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1.
Sci Rep ; 11(1): 7419, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795757

RESUMO

Recent studies on water retention behaviour of biochar amended soil rarely considers the effect of pyrolysis temperature and also feedstock type into account. It is well known that pyrolysis temperature and feedstock type influences the physical and chemical properties of biochar due to stagewise decomposition of structure and chemical bonds. Further, soil density, which is in a loose state (in agricultural applications) and dense (in geo-environmental engineering applications) can also influence water retention behaviour of biochar amended soils. The major objective of this study is to investigate the water retention properties of soil amended with three different biochars in both loose and dense state. The biochars, i.e. water hyacinth biochar (WHB), chicken manure biochar (CMB) and wood biochar (WB) were produced in-house at different pyrolysis temperature. After then, biochars at 5% and 10% (w/w%) were amended to the soil. Water retention behaviour (soil suction and gravimetric water content) was studied under drying and wetting cycle simulated by varying relative humidity (RH, 50-90%). Results show that 10% WHB produced at 300 °C were found to possess highest water retention. CMB is found to possess higher water retention than WB for 10% amendment ratio. In general, the addition of three biochars (at both 300 °C and 600 °C) at 10% (w/w) significantly improved the water retention at all suction ranges in both loose and dense compaction state as compared to that of the bare soil. The adsorption (wetting) and desorption (drying) capacity of biochar amended soils is constant at corresponding RH.

2.
Brief Bioinform ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33834194

RESUMO

Transcriptional regulation is associated with complicated mechanisms including multiple molecular interactions and collaborative drive. Long noncoding RNAs (lncRNAs) have highly structured characteristics and play vital roles in the regulation of transcription in organisms. However, the specific contributions of conformation feature and underlying molecular mechanisms are still unclear. In the present paper, a hypothesis regarding molecular structure effect is presented, which proposes that lncRNAs fold into a complex spatial architecture and act as a skeleton to recruit transcription factors (TF) targeted binding, and which is involved in cooperative regulation. A candidate set of TF-lncRNA coregulation was constructed, and it was found that structural accessibility affected molecular binding force. In addition, transcription factor binding site (TFBS) regions of myopia-related lncRNA transcripts were disturbed, and it was discovered that base mutations affected the occurrence of significant molecular allosteric changes in important elements and variable splicing regions, mediating the onset and development of myopia. The results originated from structureomics and interactionomics and created conditions for systematic research on the mechanisms of structure-mediated TF-lncRNA coregulation in transcriptional regulation. Finally, these findings will help further the understanding of key regulatory roles of molecular allostery in cell physiological and pathological processes.

3.
Org Lett ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33793241

RESUMO

The geminal difluorocyclobutane core is a valuable structural element in medicinal chemistry. Strategies for gem-difluorocyclobutanes, especially the 2-substituted cases, are limiting and often suffer from harsh reaction conditions. Reported herein is a migratory gem-difluorination of aryl-substituted methylenecycloproanes (MCPs) for the synthesis of 2-arylsubstituted gem-difluorocyclobutanes. Commercially available Selectfluor (F-TEDA-BF4) and Py·HF were used as the fluorine sources. The protocol proceeds via a Wagner-Meerwein rearrangement with mild reaction conditions, good functional group tolerance, and moderate to good yields. The product could be readily transformed to gem-difluorocyclobutane-containing carboxylic acid, amine, and alcohol, all of which are useful building blocks for biologically active molecule synthesis.

4.
BMC Cancer ; 21(1): 217, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653301

RESUMO

BACKGROUND: Certain sequences of genomic mutations can lead to cancer formation and affect treatment outcomes and drug resistance. We constructed a cancer evolutionary tree using bulk-targeted deep sequencing to explore the impact of sequential and co-occurring somatic mutations on patients with stage III colorectal cancer (CRC). METHODS: A total of 108 stage III CRC patients from National Cheng Kung University Hospital (NCKUH) were recruited for this study between Jan. 2014 and Jan. 2019. Clinical information and tumor-targeted deep sequencing data were collected. Phylogenetic trees were reconstructed for evolutionary trajectories. We used a machine learning model for survival analysis. RESULTS: Six sequential somatic mutations stratified patients into seven subgroups based on survival. Patients carrying sequential germline followed by DNA damage response-related ATM or BRCA2 somatic mutations or non-TP53, APC somatic mutations had a better outcome than those without such mutations. The 4-year recurrence-free survival (RFS) probability was 88% in the low-risk group (G1) and 46% in the high-risk group (G2) (log-rank p-value 2e-05). The predictive efficacy by the area under the curve (AUC) was 0.73, 0.7, 0.797, and 0.88 at 2, 4, 6, and 8 years, respectively. The mutation status of mismatch repair (MMR) genes was not associated with RFS. Different genomic features were found between the groups. The orders of APC, KRAS and APC, BRCA2 sequential somatic mutations were associated with clinical outcomes. The occurrence of somatic mutations in BRCA2, such as TP53 somatic mutations, affected recurrence-free survival. CONCLUSIONS: According to the evolution model, DNA damage response (DDR)-related ATM or BRCA2 somatic mutations are promising biomarkers for assessing the response of stage III CRC patients to oxaliplatin-based chemotherapy. The sequential order and co-occurring DDR somatic mutations are associated with recurrence-free survival.

