Publications by authors named "Wenbo Tang"

77 Publications

Safety and effectiveness of dabigatran in routine clinical practice: the RE-COVERY DVT/PE study.

J Thromb Thrombolysis 2021 Aug 28. Epub 2021 Aug 28.

Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON, Canada.

RE-COVERY DVT/PE is a two-phase, international, observational study of anticoagulant therapy in patients with deep vein thrombosis and/or pulmonary embolism (DVT/PE). The objective of the second phase was to compare the safety and effectiveness of dabigatran versus a vitamin K antagonist (VKA) over 1 year of follow-up. Primary safety and effectiveness outcomes were major or clinically relevant nonmajor bleeding events (MBE/CRNMBEs) and symptomatic recurrent venous thromboembolism (VTE) (including deaths related to recurrent VTE). To minimize bias due to unbalanced patient characteristics, only patients in an overlapping range of estimated propensity scores were included (analytic set), and propensity score weighting was applied to compare outcomes. Outcome analysis used an as-treated approach, censoring patients after they stopped or switched their initial anticoagulant. Overall, 3009 patients enrolled from 2016 to 2018 were eligible: 60% were diagnosed with DVT alone, 21% with PE alone, and 19% with DVT plus PE. The analytic set consisted of 2969 patients. The incidence rate in %/year (95% confidence interval [CI]) of MBE/CRNMBEs was 2.63 (1.79-3.74) with dabigatran versus 4.48 (3.23-6.06) with warfarin; hazard ratio 0.63 (95% CI 0.32-1.25). For symptomatic recurrent nonfatal or fatal VTE the incidence rate was 1.53 (0.91-2.42) with dabigatran versus 2.01 (1.21-3.14) with VKAs; hazard ratio 0.78 (95% CI 0.30-2.02). In conclusion, we found lower annualized rates of MBE/CRNMBEs with dabigatran than VKA, although the difference was not statistically significant. Annualized rates of symptomatic VTE or related mortality were similar with dabigatran and VKA. These observational results with 1 year of follow-up reflect those of the randomized clinical trials. Trial registration: ClinicalTrials.gov identifier NCT02596230, first registered November 4, 2015.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-021-02463-xDOI Listing
August 2021

Early Drain Removal is Safe in Patients With Low or Intermediate Risk of Pancreatic Fistula After Pancreaticoduodenectomy: A Multicenter, Randomized Controlled Trial.

Ann Surg 2021 Jun 11. Epub 2021 Jun 11.

Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China Department of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, P.R China Department of General Surgery, Beijing Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R China Department of Hepatobiliary & Pancreatic Surgical Oncology, Chinese People's Liberation Army, General Hospital, Beijing 100853, P.R China Department of Hepato-Biliary-Pancreatic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R China Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R China Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, 06120, Halle (Saale), Germany.

Objective: This multi-center randomized controlled trial (RCT) was designed to test the hypothesis that early drain removal (EDR) could decrease the incidence of grade 2-4 complications for patients undoing pancreaticoduodenectomy (PD) with low or intermediate risk of postoperative fistula (POPF).

Background: The safety and effects of EDR on postoperative complications after PD are still controversial.

Methods: A multi-center RCT at six tertiary referral hospitals was carried out (NCT03055676). Patients who met the inclusion criteria, including drain amylase level less than 5000 U/L on postoperative day (POD) 1 and POD 3, and drain output less than 300 ml per day within 3 days after surgery, were enrolled. Patients were then randomized to the EDR group or the routine drain removal (RDR) group. In the EDR group, all drainage tubes were removed on POD3. In the RDR group, drainage tubes were removed on POD 5 or beyond. Primary outcome was the incidence of Clavien-Dindo grade 2-4 complications. Secondary outcomes were comprehensive complication index (CCI), grade B/C postoperative pancreatic fistula (POPF), total medical expenses and post-operative in-hospital stay etc., within 90 days after surgery.

Results: A total of 692 patients were screened, and 312 patients were eligible for randomization. Baseline characteristics were well balanced between the two groups and 96.8% of these 312 patients had low or intermediate risk of POPF, according to the 10-point fistula risk score. A total of 20.5% of the patients in the EDR group suffered at least one grade 2-4 complication, versus 26.3% in the RDR group (P = 0.229). Multi-variate analysis showed older age (> 65 years old) and blood transfusion were independent risk factors for grade 2-4 complications. The rate of grade B/C POPF was low in either group (3.8% vs 6.4%, P = 0.305). The CCI of the two groups was also comparable (20.9 vs 20.9, P = 0.253). Total medical expenses were not significantly different. Post-operative in-hospital stay was clinically similar (15 d vs 16 d, P = 0.010).

Conclusions: Nearly half of the patients undergoing PD met the inclusion criteria, predicting low incidence of grade B/C POPF and major complications. EDR was safe in these patients but did not significantly decrease major complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000004992DOI Listing
June 2021

Increased AOC1 Expression Promotes Cancer Progression in Colorectal Cancer.

Front Oncol 2021 5;11:657210. Epub 2021 May 5.

Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Amine oxidase copper containing 1 () is a gene whose biological function in colorectal cancer (CRC) has not been elucidated. Therefore, the purpose of this study was to investigate the clinical significance of expression in CRC and its biological function in CRC cell lines.

Materials And Methods: expression levels were examined in paired CRC and peritumoral tissues, and distant liver metastatic tissues were examined using quantitative real-time PCR, western blotting, and immunohistochemistry staining. The log-rank test and Cox regression model were used to analyze the relationship between expression and prognosis. Proliferation assays (Cell Counting Kit-8 and colony formation assays), migration assays (Transwell and wound healing assays) and xenograft tumor formation in nude mice were performed to assess the biological role of in CRC cells.

Results: expression significantly increased in human CRC tissues, especially in liver metastases, and was associated with a worse prognosis. In addition, had higher expression in tumor organoids than in normal organoids, suggesting that it was highly expressed in the tumor epithelium. Functional analysis demonstrated that knockdown inhibited the proliferation and migration of CRC cells by inducing EMT . Xenograft tumor formation in nude mice showed that knockdown of inhibited the tumor xenografts growth .

Conclusion: High expression of was significantly associated with worse clinical outcomes, was an independent risk factor for poor prognosis, and promoted aggressive CRC cell phenotypes. is expected to become a novel biomarker for predicting the prognosis of patients with CRC and an effective therapeutic target in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.657210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131869PMC
May 2021

Profile of Patients with Isolated Distal Deep Vein Thrombosis versus Proximal Deep Vein Thrombosis or Pulmonary Embolism: RE-COVERY DVT/PE Study.

Semin Thromb Hemost 2021 May 10. Epub 2021 May 10.

Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Isolated distal deep vein thrombosis (IDDVT) is presumed to be more benign than proximal DVT (PDVT) or pulmonary embolism (PE), suggesting a need for different management approaches. This subgroup analysis of the RE-COVERY DVT/PE global, observational study investigated patient characteristics, hospitalization details, and anticoagulant therapy in patients with IDDVT in real-world settings in 34 countries enrolled from January 2016 to May 2017. Data were analyzed descriptively according to the type and location of the index venous thromboembolism (VTE): IDDVT, PDVT ± distal DVT (DDVT), and PE ± DVT. Of the 6,095 eligible patients, 323 with DVT located outside the lower limb and no PE were excluded. Of the remaining 5,772 patients, 17.6% had IDDVT, 39.9% had PDVT ± DDVT, and 42.5% had PE ± DVT. IDDVT patients were younger and had fewer risk factors for VTE than the other groups. Other comorbidities were less frequent in the IDDVT group, except for varicose veins, superficial thrombophlebitis, and venous insufficiency. IDDVT patients were less likely to be diagnosed in an emergency department (22.3 vs. 29.7% for PDVT ± DDVT and 45.4% for PE ± DVT) or hospitalized for VTE (29.2 vs. 48.5% for PDVT ± DDVT and 75.0% for PE ± DVT). At hospital discharge or 14 days after diagnosis (whichever was later), non-vitamin K antagonist oral anticoagulants were the most commonly used anticoagulants (55.6% for IDDVT, 54.7% for PDVT ± DDVT, and 52.8% for PE ± DVT). Although differences in patient characteristics, risk factors, and clinical management were identified, anticoagulant treatment of IDDVT was almost equal to that of PDVT or PE. Prospective studies should investigate whether, in a global perspective, this is an appropriate use of anticoagulants. TRIAL REGISTRATION NUMBER:  ClinicalTrials.gov NCT02596230.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-1729169DOI Listing
May 2021

Patient perceptions of anticoagulant treatment with dabigatran or a vitamin K antagonist for stroke prevention in atrial fibrillation according to region and age: an exploratory analysis from the RE-SONANCE study.

J Thromb Thrombolysis 2021 Apr 30. Epub 2021 Apr 30.

Faculty of Medicine in Hradec Kralove, Charles University and Edumed s.r.o, Broumov, Czech Republic.

Background: The oral anticoagulant dabigatran offers an effective alternative to vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF), yet patient preference data are limited. The prospective observational RE-SONANCE study demonstrated that patients with AF, newly initiated on dabigatran, or switching to dabigatran from long-term VKA therapy, reported improved treatment convenience and satisfaction compared with VKA therapy. This pre-specified sub-study aimed to assess the impact of country and age on patients' perceptions of dabigatran or VKA therapy in AF.

Methods: RE-SONANCE was an observational, prospective, multi-national study (NCT02684981) that assessed treatment satisfaction and convenience in patients switching from VKAs to dabigatran (Cohort A), or newly diagnosed with AF receiving dabigatran or VKAs (Cohort B), using the PACT-Q questionnaire. Pre-specified exploratory outcomes: variation in PACT-Q2 scores by country and age (< 65, 65 to < 75, ≥ 75 years) (both cohorts); variation in PACT-Q1 responses at baseline by country and age (Cohort B).

Results: Patients from 12 countries (Europe/Israel) were enrolled in Cohort A (n = 4103) or B (n = 5369). In Cohort A, mean (standard deviation) PACT-Q2 score increase was highest in Romania (convenience: 29.6 [23.6]) and Hungary (satisfaction: 26.0 [21.4]) (p < 0.001). In Cohort B, mean (standard error) increase in PACT-Q2 scores between dabigatran and VKAs was highest in Romania (visit 3: 29.0 [1.3]; 24.5 [0.9], p < 0.001). Mean PACT-Q2 score increase by age (all p < 0.001) was similar across ages. PACT-Q1 responses revealed lowest expectations of treatment success in Romania and greatest concerns about payment in Estonia, Latvia, and Romania, but were similar across ages.

Conclusions: Treatment satisfaction and convenience tended to favor dabigatran over VKAs. Regional differences in treatment expectations exist across Europe.

Trial And Clinical Registry: Trial registration number: ClinicalTrials.gov NCT02684981. Trial registration date: February 18, 2016.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-021-02450-2DOI Listing
April 2021

Development of a rapid and sensitive UPLC-MS/MS assay for simultaneous quantitation of Vorolanib and its metabolite in human plasma and application to a pharmacokinetics study.

J Pharm Biomed Anal 2021 May 22;199:114034. Epub 2021 Mar 22.

Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address:

Vorolanib is an oral tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). A sensitive and specific LC-MS/MS assay was developed and fully validated for simultaneous quantification of vorolanib and its main metabolite X297 in human plasma. The two analytes were extracted from K2-EDTA plasma samples by protein precipitation (PP) with acetonitrile, and chromatographically separated on a C18 reverse-phase column using a gradient elution. A SCIEX 5500 QTRAP® mass spectrometer system was operated in multiple-reaction monitoring mode (MRM) and all components were detected using positive electrospray ionization (ESI). The results successfully demonstrated that the method had satisfactory linearity, sensitivity, and selectivity in the concentration ranges of vorolanib (1.00-1000 ng/mL) and X297 (0.500-500 ng/mL). In this study, two concentration related peaks in the vorolanib and X297 detection channels were observed, which were speculated to be isomers of vorolanib and X297. In order to standardize the sample pretreatment process, the effect of lamp light and pH on the isomer reconversion was evaluated. The results indicated, that the exposure of samples to lamp light during the handling procedures, did not cause the conversion of the isomers. For the first time a robust and specific ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the high-throughput quantification of vorolanib and X297 in human plasma was established and validated following bioanalytical validation guidelines. The proposed method was successfully applied to clinical trials evaluating the pharmacokinetics of vorolanib tablets in Chinese advanced solid tumor patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2021.114034DOI Listing
May 2021

Second-line Afatinib or Chemotherapy Following Immunochemotherapy for the Treatment of Metastatic, Squamous Cell Carcinoma of the Lung: Real-world Effectiveness and Safety From a Multisite Retrospective Chart Review in the USA.

Clin Lung Cancer 2021 07 16;22(4):292-300.e1. Epub 2021 Feb 16.

Division of Oncology, Saint Luke's Cancer Institute, Kansas City, MO, USA; Center for Precision Oncology, Saint Luke's Cancer Institute, Kansas City, MO, USA.

Background: The ErbB family blocker, afatinib, is approved for patients with squamous cell carcinoma (SqCC) of the lung following platinum-doublet chemotherapy but has not been explored following immunochemotherapy. Here, we assessed the characteristics and outcomes of patients with SqCC of the lung who received second-line afatinib or chemotherapy after first-line pembrolizumab plus chemotherapy in a "real-world" setting.

