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1.
Ann Surg ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33938492

RESUMO

OBJECTIVE: To determine whether robotic-assisted lobectomy (RAL) affects perioperative outcomes and long-term efficacy in non-small cell lung cancer (NSCLC) patients, compared with traditional video-assisted lobectomy (VAL). SUMMARY BACKGROUND DATA: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. METHODS: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. RESULTS: The 320 enrolled patients were randomly assigned to the RAL group (n = 157) and the VAL group (n = 163). Perioperative outcomes were comparable between the two groups, including the length of hospital stay (P = 0.76) and the rate of postoperative complications (P = 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage (830 ml [IQR, 550-1130 ml] vs. 685 ml [IQR, 367.5-1160 ml], P = 0.007) and hospitalization costs ($12821 [IQR, $12145-$13924] vs. $8009 [IQR, $7014-$9003], P < 0.001) were significantly higher in the RAL group. RAL group had a significantly higher number of lymph nodes (LNs) harvested (11 [IQR, 8-15] vs. 10 [IQR, 8-13], P = 0.02), higher number of N1 LNs (6 [IQR, 4-8] vs. 5 [IQR, 3-7], P = 0.005), and more LN stations examined (6 [IQR, 5-7] vs. 5 [IQR, 4-6], P < 0.001). CONCLUSIONS: Both RAL and VAL are safe and feasible for the treatment of NSCLC. RAL achieved similar perioperative outcomes, together with higher LN yield. Further follow-up investigations are required to evaluate the long-term efficacy of RAL. (ClinicalTrials.gov identifier: NCT03134534).

2.
Artigo em Inglês | MEDLINE | ID: mdl-33904728

RESUMO

A superflexible hydrophobic silica-based aerogel (FHSA) was prepared via a facile sol-gel process and ambient pressure drying method. The FHSA was treated at different temperatures varying from -196 to 450 °C to evaluate its thermal and mechanical performances. The evolutions of the physical property, hydrophobicity, microstructure, pore structure, and chemical structure of the FHSA with the various treatment temperatures were investigated comprehensively. The structure of the FHSA did not show an obvious change after treatment in the liquid nitrogen. The bulk density of the FHSA increased from 0.047 to 0.077 g cm-3 when the thermal treatment temperature increased from 25 to 450 °C. The specific surface area and pore volume of the FHSA increased with the treatment temperature owing to the decomposition of the organic moieties. The Fourier transform infrared spectra showed that the methyl groups in the FHSA had excellent thermostability up to 400 °C. The water contact angles of the FHSA after treatment at -196, 25, 200, 300, 350, 400, and 450 °C were 131, 151, 162, 150, 132, 119, and 34°, respectively. The thermal conductivity of the FHSA at a low temperature of -10 °C was 0.022 W m-1 K-1. The reversible deformation rate of the FHSA was more than 80% within 100 compression cycles. After treatment in liquid nitrogen, the reversible deformation rate of the FHSA remained at 50%. The synthesis method of the FHSA is simple, the resulting FHSA showed good performance both in thermostability and flexibility, and it is promisingly applied for thermal insulation and sealing in ultralow-temperature environments.

