Publications by authors named "Jinfeng Wu"

102 Publications

The mental health status among nurses from low-risk areas under normalized COVID-19 pandemic prevention and control in China: A cross-sectional study.

Int J Ment Health Nurs 2021 Apr 2. Epub 2021 Apr 2.

Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

This study aimed to investigate the mental health status of nurses from low-risk areas of novel coronavirus (COVID-19) pandemic, its potential impact factors, and the main stressors under the normalized prevention and control in China. A mobile phone app-based survey was conducted among registered nurses in Jiangsu province via a region-stratified sampling method. The questionnaire consisted of items on the demographic characteristics of the nursing staff and their Depression, Anxiety, Stress Scale-21 (DASS-21) along with questions for self-assessment of stressors that are associated with COVID-19. STROBE guideline was used. Among 1803 nurses who were working in the low-risk areas in Jiangsu, 22.0%, 29.8%, and 16.1% of them reported moderate to extreme levels of depression, anxiety, and stress, respectively. Having 11-15 years of working experience and being a fixed-term contract nurse were associated with experiencing worse mental health outcomes while supporting-Wuhan working experience and having mental health preparation course training were independent factors that had beneficial impact on their psychological well-being afterward. In terms of source of pressure, a key finding of this study is that the main stressor among these nurses was the lack of patient's understanding and cooperation (71.2%) which calls for better psychosocial communication between nurses and patients. The present findings would provide information for other regions at low risk of COVID-19 and may aid the provision of support and interventions for the benefit of the psychological well-being of nurses who are exposed to life-threatening occupational risks and are more vulnerable to the pandemic than others.
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http://dx.doi.org/10.1111/inm.12852DOI Listing
April 2021

Comment on: "Laparoscopic treatment (reTAPP) for recurrence after laparoscopic inguinal hernia repair".

Hernia 2021 Mar 25. Epub 2021 Mar 25.

Department of General Surgery, Tongde Hospital of Zhejiang Province, 234 Gucui RD, Hangzhou, 310012, China.

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http://dx.doi.org/10.1007/s10029-021-02386-9DOI Listing
March 2021

Aberrant activation of Wnt/catenin signaling and overexpression of ABCG2 contributes to apoptosis down regulation and tumor progression of high grade ovarian cancer.

Acta Biochim Pol 2021 Feb;68(1):127-133

1Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 2Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 3Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China.

Side Population (SP) cells are the small pool of CSC like progenitor cells, which are drug resistant and recapitulate tumor generation. The occurrence of SP cells is the major inference for attaining a better treatment and improved patient survival. In this work, we have isolated 6% SP cells from a high grade ovarian carcinoma. Our functional characterization of SP cells revealed that elevated ABCG2 and anti-apoptotic factors contribute to chemoresistance and increased life span of SP cells. Further, the overexpression of surface antigens, such as CD133 and CD117 in SP cells, are the key driving forces for high clonogenic and invasion properties of SP cells. More importantly, we found by RT-PCR aberrant activation and upregulation of Wnt/ β-catenin and its downstream targeting genes, such as DKK1 and AXIN2 in SP cells. These findings suggest that development of new anticancer drugs which target Wnt/β-catenin signaling might effectively exterminate the SP cells and aid in disease free survival.
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http://dx.doi.org/10.18388/abp.2020_5488DOI Listing
February 2021

Long-term micro-structure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations.

J Clin Invest 2021 Feb 25. Epub 2021 Feb 25.

Department of Radiology, Tongi Medical College, Huazhong University of Science and Technology, Wuhan, China.

The coronavirus disease 2019 (COVID-19) rapidly progressed to a global pandemic. Although patients totally recover from COVID-19 pneumonia, long-term effects on the brain still need to be explored. Here, two subtypes (mild type-MG and severe type-SG) with no specific neurological manifestations at the acute stage and no obvious lesions on the conventional MRI three months after discharge were recruited. Changes in gray matter morphometry, cerebral blood flow (CBF) and white matter (WM) microstructure were investigated using MRI. The relationship between brain imaging measurements and inflammation markers were further analyzed. Compared with healthy controls, the decrease in cortical thickness/CBF, and the changes in WM microstructure were observed to be more severe in the SG than MG, especially in the frontal and limbic systems. Furthermore, changes in brain microstructure, CBF and tracts parameters were significantly correlated with inflammatory markers. The indirect injury related to inflammatory storm may damage the brain, that led to these interesting observations. There are also other likely potential causes, such as hypoxemia and dysfunction of vascular endothelium, et al. The abnormalities in these brain areas need to be monitored in the process of complete recovery, which could help clinicians to understand the potential neurological sequelae of COVID-19.
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http://dx.doi.org/10.1172/JCI147329DOI Listing
February 2021

Etiology, clinical characteristics and coinfection status of bronchiolitis in Suzhou.

BMC Infect Dis 2021 Feb 1;21(1):135. Epub 2021 Feb 1.

Department of Clinical Laboratory, Children's Hospital of Soochow University, Suzhou, China.

Background: Bronchiolitis is a clinical syndrome commonly encountered in practice, particularly among infants and young children. To investigate the prevalence of pathogens in hospitalized children with bronchiolitis and study the clinical characteristics of bronchiolitis with or without coinfections.

Methods: We investigated the respiratory specimens and clinical data of 1012 children with bronchiolitis who were treated at the Children's Hospital of Soochow University between November 2011 and December 2018. The nasopharyngeal aspirates were examined to detect viruses by direct immunofluorescence assay or polymerase chain reaction (PCR). Mycoplasma pneumoniae (MP) was tested by PCR and enzyme-linked immunosorbent assay.

