Publications by authors named "Wei-Dong Liu"

126 Publications

Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer.

EBioMedicine 2021 Nov 21;74:103714. Epub 2021 Nov 21.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address:

Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management.

Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280-473 days), and an independent case-control study from Beijing (n = 99).

Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78-0.99) vs. 0.56 (0.36-0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins.

Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention.

Funding: The funders are listed in the Acknowledgement.
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http://dx.doi.org/10.1016/j.ebiom.2021.103714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617343PMC
November 2021

Circular RNA circ_0002137 regulated the progression of osteosarcoma through regulating miR-433-3p/ IGF1R axis.

J Cell Mol Med 2021 Feb 23. Epub 2021 Feb 23.

Department of Orthopedic, The Affiliated Huaian NO. 1 people's Hospital of Nanjing Medical University, Huaian, China.

Current clinical treatment targeting osteosarcoma (OS) are limited for OS patients with pulmonary metastasis or relapse, which led to high mortality (70%-85%) for advanced osteosarcoma patients. Although ongoing efforts have been made to illustrate the mechanisms of tumorigenesis and progression in OS; however, it was far for us to learn a comprehensive molecular mechanism implies in OS development. In our study, we implicated a circRNA hsa_circ_0002137, which was higher expressed in osteosarcoma tumours compared with paracancerous tissue. The dysregulated expression pattern was also found in osteosarcoma cell lines. The role of circ_0002137 was explored via down- or up-regulated experiments. It was proved that down-regulation of circ_0002137 suppressed the progress of OS, including cell invasion, cell cycle and cell apoptosis. Furthermore, the correlation between circ_0002137 and miR-433-3p was predicted using bioinformatic tools and verified utilizing RNA pull-down assay and luciferase reporter assay. Interestingly, we found that the inhibitory effect of circ_0002137 on OS was dependent of insulin-like growth factor-1 receptor (IGF1R). In conclusion, it was demonstrated that circ_0002137 could restrain the progression of OS through regulating miR-433-3p/IGF1R axis, providing a comprehensive landscape of circ_0002137 in the generation and development of OS.
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http://dx.doi.org/10.1111/jcmm.16166DOI Listing
February 2021

Microbiota alteration at different stages in gastric lesion progression: a population-based study in Linqu, China.

Am J Cancer Res 2021 1;11(2):561-575. Epub 2021 Feb 1.

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

In addition to Helicobacter pylori (H.pylori), gastric microbiota may be involved in carcinogenesis process. However, the longitudinal study to assess changes in the gastric microbiota associated with the development of gastric carcinogenesis is still limited. The aim of this study is to explore dynamic microbial alterations in gastric cancer (GC) development based on a 4-year endoscopic follow-up cohort in Linqu County, China. Microbial alterations were investigated by deep sequencing of the microbial 16S ribosomal RNA gene in 179 subjects with various gastric lesions, and validated in paired gastric biopsies prospectively collected before and after lesion progression and in non-progression controls. Significant differences were found in microbial diversity and community structure across various gastric lesions, with 62 candidate differential taxa between at least two lesion groups. Further validations identified Helicobacter, Bacillus, Capnocytophaga and Prevotella to be associated with lesion progression-to-dysplasia (DYS)/GC (all P < 0.05), especially for subjects progressing from intestinal metaplasia (IM) to DYS/GC. The combination of the four genera in a microbial dysbiosis index showed a significant difference after lesion progression-to-DYS/GC compared to controls (P = 0.027). The panel including the four genera identified subjects after progression-to-DYS/GC with an area under the receiver-operating curve (AUC) of 0.941. Predictive significance was found before lesion progression-to-DYS/GC with an AUC = 0.776 and an even better AUC (0.927) for subjects progressing from IM to DYS/GC. Microbiota may play different roles at different stages in gastric carcinogenesis. A panel of bacterial genera associated with gastric lesions may help to assess gastric microbial dysbiosis and show potential predictive values for lesion progression. Our findings provide new clues for the microbial mechanism of H.pylori-associated carcinogenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868750PMC
February 2021

Visible-Light Photoredox Catalyzed Double C-H Functionalization: Radical Cascade Cyclization of Ethers with Benzimidazole-Based Cyanamides.

Org Lett 2021 Feb 13;23(3):692-696. Epub 2021 Jan 13.

National Engineering Research Center for Agrochemicals, Hunan Research Institute of Chemical Industry, Changsha 410007, China.

A visible-light photoredox catalyzed radical cascade cyclization of simple ethers with cyanamides is developed at room temperature. This strategy involves sequential inert C-H/C-H functionalizations through intermolecular addition reaction of oxyalkyl radicals to -cyano groups followed by radical cyclization of iminyl radicals generated with C-2 aryl rings. This method allows for efficient synthesis of tetracyclic benzo[4,5]imidazo[1,2-]quinazolines. Importantly, this is the first example of an intermolecular-intramolecular radical cascade cyclization reaction of cyanamides.
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http://dx.doi.org/10.1021/acs.orglett.0c03853DOI Listing
February 2021

Suppression of Helicobacter pylori infection by daily cranberry intake: A double-blind, randomized, placebo-controlled trial.

J Gastroenterol Hepatol 2021 Apr 23;36(4):927-935. Epub 2020 Aug 23.

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

Background And Aim: Dietary strategies that contribute to reducing incidence of Helicobacter pylori infection without negative side effects are highly desirable owing to worldwide bacterial prevalence and carcinogenesis potential. The aim of this study was to determine dosage effect of daily cranberry consumption on H. pylori suppression over time in infected adults to assess the potential of this complementary management strategy in a region with high gastric cancer risk and high prevalence of H. pylori infection.

Methods: This double-blind, randomized, placebo-controlled trial on 522 H. pylori-positive adults evaluated dose-response effects of proanthocyanidin-standardized cranberry juice, cranberry powder, or their placebos on suppression of H. pylori at 2 and 8 weeks by C-urea breath testing and eradication at 45 days post-intervention.

