Publications by authors named "Hong Qian"

395 Publications

Melatonin Inhibits Migration and Invasion in LPS-Stimulated and -Unstimulated Prostate Cancer Cells Through Blocking Multiple EMT-Relative Pathways.

J Inflamm Res 2021 25;14:2253-2265. Epub 2021 May 25.

Department of Urology, Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, People's Republic of China.

Purpose: Gram-negative bacteria are usually found in prostate cancer (PCa) tissues. This study aims to investigate the role of lipopolysaccharide (LPS), a glycolipid compound found in the outer membrane of gram-negative bacteria, on the migration and invasion of PCa cells, and to evaluate the protective effect of melatonin.

Materials And Methods: DU145, PC-3 and LNCaP cells were incubated with LPS in the presence or absence of melatonin. Wound healing and Transwell assays were used to analyze migration and invasion of PCa cells. RT-PCR and Western blotting were used to assess the mRNA and protein levels, respectively. Co-IP was used to analyze β-catenin ubiquitination.

Results: Our results showed that LPS promoted migration and invasion of PCa cells. In addition, LPS stimulated inflammatory reaction and induced epithelial-mesenchymal transition (EMT) in PCa cells by activating several TLR4 downstream pathways. Specifically, LPS promoted NF-κB/IL-6/STAT3 signal transduction. In addition, LPS upregulated phosphorylation levels of cytoplasmic AKT and GSK-3β. Moreover, LPS induced phosphorylation of GSK-3β in the "disruption complex", and then inhibited phosphorylation and ubiquitination of cytoplasmic β-catenin, leading to β-catenin nuclear translocation. Interestingly, melatonin inhibited invasion and migration not only in LPS-stimulated but also in LPS-unstimulated PCa cells. Melatonin suppressed PCa cells migration and invasion by blocking EMT mediated by IL-6/STAT3, AKT/GSK-3β and β-catenin pathways.

Conclusion: This study provides evidence that melatonin inhibits migration and invasion through blocking multiple TLR4 downstream EMT-associated pathways both in LPS-stimulated and -unstimulated PCa cells. Our results provide new insights into the role of bacterial infection in PCa metastasis and a potential therapeutic agent.
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http://dx.doi.org/10.2147/JIR.S305450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164707PMC
May 2021

Comfort nursing can alleviate pain and negative emotion of patients after surgery for LVCFs and improve their living ability.

Am J Transl Res 2021 15;13(4):2939-2946. Epub 2021 Apr 15.

Department of Nephrology, Affiliated Hospital of Jiangnan University Wuxi 214125, Jiangsu Province, China.

Objective: To determine the effect of comfort nursing in elderly patients with lumbar vertebral compression fractures (LVCFs).

Methods: A total of 194 elderly patients with LVCFs were enrolled, and assigned to two groups based on different nursing intervention methods. Among them, 93 patients were given routine nursing intervention as a control group (CON group), while the rest 101 patients were given comfort nursing as an intervention group (INT group). The visual analog scale (VAS) was adopted to evaluate patients' pain and Japanese Orthopaedic Association score (JOA) to evaluate their dysfunction. In addition, Barthel score was used to evaluate patients' self-care ability, and the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were adopted to score their anxiety and depression. Moreover, the compliance and nursing satisfaction of the two groups were investigated.

Results: After nursing, t VAS, SAS, and SDS scores of both groups declined significantly, and these scores of the INT group declined more notably. After nursing, the JOA and Barthel scores of the two groups increased greatly, and both scores of the INT group were significantly higher than those of the CON group. Additionally, the INT group consumed significantly less analgesic drugs and experienced significantly shorter hospital stay than the CON group. Moreover, according to the survey on nursing compliance and nursing satisfaction, the INT group showed significantly higher nursing compliance and nursing satisfaction than the CON group.

Conclusion: For elderly patients with LVCFs, comfort nursing can effectively relieve their postoperative pain and negative emotion and improve their daily living ability.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129384PMC
April 2021

Acupuncture for acute low back pain: a systematic review and meta-analysis.

Ann Palliat Med 2021 Apr 8;10(4):3924-3936. Epub 2021 Apr 8.

Clinical Research and Data Center, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Acupuncture has been widely used for acute low back pain (LBP), yet there remains continued controversy regarding its efficacy. Therefore, we aimed to critically evaluate the evidence for acupuncture as an effective treatment for acute LBP.

Methods: English and Chinese databases were searched for randomized controlled trials (RCTs) that involved acupuncture for acute LBP published up to May 2020. Data on the outcomes of pain intensity, functional status, and analgesic use were extracted. The meta-analysis was performed using the Cochrane Collaboration's RevMan 5.3, and pooled data were expressed as mean differences (MD) with 95% confidence intervals (CIs).

Results: Of the 13 eligible RCTs identified, 11 RCTs (involving 707 patients) provided moderate-quality evidence that acupuncture has a statistically significant association with improvements in VAS (visual analog scale) score [MD: -1.75 (95% CI: -2.39, -1.12)]. Two studies indicated that acupuncture did not influence the RMDQ (Roland-Morris Disability Questionnaire) scores more than the control treatment [MD: -2.34 (95% CI: -5.34, 0.67)]. Three studies suggested that acupuncture influenced the ODI (Oswestry Disability Index) scores more than the control treatment [MD: -12.84 (95% CI: -23.94, -1.74)]. Two studies suggested that acupuncture influenced the number of pills more than the control treatment [MD: -3.19 (95% CI: -3.45, -2.92)].

