Publications by authors named "Zhan Shi"

273 Publications

"Fishing net" suture augmenting tension-band wiring fixation in the treatment of inferior pole fracture of the patella.

Arch Orthop Trauma Surg 2021 Aug 3. Epub 2021 Aug 3.

Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China.

Introduction: Inferior pole fracture of the patella (IPFP) is difficult to repair and stabilize clinically. Although various fixation techniques have been developed, fixation strength and mobility remain daunting challenges to orthopedic surgeons. The goal of this research is to evaluate the biomechanical strength and clinical outcomes of a novel "fishing net" suture fixation procedure.

Materials And Methods: Four finite element models, modified tension-band wiring fixation, anchor suture fixation, basket plate fixation and "fishing net" suture fixation were built to compare the fixing efficacy of "fishing net" suture fixation with three other fixation methods during IPFP fixation. From January 2018 to February 2019, 17 patients who suffered IPFP and treated by "fishing net" suture (FNS) fixation were compared with 20 patients treated by tension-band wiring (TBW) fixation in database and the two groups were evaluated postoperatively using the modified Cincinnati knee rating system.

Results: Biomechanical evaluation showed that the relative displacement values of proximal patella measured by three pairs of points on both sides of the fracture line were the lowest using the "fishing net" suture fixation, while fixation using tension-band wiring and basket plate showed similar levels of stability that were less desirable than the "fishing net" method. As to clinical outcomes, there were 17 (100%) patients exhibited excellent or good results with no internal fixation failures in the FNS group compared to three internal fixation failures in the TBW group.

Conclusion: The biomechanical and clinical results suggest that the "fishing net" suture fixation is a viable candidate for fixation of IPFP.
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http://dx.doi.org/10.1007/s00402-021-04089-3DOI Listing
August 2021

Enhanced interfragmentary stability and improved clinical prognosis with use of the off-axis screw technique to treat vertical femoral neck fractures in nongeriatric patients.

J Orthop Surg Res 2021 Jul 31;16(1):473. Epub 2021 Jul 31.

Department of Orthopedic Surgery and Orthopedic Biomechanical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China.

Background: The optimal internal fixation strategy for vertical femoral neck fractures (VFNFs) in nongeriatric patients remains uncertain. Therefore, the purpose of this study was to compare the clinical prognoses and underlying mechanical characteristics of a novel off-axis screw technique with dynamic hip screws (DHSs) and three traditional parallel screws.

Methods: This study included a clinical investigation and a patient-specific finite element analysis (FEA). In the clinical investigation, VFNF patients were grouped by fixation type: (1) use of three parallel screws (G-TRI); (2) augmentation with an off-axis screw (G-ALP); and (3) DHS with an anti-rotational screw (G-DHS). Fixation failures (nonunion, femoral neck shortening (FNS), varus deformation, screw cut-out) and avascular necrosis (AVN) consequent to the three types of fixations were compared. In the FEA, twenty-four fixation models with the three fixation types were created based on the data of eight healthy volunteers. Models were assessed under walking conditions. Stiffness, interfragmentary motion (IFM), and implant stress were evaluated.

Results: In the clinical investigation, the fixation failure rate was significantly (p < 0.05) lower in G-ALP (18.5%) than in G-DHS (37.5%) and G-TRI (39.3%). No significant difference in AVN was observed among the three fixation groups. In the FEA, stiffness and implant stress in the G-DHS models were significantly (p < 0.05) higher, and the IFM of G-ALP was significantly (p < 0.05) lower among the groups.

Conclusions: Among fixation types for VFNFs, the off-axis screw technique exhibited better interfragmentary stability (lowest IFM) and a lower fixation failure rate (especially FNS). Analyzing interfragmentary stability in biomechanical experiments is more consistent with clinical prognosis than construct stability for VFNFs, suggesting that internal fixations should aim for this outcome.
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http://dx.doi.org/10.1186/s13018-021-02619-8DOI Listing
July 2021

Effect of the Hypoxia Inducible Factor on Sorafenib Resistance of Hepatocellular Carcinoma.

Front Oncol 2021 7;11:641522. Epub 2021 Jul 7.

The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, China.

Sorafenib a multi-target tyrosine kinase inhibitor, is the first-line drug for treating advanced hepatocellular carcinoma (HCC). Mechanistically, it suppresses tumor angiogenesis, cell proliferation and promotes apoptosis. Although sorafenib effectively prolongs median survival rates of patients with advanced HCC, its efficacy is limited by drug resistance in some patients. In HCC, this resistance is attributed to multiple complex mechanisms. Previous clinical data has shown that HIFs expression is a predictor of poor prognosis, with further evidence demonstrating that a combination of sorafenib and HIFs-targeted therapy or HIFs inhibitors can overcome HCC sorafenib resistance. Here, we describe the molecular mechanism underlying sorafenib resistance in HCC patients, and highlight the impact of hypoxia microenvironment on sorafenib resistance.
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http://dx.doi.org/10.3389/fonc.2021.641522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292964PMC
July 2021

[Effect of high-flow nasal cannula oxygen on patients with chronic obstructive pulmonary disease and mild hypercapnia: a retrospective cohort study based on the Medical Information Mart for Intensive Care-IV database].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jun;33(6):686-691

Department of Medical ICU, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China. Corresponding author: Du Bin, Email:

Objective: To observe the effect of high-flow nasal cannula oxygen therapy (HFNC) in patients with chronic obstructive pulmonary disease (COPD) and mild hypercapnia, and to evaluate the early predictive ability of physiological parameters in these patients.

Methods: A retrospective cohort study was conducted based on Medical Information Mart for Intensive Care-IV (MIMIC-IV) updated in September 2020 and the data of adult patients with COPD and mild hypercapnia [45 mmHg (1 mmHg = 0.133 kPa) < arterial partial pressure of carbon dioxide (PaCO) ≤ 60 mmHg] from 2008 to 2019 were collected. These patients were assigned to the HFNC group or non-invasive ventilation (NIV) group according to whether they received HFNC or NIV. Baseline data such as gender, age, body mass index (BMI), simplified acute physiology score II (SAPS II), Charlson comorbidity index (CCI) and physiological parameters were collected. A propensity score matching was conducted according to the baseline data of the HFNC group patients. The 48-hour and 28-day intubation rates, 28-day mortality, length of intensive care unit (ICU) stay, the length of hospital stay, and the changes in physiological parameters within 48 hours after treatment were compared between the two groups. The receiver operating characteristic curve (ROC curve) was drawn and the ratio of heart rate over pulse oxygen saturation (HR/SpO) and ROX index [SpO/(inhaled oxygen concentration, FiO×respiratory rate, RR)] were analyzed to predict the 24-hour and 48-hour intubation rates.