Results: Of the 1134 children less than 2 years with bronchiolitis, 122 were excluded by exclusion criteria. Causative pathogen was detected in 83.2% (842 of 1012). The majority of these (614 [72.9%] of 842) were single virus infection. The most common pathogens detected were respiratory syncytial virus (RSV) (44.4%), MP (15.6%), and human rhinovirus (HRV) (14.4%). Coinfection was identified in 13.5% (137 of 1012) of the patients. Coinfection included mixed virus infection and virus infection with MP infection. Children with single virus infection had a higher rate of oxygen therapy compared with single MP infection.

Conclusions: The most common pathogen detected in children with bronchiolitis is RSV, followed by MP and HRV. Coinfection leads to a longer period of illness, increased severity of the symptoms and increased risk of hypoxemia.
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http://dx.doi.org/10.1186/s12879-021-05772-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851904PMC
February 2021

Nitrogen and litter addition decreased sexual reproduction and increased clonal propagation in grasslands.

Oecologia 2021 Jan 24;195(1):131-144. Epub 2021 Jan 24.

Key Laboratory of Vegetation Ecology, Ministry of Education, Institute of Grassland Science, Northeast Normal University, Changchun, China.

The trade-offs between sexual reproduction and clonal propagation are of great significance in terms of ecology and evolution for clonal plants, and they vary with environmental change. Nitrogen (N) deposition can increase litter accumulation in grassland and promote litter decomposition and consequently increase nutrient availability. However, the response of plant reproduction to N and litter addition in grasslands remains unclear. We examined the combined effects of N addition and litter manipulation (i.e. initial litter, removal, addition) on sexual reproduction and clonal propagation of a perennial clonal grass, Leymus chinensis, at the population (total number) and individual (number per ramet) levels in an 11-year field experiment. Nitrogen addition and litter additionally decreased spike and seed number at the population level, and N addition reduced those at the individual level. Nitrogen addition and litter interactively affected bud number at the two levels, and N addition decreased bud number in the litter removal treatments and increased that in the litter addition treatments. The increased soil available N, rather than light and soil water content, explained the change in sexual reproduction and clonal propagation. The positive effects of litter addition on bud number in the treatments with N addition, suggested that the N deposition increased litter accumulation could intensify clonal propagation of perennial grasses and increase their dominance in grasslands. Grassland management that reduces litter accumulation, such as grazing and mowing, can therefore, help alleviate the negative effects of N deposition on plant diversity through decreasing clonal propagation of the dominant species.
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http://dx.doi.org/10.1007/s00442-020-04812-8DOI Listing
January 2021

Prediction of risk factors of bronchial mucus plugs in children with Mycoplasma pneumoniae pneumonia.

BMC Infect Dis 2021 Jan 13;21(1):67. Epub 2021 Jan 13.

Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou, 215003, China.

Background: Recently, many cases of pneumonia in children with Mycoplasma pneumoniae infection have been shown to have varying degrees of intrabronchial mucus plug formation. The clinical, laboratory, radiological characteristics, and treatment of patients with Mycoplasma infection are analyzed in this study. The risk factors for M. pneumoniae pneumonia (MPP) mucus plug formation in children are explored, and a risk factor scoring system is established.

Methods: MPP patients treated with bronchoscopy were retrospectively enrolled in the study from February 2015 to December 2019. The children were divided into a mucus plug group and a control group according to the presence or absence of mucus plug formation. The clinical, laboratory, radiological characteristics, and treatment of the two groups of children were compared. Univariate and multivariate logistic regression models were used to identify the risk factors for MPP mucus plug formation. The receiver operating characteristic (ROC) curve was drawn to evaluate the regression model and establish the MPP mucous plug risk factor scoring system.

Results: A univariate analysis showed that the children in the mucous group were older and had a longer fever duration, longer hospital stay, higher fever peak, more cases of wheezing symptoms and allergies, and azithromycin or corticosteroids were administered later. In addition, neutrophil, C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (DD), sputum MP-DNA copy number, and total immunoglobulin A (IgA) levels were higher, while prealbumin (PA) levels were lower. The ROC curve analysis showed that children with MPP had PA ≤144.5 mg/L, had used corticosteroids during the course of the illness of ≥4.5 days, CRP ≥12.27 mg/L, an LDH ≥ 462.65 U/L, and there was a possibility of intra-airway mucus formation. The independent risk factors were scored according to their odds ratio (OR) value. Among the 255 children with MPP, the high-risk group had 44 (83.02%) mucus plugs out of 53; the middle-risk group had 35 (34.3%) mucus plugs out of 102; and the low-risk group had 11 (11%) mucus plugs out of 100.

Conclusions: PA levels, timing of corticosteroid use (use in the first few days), CRP levels, and LDH levels were independent risk factors for MPP mucus plug formation. This provides a basis for the early identification of MPP in children combined with mucus plug formation.
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http://dx.doi.org/10.1186/s12879-021-05765-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805118PMC
January 2021

Laser ultrasonic imaging for defect detection on metal additive manufacturing components with rough surfaces.