Conclusions: Acupuncture treatment of acute LBP was associated with modest improvements in the VAS score, ODI score, and the number of pills, but not the RMDQ score. Our findings should be considered with caution due to the low power original studies. High-quality trials are needed to assess further the role of acupuncture in the treatment of acute LBP.
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http://dx.doi.org/10.21037/apm-20-1998DOI Listing
April 2021

Independent and combined associations of urinary heavy metals exposure and serum sex hormones among adults in NHANES 2013-2016.

Environ Pollut 2021 Jul 8;281:117097. Epub 2021 Apr 8.

State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. Electronic address:

Accumulating evidences indicated that heavy metals may disrupt human sex hormones. However, the combined effects of heavy metals on sex hormones remain to be clarified. To explore the independent and combined associations between heavy metal exposure and serum sex hormones among adults, data of 2728 adults from the National Health and Nutrition Examination Survey (NHANES) was applied. We examined independent and combined associations of fourteen urinary heavy metals and three serum sex steroid hormones (total testosterone (TT), estradiol (E2) and sex hormone-binding globulin (SHBG)). Multivariate linear regression was used to evaluate the independent associations between metal exposure and sex hormone alterations. Principle component analysis -weighted quantile sum regression (PCA-WQSR) model was performed to estimate the combined associations in our individuals. In the co-exposure model, we determined that weighted quantile sum (WQS) index of industrial pollutants was negatively associated with E2 in females (WQS Percent change = -20.6%; 95% CI: -30.1%, -9.96%), while in males WQS index of water pollutants was negatively related to SHBG (WQS Percent change = -5.35%; 95% CI: -9.88%, -0.598%). Cadmium (Cd), tin (Sn) and lead (Pb) were the dominating metals of female E2-negative association while Ba was the leading contributor related to male SHBG reduction, which was consistent with the results of multivariate linear regression. Additionally, in postmenopausal women, the associations of E2 decrease with heavy metal co-exposure remained significant while Cd and monomethylarsonic acid (MMA) were identified as hazardous metals in the mixture. We concluded that the exposure to heavy metals was associated with human sex hormone alterations in independent or combined manners. Considering the design of NHANES study, further studies from other national-representative surveys are necessary.
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http://dx.doi.org/10.1016/j.envpol.2021.117097DOI Listing
July 2021

Publisher Correction: Evolutionary assembly of flowering plants into sky islands.

Nat Ecol Evol 2021 Jun;5(6):863

Univ. Grenoble Alpes, Univ. Savoie Mont Blanc, CNRS, LECA, Laboratoire d'Ecologie Alpine, Grenoble, France.

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http://dx.doi.org/10.1038/s41559-021-01465-5DOI Listing
June 2021

Urinary polycyclic aromatic hydrocarbons and sex hormones in children and adolescents: Evidence from NHANES.

Ecotoxicol Environ Saf 2021 Apr 13;216:112215. Epub 2021 Apr 13.

State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address:

Background: Evidences showed that polycyclic aromatic hydrocarbons (PAHs) do harm to human body. However, the association between PAHs and sex hormones in children and adolescents remains unclear.

Objectives: The study aims to investigate the associations between PAHs and sex hormones in the general children and adolescent population.

Methods: 967 participants aged 6-19 with complete data of PAHs exposure biomarkers, covariates and sex hormones [total testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG)] were recruited from National Health and Nutrition Examination Survey (NHANES), 2013-2016. Free androgen index (FAI) was calculated with TT/SHBG. Multivariate linear regression models were performed in six subgroups (male children, male adolescents, male late adolescents, female children, female adolescents and female late adolescents) to estimate the associations between sex hormone alterations and PAHs exposure.

Results: In male puberty adolescents, weighted multivariate linear regression indicated that negative trends for 2-Hydroxynaphthalene, 1-Hydroxyphenanthrene, 2&3-Hydroxyphenanthrene and E2 (2-Hydroxynaphthalene: β: -0.104, 95%CI: -0.180, -0.029, P < 0.01; 1-Hydroxyphenanthrene: β: -0.112, 95%CI: -0.206, -0.018, P = 0.019; 2&3-Hydroxyphenanthrene: β: -0.125, 95%CI: -0.232, -0.018, P = 0.022), while exposure to 2-Hydroxynaphthalene was related to TT reduction (β: -0.099, 95%CI: -0.177, -0.020, P = 0.014). Same pattern between 2&3-Hydroxyphenanthrene and E2 alteration (2&3-Hydroxyphenanthrene: β: -0.139, 95%CI: -0.236, -0.041, P < 0.01) was also observed in male late adolescents. In male children, we determined that 1-Hydroxyphenanthrene was negatively associated with SHBG (β: -0.121, 95%CI: -0.205, -0.037, P < 0.01), while the same patterns were observed in male puberty children. We did not observe any significant result in female subgroups. All these results above were determined to have q value < 0.05.

Conclusion: PAHs exposure was associated with the alterations of sex hormones in male adolescents and children. Considering the cross-sectional study design, further large-scale epidemiological study is necessary.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112215DOI Listing
April 2021

Study on the gene signature related to immune microenvironment on viral and nonviral infections of hepatocellular carcinoma.

Medicine (Baltimore) 2021 Apr;100(15):e25374

The First Hospital of Lanzhou University, Lanzhou.

