Publications by authors named "Li Cai"

844 Publications

Dual effect of IL-7/IL-7R signalling on the osteoimmunological system: a potential therapeutic target for rheumatoid arthritis.

Immunology 2021 May 1. Epub 2021 May 1.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

The IL-7/IL-7R pathway plays a vital role in the immune system, especially in the inflammatory response. Monocytes/macrophages (osteoclast precursors) have been recently recognized as important participants in the osteoclastogenesis of rheumatoid arthritis (RA) patients. Here, we aimed to investigate the therapeutic potential of IL-7/IL-7R pathway in RA and to determine whether it could restrain osteoclastogenic functions and thereby ameliorate RA. Firstly, collagen-induced arthritis (CIA) mice were administered with IL-7Rα-target antibodies to assess their therapeutic effect on arthritis. We found that blockade of the IL-7/IL-7R pathway protected CIA mice from bone destruction in addition to inducing inflammatory remission, by altering the RANKL/RANK/OPG ratio and consequently decreasing osteoclast formation. To explore the effect and mechanism of this pathway, bone marrow cells were induced to osteoclasts and treated with IL-7, a STAT5 inhibitor, or supernatants from T cells. The results showed that the IL-7/IL-7R pathway played a direct inhibitory role in osteoclast differentiation via STAT5 signalling pathway in a RANKL-induced manner. We applied flow cytometry to analyze the effect of IL-7 on T cell RANKL expression, and found that IL-7/IL-7R pathway had an indirect role in the osteoclast differentiation process by enhancing the RANKL expression on T cells. In conclusion, the IL-7/IL-7R pathway exhibited a dual effect on osteoclastogenesis of CIA mice by interacting with osteoimmunology processes and could be a novel therapeutic target for autoimmune diseases such as RA.
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http://dx.doi.org/10.1111/imm.13351DOI Listing
May 2021

Gsx1 promotes locomotor functional recovery after spinal cord injury.

Mol Ther 2021 Apr 23. Epub 2021 Apr 23.

Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, USA. Electronic address:

Promoting residential cells, particularly endogenous neural stem and progenitor cells (NSPCs), for tissue regeneration represents a potential strategy for the treatment of spinal cord injury (SCI). However, adult NSPCs differentiate mainly into glial cells and contribute to glial scar formation at the site of injury. Gsx1 is known to regulate the generation of excitatory and inhibitory interneurons during embryonic development of the spinal cord. In this study, we show that lentivirus-mediated expression of Gsx1 increases the number of NSPCs in a mouse model of lateral hemisection SCI during the acute stage. Subsequently, Gsx1 expression increases the generation of glutamatergic and cholinergic interneurons and decreases the generation of GABAergic interneurons in the chronic stage of SCI. Importantly, Gsx1 reduces reactive astrogliosis and glial scar formation, promotes serotonin (5-HT) neuronal activity, and improves the locomotor function of the injured mice. Moreover, RNA sequencing (RNA-seq) analysis reveals that Gsx1-induced transcriptome regulation correlates with NSPC signaling, NSPC activation, neuronal differentiation, and inhibition of astrogliosis and scar formation. Collectively, our study provides molecular insights for Gsx1-mediated functional recovery and identifies the potential of Gsx1 gene therapy for injuries in the spinal cord and possibly other parts of the central nervous system.
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http://dx.doi.org/10.1016/j.ymthe.2021.04.027DOI Listing
April 2021

Selective hydrogenation of acetylene on Cu-Pd intermetallic compounds and Pd atoms substituted Cu(111) surfaces.

Phys Chem Chem Phys 2021 Apr 29;23(14):8653-8660. Epub 2021 Mar 29.

Hunan University, College of Materials Science and Engineering, Changsha 410082, China.

The selective hydrogenation of acetylene was studied on the ordered Cu-Pd intermetallic compounds (L1-type CuPd, L1-type CuPd, and L1-type CuPd) and Pd-modified Cu(111) surfaces through first-principles calculations. The catalytic selectivity and activity of Cu-Pd alloy catalysts are closely related to the crystal structure and composition of Cu-Pd intermetallic compounds and the size of Pd ensembles of Cu-based dilute alloy surface for the selective hydrogenation of acetylene to ethylene. Significantly, we found that the ordered Cu-Pd alloy surface containing isolated Pd atoms (i.e., L1-type CuPd(111) surface) is highly efficient for the selective hydrogenation reaction of CH + H→ CH. The contiguous Pd atom ensembles (Pd dimer and trimer) are catalytically active towards CH + H → CH and CH + H → CH reactions than the single Pd atom on a Pd-decorated Cu(111) surface. However, the small Pd ensembles on Cu(111) present a low chemical activity for H dissociation compared with the ordered Cu-Pd intermetallic compounds. Our theoretical results provide a strategy of crystal phase and composition control for enhancing the selectivity and activity of Cu-Pd catalysts towards acetylene selective hydrogenation.
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http://dx.doi.org/10.1039/d0cp05285jDOI Listing
April 2021

The decomposition of macrozoobenthos induces large releases of phosphorus from sediments.

Environ Pollut 2021 Apr 10;283:117104. Epub 2021 Apr 10.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, 210008, China.

Lake eutrophication and algal blooms may result in the mortality of macrozoobenthos. However, it is still not clear how macrozoobenthos decomposition affect phosphorus (P) mobility in sediments. High-resolution dialysis (HR-Peeper) and the diffusive gradients in thin films (DGT) technique were used in this study to assess the dissolved organic matter (DOM), dissolved/DGT-labile iron (Fe), P, and sulfur (S(-II)) profiles at a millimeter resolution. The decomposition of Bellamya aeruginosa significantly increased the internal loading of sediments P. The Fe(III) and sulfate were reduced under anaerobic conditions and promoted P desorption from sediments. This was supported by the significant increase in DGT-labile S(-II) and dissolved/DGT-labile P, Fe(II) and the significant positive correlation between Fe and P on day 8. The simultaneous increase in DOM and soluble reactive phosphorus (SRP) and the significant positive relationship between these factors were observed during the decomposition of B. aeruginosa. This suggested that complexation of DOM with metals may promotes the release of P from sediments.
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http://dx.doi.org/10.1016/j.envpol.2021.117104DOI Listing
April 2021

MicroRNA-26b-5p Targets DAPK1 to Reduce Intestinal Ischemia/Reperfusion Injury via Inhibition of Intestinal Mucosal Cell Apoptosis.

