Publications by authors named "Ling Dai"

73 Publications

Synthesis of Imidazoles and Oxazoles via a Palladium-Catalyzed Decarboxylative Addition/Cyclization Reaction Sequence of Aromatic Carboxylic Acids with Functionalized Aliphatic Nitriles.

Org Lett 2021 Jul 12. Epub 2021 Jul 12.

College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, People's Republic of China.

We herein report an efficient approach for the assembly of multiply substituted imidazoles and oxazoles in a single-step manner. These transformations are based on a decarboxylation addition and annulation of readily accessible aromatic carboxylic acids and aliphatic nitriles and exhibit good functional group compatibility and a high step economy. The reaction is scalable, and as-prepared products could be transformed into practical skeletons. Importantly, the late-stage derivatization of Momelotinib highlights the potential utility of this methodology.
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http://dx.doi.org/10.1021/acs.orglett.1c01762DOI Listing
July 2021

Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC.

Cancer Immunol Immunother 2021 Jun 15. Epub 2021 Jun 15.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Oncology II, Peking University Cancer Hospital & Institute, Haidian District, 52# Fucheng Road, Beijing, 100142, China.

Background: The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy.

Materials And Methods: The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity.

Results: Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p  = 0.05). There was no significant difference in grade 3-4 adverse events (AEs) between the two groups (p = 0.253).

Conclusions: The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.
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http://dx.doi.org/10.1007/s00262-021-02964-xDOI Listing
June 2021

A deep learning system for detecting diabetic retinopathy across the disease spectrum.

Nat Commun 2021 05 28;12(1):3242. Epub 2021 May 28.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai, 200233, China.

Retinal screening contributes to early detection of diabetic retinopathy and timely treatment. To facilitate the screening process, we develop a deep learning system, named DeepDR, that can detect early-to-late stages of diabetic retinopathy. DeepDR is trained for real-time image quality assessment, lesion detection and grading using 466,247 fundus images from 121,342 patients with diabetes. Evaluation is performed on a local dataset with 200,136 fundus images from 52,004 patients and three external datasets with a total of 209,322 images. The area under the receiver operating characteristic curves for detecting microaneurysms, cotton-wool spots, hard exudates and hemorrhages are 0.901, 0.941, 0.954 and 0.967, respectively. The grading of diabetic retinopathy as mild, moderate, severe and proliferative achieves area under the curves of 0.943, 0.955, 0.960 and 0.972, respectively. In external validations, the area under the curves for grading range from 0.916 to 0.970, which further supports the system is efficient for diabetic retinopathy grading.
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http://dx.doi.org/10.1038/s41467-021-23458-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163820PMC
May 2021

Do carbon emissions accelerate low-carbon innovation? Evidence from 285 Chinese prefecture-level cities.

Environ Sci Pollut Res Int 2021 May 7. Epub 2021 May 7.

Cornell Institute for Public Affairs, Cornell University, Ithaca, NY, 14850, USA.

Climate change caused by carbon emissions has a strong influence on the economy and human society. Though numerous previous studies have emphasized the importance of low-carbon innovation on curbing or mitigating carbon emissions, not much attention has been given to the reverse effect. We used a panel of 285 Chinese prefecture-level cities from 2005 to 2016 and Cooperative Patent Classification (CPC)-Y02 patents as low-carbon innovation indicators. The results show that the increasing carbon emissions accelerate cities' low-carbon innovation in China, and the predicted effect varies across low-carbon innovation types. As carbon emissions rise, more low-carbon innovation will occur in activities with higher carbon emissions. Besides, we explore environmental awareness as the mediation channel for carbon emissions to impact low-carbon innovation. With the help of media, government, and enterprises, the growing carbon emissions promote public environmental awareness and change consumers' behaviors, motivating companies to speed up low-carbon innovation.
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http://dx.doi.org/10.1007/s11356-021-14291-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103885PMC
May 2021

Immune-Related Adverse Events and Their Association With the Effectiveness of PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer: A Real-World Study From China.

Front Oncol 2021 5;11:607531. Epub 2021 Mar 5.

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

Background: Programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors are increasingly used in China, but no real-world data are available about the immune-related adverse events (irAEs). This real-world retrospective study aimed to assess the safety and effectiveness of PD-1/PD-L1 inhibitors in patients with non-small cell lung cancer (NSCLC) and to analyze the association between irAEs and effectiveness.

Methods: This was a retrospective study of the clinical data of patients with NSCLC treated with PD-1/PD-L1 inhibitors from August 2016 to November 2019 at Beijing Cancer Hospital. The patients were divided into the irAE or non-irAE groups. Overall adverse events, the impact of irAE on tumor response, and the association of irAEs with effectiveness were evaluated.

Results: One hundred and ninety-one patients were included, including 70 (36.6%) patients in the irAE group and 121 (63.4%) patients in the non-irAE group. AE, grades 3-5 AEs, and irAE occurred in 107 (56.0%), 24 (12.6%), and 70 (36.6%) of the patients, respectively. The objective response rate (ORR) and disease control rate (DCR) were higher in the irAE group compared with the non-irAE group (42.0% vs. 25.8%, P=0.038; 91.9% vs. 70.8%, P=0.002). Multivariable analyses identified that irAE were associated with progression-free survival (HR=0.62, 95%CI: 0.43-0.91; P=0.015), but not with overall survival (HR=0.76, 95%CI: 0.44-1.28; P=0.299).