Abstract: The pathogenesis of hepatocellular carcinoma (HCC) can be divided into viral infection (VIR) and nonviral (NVIR) infection. Two types of HCC performed different tumor immune microenvironment (TIME) which directly affected prognosis of HCC. This study aimed to identify an effective 2 types of HCC prognostic gene signature that related to immune TIME.The differential expression genes (DEGs) were analyzed by Limma R package from the Cancer Genome Atlas. Immune related genes getting from IMMport database were matched to DEGs for testing prognosis. Prognostic index (PI) consisted of prognostic immune related genes was calculated in different types of HCC by COX regression and the correlation with the abundance of immune infiltrates, including 6 type cells, via gene modules. Tumor immune estimation resource database was applied to analyze TIME. Finally, the correlations between PI of DEGs and TIICs were analyzed by the Spearman method.Results showed that PI consisted of 11 messenger RNAs in VIR and 12 messenger RNAs in NVIR groups. The PI related to HCC prognosis has different correlations with immune infiltrating cells in VIR and NVIR groups. The PI value of DEGs has significant correlations with neutrophils (R = 0.22, P-value = .029) and dendritic (R = 0.21, P-value = .036) infiltration levels in VIR group. However, in NVIR group, the result showed there were no significant correlations between PI and other 5 type cell infiltration levels (P-value > .05).The 11-gene signature in VIR and 12-gene signature in NVIR group selected based on data from the Cancer Genome Atlas database had a different correlation with immune infiltrating cells of HCC patients.
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http://dx.doi.org/10.1097/MD.0000000000025374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052083PMC
April 2021

Analysis of Saccharification Products of High-Concentration Glutinous Rice Fermentation by Q3 and Alcoholic Fermentation of GY-1.

ACS Omega 2021 Mar 18;6(12):8038-8044. Epub 2021 Mar 18.

Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Ministry of Education and School of Life Science, Yunnan Normal University, Kunming 650500, P. R. China.

A two-stage process was used to prepare rice alcohol, i.e., saccharification of glutinous rice by Q3, followed by fermentation. Q3 was cultured during the saccharification stage, and GY-1 was added in the fermentation stage. Total sugar content and reducing sugar content in these two stages were analyzed. The relationship between the production proportion and consumption of the reducing sugar in the saccharification interval was analyzed using reducing sugar indices. It is an important rule that the high-concentration syrup and oligosaccharides prepared by glutinous rice could reach 42°Bx and 250 mg/mL by high-concentration fermentation in the growth stage of Q3.
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http://dx.doi.org/10.1021/acsomega.0c05452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014914PMC
March 2021

Proteomic analysis reveals rotator cuff injury caused by oxidative stress.

Ther Adv Chronic Dis 2021 17;12:2040622320987057. Epub 2021 Mar 17.

Department of Orthopedics, Nanjing Jinling Hospital, 305 Zhongshan East Road, Nanjing 210002, China The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China Department of Orthopedics, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.

Background And Aims: Rotator cuff tendinopathy is common and is related to pain and dysfunction. However, the pathological mechanism of rotator cuff injury and shoulder pain is unclear. Objective: to investigate the pathological mechanism of rotator cuff injury and shoulder pain, and screen out the marker proteins related to rotator cuff injury by proteomics.

Methods: Subacromial synovium specimens were collected from patients undergoing shoulder arthroscopic surgery. The experimental group were patients with rotator cuff repair surgery, and the control group were patients with habitual dislocation of the shoulder joint. Pathological examination was performed, and then followed by non-labeled quantitative proteomic detection. Finally, from analysis of the biological information of the samples, specific proteins related to rotator cuff injury and shoulder pain were deduced by functional analysis of differential proteins.

Results: All the patients in experimental groups were representative. A large number of adipocytes and inflammatory cells were found in the pathological sections of the experimental group; the proteomics analysis screen identified 80 proteins with significant differences, and the analysis of protein function revealed that S100A11 ( = 0.011), PLIN4 ( = 0.017), HYOU1 ( = 0.002) and CLIC1 ( = 0.007) were closely related to oxidative stress and chronic inflammation.

Conclusion: Rotator cuff injury is closely related to oxidative stress and chronic inflammatory response, and the results suggest that the expression of S100A11, PLIN4, HYOU1 and CLIC1 in the synovium of rotator cuff injury provides a new marker for the study of its pathological mechanism.
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http://dx.doi.org/10.1177/2040622320987057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975570PMC
March 2021

Circulating Tfh cell and subsets distribution are associated with low-responsiveness to hepatitis B vaccination.

Mol Med 2021 04 1;27(1):32. Epub 2021 Apr 1.

Department of Epidemiology and Biostatistics, Guangdong Medical University, No.1 Xincheng Road, 523808, Dongguan, China.

Background: An estimated 5-10 % of healthy vaccinees lack adequate antibody response following receipt of a standard three-dose hepatitis B vaccination regimen. The cellular mechanisms responsible for poor immunological responses to hepatitis B vaccine have not been fully elucidated to date.

Methods: There were 61 low responders and 56 hyper responders involved in our study. Peripheral blood samples were mainly collected at D7, D14 and D28 after revaccinated with a further dose of 20 µg of recombinant hepatitis B vaccine.

Results: We found low responders to the hepatitis B vaccine presented lower frequencies of circulating follicular helper T (cTfh) cells, plasmablasts and a profound skewing away from cTfh2 and cTfh17 cells both toward cTfh1 cells. Importantly, the skewing of Tfh cell subsets correlated with IL-21 and protective antibody titers. Based on the key role of microRNAs involved in Tfh cell differentiation, we revealed miR-19b-1 and miR-92a-1 correlated with the cTfh cell subsets distribution and antibody production.

Conclusions: Our findings highlighted a decrease in cTfh cells and specific subset skewing contribute to reduced antibody responses in low responders.
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http://dx.doi.org/10.1186/s10020-021-00290-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015036PMC
April 2021

Evolutionary assembly of flowering plants into sky islands.

