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1.
Int J Cancer ; 146(1): 169-180, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31090062

RESUMO

Our previous study demonstrated that heterogeneous nuclear ribonucleoprotein AB (HNRNPAB) is a key gene that facilitates metastasis of hepatocellular carcinoma (HCC). However, the molecular mechanisms behind this relationship are not fully understood. In our study, we utilized long-noncoding RNA (lncRNA) microarrays to identify a HNRNPAB-regulated lncRNA named lnc-ELF209. Our findings from chromatin immunoprecipitation assays indicate that HNRNPAB represses lnc-ELF209 transcription by directly binding to its promoter region. We also analyzed clinical samples from HCC patients and cell lines with quantitative real-time polymerase chain reactions, RNA in situ hybridization and immunohistochemistry, and found that there is a negative relationship between HNRNPAB and lnc-ELF209 expression. Up/downregulation assays and rescue assays indicate that lnc-ELF209 inhibits cell migration, invasion and epithelial-mesenchymal transition regulated by HNRNPAB. This suggests a new regulatory mechanism for HNRNPAB-promoted HCC progression. RNA pull-down and LC-MS/MS were used to determine triosephosphate isomerase, heat shock protein 90-beta and vimentin may be involved in the tumor-suppressed function of lnc-ELF209. Furthermore, we found lnc-ELF209 could stabilize TPI protein expression. We also found that lnc-ELF209 overexpression in HCCLM3 cell resulted in a lower rate of lung metastatic, which suggested a less aggressive HCC phenotype. Collectively, these findings offer new insights into the regulatory mechanisms that underlie HNRNPAB cancer-promoting activities and demonstrate that lnc-ELF209 is a HNRNPAB-regulated lncRNA that may play an important role in the inhibition of HCC progression.

2.
J Cell Biochem ; 121(1): 443-457, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31231887

RESUMO

Accumulating findings reveal that long noncoding RNAs (lncRNAs) as crucial regulatory molecules serve vital functions in the progression of hepatocellular carcinoma (HCC). This study aims to investigate the biological roles and mechanisms of lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in HCC cells based on transcriptome analysis. The Cancer Genome Atlas data analysis and experimental validation showed that HOXD-AS1 was increased in HCC tissues/cell lines and positively relevant to histologic grade. The subcellular localization results indicated HOXD-AS1 was dispersed both in the nucleus as well as the cytoplasm of HCC cells. In vitro loss-of-function experiments revealed that silencing of HOXD-AS1 could dramatically suppress the proliferation, migration, and invasion, and induce S or/and G2/M phase cell cycle arrest as well as apoptosis of Bel-7402 and MHCC97H cells accompanying the changes in expression levels of cyclin B1, cyclin D1, BCL-2, BAX, and MMP2. In vivo assay also showed that HOXD-AS1 silencing could markedly reduce xenograft tumor volume and weight of HCC cells. Transcriptome and bioinformatic analysis indicated that a total of 1103 genes were significantly altered by HOXD-AS1 silencing, of which 132 genes exhibited a significant correlation with HOXD-AS1 expression in HCC tissues. Gene Ontology (GO) enrichment analysis revealed differentially expressed genes were remarkably enriched in several cancer-related biological processes (cell proliferation, cell cycle, apoptosis, migration, angiogenesis, and hypoxic response). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that HOXD-AS1 has the potential to affect p53, tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK) pathway, and Western blot results further validated that HOXD-AS1 silencing could inhibit the MEK/ERK pathway in Bel-7402 cells. Collectively, HOXD-AS1, as an oncogenic lncRNA, might exert crucial functions in HCC progression and serve as a potential diagnostic biomarker and therapeutic target for HCC.