Dig Dis Sci 2021 Apr 10. Epub 2021 Apr 10.

Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Background: Emerging evidence has suggested that miRNAs are important regulators of intestinal I/R injury, but their function in this context remains elusive.

Aims: To evaluate the role of miR-26b-5p in intestinal I/R injury.

Methods: We utilized in vivo murine models of intestinal I/R and in vitro Mode-K cell-based models of oxygen and glucose deprivation/reperfusion (OGD/R) to examine the function of miR-26b-5p in intestinal I/R injury. The expression of miR-26b-5p in intestinal mucosa and Mode-K cell was detected by RT-PCR. HE staining and Chiu's score were used to evaluate intestinal mucosa injury severity. Apoptosis was detected by TUNEL stain, flow cytometry, and western blot. TargetScan and StarBase prediction algorithms were applied to predict putative target genes of miR-26b-5p and validated by luciferase reporter analyses.

Results: We found that the expression of miR-26b-5p in intestinal mucosa was markedly decreased during I/R injury. We additionally found miR-26b-5p overexpression to markedly disrupt intestinal I/R- or OGD/R-induced injury in vivo and in vitro, whereas inhibiting this miRNA had an adverse impact and resulted in increased intestinal tissue injury and Mode-K cell damage. From a mechanistic perspective, miR-26b-5p was predicted to target DAPK1, which was related to cellular apoptosis. Luciferase reporter assay results confirmed that miR-26b-5p directly targets DAPK1 in Mode-K cells, thereby suppressing OGD/R-induced cell apoptosis.

Conclusion: Our findings show that miR-26b-5p may prevent intestinal I/R injury via targeting DAPK1 and inhibiting intestinal mucosal cell apoptosis, suggesting that this miRNA may be a viable target for the treatment of intestinal I/R injury.
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http://dx.doi.org/10.1007/s10620-021-06975-7DOI Listing
April 2021

[Pathologic tumor volume predicting survival outcomes of patients with local advanced glottic carcinoma].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Apr;35(4):316-320

Department of Otolaryngology Head and Neck Surgery,Eye & ENT Hospital of Fudan University,Shanghai,200031,China.

The aim of this study was to evaluate the predicting role of tumor volume as evaluated by postoperative pathologic examination on overall survival(OS) and disease free survival(DFS) in patients with local advanced glottic carcinoma. In this study, the records of 406 consecutive patients with local advanced glottic carcinoma(T3-T4 stages) who underwent surgery ± chemoradiotherapy from January 2005 to December 2010 were retrospectively reviewed and followed up. The demographic characteristics, disease staging, and pathologic tumor volume were analyzed. The optimal cutoff values of tumor volume for OS and DFS were obtained by using receiver operating characteristic(ROC) curves. The association of tumor volume with T stages were assessed by using Logistic regression model, and the relationship between tumor volume and OS and DFS rates were evaluated by using Cox regression models. The 5-and 10-year OS rates were 62.9% and 55.4%, respectively. The 5-and 10-year DFS rates were 55.5% and 50.8%, respectively. The mean tumor volume was(5.1±6.7) cm³, T4 stage patients had higher tumor volume than those of patients with T3 stage(<0.001). The factor of tumor volume was correlated with T stages by using Logistic regression analyses(=13.81, 95%: 6.03-31.59, <0.001). The optimal cutoff values of tumor volume that were both at 3 cm³ for OS and DFS rates were obtained by using ROC curve plots. The OS and DFS rates of glottic carcinoma patients with tumor volume ≤ 3 cm³ were better when compared with those of patients with tumor volume>3 cm³(<0.001). Upon multivariate analyses, tumor volume was strongly correlated with poorer OS and DFS rates and remained independent prognostic factors for both the OS and DFS of patients with glottic carcinoma(OS: =1.59, 95%: 1.09-2.32, =0.017; DFS: =1.54, 95%: 1.08-2.20, =0.016). This study demonstrates that tumor volume is correlated with T stages, and this factor is an independent predictive factor of survival outcomes in patients with local advanced glottic carcinoma.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.04.007DOI Listing
April 2021

The gut microbiota metabolite capsiate promotes Gpx4 expression by activating to inhibit intestinal ischemia reperfusion-induced ferroptosis.

Gut Microbes 2021 Jan-Dec;13(1):1-21

Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Ferroptosis, a new type of cell death has been found to aggravate intestinal ischemia/reperfusion (I/R) injury. However, little is known about the changes of gut microbiota and metabolites in intestinal I/R and the role of gut microbiota metabolites on ferroptosis-induced intestinal I/R injury. This study aimed to establish a mouse intestinal I/R model and ileum organoid hypoxia/reoxygenation (H/R) model to explore the changes of the gut microbiota and metabolites during intestinal I/R and protective ability of capsiate (CAT) against ferroptosis-dependent intestinal I/R injury. Intestinal I/R induced disturbance of gut microbiota and significant changes in metabolites. We found that CAT is a metabolite of the gut microbiota and that CAT levels in the preoperative stool of patients undergoing cardiopulmonary bypass were negatively correlated with intestinal I/R injury. Furthermore, CAT reduced ferroptosis-dependent intestinal I/R injury in vivo and in vitro. However, the protective effects of CAT against ferroptosis-dependent intestinal I/R injury were abolished by RSL3, an inhibitor of glutathione peroxidase 4 (Gpx4), which is a negative regulator of ferroptosis. We also found that the ability of CAT to promote Gpx4 expression and inhibit ferroptosis-dependent intestinal I/R injury was abrogated by JNJ-17203212, an antagonist of transient receptor potential cation channel subfamily V member 1 (TRPV1). This study suggests that the gut microbiota metabolite CAT enhances Gpx4 expression and inhibits ferroptosis by activating TRPV1 in intestinal I/R injury, providing a potential avenue for the management of intestinal I/R injury.
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http://dx.doi.org/10.1080/19490976.2021.1902719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009132PMC
March 2021

Epidemiological features of primary breast lymphoma patients and development of a nomogram to predict survival.