3.
Chin J Dent Res ; 24(1): 21-31, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33890452

RESUMO

OBJECTIVE: To explore the potential therapies for infantile haemangiomas by targeting survivin, a member of the inhibitor of apoptosis protein family, using its specific small molecule inhibitor YM155. METHODS: The expression of survivin in human haemangioma tissue was explored using immunohistochemistry and immunohistofluorescence. Cell cycle analysis and EdU assays were used to measure cell proliferation. Heochst33342 and Annexin V/PI double staining were performed to measure cell apoptosis. The capacity for self-renewal and multilineage differentiation potential of haemangioma stem cells (HemSCs) were measured by clone formation assays and multiple differentiation assays. Murine haemangioma models were established to explore the therapeutic efficacy of YM155 in vivo. RESULTS: Strong staining of survivin in stromal cells was observed in the proliferative haemangioma tissue. In vitro studies demonstrated that YM155 induced cell cycle arrest and proliferation suppression of HemSCs, and also caused cell apoptosis at a higher concentration. YM155 impaired the self-renewal capacities and damaged multiple differentiation potentials of HemSCs. Importantly, YM155 suppressed blood vessel formation and cell proliferation, and induced cell apoptosis in murine haemangioma models. CONCLUSION: The present study demonstrated that targeting survivin using its specific suppressant, YM155, prevented the progression of infantile haemangioma by suppressing cell proliferation, inducing cell apoptosis and disrupting the differentiation potential of HemSCs. These results indicate a novel and promising therapeutic approach for the treatment of infantile haemangioma.


Assuntos
Antineoplásicos , Hemangioma , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Hemangioma/tratamento farmacológico , Humanos , Camundongos , Células-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Cell Stem Cell ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33711283

RESUMO

Impaired ribosome function is the underlying etiology in a group of bone marrow failure syndromes called ribosomopathies. However, how ribosomes are regulated remains poorly understood, as are approaches to restore hematopoietic stem cell (HSC) function loss because of defective ribosome biogenesis. Here we reveal a role of the E3 ubiquitin ligase HectD1 in regulating HSC function via ribosome assembly and protein translation. Hectd1-deficient HSCs exhibit a striking defect in transplantation ability and ex vivo maintenance concomitant with reduced protein synthesis and growth rate under stress conditions. Mechanistically, HectD1 ubiquitinates and degrades ZNF622, an assembly factor for the ribosomal 60S subunit. Hectd1 loss leads to accumulation of ZNF622 and the anti-association factor eIF6 on 60S, resulting in 60S/40S joining defects. Importantly, Znf622 depletion in Hectd1-deficient HSCs restored ribosomal subunit joining, protein synthesis, and HSC reconstitution capacity. These findings highlight the importance of ubiquitin-coordinated ribosome assembly in HSC regeneration.

5.
Brain ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33729480

RESUMO

Cavernous malformations (CMs) affecting the central nervous system occur in approximately 0.16% to 0.4% of the general population. The majority (85%) of the CMs are in a sporadic form, but the genetic background of sporadic CMs remains enigmatic. Of the 81 patients, 73 (90.1%) patients were detected carrying somatic missense variants in 2 genes: MAP3K3 and PIK3CA by whole-exome sequencing (WES). The mutation spectrum correlated with lesion size (P = 0.001), anatomical distribution (P < 0.001), MRI appearance (P = 0.004) and haemorrhage events (P = 0.006). PIK3CA mutation was a significant predictor of overt haemorrhage events (P = 0.003, OR = 11.252, 95% CI = 2.275-55.648). Enrichment of endothelial cell (EC) population was associated with a higher fractional abundance of the somatic mutations. Overexpression of the MAP3K3 mutation perturbed angiogenesis of EC models in vitro and zebrafish embryos in vivo. Distinct transcriptional signatures between different genetic subgroups of sporadic CMs were identified by single-cell RNA-sequencing (scRNA-seq) and verified by pathological staining. Significant apoptosis in MAP3K3 mutation carriers and overexpression of GDF15 and SERPINA5 in PIK3CA mutation carriers contributed to their phenotype. We identified activating MAP3K3 and PIK3CA somatic mutations in the majority (90.1%) of sporadic CMs and PIK3CA mutations could confer a higher risk for overt haemorrhage. Our data provide insights into genomic landscapes, propose a mechanistic explanation and underscore the possibility of a molecular classification for sporadic CMs.

