Publications by authors named "Wei Yu"

1,678 Publications

  • Page 1 of 1

A SARS-CoV-2 antigen rapid diagnostic test for resource limited settings.

Sci Rep 2021 Nov 26;11(1):23009. Epub 2021 Nov 26.

Exosome Diagnostics, A Bio-Techne Brand, Waltham, MA, USA.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 disease. RT-qPCR has been the primary method of diagnosis; however, the required infrastructure is lacking in many developing countries and the virus has remained a global challenge. More inexpensive and immediate test methods are required to facilitate local, regional, and national management strategies to re-open world economies. Here we have developed a SARS-CoV-2 antigen test in an inexpensive lateral flow format to generate a chromatographic result identifying the presence of the SARS-CoV-2 antigen, and thus an active infection, within a patient anterior nares swab sample. Our 15-min test requires no equipment or laboratory infrastructure to administer with a limit of detection of 2.0 × 10 TCID/mL and 87.5% sensitivity, 100% specificity when tested against 40 known positive and 40 known negative patient samples established by a validated RT-qPCR test.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-02128-yDOI Listing
November 2021

A Moving Ship Detection and Tracking Method Based on Optical Remote Sensing Images from the Geostationary Satellite.

Sensors (Basel) 2021 Nov 13;21(22). Epub 2021 Nov 13.

Aerospace Information Research Institute, Chinese Academy of Sciences, Beijing 100094, China.

Geostationary optical remote sensing satellites, such as the GF-4, have a high temporal resolution and wide coverage, which enables the continuous tracking and observation of ship targets over a large range. However, the ship targets in the images are usually small and dim and the images are easily affected by clouds, islands and other factors, which make it difficult to detect the ship targets. This paper proposes a new method for detecting ships moving on the sea surface using GF-4 satellite images. First, the adaptive nonlinear gray stretch (ANGS) method was used to enhance the image and highlight small and dim ship targets. Second, a multi-scale dual-neighbor difference contrast measure (MDDCM) method was designed to enable detection of the position of the candidate ship target. The shape characteristics of each candidate area were analyzed to remove false ship targets. Finally, the joint probability data association (JPDA) method was used for multi-frame data association and tracking. Our results suggest that the proposed method can effectively detect and track moving ship targets in GF-4 satellite optical remote sensing images, with better detection performance than other classical methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21227547DOI Listing
November 2021

Cell Differentiation Trajectory-Associated Molecular Classification of Osteosarcoma.

Genes (Basel) 2021 Oct 23;12(11). Epub 2021 Oct 23.

Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88, Jiefang Road, Hangzhou 310009, China.

This study aims to investigate the differentiation trajectory of osteosarcoma cells and to construct molecular subtypes with their respective characteristics and generate a multi-gene signature for predicting prognosis. Integrated single-cell RNA-sequencing (scRNA-seq) data, bulk RNA-seq data and microarray data from osteosarcoma samples were used for analysis. Via scRNA-seq data, time-related as well as differentiation-related genes were recognized as osteosarcoma tumor stem cell-related genes (OSCGs). In Gene Expression Omnibus (GEO) cohort, osteosarcoma patients were classified into two subtypes based on prognostic OSCGs and it was found that molecular typing successfully predicted overall survival, tumor microenvironment and immune infiltration status. Further, available drugs for influencing osteosarcoma via prognostic OSCGs were revealed. A 3-OSCG-based prognostic risk score signature was generated and by combining other clinic-pathological independent prognostic factor, stage at diagnosis, a nomogram was established to predict individual survival probability. In external independent TARGET cohort, the molecular types, the 3-gene signature as well as nomogram were validated. In conclusion, osteosarcoma cell differentiation occupies a crucial position in many facets, such as tumor prognosis and microenvironment, suggesting promising therapeutic targets for this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes12111685DOI Listing
October 2021

Role of carbon and nutrient exports from different land uses in the aquatic carbon sequestration and eutrophication process.

Sci Total Environ 2021 Nov 23:151917. Epub 2021 Nov 23.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, CAS, Guiyang 550081, China; University of Chinese Academy of Sciences, Beijing 100049, China; Resources and Environmental Engineering, Guizhou Institute of Technology, Guiyang 550008, Guizhou, China.

The hydrochemical features affected by differing land uses play a key role in regulating both the primary production of aquatic photosynthetic organisms and the formation of autochthonous organic carbon (AOC); this impacts eutrophication and the global carbon cycle. In shallow water environments where phytoplankton and submerged plants coexist, the C-N-P limitations on the primary production of these aquatic organisms, and the mechanisms by which they promote the formation of AOC are poorly understood. In this study, over the hydrological year September 2018 to August 2019, a large-scale field simulation experiment at the Shawan Karst Test Site (SW China) with various types of land use was systematically conducted to investigate the C-N-P limitations on the primary production of phytoplankton and submerged plants. The results indicate that (1) phytoplankton are co-limited by nitrogen (N) and phosphorus (P) but with the N more important, while submerged plants are limited by carbon (C); (2) Chlorophyta and Bacillariophyta display a stronger competitive advantage than Cyanophyta in aqueous environments with high C but low N-P; (3) there is a seasonal difference in the contribution of phytoplankton and submerged plants to the formation of AOC, however, throughout the year, the contributions of phytoplankton (27%) and submerged plants biomass (28%) to AOC concentrations in the water were similar, combinedly accounting for approximately 17% of the formed AOC. It is concluded that natural restoration of vegetation, or injecting CO into water, which results in higher C but lower N-P loadings, may simultaneously help to mitigate eutrophication (with changes in biological structure and species) and increase C sequestration in surface waters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.151917DOI Listing
November 2021

Photoinduced C(sp)-H chlorination of amides with tetrabutyl ammonium chloride.

Authors:
Yanshuo Zhu Wei Yu

Org Biomol Chem 2021 Nov 22. Epub 2021 Nov 22.

State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.