Conclusion: In NSCLC treated with PD-1/PD-L1 inhibitors, patients with irAEs showed improved effectiveness over patients without irAEs. Future studies of anti-PD-1/PD-L1 immunotherapy should explore this association and the underlying biological mechanisms of efficacy.
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http://dx.doi.org/10.3389/fonc.2021.607531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973369PMC
March 2021

The "Traditional Chinese medicine regulating liver regeneration" treatment plan for reducing mortality of patients with hepatitis B-related liver failure based on real-world clinical data.

Front Med 2021 Jun 12;15(3):495-505. Epub 2021 Jan 12.

Institute of Liver Diseases, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China.

On the basis of real-world clinical data, the study aimed to explore the effect and mechanisms of the treatment plan of "traditional Chinese medicine (TCM) regulating liver regeneration." A total of 457 patients with HBV-related liver failure were retrospectively collected. The patients were divided into three groups: the modern medicine control group (MMC group), patients treated with routine medical treatment; the control group combining traditional Chinese and Western medicine (CTW), patients treated with routine medical treatment plus the common TCM formula; and the treatment group of "TCM regulating liver regeneration" (RLR), patients treated with both routine medical treatment and the special TCM formula of RLR. After 8 weeks of treatment, the mortality of patients in the RLR group (12.31%) was significantly lower than those in the MMC (50%) and CTW (29.11%) groups. Total bilirubin level significantly decreased and albumin increased in the RLR group when compared with the MMC and CTW groups (P < 0.05). In addition, there were significant differences in the expression of several cytokines related to liver regeneration in the RLR group compared with the MMC group. RLR treatment can decrease jaundice, improve liver function, and significantly reduce the mortality in patients with HBV-related liver failure. The mechanism may be related to the role of RLR treatment in influencing cytokines related to liver regeneration.
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http://dx.doi.org/10.1007/s11684-020-0790-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801774PMC
June 2021

Palladium-catalyzed C-H activation of simple arenes and cascade reaction with nitriles: access to 2,4,5-trisubstituted oxazoles.

Chem Commun (Camb) 2021 Feb 12;57(11):1376-1379. Epub 2021 Jan 12.

College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, China.

An efficient and straightforward protocol for the assembly of the pharmaceutically and biologically valuable oxazole skeleton is achieved for the first time from readily available simple arenes and functionalized aliphatic nitriles. This transformation involves palladium-catalyzed C-H activation, carbopalladation and a tandem annulation sequence in one pot. Notably, the reaction proceeds efficiently under redox-neutral conditions, and exhibits high atom-economy. Deuterium-labeling experiments suggested that C-H bond cleavage of the simple arenes might be the rate-determining step.
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http://dx.doi.org/10.1039/d0cc07547gDOI Listing
February 2021

Women's experience of psychological birth trauma in China: a qualitative study.

BMC Pregnancy Childbirth 2020 Oct 27;20(1):651. Epub 2020 Oct 27.

School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.

Background: The psychological birth trauma is a universal phenomenon in childbearing women. The influences could extend in a wide range, which includes the mothers' health, mother-infant relationship, partner relationship. The medical staff could even choose to quit playing their part in the birthing process. The phenomenon has gradually garnered attention around the world. However, it has rarely been discussed under Chinese special conditions. The study was to explore Chinese women's lived experiences of psychological birth trauma during labor and birth.

Methods: A descriptive phenomenological approach was adopted in this study. Twenty-four women were recruited, who reported having experienced psychological birth trauma. In-depth interviews were conducted within 1 week after birth. Colaizzi's method was used to analyze the data.

Results: Twenty-four women participated in the study. Four themes emerged to describe the women's experience of psychological birth trauma: "How am I supposed to relieve the endless pain?" " Can't I be weak?" "Am I not important?" "What uncertainties are waiting for me?"

Conclusions: The findings provide deep insight into Chinese women's unique experience of psychological birth trauma. The social and health system could prevent psychological harm during birth and promote maternal health by measures of pain management, thoughtful attention, adequate caring, and prenatal preparation.
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http://dx.doi.org/10.1186/s12884-020-03342-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590597PMC
October 2020

Pd-Catalyzed Approach for Assembling 9-Arylacridines via a Cascade Tandem Reaction of 2-(Arylamino)benzonitrile with Arylboronic Acids in Water.

J Org Chem 2020 10 30;85(20):13004-13014. Epub 2020 Sep 30.

College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, China.

A novel palladium-catalyzed protocol for the synthesis of 9-arylacridines via tandem reaction of 2-(arylamino)benzonitrile with arylboronic acids in water has been developed with good functional group tolerance. The present synthetic route could be readily scaled up to gram quantity without difficulty. This methodology was further extended to the synthesis of a 4'-OH derivative, which showed estrogenic biological activity. Preliminary mechanistic experiments showed that this transformation involves a nucleophilic addition of aryl palladium species to the nitrile to generate an aryl ketone intermediate followed by an intramolecular Friedel-Crafts acylation and dehydration to acridines.
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http://dx.doi.org/10.1021/acs.joc.0c01654DOI Listing
October 2020

A phase II study of anlotinib in 45 patients with relapsed small cell lung cancer.