3.
Sci Total Environ ; 698: 134298, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505343

RESUMO

Many studies have examined the acute toxicity of nanoparticles (NPs) towards model bacteria. In this study, we report the time-dependent effects of ZnO NPs on native, selected Zn-resistant and dominant bacteria in estuarine waters. An initial inhibition of bacterial growth followed by a recovery at 24 h was observed, and this rebound phenomenon was particularly notable when the raw water samples were treated with relatively high ZnO NP concentrations (1 and 10 mg/L).By comparing the groups treated with Zn2+, Zn2+ was shown to largely explain the acute cytotoxic effect of ZnO NPs on bacteria in raw waters. Furthermore, similar to the native bacteria, especially the dominant bacteria, the viability of Escherichia coli (E. coli) decreased with the increasing treatments time and the concentrations of ZnO NPs in water with different salinities. Moreover, the expression of Zn-resistance genes including zntA and zntR in E. coli suggested that the Zn-resistance system in E. coli can be activated to defend against the stress of Zn2+ released from ZnO NPs, and salinity may promote this process in estuarine aquatic systems. Thus, the effect of ZnO NPs on bacteria in estuarine water bodies is likely determined by the synergistic effect of environmental salinity and dissolved Zn ions. As such, our findings are of high relevance and importance for understanding the ecological disturbances caused by anthropogenic NPs in estuarine environments.

4.
Biomolecules ; 9(12)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795147

RESUMO

Secondary metabolites of lichens are promising bioresources for candidate anti-cancer drugs. Accordingly, several approaches have been proposed for screening these molecules for novel anti-cancer lead compounds. In this study, we found that a non-toxic concentration of physciosporin, a compound isolated from Pseudocyphellaria granulata, significantly decreased colony formation on soft agar and spheroid formation by CSC221 cancer stem-like cells. Physciosporin also decreased spheroid formation in other colorectal cancer cell lines, including DLD1, Caco2, and HT29. Aldehyde dehydrogenase-1 (ALDH1), the most important cancer stem marker, was sharply downregulated at both the protein and mRNA level following treatment with physciosporin. Physciosporin also decreased the transcriptional activity of the glioma-associated oncogene homolog zinc finger protein (Gli), as well as the Hes1 and CSL promoters, in reporter assays. Moreover, the drug significantly suppressed spheroid formation in CSC221 cells overexpressing Gli1/2 or EN1 (an S2-cleaved but membrane-tethered form of human Notch1) but did not suppress spheroid formation in cells overexpressing both Gli1/2 and ∆EN1, suggesting that physciosporin suppresses colon cancer cell stemness through the Sonic hedgehog and Notch signaling pathways. Together, these results demonstrate for the first time that physciosporin is a potent inhibitor of colorectal cancer cell stemness.

5.
Breast Cancer Res ; 21(1): 131, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783895

RESUMO

BACKGROUND: Breast cancer is a leading cause of cancer-related death for women in the USA. Thus, there is an increasing need to investigate novel prognostic markers and therapeutic methods. Inflammation raises challenges in treating and preventing the spread of breast cancer. Specifically, the nuclear factor kappa b (NFκB) pathway contributes to cancer progression by stimulating proliferation and preventing apoptosis. One target gene of this pathway is PTGS2, which encodes for cyclooxygenase 2 (COX-2) and is upregulated in 40% of human breast carcinomas. COX-2 is an enzyme involved in the production of prostaglandins, which mediate inflammation. Here, we investigate the effect of Singleminded-2s (SIM2s), a transcriptional tumor suppressor that is implicated in inhibition of tumor growth and metastasis, in regulating NFκB signaling and COX-2. METHODS: For in vitro experiments, reporter luciferase assays were utilized in MCF7 cells to investigate promoter activity of NFκB and SIM2. Real-time PCR, immunoblotting, immunohistochemistry, and chromatin immunoprecipitation assays were performed in SUM159 and MCF7 cells. For in vivo experiments, MCF10DCIS.COM cells stably expressing SIM2s-FLAG or shPTGS2 were injected into SCID mice and subsequent tumors harvested for immunostaining and analysis. RESULTS: Our results reveal that SIM2 attenuates the activation of NFκB as measured using NFκB-luciferase reporter assay. Furthermore, immunostaining of lysates from breast cancer cells overexpressing SIM2s showed reduction in various NFκB signaling proteins, as well as pAkt, whereas knockdown of SIM2 revealed increases in NFκB signaling proteins and pAkt. Additionally, we show that NFκB signaling can act in a reciprocal manner to decrease expression of SIM2s. Likewise, suppressing NFκB translocation in DCIS.COM cells increased SIM2s expression. We also found that NFκB/p65 represses SIM2 in a dose-dependent manner, and when NFκB is suppressed, the effect on the SIM2 is negated. Additionally, our ChIP analysis confirms that NFκB/p65 binds directly to SIM2 promoter site and that the NFκB sites in the SIM2 promoter are required for NFκB-mediated suppression of SIM2s. Finally, overexpression of SIM2s decreases PTGS2 in vitro, and COX-2 staining in vivo while decreasing PTGS2 and/or COX-2 activity results in re-expression of SIM2. CONCLUSION: Our findings identify a novel role for SIM2s in NFκB signaling and COX-2 expression.