5.
Nanomaterials (Basel) ; 11(3)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673658

RESUMO

We present four designs of tunable split-disk metamaterial (SDM) absorbers. They consist of a bottom gold (Au) mirror layer anchored on Si substrate and a suspended-top SDM nanostructure with one, two, three, and four splits named SDM-1, SDM-2, SDM-3, and SDM-4, respectively. By tailoring the geometrical configurations, the four SDMs exhibit different tunable absorption resonances spanning from 1.5 µm to 5.0 µm wavelength range. The resonances of absorption spectra can be tuned in the range of 320 nm, and the absorption intensities become lower by increasing the gaps of the air insulator layer. To increase the sensitivity of the proposed devices, SDMs exhibit high sensitivities of 3312 nm/RIU (refractive index unit, RIU), 3362 nm/RIU, 3342 nm/RIU, and 3567 nm/RIU for SDM-1, SDM-2, SDM-3, and SDM-4, respectively. The highest correlation coefficient is 0.99999. This study paves the way to the possibility of optical gas sensors and biosensors with high sensitivity.

6.
FASEB J ; 35(4): e21485, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33709562

RESUMO

Cognitive dysfunction often occurs in diabetes mellitus patients. This study aimed to investigate the efficacy of melatonin (MLT) in improving diabetes-associated cognitive decline and the underlying mechanism involved. Type 2 diabetic mice and palmitic acid (PA)-stimulated BV-2 cells were treated by MLT, and the potential mechanisms among MLT, cognition, and autophagy were explored. The results showed that type 2 diabetic mice showed obvious learning and memory impairments in the Morris water maze test compared with normal controls, which could be ameliorated by MLT treatment. Meanwhile, MLT administration significantly improved neuroinflammation and regulated microglial apoptosis. Furthermore, autophagy inhibitor 3-methyladenine (3-MA) increased the microglial inflammation and apoptosis, indicating that the treatment effect of MLT was mediated by autophagy. Lastly, MLT treatment significantly decreased the levels of toll-like receptors 4 (TLR4), phosphorylated-protein kinase B (Akt), and phosphorylated-mechanistic target of rapamycin (mTOR), indicating that blocking TLR4/Akt/mTOR pathway might be an underlying basis for the anti-inflammatory and anti-apoptosis effects of MLT. Collectively, our study suggested that MLT could improve learning and memory in type 2 diabetic mice by activating autophagy via the TLR4/Akt/mTOR pathway, thereby inhibiting neuroinflammation and microglial apoptosis.

7.
Zhongguo Zhong Yao Za Zhi ; 46(3): 638-644, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645031

RESUMO

According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 µmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.


Assuntos
Carboxilesterase , Carboxilesterase/antagonistas & inibidores , Carboxilesterase/metabolismo , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas
8.
Oncol Rep ; 45(3): 1033-1043, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33650658

RESUMO

Bladder cancer is a common tumor type of the urinary system, which has high levels of morbidity and mortality. The first­line treatment is cisplatin­based combination chemotherapy, but a significant proportion of patients relapse due to the development of drug resistance. Therapy­induced senescence can act as a 'back­up' response to chemotherapy in cancer types that are resistant to apoptosis­based anticancer therapies. The circadian clock serves an important role in drug resistance and cellular senescence. The aim of the present study was to investigate the regulatory effect of the circadian clock on paclitaxel (PTX)­induced senescence in cisplatin­resistant bladder cancer cells. Cisplatin­resistant bladder cancer cells were established via long­term cisplatin incubation. PTX induced apparent senescence in bladder cancer cells as demonstrated via SA­ß­Gal staining, but this was not observed in the cisplatin­resistant cells. The cisplatin­resistant cells entered into a quiescent state with prolonged circadian rhythm under acute PTX stress. It was identified that the circadian protein cryptochrome1 (CRY1) accumulated in these quiescent cisplatin­resistant cells, and that CRY1 knockdown restored PTX­induced senescence. Mechanistically, CRY1 promoted p53 degradation via increasing the binding of p53 with its ubiquitin E3 ligase MDM2 proto­oncogene. These data suggested that the accumulated CRY1 in cisplatin­resistant cells could prevent PTX­induced senescence by promoting p53 degradation.

