Publications by authors named "Shanshan Shen"

77 Publications

AGR2-dependent nuclear import of RNA polymerase II constitutes a specific target of pancreatic ductal adenocarcinoma in the context of wild-type p53.

Gastroenterology 2021 Jul 22. Epub 2021 Jul 22.

Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China; Department of Surgery, Ulm University Hospital, Ulm University, Ulm, Germany. Electronic address:

Background And Aim: Promoted by pancreatitis, oncogenic Kras triggers acinar cells' neoplastic transformation through acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). Agr2 (anterior gradient 2), a known inhibitor of p53, is detected at early stage of pancreatic ductal adenocarcinoma (PDAC) development. RNA polymerase II (RNAPII) is a key nuclear enzyme; regulation of its nuclear localization in mammalian cells represents a potential therapeutic target.

Methods: A mouse model of inflammation-accelerated Kras-driven ADM and PanIN development was used. Pancreas-specific Agr2 ablation was performed to access its role in pancreatic carcinogenesis. Hydrophobic hexapeptides loaded in liposomes were developed to disrupt Agr2-RNAPII complex.

Results: We found that Agr2 is upregulated in ADM-to-PanIN transition in inflammation and Kras-driven early pancreatic carcinogenesis. Genetic ablation of Agr2 specifically blocks this metaplastic-to-neoplastic process. Mechanistically, Agr2 directs the nuclear import of RNAPII via its C-terminal nuclear localization signal, undermining the ATR-dependent p53 activation in ADM lesions. Since Agr2 binds to the largest subunit of RNAPII in a peptide motif-dependent manner, we developed a hexapeptide to interfere with the nuclear import of RNAPII by competitively disrupting the Agr2-RNAPII complex. This novel hexapeptide leads to dysfunction of RNAPII with concomitant activation of DNA damage response in early neoplastic lesions; hence, it dramatically compromises PDAC initiation in vivo. Moreover, the hexapeptide sensitizes PDAC cells and patient-derived organoids harbouring wild-type p53 to RNAPII inhibitors and first-line chemotherapeutic agents in vivo. Of note, this therapeutic effect is efficient across various cancer types.

Conclusion: Agr2 is identified as a novel adaptor protein for nuclear import of RNAPII in mammalian cells. Also, we provide genetic evidence defining Agr2-dependent nuclear import of RNAPII as a pharmaceutically accessible target for prevention and treatment in PDAC in the context of wild-type p53.
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http://dx.doi.org/10.1053/j.gastro.2021.07.030DOI Listing
July 2021

Differential prognostic implications of gastric adenocarcinoma based on Lauren's classification: a Surveillance, Epidemiology, and End Results (SEER)-based cohort study.

Ann Transl Med 2021 Apr;9(8):646

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.

Background: Our study aims to analyze the association between Lauren's classification and gastric adenocarcinoma prognosis using comprehensive statistical analyses.

Methods: According to the selection criteria, patients were included from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression, propensity score matching, and a multivariate competing risk model were used to investigate the association between Lauren's classification and prognosis. Subgroup analysis was used to investigate the role of confounding factors on the association between Lauren types and prognosis.

Results: After exclusion, a total of 20,218 patients from the SEER database were included, with 14,374 intestinal types and 5,844 diffuse types. The univariate Cox regression analysis revealed that the diffuse type had a poorer cancer-specific survival (CSS) rate [hazard ratio (HR), 1.44; 95% confidence interval (CI), 1.38-1.50]. After adjusting for confounding variables, the diffuse type also showed a higher risk of cancer-specific death (HR, 1.20; 95% CI, 1.15-1.20). Sensitivity analysis showed that after propensity score matching, the diffuse type had a poorer CSS rate (HR, 1.23; 95% CI, 1.10-1.36), and the competing risk model further validated these results [subdistribution HR (SHR), 1.32; 95% CI, 1.23-1.41]. Moreover, subgroup analysis demonstrated stable results in the subgroups, except for patients with T1 stage (HR, 1.06; 95% CI, 0.87-1.28) and a tumor size <2 cm (HR, 1.00; 95% CI, 0.83-1.21).

Conclusions: Diffuse-type gastric adenocarcinoma had an overall poorer prognosis compared to the intestinal type. However, in patients with T1 stage and tumor size <2 cm, the diffuse type had a comparable survival rate with the intestinal type.
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http://dx.doi.org/10.21037/atm-20-7953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106066PMC
April 2021

GPRC5A: An emerging prognostic biomarker for predicting malignancy of Pancreatic Cancer based on bioinformatics analysis.

J Cancer 2021 2;12(7):2010-2022. Epub 2021 Feb 2.

Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, People's Republic of China.

Pancreatic cancer (PaCa) is a highly lethal malignancy. The treatment options for PaCa lack efficacy. The study aimed to explore the molecular biomarkers for predicting survival of PaCa and identify the potential carcinogenic mechanisms of the selected gene. Based on public databases of PaCa, differentially expressed genes (DEGs) were identified using Networkanalyst. Survival analyses were exerted on GEPIA. Oncomine and The Human Protein Atlas were used for verifying the expression on mRNA and protein levels. Enrichment analyses were generated on Metascape and gene set enrichment analysis (GSEA). Univariate analyses were performed to determine the clinical factors associated with the expression of GPRC5A. GPRC5A was identified as the most valuable gene in predicting survival of PaCa patients. Patients with high expression of GPRC5A showed larger tumor size, higher TNM stages, higher tumor grade, and more positive resection margin. In mutant KRAS, TP53, CDKN2A and SMAD4 group, the expression of GPRC5A was higher than non-mutant group. Mechanistically, GPRC5A may promote metastasis of PaCa mainly via regulating epithelial-mesenchymal transition (EMT) and neuroactive ligand-receptor interaction. GPRC5A may act as an oncogene in the progression of PaCa and could be a prognostic biomarker in predicting survival of PaCa.
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http://dx.doi.org/10.7150/jca.52578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974517PMC
February 2021

The Impact of Intrinsic Capacity on Adverse Outcomes in Older Hospitalized Patients: A One-Year Follow-Up Study.

