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1.
Neural Regen Res ; 16(2): 264-269, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32859773

RESUMO

More than half of stroke patients live with different levels of motor dysfunction after receiving routine rehabilitation treatments. Therefore, new rehabilitation technologies are urgently needed as auxiliary treatments for motor rehabilitation. Based on routine rehabilitation treatments, a new intelligent rehabilitation platform has been developed for accurate evaluation of function and rehabilitation training. The emerging intelligent rehabilitation techniques can promote the development of motor function rehabilitation in terms of informatization, standardization, and intelligence. Traditional assessment methods are mostly subjective, depending on the experience and expertise of clinicians, and lack standardization and precision. It is therefore difficult to track functional changes during the rehabilitation process. Emerging intelligent rehabilitation techniques provide objective and accurate functional assessment for stroke patients that can promote improvement of clinical guidance for treatment. Artificial intelligence and neural networks play a critical role in intelligent rehabilitation. Multiple novel techniques, such as brain-computer interfaces, virtual reality, neural circuit-magnetic stimulation, and robot-assisted therapy, have been widely used in the clinic. This review summarizes the emerging intelligent rehabilitation techniques for the evaluation and treatment of motor dysfunction caused by nervous system diseases.

2.
J Cancer Res Ther ; 16(5): 960-966, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004735

RESUMO

As a treatment option for cancer, thermal ablation has satisfactory effects on many types of solid tumors (such as liver and renal cancers). However, its clinical applications for the treatment of thyroid nodules and metastatic cervical lymph nodes are still under debate both in China and abroad. In 2015, the "Zhejiang Expert consensus on thermal ablation for thyroid benign nodules, microcarcinoma, and metastatic cervical lymph nodes (2015 edition)," was released by the Thyroid Cancer Committee of Zhejiang Anti-Cancer Association, China. To further standardize the application of thermal ablation for thyroid tumors, the Thyroid Tumor Ablation Experts Group of Chinese Medical Doctor Association has organized many seminars and finally produced a consensus to formulate the "Expert consensus workshop report: Guidelines for thermal ablation of thyroid tumors (2019 edition)."

3.
J Cancer Res Ther ; 16(5): 1056-1062, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004747

RESUMO

Context: We analyzed the clinical features and ultrasound image features of follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). Aims: This study aimed to identify ultrasonographic differences and correlations between FTC and FTA. Meanwhile, ultrasonographic manifestations of thyroid follicular tumor were also retrospectively analyzed. Settings and Design: Using pathological results as the gold standard, the clinical and ultrasonic image characteristics of FTA and FTC were statistically analyzed, and the differences were analyzed. Materials and Methods: A total of 304 patients who were diagnosed with FTC or FTA by pathology after thyroidectomy from March 2009 to March 2018 were enrolled in this study. Their ultrasonic images were analyzed; image features were extracted and correlation analyses for these features were conducted. Differences in ultrasonic images between FTC and FTA were also compared. Statistical Analysis Used: Independent sample t-test; Wilcoxon rank sum test; A Chi-square test: Univariate and multivariate logistic regression analyses. Results: When performing ultrasound diagnosis, attention should be paid to identify FTC and FTA in terms of age, nodular goiter conditions, nodular boundary conditions, internal echo, calcification, blood flow signals, thyroid imaging reporting and data system (TI-RADS) grading and cystic solidity conditions. Moreover, a multivariate logistic regression showed that the boundaries were unclear, and cystic degeneration, TI-RADS, hypoecho, nodular goiter, macrocalcification and microcalcification were associated with FTC. Among them, macrocalcification is a protective factor for thyroid follicular tumors, and other indicators are risk factors. Conclusion: Ultrasound can provide valuable information for the identification of follicular neoplasms, but further research in this area is still necessary.

