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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1750-1756, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067985

RESUMO

OBJECTIVE: To investigate the safety and efficacy of tumor-associated antigen-specific cytotoxic T lympho- cytes (TAA-CTL) in the treatment of multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). METHODS: Peripheral blood mononuclear cells (PBMNC)of patients were collected. Dendritic cells (DC) were loaded with multiple tumor-associated antigens (TAA) (NY-ESO-1, MAGE-A3, MAGE-A4, WT1, Survivin, PRAME, LMP1 and LMP2A), then co-cultured with PBMNC to induce cytotoxic T lymphocytes (CTL). The phenotypes of cell products were detected, and the disease statuse was evaluated in 7 patients during or after infusion. The changes of TAA-CTL amount in the PBMNC of patients were measured by using IFN-γ ELISpot assay. RESULTS: TAA-CTL products were generated comprising CD3+ T cells (mean 82.98%) with a mixture of CD4+ (mean 42.09%) and CD8+ (mean 25.32%) T cells. Among them, 70% expressed effectors memory markers (CD45RO+CD62L-CCR7-). Each patient received TAA-CTL infusions for 1-4 times, and none of them showed obvious adverse reactions. The clinical symptoms and laboratory or imaging examination of 5 patients achieved positive effects. After cell therapy, the spot-forming cells (SFC) levels of most patients gradually increased and the peak often appeared about 2-3 weeks after the infusion. CONCLUSION: TAA-CTLs preliminarily show its safety and efficacy in MM and NHL patients, however, a larger population sample is needed to explore its clinical application value.

2.
Ann Palliat Med ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32921115

RESUMO

Acute hemorrhagic necrotizing enteritis (AHNE) is a potentially fatal infection, triggered by beta toxin produced by Clostridium perfringens type C and characterized by extensive hemorrhagic, inflammatory, or ischemic necrosis that mainly affects the small bowel, clinically presenting as diarrhea, hematochezia, abdominal pain and hypotensive shock. AHNE is rarely reported in humans nowadays, we present a case of AHNE in a 51-year-old man presenting as watery diarrhea, hematochezia and abdominal pain along with shortness of breath who unfortunately died of the disease despite active medical treatment and multiple surgical interventions. We aim to improve awareness of clinicians on this fulminant disease, associated with high mortality rates. This is the first case report that attempts to summarize the pathogenesis, clinical characteristics, diagnostic methods, treatment and prognosis of AHNE based on the current English literature. AHNE, which is exceedingly rare in clinical practice, has been associated with poorly specific clinical manifestations, high rates of misdiagnosis in its early stages and mortality rates in severe cases. In patients with a history of ingesting contaminated food and presenting with sudden progressively worsening abdominal pain, diarrhea, hematochezia, accompanied by hypotensive shock or ileus, AHNE should be highly suspected. In order to reduce the mortality of this disease, emphasis should be laid on early recognition and timely surgical intervention in AHNE. In severe cases, death cannot be avoided despite adopting active supportive treatment and timely surgical intervention.

3.
Int J Med Sci ; 17(15): 2248-2256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922188

RESUMO

Osteosarcoma (OS) is the most common type of malignant bone tumor that affects children and adolescents. Still, the cellular and molecular mechanisms driving the development of this disease remain poorly understood. In this study, numerous dysregulated lncRNAs were identified by RNA-seq. As a result, we were able to find a novel lncRNA Lnc-MAP6-1:3 which is highly expressed in osteosarcoma. Using a set of approaches including gene knockdown, RT-PCR, oncogenic function assay and western blotting, we observed that knockdown of Lnc-MAP6-1:3 expression suppressed cell proliferation and colony formation, and promoted apoptosis in vitro. For the first time, we have identified that Lnc-MAP6-1:3 potentially influence the malignant behavior of osteosarcoma via Bax/Bcl-2 and Wnt/ß-catenin signaling pathways. Henceforth, Lnc-MAP6-1:3 may provide a new molecular route of research and therapeutic applications for the diagnosis and treatment of osteosarcoma.