Breast 2021 Jun 17;57:49-61. Epub 2021 Mar 17.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Background: Studies on the epidemiology and prognosis of primary breast lymphoma (PBL) are lack for low incidence. Therefore, we aimed to investigate the epidemiological characteristics of PBL and develop nomograms to predict patient survival.

Methods: Data of patients who were diagnosed with PBL from 1975 to 2011 and incidence rate of PBL from 1975 to 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Time-varying multivariable Cox regression analysis was performed to identify independent prognostic factors for overall survival (OS) and disease-specific survival (DSS). Nomograms were constructed based on the independent prognostic factors identified in multivariate Cox regression analysis.

Results: A total of 1427 patients diagnosed with PBL were identified with the average age of 67.1 years. The overall incidence of PBL is 1.35/1,000,000 (adjusted to the United States standard population in 2000) from 1975 to 2017, with a significant upward trend by an annual percentage change (APC) of 2.91 (95%CI 2.29-3.94, P < 0.05). Age, sex, race, year of diagnosis, marital status, histological subtype, Ann Arbor Stage, and treatment modality were assessed as independent prognostic factors for OS and DSS by multivariable Cox regression (P < 0.05). Nomograms were constructed to predict the 1-, 3-, 5-, and 10- year OS and DSS. The concordance index (C-index) and calibration plots showed robustness and accuracy of the nomogram.

Conclusion: The overall incidence of PBL was steadily increasing over the past four decades. Nomograms constructed can predicting 1-, 3-, 5-, and 10-year OS and identify patients with high-risk PBL.
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http://dx.doi.org/10.1016/j.breast.2021.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027901PMC
June 2021

Telecoupling cropland soil erosion with distant drivers within China.

J Environ Manage 2021 Jun 22;288:112395. Epub 2021 Mar 22.

State Environmental Protection Key Laboratory of Soil Health and Green Remediation, Huazhong Agricultural University, Wuhan 430072, China; CAS Center for Excellence in Quaternary Science and Global Change, Xi'an 710061, China. Electronic address:

Soil erosion on cropland is a result of the interaction between nature and human activities. The socioeconomic influencing factors of soil erosion have been less studied than the biophysical processes and previous studies have mainly focused on the impacts of local socioeconomic factors on soil erosion in the same region. However, since agricultural activities are densely connected to other socio-economic activities, the need for agricultural products from distant regions could potentially drive local soil erosion accompanying agricultural production. To the best of our knowledge, these telecoupling effects have not been studied. Here, we combined the Revised Universal Soil Loss Equation (RUSLE) and multiregional input-output analysis (MRIO) models to quantify the contribution of China's cross-provincial economic demand to local soil erosion at the provincial, sectoral, and supply chain levels. Our results show that a large amount of soil erosion in the southwest, northeast, and central regions is linked to the economic needs across provinces. Agriculture and food processing are the most important distant driving sectors. The driving effect of household consumption on soil erosion mainly occurs on shorter supply chains, while exports and capital formation drive soil erosion through longer chains. Our results indicate that local soil erosion management must consider the impact of distant agricultural product needs and coordinate food production and supply on a national scale to protect the ecological function of the land.
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http://dx.doi.org/10.1016/j.jenvman.2021.112395DOI Listing
June 2021

Impact of chemotherapy on lymphocytes and serological memory in recovered COVID-19 patients with acute leukemia.

J Cancer 2021 1;12(8):2450-2455. Epub 2021 Mar 1.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Chemotherapy is the major method of treatment for acute leukemia to date, while intensive chemotherapy may impair immunity. We previously reported that leukemia patients were more susceptible to COVID-19 than the overall population. However, for COVID-19 recovered patients with leukemia, the impacts of intensive chemotherapy on the immune memory of COVID-19 are unknown. This study characterized the changes in immune cells and SARS-CoV-2 antibodies in acute leukemia patients, who underwent chemotherapy after recovering from COVID-19. The study enrolled three groups of individuals. One group was a total of three acute leukemia patients, who recovered well from COVID-19 before the last cycle of chemotherapy. The other two groups were six COVID-19 recovered healthy people, and six normal uninfected healthy people, respectively. Levels of B cells, T cells, and NK cells in peripheral blood were analyzed by multiparameter flow cytometry. Besides, the SARS-CoV-2 antibodies were monitored. The results showed that B cells were severely decreased after chemotherapy, especially memory B cells. Most of the T cells and NK cells showed only minor changes after chemotherapy, except for γδ T cells. The serum levels of SARS-CoV-2 antibodies were not significantly affected after chemotherapy in two leukemia patients. However, interestingly, one leukemia patient's SARS-CoV-2 IgM showed dramatically increase, suggesting possible loss of serological memory after chemotherapy. These findings raised the concern for the stability of immune memory against SARS-CoV-2 during chemotherapy and the choice of anti-leukemia treatment in the COVID-19 pandemic.
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http://dx.doi.org/10.7150/jca.53863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974873PMC
March 2021

Intratumor heterogeneity of breast cancer detected by epialleles shows association with hypoxic microenvironment.

Theranostics 2021 4;11(9):4403-4420. Epub 2021 Mar 4.

State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, 51000, China.

In breast cancer, high intratumor DNA methylation heterogeneity can lead to drug-resistant, metastasis and poor prognosis of tumors, which increases the complexity of cancer diagnosis and treatment. However, most studies are limited to average DNA methylation level of individual CpGs and ignore heterogeneous DNA methylation patterns of cell subpopulations within the tumor. Thus, quantifying the variability in DNA methylation pattern in sequencing reads is valuable for understanding intratumor heterogeneity. We performed Reduced Representation Bisulfite Sequencing and RNA sequencing for tumor core and tumor periphery regions within one breast tumor. By developing a method named "epialleJS" based on Jensen-Shannon divergence, we detected the differential epialleles between tumor core and tumor periphery (CPDEs). We then explored the correlation between intratumor methylation heterogeneity and hypoxic microenvironment in TCGA breast cancer cohort. More than 70% of CPDEs had higher epipolymorphism in tumor core than tumor periphery, and these CPDEs had lower methylation in tumor core. The CPDEs with lower methylation in tumor core may associate with hypoxic tumor microenvironment. Moreover, we identified a signature of five hypoxia-related DNA methylation markers which can predict the prognosis of breast cancer patients, including a CpG site cg15190451 in gene . Furthermore, immunohistochemical analysis confirmed that the expression of was associated with clinicopathological characteristics and survival of breast cancer patients. The analysis of intratumor DNA methylation heterogeneity based on epialleles reveals that disordered methylation patterns in tumor core are associated with hypoxic microenvironment, which provides a framework for understanding biological heterogeneous behavior and guidance for developing effective treatment schemes for breast cancer patients.
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http://dx.doi.org/10.7150/thno.53737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977462PMC
March 2021

Circulating Plasma Cells as a Biomarker to Predict Newly Diagnosed Multiple Myeloma Prognosis: Developing Nomogram Prognostic Models.