Results: H. pylori-negative rates in placebo, low-proanthocyanidin, medium-proanthocyanidin, and high-proanthocyanidin cranberry juice groups at week 2 were 13.24%, 7.58%, 1.49%, and 13.85% and at week 8 were 7.35%, 7.58%, 4.48%, and 20.00%, respectively. Consumption of high-proanthocyanidin juice twice daily (44 mg proanthocyanidin/240-mL serving) for 8 weeks resulted in decreased H. pylori infection rate by 20% as compared with other dosages and placebo (P < 0.05). Percentage of H. pylori-negative participants increased from 2 to 8 weeks in subjects who consumed 44 mg proanthocyanidin/day juice once or twice daily, showing a statistically significant positive trend over time. Encapsulated cranberry powder doses were not significantly effective at either time point. Overall trial compliance was 94.25%. Cranberry juice and powder were well-tolerated.

Conclusions: Twice-daily consumption of proanthocyanidin-standardized cranberry juice may help potentiate suppression of H. pylori infection.

Trial Registration: ChiCTR1800017522, per WHO ICTRP.
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http://dx.doi.org/10.1111/jgh.15212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246812PMC
April 2021

Association Between Lifestyle Factors, Vitamin and Garlic Supplementation, and Gastric Cancer Outcomes: A Secondary Analysis of a Randomized Clinical Trial.

JAMA Netw Open 2020 06 1;3(6):e206628. Epub 2020 Jun 1.

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

Importance: The associations of lifestyle factors with gastric cancer (GC) are still underexplored in populations in China. Long-term nutritional supplementation may prevent GC in high-risk populations, but the possible effect modification by lifestyle factors remains unknown.

Objective: To evaluate how lifestyle factors, including smoking, alcohol intake, and diet, may change the risk of GC incidence and mortality and whether the effects of vitamin and garlic supplementation on GC are associated with major lifestyle factors.

Design, Setting, And Participants: This is a secondary analysis of the Shandong Intervention Trial, a masked, randomized, placebo-controlled trial that aimed to assess the effect of vitamin and garlic supplementations and Helicobacter pylori treatment on GC in a factorial design with 22.3 years of follow-up. The study took place in Linqu County, Shandong province, China, a high-risk area for GC. Data were collected from Jully 1995 to December 2017. Overall, 3365 participants aged 35 to 64 years identified in 13 randomly selected villages who agreed to undergo gastroscopy were invited to participate in the trial and were included in the analysis. Data analysis was conducted from March to May 2019.

Interventions: Participants received vitamin and garlic supplementation for 7.3 years, H pylori treatment for 2 weeks (among participants with H pylori ), or placebo.

Main Outcomes And Measures: The primary outcomes were GC incidence and GC mortality (1995-2017). We also examined the progression of gastric lesions (1995-2003) as a secondary outcome.

Results: Of the 3365 participants (mean [SD] age, 47.1 [9.2] years; 1639 [48.7%] women), 1677 (49.8%) were randomized to receive active vitamin supplementation, with 1688 (50.2%) receiving placebo, and 1678 (49.9%) receiving active garlic supplementation, with 1687 (50.1%) receiving placebo. Overall, 151 GC cases (4.5%) and 94 GC deaths (2.8%) were identified. Smoking was associated with increased risk of GC incidence (odds ratio, 1.72; 95% CI, 1.003-2.93) and mortality (hazard ratio [HR], 2.01; 95% CI, 1.01-3.98). Smoking was not associated with changes to the effects of vitamin or garlic supplementation. The protective effect on GC mortality associated with garlic supplementation was observed only among those not drinking alcohol (never drank alcohol: HR, 0.33; 95% CI, 0.15-0.75; ever drank alcohol: HR, 0.92; 95% CI, 0.55-1.54; P for interaction = .03), and significant interactions were only seen among participants with H pylori (never drank alcohol: HR, 0.31; 95% CI, 0.12-0.78; ever drank alcohol: HR, 0.91; 95% CI, 0.52-1.60; P for interaction = .04). No significant interactions between vitamin supplementation and lifestyle factors were found.

Conclusions And Relevance: In this secondary analysis of a randomized clinical trial, smoking was associated with an increased risk of GC incidence and mortality. Not drinking alcohol was associated with a stronger beneficial effect of garlic supplementation on GC prevention. Our findings provide new insights into lifestyle intervention for GC prevention, suggesting that mass GC prevention strategies may need to be tailored to specific population subgroups to maximize the potential beneficial effect.

Trial Registration: ClinicalTrials.gov Identifier: NCT00339768.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.6628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320300PMC
June 2020

Association of infection with colorectal polyps and malignancy in China.

World J Gastrointest Oncol 2020 May;12(5):582-591

Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China.

Background: Gastric () infection is related to chronic gastritis, gastroduodenal ulcer, and gastric malignancies; whether this infection is related to colorectal polyps and colorectal cancer (CRC), remains debatable.

Aim: To investigate the relationship between gastric infection and the risk of colorectal polyps and CRC.

Methods: We retrospectively analyzed 3872 patients with colorectal polyps who underwent colonoscopy and pathological diagnosis. We also analyzed 304 patients with primary CRC. The characteristics of these patients were compared with those of the control group, which included 2362 patients with the normal intestinal mucosa. All subjects completed a C-urea breath test, bidirectional gastrointestinal endoscopy, and a biopsy on the same day. Data on the number, size, location, and pathology of the polyps, the location, and pathology of the CRC, the detection of , and the incidence of -associated atrophic gastritis or intestinal metaplasia were obtained. A logistic regression model was used to analyze the relationship between gastric infection due to , and the incidence of colorectal polyps and CRC.