4.
Mol Immunol ; 127: 136-145, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32971400

RESUMO

Sepsis-induced inflammatory damage is a crucial cause of acute kidney injury (AKI), and AKI is an ecumenical fearful complication in approximately half of patients with sepsis. CCAAT/enhancer-binding protein ß (C/EBPß) plays roles in regulating acute phase responses and inflammation. However, the role and mechanism of C/EBPß in AKI are unclear. LPS combined with ATP-treated renal epithelial cells HK2 and cecal ligation-peferation (CLP)-mice were used as models of AKI in vitro and in vivo. Cell damage, the secretion of interleukin-1 beta (IL-1ß), IL-18 and cysteinyl aspartate specific proteinase 1 (caspase-1) activity were tested by LDH, ELISA assay and flow cytometry analysis, respectively. The expression levels of TFAM, C/EBPß, and pyroptosis-related molecules were tested by qRT-PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assessed the interaction between C/EBPß with TFAM. Hematoxylin-Eosin (H&E) staining detected pathological changes of kidney tissues, and immunohistochemistry measured TFAM and C/EBPß in mice kidney tissues. C/EBPß or TFAM were up-regulated in LPS combined with ATP -induced HK2 cells. Knockdown of C/EBPß could suppress cell injury and the secretion of IL-1ß and IL-18 induced by LPS combined with ATP. Furthermore, C/EBPß up-regulated the expression levels of TFAM via directly binding to TFAM promoter. Overexpression of TFAM reversed the effects of C/EBPß deficiency on pyroptosis. Knockdown of C/EBPß could inhibit NLRP3 inflammasome-mediated caspase-1 signaling pathway by inactivating TFAM/RAGE pathway. It was further confirmed in the AKI mice that C/EBPß and TFAM promoted AKI by activating NLRP3-mediated pyroptosis. The interaction of between C/EBPß and TFAM facilitated pyroptosis by activating NLRP3/caspase-1 signal axis, thereby promoting the occurrence of AKI.

5.
Radiat Environ Biophys ; 59(4): 663-682, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32951082

RESUMO

Radioactive cerium and other lanthanides can be transported through the aquatic system into foodstuffs and then be incorporated by humans. Information on the uncertainty of reported dose coefficients for exposed members of the public is then needed for risk analysis. In this study, uncertainties of dose coefficients due to the ingestion of the radionuclides 141Ce and 144Ce were estimated. According to the schema of internal dose calculation, a general statistical method based on the propagation of uncertainty was developed. The method takes into account the uncertainties contributed by the biokinetic models and by the so-called S values. These S-values were derived by using Monte Carlo radiation transport simulations with five adult non-reference voxel computational phantoms that have been developed at Helmholtz Zentrum München, Germany. Random and Latin hypercube sampling techniques were applied to sample parameters of biokinetic models and S values. The uncertainty factors, expressed as the square root of the 97.5th and 2.5th percentile ratios, for organ equivalent dose coefficients of 141Ce were found to be in the range of 1.2-5.1 and for 144Ce in the range of 1.2-7.4. The uncertainty factor of the detriment-weighted dose coefficient for 141Ce is 2.5 and for 144Ce 3.9. It is concluded that a general statistical method for calculating the uncertainty of dose coefficients was developed and applied to the lanthanide cerium. The dose uncertainties obtained provide improved dose coefficients for radiation risk analysis of humans. Furthermore, these uncertainties can be used to identify those parameters most important in internal dose calculations by applying sensitivity analyses.

6.
Acta Pharmacol Sin ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32918045

RESUMO

The ROS1 fusion kinase is an attractive antitumor target. Though with significant clinical efficacy, the well-known first-generation ROS1 inhibitor (ROS1i) crizotinib inevitably developed acquired resistance due to secondary point mutations in the ROS1 kinase. Novel ROS1is effective against mutations conferring secondary crizotinib resistance, especially G2032R, are urgently needed. In the present study, we evaluated the antitumor efficacy of SAF-189s, the new-generation ROS1/ALK inhibitor, against ROS1 fusion wild-type and crizotinib-resistant mutants. We showed that SAF-189s potently inhibited ROS1 kinase and its known acquired clinically resistant mutants, including the highly resistant G2032R mutant. SAF-189s displayed subnanomolar to nanomolar IC50 values against ROS1 wild-type and mutant kinase activity and a selectivity vs. other 288 protein kinases tested. SAF-189s blocked cellular ROS1 signaling, and in turn potently inhibited the cell proliferation in HCC78 cells and BaF3 cells expressing ROS1 fusion wild-type and resistance mutants. In nude mice bearing BaF3/CD74-ROS1 or BaF3/CD74-ROS1G2032R xenografts, oral administration of SAF-189s dose dependently suppressed the growth of both ROS1 wild-type- and G2032R mutant-driven tumors. In a patient-derived xenograft model of SDC4-ROS1 fusion NSCLC, oral administration of SAF-189s (20 mg/kg every day) induced tumor regression and exhibited notable prolonged and durable efficacy. In addition, SAF-189s was more potent than crizotinib and comparable to lorlatinib, the most advanced ROS1i known against the ROS1G2032R. Collectively, these results suggest the promising potential of SAF-189s for the treatment of patients with the ROS1 fusion G2032R mutation who relapse on crizotinib. It is now recruiting both crizotinib-relapsed and naive ROS1-positive NSCLC patients in a multicenter phase II trial (ClinicalTrials.gov Identifier: NCT04237805).

