Publications by authors named "Yan Kong"

298 Publications

Association of NRAS Mutation With Clinical Outcomes of Anti-PD-1 Monotherapy in Advanced Melanoma: A Pooled Analysis of Four Asian Clinical Trials.

Front Immunol 2021 5;12:691032. Epub 2021 Jul 5.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China.

Background: Anti-PD-1 monotherapy is the standard therapy for advanced melanoma patients, including those with NRAS mutations. The influence of NRAS mutation on immunotherapy, especially in noncutaneous melanoma, is largely uncharacterized.

Materials And Methods: We analyzed clinical data of four clinical trials for advanced melanoma patients treated with anti-PD-1 monotherapy between 2016 and 2019. The impact of NRAS mutation on efficacy and outcome of immunotherapy were analyzed in cutaneous and noncutaneous groups separately.

Results: A total of 206 patients were assessed, including 92 cutaneous melanoma patients with 12 NRAS mutations and 114 noncutaneous melanoma patients with 21 NRAS mutations. In cutaneous melanoma, the response rates of NRAS mutant patients were lower than patients without NRAS mutations (9.5% . 23.9%), the median progression-free survival (PFS) and median overall survival (OS) were shorter for patients with NRAS mutations, although without significant difference for OS (P=0.081). In noncutaneous melanoma, the response rates were 0 and 13.7% for NRAS mutant and wild-type patients, the median PFS were 3.6 months (95% CI: 0.9-6.3) and 4.3 months (95%CI: 2.9-5.7) (P=0.015), and the median OS were 10.8 months (95% CI: 1.5-20.1) and 15.3 months (95% CI: 13.2-17.4) (P=0.025), respectively. In multivariate analysis, NRAS mutation, along with ECOG performance score and LDH level, was negatively associated with both PFS (HR 1.912, P=0.044) and OS (HR 2.210, P=0.025) in noncutaneous melanoma.

Conclusion: In advanced Asian melanoma treated with anti-PD-1 monotherapy, NRAS mutant patients had lower response rates and poorer prognoses compared to wild-type patients, especially in noncutaneous subtypes.
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http://dx.doi.org/10.3389/fimmu.2021.691032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289467PMC
July 2021

Gadolinium enhancement of atherosclerotic plaque in the intracranial artery.

Neurol Res 2021 Jul 6:1-10. Epub 2021 Jul 6.

Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

: Gadolinium enhancement on high resolution magnetic resonance imaging (HR-MRI) has been considered a sign of instability and inflammation of intracranial atherosclerotic plaques. Our research objective was to explore the relationship between the extent of plaque enhancement (PE), the degree of intracranial artery stenosis, and acute ischemic stroke events. HR-MRI was performed in 91 patients with intracranial vascular stenosis to determine the existence and intensity of PE. Among 91 patients enrolled in the trial, there were 43 patients in the acute/subacute group (≤1 month from ischemic stroke event), 15 patients in the chronic group (>1 month from ischemic stroke event), and 33 patients in the non-culprit plaques group (no ischemic stroke event). A total of 105 intracranial atherosclerotic plaques were detected in 91 patients. 14 (13.3%) were mild-stenosis plaques, 22 (21.0%) were moderate-stenosis plaques, and 69 (65.7%) were severe-stenosis plaques. There were 12 (11.4%), 18 (17.1%), and 75 (71.4%) plaques in the non-enhanced plaque group, the mild-enhancement group, and the significant-enhancement group, respectively. The degree of PE among the acute/subacute group, the chronic group, and the non-culprit plaque group had a significant difference (P = 0.005). Enhanced plaques were more often observed in culprit plaques (acute/subacute group and chronic group) than non-culprit plaques (96.7% vs 77.3%). Non-enhanced plaques were more often observed in non-culprit plaques than culprit plaques (acute/subacute group and chronic group) (22.7% vs 3.3%). And 36.6% of the enhanced plaques were non-culprit plaques. After performing univariate and multivariate logistic regression analysis, the results showed that strong plaque enhancement (P = 0.025, odds ratio [OR] 3.700, 95% confidence interval [95% CI] 1.182-11.583) and severe stenosis (P = 0.008, OR 4.393, 95%CI 1.481-13.030) were significantly associated with acute ischemic events. Enhanced plaques were more often observed in culprit plaques, and non-enhanced plaques were more often observed in non-culprit plaques. Moreover, significant plaque enhancement and severe ICAS were closely associated with acute ischemic events.
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http://dx.doi.org/10.1080/01616412.2021.1949682DOI Listing
July 2021

Prevalence of Research Misconduct and Questionable Research Practices: A Systematic Review and Meta-Analysis.

Sci Eng Ethics 2021 Jun 29;27(4):41. Epub 2021 Jun 29.

School of Humanities and Social Sciences, University of Science and Technology of China, Jinzhai Road 96, Hefei, 230026, Anhui, People's Republic of China.

Irresponsible research practices damaging the value of science has been an increasing concern among researchers, but previous work failed to estimate the prevalence of all forms of irresponsible research behavior. Additionally, these analyses have not included articles published in the last decade from 2011 to 2020. This meta-analysis provides an updated meta-analysis that calculates the pooled estimates of research misconduct (RM) and questionable research practices (QRPs), and explores the factors associated with the prevalence of these issues. The estimates, committing RM concern at least 1 of FFP (falsification, fabrication, plagiarism) and (unspecified) QRPs concern 1 or more QRPs, were 2.9% (95% CI 2.1-3.8%) and 12.5% (95% CI 10.5-14.7%), respectively. In addition, 15.5% (95% CI 12.4-19.2%) of researchers witnessed others who had committed at least 1 RM, while 39.7% (95% CI 35.6-44.0%) were aware of others who had used at least 1 QRP. The results document that response proportion, limited recall period, career level, disciplinary background and locations all affect significantly the prevalence of these issues. This meta-analysis addresses a gap in existing meta-analyses and estimates the prevalence of all forms of RM and QRPs, thus providing a better understanding of irresponsible research behaviors.
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http://dx.doi.org/10.1007/s11948-021-00314-9DOI Listing
June 2021

REPAID: resolution-enhanced plenoptic all-in-focus imaging using deep neural networks.

Opt Lett 2021 Jun;46(12):2896-2899

Due to limited depth-of-focus, classical 2D images inevitably lose details of targets out of depth-of-focus, while all-in-focus images break through the limit by fusing multi-focus images, thus being able to focus on targets in extended depth-of-view. However, conventional methods can hardly obtain dynamic all-in-focus imaging in both high spatial and temporal resolutions. To solve this problem, we design REPAID, meaning resolution-enhanced plenoptic all-in-focus imaging using deep neural networks. In REPAID, multi-focus images are first reconstructed from a single-shot plenoptic image, then upsampled using specially designed deep neural networks suitable for real scenes without ground truth to finally generate all-in-focus image in both high temporal and spatial resolutions. Experiments on both static and dynamic scenes have proved that REPAID can obtain high-quality all-in-focus imaging when using simple setups only; therefore, it is a promising tool in applications especially intended for imaging dynamic targets in large depth-of-view.
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http://dx.doi.org/10.1364/OL.430272DOI Listing
June 2021

Risk Models for Advanced Melanoma Patients Under Anti-PD-1 Monotherapy- Analyses of Pooled Data From Two Clinical Trials.