Methods: In this retrospective, multisite cohort study, community oncologists identified eligible patients and extracted data from electronic health records. Primary outcome measures were patient demographics and clinical characteristics, time on treatment, and incidence of severe immune-related adverse events (irAEs).

Results: Two hundred patients were included: 99 received second-line afatinib and 101 received second-line chemotherapy. Median age was 68 and 66 years, respectively; 35% and 3% of patients had mixed histology tumors, and 39% and 5% of tumors were epidermal growth factor receptor (EGFR) mutation-positive (EGFRm). Median time on treatment was 7.3 months with afatinib (mixed histology/SqCC tumors: 8.1/5.8 months; EGFRm/EGFRm tumors: 7.4/5.9 months) and 4.2 months with chemotherapy. Grade 3/4 irAEs were observed in 6 patients in the afatinib cohort (all had a prior grade 3/4 irAE during first-line therapy) and no patients in the chemotherapy cohort. The most common adverse drug reactions with afatinib were diarrhea (26%), rash (6%), stomatitis, fatigue, and nausea (5% each).

Conclusion: Encouraging time on treatment, and absence of newly diagnosed irAEs, indicate that afatinib is a treatment option following immunochemotherapy in patients with SqCC of the lung, and is currently the only approved oral agent in this setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cllc.2021.02.006DOI Listing
July 2021

Human Adipose-derived mesenchymal stem cells promote lymphocyte apoptosis and alleviate atherosclerosis via miR-125b-1-3p/BCL11B signal axis.

Ann Palliat Med 2021 Feb;10(2):2123-2133

Department of Vascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

Background: Mesenchymal stem cells (MSCs) have shown great potential in the treatment of cardiovascular diseases, with fat being a more accessible source of MSCs. This study investigated the effect of human adipose-derived mesenchymal stem cells (hMSCs-Ad) exosomes on T lymphocytes and its role in atherosclerosis (AS).

Methods: The exosomes were preliminarily isolated hMSCs-Ad and co-cultured with human H9 T lymphocytes. The effects of hMSCs-Ad exosomes on the proliferation and apoptosis of H9 were examined by performing functional experiments. The serum lipid level and inflammatory factor level in tail vein of mice were measured by biochemical analyzer and enzyme linked immunosorbent assay (ELISA) respectively.

Results: The hMSCs-Ad-derived exosomes up-regulate the expression of micro (mi)R-125b-1-3p in H9 and AS arterial tissues. miR-125b-1-3p shared a targeted binding site with B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B gene (BCL11B). miR-125b-1-3p negatively regulated the expression of BCL11B in H9, and that knocking down BCL11B in H9 promoted its apoptosis. Injection of hMSCs-Ad-derived exosomes via the tail vein effectively reduced blood lipid and inflammatory factors, and that relieved the symptoms of AS in AS model mice.

Conclusions: miR-125b-1-3p was expressed in hMSCs-Ad exosomes and can promote T lymphocyte apoptosis and alleviate AS by down-regulating BCL11B expression. It provides potential molecular targets for the clinical treatment of AS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-21-49DOI Listing
February 2021

Contrast-enhanced ultrasound to assess gallbladder polyps.

Clin Imaging 2021 Oct 11;78:8-13. Epub 2021 Feb 11.

Department of Ultrasound, the First Medical Center, Chinese PLA General Hospital, No. 28, Fuxing Road, Beijing 100853, China. Electronic address:

Purpose: To assess the value of contrast-enhanced ultrasound (CEUS) in distinguishing adenomatous gallbladder polyps from cholesterol gallbladder polyps.

Methods: A total of 164 patients with gallbladder polyps were retrospectively analyzed. All patients underwent B-mode ultrasound (US) and CEUS before cholecystectomy. Gallbladder polyps were divided into cholesterol polyp group and adenomatous polyp group according to pathology. Differences in patient's age, gender, maximum polyp size, number, presence of gallstones, vascularity and stalk width measured by US and vascular stalk width measured by CEUS were tested between the two groups. The diagnostic performance of specific US features was evaluated. The independent factors related with adenomatous polyps were analyzed by multiple logistic regression analyses.

Results: There were 114 cholesterol polyps and 50 adenomatous polyps in 164 patients analyzed in the study. Differences in maximum size, vascularity, and stalk width of the gallbladder polyp were significant between the two groups (p < 0.05), whereas differences in patient's age, gender, number of gallbladder polyp, and presence of gallstones between the two groups were not (p > 0.05). Stalk width was wider than vascular stalk width between the two groups (p < 0.05). Vascular stalk width was also statistically different between the two groups (p < 0.05). The diagnostic performance of vascular stalk width was more significant than stalk width. Only vascular stalk width and vascularity were independent factors related with adenomatous polyps.

Conclusion: Vascular stalk width measured by CEUS is more accurate than stalk width measured by grayscale US in distinguishing adenomatous polyps from cholesterol polyps.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinimag.2021.02.015DOI Listing
October 2021

Multiple time-scales of decision-making in the hippocampus and prefrontal cortex.

Elife 2021 Mar 8;10. Epub 2021 Mar 8.

Graduate Program in Neuroscience, Brandeis University, Waltham, United States.

The prefrontal cortex and hippocampus are crucial for memory-guided decision-making. Neural activity in the hippocampus exhibits place-cell sequences at multiple timescales, including slow behavioral sequences (~seconds) and fast theta sequences (~100-200 ms) within theta oscillation cycles. How prefrontal ensembles interact with hippocampal sequences to support decision-making is unclear. Here, we examined simultaneous hippocampal and prefrontal ensemble activity in rats during learning of a spatial working-memory decision task. We found clear theta sequences in prefrontal cortex, nested within its behavioral sequences. In both regions, behavioral sequences maintained representations of current choices during navigation. In contrast, hippocampal theta sequences encoded alternatives for deliberation and were coordinated with prefrontal theta sequences that predicted upcoming choices. During error trials, these representations were preserved to guide ongoing behavior, whereas replay sequences during inter-trial periods were impaired prior to navigation. These results establish cooperative interaction between hippocampal and prefrontal sequences at multiple timescales for memory-guided decision-making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.66227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993991PMC
March 2021

Roles of Non-coding RNAs in Central Nervous System Axon Regeneration.

Front Neurosci 2021 1;15:630633. Epub 2021 Feb 1.

Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China.

Axons in the central nervous system often fail to regenerate after injury due to the limited intrinsic regeneration ability of the central nervous system (CNS) and complex extracellular inhibitory factors. Therefore, it is of vital importance to have a better understanding of potential methods to promote the regeneration capability of injured nerves. Evidence has shown that non-coding RNAs play an essential role in nerve regeneration, especially long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA). In this review, we profile their separate roles in axon regeneration after CNS injuries, such as spinal cord injury (SCI) and optic nerve injury. In addition, we also reveal the interactive networks among non-coding RNAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2021.630633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882506PMC
February 2021

Value of high frame rate contrast-enhanced ultrasound in distinguishing gallbladder adenoma from cholesterol polyp lesion.