A new protocol was developed for the site-selective C(sp)-H chlorination of amides with tetrabutyl ammonium chloride as the chlorinating agent. The reaction features a tandem sequence that involves a (diacetoxyiodo)benzene-mediated and chloride anion-involved N-H chlorination followed by photoinitiated chlorine atom transfer. A wide variety of carboxamides and sulfonamides were chlorinated at the δ-position by using this method.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1ob02081aDOI Listing
November 2021

Clinical Trial Participation: A Pilot Study of Patient-Identified Barriers.

Clin J Oncol Nurs 2021 12;25(6):647-654

Background: Clinical trial enrollment in the United States is lacking, particularly among older adult and ethnic and racial minority populations.

Objectives: The aim of the current study was to identify patient-related barriers to clinical trial participation using a mixed-methods patient survey and to offer insights to develop evidence-based implementation strategies to address these barriers.

Methods: A retrospective survey was conducted of patients who were not interested in participating in a clinical trial to quantify the reasons these patients chose not to participate. Directed qualitative content analysis was used to identify themes that emerged from the write-in responses.

Findings: The greatest patient-reported barriers were misperceptions about placebos, a desire to not feel like a human guinea pig, uncertainty surrounding clinical trial treatment effectiveness compared to standard care, and concerns about additional appointments or tests. Oncology nurses can address patient enrollment barriers by providing targeted education and participating in the informed consent process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1188/21.CJON.647-654DOI Listing
December 2021

The correlation between lipoprotein associated phospholipase A and central overweight status.

Int J Immunopathol Pharmacol 2021 Jan-Dec;35:20587384211048562

Department of Family Medicine, 38014Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.

Objective: Being overweight is associated with an increased risk of diabetes mellitus, hypertension, and cardiovascular disease. Lipoprotein-associated phospholipase A (Lp-PLA) can independently predict the risk of cardiovascular disease. This study is aimed to investigate whether Lp-PLA was associated with an overweight status.

Methods: This was a cross-sectional study that enrolled 3760 Chinese adults (age, 18-50 years) who underwent medical examination department of Xiamen Chang-Gung Hospital (XCGH) from 2018 to 2020. To explore the distribution of overweight classifications in the Chinese population, we evaluated the correlation of the overweight status with Lp-PLA, after correcting for possible influencing factors.

Results: The Lp-PLA level was greater in male than in female subjects ( < 0.001). Subjects with a central overweight status had a greater Lp-PLA level than those with normal weight and a peripheral overweight status, in both male and female cohorts. The Lp-PLA level was significantly greater in those with additional comorbidities (namely diabetes mellitus (DM), hypertension (HTN), overweight, and metabolic syndrome (MetS)). The age-adjusted and LDL-adjusted Lp-PLA level also was significantly higher in the DM (+) and HTN (-) subgroups than in the DM (-), HTN (-), DM (-), and HTN (+) subgroups.

Conclusion: Lp-PLA is associated with sex, central overweight status, diabetes, hypertension, and MetS in adults aged < 50 years and the age-adjusted and LDL-adjusted Lp-PLA was significantly higher in the DM (+) and HTN (-) subgroups than in the DM (-) and HTN (-) and DM (-) and HTN (+) subgroups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/20587384211048562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606953PMC
November 2021

Bone Impairment in a Large Cohort of Chinese Patients with Tumor-induced Osteomalacia Assessed by HR-pQCT and TBS.

J Bone Miner Res 2021 Nov 19. Epub 2021 Nov 19.

Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Tumor-induced osteomalacia TIO is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 FGF23 by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density aBMD in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral distal radius and tibia and axial lumbar spine skeleton using high-resolution peripheral quantitative computed tomography HR-pQCT and trabecular bone score TBS and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry DXA or HR-pQCT scans were enrolled. Compared with age-, sex- and BMI-matched healthy controls, TIO patients n=113 had lower vBMD, damaged microstructure and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS <1.35 was higher than that with low L1-4 aBMD Z-score Z≤-2 43.9% vs. 89.6%, p < 0.001. Higher intact fibroblast growth factor 23 iFGF23, intact parathyroid hormone iPTH, alkaline phosphatase and β-isomerized C-terminal telopeptide of type I collagen β-CTx levels, more severe mobility impairment and a history of fracture were associated with poorer HR-pQCT parameters but not with lower TBS. However, greater height loss and longer disease duration were correlated with worse HR-pQCT parameters and TBS. Moreover, TBS was correlated with both trabecular and cortical HR-pQCT parameters in TIO. In conclusion, we revealed impaired bone microarchitecture in the axial and peripheral skeleton in a large cohort of Chinese TIO patients. HR-pQCT parameters and TBS showed promising advantages over aBMD for assessing bone impairment in patients with TIO. A longer follow-up period is needed to observe changes in bone microarchitecture after tumor resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.4476DOI Listing
November 2021

Effect of Shenfu injection on the level of acetylcholine in acute liver injury of young rats with sepsis.

Minerva Gastroenterol (Torino) 2021 Nov 18. Epub 2021 Nov 18.

Department of Pediatrics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China -

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S2724-5985.21.03064-3DOI Listing
November 2021

CircANTXR1 Contributes to the Malignant Progression of Hepatocellular Carcinoma by Promoting Proliferation and Metastasis.

J Hepatocell Carcinoma 2021 9;8:1339-1353. Epub 2021 Nov 9.

Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, People's Republic of China.

Background: Circular RNA (circRNA) is a key regulator for the malignant progression of cancer. However, the role of circRNA anthrax toxin receptor 1 (circANTXR1) in hepatocellular carcinoma (HCC) is still unclear.

Methods: Quantitative real-time PCR was performed to detect RNA expression. Cell proliferation, migration and invasion were determined using MTT assay, EdU staining, colony formation assay, wound healing assay and transwell assay. The protein levels of metastasis markers, x-ray repair cross complementing 5 (XRCC5) and exosome markers were examined using Western blot analysis. Xenograft tumor models were built to investigate the role of circANTXR1 in HCC tumorigenesis. The relationship between microRNA (miR)-532-5p and circANTXR1 or XRCC5 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. The identification of exosomes were performed using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA).