Gerontology 2021 18;67(3):267-275. Epub 2021 Mar 18.

Department of Geriatric, Zhejiang Hospital, Hangzhou, China.

Background: Intrinsic capacity (IC) is a novel view focusing on healthy aging. The effect of IC on adverse outcomes in older hospitalized Chinese adults is rarely studied.

Objectives: This study focused on investigating the impact of IC domains on the adverse health outcomes including new activities of daily living (ADL) dependency, new instrumental activities of daily living (IADL) dependency, and mortality over a 1-year follow-up.

Methods: In a retrospective observational population-based study, a total of 329 older hospitalized patients from Zhejiang Hospital in China were enrolled and completed 1-year follow-up. The 5 domains of IC including cognition, locomotion, sensory, vitality, and psychological capacity were assessed at admission. The IC composite score was calculated based on these domains, and the higher IC composite score indicated the greater amount of functional capacities reserved. Multivariate logistic regression models were used to explore the association between IC at baseline and 1-year adverse outcomes.

Results: During the 1-year follow-up, 69 patients (22.5%) experienced new ADL dependency, 103 patients (33.6%) suffered from new IADL dependency, and 22 patients (6.7%) died. After adjusting for age, sex, education level, comorbidities, and polypharmacy, low Mini-Mental State Examination (MMSE) scores at admission predicted 1-year new ADL dependency (odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.12-4.78) and new IADL dependency (OR = 2.15, 95% CI: 1.14-4.04) among older hospitalized patients, but no significance was obtained between IC domains and mortality. Higher IC composite score at admission was associated with decreased risks of 1-year new ADL dependency (OR = 0.53, 95% CI: 0.40-0.70) and new IADL dependency (OR = 0.76, 95% CI: 0.61-0.95), and 1-year mortality (OR = 0.48, 95% CI: 0.31-0.74) after adjustment for the possible confounders.

Conclusions: Loss of ICs at admission predicted adverse health outcomes including new ADL and IADL dependency and mortality 1 year after discharge among older hospitalized patients.
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http://dx.doi.org/10.1159/000512794DOI Listing
March 2021

Characterizing volatile metabolites in raw Pu'er tea stored in wet-hot or dry-cold environments by performing metabolomic analysis and using the molecular sensory science approach.

Food Chem 2021 Jul 6;350:129186. Epub 2021 Feb 6.

State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, 130 Changjiang West Road, Hefei, Anhui 230036, China. Electronic address:

The aroma profile of raw pu'er tea (RPT) depends on its storage duration (2-10 years) and storage conditions (wet-hot or dry-cold environment). We analyzed the major odorants of RPT samples by performing metabolomic analysis and by using the molecular sensory science approach. Under dry-cold storage conditions, tea leaves had more carotenoid derivatives, glycoside-derived volatiles, and phenolic volatiles, resulting in "fresh," "floral," and "sweet" aroma. Under wet-hot storage conditions, tea leaves had more methoxybenzenes, which contributed considerably to their "stale" and "woody" aroma. We identified 11 and 4 compounds as the odor markers of RPTs when stored in dry-cold and wet-hot environments, respectively. Our findings provide a scientific basis for optimal storage that yields the desired aroma profile.
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http://dx.doi.org/10.1016/j.foodchem.2021.129186DOI Listing
July 2021

A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell Carcinoma.

Front Oncol 2020 19;10:593601. Epub 2021 Jan 19.

Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Background: Clear cell renal cell carcinoma (ccRCC) is a urinary disease with high incidence. The high incidence of metastasis is the leading cause of death in patients with ccRCC. This study was aimed to identify the gene signatures during the metastasis of ccRCC.

Methods: Two datasets, including one gene expression profile dataset and one microRNA (miRNA) expression profile dataset, were downloaded from Gene Expression Omnibus (GEO) database. The integrated bioinformatics analysis was performed using the (limma) R package, miRWalk, DAVID, STRING, Kaplan-Meier plotter databases. Quantitative real-time polymerase chain reaction (qPCR) was conducted to validate the expression of differentially expressed genes (DEGs) and DE-miRNAs.

Results: In total, 84 DEGs (68 up-regulated and 16 down-regulated) and 41 DE-miRNAs (24 up-regulated and 17 down-regulated) were screened from GSE22541 and GSE37989 datasets, respectively. Furthermore, 11 hub genes and 3 key miRNAs were identified from the PPI network, including FBLN1, THBS2, SCGB1A1, NKX2-1, COL11A1, DCN, LUM, COL1A1, COL6A3, SFTPC, SFTPB, miR-328, miR-502, and miR-504. The qPCR data showed that most of the selected genes and miRNAs were consistent with that in our integrated analysis. A novel mRNA-miRNA network, SFTPB-miR-328-miR-502-miR-504-NKX2-1 was found in metastatic ccRCC after the combination of data from expression, survival analysis, and experiment validation.

Conclusion: In conclusion, key candidate genes and miRNAs were identified and a novel mRNA-miRNA network was constructed in ccRCC metastasis using integrated bioinformatics analysis and qPCR validation, which might be utilized as diagnostic biomarkers and molecular targets of metastatic ccRCC.
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http://dx.doi.org/10.3389/fonc.2020.593601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851075PMC
January 2021

Gas-phase amination of aromatic hydrocarbons by corona discharge-assisted nitrogen fixation.

Sci Rep 2021 Feb 2;11(1):2841. Epub 2021 Feb 2.

Department of Chemistry, Zhejiang University, Hangzhou, 310027, People's Republic of China.