9.
Chest ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33745993

RESUMO

BACKGROUND: Visceral pleural invasion (VPI) with PL1 or PL2 increases the T classification from T1 to T2 in non-small cell lung cancers (NSCLCs) 3 cm or less. We proposed a modified T classification based on VPI to guide adjuvant therapy. RESEARCH QUESTION: Is it reasonable to upstage PL1-positive cases from T1 to T2 for NSCLCs 3 cm or less? STUDY DESIGN AND METHODS: In total, 1,055 resected NSCLC patients were retrospectively included. Tumor sections were re-stained with hematoxylin and eosin stain and Vitoria blue's elastic stain for the elastic layer. Disease-free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Subgroup analysis and a Cox proportional hazards model were used to further determine the impact of VPI on survival. RESULTS: The extent of VPI was diagnosed as PL0 in 824 patients, PL1 in 133 patients, and PL2 in 98 patients. The 5-year DFS rates of patients with PL0, PL1, and PL2 were 62.6%, 60.2%, and 28.8% (P<0.01), respectively, while the corresponding 5-year OS rates were 78.6%, 74.4%, and 50.0% (P<0.01). As predicted, the DFS and OS of PL2 patients were much worse than those of PL0 (P<0.01) and PL1 (P<0.01) patients. However, both the DFS and OS of PL0 and PL1 patients were comparable (DFS, P=0.198; OS, P=0.150). For node-negative cases, the DFS and OS of PL0 and PL1 patients were also comparable (DFS, P=0.468; OS, P=0.388), but PL2 patients again had much worse DFS and OS than PL0 (P<0.01) and PL1 (P<0.01) patients. Multivariable analyses suggested that PL2, together with node positivity and poor cell differentiation, was an independent adverse prognostic factor. INTERPRETATION: In NSCLCs 3 cm or less, tumors with PL1 should remain defined as T1, not T2. Overtreatment by adjuvant chemotherapy in node-negative NSCLCs 3 cm or less might be avoided in PL1 cases.

10.
Theranostics ; 11(10): 4672-4687, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754020

RESUMO

Rationale: Oxaliplatin-induced peripheral neuropathy (OIPN) is a common adverse effect that causes delayed treatment and poor prognosis among colorectal cancer (CRC) patients. However, its mechanism remains elusive, and no effective treatment is available. Methods: We employed a prospective cohort study of adult patients with pathologically confirmed stage III CRC receiving adjuvant chemotherapy with an oxaliplatin-based regimen for investigating OIPN. To further validate the clinical manifestations and identify a potential therapeutic strategy, animal models, and in vitro studies on the mechanism of OIPN were applied. Results: Our work found that (1) consistent with clinical findings, OIPN was observed in animal models. Targeting the enzymatic activity of cathepsin S (CTSS) by pharmacological blockade and gene deficiency strategy alleviates the manifestations of OIPN. (2) Oxaliplatin treatment increases CTSS expression by enhancing cytosol translocation of interferon response factor 1 (IRF1), which then facilitates STIM-dependent store-operated Ca2+ entry homeostasis. (3) The cytokine array demonstrated an increase in anti-inflammatory cytokines and suppression of proinflammatory cytokines in mice treated with RJW-58. (4) Mechanistically, inhibiting CTSS facilitated olfactory receptors transcription factor 1 release from P300/CBP binding, which enhanced binding to the interleukin-10 (IL-10) promoter region, driving IL-10 downstream signaling pathway. (5) Serum CTSS expression is increased in CRC patients with oxaliplatin-induced neurotoxicity. Conclusions: We highlighted the critical role of CTSS in OIPN, which provides a therapeutic strategy for the common adverse side effects of oxaliplatin.