Results: A total of 524 520 inpatient records were screened and 153 patients were included, while 37 patients in the HFNC group and 116 patients in NIV group. There were 31 patients in the HFNC group and 84 patients in the NIV group remained after propensity score matching according to the baseline data. There were no significant differences in the baseline data of gender, age, BMI, SAPS II, CCI score, physiological parameters and prognosis data except the length of ICU stay. The length of ICU stay in HFNC group was significant longer than that of the NIV group [days: 4.6 (3.1, 10.0) vs. 3.1 (1.6, 5.8), P < 0.05]. HR and RR at 40-48 hours were significantly lower than those at 0-8 hours after treatment only in the HFNC group [HR (bpm): 84.1±12.2 vs. 91.1±16.4, RR (times/min): 19.8±4.9 vs. 21.6±4.1, both P < 0.05]. Both in the HFNC group and NIV group the pH increased (7.42±0.08 vs. 7.36±0.05 and 7.41±0.06 vs. 7.36±0.05, both P < 0.05) and PaCO decreased significantly [mmHg: 46.3 (39.5, 51.0) vs. 49.8 (45.5, 54.0) and 46.0 (40.5, 51.5) vs. 49.5 (45.5, 55.3), both P < 0.05]. The HR, PaO were higher in the HFNC group than those in the HFNC group at 40-48 hours after treatment [HR (bpm): 91.1±15.4 vs. 84.1±12.2, PaO (mmHg): 99.5 (86.0, 132.3) vs. 85.8 (76.5, 118.0), both P < 0.05], PaO/FiO were lower in the HFNC group than that in the HFNC group at 40-48 hours after treatment [mmHg: 223.8 (216.5, 285.0) vs. 278.0 (212.3, 306.0), P < 0.05]. Both HR/SpO and ROX index at 4 hours after treatment had predictive value for 24-hour and 48-hour intubation in the HFNC group. The areas under ROC curve (AUC) of HR/SpO at 4 hours after treatment in the HFNC group were larger than those of ROX index for predicting 24-hour and 48-hour intubation (24-hour: 0.649 vs. 0.574, 48-hour: 0.692 vs. 0.581, both P < 0.01); the 95% confidence interval (95%CI) of 4 hours HR/SpO and for ROX index predicting 24 hours and 48 hours intubation were 0.497-0.780, 0.567-0.799, 0.450-0.694 and 0.454-0.716, respectively. The high sensitivity of HR/SpO and ROX index in predicting 24-hour and 48-hour intubation were 84.6%, 92.9%, 88.2% and 94.4%, respectively, and the low specificity were 52.3%, 23.7%, 54.7% and 29.6%, respectively.

Conclusions: HFNC can be used in COPD patients with mild hypercapnia, but it cannot replace NIV. The accuracy of ROX index at 4 hours after HFNC treatment in predicting intubation in COPD patients with mild hypercapnia is poor.
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http://dx.doi.org/10.3760/cma.j.cn121430-20210219-00258DOI Listing
June 2021

Long-term differences in clinical prognosis between crossed- and parallel-cannulated screw fixation in vertical femoral neck fractures of non-geriatric patients.

Injury 2021 Jul 10. Epub 2021 Jul 10.

Department of Orthopedic Surgery & Department of Orthopedic Surgery and Orthopedic Biomechanical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. Electronic address:

Background And Purpose: Vertical femoral neck fractures (VFNFs) are one of the most difficult fractures to stabilize, with high non-union (17%), avascular necrosis (AVN, 21%), and femoral neck shortening (FNS, 29.0%) rates. The objective of this investigation was to directly compare the long-term clinical complication rates of VFNFs repaired by crossed (Alpha fixation) or parallel screws in non-geriatric patients.

Patients And Methods: We conducted a retrospective comparative study of VFNFs in patients (<60 years) between January 2014 and December 2017, with at least 2 years of follow-up. VFNFs were fixed with either three parallel screws (G-TRI) or augmented with a crossed screw (G-ALP). Confounding variables included age, gender, initial displacement, ISS (Injury Severity Score), general comorbidities, combined fractures, Pauwels angle, reduction quality. Complications, including non-union, AVN of the femoral head and FNS were compared as outcome indicators. Risk factors associated with these variables were further analysed using multivariate analysis.

Results: A total of 157 patients (97 G-TRI; 60 G-ALP) met inclusion criteria. G-ALP had a significantly lower rate of FNS (8.3% vs. 28.9%, p = 0.039) than that of G-TRI. non-union (3.3% vs. 11.3%), AVN (21.7% vs. 25.8%), and reoperation rates (21.7% vs. 23.7%) were lower in G-ALP than G-TRI but was not statistically significant. Multivariate analyses showed significant relationships between NU and unacceptable reduction quality (OR=7.610; 1.823-31.770, adjusted-p = 0.015); between AVN and initial displacement (Garden III and IV) (OR=7.885; 1.739-35.744, adjusted-p = 0.021); and between FNS and screw configuration (OR=5.713; 1.839-17.743, adjusted-p = 0.009).

Conclusion: For the treatment of VFNFs, satisfactory reduction still remains the key surgical goal that prevents NU, while the incidence of AVN strongly depends on the initial displacement at the time of injury. Crossed screws were associated with a markedly lower FNS rate than parallel screws, which promote further randomised controlled trials to establish a guideline for optimal fixation selection in VFNFs.
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http://dx.doi.org/10.1016/j.injury.2021.07.014DOI Listing
July 2021

Depletion of Kruppel-like factor 15 sensitized gliomas to temozolomide cytotoxicity through -methylguanine-DNA methyl-transferase.

Biochem Biophys Rep 2021 Sep 23;27:101058. Epub 2021 Jun 23.

Department of General Internal Medicine, Linyi People's Hospital, Shandong, 276003, China.

Temozolomide (TMZ)-based chemotherapy is a standard strategy for gliomas, although chemoresistance remains a major therapeutic challenge. The chemical mechanism by which TMZ induces cell death is DNA methylation, leading to double-stranded breaks (DSBs) and thus to apoptosis. However, TMZ-induced N6-meG sites are efficiently repaired and mediated by the DNA repair protein -methylguanine-DNA methyl-transferase (MGMT), leading to TMZ resistance. KLF15, a member of the Kruppel-like factors family, mainly functions as transcription factor and potential suppressor gene by inhibiting proliferation, migration, and inducing apoptosis. However, the roles and regulatory mechanisms of KLF15 in glioma tumorigenesis and chemoresistance are poorly understood. In this study, KLF15 expression was upregulated in glioma tissues and cell lines upon TMZ treatment. Knockdown of KLF15 amplified TMZ-induced repression of cell proliferation, while KLF15 overexpression reversed this process. Mechanistically, KLF15 functioned as a transcriptional activator of MGMT. Moreover, KLF15 knockdown sensitized tumors to TMZ treatment in vivo. Taken together, these results suggested that KLF15 up-regulated MGMT through direct binding to the promoter of MGMT, which plays an important role in glioma resistance to TMZ, and which may be a potential target for cancer diagnosis and treatment.
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http://dx.doi.org/10.1016/j.bbrep.2021.101058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242961PMC
September 2021

Tumor-Associated-Macrophage-Membrane-Coated Nanoparticles for Improved Photodynamic Immunotherapy.

