Publications by authors named "Yan Du"

575 Publications

Diprenylated flavonoids from licorice induce death of SW480 colorectal cancer cells by promoting autophagy: Activities of lupalbigenin and 6,8-diprenylgenistein.

J Ethnopharmacol 2022 Jun 18;296:115488. Epub 2022 Jun 18.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. Electronic address:

Ethnopharmacological Relevance: Licorice is a well-known herbal medicine, and we previously found that several licorice prenylated flavonoids could cause death of SW480 colorectal cancer cells by promoting autophagy. Given many kinds of prenylated flavonoids in licorice, the activities of other compounds deserve further investigation. In addition, the contribution of isoprenyl groups on the autophagy promotion activities has not been clarified.

Aim Of The Study: This study aimed to investigate whether lupalbigenin (LPB) and 6,8-diprenylgenistein (DPG), two licorice diprenylated flavonoids, could induce autophagic cell death of SW480 cells, and clarify the contribution of isoprenyl groups.

Materials And Methods: Cytotoxic activities of LPB and DPG were tested by using an MTT method, and apoptosis induction effects were evaluated by PI-Annexin V staining-based flow cytometry and protein levels of caspase-3 and PARP-1. Autophagy promotion effects of LPB and DPG were assessed by protein levels of LC3, p62, Akt and mTOR as well as number of autophagosomes in cells, and autophagy inhibitor chloroquine (CQ) was involved to identify the role of autophagy on LPB or DPG-caused death of SW480 cells. In addition, two groups of structurally similar diprenylated, mono-prenylated and free flavonoids were obtained from licorice, which were used to investigate the contribution of isoprenyl groups on their autophagy promotion activities.

Results: Both LPB and DPG significantly induced apoptosis of SW480 cells with strong cytotoxic activities, and meanwhile, they also promoted autophagy probably through the Akt/mTOR signaling pathway. Further studies indicated that LPB and DPG could induce autophagic cell death of SW480 cells. Moreover, isoprenyl groups contributed mainly to the cytotoxic and autophagy promotion activities of licorice prenylated flavonoids.

Conclusion: This study reported for the first time that licorice diprenylated flavonoids LPB and DPG induced death of SW480 cells by promoting autophagy, which was mainly attributed to the isoprenyl groups. The results provided theoretical basis for researches on anti-colorectal cancer drugs and their structural modification.
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http://dx.doi.org/10.1016/j.jep.2022.115488DOI Listing
June 2022

Identification and Verification of Ubiquitin D as a gene associated with HCV-induced HCC.

Intervirology 2022 Jun 21. Epub 2022 Jun 21.

Introduction: Accumulated studies have suggested that hepatitis C virus (HCV) infection is one of the leading causes for hepatocellular carcinoma (HCC). However, the mechanisms underlying the effect of HCV on the occurrence of HCC is still poorly understood.

Methods: HCV infection datasets (GSE82177 and GSE17856) and HCC datasets (TCGA-LIHC (The Cancer Genome Atlas Liver Hepatocellular Carcinoma) and GSE89377) were downloaded from Gene Expression Omnibus (GEO) or TCGA for analysis. The common differentially expressed genes (DEGs) in the above four datasets were identified by R software. The expression of Ubiquitin D (UBD) in HCV infected HepG2 cells was detected by RT-qPCR and western blot, respectively. The interaction between NS3 and p53 was detected by Co-Immunoprecipitation. The influence of UBD on the proliferation and migration ability of HepG2 cells was evaluated by CCK-8 and wound healing assay, respectively.

Results: UBD was upregulated in both HCV infected samples and HCC samples. HCV NS3 interacted with p53 and inhibited its expression. HCV NS3 induced UBD promoted the proliferation and migration of HepG2 cells.

Conclusion: Our results suggest that HCV NS3 induced UBD is positively correlated with the development of HCV-related HCC during HCV infection. Targeting UBD could be a potential strategy for preventing and treating HCV-induced HCC.
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http://dx.doi.org/10.1159/000525543DOI Listing
June 2022

Ct-OATP1B3 promotes high-grade serous ovarian cancer metastasis by regulation of fatty acid beta-oxidation and oxidative phosphorylation.

Cell Death Dis 2022 Jun 18;13(6):556. Epub 2022 Jun 18.

Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China.

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy mainly due to its extensive metastasis. Cancer-type organic anion transporting polypeptide 1B3 (Ct-OATP1B3), a newly discovered splice variant of solute carrier organic anion transporter family member 1B3 (SLCO1B3), has been reported to be overexpressed in several types of cancer. However, the biological function of Ct-OATP1B3 remains largely unknown. Here, we reveal that Ct-OATP1B3 is overexpressed in HGSOC and promotes the metastasis of HGSOC in vivo and in vitro. Mechanically, Ct-OATP1B3 directly interacts with insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an RNA-binding protein, which results in enhancement of the mRNA stability and expression of carnitine palmitoyltransferase 1A (CPT1A) and NADH:Ubiquinone Oxidoreductase Subunit A2 (NDUFA2), leading to increased mitochondrial fatty acid beta-oxidation (FAO) and oxidative phosphorylation (OXPHOS) activities. The increased FAO and OXPHOS activities further facilitate adenosine triphosphate (ATP) production and cellular lamellipodia formation, which is the initial step in the processes of tumor cell migration and invasion. Taken together, our study provides an insight into the function and underlying mechanism of Ct-OATP1B3 in HGSOC metastasis, and highlights Ct-OATP1B3 as a novel prognostic marker as well as therapeutic target in HGSOC.
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http://dx.doi.org/10.1038/s41419-022-05014-1DOI Listing
June 2022

Evidence for Dopamine Abnormalities Following Acute Methamphetamine Exposure Assessed by Neuromelanin-Sensitive Magnetic Resonance Imaging.

Front Aging Neurosci 2022 30;14:865825. Epub 2022 May 30.

Department of Radiology, Second Xiangya Hospital of Central South University, Changsha, China.

Background: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) is a newly developed MRI technique that provides a non-invasive way to indirectly measure of dopamine (DA) function. This study aimed to determine NM concentrations in brain regions following acute methamphetamine (MA) administration using NM-MRI and to explore whether NM-MRI can be used as a biomarker of DA function in non-neurodegenerative diseases.

Methods: Baseline NM-MRI, T1-weighted and T2-weighted images were acquired from 27 rats before drug/placebo injection. The control group ( = 11) received acute placebo (Normal saline), while the experimental group ( = 16) received acute MA. NM-MRI scans were performed 5, 30, 60 and 90 min after injection. Regions of interest (ROIs), including the caudate putamen (CP), nucleus accumbens (NAc), hippocampus (HIP), substantia nigra (SN) and crus cerebri (CC), were manually drawn by an experienced radiologist. NM-MRI signal intensity in five brain regions at different time points (baseline and 5, 30, 60, and 90 min) were analyzed.

