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1.
Front Cardiovasc Med ; 9: 827860, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369329

RESUMO

Background: The thoracoscopic trans-mitral approach can not only facilitate exposure of the ventricular septum, mitral valve, and subvalvular apparatus, it also enables the surgeons to perform concomitant mitral valve intervention. This study aimed to determine the safety and efficacy of thoracoscopic trans-mitral septal myectomy in elderly patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: We reviewed the demographic to clinical characteristics and outcomes of patients who underwent thoracoscopic trans-mitral septal myectomy in our center between April 2019 and April 2021. The population was divided into a younger group (<60 years) and an elderly group (≥60 years). Results: There were 46 and 20 patients in the younger and elderly groups, respectively. The majority of patients in the elderly group were female (39.1 vs. 80.0%, P < 0.01). Patients in the elderly group were more likely to be in New York Heart Association Class IV (2.2 vs. 80.0%, P < 0.01). The European System for Cardiac Operation Risk Evaluation II predicted mortality rates were significantly higher (3.97 ± 1.81 vs. 1.62 ± 0.86%, P < 0.01) in the elderly group. In the elderly group, a patient converted to median sternotomy due to left ventricular posterior free wall rupture following septal myectomy and mitral bioprosthetic valve replacement. The patient then underwent double-patch sandwich repair for rupture and mitral mechanical valve replacement and was eventually discharged. All patients in the elderly group were discharged, while one in the younger group died. No patient in the elderly group required permanent pacemaker implantation vs. one in the younger group. Patients in the elderly group were more likely to spend more time in the intensive care unit than those in the younger group (5.44 ± 5.80 days vs. 3.07 ± 2.72, P < 0.05). However, there was no significant intergroup difference in in-hospital mortality or complications. Importantly, the left ventricular outflow tract pressure gradient was significantly decreased from 96.15 ± 32.89 mmHg to 8.2 ± 3.42 mmHg with no residual obstruction in the elderly group. The interventricular septal thickness was significantly decreased from 19.73 ± 3.14 mm to 11.30 ± 2.23 mm. Postoperative mitral regurgitation severity was significantly improved in the elderly group. Conclusion: This study demonstrated that thoracoscopic trans-mitral septal myectomy is a feasible option for selected elderly patients with satisfactory outcomes similar to those of young patients.

2.
Inorg Chem ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083838

RESUMO

How to accurately detect and efficiently sweep Cr(VI) from contaminated water has come into focus. Zirconium-based metal-organic frameworks (MOFs) play vital roles in water environmental chemistry due to excellent hydrolysis-resistant stability. However, as photochemical probes and photocatalysts, poor performances in detection sensitivity, selectivity, and photosensitiveness limit sole Zr-MOFs' applications. So, it is urgent to quest valid strategies to break through the dilemmas. Embedding luminous dyes into MOFs has been considered one of the most feasible avenues. Herein, a dual-emissive RhB@Zr-MOF with orange-yellow fluorescence has been assembled by in situ-encapsulating rhodamine B (RhB) into a zirconium-biquinoline-based MOF. Actually, within RhB@Zr-MOF, the aggregation fluorescence quenching (ACQ) effect of RhB molecules was effectively avoided. Notably, RhB@Zr-MOF exhibits a rapid fluorescence quenching response toward Cr(VI) ions with high selectivity, sensitivity, and anti-interference abilities. More interestingly, unlike the most widely reported fluorescence resonance energy transfer (FRET) between MOFs and encapsulated guest modules, photoinduced electron transfer from RhB to Zr-MOF has been confirmed by modeling the ground state and excited states of RhB@Zr-MOF using density functional theory (DFT) and time-dependent DFT (TD-DFT). The effective electron transfer makes RhB@Zr-MOF more sensitive in probing Cr2O72- and CrO42- ions with ultralow detection limit (DL) values of 6.27 and 5.26 ppb, respectively. Prominently, the detection sensitivity based on DL values has been increased about 6 and 9 times, respectively, compared with pristine Zr-MOF. Moreover, rather negative CB and positive VB potentials make RhB@Zr-MOF have excellent photochemical scavenging ability toward Cr(VI) and MO.