Results: The prevalence of infection was higher in the multiple polyps group than in the solitary polyp group and the control group [95% confidence interval (CI) = 1.02-1.31, = 0.03; 95%CI: 2.12-2.74, < 0.001]. The patients with adenomatous polyps had a higher incidence of infection than patients with non-adenomatous polyps [59.95% 51.75%, adjusted odds ratio (OR) = 1.41, 95%CI: 1.24-1.60, < 0.01]. Patients with -associated atrophic gastritis or intestinal metaplasia were at high risk of CRC (adjusted OR = 3.46, 95%CI: 2.63-4.55, < 0.01; adjusted OR = 4.86, 95%CI: 3.22-7.34, < 0.01, respectively). The size and location of the polyps, the histopathological characteristics and the location of CRC were not related to infection.

Conclusion: Our study demonstrates that the incidence of gastric infection and -associated atrophic gastritis or intestinal metaplasia elevates the risk of colorectal polyps and CRC.
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http://dx.doi.org/10.4251/wjgo.v12.i5.582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235179PMC
May 2020

Comprehensive analysis of key lncRNAs in ischemic stroke.

Math Biosci Eng 2019 11;17(2):1318-1328

TCM Department, Shanghai Seventh People's Hospital, Shanghai 200137, China.

Ischemic stroke (IS) is a leading cause of mortality and disability worldwide. However, the treatments for ischemic stroke remained inadequate. The mechanisms underlying ischemic stroke are still not completely understood. the present study identified 19 lncRNAs related to stroke recovery by analyzing a public dataset GSE37587. A co-expression network included 24 lncRNAs, 1668 mRNAs and 3542 edges were constructed in the present study. Bioinformatics analysis showed these lncRNAs were involved in regulating multiple biological processes and pathways, such as mRNA nonsense-mediated decay, translation, cell-cell adhesion. Three lncRNAs, including DLEU1, LOC432369, and LOC338799, were identified as key lncRNAs in stroke. Bioinformatics showed DLEU1 was involved in regulating oxidative phosphorylation, and ubiquitin-mediated proteolysis. LOC432369 was associated with oxidative phosphorylation. LOC338799 was associated with clathrin-dependent endocytosis, the establishment of organelle localization and ribonucleoprotein complex assembly. We thought this study could provide useful information to understand the mechanisms underlying stroke progression.
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http://dx.doi.org/10.3934/mbe.2020066DOI Listing
November 2019

Roles of PTBP1 in alternative splicing, glycolysis, and oncogensis.

J Zhejiang Univ Sci B 2020 Feb.;21(2):122-136. Epub 2020 Feb 5.

NHC Key Laboratory of Carcinogenesis (Central South University) and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.

Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and is expressed in almost all cell types in humans, unlike the other proteins of the PTBP family. PTBP1 mediates several cellular processes in certain types of cells, including the growth and differentiation of neuronal cells and activation of immune cells. Its function is regulated by various molecules, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and RNA-binding proteins. PTBP1 plays roles in various diseases, particularly in some cancers, including colorectal cancer, renal cell cancer, breast cancer, and glioma. In cancers, it acts mainly as a regulator of glycolysis, apoptosis, proliferation, tumorigenesis, invasion, and migration. The role of PTBP1 in cancer has become a popular research topic in recent years, and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer. In this review, we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.
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http://dx.doi.org/10.1631/jzus.B1900422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076342PMC
December 2020

Construction of efficient "on-off-on" fluorescence aptasensor for ultrasensitive detection of prostate specific antigen via covalent energy transfer between g-CN quantum dots and palladium triangular plates.

Anal Chim Acta 2020 Apr 8;1104:53-59. Epub 2020 Jan 8.

College of Geography and Environmental Sciences, College of Chemistry and Life Sciences, Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Zhejiang Normal University, Jinhua, 321004, China. Electronic address:

Development of ultra-sensitive and high specific aptasensors is important for early diagnosis of prostate cancer. Herein, ultrasensitive detection of prostate specific antigen (PSA) aptasensor was realized based on the "on-off-on" model via fluorescence (FL) covalent energy transfer between g-CN quantum dot (g-CNQDs) and palladium triangular plates (Pd TPs). Specifically, the Pd TPs were primarily linked with PSA aptamer (PA) as the reporter probe, followed by attaching them onto the g-CNQDs surfaces, causing the highly enlarged FL quenching rate (ca. 75%). After the introduction of PSA, the FL intensities recovered again because of the distinctively stronger affinity of PA to PSA than that of g-CNQDs. The bond of pyridine N with Pd was identified as efficient energy transfer pathway through the X-ray photoelectron spectroscopy (XPS) and FL measurements. The surface plasmon resonance (SPR) experiments certified the remarkably different affinity of PA towards g-CNQDs and PSA. The as-constructed FL aptasensor can accurately quantify PSA with wide linear range of 10 pg mL-50 ng mL and ultra-low limit of detection (LOD, 4.2 pg mL), indicating the promising applications in clinical assay and biological detection.
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http://dx.doi.org/10.1016/j.aca.2020.01.009DOI Listing
April 2020

Telomere Length of Circulating Cell-Free DNA and Gastric Cancer in a Chinese Population at High-Risk.

Front Oncol 2019 17;9:1434. Epub 2019 Dec 17.