Results: In both the control and experimental groups, at each time point (baseline and 5, 30, 60, and 90 min), the SN exhibited significantly higher NM-MRI signal intensity than the other brain regions ( < 0.05). In addition, acute MA administration resulted in a continuous upward trend in NM-MRI signal intensity in each brain region over time. However, there was no such trend over time in the control group. The NM-MRI signal intensity of SN in the experimental group was significantly higher at the 60 and 90 min compared with that in the control group ( values were 0.042 and 0.042 respectively). Within experimental group, the NM-MRI signal intensity of SN was significantly higher at the 60 and 90 min compared with that before MA administration ( values were 0.023 and 0.011 respectively). Increased amplitudes and rates of NM-MRI signal intensity were higher in the SN than in other brain regions after MA administration.

Conclusion: Our results indicated that NM was mainly deposited in the SN, and the conversion of DA to NM was most significant in the SN after acute MA exposure. Increased DA release induced by acute MA exposure may lead to increased accumulation of NM in multiple brain regions that can be revealed by NM-MRI. NM-MRI may serve as a powerful imaging tool that could have diverse research and clinical applications for detecting pathological changes in drug addiction and related non-neurodegenerative diseases.
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http://dx.doi.org/10.3389/fnagi.2022.865825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190254PMC
May 2022

Association of MTHFR 677C>T polymorphism with pregnancy outcomes in IVF/ICSI-ET recipients with adequate synthetic folic acid supplementation.

Biosci Trends 2022 Jun 10. Epub 2022 Jun 10.

Laboratory for Reproductive Immunology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphism rs1801133 (677C>T) will decrease the utilization of folate. Folate deficiency and its resulting homocysteine (HCY) accumulation can impair female fertility. Folic acid (FA) supplementation is necessary in pregnant women who are undergoing in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) - embryo transfer (ET), and especially in women with MTHFR rs1801133 C-to-T mutations. At present, affordable and accessible synthetic FA is mainly used. However, some studies have suggested that 5-methylenetetrahydrofolate (5-MTHF), a type of active FA, may be more suitable for women with the MTHFR 677C>T polymorphism, since it is safer and more effective. This retrospective study aimed to evaluate whether the MTHFR rs1801133 gene polymorphism is related to the pregnancy outcomes of IVF/ICSI-ET recipients after sufficient supplementation with FA instead of 5-MTHF. Data on 692 women undergoing IVF/ICSI-ET and taking adequate FA were collected. Participant characteristics were compared using the Kruskal-Wallis test and Pearson chi-square test. Logistic regressions were used to calculate the odds ratio (OR) and 95% confidence interval (95% CI), after adjusting for age, BMI, method of fertilization, method of embryo transfer and number of embryos transferred. An additive model (T/T vs. C/C), dominant model (C/T + T/T vs. C/C), and recessive model (T/T vs. C/T + C/C) were evaluated. Analysis revealed that MTHFR rs1801133 in IVF/ICSI-ET women with adequate FA supplementation was not associated with the pregnancy rate but with age (OR = 0.91, 95% CI = 0.88, 0.94, P < 0.001) and BMI (OR = 0.95, 95% CI = 0.90, 0.997, P = 0.037). In 349 clinically pregnant women, no association of the MTHFR 677C>T with pregnancy outcomes was found in the additive model, dominant model, or recessive model. Of the 273 women with positive pregnancy outcomes, 34 had a preterm delivery. MTHFR 677C>T was not associated with a preterm delivery after adjusting for age and BMI. The current results indicated that MTHFR polymorphism rs1801133 was not related to the pregnancy rate or pregnancy outcomes of women undergoing IVF/ICSI-ET with adequate synthetic FA supplementation, suggesting that simple supplementation with less expensive and readily available FA, rather than expensive 5-MTHF, appeared to be appropriate.
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http://dx.doi.org/10.5582/bst.2021.01306DOI Listing
June 2022

The Role of Cancer-Associated Fibroblasts in Ovarian Cancer.

Cancers (Basel) 2022 May 26;14(11). Epub 2022 May 26.

Clinical Research Unit, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.

Ovarian cancer is a lethal gynecologic tumor and is generally resistant to conventional treatments. Stable cancer-associated fibroblasts (CAFs) are important cellular components in the ovarian cancer tumor microenvironment and may provide novel resources for future treatment strategies. Different subtypes of CAFs display specific functions in tumor pathogenesis and various CAF markers suggest potential treatment targets, such as FAP and GPR77. Both autocrine and paracrine cytokines play important roles in the CAF activation process and regulate tumor progression. Downstream mediators and pathways, including IL-6, TGF-β, NF-κB, mitogen-activated protein kinase (MAPK), and AKT/mTOR/(p70S6K), play important roles in the initiation, proliferation, invasiveness, and metastasis of ovarian cancer cells and also participate in angiogenesis, therapeutic resistance, and other biological processes. Several clinical or preclinical trials have targeted stromal fibroblasts and focused on the properties of CAFs to enhance ovarian cancer treatment outcomes. This review concentrates on the origins, subtypes, and activation of CAFs, as well as specific roles of CAFs in regulating tumor development and drug resistance, and aims to provide potential and prospective targets for improving the therapeutic efficacy of ovarian cancer treatment.
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http://dx.doi.org/10.3390/cancers14112637DOI Listing
May 2022

Activation of CD44 signaling in leader cells induced by tumor-associated macrophages drives collective detachment in luminal breast carcinomas.

Cell Death Dis 2022 Jun 9;13(6):540. Epub 2022 Jun 9.

Department of Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Collective detachment of cancer cells at the invading front could generate efficient metastatic spread. However, how cancer cell clusters shed from the leading front remains unknown. We previously reported that the dynamic expression of CD44 in breast cancers (BrCas) at collectively invading edges was associated with tumor-associated macrophages (TAMs). In this study, we first observed that the highly expressed CD44 (CD44) cancer cell clusters were located in the BrCa circulating vessels, accompanied by CD206 TAMs. Next, we identified that the cancer cell clusters can be converted to an invasive CD44 state which was induced by TAMs, thus giving rise to CD44-associated signaling mediated cohesive detachment. Then, we showed that disrupting CD44-signaling inhibited the TAMs triggered cohesive detaching using 3D organotypic culture and mouse models. Furthermore, our mechanistic study showed that the acquisition of CD44 state was mediated by the MDM2/p53 pathway activation which was induced by CCL8 released from TAMs. Blocking of CCL8 could inhibit the signaling cascade which decreased the CD44-mediated cohesive detachment and spread. Our findings uncover a novel mechanism underlying collective metastasis in BrCas that may be helpful to seek for potential targets.
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http://dx.doi.org/10.1038/s41419-022-04986-4DOI Listing
June 2022

Magnetic polyimide nanosheet microspheres for trace analysis of estrogens in aqueous samples by magnetic solid-phase extraction-gas chromatography-mass spectrometry.