Appl Opt 2020 Nov;59(33):10380-10388

Defects or discontinuities are inevitable during the melting and consolidation process of metal additive manufacturing. Online inspection of microdefects during the processing of layer-by-layer fusion is urgently needed for quality control. In this study, the laser ultrasonic C-scan imaging system is established to detect the surface defects of selective laser melting (SLM) samples that have a different surface roughness. An autosizing method based on the maximum correlation coefficient and lag time is proposed to accurately measure the defect length. The influences of the surface roughness on the laser ultrasound signal-to-noise ratio distribution and defect sizing accuracy are also studied. The results indicate that the proposed system can detect notches with a depth of 50 µm and holes with a diameter of 50 µm, comparable in size to raw powder particles. The average error for the length measurement can reach 1.5% if the notch is larger than 2 mm. Meanwhile, the sizing error of a 1 mm length notch is about 9%. In addition, there is no need to remove the rough surface of the as-built SLM samples during the detection process. Hence, we propose that the laser ultrasonic imaging system is a potential method for online inspection of metal additive manufacturing.
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http://dx.doi.org/10.1364/AO.405284DOI Listing
November 2020

Over expression of PTEN induces apoptosis and prevents cell proliferation in breast cancer cells.

Acta Biochim Pol 2020 Dec;67(4):515-519

1Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 2Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 3Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China.

The phosphatase and tensin homolog (PTEN) is a tumor suppressor lipid phosphatase frequently mutated or deleted in breast cancer cells. Loss of PTEN is associated with aberrant activation of P13K/AKT signaling pathways, which are responsible for uncontrolled cell cycle, migration and prolonged survival. Therefore, stability and functional PTEN is essential for prevention of cancer growth and migration. In the present study, we have determined the effect of PTEN over expression in apoptosis induction and cell proliferation in breast cancer cells. We showed that PTEN over expression significantly declined the cell proliferation rate during logarithmic growth phase. Furthermore, the PTEN over expression leads to the activation of mitochondrial based intrinsic apoptosis pathways, which is confirmed by the activation and over expression of caspases 9 and caspases 3. In addition, the number of apoptotic cells are significantly more in PTEN over expressed cells, where they showed more apoptotic bodies in AO-EtBr and Hoechst 33344 staining. Finally, PTEN over expressed cells showed decreased chemo resistance as chemotherapeutic drugs kill them efficiently. Therefore, our findings suggest that tumor suppressive effect of PTEN is crucial for cancer prevention and thus PTEN might be a potential target for anti-cancer drugs.
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http://dx.doi.org/10.18388/abp.2020_5371DOI Listing
December 2020

Histone Demethylases Coordinate the Antagonistic Interaction Between Abscisic Acid and Brassinosteroid Signaling in .

Front Plant Sci 2020 25;11:596835. Epub 2020 Nov 25.

Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Japan.

Abscisic acid (ABA) interacts antagonistically with brassinosteroids (BRs) to control plant growth and development in response to stress. The response to environmental cues includes hormonal control via epigenetic regulation of gene expression. However, the details of the ABA-BR crosstalk remain largely unknown. Here, we show that JUMONJI-C domain containing histone demethylases (JMJs) coordinate the antagonistic interaction between ABA and BR signaling pathways during the post-germination stage in . BR blocks ABA-mediated seedling arrest through repression of . JMJs remove the repressive histone marks from the () locus for its activation to balance ABA and BR signaling pathways. JMJs and BZR1 co-regulate genes encoding three membrane proteins, a regulator of vacuole morphology, and two lipid-transfer proteins, each of which play a different role in transport. BZR1 also regulates stimuli-related target genes in a JMJ-independent pathway. Our findings suggest that the histone demethylases integrate ABA and BR signals, leading to changes in growth program after germination.
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http://dx.doi.org/10.3389/fpls.2020.596835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724051PMC
November 2020

Icaritin Inhibits Skin Fibrosis through Regulating AMPK and Wnt/β-catenin Signaling.

Cell Biochem Biophys 2020 Oct 30. Epub 2020 Oct 30.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Skin fibrosis is one of the major features of scleroderma. WNT/β-catenin signaling is associated with the progression of skin fibrosis. In this study, we aimed to determine the effect of icaritin (IT), a natural compound, on scleroderma-related skin fibrosis and its mechanisms. We found that IT could reduce the expression of COL1A1, COL1A2, COL3A1, CTGF, and α-SMA in human foreskin fibroblasts (HFF-1 cells), scleroderma skin fibroblasts (SSF cells), and TGF-β-induced HFF-1 cells. Wnt/β-catenin signaling was shown to be suppressed by IT. Additionally, IT activated AMPK signaling in HFF-1 cells. In conclusion, IT has an anti-skin fibrotic effect through activation of AMPK signaling and inhibition of WNT/β-catenin signaling. Our findings indicate the potential role of IT in the treatment of scleroderma and provide novel insight for the selection of drug therapy for scleroderma.
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http://dx.doi.org/10.1007/s12013-020-00952-zDOI Listing
October 2020

The emerging role of co-stimulatory molecules and their agonistic mAb-based combination therapies in melanoma.

Int Immunopharmacol 2020 Dec 19;89(Pt B):107097. Epub 2020 Oct 19.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, PR China. Electronic address:

Although anti-PD-1/L1 and anti-CTLA-4 antibodies, the validated immune checkpoint blockades, can elicit durable long-lasting antitumor immunity and improve the clinical outcomes of melanoma treatment, there are still a fraction of patients who did not receive therapeutic benefits as expected. In addition to findings of blocking the co-inhibitory pathways, the preclinical and clinical evidence suggests that triggering the co-stimulatory pathways through agonists such as CD137, OX40, CD40, GITR and CD27 may be a rational next step for melanoma therapy. In this review, we discuss the progress of studies on these co-stimulatory molecules in terms of their promising therapeutic effects and underlying antitumor mechanisms, and provide a review of the possible combinations that orchestrate the interplay of co-stimulatory agonistic mAbs and other therapies for treating melanoma, including inhibitory immune checkpoint mAbs, adoptive T cell therapy, chemotherapy and radiotherapy. We also briefly present the limitations and challenges involved in these co-stimulatory agonistic mAb-based combination strategies for melanoma patients.
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http://dx.doi.org/10.1016/j.intimp.2020.107097DOI Listing
December 2020

Comparative effectiveness of different consolidation chemotherapy regimens for pediatric acute lymphoblastic leukemia: A protocol for systematic review and network meta analysis.