Eur Radiol 2021 Sep 10;31(9):6717-6725. Epub 2021 Feb 10.

Department of Ultrasound, the First Medical Center, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing, 100853, China.

Objectives: To compare the diagnostic value of high frame rate contrast-enhanced ultrasound (H-CEUS) in distinguishing gallbladder adenomas from cholesterol polyp lesions with that of CEUS.

Methods: This study enrolled 94 patients with gallbladder polyp lesions (GPLs) who underwent laparoscopic cholecystectomy. CEUS and H-CEUS were performed before surgery. The perfusion features of GPLs and the final diagnosis as determined by both technologies were compared.

Results: There were differences in vascular types between gallbladder adenomas and cholesterol polyp lesions observed on H-CEUS (p < 0.05), while there were no differences in vascular types between gallbladder adenomas and cholesterol polyp lesions observed on CEUS (p > 0.05). In the cholesterol polyp lesion group, there were no differences in vascular types between CEUS and H-CEUS (p > 0.05), while the vascular types were different between CEUS and H-CEUS in the gallbladder adenoma group (p < 0.05). The diagnostic value of H-CEUS in distinguishing gallbladder adenomas from cholesterol polyp lesions was better than that of CEUS.

Conclusions: H-CEUS improved the time resolution by increasing the frame rate, which helped to accurately reflect the difference in the microcirculation of GPLs and improved the ability of a differential diagnosis between cholesterol polyp lesions and adenomas. H-CUES may provide an effective means of imaging for patients with GPLs regarding the choice of treatment options.

Key Points: • High frame rate CEUS improves the time resolution of CEUS by increasing the frame rate. • High frame rate CEUS is helpful to accurately evaluate the microvascular morphology of a gallbladder polyp lesion in the arterial phase. • High frame rate CEUS helps patients with gallbladder polyp lesions to choose the appropriate treatment means.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-021-07730-2DOI Listing
September 2021

Afatinib in EGFR TKI-naïve patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer: Interim analysis of a Phase 3b study.

Lung Cancer 2021 02 17;152:127-134. Epub 2020 Dec 17.

Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.

Objectives: Randomized controlled trials have demonstrated that afatinib is a suitable treatment option for patients with epidermal growth factor receptor mutation-positive (EGFRm +) non-small cell lung cancer (NSCLC). However, such studies often exclude patients treated in routine clinical practice. We report interim results from a Phase 3b, open-label, multicenter, single-arm, exploratory trial, in which afatinib was investigated in a real-world setting.

Materials And Methods: Patients with EGFRm + tyrosine kinase inhibitor (TKI)-naïve NSCLC received afatinib 40 mg orally, once-daily, until disease progression, or voluntary withdrawal. Primary objective was safety.

Results: Overall, 479 patients received afatinib: median age 65 years, 8 % of patients had an ECOG performance status ≥ 2, 17 % had brain metastases, and 13 % had tumors containing uncommon mutations only. All but one patient (99.8 %) had an adverse event (AE). Treatment-related AEs (TRAEs; any/grade ≥ 3) occurred in 97 %/44 % of patients; most common were diarrhea (87 %/16 %) and rash (51 %/11 %). AEs leading to afatinib dose-reduction were reported in 258 patients (54 %), and 37 patients (8 %) discontinued treatment due to a TRAE. Objective response rate was 45.5 %, median duration of response was 14.1 months (95 % CI: 12.2-16.4). Overall median time to symptomatic progression and progression-free survival were 14.9 months (95 % CI: 13.8-17.6) and 13.4 months (95 % CI: 11.8-14.5), respectively, in the overall population and 19.3 months (95 % CI: 15.6-21.8) and 15.9 months (95 % CI: 13.9-19.1) in patients with EGFR exon 19 deletions.

Conclusions: Afatinib administration in routine clinical practice was well tolerated with no new safety signals and demonstrated promising efficacy in patients with EGFRm + NSCLC. TRAEs were generally manageable with tolerability-guided dose reductions. Overall, these data independently support findings from randomized controlled trials of afatinib in EGFRm + NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2020.12.011DOI Listing
February 2021

Bioinformatics analysis of long non-coding RNAs involved in nerve regeneration following sciatic nerve injury.

Mol Pain 2020 Jan-Dec;16:1744806920971918

Department of Anesthesiology, 85024Shengjing Hospital of China Medical University, Shenyang, China.

Little is known about the role of epigenetic modification in axon regeneration following peripheral nerve injury. The purpose of the present study was to investigate the role of long non-coding RNAs (lncRNAs) in the regulation of axon regeneration. We used bioinformatics to perform microarray analysis and screened total 476 lncRNAs and 129 microRNAs (miRNAs) of differentially expressed genes after sciatic nerve injury in mice. lncRNA-GM4208 and lncRNA-GM30085 were examined, and the changes in lncRNA expression in the L4-L6 dorsal root ganglia (DRG) following sciatic nerve crush injury were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of lncRNAs in the DRG changed, indicating that they might be related to nerve regeneration in the DRG following peripheral nerve injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1744806920971918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705388PMC
August 2021

Profile of patients diagnosed with acute venous thromboembolism in routine practice according to age and renal function: RE-COVERY DVT/PE study.

J Thromb Thrombolysis 2021 Apr;51(3):561-570

Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

In randomized clinical trials (RCTs) of nonvitamin K antagonist oral anticoagulants (NOACs) for acute venous thromboembolism (VTE), ~ 12-13% of patients were elderly and ~ 26% had mild-to-moderate renal impairment. Observational studies are not restricted by the selection and treatment criteria of RCTs. In this ancillary analysis of the RE-COVERY DVT/PE global observational study, we aimed to describe patient characteristics, comorbidities, and anticoagulant therapy for subgroups of age (< or ≥ 75 years) and renal impairment (creatinine clearance [CrCl; estimated with Cockcroft-Gault formula] < 30 [severe], 30 to < 50 [moderate], 50 to < 80 [mild], ≥ 80 [normal] mL/min). Of 6095 eligible patients, 25.3% were aged ≥ 75 years; 38.2% (1605/4203 with CrCl values) had mild-to-moderate renal impairment. Comorbidities were more common in older patients (73.9% aged ≥ 75 vs. 58.1% < 75 years) and in those with mild or moderate versus no renal impairment (75.9%, 80.9%, and 59.3%, respectively). At hospital discharge or 14 days after diagnosis (whichever was later), most patients (53.7% and 55.1%, respectively) in both age groups received NOACs; 20.8% and 23.4%, respectively, received vitamin K antagonists, 19.0% and 21.8% parenteral therapy, 2.3% and 3.8% other anticoagulant treatments. Use of NOACs decreased with worsening renal impairment (none 58.5%, moderate 49.6%, severe 25.7%) and, in younger versus older patients with moderate renal impairment (33.1% vs. 56.1%). In routine practice, there are more elderly and renally impaired patients with VTE than represented in RCTs. Decreasing renal function, but not older age, was associated with less NOAC use. Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT02596230. Decreasing renal function, particularly in the subgroup with CrCl < 30 mL/min, but not older age, was associated with less use of nonvitamin K antagonist oral anticoagulants (NOACs). Nevertheless, more than half of the older patients with moderate renal impairment received a NOAC as their oral anticoagulant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-020-02239-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049914PMC
April 2021

Bradykinin 1 Receptor Antagonist BI1026706 Does Not Reduce Central Retinal Thickness in Center-Involved Diabetic Macular Edema.