This paper reports on the gas-phase amination reaction of aromatic hydrocarbons occurring under corona discharge conditions with N gas as the nitrogen source. The corona discharge device within an atmospheric pressure chemical ionization source was employed to achieve the plasma-assisted N fixation, and the coupled ion trap mass spectrometer (IT-MS) was used to detect positively charged product ions. In the model case, under APCI conditions, unusual product ions, [M + 16] and [M + 14], were observed. Based on the high resolution MS data and tandem mass spectrometric information, [M + 16] was confirmed to be protonated p-toluidine and [M + 14] was confirmed to be p-methylphenylnitrenium ion. According to the experimental results of the isotopic labelling and substituent effect, one feasible mechanism is proposed as follows. Firstly, N is activated by plasma caused via the corona discharge and then electrophilically attacks toluene, yielding the key intermediate, p-methylphenylnitrenium; secondly, the intermediate undergoes double-hydrogen transfer reaction to give rise to the final product ion, protonated p-toluidine. This study may provide a novel idea to explore new and green method for the synthesis of anilines.
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http://dx.doi.org/10.1038/s41598-021-82190-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854734PMC
February 2021

Hypoxia promotes the metastasis of pancreatic cancer through regulating NOX4/KDM5A-mediated histone methylation modification changes in a HIF1A-independent manner.

Clin Epigenetics 2021 01 26;13(1):18. Epub 2021 Jan 26.

Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.

Background: Hypoxia is a characteristic of the tumor microenvironments within pancreatic cancer (PC), which has been linked to its malignancy. Recently, hypoxia has been reported to regulate the activity of important carcinogenic pathways by changing the status of histone modification. NOX4, a member of NADPH oxidase (NOX), has been found to be activated by hypoxia and promote cancer progression in several cancers. But whether it is involved in the epigenetic changes of tumor cells induced by hypoxia is still unclear, and its biological roles in PC also need to be explored.

Methods: A hypoxic-related gene signature and its associated pathways in PC were identified by analyzing the pancreatic cancer gene expression data from GEO and TCGA database. Candidate downstream gene (NOX4), responding to hypoxia, was validated by RT-PCR and western blot. Then, we evaluated the relationship between NOX4 expression and clinicopathologic parameters in 56 PC patients from our center. In vitro and in vivo assays were preformed to explore the phenotype of NOX4 in PC. Immunofluorescence, western blot and chromatin immunoprecipitation assays were further applied to search for a detailed mechanism.

Results: We quantified hypoxia and developed a hypoxia signature, which was associated with worse prognosis and elevated malignant potential in PC. Furthermore, we found that NADPH oxidase 4 (NOX4), which was induced by hypoxia and upregulated in PC in a HIF1A-independent manner, caused inactivation of lysine demethylase 5A (KDM5A), increased the methylation modification of histone H3 and regulated the transcription of EMT-associated gene_ snail family transcriptional repressor 1 (SNAIL1). This served to promote the invasion and metastasis of PC. NOX4 deficiency repressed hypoxia-induced EMT, reduced expression of H3K4ME3 and impaired the invasion and metastasis of PC cells; however, knockdown of KDM5A reversed the poor expression of H3KEME3 induced by NOX4 deficiency, thereby promoting EMT.

Conclusions: This study highlights the prognostic role of hypoxia-related genes in PC and strong correlation with EMT pathway. Our results also creatively discovered that NOX4 was an essential mediator for hypoxia-induced histone methylation modification and EMT in PC cells.
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http://dx.doi.org/10.1186/s13148-021-01016-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836598PMC
January 2021

Identification of Critical Genes and Proteins for Stent Restenosis Induced by Esophageal Benign Hyperplasia in Esophageal Cancer.

Front Genet 2020 17;11:563954. Epub 2020 Dec 17.

Department of Intervention, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

This study was conducted to explore the potential genes and proteins associated with esophagus benign hyperplasia induced by esophageal stents. Five patients with esophageal cancer subjected to esophageal stent placement were enrolled in this study. Long non-coding RNA (lncRNA) sequencing and tandem mass tag quantitative proteomics analysis were performed by using the collected hyperplastic samples and adjacent non-hyperplastic tissues. Differentially expressed (DE) RNAs and proteins were analyzed, followed by functional enrichment analysis, protein-protein interaction (PPI) network analysis, and competitive endogenous RNA (ceRNA) network construction. Venn analysis was performed to extract the overlaps between DE mRNAs and DE proteins and the expression correlations between DE mRNA and proteins were analyzed. Results showed that total 642 DE RNAs (457 mRNA and 185 lncRNAs) and 256 DE proteins were detected. DE mRNAs (such as , , and ) were enriched in oxidation-reduction process-associated functions. PPI network was comprised of 175 nodes and 425 edges. VEGFA was a significant node with the highest degree. LncRNA-mRNA network with three subnetworks (C1, C2, C3) was constructed for lncRNAs with more than 15 gene targets. RP11-58O9.2 was a significant lncRNA with the most target genes and RP11-667F14.1 regulated more than 20 targets. was a common target of the two lncRNAs. Function analysis showed that DE lncRNAs were involved in the HTLV-I infection (RP11-58O9.2 and RP11-667F14.1) and IL-17 signaling pathways (RP11-5O24.1 and RP11-58O9.2). Total 11 DE mRNAs were overlapped with DE proteins, among which MAOB and SDR16C5 showed positive correlations between mRNA and protein expression. Function analysis showed that was enriched in oxidation-reduction process and its protein was closely related with response to lipopolysaccharide. , , , , RP11-58O9.2, RP11-667F14.1, and RP11-288A5.2 may be served as genetic targets for preventing stent restenosis in esophageal cancer.
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http://dx.doi.org/10.3389/fgene.2020.563954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773907PMC
December 2020

mTORC1 and mTORC2 Converge on the Arp2/3 Complex to Promote Kras-Induced Acinar-to-Ductal Metaplasia and Early Pancreatic Carcinogenesis.

Gastroenterology 2021 Apr 1;160(5):1755-1770.e17. Epub 2021 Jan 1.

Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China; German Cancer Consortium at the partner site Munich, Munich, Germany. Electronic address:

Background & Aims: Oncogenic Kras induces neoplastic transformation of pancreatic acinar cells through acinar-to-ductal metaplasia (ADM), an actin-based morphogenetic process, and drives pancreatic ductal adenocarcinoma (PDAC). mTOR (mechanistic target of rapamycin kinase) complex 1 (mTORC1) and 2 (mTORC2) contain Rptor and Rictor, respectively, and are activated downstream of Kras, thereby contributing to PDAC. Yet, whether and how mTORC1 and mTORC2 impact on ADM and the identity of the actin nucleator(s) mediating such actin rearrangements remain unknown.