Medicine (Baltimore) 2020 Sep;99(38):e22208

Shunde Hospital of Guangzhou University of Chinese Medicine, Foshan, China.

Background: Acute lymphoblastic leukemia (ALL) is one of the most commonly seen cancers in children, which mainly relates with inherited genetic variations. Consolidation chemotherapy is usually given to the pediatric ALL patients, however there is no meta-analysis and network analysis conducting the efficacy of the chemotherapy. Therefore, we perform a protocol to assess the efficacy of chemotherapeutics for pediatric ALL.

Methods: A literature search for randomized controlled trials about some specific chemotherapy regimens for pediatric ALL will be carried out in 7 electronic databases from their establishment to June 2019: the Cochrane Library, Embase, MEDLINE, the Chinese National Knowledge Infrastructure (CNKI), the Sino Med, the Chinese Scientific Journal Database (VIP) and the Wanfang Database. Complete continuous remission will be measured as primary outcome. Stata 14.0 will be utilized to perform a standard pairwise meta-analysis and the NMA, as well as draw Network Plots of Network Meta.

Results: This network meta-analysis will evaluate the efficacy of different consolidation chemotherapy regimens.

Conclusion: This study will furnish decision-making reference on optimum proposal of chemotherapy regimens for pediatric ALL.

Prospero Registration Number: PROSPERO CRD42019134518.
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http://dx.doi.org/10.1097/MD.0000000000022208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505343PMC
September 2020

Reliability map of individual differences reflected in inter-subject correlation in naturalistic imaging.

Neuroimage 2020 12 18;223:117277. Epub 2020 Aug 18.

Laboratory of Psychological Heath and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Psychological and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Understanding individual differences in brain function is an essential aim of neuroscience. Naturalistic imaging links neural activity to real-life contexts and reflects individual differences in brain response. These unique features make it a promising tool for individualized psychiatry. An essential prerequisite for the extensive use of this paradigm is the reliable representation of inter-individual relationships. We used a test-retest approach to examine whether the naturalistic paradigm reliably represents inter-individual differences, which brain regions have the superior capability, and whether the ability alters with the contents of the stimuli. We quantified the reliability of the inter-subject relationships in repeated scans of two movie clips: a natural sight view and an emotion-evoking story. Besides statistical inference, we included resting-state scans, behavioral tests, and questionnaires as references for the comparison. The results showed that over one-third area of the brain could reliably characterize the inter-individual relationship, and the superior temporal lobe demonstrated comparable reliability representation with the State and Trait Anxiety Inventory. Furthermore, the temporal lobe regions could retain this capability across emotional movies with different contents. This study provides a base for pushing the naturalistic imaging paradigm towards clinical applications and proposes reliable target brain regions for future studies.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117277DOI Listing
December 2020

Scrotoscopy and traditional open surgery shows a high degree of consistency in the diagnosis of testicular torsion: An initial report.

Medicine (Baltimore) 2020 Jul;99(31):e21545

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

Traditional open surgery (OS) is usually necessary when testicular torsion (TT) cannot be excluded by scrotal ultrasound. Scrotoscopy has been used as a minimally invasive technique to diagnose or treat scrotal diseases, and it may also play a role in diagnosing TT.A retrospective analysis was performed for patients with TT to evaluate the consistency of scrotoscopy and OS in the diagnosis of TT. In the cases where preoperational Color Doppler ultrasonography was performed, scrotoscopy, open surgery, and confirmed TT were included for future analysis.A total of 43 patients were studied. Twisted testes were retained in 11 cases (25.59%), and the remaining 32 patients (74.41%) underwent orchiectomy. There were significant differences in the diagnostic value between the grading of scrotoscopy and ultrasound, as well as between ultrasound grading and blood supply grading (BSG) (both P < .05). However, no significant difference was observed between the grading of scrotoscopy and BSG in traditional OS (P > .05), but a high degree of consistency existed between scrotoscopy grading and BSG in traditional OS (Kappa = 0.733, P ≤ .001).Our limited data indicate that the diagnosis of testicular torsion by scrotoscopy is highly consistent with that of traditional surgical exploration. Therefore, further studies are necessary to confirm its application value in the future. Scrotoscopy may have potential application value for the patients whom testicular torsion are insufficiently diagnosed but cannot be excluded.
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http://dx.doi.org/10.1097/MD.0000000000021545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402747PMC
July 2020

Bu-Shen-Fang-Chuan formula attenuates cigarette smoke-induced inflammation by modulating the PI3K/Akt-Nrf2 and NF-κB signalling pathways.

J Ethnopharmacol 2020 Oct 10;261:113095. Epub 2020 Jun 10.

Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China. Electronic address:

Ethnopharmacological Relevance: Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Unlike asthma, COPD is insensitive to glucocorticoid treatment; thus, it is of great importance to find alternative medications, including Chinese medicine, to suppress inflammation. Bu-Shen-Fang-Chuan formula (BSFCF) is commonly used for the treatment of COPD in China. However, the mechanisms of BSFCF in COPD treatment are still unclear.