Int J Cancer 2020 12 26;147(12):3453-3460. Epub 2020 Jun 26.

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

The purpose of this prospective phase II clinical trial was to investigate the efficacy and safety of anlotinib in patients with relapsed small cell lung cancer (SCLC). Forty-five patients with relapsed SCLC were enrolled and treated with anlotinib (one cycle of 12 mg daily for 14 days, discontinued for 7 days, and repeated every 21 days) until disease progression or intolerance of treatment. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), disease control rate (DCR), objective control rate (ORR) and toxicity. The median PFS was 4.1 months (95% confidence interval [CI] 2.4-5.8) and the median OS was 6.1 months (95% CI 2.2-10.0). The OS for the limited-stage subgroup was significantly longer than that of the extensive-stage subgroup (P = .02). The DCR was 67%, and the ORR was 11%. The most common adverse event was hypertension (13%), which was controlled well with antihypertensive drugs. In conclusion, anlotinib has likely efficacy in patients with relapsed SCLC, and the side effects can be well tolerated. A longer OS was observed in limited-stage SCLC patients treated with anlotinib.
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http://dx.doi.org/10.1002/ijc.33161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689882PMC
December 2020

Automatic Grading System for Diabetic Retinopathy Diagnosis Using Deep Learning Artificial Intelligence Software.

Curr Eye Res 2020 12 15;45(12):1550-1555. Epub 2020 May 15.

Department of Ophthalmology, Shanghai Jiaotong University Affiliated Sixth People's Hospital , Shanghai, China.

: To describe the development and validation of an artificial intelligence-based, deep learning algorithm (DeepDR) for the detection of diabetic retinopathy (DR) in retinal fundus photographs. : Five hundred fundus images, which had detailed labelling of DR lesions, were transmitted to be analysed, including localization of the optic disk and macular, vessel segmentation, detection of lesions, and grading of DR. The multi-level iterative method of convolutional neural network and the strategy of enhanced learning were used to improve the accuracy of the system (DeepDR) for grading DR. Three public data sets were used to further train the software. The final grading results were tested based on the fundus images provided by the hospitals. : For 6788 fundus images (both macular and disc centred) of two Hospital Eye Center, the detection of microaneurysm, haemorrhage and hard exudates had an accuracy of 99.7%, 98.4% and 98.1%, respectively. The current algorithm accuracy was 0.96. Another 20,000 fundus images from community screening were selected, and 7593 photos of poor quality were excluded according to quality standards. Accuracy for accurate staging of fundus photos: accuracy was 0.9179. The sensitivity, specificity and area under the curve (AUC) were 80.58%, 95.77% and 0.9327, respectively. : This artificial intelligence-based DeepDR can be used with high accuracy for the detection of DR in retinal images. This technology offers the potential to increase the efficiency and accessibility of DR screening programs.
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http://dx.doi.org/10.1080/02713683.2020.1764975DOI Listing
December 2020

"Efficacy and safety of Liangxue Jiedu decoction for the treatment of progressive psoriasis vulgaris: a multicenter, randomized, controlled study".

J Tradit Chin Med 2020 04;40(2):296-304

Dermatology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China.

Objective: To determine the clinical efficacy and safety of Liangxue Jiedu decoction (LJD) for the treatment of progressive psoriasis vulgaris and to provide the basis for the development of a standardized treatment protocol for psoriasis vulgaris.

Methods: In this multicenter, randomized, controlled study, patients with blood-heat type psoriasis were randomly assigned to receive either Chinese herbal medicine (LJD; treatment group) or Western Medicine (cetirizine hydrochloride, vitamin C, and vitamin B complex; control group). Psoriasis Area and Severity Index (PASI) scores were calculated in addition to the number of patients who achieved ≥ 50% or ≥ 75% improvement in PASI score from baseline. The change in symptoms of Chinese medicine (color of rash, burning sensation, itchiness, severity of irritation, and anger) was evaluated and safety was assessed as adverse events and laboratory analysis. t test, independent sample non-parametric test and χ2 test were used to analyze the results.

Results: A total of 238 participants were included in the study [treatment group, n = 122 (PP analysis 117); control group, n = 116 (PP analysis 104)]. LJD treatment was associated with a significant improvement in skin lesions and symptoms compared with Western Medicine treatment. At the end of the 8-week treatment period, 23.77% (PP analysis 24.79%) of patients in the treatment group had achieved PASI75 and 57.38% (PP analysis 58.97%) had achieved PASI50; the corresponding figures in the control group were 9.48% (9.62%) and 25.00% (25.00%), respectively. The between-group differences were statistically significant (P < 0.05).

Conclusion: Treatment of psoriasis vulgaris of the blood-heat type using LJD was associated with significantly better outcomes compared with those achieved using standard Western Medicine.
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April 2020

Applying CRISPR-Cas12a as a Signal Amplifier to Construct Biosensors for Non-DNA Targets in Ultralow Concentrations.

ACS Sens 2020 04 20;5(4):970-977. Epub 2020 Mar 20.

Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing 400016, China.