3.
Chin Med J (Engl) ; 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36070458

RESUMO

BACKGROUND: Corneal confocal microscopy (CCM) is a noninvasive technique to detect early nerve damage of diabetic sensorimotor polyneuropathy (DSPN). Time in range (TIR) is an emerging metric of glycemic control which was reported to be associated with diabetic complications. We sought to explore the relationship between TIR and corneal nerve parameters in asymptomatic patients with type 2 diabetes (T2DM). METHODS: In this cross-sectional study, 206 asymptomatic inpatients with T2DM were recruited. After 7 days of continuous glucose monitoring, the TIR was calculated as the percentage of time in the glucose range of 3.9 to 10.0 mmol/L. CCM was performed to determine corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length (CNFL). Abnormal CNFL was defined as ≤15.30 mm/mm2. RESULTS: Abnormal CNFL was found in 30.6% of asymptomatic subjects. Linear regression analyses revealed that TIR was positively correlated with CCM parameters both in the crude and adjusted models (all P  < 0.05). Each 10% increase in TIR was associated with a 28.2% (95% CI: 0.595-0.866, P = 0.001) decreased risk of abnormal CNFL after adjusting for covariates. With the increase of TIR quartiles, corneal nerve fiber parameters increased significantly (all P for trend <0.01). The receiver operating characteristic curve indicated that the optimal cutoff point of TIR was 77.5% for predicting abnormal CNFL in asymptomatic patients. CONCLUSIONS: There is a significant independent correlation between TIR and corneal nerve fiber loss in asymptomatic T2DM patients. TIR may be a useful surrogate marker for early diagnosis of DSPN.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36071542

RESUMO

BACKGROUND: It remains unclear whether the thyroid system could regulate the atherogenic remnant cholesterol (RC) levels in euthyroid status. We aimed to investigate the relationship between sensitivity to thyroid hormones and RC levels in Chinese euthyroid population. METHODS: This study included 18766 euthyroid adults. High RC levels were defined as the upper quartile of RC levels. The thyroid hormone sensitivity indices including thyroid feedback quantile-based index (TFQI), thyroid-stimulating hormone index (TSHI), thyrotrophic thyroxine resistance index (TT4RI) and free triiodothyronine to free thyroxine (FT3/FT4) ratio were calculated. Linear and Binary logistic regression analysis were applied to determine the associations between those composite indices with RC levels by genders. RESULTS: Both females and males with high RC levels exhibited co-existing higher TSH and FT4 levels. Linear regression analysis revealed that TFQI, TSHI and TT4RI were positively, while FT3/FT4 ratio levels were negatively associated with serum RC levels. The odds ratios (ORs) (95% confidence intervals (CIs)) for high RC levels were increased with rising TFQI quartiles (Q) [females: Q3 1.41 (1.22-1.63), Q4 1.61 (1.39-1.86); males: Q3 1.25 (1.09-1.45), Q4 1.38 (1.19-1.59), all P for trend < 0.001] after full adjustment, with Q1 as the reference. TSHI and TT4RI yielded similar results. By contrast, the ORs (95% CI) for high RC levels were decreased with increasing FT3/FT4 ratio quartiles in both genders (P for trend < 0.001). CONCLUSIONS: In euthyroid adults, reduced sensitivity to thyroid hormones was associated with high RC levels. Our results suggested an additive cardiometabolic risk of euthyroid population with thyroid hormones insensitivity.

5.
Asian J Androl ; 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36073562

RESUMO

The circadian clock is an evolutionary molecular product that is associated with better adaptation to changes in the external environment. Disruption of the circadian rhythm plays a critical role in tumorigenesis of many kinds of cancers, including prostate cancer (PCa). Integrating circadian rhythm into PCa research not only brings a closer understanding of the mechanisms of PCa but also provides new and effective options for the precise treatment of patients with PCa. This review begins with patterns of the circadian clock, highlights the role of the disruption of circadian rhythms in PCa at the epidemiological and molecular levels, and discusses possible new approaches to PCa therapy that target the circadian clock.

6.
Front Bioeng Biotechnol ; 10: 947918, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147537

RESUMO

Recent advances in the field of optical tweezer technology have shown intriguing potential for applications in cardiovascular medicine, bringing this laboratory nanomechanical instrument into the spotlight of translational medicine. This article summarizes cardiovascular system findings generated using optical tweezers, including not only rigorous nanomechanical measurements but also multifunctional manipulation of biologically active molecules such as myosin and actin, of cells such as red blood cells and cardiomyocytes, of subcellular organelles, and of microvessels in vivo. The implications of these findings in the diagnosis and treatment of diseases, as well as potential perspectives that could also benefit from this tool, are also discussed.