11.
Artigo em Chinês | MEDLINE | ID: mdl-33540999

RESUMO

Objective:The aim of this stusy is to study the effect of endoscopic surgery quality on the recurrence of nasal polyps. Methods:A total of 32 patients(64 sides) with recurrent nasal polyps were collected from December 2016 to June 2018, all of which were bilateral type Ⅱ diffuse nasal polyps in stage 3. According to the post-operative pathological results, patients were divided into eosinophilic nasal polyps group(EOS) and non-eosinophilic nasal polyps group(NEOS). All patients underwent sinus CT scan and three-dimensional reconstruction, combined with the sinus CT image performance and intraoperative findings, the quality of the patients' previous endoscopic sinus surgery was analyzed, and the CT L-M scores of sinuses before and after reoperation were compared between the two groups. Endoscopic L-K score, nasal symptoms VAS score, quality of life Snot-20 score. Results:Among 32 patients with recurrent nasal polyps, 17 cases (53.1%) of EOS nasal polyps were confirmed pathologically after surgery, and 15 cases (46.9%) of NEOS nasal polyps were confirmed. After the previous operation, the patient still has 60 sides(93.8%) of ethmoidal cells or ethmoidal septum, 56 sides(87.5%) of bone hyperplasia, 50 sides(78.1%) of bones in frontal recess air-cell or bone air-cell, and nasal cavity adhesion there were 10 sides(15.6%), residual uncinate process 8(12.5%), improper treatment of maxillary sinus ostia or atresia were 6(9.4%), sphenoid sinus not open or atresia were 8(12.5%), nasal septal deviation untreated were 4 cases(12.5%), 1 case(3.1%) had recurrence without ethmoidal cells and residual bone interval. Patients both in the EOS group or the NEOS group were followed up with L-M score, L-K score, VAS score, and Snot-20 score after surgery, the result were significantly improved compared with the preoperative results. After follow-up of 1.5-3 years, 25 cases of polyps were completely controlled and 7 cases were partially controlled. Among them, 2 cases of EOS nasal polyps and asthma patients still had some polypoid changes in local mucosa one year after operation and was currently under medication control. Conclusion:Although the recurrence of nasal polyps is closely related to its intrinsic type, the technique of endoscopic surgery is also an important factor affecting the recurrence of nasal polyps. For patients with bilateral symmetric diffuse nasal polyps, high-quality sinus surgery of first time combined with standardized follow-up can reduce the recurrence rate of nasal polyps and prolong the relapse time.


Assuntos
Pólipos Nasais , Sinusite , Doença Crônica , Endoscopia , Humanos , Pólipos Nasais/cirurgia , Qualidade de Vida , Recidiva
12.
BMC Gastroenterol ; 21(1): 59, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568088

RESUMO

BACKGROUND: To explore the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients with stage IB/IIA, using a prognostic score (PS). METHODS: Stage IB/IIA ESCC patients who underwent esophagectomy from 1999 to 2010 were included. We retrospectively recruited 153 patients and extracted their medical records. Moreover, we analyzed the programmed death ligand-1 (PD-L1) expression of their paraffin tissue. The cohort were randomly divided into a training group (N = 123) and a validation group (N = 30). We selected overall survival (OS) as observed endpoint. Prognostic factors with a multivariable two-sided P < 0.05 met standard of covariate inclusion. RESULTS: Univariable and multivariable analyses identified pTNM stage, the number of lymph nodes (NLNs) and PD-L1 expression as independent OS predictors. Primary prognostic score which comprised above three covariates adversely related with OS in two cohorts. PS discrimination of OS was comparable between the training and internal validation cohorts (C-index = 0.774 and 0.801, respectively). In addition, the PS system had an advantage over pTNM stage in the identification of high-risk patients (C-index = 0.774 vs. C-index = 0.570, P < 0.001). Based on PS cutoff, training and validation datasets generated low-risk and high-risk groups with different OS. Our three-factor PS predicted OS (low-risk subgroup vs. high-risk subgroup 60-month OS, 74% vs. 23% for training cohort and 83% vs. 45% for validation cohort). CONCLUSION: Our study suggested a PS for significant clinical stratification of IB/IIA ESCC to screen out subgroups with poor prognosis.