6.
J Mol Biol ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31786267

RESUMO

Huntington's disease is a monogenetic neurodegenerative disease, which serves as a model of neurodegeneration with protein aggregation. Autophagy has been suggested to possess a great value to tackle protein aggregation toxicity and neurodegenerative diseases. Current studies suggest that autophagy-endolysosomal pathways are critical for HD pathology. Here we review recent advancement in the studies of autophagy and selective autophagy relating Huntington's disease. Restoration of autophagy flux and enhancement of selective removal of mutant huntingtin/disease-causing protein would be effective approaches towards tackling HD as well as other similar neurodegenerative disorders.

7.
World Neurosurg ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31786380

RESUMO

PURPOSE: To evaluate clinical and radiographical outcomes. METHODS: Patients with thoracolumbar burst fractures and neurological deficits underwent minimally invasive decompression and intracorporeal bone grafting combined with percutaneous short-segment stabilization. Instrumentation was removed approximately 1 year after vertebral fracture union. Clinical and radiographical outcomes were analyzed. RESULTS: The mean operative duration and intraoperative bleeding volume were 135±63 min and 120±200 ml, respectively. The average American Spinal Injury Association (ASIA) impairment scale scores were significantly improved at the final follow-up. The visual analog scale (VAS) score decreased from 7.8±1.1 preoperatively to less than 2.9±1.3 (P<0.05) 1 week postoperatively. The Oswestry Disability Index (ODI) decreased from 86.1±8.8 preoperatively to 15.9±6.4 (P<0.05) 1 year later. The canal stenosis index (CSI) improved from 43.4±12.0% to 93.8±4.8% (P<0.05). The sagittal Cobb angle (CA) was corrected from 17.8±7.5° to 4.0±1.9° (P<0.05) and remained at 4.9±2.0° (P>0.05) 1 year later. The sagittal index (SI) was corrected from 16.6±6.1° to 0.3±4.6° (P<0.05) and remained at 1.5+4.5° (P>0.05) 1 year later. The anterior vertebral height (AVH) increased from 49.3±11.1% to 97.6±6.5% (P<0.05) and remained at 95.7±6.0% (P>0.05) 1 year later. After implant removal, the total kyphosis correction losses were 1.5±0.8° for the CA, 2.0±1.1° for the SI and 3.4±2.1% for the AVH. One pullout screw and 1 broken rod were found in 2 patients. CONCLUSIONS: Minimally invasive decompression and intracorporeal bone grafting combined with percutaneous short-segment fixation yielded satisfactory results in decompression and immediate kyphosis correction. Additionally, this procedure resulted in maintenance of the vertebral height and prevented late correction loss after implant removal.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31789820