Nat Ecol Evol 2021 05 29;5(5):640-646. Epub 2021 Mar 29.

Univ. Grenoble Alpes, Univ. Savoie Mont Blanc, CNRS, LECA, Laboratoire d'Ecologie Alpine, Grenoble, France.

Alpine floras (plants in the vegetation belts above the climatic treelines) experience cold climates, particularly in temperate mountains during winter, but they are generally species-rich. Yet, biogeographers have not determined whether these floras represent evolutionarily independent but convergent assemblages drawn from their regional floras, or whether they originated from particular clades pre-adapted to harsh conditions. Here, we analyse the evolutionary relationships of angiosperm (flowering plant) species in 63 alpine floras worldwide (~7,000 species) in comparison with their regional floras (~94,000 species) and with the entire global flora. We find that each of the alpine floras represents an assemblage of more closely related species than their respective regional floras. The degree of phylogenetic clustering of species in alpine floras in tropical mountains exceeds that in temperate mountains. However, in relation to the global flora, temperate alpine floras are phylogenetically closely related subsets of floras that colonized cold temperate areas during interglacial periods. We conclude that alpine floras include a few dominant families that have evolved tolerance to low temperature, and that evolutionary niche conservatism explains their phylogenetic clustering, compared with species in their regional species pools.
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http://dx.doi.org/10.1038/s41559-021-01423-1DOI Listing
May 2021

Geranylgeranyl diphosphate synthase deficiency hyperactivates macrophages and aggravates lipopolysaccharide-induced acute lung injury.

Am J Physiol Lung Cell Mol Physiol 2021 Jun 17;320(6):L1011-L1024. Epub 2021 Mar 17.

Department of Respiratory and Critical Care Medicine, Jinling Hospital, the First School of Clinical Medicine, Southern Medical University (Guangzhou), Nanjing, China.

Macrophage activation is a key contributing factor for excessive inflammatory responses of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Geranylgeranyl diphosphate synthase (GGPPS) plays a key role in the development of inflammatory diseases. Our group previously showed that GGPPS in alveolar epithelium have deleterious effects on acute lung injury induced by LPS or mechanical ventilation. Herein, we examined the role of GGPPS in modulating macrophage activation in ALI/ARDS. We found significant increased GGPPS expression in alveolar macrophages in patients with ARDS compared with healthy volunteers and in ALI mice induced by LPS. GGPPS-floxed control () and myeloid-selective knockout () mice were then generated. Interestingly, using an LPS-induced ALI mouse model, we showed that myeloid-specific GGPPS knockout significantly increased mortality, aggravated lung injury, and increased the accumulation of inflammatory cells, total protein, and inflammatory cytokines in BALF. In vitro, GGPPS deficiency upregulated the production of LPS-induced IL-6, IL-1β, and TNF-α in alveolar macrophages, bone marrow-derived macrophages (BMDMs), and THP-1 cells. Mechanistically, GGPPS knockout increased phosphorylation and nuclear translocation of NF-κB p65 induced by LPS. In addition, GGPPS deficiency increased the level of GTP-Rac1, which was responsible for NF-κB activation. In conclusion, decreased expression of GGPPS in macrophages aggravates lung injury and inflammation in ARDS, at least partly by regulating Rac1-dependent NF-κB signaling. GGPPS in macrophages may represent a novel therapeutic target in ARDS.
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http://dx.doi.org/10.1152/ajplung.00281.2020DOI Listing
June 2021

Association between maternal diabetes mellitus and allergic diseases in children - A systematic review and meta-analysis.

Pediatr Allergy Immunol 2021 Mar 11. Epub 2021 Mar 11.

State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

Background: Existing knowledge suggests that gestational diabetes mellitus was inconsistently associated with offspring allergic diseases. The aim of this study was to identify the association between maternal diabetes mellitus and the risk of offspring allergic diseases by systematic review.

Methods: We searched and retrieved three databases (PubMed, Web of Science, and Cochrane Library) for articles on the association between maternal diabetes mellitus and offspring allergic diseases published before December 31, 2019. Stata software version 16.0 was used for statistical analysis.

Results: Eight published studies were included in this meta-analysis. The pooled effect estimates showed the association between maternal diabetes mellitus and allergic outcomes, including asthma (OR: 1.13, 95% CI: 1.01-1.27), wheezing (OR: 1.13, 95% CI: 1.07-1.21), and atopic dermatitis (OR: 1.43, 95% CI: 1.22-1.57). Maternal diabetes mellitus was not associated with the risk of allergic sensitization, with a pooled effect estimate of 1.07 (95% CI: 0.45, 2.58).

Conclusion: Maternal diabetes mellitus may increase the risk of allergic diseases in their children. However, this finding should be validated with future large-sample epidemiological studies covering a wider spectrum of allergic diseases.
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http://dx.doi.org/10.1111/pai.13498DOI Listing
March 2021

Impact of concomitant tricuspid annuloplasty on right ventricular remodeling in patients with rheumatic mitral valve disease.

Cardiovasc Ultrasound 2021 Mar 4;19(1):16. Epub 2021 Mar 4.

Department of Cardiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China.

Background: Studies on the management of functional tricuspid regurgitation (TR) during mitral valve operations have drawn inconsistent conclusions. This study was designed to compare the treatment strategy of concomitant tricuspid annuloplasty (TAP) against isolated mitral valve replacement (MVR) in rheumatic mitral valve disease patients, and to assess the effect of concomitant TAP on postoperative right ventricular (RV) remodeling and function.

Methods: One hundred-seventy patients with rheumatic mitral valve disease receiving MVR were categorized into TAP group (n = 124) and non-TAP group (n = 46). Clinical and echocardiographic data were collected preoperatively and at 1-year follow-up. Three-dimensional echocardiographic indices of RV geometry and function were analyzed.