Aim Of The Study: To verify the anti-inflammatory efficacy of BSFCF in COPD and to explore the possible mechanisms underlying its anti-inflammatory efficacy based on the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)-Nuclear factor erythroid 2-related factor 2 (Nrf2) and Nuclear factor (NF)-κB signalling pathways.

Materials And Methods: A rat model of COPD was established by chronic exposure to cigarette smoke (CS) for 6 months. Bronchoalveolar lavage fluid (BALF) and blood were obtained to detect inflammatory cytokines. Lung samples were harvested, and part of each sample was fixed for subsequent H&E staining and immunohistochemical (IHC) analysis. The remaining lung tissues were used for RNA sequencing analysis and western blotting.

Results: BSFCF significantly reduced inflammatory infiltration in the lungs of CS-exposed rats and decreased the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in both the BALF and serum. Additionally, BSFCF evidently attenuated NF-κB activation and downregulation of glucocorticoid receptor (GR) caused by CS. Furthermore, BSFCF increased the activation of PI3K/Akt-Nrf2 signalling in response to CS.

Conclusions: BSFCF attenuated CS-induced inflammation in COPD, which was partially achieved through the PI3K/Akt-Nrf2 and NF-κB signalling pathways.
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http://dx.doi.org/10.1016/j.jep.2020.113095DOI Listing
October 2020

Juglone potentiates BRAF inhibitor‑induced apoptosis in melanoma through reactive oxygen species and the p38‑p53 pathway.

Mol Med Rep 2020 Jul 28;22(1):566-574. Epub 2020 Apr 28.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.

BRAF inhibitors are some of the most effective drugs against melanoma; however, their clinical application is largely limited by drug resistance. Juglone, isolated from walnut trees, has demonstrated anti‑tumour activity. In the present study, it was investigated whether juglone could enhance the responses to a BRAF inhibitor in melanoma cells (A375R and SK‑MEL‑5R) with an acquired resistance. These cells were treated with juglone alone, BRAF inhibitor (PLX4032) alone, or juglone combined with PLX4032. It was demonstrated that the combination of juglone and PLX4032 had synergistic effects on BRAF inhibitor‑resistant melanoma cells. Juglone potentiated PLX4032‑induced cytotoxicity and mitochondrial apoptosis in both A375R and SK‑MEL‑5R cells, which was accompanied by a decline in mitochondrial membrane potential and a decrease in Bcl‑2/Bax ratio. Moreover, juglone combined with PLX4032 markedly increased the intracellular level of reactive oxygen species (ROS) and activated p38 and p53, as compared with juglone alone or PLX4032 alone. Pre‑treatment with N‑acetyl‑L‑cysteine, a ROS scavenger, completely reversed the cytotoxicity induced by juglone combined with PLX4032. In conclusion, juglone potentiated BRAF inhibitor‑induced apoptosis in resistant melanoma cells, and these effects occurred partially through ROS and the p38‑p53 pathway, suggesting the potential of juglone as a sensitizer to BRAF inhibitors in the treatment of melanoma.
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http://dx.doi.org/10.3892/mmr.2020.11095DOI Listing
July 2020

Upregulation of cell surface GD3 ganglioside phenotype is associated with human melanoma brain metastasis.

Mol Oncol 2020 08 5;14(8):1760-1778. Epub 2020 Jun 5.

Department of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI), Santa Monica, CA, USA.

Melanoma metastasis to the brain is one of the most frequent extracranial brain tumors. Cell surface gangliosides are elevated in melanoma metastasis; however, the metabolic regulatory mechanisms that govern these specific changes are poorly understood in melanoma particularly brain metastases (MBM) development. We found ganglioside GD3 levels significantly upregulated in MBM compared to lymph node metastasis (LNM) but not for other melanoma gangliosides. Moreover, we demonstrated an upregulation of ST8SIA1 (GD3 synthase) as melanoma progresses from melanocytes to MBM cells. Using RNA-ISH on FFPE specimens, we evaluated ST8SIA1 expression in primary melanomas (PRM) (n = 23), LNM and visceral metastasis (n = 45), and MBM (n = 39). ST8SIA1 was significantly enhanced in MBM compared to all other specimens. ST8SIA1 expression was assessed in clinically well-annotated melanoma patients from multicenters with AJCC stage III B-D LNM (n = 58) with 14-year follow-up. High ST8SIA1 expression was significantly associated with poor overall survival (HR = 3.24; 95% CI, 1.19-8.86, P = 0.02). In a nude mouse human xenograft melanoma brain metastasis model, MBM variants had higher ST8SIA1 expression than their respective cutaneous melanoma variants. Elevated ST8SIA1 expression enhances levels of cell surface GD3, a phenotype that favors MBM development, hence associated with very poor prognosis. Functional assays demonstrated that ST8SIA1 overexpression enhanced cell proliferation and colony formation, whereby ST8SIA1 knockdown had opposite effects. Icaritin a plant-derived phytoestrogen treatment significantly inhibited cell growth in high GD3-positive MBM cells through targeting the canonical NFκB pathway. The study demonstrates GD3 phenotype associates with melanoma progression and poor outcome.
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http://dx.doi.org/10.1002/1878-0261.12702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400791PMC
August 2020

Icariside II overcomes BRAF inhibitor resistance in melanoma by inducing ROS production and inhibiting MITF.

Oncol Rep 2020 Jul 15;44(1):360-370. Epub 2020 Apr 15.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.