Front Oncol 2021 5;11:639528. Epub 2021 Mar 5.

Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

To investigate the prognostic value of circulating plasma cells (CPC) and establish novel nomograms to predict individual progression-free survival (PFS) as well as overall survival (OS) of patients with newly diagnosed multiple myeloma (NDMM). One hundred ninetyone NDMM patients in Wuhan Union Hospital from 2017.10 to 2020.8 were included in the study. The entire cohort was randomly divided into a training ( = 130) and a validation cohort ( = 61). Univariate and multivariate analyses were performed on the training cohort to establish nomograms for the prediction of survival outcomes, and the nomograms were validated by calibration curves. When the cut-off value was 0.038%, CPC could well distinguish patients with higher tumor burden and lower response rates ( < 0.05), and could be used as an independent predictor of PFS and OS. Nomograms predicting PFS and OS were developed according to CPC, lactate dehydrogenase (LDH) and creatinine. The C-index and the area under receiver operating characteristic curves (AUC) of the nomograms showed excellent individually predictive effects in training cohort, validation cohort or entire cohort. Patients with total points of the nomograms ≤ 60.7 for PFS and 75.8 for OS could be defined as low-risk group and the remaining as high-risk group. The 2-year PFS and OS rates of patients in low-risk group was significantly higher than those in high-risk group ( < 0.001). CPC is an independent prognostic factor for NDMM patients. The proposed nomograms could provide individualized PFS and OS prediction and risk stratification.
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http://dx.doi.org/10.3389/fonc.2021.639528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973368PMC
March 2021

The Relationship Among Trait Mindfulness, Attention, and Working Memory in Junior School Students Under Different Stressful Situations.

Front Psychol 2021 2;12:558690. Epub 2021 Mar 2.

Department of Applied Psychology, College of Humanities and Social Sciences, Harbin Engineering University, Harbin, China.

Attention and working memory are important cognitive functions that affect junior school students' learning ability and academic performance. This study aimed to explore the relationships among trait mindfulness, attention, and working memory and to explore differences in performance between a high trait mindfulness group and a low one in attention and working memory under different stressful situations. In study 1, 216 junior school students completed the Five Facet Mindfulness Questionnaire (FFMQ), and their attention and working memory were tested in a non-pressure situation. The results showed that attention had a partial mediating effect between mindfulness and working memory. In study 2, the high trait mindfulness group and the low one were tested for attention and working memory under situations with single and multiple pressures. One notable result was that the attention and working memory performances of the high mindfulness group were all significantly higher than those of the low mindfulness group in every stress situation (no stress, single stress, and multiple stresses). Other important results were that trait mindfulness moderates the relationship between stress and attention and between stress and working memory. These results suggest that trait mindfulness has a protective effect in the process by which various stresses affect attention and working memory. These findings indicate that trait mindfulness is an important psychological quality that affects the attention and working memory of junior school students, and it is also an important psychological resource for effectively coping with the impact of stress on attention and working memory. Therefore, it is possible that improving trait mindfulness may help to improve junior school students' attention and working memory and enable them to cope better with stress, thereby helping to improve academic performance. This research is of great significance for understanding the association between key psychological qualities and cognitive functions in different stressful situations. These findings also provide insight for future studies in educational psychology.
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http://dx.doi.org/10.3389/fpsyg.2021.558690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960675PMC
March 2021

Combining dual isotopes and a Bayesian isotope mixing model to quantify the nitrate sources of precipitation in Ningbo, East China.

Sci Total Environ 2021 Mar 8;778:146297. Epub 2021 Mar 8.

College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.

Nitrate (NO) is becoming a significant contributor to acid deposition in many cities in China. Based on the chemical compositions and stable isotopes of NO in precipitation (δN-NO and δO-NO), the NO sources and their formation pathways were determined to aid in reducing NO emissions in Ningbo, an important port city. The acid rain frequency in Ningbo was 67%, and the mean SO/NO ratio was 1.07. The δO-NO (49.5‰-82.8‰) and δN-NO values (-4.3‰-2.7‰) both varied seasonally, with high values during the cold season and low values during the warm season. The seasonal variations in the δO-NO values were mainly controlled by the NO formation pathways, following the OH· pathway during the warm season and NO pathway during the cold season. The Monte Carlo simulation results indicated that the contributions of the OH· pathway ranged from 28.3% to 75.4%, with the remainder contributed by the NO pathway. The improved Bayesian model incorporating nitrogen (N) isotopic fractionation (Ԑ = 4‰) indicated that mobile sources, including ship emissions (35.0%) > coal combustion (26.0%) > biomass burning (20.0%) > soil emissions (19.0%), were the major sources of NO emissions in Ningbo. The results indicate that the influence of isotopic fractionation on source apportionment must be considered in a Bayesian model.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146297DOI Listing
March 2021

Pre-operative N-terminal pro-B-type natriuretic peptide for prediction of acute kidney injury after noncardiac surgery: A retrospective cohort study.

Eur J Anaesthesiol 2021 Mar 11. Epub 2021 Mar 11.

From the Department of Anaesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (B-CZ, P-PZ, S-HL, S-DQ, XY, CL, W-FL, K-XL).

Background: Acute kidney injury (AKI) is associated with poor outcomes after noncardiac surgery. Whether pre-operative N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts AKI after noncardiac surgery is unclear.

Objective: To investigate the predictive role of pre-operative NT-proBNP on postoperative AKI.