Methods: A mouse model of inflammation-accelerated Kras-driven early pancreatic carcinogenesis was used. Rptor, Rictor, and Arpc4 (actin-related protein 2/3 complex subunit 4) were conditionally ablated in acinar cells to deactivate the function of mTORC1, mTORC2 and the actin-related protein (Arp) 2/3 complex, respectively.

Results: We found that mTORC1 and mTORC2 are markedly activated in human and mouse ADM lesions, and cooperate to promote Kras-driven ADM in mice and in vitro. They use the Arp2/3 complex as a common downstream effector to induce the remodeling the actin cytoskeleton leading to ADM. In particular, mTORC1 regulates the translation of Rac1 (Rac family small GTPase 1) and the Arp2/3-complex subunit Arp3, whereas mTORC2 activates the Arp2/3 complex by promoting Akt/Rac1 signaling. Consistently, genetic ablation of the Arp2/3 complex prevents Kras-driven ADM in vivo. In acinar cells, the Arp2/3 complex and its actin-nucleation activity mediated the formation of a basolateral actin cortex, which is indispensable for ADM and pre-neoplastic transformation.

Conclusions: Here, we show that mTORC1 and mTORC2 attain a dual, yet nonredundant regulatory role in ADM and early pancreatic carcinogenesis by promoting Arp2/3 complex function. The role of Arp2/3 complex as a common effector of mTORC1 and mTORC2 fills the gap between oncogenic signals and actin dynamics underlying PDAC initiation.
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http://dx.doi.org/10.1053/j.gastro.2020.12.061DOI Listing
April 2021

Response to Dr. Frieling.

Endoscopy 2021 01 17;53(1):99. Epub 2020 Dec 17.

Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.

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http://dx.doi.org/10.1055/a-1214-6170DOI Listing
January 2021

Potential of smartphone-coupled micro NIR spectroscopy for quality control of green tea.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Feb 24;247:119096. Epub 2020 Oct 24.

State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, China. Electronic address:

Green tea adulterated with sugar and glutinous rice flour has an increased sensitivity to water, which affects the safety of the tea. A total of 475 samples of pure tea, sugar-adulterated tea, and glutinous-rice-flour-adulterated tea were prepared and scanned using micro near infrared spectroscopy (NIRS). The collected NIRS data were qualitatively and quantitatively detected by a multi-layer algorithm model. Principal component analysis indicated that the three sample groups had an obvious separation trend. The discriminate rate of the optimal qualitative model, namely support vector machine, was 97.47% for the prediction set. A total of three wavelength selection methods were used to improve the performances of partial least squares regression and support vector machine regression (SVR) models. The nonlinear SVR models based on characteristic wavelengths selected by iteratively retaining informative variables algorithm provided satisfactory results for the identification of sugar and glutinous rice flour adulteration. The correlation coefficients for prediction (Rp) were >0.94, and the residual prediction deviation were >3. The results indicated that smartphone-based micro NIRS can be effectively used to qualitatively and quantitatively analyze adulterants in green tea.
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http://dx.doi.org/10.1016/j.saa.2020.119096DOI Listing
February 2021

Reply to Zhai and Bi.

Endoscopy 2020 08 28;52(8):712. Epub 2020 Jul 28.

Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.

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http://dx.doi.org/10.1055/a-1176-1431DOI Listing
August 2020

CircRHOT1 mediated cell proliferation, apoptosis and invasion of pancreatic cancer cells by sponging miR-125a-3p.

J Cell Mol Med 2020 09 22;24(17):9881-9889. Epub 2020 Jul 22.

Medical School of Southeast University, Nanjing, Jiangsu, China.

Pancreatic cancer patients are asymptomatic at early stages and leading to late diagnoses. Additionally, pancreatic cancer easily metastasizes and is resistant to radiotherapy and chemotherapy. Therefore, it is critical to understand the underlying molecular mechanisms involved in pancreatic cancer to develop more efficient diagnostic and treatment strategies. In this study, we demonstrated that circRHOT1 was overexpressed in pancreatic cancer tissues and cell lines, and it was found to directly bind to miR-125a-3p, acting as an endogenous sponge to inhibit its activity. Knockdown of circRHOT1 expression significantly inhibited proliferation as well as invasion, and it promoted apoptosis of pancreatic cancer cells via the regulation of E2F3 through the targeting of miR-125a-3p. Taken together, our results showed that circRHOT1 plays critical roles in regulating the biological functions of pancreatic cancer cells, suggesting that circRHOT1 may serve as a potential diagnostic marker and therapeutic target for patients with pancreatic cancer.
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http://dx.doi.org/10.1111/jcmm.15572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520287PMC
September 2020

EUS-guided portal pressure gradient measurement in patients with acute or subacute portal hypertension.

Gastrointest Endosc 2021 03 29;93(3):565-572. Epub 2020 Jun 29.

Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Background And Aims: EUS-guided portal pressure gradient (EUS-PPG) measurement is a novel method to evaluate portal hypertension severity. In this study, we determined the consistency between EUS-PPG and hepatic venous pressure gradient (HVPG) measurements in patients with acute or subacute portal hypertension.

Methods: Twelve patients were prospectively enrolled. EUS-PPG measurements were performed using a 22-gauge FNA needle and a central venous pressure measurement monitor. The HVPG measurements were performed using the transjugular approach. If an HVPG measurement was not attainable and the patient underwent transjugular intrahepatic portosystemic shunt (TIPS) treatment, a PPG was recorded as a reference standard during the procedure. We assessed the feasibility and safety of EUS-PPG and calculated the correlation between the 2 measurements.

Results: EUS-PPG measurements were successful in 11 patients (91.7%). Subsequent HVPG measurements failed in 2 patients with Budd-Chiari syndrome (hepatic vein occlusion subtype), 1 of whom underwent TIPS treatment to obtain transjugular PPG data. A small shunt was found during 1 HVPG measurement that introduced inaccuracy. Nine patients were included in the statistical analysis. Mean EUS-PPG and HVPG/PPG (transjugular) were 18.07 ± 4.32 mm Hg and 18.82 ± 3.43 mm Hg, respectively. Pearson's correlation coefficient between the 2 methods was .923 (P < .001).