RESUMO

The renal injury caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are characterized by few or no immune deposits in glomerulus. A growing number of AAV patients with glomerular immunoglobulin (Ig)A deposits have been reported. We retrospectively investigated all AAV patients with glomerular IgA deposits diagnosed in our center. Serum galactose-deficient IgA1 (Gd-IgA1) level and glomerular Gd-IgA1 and IgA staining were measured. Moreover, we detected complement pathway components in their sera. A total of 168 AAV patients were enrolled, including 26 patients with glomerular IgA deposition and 142 patients with pauci-immune-complex deposition. The AAV patients with IgA deposition had a tendency of lower systemic disease activity, presenting with lower erythrocyte sedimentation rate, lower myeloperoxidase-ANCA, and tendency of lower C reactive protein and Birmingham Vasculitis Activity Score. For renal injury, there were no significant differences in clinical data, pathologic parameters, or renal outcome between groups. The serum level of Gd-IgA1 and intensity of glomerular Gd-IgA1 staining in IgA deposition AAV patients were similar to IgA nephropathy patients. All patients in the IgA nephropathy group and AAV groups with or without IgA deposition had the activation of the alternative complement pathway, whereas AAV patients with IgA deposition also had the activation of the classic complement pathway. Correlation analysis showed serum C1q level correlated directly with serum globulin and IgA levels. In conclusion, AAV patients with IgA deposition had the basis of IgA nephropathy and may present lower systemic disease activity. But it differs from pauci-immune AAV or IgA nephropathy by the possible activation of the classic complement pathway.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31784083

RESUMO

Interleukin-17 (IL-17) and interferon-γ (IFN-γ), two inflammatory cytokines, are present in cancerous liver tissues. IL-17 was recently identified as an oncogenic factor in hepatocellular carcinoma (HCC), but its underlying mechanisms are largely obscure. Here, we aimed to investigate the interaction between IL-17 and IFN-γ and its influence on HCC cell apoptosis and growth in vitro and in vivo. We found that the expression of IL-17, but not IFN-γ, was obviously increased in HCC tissues. Higher IL-17 expression in tumor tissues correlated with shorter survival times. IFN-γ apparently increased apoptosis of HCC cells. IL-17 alone had no effect on apoptosis of HCC cells but reversed apoptosis induced by IFN-γ. IFN-γ mildly promoted the expression of protein inhibitor of activated signal transducer and activators of transcription 1 (PIAS1) and the activation of NF-κB, and these effects were greatly enhanced when combined with IL-17. PIAS1 silencing not only further amplified apoptosis induced by IFN-γ alone but also abolished the inhibitory effects of IL-17 on IFN-γ-induced apoptosis in HCC cells. An NF-κB inhibitor obviously decreased the upregulated expression of PIAS1 induced by IFN-γ plus IL-17 and IFN-γ alone. IFN-γ treatment retarded the tumor growth of HCC cells in an in vivo xenograft tumor model, which could be largely inhibited by combined treatment with IL-17. In conclusion, IL-17 obviously inhibits the antitumor effects of IFN-γ in hepatoma cells and, in turn, accelerates HCC development through upregulating the expression of the negative feedback regulator PIAS1 of the JAK/STAT1 pathway via enhancing activation of NF-κB.

10.
BMJ Open ; 9(11): e032417, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31784442

RESUMO

INTRODUCTION: Postoperative nausea and vomiting (PONV) is among the most common adverse reactions following anaesthesia and surgery. Recent clinical studies have reported that the average incidence is about 30%, while in patients specifically undergoing neurosurgery, the incidence can be as great as 73%. Studies also suggest that its occurrence increases the risk of intracranial haematoma and haemorrhage. The objective of this study is to evaluate the effectiveness of intradermal thumbtack needle buried Neiguan (pericardium 6 (P6)) point therapy in the prevention of PONV in patients undergoing craniotomy under general anaesthesia. METHODS AND ANALYSIS: This is a single-centre, three-arm, randomised controlled trial. 180 participants are randomly assigned to either an acupuncture, intradermal thumbtack needle or control group in a 1:1:1 ratio. The P6 of the acupuncture group is punctured at both sides perpendicularly to a depth of 20 mm. Needles are retained for 30 min and stimulated every 10 min to maintain the de qi. The therapy includes two treatments; the acupuncture is administered immediately after and 24 hours after surgery. For the intradermal thumbtack needle group, the intradermal thumbtack needle is quickly inserted into the skin and embedded at P6 acupoints bilaterally. Patients and their families are asked to press the needlepoint with the onset of nausea, vomiting, bloating, pain and other reported discomforts. The needle is replaced after 24 hours. The therapy is administered immediately after and 24 hours after surgery. For the control group, no intervention is carried out. The incidence of PONV within 48 hours after craniotomy across the three groups is observed. Other observations include: (1) assessment of nausea score (severity of nausea) and pain score (visual analogue scale) 0-2, 2-6, 6-24 and 24-48 hours after craniotomy under general anaesthesia; (2) assessment of total rescue antiemetic dosage 0-48 hours after craniotomy under general anaesthesia; (3) length of hospital stay and (4) patient satisfaction score with PONV management. We will perform all statistical analysis following the intention-to-treat principle. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Bioethics Subcommittee of the West China Hospital, Sichuan University: the approval number is 2018 (number 231). Results will be expected to be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR1800017173.