7.
Antioxidants (Basel) ; 11(9)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36139732

RESUMO

Fructo-oligosaccharides (FOS) have well-known bifidogenic effects as probiotics. In this study, esterification was adopted for FOS modification to produce better prebiotic properties. We synthesized and characterized acetylated fructo-oligosaccharides (Ac-FOS) and butyrylated fructo-oligosaccharides (Bu-FOS) as candidate prebiotics. Antioxidant activity and prebiotic esactiviti were evaluated as important indicators. We found, surprisingly, that butyrylation was an effective method in significantly improving the antioxidant activity of FOS. The fermentation products of feces from mice added to Ac-FOS and Bu-FOS, were investigated in vitro, including changes of pH values, short-chain fatty acids (SCFAs) production, and microbiota composition. Supplementation of Ac-FOS or Bu-FOS increased pH values and promoted the growth and activity of beneficial intestinal bacteria, such as Bifidobacteria and Lactobacillus. More importantly, the levels of prebiotic SCFAs were obviously elevated as detected by Gas Chromatography-Mass Spectrometry (GC-MS). Results suggest that Ac-FOS and Bu-FOS have great potential applications in SCFA delivery systems and gut microbiota regulation.

8.
Int J Mol Sci ; 23(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36142130

RESUMO

Stably Expressed Genes (SEGs) are a set of genes with invariant expression. Identification of SEGs, especially among both healthy and diseased tissues, is of clinical relevance to enable more accurate data integration, gene expression comparison and biomarker detection. However, it remains unclear how many global SEGs there are, whether there are development-, tissue- or cell-specific SEGs, and whether diseases can influence their expression. In this research, we systematically investigate human SEGs at single-cell level and observe their development-, tissue- and cell-specificity, and expression stability under various diseased states. A hierarchical strategy is proposed to identify a list of 408 spatial-temporal SEGs. Development-specific SEGs are also identified, with adult tissue-specific SEGs enriched with the function of immune processes and fetal tissue-specific SEGs enriched in RNA splicing activities. Cells of the same type within different tissues tend to show similar SEG composition profiles. Diseases or stresses do not show influence on the expression stableness of SEGs in various tissues. In addition to serving as markers and internal references for data normalization and integration, we examine another possible application of SEGs, i.e., being applied for cell decomposition. The deconvolution model could accurately predict the fractions of major immune cells in multiple independent testing datasets of peripheral blood samples. The study provides a reliable list of human SEGs at the single-cell level, facilitates the understanding on the property of SEGs, and extends their possible applications.

9.
Int J Mol Sci ; 23(18)2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36142197

RESUMO

Powdery mildew caused by Blumeria graminis f. sp. tritici is a devastating disease that reduces wheat yield and quality worldwide. The exploration and utilization of new resistance genes from wild wheat relatives is the most effective strategy against this disease. Psathyrostachys huashanica Keng f. ex P. C. Kuo (2n = 2x = 14, NsNs) is an important tertiary gene donor with multiple valuable traits for wheat genetic improvement, especially disease resistance. In this study, we developed and identified a new wheat-P. huashanica disomic addition line, 18-1-5-derived from a cross between P. huashanica and common wheat lines Chinese Spring and CSph2b. Sequential genomic and multicolor fluorescence in situ hybridization analyses revealed that 18-1-5 harbored 21 pairs of wheat chromosomes plus a pair of alien Ns chromosomes. Non-denaturing fluorescence in situ hybridization and molecular marker analyses further demonstrated that the alien chromosomes were derived from chromosome 7Ns of P. huashanica. The assessment of powdery mildew response revealed that line 18-1-5 was highly resistant at the adult stage to powdery mildew pathogens prevalent in China. The evaluation of agronomic traits indicated that 18-1-5 had a significantly reduced plant height and an increased kernel length compared with its wheat parents. Using genotyping-by-sequencing technology, we developed 118 PCR-based markers specifically for chromosome 7Ns of P. huashanica and found that 26 of these markers could be used to distinguish the genomes of P. huashanica and other wheat-related species. Line 18-1-5 can therefore serve as a promising bridging parent for wheat disease resistance breeding. These markers should be conducive for the rapid, precise detection of P. huashanica chromosomes and chromosomal segments carrying Pm resistance gene(s) during marker-assisted breeding and for the investigation of genetic differences and phylogenetic relationships among diverse Ns genomes and other closely related ones.