Results: CircANTXR1 was a stable and highly expressed circRNA in HCC. Silenced circANTXR1 inhibited the proliferation, migration and invasion of HCC cells in vitro, and suppressed HCC tumor growth in vivo. MiR-532-5p could be sponged by circANTXR1, and its inhibitor could reverse the inhibition of circANTXR1 silencing on HCC cells progression. In addition, we discovered that XRCC5 was a target of miR-532-5p. Furthermore, XRCC5 overexpression could reverse the suppressive effect of miR-532-5p overexpression on HCC cell proliferation, migration and invasion. Exosome was involved in the transport of circANTXR1 in HCC cells. Exosome circANTXR1 might be a potential serum biomarker for HCC patients.

Conclusion: CircANTXR1 promotes the progression of HCC through the miR-532-5p/XRCC5 axis, which might be a potential serum biomarker and therapeutic target of HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/JHC.S317256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590609PMC
November 2021

Partial nephrectomy through retroperitoneal approach with a new surgical robot system, KD-SR-01.

Int J Med Robot 2021 Nov 12:e2352. Epub 2021 Nov 12.

Department of Urology, Peking University First Hospital. Institute of Urology, Peking University, National Urological Cancer Center, Beijing, China.

Background: To present our experiences with partial nephrectomy (PN) through retroperitoneal approach (RP) with the Kangduo robotic system.

Methods: From December 2020 to February 2021, the perioperative data of 11 patients underwent PN through RP with the Kangduo robotic system were collected prospectively.

Results: For the R.E.N.A.L. nephrometry score, 72.7% of patients had a low score (4-6) and 27.3% of patients had a medium score (7-9). Seven tumours were posterior (P), four tumours were on the midline (X). All procedures were completed successfully. The median warm ischemia time was 18.5 (IQR, 13.7-21.0) min. None of the patients had positive surgical margins at definitive histology (all pT1a). No high-grade perioperative complications or device-related adverse events occurred. At a mean follow-up of 8 ± 0.8 months, no complications occurred in all patients.

Conclusions: RPPN using the novel Kangduo robotic system is a safe and effective option for managing posterior and lateral renal tumours with R.E.N.A.L. nephrometry scores ≤9.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rcs.2352DOI Listing
November 2021

Amide-Assisted Rearrangement of Hydroxyarylformimidoyl Chloride to Diarylurea.

Molecules 2021 Oct 25;26(21). Epub 2021 Oct 25.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.

A novel amide-assisted rearrangement reaction of hydroxybenzimidoyl chloride has been established for the efficient synthesis of 1,3-diphenylurea derivatives. A variety of electronically and sterically different 1,3-diphenylurea derivatives can be obtained in good to excellent yields, and a proposed reaction mechanism is also presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26216437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587945PMC
October 2021

[Establishment and application of high performance liquid chromatography-inductively coupled plasma mass spectrometry method for the determination of iodine species in serum].

Wei Sheng Yan Jiu 2021 Sep;50(5):788-798

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Objective: To establish a method for the determination of iodine species in human serum by inductively coupled plasma mass spectrometry(ICP-MS).

Methods: Total iodine was determined by ICP-MS in helium mode after dilution of serum with tetramethylammonium hydroxide solution. The serum was added to methanol solution to precipitate the protein, and the supernatant was separated by liquid chromatography(LC) followed by ICP-MS for the determination of inorganic iodine.

Results: The limit of detection(LOD) of serum I~- by ICP-MS was 0.17 μg/L, the limit of quantification(LOQ) was 0.57 μg/L, and the linear correlation coefficient R~2=0.9998; the LOD of serum IO_3~- was 0.16 μg/L, the LOQ was 0.55 μg/L, and the linear correlation coefficient R~2=0.9998.The I~- recoveries were 96.2%-104.5% for the total serum iodine assay and 93.7%-98.6% for the inorganic iodine assay. Analysis of the iodine species of the actual serum samples showed that the I~- content was 2.6-12.2 μg/L, the organic iodine content was 45.3-66.0 μg/L, and the serum samples were essentially free of IO_3~-.

Conclusion: A convenient, efficient and accurate method for the determination of serum iodine species was established using high performance liquid chromatography tandem with inductively coupled plasma mass spectrometry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2021.05.014DOI Listing
September 2021

Stepwise tracking strategy to screen ingredient from Galla Chinensis based on the "mass spectrometry guided preparative chromatography coupled with systems pharmacology".

J Ethnopharmacol 2021 Oct 30;284:114533. Epub 2021 Oct 30.

School of Pharmacy/Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Shihezi University, Shihezi, 832003, PR China; Sinopharm XinJiang Pharmaceutical Co., Ltd, Urumqi, 830000, PR China. Electronic address:

Ethnopharmacological Relevance: Galla chinensis, a traditional Chinese herbal medicine, was widely used to treat ulcerative colitis (UC) in folk prescriptions, however, its active ingredients and mechanism of action in the treatment of UC remain unclear.

Aim Of The Study: The aim of our study was to discover the lead compounds and anti-inflammatory active ingredients of Galla chinensis and clarify their molecular mechanism for UC treatment.

Materials And Methods: The ingredients of Galla chinensis were prepared by column and mass spectrometry guided preparative chromatography. Besides, the relationship among the ingredients of Galla chinensis and targets was predicted by systems pharmacology. Additionally, Lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as in vitro model. The cell viability, the level of the pro-inflammatory factors, the generation of reactive oxygen species (ROS), and trans epithelial electric resistance (TEER) values were detected to screen out the active ingredients of Galla chinensis. Moreover, 4% dextran sodium sulfate (DSS)-induced ulcerative colitis mice were used as the UC animal model. The disease activity index (DAI), pathological degree of colon tissue, activities of antioxidant-related enzymes and expression level of pro-inflammatory cytokines were performed to assess the anti-UC effects of the active ingredients. Meanwhile, the mRNA expression level of inflammatory factors and antioxidant related genes were analyzed by real-time quantitative polymerase chain reaction (Q-PCR). And the expression of nuclear factor erythroid-2 related factor 2 (Nrf2) pathway related proteins, intestinal mucosal proteins and nuclear factor kappa-B (NF-κB) pathway related proteins in colon tissues were analyzed by Western Blotting.