7.
Surg Endosc ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32880750

RESUMO

BACKGROUND: Though biliary obstruction is a common clinical situation, it is rarely caused by transjugular intrahepatic portosystemic shunt (TIPS) placement. When TIPS-induced intractable biliary obstruction happens, liver transplantation seems to be the only resort to cure this condition. METHODS: Herein, we describe a patient who suffered from intractable biliary obstruction following TIPS placement. RESULTS: The patient was finally cured by magnet-assisted endoscopic biliary-duodenal anastomosis, without further requirement of liver transplantation. After more than 6 months of follow-up, this patient recovered well, and recurrence of biliary obstruction was not observed. CONCLUSION: We showed that magnet-assisted endoscopic biliary-duodenal anastomosis is a safe method, which is easy to perform and worthy of popularizing.

8.
Math Biosci Eng ; 17(4): 3909-3924, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32987560

RESUMO

Objective: This study was aimed to identify prognostic factors in glioma by analysis of the gene expression and DNA methylation data. Methods: The RNAseq and DNA methylation data associated with glioma were downloaded from GEO and TCGA databases to analyze the differentially expressed genes (DEGs) and methylated genes between tumor and normal tissues. Function and pathway analyses, co-expression network and survival analysis were performed based on these DEGs. The intersection genes of DEGs and differentially methylated genes were obtained followed by function analysis. Results: Total 2190 DEGs were identified between tumor and normal tissues, which were significantly enriched in neuron differentiation associated functions, as well as ribosome pathway. There were 6186 methylation sites (2834 up-regulated and 3352 down-regulated) with significant differences in tumor vs. normal. In the constructed co-expression network, DPP6, MAPK10 and RPL3 were hub genes. Survival analysis of 20 DEGs obtained 18 prognostic genes, among which 9 were differentially methylated, such as LHFPL tetraspan subfamily member 3 (LHFPL3), cadherin 20 (CDH20), complexin 2 (CPLX2), and tenascin R (TNR). The intersection of DEGs and differentially methylated genes (632 genes) were significantly enriched in functions of neuron differentiation. Conclusion: DPP6, MAPK10 and RPL3 may play important roles in tumorigenesis of glioma. Additionally, methylation of LHFPL3, CDH20, CPLX2, and TNR may serve as prognostic factors of glioma.

9.
Phytother Res ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32869425

RESUMO

Oridonin (Ori) is a natural tetracyclic diterpenoid active compound with excellent antitumor activity, but the mechanism of Ori on esophageal cancer cell, TE1, remains unclear. In this study, we examined the levels of intracellular iron, malondialdehyde, and reactive oxygen species after Ori treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1 cell proliferation is associated with ferroptosis. To understand the molecular mechanism of Ori, we performed UPLC-MS/MS metabolomics profiling on TE1 cells, which show that gamma-glutamyl amino acids (gamma-glutamylleucine, gamma-glutamylvaline), 5-oxoproline, glutamate, GSH, and GSSG are changed significantly after Ori treatment. Meanwhile, the activity of gamma-glutamyl transpeptidase 1 (GGT1) decreased. This revealed that Ori inhibited the gamma-glutamyl cycle in TE1 cells. Furthermore, we found that Ori can covalently bind to cysteine to form the conjugate oridonin-cysteine (Ori-Cys), resulting in the inhibition of glutathione synthesis, which is consistent with the decrease in the enzymatic activity of glutamate cysteine ligase catalytic subunit (GCLC). Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased. In conclusion, our experiments indicated that Ori can inhibit the gamma-glutamyl cycle, thereby inducing ferroptosis to exert anti-cancer activity.