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

Telomeres have long been found to be involved in cancer development, while little was known about the dynamic changes of telomere length in carcinogenesis process. The present study longitudinally investigated telomere alterations of cell-free DNA (cfDNA) in 86 gastric cancer (GC) subjects recruited through a 16-year prospective cohort with 2-4 serums collected before each GC-diagnosis from baseline and three follow-up time-points (a total of 276 samples). As the control, 86 individual-matched cancer-free subjects were enrolled with 276 serums from the matched calendar year. In the 73 pairs of baseline serums from GC and control subjects, shortened telomeres showed increased subsequent GC risk [odds ratio (OR) = 9.17, 95% CI: 2.72-31.25 for 1 unit shortening]. In each baseline gastric lesion category, higher risks of GC progression were also found with shortened cfDNA telomeres; ORs per 1 unit shortening were 6.99 (95% CI: 1.63-30.30) for mild gastric lesions, 6.06 (95% CI: 1.89-19.61) for intestinal metaplasia and 15.63 (95% CI: 1.91-125.00) for dysplasia. With all measurements from baseline and follow-up time-points, shortened telomeres also showed significant association with GC risk (OR = 7.37, 95% CI: 2.06-26.32 for 1 unit shortening). In temporal trend analysis, shortened telomeres were found in GC subjects compared to corresponding controls more than 3 years ahead of GC-diagnosis (most < 0.05), while no significant difference was found between two groups within 3 years approaching to GC-diagnosis. Our findings suggest that telomere shortening may be associated with gastric carcinogenesis, which supports further etiological study and potential biomarker for risk stratification.
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http://dx.doi.org/10.3389/fonc.2019.01434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928050PMC
December 2019

Effect of on gastrointestinal microbiota: a population-based study in Linqu, a high-risk area of gastric cancer.

Gut 2020 09 19;69(9):1598-1607. Epub 2019 Dec 19.

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

Objective: Gastrointestinal microbiota may be involved in associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential dysbiosis arising from infection.

Design: Deep sequencing of the microbial 16S ribosomal RNA gene was used to investigate alterations in paired gastric biopsies and stool samples in 58 subjects with successful and 57 subjects with failed anti- treatment, relative to 49 negative subjects.

Results: In positive subjects, richness and Shannon indexes increased significantly (both p<0.001) after successful eradication and showed no difference to those of negative subjects (p=0.493 for richness and p=0.420 for Shannon index). Differential taxa analysis identified 18 significantly altered gastric genera after eradication. The combination of these genera into a Microbial Dysbiosis Index revealed that the dysbiotic microbiota in positive mucosa was associated with advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia/dysplasia) and could be reversed by eradication. Strong coexcluding interactions between and , , , , were found only in advanced gastric lesion patients, and were absent in normal/superficial gastritis group. Changes in faecal microbiota included increased after successful eradication and more upregulated drug-resistant functional orthologs after failed treatment.

Conclusion: infection contributes significantly to gastric microbial dysbiosis that may be involved in carcinogenesis. Successful eradication potentially restores gastric microbiota to a similar status as found in uninfected individuals, and shows beneficial effects on gut microbiota.
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http://dx.doi.org/10.1136/gutjnl-2019-319696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456744PMC
September 2020

Roles of extracellular polymeric substances in uranium immobilization by anaerobic sludge.

AMB Express 2019 Dec 11;9(1):199. Epub 2019 Dec 11.

School of Environment and Resources, Southwest University of Science & Technology, Mianyang, 621010, Sichuan, China.

The specific roles of extracellular polymeric substances (EPS) and how factors influenced EPS's roles during U(VI) immobilization are still unclear. In this study, high content of U with the main form of nanoparticles was detected in EPS, accounting for 10-42% of total U(VI) removal. EPS might be utilized as energy source or even as electron donors when external carbon source was unavailable. The influencing degree of each experimental parameter to uranium (U) removal process was elucidated. The influential priority to U(IV)/U(VI) ratios in sludge was as follows: acetate, U(VI), and nitrate. The influential priority to total EPS contents was as follows: U(VI), nitrate and acetate. The complex interaction mechanism between U(VI) and EPS in the U immobilization process was proposed, which might involve three ways including biosorption, bioreduction and bioprecipitation. These results indicate important and various roles of EPS in U(VI) immobilization.
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http://dx.doi.org/10.1186/s13568-019-0922-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906280PMC
December 2019

Effects of treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial.

BMJ 2019 Sep 11;366:l5016. Epub 2019 Sep 11.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Haidian District, Beijing 100142, China.

Objective: To assess the effects of treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer.

Design: Blinded randomized placebo controlled trial.

Setting: Linqu County, Shandong province, China.

Participants: 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to were randomly assigned to treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design.

Interventions: treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003).

Main Outcome Measures: Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease.

Results: 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease.

Conclusions: treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer.

Trial Registration: ClinicalTrials.gov NCT00339768.
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http://dx.doi.org/10.1136/bmj.l5016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737461PMC
September 2019

[Clinical evaluation of modified Xiaoyao pill on the treatment of oral lichen planus patients with anxiety or depression].

Shanghai Kou Qiang Yi Xue 2019 Jun;28(3):312-316

Department of Stomatology, Shandong Provincial Hospital. Jinan 250000, China.

Purpose: To investigate the clinical effect and safety of modified Xiaoyao pill on the treatment of oral lichen planus (OLP) patients with anxiety or depression.

Methods: Sixty OLP patients with anxiety and depression were randomly divided into 2 groups, treated separately with hydroxychloroquine(HCQ, control group) and HCQ+modified Xiaoyao pill(experimental group). The results were measured with semi quantitative reticular erosive and ulcerative lesion (REU) and visual analogue scale(VAS) scoring system at the first visit, the second week, the fourth week and the eighth week, respectively. Data analysis was performed using SPSS 18.0 software package.

Results: The clinical effect of HCQ+modified Xiaoyao pill was better than that of the HCQ. The REU, VAS scores were lower after treatment in both groups (P<0.05), but the effect of the experimental group was more remarkable in reducing the pain indexes, accelerating the healing of erosive lesion and preventing recurrence than the control group. There was no significant difference in the overall effective rate between the two groups (P>0.05).

Conclusions: Modified Xiaoyao pill was effective and safe in the treatment of OLP patients with anxiety or depression, especially for EOLP.
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June 2019

The regulatory network of nasopharyngeal carcinoma metastasis with a focus on EBV, lncRNAs and miRNAs.

Am J Cancer Res 2018 1;8(11):2185-2209. Epub 2018 Nov 1.