Results: Herein, a stepwise tracking strategy was adopted to screen out the anti-inflammatory active ingredients of Galla Chinensis based on "preparative chromatography pharmacology combined with mass spectrometry guidance and system". 11 categories of ingredients of Galla chinensis were prepared and ethyl gallate (EG) was screened out the lead compound and anti-inflammatory active ingredient of Galla Chinensis through in silico, in vitro and in vivo studies. In addition, EG had a significant therapeutic effect on ameliorating DSS-induced UC mice and protected intestinal mucosal integrity through Nrf2 and NF-κB signaling pathway.

Conclusion: Ethyl gallate was the lead compound and anti-inflammatory active ingredient in Galla chinensis. And it was discovered for the first time that EG could treat mice with ulcerative colitis. This research not only found the lead compound of Galla Chinensis for UC treatment and determined the possible mechanism, but also provided valuable references for finding lead compounds from natural products by systems pharmacology coupled with equivalent components group technology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114533DOI Listing
October 2021

Novel Androgen Receptor Inhibitors in Non-Metastatic, Castration-Resistant Prostate Cancer: A Systematic Review and Network Meta-Analysis.

Front Oncol 2021 15;11:733202. Epub 2021 Oct 15.

Department of Urology, Peking University First Hospital, Beijing, China.

Introduction: Enzalutamide, apalutamide, and darolutamide have all been approved by Food and Drug Administration to treat high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) since 2018 based on interim results of several phase III clinical trials. Final analyses of long-term overall survival (OS) and adverse events (AEs) results of these trials have been successively published recently. To help clinical practice to precisely select optimal treatment for high-risk nmCRPC patients, we performed a network meta-analysis to indirectly compare the final long-term results among these medications.

Methods: PubMed, EMBASE, and Cochrane Libraries were searched for phase III clinical trial that reports OS and AEs results in nmCRPC patients published before January 30, 2021. Primary outcome was OS; secondary outcomes were Time to first chemotherapy, Subsequent antineoplastic therapy rate, and AEs. Firstly, class-level effect was assessed as the second-generation androgen receptor antagonists (SGARAs) were regarded as one whole class compared with placebo through traditional meta-analysis by using Revman 5.4, then a Bayesian network meta-analysis was conducted to give indirect comparison among SGARAs by using R 3.5.3 software. Subgroup analysis of OS was only conducted in the certain subgroups which were available in all included studies.

Results: Three eligible studies including 4,104 participants were finally selected. OS was significantly improved by the SGARAs as a class compared with placebo (HR, 0.74; 95% CI, 0.66-0.84). Darolutamide had the highest likelihood of providing best OS (p-score=0.802). SGARAs also significantly delayed the first time to chemotherapy (HR, 0.58; 95% CI, 0.50-0.66). Patients who received darolutamide experienced similar toxicity compared with placebo regarding AEs of grade 3 or higher (OR, 1.3; 95% CI, 1.0-1.7) and serious AEs (OR, 1.3; 95% CI, 0.99-1.6). When compared with darolutamide, enzalutamide caused significantly higher toxicity in terms of any AEs (OR, 2.3; 95% CI,1.5-3.7) and AEs of grade 3 or higher (OR, 1.6; 95% CI, 1.1-2.2), apalutamide caused significantly more AEs of grade 3 or higher (OR, 1.9; 95% CI, 1.4-2.7) and serious AEs (OR, 1.9; 95% CI, 1.3-2.8). Subgroup analysis showed that SGARAs as a group significantly improved OS in ECOG=1 population, although insignificant results were found in these patients from included studies.

Conclusions: SGARAs combined with ADT significantly improved OS when compared with ADT alone in high-risk nmCRPC patients. Darolutamide may not only provide best OS but also have the most favorable safety profile among the included SGARAs in high-risk nmCRPC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.733202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555656PMC
October 2021

SPP1 Promotes Enzalutamide Resistance and Epithelial-Mesenchymal-Transition Activation in Castration-Resistant Prostate Cancer via PI3K/AKT and ERK1/2 Pathways.

Oxid Med Cell Longev 2021 22;2021:5806602. Epub 2021 Oct 22.

Department of Pharmacy, Peking University First Hospital, Beijing 100034, China.

The bottleneck arising from castration-resistant prostate cancer (CRPC) treatment is its high metastasis potential and antiandrogen drug resistance, which severely affects survival time of prostate cancer (PCa) patients. Secreted phosphoprotein 1 (SPP1) is a cardinal mediator of tumor-associated inflammation and facilitates metastasis. In our previous study, we firstly revealed SPP1 was a potential hub signature for predicting metastatic CRPC (mCRPC) development. Herein, we integrated multiple databases to explore the association of SPP1 expression with prognosis, survival, and metastatic levels in CRPC progression and investigated SPP1 expression in PCa tissues and cell lines. Next, PCa cell lines with overexpression or depletion of SPP1 were established to study the effect of SPP1 on enzalutamide sensitivity and adhesion and migration of prostate cancer cell lines and further explore the underlying regulatory mechanisms. Bioinformatics analysis, polymerase chain reaction (PCR), immunohistochemical staining, and western blot results suggested SPP1 upregulation had strong relationship with the malignant progression of CRPC and enzalutamide resistance. SPP1 knockdown enhanced enzalutamide sensitivity and repressed invasion and migration of prostate cancer cells. Importantly, upregulating SPP1 promoted, while silencing SPP1 attenuated epithelial-mesenchymal-transition (EMT). Our results further demonstrated that SPP1 overexpression maintains the activation of PI3K/AKT and ERK1/2 signaling pathways. Overall, our findings unraveled the functional role and clinical significance of SPP1 in PCa progression and help to discover new potential targets against mCRPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5806602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556132PMC
October 2021

Hepatic Stellate Cell: A Double-Edged Sword in the Liver.