Metastatic melanoma is the most aggressive skin cancer. Although BRAF inhibitor treatment has achieved great success in melanoma, resistance develops within 12 months. Icariside II (IS), a natural compound extracted from Herba Epimedii, exerts anticancer properties. In the present study, we determined by MTT, flow cytometry and western blotting, respectively that IS potentiated the PLX4032‑induced downregulation of cell viability and increase in apoptosis and autophagy in BRAF inhibitor‑resistant melanoma. In addition, we also revealed by flow cytometry and western blotting, respectively, that IS combined with PLX4032 increased mitochondrial and intracellular reactive oxygen species (ROS) generation and subsequently promoted depolarization of mitochondria and release of apoptotic proteins. N‑acetyl cysteine (NAC) and glutathione (GSH), ROS scavengers, reversed the IS‑induced enhancement of the response to PLX4032. Microphthalmia‑associated transcription factor (MITF) and tyrosine‑protein kinase Met (c‑Met) are well‑known factors that contribute to BRAF inhibitor resistance. Furthermore, c‑Met is a direct transcriptional target of MITF in melanocytes and melanoma cells. It was also revealed that IS markedly inhibited MITF and c‑Met expression partially by increasing ROS production in BRAF inhibitor‑resistant melanoma cells.
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http://dx.doi.org/10.3892/or.2020.7582DOI Listing
July 2020

Decreased expression of microRNA-510 in intestinal tissue contributes to post-infectious irritable bowel syndrome via targeting PRDX1.

Am J Transl Res 2019 15;11(12):7385-7397. Epub 2019 Dec 15.

School of Nursing, Yangzhou University Yangzhou, China.

Objective: Post-infectious irritable bowel syndrome (PI-IBS) is a common functional gastrointestinal (GI) disorder that occurs after acute GI infection. Recent studies showed that microRNAs were involved in the occurrence and development of IBS. Here, we elaborated the role of miR-510 in the occurrence of PI-IBS and analyzed its mechanism.

Methods: We detected the expressions of miR-510 and PRDX1 in colonic mucosal tissues by qRT-PCR, Western blot and immunohistochemistry. Furthermore, we transfected Caco-2 cells with miR-510 mimic, anti-miR-510, si-PRDX1, and control, then evaluated the cell viability and apoptosis by CCK8 assay and flow cytometry, assessed expression levels of PRDX1 by qRT-PCR and Western blot analysis, and pro-inflammatory cytokines by qRT-PCR and ELISA.

Results: MiR-510 expression was downregulated and negatively correlated with TNF-α, whereas PRDX1 expression was upregulated in PI-IBS colonic mucosal tissues. LPS at concentrations of 5 and 10 μg/ml can significantly induce inflammatory injury in Caco-2 cells. MiR-510 overexpression aggravated the injury induced by LPS, as reflected by increased cell viability, decreased apoptosis, and less production of pro-inflammatory cytokines. miR-510 mimic transfection in cells significantly suppressed the mRNA and protein expression levels of PRDX1. Furthermore, the inflammatory injury induced by LPS was exacerbated by upregulating PRDX1 expression when miR-510 was knocked down.

Conclusion: MiR-510 downregulation in intestinal tissue might contribute to PI-IBS via targeting PRDX1. The results of this study will not only enrich the pathogenesis of PI-IBS but also make us understand the biological activity of miR-510 and provide important experimental basis for PI-IBS clinical treatment targeting miR-510.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943457PMC
December 2019

Bu-Shen-Fang-Chuan formula attenuates T-lymphocytes recruitment in the lung of rats with COPD through suppressing CXCL9/CXCL10/CXCL11-CXCR3 axis.

Biomed Pharmacother 2020 Mar 18;123:109735. Epub 2019 Dec 18.

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China. Electronic address:

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by irreversible airflow limitation. The current medications show limited effects on the decline of pulmonary function in COPD. Our multicenter clinical trial found that Bu-Shen-Fang-Chuan fomula (BSFCF), a Chinese herbal formula, markedly reduced the frequencies of acute exacerbation of COPD and delayed lung function decline. However, the underlying mechanisms are still unclear. In this study, we established a COPD rat model through a 6-month exposure to cigarette smoke (CS) and found that BSFCF (7.2 g/kg) effectively improved CS-induced reduction in pulmonary function and remarkably decreased the numbers of inflammatory cells in bronchoalveolar lavage fluid (BALF). Importantly, BSFCF treatment notably prevented the accumulation of T-lymphocytes (especially CD8 T-cells) in the lung of COPD rats. RNA sequencing analysis of lung tissue demonstrated that CXCL9/CXCL10/CXCL11-CXCR3 chemokine axis in the lung of CS-exposed rats was significantly suppressed by BSFCF. Moreover, our Real-time PCR data verified that BSFCF evidently inhibited the mRNA expressions of CXCL9, CXCL10, CXCL11 and CXCR3. Conclusively, BSFCF markedly improved pulmonary function and attenuated CD8 T-cells recruitment in the lung of CS-exposed rats, which were partially through inhibition of CXCL9/CXCL10/CXCL11-CXCR3 axis.
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http://dx.doi.org/10.1016/j.biopha.2019.109735DOI Listing
March 2020

Curcumin inhibits cigarette smoke-induced inflammation via modulating the PPARγ-NF-κB signaling pathway.

Food Funct 2019 Dec;10(12):7983-7994

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.

Peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated nuclear hormone receptor, is considered to be a potential target for the anti-inflammatory treatment of COPD, and its anti-inflammatory efficacy is likely related to the inhibition of transcriptional regulation of nuclear factor (NF)-κB. Curcumin, a dietary polyphenol isolated from the rhizome of turmeric, has been found to have therapeutic benefits in chronic obstructive pulmonary disease (COPD) via inhibiting NF-κB. However, whether the anti-inflammatory efficacy of curcumin in COPD is associated with PPARγ has scarcely been investigated before. The purpose of this study was to validate the relationship between PPARγ and NF-κB in cigarette smoke (CS)-induced COPD models, and then to investigate whether the therapeutic effect of curcumin on COPD is achieved through modulating the PPARγ-NF-κB signaling pathway. Our experiments in vitro illustrated that PPARγ might be upstream of NF-κB in cigarette smoke extract (CSE)-treated Beas-2B cells, and that curcumin could significantly ameliorate CSE-induced cell viability reduction and inflammation though up-regulating PPARγ and inhibiting NF-κB activation. Importantly, we found that the inhibitory effect on NF-κB by curcumin was dependent on PPARγ in T0070907-treated or PPARγ shRNA-transfected Beas-2B cells, indicating that curcumin inhibited CSE-induced inflammation partially through modulating the PPARγ-NF-κB pathway. Furthermore, we also observed that the effect of curcumin on PPARγ protein expression and NF-κB activation in CS-exposed rats was consistent with the results from experiments in vitro, and curcumin effectively attenuated pulmonary function decline and inflammatory responses in CS-exposed rats. In conclusion, all the results revealed that curcumin attenuated CS-induced inflammation both in vivo and in vitro, presumably by modulating the PPARγ-NF-κB pathway.
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http://dx.doi.org/10.1039/c9fo02159kDOI Listing
December 2019

E2F1/IGF-1R Loop Contributes to BRAF Inhibitor Resistance in Melanoma.

J Invest Dermatol 2020 06 6;140(6):1295-1299.e1. Epub 2019 Nov 6.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2019.09.025DOI Listing
June 2020

Scrotoscopy exploration of testicular rupture: A pilot study.

Medicine (Baltimore) 2019 Oct;98(41):e17389

Shengli Clinical Medical College of Fujian Medical University.

To examine whether scrotoscopy could be used to diagnose testicular rupture (TR) with accuracy.This retrospective study included all patients receiving scrotoscopy followed by immediate open exploration (OE) for suspected TR at two Chinese tertiary care centers between March 2014 and March 2018.Fifteen patients suspected of having TR were included. TR was considered in 8 patients (8/15) via emergency scrotal ultrasound (ESU) examination. Of these 8 patients, 6 cases as well as 3 other cases, a total of 9 cases (9/15) were confirmed TR by scrotoscopy and OE; the remaining 6 patients (6/15) were found disease free. The presence/absence of TR was identified correctly with scrotoscopy in all 15 cases. The rupture size of the testicular tunica albuginea (TTA) varied from 0.5 to 2 cm. Only 3 cases (3/15) had scrotal wall edema and all quickly recovered. The testis was normal in size and blood flow at 6-month follow-up visit.Scrotoscopy accurately diagnoses TR, and may avoid unnecessary OE, especially for the patients confirmed free of disease.
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http://dx.doi.org/10.1097/MD.0000000000017389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799513PMC
October 2019

Individualized psychiatric imaging based on inter-subject neural synchronization in movie watching.

Neuroimage 2020 08 27;216:116227. Epub 2019 Sep 27.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Psychological and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China; Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

The individual heterogeneity is a challenge to the prosperous promises of cutting-edge neuroimaging techniques for better diagnosis and early detection of psychiatric disorders. Individuals with similar clinical manifestations may result from very different pathophysiology. Conventional approaches based on comparing group-averages provide insufficient information to support the individualized diagnosis. Here we present an individualized imaging methodology that combines naturalistic imaging and the normative model. This paradigm adopts video clips with rich cognitive, social, and emotional contents to evoke synchronized brain dynamics of healthy participants and builds a spatiotemporal response norm. By comparing individual brain responses with the response norm, we could recognize patients using machine learning techniques. We applied this methodology to recognize first-episode drug-naïve schizophrenia patients in a dataset containing 72 patients and 54 healthy controls. Some segments of the video evoked more synchronized brain activity in the healthy controls than in the schizophrenia patients. We built a spatiotemporal response norm by averaging the brain responses of the healthy controls in a training set, and trained a classifier to recognize patients based on the differences between individual brain responses and the norm. The performance of the classifier was then evaluated using an independent test set. The mean accuracies from a 5-fold cross-validation were 0.71-0.78 depending on the parameters such as the number of features and the width of the sliding windows. These findings reflected the potential of this methodology towards a clinical tool for individualized diagnosis.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116227DOI Listing
August 2020

Segregated precuneus network and default mode network in naturalistic imaging.

Brain Struct Funct 2019 Dec 12;224(9):3133-3144. Epub 2019 Sep 12.