Efficient signal amplification is essential to construct ultrasensitive biosensors for biologically relevant species with abundant concomitant interferences. Here, we apply LbaCas12a as a signal amplifier to develop a versatile CRISPR-Cas12a platform to detect a wide range of analytes in ultralow concentrations. The platform relies on the indiscriminate single-stranded DNase activity of LbaCas12a, which recognizes single-stranded DNA intermediates generated by non-DNA targets down to femtomolar concentrations and subsequently enhances the fluorescence signal output. With the help of functional nucleotides (DNAzyme and aptamer), ultrasensitive bioassays for Pb and have been designed with a limit of detection down to ∼0.053 nM and ∼3 CFU/mL, respectively. It also allows simultaneous detection of four microRNAs (miRNAs) at a picomolar concentration without significant interferences by other counterparts, suggesting the potential of multiplexed miRNA expression profiles analysis in high throughput. Given the versatility and generality of the CRISPR-Cas12a platform, we expect the current work to advance the application of CRISPR-Cas-based platforms in bioanalysis and provide new insights into ultrasensitive biosensor design.
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http://dx.doi.org/10.1021/acssensors.9b02305DOI Listing
April 2020

Domain-invariant interpretable fundus image quality assessment.

Med Image Anal 2020 04 30;61:101654. Epub 2020 Jan 30.

Department of Radiology and Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27510, USA; Department of Brain and Cognitive Engineering, Korea University, Seoul 02841, Republic of Korea. Electronic address:

Objective and quantitative assessment of fundus image quality is essential for the diagnosis of retinal diseases. The major factors in fundus image quality assessment are image artifact, clarity, and field definition. Unfortunately, most of existing quality assessment methods focus on the quality of overall image, without interpretable quality feedback for real-time adjustment. Furthermore, these models are often sensitive to the specific imaging devices, and cannot generalize well under different imaging conditions. This paper presents a new multi-task domain adaptation framework to automatically assess fundus image quality. The proposed framework provides interpretable quality assessment with both quantitative scores and quality visualization for potential real-time image recapture with proper adjustment. In particular, the present approach can detect optic disc and fovea structures as landmarks, to assist the assessment through coarse-to-fine feature encoding. The framework also exploit semi-tied adversarial discriminative domain adaptation to make the model generalizable across different data sources. Experimental results demonstrated that the proposed algorithm outperforms different state-of-the-art approaches and achieves an area under the ROC curve of 0.9455 for the overall quality classification.
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http://dx.doi.org/10.1016/j.media.2020.101654DOI Listing
April 2020

Fulleropillar[4]arene: The Synthesis and Complexation Properties.

Org Lett 2020 03 24;22(6):2118-2123. Epub 2020 Jan 24.

Key Laboratory of Green Chemistry & Technology, College of Chemistry, and Healthy Food Evaluation Research Center, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, China.

A multihydroquinone ether dialdehyde derivative was incidentally obtained through an unexpected ring opening of pillar[4]arene[1]quinone . And the Prato reaction of with [60]fullerene led to [60]fullerene bisadducts, from which cyclic regioisomer was isolated and characterized. The fulleropillar[4]arene showed a larger cavity and can accommodate a viologen derivative with a much stronger affinity than permethyl pillar[5]arene () and pillar[4]arene[1]quinone .
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http://dx.doi.org/10.1021/acs.orglett.9b04607DOI Listing
March 2020

Electrochemical competitive immunodetection of messenger RNA modified with N6-methyladenosine by using DNA-modified mesoporous PtCo nanospheres.

Mikrochim Acta 2019 12 9;187(1):31. Epub 2019 Dec 9.

Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

N-Methyladenosine (mA) is the most abundant RNA modification in eukaryotic messenger RNA (mRNA). A highly sensitive electrochemical immunosensor is described for the determination of mA-RNA. The method is based on the use of antibody (anti-mA) and PtCo mesoporous nanospheres (MPNs). The analogously modified probe of type mA-DNA-PtCo competes with mA-RNA for antibodies on the gold electrode as an electrical signal probe. The electrical signal, best acquired at a working potential of -0.37 V (vs. Ag/AgCl) reflects the concentration of mA. The PtCo MPNs catalyze the reduction of HO, and this amplifies the current and enhances sensitivity. The detection time of the assay is <1.5 h. Under optimal conditions, response is linear in the 0.005 to 100 nM mA RNA concentration range, and the detection limit is 2.1 pM. The results obtained by this immunoassay with human cell lines are comparable to those obtained with a commercial kit. Graphical abstractSchematic representation of a method for electrochemical determination of mA-modified mRNA. Anti-mA Ab: antibody against mA; BSA: bovine serum albumin; PtCo: PtCo mesoporous nanospheres; SH-mA-DNA: DNA modified with both mA and thiol groups; DPV: differential pulse voltammetry.
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http://dx.doi.org/10.1007/s00604-019-4010-8DOI Listing
December 2019

Treatment Of Magnesium-L-Threonate Elevates The Magnesium Level In The Cerebrospinal Fluid And Attenuates Motor Deficits And Dopamine Neuron Loss In A Mouse Model Of Parkinson's disease.

Neuropsychiatr Dis Treat 2019 11;15:3143-3153. Epub 2019 Nov 11.

Department of Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin 541004, Guangxi, People's Republic of China.