Physiol Res 2021 Oct 30;70(6). Epub 2021 Oct 30.

Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.

Hepatic stellate cells (HSCs) are located in the space of Disse, between liver sinusoidal endothelia cells (LSECs) and hepatocytes. They have surprised and excited hepatologists for their biological characteristics. Under physiological quiescent conditions, HSCs are the major vitamin A-storing cells of the liver, playing crucial roles in the liver development, regeneration, and tissue homeostasis. Upon injury-induced activation, HSCs convert to a pro-fibrotic state, producing the excessive extracellular matrix (ECM) and promoting angiogenesis in the liver fibrogenesis. Activated HSCs significantly contribute to liver fibrosis progression and inactivated HSCs are key to liver fibrosis regression. In this review, we summarize the comprehensive understanding of HSCs features, including their roles in normal liver and liver fibrosis in hopes of advancing the development of emerging diagnosis and treatment for hepatic fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2021

High-Yield Exfoliation of Monolayer 1T'-MoTe as Saturable Absorber for Ultrafast Photonics.

ACS Nano 2021 Oct 29. Epub 2021 Oct 29.

Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.

Liquid-phase exfoliation can be developed for the large-scale production of two-dimensional materials for photonic applications. Although atomically thin 2D transition metal dichalcogenides (TMDs) show enhanced nonlinear optical properties or photoluminescence quantum yield relative to the bulk phase, these properties are weak in the absolute sense due to the ultrashort optical path, and they are also sensitive to layer-dependent symmetry properties. Another practical issue is that the chemical stability of some TMDs (e.g., Weyl semimetals) decreases dramatically as the thickness scales down to monolayer, precluding application as optical components in air. To address these issues, a way of exfoliating TMDs that ensures instantaneous passivation needs to be developed. Here, we employed a polymer-assisted electrochemical exfoliation strategy to synthesize PVP-passivated TMDs monolayers that could be spin coated and restacked into organic-inorganic superlattices with well-defined X-ray diffraction patterns. The segregation of restacked TMDs (e.g., MoS) by PVP allows the inversion asymmetry of individual layers to be maintained in these superlattices, which allows second harmonic generation and photoluminescence to be linearly scaled with thickness. PVP-passivated monolayer 1T'-MoTe saturable absorber fabricated from these flakes exhibits fast response and recovery time (<150 fs) and pulse stability. Continuous-wave mode-locking based on 1T'-MoTe saturable absorber in a fiber ring laser cavity has been realized, attaining a fundamental repetition rate of 3.15 MHz and pulse duration as short as 867 fs at 1563 nm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.1c08093DOI Listing
October 2021

New options for bloodstream infections caused by colistin- or ceftazidime/avibactam-resistant Klebsiella pneumoniae.

Int J Antimicrob Agents 2021 Oct 25:106458. Epub 2021 Oct 25.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Concerns regarding carbapenem-resistant Klebsiella pneumoniae (CR-Kp), especially in bloodstream infections (BSIs), are continuing to increase worldwide. Several novel agents with activity against BSI CR-Kp have been approved or are in late-stage clinical development. In this study, the antibacterial effects of ceftazidime/avibactam (CZA), aztreonam/avibactam (AZA), meropenem/vaborbactam (MEV), imipenem-cilastatin/relebactam (ICR) and eravacycline (ERV) against three colistin-resistant CR-Kp (COLR-Kp) and four CZA-resistant CR-Kp (CZAR-Kp) were tested by time-kill assay. Klebsiella pneumoniae ATCC® BAA-1705TM was used as a control strain. Two COLR-Kp isolates carried the blaKPC-2 gene and four CAZR-Kp isolates carried metallo-β-lactamase genes. The results revealed that ERV resulted in re-growth of seven tested isolates. CZA and MEV showed a bactericidal effect against isolates harbouring blaKPC-2. ICR reduced the population of six isolates to >5 log10 CFU/mL compared with the initial count. AZA showed a bactericidal effect (>5 log10 CFU/mL) against seven isolates and a bacteriostatic effect (<3 log10 CFU/mL) against one CZAR-Kp isolate. Therefore, AZA and ICR are effective therapeutic candidates for COLR-Kp and CZAR-Kp isolates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijantimicag.2021.106458DOI Listing
October 2021

19-Hydroxybufalin inhibits non-small cell lung cancer cell proliferation and promotes cell apoptosis via the Wnt/β-catenin pathway.

Exp Hematol Oncol 2021 Oct 25;10(1):48. Epub 2021 Oct 25.

School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.

Background: Bufadienolides derived from the skin of toads are often regarded as the main active components with antitumor effects. 19-Hydroxybufalin (19-HB) is a monomer of bufadienolides; however, its effects and underlying molecular mechanisms on tumor growth remain to be ascertained. In this report, we focused on the antitumor effects of 19-HB on non-small cell lung cancer to provide a scientific basis for its further development and utilization.

Methods: The antitumor effects of 19-HB on the human NSCLC cell lines NCI-H1299 and NCI-H838 were examined in vitro. The cells were treated with different concentrations of 19-HB, and the inhibition of cell growth was measured by CCK-8 and colony formation assays. Furthermore, cell apoptosis was analyzed by flow cytometry, TUNEL staining, JC-1 staining, and western blotting. The effects on migration and invasion were evaluated by wound-healing assay, transwell assay, and western blotting. Finally, the antitumor effects of 19-HB were evaluated in vivo using a xenograft mouse model.

Results: 19-HB-treated NSCLC cells showed inhibited cell viability and increased apoptosis. The expression levels of cleaved caspase-3, cleaved-PARP, and Bax/Bcl-2 were upregulated, while the mitochondrial membrane potential decreased. In contrast, migration, invasion, as well as the expression of MMP2, MMP7, MMP9, the epithelial-mesenchymal transition-related proteins N-cadherin and Vimentin, and the transcription factors Snail and Slug were inhibited. Furthermore, the expression levels of the key molecules in the Wnt/β-catenin signaling pathway (CyclinD1, c-Myc, and β-catenin) were decreased. In vivo, the growth of xenograft tumors in nude mice was also significantly inhibited by 19-HB, and there were no significant changes in biochemical indicators of hepatic and renal function.