Front Oncol 2021 20;11:639085. Epub 2021 May 20.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma, Peking University Cancer Hospital and Institute, Beijing, China.

The best response and survival outcomes between advanced melanoma patients treated with the anti-PD-1 monotherapy vary greatly, rendering a risk model in need to optimally stratify patients based on their likelihood to benefit from the said treatment. We performed an analysis of 89 advanced melanoma patients treated with the anti-PD-1 monotherapy from two prospective clinical trials at the Peking University Cancer Hospital from April 2016 to May 2018. Clinicodemographical characteristics, baseline and early-on-treatment (median 0.6 months after anti-PD-1 monotherapy initiation) routine laboratory variables, including complete blood count and general chemistry, and best response/survival data were extracted and analyzed in both univariate and multivariate logistic and Cox proportional hazard models. After three rounds of screening, risk factors associated with a poorer PFS included a high pre-treatment neutrophil, derived neutrophil-lymphocyte ratio (dNLR), low pre-treatment hemoglobin, and low early-on-/pre-treatment fold change of eosinophil; those with a poorer OS included a high pre-treatment neutrophil, eosinophil, PLT, early-on/pre-treatment fold change of LDH and neutrophil; and those with a poorer best response included a high pre-treatment NLR and early-on-/pre-treatment LDH fold change. Risk models (scale: low, median-low, median high, and high risk) were established based on these risk factors as dichotomous variables and M stage (with vs. without distant metastasis) for PFS (HR 1.976, 95% CI, 1.507-2.592, < 0.001), OS (HR 2.348, 95% CI, 1.688-3.266), and non-responder (OR 3.586, 95% CI, 1.668-7.713, = 0.001), respectively. For patients with low, median-low, median-high, and high risks of developing disease progression (PD), six-month PFS rates were 64.3% (95% CI, 43.5-95.0%), 37.5% (95% CI, 22.4-62.9%), 9.1% (95% CI, 3.1-26.7%), and 0%, respectively. For patients with OS risks of low, median-low, median-high, and high, OS rates at 12 months were 82.5% (95% CI, 63.1-100%), 76.6% (95% CI, 58.4-100%), 42.1% (95% CI, 26.3-67.3%), and 23.9% (95% CI, 11.1-51.3%), respectively. For patients with risks of low, median-low, median-high, and high of being a non-responder, objective response rates were 50.0% (95% CI, 15.7-84.3%), 27.8% (95% CI, 9.7-53.5%), 10.3% (95% CI, 2.9-24.2%), and 0%, respectively. A risk scoring model based on the clinicodemographical characteristics and easily obtainable routinely tested laboratory biomarkers may facilitate the best response and survival outcome prediction and personalized therapeutic decision making for the anti-PD-1 monotherapy treated advanced melanoma patients in Asia.
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http://dx.doi.org/10.3389/fonc.2021.639085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174451PMC
May 2021

Tight Covalent Organic Framework Membranes for Efficient Anion Transport via Molecular Precursor Engineering.

Angew Chem Int Ed Engl 2021 Jun 1. Epub 2021 Jun 1.

Key Laboratory for Green Chemical Technology of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.

Fabricating covalent organic frameworks (COFs) membranes with tight structure, which can fully utilize well-defined framework structure and thus achieve superior conduction performance, remains a grand challenge. Herein, through molecular precursor engineering of COFs, we reported the fabrication of tight COFs membrane with the ever-reported highest hydroxide ion conductivity over 200 mS cm at 80 °C, 100 % RH. Six quaternary ammonium-functionalized COFs were synthesized by assembling functional hydrazides and different aldehyde precursors. In an organic-aqueous reaction system, the impact of the aldehyde precursors with different size, electrophilicity and hydrophilicity on the reaction-diffusion process for fabricating COFs membranes was elucidated. Particularly, more hydrophilic aldehydes were prone to push the reaction zone from the interface region to the aqueous phase of the reaction system, the tight membranes were thus fabricated via phase-transfer polymerization process, conferring around 4-8 times the anion conductivity over the loose membranes via interfacial polymerization process.
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http://dx.doi.org/10.1002/anie.202105190DOI Listing
June 2021

Scalable Fabrication of Crystalline COF Membranes from Amorphous Polymeric Membranes.

Angew Chem Int Ed Engl 2021 Jun 1. Epub 2021 Jun 1.

Key Laboratory for Green Chemical Technology of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.

Covalent organic framework (COF) membranes hold potential for widespread applicability, but scalable fabrication is challenging. Here, we demonstrate the disorder-to-order transformation from amorphous polymeric membrane to crystalline COF membrane via monomer exchange. Solution processing is used to prepare amorphous membrane and the replacing monomer is selected based on the chemical and thermodynamical stability of the final framework. Reversible imine bonds allow the extraneous monomers to replace the pristine monomers within amorphous membrane, driving the transformation from disordered network to ordered framework. Incorporation of intramolecular hydrogen bonds enables the crystalline COF to imprint the amorphous membrane morphology. The COF membranes harvest proton conductivity up to 0.53 S cm at 80 °C. Our strategy bridges amorphous polymeric and crystalline COF membranes for large-scale fabrication of COF membranes and affords guidance on materials processing.
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http://dx.doi.org/10.1002/anie.202102965DOI Listing
June 2021

Genetic alteration of Chinese patients with rectal mucosal melanoma.

BMC Cancer 2021 May 27;21(1):623. Epub 2021 May 27.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Fucheng Road No.52, Haidian District, Peking, 100142, Beijing, People's Republic of China.

Background: Rectal mucosal melanoma (RMM) is a rare and highly aggressive disease with a poor prognosis. Due to the rarity of RMM, there are few studies focusing on its genetic mechanism. This retrospective study aimed to analyze the genetic spectrum and prognosis of RMM in China and lay a foundation for targeted therapy.

Methods: 36 patients with primary RMM from Peking University Cancer Hospital were enrolled in this study. The Next-generation sequencing (NGS) data of the tumor samples were fitted into the TruSight™ Oncology 500 (TSO500) Docker pipeline to detect genomic variants. Then, the univariate and multivariate Cox hazard analysis were performed to evaluate the correlations of the variants with the overall survival (OS), along with Kaplan-Meier and log-rank test to determine their significance.