13.
Signal Transduct Target Ther ; 6(1): 64, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33589597

RESUMO

Genomic sequencing analysis of tumors provides potential molecular therapeutic targets for precision medicine. However, identifying a key driver gene or mutation that can be used for hepatocellular carcinoma (HCC) treatment remains difficult. Here, we performed whole-exome sequencing on genomic DNA obtained from six pairs of HCC and adjacent tissues and identified two novel somatic mutations of UBE2S (p. Gly57Ala and p. Lys63Asn). Predictions of the functional effects of the mutations showed that two amino-acid substitutions were potentially deleterious. Further, we observed that wild-type UBE2S, especially in the nucleus, was significantly higher in HCC tissues than that in adjacent tissues and closely related to the clinicopathological features of patients with HCC. Functional assays revealed that overexpression of UBE2S promoted the proliferation, invasion, metastasis, and G1/S phase transition of HCC cells in vitro, and promoted the tumor growth significantly in vivo. Mechanistically, UBE2S interacted with TRIM28 in the nucleus, both together enhanced the ubiquitination of p27 to facilitate its degradation and cell cycle progression. Most importantly, the small-molecule cephalomannine was found by a luciferase-based sensitive high-throughput screen (HTS) to inhibit UBE2S expression and significantly attenuate HCC progression in vitro and in vivo, which may represent a promising strategy for HCC therapy.

14.
Neuroradiology ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33611621

RESUMO

PURPOSE: The importance of supplementary motor area (SMA) for motor function and compensation for primary motor area (M1) has received increased attention. METHODS: We used diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS) to evaluate structure and function of corticospinal projection originating from SMA. Fibers of corticospinal projection originating from M1 (CST) and SMA (ACST) were analyzed. ACST originating from mesial SMA area formed separate white matter bundles leaving the anterior part of M1 area, which then entered the posterior limb of the internal capsule. Projection and overlap of both CST and ACST were detected on medulla. RESULTS: Fibers of contralesional ACST were more than that of ipsilesional ACST in patients with SMA tumors (p<0.05). In patients with SMA tumor, all patients experienced temporary akinesia postoperatively. Seven hundred forty-one fibers of ipsilateral ACST and no fibers of ipsilateral CST were detected in the patient with M1 glioma, while most of contralateral limb movement was preserved. MEP could be evoked by stimulating SMA area as well as M1 area. ACST originated from SMA area and projected to the medial medulla. CONCLUSION: SMA area and ACST integrity contributed to contralateral motor function and were a compensation for M1 lesion and damaged CST.

15.
Genome ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33617368

RESUMO

The purpose of this study was to explore the relationship between autophagy and DNA methylation, and to identify key genes for autophagy-regulated thyroid cancer progression. We divided patients with thyroid cancer into high-autophagy score (AS) group and low-AS group based on their AS values. The results found that AS was associated with the distant metastasis of thyroid cancer, and adversely affected prognosis. Then, we screened 359 differently expressed genes (DEGs) with DNA methylation status consistent with gene expression change. Functional classification analysis demonstrated that the 359 DEGs consistent with DNA methylation status were significantly involved in adhesion, migration and differentiation of immune cells. To further screen the key genes in the autophagy-related thyroid cancer progression, we constructed a protein-protein interactions (PPI) network and performed prognostic analysis. B cell linker (BLNK) was identified as the key potential gene affecting autophagy-related thyroid cancer progression. Finally, we verified that BLNK promoted the proliferation of thyroid cancer cells, and BLNK expression was regulated by DNA methylation. Our research provides a new perspective for exploring the relationship between autophagy and DNA methylation during the progression of thyroid cancer, and provides a new target for the treatment of metastatic thyroid cancer.

16.
Ann Thorac Surg ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33621558

RESUMO

BACKGROUND: The effectiveness and survival benefit of minimally invasive esophagectomy compared to open esophagectomy (OE) remain controversial. The aim of this study was to evaluate the safety, efficacy and oncological outcomes of McKeown's total minimally invasive esophagectomy (tMIE) and McKeown's OE in the treatment of patients with esophageal squamous cell carcinoma. METHODS: A series of consecutive 917 patients (306 OE and 611 tMIE) who underwent McKeown's esophagectomy for esophageal squamous cell carcinoma in the Department of Thoracic Surgery at Sun Yat-sen University Cancer Center from January 2011 to December 2016 were evaluated. We performed propensity matching between the tMIE and OE groups on the basis of estimated propensity scores for each patient. RESULTS: After propensity-matched analysis, 288 patients were selected from each group. The rate of postoperative complications, such as pneumonia, respiratory insufficiency, cervical anastomotic leakage and wound infection, in the OE group was significantly higher than that in the tMIE group. Intraoperative blood loss and operative duration were not significantly different between the matched groups, whereas the tMIE group had a shorter length of intensive care unit stay and postoperative hospital stay than the OE group. The R0 resection rate and the number of lymph nodes harvested were not significantly different between groups. There was no significant difference in median overall survival between the two groups after matching. CONCLUSIONS: McKeown's tMIE was shown to be a safe and effective procedure with long-term survival comparable to that of OE for the patients with esophageal squamous cell carcinoma.