10.
Zhongguo Zhen Jiu ; 40(8): 907-12, 2020 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-32869605

RESUMO

The research progress of acupuncture analgesia in recent years is analyzed to summarize the analgesic mechanism of acupuncture on neuropathic pain. The analgesic mechanism of acupuncture on neuropathic pain is discussed from peripheral level and central level, including peripheral sensitization and immune inflammatory response, changes of ion channel, central sensitization, regulation of cell signal pathway, activation of spinal glial cells, etc. It is suggested that the focus of future research should include conducting in-vitro studies with the help of multi-omics technology to detect the changes of metabolic substances and signal pathway molecules in patients with neuropathic pain before and after acupuncture to further clarify the mechanism of acupuncture analgesia.

11.
Minerva Chir ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32975382

RESUMO

BACKGROUND: This study aimed to evaluate the feasibility and effectiveness of intraoperative nerve monitoring (IONM) for reducing the recurrent laryngeal nerve (RLN) injury risk during central compartment lymph node dissection in endoscopic thyroidectomy of papillary thyroid carcinoma (PTC). METHODS: The prospective cohort consisted of 69 patients diagnosed with PTC undergoing endoscopic thyroidectomy via the areola approach with (n=42) or without IONM (n=27). Multiple logistic regression models were used to assess the association between IONM and postoperative temporary vocal cord palsy or number of retrieved lymph nodes. RESULTS: IONM was a protective factor against temporary RLN injury. IONM use was positively correlated with number of retrieved lymph nodes (ß=1.563, P=0.003). After adjustment for operation type, the result remained significant (ß=1.581, P<0.001). CONCLUSIONS: IONM use reduced the risk of temporary vocal cord palsy and increased the number of retrieved lymph nodes in endoscopic thyroidectomy via the areola approach for patients with PTC.

12.
Ecotoxicol Environ Saf ; 204: 110977, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32739673

RESUMO

Indirect oxidation induced by reactive free radicals, such as hydroxyl radical (HO), sulfate radical (SO4-) and carbonate radical (CO3-), plays an important or even crucial role in the degradation of micropollutants. Thus, the coadjutant degradation of phenacetin (PNT) by HO, SO4- and CO3-, as well as the synergistic effect of O2 on HO and HO2 were studied through mechanism, kinetics and toxicity evaluation. The results showed that the degradation of PNT was mainly caused by radical adduct formation (RAF) reaction (69% for Г, the same as below) and H atom transfer (HAT) reaction (31%) of HO. For the two inorganic anionic radicals, SO4- initiated PNT degradation by sequential radical addition-elimination (SRAE; 55%), HAT (28%) and single electron transfer (SET; 17%) reactions, while only by HAT reaction for CO3-. The total initial reaction rate constants of PNT by three radicals were in the order: SO4- > HO > CO3-. The kinetics of PNT degradation simulated by Kintecus program showed that UV/persulfate could degrade target compound more effectively than UV/H2O2 in ultrapure water. In the subsequent reaction of PNT with O2, HO and HO2, the formation of mono/di/tri-hydroxyl substitutions and unsaturated aldehydes/ketones/alcohols were confirmed. The results of toxicity assessment showed that the acute and chronic toxicity of most products to fish increased and to daphnia decreased, and acute toxicity to green algae decreased while chronic toxicity increased.


Assuntos
Carbonatos/toxicidade , Peróxido de Hidrogênio/toxicidade , Fenacetina/toxicidade , Sulfatos/toxicidade , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Animais , Carbonatos/química , Clorófitas/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Peixes , Peróxido de Hidrogênio/química , Íons/química , Íons/toxicidade , Cinética , Modelos Químicos , Oxigênio/química , Fenacetina/química , Sulfatos/química , Água/química
13.
J Hazard Mater ; 401: 123396, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32763693

RESUMO

Aromatic compounds (ACs) give a substantial contribution to the anthropogenic emissions of volatile organic compounds. Nitrate radicals (NO3) are significant oxidants in the lower troposphere during nighttime, with concentrations of (2-20) × 108 molecules cm-3. In this study, the tropospheric gas and liquid phase reactions of ACs with nitrate radical are investigated using theoretical computational methods, which can give a deep insight into the reaction mechanisms and kinetics. Results show that the reactivity of ACs with nitrate radicals decreases as the electron donating characteristics of the functional group on the ACs decrease, as ΔG≠ of the reaction with NO3 increasing from -1.17 to 17.84 kcal mol-1. The reaction of NO3 towards ACs in the aqueous phase is more preferable, with the atmospheric lifetime 0.07-1281 min. An assessment of the aquatic toxicity of ACs and their degradation products indicated that the risk of their degradation products remains and should be given more attention.

