosarcoma.

Cell Death Dis 2021 02 8;12(2):164. Epub 2021 Feb 8.

Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

In this study, we identified the multifaceted effects of atezolizumab, a specific monoclonal antibody against PD-L1, in tumor suppression except for restoring antitumor immunity, and investigated the promising ways to improve its efficacy. Atezolizumab could inhibit the proliferation and induce immune-independent apoptosis of osteosarcoma cells. With further exploration, we found that atezolizumab could impair mitochondria of osteosarcoma cells, resulting in increased release of reactive oxygen species and cytochrome-c, eventually leading to mitochondrial-related apoptosis via activating JNK pathway. Nevertheless, the excessive release of reactive oxygen species also activated the protective autophagy of osteosarcoma cells. Therefore, when we combined atezolizumab with autophagy inhibitors, the cytotoxic effect of atezolizumab on osteosarcoma cells was significantly enhanced in vitro. Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.
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http://dx.doi.org/10.1038/s41419-021-03449-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870858PMC
February 2021

An oblique projection modification technique (OPMT) for fast multispectral CT reconstruction.

Phys Med Biol 2021 Mar 2;66(6):065003. Epub 2021 Mar 2.

School of Mathematical Sciences, Capital Normal University, Beijing, People's Republic of China. Beijing Advanced Innovation Center for Imaging Technology, Capital Normal University, Beijing, People's Republic of China.

In x-ray multispectral (or photon-counting) computed tomography (MCT), the object of interest is scanned under multiple x-ray spectra, and it can acquire more information about the scanned object than conventional CT, in which only one x-ray spectrum is used. The obtained polychromatic projections are utilized to perform material-selective and energy-selective image reconstruction. Compared with the conventional single spectral CT, MCT has a superior material distinguishability. Therefore, it has wide potential applications in both medical and industrial areas. However, the nonlinearity and ill condition of the MCT problem make it difficult to get high-quality and fast convergence of images for existing MCT reconstruction algorithms. In this paper, we proposed an iterative reconstruction algorithm based on an oblique projection modification technique (OPMT) for fast basis material decomposition of MCT. In the case of geometric inconsistency, along the current x-ray path, the oblique projection modification direction not only relates to the polychromatic projection equation of the known spectrum, but it also comprehensively refers to the polychromatic projection equation information of the unknown spectra. Moreover, the ray-by-ray correction makes it applicable to geometrically consistent projection data. One feature of the proposed algorithm is its fast convergence speed. The OPMT considers the information from multiple polychromatic projection equations, which greatly speeds up the convergence of MCT reconstructed images. Another feature of the proposed algorithm is its high flexibility. The ray-by-ray correction will be suitable for any common MCT scanning mode. The proposed algorithm is validated with numerical experiments from both simulated and real data. Compared with the ASD-NC-POCS and E-ART algorithms, the proposed algorithm achieved high-quality reconstructed images while accelerating the convergence speed of them.
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http://dx.doi.org/10.1088/1361-6560/abe028DOI Listing
March 2021

Jingshu Keli for treating cervical spondylotic radiculopathy: The first multicenter, randomized, controlled clinical trial.

J Orthop Translat 2021 Mar 21;27:44-56. Epub 2020 Dec 21.

Department of Orthopedics, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi China.

Background: Jingshu Keli (or Jingshu granules), a traditional Chinese medicine, are widely used for treating cervical spondylotic radiculopathy in China; however, no randomized, double-blind, controlled study has verified their effectiveness.

Purpose: To evaluate the efficacy and safety of Jingshu Keli for the treatment of cervical spondylotic radiculopathy in a randomized controlled trial.

Design: From August 2015 to July 2017, a multicenter, randomized, double-blind, placebo-controlled trial was conducted at 13 large- and medium-sized hospitals in China.

Patient Sample: A total of 360 and 120 patients were initially enrolled in the Jingshu and control groups, respectively; 386 patients completed the study, with 299 in the Jingshu group and 87 in the control group.

Outcome Measures: The main index for evaluating the curative effect was the pain score on a visual analogue scale (VAS; 0-100 points).

Methods: All patients were administered a bag of Jingshu Keli or placebo 3 times a day for 4 weeks, and were interviewed at the second and fourth weeks. The decrease in pain scores and rate of change in pain scores after treatment were calculated, related laboratory indices were reviewed, and adverse reactions were recorded.