Nano Lett 2021 07 16;21(13):5522-5531. Epub 2021 Jun 16.

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), International Research Center for Chemistry-Medicine Joint Innovation, College of Chemistry, Jilin 130012, China.

Cell-membrane-coated nanoparticles have emerged as a promising antitumor therapeutic strategy. However, the immunologic mechanism remains elusive, and there are still crucial issues to be addressed including tumor-homing capacity, immune incompatibility, and immunogenicity. Here, we reported a tumor-associated macrophage membrane (TAMM) derived from the primary tumor with unique antigen-homing affinity capacity and immune compatibility. TAMM could deplete the CSF1 secreted by tumor cells in the tumor microenvironment (TME), blocking the interaction between TAM and cancer cells. Especially, after coating TAMM to upconversion nanoparticle with conjugated photosensitizer ([email protected]), [email protected] photodynamic immunotherapy switched the activation of macrophages from an immunosuppressive M2-like phenotype to a more inflammatory M1-like state, induced immunogenic cell death, and consequently enhanced the antitumor immunity efficiency via activation of antigen-presenting cells to stimulate the production of tumor-specific effector T cells in metastatic tumors. This TAM-membrane-based photodynamic immunotherapy approach offers a new strategy for personalized tumor therapy.
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http://dx.doi.org/10.1021/acs.nanolett.1c00818DOI Listing
July 2021

HIF-1α-activated TM4SF1-AS1 promotes the proliferation, migration, and invasion of hepatocellular carcinoma cells by enhancing TM4SF1 expression.

Biochem Biophys Res Commun 2021 Aug 10;566:80-86. Epub 2021 Jun 10.

The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China. Electronic address:

Long non-coding RNAs (lncRNAs) are essential drivers or suppressors in human hepatocellular carcinoma (HCC) by participating in controlling transcription, translation, mRNA stability, and protein degradation protein-protein interaction. TM4SF1-AS1 is recently identified as a tumor-promoting factor in lung cancer. Nevertheless, its function in HCC and related molecular mechanisms remain unknown. Here, our data indicated that either hypoxia or hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (DMOG) induced the upregulation of TM4SF1-AS1 in HCC cells. HIF-1α knockdown rather than HIF-2α silencing remarkably abrogated hypoxia-upregulated TM4SF1-AS1 expression. Furthermore, we confirmed the elevated expression of TM4SF1-AS1 in HCC tissue samples and cell lines. The silencing of TM4SF1-AS1 prominently inhibited the proliferative, migratory, and invasive abilities of HCC cells. TM4SF1-AS1 depletion significantly blocked hypoxia-enhanced Hep3B cell proliferation and mobility. Interfering TM4SF1-AS1 remarkably reduced TM4SF1 mRNA and protein levels in HCC cells. But TM4SF1-AS1 knockdown did not impact the stability of TM4SF1 mRNA. Hypoxia enhanced the expression of TM4SF1 mRNA, which was subsequently decreased by TM4SF1-AS1 knockdown in HCC cells. We confirmed the positive correlation between TM4SF1 mRNA and TM4SF1-AS1 expression in HCC specimens. Finally, TM4SF1 prominently reversed the inhibitory role of TM4SF1-AS1 depletion in Hep3B cells. In summary, hypoxia-responsive TM4SF1-AS1 was overexpressed in human HCC and contributed to the malignant behaviors of tumor cells by enhancing TM4SF1-AS1 expression.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.011DOI Listing
August 2021

CSNK2A1-mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer.

FEBS Open Bio 2021 Jun 11. Epub 2021 Jun 11.

Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

The development of chemoresistance reduces the efficacy of anti-cancer drugs. Cervical cancer is still one of the most common cancer types in developing countries. The oncogenic protein high mobility group AT-hook 2 (HMGA2) is involved in the development and progression of tumors, although its role in chemoresistance of cervical cancer remains unclear. Here, we report that HMGA2 is highly expressed in cervical cancer and negatively correlated with cisplatin-induced cell death. We performed liquid chromatography-tandem mass spectrometry to demonstrate that HMGA2 has high potential to interact with casein kinase II A1 (CSNK2A1). Moreover, we observed that HMGA2 co-localizes with CSNK2A1 in the nucleus by immunofluorescence. Binding of HMGA2-CSNK2A1 was detected by immunoprecipitation assays. In addition, we identified that cisplatin induces an interaction between CSNK2A1 and HMGA2, thereby promoting the phosphorylation of HMGA2. CX-4945, a CSNK2A1 inhibitor, could inhibit the phosphorylation of HMGA2 and sensitize tumor cells to cisplatin. Our results reveal that CSNK2A1-dependent HMGA2 phosphorylation may partially underlie cisplatin-resistance in cervical cancer, suggesting that HMGA2 phosphorylation may have potential as a predicative biomarker and therapeutic target to improve chemotherapeutic efficacy.
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http://dx.doi.org/10.1002/2211-5463.13228DOI Listing
June 2021

Relationship between multimorbidity, disease cluster and all-cause mortality among older adults: a retrospective cohort analysis.

BMC Public Health 2021 06 5;21(1):1080. Epub 2021 Jun 5.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, People's Republic of China.

Background: Previous studies have evaluated the association of multimorbidity with higher mortality, but epidemiologic data on the association between the disease clusters and all-cause mortality risk are rare. We aimed to examine the relationship between multimorbidity (number/ cluster) and all-cause mortality in Chinese older adults.

Methods: We conducted a population-based study of 50,100 Chinese participants. Multiple logistic regression analysis was used to estimate the impact of long-term conditions (LTCs) on all-cause mortality.