10.
Asian J Androl ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36124532

RESUMO

We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). We conducted all analyses using R software and its suitable packages. Twelve genes, namely, secreted frizzled-related protein 4 (SFRP4), DNA topoisomerase II alpha (TOP2A), pleiotrophin (PTN), family with sequence similarity 107 member A (FAM107A), C-X-C motif chemokine ligand 14 (CXCL14), prostate androgen-regulated mucin-like protein 1 (PARM1), leucine zipper protein 2 (LUZP2), cluster of differentiation 38 (CD38), cartilage oligomeric matrix protein (COMP), vestigial-like family member 3 (VGLL3), apolipoprotein E (APOE), and aldehyde dehydrogenase 2 family member (ALDH2), were eventually used to subtype PCa patients from The Cancer Genome Atlas (TCGA) database and GSE116918, and the molecular subtypes showed good correlations with clinical features. In terms of the tumor immune environment (TME) analysis, compared with cluster 1, cancer-associated fibroblasts (CAFs) scored significantly higher, while endothelial cells scored lower in cluster 2 in TCGA database. There was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence (BCR)-free survival for PCa patients undergoing RP. For the GSE116918 database, cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal, immune, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores than cluster 1; in addition, patients with high levels of CAFs, stromal scores, immune scores, and ESTIMATE scores and low levels of tumor purity tended to suffer from BCR. Based on the median of differentially expressed checkpoints, high expression of CD96, hepatitis A virus cellular receptor 2 (HAVCR2), and neuropilin 1 (NRP1) in GSE116918 and high expression of CD160 and tumor necrosis factor (ligand) superfamily member 18 (TNFSF18) in TCGA database were associated with a significantly higher risk of BCR than their counterparts. In conclusion, we first constructed distinct molecular subtypes and critical genes for PCa patients undergoing RP or RT from the fresh perspective of senescence.

12.
Chem Commun (Camb) ; 58(76): 10635-10638, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36047442

RESUMO

We developed a fluorescent probe Sth-NH by introducing a 6-hydroxypyridone skeleton. The presence of an active proton enables the probe to transform from a deprotonated azo form to a hydrazone form in a strongly acidic environment to realize fluorescence light-up behavior, thus monitoring the lower lysosomal pH of cancer cells and distinguishing them from normal cells.

13.
Phytomedicine ; 106: 154417, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36063584

RESUMO

BACKGROUND: Securinine is an alkaloid identified from the roots and leaves of the shrub Flueggea suffruticosa (Pall.) Baill. The molecular structure of securinine consists of four rings, including three chiral centers. It has been suggested that securinine can be chemically synthesized from tyrosine and lysine. Securinine has long been used to treat central nervous system diseases. In recent years, more and more evidence shows that securinine also has anticancer activity, which has not been systematically discussed and analyzed. PURPOSE: This study aims to propose an overall framework to describe the molecular targets of securinine in different signal pathways, and discuss the current status and prospects of each pathway, so as to provide a theoretical basis for the development securinine as an effective anticancer drug. METHODS: The research databases on the anticancer activity of securinine from PubMed, Scopus, Web of Science and ScienceDirect to 2021 were systematically searched. This paper follows the Preferred Reporting Items and Meta-Analysis guidelines. RESULTS: Securinine has the ability to kill a variety of human cancer cells, including, leukemia as well as prostate, cervical, breast, lung, and colon cancer cells. It can regulate the signal pathways of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, Wnt and Janus kinase-signal transducer and activator of transcription, promote cancer cell apoptosis and autophagy, and inhibit cancer cell metastasis. Securinine also has the activity of inducing leukemia cell differentiation. CONCLUSION: Although there has been some experimental evidence indicating the anticancer effect of securinine and its possible pharmacology, in order to design more effective anticancer drugs, it is necessary to study the synergy of intracellular signaling pathways. More in vivo experiments and even clinical studies are needed, and the synergy between securinine and other drugs is also worth studying.