Results: BRAF mutations, NRG1 deletions and mitotic index were significant prognostic factors in the univariate analysis. In multivariable analysis of the OS-related prognostic factors in primary RMM patients, it revealed 2 significant alterations: BRAF mutations [HR 7.732 (95%CI: 1.735-34.456), P = 0.007] and NRG1 deletions [HR 14.976 (95%CI: 2.305-97.300), P = 0.005].

Conclusions: This is the first study to show genetic alterations exclusively to Chinese patients with RMM. We confirmed genetic alterations of RMM differ from cutaneous melanoma (CM). Our study indicates that BRAF and NRG1 were correlated with a poor prognostic of RMM and may be potential therapeutic targets for RMM treatment.
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http://dx.doi.org/10.1186/s12885-021-08383-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161925PMC
May 2021

Berberine Slows the Progression of Prediabetes to Diabetes in Zucker Diabetic Fatty Rats by Enhancing Intestinal Secretion of Glucagon-Like Peptide-2 and Improving the Gut Microbiota.

Front Endocrinol (Lausanne) 2021 7;12:609134. Epub 2021 May 7.

National Health Council (NHC) Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.

Background: Berberine is a plant alkaloid that has multiple beneficial effects against intestine inflammation. In our previous study, we have found that berberine also possesses an antidiabetic effect. However, whether berberine is useful in the prevention of type 2 diabetes mellitus (T2DM) through its effect on intestine endocrine function and gut microbiota is unclear.

Aim: To investigate the effects of berberine in the prevention of T2DM, as well as its effects on intestine GLP-2 secretion and gut microbiota in ZDF rats.

Methods: Twenty Zucker Diabetic Fatty (ZDF) rats were fed a high-energy diet until they exhibited impaired glucose tolerance (IGT). The rats were then divided into two groups to receive berberine (100 mg/kg/d; berberine group) or vehicle (IGT group) by gavage for 3 weeks. Five Zucker Lean (ZL) rats were used as controls. Fasting blood glucose (FBG) was measured, an oral glucose tolerance test was performed, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated. Intestinal expression of TLR-4, NF-κB, TNF-α, mucin, zona occludens-1 (ZO-1) and occludin were assessed (immunohistochemistry). Plasma levels and glutamine-induced intestinal secretion of glucagon-like peptide-1 (GLP-1) and GLP-2 were measured (enzyme-linked immunosorbent assay). The plasma lipopolysaccharide (LPS) level was measured. Fecal DNA extraction, pyrosequencing, and bioinformatics analysis were performed.

Results: After 3 weeks of intervention, diabetes developed in all rats in the IGT group, but only 30% of rats in the berberine group. Treatment with berberine was associated with reductions in food intake, FBG level, insulin resistance, and plasma LPS level, as well as increases in fasting plasma GLP-2 level and glutamine-induced intestinal GLP-2 secretion. Berberine could increase the goblet cell number and villi length, and also reverse the suppressed expressions of mucin, occludin, ZO-1 and the upregulated expressions of TLR-4, NF-κB and TNF-α induced in IGT rats (P<0.05). Berberine also improved the structure of the gut microbiota and restored species diversity.

Conclusion: Berberine may slow the progression of prediabetes to T2DM in ZDF rats by improving GLP-2 secretion, intestinal permeability, and the structure of the gut microbiota.
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http://dx.doi.org/10.3389/fendo.2021.609134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138858PMC
May 2021

Effects of a theory of planned behavior-based intervention on breastfeeding behaviors after cesarean section: A randomized controlled trial.

Int J Nurs Sci 2021 Apr 24;8(2):152-160. Epub 2021 Mar 24.

Qingdao Women and Children's Hospital, Qingdao, China.

Objectives: To examine the efficacy of an intervention based on the theory of planned behavior (TPB) in improving breastfeeding behavior among women with cesarean sections (C-sections).

Methods: This research was a randomized controlled trial. Women with planned elective C-sections were recruited to participate in a randomized controlled trial between June and September 2020. One hundred thirty-two women were divided randomly into the intervention ( = 66) and control group ( = 66) by systematic random sampling. In the intervention group, an intervention project was implemented after the C-section to establish positive breastfeeding attitudes, cultivate supportive subjective norms, enhance perceived behavioral control, and strengthen breastfeeding intention to change behaviors. Those in the control group received routine pre-and post-delivery care. Exclusive breastfeeding rate and breast problem were collected at 5 days, 2 weeks, and 1 month after C-section. The modified Breastfeeding Attrition Prediction Tool (BAPT) on the first day in the hospital, two weeks, and one month after C-section and Numerical Rating Scale (NRS) 24 h postoperatively were used to compare the intervention effect between the two groups.

Results: After the intervention, the intervention group had significantly higher exclusive breastfeeding rates than the control group at five days (86.4% vs. 60.6%), two weeks (77.3% vs. 57.6%), and one month (74.2% vs. 50.0%) after the C-section. Besides, the intervention group was less likely to have sore nipples at five days (6.1% vs. 18.2% in the control group,  < 0.05) and two weeks (9.1% vs. 12.1% in the control group,  < 0.05). After two weeks of intervention, attitude scores (90.64 ± 8.31 vs. 87.20 ± 8.15,  < 0.05), subjective norm scores (88.07 ± 24.65 vs. 79.42 ± 19.47,  < 0.05)and behavior control scores in the intervention group were significantly higher than those in the control group. After one month of intervention, attitude scores (90.34 ± 10.35 vs. 84.22 ± 10.51,  < 0.05) and behavior control scores (43.13 ± 5.02 vs. 39.15 ± 4.69,  < 0.05)in the intervention group were significantly higher than those in the control group, which resulted in the higher breastfeeding intention in the intervention group.

Conclusion: This study indicated that the TPB-based interventions effectively improved women's breastfeeding behaviors after C-sections.
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http://dx.doi.org/10.1016/j.ijnss.2021.03.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105542PMC
April 2021

Clinical significance of CCNE1 copy number gain in acral melanoma patients.

Melanoma Res 2021 08;31(4):352-357

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing.