Results: In the Per Protocol Set (PPS) analysis, the baseline pain VAS scores in the control and Jingshu groups were 49.31 ​± ​6.97 and 50.06 ​± ​7.33, respectively, with no significant difference between the groups (P ​> ​0.05). While there were no differences at 2 weeks between groups, at four weeks the pain VAS scores in the control and Jingshu groups decreased by 12.86 ​± ​13.45 and 22.72 ​± ​15.08, respectively relative to the values at baseline, with significant group differences (P ​< ​0.0001). While there were similar significant differences between the groups (P ​< ​0.0001) in the Full Analysis Set (FAS) analyses neither group achieved the minimal clinically important difference at any time point.

Conclusions: Jingshu Keli are effective for the treatment of cervical spondylotic radiculopathy.

Translational Potential Statement: This is the first prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial that confirmed the clinical efficacy and safety of Jingshu Keli for treating cervical spondylotic radiculopathy, which can provide evidence for clinical treatment.
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http://dx.doi.org/10.1016/j.jot.2020.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758457PMC
March 2021

A novel in vivo mouse intervertebral disc degeneration model induced by compressive suture.

Exp Cell Res 2021 01 20;398(1):112359. Epub 2020 Nov 20.

Department of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address:

Intervertebral disc degeneration (IDD) is the root cause of many musculoskeletal disorders of the spine. However, the etiology of IDD is complex and still not well understood. Animal models of IDD would be useful in deciphering the underlying mechanisms. But the existing animal models have their limitations. Therefore, to establish a novel mouse model that can simulate the human IDD process in vivo, we proposed to carefully circumcise the 2 mm-wide tail skin and then compressively sutured the defect with a simple end-to-end suture to exert excessive pressure on the disc. After 1-week, 2-week, and 4-week compression, the mice were sacrificed and the intervertebral discs were harvested for tissue analysis. The radiological, morphological, and molecular modifications of intervertebral discs were measured to characterize this model. Radiologically, the water content of the intervertebral disc decreased significantly after 2-week compression. Morphologically, the nucleus pulposus showed a decrease in volume and the number of notochordal cells. The compressive suture also broke the balance between anabolic and catabolic enzymes in nucleus pulposus, which led to the remodeling of the extracellular matrix in nucleus pulposus as the content of aggrecan and collagen II decreased. The compressive suture could induce intervertebral discs degeneration in a more reasonable way, which was solely influenced by mechanical loading, as the mice caudal vertebrae still moved freely after the operation. This kind of animal model could be adapted as a reliable in vivo mouse IDD model for the research regarding the etiology and treatments of IDD.
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http://dx.doi.org/10.1016/j.yexcr.2020.112359DOI Listing
January 2021

Demographically Corrected Normative Z Scores on the Neuropsychological Test Battery in Cognitively Normal Older Chinese Adults.

Dement Geriatr Cogn Disord 2020 11;49(4):375-383. Epub 2020 Nov 11.

Shanghai Institute of Geriatrics and Gerontology, Shanghai Key Laboratory of Clinical Geriatrics, Department of Geriatrics, Huadong Hospital, and Research Center of Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai, China.

Background: Subjective questionnaires used for the diagnosis of pre-mild cognitive impairment (pre-MCI) and conventional criteria for MCI might mainly result in false-positive diagnostic errors. The integrated criteria based on demographically adjusted total and process Z scores on neuropsychological tests have been validated to be sensitive for measuring pre-MCI, MCI, and MCI subtypes. However, the underrepresentativity of Chinese populations and the complexity in some tests limit the use of the established Z scores in the elderly Chinese population.

Objective: The aim of this study was to develop a useful Z score calculator to assess individual cognitive performance after adjustment of the scores on each of the neuropsychological tests according to sex, age, and education and to establish preliminary norms for the objective assessment of cognition function in elderly Chinese individuals.

Methods: The neuropsychological test battery consists of measures of performance on different cognitive domains, including episodic memory, language, executive function, processing speed, and attention. Data were obtained from 220 clinically cognitively normal Chinese volunteers aged 60 years or older from the cohort of the Shanghai study of health promotion among frail elderly individuals. Regression models were used to investigate the impact of age, education, and sex on test scores. Z scores were estimated for the different scores by subtracting the predicted mean from the raw score and dividing it by the root mean square error term for any given linear regression model.

Results: Preliminary analyses indicated that age, sex, or level of education significantly affected test scores. A series of linear regression models was constructed for all instruments, i.e.: the Trail-Making Test A and B, to assess executive function or attention; the Boston Naming Test and animal list generation, to assess language; delayed free correct responses and the Hopkins Verbal Learning Test-Revised (HVLT-R) recognition, as well as three process scores, i.e., intrusion errors, learning slope, and retroactive interference, from the HVLT-R, to assess memory, by adjusting for the covariates of age, sex, and level of education concurrently. The Z scores on all neuropsychological tests were estimated based on the corresponding regression coefficients.