Transl Vis Sci Technol 2020 03 30;9(4):25. Epub 2020 Mar 30.

Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.

Purpose: The bradykinin 1 receptor may be important in inflammatory retinal vascular leakage in diabetic macular edema. BI 1026706 is an antagonist of bradykinin 1 receptor that has demonstrated efficacy in preclinical studies. Boehringer Ingelheim trial 1320.22 (NCT02732951) was a randomized, double-blind, placebo-controlled study. The pharmacodynamics, safety, and tolerability of oral BI 1026706 for 12 weeks were evaluated in patients with type 1 or type 2 diabetes mellitus and mild visual impairment owing to center-involved diabetic macular edema.

Methods: Patients ( = 105) were randomized to receive either oral BI 1026706 100 mg twice daily (morning and evening) or placebo for 12 weeks. The primary end point of the study was week 12 change from baseline in central subfield foveal thickness (CSFT) by spectral domain optical coherence tomography. Additional end points included absolute CSFT values, safety, and pharmacokinetics.

Results: After 12 weeks of treatment, there was no meaningful change from baseline in the adjusted mean CSFT in either treatment group (BI 1026706, 10.3 µm; placebo, -6.2 µm; adjusted mean treatment difference, 16.5 µm [95% confidence interval, -16.2 to 49.1]). There were also no differences in best-corrected visual acuity outcomes between treatment groups. Most reported adverse events were of mild or moderate intensity, and were balanced between treatment groups.

Conclusions: BI 1026706 was not superior to placebo in CSFT week-12 change from baseline. Therefore, BI 1026706 does not reduce CSFT, a morphologic sign of diabetic macular edema.

Translational Relevance: Kinin-kallikrein inhibition effects may not be apparent over 12 weeks for bradykinin 1 receptor inhibition alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/tvst.9.4.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396196PMC
March 2020

Making the case for EGFR TKI sequencing in mutation-positive NSCLC: a GioTag study US patient analysis.

Future Oncol 2020 Aug 6;16(22):1585-1595. Epub 2020 Aug 6.

Department of Respiratory & Critical Care Medicine, Karl Landsteiner Institute of Lung Research & Pulmonary Oncology, Vienna, Austria.

To assess time-to-treatment failure (TTF) in US patients with mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib-osimertinib treatment in the global, observational GioTag study. Patients had T790M mutation-positive disease after first-line afatinib and subsequently received osimertinib. The primary outcome was TTF. In 129 patients at US centers, median TTF was 28.4 months (90% CI: 27.0-34.1). Median overall survival was 47.6 months (90% CI: 35.5-51.5). Sequential afatinib-osimertinib in this US-treated population was associated with long median TTF and represents an effective, evidence-based treatment option for US patients with mutation-positive NSCLC not presenting with active brain metastases or T790M. : NCT03370770 (ClinicalTrials.gov).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/fon-2020-0188DOI Listing
August 2020

Profile of Patients Diagnosed With Acute Venous Thromboembolism in Routine Clinical Practice: The RE-COVERY DVT/PE™ Study.

Am J Med 2020 08 20;133(8):936-945. Epub 2020 Apr 20.

Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, Ontario, Canada; Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia.

Background: The safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) have been established in randomized controlled trials, but limited data are available on their use in clinical practice across geographical regions.

Methods: In the international RE-COVERY DVT/PE observational study (enrollment January 2016 to May 2017), we sought to characterize the patient population and describe the prescribed anticoagulant. Patient characteristics and anticoagulants administered after objective diagnosis of VTE were recorded at the baseline visit and again at hospital discharge or at 14 days after the diagnosis, whichever was later.

Results: A total of 6095 patients were included, 50.2% were male, and the mean age was 61.5 years. The most common comorbidities were hypertension (35%), diabetes mellitus (11%), cancer (11%), prior VTE(11%), and trauma/surgery (7%). Overall, 77% of patients received oral anticoagulants, with 54% on NOACs and 23% on vitamin K antagonists (VKAs); 20% received parenteral anticoagulation only. NOACs comprised about 60% of anticoagulant treatment in Europe and Asia but substantially less in Latin America (29%) and the Middle East (21%). For NOAC therapies, the distribution (as a percentage of the total cohort) was rivaroxaban 25.6%, dabigatran 15.5%, apixaban 11.3%, and edoxaban 1.7%. Treatment with NOACs was less frequent in patients who had cancer, chronic renal disease, heart failure, or stroke.

Conclusions: These findings enhance our understanding of baseline characteristics and the initial management of patients with VTE in routine practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjmed.2020.03.036DOI Listing
August 2020

Patient perception of anticoagulant treatment for stroke prevention (RE-SONANCE study).

Open Heart 2020 24;7(1):e001202. Epub 2020 Mar 24.

Department of Cardiology, General Hospital Celje, Celje, Slovenia.

Objective: We evaluated atrial fibrillation (AF) patients' perceptions of anticoagulation treatment with dabigatran or a vitamin K antagonist (VKA) for stroke prevention, according to accepted indications.

Methods: The RE-SONANCE observational, prospective, multicentre, international study used the validated Perception on Anticoagulant Treatment Questionnaire (PACT-Q) to assess patients with AF already taking a VKA who were switched to dabigatran (cohort A), and newly diagnosed patients initiated on either dabigatran or a VKA (cohort B). Visit 1 (V1) was at baseline, and visit 2 (V2) and visit 3 (V3) were at 30-45 and 150-210 days after baseline, respectively. Primary outcomes were treatment satisfaction and convenience in cohort A at V2 and V3 versus baseline, and in cohort B for dabigatran and a VKA at V2 and V3.

Results: The main analysis set comprised 4100 patients in cohort A and 5365 in cohort B (dabigatran: 3179; VKA: 2186). In cohort A, PACT-Q2 improved significantly (p<0.001 for all) for treatment convenience (mean change V1 vs V2=20.72; SD=21.50; V1 vs V3=24.54; SD=22.85) and treatment satisfaction (mean change V1 vs V2=17.60; SD=18.76; V1 vs V3=21.04; SD=20.24). In cohort B, mean PACT-Q2 scores at V2 and V3 were significantly higher (p<0.001 for all) for dabigatran versus a VKA for treatment convenience (V2=18.38; SE =0.51; V3=23.34; SE=0.51) and satisfaction (V2=15.88; SE=0.39; V3=19.01; SE=0.41).