6.
Plant Physiol Biochem ; 162: 624-633, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33774467

RESUMO

Okra (Abelmoschus esculentus L. Moench) is an important tropical and subtropical crop species, but okra pods age rapidly after they meet harvest standards. The underlying mechanisms by which okra pods harden are unclear. In this study, we determined the cellulose and lignin contents of 'Chaowuxing' okra pods from 4 to 14 days postanthesis (DPA). Based on the histochemical staining of okra fruit during the active period of cellulose accumulation, we found that the hardening of okra fruit is due to the rapid accumulation of cellulose in the cell walls of vascular cells in the pulp. We used RNA-sequencing (RNA-Seq) analyses to investigate the genes that regulate okra fruit aging. Transcriptome sequencing data showed that after 7 DPA, expression of the cellulose synthase gene (CesA) decreased with time. In addition, expression of the gene encoding the first functional enzyme involved in cellulose hydrolysis (endoglucanase) also decreased, but its rate of decrease was much faster than that of the CesA. The quantitative real-time PCR (qRT-PCR) results were consistent with the RNA-Seq data. Accordingly, we speculate that the accumulation of cellulose during okra pod hardening occurs via a reduction in cellulose hydrolysis activity. The above results suggest that thickening of the cell wall caused by a significant increase in cellulose content in the vascular bundles causes okra hardening. The accumulation of cellulose is not directly achieved via increased expression of CesA but rather indirectly via decreased hydrolysis of cellulose.


Assuntos
Abelmoschus , Parede Celular , Celulose , Frutas
7.
Breast Cancer Res ; 23(1): 29, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663585

RESUMO

BACKGROUND: MDM2/MDMX proteins are frequently elevated in hormone receptor-positive (ER+) breast cancer. We sought to determine the antitumor efficacy of the combination of ALRN-6924, a dual inhibitor of MDM2/MDMX, with chemotherapy in ER+ breast cancer models. METHODS: Three hundred two cell lines representing multiple tumor types were screened to confirm the role of TP53 status in ALRN-6924 efficacy. ER+ breast cancer cell lines (MCF-7 and ZR-75-1) were used to investigate the antitumor efficacy of ALRN-6924 combination. In vitro cell proliferation, cell cycle, and apoptosis assays were performed. Xenograft tumor volumes were measured, and reverse-phase protein array (RPPA), immunohistochemistry (IHC), and TUNEL assay of tumor tissues were performed to evaluate the in vivo pharmacodynamic effects of ALRN-6924 with paclitaxel. RESULTS: ALRN-6924 was active in wild-type TP53 (WT-TP53) cancer cell lines, but not mutant TP53. On ER+ breast cancer cell lines, it was synergistic in vitro and had enhanced in vivo antitumor activity with both paclitaxel and eribulin. Flow cytometry revealed signs of mitotic crisis in all treatment groups; however, S phase was only decreased in MCF-7 single agent and combinatorial ALRN-6924 arms. RPPA and IHC demonstrated an increase in p21 expression in both combinatorial and single agent ALRN-6924 in vivo treatment groups. Apoptotic assays revealed a significantly enhanced in vivo apoptotic rate in ALRN-6924 combined with paclitaxel treatment arm compared to either single agent. CONCLUSION: The significant synergy observed with ALRN-6924 in combination with chemotherapeutic agents supports further evaluation in patients with hormone receptor-positive breast cancer.

8.
Cancer ; 127(11): 1880-1893, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33784413

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

9.
Cancer Sci ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33686769

RESUMO

The unfolded protein response (UPR) plays an important role in carcinogenesis, but the functional role and mechanism of UPR-associated bladder carcinogenesis remain to be characterized. Upon UPR activation, ATF6α is activated to upregulate the transcription of UPR target genes. Although the mechanism of ATF6 activation has been studied extensively, the negative regulation of ATF6 stabilization is not well understood. Here, we report that the deubiquitinase otubain 1 (OTUB1) facilitates bladder cancer progression by stabilizing ATF6 in response to endoplasmic reticulum stress. OTUB1 expression is raised in bladder cancer patients. Genetic ablation of OTUB1 markedly inhibited bladder cancer cell proliferation, viability, and migration both in vitro and in vivo. Mechanistically, luciferase pathway screening showed that ATF6 signaling was clearly activated compared with other pathways. OTUB1 was found to activate ATF6 signaling by inhibiting its ubiquitylation, thereby remodeling the stressed cells through transcriptional regulation. Our results show that high OTUB1 expression promotes bladder cancer progression by stabilizing ATF6 and that OTUB1 is a potential therapeutic target in bladder cancer.