14.
Dis Markers ; 2022: 1724301, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124029

RESUMO

Background: Several studies have demonstrated that acetylation was involved in the process of liver cancer. This study aimed to establish an effective predictive prognostic model using acetylation regulation genes in liver cancer. Methods: Two datasets were downloaded from the Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database. Differentially expressed acetylation regulation genes were identified in the TCGA-LIHC dataset, and then, Gene Ontology (GO) functional annotation analysis was used to investigate the molecular mechanism. After grouping the patients into clusters based on consensus clustering, we explored the correlation between clusters and clinical characteristics. A risk model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis to calculate the risk score. Patients were divided into high-risk and low-risk groups according to the risk score using the acetylation regulation genes. Data downloaded from LIRI-JP were used for external validation. Univariate and multivariate Cox regressions were performed to identify independent risk factors. A prognostic nomogram was constructed according to the TCGA-LIHC dataset. The effect of HDAC11 expression on the proliferation and migration of liver cancer was detected by the CCK-8 method and cell scratch test, respectively. Results: Eleven of 29 acetylation regulation genes were identified as upregulated differentially expressed genes. Go enrichment analysis showed that they were involved in "protein and histone deacylation and deacetylation." Patients were categorized into two clusters according to the expression of 29 acetylation regulation genes. Compared with cluster 2, cluster 1 correlated with shorter overall survival (OS) and higher expression. Stage, T stage, grade, gender, age, and follow-up state were significantly different between two clusters. Pathways involved in DNA repair were significantly enriched in cluster 1. The risk score was calculated by HDAC1, HDAC2, HDAC4, HDAC11, HAT1, and SIRT6. Patients in the high-risk group had a worse prognosis in both datasets. Risk score was not only an independent prognostic marker but could also predict the clinicopathological features of liver cancer. A nomogram containing risk score, T stage, and M stage was built to predict overall survival. After transfection with HDAC11 overexpression plasmid, the proliferation ability of HepG2 cells increased, while the migration ability had no change. Conclusions: Our findings suggested that acetylation regulation genes contribute to malignant progression and have a clinical prognostic impact on liver cancer.


Assuntos
Neoplasias Hepáticas , Sirtuínas , Acetilação , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/genética , Prognóstico , Sincalida/metabolismo , Sirtuínas/metabolismo
15.
Comput Intell Neurosci ; 2022: 5195909, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045990

RESUMO

In order to understand the mental health status of contemporary college students, the research team of "College Students' psychological quality training" conducted mental health examination on nearly 6000 Chinese college students from 23 colleges and universities across the country. The results showed that about 16.51% of Chinese college graduates had serious mental health problems. The results of several recent studies on the mental health status of college graduates across the country show that the accuracy rate of mental behavior examination among college graduates across the country is about 16%, and the rate of people with unsound psychology or in a state of mental sub-health is higher, and there has been a psychological poverty group among college students. A large number of educational facts and scientific research have confirmed that sports are one of the most effective ways to promote students' physical and mental development, and it can be said that there is a very close relationship between college sports and the physical and mental health of college graduates. In order to promote the organic combination of college mental health education and college physical education, the research results will be based on in-depth investigation and understanding of the current situation of college students' psychological development under the new situation, and a systematic study of the relationship between college graduates' physical, sports, mental health knowledge, and psychological level. This paper establishes a theoretical model for the organic combination of mental health education and physical education in colleges and universities, and provides specific countermeasures for integrating psychological teaching into college physical education courses, providing a theoretical basis and reference for developing college physical education courses and improving psychological teaching.


Assuntos
Educação Física e Treinamento , Estudantes , Educação em Saúde , Humanos , Saúde Mental , Estudantes/psicologia , Universidades
16.
Contrast Media Mol Imaging ; 2022: 8440977, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082065

RESUMO

The effects of the enhanced recovery after surgery (ERAS) concept combined with postoperative leg pad elevation on knee enhancement, quality of life, and pain in sufferers after high tibial osteotomy (HTO) are investigated. A total of 98 sufferers who underwent high tibial osteotomy in our hospital from January 2020 to May 2021 were selected as the study subjects. Two sets of sufferers are randomly divided into the study set and the routine set by the random number table method, with 49 cases in each set. The contrast set is given routine nursing intervention, and the ERAS concept combined with self-made raising leg pad nursing is given to the study set on the basis of the contrast set. Efficacy, joint pain, knee function, SF-36 fraction, quality of life fraction, and psychological status fraction are observed in 2 sets. Experimental results show that for sufferers after HTO surgery, the application of the ERAS concept combined with leg pad nursing therapy can effectively enhance postoperative knee function and adverse mood, reduce postoperative pain, and enhance postoperative quality of life.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Osteoartrite do Joelho , Humanos , Perna (Membro) , Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Dor , Qualidade de Vida , Tíbia/cirurgia , Resultado do Tratamento
17.
Cureus ; 14(9): e28691, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36105899