Conclusions: 19-HB inhibited the proliferation, migration, and invasion, and promoted the apoptosis of NSCLC cells via the Wnt/β-catenin pathway. In addition, 19-HB inhibited the growth of xenograft tumors in nude mice with little toxicity to the liver and kidney. Thus, 19-HB may be a potential antitumor agent for treating NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40164-021-00243-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543904PMC
October 2021

Mouse Model of Critical Persistent Inflammation, Immunosuppression, and Catabolism Syndrome.

Shock 2021 Oct 20. Epub 2021 Oct 20.

Department of Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, China Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, China.

Abstract: Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is a growing challenge in intensive care units (ICUs). PIICS causes a severe illness with high mortality. Currently, treatment is expensive, and the outcomes are dismal. Herein, we established a PIICS model to study the disease pathophysiology and its potential treatment. Using a modified sublethal cecal ligation and puncture (CLP) to induce sepsis (day 1) and the injection of lipopolysaccharide (LPS) to induce an aggravated inflammation response (day 11), CLP + LPS mice recapitulating PIICS features were successfully generated (day 14). Adult male mice were divided into CLP + LPS, CLP + daily chronic stress (DCS), CLP, DCS, LPS, and sham control groups. A survival curve was generated, and phenotypes were analyzed using markers for catabolism, inflammation, and immunosuppression. The CLP + LPS model showed two mortality peaks (after CLP and after LPS), whereas the CLP + DCS and CLP groups showed one peak. Surviving CLP + LPS mice exhibited significantly increased catabolism and inflammatory cytokine levels and aggravated inflammation, including organ inflammation. CLP + LPS mice exhibited strong immune suppression as evidenced by decreased splenic cluster of differentiation (CD)8+ and interferon-γ+CD8+ T cell counts and a concomitant and significant increase in the myeloid-derived suppressor cell population. This CLP+LPS-induced PIICS model differs from acute sepsis models, showing two mortality peaks and a protracted course of 14 days. Compared to previous PIICS models, ours shows a re-aggravated status and higher catabolism, inflammation, and immunosuppression levels. Our aim was to use the PIICS model to simulate PIICS pathophysiology and course in the ICU, enabling investigation of its mechanism and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SHK.0000000000001878DOI Listing
October 2021

Iron-Catalyzed 1,4-Phenyl Migration/Ring Expansion of α-Azido -Phenyl Amides.

Org Lett 2021 Nov 22;23(21):8650-8654. Epub 2021 Oct 22.

State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.

Herein, we report a novel iron-catalyzed skeleton rearrangement of alkyl azides. Upon treatment with FeCl and N-heterocyclic carbene SIPr·HCl in the presence of HO and EtN, 2-azido-,-diphenylamides underwent 1,4-phenyl migration and ring expansion to give azepin-2-ones in good yield. The reaction proceeds via intramolecular nitrene cycloaddition followed by C-N cleavage, water addition, and electrocyclic ring opening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c03509DOI Listing
November 2021

Injectable hydrogel mediated delivery of gene-engineered adipose-derived stem cells for enhanced osteoarthritis treatment.

Biomater Sci 2021 Nov 9;9(22):7603-7616. Epub 2021 Nov 9.

Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.

Osteoarthritis (OA), a chronic and degenerative joint disease, remains a challenge in treatment due to the lack of disease-modifying therapies. As a promising therapeutic agent, adipose-derived stem cells (ADSCs) have an effective anti-inflammatory and chondroprotective paracrine effect that can be enhanced by genetic modification. Unfortunately, direct cell delivery without matrix support often results in poor viability of therapeutic cells. Herein, a hydrogel implant approach that enabled intra-articular delivery of gene-engineered ADSCs was developed for improved therapeutic outcomes in a surgically induced rat OA model. An injectable extracellular matrix (ECM)-mimicking hydrogel was prepared as the carrier for cell delivery, providing a favorable microenvironment for ADSC spreading and proliferation. The ECM-mimicking hydrogel could reduce cell death during and post injection. Additionally, ADSCs were genetically modified to overexpress transforming growth factor-β1 (TGF-β1), one of the paracrine factors that exert an anti-inflammatory and pro-anabolic effect. The gene-engineered ADSCs overexpressing TGF-β1 (T-ADSCs) had an enhanced paracrine effect on OA-like chondrocytes, which effectively decreased the expression of tumor necrosis factor-alpha and increased the expression of collagen II and aggrecan. In a surgically induced rat OA model, intra-articular injection of the T-ADSC-loaded hydrogel markedly reduced cartilage degeneration, joint inflammation, and the loss of the subchondral bone. Taken together, this study provides a potential biomaterial strategy for enhanced OA treatment by delivering the gene-engineered ADSCs within an ECM-mimicking hydrogel.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1bm01122gDOI Listing
November 2021

Combination of albumin concentration and neutrophil-to-lymphocyte ratio for predicting overall survival of patients with non-small cell lung cancer.

J Thorac Dis 2021 Sep;13(9):5508-5516

Department of Thoracic Surgery, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China.

Background: Lung cancer contributes significantly to the total of cancer-linked deaths globally, accounting for 1.3 million deaths each year. Preoperative albumin (Alb) concentration and neutrophil-to-lymphocyte ratio (NLR) may reflect chronic inflammation and be used to predict lung cancer outcomes.

Methods: The clinical records of 293 patients with non-small cell lung cancer (NSCLC) in Fujian Medical University Cancer Hospital & Fujian Cancer Hospital were reviewed retrospectively in this current study. Clinicopathologic pretreatment, including NLR, Glasgow prognostic score (GPS), and post-treatment value, such as tumor-node-metastasis (TNM) were documented. The cut-off finder application was employed to calculate the optimal threshold values. The significance of Alb concentration combined with NLR (COA-NLR) on the prediction of overall survival (OS) was explored using Kaplan-Meier analysis along with Cox proportional hazards.