Results: The prevalence of multimorbidity was 31.35% and all-cause mortality was 8.01% (50,100 participants). In adjusted models, the odds ratios (ORs) and 95% confidence intervals (CIs) of all-cause mortality risk for those with 1, 2, and ≥ 3 LTCs compared with those with no LTCs was 1.45 (1.32-1.59), 1.72 (1.55-1.90), and 2.15 (1.85-2.50), respectively (P < 0.001). In the LTCs ≥2 category, the cluster of chronic diseases that included hypertension, diabetes, CHD, COPD, and stroke had the greatest impact on mortality. In the stratified model by age and sex, absolute all-cause mortality was higher among the ≥75 age group with an increasing number of LTCs. However, the relative effect size of the increasing number of LTCs on higher mortality risk was larger among those < 75 years.

Conclusions: The risk of all-cause mortality is increased with the number of multimorbidity among Chinese older adults, particularly disease clusters.
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http://dx.doi.org/10.1186/s12889-021-11108-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180153PMC
June 2021

Screening of Biological Target Molecules Related to Glucocorticoid-Induced Cataract (GIC) on the Basis of Constructing ceRNA Network.

Biochem Genet 2021 Jun 2. Epub 2021 Jun 2.

Department of Ophthalmology, The First Affiliated Hospital, Harbin Medical University, No. 23 Post Street, Nangang District, Harbin City, Heilongjiang Province, China.

Glucocorticoid-induced cataract (GIC)-associated biomarkers were screened by ceRNA network construction. The GIC samples' GSE3040 were obtained from the NCBI-GEO database. R's Limma package was used to identify differentially expressed RNAs (DERs) between the normal and GIC samples group (4- and 16-h). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis for the mRNAs in the constructed GIC lncRNA-miRNA-mRNA ceRNA regulation network was implemented. A total of 1665 and 1443 DERs were obtained in the 4- and 16-h group, respectively. At two time points, 256 overlapping DERs were identified, of which 210 (17 lncRNAs and 203 mRNAs) had significant differential expression (4 down- and 206 up-regulated). A total of 534 co-expressed ligation pairs (all up-regulated) were obtained. A ceRNA regulation network was constructed. RPS6KA5, GAB1, CCR7, CCL2, COL4A4, and PPARG were obtained and significantly enriched in the 4 KEGG signaling pathways and were featured as GIC target molecules.
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http://dx.doi.org/10.1007/s10528-021-10078-3DOI Listing
June 2021

The Effects of Mindfulness-Based Stress Reduction on Negative Self-Representations in Social Anxiety Disorder-A Randomized Wait-List Controlled Trial.

Front Psychiatry 2021 12;12:582333. Epub 2021 May 12.

School of Psychology, Shenzhen University, Shenzhen, China.

This study examines the impact of mindfulness-based stress reduction (MBSR) vs. wait list (WL) on the self-reference effect involving negative adjectives in individuals with social anxiety disorder (SAD). Eighty-five participants with SAD were randomly assigned to 12 weeks of MBSR or WL and completed an incidental SRE task that assessed treatment-related negative self-representations. Self-related negative adjectives were worse remembered in MBSR than in WL, and other-related negative adjectives were better remembered in MBSR than in WL. No differences emerged between the levels of self- and other-related processing for adjectives in MBSR. Moreover, the MBSR-related decreases in the difference in recognition memory performance between self and other conditions, that is, the treatment-related equilibrium, could predict the MBSR-related decreases in social anxiety symptoms. The selfless functioning and self-other control that can provide reasonable interpretations for these findings were discussed.
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http://dx.doi.org/10.3389/fpsyt.2021.582333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149603PMC
May 2021

Identification of Novel Carbocyclic Pyrimidine Cyclic Dinucleotide STING Agonists for Antitumor Immunotherapy Using Systemic Intravenous Route.

J Med Chem 2021 05 17;64(10):6902-6923. Epub 2021 May 17.

Stimulator of Interferon Genes (STING) plays an important role in innate immunity by inducing type I interferon production upon infection with intracellular pathogens. STING activation can promote increased T-cell activation and inflammation in the tumor microenvironment, resulting in antitumor immunity. Natural and synthetic cyclic dinucleotides (CDNs) are known to activate STING, and several synthetic CDN molecules are being investigated in the clinic using an intratumoral administration route. Here, we describe the identification of STING agonist , a cyclic dinucleotide structurally diversified from natural ligands with optimized properties for systemic intravenous (iv) administration. Our studies have shown that STING activation by leads to an acute innate immune response as measured by cytokine secretion and adaptive immune response via activation of CD8+ cytotoxic T-cells, which ultimately provides robust antitumor efficacy.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00374DOI Listing
May 2021

Benefits of Early Ambulation in Elderly Patients Undergoing Lumbar Decompression and Fusion Surgery: A Prospective Cohort Study.

Orthop Surg 2021 Jun 7;13(4):1319-1326. Epub 2021 May 7.

Department of Spine Surgery, Beijing Jishuitan Hospital, Beijing, China.

Objective: To evaluate the effects of early ambulation on elderly patients' postoperative physical functional outcomes, complications, 90-day readmission rate, and the length of postoperative hospital stay.

Methods: This is a prospective cohort study conducted between June 2019 and December 2019. The study enrolled 86 elderly patients (39 males) with newly diagnosed lumbar degenerative disease undergoing single-segment decompression and fusion surgerywere enrolled. Of all 86 patients, 39 voluntarily joined the early ambulation group, and 47 joined the regular ambulation group. The early ambulation group included patients ambulated within 4 h postoperatively, whereas the regular ambulation group included patients who were ambulatory at a minimum of 24 h after surgery. Participants' baseline characteristics, surgical information, ambulation ability, degree of pain, functional scores, postoperative complications, 90-day readmission rate, and length of postoperative hospital stay were recorded.

Results: Participants' baseline demographic characteristics were balanced between the early ambulation group and the regular ambulation group. The operative time and blood loss were similar between groups. The time before the first-time ambulation was 4 ± 0.5 h in the early ambulation group and 28 ± 4.5 h in the regular ambulation group. Ambulating distance was significantly longer in the early ambulation group compared with the regular ambulation group on the 1st (63 ± 45 vs 23 ± 60 m), the 2nd (224 ± 100 vs 101 ± 130 m), and the 3rd (280 ± 102.5 vs 190 ± 170 m) ambulation days based on generalized estimating equation analyses. Generalized estimating equation analyses also demonstrated that the ambulating time was longer in the early ambulation group compared with the regular ambulation group on the 1st (10 ± 5 vs 10 ± 5 min), the 2nd (19 ± 7 vs 15 ± 5 min), and the 3rd (22 ± 16.5 vs 27 ± 12 min) ambulation days. Patients in the regular ambulation group experienced a higher degree of pain than the early ambulation group patients, with an odds ratio of 1.627 (P = 0.002). Short-term functional independence was superior in the early ambulation group, with a lower Roland-Morris disability questionnaire score (P = 0.008) and Oswestry disability index (P < 0.001). The incidences of postoperative urinary retention (early ambulation group: 7.7%, regular ambulation group: 25.5%, P = 0.030) and ileus (early ambulation group: 0%, regular ambulation group: 12.8%, P = 0.030) were significantly higher in the regular ambulation group. The prevalence of at least one complication rate was significantly lower in the early ambulation group than in the regular ambulation group (early ambulation group, 23.1%; regular ambulation group, 46.8%, P = 0.022). The duration of indwelling of the drainage catheter was shorter in the early ambulation group (early ambulation group, 68 ± 24 h; regular ambulation group, 78 ± 20 h, P = 0.001), and the length of the postoperative hospital stay was also shorter in the early ambulation group (early ambulation group, 4 ± 0 days; regular ambulation group: 5 ± 2 days, P < 0.001). However, there was no statistical difference in the 90-day readmission rate between groups.