10.
Front Endocrinol (Lausanne) ; 12: 595933, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33776909

RESUMO

Background: There is no doubt that thyroid dysfunction is associated with psychiatric disorders. A large amount of thyroid carcinoma patients displayed mood disorders after the withdrawal of levothyroxine (LT4). However, it is unclear whether the disorders are related to the transient withdrawal of LT4, and if yes, what the possible underlying mechanism is. This study aims to investigate the abnormal regional cerebral glucose metabolism (rCMRglu) in a group of papillary thyroid cancer (PTC) patients without LT4 for 4 weeks and prove the relationship between the abnormal rCMRglu with depression and anxiety. Methods: Brain 18F-FDG PET/CT data of 38 consecutive PTC patients with high/intermediate-risk from June 2016 to December 2017 have been analyzed. Of the 38 patients, 23 are in the LT4 withdrawal group (WG) and 15 in the LT4 replacement group (RG). These patients were also evaluated for depressive and anxiety symptoms within 24 h after the scans based on the Hamilton Depression Rating Scale (17 items, HRDS-17) and the Hamilton Anxiety Rating Scale (HAMA) respectively. Results: Thirty-eight patients (12 men, 26 women; age range, 25-69 years; mean age, 45.8 years) were selected in the study. Compared with the RG, patients in WG showed depression and anxiety with higher total scores of HRDS-17 and HAMA (14.7 ± 5.8 vs 3.8 ± 5.5, t = -5.74, p = 0.00; 9.3 ± 4.3 vs 2.7 ± 4.1, t = -4.74, p = 0.00, respectively). In the brain glucose metabolism analysis, the WG patients showed lower rCMRglu in Occipital_Mid_R and Postcentral_L. On the other hand, data illustrated significant rCMRglu increases in the Frontal_Sup_Orb_L. Compared with the healthy group (HG), the rCMRglu of the Postcentral_L and Precuneus_L showed hypoactivity, but the Hippocampus_R and the Temporal_Inf_L showed hyperactivity. This analysis yielded a significant correlation between abnormal rCMRglu with the free thyroxine level, the serum thyroid-stimulating hormone level, HRDS-17, and HAMA scores. Conclusions: The findings showed that more PTC patients exhibited depression and anxiety after LT4 withdrawal for 4 weeks. More attention should be paid to these hypothyroid patients while they were in the hospital. Such a short-term LT4 withdrawal also likely induced abnormal rCMRglu. Our study attempts to explain the possible mechanism of mood disorders related to transient hypothyroidism.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 167-171, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554814

RESUMO

OBJECTIVE: To explore the expression of CD40/CD40L in multiple myeloma(MM) patients and its influence on prognosis. METHODS: Thirty patients with MM treated in Cangzhou People's Hospital from May 2016 to June 2017 were selected and divided into MM group, then 30 healthy people with a physical examination in our hospital at the same time were selected as the normal group. The serum CD40/CD40L levels of the patients in the two groups was detected by flow cytometry, and its correlation with the lymphocyte population, pathological grade and prognostic significance of MM patients was anaysis. RESULTS: The expression of CD40 in serum of the patients in MM group was significantly higher than those in normal group (P<0.05). The expression of CD40L in serum of the patients in MM group showed no significant difference as compared with those in normal group (P>0.05). The levels of CD40 and CD40L in the patients before and after chemotherapy showed no difference(P>0.05). The levels of Ts and NK cells in the patients of MM group were lower than those in normal group (P<0.05). The proportion of total B lymphocytes, Th and Th/Ts cells between the two groups showed no significant difference (P>0.05). The CD40 level was correlated with the serum total B lymphocyte level of the patients in MM group (r=0.877, P=0.005). There was a correlation with CD40L and Th cells in the serum of MM patients (r=-0.783, P=0.035). The expression of serum CD40 in the patients at phase III-IV was higher than those of the patients at phase I-II, the levels of serum CD40L in MM patients at different periods showed no significant difference(P>0.05). The survival rate of MM patients with high CD40 expression was lower than that of MM patients with low CD40 expression (χ2=1.639, P=0.201). The high level CD40 was the main factor affecting the prognosis of MM patients (95%CI: 1.156-4.125). CONCLUSION: The increasing of CD40 level in MM patients is related to the pathological grade of the patients. Chemotherapy can reduce the level of CD40. The increasing of CD40 is an important factor for the poor prognosis of MM patients. CD40L level is not meaningful for MM treatment and prognosis.