4.
Micromachines (Basel) ; 11(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33008069

RESUMO

Automobile and household appliance panels require steel strips with extremely high-quality surfaces. Therefore, an in-depth study of the surface topography transfer of the steel strip during the rolling process is of considerable significance for improving product quality. In this study, the scale-invariant feature transform (SIFT) algorithm is used to realize the large-field stitching and the correspondence measurement of the surface topography of the roll and strip. The surface topography transfer mechanism and microconvex change law during cold rolling are revealed. Further analysis is conducted regarding the effects of different reduction rates and the initial surface topography of the roll on the formation of strip surface topography. Experimental results reveal that the furrow phenomenon occurs during the rolling process owing to the backward slip effect but is eliminated by the elastoplastic deformation of the matrix and the forward slip action. No furrow occurred along the width direction of the strip. With an increase in the rolling reduction rate, the transfer rate increases, and the strip surface topography is closer to the roll surface topography. Under the same rolling roughness condition and a small reduction rate (5%), the transfer degree increases remarkably with a rise in the reduction rate and increases slowly as the reduction rate continues to grow (from 7% to 10%). This study serves as a theoretical basis for the subsequent improvement of the surface quality of cold rolled strips.

5.
Chin Med J (Engl) ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33009021

RESUMO

BACKGROUND: Endometrial cancer is one of the most common malignancies of the reproductive system. Effective and cost-effective screening method for populations at high risk is not available. This study aimed to investigate specimen adequacy and the influencing factors in microscale endometrial sampling biopsy and to evaluate the diagnostic accuracy and medical cost of biopsy in endometrial cancer and atypical hyperplasia screenings in comparison with hysteroscopic endometrial biopsy. METHODS: A total of 1551 patients at high risk for endometrial lesions who required hysteroscopic endometrial biopsy from November 2017 to August 2018 were included. Microscale endometrial sampling biopsy was performed, followed by hysteroscopic endometrial biopsy. We evaluated the specimen adequacy and influencing factors of microscale endometrial sampling. Diagnostic consistency between microscale endometrial sampling biopsy and hysteroscopic endometrial biopsy was evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value of microscale endometrial sampling biopsy in screening for endometrial cancer and atypical hyperplasia were analyzed, and the medical costs of the two procedures were compared. RESULTS: The specimen adequacy was 81.2%. Patient age, menopausal status, endometrial thickness, and endometrial lesion type were correlated with specimen adequacy. There was good consistency in distinguishing benign and malignant endometrial diseases between microscale endometrial sampling biopsy and hysteroscopic biopsy (kappa 0.950, 95% CI 0.925-0.975). The sensitivity, specificity, positive predictive value, and negative predictive value of microscale endometrial sampling biopsy were 91.7%, 100.0%, 100.0%, and 99.3% for endometrial cancer screening, respectively, and 82.0%, 100.0%, 100.0%, and 99.4% for atypical hyperplasia screening. The medical cost of endometrial sampling biopsy was only 22.1% of the cost of hysteroscopic biopsy. CONCLUSIONS: Microscale endometrial sampling biopsy is a minimally invasive alternative technique for obtaining adequate endometrial specimens for histopathological examination. It has the potential to be used in detecting endometrial cancer and atypical hyperplasia with high efficiency and low cost.

6.
Transbound Emerg Dis ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048441

RESUMO

Anthrax is a natural foci disease in Inner Mongolia, which poses a severe threat to public health. In this study, the incidence number, rate, and constituent ratio were used to describe the epidemiological characteristics of anthrax in the region from 1956-2018. The molecular correlation and genetic characteristics of the strains were investigated using canonical single-nucleotide polymorphisms (CanSNP), multiple-locus variable-number tandem repeat analysis (MLVA-15), and whole genome sequencing (WGS). The epidemiological characteristics of anthrax in Inner Mongolia have altered significantly. The incidence of anthrax has decreased annually without vaccination, and the regional distribution of anthrax gradually transferred from central and western regions to the eastern. Moreover, the occupation distribution evolved from multiple early occupations to predominated by farmers and herdsmen. This change is closely its related to policy factors and to changes in the means of production and the living habits of the local population. This indicates that reformulate the control and prevention strategies is essential. Both A. Br. Ames and A. Br. 001/002 subgroups were the predominant CanSNP genotypes of Bacillus anthracis in Inner Mongolia. A total of 36 strains constituted six shared MLVA-15 genotypes, suggesting an epidemiological link between the strains of each shared genotype. The six shared genotypes ((GT1, 9, 11, and 15) and (GT8 and 12)) consisting of 2-7 strains confirmed the occurrence of multiple point outbreaks and cross-regional transmission caused by multiple common sources of infection. Phylogenetic analysis based on the WGS core genome showed that strains from this study formed an independent clade (C.V.), and they were positioned close to each other, suggesting a common origin. Further comparison analysis should be performed to ascertain the geographic origin of these strains.