Conclusions: EUS-PPG measurement using a 22-gauge FNA needle was a safe and accurate method to evaluate portal hypertension and has the potential to supplement the measurement of HVPG in liver diseases. (Clinical trial registration number: ChiCTR1800017317.).
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http://dx.doi.org/10.1016/j.gie.2020.06.065DOI Listing
March 2021

ALDH1A3 Accelerates Pancreatic Cancer Metastasis by Promoting Glucose Metabolism.

Front Oncol 2020 16;10:915. Epub 2020 Jun 16.

Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

The aldehyde dehydrogenase 1 family member A3 (ALDH1A3) is a key enzyme associated with a variety of metabolic processes, including glucose metabolism. We recently uncovered that glucose metabolism played an essential role in promoting metastasis of pancreatic ductal adenocarcinoma (PDAC). As ALDH1A3 labels an aggressive subtype of PDAC, we hypothesized that ALDH1A3 functionally promoted PDAC metastasis via its metabolic effect on glucose metabolism. Expression of ALDH1A3 was detected in human PDAC tissues by immunohistochemistry. ALDH1A3 was knocked down or overexpressed in PDAC cells by either shRNA or overexpression vector. The functional roles of ALDH1A3 were characterized and . Transcriptional profiling via RNA-sequencing was used to explore the possible underlying molecular mechanisms. Glucose uptake, extracellular lactate, and ATP production were measured to access the metabolic influence of ALDH1A3 on PDAC cells. ALDH1A3 was associated with poor prognosis in PDAC patients. Functionally, ALDH1A3 promoted PDAC metastasis and . Further studies revealed that ALDH1A3 activated PI3K/AKT/mTOR signaling pathway and its downstream target-PPARγ (peroxisome proliferator-activated receptor gamma). This led to increase the expression of HK2 (hexokinase 2), which subsequently enhanced the glycolysis in PDAC cells. Additionally, the pharmacological inhibition of PPARγ activity in ALDH1A3-positive cells impaired glycolytic genes expression, PI3K/AKT/mTOR activity and cellular glycolysis. ALDH1A3 promotes PDAC metastasis via its metabolic influence on glucose metabolism. PPARγ and its downstream PI3K/AKT/mTOR signaling pathway maybe involved in this process.
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http://dx.doi.org/10.3389/fonc.2020.00915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308463PMC
June 2020

Comparison of prognostic prediction models for rectal gastrointestinal stromal tumor.

Aging (Albany NY) 2020 06 20;12(12):11416-11430. Epub 2020 Jun 20.

Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Rectal gastrointestinal stromal tumors (RGISTs) are biologically characterized tumors that are relatively rare. Thus, few studies have reported a specific prognostic system for this subset of tumors but integrated it into parallel systems, such as small intestine. Our aim is to develop a new predictive staging system nomogram (named FD-ZS system) for RGISTs.

Results: Tumor size and mitotic rate were independent risk factors for tumor recurrence in RGISTs according to univariate and multivariate survival analyses. A prognostic predictive nomogram was developed, and a cut-off value of 65 points was calculated by X-tile to discriminate risk based on tumor size and mitotic rate. The C-indices for the FD-ZS, FD-Hou, NIH, and WHO systems were 0.706, 0.693, 0.687, and 0.680, respectively.

Conclusion: In the present study, a concise two-tier grading system (FD-ZS) for prognostic prediction of RGISTs that is simpler to several reported systems was developed, and a cut-off value was established to help RGIST patients determine whether to undergo adjuvant imatinib treatment.

Methods: A nomogram was employed, and its predictive accuracy and discriminative ability were determined by concordance index (C-index) and calibration curve analyses. The nomogram was then compared with three stratification systems used for GISTs (FD-Hou, NIH, and WHO).
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http://dx.doi.org/10.18632/aging.103204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343501PMC
June 2020

A novel G6PD gene variant in a Chinese girl with favism.

J Clin Lab Anal 2020 Sep 17;34(9):e23402. Epub 2020 Jun 17.

Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan City, China.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The human G6PD gene is highly polymorphic, and over 200 mutations have been identified, many of which are associated with hemolytic anemia. Here, we analyzed the clinical genetics data of a Chinese girl with favism who developed acute hemolytic anemia after fava bean ingestion.

Methods: The clinical genetics data of the proband who developed acute hemolytic anemia were collected and analyzed, and G6PD gene exons were sequenced in the proband and her family.

Results: We reported for the first time a novel G6PD gene variant in a Chinese girl, which we named "G6PD Wuhan." This variant is localized exon 3 of the G6PD gene at genomic position 141G > C, that is a change from p.Lys47 to Asn. The bioinformatics analysis and protein modeling study indicated this variant may have negative effects on the enzyme activity of G6PD.

Conclusions: Our results indicated that favism in the proband was caused by this novel heterozygous variant (c.141G > C) in G6PD. The variant in G6PD has implications for genetic counseling and could provide insights into the functional roles of G6PD mutations.
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http://dx.doi.org/10.1002/jcla.23402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521235PMC
September 2020

Association between motoric cognitive risk syndrome and frailty among older Chinese adults.

BMC Geriatr 2020 03 19;20(1):110. Epub 2020 Mar 19.

Department of Geriatric, Zhejiang Hospital, No. 12 Lingyin Road, Hangzhou, 310013, Zhejiang Province, China.

Background: Motoric cognitive risk syndrome (MCR) is a newly proposed predementia syndrome incorporating subjective cognitive complaints and slow gait. Previous studies have reported that subjective cognitive complaints and slow gait are associated with frailty in cognitively unimpaired older adults, but little is known about the link between MCR and frailty in older adults. Therefore, the aim of the study was to explore the associations of MCR and its components with frailty in older Chinese adults.

Methods: In an observational cross-sectional study, a total of 429 older adults aged 60 years and older were admitted to the geriatric department. According to MCR criteria, all participants were classified into 4 groups: 1) the MCR group; 2) the subjective cognitive complaints only group; 3) the slow gait only group; and 4) the healthy control group. Physical frailty was assessed by the Clinical Frailty Scale (CFS). Multivariate logistic regression analysis was used to examine the association between MCR and frailty in older adults.