The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University Changsha 410008, Hunan, P. R. China.

Metastasis of nasopharyngeal carcinoma (NPC) remains a main cause of death for NPC patients even though great advances have been made in therapeutic approaches. An in-depth study into the molecular mechanisms of NPC metastasis will help us combat NPC. Epstein-Barr virus (EBV) infection is an evident feature of nonkeratinizing NPC and is strongly associated with tumor metastasis. Recently, long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have become a hot topic of research due to their epigenetic regulatory roles in NPC metastasis. The EBV products, lncRNAs and miRNAs can target each other and share several common signaling pathways, which form an interconnected, complex molecular regulatory network. In this review, we discuss the features of this regulatory network and summarize the molecular mechanisms of NPC metastasis, focusing on EBV, lncRNAs and miRNAs with updated knowledge.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291648PMC
November 2018

Methylation and Expression of Nonclustered Protocadherins Encoding Genes and Risk of Precancerous Gastric Lesions in a High-Risk Population.

Cancer Prev Res (Phila) 2018 11 13;11(11):717-726. Epub 2018 Sep 13.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.

Nonclustered protocadherins (PCDH) family is a group of cell-cell adhesion molecules. We have found differentially methylated genes in the nonclustered PCDHs family associated with () infection in prior genome-wide methylation analysis. To further investigate the methylation and expression of nonclustered PCDHs encoding genes in -related gastric carcinogenesis process, four candidate genes including and were selected, which were reported to be tumor suppressors for digestive cancers. A total of 747 participants with a spectrum of gastric lesions were enrolled from a high-risk population of gastric cancer. Promoter methylation levels of four genes were significantly higher in positive subjects than the negative group (all < 0.001). Elevated methylation levels of and were observed with the increasing severity of gastric lesions (both < 0.001). In the protein expression analysis, PCDH17 expression was inversely associated with gastric lesions; the OR [95% confidence interval (CI)] was 0.49 (0.26-0.95) for chronic atrophic gastritis (CAG), 0.31 (0.15-0.63) for intestinal metaplasia, and 0.38 (0.19-0.75) for indefinite dysplasia and dysplasia, compared with superficial gastritis. In addition, PCDH10 expression was significantly lower in CAG (OR, 0.40; 95% CI, 0.24-0.68). The inverse association between methylation and protein expression of and 7 was further supported when we explored the methylation and mRNA expression in The Cancer Genome Atlas database (all < 0.001). Our study found elevated promoter methylation and decreased expression of and in advanced gastric lesions, suggesting that elevated and methylation may be an early event in gastric carcinogenesis. .
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http://dx.doi.org/10.1158/1940-6207.CAPR-18-0119DOI Listing
November 2018

Association Between Gut Microbiota and -Related Gastric Lesions in a High-Risk Population of Gastric Cancer.

Front Cell Infect Microbiol 2018 19;8:202. Epub 2018 Jun 19.

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

Eradication of has been found to be effective for gastric cancer prevention, but uncertainties remain about the possible adverse consequences such as the potential microbial dysbiosis. In our study, we investigated the association between gut microbiota and -related gastric lesions in 47 subjects by deep sequencing of microbial 16S ribosomal RNA (rRNA) gene in fecal samples. The dominant phyla in fecal samples were , and with average relative abundances of 54.77, 31.37 and 12.91%, respectively. Microbial diversity analysis showed that observed species and Shannon index were increased in subjects with past or current infection compared with negative subjects. As for the differential bacteria, the average relative abundance of was found to significantly decrease from negative (66.16%) to past infection group (33.01%, = 0.007), as well as from normal (76.49%) to gastritis (56.04%) and metaplasia subjects (46.83%, = 0.027). For and , the average relative abundances showed elevated trends in the past infection group (47.11, 20.53%) compared to negative group (23.44, 9.05%, = 0.068 and 0.246, respectively), and similar increased trends were also found from normal (18.23, 5.05%) to gastritis (35.31, 7.23%, = 0.016 and 0.294, respectively) or metaplasia subjects (32.33, 20.07%, both < 0.05). These findings suggest that the alterations of fecal microbiota, especially the dominant phyla of and , may be involved in the process of -related gastric lesion progression and provide hints for future evaluation of microbial changes after eradication.
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http://dx.doi.org/10.3389/fcimb.2018.00202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018392PMC
July 2019

Roles of flotillins in tumors.

J Zhejiang Univ Sci B 2018 Mar.;19(3):171-182

Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Central South University, Changsha 410078, China.

The identification and use of molecular biomarkers have greatly improved the diagnosis and treatment of malignant tumors. However, a much deeper understanding of oncogenic proteins is needed for the benefit to cancer patients. The lipid raft marker proteins, flotillin-1 and flotillin-2, were first found in goldfish retinal ganglion cells during axon regeneration. They have since been found in a variety of cells, mainly on the inner surface of cell membranes, and not only act as a skeleton to provide a platform for protein-protein interactions, but also are involved in signal transduction, nerve regeneration, endocytosis, and lymphocyte activation. Previous studies have shown that flotillins are closely associated with tumor development, invasion, and metastasis. In this article, we review the functions of flotillins in relevant cell processes, their underlying mechanisms of action in a variety of tumors, and their potential applications to tumor molecular diagnosis and targeted therapy.
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http://dx.doi.org/10.1631/jzus.B1700102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854633PMC
September 2018

MicroRNA-34a promotes cell cycle arrest and apoptosis and suppresses cell adhesion by targeting DUSP1 in osteosarcoma.

Am J Transl Res 2017 15;9(12):5388-5399. Epub 2017 Dec 15.

Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical UniversityHuai'an, China.