7.
Medicine (Baltimore) ; 99(40): e22399, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019414

RESUMO

BACKGROUND: Essential hypertension remains an enormous public health concern, imposing a major burden of morbidity and mortality worldwide. Relevant studies showed that acupuncture therapy might be effective in treating essential hypertension. However, there is no consistent conclusion so far. The aim of this study was to assess the efficacy and safety of acupuncture therapy for patients with essential hypertension. METHODS: We searched the PubMed, Embase, the Cochrane Library, Web of Science, the Chinese National Knowledge Infrastructure (CNKI), and the Wan-fang databases from inception through November 29, 2019. Randomized controlled trials investigating acupuncture therapy for hypertension were included. We will use Endnote software X8 for studies selection, Review Manager software 5.3 for the data analysis. RESULTS: We will synthesize current studies to evaluate the safeties and effectiveness of acupuncture for essential hypertension. CONCLUSIONS: Our study will provide the evidence of acupuncture therapy for essential hypertension.

8.
Hepatol Int ; 14(5): 723-732, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33026573

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly become a major international public health concern. This study was designed to evaluate the clinical characteristics and risk factors of COVID-19-associated liver injury. METHODS: A fraction of 657 COVID-19 patients were retrospectively analyzed. Clinical and laboratory data were derived from electronic medical records and compared between patients with or without liver injury. Multivariate logistic regression method was used to analyze the risk factors for liver injury. RESULTS: Among 657 patients, 303 (46.1%) patients had liver injury with higher rate in severe/critically ill patients [148/257 (57.6%)] than those in moderate cases [155/400 (38.8%)]. The incidence of liver injury was much higher in male [192/303 (63.4%)] than female [111/303 (36.6%)], and in severe/critical patients [148/303 (48.8%)] with percutaneous oxygen saturation ≤ 93% [89/279 (31.9%)] or peak body temperature ≥ 38.5 °C [185/301 (61.5%)] on admission. Liver injury-related inflammations included increased white blood cells, neutrophils and decreased lymphocytes. More patients with liver injury than without had increased serum IL-2R, TNFα, ferritin, hsCRP, PCT, ESR, γ-GT, and LDH. Multivariate regression analysis revealed that increasing odds of liver injury were related to male, higher serum hsCRP (≥ 10 mg/L), and neutrophil-to-lymphocyte ratio (NLR) (≥ 5). Moreover, more deceased patients (14/82 (17%)) had significantly elevated serum TBIL than discharged patients [25/532 (4.7%)]. CONCLUSION: Liver injury is a common complication in COVID-19 patients. The potential risk factors of liver injury include male, hsCRP and NLR score. A close monitor of liver function should be warned in COVID-19 patients, especially in severe/critical individuals.