Assuntos
Antígenos CD40 , Ligante de CD40 , Linfócitos B , Humanos , Subpopulações de Linfócitos , Prognóstico
12.
Micron ; 144: 103015, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33631679

RESUMO

In this paper, two kinds of Al-Zn-Mg-Cu alloys with high Zn content (Al-8.1Zn-2.0Mg-2.3Cu-0.12Zr-0.12Sc and Al-10.5Zn-2.5Mg-1.5Cu-0.12Zr-0.12Sc) are fabricated by powder hot extrusion. Microstructure and mechanical properties are investigated by optical microscopy (OM), scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM) and tensile tests. The results show that the formation of ultrafine grains and homogeneous second phases in as-extruded alloys is achieved by perfect metallurgical bonding during severe plastic deformation. After the optimal solution treatment and peak aging treatment, the strength of the two alloys reaches up to 734 MPa and 802 MPa, and the elongation is 9.8 % and 5.3 %, respectively. The excellent mechanical properties are attributed to the grain boundary strengthening, precipitation strengthening and homogenous microstructure. The element content has little effect on the grain size of the powder hot-extruded Al-Zn-Mg-Cu alloy, but high Zn and Mg contents can improve the density of strengthening phases while low Cu content can reduce the difficulty of solution treatment by inhibiting the precipitation of S(Al2CuMg) phase.

13.
Kaohsiung J Med Sci ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33611825

RESUMO

Dysregulation of the long intergenic noncoding RNA 01315 (LINC01315) has recently been demonstrated in cancer. However, the role of LINC01315 in papillary thyroid cancer (PTC) has not been determined. We attempted to determine the function of LINC01315 in PTC. The levels of LINC01315 were higher in thyroid carcinoma tissues and cell lines compared with that in noncancerous tissues or normal cells, respectively. LINC01315 knockdown significantly inhibited the in vitro colony formation and invasion of PTC cells. Upregulation of LINC01315 produced opposite effects. Bioinformatic analysis and luciferase reporter assays indicated direct binding of miR-497-5p to LINC01315. Gain- and loss-of-function assays indicated that miR-497-5p acts as a suppressive miRNA in PTC. Furthermore, LINC01315 facilitated the growth and invasion of PTC cells by sponging miR-497-5p. Our results demonstrated the critical role of the LINC01315-miR-497-5p axis in the growth and invasion of PTC cells.