MicroRNAs are often deregulated in most cancer types and have important functions in carcinogenesis and cancer progression. Here, we studied the function of microRNA-34 (miR-34a) in osteosarcoma MG63 and U-2OS cells by expressed with pre-miR-34a, anti-miR-34a and corresponding negative controls, respectively. Cells proliferation, cell cycle and apoptosis was measured by MTT and flow cytometry assay. The effect of miR-34a on DUSP1 expression was evaluated by luciferase assays, real-time PCR and western blot assay. The data showed that miR-34a reduced the proliferation of MG63 cells through prompting cell cycle arrest at G0/G1 phase, cell apoptosis, and suppressed cell adhesion ability. Whereas anti-miR-34a increases U-2OS cell proliferation by preventing cell apoptosis, and promotes cell adhesion. Finally, we identified Dual-specificity phosphatase 1 (DUSP1) as the target gene of miR-34a in osteosarcoma cells and confirmed that DUSP1 enhanced the proliferation through inhibiting cell cycle arrest at G0/G1 phase and apoptosis, and inhibits the decreased cell adhesion induced by miR-34a. However, inhibition of DUSP1 resulted in substantially decreased proliferation and adhesion, and cell cycle arrest in G0/G1 phase and cell apoptosis similar to that observed with miR-34a in U-2OS cells. Our findings find out an important function of miR-34a as a novel tumor-suppressor in osteosarcoma pathogenesis through inhibition of DUSP1.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752889PMC
December 2017

A novel label-free electrochemical immunosensor for ultra-sensitively detecting prostate specific antigen based on the enhanced catalytic currents of oxygen reduction catalyzed by core-shell [email protected] nanocrystals.

Biosens Bioelectron 2018 Apr 11;102:276-281. Epub 2017 Nov 11.

Key laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Chemistry and Life Sciences, College of Geography and Environmental Sciences, Zhejiang Normal University, Jinhua 321004, China. Electronic address:

Herein, bimetallic core-shell [email protected] nanocrystals ([email protected] NCs) were prepared by a simple one-pot aqueous method using 2-pyrrolidone-5-carboxylic acid sodium salt (PCA-Na) as a new and green growth-directing agent. The obtained architectures displayed excellent catalytic activity towards oxygen reduction reaction (ORR) compared with commercial Pt/C catalyst. A novel immunosensor was constructed via assembly prostate specific antibody on the surface of [email protected] NCs. It was found that the ORR currents were significantly suppressed due to the specific antigen-antibody reaction. The ultra-sensitive determination of prostate specific antigen (PSA) was realized on account of the immunocomplex impeding the redox probe accessible to the electrode. The immunosensor exhibited good analytical performance for the assay of PSA with the wide linear range of 0.1 ~ 50ngmL and low detection limit of 0.018ngmL (S/N = 3), coupled with the improved stability, reproducibility and selectivity.
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http://dx.doi.org/10.1016/j.bios.2017.11.041DOI Listing
April 2018

A new label-free electrochemical immunosensor based on dendritic core-shell [email protected] nanocrystals for highly sensitive detection of prostate specific antigen.

Biosens Bioelectron 2018 Jan 10;99:458-463. Epub 2017 Aug 10.

College of Chemistry and Life Science, College of Geography and Environmental Science, Zhejiang Normal University, Jinhua 321004, China. Electronic address:

Herein, bimetallic dendritic core-shell [email protected] nanocrystals ([email protected] NCs) were prepared by a simple one-pot aqueous method using xanthine as a green growth-directing agent. By virtue of the enhanced peak currents in the HO reduction catalyzed by [email protected] NCs, a label-free immunosensor was constructed for the detection of prostate specific antigen (PSA). The immunosensor exhibited significantly improved analytical performance for the assay of PSA with wide linear range of 0.1-50ngmL and low detection limit of 0.078ngmL (S/N = 3), coupled with the improved stability, reproducibility and selectivity. It provides a promising platform for clinical research and diagnosis.
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http://dx.doi.org/10.1016/j.bios.2017.08.010DOI Listing
January 2018

Cut-off optimization for C-urea breath test in a community-based trial by mathematic, histology and serology approach.

Sci Rep 2017 05 18;7(1):2072. Epub 2017 May 18.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing, 100142, China.

The performance of diagnostic tests in intervention trials of Helicobacter pylori (H.pylori) eradication is crucial, since even minor inaccuracies can have major impact. To determine the cut-off point for C-urea breath test (C-UBT) and to assess if it can be further optimized by serologic testing, mathematic modeling, histopathology and serologic validation were applied. A finite mixture model (FMM) was developed in 21,857 subjects, and an independent validation by modified Giemsa staining was conducted in 300 selected subjects. H.pylori status was determined using recomLine H.pylori assay in 2,113 subjects with a borderline C-UBT results. The delta over baseline-value (DOB) of 3.8 was an optimal cut-off point by a FMM in modelling dataset, which was further validated as the most appropriate cut-off point by Giemsa staining (sensitivity = 94.53%, specificity = 92.93%). In the borderline population, 1,468 subjects were determined as H.pylori positive by recomLine (69.5%). A significant correlation between the number of positive H.pylori serum responses and DOB value was found (r = 0.217, P < 0.001). A mathematical approach such as FMM might be an alternative measure in optimizing the cut-off point for C-UBT in community-based studies, and a second method to determine H.pylori status for subjects with borderline value of C-UBT was necessary and recommended.
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http://dx.doi.org/10.1038/s41598-017-02180-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437005PMC
May 2017

Folic acid-tagged titanium dioxide nanoparticles for enhanced anticancer effect in osteosarcoma cells.

Mater Sci Eng C Mater Biol Appl 2017 Jul 6;76:1181-1187. Epub 2017 Mar 6.

Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, 223300, China. Electronic address:

In this study, folic acid surface modified-Titanium dioxide nanoparticles (FA-TiNP) were prepared as a suitable alternative to conventional chemotherapeutic agents to treat human osteosarcoma. The particle size of TiNP increased marked after polymer assembly on the nanoparticles (NP) surface with a spherical morphology. FA-TiNP exhibited a superior anticancer effect in osteosarcoma cancer cells compared to that of bare TiNP. The reason might due to the specific interaction of FA with the folate receptor which is overexpressed in the cancer cells. Especially, FA-TiNP treated cells exhibited chromatin condensation, cell shrinkage and membrane blebbing. FA-TiNP showed significantly higher cancer cell apoptosis with nearly 38% of cells in apoptosis chamber (early and late) compared to only ~16% for TiNP. The higher proportion of Annexin V positive cells for FA-TiNP treated group was mainly attributed to the higher intracellular uptake of the TiO2. Importantly, FA-TiNP increased the sub-G0 population to ~25% indicating its superior anticancer effect. The results clearly indicated that FA-TiNP induced greater reactive oxygen species (ROS) generation that resulted in higher sub-G0 cell population with higher cell apoptosis. FA-TiNP showed a remarkably higher expression of cytochrome C (Cyt C) with a marked increase in the expression of cleaved caspase-3 and PARP. Overall, results suggest that surface modification of TiNP with a specific targeting moiety could enhance the chances of having successful therapies for cancer diseases.
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http://dx.doi.org/10.1016/j.msec.2017.03.027DOI Listing
July 2017

A novel label-free electrochemical immunosensor based on the enhanced catalytic currents of oxygen reduction by AuAg hollow nanocrystals for detecting carbohydrate antigen 199.

Biosens Bioelectron 2017 Oct 4;96:152-158. Epub 2017 May 4.

College of Chemistry and Life Science, College of Geography and Environmental Science, Zhejiang Normal University, Jinhua 321004, China. Electronic address:

Herein, bimetallic alloyed AuAg hollow nanocrystals (AuAg HNCs) were prepared by a simple one-pot aqueous method using polycytidysic acid (PCA) as the green growth-directing agent. The novel immunosensor for carbohydrate antigen 199 (CA199) was further constructed based on the enhanced catalytic currents of oxygen reduction reaction (ORR) by AuAg HNCs. By virtue of the good biocompatibility and catalytic activity of AuAg HNCs, the immunosensor exhibited superior analytical performance for the assay of CA199 under the optimal experimental conditions, the ORR signals linearly decreased with the increased CA199 concentrations in the range of 1 ~ 30UmL, with the low detection limit of 0.228UmL, improved stability, reproducibility and selectivity.
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http://dx.doi.org/10.1016/j.bios.2017.05.007DOI Listing
October 2017

Association of connexin gene polymorphism with essential hypertension in Kazak and Han Chinese in Xinjiang, China.

J Huazhong Univ Sci Technolog Med Sci 2017 Apr 11;37(2):197-203. Epub 2017 Apr 11.

Department of Physiology, Medical College of Shihezi University, Shihezi, 832002, China.

Essential hypertension (EH) is affected by both genetic and environmental factors. The polymorphism of connexin (Cx) genes is found associated with the development of hypertension. However, the association of the polymorphism of Cxs with EH has not been investigated. This study aimed to investigate the association of the polymorphism of connexin (Cx) genes Cx37, Cx40, and Cx43 with EH in Kazak and Han Chinese in Xinjiang, China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were used to analyze the polymorphism of Cx genes in Kazak and Han EH patients as well as their normotensive controls. The results showed that there were no significant differences in the frequencies of different three genotypes (A/A, A/G, and G/G) and A and G alleles of Cx40 rs35594137 and rs11552588 between EH patients and normotensive controls. However, in Kazak EH patients, the frequencies of three genotypes (A/A, A/G, and G/G) of Cx37 rs1630310 were 24.8%, 47.2% and 28.0%, respectively, which were significantly different from those in Han EH patients. In Han EH patients, the frequencies of the three genotypes (C/C, C/G and G/G) of Cx43 rs1925223 were 6.4%, 35.6% and 58.0%, respectively. Frequencies of the other four genotypes had no statistical differences among Kazak and Han EH patients and their normotensive controls. These results suggest polymorphisms of Cx37 rs1630310 and Cx43 rs1925223 genes may be associated with the pathogenesis of EH. Carrying Cx37 rs1630310-A or Cx43 rs1925223-G genotypes may protect against the development of EH.
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http://dx.doi.org/10.1007/s11596-017-1715-yDOI Listing
April 2017

Enhanced expression of Cx43 and gap junction communication in vascular smooth muscle cells of spontaneously hypertensive rats.

Mol Med Rep 2016 Nov 26;14(5):4083-4090. Epub 2016 Sep 26.

Department of Physiology, Medical College of Shihezi University, Shihezi, Xinjiang 832002, P.R. China.

Niflumic acid (NFA) is a novel gap junction (GJ) inhibitor. The aim of the present study was to investigate the effect of NFA on GJ communication and the expression of connexin (Cx) in vascular smooth muscle cells (VSMCs) of mesenteric arterioles of spontaneously hypertensive rats (SHR). Whole‑cell patch clamp recording demonstrated that NFA at 1x10‑4 M significantly inhibited the inward current and its effect was reversible. The time for charging and discharging of cell membrane capacitance (Cinput) reduced from 9.73 to 0.48 ms (P<0.05; n=6). Pressure myograph measurement showed that NFA at 3x10‑4 M fully neutralized the contraction caused by phenylephrine. The relaxation responses of normotensive control Wistar Kyoto (WKY) rats were significantly higher, compared with those of the SHRs (P<0.05; n=6). Western blot and reverse transcription‑quantitative polymerase chain reaction analyses showed that the mRNA and protein expression levels of Cx43 of the third‑level branch of mesenteric arterioles of the SHRs and WKY rats were higher, compared with those of the first‑level branch. The mRNA and protein expression levels of Cx43 of the primary and third‑level branches of the mesenteric arterioles in the SHRs were higher, compared with those in the WKY rats (P<0.05; n=6). The mRNA levels of Cx43 in the mesenteric arterioles were significantly downregulated by NFA in a concentration‑dependent manner (P<0.01; n=6). The protein levels of Cx43 in primary cultured VSMCs isolated from the mesenteric arterioles were also significantly downregulated by NFA in a concentration‑dependent manner (P<0.01; n=6). These results showed that the vasorelaxatory effects of GJ inhibitors were reduced in the SHRs, which was associated with a higher protein expression level of Cx43 in the mesenteric arterioles of the SHRs. NFA also relaxed the mesenteric arterioles by reducing the expression of Cx43, which decreased blood pressure. Therefore, regulation of the expression of GJs may be a therapeutic target for the treatment of hypertension.
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http://dx.doi.org/10.3892/mmr.2016.5783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101886PMC
November 2016

Surgical Revascularization of Symptomatic Kinking of the Internal Carotid Artery.