Conclusions: We constructed a multivariable regression-based normative Z score method for the measurement of cognition among older Chinese individuals in the community. The normative score will be useful for the accurate diagnosis of different subtypes of pre-MCI and MCI after preliminary rapid screening in the community.
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http://dx.doi.org/10.1159/000505618DOI Listing
May 2021

Clinical factors affecting prognosis of limb osteosarcoma in China: a multicenter retrospective analysis.

J Int Med Res 2020 Aug;48(8):300060520930856

Department of Orthopedics, PLA 960th Hospital, Jinan City, Shandong Province, China.

Objective: This study was performed to explore the relationship between various clinical factors and the prognosis of limb osteosarcoma.

Methods: We retrospectively analyzed the clinical data of 336 patients with limb osteosarcoma treated from June 2000 to August 2016 at 7 Chinese cancer centers. Data on the patients' clinical condition, treatment method, complications, recurrences, metastasis, and prognosis were collected and analyzed. Kaplan-Meier analysis and Cox regression models were used to analyze the data.

Results: The patients comprised 204 males and 132 females ranging in age from 6 to 74 years (average, 21.1 years). The overall 3- and 5-year survival rates were 65.0% and 55.0%, respectively. The 5-year overall survival rate was 64.0% with standard chemotherapy and 45.6% with non-standard chemotherapy. Cox regression analysis demonstrated that standard chemotherapy, surgery, recurrence, and metastasis were independent factors associated with the prognosis of limb osteosarcoma.

Conclusion: The survival of patients with limb osteosarcoma can be significantly improved by combining standard chemotherapy and surgery. The overall survival rate can also be improved by adding methotrexate to doxorubicin-cisplatin-ifosfamide triple chemotherapy.
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http://dx.doi.org/10.1177/0300060520920053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469730PMC
August 2020

Tubeimoside I-induced lung cancer cell death and the underlying crosstalk between lysosomes and mitochondria.

Cell Death Dis 2020 08 26;11(8):708. Epub 2020 Aug 26.

Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China.

Cancer cells have developed chemoresistance and have improved their survival through the upregulation of autophagic mechanisms that protect mitochondrial function. Here, we report that the traditional Chinese anticancer agent tubeimoside I (Tub), which is a potent inhibitor of autophagy, can promote mitochondria-associated apoptosis in lung cancer cells. We found that Tub disrupted both mitochondrial and lysosomal pathways. One of its mechanisms was the induction of DRP1-mediated mitochondrial fragmentation. Another mechanism was the blocking of late-stage autophagic flux via impairment of lysosomal acidification through V-ATPase inhibition; this blocks the removal of dysfunctional mitochondria and results in reactive oxygen species (ROS) accumulation. Excessive ROS accumulation causes damage to lysosomal membranes and increases lysosomal membrane permeability, which leads to the leakage of cathepsin B. Finally, cathepsin B upregulates Bax-mediated mitochondrial outer membrane permeability and, subsequently, cytosolic cytochrome C-mediated caspase-dependent apoptosis. Thus, the cancer cell killing effect of Tub is enhanced through the formation of a positive feedback loop. The killing effect of Tub on lung cancer cells was verified in xenografted mice. In summary, Tub exerts a dual anticancer effect that involves the disruption of mitochondrial and lysosomal pathways and their interaction and, thereby, has a specific and enhanced killing effect on lung cancer cells.
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http://dx.doi.org/10.1038/s41419-020-02915-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449972PMC
August 2020

Isolation of extracellular vesicle with different precipitation-based methods exerts a tremendous impact on the biomarker analysis for clinical plasma samples.

Cancer Biomark 2020 ;29(3):373-385

Department of Orthopaedics, Ruijin Hospital, Shanghai, China.

Background: Extracellular vesicles(EVs) is an emerging approach of cancer liquid biopsy. Although the precipitation-based method with commercial kits has gained popularity as the second most commonly used technique, these protocols vary tremendously with many included reagents still unknown to the community.

Methods: In this study, we assigned each of the 3 clinical plasma samples into 6 aliquots to assess five commercial EV isolation kits, in comparison with ultracentrifugation(UC). We implemented a standardized EV preparation and transcriptome analysis workflow except the EV isolation methods used. The metrics of EVs and its RNA cargo (evRNA) were compared to assess the technical variations versus the biological variations in the clinical setting.

Results: Although the size range of the isolated EVs demonstrated a similar distribution, we found significant technical variability among these methods, in terms of EV amount, purity, subpopulations and RNA integrity. Such variabilities were further relayed to a drastic divergence of evRNA expression on a transcriptome-wide fashion.