J Chromatogr A 2022 Jul 31;1675:463184. Epub 2022 May 31.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, State Key Laboratory Base of Novel Functional Materials and Preparation Science, School of Materials Science & Chemical Engineering, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address:

Magnetic polyimide nanosheet microspheres (PI-NMs) were used for magnetic solid-phase extraction (MSPE) for the first time. The PI-NMs were modified with magnetic FeO nanoparticles by chemical coprecipitation to produce the PI-NM/FeO composite. The prepared composite possessed a nanosheet structure, large specific surface area (71.5 m/g), high saturation magnetization (19.1 emu/g), large adsorption capacity (≥ 676 ng/mg for selected estrogens), and good extraction stability (> 10 times). Trace estrogens in environmental water and urine samples were extracted by the PI-NM/FeO composite, desorbed, derivatized, and analyzed by gas chromatography-mass spectrometry (GC-MS). The derivatization, extraction, and desorption conditions were optimized. Extraction equilibrium was achieved within 1 min due to the good dispersibility and large specific surface area of the PI-NM/FeO composite. Under the optimized conditions, the MSPE/GC-MS method validation results showed wide linearity (0.02-50 µg/L or 0.05-50 µg/L), high determination coefficients (R ≥ 0.9983), good intraday and interday precisions (expressed as relative standard deviation, RSDs ≤ 8.2%), and low limits of detection (LODs, 0.001-0.015 µg/L). For the real environmental water and urine samples, the recoveries and RSDs were 77.0-112.5% and 0.1-10.7%, respectively. The performance of the MSPE/GC-MS method proved that the PI-NM/FeO composite was a good alternative material for the extraction of organic pollutants in aqueous samples.
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http://dx.doi.org/10.1016/j.chroma.2022.463184DOI Listing
July 2022

A nomogram for predicting survival in patients with advanced (stage III/IV) pancreatic body tail cancer: a SEER-based study.

BMC Gastroenterol 2022 Jun 3;22(1):279. Epub 2022 Jun 3.

The First Clinical Medical College, Lanzhou University, Lanzhou, China.

Objective: Pancreatic body tail carcinoma (PBTC) is a relatively few pancreatic cancer in clinical practice, and its specific clinicopathological features and prognosis have not been fully described. In this study, we aimed to create a nomogram to predict the overall survival (OS) of patients with advanced PBTC.

Methods: We extracted clinical and related prognostic data of advanced PBTC patients from 2000 to 2018 from the Surveillance, Epidemiology, and End Results database. Independent prognostic factors were selected using univariate and multivariate Cox analyses, and a nomogram was constructed using R software. The C-index, area under the curve (AUC) of receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to assess the clinical utility of the nomogram. Finally, OS was assessed using the Kaplan-Meier method.

Results: A total of 1256 patients with advanced PBTC were eventually included in this study. Age, grade, N stage, M stage, surgery, and chemotherapy were identified as independent risk factors using univariate and multivariate Cox regression analyses (p < 0.05). In the training cohort, the calibration index of the nomogram was 0.709, while the AUC values of the nomogram, age, grade, N stage, M stage, surgery, and chemotherapy were 0.777, 0.562, 0.621, 0.5, 0.576, 0.632, and 0.323, respectively. Meanwhile, in the validation cohort, the AUC values of the nomogram, age, grade, N stage, M stage, surgery, and chemotherapy were 0.772, 0.551, 0.629, 0.534, 0.577, 0.606, and 0.639, respectively. Good agreement of the model in the training and validation cohorts was demonstrated in the calibration and DCA curves. Univariate survival analysis showed a statistically significant effect of age, grade, M stage, and surgery on prognosis (p < 0.05).

Conclusion: Age, grade, M stage, and surgery were independently associated with OS, and the established nomogram was a visual tool to effectively predict OS in advanced PBTC patients.
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http://dx.doi.org/10.1186/s12876-022-02362-2DOI Listing
June 2022

MicroRNA-27a-3p inhibits lung and skin fibrosis of systemic sclerosis by negatively regulating SPP1.

Genomics 2022 May 26;114(4):110391. Epub 2022 May 26.

Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China. Electronic address:

Objective: To investigate the role and mechanism of microRNAs (miRNAs) in fibrotic processes involved in the pathology of systemic sclerosis (SSc).

Methods: R language and bioinformatics methods were used to identify differential miRNAs and mRNAs and analyze their biological functions. Transfection experiments were performed to evaluate the function and regulatory mechanism of miR-27a-3p in vitro. Levels of fibrosis-related genes, SPP1 and cell proliferation were assessed.

Results: MiR-27a-3p is reduced both in SSc lung and skin tissues. Overexpression of miR-27a-3p significantly inhibited fibrosis-related genes expression and protein abundance and cell proliferation, whereas inhibition of miR-27a-3p significantly enhanced these phenomena. Moreover, miR-27a-3p exerts its anti-fibrosis effect by negatively regulating SPP1 and ERK signal, more prominent in fibroblasts.

Conclusions: Our findings show that miR-27a-3p regulates a common mechanism in the process of SSc skin and lung fibrosis. MiR-27a-3p/SPP1/ERK1/2 axis may be an important target for delaying the progression of SSc fibrosis.
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http://dx.doi.org/10.1016/j.ygeno.2022.110391DOI Listing
May 2022

The Velvet Protein UvVEA Regulates Conidiation and Chlamydospore Formation in .

J Fungi (Basel) 2022 May 4;8(5). Epub 2022 May 4.

Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China.

Rice false smut, caused by , is a serious disease of rice worldwide, severely reducing the quantity and quality of rice production. The conserved fungal velvet proteins are global regulators of diverse cellular processes. We identified and functionally characterized two velvet genes, and , in . The deletion of these genes affected the conidiation of but had no effect on the virulence of this pathogen. Interestingly, the Δ mutants appeared in the form of smaller false smut balls with a reduced number of chlamydospores compared with the wide-type strains. In addition, the deletion of affected the expression of some transmembrane transport genes during chlamydospore formation and rice false smut balls development. Furthermore, the Δ mutants were shown to be defective in the utilization of glucose. These findings proved the regulatory mechanism underlying the formation of rice false smut balls and chlamydospores and provided a basis for the further exploration of the mechanism of these processes.
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http://dx.doi.org/10.3390/jof8050479DOI Listing
May 2022

Dietary Factors and Incidence of Hydatidiform Mole: An Ecological Study.