Conclusion: Early ambulation improved patients' postoperative functional status, decreased the incidence of complications, and shortened postoperative hospital stay in elderly patients undergoing lumbar decompression and fusion surgery.
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http://dx.doi.org/10.1111/os.12953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274205PMC
June 2021

LINC00518 Promotes Cell Proliferation by Regulating the Cell Cycle of Lung Adenocarcinoma Through miR-185-3p Targeting MECP2.

Front Oncol 2021 15;11:646559. Epub 2021 Apr 15.

Department of Thoracic and Cardiovascular Surgery, The Sixth Affiliated Hospital of Nantong University, Yancheng, China.

Previous studies have shown that long intergenic non-protein coding RNA 00518 (LINC00518) are essential for the cell growth and metastasis of human cancer. However, the role of LINC00518 in lung adenocarcinoma (LUAD) is still unknown. This research put emphasis on the function of LINC00518 on the cell growth of LUAD. The lncRNA, miRNA and mRNA expression were measured by using qRT-PCR. Protein levels were measured by using Western blotting. CCK-8, colony formation assays and transwell assay were performed to evaluate the cell proliferation ability and invasion. Bioinformatic analysis and luciferase reporter assays were chosen to confirm the mechanism of LINC00518 in LUAD. We found that LINC00518 was highly expressed in LUAD specimens and the high-expression was negatively correlated with the overall survival rates. This finding was also proved in the LUAD cell lines. Through a series of experiments, we proved that LICN00518 promoted the cell growth of LUAD by regulating the cell cycle. Moreover, LICN00518 upregulated the expression of MECP2 by mutagenesis of miR-185-3p. The results suggested that LICN00518 could be used as a survival indicator and potential therapeutic target for LUAD patients.
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http://dx.doi.org/10.3389/fonc.2021.646559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081883PMC
April 2021

Highly Active Heterogeneous Catalyst for Ethylene Dimerization Prepared by Selectively Doping Ni on the Surface of a Zeolitic Imidazolate Framework.

J Am Chem Soc 2021 May 28;143(18):7144-7153. Epub 2021 Apr 28.

Advanced Membranes and Porous Materials Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.

The production of 1-butene by ethylene dimerization is an important chemical industrial process currently implemented using homogeneous catalysts. Here, we describe a highly active heterogeneous catalyst (Ni-ZIF-8) for ethylene dimerization, which consists of isolating Ni-active sites selectively located on the crystal surface of a zeolitic imidazolate framework. Ni-ZIF-8 can be easily prepared by a simple one-pot synthesis method in which site-specific anchoring of Ni is achieved spontaneously because of the incompatibility between the d electronic configuration of Ni and the three-dimensional framework of ZIF-8. The full exposure and square-planar coordination of the Ni sites accounts for the high catalytic activity of Ni-ZIF-8. It exhibits an average ethylene turnover frequency greater than 1 000 000 h (1-butene selectivity >85%) at 35 °C and 50 bar, far exceeding the activities of previously reported heterogeneous catalysts and many homogeneous catalysts under similar conditions. Moreover, compared to molecular Ni complexes used as homogeneous catalysts for ethylene dimerization, Ni-ZIF-8 has significantly higher stability and shows constant activity during 4 h of continuous reaction. Isotopic labeling experiments indicate that ethylene dimerization over Ni-ZIF-8 follows the Cossee-Arlman mechanism, and detailed characterizations combined with density functional theory calculations rationalize this observed high activity.
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http://dx.doi.org/10.1021/jacs.1c02272DOI Listing
May 2021

Association of changes in waist circumference with cardiovascular disease and all-cause mortality among the elderly Chinese population: a retrospective cohort study.

J Geriatr Cardiol 2021 Mar;18(3):185-195

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.

Background: To examine the association of baseline waist circumference (WC) and changes in WC with cardiovascular disease (CVD) and all-cause mortality among elderly people.

Methods: A total of 30,041 eligible participants were included from a retrospective cohort in China. The same questionnaire, anthropometric and laboratory measurements were performed at baseline (2010) and the first follow-up (2013). The percent change in WC between baseline and the first follow-up was calculated to evaluate three years change of WC. We collected the occurrence of CVD and all-cause death from the first follow-up to December 31, 2018. Restricted cubic splines and Cox proportional-hazards regression models were used to evaluate the relationship between baseline WC/ changes in WC and mortality.

Results: The dose-response relationships between baseline WC and CVD mortality were U- or J-shaped. In low WC group, compared with stable group, the fully adjusted hazard ratio (aHR) for CVD mortality was 1.60 (95% CI: 1.24-2.06) in WC gain group among men. In normal WC group, the CVD mortality risk increased with WC gain (men: aHR = 1.86, 95% CI: 1.36-2.56; women: aHR = 1.83, 95% CI: 1.29-2.58). In moderate-high WC group, the CVD mortality risk increased with WC gain (men: aHR = 1.76, 95% CI: 1.08-2.88; women: aHR = 1.46, 95% CI: 1.04-2.05) and risk decreased with WC loss (men: aHR = 0.54, 95% CI: 0.30-0.98; women: aHR = 0.59, 95% CI: 0.37-0.96).

Conclusions: For the elderly population, WC gain may increase CVD mortality risk regardless of baseline WC, whereas WC reduction could decrease the risk only in the moderate-high WC group.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2021.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047181PMC
March 2021

Finite element analysis of biomechanical effects of residual varus/valgus malunion after femoral fracture on knee joint.

Int Orthop 2021 07 20;45(7):1827-1835. Epub 2021 Apr 20.

Trauma Emergency Center, the Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang, 050051, People's Republic of China.