14.
Front Genet ; 11: 738, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765588

RESUMO

Background and Aims: Hirschsprung's disease (HSCR) is a rare genetically heterogeneous congenital disorder. A recent study based on whole genome sequencing demonstrated that common variants at four novel loci, which contained two intronic variants on CASQ2 and PLD1, and intergenic variants located between SLC4A7 and EOMES at 3p24.1, and between LINC01518 and LOC283028 at 10q11.21, were associated with HSCR susceptibility. To validate these associations with HSCR susceptibility, we performed a case-control study in a Han Chinese sample set. Methods: We selected four previously identified single nucleotide polymorphisms (SNPs) for replication, along with tag SNPs to cover the four associated regions. In total, 61 SNPs were genotyped in 420 HSCR patients and 1,665 healthy controls from the Han Chinese population. Results: None of the 14 tag SNPs in the CASQ2 gene region, including the previously associated rs9428225, showed an association with HSCR. Among the 24 tag SNPs from the SLC4A7-EOMES region at 3p24.1, rs2642925 [odds ratio (OR) = 1.41, 95% confidence interval (95% CI) = 1.10-1.79; P Additive = 0.007] and the previously associated SNP rs9851320 showed a suggestive association (OR = 1.22, 95% CI = 1.01-1.47; P Additive = 0.042). A non-synonymous SNP, rs2287579, in PLD1 showed a suggestive association with HSCR susceptibility (OR = 1.71, 95% CI = 1.18-2.46; P Additive = 0.004). Additionally, the previously associated PLD1 SNP rs12632766 showed a suggestive significance (OR = 1.20, 95% CI = 1.01-1.42, P Additive = 0.038). In the LINC01518-LOC283028 region at 10q11.21, three SNPs meet the study-wide significance threshold. Rs17153309 was the most associated SNP (OR = 1.60, 95% CI = 1.34-1.90; P Additive = 1.13 × 10-7). The previously associated SNP rs1414027 also showed significant association (OR = 1.43, 95% CI = 1.20-1.70, P Additive = 3.92 × 10-5). Two associated SNPs at 10q11.21 (rs1414027 and rs624804) were expression quantitative trait loci in digestive tract tissues from GTEx databases. Conclusions: Our results confirmed that variants of the LINC01518-LOC283028 region were associated with HSCR in the Han Chinese population. Additionally, the susceptibility of SNPs in the LINC01518-LOC283028 region were associated with the expression levels of nearby genes. These results provide new insight into the pathogenesis of HSCR.

15.
AJR Am J Roentgenol ; 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32845712

RESUMO

Background: Sinistral portal hypertension (SPH) is caused by an obstruction of the splenic vein and is a potential cause of upper gastrointestinal bleeding. Although splenic artery embolization (SAE) and splenic vein stenting (SVS) are accepted treatment options for SPH, their outcomes have not been compared directly. Objective: This retrospective study aimed to compare the outcomes of SVS and SAE for SPH-related gastrointestinal bleeding. Methods: The data of patients with SPH treated by interventional radiology between Jan 1, 2013 and Jun 1, 2019 and with at least 6-months of clinical follow-up were retrospectively identified from the hospital electronic database. Patients were divided into the SAE group (SAE alone), SVS-SAE group (SAE immediately after SVS failure according to the same procedure as in the SAE group), and SVS group (successful treatment with SVS). The patients' baseline characteristics and follow-up data were retrieved, and their clinical outcomes were compared. Results: Thirty-seven patients with SPH were included. A total of 11, 12, and 14 patients were classified into the SAE, SVS-SAE, and SVS groups, respectively. Rebleeding (e.g., hematemesis and/or melena) was significantly less common (P = 0.013) in the SVS group (7.1%, 1/14) than in the SAE and SVS-SAE groups combined (47.8%, 11/23). Splenectomy because of rebleeding was not significantly different (P = 0.630) between the SVS group (7.1%, 1/14) and the SAE and SVS-SAE groups combined (17.4%, 4/23). No interventional procedure-related mortality was observed during follow-up in any group. Conclusion: When feasible, SVS is a safe and effective treatment for SPH-related gastrointestinal bleeding that appears to better prevent rebleeding than SAE. Clinical Impact: When feasible, SVS should be recommended over SAE for the treatment of SPH-related upper gastrointestinal bleeding.