9.
Sci Rep ; 10(1): 16840, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033325

RESUMO

Evolution of resistance by pests reduces the benefits of transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt). Here we analyzed resistance to Bt toxin Cry1Ac in a field-derived strain of pink bollworm (Pectinophora gossypiella), a global pest of cotton. We discovered that the r14 allele of the pink bollworm cadherin gene (PgCad1) has a 234-bp insertion in exon 12 encoding a mutant PgCad1 protein that lacks 36 amino acids in cadherin repeat 5 (CR5). A strain homozygous for this allele had 237-fold resistance to Cry1Ac, 1.8-fold cross-resistance to Cry2Ab, and developed from neonate to adult on Bt cotton producing Cry1Ac. Inheritance of resistance to Cry1Ac was recessive and tightly linked with r14. PgCad1 transcript abundance in midgut tissues did not differ between resistant and susceptible larvae. Toxicity of Cry1Ac to transformed insect cells was lower for cells expressing r14 than for cells expressing wild-type PgCad1. Wild-type PgCad1 was transported to the cell membrane, whereas PgCad1 produced by r14 was not. In larval midgut tissue, PgCad1 protein occurred primarily on the brush border membrane only in susceptible larvae. The results imply r14 mediates pink bollworm resistance to Cry1Ac by reduced translation, increased degradation, and/or mislocalization of cadherin.

10.
Viruses ; 12(10)2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33050079

RESUMO

Quebec is the third-largest wine grape producing province in Canada, and the industry is constantly expanding. Traditionally, 90% of the grapevine cultivars grown in Quebec were winter hardy and largely dominated by interspecific hybrid Vitis sp. cultivars. Over the years, the winter protection techniques adopted by growers and climate changes have offered an opportunity to establish V. vinifera L. cultivars (e.g., Pinot noir). We characterized the virome of leafroll-infected interspecific hybrid cultivar and compared it to the virome of V. vinifera cultivar to support and facilitate the transition of the industry. A dsRNA sequencing method was used to sequence symptomatic and asymptomatic grapevine leaves of different cultivars. The results suggested a complex virome in terms of composition, abundance, richness, and phylogenetic diversity. Three viruses, grapevine Rupestris stem pitting-associated virus, grapevine leafroll-associated virus (GLRaV) 3 and 2 and hop stunt viroid (HSVd) largely dominated the virome. However, their presence and abundance varied among grapevine cultivars. The symptomless grapevine cultivar Vidal was frequently infected by multiple virus and viroid species and different strains of the same virus, including GLRaV-3 and 2. Our data show that viruses and viroids associated with the highest number of grapevines expressing symptoms included HSVd, GLRaV-3 and GLRaV-2, in gradient order. However, co-occurrence analysis revealed that the presence of GLRaV species was randomly associated with the development of virus-like symptoms. These findings and their implications for grapevine leafroll disease management are discussed.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33035163

RESUMO

Typical neural architecture search methods usually restrict the search space to the pre-defined block types for a fixed macro-architecture. However, this strategy will affect the search space and architecture flexibility if block proposal search (BPS) is not considered for NAS. As a result, block structure search is the bottleneck in many previous NAS works. In this paper, we propose a new evolutionary algorithm referred as latency EvoNAS (LEvoNAS) for block structure search, and also introduce it to the NAS framework by developing a novel two-stage framework called Block Proposal NAS (BP-NAS). Comprehensive experimental results across multiple computer vision tasks demonstrate the superiority of our approaches over the state-of-the-art lightweight models. For the classification task on the ImageNet dataset, our BPN-A is better than 1.0-MobileNetV2 [1] with similar latency, and our BPN-B saves 23.7% latency when compared with 1.4-MobileNetV2 with higher top-1 accuracy. Furthermore, for the object detection task on the COCO dataset, the face identification task on the MegaFace dataset, and the re-identification task on Market-1501 dataset, our methods outperform MobileNetV2, which demonstrates the generalization capability of our newly proposed framework.

12.
Water Sci Technol ; 82(5): 877-886, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33031067

RESUMO

Water pollution from antibiotics has attracted a lot of attention for its serious threat to human health. In this study, a magnetic adsorbent (zinc ferrite/activated carbon (ZnFe2O4/AC) was synthesized via microwave method to effectively remove gemifioxacin mesylate (GEM) and moxifloxacin hydrochloride (MOX). Based on the porosity of AC and the magnetism of ZnFe2O4, the resulting ZnFe2O4/AC has high adsorption capacities and can be easily separated from the solid-liquid system via a magnetic field. The largest adsorption capacities for GEM and MOX can reach up to 433.4 mg g-1 and 388.8 mg g-1, respectively, higher than those of reported adsorbents such as MIL-101 and MOF-808. Fastest adsorptions of GEM and MOX were found at 5 min, and solution pH and coexisting salts do not have a significant influence on the adsorption process. The adsorption mechanism analysis indicates that electrostatic interaction and H-bond interaction contribute to the effective adsorption.