Design: Retrospective cohort study.

Setting: Nanfang Hospital, Southern Medical University, China.

Patients: Adult patients who had a serum creatinine and NT-proBNP measurement within 30 pre-operative days and at least one serum creatinine measurement within 7 days after noncardiac surgery between February 2008 and May 2018 were identified.

Main Outcome Measures: The primary outcome was postoperative AKI, defined by the kidney disease: improving global outcomes creatinine criteria.

Results: In all, 6.1% (444 of 7248) of patients developed AKI within 1 week after surgery. Pre-operative NT-proBNP was an independent predictor of AKI after adjustment for clinical variables (OR comparing top to bottom quintiles 2.29, 95% CI, 1.47 to 3.65, P < 0.001 for trend; OR per 1-unit increment in natural log transformed NT-proBNP 1.27, 95% CI, 1.16 to 1.39). Compared with clinical variables alone, the addition of NT-proBNP improved model fit, modestly improved the discrimination (change in area under the curve from 0.764 to 0.773, P = 0.005) and reclassification (continuous net reclassification improvement 0.210, 95% CI, 0.111 to 0.308, improved integrated discrimination 0.0044, 95% CI, 0.0016 to 0.0072) of AKI and non-AKI cases, and achieved higher net benefit in decision curve analysis.

Conclusions: Pre-operative NT-proBNP concentrations provided predictive information for AKI in a cohort of patients undergoing noncardiac surgery, independent of and incremental to conventional risk factors. Prospective studies are required to confirm this finding and examine its clinical impact.

Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR1900024056. Website: www.chictr.org.cn/showproj.aspx?proj=40385.
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http://dx.doi.org/10.1097/EJA.0000000000001495DOI Listing
March 2021

Mesoscopic fluorescence lifetime imaging: Fundamental principles, clinical applications and future directions.

J Biophotonics 2021 Mar 12:e202000472. Epub 2021 Mar 12.

Department of Biomedical Engineering, University of California, Davis, Davis, California, USA.

Fluorescence lifetime imaging (FLIm) is an optical spectroscopic imaging technique capable of real-time assessments of tissue properties in clinical settings. Label-free FLIm is sensitive to changes in tissue structure and biochemistry resulting from pathological conditions, thus providing optical contrast to identify and monitor the progression of disease. Technical and methodological advances over the last two decades have enabled the development of FLIm instrumentation for real-time, in situ, mesoscopic imaging compatible with standard clinical workflows. Herein, we review the fundamental working principles of mesoscopic FLIm, discuss the technical characteristics of current clinical FLIm instrumentation, highlight the most commonly used analytical methods to interpret fluorescence lifetime data and discuss the recent applications of FLIm in surgical oncology and cardiovascular diagnostics. Finally, we conclude with an outlook on the future directions of clinical FLIm.
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http://dx.doi.org/10.1002/jbio.202000472DOI Listing
March 2021

Neural Fuyuan Formula promotes neural plasticity through BDNF/Trkβ signaling pathway.

Ann Palliat Med 2021 Mar 10;10(3):2926-2934. Epub 2021 Mar 10.

Department of Neurology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Depression after stroke is usually a chronic process, which was associated with many health problems. This study was aimed to investigate the underline mechanism of the effect of Neural Fuyuan Formula (NFF) in post-stroke depression and the role of brain-derived neurotrophic factor (BDNF) in the signal pathway regulated by NFF.

Methods: A rat post-stroke depression model was established. Synaptic plasticity of rat was detected by Electron microscopy. The expression of BDNF signaling proteins and synapse related proteins were measured by Western blot. The expression of Synapsin-1 (SYN1) in rat and the culture neurons was detected by Western blot and immunofluorescence. Dendritic complexity was also measured.

Results: NFF could attenuate the synapse change in the post-stroke depression (PSD) model rat. NFF increased the expression of BDNF signaling proteins and synapse related proteins of the PSD model rat (P&0.05). NFF increased the expression of SYN1 in rat and the culture neurons (P&0.05). NFF could also increase the dendritic complexity in culture neurons (P&0.05).

Conclusions: NFF promoted recovery of neurological function through BDNF signaling pathways, which further affirm the curative effect of NFF for treatment of post-stroke depression.
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http://dx.doi.org/10.21037/apm-19-533DOI Listing
March 2021

Assessment of Prognostic Factors of Racial Disparities in Testicular Germ Cell Tumor Survival in the United States (1992-2015).

Biomed Environ Sci 2021 Feb;34(2):152-162

State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China;Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 200000, China.

Objective: Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed.

Methods: The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT.

Results: Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality.

Conclusion: Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.
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http://dx.doi.org/10.3967/bes2021.021DOI Listing
February 2021

ERO1L Promotes Hepatic Metastasis through Activating Epithelial-Mesenchymal Transition (EMT) in Pancreatic Cancer.

J Immunol Res 2021 23;2021:5553425. Epub 2021 Feb 23.

The First Affiliated Hospital of Soochow University, Suzhou, China.

Background: Endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) serves as an effector for tumor growth in human malignancies. However, the mechanism of ERO1L on promoting metastasis of pancreatic ductal adenocarcinoma (PDAC) remains to be further explored.

Methods: Bioinformatics analysis of public databases and large-scale metastatic PDAC sequencing was performed to determine the expression profile and prognostic value of ERO1L in PDAC. The effect of ERO1L on metastasis of PDAC was analyzed in vitro and in vivo, via cell biological, molecular, and biochemical approaches.

Results: ERO1L in PDAC hepatic metastatic tissues were highly expressed and related to disease-free survival (DFS). Genetic silencing and pharmacological inhibition of ERO1L with EN460 suppressed cell migration and invasion of PDAC. Furthermore, EN460 also suppressed hepatic metastasis of PDAC in vivo. Using shRNAs and EN460 to inhibit the ERO1L expression in Capan-2 and MiaPaca-2 led to the remarkable change of EMT-related protein Vimentin and E-cadherin, which indicated that EMT acted as a key pathway for ERO1L to promote invasion, dissemination, colonization, and growth of hepatic metastasis in PDAC.