Results: The results revealed that COA-NLR could independently assess the OS of patients with NSCLC [hazard ratio (HR) =1.952, 95% confidence interval (CI): 1.367 to 2.647, P<0.001]. Moreover, the 3-year OS rates were 87.2%, 68.5%, and 52.8% for the COA-NLR =0, COA-NLR =1, and COA-NLR =2, respectively (P<0.001).

Conclusions: Preoperative COA-NLR value can effectively stratifies prognosis in NSCLC patients by classified patients into three independent groups. It can be adopted as an effective biomarker for prognosis in NSCLC patients treated with resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd-21-1320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482340PMC
September 2021

Impact of Muscle Mass on Survival in Patients with Sepsis: A Systematic Review and Meta-Analysis.

Ann Nutr Metab 2021 Oct 15:1-7. Epub 2021 Oct 15.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Introduction: The aim of this study is to investigate the association between loss of muscle mass and prognosis of sepsis.

Methods: Six databases, including PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Ovid, were searched by the deadline of August 18, 2020. A meta-analysis was conducted on the collected data by means of a random-effects model. The quality of each included article was assessed according to the Newcastle-Ottawa Scale.

Results: Out of 1,819 references, 6 articles and 1 conference abstract were included. Sepsis patients with a loss of muscle mass or sarcopenia had higher mortality (risk ratio [RR]: 1.94, 95% confidence intervals [CI]: 1.59-2.37; I-squared = 18.7%, p < 0.001). The RR of mortality within 30 days (RR: 2.31, 95% CI: 1.78-2.99, p < 0.001) was higher than that of mortality over 30 days. Loss of psoas muscle mass, as evaluated by CT, showed the highest RR of sepsis mortality. In addition, based on data on overall survival retrieved from 4 trials, the pooled hazard ratio (HR) for patients with a loss of muscle mass or sarcopenia was 3.04. Subgroup analysis showed that survival time was the main source of heterogeneity for the overall HR. Furthermore, the scanning areas of muscle mass in survival patients were 0.33 cm2/m2 higher than those measured in deceased patients.

Conclusion: A loss of muscle mass, as evaluated by CT scan, was associated with a poor outcome in sepsis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000519642DOI Listing
October 2021

Inherited Mutations in Chinese Men With Prostate Cancer.

J Natl Compr Canc Netw 2021 Oct 15:1-9. Epub 2021 Oct 15.

1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai.

Background: Although China accounts for 7.8% of worldwide new prostate cancer (PCa) cases and 14.5% of new deaths according to GLOBOCAN 2020, the risk of PCa associated with germline mutations is poorly defined, hampered in part by lack of nationwide evidence. Here, we sequenced 19 PCa predisposition genes in 1,836 Chinese patients with PCa and estimated disease risk associated with inherited mutations.

Patients And Methods: Patients were recruited from 4 tertiary cancer centers (n=1,160) and a commercial laboratory (n=676). Germline DNA was sequenced using a multigene panel, and pathogenic/likely pathogenic (P/LP) mutation frequencies in patients with PCa were compared with populations from the gnomAD (Genome Aggregation Database) and ChinaMAP (China Metabolic Analytics Project) databases. Clinical characteristics and progression-free survival were assessed by mutation status.

Results: Of 1,160 patients from hospitals, 89.7% had Gleason scores ≥8, and 65.6% had metastases. P/LP mutations were identified in 8.49% of Chinese patients with PCa. Association with PCa risk was significant for mutations in ATM (odds ratio [OR], 5.9; 95% CI, 3.1-11.1), BRCA2 (OR, 15.3; 95% CI, 10.0-23.2), MSH2 (OR, 15.8; 95% CI, 4.2-59.6), and PALB2 (OR, 5.9; 95% CI, 2.7-13.2). Compared with those without mutations, patients with mutations in ATM, BRCA2, MSH2, or PALB2 showed a poor outcome with treatment using androgen deprivation therapy and abiraterone (hazard ratio, 2.19 [95% CI, 1.34-3.58] and 2.47 [95% CI, 1.23-4.96], respectively) but similar benefit from docetaxel.

Conclusions: The present multicenter study confirmed that a significant proportion of Chinese patients with PCa had inherited mutations and identified predisposition genes in this underreported ethnicity. These data provide empirical evidence for precision prevention and prognostic estimation in Chinese patients with PCa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6004/jnccn.2021.7010DOI Listing
October 2021

Flexor carpi radialis brevis muscle, a rare anomalous muscle of the forearm; a case report and literature review.

Am J Transl Res 2021 15;13(9):10850-10855. Epub 2021 Sep 15.

Department of Orthopedics, The Third Hospital of Mianyang·Sichuan Mental Health Center Mianyang 621000, Sichuan, China.

The flexor carpi radialis brevis (FCRB) is a rare abnormal muscle of the distal forearm or wrist. Its incidence varies in different reports, which oscillating between 2-8%. This paper reports a case of FCRB found in the anatomy of the forearm. The abnormal muscle, which started from the facies volaris distal radii, occupies the terminus of pronator quadratus, and was observed with dysplasia in the pronator quadratus. We also reviewed the literature on FCRB anatomy, especially the surgical exposure of distal radius fractures and the clinical symptoms caused by FCRB. Knowledge of the anomalous muscles of the forearm and wrist can highly improve clinician's understanding of the disease during surgery and imaging examination, and reduce unnecessary trauma caused by misdiagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507061PMC
September 2021

Identification of Novel Diagnosis Biomarkers for Therapy-Related Neuroendocrine Prostate Cancer.

Pathol Oncol Res 2021 27;27:1609968. Epub 2021 Sep 27.

Department of Urology, Peking University First Hospital Institute of Urology, National Urological Cancer Center, Peking University, Beijing, China.