Conclusions: Switching to dabigatran from long-term VKA therapy or newly initiated dabigatran is associated with improved patient treatment convenience and satisfaction compared with VKA therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/openhrt-2019-001202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103803PMC
June 2020

The coupling of Phanerozoic continental weathering and marine phosphorus cycle.

Sci Rep 2020 04 2;10(1):5794. Epub 2020 Apr 2.

Key Laboratory of Orogenic Belts and Crustal Evolution, MOE & School of Earth and Space Sciences, Peking University, Beijing, 100871, China.

Organic matter production and decomposition primarily modulate the atmospheric O and CO levels. The long term marine primary productivity is controlled by the terrestrial input of phosphorus (P), while the marine P cycle would also affect organic matter production. In the past 540 million years, the evolution of terrestrial system, e.g. colonization of continents by vascular land plants in late Paleozoic, would certainly affect terrestrial P input into the ocean, which in turn might have impacted the marine primary productivity and organic carbon burial. However, it remains unclear how the marine P cycle would respond to the change of terrestrial system. Here we reconstruct the secular variations of terrestrial P input and biological utilization of seawater P in Phanerozoic. Our study indicates that riverine dissolved P input and marine P biological utilization (i.e. the fraction of P being buried as organophosphorus) are inversely correlated, suggesting the coupling of continental P input and marine P cycle. We propose an increase of P input would elevate surface ocean productivity, which in turn enhances marine iron redox cycle. Active Fe redox cycle favors the scavenging of seawater P through FeOOH absorption and authigenic phosphate formation in sediments, and accordingly reduces the bioavailability of seawater P. The negative feedback of marine P cycle to terrestrial P input would keep a relatively constant organic carbon burial, limiting the variations of surface Earth temperature and atmospheric O level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-62816-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118102PMC
April 2020

MiR-638 Repressed Vascular Smooth Muscle Cell Glycolysis by Targeting LDHA.

Open Med (Wars) 2019 31;14:663-672. Epub 2019 Dec 31.

Department of Vascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Changhuai Road 287, 233003 Bengbu City, China.

Background: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) accelerated vascular diseases progression, like atherosclerosis and restenosis. MicroRNAs were reported to participate in modulating diverse cellular processes. Here, we focused on exploring the role of miR-638 in VSMCs glycolysis and underlying mechanism.

Methods: Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability. Western blot assay was conducted to determine the expression of cell proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67, as well as Lactate dehydrogenase A (LDHA). VSMCs migration and invasion were evaluated by Transwell assay. Luciferase reporter gene assay and RNA immunoprecipitation were performed to validate the target relationship between miR-638 and LDHA. LDHA and miR-638 expression were also determined. Glycolysis of VSMCs was tested by corresponding Kits.

Results: Platelet-derived growth factor-bb (PDGF-bb) promoted the VSMCs viability and down-regulated miR-638. Overexpression of miR-638 inhibited cell proliferation, migration and invasion of VSMCs. LDHA was identified as a target of miR-638, and counter-regulated by miR-638. Loss of miR-638 attenuated the suppressor effects on the proliferation, migration and invasion of VSMCs induced by LDHA down-regulation. MiR-638 inhibited the glycolysis of VSMCs by targeting LDHA.

Conclusion: MiR-638 is down-regulated by PDGF-bb treatment and suppressed the glycolysis of VSMCs via targeting LDHA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/med-2019-0077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972283PMC
December 2019

miR-107 inhibits PDGF-BB-induced proliferation of human pulmonary arterial smooth muscle cells and migration through targeting NOR1.

Int J Clin Exp Pathol 2019 1;12(5):1599-1608. Epub 2019 May 1.

Department of Vascular Surgery, The First Affiliated Hospital of Bengbu Medical College Changhuai Road 287, Bengbu 233003, China.

Background: Abnormal proliferation of PASMCs is the main phenotype of pulmonary arterial hypertension (PAH). MicroRNAs (miRNAs) were reported to participate in regulating the progression of PAH. Here, we aimed to investigate the impact of miR-107 on proliferation and migration of PASMCs and potential mechanism.

Methods: MTT assay was carried out to examine the cell viability of PASMCs. PASMC migration ability was verified through Transwell assay. RT-qPCR was performed to detect the expression of miR-107 and NOR1. Western blot was conducted to detect the expression of cell proliferation markers Ki-67, p27 and Cyclin D1, as well as NOR1. Bioinformatics analysis was conducted to verify whether the 3'-untranslated region (3'-UTR) of NOR1 contains a binding site for miR-107, and luciferase reporter assay and RNA immunoprecipitation (RIP) were employed to confirm the relationship between miR-107 and NOR1.

Results: Platelet-derived growth factor (PDGF)-BB promoted the cell viability and migration of PASMCs, and suppressed miR-107 expression in a time-dependent and concentration-dependent manner. Introduction of miR-107 inhibited the promotion of proliferation and migration of PASMCs stimulated by PDGF-BB, while loss of miR-107 facilitated PDGF-BB-induced promoted effects. NOR1 was identified as a downstream gene of miR-107 and down-regulated by miR-107. Knockout of NOR1 also repressed the promotion of proliferation and migration of PASMCs stimulated by PDGF-BB. Additionally, restoration of NOR1 attenuated the inhibition of miR-107 on the cell viability and migration ability of PASMCs.

Conclusion: miR-107 inhibits PDGF-BB-induced PASMCs proliferation and migration through targeting NOR1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947117PMC
May 2019

Machine Learning to Identify Predictors of Glycemic Control in Type 2 Diabetes: An Analysis of Target HbA1c Reduction Using Empagliflozin/Linagliptin Data.

Pharmaceut Med 2019 06;33(3):209-217

Florida Hospital Diabetes Institute, AdventHealth Translational Research Institute for Metabolism and Diabetes, 301 Princeton Ave, Orlando, FL, 32804, USA.

Introduction: Outcomes in type 2 diabetes mellitus (T2DM) could be optimized by identifying which treatments are likely to produce the greatest improvements in glycemic control for each patient.

Objectives: We aimed to identify patient characteristics associated with achieving and maintaining a target glycated hemoglobin (HbA1c) of ≤ 7% using machine learning methodology to analyze clinical trial data on combination therapy for T2DM. By applying a new machine learning methodology to an existing clinical dataset, the practical application of this approach was evaluated and the potential utility of this new approach to clinical decision making was assessed.