16.
Biomed Res Int ; 2020: 3708231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802843

RESUMO

Energy metabolic processes play important roles for tumor malignancy, indicating that related protein-coding genes and regulatory upstream genes (such as long noncoding RNAs (lncRNAs)) may represent potential biomarkers for prognostic prediction. This study will develop a new energy metabolism-related lncRNA-mRNA prognostic signature for lower-grade glioma (LGG) patients. A GSE4290 dataset obtained from Gene Expression Omnibus was used for screening the differentially expressed genes (DEGs) and lncRNAs (DELs). The Cancer Genome Atlas (TCGA) dataset was used as the prognosis training set, while the Chinese Glioma Genome Atlas (CGGA) was for the validation set. Energy metabolism-related genes were collected from the Molecular Signatures Database (MsigDB), and a coexpression network was established between energy metabolism-related DEGs and DELs to identify energy metabolism-related DELs. Least absolute shrinkage and selection operator (LASSO) analysis was performed to filter the prognostic signature which underwent survival analysis and nomogram construction. A total of 1613 DEGs and 37 DELs were identified between LGG and normal brain tissues. One hundred and ten DEGs were overlapped with energy metabolism-related genes. Twenty-seven DELs could coexpress with 67 metabolism-related DEGs. LASSO regression analysis showed that 9 genes in the coexpression network were the optimal signature and used to construct the risk score. Kaplan-Meier curve analysis showed that patients with a high risk score had significantly worse OS than those with a low risk score (TCGA: HR = 3.192, 95%CI = 2.182-4.670; CGGA: HR = 1.922, 95%CI = 1.431-2.583). The predictive accuracy of the risk score was also high according to the AUC of the ROC curve (TCGA: 0.827; CGGA: 0.806). Multivariate Cox regression analyses revealed age, IDH1 mutation, and risk score as independent prognostic factors, and thus, a prognostic nomogram was established based on these three variables. The excellent prognostic performance of the nomogram was confirmed by calibration and discrimination analyses. In conclusion, our findings provided a new biomarker for the stratification of LGG patients with poor prognosis.

17.
BMC Cancer ; 20(1): 801, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831061

RESUMO

BACKGROUND: The main treatment methods for early gastric cancer (EGC) include endoscopic submucosal dissection (ESD) and radical gastrectomy. However, appropriate treatment for patients who exceed the absolute indications for ESD remains unestablished. In China, evidence-based medicine for the expanding indications of ESD and accurate diagnostic staging for EGC patients are lacking. Thus, clinical studies involving Chinese patients with EGC are necessary to select appropriate treatment options and promote China's expanded indications for ESD and diagnostic staging scheme. METHODS: This is a multicenter, ambispective, observational, open-cohort study that is expected to enroll 554 patients with EGC. The study was launched in May 2018 and is scheduled to end in March 2022. All enrolled patients should meet the inclusion criteria. Case report forms and electronic data capture systems are used to obtain clinical data, which includes demographic information, results of perioperative blood- and auxiliary examinations, surgical information, results of postoperative pathology, and the outcomes of postoperative recovery and follow-up. Patients are followed up every 6 months after surgery for a minimum of 5 years. The primary endpoint is the rate of lymph node metastasis (LNM), whereas the secondary endpoints include the following: consistency, sensitivity, and specificity of the results of preoperative examinations and postoperative pathology; cut-off values for LNM; logistic regression model of expanded indications for ESD; and incidence of postoperative complications within the 30-day and 5-year relapse-free survival rates. DISCUSSION: This study will explore and evaluate expanded indications for ESD that match the characteristics of the Chinese population in patients with EGC and will introduce a related staging procedure and examination scheme that is appropriate for China. Ethical approval was obtained from all participating centers. The findings are expected to be disseminated through publications or presentations and will facilitate clinical decision-making in EGC. TRIAL REGISTRATION: The name of the registry is ChiCTR. It was registered on May 9, 2018, with the registration number ( ChiCTR1800016084 ). The clinical trial was launched in May 2018 and will end in March 2022, with enrollment to be completed by December 2021. Trial status: Ongoing.