Assuntos
Carvão Vegetal , Poluentes Químicos da Água , Adsorção , Antibacterianos , Magnetismo
13.
J Phys Chem Lett ; : 9110-9116, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049137

RESUMO

State coupling certainly determines the topologic features of the molecular potential energy surface (PES) and potentially diversifies chemical reaction pathways. Here we report the new PESs of BrCN- in the low-lying electronic states that are distinctly different from the previous predictions in the short Br-CN bond region but validated by the high-resolution ion velocity imaging measurements of low-energy dissociative electron attachment (DEA) to BrCN. Besides the vibrating CN- ions produced in the fast Br-CN bond stretching motions, we confirm that the ro-vibrating CN- ions with a nearly isotropic angular distribution are produced by receiving a torque in the combinational motion of Br-CN bond bending and stretching. The latter process is closely related to the potential well of BrCN- at the first excited state A2Π3/2 that arises from the Π-Σ state couplings. Our findings not only suggest that the PESs of other anionic cyanogen halides are in dire need of reexamination but also show that ion velocity imaging of the DEA process is a powerful experimental method for evaluating the theoretical PESs of molecular anions.

15.
Nat Commun ; 11(1): 4980, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020477

RESUMO

The functions of the proto-oncoprotein c-Myc and the tumor suppressor p53 in controlling cell survival and proliferation are inextricably linked as "Yin and Yang" partners in normal cells to maintain tissue homeostasis: c-Myc induces the expression of ARF tumor suppressor (p14ARF in human and p19ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1570-1577, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067956

RESUMO

AbstractObjective:To investigate the expression of miR-215 and KDM1B in DLBCL patients, and to analysis its clinical significance. METHODS: Fifty patients with DLBCL treated in our hospital were selected as DLBCL group, and 30 cases of reactive proliferative lymphadenitis(RPL) were selected as controls. RQ-PCR was used to detect the expression level of miR-215, and immunohistochemistry was used to detect the expression of KDM1B protein. The expression of miR-215 and KDM1B in patients with different clinical characteristics and the survival rate of patients with different expression of miR-215 and KDM1B was compared. miR-215 mimics was transfected into SU-DHL-4 cells. Cell proliferation was detected by CCK-8. Cell apoptosis was measured by flow cytometry. The expression of KDM1B protein was detected by Western blot. RESULTS: The expression of miR-215 in DLBCL patients was significantly lower than that in control group, and the positive expression of KDM1B protein was higher, the difference was statistically significant(P<0.01). Spearman rank correlation analysis showed that the expression of miR-215 negatively correlated with KDM1B (r=-0.751,P<0.05). There was significant correlation of miR-215, KDM1B expression with symptoms of B,Serum level of LDH, International Prognostic Index(IPI), Ann Arbor stage,Tumor size, respectively in patients(P<0.05). Kaplan-Meier showed that 5-year overall survival rate of patients with high miR-215 expression was significantly longer than that with low miR-215 expression (P=0.013). The 5-year survival rate of the patients with high positive KDM1B expression was significantly lower than that with low positive expression(P=0.024). KDM1B protein was suppressed by the transfection of miR-215 mimics for 72 h, the cell proliferation rate in miR-215 mimics group was significantly lower than that in control group and NC mimics group (P<0.05), but cell apoptotic rate of miR-215 mimics were significantly higher(P<0.05). The expression of KDM1B protein was significantly lower than that in control and NC group(P<0.05). CONCLUSION: There are low expression of miR-215 and high expression of KDM1B protein in patients with DLBCL, suggesting that they may be the diagnostic and prognostic indicators of DLBCL. miR-215 can directly target KDM1B to inhibit cell growth and induce apoptosis.