Results: The prevalence rates of subjective cognitive complaints, slow gait and MCR were 15.9, 10.0 and 4.0%, respectively. After adjusting for confounding variables, the logistic regression analysis showed that slow gait (odds ratio [OR]: 3.40, 95% confidence interval [CI]: 1.40-8.23, P = 0.007) and MCR (OR: 5.53, 95% CI: 1.46-20.89, P = 0.012) were independently associated with frailty, but subjective cognitive complaints were not.

Conclusions: MCR and slow gait were significantly associated with frailty in older Chinese adults. Further studies should prospectively determine the causal relationship between MCR and frailty.
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http://dx.doi.org/10.1186/s12877-020-01511-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081673PMC
March 2020

Association Between Body Composition and Frailty in Elder Inpatients.

Clin Interv Aging 2020 4;15:313-320. Epub 2020 Mar 4.

Department of Geriatrics, Zhejiang Hospital, Hangzhou 310013, People's Republic of China.

Purpose: The study aimed to investigate the association between body composition and frailty in elder inpatients.

Patients And Methods: This is a cross-sectional study including 656 elder inpatients (275 females and 381 males) aged ≥65 years, from department of geriatrics of Zhejiang Hospital between January 2018 and March 2019. Sociodemographic, health-related data and anthropometric measurements were evaluated. Body composition was assessed by bioimpedance analysis (BIA), mainly including skeletal muscle mass, body fat mass, total body water, fat-free mass,percent body fat, basal metabolic rate. Frailty was assessed by Clinical Frailty Scale (CFS). Univariate logistic regression was used to analyze the association between body composition and frailty.

Results: Frailty was present in 43.9% of the participants. Frail inpatients showed higher waist circumference, body fat mass and percent body fat, non-frail inpatients showed greater upper arm circumference, calf circumference, skeletal muscle mass, total body water, fat-free mass and basal metabolic rate. Subjects with underweight (body mass index (BMI)<18.5 kg/m; odds ratio (OR), 95% confidence interval (CI)=4.146 (1.286-13.368) P=0.017) and those with high waist circumference (OR 95% CI=1.428 (0.584-3.491) P<0.001), body fat mass (OR, 95% CI=1.143 (0.892-1.315) P<0.001) presented a higher risk of frailty compared to normal subjects. Skeletal muscle mass (OR; 95% CI=0.159 (0.064-0.396) P<0.001) was a protective factor for frailty.

Conclusion: Frailty in elder Chinese inpatients was characterized by a body composition phenotype with underweight, high waist circumference, low skeletal muscle mass and high body fat mass. Underweight, abdominal obesity and sarcopenic obesity may, therefore, be targets for intervention of frailty.
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http://dx.doi.org/10.2147/CIA.S243211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061425PMC
September 2020

Therapeutic Rationale to Target Highly Expressed Aurora kinase A Conferring Poor Prognosis in Cholangiocarcinoma.

J Cancer 2020 3;11(8):2241-2251. Epub 2020 Feb 3.

Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.

: Cholangiocarcinoma is a highly lethal neoplasm for which the currently available chemotherapeutic agents are suboptimal. Numerous studies show that alterations in expression of genes related to mitotic spindle and mitotic checkpoint are involved in chromosomal instability and tumor progression in various malignancies. This study aimed to evaluate these genes in cholangiocarcinoma patients. : Different public datasets were analyzed to examine the expression of 76 selected mitotic spindle checkpoint genes including Aurora Kinase A (AURKA) in cholangiocarcinoma. Afterwards, cell number counting, CCK-8 assay, and Caspase 3/7 assay were used to explore the antitumor effect of AURKA inhibitor Alisertib . In addition, xenograft model was used to evaluate the antitumor effect of Alisertib . Furthermore, siRNA mediated silencing of AURKA was used to verify the function of AURKA in cholangiocarcinoma. : Components of the mitotic spindle checkpoint, including AURKA, were broadly dysregulated in human cholangiocarcinoma. High AURKA mRNA expression was associated with poor survival in cholangiocarcinoma patients within different datasets. AURKA specific inhibitor Alisertib, inhibited cell growth, induced cell cycle arrest in G2/M phase, and promoted apoptosis in cholangiocarcinoma cell lines. Additionally, Alisertib also inhibited tumor growth in a cholangiocarcinoma xenograft mouse model. Furthermore, AURKA knockdown by siRNA recapitulated the antitumor effect of Alisertib. AURKA expression was also highly correlated with its interaction proteins Polo-like kinase 1(PLK1) and Targeting protein for xenopus kinesin-like protein2 (TPX2) in different cholangiocarcinoma datasets. : Highly expressed AURKA confers poor outcomes in cholangiocarcinoma and may represent a rational therapeutic target.
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http://dx.doi.org/10.7150/jca.31989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052919PMC
February 2020

Gastric peroral endoscopic pyloromyotomy versus gastric electrical stimulation in the treatment of refractory gastroparesis: a propensity score-matched analysis of long term outcomes.

Endoscopy 2020 05 21;52(5):349-358. Epub 2020 Feb 21.

Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia, United States.