Nutr Cancer 2022 May 27:1-8. Epub 2022 May 27.

Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.

The current ecological study aims to explore the association between dietary factors and hydatidiform mole (HM) incidence in Japan and China. HM incidence in Japan gradually declined from 1970s to 1990s, while the dietary structure also changed during the same period, mainly characterized by a decrease in the consumption of cereals and an increase in the consumption of meat, eggs, and dairy products. In China, HM incidence varied by regions, and it positively correlated with the per capita intake of rice, fish and shrimp, and animal fat, as well as the proportion of GDP of primary industry; and negatively correlated with the per capita intake of wheat flour, starch and sugar, protein, and iron, and the proportion of protein in the caloric nutrients and the proportion of nonagricultural population. In partial analysis, the correlations of HM incidence with rice, fish and shrimp, iron, and the proportion of protein in caloric nutrients remained significant. Meanwhile, alcoholic beverage consumption and the proportion of empty calories in caloric food were also found to be positively correlated with HM incidence, while phosphorus consumption was negatively correlated. Our results suggested that HM incidence could be influenced by dietary factors.
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http://dx.doi.org/10.1080/01635581.2022.2079688DOI Listing
May 2022

Diagnosis of disease relevant nucleic acid biomarkers with off-the-shelf devices.

Authors:
Lijuan Qi Yan Du

J Mater Chem B 2022 Jun 1;10(21):3959-3973. Epub 2022 Jun 1.

State key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Jilin, P. R. China.

Changes in the level of nucleic acids in blood may be correlated with some clinical disorders like cancer, stroke, trauma and autoimmune diseases, and thus, nucleic acids can serve as potential biomarkers for pathological processes. The requirement of technical equipment and operator expertise in effective information readout of modern molecular diagnostic technologies significantly restricted application outside clinical laboratories. The ability to detect nucleic acid biomarkers with off-the-shelf devices, which have the advantages of portability, simplicity, low cost and short response time, is critical to provide a prompt clinical result in circumstances where the laboratory instruments are not available. This review throws light on the current strategies and challenges for nucleic acid diagnosis with commercial portable devices, indicating the future prospect of portable diagnostic devices and making a great difference in improving the healthcare and disease surveillance in resource-limited areas.
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http://dx.doi.org/10.1039/d2tb00232aDOI Listing
June 2022

High-coverage lipidomics analysis reveals biomarkers for diagnosis of acute exacerbation of chronic obstructive pulmonary disease.

J Chromatogr B Analyt Technol Biomed Life Sci 2022 Jun 5;1201-1202:123278. Epub 2022 May 5.

Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases co-constructed by Henan Province & Education Ministry of P.R. China, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, PR China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, PR China; The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, PR China. Electronic address:

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the leading cause of morbidity and mortality in COPD management. However, detecting the progression from the stable stage to acute exacerbation mainly depends on doctors' judgment of clinical symptoms, and there is no biomarker that can be used for auxiliary clinical diagnosis. In this work, serum samples from COPD patients (n = 82) and healthy subjects (n = 29) were collected and analyzed. Patients with COPD were divided into stable COPD (SCOPD) and AECOPD groups, with the latter comprising subtypes 1 and 2. High-coverage lipidomics profiling of 913 lipids belonging to 19 subclasses was carried out by liquid chromatography-Q-Exactive orbitrap mass spectrometry. We performed 4 cross-comparisons to characterize metabolic disturbances associated with the progression of stable COPD to AECOPD-ie, SCOPD vs healthy subjects, AECOPD vs SCOPD, AECOPD subtype 1 vs SCOPD, and AECOPD subtype 2 vs SCOPD. We tentatively identified 86 lipids with differential abundance among groups, lipids that were altered from the stable stage of disease to AECOPD included sphingolipids, ether-containing glycerophospholipids, phosphatidylglycerols, and glycerol lipids. Three panels of lipid biomarkers specific to AECOPD, AECOPD subtypes 1 and 2 vs SCOPD yielded areas under the receiver operating characteristic curve of 0.788, 0.921 and 0.920, respectively, with sensitivity of 77.5%, 80.7% and 91.3%, respectively, and specificity of 75.8%, 97.0% and 87.9%, respectively. The result indicated differences in lipid metabolism may underlie AECOPD and its 2 subtypes and can serve as biomarkers for early diagnosis, and high-coverage lipidomics proved to be an accurate approach to profile the lipid metabolism in biological samples.
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http://dx.doi.org/10.1016/j.jchromb.2022.123278DOI Listing
June 2022

Synthesis of Molecularly Imprinted Polymers Based on a New Monomer "2-(4-Vinylphenyl) Quinoline-4-Carboxylic Acid" for the Selective Solid-Phase Extraction of Lamotrigine.

J Chromatogr Sci 2022 May 10. Epub 2022 May 10.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.

A new molecularly imprinted polymers (MIPs) have been prepared for the high selective extraction of lamotrigine (LTG), a widely used antiepileptic drug, in human serum. The MIPs were polymerized by bulk polymerization using our synthesized compound, 2-(4-vinylphenyl) quinolin-4-carboxylic acid, as functional monomer, which achieved better adsorption specificity than universal MIPs. Then, the molecularly imprinted solid phase extraction (MISPE) based on this material was coupled with high-performance liquid chromatography (HPLC) for the detection of LTG in human serum. The results of method validation showed that the developed method presented a good precision and accuracy, and the linearity was in the range of 1.50-40.00 mg/mL with the limit of quantitation (LOQ) at 0.20 mg/mL. The recovery ranged from 80.8% to 83.8% with RSD ranges from 5.5% to 11.1%. The validated method was successfully used to determine the concentration of LTG in human simulate serum samples.
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http://dx.doi.org/10.1093/chromsci/bmac037DOI Listing
May 2022

[Association of Dietary Diversity with Growth and Development of Children in Multi-ethnic Rural Areas of Sichuan Province].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2022 Apr;44(2):236-243

Department of Health Behavior and Social Medicine, West China School of Public Health and West China Fourth Hospital,Sichuan University,Chengdu 610041,China.