18.
Medicine (Baltimore) ; 99(34): e21865, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846839

RESUMO

RATIONALE: Recently, patients with COVID-19 who showed persistently positive SARS-CoV-2 nucleic acid test results despite resolved clinical symptoms have attracted a lot of attention. We report the case of a patient with mild symptoms of coronavirus disease (COVID-19), who achieved clinical recovery but showed persistently positive SARS-CoV-2 nucleic acid test results until Day 92 after disease onset. PATIENT CONCERNS: The patient is a 50-year-old man with mild symptoms of coronavirus disease (COVID-19). DIAGNOSES: COVID-19 pneumonia. INTERVENTIONS: The patient was quarantined for 105 days. Of these, inpatient quarantine lasted for 75 days. When the nucleic acid test results were negative for 3 consecutive days, the patient was discharged at Day 75 after disease onset. During this period, multiple samples were collected from the patient's body surface, the surrounding environment, and physical surfaces, but none of these tested positive for SARS-CoV-2. These samples included those from anal swabs, hands, inner surface of mask, cell phone, bed rails, floor around the bed, and toilet bowl surface. However, nucleic acid retest results on Day 80 and Day 92 after disease onset were positive for SARS-CoV-2 nucleic acids. OUTCOMES: The patient continued with quarantine and observation at home. After the test results on Days 101 and 105 after disease onset were negative, quarantine was terminated at last. LESSONS: Per our knowledge, this is the longest known time that a patient has tested positive for SARS-CoV-2 nucleic acids. No symptoms were observed during follow-up. During hospitalization, the SARS-CoV-2 nucleic acid positivity was not observed in samples from the body surface and surrounding environment, and no verified transmission event occurred during the quarantine at home. After undergoing clinical recovery a minority of patients with COVID-19 have shown long-term positive results for the presence of the SARS-CoV-2 nucleic acid. This has provided new understanding and research directions for coronavirus infection. Long-term follow-up and quarantine measures have been employed for such patients. Further studies are required to analyze potential infectivity in such patients and determine whether more effective antiviral drugs or regimens to enable these patients to completely clear viral infection should be researched.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico , Pandemias , Pneumonia Viral/tratamento farmacológico , Fatores de Tempo
19.
Sci Total Environ ; 750: 141685, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32862004

RESUMO

Human exposure to bisphenol A (BPA) is unavoidable in daily life. Recently, research has showen that BPA could induce oxidative imbalance, thereby causing reproductive toxicity and liver dysfunction. Accumulated evidence has demonstrated that metformin possesses strong anti-oxidative properties. This study aimed to study the mechanism underlying the hepatic-protective effect of metformin on liver injury induced by BPA in rats via the UPLC-MS/MS metabolomics approach. Forty-two male rats were randomly divided into six groups (n = 7), namely the saline group (control), the corn oil group (vehicle), the metformin group (Met), the bisphenol A group (BPA), the bisphenol A and metformin group (BPA + Met), and the bisphenol A and diammonium glycyrrhizinate (positive control) group (BPA + DG). Serum was collected for biochemical analysis and metabolomics, and liver tissue was collected for histopathology and metabolomics in each group. We found that metformin could significantly reduce the levels of liver function enzymes (ALT, AST and GGT) and ameliorate inflammatory cell infiltration and hepatocyte necrosis induced by BPA. On the other hand, metformin could significantly enhance the total antioxidant capacity in BPA rats. Notably, metabolomics data indicated that the principal altered metabolic pathways based on the 26 differential metabolites in liver tissue, and 21 in serum among vehicle, BPA and BPA + Met groups, respectively, including cysteine and methionine metabolism, glutathione metabolism, and arginine biosynthesis and purine metabolism. Additionally, metformin significantly increased cystathionine ß synthase (CBS) and cystathionine γ lyase (CSE), thus reducing serum levels of homocysteine and increasing hepatic levels of cysteine and glutathione in BPA-treated rats. Overall, this study's results provided new insights into the role and mechanism of metformin in BPA-induced liver injury in rats.

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