Key Laboratory of Behavioral Sciences, Research Center for Lifespan Development of Mind and Brain, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

A resting-state network centered at the precuneus has been recently proposed as a precuneus network (PCUN) or "parietal memory network". Due to its spatial adjacency and overlapping with the default mode network (DMN), it is still not consensus to consider PCUN and DMN separately. Whether considering PCUN and DMN as different networks is a critical question that influences our understanding of brain functions and impairments. Previous resting-state studies using multiple methodologies have demonstrated a robust separation of the two networks. However, since there is no gold standard in justifying the functional difference between the networks in resting-state, we still lack of biological evidence to directly support the separation of the two networks. This study compared the responses and functional couplings of PCUN and DMN when participants were watching a movie and examined how the continuity of the movie context modulated the response of the networks. We identified PCUN and DMN in resting-state fMRI of 48 healthy subjects. The networks' response to a context-rich video and its context-shuffled version was characterized using the variance of temporal fluctuations and functional connectivity metrics. The results showed that (1) scrambling the contextual information altered the fluctuation level of DMN and PCUN in reversed ways; (2) compared to DMN, the FC within PCUN showed significantly higher sensitivity to the contextual continuity; (3) PCUN exhibited a significantly stronger functional network connectivity with the primary visual regions than DMN. These findings provide evidence for the distinct functional roles of PCUN and DMN in processing context-rich information and call for separately considering the functions and impairments of these networks in resting-state studies.
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http://dx.doi.org/10.1007/s00429-019-01953-2DOI Listing
December 2019

Agent-based simulations of China inbound tourism network.

Sci Rep 2019 08 23;9(1):12325. Epub 2019 Aug 23.

Department of Recreation, Park, and Tourism Management, School of Health and Human Development, Pennsylvania State University, University Park, Pennsylvania, 16802, USA.

Based on the results of a large-scale survey, we construct an agent-based network model for the China independent inbound tourism system and, by the approach of numerical simulation, investigate the responses of the tourist behaviors to perturbations in different scenarios, including the closure of a tourism city, the opening of a new port city in western China, and the increase of the tourism attractiveness of a specific city. Numerical results show that: (1) the closure of a single city in general will affect the tourist visitations of many other cities and, comparing to the non-port cities, the overall visitation volume of the system is more influenced by closing a port city; (2) the opening of a new port city in western China will attract more tourists to the western cities, but has a negligible impact on either the overall visitation volume or the imbalanced tourist distribution; and (3) the increase of the tourism attractiveness of a non-port (port) city normally increases (decreases) the overall visitation volume, yet there are exceptions due to the spillover effect. Furthermore, by increasing the tourism attractiveness of a few cities simultaneously, we investigate also the strategy of multiple-city-upgrade in tourism development. We find that the overall tourist volume is better improved by upgrading important non-port cities that are geographically distant from each other. The study reveals the rich dynamic inherent in complex tourism network, and the findings could be helpful to the development and management of China inbound tourism.
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http://dx.doi.org/10.1038/s41598-019-48668-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707315PMC
August 2019

The Maize Clade A PP2C Phosphatases Play Critical Roles in Multiple Abiotic Stress Responses.

Int J Mol Sci 2019 Jul 22;20(14). Epub 2019 Jul 22.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China.

As the core components of abscisic acid (ABA) signal pathway, Clade A PP2C (PP2C-A) phosphatases in ABA-dependent stress responses have been well studied in . However, the roles and natural variations of maize PP2C-A in stress responses remain largely unknown. In this study, we investigated the expression patterns of treated with multiple stresses and generated transgenic plants overexpressing most of the genes. The results showed that the expression of most were dramatically induced by multiple stresses (drought, salt, and ABA), indicating that these genes may have important roles in response to these stresses. Compared with wild-type plants, , , and overexpression plants had higher germination rates after ABA and NaCl treatments. and negatively regulated drought responses as the plants overexpressing these genes had lower survival rates, higher leaf water loss rates, and lower proline accumulation compared to wild type plants. The natural variations of associated with drought tolerance were also analyzed and favorable alleles were detected. We widely studied the roles of genes in stress responses and the natural variations detected in these genes have the potential to be used as molecular markers in genetic improvement of maize drought tolerance.
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http://dx.doi.org/10.3390/ijms20143573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679055PMC
July 2019

Functional Connectivity Between Sensory-Motor Subnetworks Reflects the Duration of Untreated Psychosis and Predicts Treatment Outcome of First-Episode Drug-Naïve Schizophrenia.

Biol Psychiatry Cogn Neurosci Neuroimaging 2019 08 15;4(8):697-705. Epub 2019 Apr 15.

Laboratory of Psychological Health and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China; Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Background: Somatic symptoms and motor abnormalities have been consistently reported as typical symptoms of schizophrenia, but evidence linking impaired functional connectivity among the primary sensory-motor network and its associations to schizophrenia is largely lacking. The present study aims to examine abnormal functional connectivity in the sensory-motor network in schizophrenia and its associations with the duration of untreated psychosis and medication treatment effects. We hypothesize that patients with schizophrenia suffer from disrupted functional connectivity between the sensory-motor subnetworks. The degree of impairment in the connectivity could reflect the duration of untreated psychosis and predict outcomes of medication treatment.

Methods: At baseline, resting-state functional magnetic resonance imaging data were acquired from 60 first-episode patients with drug-naïve schizophrenia (36 were female) and 60 matching normal control subjects (31 were female). After 2 months, 23 patients who received medication treatment and 32 normal control subjects were rescanned. Functional connectivity among subnetworks in the sensory-motor system was compared between the groups and correlated with the duration of untreated psychosis and the treatment outcome.

Results: Patients with schizophrenia showed significantly disrupted functional connectivity in the sensory-motor network. The degree of impairment reflected the duration of untreated psychosis and motor-related symptoms. It further predicted the improvement of positive scores after medication.

Conclusions: These findings suggest that functional connectivity in the sensory-motor network could indicate the severity of neural impairment in schizophrenia, and it deserves more attention in the search for neuroimaging markers for evaluating neural impairment and prognosis.
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http://dx.doi.org/10.1016/j.bpsc.2019.04.002DOI Listing
August 2019