Objective To understand the growth and dietary diversity status of children in multi-ethnic areas of Sichuan province,and to explore the associations of dietary diversity with growth and development indicators. Methods Children of 18-36 months old and their primary caregivers were selected with multi-stage cluster random sampling method from rural areas of Han,Tibetan,and Yi ethnic groups in Sichuan province. The sociodemographic information of children and their caregivers was collected using self-designed questionnaire.The dietary diversity score(DDS)was calculated according to the criteria in the released by the Food and Agriculture Organization of the United Nations.The body height(length)and body weight of each child were measured by standard equipment for anthropological measurement,and the height for age Z score(HAZ),weight for age Z score(WAZ),and weight for height Z score(WHZ) were calculated.Multivariate linear regression was performed to analyze the relationship between dietary diversity and growth indicators of children. Results A total of 1092 children were enrolled in this study,and the prevalence of stunting(HAZ<-2),underweight(WAZ<-2),and wasting(WHZ<-2)was 21.1%,4.9%,and 2.5%,respectively.The children had the mean DDS of 4.8±1.7,and 45.3% of children had poor dietary diversity(DDS≤4).The children of Han ethnic group(5.8±1.4)had higher DDS than those of Tibetan ethnic group(4.9±1.6)and Yi ethnic group(3.9±1.6)(<0.001).The results of multivariate linear regression indicated that DDS was positively correlated with HAZ(=0.206,95%=0.158-0.254,<0.001)after adjustment of sex,age,birth weight,preterm birth,and parental body height.After further adjustment of family fixed assets,ethnic group,caregiver's type,and caregiver's education background,the correlation between DDS and HAZ remained significant(=0.077,95%=0.026-0.128, =0.003). Conclusions The children in the multi-ethnic rural areas of Sichuan province showed troublesome growth and development status and low dietary diversity,which were conspicuously different between ethnic groups,especially in the rural areas of Yi ethnic group.The dietary diversity was positively associated with HAZ.It is recommended to carry out nutrition and health education according to the local dietary characteristics and thus improve the growth and development of children in multi-ethnic rural areas in Sichuan.
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http://dx.doi.org/10.3881/j.issn.1000-503X.14272DOI Listing
April 2022

[Evaluation of Accuracy and Influencing Factors for Diagnosis of Two Chronic Diseases by Primary Healthcare Providers in Sichuan Rural Areas Based on Standardized Patients].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2022 Apr;44(2):213-220

Department of Health Behavior and Social Medicine,West China School of Public Health and West China Fourth Hospital, Sichuan University,Chengdu 610041,China.

Objective We used standardized patients to evaluate the accuracy and explore the influencing factors of the diagnosis of unstable angina pectoris and type 2 diabetes by primary healthcare providers in Sichuan rural areas,aiming to provide a scientific basis for improving the diagnosis accuracy of primary healthcare providers for the two chronic diseases. Methods A multi-stage stratified random cluster sampling method was adopted to select 100 villages from 50 townships in 5 districts/counties in Zigong city,Sichuan province. General and internal medicine practioners who were on duty on the survey day were enrolled in the survey.Two rounds of data collection were conducted.In the first round,the basic information of providers from township health centers and village clinics was collected.One month after the the first survey,standardized patients were used to collect the information related to the diagnosis of unstable angina pectoris and type 2 diabetes by rural primary providers.Logistic regression was carried out to analyze the factors influencing the diagnosis accuracy. Results A total of 172 rural primary healthcare providers were enrolled in the survey,who completed 186 standardized patient visits and showed the correct diagnosis rate of 48.39%.Specifically,the correct diagnosis rates of unstable angina pectoris and type 2 diabetes were 18.68%(17/91) and 76.84%(73/95),respectively.The providers with medical practitioner qualifications were more likely to make correct diagnosis(=4.857,95%=1.076-21.933, =0.040).The providers who involved more necessary consultation and examination items in the diagnosis process had higher probability of correct diagnosis(=1.627,95%=1.065-2.485, =0.024).Additionally,the providers were more likely to make a correct diagnosis for type 2 diabetes than for unstable angina pectoris(=6.306,95%=3.611-11.013, <0.001). Conclusions The overall diagnosis accuracy of unstable angina pectoris and type 2 diabetes was relatively low among primary healthcare providers in Sichuan rural areas.The training of diagnosis process can be taken as a key for improving providers' practice ability so as to increase the diagnosis accuracy of chronic diseases.
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http://dx.doi.org/10.3881/j.issn.1000-503X.14218DOI Listing
April 2022

[Psychological Status and Influencing Factors of Staff at Centers for Disease Control and Prevention in Sichuan Province during the Outbreak of Coronavirus Disease 2019].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2022 Apr;44(2):199-207

Department of Health Behavior and Social Medicine,West China School of Public Health and West China Fourth Hospital, Sichuan University,Chengdu 610041,China.

Objective To assess the psychological status of staff at the centers for disease control and prevention(CDC) in Sichuan during the outbreak of coronavirus disease 2019(COVID-19) and explore the influencing factors. Methods The staff at Sichuan provincial,municipal,and county(district)-level CDC were selected by convenience sampling.Their basic information,work status,training status,work difficulties,and support from the work group were collected from the self-filled questionnaires online.The Generalized Anxiety Disorder Scale and the 9-question Patient Health Questionnaire were respectively employed to measure the anxiety and depression of the staff.The stepwise Logistic regression was carried out to analyze the influencing factors of anxiety and depression in CDC staff. Results Among the 653 staff,58.35% and 50.06% presented anxiety and depression,respectively.The regression results showed that age(=0.95,95%=0.92-0.97) and mental support from the work group(=0.61,95%=0.45-0.82) were the protective factors while physical fatigue(=1.82,95%=1.20-2.74),work pressure(=1.61,95%=1.21-2.12),and insufficient protective equipment(=1.92,95%=1.06-3.49) were the risk factors for depression of CDC staff.Age(=0.97,95%=0.94-0.99),length of sleep per day(=0.74,95%=0.56-0.96),and participation in technical training(=0.33,95%=0.12-0.95) were the protective factors while mental fatigue(=1.68,95%=1.18-2.41),work pressure(=2.94,95%=2.08-4.17),and unclear incentive system for overtime(=1.99,95%=1.23-3.23) were the risk factors for the anxiety of CDC staff. Conclusion The anxiety and depression status of CDC staff during the COVID-19 outbreak were worrying,which were mainly affected by age,sleep,supply of protective equipment,incentive system,fatigue,and work pressure.
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http://dx.doi.org/10.3881/j.issn.1000-503X.14151DOI Listing
April 2022

Associations of physical activity with sarcopenia and sarcopenic obesity in middle-aged and older adults: the Louisiana osteoporosis study.