17.
Pharm Dev Technol ; : 1-9, 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33070673

RESUMO

Multidrug resistance (MDR) is a serious challenge in chemotherapy and also a major threat to breast cancer treatment. As an intracellular energy factory, mitochondria provide energy for drug efflux and are deeply involved in multidrug resistance. Mitochondrial targeted delivery of doxorubicin can overcome multidrug resistance by disrupting mitochondrial function. By incorporating a reactive oxygen species (ROS)-responsive hydrophobic group into the backbone structure of hyaluronic acid - a natural ligand for the highly expressed CD44 receptor on tumor surfaces, a novel ROS-responsive and CD44-targeting nano-carriers was constructed. In this study, mitochondria-targeted triphenylphosphine modified-doxorubicin (TPP-DOX) and amphipathic ROS-responsive hyaluronic acid derivatives (HA-PBPE) were synthesized and confirmed by 1H NMR. The nanocarriers TPP-DOX @ HA-PBPE was prepared in a regular shape and particle size of approximately 200 nm. Compared to free DOX, its antitumor activity in vitro and tumor passive targeting in vivo has been enhanced. The ROS-responsive TPP-DOX@HA-PBPE nanocarriers system provide a promising strategy for the reverse of MDR and efficient delivery of doxorubicin derivatives into drug-resistant cancer cells.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32924190

RESUMO

Cryptocaryon irritans, a pathogen model for fish mucosal immunity, causes skin mucosal and systematic humoral immune response. Where and how MHC II antigen presentation occurs in fish infected with C. irritans remain unknown. In this study, the full-length cDNA of the grouper cysteine protease CTSS was cloned. The expression distributions of six genes (CTSB, CTSL, CTSS, GILT, MHC IIA and MHC IIB) involved in MHC II antigen presentation pathway were tested. These genes were highly expressed in systematic immune tissues and skin and gill mucosal-associated immune tissues. All six genes were upregulated in skin at most time points. Five genes expected CTSS was upregulated in spleen at most time points. CTSB, CTSL and MHC IIA were upregulated in the gill and head kidney at some time points. These results indicate that the presentation of MHC II antigen intensively occurred in local infected skin and gill. Spleen, not head kidney, had the most extensive systematic antigen presentation. In skin, six genes most likely peaked at day 2, earlier than in spleen (5-7 days), marking an earlier skin antibody peak than any recorded in serum previously. This significant and earlier mucosal antigen presentation indicates that specific immune response occurs in local mucosal tissues.