Conclusions: Our study demonstrated a highly variable result from polymeric precipitation-based EV isolation methods, making EVs based biomarker analysis difficult to interpret and reproduce. We highlighted the importance of benchmarking and transparent reporting of the precipitation-based protocols in the liquid biopsy research.
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http://dx.doi.org/10.3233/CBM-201651DOI Listing
January 2020

Analysis of contrast-enhanced ultrasound features of hepatocellular adenoma according to different pathological molecular classifications.

Clin Hemorheol Microcirc 2020 ;76(3):391-403

Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China.

Objective: To explore the specific contrast-enhanced ultrasound (CEUS) features of hepatocellular adenomas (HCA) according to their pathological molecular classifications.

Methods & Materials: In this retrospective study, fifty-three histopathologically proved HCA lesions (mean size, 39.7±24.9 mm) were included. Final histopathological diagnosis of HCA lesions were identified by surgical resection (n = 51) or biopsy (n = 2) specimens. CEUS imaging features were compared among four subgroups according to World Health Organization (WHO) 2019 pathological molecular classifications standards. Analysis of variance (ANOVA) were used for statistical analysis of continuous variables. Fisher's exact test were used for categorical variables. The sensitivity (SE), specificity (SP), and accuracy of CEUS feature in diagnosis of each HCA subtype were calculated and compared.

Results: Final histopathological diagnosis included HNF-1α inactivated HCAs (H-HCA, n = 12), β-catenin activated HCAs (B-HCA, n = 8), inflammatory HCAs (I-HCA, n = 31), and unclassified HCAs (U-HCA, n = 2). During arterial phase of CEUS, all HCAs were hyper-enhanced, 66.6% (8/12) of H-HCAs and 50% (4/8) of B-HCAs displayed complete hyperenhancement, whereas 58.0% (18/31) of I-HCAs showed centripetal filling hyperenhancement pattern (P = 0.016). Hyper-enhanced subcapsular arteries could be detected in 64.5% (20/31) I-HCAs during early arterial phase. During portal venous and late phase, sustained hyper- or iso-enhancement were observed in 91.7% (11/12) of H-HCAs, while most of I-HCAs (61.3%, 19/31) and B-HCAs (7/8, 87.5%) were hypo-enhanced (P = 0.000). Central unenhanced areas were most commonly observed in I-HCAs (29.0%, 9/31) (P = 0.034).

Conclusion: Depending on its unique imaging features including enhancement filling pattern, hyper-enhanced subcapsular artery and presence of washout, CEUS might provide helpful diagnostic information for preoperative prediction of various HCA molecular subtypes.
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http://dx.doi.org/10.3233/CH-200899DOI Listing
February 2021

Insights into Ion Occupancy Manipulation of Fe-Co Oxide Free-Standing Cathodes for Li-O Batteries with Enhanced Deep Charge Capability and Long-Term Capability.

ACS Appl Mater Interfaces 2020 Jul 26;12(27):30268-30279. Epub 2020 Jun 26.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials (Ministry of Education), Shandong University, Jinan 250061, China.

The merits of Li-O batteries due to the huge energy density are shadowed by the sluggish kinetics of oxygen redox and massive side reactions caused by conductive carbon and a binder. Herein, Fe-Co inverse spinel oxide nanowires grown on Ni foam are fabricated as carbon-free and binder-free cathodes for Li-O batteries. Superior high rate cycle durability and deep charge capability are obtained. For example, 300 cycles with a low overpotential under a fixed capacity of 500 mAh g are achieved at a high current density of 500 mA g. In the deep discharge/charge mode at 500 mA g, the optimized Fe-Co oxide cathode can stably work for more than 30 cycles with the capacity maintained at about 2100 mAh g. Owing to the appreciable incorporation of Fe into the surface of stable inverse spinel oxides, the regulated Fe-Co oxide cathodes possess a more stable and higher ratio of Co/Co, which offers improved adsorption ability of reactive oxygen intermediates and thus achieves the enhanced electrocatalytic performance in the higher current density. In addition, the morphology evolution from array to pyramid-like structure of nanowires further provides assurance in the superior cycle capability. By coupling pyramid-shaped nanowires with binary inverse spinel, the obtained Fe-Co oxide becomes a promising material for practical applications in Li-O batteries. This work offers a general strategy to design efficient mixed metal oxide-based electrodes for the critical energy storage fields.
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http://dx.doi.org/10.1021/acsami.0c02087DOI Listing
July 2020

Structural, mechanical and electronic properties and hardness of ionic vanadium dihydrides under pressure from first-principles computations.

Sci Rep 2020 Jun 1;10(1):8868. Epub 2020 Jun 1.

Department of Physics and Optoelectronic Engineering, Yangtze University, Jingzhou, 434023, China.