18.
Hum Genomics ; 15(1): 3, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431054

RESUMO

BACKGROUND: Functional disruptions by large germline genomic structural variants in susceptible genes are known risks for cancer. We used deletion structural variants (DSVs) generated from germline whole-genome sequencing (WGS) and DSV immune-related association tumor microenvironment (TME) to predict cancer risk and prognosis. METHODS: We investigated the contribution of germline DSVs to cancer susceptibility and prognosis by silicon and causal inference models. DSVs in germline WGS data were generated from the blood samples of 192 cancer and 499 non-cancer subjects. Clinical information, including family cancer history (FCH), was obtained from the National Cheng Kung University Hospital and Taiwan Biobank. Ninety-nine colorectal cancer (CRC) patients had immune response gene expression data. We used joint calling tools and an attention-weighted model to build the cancer risk predictive model and identify DSVs in familial cancer. The survival support vector machine (survival-SVM) was used to select prognostic DSVs. RESULTS: We identified 671 DSVs that could predict cancer risk. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of the attention-weighted model was 0.71. The 3 most frequent DSV genes observed in cancer patients were identified as ADCY9, AURKAPS1, and RAB3GAP2 (p < 0.05). The DSVs in SGSM2 and LHFPL3 were relevant to colorectal cancer. We found a higher incidence of FCH in cancer patients than in non-cancer subjects (p < 0.05). SMYD3 and NKD2DSV genes were associated with cancer patients with FCH (p < 0.05). We identified 65 immune-associated DSV markers for assessing cancer prognosis (p < 0.05). The functional protein of MUC4 DSV gene interacted with MAGE1 expression, according to the STRING database. The causal inference model showed that deleting the CEP72 DSV gene affect the recurrence-free survival (RFS) of IFIT1 expression. CONCLUSIONS: We established an explainable attention-weighted model for cancer risk prediction and used the survival-SVM for prognostic stratification by using germline DSVs and immune gene expression datasets. Comprehensive assessments of germline DSVs can predict the cancer risk and clinical outcome of colon cancer patients.

19.
PLoS One ; 16(1): e0245769, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33493221

RESUMO

Smoking is the leading preventable cause of death and disability from cancer in China. To provide a scientific basis for tobacco control strategies and measures, this study investigated cancer deaths attributed to smoking from 2005 to 2017 and predicted mortality trends from 2018 to 2020 in Qingdao. We used time series analysis to evaluate the number of deaths attributed to smoking among residents over 35 years old in Qingdao and predicted mortality trends. The number of cancer deaths attributed to smoking in Qingdao from 2005 to 2016 was between 170 and 407, showing an upward trend and a certain periodicity. The best model is the ARIMA (2,1,0)×(3,1,0)12, with the lowest BIC (6.640) and the highest stationary R2 (0.500). The predicted cancer deaths curve attributed to smoking in 2017 is consistent with the actual curve, with an average relative error of 5.74%. Applying this model to further predict the number of cancer deaths attributed to smoking in Qingdao from January 2018 to December 2020, the predicted results were 5,249, 5,423 and 6,048, respectively. The findings emphasized the need to further strengthen tobacco control measures to reduce the burden of disease caused by tobacco.

20.
J Med Virol ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33448453

RESUMO

The CRF01_AE and CRF07_BC clades dominate the human immunodeficiency virus (HIV) epidemics in China. Both clades have been identified in the men who have sex with men (MSM) population in Guangdong province, raising a serious concern of possible complex recombination events ahead. Here, we report the first case of CRF01_AE/CRF07_BC recombinant sampled from a MSM patient in southern China. The genomic structure of this case is a mosaic with some regions resembling the CRF01_AE and CRF07_BC clades. Our phylogenetic analyses show that the two parental lineages of this recombinant virus were mainly found in the MSM population. This case has a different genomic composition compared with other recombinants descended from the same parental clades CRF01_AE and CRF07_BC. Our finding suggests that the MSM populations have become a hotspot for expanding viral diversity through the viral recombination mechanism. Therefore, further epidemiologic surveillance and monitoring should be conducted within the MSM populations to help advance our knowledge of viral transmission mechanisms. Additionally, these measures will serve to enhance the control and prevention of HIV/acquired immunodeficiency syndrome in China.

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