BACKGROUND : Gastric peroral endoscopic pyloromyotomy (G-POEM) and gastric electrical stimulation (GES) have been reported as treatment options for refractory gastroparesis. In this study, we compared the long term clinical outcomes of G-POEM versus GES in the treatment of such patients. METHODS : We retrospectively evaluated 111 consecutive patients with refractory gastroparesis between January 2009 and August 2018. To overcome selection bias, we used propensity score matching (1:1) between G-POEM and GES treatment. The primary outcome was the duration of clinical response. RESULTS : After propensity score matching, 23 patients were included in each group. After a median follow-up of 27.7 months, G-POEM had a significantly better and longer clinical response than GES (hazard ratio [HR] for clinical recurrence 0.39, 95 % confidence interval [CI] 0.16 - 0.95;  = 0.04). The median duration of response was 25.4 months (95 %CI 8.7 - 42.0) in the GES group and was not reached in the G-POEM group. The Kaplan - Meier estimate of 24-month clinical response rate was 76.6 % with G-POEM vs. 53.7 % with GES. GES appeared to have little effect on idiopathic gastroparesis (HR for recurrence with G-POEM vs. GES 0.35, 95 %CI 0.13 - 0.95;  = 0.05). The incidence of adverse events was higher in the GES group (26.1 % vs. 4.3 %;  = 0.10). CONCLUSION : Among patients with refractory gastroparesis, clinical response was better and lasted longer with G-POEM than with GES. The positive outcomes with G-POEM are likely to derive from the superior clinical response in patients with idiopathic gastroparesis. Further studies are needed to confirm these findings.
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http://dx.doi.org/10.1055/a-1111-8566DOI Listing
May 2020

Prevalence and genetic analysis of thalassemia in neonates in Wuhan area: a national megacity in central China.

J Matern Fetal Neonatal Med 2021 Jul 11;34(14):2240-2247. Epub 2019 Sep 11.

Eugenic Genetics Laboratory, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People's Republic of China.

Background: Thalassemia is one of the most common genetic diseases in southern China. Accurate population frequency data regarding the occurrence and distribution of thalassemia is important for designing appropriate prevention strategies of thalassemia.

Objective: The aim of this study is to reveal the prevalence and the mutation spectrum of thalassemia in neonates in the Wuhan region of central China.

Methods: About 3796 neonates in Wuhan area of China were analyzed by hematological and genetic analysis.

Results: About 2174 subjects were genetically diagnosed as thalassemia carriers or patients, including 1415 cases of α-thalassemia (65.89%), 731 cases of β-thalassemia (33.62%), and 28 cases of α-composite β-thalassemia (1.29%). A total of 11 genotypes and 6 gene mutations were identified in α-thalassemia anomalies, with -/deletion (50.72%), -α/deletion (36.36%), and -α/deletion (7.38%) being the most common α-thalassemia mutations. β-thalassemia anomalies were associated with 17 genotypes and 12 gene mutations; IVS-2-654 mutation was the most common (41.18%), followed by CD41-42 (23.14%), CD17 (14.64%), CD26 (7.32%), and CD27-28 (4.58%) mutations. In addition, 13 genotypes were identified in α-composite β-thalassemia in thalassemia carrier, with the top six genotypes being IVS-2-654/N/-/αα (17.86%), CD17/N/-α/αα (17.86%), IVS-2-654/N/-α/αα (14.29%), CD41-42/N/-/αα (10.71%), CD71-72/N/-α/αα (7.14%), and Cap/N/-/αα (7.14%).

Conclusion: There was high heterogeneity and extensive spectrum of thalassemia in the neonates in Wuhan populations. The findings will be useful for genetic counseling and prenatal diagnosis of thalassemia in the Wuhan region.
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http://dx.doi.org/10.1080/14767058.2019.1662780DOI Listing
July 2021

Fulminant bilateral acute retinal necrosis complicated with secondary herpes simplex type-1 viral encephalitis: A case report.

Medicine (Baltimore) 2019 Aug;98(35):e17001

Department of Neurology.

Rationale: Acute retinal necrosis (ARN), which is characterized by peripheral necrotizing retinitis, severe retinal arteritis, and progressive inflammatory reaction in the vitreous and anterior chambers, has been reported in cases with herpes simplex encephalitis (HSE). It is a relatively rare complication secondary to HSE. However, cases presented with viral encephalitis following ARN were seldom reported.

Patient Concerns: A 43-year-old immunocompetent male patient manifested the aforesaid reverse situation. He developed HSE following 3-day systemic steroid therapy for abrupt ocular pain and rapidly decreased visual acuity, which was later diagnosed as ARN. Polymerase chain reaction (PCR) analysis of vitreous specimen verified herpes simplex virus-1 (HSV-1) infection.

Diagnosis: HSE associated with ARN.

Interventions: The patient was treated with intravenous acyclovir (500 mg every 8 h) for 21 days. A pulse of intravenous methylprednisolone, 500 mg/d for 5 days was given as an anti-inflammatory therapy, followed by prednisone taper.

Outcomes: The patient's neurological symptoms got improved very soon after the therapy, but his vision acuity remained no perception of light in both eyes.

Lessons: The present case indicates that ARN can also be a risk factor for HSE. Once ARN was suspected, corticosteroid should be applied with caution and in combination with antiviral treatment to avoid progressive duplication of virus and its spread to the brain.
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http://dx.doi.org/10.1097/MD.0000000000017001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736140PMC
August 2019

CDK7 inhibitor THZ1 inhibits MCL1 synthesis and drives cholangiocarcinoma apoptosis in combination with BCL2/BCL-XL inhibitor ABT-263.

Cell Death Dis 2019 08 9;10(8):602. Epub 2019 Aug 9.

Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China.

Cholangiocarcinoma (CCA) is a fatal disease without effective targeted therapy. We screened a small-molecule library of 116 inhibitors targeting different targets of the cell cycle and discovered several kinases, including Cyclin-dependent kinase 7 (CDK7) as vulnerabilities in CCA. Analysis of multiple CCA data sets demonstrated that CDK7 was overexpressed in CCA tissues. Further studies demonstrated that CDK7 inhibitor THZ1 inhibited cell viability and induced apoptosis in CCA cells. We also showed that THZ1 inhibited CCA cell growth in a xenograft model. RNA-sequencing followed by Gene ontology analysis showed a striking impact of THZ1 on DNA-templated transcriptional programs. THZ1 downregulated CDK7-mediated phosphorylation of RNA polymerase II, indicative of transcriptional inhibition. A number of oncogenic transcription factors and survival proteins, like MCL1, FOSL1, and RUNX1, were repressed by THZ1. MCL1, one of the antiapoptotic BCL2 family members, was significantly inhibited upon THZ1 treatment. Accordingly, combining THZ1 with a BCL2/BCL-XL inhibitor ABT-263 synergized in impairing cell growth and driving apoptosis. Our results demonstrate CDK7 as a potential target in treating CCA. Combinations of CDK7 inhibition and BCL2/BCL-XL inhibition may offer a novel therapeutic strategy for CCA.
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http://dx.doi.org/10.1038/s41419-019-1831-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688996PMC
August 2019

Targeting sphingosine kinase 2 suppresses cell growth and synergizes with BCL2/BCL-XL inhibitors through NOXA-mediated MCL1 degradation in cholangiocarcinoma.