11.
BMC Evol Biol ; 19(1): 219, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791235

RESUMO

BACKGROUND: Phylogenetic species trees are widely used in inferring evolutionary relationships. Existing software and algorithms mainly focus on phylogenetic inference. However, less attention has been paid to intermediate steps, such as processing extremely large sequences and preparing configure files to connect multiple software. When the species number is large, the intermediate steps become a bottleneck that may seriously affect the efficiency of tree building. RESULTS: Here, we present an easy-to-use pipeline named PhySpeTree to facilitate the reconstruction of species trees across bacterial, archaeal, and eukaryotic organisms. Users need only to input the abbreviations of species names; PhySpeTree prepares complex configure files for different software, then automatically downloads genomic data, cleans sequences, and builds trees. PhySpeTree allows users to perform critical steps such as sequence alignment and tree construction by adjusting advanced options. PhySpeTree provides two parallel pipelines based on concatenated highly conserved proteins and small subunit ribosomal RNA sequences, respectively. Accessory modules, such as those for inserting new species, generating visualization configurations, and combining trees, are distributed along with PhySpeTree. CONCLUSIONS: Together with accessory modules, PhySpeTree significantly simplifies tree reconstruction. PhySpeTree is implemented in Python running on modern operating systems (Linux, macOS, and Windows). The source code is freely available with detailed documentation (https://github.com/yangfangs/physpetools).

12.
Insect Sci ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793737

RESUMO

Apoptosis play critical roles in multiple biological processes in multicellular organisms. Caspases are known as important participator and regulator of apoptosis. Here, four novel caspase genes of Spodoptera exigua were cloned and characterized, which were designated as SeCasp-1, SeCasp-6, SeCasp-7 and SeCasp-8. Analysis of the putative encoded protein sequences of these SeCasps indicated that SeCasp-1 and SeCasp-7 were possible homologues of executor caspases; SeCasp-8 was a possible homologue of initiator caspases; and SeCasp-6 was a unique caspase of S. exigua that shares low similarity with all the identified insect caspases. Based on baculovirus expression system analyses, SeCasp-1 exhibited similar caspase activity to human caspase-1, -3, -4, -6, -8 and -9; SeCasp-6 presented similar caspase activity to human caspase-2, -3, -4, -6, -8 and -9; SeCasp-7 exhibited similar caspase activity to human caspase-2, -3 and -6; and SeCasp-8 presented similar caspase activity only to human caspase-8. Induction with different chemicals revealed that SeCasp-1 showed extreme upregulation after 24 h in the treated fat body cell line (IOZCAS-Spex-II) of S. exigua. Developmental expression analysis revealed that SeCasp-1 was highly transcribed in the larval stages, while SeCasp-6, SeCasp-7, SeCasp-8 were down-regulated. The in vivo detection of the relative expression levels of SeCasps in S. eixgua larvae inoculated with different pathogens suggested that SeCasp-1 was sensitive to Bacillus thuringiensis infection and that SeCasp-6 was sensitive to baculovirus infection. SeCasp-7 and SeCasp-8 showed slight changes under either in vitro chemical apoptosis induction or in vivo pathogen infection. This article is protected by copyright. All rights reserved.