BMC Public Health 2022 05 5;22(1):896. Epub 2022 May 5.

Center for Bioinformatics and Genomics, School of Medicine, Tulane University; New Orleans, LA, New Orleans, United States of America.

Background: This study examined the associations between physical activity, obesity, and sarcopenia in middle-aged and older adults.

Methods: We analyzed the data of 8, 919 study participants aged between 45 to 97 (mean age = 57.2 ± 8.8) from a Southern state in the United States. Self-reported physical activity was classified to regular exercise ≥ 3 times/week, < 3 times/week, and no regular exercise. Associations between physical activity, obesity and sarcopenia were explored with generalized linear models and ordinal logistic regressions stratified by age (middle-aged and older adults) and gender adjusting for covariates.

Results: In middle-aged and older adults, all examined obesity related traits (e.g., body mass index, waist circumference) were inversely associated with physical activity levels (p < 0.01) in both genders. Exercising ≥ 3 times/week was negatively associated with lean mass indicators (e.g., appendicular lean mass) in middle-aged and older females (p < 0.01), while the negative associations become positive after adjusting for weight. Positive associations between physical activity and grip strength were only found in middle-aged males (p < 0.05). Ordinal logistic regression revealed that those exercising ≥ 3 times/week were less likely to have obesity, sarcopenia, and sarcopenia obesity in all groups (p < 0.01), except for sarcopenia in older males and females (p > 0.05). Positive associations of exercising < 3 times/week with sarcopenia and sarcopenia obesity were only found in middled adults.

Conclusion: The associations of exercise frequency with obesity and sarcopenia vary considerably across gender and age groups. Exercise programs need to be individualized to optimize health benefits. Future research exploring physical activity strategies to balance weight reduction and lean mass maintaining is warranted in middle-aged and especially older adults.
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http://dx.doi.org/10.1186/s12889-022-13288-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074188PMC
May 2022

A Valence-Engineered Self-Cascading Antioxidant Nanozyme for the Therapy of Inflammatory Bowel Disease.

Angew Chem Int Ed Engl 2022 Apr 22:e202201101. Epub 2022 Apr 22.

College of Engineering and Applied Sciences, Nanjing National Laboratory of Microstructures, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, Jiangsu, 210023, China.

Antioxidant treatment strategy by scavenging reactive oxygen species (ROS) is a highly effective disease treatment option. Nanozymes with multiple antioxidant activities can cope with the diverse ROS environment. However, lack of design strategies and limitation of negative correlation for nanozymes with multiple antioxidant activities hindered their development. To overcome these difficulties, here we used ZnMn O as a model to explore the role of Mn valency at the octahedral site via a valence-engineered strategy, and found that its multiple antioxidant activities are positively correlated with the content of Mn . Therefore, through this strategy, a self-cascading antioxidant nanozyme LiMn O was constructed, and its efficacy was verified at the cellular level and in an inflammatory bowel disease model. This work not only provides guidance for the design of multiple antioxidant nanozymes, but also broadens the biomedical application potential of multiple antioxidant nanozymes.
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http://dx.doi.org/10.1002/anie.202201101DOI Listing
April 2022

Identification of Differentially Expressed Genes Reveal Conserved Mechanisms in the Rice- Interaction.

Front Plant Sci 2022 5;13:723356. Epub 2022 Apr 5.

Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences (JAAS), Nanjing, China.

causes rice blast disease and is responsible for major losses in rice production worldwide. Although numerous studies have focused on the interactions between and , to date, the conserved mechanisms remain in part unclear. In this study, a comparative analysis of transcriptomes of L. ssp. cv. 'Nipponbare' interacting with three strains (248, 235, and 163) were performed to explore the conserved molecular mechanisms. Differentially expressed genes with similar expression patterns in the interactions between cultivar 'Nipponbare' and three strains were defined as Conserved Differentially Expressed Genes (CDEGs). These included 3,647 CDEGs and 3,655 CDEGs. Four rice CDEGs (, , , and ) encoding universal stress protein (USP) were induced within 24 h post-inoculation (hpi) by three strains. Meanwhile, overexpression of resulted in enhanced rice resistance against . Furthermore, four rice genes coding light-harvesting chlorophyll a/b-binding (LHC) protein (, , , ) were also identified as CDEGs and were induced at 48 hpi, which might contribute to blast resistance through reactive oxygen species (ROS) accumulation. is effector inducing rice cell death and were verified that include AA9 CAZy domain (namely GH61 domain). In this study, we found seven homologous genes coding proteins with signal peptides and AA9 CAZy domains, which were continuously up-regulated across all infection stages relative to uninoculated control. This study uncovered that genes are required for conserved mechanisms of rice- interaction, which includes rice genes encoding USP proteins and LHC proteins, as well as genes encoding AA9 proteins. This study will help us to understand how responds to infections and the molecular mechanisms of pathogenicity.
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http://dx.doi.org/10.3389/fpls.2022.723356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016282PMC
April 2022

Development and evaluation of a simple and easy high-performance liquid chromatography-ultraviolet system simultaneously suitable for determination of 24 anti-epileptic drugs in plasma.

J Sep Sci 2022 Apr 20. Epub 2022 Apr 20.

Jiangsu Key Laboratory of New Drug and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, P. R. China.

This paper aims to establish a simple and easy high-performance liquid chromatography system coupled with an ultraviolet detector suitable for simultaneous determination of 24 antiepileptic drugs in human plasma. Optimized chromatographic separation was performed on a ZORBAX Eclipse Plus-C18 (4.6 × 150 mm , 3.5 μm) column with acetonitrile and 5 mM potassium dihydrogen phosphate water solution as mobile phase. Note that, 24 antiepileptic drugs were divided into three groups and eluted with different gradient procedures, respectively. The column temperature was maintained at 35°C and the detection wavelength was set at 210 nm. Plasma was processed with ethyl acetate or acetonitrile. The calibration curves of 24 antiepileptic drugs demonstrated good linearity within the test range (r > 0.996). The intra- and inter-batch precision and accuracy were all less than 15%, while extraction recoveries were in the range of 74.57%-90.89% with the relative standard deviation values less than 15%. The validated methods have been successfully applied to determination of some antiepileptic drugs in rat or patient plasma. Those results indicated that the developed methods were simple and easy, and could be suitable for the determination of 24 antiepileptic drugs in plasma just by changing the gradient elution procedures of mobile phase.
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http://dx.doi.org/10.1002/jssc.202200246DOI Listing
April 2022

Development of magnetic molecularly imprinted polymers with double templates for the rapid and selective determination of carbamazepine and lamotrigine in serum.