Vasc Endovascular Surg 2016 Oct 28;50(7):470-474. Epub 2016 Sep 28.

School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia

Objective: To evaluate the safety and outcomes of surgical revascularization for patients with symptomatic kinking of the internal carotid artery (ICA).

Methods: Twenty-five consecutive patients presented with symptomatic kinking of the ICA and a history of transient ischemic attack (TIA) or stroke were prospectively enrolled in this study. All patients were treated with ICA transection and end-to-side reimplantation at the level of the carotid bulb. Patients were followed up for a median of 32 months.

Results: There were no deaths or strokes within the 30 days of the treatment. No postprocedural thrombosis or narrowing of the ipsilateral ICA was observed. One (4%) patient had temporary recurrent nerve palsy, which was completely recovered at 4-week follow-up. One (4%) patient had a myocardial ischemic event. At the end of the 32-month follow-up, 1 (4%) patient developed ipsilateral minor stroke. No recurrent stenosis was detected by Doppler ultrasound.

Conclusion: Surgical treatment for isolated, symptomatic kinking of the ICA and a history of TIA or stroke is safe, and the outcomes are acceptable.
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http://dx.doi.org/10.1177/1538574416671246DOI Listing
October 2016

Inhibition of Growth and Metastasis of Tumor in Nude Mice after Intraperitoneal Injection of Bevacizumab.

Orthop Surg 2016 May;8(2):234-40

Department of Orthopaedics, Huaian First People's Hospital, Nanjing Medical University, Huaian, China.

Objective: To explore the inhibitory effect of bevacizumab, a vascular endothelial growth factor antibody, on angiogenesis in human osteosarcoma of nude mice.

Methods: Twenty-one nude mice were inoculated with red fluorescent protein (RFP)-labeled human osteosarcoma cell line 143B-RFP, that is, clones that expressed RFP in the cytoplasm, and randomly assigned to one of three groups: G1 (Control group, injected with saline solution); G2 (intraperitoneal bevacizumab 2 mg/kg twice per week) and G3 (intraperitoneal bevacizumab 5 mg/kg, twice per week). The tumor-bearing mice were examined in a fluorescence light box that was illuminated periodically. The primary tumors were measured by fluorescence imaging weekly and their volumes calculated.

Results: The mean tumor volumes were significantly smaller in the G3 (186.4 ± 100.8 mm(3) ) than the control group (587.0 ± 406.8 mm(3) ) (P < 0.05) on Day 31, and again significantly smaller in the G3 (677.3 ± 461.9 mm(3) ) than the control group (3162.6 ± 1529.2 mm(3) ) on Day 38 (P < 0.01). The average tumor volume in the G2 group was 493.5 ± 425.4 mm(3) on Day 31 and 1870.1 ± 1524.8 mm(3) on Day 38. The effect on tumor volume was greater in the G3 than the G2 group. Three mice in the G2 group, four in the G3 group and four in the control group developed lung metastases that were confirmed by pathological examination; these differences were not statistically significant (P < 0.05).

Conclusions: Bevacizumab exhibits strong antiangiogenesis activity in experimental osteosarcoma in a nude mouse model but does not influence the incidence of lung metastasis. Our findings may have considerable potential for the treatment of osteosarcoma.
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http://dx.doi.org/10.1111/os.12236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593177PMC
May 2016

Disposal of Occipital Condyle in Far Lateral Approach for Ventrolateral Foramen Magnum Meningiomas.

World Neurosurg 2016 Sep 27;93:29-37. Epub 2016 May 27.

Department of Neurosurgery, Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, China.

Objective: To investigate the necessity of drilling the occipital condyle in a tailored far lateral approach for resection of ventrolateral foramen magnum meningiomas (FMMs).

Methods: Clinical data of 15 patients with ventrolateral FMMs who underwent surgery during a 6-year period were reviewed retrospectively.

Results: A retrocondylar approach was performed in 8 cases (6 above the vertebral artery [VA] and 2 below the VA) in which the dural attachment was surgically accessible with no restriction of the initial part of the V4 segment of the VA, and a partial transcondylar approach was performed in 7 cases on both sides of the VA where the dural attachment associated with the VA auxiliary space was reached by superolateral displacement of the VA by drilling of the condyle. Exposure of the V3 segment of the VA was performed in all patients, but no circumcision of the dural ring along with transposition of the VA was needed. Simpson grade II resection was achieved in all patients. Postoperative complications were encountered in 20% of patients, predominantly associated with cranial nerve impairment. No tumor recurrence was demonstrated during follow-up lasting 7-68 months (mean 29.2 months).

Conclusions: The surgical approach for ventrolateral FMMs varies depending on the location of dural attachment with reference to VA dural entry. Bone removal is warranted in FMMs arising from both sides of the VA to allow superolateral displacement of the VA to some extent, improving surgical accessibility to the hidden VA auxiliary space and achieving a more radical tumor resection. It should be a reasonable alternative to the conventional aggressive VA transposition in cases of ventrolateral FMMs.
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http://dx.doi.org/10.1016/j.wneu.2016.05.048DOI Listing
September 2016
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