Based on a combination of the CALYPSO method for crystal structure prediction and first-principles calculations, we explore the crystal structures of VH under the pressure range of 0-300 GPa. The cubic Fm-3m phase with regular VH cubes is predicted to transform into orthorhombic Pnma structure with fascinating distorted VH tetrakaidecahedrons at 47.36 GPa. Both the Fm-3m phase at 0 GPa and the Pnma phase at 100 GPa are mechanically and dynamically stable, as verified with the calculations of elastic constants and phonon dispersions, respectively. Moreover, the calculated electronic band structure and density of states indicate both stable phases are metallic. Remarkably, the analyses of the Poisson's ratio, electron localization function (ELF) and Bader charge substantiate that both stable phases are ionic crystals on account of effective charges transferring from V atom to H. On the basis of the microscopic hardness model, the Fm-3m and Pnma crystals of VH are potentially incompressible and hard materials with the hardness values of 17.83 and 17.68 GPa, respectively.
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http://dx.doi.org/10.1038/s41598-020-65910-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264295PMC
June 2020

Characterization of the hydrolysate and catalytic cavity of α-agarase AgaD.

Biotechnol Lett 2020 Oct 13;42(10):1919-1925. Epub 2020 May 13.

School of Medicine and Pharmacy, Key Laboratory of Marine Drugs, Chinese Ministry of Education, Key Laboratory of Glycoscience & Glycotechnology of Shandong Province, Ocean University of China, Qingdao, 266003, China.

Objective: To characterize the hydrolysis product and the substrate binding in the catalytic cavity of α-agarase AgaD.

Results: The time course curve showed that AgaD degraded agarose by the endo-type cleavage. AgaD did not degrade agarobiose (A2) and agarotetraose (A4). The minimum-length substrate was agarohexaose (A6), which was cleaved into A2 and A4. Agarooctaose (A8) was cleaved into two molecules of A4. Consistently, TLC and NMR data identified agarotetraose (A4) as the main hydrolysate when agarose was degraded by AgaD.

Conclusion: This study confirms AgaD is an endo-type α-agarase and A4 as the main hydrolysis product of AgaD, which suggests the catalytic cavity of AgaD accommodates eight sugar units spanning from - 4 to + 4.
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http://dx.doi.org/10.1007/s10529-020-02901-5DOI Listing
October 2020

Changes of cropland evapotranspiration and its driving factors on the loess plateau of China.

Sci Total Environ 2020 Aug 12;728:138582. Epub 2020 Apr 12.

State Key Laboratory of Remote Sensing Science, Institute of Remote Sensing and Digital Earth, Chinese Academy of Sciences, Beijing 100094, China.

Agricultural water resource, mainly consumed through evapotranspiration, plays a critical role in agricultural production of arid and semiarid regions. Quantifying the changes of evapotranspiration in cropland (ETc), and its driving factors, may provide rich information for improving human land-use and water resource management. Here we first investigated the multi-year (2000-2015) changes in the ETc (mm yr) and associated driving factors of the Loess Plateau (LP), using a combination of the Vegetation Interfaces Processes model and a factorial analysis of variance. We found that the ETc of the LP showed a significant upward trend of 0.31 km yr (3.33 mm yr) (p < .05) over the last 16 years, mainly driven by cropland changes (3.77% per year), which combined the contribution of cropland area changes and cropland leaf area index (LAIc) changes. We then examined the changes of the dominant driving factor: cropland, and results indicated that the cropland changes consisted of the decrease in cropland area (net decrease of 10.50 × 10 km) and the increase in LAIc (increased by 10.72%), which suggest the actual contribution of the ETc uptrend was the increasing LAIc. Our further analysis on the causes of the increasing LAIc by correlating the LAIc with land-use management factors revealed that the cropland greening on the LP showed high positive correlations with the increasing inputs of total power of agriculture machinery and farm plastic film, followed by chemical fertilizer. The increase of LAIc was also promoted by the increased ratio of the garden fruits output to total crops output (increased by 67.12%) and multiple cropping (increased by 21.66%). These results suggest that the ETc uptrend can be related to the agricultural intensification. Our study highlights the need for a realistic representation of socio-economic development and human land-use practices in the sustainable optimal allocation of agricultural water resources on the LP.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138582DOI Listing
August 2020

Establishment of a dynamic osteosarcoma biobank: Ruijin experience.

Cell Tissue Bank 2020 Sep 15;21(3):447-455. Epub 2020 Apr 15.

Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197 Ruijin er Road, Shanghai, China.