Results: At baseline, concomitant TAP group had larger RV end-diastolic volume, more decreased RV ejection fraction and RV longitudinal strain than non-TAP group (all P <  0.001). At 1-year follow-up, TAP group had improved RV geometry and function. While adverse changes were observed in non-TAP group. In analysis of variance, the above indices demonstrated significant interaction with different treatment group (all P <  0.001). In multivariate regression analysis, independent of age and Maze procedure, concomitant TAP was associated with postoperative RV volume reduction (P <  0.001), improvement of RV ejection fraction (P <  0.001), and relieved postoperative functional TR severity (P = 0.025).

Conclusions: Our results suggest that concomitant TAP could improve RV remodeling and function for rheumatic mitral valve disease patients, while those with mild preoperative functional TR who had isolated MVR might experience RV dilation and deterioration of RV function at follow-up. Concomitant surgery for functional TR could be considered for patients undergoing MVR with rheumatic mitral valve disease.
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http://dx.doi.org/10.1186/s12947-021-00245-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934510PMC
March 2021

BAY11-7082 inhibits the expression of tissue factor and plasminogen activator inhibitor-1 in type-II alveolar epithelial cells following TNF-α stimulation via the NF-κB pathway.

Exp Ther Med 2021 Feb 28;21(2):177. Epub 2020 Dec 28.

Department of Critical Care Medicine, Guizhou Medical University Affiliated Hospital, Guiyang, Guizhou 550001, P.R. China.

Pulmonary inflammation strongly promotes alveolar hypercoagulation and fibrinolytic inhibition. NF-κB signaling regulates the expression of molecules associated with coagulation and fibrinolytic inhibition in type-II alveolar epithelial cells (AECII) stimulated by lipopolysaccharide. However, whether TNF-α-induced alveolar hypercoagulation and fibrinolysis inhibition is also associated with the NF-κB pathway remains to be determined. The aim of the present study was to determine whether BAY11-7082, an inhibitor of the NF-κB pathway, inhibits the expressions of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) in AECⅡ in response to TNF-α. Rat AECII were treated with BAY11-7082 for 24 h and stimulated with TNF-α for 1 h. The expression of TF and PAI-1 were determined using western blotting and reverse transcription-quantitative PCR. The concentrations of TF and PAI-1 in culture supernatant were also measured by ELISA. Moreover, levels of NF-κB p65 (p65), phosphorylated (p)-p65 (p-p65), inhibitor of NF-κB α (IκBα) and p-IκBα were also evaluated. Immunofluorescence was used to detect p65 levels in cell nuclei. TNF-α significantly promoted TF and PAI-1 expression either at the mRNA or protein level in AECII cells. Concentrations of TF and PAI-1 in supernatant also significantly increased upon TNF-α stimulation. Furthermore, TNF-α upregulated the levels of p-IκBα, p65, and p-p65 in the cytoplasm. Immunofluorescence analysis indicated that TNF-α increased p65 translocation from the cytoplasm to the nucleus. However, AECII pre-treated with BAY11-7082 expressed lower levels of TF and PAI-1 following TNF-α treatment. Levels of p-IκBα, p65 and p-p65 in the cytoplasm also decreased, and translocation of p65 from cytoplasm into the nucleus was inhibited by BAY11-7082 pretreatment. These findings suggest that BAY11-7082 improves the hypercoagulation and fibrinolytic inhibition induced by TNF-α in alveolar epithelial cells via the NF-κB signaling pathway. BAY11-7082 might represent a therapeutic option for alveolar hypercoagulation and fibrinolytic inhibition in acute respiratory distress syndrome.
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http://dx.doi.org/10.3892/etm.2020.9608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797938PMC
February 2021

Regional disparity in extinction risk: Comparison of disjunct plant genera between eastern Asia and eastern North America.

Glob Chang Biol 2021 05 13;27(9):1904-1914. Epub 2021 Feb 13.

Zhejiang Tiantong Forest Ecosystem National Observation and Research Station, Research Center for Global Change and Ecological Forecasting, School of Ecological and Environmental Sciences, East China Normal University, Shanghai, China.

Climate and land cover changes are increasing threats to biodiversity globally. However, potentially varying biotic sensitivity is a major source of uncertainty for translating environmental changes to extinction risks. To reduce this uncertainty, we assessed how extinction risks will be affected by future human-driven environmental changes, focusing on 554 species from 52 disjunct plant genera between eastern Asia (EAS) and eastern North America (ENA) to control for differences in environmental sensitivity at the genus level. Species distribution models were used to estimate and compare the vulnerability of species in disjunct genera between the two regions under two climate and land cover change scenarios (RCP2.6 and RCP8.5) in the 2070s, allowing to assess the effects of differences in climate and land cover pressures. Compared with ENA, stronger pressures from climate and land cover changes along with smaller range sizes in EAS translate into a larger number and proportion of species in disjunct genera becoming threatened by the 2070s. These regional differences are more pronounced under a best-case climate scenario (RCP2.6), illustrating that strong climate change (RCP8.5) may override any regional buffer capacities. The main variables determining extinction risks differed between the two continental regions, with annual temperature range and cropland expansion being important in EAS, and annual precipitation being important in ENA. These results suggest that disparities in regional exposure to anthropogenic environmental changes may cause congeneric species with relatively similar sensitivity to have different future risks of extinction. Moreover, the findings highlight the context-specific nature of anthropogenic effects on biodiversity and the importance of making region-specific policies for conservation and restoration in response to the intensifying global changes.
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http://dx.doi.org/10.1111/gcb.15525DOI Listing
May 2021

Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer.