14.
Radiother Oncol ; 157: 114-121, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33516790

RESUMO

BACKGROUND AND PURPOSE: To explore the prognostic value of different radiologic extranodal extension (rENE) grades and their potential improvement for the 8th edition N category in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From 2009 to 2013, a cohort of 1887 patients with NPC was retrospectively enrolled and randomized to the training (n = 955) and validation (n = 932) groups. rENE was categorized as follows: grade 0, nodes without rENE; grade 1, nodes with rENE infiltrating the surrounding fat only; grade 2, matted nodes; grade 3, nodes with rENE infiltrating adjacent structures. RESULTS: The percentage of patients with MRI-positive cervical nodes was 66.5% (1254/1887), of whom grade 0, 1, 2 and 3 rENE cases accounted for 33.2% (416/1254), 14.9% (187/1254), 36.5% (458/1254) and 15.4% (193/1254), respectively. The kappa coefficients for the inter-rater and intra-rater assessments were 0.63, 0.51, 0.65 and 0.93, and 0.76, 0.69, 0.72 and 1.0 in grade 0, 1, 2 and 3 rENE, respectively. Grade 3 rENE rather than grades 0-2 rENE was an independent unfavorable predictor of overall survival and disease-free survival (P < 0.001). Recursive partitioning analysis was applied to refine the N category: eN0 (N0), eN1 (N1 without grade 3), eN2 (N2 without grade 3), and eN3 (N1/N2 with grade 3, N3). Compared to the current system, the proposed N category performed better in hazard consistency, hazard discrimination, sample size balance and outcome prediction. CONCLUSION: Grade 3 rENE was an independent unfavorable indicator of NPC. Upstaging patients in N1-2 with grade 3 rENE to N3 led to a superior prognostic performance.


Assuntos
Extensão Extranodal , Neoplasias Nasofaríngeas , Humanos , Imagem por Ressonância Magnética , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
15.
Org Lett ; 23(1): 118-123, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33351637

RESUMO

With the assistance of a practical directing group (COAQ), the first catalytic protocol for the palladium-catalyzed C(sp3)-H monoarylation of methanol has been developed, offering an invaluable synthesis means to establish extensive derivatives of crucial arylmethanol functional fragments. Furthermore, the gram-scale reaction, broad substrate scope, excellent functional group compatibility, and even the practical synthesis of medicines further demonstrate the usefulness of this strategy.

16.
Comput Struct Biotechnol J ; 18: 3361-3367, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294132

RESUMO

Cancer staging provides a common language that is used to describe the severity of an individual's cancer, which plays a critical role in optimizing cancer treatment. Recursive partitioning analysis (RPA) is the most widely accepted method for cancer staging. Despite its widespread use, to date, only limited tools have been developed to implement the RPA algorithm for cancer staging. Moreover, most of the available tools can be accessed only from command lines and also lack visualization, making them difficult for clinical investigators without programing skills to use. Therefore, we developed a web server called autoRPA that is dedicated to supporting the construction of prognostic staging models and performance comparisons among different staging models. Based on the RPA algorithm and log-rank test statistics, autoRPA can establish a decision-making tree from survival data and provide clinicians an intuitive method to further prune the decision tree. Moreover, autoRPA can evaluate the contribution of each submitted covariate that is involved in the grouping process and help identify factors that significantly contribute to cancer staging. Four indicators, including hazard consistency, hazard discrimination, percentage of variation explained, and sample size balance, are introduced to validate the performance of the designed staging models. In addition, autoRPA can also be used to compare the performance of different prognostic staging models using a standard bootstrap evaluation method. The web server of autoRPA is freely available at http://rpa.renlab.org.

17.
World Neurosurg ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33276173

RESUMO

BACKGROUND: This study established novel technique nuances in surgery for ventral foramen magnum meningiomas (vFMMs) via a dorsal lateral approach. METHODS: From July 2012 to July 2019, 37 patients with ventral foramen magnum meningiomas underwent tumor resection surgeries and were operated on with a dorsal lateral approach. Two safe zones were selected as the entrance of the surgical corridor. Safe zone I was located between the dural attachment of the first dental ligament (FDL) and the branches of C1; safe zone II lay between the dural attachment of the FDL and the jugular foramen. The tumor was debulked first through safe zone I and then through safe zone II. The tumor was removed through a trajectory from the caudal to cephalad to allow tumor debulking from below and downward delivery, away from the brainstem and lower cranial nerves. RESULTS: Thirty-three patients underwent gross total resection, and four patients underwent subtotal resection. Four patients transiently required a nasogastric feeding tube. All patients recovered within 3 months postoperatively. Three patients (8.1%) developed permanent mild hoarseness and dysphagia due to postoperative damage of cranial nerves IX and X. One patient underwent tracheotomy. No patient experienced tumor recurrence during the follow-up period. CONCLUSIONS: We established a minimal retraction principle, where the selection of two safe zones as the entrance of the surgical corridor, tumor removal from the inferior to superior direction, and debulking followed by devascularization were the key elements to implement the minimal retraction principle in ventral foramen magnum meningioma surgery.