Copy number variations are frequently observed in cell cycle-related genes in acral melanoma. However, the clinical significance of copy number gain of CCNE1 in acral melanoma has not been fully elucidated. In this study, 490 acral melanoma samples were examined for CCNE1 copy number using the QuantiGenePlex DNA Assay. Correlation between CCNE1 copy number and acral melanoma patients' clinicopathologic features were analyzed using Chi-squared test. The impact of CCNE1 copy number on patients' progression-free survival (PFS) and overall survival (OS) probability were analyzed using Kaplan-Meier analysis. The impact of CCNE1 copy number on patients' median PFS after receiving chemotherapy was also evaluated. The results showed that CCNE1 copy number gain was observed in 28.30% of patients, with 3.16% of patients carrying both CCNE1 copy number gain and BRAF mutation and 4.34% of patients carrying both CCNE1 copy number gain and NRAS mutation. The median PFS time for patients with CCNE1 copy number gain was shorter than that of patients without CCNE1 copy number gain (17.0 vs. 27.0 months, P = 0.002).In the cohort that received chemotherapy (n = 82), the median PFS time for patients with CCNE1 copy number gain was shorter than that of patients without CCNE1 copy number gain (4.8 vs. 7.4 months, P = 00.006). CCNE1 copy number gain was an independent prognostic marker for acral melanoma patients' PFS. Our study indicates that CCNE1 copy number gain is frequent in acral melanoma and may be a biomarker to predict acral melanoma patients' outcomes after receiving chemotherapy.
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http://dx.doi.org/10.1097/CMR.0000000000000742DOI Listing
August 2021

The relationship between COVID-19's severity and ischemic stroke: a systematic review and meta-analysis.

Neurol Sci 2021 Jul 5;42(7):2645-2651. Epub 2021 May 5.

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

Objective: We aim to determine the risk of acute ischemic stroke in patients with severe and non-severe coronavirus disease 2019 (COVID-19).

Methods: A literature search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases until October 28, 2020. Studies covering COVID-19's severity classification data and COVID-19 patients with acute ischemic stroke were included. Two independent evaluators extracted data, and the random effects model was used to calculate the risk ratios (RR) and 95% confidence interval (95% CI) of acute ischemic stroke associated with COVID-19's severity.

Results: A total of 8 studies were included, involving 5266 patients. Among all COVID-19 patients, the total incidence of ischemic stroke was 1.76% (95% CI: 0.82-3.01). Severe patients have an increased risk of acute ischemic stroke compared with non-severe patients (RR = 3.53, 95% CI: 2.06-6.07, P < 0.0001; I = 12%). This association was also observed when COVID-19's severity was defined by clinical parameters (RR 2.91, 95% CI: 1.17-7.26, P = 0.02; I = 29%) and the need for intensive care (RR 4.47, 95% CI: 2.40-8.31, P < 0.0001; I = 0%).

Conclusions: This meta-analysis shows that the severe course of COVID-19 is associated with an increased risk of acute ischemic stroke.
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http://dx.doi.org/10.1007/s10072-021-05299-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098783PMC
July 2021

Long intergenic noncoding RNA 00665 promotes proliferation and inhibits apoptosis in colorectal cancer by regulating miR-126-5p.

Aging (Albany NY) 2021 04 20;13(10):13571-13584. Epub 2021 Apr 20.

Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, People's Republic of China.

Long intergenic noncoding RNAs (lincRNAs) regulate a series of biological processes, and their anomalous expression plays critical roles in the progression of multiple malignancies, including colorectal cancer (CRC). Although many studies have reported the oncogenic function of LINC00665 in multiple cancers, few studies have explored its role in CRC. The aim of this study was to assess the effect of LINC00665 on the malignant behaviors of CRC and explore the underlying regulatory mechanism of LINC00665. LINC00665 was significantly upregulated in CRC. A loss-of-function assay revealed that LINC00665 downregulation inhibited the proliferation and promoted the apoptosis of CRC cells, which was mediated by cyclin D1, CDK4, caspase-9 and caspase-3. Through mechanistic exploration, we found that miR-126-5p directly bound to LINC00665. Moreover, LINC00665 and miR-126-5p both regulated PAK2 and FZD3 expression. Mechanistically, miR-126-5p was predicted and further verified as a target of both PAK2 and FZD3. These findings demonstrate that LINC00665 might play an important pro-proliferative and antiapoptotic role in CRC and might be a potential biomarker and a new therapeutic target for CRC.
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http://dx.doi.org/10.18632/aging.202874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202867PMC
April 2021

In vivo self-assembled small RNAs as a new generation of RNAi therapeutics.

Cell Res 2021 Jun 29;31(6):631-648. Epub 2021 Mar 29.

Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, Chinese Academy of Medical Sciences Research Unit of Extracellular RNA, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Institute of Artificial Intelligence Biomedicine, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.

RNAi therapy has undergone two stages of development, direct injection of synthetic siRNAs and delivery with artificial vehicles or conjugated ligands; both have not solved the problem of efficient in vivo siRNA delivery. Here, we present a proof-of-principle strategy that reprogrammes host liver with genetic circuits to direct the synthesis and self-assembly of siRNAs into secretory exosomes and facilitate the in vivo delivery of siRNAs through circulating exosomes. By combination of different genetic circuit modules, in vivo assembled siRNAs are systematically distributed to multiple tissues or targeted to specific tissues (e.g., brain), inducing potent target gene silencing in these tissues. The therapeutic value of our strategy is demonstrated by programmed silencing of critical targets associated with various diseases, including EGFR/KRAS in lung cancer, EGFR/TNC in glioblastoma and PTP1B in obesity. Overall, our strategy represents a next generation RNAi therapeutics, which makes RNAi therapy feasible.
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http://dx.doi.org/10.1038/s41422-021-00491-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169669PMC
June 2021

Palbociclib in advanced acral melanoma with genetic aberrations in the cyclin-dependent kinase 4 pathway.

Eur J Cancer 2021 May 23;148:297-306. Epub 2021 Mar 23.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma, Peking University Cancer Hospital & Institute, Beijing, China. Electronic address:

Background: Genetic aberrations in the cyclin-dependent kinase (CDK)4 pathway occur in 82% of patients with acral melanoma (AM), which is the predominant subtype of melanoma in China. We aimed to evaluate the anti-tumour activity of palbociclib, a selective CDK4/6 inhibitor, in patients with advanced AM with CDK4 pathway gene aberrations.

Methods: In this phase II trial, patients with advanced AM with CDK4 or/and CCND1 gain or/and CDKN2A loss were treated with oral palbociclib (125 mg) on days 1-21 of a 28-day cycle. The primary end-point was overall response rate (ORR). Secondary end-points were progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Whole-exome sequencing and multiplex immunohistochemistry of the available formalin-fixed, paraffin-embedded samples of nine patients were analysed to explore the predictive biomarkers of palbociclib response.

Results: Fifteen patients were enrolled. Three (20.0%) patients achieved tumour shrinkage at 8 weeks, including one with confirmed partial response. At data cut-off date, treatment was ongoing for one patient. The median PFS was 2.2 mo (range: 1.5-13.3 mo; 95% confidence interval [CI]: 1.9-2.5), and the median OS was 9.5 mo (range: 2.6-14.1 mo, 95% CI: 5.7-13.4). Eight patients died due to disease progression. The most common TRAEs were leukopenia (87%; Grade III/IV, 27%), neutropenia (80%; grade III/IV, 27%), and fatigue (53%; grade III/IV, 7%). Significant JAK2 deletions and SH2B3 amplifications were observed in patients who did not achieve any clinical benefit (CB) with palbociclib treatment. MCM7 amplification or protein expression level was found to be associated with CB.