Signal Transduct Target Ther 2021 Jan 20;6(1):26. Epub 2021 Jan 20.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.

Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world. Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years, their efficacy is still unsatisfactory overall. Therefore, there is an urgent unmet clinical need for lung cancer treatment. Here, we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm, 2 medical centers, pilot study initiated by the investigator (ChiCTR-ONC-16009100, NCT02956551). The patients enrolled were patients with heavily treated metastatic lung cancer. Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis. A total of 12 patients were enrolled in this study. A total of 85 vaccine treatments were administered with a median value of 5 doses/person (range: 3-14 doses/person). In total, 12-30 peptide-based neoantigens were selected for each patient. All treatment-related adverse events were grade 1-2 and there were no delays in dosing due to toxic effects. The objective effectiveness rate was 25%; the disease control rate was 75%; the median progression-free survival was 5.5 months and the median overall survival was 7.9 months. This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.
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http://dx.doi.org/10.1038/s41392-020-00448-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817684PMC
January 2021

An unusual left ventricle pseudo-aneurysm with progressive mitral regurgitation.

Eur Heart J 2021 02;42(8):873

Department of Cardiology, West China Hospital, Sichuan University, No. 37 GuoXue Xiang, Chengdu, Sichuan 610041, China.

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http://dx.doi.org/10.1093/eurheartj/ehaa1076DOI Listing
February 2021

Liposomal doxorubicin-related palmar-plantar erythrodysesthesia (hand-foot syndrome): a case report.

J Int Med Res 2020 Dec;48(12):300060520974854

Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Hand-foot syndrome (HFS) is a skin toxicity that occurs in areas of compressed skin. HFS manifests mainly in insensitive palms and the soles of the feet or in erythematous areas on the extremities caused by chemotherapy, which may be related to the dosage. This paper reports a case of HFS caused by liposomal doxorubicin. A 64-year-old Asian woman presented with severe erythema, ulceration, pruritus, and edema-related pain in her back, hands, and feet after receiving four cycles of liposomal doxorubicin. Clinicians and a pharmacist analyzed and evaluated the patient's adverse reactions. After symptomatic treatment and patient education, her HFS symptoms were significantly relieved. The purpose of this study was to raise clinical awareness regarding adverse events following liposomal doxorubicin injection, and to provide new ideas for the clinical treatment of these adverse events.
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http://dx.doi.org/10.1177/0300060520974854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770262PMC
December 2020

Liposomal doxorubicin-related palmar-plantar erythrodysesthesia (hand-foot syndrome): a case report.

J Int Med Res 2020 Dec;48(12):300060520974854

Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Hand-foot syndrome (HFS) is a skin toxicity that occurs in areas of compressed skin. HFS manifests mainly in insensitive palms and the soles of the feet or in erythematous areas on the extremities caused by chemotherapy, which may be related to the dosage. This paper reports a case of HFS caused by liposomal doxorubicin. A 64-year-old Asian woman presented with severe erythema, ulceration, pruritus, and edema-related pain in her back, hands, and feet after receiving four cycles of liposomal doxorubicin. Clinicians and a pharmacist analyzed and evaluated the patient's adverse reactions. After symptomatic treatment and patient education, her HFS symptoms were significantly relieved. The purpose of this study was to raise clinical awareness regarding adverse events following liposomal doxorubicin injection, and to provide new ideas for the clinical treatment of these adverse events.
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http://dx.doi.org/10.1177/0300060520974854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770262PMC
December 2020

[The Feasibility and Repeatability of Ultrasound Microbubble Angiography in the Determination of Pulmonary Blood Volume in Animal Models].

Sichuan Da Xue Xue Bao Yi Xue Ban 2020 Nov;51(6):839-846

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To investigate the feasibility of measuring pulmonary blood volume (PBV) by ultrasound microbubble angiography, which may provide a feasible method for further detection of PBV changes.

Methods: Ultrasound microbubble angiography was used to calculate the PBV by detecting pulmonary transit time (PTT) and heart rate-normalized pulmonary transit time (nPTT). To evaluate the consensus degree based on the intra-, inter-observer and within-day variation in order to determine the repeatability. The method was used for acute left ventricular dysfunction models to determine the feasibility as well.

Results: The Bland-Atlman plots showed good intra-observer, within-day, and inter-observer consistency of measurement results. Application in acute left ventricular dysfunction models showed that, compared with the control, left heart failure models had higher PTT, nPTT and PBV ( <0.05).

Conclusion: Detection of PTT/nPTT to calculate PBV by ultrasound microbubble angiography is simple and feasible, it is not easy to produce miscarriage of justice, with good intra- and inter-observer consistency of repeatability test results. The method has certain feasibility.
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http://dx.doi.org/10.12182/20201160106DOI Listing
November 2020

Impact of heating and drying temperatures on the properties of konjac glucomannan/curdlan blend films.

Int J Biol Macromol 2021 Jan 17;167:1544-1551. Epub 2020 Nov 17.