19.
World J Gastroenterol ; 26(35): 5287-5301, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994688

RESUMO

BACKGROUND: Serum amyloid A1 (SAA1) is an acute-phase protein involved in acute or chronic hepatitis. Its function is still controversial. In addition, the effect of the expression of SAA1 and its molecular function on the progression in hepatocellular carcinoma (HCC) is still unclear. AIM: To demonstrate the expression of SAA1 and its effect on the prognosis in HCC and explain further the correlation of SAA1 and immunity pathways. METHODS: SAA1 expression in HCC was conducted with The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) in GEPIA tool, and the survival analysis based on the SAA1 expression level was achieved in the Kaplan-Meier portal. The high or low expression group was then drawn based on the median level of SAA1 expression. The correlation of SAA1 and the clinical features were conducted in the UALCAN web-based portal with TCGA-LIHC, including tumor grade, patient disease stage, and the TP53 mutation. The correlation analysis between SAA1 expression and TP53 mutation was subjected to the TCGA portal. The tumor purity score and the immune score were analyzed with CIBERSORT. The correlation of SAA1 expression and tumor-infiltrating lymphocytes was achieved in TISIDB web-based integrated repository portal for tumor-immune system interactions. GSE125336 dataset was used to test the SAA1 expression in the responsive or resistant group with anti-PD1 therapy. Gene set enrichment analysis was applied to evaluate the gene enrichment signaling pathway in HCC. The similar genes of SAA1 in HCC were identified in GEPIA, and the protein-protein interaction of SAA1 was conducted in the Metascape tool. The expression of C-X-C motif chemokine ligand 2, C-C motif chemokine ligand 23, and complement C5a receptor 1 was studied and overall survival analysis in HCC was conducted in GEPIA and Kaplan-Meier portal, respectively. RESULTS: SAA1 expression was decreased in HCC, and lower SAA1 expression predicted poorer overall survival, progression-free survival, and disease-specific survival. Furthermore, SAA1 expression was further decreased with increased tumor grade and patient disease stage. Also, SAA1 expression was further downregulated in patients with TP53 mutation compared with patients with wild type TP53. SAA1 expression was negatively correlated with the TP53 mutation. Lower SAA1 predicted poorer survival rate, especially in the patients with no hepatitis virus infection, other than those with hepatitis virus infection. Moreover, the SAA1 expression was negatively correlated with tumor purity. In contrast, SAA1 expression was positively correlated with the immune score in HCC, and the correlation analysis between SAA1 expression and tumor-infiltrating lymphocytes also showed a positive correlation in HCC. Decreased SAA1 was closely associated with the immune tolerance of HCC. C-X-C motif chemokine ligand 2 and C-C motif chemokine ligand 23 genes were identified as the hub genes associated with SAA1, which could also serve as favorable prognosis markers for HCC. CONCLUSION: SAA1 is downregulated in the liver tumor, and it is closely involved in the progression of HCC. Lower SAA1 expression indicates lower survival rate, especially for those patients without hepatitis virus infection. Lower SAA1 expression also suggests lower immune infiltrating cells, especially for those with immune cells exerting anti-tumor immune function. SAA1 expression is closely associated with the anti-tumor immune pathways.

20.
World J Gastroenterol ; 26(35): 5314-5327, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994690

RESUMO

BACKGROUND: It is unclear whether immune escape-associated mutations in the major hydrophilic region of hepatitis B virus surface antigen (HBsAg) are associated with nucleoside/nucleotide analog resistance. AIM: To evaluate the association between immune escape-associated mutations and nucleoside/nucleotide analog resistance mutations. METHODS: In total, 19440 patients with chronic hepatitis B virus infection, who underwent resistance testing at the Fifth Medical Center of Chinese PLA General Hospital between July 2007 and December 2017, were enrolled. As determined by sequence analysis, 6982 patients harbored a virus with resistance mutations and 12458 harbored a virus lacking resistance mutations. Phenotypic analyses were performed to evaluate HBsAg production, replication capacity, and drug-induced viral inhibition of patient-derived drug-resistant mutants with or without the coexistence of sA159V. RESULTS: The rate of immune escape-associated mutation was significantly higher in 9 of the 39 analyzed mutation sites in patients with resistance mutations than in patients without resistance mutations. In particular, these mutations were sQ101H/K/R, sS114A/L/T, sT118A/K/M/R/S/V, sP120A/L/Q/S/T, sT/I126A/N/P/S, sM133I/L/T, sC137W/Y, sG145A/R, and sA159G/V. Among these, sA159V was detected in 1.95% (136/6982) of patients with resistance mutations and 1.08% (134/12,458) of patients lacking resistance mutations (P < 0.05). The coexistence of sA159V with lamivudine (LAM) and entecavir (ETV)-resistance mutations in the same viral genome was identified during follow-up in some patients with drug resistance. HBsAg production was significantly lower and the replication capacity was significantly higher, without a significant difference in LAM/ETV susceptibility, in sA159V-containing LAM/ETV-resistant mutants than in their sA159V-lacking counterparts. CONCLUSION: In summary, we observed a close link between the increase in certain immune escape-associated mutations and the development of resistance mutations. sA159V might increase the fitness of LAM/ETV-resistant mutants under environmental pressure in some cases.

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