RSC Adv 2022 Mar 30;12(16):10051-10061. Epub 2022 Mar 30.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University Xuzhou 221004 China.

A dual-template magnetic molecularly imprinted polymer (Dt-MMIP) with a specific recognition capability for carbamazepine (CBZ) and lamotrigine (LTG) was synthesized using methacrylic acid as a functional monomer, and ethylene glycol dimethylmethacrylate as a cross-linking agent. A magnetic non-molecularly imprinted polymer without templates (MNIP) was also prepared using the same procedure. The prepared polymers were characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy and adsorption experiments. Results indicated that both Dt-MMIPs and MNIPs were microspherical nanoparticles, and the surface of the Dt-MMIP was rougher than that of the MNIP. In addition, the prepared Dt-MMIPs possessed a higher adsorption capacity and better selectivity for CBZ and LTG than the MNIPs. The maximum static adsorption capacities of Dt-MMIP for CBZ and LTG were 249.5 and 647.9 μg g, respectively, whereas those of MNIP were 75.8 and 379.8 μg g, respectively. The obtained Dt-MMIPs were applied as a magnetic solid-phase extraction sorbent for the rapid and selective extraction of CBZ and LTG in rat serum samples, and determination was performed by high-performance liquid chromatography with UV detection (HPLC-UV). The developed method of dispersive SPE based on Dt-MMIPs coupled to HPLC-UV has good rapidity and selectivity, and application prospects in serum.
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http://dx.doi.org/10.1039/d1ra09306aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966734PMC
March 2022

Clinical significance of anti-transcriptional intermediary factor 1-γ antibody in patients with dermatomyositis: a monocentric cross-sectional study.

Clin Rheumatol 2022 Apr 14. Epub 2022 Apr 14.

Department of Rheumatology, The Second Affiliate Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.

Objectives: To determine the prevalence of anti-transcriptional intermediary factor 1-γ antibody (anti-TIF1-γ-Ab) and to explore its associations with clinical features in patients with dermatomyositis.

Methods: Sixteen kinds of myositis-specific/associated antibodies were examined in 141 dermatomyositis patients by western blotting. Clinical features and laboratory data were collected. The frequency of anti-TIF1-γ-Ab positivity and its correlations with clinical phenotypes were analyzed using SPSS 23.0 software.

Results: Dermatomyositis patients with anti-TIF1-γ-Ab were prone to malignancy (P < 0.001); were more likely to present with heliotrope rash (P = 0.007), shawl sign (P < 0.001), and V sign (P < 0.001); and had relatively longer disease duration (P = 0.031), but were less likely to present with interstitial lung disease (P < 0.001) and mechanic's hand (P = 0.003) than the anti-TIF1-γ-Ab-negative subgroup. Anti-TIF1-γ-Ab status was independently associated with the presence of malignancy during multivariate logistic regression analysis. Among the anti-TIF1-γ-Ab-positive dermatomyositis patients, the subgroup with malignancy was prone to present with all types of rashes (87.5% vs. 13.3%, P = 0.001) and has higher incidence of male than the without-malignancy subgroup (50% vs. 6.7%, P = 0.033).

Conclusions: Anti-TIF1-γ-Ab positivity was identified as a specific serological indicator of dermatomyositis with malignancy. Men with anti-TIF1-γ-Ab positivity were more likely to have malignancy than women. Increasing types of rashes were associated with greater likelihood of developing malignancy. Key Points • The clinical features of anti-TIF1-γ-Ab in patients with dermatomyositis.
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http://dx.doi.org/10.1007/s10067-022-06170-7DOI Listing
April 2022

Femur-tibia angle and patella-tibia angle: new indicators for diagnosing anterior cruciate ligament tears in magnetic resonance imaging.

BMC Sports Sci Med Rehabil 2022 Apr 13;14(1):66. Epub 2022 Apr 13.

Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.

Background: Femur-tibia angle (FTA) and patella-tibia angle (PTA) are two MRI measurements that reflect the rotation of the knee joint. The purposes of this study were to assess whether FTA and PTA are associated with ACL tear and to explore their roles in ACL tear diagnosis.

Methods: FTA, PTA, ACL angle and anterior tibial subluxation were compared between the two matched groups: ACL tear group and control group (each n = 20). Diagnostic performance was evaluated in a consecutive 120-patient cohort who underwent MR imaging of the knee and subsequently had arthroscopy. Different measurements were assessed by area under the curve (AUC) of receiver operating characteristic (ROC) curve.

Results: FTA and PTA increased significantly in ACL tears group when compared to the control group (4.79 and 7.36 degrees, respectively, p < 0.05). In distinguishing complete ACL tear, ACL angle had the highest AUC of 0.906 while AUC of PTA and FTA were 0.849 and 0.809. The cutoff of FTA was 80 degrees with a sensitivity of 82% and specificity of 68%, while the cutoff of PTA was 91 degrees with a sensitivity of 82% and specificity of 74%. In distinguishing partial ACL tear, FTA and PTA had the highest AUCs of 0.847 and 0.813, respectively. The calculated cutoff of FTA was 84 degrees with a sensitivity of 90% and specificity of 81%, while the cutoff of PTA was 92 degrees with a sensitivity of 80% and specificity of 77%.

Conclusion: FTA and PTA increased when ACL tears and they might be valuable in diagnosing ACL tears, especially in distinguishing partial ACL tear from intact ACL.
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http://dx.doi.org/10.1186/s13102-022-00462-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009057PMC
April 2022

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IA1 with LVSI, IA2): study protocol of the LAUNCH 1 trial.

BMC Cancer 2022 Apr 9;22(1):384. Epub 2022 Apr 9.

Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.

Background: A retrospective study and a randomized controlled trial published in a high quality journal in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology, therefore this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stage IA1 with LVSI, IA2) patient survival under stringent operation standards and consistent tumor-free technique. This paper reports the rationale, design, and implementation of the trial.

Methods: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 690 patients with stage IA1 (with intravascular), and IA2 cervical cancer will be enrolled over a period of three years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed-up for at least five years. The primary endpoint will be 5-year progression-free survival. Secondary endpoints will include 5-year overall survival rates, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and quality of life.

Discussion: The results of the trial will provide valuable evidence for guiding clinical decision of choosing appropriate treatment strategies for stage IA1 (LVSI) and stage IA2 cervical cancer patients.

Trial Registration: ClinicalTrials.gov ( NCT04934982 , Registered on 22 June 2021).
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http://dx.doi.org/10.1186/s12885-022-09494-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994356PMC
April 2022

A multicenter non-inferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stages IB1, IB2, and IIA1): study protocol of the LAUNCH 2 trial.