Yellow Crane Tower Science and Technology Park (Group) Co., Ltd., Wuhan 430040, Hubei, China. Electronic address:

The impact of preparation conditions including heating temperature (from 60 °C to 90 °C) and drying temperatures (from 25 °C to 90 °C) on the properties of pure curdlan film and konjac glucomannan (KGM) and curdlan blend films were analyzed. Microstructure analysis indicated the KGM addition could significantly improve the relatively poor film-forming property of curdlan. FTIR and X-ray analysis showed that at high heating temperature 90 °C, molecular interaction might be enhanced in the films due to the stretched structure of curdlan and dissociation of curdlan bundles or triple-helix structure. This was supported by the changes in the mechanical property, surface hydrophobicity, moisture barrier, and moisture tolerance property. The impacts of drying temperature were some different for the curdlan film and KGM/curdlan blend film, and were explained from the molecular hydrophilicity-hydrophobicity, compactness of the films, curdlan conformation, and molecular interaction. This work guided biodegradable film production especially with curdlan added.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.108DOI Listing
January 2021

Improving konjac glucomannan-based aerogels filtration properties by combining aerogel pieces in series with different pore size distributions.

Int J Biol Macromol 2021 Jan 9;166:1499-1507. Epub 2020 Nov 9.

Yellow Crane Tower Science and Technology Park (Group) Co., Ltd., Wuhan 430040, Hubei, China. Electronic address:

The pore size distribution of konjac glucomannan (KGM)-based aerogels seriously impacted the air filtration efficiency and filtration resistance. This study aimed to investigate the pore size distribution control of KGM-based aerogels through total solid concentration of the sol and to improve the filtration performance by preparing aerogel stacks, which were made by combining KGM-based aerogels with different pore size distribution (range: 0-180 μm). Results indicated that with increased total solid concentration from 50% to 100% of the origin formulae, aerogel pore size became smaller and the porosity was decreased for all the three sample formulae. Meanwhile, the aerogel mechanical property and filtration efficiency were both strengthened with increased total solid concentration, but the air resistance became significantly higher. The changing extent and rule were influenced by the sample components (KGM, starch, gelatin, wheat straw). The aerogel stacks prepared by in series combining the aerogel pieces with different pore size distribution (from large size to small size) was found to improve filtration efficiency (e.g. from 70% to 80% for K1G2S4WS2) and significantly lower the air resistance (e.g. from 270 Pa to 190 Pa for K1G2S4WS2). This study could guide the filtration performance improvement of aerogels.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.029DOI Listing
January 2021

Dumbbell on the heart: two giant left coronary artery aneurysms in an adolescent.

Eur Heart J 2020 Nov 3. Epub 2020 Nov 3.

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Guoxuexiang 37th, Chengdu, Sichuan 610041, P.R. China.

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http://dx.doi.org/10.1093/eurheartj/ehaa711DOI Listing
November 2020

[Reflections on the Key Points in the Establishment of the Guidelines for Class II Medical Device Technical Review-Example of Intraoral Digital Dental Impression].

Authors:
Hong Qian

Zhongguo Yi Liao Qi Xie Za Zhi 2020 Oct;44(5):425-429

Center for Certification and Evaluation, Shanghai Food and Drug Administration, Shanghai, 200020.

Technical Review Guidelines of Medical Devices are standards to standardize and unify registration review of medical devices marketed in China. The writing quality of the guidelines affects not only the time for technical evaluation, but also the safety and effectiveness of approved products. Based on authors' practices of nearly 30 class II medical equipment technical guidelines written and 20-year experience in class II medical device evaluation, this study takes intraoral digital dental impressions as an example to put forward several key points of sections "summary" and "research data" in the guidelines, for researchers on class II medical equipment technical guidelines reference.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2020.05.010DOI Listing
October 2020

ROS-mediated genotoxic stress is involved in NaAsO-induced cell cycle arrest, stemness enhancement and chemoresistance of prostate cancer cells in a p53-independent manner.

Ecotoxicol Environ Saf 2021 Jan 9;208:111436. Epub 2020 Oct 9.

Department of Toxicology, Anhui Medical University, Hefei 230032, China; Laboratory of Environmental Toxicology, Anhui Medical University, Hefei 230032, China. Electronic address:

Several epidemiological studies reported that chronic arsenic exposure increased risk of prostate cancer. This study aimed to investigate whether chronic NaAsO exposure elevates stemness and chemoresistance in prostate cancer cells. DU145 (wild-type p53) and PC-3 (p53-null) cells were exposed to NaAsO (2 μmol/L) for 30 generations. IC50s to docetaxel and cisplatin were increased in NaAsO-exposed DU145 and PC-3 cells. The number of tumor spheres was elevated in NaAsO-exposed DU145 and PC-3 cells. Nanog, SOX-2 and ALDH1A1, three markers of cancer stemness, were upregulated in NaAsO-exposed PC-3 spheres. Moreover, NaAsO-exposed DU145 and PC-3 cells were arrested in G2/M phase. Histone H2AX phosphorylation on Ser139, an indicator for DNA double-strand break, was upregulated in NaAsO-exposed DU145 and PC-3 cells. ATM phosphorylation on Ser1981, a key sensor of genotoxic stress, was rapidly elevated in NaAsO-exposed DU145 cells. Phosphor-p53, a downstream molecule of ATM signaling, and p21, a direct target of p53, were upregulated in NaAsO-exposed DU145 cells. Unexpectedly, p21 was also elevated in NaAsO-exposed p53-null PC-3 cells. Antioxidant NAC alleviated NaAsO-induced ATM phosphorylation, cell cycle arrest, and subsequent stemness enhancement and chemoresistance in both DU145 and PC-3 cells. These results suggest that ROS-mediated genotoxic stress is involved in NaAsO-induced cell cycle arrest, stemness enhancement and chemoresistance of prostate cancer cells in a p53-independent manner.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111436DOI Listing
January 2021

Transcatheter Aortic Valve Implantation With J-Valve: 2-Year Outcomes From a Multicenter Study.

Ann Thorac Surg 2021 05 24;111(5):1530-1536. Epub 2020 Sep 24.