Methods: Data were pooled from two phase III, randomized, double-blind, parallel-group studies of empagliflozin/linagliptin single-pill combination therapy versus each monotherapy in patients who were treatment-naïve or receiving background metformin. Descriptive analysis was used to assess univariate associations between HbA1c target categories and each baseline characteristic. After the descriptive analysis results, a machine learning analysis was performed (classification tree and random forest methods) to estimate and predict target categories based on patient characteristics at baseline, without a priori selection.

Results: In the descriptive analysis, lower mean baseline HbA1c and fasting plasma glucose (FPG) were both associated with achieving and maintaining the HbA1c target. The machine learning analysis also identified HbA1c and FPG as the strongest predictors of attaining glycemic control. In contrast, covariates including body weight, waist circumference, blood pressure, or other variables did not contribute to the outcome.

Conclusions: Using both traditional and novel data analysis methodologies, this study identified baseline glycemic status as the strongest predictor of target glycemic control attainment. Machine learning algorithms provide an hypothesis-free, unbiased methodology, which can greatly enhance the search for predictors of therapeutic success in T2DM. The approach used in the present analysis provides an example of how a machine learning algorithm can be applied to a clinical dataset and used to develop predictions that can facilitate clinical decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40290-019-00281-4DOI Listing
June 2019

Fast and High Strength Soft Tissue Bioadhesives Based on a Peptide Dendrimer with Antimicrobial Properties and Hemostatic Ability.

ACS Appl Mater Interfaces 2020 Jan 14;12(4):4241-4253. Epub 2020 Jan 14.

College of Materials Science and Engineering , Nanjing Tech University , Nanjing 211816 , P.R. China.

Due to the inconvenience of application, risk of extra damage to fragile soft tissues, and the high incidence of late-stage complications, significant research endeavors have been focused on developing safe and effective bioadhesives to replace or assist the traditional suture techniques for wound closure. Here, we describe a fast and high strength bioadhesive based on polysaccharides and peptide dendrimers (OCMC/G3KP) with inherent hemostatic ability and antibacterial properties. Compared with the commercial bioadhesive Coseal, the OCMC/G3KP hydrogel shows a remarkable 5-fold increase in adhesion strength. The in vivo studies further confirm the superior wound healing performance of the OCMC/G3KP hydrogel in contrast with Coseal and conventional sutures. The OCMC/G3KP hydrogels are efficient and biocompatible bioadhesives with precise controllability that could be flexibly modulated to meet diverse clinical demands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.9b18720DOI Listing
January 2020

Dynamics of Awake Hippocampal-Prefrontal Replay for Spatial Learning and Memory-Guided Decision Making.

Neuron 2019 12 30;104(6):1110-1125.e7. Epub 2019 Oct 30.

Graduate Program in Neuroscience, Brandeis University, Waltham, MA 02453, USA; Neuroscience Program, Department of Psychology, and Volen National Center for Complex Systems, Brandeis University, Waltham, MA 02453, USA. Electronic address:

Spatial learning requires remembering and choosing paths to goals. Hippocampal place cells replay spatial paths during immobility in reverse and forward order, offering a potential mechanism. However, how replay supports both goal-directed learning and memory-guided decision making is unclear. We therefore continuously tracked awake replay in the same hippocampal-prefrontal ensembles throughout learning of a spatial alternation task. We found that, during pauses between behavioral trajectories, reverse and forward hippocampal replay supports an internal cognitive search of available past and future possibilities and exhibits opposing learning gradients for prediction of past and future behavioral paths, respectively. Coordinated hippocampal-prefrontal replay distinguished correct past and future paths from alternative choices, suggesting a role in recall of past paths to guide planning of future decisions for spatial working memory. Our findings reveal a learning shift from hippocampal reverse-replay-based retrospective evaluation to forward-replay-based prospective planning, with prefrontal readout of memory-guided paths for learning and decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2019.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923537PMC
December 2019

miR‑455 targets FABP4 to protect human endometrial stromal cells from cytotoxicity induced by hydrogen peroxide.

Mol Med Rep 2019 Dec 4;20(6):4781-4790. Epub 2019 Oct 4.

Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China.

Oxidative stress and dysregulation of antioxidant systems are associated with various complications in pregnancy. Endometriosis is a common gynecologic disease that affects women of reproductive age. Recent studies have indicated that oxidative stress may be involved in the pathophysiology of endometriosis. It has been reported that microRNAs can regulate the cellular response to oxidative stress, and mounting evidence indicates that fatty acid binding protein 4 (FABP4) plays an essential role in the regulation of systemic redox capacity. In the present study, we demonstrated that miR‑455 is a putative FABP4‑targeting miRNA. A luciferase activity assay revealed that miR‑455 can successfully bind to the 3'‑UTR of FABP4. Overexpression of miR‑455 led to the downregulation of FABP4 at both the mRNA and protein levels in a human endometrial stromal cell line. Then, the roles of miR‑455 and FABP4 in oxidative stress induced by hydrogen peroxide (H2O2) in human endometrial stromal cells were examined. We found that ectopic expression of miR‑455 protected cells from damage caused by H2O2. Further investigation found that forced expression of miR‑455 reduced the level of reactive oxygen species (ROS) and malondialdehyde (MDA), while the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‑Px) were promoted. Silencing of FABP4 also generated cytoprotective effects against H2O2 in human endometrial stromal cells. Moreover, overexpression FABP4 abrogated the miR‑455‑mediated antioxidative stress effects in cells. Taken together, we propose that miR‑455 protects human endometrial stromal cells from oxidative stress at least partly via regulation of FABP4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2019.10727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854537PMC
December 2019

First-line afatinib for advanced EGFRm+ NSCLC: Analysis of long-term responders in the LUX-Lung 3, 6, and 7 trials.

Lung Cancer 2019 07 8;133:10-19. Epub 2019 Apr 8.

National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan. Electronic address:

Objectives: In patients with advanced epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC), first-line afatinib significantly improved progression-free survival (PFS) and objective response vs. platinum-doublet chemotherapy in the phase III LUX-Lung 3 and LUX-Lung 6 trials, and significantly improved PFS, time to treatment failure and objective response vs. gefitinib in the phase IIb LUX-Lung 7 trial. We report post-hoc analyses of efficacy, safety and patient-reported outcomes (PROs) in afatinib long-term responders (LTRs) in these trials.

Methods: Treatment-naïve patients with stage IIIB/IV EGFRm + NSCLC randomized to afatinib in LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 were included in the analysis. Patients treated with afatinib for ≥ 3 years were defined as LTRs.

Results: In LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7, 24/229 (10%), 23/239 (10%) and 19/160 (12%) afatinib-treated patients were LTRs. Baseline characteristics were similar to the study populations, except for the proportions of women (LUX-Lung 3/LUX-Lung 6 only; 92/78% vs. 64% overall) and Del19-positive patients (63-79% vs. 49-58% overall). Median treatment duration among LTRs was 50, 56 and 42 months, and median PFS was 49.5, 55.5, and 42.2 months in LUX-Lung 3/LUX-Lung 6/LUX-Lung 7, respectively. Median overall survival could not be estimated. Frequency of afatinib dose reduction was consistent with the LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 overall populations. PROs were stable in LTRs, with slight improvements after 3 years of afatinib treatment vs. baseline scores.