Am J Cancer Res 2019 1;9(3):546-561. Epub 2019 Mar 1.

Department of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University Nanjing 210008, Jiangsu, China.

Sphingosine kinase 2 (SPHK2) is a key factor within sphingolipid metabolism, responsible for the conversion of pro-apoptotic sphingosine to the pro-survival sphingosine-1-phosphate. We have previously shown that ABC294640, a first-in-class SPHK2 inhibitor, inhibits growth of cholangiocarcinoma cells. In a Phase I study of ABC294640 in tumors, the best response was achieved in a cholangiocarcinoma patient. These data suggest SPHK2 as a novel therapeutic target of cholangiocarcinoma. However, the antitumor mechanism of ABC294640 in cholangiocarcinoma remains not clear. In the current study, we found that ABC294640 upregulated expression of pro-apoptotic NOXA. In cholangiocarcinoma patients, high NOXA mRNA expression was associated with better overall survival. Also, SPHK2 mRNA expression was negatively correlated with NOXA mRNA expression. NOXA is known to degrade MCL1, an anti-apoptotic BCL2 protein. We showed that ABC294640 directed MCL1 for proteasome degradation. Knockdown of NOXA prevented ABC294640-induced MCL1 degradation and apoptosis. In addition, ABC294640 had a synergistic effect with BCL2/BCL-XL inhibitors ABT-263 and Obatoclax in inhibiting cell growth. Combined treatment with ABC294640 and BCL2/BCL-XL inhibitors induced potent apoptosis. Silencing of MCL1 also potentiated ABT-263-induced cytotoxicity. Furthermore, we found that both SPHK2 and MCL1 protein expression were significantly higher in cholangiocarcinoma than that in nontumoral bile ducts. SPHK2 expression correlated significantly with MCL1 expression. Our study reveals that ABC294640 inhibits cholangiocarcinoma cell growth and sensitizes the antitumor effect of BCL2/BCL-XL inhibitors through NOXA-mediated MCL1 degradation. Combinations of ABC294640 with BCL2/BCL-XL inhibitors may provide novel strategies for the treatment of cholangiocarcinoma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448062PMC
March 2019

Application of Computed Tomography to Diagnose Fungal Esophagitis: One Case Report.

AIDS Res Hum Retroviruses 2019 05 11;35(5):425-427. Epub 2019 Mar 11.

Radiology Department, Hebei General Hospital, Hebei, China.

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http://dx.doi.org/10.1089/aid.2018.0281DOI Listing
May 2019

Examining Effects of Self-Efficacy on Research Motivation Among Chinese University Teachers: Moderation of Leader Support and Mediation of Goal Orientations.

J Psychol 2019 22;153(4):414-435. Epub 2019 Jan 22.

b Changchun University of Science and Technology.

Utilizing the Social Cognitive Career Theory (SCCT) as the theoretical framework, this study proposed a moderated mediation model investigating the complex functioning mechanisms of how self-efficacy beliefs and leader support can be related to research motivation among Chinese university teachers. A group of 310 Chinese teachers working in different universities completed an online survey. Results from structural equation modeling (SEM) analysis revealed distinct influencing paths from the predictor variables (i.e., self-efficacy and leader support) to the outcome variables (i.e., intrinsic and extrinsic research motivation). Specifically, self-efficacy beliefs predicted both mastery and performance goal orientations; mastery goal orientation, in turn, positively affected intrinsic and extrinsic research motivation. In contrast, leader support was non-significant for the both types of goal orientations, but exerted strong direct influences on the both types of research motivation. Bootstrapping methods in SEM showed that it was primarily the mastery goal orientation that mediated the relationships between self-efficacy beliefs and research motivation. Furthermore, the results from the SEM and simple slope analysis revealed that leader support moderated the association between self-efficacy and extrinsic research motivation.
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http://dx.doi.org/10.1080/00223980.2018.1564230DOI Listing
June 2019

Relationship between nutritional status and frailty in hospitalized older patients.

Clin Interv Aging 2019 10;14:105-111. Epub 2019 Jan 10.

Department of Geriatrics, Zhejiang Hospital, Hangzhou 310013, People's Republic of China,

Objective: The definition of frailty still lacks quantitative biomarkers. This study aimed to investigate the relationship between nutrition-related biomarkers and frailty in hospitalized older patients.

Materials And Methods: This is a cross-sectional study including 380 hospitalized older patients. The patients were categorized as nonfrail (n=140), prefrail (n=81), and frail (n=159) by the criteria of frailty phenotype. The nutritional status was assessed using the mini nutritional assessment-short form (MNA-SF), levels of serum transferrin (TNF), prealbumin (PA), total protein (TP), albumin (ALB), retinol-binding protein (RBP), and hemoglobin (Hb).

Results: The grip strength, levels of serum TFN, TP, ALB, Hb, and MNA-SF scores all decreased significantly in the order of nonfrail, prefrail, and frail groups (<0.01). Older ages, more fall incidents, and higher polypharmacy ratio were observed in the frail and prefrail groups than in the nonfrail group (<0.05). Univariate logistic regression analysis showed that frailty was positively related to age, polypharmacy, fall history, nutritional status, levels of TFN, PA, TP, ALB, RBP, and Hb, but was negatively related to grip strength. Ordinal logistic regression analysis showed that older patients who were well nourished, with higher levels of TFN, TP, and ALB were less likely to develop into frailty.

Conclusion: Hospitalized older patients with better nutritional status and higher levels of TFN, TP, and ALB were less likely to develop into frailty. These nutrition-related biomarkers may be used for the evaluation of nutritional status and frailty in older patients.
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http://dx.doi.org/10.2147/CIA.S189040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330965PMC
March 2019
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