Purpose: Epidemiology research has demonstrated that magnesium (Mg) deficiency is associated with a high incidence of Parkinson's disease (PD). It is known that the systemic administration of MgSO is not able to elevate the Mg concentration in cerebrospinal fluid (CSF). This study aims to verify the protective effect of magnesium-L-threonate (MgT) in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model.

Methods: C57BL/6J mice were orally administered MgT or MgSO for 4 weeks, and received MPTP in the third week. After analysis of open-field and rotarod tests on the last day, tyrosine hydroxylase (TH) immunopositive cells and protein levels were quantified in the substantia nigra pars compacta (SNpc) and striatum. The expression of inducible nitric oxide synthase (iNOS) level was evaluated. Mg concentration in serum and CSF was measured after oral administration of MgSO or MgT in normal mice. Mg concentration in the CSF was increased in the mice treated with MgT but not MgSO.

Results: The total distance and mean speed in open-field tests, and the time spent on rotarod in the MgT group were increased, compared with MPTP group. The MgT treatment but not MgSO dose-dependently attenuated the loss of TH-positive neurons, and the reduction of the TH expression in the SNpc. The MgT treatment also inhibited the expression of iNOS as measured by immunohistochemistry and Western blots. Double-immunofluorescence staining of TH and iNOS showed iNOS-positive cells were collocalized for TH-positive cells.

Conclusion: The treatment with MgT is associated with an increase of Mg in the CSF. MgT, rather than MgSO4, can significantly attenuate MPTP-induced motor deficits and dopamine (DA) neuron loss.
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http://dx.doi.org/10.2147/NDT.S230688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857673PMC
November 2019

IDRiD: Diabetic Retinopathy - Segmentation and Grading Challenge.

Med Image Anal 2020 01 3;59:101561. Epub 2019 Oct 3.

Individual Researcher, India.

Diabetic Retinopathy (DR) is the most common cause of avoidable vision loss, predominantly affecting the working-age population across the globe. Screening for DR, coupled with timely consultation and treatment, is a globally trusted policy to avoid vision loss. However, implementation of DR screening programs is challenging due to the scarcity of medical professionals able to screen a growing global diabetic population at risk for DR. Computer-aided disease diagnosis in retinal image analysis could provide a sustainable approach for such large-scale screening effort. The recent scientific advances in computing capacity and machine learning approaches provide an avenue for biomedical scientists to reach this goal. Aiming to advance the state-of-the-art in automatic DR diagnosis, a grand challenge on "Diabetic Retinopathy - Segmentation and Grading" was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI - 2018). In this paper, we report the set-up and results of this challenge that is primarily based on Indian Diabetic Retinopathy Image Dataset (IDRiD). There were three principal sub-challenges: lesion segmentation, disease severity grading, and localization of retinal landmarks and segmentation. These multiple tasks in this challenge allow to test the generalizability of algorithms, and this is what makes it different from existing ones. It received a positive response from the scientific community with 148 submissions from 495 registrations effectively entered in this challenge. This paper outlines the challenge, its organization, the dataset used, evaluation methods and results of top-performing participating solutions. The top-performing approaches utilized a blend of clinical information, data augmentation, and an ensemble of models. These findings have the potential to enable new developments in retinal image analysis and image-based DR screening in particular.
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http://dx.doi.org/10.1016/j.media.2019.101561DOI Listing
January 2020

Exploring Contributing Factors to Psychological Traumatic Childbirth from the Perspective of Midwives: A Qualitative Study.

Asian Nurs Res (Korean Soc Nurs Sci) 2019 Oct 9;13(4):270-276. Epub 2019 Oct 9.

Department of Nursing, Tongji Hosptial, Huazhong University of Science & Technology, Wuhan, Hubei, China.

Purpose: As midwives witness and attend the whole process of childbirth, they have a better understanding of which factors may cause traumatic childbirth. However, because most of the studies paid their attention on mothers, little is known about psychological birth trauma from the perspective of midwives. This study aims to gain a full understanding of which factors may contribute to psychological traumatic childbirth from the perspective of midwives.

Methods: A qualitative research was conducted using in-depth interviews, which involved fourteen midwives from the maternal ward of a tertiary hospital. The interviews were recorded and transcribed, and then, Colaizzi's method was used to analyze the contents of the interviews.

Results: We proposed four themes and eight subthemes on the influencing factors of psychological traumatic childbirth from the perspective of midwives: low perceived social support (lack of support from family and lack of support from medical staff), hard times (protracted labor in the first stage and futile efforts during the second stage), poor birth outcomes (poor birth outcomes of the mother and poor birth outcomes of the baby), and excruciating pain (unbearable pain of uterine contraction and labor pain was incongruent with the mother's expectations).

Conclusion: Medical staff should pay attention to psychological traumatic childbirth and its effects, and emphasis on the screening and assessment of birthing women with negative feelings so that their psychological traumatic childbirth can be prevented and decreased.
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http://dx.doi.org/10.1016/j.anr.2019.10.002DOI Listing
October 2019

Pd-Catalyzed Tandem Reaction of 2-Aminostyryl Nitriles with Arylboronic Acids: Synthesis of 2-Arylquinolines.

J Org Chem 2019 Nov 3;84(21):13604-13614. Epub 2019 Oct 3.