Trials 2022 Apr 8;23(1):269. Epub 2022 Apr 8.

Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.

Background: A retrospective study and a randomized controlled trial published in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early-stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology; therefore, this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB1, IB2, and IIA1) patient survival under stringent operation standards and consistent surgical oncologic principles.

Methods/design: This is an investigator-initiated, Prospective, Randomized, Open, Blinded End-point (PROBE)-controlled non-inferiority trial. A total of 780 patients with stage IB1, IB2, and IIA1 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary endpoint will be 5-year progression-free survival, and secondary endpoints include 5-year overall survival, recurrence, and quality of life measurements.

Discussion: The debate on laparoscopic versus abdominal RH is still ongoing, and high-quality evidences are needed to guide clinical practice. The study results will provide more convincing evidence-based information for early-stage cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method.

Trial Registration: ClinicalTrials.gov NCT04929769 . Registered on 18 June 2021.
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http://dx.doi.org/10.1186/s13063-022-06245-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991786PMC
April 2022

Role of dopamine D3 receptors in methamphetamine-induced behavioural sensitization and the characterization of dopamine receptors (D1R-D5R) gene expression in the brain.

Folia Neuropathol 2022 ;60(1):105-113

College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, China.

Introduction: As a central nervous system stimulant, methamphetamine (METH) can cause lasting changes after being abused, including possible changes of gene expression in the brain. The dopamine (DA) system plays a fundamental role in METH-induced behavioural changes, but the expression levels of various subtypes of DA receptors, especially the dopamine D3 receptor (D3R), remains unclear.

Material And Methods: We explored the effect of the D3R on METH-induced behavioural sensitization by comparing D3R knockout (D3R-/-) mice with wild type (WT) mice. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of the five DA receptor (D1R, D2R, D3R, D4R, and D5R) genes in four brain regions: the prefrontal cortex (PFc), nucleus accumbens (NAc), caudate-putamen (CPu), and hippocampus (Hip).

Results: The behavioural test results revealed that METH could induce behavioural sensitization both in WT and D3R-/- mice. Moreover, in D3R-/- mice, the increase in movement distance induced by methamphetamine was significantly less than that of wild-type mice. The response of the five DA receptors to METH exposure varies in different brain regions. To be more specific, METH increased the expression of the D3R gene in most brain regions of WT mice, decreased D1R and D2R gene expression both in the NAc and CPu of WT mice and in CPu of D3R-/- mice.

Conclusions: These results suggested that D3R may play a positive regulatory role in the locomotor effects of METH, and five DA receptors, especially D1R, D2R, and D3R, may concurrently participate in the adaptive changes and the regulation of METH-induced behavioural sensitization.
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http://dx.doi.org/10.5114/fn.2022.114021DOI Listing
April 2022

Lipid metabolism disorders and lipid mediator changes of mice in response to long-term exposure to high-fat and high sucrose diets and ameliorative effects of mulberry leaves.

Food Funct 2022 Apr 20;13(8):4576-4591. Epub 2022 Apr 20.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.

Mulberry leaves exhibit anti-lipogenic and lipid-lowering effects. However, the lipid biomarkers and underlying mechanisms for the improvement of the action of mulberry leaves on obesity and lipid metabolism disorders have not been sufficiently investigated yet. Herein, biochemical analysis combined with metabolomics targeting serum lipid mediators (oxylipins) were used to explore the efficacy and underlying mechanisms of mulberry leaf water extract (MLWE) in high-fat and high-sucrose diet (HFHSD)-fed mice. Our results showed that MLWE supplementation not only decreased body weight gain, serum total triglycerides, low-density lipoprotein cholesterol, alanine transaminase and aspartate transaminase levels, but also increased the serum level of high-density lipoprotein cholesterol. In addition, MLWE supplementation also ameliorated hepatic steatosis and lipid accumulation. These beneficial effects were associated with down-regulating genes involved in oxidative stress, inflammation, and lipogenesis such as acetyl-CoA carboxylase and fatty acid synthase, and up-regulating genes related to lipolysis that encoded peroxisome proliferator-activated receptor α, adiponectin (ADPN), adiponectin receptor (AdipoR) 1, AdipoR2, adenosine monophosphate-activated protein kinase (AMPK) and hormone-sensitive lipase. Moreover, a total of 54 serum lipid mediators were differentially changed in HFHSD-fed mice, among which 11 lipid mediators from n-3 polyunsaturated fatty acids (PUFAs) were apparently reversed by MLWE. These findings indicated that the ADPN/AMPK pathway, anti-inflammation, anti-oxidation, and n-3 PUFA metabolism played important roles in anti-obesity and improvement of lipid metabolism disorders modulated by MLWE supplementation.
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http://dx.doi.org/10.1039/d1fo04146kDOI Listing
April 2022

Analysis of plasma free amino acids in diabetic rat and the intervention of Ginkgo biloba leaves extract using hydrophilic interaction liquid chromatography coupled with tandem mass-spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2022 Apr 25;1196:123230. Epub 2022 Mar 25.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China; Department of Pharmacy, Suining People's Hospital, Suining, China; Department of Pharmaceutical Analysis, Xuzhou Medical University, Xuzhou, China. Electronic address:

Amino acids (AAs) are important metabolites that are related with diabetes. However, their roles in the initiation and development of diabetes mellitus (DM), especially in the treatment of Ginkgo biloba leaves extract (GBE) have not been fully explored. Thus, we investigated the roles that AAs played in the progression and GBE supplementation of DM rat induced by streptozotocin. The rats were randomly divided into a normal control group treated with drug-free solution, a normal control group treated with GBE, a DM group treated with drug-free solution, and DM group treated with GBE; and maintained on this protocol for 9 weeks. Rat plasma was collected from the sixth week to the ninth week and then analyzed with the optimized hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry method. A total of 17 AAs with differential levels were monitored to indicate dysfunction of AAs metabolism to confirm the occurrence and development of DM. Treatment with GBE partially reversed the changes seen in seven AAs including leucine, isoleucine, tyrosine, glutamic acid, asparagines, lysine and alanine in DM rats, indicating that GBE could prevent the occurrence and development of DM by acting on AAs metabolism. The improvement of those AAs metabolism disorders may play a considerable role in the treatment of GBE on the occurrence and development of DM. Those findings potentially promote the understanding of the pathogenic progression of DM and reveal the therapeutic mechanism of GBE against DM.
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http://dx.doi.org/10.1016/j.jchromb.2022.123230DOI Listing
April 2022
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