Outcomes for patients with metastatic and recurrent osteosarcoma remain poor and a better understanding of the biology of this malignancy is critical to the development of prognostic biomarkers and novel therapies. The purpose of this study was to establish a biobank of osteosarcoma which has the potential of monitoring tumors dynamically with exosomes, to facilitate clinical and basic scientific research. The osteosarcoma biological specimen and clinical data of osteosarcoma were collected in Ruijin Hospital in two stages. In the first stage (2015-2017), the collection of tissue specimens and blood samples were performed at diagnostic biopsy, definitive surgery, recurrence and lung metastasis, according to the Children's Oncology Group protocol. In the second stage (2017-2019), the tissue specimens were collected the same as before, but the blood samples were collected at the beginning of each MAP-I (methotrexate, cisplatin, doxorubicin, ifosfamide) chemotherapy cycle, and every 6 months after the last chemotherapy up to 3 years, according to our modified protocol, to dynamically monitor the status of possible alteration of gene expression profiling in the osteosarcoma. A total of 268 patients with osteosarcoma were enrolled in this study, 161 were men and 107 were women, with the mean age of 24.51 ± 15.58 years. Local recurrence occurred in 29 patients and lung metastasis in 51. The numbers of tissue and blood specimens reached 360 and 1023, respectively. 11 specimens were from recurrent osteosarcoma and 25 were from lung metastasis. The corresponding clinical and demographic data were collected in our electronic database. The osteosarcoma biobank built with our modified protocol mentioned above has the potential of monitoring tumors dynamically with exosomes and could provide specimens to the researches improving the biological understanding and outcome of this disease.
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http://dx.doi.org/10.1007/s10561-020-09831-6DOI Listing
September 2020

High throughput screening of MC MXenes for efficient CO reduction conversion into hydrocarbon fuels.

Nanoscale 2020 Apr 1;12(14):7660-7673. Epub 2020 Apr 1.

Institute of Materials Science, TU Darmstadt, 64287 Darmstadt, Germany.

The electrocatalytic reduction conversion of CO to produce methane (CH) as a fuel has attracted intensive attention for renewable energy. Density functional theory (DFT) calculations with a computational hydrogen electrode (CHE) model are applied to study the hydrogenation of CO on the two-dimensional (2D) MC transition metal carbide (MXenes) surface. It is demonstrated that the adsorbed CO is activated and can combine with surface hydrogen to form bicarbonate species, thus leading to more competitive selectivity for the CORR than the HER. All possible conversion pathways for carbon dioxide to methane are explored, and it is found that the formation of the bicarbonate (HCO) species is energetically the most favourable reaction pathway, whereas the main intermediate of the CORR is HCHO. Detailed characterization of the initial activation, scaling relationships, protonation steps and electrode overpotential, together with the evaluation of the limiting potentials for several reaction mechanisms, reveals that MXene MC exhibits a high catalytic performance for CO, providing novel fuel cells.
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http://dx.doi.org/10.1039/c9nr10598kDOI Listing
April 2020

Interfacial Superassembly of Grape-Like [email protected] Frameworks for Superior Lithium Storage.

ACS Appl Mater Interfaces 2020 Mar 25;12(12):13770-13780. Epub 2020 Feb 25.

Department of Chemistry, Laboratory of Advanced Materials, Fudan University, Shanghai 200433, P. R. China.

Despite the excellent electrochemical performance of MnO-based electrodes, a large capacity increase cannot be avoided during long-life cycling, which makes it difficult to seek out appropriate cathode materials to match for commercial applications. In this work, a grape-like [email protected] framework from interfacial superassembly with remarkable electrochemical properties was fabricated as anode materials for lithium-ion batteries. Electrochemical analysis indicates that the introduction of Ni not only contributes to the excellent rate capability and high specific capacity but also prevents further oxidation of MnO to the higher valence states for ultrastable long-life cycling performance. Furthermore, thermodynamic calculation proves that the ultrastable long cycling life of the Ni-Mn-O system originated from a buffer composition region to stabilize the MnO structure. Because of the unique grape-like structure and performance of the Ni-Mn-O system, the [email protected] electrode displayed an invertible specific capacity of 706 mA h g after 200 cycles at a current density of 0.1 A g and excellent cycling stability maintained a capacity of 476.8 mA h g after 2100 cycles at 1.0 A g without obvious capacity change. This new nanocomposite material could offer a novel fabrication strategy and insight for MnO-based materials and other metal oxides as anodes for improved electrochemical performance.
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http://dx.doi.org/10.1021/acsami.9b20317DOI Listing
March 2020

MicroRNA-200a induces immunosuppression by promoting PTEN-mediated PD-L1 upregulation in osteosarcoma.

Aging (Albany NY) 2020 01 24;12(2):1213-1236. Epub 2020 Jan 24.