Conclusion: Our findings uncover ERO1L contributes to hepatic metastasis in PDAC via epithelial-mesenchymal transition (EMT) process and indicate a promising therapeutic strategy for PDAC hepatic metastasis.
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http://dx.doi.org/10.1155/2021/5553425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925037PMC
February 2021

Preoperative tracheotomy as reflection of tumor size impacting oncologic outcomes of patients with advanced stage glottic carcinoma.

Eur Arch Otorhinolaryngol 2021 Mar 6. Epub 2021 Mar 6.

Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.

Purpose: The aim of this study was to evaluate the influence of preoperative tracheotomy on oncologic outcomes of advanced stage glottic carcinoma patients, and to explore the potential reason.

Methods: We retrospectively analyzed 413 consecutive advanced stage glottic carcinoma patients from January 2005 to December 2010. The correlation of preoperative tracheotomy and potential impacting factor of tumor size involving tumor diameter and tumor area with overall survival (OS) and disease-free survival (DFS) was fully assessed.

Results: Our cohort consisted of 302 (73.1%) patients with T3 and 111 (26.9%) patients with T4, and 98 (23.7%) patients received preoperative tracheotomy. The OS and DFS rates of patients receiving preoperative tracheotomy were worse than those without (5-year OS: 49.3% versus 69.8%; 5-year DFS: 45.3% versus 61.0%). The mean tumor diameter and tumor area of patients with preoperative tracheotomy were greater than those without (3.3 cm versus 2.4 cm, 8.9 cm versus 4.7 cm). The optimal cutoff values of tumor diameter and tumor area for tracheotomy were 2.85 cm and 6.64 cm. Tumor diameter and tumor area were correlated with tracheotomy intervention. Furthermore, when considering the potential effect of tumor area in multivariate model, we found that it was a significant factor in survival outcomes but variable of preoperative tracheotomy was not.

Conclusion: This study indicates that tumor size is correlated with preoperative tracheotomy, and tracheotomy intervention may be reflection from effect of great tumor size that is a true adverse factor influencing oncologic outcomes of advanced stage glottic carcinoma patients.
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http://dx.doi.org/10.1007/s00405-021-06721-9DOI Listing
March 2021

Association between residential greenness and glycosylated hemoglobin in pregnant women: Findings from the baseline data of Yuexiu birth cohort.

Int J Hyg Environ Health 2021 May 2;234:113721. Epub 2021 Mar 2.

Department of Maternal and Child Health, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China. Electronic address:

Background: Previous studies have indicated that residential greenness can affect human health, but limited studies have examined the association between residential greenness and glucose homeostasis during pregnancy. We aimed to investigate the associations of residential greenness with plasma glucose, glycosylated hemoglobin (HbA1c) and gestational diabetes mellitus (GDM).

Methods: We recruited a total of 587 pregnant women aged 20-45 years in Guangzhou, China. We extracted normalized difference vegetation index with different buffers (NDVI-250m, 500m and 1000m) from remote satellite data based on maternal residential addresses. We measured plasma glucose levels and HbA1c during 20-28 weeks' gestation, and GDM was diagnosed with a 75-g oral glucose tolerance test. We collected the information of relevant covariates by face-to-face interviews and questionnaires. We used generalized linear regression to examine the associations of residential greenness with quantitative and categorized outcomes.

Results: In the final analyses, 123 (21.0%) of the pregnant women were diagnosed as GDM at 20-28 weeks gestation. With a 0.1 unit increase in NDVI-250m, the percent of HbA1c changed by -0.05% [95% confidence interval (CI): -0.08, -0.02]. The results of HbA1c were consistent when using different resolution of NDVI [NDVI-500m: 0.03, 95%CI: -0.05, -0.01; NDVI-1000m: 0.05, 95%CI: -0.08, -0.02]. We observed non-significant associations of glucose levels and the risk of GDM in relation to NDVI with different resolutions when adjusted for confounding. The results remained robust in sensitivity analyses.

Conclusion: The present study in Guangzhou, China was the first to identify negative association of NDVI with HbA1c in pregnant women, but we did not observe its association with plasma glucose levels or the risk of GDM. The results support that building sufficient green infrastructure could be considered in urban design and planning to promote maternal health.
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http://dx.doi.org/10.1016/j.ijheh.2021.113721DOI Listing
May 2021

Dietary Adherence, Self-Regulatory Fatigue and Trait Self-Control Among Chinese Patients with Peritoneal Dialysis: A Cross-Sectional Study.

Patient Prefer Adherence 2021 25;15:443-451. Epub 2021 Feb 25.

Nursing and Health School of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Purpose: Little is known about factors that predict dietary adherence among Chinese patients undergoing peritoneal dialysis. We investigated whether self-regulatory fatigue and trait self-control influence dietary adherence among Chinese patients with peritoneal dialysis.

Methods: A total of 192 Chinese patients undergoing peritoneal dialysis were recruited at two peritoneal dialysis centers. The dietary adherence, trait self-control and self-regulatory fatigue of these patients were assessed using self-administered questionnaires. Clinical data were extracted from the hospital medical records. The significance of several social demographic factors on dietary adherence was analyzed using One-way ANOVA was used to analyze, whereas the association between dietary adherence and self-regulatory fatigue as well as trait self-control were analyzed using Pearson correlation. The independence association between dietary adherence and other influencing factors was assessed using Multivariable linear regression analyses.

Results: We found that peritoneal dialysis patients only moderately adhere to dietary prescriptions. The top three least adherences were observed for salt intake (1.89±0.36), face of difficulty (2.86±0.26) and fluid restriction adherence intake (2.97±0.30). Multivariable linear regression analysis revealed that education level (β=0.339, P<0.001), residence (β=-0.151, P=0.015), self-regulatory fatigue (β= -0.648, P<0.001), and trait self-control (β=0.118, P=0.022) were independent predictors of dietary adherence.

Conclusion: Education level and residence strongly influence dietary adherence among Chinese peritoneal dialysis patients. On the other hand, Self-regulatory fatigue and trait self-control are independent predictors of dietary adherence among peritoneal dialysis patients. These findings can guide the enhancement of dietary adherence of peritoneal dialysis patients.
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http://dx.doi.org/10.2147/PPA.S298231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920602PMC
February 2021

Endocrine Therapy for Hormone Receptor-Positive Advanced Breast Cancer: A Nation-Wide Multicenter Epidemiological Study in China.