Objective: Post-operative femoral shaft fractures are often accompanied by a residual varus/valgus deformity, which can result in osteoarthritis in severe cases. The purpose of this study was to investigate the biomechanical effects of residual varus/valgus deformities after middle and lower femoral fracture on the stress distribution and contact area of knee joint.

Methods: Thin-slice CT scanning of lower extremities and MRI imaging of knee joints were obtained from a healthy adult male to establish normal lower limb model (neutral position). Then, the models of 3°, 5°, and 10° of varus/valgus were established respectively by modifying middle and lower femur of normal model. To validate the modifying, a patient-specific model, whose BMI was same to former and had 10° of varus deformity of tibia, was built and simulated under the same boundary conditions.

Result: The contact area and maximum stress of modified models were similar to those of patient-specific model. The contact area and maximum stress of medial tibial cartilage in normal neutral position were 244.36 mm and 0.64 MPa, while those of lateral were 196.25 mm and 0.76 MPa. From 10° of valgus neutral position to 10° of varus, the contact area and maximum stress of medial tibial cartilage increased, and the lateral gradually decreased. The contact area and maximum stress of medial meniscus in normal neutral position were 110.91 mm and 3.24 MPa, while those of lateral were 135.83 mm and 3.45 MPa. The maximum stress of medial tibia subchondral bone in normal neutral position was 1.47 MPa, while that of lateral was 0.65 MPa. The variation trend of medial/lateral meniscus and subchondral bone was consistent with that of tibial plateau cartilage in the contact area and maximum stress.

Conclusion: This study suggested that varus/valgus deformity of femur had an obvious effect on the contact area and stress distribution of knee joint, providing biomechanical evidence and deepening understanding when performing orthopedic trauma surgery or surgical correction of the already existing varus/valgus deformity.
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http://dx.doi.org/10.1007/s00264-021-05039-9DOI Listing
July 2021

Dissipativity-Based Fault-Tolerant Control for Stochastic Switched Systems With Time-Varying Delay and Uncertainties.

IEEE Trans Cybern 2021 Apr 19;PP. Epub 2021 Apr 19.

This article investigates the fault-tolerant control problem for stochastic switched interval type-2 (IT2) fuzzy time-delayed uncertain systems based on unknown input observer synthesis, which can avoid uneasy measurement on the time derivative of output, and estimate unavailable or partially measurable states, including sensor and actuator faults accurately. First, a desired fuzzy observer is designed to ensure the observer-based dynamic error system mean-square exponentially stable with sufficient condition of a strict (ℓ,ℏ,℘)-℧-dissipative performance, which is a unified framework of passivity, and H∞ provides results with less conservativeness. Then, we concentrate on stability analyses on dissipativity-based switched IT2 fuzzy systems with stochastic perturbation through linear matrix inequalities, Lyapunov function, free-weighting matrices, and average dwell time, discussing it according to different values of disturbance. Finally, simulation examples are listed to account for availability and effectiveness of the research methodology.
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http://dx.doi.org/10.1109/TCYB.2021.3068631DOI Listing
April 2021

LncRNA MTX2-6 Suppresses Cell Proliferation by Acting as ceRNA of miR-574-5p to Accumulate SMAD4 in Esophageal Squamous Cell Carcinoma.

Front Cell Dev Biol 2021 23;9:654746. Epub 2021 Mar 23.

Department of Cardiothoracic Surgery, Yancheng Third People's Hospital, The Sixth Affiliated Hospital of Nantong University, Yancheng, China.

Esophageal squamous cell carcinoma (ESCC) has been one of the key causes of cancer deaths worldwide. It has been found that long non-coding RNA (lncRNA) is related to the generation and progression of various cancers (including ESCC). However, there are still many lncRNAs related to ESCC whose functions and molecular mechanisms have not been clearly elucidated. In this study, we first reported that lncRNA MTX2-6 was significantly downregulated in ESCC tissues and cell lines. The decreased expression of MTX2-6 is closely related to larger tumor and worse prognosis of ESCC patients. Through a series of functional experiments, we detected that overexpressed MTX2-6 inhibited cell proliferation and promoted cell apoptosis of ESCC and . Further studies showed that MTX2-6 exerts as a competing endogenous RNA (ceRNA) by binding miR-574-5p and elevates the expression of SMAD4 in ESCC. In summary, our results clarify the tumor suppressor roles of MTX2-6/miR-574-5p/SMAD4 axis in the progression of ESCC and provide emerging therapeutic targets for ESCC patients.
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http://dx.doi.org/10.3389/fcell.2021.654746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044847PMC
March 2021

Luminescence and Energy Transfer of Color-Tunable YMgAlSiO:Eu,Ce Phosphors.

Inorg Chem 2021 Apr 3;60(8):5908-5916. Epub 2021 Apr 3.

College of Chemistry, Jilin University, Qianjin Street 2699, Changchun 130012, China.

Color-tunable phosphors can be obtained through codoping strategies and energy transfer regulation. Ce and Eu are the most common and effective activator ions used in phosphor materials. However, the energy transfer from Eu to Ce is rarely reported. In this work, YMgAlSiO(YMAS):Eu,Ce phosphors were successfully synthesized, which was confirmed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Rietveld refinement, scanning electron microscopy (SEM) and element mapping images, and spectral information. The luminescent color of YMAS:Eu,Ce phosphors could be tuned from blue to cyan to light green to yellow-green and finally to green-yellow, which was achieved by adjusting the energy transfer between different dopants. The energy transfer from Eu to Ce was confirmed by photoluminescence spectra and fluorescence decay curves. Within the experimental gradient, the energy transfer efficiency could reach up to 48%. At 373 K, the YMgAlSiO:0.01Eu,0.01Ce (YMAS:0.01Eu,0.01Ce) phosphor exhibited a total integral emission loss of only 8%, and the emission peak intensity decreased to 95%, indicating the excellent thermal stability. The white light-emitting diode (WLED) fabricated by the YMAS:0.01Eu,0.01Ce phosphor has the same level correlated color temperature (CCT = 5841 K), greatly improved color rendering index ( = 87.8), and higher quality white light color (CIE = (0.3258, 0.3214)) than the WLED made by the YMAS:0.01Eu phosphor, indicating that the performance of the phosphor was significantly improved by introducing Ce. This work provides an effective guide for the design and development of highly efficient color-tunable phosphors involving energy transfer from Eu to Ce in some specific materials, such as garnet structures.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00317DOI Listing
April 2021

Single-Cell Sequencing Confirms Transcripts and VDJ Rearrangements of Immunoglobulin Genes in Human Podocytes.

Genes (Basel) 2021 03 25;12(4). Epub 2021 Mar 25.