Therapy-related neuroendocrine prostate cancer (NEPC) is a lethal castration-resistant prostate cancer (CRPC) subtype that, at present, lacks well-characterized molecular biomarkers. The clinical diagnosis of this disease is dependent on biopsy and histological assessment: methods that are experience-based and easily misdiagnosed due to tumor heterogeneity. The development of robust diagnostic tools for NEPC may assist clinicians in making medical decisions on the choice of continuing anti-androgen receptor therapy or switching to platinum-based chemotherapy. Gene expression profiles and clinical characteristics data of 208 samples of metastatic CRPC, including castration-resistant prostate adenocarcinoma (CRPC-adeno) and castration-resistant neuroendocrine prostate adenocarcinoma (CRPC-NE), were obtained from the prad_su2c_2019 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was subsequently used to construct a free-scale gene co-expression network to study the interrelationship between the potential modules and clinical features of metastatic prostate adenocarcinoma and to identify hub genes in the modules. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to build a model to predict the clinical characteristics of CRPC-NE. The findings were then verified in the nepc_wcm_2016 dataset. A total of 51 co-expression modules were successfully constructed using WGCNA, of which three co-expression modules were found to be significantly associated with the neuroendocrine features and the NEPC score. In total, four novel genes, including NPTX1, PCSK1, ASXL3, and TRIM9, were all significantly upregulated in NEPC compared with the adenocarcinoma samples, and these genes were all associated with the neuroactive ligand receptor interaction pathway. Next, the expression levels of these four genes were used to construct an NEPC diagnosis model, which was successfully able to distinguish CRPC-NE from CRPC-adeno samples in both the training and the validation cohorts. Moreover, the values of the area under the receiver operating characteristic (AUC) were 0.995 and 0.833 for the training and validation cohorts, respectively. The present study identified four specific novel biomarkers for therapy-related NEPC, and these biomarkers may serve as an effective tool for the diagnosis of NEPC, thereby meriting further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/pore.2021.1609968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503838PMC
September 2021

IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain.

J Thorac Oncol 2021 Oct 6. Epub 2021 Oct 6.

The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Introduction: Final overall survival (OS) analyses are presented for EGFR mutations and liver or brain metastases subgroups in the phase III IMpower150 study (NCT02366143) evaluating atezolizumab+bevacizumab+carboplatin/paclitaxel (ABCP) or atezolizumab+carboplatin/paclitaxel (ACP) vs bevacizumab+carboplatin/paclitaxel (BCP).

Methods: Overall, 1202 patients (intention-to-treat [ITT] population) with chemotherapy-naive, metastatic, nonsquamous non-small cell lung cancer were randomized to ABCP, ACP or BCP. Patients with treated, stable brain metastases were permitted. OS was assessed in EGFR mutations and baseline liver metastases subgroups; rate and time to development (TTD) of new brain metastases was assessed in ITT patients.

Results: At data cutoff (September 13, 2019; median follow-up, 39.3 months), OS improvements were sustained with ABCP versus BCP in sensitizing EGFR mutations (all: hazard ratio [HR] 0.60; 95% CI: 0.31-1.14; prior tyrosine kinase inhibitor [TKI]: HR 0.74; 95% CI: 0.38-1.46) and baseline liver metastases (HR 0.68; 95% CI: 0.45-1.02) subgroups. ACP did not show survival benefit versus BCP in sensitizing EGFR mutations (all: HR 1.0; 95% CI: 0.57-1.74; prior TKI: HR 1.22; 95% CI: 0.68-2.22) or liver metastases (HR 1.01; 95% CI: 0.68-1.51) subgroups. Overall, 100 patients (8.3%) developed new brain metastases. While not formally evaluated, an improvement toward delayed TTD was seen with ABCP vs BCP (HR, 0.68; 95% CI: 0.39-1.19).

Conclusions: This final exploratory analysis showed OS benefits for ABCP versus BCP in patients with sensitizing EGFR mutations, including those with prior TKI failures, and with liver metastases, although these results should be interpreted with caution. The impact of ABCP on delaying the development of new brain lesions requires further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2021.09.014DOI Listing
October 2021

High ORAI3 expression correlates with good prognosis in human muscle-invasive bladder cancer.

Gene 2022 Jan 7;808:145994. Epub 2021 Oct 7.

Shandong University, Jinan City, Shandong Province, China.

The involvement of store-operated calcium channels (SOCCs) in tumor initiation and metastatic dissemination has been extensively studied, but how its member ORAI3 influences tumor progression is still elusive. The present study aimed to evaluate the prognostic value of ORAI3 expression and examine the correlation between ORAI3 expression and immune cell infiltration within the tumor microenvironment (TME) in human muscle-invasive bladder cancer (MIBC). We examined the expression profile of ORAI3 in MIBC using data from two databases; analyzed the correlation between ORAI3 expression and patient survival; explored cellular pathways related to ORAI3 expression by Gene Set Enrichment Analysis (GSEA); and predicted potential drugs using Connectivity Map (CMap). ORAI3 was significantly lower expressed in tumor mass compared to normal samples in MIBC, with a higher level of methylation at the promoter region in tumor than in normal tissue, indicating that ORAI3 is suppressed during cancer progression. Survival analysis showed that higher expression of ORAI3 correlated with good prognosis in MIBC. GSEA demonstrated that ORAI3 expression inversely correlated with cell differentiation, development and gene silencing, with differential expression of genes involved in epidermal and keratinocyte differentiation pathways and inflammatory responses. RNA sequencing of an ORAI3-silenced human bladder cancer cell line (T24 cells) corroborated enhancement of pro-neoplastic pathways in absence of ORAI3. Western blottingMoreover, ORAI3 facilitated the recruitment of Th17 cells and natural killer cells, whereas hampered Th2 and macrophage infiltration. Our results revealed 4 molecules with potential to be beneficial as adjuvant drugs in MIBC treatment. We concluded that high ORAI3 expression correlates with increased survival in human MIBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2021.145994DOI Listing
January 2022
-->