13.
Stem Cell Res Ther ; 10(1): 372, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801626

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have been shown to alleviate acute lung injury (ALI) via paracrine hepatocyte growth factor (HGF) and to induce the differentiation of dendritic cells (DCs) into tolerogenic dendritic cells (DCregs) and participate in the immune response. However, whether MSCs induce the production of DCregs by secreting HGF to alleviate early ALI remains unclear. We observed that the protective effect of mouse bone marrow-derived MSCs against lipopolysaccharide (LPS)-induced ALI was achieved by inducing mature DCs (mDCs) to differentiate into DCregs, and its mechanism is related to the activation of the HGF/Akt pathway. METHODS: MSCs or MSCs with overexpression or knockdown of HGF were cocultured with DCs derived from mouse bone marrow using a Transwell system for 3 days. Moreover, we used MSCs or MSCs with overexpression or knockdown of HGF to treat LPS-induced ALI mice for 24 h. Flow cytometry was performed to measure the phagocytosis, accumulation, and maturation of DCs, as well as proliferation of T cells. Lung injury was estimated by lung wet weight to body weight ratio (LWW/BW) and histopathological analysis. Furthermore, we used the Akt inhibitor MK-2206 in a coculture system to elucidate the role of the HGF/Akt pathway in regulating the differentiation of DCs into regulatory DCs and relieving lung injury in early ALI mice. RESULTS: Immature DCs (imDCs) were induced to mature after 24 h of LPS (50 ng/ml) stimulation. MSCs or HGF induced the differentiation of mDCs into regulatory DCs characterized by low expression of MHCII, CD86, and CD40 molecules, strong phagocytic function, and the ability to inhibit T cell proliferation. The effect of MSCs on DCregs was enhanced with the increase in HGF secretion and was weakened with the decrease in HGF secretion. DCregs induced by recombinant HGF were attenuated by the Akt inhibitor MK-2206. Lung DC aggregation and mDC ratio increased in LPS-induced ALI mice, while treatment with MSCs decreased lung DC aggregation and maturation and alleviated lung pathological injury. High expression of the HGF gene enhanced the above effect of MSCs, while decreased expression of HGF weakened the above effect of MSCs. CONCLUSIONS: MSCs alleviate early ALI via paracrine HGF by inducing mDCs to differentiate into regulatory DCs. Furthermore, the mechanism of HGF-induced differentiation of mDCs into DCregs is related to the activation of the Akt pathway.

14.
Dysphagia ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802198

RESUMO

The objective of this study is to investigate the changes in swallowing function after using an absorbable collagen biomembrane during anterior cervical spine surgery (ACSS). A prospective controlled study of patients who underwent two-level anterior cervical decompression and fusion (ACDF) with a zero-profile implant or single-level anterior cervical corpectomy and fusion (ACCF) with cage and plate fixation was performed in our hospital from January 2016. An absorbable collagen biomembrane was used after suturing the prevertebral fascia in the experimental groups. The thickness of prevertebral soft tissue (PST) was measured on lateral X-rays to determine the extent of swelling. In addition, the Bazaz grading system and the Swallowing-Quality of Life (SWAL-QOL) survey were used to assess the swallowing function. A total of 100 patients were included with a follow-up of 12 months. Significant differences in PST swelling were found between the experimental groups and control groups at 3 months, 6 months, and 12 months postoperatively (P < 0.05). Patients in the experimental groups had significantly increased SWAL-QOL scores compared with patients in the control groups at 3 months and 6 months after surgery (P < 0.05). A significant difference in the total incidence of dysphagia was observed at 3 months postoperatively between the experimental groups and control groups (P < 0.05). The application of absorbable collagen biomembrane in ACSS can reduce the total incidence of dysphagia and improve swallowing function early after surgery.