Department of Nephrology, Peking University Third Hospital, Beijing 100191, China.

Most glomerular diseases are associated with inflammation caused by deposited pathogenic immunoglobulins (Igs), which are believed to be produced by B cells. However, our previous study indicated that the human podocyte cell line can produce IgG. In this study, we aimed to confirm the transcripts and characterize the repertoires of Igs in primary podocytes at single cell level. First, single-cell RNA sequencing of cell suspensions from "normal" kidney cortexes by a 10xGenomics Chromium system detected Ig transcripts in 7/360 podocytes and Ig gene segments in 106/360 podocytes. Then, we combined nested PCR with Sanger sequencing to detect the transcripts and characterize the repertoires of Igs in 48 single podocytes and found that five classes of Ig heavy chains were amplified in podocytes. Four-hundred and twenty-nine VDJ rearrangement sequences were analyzed; podocyte-derived Igs exhibited classic VDJ rearrangements with nucleotide additions and somatic hypermutations, biased VH1 usage and restricted diversity. Moreover, compared with the podocytes from healthy control that usually expressed one class of Ig and one VDJ pattern, podocytes from patients expressed more classes of Ig, VDJ patterns and somatic hypermutations. These findings suggested that podocytes can express Igs in normal condition and increase diversity in pathological situations.
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http://dx.doi.org/10.3390/genes12040472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064494PMC
March 2021

Self-Reference Effect Induced by Self-Cues Presented During Retrieval.

Front Psychol 2021 16;12:562359. Epub 2021 Mar 16.

School of Psychology, Shenzhen University, Shenzhen, China.

The self-reference effect (SRE) refers to better memory for self-relevant than for other-relevant information. Generally, the SRE is found in conditions in which links between the stimuli and the self are forged in the encoding phase. To investigate the possibility that such conditions are not prerequisites for the SRE, this research developed two conditions by using two recognition tasks involving abstract geometric shapes (AGSs). One was the cue-in-encoding condition in which self- and other-cues were presented to construct links with AGSs during the encoding phase, and the other was the cue-in-retrieval condition in which self- and other-cues were presented to construct links with AGSs during the retrieval phase. The SRE was found in both conditions. The findings reveal that self-cues merely presented during the retrieval phase are sufficient to induce the SRE. Links between the stimuli and the self constructed during the encoding phase may not be necessary prerequisites for the SRE.
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http://dx.doi.org/10.3389/fpsyg.2021.562359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007774PMC
March 2021

Expression of immunoglobulin G in human proximal tubular epithelial cells.

Mol Med Rep 2021 05 24;23(5). Epub 2021 Mar 24.

Department of Nephrology, Peking University Third Hospital, Beijing 100191, P.R. China.

Proximal tubular epithelial cells (PTECs) have innate immune characteristics, and produce proinflammatory factors, chemokines and complement components that drive epithelial‑mesenchymal transition (EMT). Our previous studies revealed that human mesangial cells and podocytes were able to synthesize and secrete immunoglobulin (Ig)A and IgG, respectively. The aim of the present study was to evaluate the expression of Igs in PTECs. Firstly, IgG was detected in the cytoplasm, the cell membrane and the lumen of PTECs in the normal renal cortex by immunohistochemistry. Secondly, Igγ gene transcription and V(D)J recombination were detected in single PTECs by nested PCR and Sanger sequencing. Thirdly, Igγ, Igκ and Igλ were clearly detected in an immortalized PTEC line (HK‑2) by immunostaining and western blotting, in which RP215 (an antibody that predominantly binds to non‑B cell‑derived IgG) was used. In addition, Igγ, Igκ and Igλ gene transcripts, conservative V(D)J recombination in the Igγ variable region, recombination activating gene 1/2 and activation‑induced cytidine deaminase were all detected in HK‑2 cells. These data suggested that PTECs may express IgG in a similar manner to B cells. Furthermore, IgG expression was upregulated by TGF‑β1 and may be involved in EMT.
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http://dx.doi.org/10.3892/mmr.2021.11966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974459PMC
May 2021

Identification of a Prognostic Signature Model with Tumor Microenvironment for predicting Disease-free Survival after Radical Prostatectomy.

J Cancer 2021 22;12(8):2371-2384. Epub 2021 Feb 22.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

The tumor microenvironment (TME) and immune checkpoint inhibitors have been shown to promote active immune responses through different mechanisms. We attempted to identify the important prognostic genes and prognostic characteristics related to TME in prostate cancer (PCa). The gene transcriptome profiles and clinical information of PCa patients were obtained from The Cancer Genome Atlas (TCGA) database, and the immune and stromal scores were calculated by the ESTIMATE algorithm. We evaluated the prognostic value of the risk score (RS) model based on univariate Cox analysis and least absolute shrinkage and selection operation (LASSO) Cox regression analysis and established a nomogram to predict disease-free survival (DFS) in PCa patients. The GSE70768 dataset was utilized for external validation. Twenty-two subsets of tumor-infiltrating immune cells were analyzed using the CIBERSORT algorithm. In this study, the patients with higher immune/stromal scores were associated with a worse DFS, higher Gleason score, and higher pathological T stage. Based on the immune and stromal scores, 515 differentially expressed genes (DEGs) were identified. The univariate Cox and LASSO Cox regression models were employed to select 18 DEGs from 515 DEGs and construct an RS model. The DFS of the high-RS group was significantly lower than that of the low-RS group (<0.001). The AUCs for the 1-year, 3-year and 5-year DFS rates in the RS model were 0.890, 0.877 and 0.841, respectively. A nomogram of DFS was established based on the RS and Gleason score, and the AUCs for the 1-year, 3-year and 5-year DFS rates in the nomogram were 0.907, 0.893, and 0.872, respectively. These results were further validated in the GSE70768 dataset. In addition, the proportion of Tregs was determined to be higher in high-RS patients (<0.05), and the expression levels of five immune checkpoints (CTLA-4, PD-1, LAG-3, TIM-3 and TIGIT) were observed to be higher in high-RS patients (<0.05). Our study established and validated an 18-gene prognostic signature model associated with TME, which might serve as a prognosis stratification tool to predict DFS in PCa patients after radical prostatectomy.
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http://dx.doi.org/10.7150/jca.51173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974886PMC
February 2021

Radiomic model for differentiating parotid pleomorphic adenoma from parotid adenolymphoma based on MRI images.

BMC Med Imaging 2021 Mar 20;21(1):54. Epub 2021 Mar 20.

The Department of Radiology, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.

Background: Distinguishing parotid pleomorphic adenoma (PPA) from parotid adenolymphoma (PA) is important for precision treatment, but there is a lack of readily available diagnostic methods. In this study, we aimed to explore the diagnostic value of radiomic signatures based on magnetic resonance imaging (MRI) for PPA and PA.