Conclusions: Palbociclib monotherapy demonstrated preliminary efficacy and an acceptable safety profile in advanced AM patients with CDK4 pathway aberrations. Patients with amplification or high protein levels of MCM7 were more prone to benefit from palbociclib. The JAK-STAT pathway might play a role in the mechanism of action of palbociclib in AM.

Trial Registration Number: NCT03454919.

The Date Of Registration: March 6, 2018.
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http://dx.doi.org/10.1016/j.ejca.2021.02.021DOI Listing
May 2021

Serum Levels of S100A11 and MMP-9 in Patients with Epithelial Ovarian Cancer and Their Clinical Significance.

Biomed Res Int 2021 3;2021:7341247. Epub 2021 Mar 3.

Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.

Objective: To investigate the serum levels of calgizzarin (S100A11) and matrix metalloproteinase-9 (MMP9) in patients with epithelial ovarian cancer (EOC) and determine their clinical significance.

Methods: Serum levels of S100A11 and MMP9 were detected in patients with EOC, patients with benign ovarian tumor, and healthy women. The correlation between the two markers and clinicopathological characteristics of ovarian cancer was analysed.

Results: The serum levels of S100A11 and MMP-9 in patients with EOC were higher than those in patients with benign ovarian tumor and in healthy women, and the expression levels of S100A11 and MMP-9 were positively correlated. S100A11 and MMP-9 were correlated with tumor staging, postoperative residual foci, ascites volume, serum CA125 level, chemotherapy response, and lymph node metastasis, while S100A11 and MMP-9 were not associated with the bilevel classification, histological type, age, and degree of differentiation.

Conclusion: S100A11 and MMP-9 were both highly expressed in the serum of patients with EOC and were associated with cancer development, invasion, and metastasis. Therefore, they can be used as an important reference maker in the diagnosis and treatment of ovarian cancer.
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http://dx.doi.org/10.1155/2021/7341247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952149PMC
May 2021

Gastrointestinal stromal tumor with multisegmental spinal metastases as first presentation: A case report and review of the literature.

World J Clin Cases 2021 Feb;9(6):1490-1498

Department of Orthopedics, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China.

Background: Gastrointestinal stromal tumor (GIST) usually originates in the stomach, followed by the small intestine, rectum, and other parts of the gastrointestinal tract. The most common sites of metastasis are the liver and peritoneum, whereas spinal metastases from GIST are extremely rare.

Case Summary: We found a case of GIST with the first presentation of multilevel spinal metastases involving the thoracic and lumbar vertebrae. A 61-year-old Chinese man presented to our clinic because of pain in his lower back and hip for 10 d without cause. Subsequently, computed tomography (CT) and magnetic resonance imaging (MRI) revealed abnormal signals in the vertebral appendages of T12 and L4 accompanied by spinal canal stenosis, which was considered as tumor metastasis. As there were no metastases to vital organs, posterior thoracic and lumbar spinal decompression + adnexal mass resection + pedicle internal fixation was adopted to achieve local cure and prevent nerve compression. The results of histopathological studies were consistent with the metastasis of GIST. No local recurrence or new metastases were found at the 6-mo follow-up at the surgical site. The patient has no neurological symptoms at present. It is worth mentioning that a rectal mass was found and surgically removed 1 mo after the patient was discharged from hospital, and the pathological diagnosis of the mass was GIST.

Conclusion: By reviewing 26 previously reported cases of spinal metastasis in GIST, it was found that spinal metastasis of GIST has become more common in recent years, so the possibility of early spinal metastasis should be recognized. CT and MRI are of great value in the diagnosis of spinal metastatic tumors, and pathological biopsy is the gold standard for the diagnosis of metastatic tumors. It is safe and feasible to treat isolated spinal metastasis in GIST by excising metastatic masses, decompressing the spinal canal, and stabilizing the spine.
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http://dx.doi.org/10.12998/wjcc.v9.i6.1490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896676PMC
February 2021

Inhibition of the Otub1/c-Maf axis by the herbal acevaltrate induces myeloma cell apoptosis.

Cell Commun Signal 2021 02 24;19(1):24. Epub 2021 Feb 24.

Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People's Republic of China.

Background: The oncogenic transcript factor c-Maf is stabilized by the deubiquitinase Otub1 and promotes myeloma cell proliferation and confers to chemoresistance. Inhibition of the Otub1/c-Maf axis is a promising therapeutic target, but there are no inhibitors reported on this specific axis.

Methods: A luciferase assay was applied to screen potential inhibitors of Otub1/c-Maf. Annexin V staining/flow cytometry was applied to evaluate cell apoptosis. Immunoprecipitation was applied to examine protein ubiquitination and interaction. Xenograft models in nude mice were used to evaluate anti-myeloma activity of AVT.

Results: Acevaltrate (AVT), isolated from Valeriana glechomifolia, was identified based on a bioactive screen against the Otub1/c-Maf/luciferase system. AVT disrupts the interaction of Otub1/c-Maf thus inhibiting Otub1 activity and leading to c-Maf polyubiquitination and subsequent degradation in proteasomes. Consistently, AVT inhibits c-Maf transcriptional activity and downregulates the expression of its target genes key for myeloma growth and survival. Moreover, AVT displays potent anti-myeloma activity by triggering myeloma cell apoptosis in vitro and impairing myeloma xenograft growth in vivo but presents no marked toxicity.

Conclusions: The natural product AVT inhibits the Otub1/c-Maf axis and displays potent anti-myeloma activity. Given its great safety and efficacy, AVT could be further developed for MM treatment. Video Abstract.
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http://dx.doi.org/10.1186/s12964-020-00676-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905600PMC
February 2021

Boosting Electroreduction Kinetics of Nitrogen to Ammonia via Tuning Electron Distribution of Single-Atomic Iron Sites.

Angew Chem Int Ed Engl 2021 Apr 5;60(16):9078-9085. Epub 2021 Mar 5.

Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.