15.
Crit Care Med ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804299

RESUMO

OBJECTIVES: We performed a national cross-sectional survey to determine the epidemiologic characteristics of patients with sepsis in ICU in China. DESIGN: A cross-section survey study. SETTING: Forty-four hospitals in mainland China from December 1, 2015, to January 31, 2016. PATIENTS: All septic patients diagnosed according sepsis-1 criteria admitted to participating ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We recorded demographic, physiologic, and microbiological data with follow-up for 90 days or death, if sooner. The frequency of sepsis and 90-day mortality rate were computed, and the relationship with gross domestic product determined. Multivariate logistic regression analysis was used to determine risk factors for 90-day mortality in patients with sepsis. Two-thousand three-hundred twenty-two patients with sepsis were included in the analysis, of whom 786 patients (33.9%) had hospital-acquired sepsis. The most common infection site was the lung (68.2%), followed by abdomen (26.6%) and bloodstream (7.8%). The frequency of sepsis in the ICU was 20.6 cases per 100 ICU admissions (95% CI, 15.8-25.4) with a 90-day mortality of 35.5%. The proportion of sepsis, severe sepsis, and septic shock were 3.10%, 43.6%, and 53.3% with a 90-day mortality of 2.78%, 17.69%, and 51.94%, respectively. Older age, low body weight, higher Sequential Organ Failure Assessment score, the number of systemic inflammatory response syndrome criteria, comorbid with heart failure, hematologic cancer, immunosuppression, higher level of lactate, infection site (pneumonia and bloodstream) were associated with 90-day mortality. CONCLUSIONS: Sepsis affects a fifth of patients admitted to ICUs in mainland China with a 90-day mortality rate of 35.5%. Our findings indicate that a large burden of sepsis, and we need to focus on sepsis as a quality improvement target in China given the high mortality. In addition, further studies are needed to delineate the epidemiology of sepsis outside the ICU.

16.
Medicine (Baltimore) ; 98(49): e18085, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804318

RESUMO

This was a prospective cohort study with a short-term follow-up. To explore whether age is a factor in the prognosis following high ligation and stripping (HLS) performed in an ambulatory care center. This study included 170 patients who underwent their first HLS for varicose veins in an ambulatory center from November 2016 to October 2017 at West China Hospital. The patients were categorized as two groups: the ≤60 years old group and the >60 years old group. We collected the two age groups data included Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification, Venous Clinical Severity Score (VCSS), Visual Analogue Score (VAS), Aberdeen Varicose Veins Questionnaire (AVVQ), Quality of Recovery (QoR-15), and postoperative complications at predetermined time points. The clinical correlation between age and prognosis following HLS in an ambulatory care center was prospectively studied after adjusting for potential confounders. The distribution of age and prognosis were also compared in the AVVQ improvement and VCSS improvement of patients at 6 weeks and 6 months after surgery. Our research comprised a total of 170 patients (236 limbs), of which 86 (50.6%) patients were female and 66 (38.8%) patients received bilateral procedures. After multivariable risk adjustment for potential confounding factors, we observed that age was not associated with the improvement of AVVQ (OR 0.3, 95%CI (1.3, 0.7), P = .54) and VCSS (OR 0.2, 95%CI (0.2, 0.6) P = .38) at 6 months after HLS, as well as AVVQ (OR 0.5,95%CI (1.2, 2.2), P = .57) at 6 weeks after HLS. However, at 6 weeks after HLS, age was related to the improvement of VCSS (OR -0.6, 95%CI (1.2, 0.1), P = .03), with the >60 years old group having a lower VCSS improvement compared to the 60 years old group. In postoperative complications, there were no significant differences in terms of complications between the two age groups (all P value >.05). Therefore, in our opinion, age is not a barrier for good outcomes following HLS in an ambulatory care center.

17.
Medicine (Baltimore) ; 98(49): e18163, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804330

RESUMO

RATIONALE: Non-traumatic bowel perforation caused by cytomegalovirus (CMV) and Mycobacterium avium complex (MAC) infections has become rare among patients with acquired immunodeficiency syndrome (AIDS) in the era of combination antiretroviral therapy (cART); however, CMV-associated and MAC-related immune reconstitution inflammatory syndrome (IRIS) has subsequently emerged owing to the wide use of integrase inhibitor-based regimens. Here we report a case of spontaneous perforation of the jejunum in a patient with human immunodeficiency virus (HIV) infection with good compliance to cART. PATIENT CONCERNS: A 32-year-old HIV-infected man developed CMV disease and DMAC infection, as unmasking IRIS, 3 days after the initiation of cART. After appropriate treatment for opportunistic infections, intermittent fever with enlarged lymph nodes in the abdomen occurred as paradoxical IRIS. The patient was administered prednisolone with subsequent tapering according to his clinical condition. DIAGNOSES: Unexpected perforation of hollow organ during the titration of steroid dose with clinical presentations of severe abdominal pain was diagnosed by chest radiography. INTERVENTIONS: He underwent surgical repair with peritoneal toileting smoothly. OUTCOMES: He was discharged well with a clean surgical wound on post-operative day 10. LESSONS: Bowel perforation may be a life-threatening manifestation of IRIS in the era of cART. Steroids should be avoided, if possible, to decrease the risk of bowel perforation, especially in IRIS occurred after opportunistic diseases involving the gastrointestinal tract.