Department of Orthopaedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

In this study, we identified microRNAs that regulate the expression of programmed death-ligand 1(PD-L1) in osteosarcoma and investigated their role in PD-L1-targeted immunotherapy. MicroRNA sequencing analysis showed that the expression of PD-L1 is regulated by microRNA-200a in U2OS, 143B, and K7 osteosarcoma cells. MicroRNA-200a overexpression induced the upregulation of PD-L1 in the osteosarcoma cells. CD8 T cells co-cultured with microRNA-200a-overexpressing osteosarcoma cells showed reduced survival, proliferation, and secretion of granzyme B and perforin. The same phenomenon was also observed in the K7-derived syngeneic mouse model, as microRNA-200a promoted tumor growth by increasing the percentage of Foxp3 regulatory T lymphocytes while reducing the proportions of CD4, CD8, and IFN-γ cytotoxic T lymphocytes. But microRNA-200a overexpression group was also more responsive to PD-L1-targeted immunotherapy than the controls. In addition, the tumor tissues from 32 osteosarcoma patients showed that high expression of microRNA-200a and PD-L1 was associated with poor tumor necrosis rate after chemotherapy. Moreover, we confirmed that tensin homolog deleted on chromosome ten (PTEN) could act as the target gene for microRNA-200a during the upregulation of PD-L1. Thus, our findings provide important and novel insight into a regulatory axis involving microRNA-200a/PTEN/ PD-L1 axis, which determines osteosarcoma growth and the efficacy of PD-L1-targeted immunotherapy.
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http://dx.doi.org/10.18632/aging.102679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053609PMC
January 2020

Establishment and characterization of a novel human osteosarcoma cell line for spontaneous pulmonary metastasis research .

Ann Transl Med 2019 Oct;7(20):573

Department of Orthopedics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Background: A large number of osteosarcoma patients are dying of pulmonary metastasis in spite of the recent progress achieved in treatment research. Therefore, there is an urgent need for an experiment, whose purpose is to investigate the growth and metastasis of human osteosarcoma tumor. In this study, a novel human osteosarcoma cell line was established and characterized for osteosarcoma metastatic research .

Methods: Small pieces of parental primary osteosarcoma samples from a 16-year-old boy were xeno-transplanted into NOD/SCID mice. Then, osteosarcoma cells from the xeno-grafts were isolated and further passaged . Expression profiling was confirmed using HE staining and immunohistochemistry. The tumorigenic and metastatic ability of the established cell line was analyzed by cell scratch and CCK8 assay , and tumor transplantation in NOD/SCID mice.

Results: Parental cells were pleomorphic and positive with ALP, SSEA-4, and CD44. Osteosarcoma cells, named Well5 cells, were successfully isolated and had the ability of adipogenesis and osteogenesis. Well5 cells were mostly positive for SSEA-4 protein, and possessed morphological characteristics such as osteoblastic nature during the cultivation and hetero transplantation. Cell scratch and CCK8 assay indicated Well5 cells obtained a better capacity for migration and proliferation than the MG63 cell line. In NOD/SCID mice, orthotopic tumors were established at the primary site, and spontaneous pulmonary metastases were developed.

Conclusions: A novel human osteosarcoma cell line was successfully established, which may be helpful for spontaneous pulmonary metastasis research .
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http://dx.doi.org/10.21037/atm.2019.09.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861804PMC
October 2019

Incidence and Mortality of Sarcomas in Shanghai, China, During 2002-2014.

Front Oncol 2019 17;9:662. Epub 2019 Jul 17.

Department of Medical Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Sarcomas are a heterogeneous group of rare but deadly malignant tumors. The aim of this study was to comprehensively describe the incidence and mortality of sarcomas in Shanghai during 2002-2014. Data were from Shanghai Cancer Registry. All new cases diagnosed with sarcomas and all death records where the cause of death listed as sarcomas were included. The characteristics of sarcomas incidence and mortality were analyzed. Age-standardized rates (ASRs) were adjusted by the world standard population. The trends were assessed by Joinpoint analysis. A total of 9,440 incident cases were identified. The ASR was 3.4/10 for all sarcomas combined. Incidence of sarcomas overall was similar in females (3.5/10) as in males (3.4/10). Except for sarcomas "Not Otherwise Specified" (NOS), the most common histological subtype was gastrointestinal stromal sarcoma (GISS) (14.8%), which was followed by fibrosarcoma (7.2%), lipoblastoma (6.7%), leiomyosarcomas (6.5%), and osteosarcoma (5.3%). Among those incident cases, 87.9% were located in soft tissue sarcomas (STS) and 12.1% in bone and joint (bone sarcomas). The ASRs for STS and bone sarcomas were 2.8/10 and 0.6/10, respectively. Incidence rates for all STS combined rose exponentially with age, while bone sarcomas had the highest incidence at age 0-19. There were 4,279 deaths during 2002-2014 with the ASR of 1.3/10. Age-adjusted mortality due to sarcomas was slightly higher in males (1.5/10) than females (1.2/10). Except for sarcomas NOS, leiomyosarcomas was the most common subtype, comprising 9.9% of deaths due to sarcomas, followed by lipoblastoma (6.4%) and osteosarcoma (6.3%). The ASRs of mortality for STS and bone sarcomas were 1.0/10 and 0.2/10, respectively. For both males and females, the age-standardized incidence for STS and bone sarcomas did not change meaningfully over the study period. In contrast, age-standardized STS mortality in females increased by 2.3% per year (95% CI: 0.3, 4.4%), but was unchanged in males. No meaningful trends in bone sarcomas mortality were observed for either males or females. This population-based study was the first report of epidemiology of sarcomas in Shanghai according to anatomic site and histologic type. The diversity and rarity of sarcomas suggested more detailed data are warranted.
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http://dx.doi.org/10.3389/fonc.2019.00662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6653066PMC
July 2019