Conclusions: In the LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 trials, 10-12% of afatinib-treated patients were LTRs. Long-term afatinib treatment was independent of tolerability-guided dose adjustment and had no detrimental impact on safety or PROs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2019.04.006DOI Listing
July 2019

Effectiveness and Postoperative Prognosis of Using Preopening and Staged Percutaneous Transluminal Angioplasty of the Inferior Vena Cava in Treating Budd-Chiari Syndrome Accompanied with Inferior Vena Cava Thrombosis.

Ann Vasc Surg 2019 Oct 12;60:52-60. Epub 2019 Jun 12.

Department of Vascular Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China.

Background: Budd-Chiari syndrome (BCS) is a rare disorder that has relatively high prevalence in the Huang-Huai area of China. Effective treatment of BCS accompanied with inferior vena cava thrombosis is challenging.

Objective: This study retrospectively analyzed the clinical effectiveness and safety of traditional open operations versus preopening and staged percutaneous transluminal angioplasty (PTA) of the inferior vena cava in treating BCS accompanied with inferior vena cava thrombosis.

Methods: Data from patients hospitalized and treated for BCS accompanied with inferior vena cava thrombosis between January 1997 and December 2017 were retrospectively analyzed. Thirty-two patients received traditional open operation (open group). Fifty-six patients received preopening and staged PTA of the inferior vena cava (PTA group). Baseline and clinical data were compared between groups. The patients were followed for up to 60 months. Postoperative recurrence rates and restenosis degree were recorded.

Results: Eighty-eight patients were included (47 males and 41 females), aged 41.82 ± 10.12 years (range 29-65). In the open group, no pulmonary arterial embolism was found during and after the operation, and the technique success rate was 100%. One patient died of intrathoracic bleeding. In the PTA group, 2 patients had shifting of thrombus in the inferior vena cava that blocked the blood flow restored by the preopening, one resulted in treatment failure, while the other had blood flow restored by dilation with a 12-mm balloon; the success rate was 55/56 (98.21%). The median follow-up time was 32 months (range 3-60). Two patients in the open group developed restenosis 2 years after operation (recurrence rate: 6.25%), and were successfully treated by balloon PTA. Seven patients in the PTA group had severe restenosis 18-42 months after operation (recurrence rate: 12.96%). No thrombosis was found in these 7 patients, and normal blood flow was restored in the inferior vena cava after balloon PTA.

Conclusions: Preopening and staged PTA of the inferior vena cava is a safe and simple method for the treatment of BCS accompanied with inferior vena cava thrombosis, with satisfactory treatment effectiveness that could be applied in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.avsg.2019.03.037DOI Listing
October 2019

Sequencing of therapy following first-line afatinib in patients with EGFR mutation-positive non-small cell lung cancer.

Lung Cancer 2019 06 10;132:126-131. Epub 2019 Apr 10.

Internal Medicine III, Wakayama Medical University, 811-1 Kimiidera, Wakayama-shi, Wakayama-ken, 641-8509, Japan. Electronic address:

Objectives: With the availability of several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), sequential therapy could potentially render EGFR mutation-positive non-small cell lung cancer a chronic disease in some patients. In this retrospective analysis of EGFR mutation-positive (Del19/L858R) patients receiving first-line afatinib in LUX-Lung 3, 6, and 7, we assessed uptake of, and outcomes following, subsequent therapies including the third-generation EGFR TKI, osimertinib.

Methods: Post-progression therapy data were prospectively collected during follow-up. Molecular testing of tumours at progression/discontinuation of afatinib was not mandatory. Duration of subsequent therapies, and survival following osimertinib, were calculated with Kaplan-Meier estimates.

Results: Among 553 patients who discontinued first-line afatinib, second-, third- and fourth-line therapy was administered in 394 (71%), 265 (48%), and 156 (28%) patients. The most common post-progression therapy was platinum-based chemotherapy (46%). Thirty-seven patients received subsequent osimertinib, 10 as second-line treatment. Median progression-free survival on afatinib in these 37 patients was 21.9 months. Median duration of osimertinib therapy was 20.2 months; median overall survival was not reached after a median follow-up of 4.7 years.

Conclusions: Most patients treated with first-line afatinib received subsequent therapy. Although limited by sample size, enrichment, and a retrospective nature, data from patients who received sequential afatinib and osimertinib are encouraging, warranting further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2019.04.014DOI Listing
June 2019

Long noncoding RNA myocardial infarction associated transcript promotes the development of thoracic aortic by targeting microRNA-145 via the PI3K/Akt signaling pathway.

J Cell Biochem 2019 09 15;120(9):14405-14413. Epub 2019 Apr 15.

Department of Vascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

The main aim of our study was to investigate the roles and molecular basis of long noncoding RNA myocardial infarction associated transcript (MIAT) in the development of thoracic aortic aneurysm. RT-qPCR assay was performed to measure the expressions of MIAT, microRNA-145 (miR-145), along with Bcl-2 and Bcl-xl messenger RNAs. Western blot assay was conducted to determine protein levels of Bcl-2, Bcl-xl, phosphorylated-Akt (p-Akt), and total Akt (t-Akt). Cell viability was detected by the (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The relationship of MIAT and miR-145 was examined by bioinformatics analysis and luciferase reporter assay. MIAT expression was significantly increased, and miR-145 expression was markedly reduced in thoracic aortic aneurysms compared with normal thoracic aortic tissues. MIAT overexpression or miR-145 depletion improved cell viability and inhibited cell apoptosis in human aortic vascular smooth muscle cells (h-VSMCs). Further exploration revealed that MIAT could inhibit miR-145 expression by direct interaction. And miR-145 upregulation abrogated MIAT-induced viability increase and apoptosis inhibition in h-VSMCs. Moreover, MIAT inhibited the activation of Akt signaling, while this effect was abated by miR-145 overexpression in h-VSMCs. The inhibition of the Akt pathway by MK-22062HCl resulted in the reduction of cell viability and the increase of cell apoptotic activity in h-VSMCs. Akt activation by HY-18749 improved cell viability and suppressed cell apoptosis in h-VSMCs. And the introduction of HY-18749 raised cell viability and curbed cell apoptosis in h-VSMCs cotransfected with MIAT overexpression plasmid and miR-145 mimic. lncRNA-MIAT could target miR-145 to affect the viability and apoptosis of h-VSMCs, which was implicated in the regulation of the PI3K/Akt signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.28695DOI Listing
September 2019
-->