College of Chemistry & Materials Engineering , Wenzhou University , Wenzhou 325035 , China.

A novel palladium-catalyzed protocol for the synthesis of 2-arylquinolines via tandem reaction of 2-aminostyryl nitriles with arylboronic acids has been developed with good functional group tolerance. The presented approach offers a new synthetic pathway toward the core structures of 2-arylquinolines compared to classical condensation reaction of ()-2-aminostyryl aryl ketones. Moreover, the present synthetic route could be readily scaled up to gram quantity without difficulty. Preliminary mechanistic experiments showed that this transformation involves a nucleophilic addition of aryl palladium species to the nitrile to generate an aryl ketone intermediate followed by an intramolecular cyclization and dehydration to quinoline ring.
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http://dx.doi.org/10.1021/acs.joc.9b01875DOI Listing
November 2019

Fluorometric determination of microRNA by using an entropy-driven three-dimensional DNA walking machine based on a catalytic hairpin assembly reaction on polystyrene microspheres.

Mikrochim Acta 2019 07 24;186(8):574. Epub 2019 Jul 24.

Key Laboratory of Laboratory Medical Diagnostics of Education, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing, 400016, People's Republic of China.

An entropy-driven 3-D DNA walking machine is presented which involves catalytic hairpin assembly (CHA) for detection of microRNA. A 3-D DNA walking machine was designed that uses streptavidin-coated polystyrene microspheres as track carriers to obtain reproducibility. The method was applied to microRNA 21 as a model analyte. Continuous walking on the DNA tracks is achieved via entropy increase. This results in a disassembly of ternary DNA substrates on polystyrene microspheres and leads to cycling of microRNA 21. The release of massive auxiliary strands from ternary DNA substrates induces the CHA. This is accompanied by in increase in fluorescence, best measured at excitation/emission wavelengths of 480/520 nm. On account of entropy-driven reaction, the assay is remarkably selective. It can differentiate microRNA 21 from homologous microRNAs in giving a signal that is less than 5% of the signal for microRNA 21 except for microRNA-200b. The assay works in the 50 pM to 20 nM concentration range and has a 41 pM detection limit. The method displays good reproducibility (between 1.1 and 4.2%) and recovery (from 99.8 to 104.0%). Graphical abstract An entropy-driven 3-D DNA walking machine is described. It is based on the use of polystyrene microspheres and of a catalytic hairpin assembly reaction for sensitive microRNA detection. Figure Notes: AS represents auxiliary strand; S represents substrate strand; LS represents link strand; F represents fuel nucleic acid; RepF represents nucleic acid labeled with FAM; RepQ represents nucleic acid labeled with BHQ1.
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http://dx.doi.org/10.1007/s00604-019-3689-xDOI Listing
July 2019

Salvage treatment with anlotinib for advanced non-small cell lung cancer.

Thorac Cancer 2019 07 10;10(7):1590-1596. Epub 2019 Jun 10.

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

Background: This real-world study assessed the efficacy and toxicity of anlotinib as salvage treatment in Chinese patients with advanced non-small cell lung cancer (NSCLC).

Methods: The medical records of 81 patients with advanced NSCLC who had failed at least two lines of chemotherapy were retrospectively collected. All patients were administered anlotinib treatment until disease progression or intolerance as a result of adverse events. Survival curves were created using the Kaplan-Meier method. The log-rank test was used for univariate analysis of progression-free survival (PFS) between groups. Cox regression was used to estimate the statistically significant factors based on univariate analysis.

Results: The median PFS was five months (95% confidence interval [CI] 3.5-6.5). The objective response rate (ORR) was 7% and the disease control rate (DCR) was 84%. The following subgroups of patients had longer PFS (P < 0.05): squamous cell carcinoma, no brain or liver metastases, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, and no previous VEGF-tyrosine kinase inhibitor treatment. The results of Cox regression indicated that an ECOG PS of 0-1 (hazard ratio 0.152, 95% CI 0.057-0.403; P = 0.00) and patients without brain metastases (hazard ratio 0.421, 95% CI 0.195-0.911; P = 0.028) had longer PFS following anlotinib treatment.

Conclusion: Anlotinib, which is well tolerated, plays a significant role in the salvage treatment of advanced NSCLC. Patients with advanced NSCLC with an ECOG PS of 0-1 and no brain metastases achieved longer PFS following anlotinib salvage treatment.
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http://dx.doi.org/10.1111/1759-7714.13120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610258PMC
July 2019

Efficacy and toxicities of gemcitabine and cisplatin combined with endostar in advanced thymoma and thymic carcinoma.

Thorac Cancer 2019 01 9;10(1):17-23. Epub 2018 Nov 9.

Department of Thoracic Oncology II, Peking University Cancer Hospital & Institute, Beijing, China.

Background: Thymoma and thymic carcinoma are rare thymic epithelial tumors. We investigated the efficacy of first-line gemcitabine and cisplatin (GP) chemotherapy versus gemcitabine and cisplatin chemotherapy combined with the anti-angiogenic drug endostar (GP + E) in advanced thymoma and thymic carcinoma.