Spatial Regulation of Polo-Like Kinase Activity During Meiosis by the Nucleoplasmic HAL-2/HAL-3 Complex.

Genetics 2019 09 25;213(1):79-96. Epub 2019 Jul 25.

Departments of Developmental Biology and Genetics, Stanford University School of Medicine, California 94305

Proper partitioning of homologous chromosomes during meiosis relies on the coordinated execution of multiple interconnected events: Homologs must locate, recognize, and align with their correct pairing partners. Further, homolog pairing must be coupled to assembly of the synaptonemal complex (SC), a meiosis-specific tripartite structure that maintains stable associations between the axes of aligned homologs and regulates formation of crossovers between their DNA molecules to create linkages that enable their segregation. Here, we identify HAL-3 (Homolog Alignment 3) as an important player in coordinating these key events during meiosis. HAL-3, and the previously identified HAL-2, are interacting and interdependent components of a protein complex that localizes to the nucleoplasm of germ cells. (or ) mutants exhibit multiple meiotic prophase defects including failure to establish homolog pairing, inappropriate loading of SC subunits onto unpaired chromosome axes, and premature loss of synapsis checkpoint protein PCH-2. Further, loss of function results in misregulation of the subcellular localization and activity of Polo-like kinases (PLK-1 and PLK-2), which dynamically localize to different defined subnuclear sites during wild-type prophase progression to regulate distinct cellular events. Moreover, loss of PLK-2 activity partially restores tripartite SC structure in a mutant background, suggesting that the defect in pairwise SC assembly in mutants reflects inappropriate PLK activity. Together, our data support a model in which the nucleoplasmic HAL-2/HAL-3 protein complex constrains both localization and activity of meiotic Polo-like kinases, thereby preventing premature interaction with stage-inappropriate targets.
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http://dx.doi.org/10.1534/genetics.119.302479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727811PMC
September 2019

The Stroke Stigma Scale: a reliable and valid stigma measure in patients with stroke.

Clin Rehabil 2019 Nov 16;33(11):1800-1809. Epub 2019 Jul 16.

Department of Nursing, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Objective: The objective of the study is to analyse the psychometric properties of the Stroke Stigma Scale, a novel scale to assess perceived stigma of patients with stroke.

Design: This is a psychometric study.

Setting: Neurology or rehabilitation units in three hospitals in China.

Subjects: A total of 288 patients with stroke.

Interventions: None.

Measures: The content validity of the Stroke Stigma Scale was assessed through expert consultation. Criterion validity was evaluated based on the scale's relationships with the Stigma Scale for Chronic Illness and the Self-rating Depression Scale. Construct validity was assessed using exploratory factor analysis, and internal consistency was tested with Cronbach's .

Results: The final version Stroke Stigma Scale consists of 16 items. It showed strong positive correlations with both the Stigma Scale for Chronic Illness ( = 0.89,  < 0.001) and the Self-rating Depression Scale ( = 0.82,  < 0.001). The exploratory factor analysis revealed four components of the Stroke Stigma Scale: internalized stigma, physical impairment, discrimination experience, and social isolation, which were strongly associated with our perceived stroke stigma model. Cronbach's for the total scale was 0.92, and that of each subscale was 0.77-0.86. The test-retest reliability with intra-class correlation coefficients of the total scale was 0.92 ( < 0.001), and intra-class correlation coefficients of each subscale were 0.74-0.89 ( < 0.001).

Conclusions: The Stroke Stigma Scale is a reliable and valid measure of perceived stigma in patients with stroke, which may be useful in stigma prevention and stroke rehabilitation.
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http://dx.doi.org/10.1177/0269215519862329DOI Listing
November 2019