18.
J Cell Mol Med ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31755214

RESUMO

Cyclin-dependent kinase 7 (CDK7) is a protein kinase that plays a major role in transcription initiation. Yes-associated protein (YAP) is a main effector of the Hippo/YAP signalling pathway. Here, we investigated the role of CDK7 on YAP regulation in human malignant pleural mesothelioma (MPM). We found that in microarray samples of human MPM tissue, immunohistochemistry staining showed correlation between the expression level of CDK7 and YAP (n = 70, r = .513). In MPM cells, CDK7 expression level was significantly correlated with GTIIC reporter activity (r = .886, P = .019). Inhibition of CDK7 by siRNA decreased the YAP protein level and the GTIIC reporter activity in the MPM cell lines 211H, H290 and H2052. Degradation of the YAP protein was accelerated after CDK7 knockdown in 211H, H290 and H2052 cells. Inhibition of CDK7 reduced tumour cell migration and invasion, as well as tumorsphere formation ability. Restoration of the CDK7 gene rescued the YAP protein level and GTIIC reporter activity after siRNA knockdown in 211H and H2052 cells. Finally, we performed a co-immunoprecipitation analysis using an anti-YAP antibody and captured the CDK7 protein in 211H cells. Our results suggest that CDK7 inhibition reduces the YAP protein level by promoting its degradation and suppresses the migration and invasion of MPM cells. Cyclin-dependent kinase 7 may be a promising therapeutic target for MPM.

19.
Chem Asian J ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31755237

RESUMO

We report herein a facile synthetic method for converting unactivated (hetero)aryl electrophiles into ß-fluoroethylated (hetero)arenes via nickel-catalyzed reductive cross-couplings. This coupling reaction features the involvement of FCH2CH2 radical intermediate rather than ß-fluoroethyl manganese species which provides effective solutions to the problematic ß-fluoride side eliminations. The practical value of this protocol is further demonstrated by the late-stage modification of several complex ArCl or ArOH-derived bioactive molecules.

20.
Bioinformatics ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755899

RESUMO

MOTIVATION: Although genome-wide association studies (GWAS) have deepened our understanding of the genetic architecture of complex traits, the mechanistic links that underlie how genetic variants cause complex traits remains elusive. To advance our understanding of the underlying mechanistic links, various consortia have collected a vast volume of genomic data that enable us to investigate the role that genetic variants play in gene expression regulation. Recently, a collaborative mixed model (CoMM) (Yang et al., 2018a) was proposed to jointly interrogate genome on complex traits by integrating both theGWAS dataset and the expression quantitative trait loci (eQTL) dataset. Although CoMM is a powerful approach that leverages regulatory information while accounting for the uncertainty in using an eQTL dataset, it requires individual-level GWAS data and cannot fully make use of widely available GWAS summary statistics. Therefore, statistically efficient methods that leverages transcriptome information using only summary statistics information from GWAS data are required. RESULTS: In this study, we propose a novel probabilistic model, CoMM-S2, to examine the mechanistic role that genetic variants play, by using only GWAS summary statistics instead of individual-level GWAS data. Similar to CoMM which uses individual-level GWAS data, CoMM-S2 combines two models: the first model examines the relationship between gene expression and genotype, while the second model examines the relationship between the phenotype and the predicted gene expression from the first model. Distinct from CoMM, CoMM-S2 requires only GWAS summary statistics. Using both simulation studies and real data analysis, we demonstrate that even though CoMM-S2 utilizes GWAS summary statistics, it has comparable performance as CoMM, which uses individual-level GWAS data. AVAILABILITY AND IMPLEMENTATION: The implement of CoMM-S2 is included in the CoMM package that can be downloaded from https://github.com/gordonliu810822/CoMM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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