Methods: The records of 45 patients with invasive metastatic thymomas or thymic carcinomas treated with GP as first-line therapy between August 2008 and July 2017 at the Department of Respiratory Medicine, Peking University Cancer Hospital and Institute were retrospectively reviewed.

Results: Eighteen patients (75%) in the GP + E group achieved a partial response and six (25%) had stable disease. In GP only group, nine (42.8%) patients achieved a partial response, 11 (52.4%) had stable disease, and one (4.8%) had progressive disease. The GP + E group had a significantly higher overall response rate (75% vs. 42.9%; P = 0.028), and median progression-free survival (PFS) and overall survival (OS) of 19 and 76 months, respectively. In the GP only group, median PFS and OS were 16 and 29 months, respectively. PFS and OS were not significantly different between the groups.

Conclusions: GP has moderate efficacy and could represent a suitable first-line therapy for thymic carcinoma and thymoma. Chemotherapy combined with endostar could improve the overall response rate, but did not prolong PFS or OS.
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http://dx.doi.org/10.1111/1759-7714.12891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312837PMC
January 2019

High expression of ALDOA and DDX5 are associated with poor prognosis in human colorectal cancer.

Cancer Manag Res 2018 29;10:1799-1806. Epub 2018 Jun 29.

Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, People's Republic of China,

Purpose: The identification of prognostic markers for colorectal cancer (CRC) is needed for clinical practice. Fructose-bisphosphate aldolase A (ALDOA) and DEAD box p68 RNA helicase (DDX5) are commonly overexpressed in cancer and correlate with tumorigenesis. However, association between expression of ALDOA and DDX5, and CRC outcome has not been reported.

Patients And Methods: We used 141 formalin-fixed paraffin-embedded (FFPE) specimens collected from 105 patients with CRC treated at the Affiliated Hospital of Guilin Medical University and the People's Hospital of Liuzhou. We performed tissue microarray based immunohistochemistry to explore expression features and prognostic value (overall survival, OS; disease-free survival, [DFS]) of ALDOA and DDX5 in CRC tissues. The prognostic values were evaluated using Kaplan-Meier analysis, and Cox regression analyses.

Results: ALDOA and DDX5 were highly expressed in CRC tissues and liver metastatic CRC tissues compared with normal glandular epithelium tissues (all <0.05). Interestingly, primary CRC tissues highly expressing ALDOA or DDX5 had poor outcome (<0.0001 for both OS and DFS for ALDOA; =0.001 for OS; and =0.011 for DFS for DDX5) compared with patients who had low expression of those proteins. Furthermore, multivariate Cox analysis showed that ALDOA/DDX5 combination was an independent risk factor for OS and ALDOA was an independent risk factor for DFS.

Conclusion: High levels of ALDOA and DDX5 contribute to the aggressiveness and poor prognosis of CRC. ALDOA/DDX5 expression could be a biomarkers for the prognosis of CRC.
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http://dx.doi.org/10.2147/CMAR.S157925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029611PMC
June 2018

Clinical Report Guided Retinal Microaneurysm Detection With Multi-Sieving Deep Learning.

IEEE Trans Med Imaging 2018 05;37(5):1149-1161

Timely detection and treatment of microaneurysms is a critical step to prevent the development of vision-threatening eye diseases such as diabetic retinopathy. However, detecting microaneurysms in fundus images is a highly challenging task due to the low image contrast, misleading cues of other red lesions, and the large variation of imaging conditions. Existing methods tend to fail in face of the large intra-class variation and small inter-class variations for microaneurysm detection in fundus images. Recently, hybrid text/image mining computer-aided diagnosis systems have emerged to offer a promise of bridging the semantic gap between images and diagnostic information. In this paper, we focus on developing an interleaved deep mining technique to cope intelligently with the unbalanced microaneurysm detection problem. Specifically, we present a clinical report guided multi-sieving convolutional neural network, which leverages a small amount of supervised information in clinical reports to identify the potential microaneurysm regions via the image-to-text mapping in the feature space. These potential microaneurysm regions are then interleaved with fundus image information for multi-sieving deep mining in a highly unbalanced classification problem. Critically, the clinical reports are employed to bridge the semantic gap between low-level image features and high-level diagnostic information. We build an efficient microaneurysm detection framework based on the hybrid text/image interleaving and validate its performance on challenging clinical data sets acquired from diabetic retinopathy patients. Extensive evaluations are carried out in terms of fundus detection and classification. Experimental results show that our framework achieves 99.7% precision and 87.8% recall, comparing favorably with the state-of-the-art algorithms. Integration of expert domain knowledge and image information demonstrates the feasibility of reducing the difficulty of training classifiers under extremely unbalanced data distributions.
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http://dx.doi.org/10.1109/TMI.2018.2794988DOI Listing
May 2018

Efficacy, safety and predictive indicators of apatinib after multilines treatment in advanced nonsquamous nonsmall cell lung cancer: Apatinib treatment in nonsquamous NSCLC.

Asia Pac J Clin Oncol 2018 Dec 24;14(6):446-452. Epub 2018 Mar 24.

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

Aim: Patients with advanced nonsquamous nonsmall cell lung cancer (NSCLC) who experienced progression with two or more lines chemotherapy have no treatment options that clearly confer a survival benefit. As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, apatinib has a certain antitumor effect for various solid tumors. The present study evaluated the efficacy and safety of apatinib in advanced nonsquamous NSCLC as salvage treatment in Chinese real-world practice.