Front Oncol 2020 11;10:599604. Epub 2021 Feb 11.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Clinical guidelines generally recommend endocrine therapy (ET) as first-line treatment of hormone receptor-positive advanced breast cancer (HR+ ABC) whereas chemotherapy (CT) should be considered in the presence of life-threatening disease or limited clinical benefit after three sequential ET regimens. However, it is unclear if real-world clinical practice is in accordance with the current guidelines. This study was to present the real-world treatment patterns and ET regimens among HR+ ABC patients in China.

Methods: Using data from the Nation-wide Multicenter Retrospective Clinical Epidemiology Study of Female Advanced Breast Cancer in China (ClinicalTrials.gov identifier: NCT03047889), we investigated the clinicopathological characteristics, clinical profiles, and treatment patterns of HR+ ABC patients from January 2012 to December 2014.

Results: A total of 2,342 patients with HR+ ABC were included in this study. Our findings revealed that, in comparisons with those receiving initial CT (n = 1445), patients initiated ET (n =402) were significantly older, later recurrent after adjuvant treatment, with a lower rate of visceral involvement and a decreasing quantity of metastatic sites. A total of 1,308 patients received palliative ET while only 18.9% patients (n = 247) reached three lines of ET. Among patients completing more than one line of ET, the median treatment duration was 8 months for the first line, 6 months for the second line, and 3 months for the third line for patients receiving ET. In the advanced setting, the choices of palliative ET regimens were diverse, yet aromatase inhibitor (AI) monotherapy was still the overall mainstay of ET; in contrast, patients were less accessible to everolimus plus AI regimen in this population.

Conclusions: Less than one quarter of patients initiated palliative ET for HR+ ABC in routine clinical practice. Patients who received multi-lines of ET experienced successive shorter durations following each line of therapy. This real-life data provides a solid overview of ET for HR+ ABC from China, indicating unmet need for treatment options that improve the effectiveness of endocrine therapy.
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http://dx.doi.org/10.3389/fonc.2020.599604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905089PMC
February 2021

Safety, immunogenicity of lyophilized purified vero cell cultured rabies vaccine administered in Zagreb and Essen regimen in post-exposure subjects: A post-marketing, parallel control clinical trial.

Hum Vaccin Immunother 2021 Feb 25:1-7. Epub 2021 Feb 25.

Department of Public Health, Wuhan Institute of Dermatology and Venereology, Wuhan, China.

To compare the safety and immunogenicity of lyophilized PVRV under Zagreb and Essen regimen.A post-marketing parallel control clinical trial was conducted. Totally 240 subjects were assigned to two groups randomly, immunized with lyophilized PVRV under Zagreb and Essen schedule. Solicited adverse events were observed after each dose and unsolicited adverse events were collected. Serum samples were collected on days 0, 7, 14, 42, 180 and 365 to be used to determine immunogenicity level. No severe adverse events (SAE) were observed. The incidence of adverse events under Zagreb and Essen were similar and there was no significant difference between the two groups and within all age groups. Fever and pain were the most frequently reported systemic and local adverse events (AEs) respectively. There were no differences in the GMT and the positive seroconversion rate between these two groups. All participants in the Zagreb group obtained protective effect on day 14, while 99.16% of the subjects obtained in the Essen group. Both groups showed similar enduring immunity. Immunizations under Zagreb and Essen regimens showed similar safety and immunogenicity. For lyophilized PVRV, Zagreb was non-inferior to Essen to patients of all age groups.
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http://dx.doi.org/10.1080/21645515.2021.1880200DOI Listing
February 2021

Surrogate models based on machine learning methods for parameter estimation of left ventricular myocardium.

R Soc Open Sci 2021 Jan 13;8(1):201121. Epub 2021 Jan 13.

School of Mathematics and Statistics, University of Glasgow, Glasgow G12 8QQ, UK.

A long-standing problem at the frontier of biomechanical studies is to develop fast methods capable of estimating material properties from clinical data. In this paper, we have studied three surrogate models based on machine learning (ML) methods for fast parameter estimation of left ventricular (LV) myocardium. We use three ML methods named K-nearest neighbour (KNN), XGBoost and multi-layer perceptron (MLP) to emulate the relationships between pressure and volume strains during the diastolic filling. Firstly, to train the surrogate models, a forward finite-element simulator of LV diastolic filling is used. Then the training data are projected in a low-dimensional parametrized space. Next, three ML models are trained to learn the relationships of pressure-volume and pressure-strain. Finally, an inverse parameter estimation problem is formulated by using those trained surrogate models. Our results show that the three ML models can learn the relationships of pressure-volume and pressure-strain very well, and the parameter inference using the surrogate models can be carried out in minutes. Estimated parameters from both the XGBoost and MLP models have much less uncertainties compared with the KNN model. Our results further suggest that the XGBoost model is better for predicting the LV diastolic dynamics and estimating passive parameters than other two surrogate models. Further studies are warranted to investigate how XGBoost can be used for emulating cardiac pump function in a multi-physics and multi-scale framework.
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http://dx.doi.org/10.1098/rsos.201121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890479PMC
January 2021

Enhanced recovery after surgery for laparoscopic gastrectomy in gastric cancer: A prospective study.

Medicine (Baltimore) 2021 Feb;100(7):e24267

Department of General Surgery.

Background: Laparoscopic distal gastrectomy (LDG) has been highlighted for its safety and better short-term clinical outcomes in treating gastric cancer. However, only a slight reduction of the post-operative hospital stay was observed in gastric cancer patients undergoing LDG with conventional perioperative management, compared to patients undergoing open surgery. Thus, an enhanced recovery after surgery (ERAS) program for LDG is needed to further reduce the post-operative hospital stays. This prospective, open-label, single-arm cohort study aimed to assess the safety and efficacy of the ERAS program for gastric cancer patients undergoing LDG.

Material And Methods: All patients with gastric cancer indicated for LDG were consecutively enrolled from December 2016 to January 2018. The ERAS program included short fasting time, effective perioperative pain management, early, goal-oriented ambulation, and oral feeding. The safety assessment was the incidence of post-operative complications, mortality, and readmission in 30 days. The primary efficacy assessment was recovery time defined by post-operative hospital stays and rehabilitative rate on post-operative day 4.