18.
Zhonghua Nan Ke Xue ; 26(4): 357-363, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33351305

RESUMO

The pathogenesis of male infertility is rather complicated. The establishment of animal models, especially mouse models, of male infertility, provides a model basis for the studies of the roles and molecular mechanisms of infertility-related genes. Currently there are mainly three types of mouse models for biomedical researches, namely, the mouse model made by the knockout, knock-in or gene capture method, transgenic mouse model, and chemically induced point mutant mouse model. This review summarizes male infertility - related gene knockout mouse models, aiming to find a suitable animal model for studying the pathogenesis of male infertility.


Assuntos
Modelos Animais de Doenças , Infertilidade Masculina , Animais , Técnicas de Inativação de Genes , Humanos , Infertilidade Masculina/genética , Masculino , Camundongos , Camundongos Knockout
19.
Front Cell Dev Biol ; 8: 593661, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240890

RESUMO

High-throughput sequencing technologies have identified millions of genetic mutations in multiple human diseases. However, the interpretation of the pathogenesis of these mutations and the discovery of driver genes that dominate disease progression is still a major challenge. Combining functional features such as protein post-translational modification (PTM) with genetic mutations is an effective way to predict such alterations. Here, we present PTMsnp, a web server that implements a Bayesian hierarchical model to identify driver genetic mutations targeting PTM sites. PTMsnp accepts genetic mutations in a standard variant call format or tabular format as input and outputs several interactive charts of PTM-related mutations that potentially affect PTMs. Additional functional annotations are performed to evaluate the impact of PTM-related mutations on protein structure and function, as well as to classify variants relevant to Mendelian disease. A total of 4,11,574 modification sites from 33 different types of PTMs and 1,776,848 somatic mutations from TCGA across 33 different cancer types are integrated into the web server, enabling identification of candidate cancer driver genes based on PTM. Applications of PTMsnp to the cancer cohorts and a GWAS dataset of type 2 diabetes identified a set of potential drivers together with several known disease-related genes, indicating its reliability in distinguishing disease-related mutations and providing potential molecular targets for new therapeutic strategies. PTMsnp is freely available at: http://ptmsnp.renlab.org.

20.
Crit Rev Food Sci Nutr ; : 1-12, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33207917

RESUMO

Approximately 50% of the world population is infected with Helicobacter pylori. Antibiotics are widely used for H. pylori infection treatment but there are drawbacks, e.g., the emergence of antibiotic-resistant bacteria. Sialic acids are a family of acylated derivatives of a nine-carbon carboxylated monosaccharide. Because sialic acid of the host cells is vital to H. pylori pathogenesis, sialic acid-guided therapies have been proposed for the prevention and treatment of H. pylori infection, including anti-adhesive therapy and site-specific delivery. This review aims to shed light on the prospects of sialic acid-based strategies in the food industry for developing functional foods with potent anti-H. pylori activity. In this work, progress on the identification of sialic acid-containing components as anti-adhesive agents against H. pylori is reviewed. The current applications of sialic acid-based delivery systems in eradicating H. pylori are discussed, including microspheres, beads, hydrogels, and nanoparticles. The challenges and future perspectives of sialic acid-guided strategies and the possibility of their applications in food industry are highlighted. Antibiotic resistance is still a major challenge and the sialic acid-based technologies have tremendous potential to be utilized to develop functional foods that hold promise to be a future trend for preventing or treating H. pylori infection.

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