Methods: The clinical characteristic and imaging data were retrospectively collected from 252 cases (126 cases in the training cohort and 76 patients in the validation cohort) in this study. Radiomic features were extracted from MRI scans, including T1-weighted imaging (T1WI) sequences and T2-weighted imaging (T2WI) sequences. The radiomic features from three sequences (T1WI, T2WI and T1WI combined with T2WI) were selected using univariate analysis, LASSO correlation and Spearman correlation. Then, we built six quantitative radiomic models using the selected features through two machine learning methods (multivariable logistic regression, MLR, and support vector machine, SVM). The performances of the six radiomic models were assessed and the diagnostic efficacies of the ideal T1-2WI radiomic model and the clinical model were compared.

Results: The T1-2WI radiomic model using MLR showed optimal discriminatory ability (accuracy = 0.87 and 0.86, F-1 score = 0.88 and 0.86, sensitivity = 0.90 and 0.88, specificity = 0.82 and 0.80, positive predictive value = 0.86 and 0.84, negative predictive value = 0.86 and 0.84 in the training and validation cohorts, respectively) and its calibration was observed to be good (p > 0.05). The area under the curve (AUC) of the T1-2WI radiomic model was significantly better than that of the clinical model for both the training (0.95 vs. 0.67, p < 0.001) and validation (0.90 vs. 0.68, p = 0.001) cohorts.

Conclusions: The T1-2WI radiomic model in our study is complementary to the current knowledge of differential diagnosis for PPA and PA.
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http://dx.doi.org/10.1186/s12880-021-00581-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981906PMC
March 2021

Small extracellular vesicles with LncRNA H19 "overload": YAP Regulation as a Tendon Repair Therapeutic Tactic.

iScience 2021 Mar 17;24(3):102200. Epub 2021 Feb 17.

Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.

Functional healing of tendon injuries remains a great challenge. Small extracellular vesicles (sEVs) have received attention as pro-regenerative agents. H19 overexpression could bring tendon regenerative ability, but the mechanism is still not fully elucidated, and reliable method for delivery of long non-coding RNAs (LncRNAs) was demanded. We identified the downstream mechanism of H19, the activation of yes-associated protein (YAP) via the H19-PP1-YAP axis. We established tendon stem/progenitor cells (TSPCs) stably overexpressing H19 with CRISPR-dCas9-based hnRNP A2/B1 activation (H19-CP-TSPCs). H19-OL-sEVs (H19 "overloading" sEVs) could be produced effectively from H19-CP-TSPCs. Only H19-OL-sEVs were able to significantly load large amounts of H19 rather than other competitors, and the potential of H19-OL-sEVs to promote tendon healing was far better than that of other competitors. Our study established a relatively reliable method for enrichment of LncRNAs into sEVs, providing new hints for modularized sEV-based therapies, and modularized sEVs represented a potential strategy for tendon regeneration.
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http://dx.doi.org/10.1016/j.isci.2021.102200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937563PMC
March 2021

Upregulated hsa_circ_0000129 expression promotes proliferation and migration of breast cancer cells.

Oncol Lett 2021 Apr 28;21(4):239. Epub 2021 Jan 28.

Department of Traditional Chinese Medicine, Huadong Hospital, Fudan University, Shanghai 200040, P.R. China.

Circular RNAs (circRNAs) are considered potential biomarkers in the pathogenesis and detection of several types of cancer. The present study aimed to investigate the role of hsa_circ_0000129 in the pathogenesis and molecular mechanism underlying breast cancer. A total of 68 pairs of breast cancer and corresponding paracancerous tissue samples, three different breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) and a normal human breast cell line (MCF-10A) were used to investigate the expression of hsa_circ_0000129. The effect of hsa_circ_0000129 on cell proliferation, migration and colony formation was assessed in MCF-7 and MDA-MB-468 cells, along with the expression of enhancer of zeste homolog 2 (EZH2). The results demonstrated that hsa_circ_0000129 expression was significantly higher in breast cancer tissues compared with normal tissues. In addition, high hsa_circ_0000129 expression was significantly associated with lymph node metastasis and a higher tumor-node-metastasis stage. Comparisons between the breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) and MCF-10A cells indicated similar results. MCF-7 cells overexpressed with hsa_circ_0000129 significantly increased cell proliferation, migration and colony formation compared with the negative control group, the effects of which were reversed following hsa_circ_0000129 knockdown in MDA-MB-468 cells. Furthermore, EZH2 expression was positively associated with hsa_circ_0000129 expression. Taken together, the results of the present study suggest that hsa_circ_0000129 may represent a promising prognostic biomarker for breast cancer. In addition, the role of hsa_circ_0000129 in breast cancer cell lines indicates a mechanism for tumorigenesis, as well as a potent target for the treatment of malignant progression.
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http://dx.doi.org/10.3892/ol.2021.12500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882879PMC
April 2021

Biomechanical evaluation of different types of lateral hinge fractures in medial opening wedge high tibial osteotomy.

Clin Biomech (Bristol, Avon) 2021 Mar 21;83:105295. Epub 2021 Feb 21.

Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China. Electronic address:

Background: Lateral hinge fractures are common complications in the medial opening wedge high tibial osteotomy for treatment of knee osteoarthritis. The rehabilitation protocols are decided depending on the remaining stability following these fractures. This study aimed to evaluate the biomechanical properties of different types of lateral hinge fractures in medial opening wedge high tibial osteotomy.

Methods: Twenty synthetic tibia models were used as test samples. A 10-mm bone wedge was removed from the medial side of the proximal tibias to create the bone defect. The samples were then divided into 4 groups: (1) intact lateral hinge; (2) Takeuchi type I fractures; (3) type II fractures; and (4) type III fractures. After fixation with a locking plate, the stability parameters including construct stiffness, wedge displacement, and construct strength were tested under compressive forces and compared among the 4 groups.

Findings: No statistical difference was found in the construct stiffness among the 4 groups (P = 0.78). The type III fractures had the largest wedge displacement compared with the other 3 groups. The failure loads on average were significantly reduced in the type III fractures compared with those with intact hinge (P < 0.01) and in type I fractures (P = 0.04). No statistical difference was observed between the type I fractures and the intact hinge in terms of wedge displacement or failure loads.

Interpretation: The type III fractures were the most unstable and patients with these fractures should be managed cautiously. Delayed weightbearing and/or additional fixation should be considered.
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http://dx.doi.org/10.1016/j.clinbiomech.2021.105295DOI Listing
March 2021
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