Electrocatalytic nitrogen reduction reaction (NRR) plays a vital role for next-generation electrochemical energy conversion technologies. However, the NRR kinetics is still limited by the sluggish hydrogenation process on noble-metal-free electrocatalyst. Herein, we report the rational design and synthesis of a hybrid catalyst with atomic iron sites anchored on a N,O-doped porous carbon (Fe -NO-C) matrix of an inverse opal structure, leading to a remarkably high NH yield rate of 31.9 μg  h  mg and Faradaic efficiency of 11.8 % at -0.4 V for NRR electrocatalysis, outperformed almost all previously reported atomically dispersed metal-nitrogen-carbon catalysts. Theoretical calculations revealed that the observed high NRR catalytic activity for the Fe -NO-C catalyst stemmed mainly from the optimized charge-transfer between the adjacent O and Fe atoms homogenously distributed on the porous carbon support, which could not only significantly facilitate the transportation of N and ions but also effectively decrease the binding energy between the isolated Fe atom and *N intermediate and the thermodynamic Gibbs free energy of the rate-determining step (*N → *NNH).
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http://dx.doi.org/10.1002/anie.202100526DOI Listing
April 2021

Ratio of the interferon-γ signature to the immunosuppression signature predicts anti-PD-1 therapy response in melanoma.

NPJ Genom Med 2021 Feb 4;6(1). Epub 2021 Feb 4.

Peking University Cancer Hospital and Institute, Beijing, China.

Immune checkpoint inhibitor (ICI) treatments produce clinical benefit in many patients. However, better pretreatment predictive biomarkers for ICI are still needed to help match individual patients to the treatment most likely to be of benefit. Existing gene expression profiling (GEP)-based biomarkers for ICI are primarily focused on measuring a T cell-inflamed tumor microenvironment that contributes positively to the response to ICI. Here, we identified an immunosuppression signature (IMS) through analyzing RNA sequencing data from a combined discovery cohort (n = 120) consisting of three publicly available melanoma datasets. Using the ratio of an established IFN-γ signature and IMS led to consistently better prediction of the ICI therapy outcome compared to a collection of nine published GEP signatures from the literature on a newly generated internal validation cohort (n = 55) and three published datasets of metastatic melanoma treated with anti-PD-1 (n = 54) and anti-CTLA-4 (n = 42), as well as in patients with gastric cancer treated with anti-PD-1 (n = 45), demonstrating the potential utility of IMS as a predictive biomarker that complements existing GEP signatures for immunotherapy.
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http://dx.doi.org/10.1038/s41525-021-00169-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862369PMC
February 2021

Clinical analysis of 12 cases of ovarian cystic mature teratoma with malignant transformation into squamous cell carcinoma.

J Int Med Res 2021 Feb;49(2):300060520981549

235960The Affiliated Hospital of Qingdao University, Department of Gynecology, Qingdao, China.

Objective: This study aimed to examine the clinicopathological characteristics, treatment, and prognostic factors in 12 cases of malignant transformation of mature cystic teratoma of the ovary (MCTO).

Methods: We performed a retrospective study of 12 patients with malignant transformation of MCTO who were admitted to the Affiliated Hospital of Qingdao University from 2003 to 2019. We examined case records, clinical parameters, and biological assessments.

Results: The median age of the patients was 56.5 years and seven of them were postmenopausal. The average tumor size was 18.5 cm. All patients had pelvic masses at their first hospital visit. Nine of the patients had discomfort in the lower abdomen, two presented with a lower abdominal palpable mass, and three were complicated by fever. The median follow-up time was 73 months (12‒193 months). Ten patients survived with a disease-free status and two died.

Conclusions: There is a low incidence of malignant transformation of MCTO, and its most common histological type is squamous cell carcinoma. Age and tumor size are important factors in malignant transformation of teratomas. While there is a lack of treatment guidelines for malignant transformation of MCTO, early diagnosis and treatment may be beneficial for these patients.
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http://dx.doi.org/10.1177/0300060520981549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871074PMC
February 2021

Insertable cardiac monitors for detection of atrial fibrillation after cryptogenic stroke: a meta-analysis.

Neurol Sci 2021 Feb 2. Epub 2021 Feb 2.

Department of Neurology, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou, Jiangsu, China.

Background: In recent years, the implantable cardiac monitors (ICM) have enhanced the recognition ability of atrial fibrillation (AF), which makes ICM have a new application in AF detection. We conducted a meta-analysis to determine the total incidence of newly found AF detected by ICM after cryptogenic stroke and to evaluate the factors related to the detection of AF.

Methods: A literature search was conducted in the PubMed, EMBASE, Web of Science, and Cochrane library databases until March 1, 2020. Studies that reported the detection rate of AF using ICM in cryptogenic stroke patients with negative initial AF screening were analyzed.

Results: A total of 23 studies were included. The overall proportion of AF detected by ICM in cryptogenic stroke patients was 25% (95% confidence interval [CI], 22-29%). The rate of AF detected by ICM was independently related to both cardiac monitoring time (coefficient = 0.0003; 95% CI, 0.0001-0.0005; P = 0.0001) and CHADS-VASc score (coefficient = 0.0834; 95% CI, 0.0339-0.1329; P = 0.001). In subgroup analysis, we found a significant difference in the detection rate of AF for monitoring duration (< 6 months: 9.6% [95% CI, 4.4-16.4%]; ≥ 6 and ≤ 12 months: 19.3% [95% CI, 15.9-23.0%]; > 12 and ≤ 24 months: 23.6% [95% CI, 19.9-27.5%]; > 24 months and ≤ 36 months: 36.5% [95% CI, 24.2-49.9%]; P < 0.001), and continent (Europe: 26.5% [95% CI, 22.2-31.0%]; North America: 16.0% [95% CI, 10.3-22.6%]; Asia: 17.4% [95% CI, 12.4-23.0%]; P = 0.005).

Conclusions: The longer the time of ICM monitoring after cryptogenic stroke, the higher the detection rate of AF. Further research is still needed to determine the optimal duration of long-term cardiac monitoring.
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http://dx.doi.org/10.1007/s10072-021-05104-6DOI Listing
February 2021

NTRK fusion analysis reveals enrichment in Middle Eastern BRAF wild-type PTC.

Eur J Endocrinol 2021 04;184(4):503-511

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Objective: Fusions involving neurotrophic tyrosine receptor kinase (NTRK) are known oncogenic drivers in a broad range of tumor types. It recently gained attention as a predictor of targeted therapy since selective NTRK inhibitors are now approved in the US and Europe for patients with solid tumors harboring gene fusions. However, estimation of NTRK gene fusion/alteration frequency and its clinicopathological characteristics in papillary thyroid cancer (PTC) is limited, especially in a population with high incidence for PTC like Middle Eastern population. This study aims to characterize the NTRK gene fusion frequency and investigate the utility of pan-Trk immunohistochemistry (IHC) as predictor of NTRK fusion in a large cohort of Middle Eastern PTC.

Methods: FISH analysis for NTRK gene fusions and pan-Trk IHC was performed on 315 Middle Eastern PTCs. Correlation of NTRK gene fusion and protein expression with clinicopathological markers and patient outcome were determined.