Results: Ninety-eight of 114 patients were finally enrolled. The incidence of post-operative complication, mortality, and readmission in 30 days was 20. 4%, 0%, 7.1%, respectively. The Clavien-Dindo grade III complication rate was 6.1%, while the pulmonary complication rate was 1% only. The median post-operative stay was 6 days (5.0-7.0 days), and the rehabilitative rate on post-operative day 4 was 78%.

Conclusions: The ERAS program might be optimal perioperative management for gastric cancer patients after LDG without compromising safety.

Trial Number: NCT03016026.
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http://dx.doi.org/10.1097/MD.0000000000024267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899858PMC
February 2021

GABARAP suppresses EMT and breast cancer progression via the AKT/mTOR signaling pathway.

Aging (Albany NY) 2021 02 11;13(4):5858-5874. Epub 2021 Feb 11.

The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150040, China.

Few studies have focused on γ-aminobutyric acid type A (GABA) receptor-associated protein (GABARAP) in tumor progression. We investigated the expression and importance of GABARAP in breast cancer. We analyzed the expression of GABARAP and its relationship with clinicopathological features and prognosis (TCGA). To explain the role and potential mechanism of GABARAP in regulating tumor development, we performed acquisition and loss of function experiments using cell lines and models of mouse xenotransplantation. We found that GABARAP inhibited proliferation, migration and invasion and . Notably, low levels of GABARAP induced the epithelial-mesenchymal transition (EMT). Low levels of GABARAP increased p-AKT and p-mTOR levels, and a specific AKT pathway inhibitor reversed the downregulation of GABARAP-induced tumor progression. GABARAP negatively correlated with advanced clinicopathological features in clinical specimens, such as tumor size and TNM stage. Notably, patients with low GABARAP levels had a poor prognosis. Immunohistochemistry (IHC) revealed that GABARAP expression negatively correlated with matrix metalloproteinase (MMP) 2 and MMP14. Conclusively, these data indicate that GABARAP suppresses the malignant behaviors of breast cancer likely via the AKT/mTOR pathway. The targeting of GABARAP may improve the certainty of diagnosis and treatment strategies for breast cancer.
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http://dx.doi.org/10.18632/aging.202510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950252PMC
February 2021

Reply to "Mortality-related immune features and COVID-19".

J Allergy Clin Immunol Pract 2021 02;9(2):1040-1041

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859731PMC
February 2021

Anterior perforated substance region aneurysms: review of a series treated with microsurgical technique.

Neurosurg Rev 2021 Feb 4. Epub 2021 Feb 4.

Arkansas Neuroscience Institute, CHI Saint Vincent Infirmary, Little Rock, AR, USA.

Aneurysms arising from the distal carotid, proximal A1, and proximal M1 that project posteriorly and superiorly toward the anterior perforated substance (APS) are rare. Their open surgical treatment is particularly difficult due to poorly visualized origin of the aneurysm and the abundance of surrounding perforators. We sought to analyze the anatomical and clinical characteristics of APS aneurysms and discuss surgical nuances that can optimize visualization, complete neck clip obliteration, and preservation of adjacent perforators. Thirty-two patients with 36 APS aneurysms were surgically treated between November 2000 and September 2017. Patients were prospectively enrolled in a cerebral aneurysm database and their clinical, imaging, and surgical records were retrospectively reviewed. Twenty-seven aneurysms originated from the distal ICA, 7 from the proximal A1, and 2 from the proximal M1; 15 patients presented with subarachnoid hemorrhage. Careful intraoperative dissection revealed 4 aneurysms originating at the takeoff of a perforator; another 25 had at least 1 adherent perforator. All aneurysms were clipped except for one that was trapped. Postoperatively, 3 patients had radiographic infarctions in perforator territory with only 1 developing delayed clinical hemiparesis. Good outcome (modified Rankin Scale, 0-2) was achieved in 28 patients (88%). APS aneurysms present a challenging subset of aneurysms due to their complex anatomical relationship with surrounding perforators. These should be identified on preoperative imaging based on location and projection. Successful microsurgical clipping relies on optimization of the surgical view, meticulous clip reconstruction, preservation of all perforators, and electrophysiological monitoring to minimize ischemic complication.
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http://dx.doi.org/10.1007/s10143-021-01485-6DOI Listing
February 2021

Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data.

Hum Genomics 2021 02 3;15(1):10. Epub 2021 Feb 3.

Department of Biostatistics, Yale University, 300 George Street, Ste 523, New Haven, CT, 06511, USA.

Background: The severity of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly heterogeneous. Studies have reported that males and some ethnic groups are at increased risk of death from COVID-19, which implies that individual risk of death might be influenced by host genetic factors.

Methods: In this project, we consider the mortality as the trait of interest and perform a genome-wide association study (GWAS) of data for 1778 infected cases (445 deaths, 25.03%) distributed by the UK Biobank. Traditional GWAS fails to identify any genome-wide significant genetic variants from this dataset. To enhance the power of GWAS and account for possible multi-loci interactions, we adopt the concept of super variant for the detection of genetic factors. A discovery-validation procedure is used for verifying the potential associations.

Results: We find 8 super variants that are consistently identified across multiple replications as susceptibility loci for COVID-19 mortality. The identified risk factors on chromosomes 2, 6, 7, 8, 10, 16, and 17 contain genetic variants and genes related to cilia dysfunctions (DNAH7 and CLUAP1), cardiovascular diseases (DES and SPEG), thromboembolic disease (STXBP5), mitochondrial dysfunctions (TOMM7), and innate immune system (WSB1). It is noteworthy that DNAH7 has been reported recently as the most downregulated gene after infecting human bronchial epithelial cells with SARS-CoV-2.

Conclusions: Eight genetic variants are identified to significantly increase the risk of COVID-19 mortality among the patients with white British ancestry. These findings may provide timely clues and potential directions for better understanding the molecular pathogenesis of COVID-19 and the genetic basis of heterogeneous susceptibility, with potential impact on new therapeutic options.
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http://dx.doi.org/10.1186/s40246-021-00306-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856608PMC
February 2021