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China. Electronic address:

Background: We report the 2-year follow-up outcomes of the J-Valve in the treatment of either aortic stenosis (AS) or pure aortic insufficiency (AI) from a multicenter study.

Methods: From March 2014 to October 2016, 107 patients with either AS (n = 63) or pure AI (n = 44) were enrolled in a trial and were treated by transcatheter aortic valve implantation with the J-Valve system. All patients except 1 completed a 2-year clinical and echocardiographic follow-up (follow-up rate of 99%). The procedural and clinical outcomes were presented according to Valve Academic Research Consortium-2 criteria.

Results: The success rate of the device was 91.5%. All-cause mortality was 4.7% and 10.3% at 30 days and 2 years, respectively. Echocardiographic follow-up showed mild prosthetic valve regurgitation in 1.0% and 6.8% of patients at 30 days and 2 years, respectively. No patient showed more than mild aortic prosthetic regurgitation. At the 2-year follow-up, 97.6% of patients had mild or less than mild paravalvular leak and 99.8% of patients experienced notable improvement in heart failure symptoms (at least 1 NYHA level reduction). We found no major differences in echocardiographic and clinical follow-up between AS and AI, except for a significantly higher transvalvular gradient in the AS cohort (P = .01).

Conclusions: This study demonstrated good midterm outcomes of transcatheter aortic valve implantation with the J-Valve system in the treatment of patients with either AS or AI. It suggests that the J-Valve system is a promising alternative therapy in high-risk patients.
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http://dx.doi.org/10.1016/j.athoracsur.2020.06.139DOI Listing
May 2021

Mussel-inspired antimicrobial gelatin/chitosan tissue adhesive rapidly activated in situ by HO/ascorbic acid for infected wound closure.

Carbohydr Polym 2020 Nov 25;247:116692. Epub 2020 Jun 25.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, 610041, PR China. Electronic address:

The development of minimally invasive surgery has created a demand for ideal medical adhesives exhibiting biocompatibility, biodegradability, antimicrobial activity, and strong adhesion to tissues in wet environments. However, as clinically approved surgical tissue glues suffer from poor adhesion activation, limited adhesion strength, and toxicity, novel tissue glues are highly sought after. Herein, a mussel-inspired injectable hydrogel was prepared from catechol- and methacrylate-modified chitosan/gelatin and shown to exhibit biocompatibility, inherent antimicrobial activity, and good adhesion to wet tissues. Moreover, as this gel could be applied onto tissue surfaces and cured in situ within seconds of body contact by a biocompatible and multifunctional redox initiator (HO-ascorbic acid), it was concluded to be a promising surgical sealant and wound dressing (even for infected wounds) accelerating wound healing.
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http://dx.doi.org/10.1016/j.carbpol.2020.116692DOI Listing
November 2020

Large Scale, Multicenter, Prospective Study of Apatinib in Advanced Gastric Cancer: A Real-World Study from China.

Cancer Manag Res 2020 6;12:6977-6985. Epub 2020 Aug 6.

Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People's Republic of China.

Background: In China, gastric cancer (GC) ranks second in incidence and mortality. Over 80% of patients with GC were diagnosed at an advanced stage with poor clinical outcome. Chemotherapy was the mainstream treatment with limited benefit. Apatinib, an inhibitor of targeting vascular endothelial growth factor receptor 2 (VEGFR2), has been approved for third-line treatment of advanced gastric cancer. However, the data of apatinib treatment in the real-world setting are limited. In this real-world study, we aimed to understand the current treatment pattern of apatinib, investigate the effectiveness and safety of apatinib in real-world settings, and explore the potential factors associated with the clinical outcomes.

Methods: This was a prospective, multicenter observational study in a real-world setting. Patients aged ≥18 years with histologic diagnosis of advanced GC were eligible for enrollment. The eligible patients received either apatinib monotherapy or apatinib plus chemotherapy by physician's discretion. Apatinib treatment could be used as first-line, second-line, or third-line and above therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), ORR, DCR, and safety profile.

Results: A total of 737 patients with advanced gastric cancer treated with apatinib were included in the FAS population. A total of 54.9% patients used apatinib monotherapy and 45.1% patients used apatinib combination therapy. A total of 44.1% patients received apatinib in first-line treatment, 28.2% in second-line, and 27.7% in third-line and above. In first-line treatment, the objective response rate (ORR) was 9.09% and 16.42% in apatinib monotherapy and combination therapy groups, and disease control rate (DCR) was 78.41% and 89.29%, respectively. Patients who received combination therapy achieved significantly longer median progression-free survival (mPFS; 6.18 vs 3.52 months, <0.01) and median overall survival (mOS; 8.72 vs 5.92 months, <0.01) compared with monotherapy. In second-line and third-line therapy, combination therapy showed a better trend in tumor response and survival outcomes compared with monotherapy. For all patients, apatinib combined with paclitaxel were associated with longer mPFS compared with other combinations (8.88 vs 6.62 months). Multivariate analysis showed that combination with paclitaxel (=0.02) and experience of apatinib-related specific AEs (<0.01) were independent predictors for PFS and OS. The safety profile was tolerable and no unexpected adverse events were reported.

Conclusion: In a real-world setting, apatinib showed a favorable effectiveness and safety profile in patients with advanced gastric cancer. Apatinib combination therapy, especially combined with paclitaxel, might lead to better survival benefit in first-line treatment. Combination with paclitaxel and the occurrence of apatinib-specific AEs were independent factors associated with better survival outcomes.

Trial Registration: NCT03333967.
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http://dx.doi.org/10.2147/CMAR.S249153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418160PMC
August 2020