Results: In our cohort, 6.0% (19/315) patients showed NTRK gene fusions and were significantly associated with pediatric PTC (P = 0.0143), lymph node metastasis (P = 0.0428) and BRAF WT tumors (P < 0.0001). Pan-Trk IHC was positive in 9.2% (29/315) of cases and significantly associated with NTRK fusions, with a sensitivity of 73.7% and specificity of 94.9% in this cohort.

Conclusions: This study confirms the presence of NTRK fusions in Middle Eastern PTC which is significantly enriched in BRAF WT as well as pediatric age group and proposes the usefulness of IHC to screen for PTC patients with NTRK fusion that might benefit from TRK inhibitors.
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http://dx.doi.org/10.1530/EJE-20-1345DOI Listing
April 2021

Promoting Breastfeeding and Lactation Among Mothers of Premature Newborns in a Hospital in China.

Nurs Womens Health 2021 Feb 13;25(1):21-29. Epub 2021 Jan 13.

Objective: To promote breastfeeding and lactation in mothers separated from their premature infants admitted to the NICU in a hospital in China.

Design: For this evidence-based practice project we used a mixed method of survey measures and interviews and were guided by the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research Into Practice framework.

Setting/local Problem: Obstetric unit of a Women and Children's Hospital in China from September 2017 to August 2018. Before the project, the partial breastfeeding rate in the hospital was 17.9%, and the exclusive breastfeeding rate of premature infants was 1.8%; these rates were much lower than the national breastfeeding rate in the country.

Participants: Seventeen nurses and 70 mothers of premature infants.

Intervention/measurements: The project included three phases: (a) finding the best evidence to promote breastfeeding in the literature and identifying the gaps between best practice and current practice, (b) implementing best practice strategies, and (c) comparing pre- and postintervention outcomes. Based on the evidence in the literature and the barriers, strategies were implemented in practice to promote breastfeeding and lactation among women separated from their preterm newborns. Chi-square and t tests were performed to compare the pre-/postintervention differences.

Results: Partial breastfeeding rates increased from 17.9% to 52.7%, and exclusive breastfeeding rates increased from 1.8% to 4.1%. Compliance with breastfeeding guidelines and measures of maternal lactation volume both improved significantly.

Conclusion: Promoting breastfeeding and lactation among mothers of premature infants requires not only scientific knowledge but also a caring environment and family-centered practice.
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http://dx.doi.org/10.1016/j.nwh.2020.11.005DOI Listing
February 2021

Randomized Phase II Study of Bevacizumab in Combination With Carboplatin Plus Paclitaxel in Patients With Previously Untreated Advanced Mucosal Melanoma.

J Clin Oncol 2021 Mar 14;39(8):881-889. Epub 2021 Jan 14.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Beijing, China.

Purpose: Mucosal melanoma (MM) is a highly vascularized tumor with an extremely poor prognosis. In this randomized, open-label, phase II study, we characterized the efficacy and safety of bevacizumab in combination with carboplatin plus paclitaxel (CPB) in patients with previously untreated advanced MM.

Patients And Methods: Patients were randomly assigned in a 2:1 ratio to receive carboplatin (area under the curve, 5) plus paclitaxel (175 mg/m) once every 4 weeks in combination with (CPB arm, 5 mg/kg) or without (CP arm) bevacizumab once every 2 weeks. Progression-free survival (PFS) was the primary end point. Secondary end points included overall survival (OS), objective response rate, and adverse events.

Results: We recruited 114 patients to our study. The median PFS was significantly longer in the CPB arm (4.8 months; 95% CI, 3.6 to 6.0 months) than in the CP arm (3.0 months; 95% CI, 1.7 to 4.3 months) (hazard ratio, 0.461; 95% CI, 0.306 to 0.695; < .001). Objective response rates were 19.7% and 13.2%, respectively ( = .384). The median OS was also significantly longer in the CPB arm than in the CP arm (13.6 9.0 months; hazard ratio, 0.611; 95% CI, 0.407 to 0.917; = .017). No new safety signals were observed.

Conclusion: PFS and OS were significantly better in patients with metastatic MM who received bevacizumab in addition to CPB than in those who received CPB alone. A phase III study should be performed to confirm these benefits (ClinicalTrials.gov identifier: NCT02023710).
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http://dx.doi.org/10.1200/JCO.20.00902DOI Listing
March 2021

Modulating proteasome inhibitor tolerance in multiple myeloma: an alternative strategy to reverse inevitable resistance.

Br J Cancer 2021 02 30;124(4):770-776. Epub 2020 Nov 30.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.

Background: Resistance to proteasome inhibitors (PIs) is a major obstacle to the successful treatment of multiple myeloma (MM). Many mechanisms have been proposed for PI resistance; however, our mechanistic understanding of how PI resistance is inevitably acquired and reversed remains incomplete.

Methods: MM patients after bortezomib relapse, MM cell lines and mouse models were used to generate matched resistant and reversed cells. RNA sequencing and bioinformatics analyses were employed to assess dysregulated epigenetic regulators. In vitro and in vivo procedures were used to characterise PI-tolerant cells and therapeutic efficacy.

Results: Upon PI treatment, MM cells enter a slow-cycling and reversible drug-tolerant state. This reversible phenotype is associated with epigenetic plasticity, which involves tolerance rather than persistence in patients with relapsed MM. Combination treatment with histone deacetylase inhibitors and high-dosage intermittent therapy, as opposed to sustained PI monotherapy, can be more effective in treating MM by preventing the emergence of PI-tolerant cells. The therapeutic basis is the reversal of dysregulated epigenetic regulators in MM patients.

Conclusions: We propose an alternative non-mutational PI resistance mechanism that explains why PI relapse is inevitable and why patients regain sensitivity after a 'drug holiday'. Our study also suggests strategies for epigenetic elimination of drug-tolerant cells.
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http://dx.doi.org/10.1038/s41416-020-01191-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884794PMC
February 2021

A new nomogram for individualized prediction of the probability of hemorrhagic transformation after intravenous thrombolysis for ischemic stroke patients.

BMC Neurol 2020 Nov 24;20(1):426. Epub 2020 Nov 24.

Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.

Background: A reliable scoring tool to detect the risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis for ischemic stroke is warranted. The present study was designed to develop and validate a new nomogram for individualized prediction of the probability of hemorrhagic transformation (HT) in patients treated with intravenous (IV) recombinant tissue plasminogen activator (rt-PA).

Methods: We enrolled patients who suffered from acute ischemic stroke (AIS) with IV rt-PA treatment in our emergency green channel between August 2016 and July 2018. The main outcome was defined as any type of intracerebral hemorrhage according to the European Cooperative Acute Stroke Study II (ECASS II). All patients were randomly divided into two cohorts: the primary cohort and the validation cohort. On the basis of multivariate logistic model, the predictive nomogram was generated. The performance of the nomogram was evaluated by Harrell's concordance index (C-index) and calibration plot.