Methods: Twenty-eight patients were enrolled in this observational study from October 2015 to May 2017. Progression-free survival (PFS) and overall survival (OS) were graphed by Kaplan-Meier curve and intergroup comparisons were carried out by log-rank test. Objective response rate (ORR), disease control rate (DCR) and adverse effects (AEs) were also evaluated.

Results: Seven patients obtained partial response, and 18 obtained stable disease, representing an ORR of 26% and a DCR of 93%. Median PFS and OS were 3 (95% confidence interval [CI] 2.6-3.4) and 7.4 (95% CI 1.3-13.5) months, respectively. The efficacy analysis showed that Eastern Cooperative Oncology Group (ECOG) performance status 0-1 was correlated with prolonged OS and PFS (P < 0.05), and hypertension during apatinib treatment was correlated with prolonged OS (P < 0.05). Cox regression showed that ECOG performance status (P < 0.01) (RR = 0.231) (95% CI 0.083-0.642) and hypertension during apatinib treatment (P = 0.05) were predictive indicators for apatinib treatment. Grade 3-4 AEs with incidences of 10% or greater were hypertension (21%), hand-foot syndrome (14%) and proteinuria (11%) which could be relieved by dose reduction.

Conclusion: In conclusion, apatinib has a certain therapeutic effect in patients with advanced nonsquamous NSCLC. ECOG performance status and hypertension during apatinib might be predictive indicators for treatment efficacy.
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http://dx.doi.org/10.1111/ajco.12870DOI Listing
December 2018

Enhanced chiral recognition by γ-cyclodextrin-cucurbit[6]uril-cowheeled [4]pseudorotaxanes.

Chem Commun (Camb) 2018 Mar;54(21):2643-2646

Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, State Key Laboratory of Biotherapy, and Healthy Food Evaluation Research Center, Sichuan University, Chengdu 610064, China.

Mixing γ-cyclodextrin (γ-CD), cucurbit[6]uril (CB[6]) and tetraammonium-bearing axles together led to a spontaneous formation of γ-CD-CB[6]-cowheeled [4]pseudorotaxanes. The well-defined unsymmetrical cavities thus formed enhance the binding affinity towards chiral amines by factors of several hundreds and show remarkably improved chiral discrimination.
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http://dx.doi.org/10.1039/c8cc00840jDOI Listing
March 2018

Upregulation of caprin1 expression is associated with poor prognosis in hepatocellular carcinoma.

Pathol Res Pract 2017 Dec 15;213(12):1563-1567. Epub 2017 Jul 15.

Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China. Electronic address:

Caprin-1 has been found to promotes osteosarcoma tumor growth, lung metastasis in mice, regulating the proliferation and invasion of human breast cancer cells and up-regulated in proton beam irradiated human melanoma cells. However, its clinical role, biological function in the hepatocellular carcinoma (HCC) remains unknown. In the present study, we investigated the clinical significance of Caprin1 in the HCC. Caprin1 expression was detected by immunohistochemistry, and the expression level was analyzed in 65 HCC tissues and paired peritumoral tissue. Prognostic value of Caprin1 in HCC was evaluated in 174 cases using Kaplan-Meier analysis. Univariate survival analysis and multiple Cox proportional hazards regression were performed using the Cox regression analysis. Immunohistochemistry revealed that Caprin1 expression in 65 HCC tissues was upregulated compared to paired peritumoral tissue (p=0.0064). Survival analysis in 174 HCC patient tissues was showed that high Caprin1 expression was significantly associated with worse overall survival (HR=1.513, p=0.042). In conclusion, high Caprin1 expression independently predicts a poor outcome for patients with HCC, supporting that Caprin1 may be a promising novel HCC prognostic factor.
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http://dx.doi.org/10.1016/j.prp.2017.07.014DOI Listing
December 2017

Role of CaMKII and PKA in Early Afterdepolarization of Human Ventricular Myocardium Cell: A Computational Model Study.

Comput Math Methods Med 2016 8;2016:4576313. Epub 2016 Dec 8.

Department of Biomedical Engineering, Zhejiang University, Hangzhou, China.

Early afterdepolarization (EAD) plays an important role in arrhythmogenesis. Many experimental studies have reported that Ca/calmodulin-dependent protein kinase II (CaMKII) and -adrenergic signaling pathway are two important regulators. In this study, we developed a modified computational model of human ventricular myocyte to investigate the combined role of CaMKII and -adrenergic signaling pathway on the occurrence of EADs. Our simulation results showed that (1) CaMKII overexpression facilitates EADs through the prolongation of late sodium current's () deactivation progress; (2) the combined effect of CaMKII overexpression and activation of -adrenergic signaling pathway further increases the risk of EADs, where EADs could occur at shorter cycle length (2000 ms versus 4000 ms) and lower rapid delayed rectifier K current () blockage (77% versus 85%). In summary, this study computationally demonstrated the combined role of CaMKII and -adrenergic signaling pathway on the occurrence of EADs, which could be useful for searching for therapy strategies to treat EADs related arrhythmogenesis.
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http://dx.doi.org/10.1155/2016/4576313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5178856PMC
March 2017
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