Results: A total of 194 patients with complete data were enrolled, of whom 131 comprised the primary cohort and 63 comprised the validation cohort, with HT rate 12.2, 9.5% respectively. The score of chronic disease scale (CDS), the global burden of cerebral small vascular disease (CSVD), National Institutes of Health Stroke Scale (NIHSS) score ≥ 13, and onset-to-treatment time (OTT) ≥ 180 were detected important determinants of ICH and included to construct the nomogram. The nomogram derived from the primary cohort for HT had C- Statistics of 0.9562 and the calibration plot revealed generally fit in predicting the risk of HT. Furthermore, we made a comparison between our new nomogram and several other risk-assessed scales for HT with receiver operating characteristic (ROC) curve analysis, and the results showed the nomogram model gave an area under curve of 0.9562 (95%CI, 0.9221-0.9904, P < 0.01) greater than HAT (Hemorrhage After Thrombolysis), SEDAN (blood Sugar, Early infarct and hyper Dense cerebral artery sign on non-contrast computed tomography, Age, and NIHSS) and SPAN-100 (Stroke Prognostication using Age and NIHSS) scores.

Conclusions: This proposed nomogram based on the score of CDS, the global burden of CSVD, NIHSS score ≥ 13, and OTT ≥ 180 gives rise to a more accurate and more comprehensive prediction for HT in patients with ischemic stroke receiving IV rt-PA treatment.
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http://dx.doi.org/10.1186/s12883-020-02002-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685652PMC
November 2020

Chemotherapy combined with antiangiogenic drugs as salvage therapy in advanced melanoma patients progressing on PD-1 immunotherapy.

Transl Oncol 2021 Jan 19;14(1):100949. Epub 2020 Nov 19.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China. Electronic address:

Background: This study aimed to evaluate the effect of salvage therapy with nab-paclitaxel (nab-p) or temozolomide (TMZ) combined with antiangiogenic drugs in programmed death 1 (PD-1) inhibitor-resistant patients with unresectable metastatic melanoma.

Methods: We conducted a retrospective review of 69 metastatic melanoma patients who received nab-p or TMZ combined with antiangiogenic drugs after developing PD-1 inhibitor resistance and were treated at the Beijing Cancer Hospital between 2016 and 2019. The disease control rate (c-DCR) and progression-free survival (c-PFS) of salvage CA (chemotherapy combined with antiangiogenic drugs) regimens were investigated. Univariate and multivariate analyses were performed to evaluate the clinical pathological factors affecting the outcomes. Then, a nomogram was formulated to predict the probability of 3-month and 6-month c-PFS based on the multivariate analysis results.

Results: The c-DCR was 63.8%, and the median c-PFS was 3.0 months. In the univariate analysis, factors associated with the c-DCR were included the melanoma subtype, baseline platelet-to-lymphocyte ratio (PLR) and best response status to PD-1 inhibitors. Factors influencing c-PFS included age, baseline lactic dehydrogenase, PLR, neutrophil-to-lymphocyte ratio (NLR), PFS duration of anti-PD-1 therapy (p-PFS), and the best response and progression pattern of PD-1 inhibitors. In the multivariate analysis, age <65 years, heterogeneous progression pattern and baseline PLR<200 were significantly associated with improved c-PFS. The concordance index (C-index) of the nomogram was equal to 0.65 (95% CI 0.566-0.734).

Conclusions: CA regimens demonstrated promising effects in PD-1 inhibitor-resistant patients. The nomogram could be a valuable predictive module for salvage therapy choice in PD-1 inhibitor-resistant patients.
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http://dx.doi.org/10.1016/j.tranon.2020.100949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689327PMC
January 2021

An exploration of the breastfeeding behaviors of women after cesarean section: A qualitative study.

Int J Nurs Sci 2020 Oct 20;7(4):419-426. Epub 2020 Jul 20.

College of Nursing at East Carolina University, Greenville, NC, USA.

Objectives: To explore the factors affecting breastfeeding behaviors in women after cesarean section.

Methods: This is a qualitative study that used a phenomenological approach. This study used individual face-to-face interviews with 19 women who underwent a cesarean section in a Women and Children's Hospital in China between July to September 2019. Information saturation was used to determine sample size. Data were analyzed using a thematic content analysis method. Themes were developed based on the theory of planned behavior.

Results: Thirteen (68.42%) had a planned cesarean section, and six (31.58%) cesarean sections were unplanned or emergent. Three major themes emerged: ambivalent attitude about breastfeeding, motivation to comply with the traditional cultural norms, and barriers and challenges. The motivating factors for breastfeeding after cesarean sections included perceived benefits of human milk, support from healthcare professionals, and responsibility for breastfeeding. The challenges for breastfeeding after cesarean sections included physical discomfort, knowledge and skills deficit of breastfeeding, lactation deficiency, and lack of knowledge and coping skills in managing their depressive mood after cesarean sections. There were a couple of neutral factors, such as the influences of family and peers. These factors could influence women either positively as facilitators or negatively as barriers.

Conclusions: The findings can offer valuable information for healthcare professionals to help women breastfeed after cesarean sections. To promote women's breastfeeding behaviors after cesarean sections, it is necessary to change women's attitudes, belief systems, and the external environments and help them become more confident.
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http://dx.doi.org/10.1016/j.ijnss.2020.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644566PMC
October 2020

Nuclear Segmentation in Histopathological Images Using Two-Stage Stacked U-Nets With Attention Mechanism.

Front Bioeng Biotechnol 2020 26;8:573866. Epub 2020 Oct 26.

SJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Nuclei segmentation is a fundamental but challenging task in histopathological image analysis. One of the main problems is the existence of overlapping regions which increases the difficulty of independent nuclei separation. In this study, to solve the segmentation of nuclei and overlapping regions, we introduce a nuclei segmentation method based on two-stage learning framework consisting of two connected Stacked U-Nets (SUNets). The proposed SUNets consists of four parallel backbone nets, which are merged by the attention generation model. In the first stage, a Stacked U-Net is utilized to predict pixel-wise segmentation of nuclei. The output binary map together with RGB values of the original images are concatenated as the input of the second stage of SUNets. Due to the sizable imbalance of overlapping and background regions, the first network is trained with cross-entropy loss, while the second network is trained with focal loss. We applied the method on two publicly available datasets and achieved state-of-the-art performance for nuclei segmentation-mean Aggregated Jaccard Index (AJI) results were 0.5965 and 0.6210, and F1 scores were 0.8247 and 0.8060, respectively; our method also segmented the overlapping regions between nuclei, with average AJI = 0.3254. The proposed two-stage learning framework outperforms many current segmentation methods, and the consistent good segmentation performance on images from different organs indicates the generalized adaptability of our approach.
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http://dx.doi.org/10.3389/fbioe.2020.573866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649338PMC
October 2020
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