RESUMO

In the United States, individuals of Black/African Ancestry (AA) have a higher incidence and mortality from colorectal cancer (CRC) compared to individuals of White/European Ancestry (EA). In order to develop an approach towards disentangling the complex effects of associated race and socioeconomic factors on CRC outcome, we have conducted a manual chart review of sporadic CRC pathological diagnoses (total n = 334) at an urban public hospital (UH) and a suburban university hospital (SH). There were significant differences between the SH and UH CRC patients with respect to Black/AA race (4.2% vs. 89.1%, p < 0.0001) and Medicaid/Self-pay insurance status (14.9% vs. 85.0%, p < 0.0001). While a higher proportion of newly diagnosed CRC patients presented with metastatic stage 4 CRC at the UH (21%) than the SH (12.5%), only the presence of symptoms was significantly associated with stage 4 CRC (odds ratio, OR 7.94, 95% confidence interval, CI 1.83- 34.54, p = 0.0057) in a multivariable generalized linear model (GLM). The proportion of asymptomatic CRC patients was ~20% at both institutions, suggesting that the UH has contributed to reducing CRC disparities. Initiation of CRC screening at the recommended age at both institutions could reduce the proportion of CRC patients presenting with metastatic spread.

19.
MedComm (2020) ; 3(3): e168, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36051984

RESUMO

Radiation-induced intestinal injury is a serious concern during abdominal and pelvic cancers radiotherapy. Ubiquitin (Ub) is a highly conserved protein found in all eukaryotic cells. This study aims to explore the role and mechanism of free Ub against radiogenic intestinal injury. We found that free Ub levels of irradiated animals and human patients receiving radiotherapy were upregulated. Radiation-induced Ub expression was associated with the activation of interferon regulatory factor 1 (IRF1). Intraperitoneal injection of free Ub significantly reduced the mortality of mice following 5-9 Gy total body irradiation (TBI) through the Akt pathway. Free Ub facilitates small intestinal regeneration induced by TBI or abdominal irradiation. At the cellular level, free Ub or its mutants significantly alleviated cell death and enhanced the survival of irradiated intestinal epithelial cells. The radioprotective role of free Ub depends on its receptor CXCR4. Mechanistically, free Ub increased fibroblast growth factor-2 (FGF2) secretion and consequently activated FGFR1 signaling following radiation in vivo and in vivo. Thus, free Ub confers protection against radiation-induced intestinal injury through CXCR4/Akt/FGF2 axis, which provides a novel therapeutic option.

20.
EPMA J ; 13(3): 499-517, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36061828

RESUMO

Background/aims: Predicting the clinical outcomes of primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) to methotrexate-based combination immunochemotherapy treatment in advance and therefore administering the tailored treatment to the individual is consistent with the principle of predictive, preventive, and personalized medicine (PPPM/3PM). The red blood cell distribution width (RDW) has been reported to be associated with the clinical outcomes of multiple cancer. However, its prognostic role in PCNS-DLBCL is yet to be evaluated. Therefore, we aimed to effectively stratify PCNS-DLBCL patients with different prognosis in advance and early identify the patients who were appropriate to methotrexate-based combination immunochemotherapy based on the pretreatment level of RDW and a clinical prognostic model. Methods: A prospective-retrospective, multi-cohort study was conducted from 2010 to 2020. We evaluated RDW in 179 patients (retrospective discovery cohorts of Huashan Center and Renji Center and prospective validation cohort of Cancer Center) with PCNS-DLBCL treated with methotrexate-based combination immunochemotherapy. A generalized additive model with locally estimated scatterplot smoothing was used to identify the relationship between pretreatment RDW levels and clinical outcomes. The high vs low risk of RDW combined with MSKCC score was determined by a minimal P-value approach. The clinical outcomes in different groups were then investigated. Results: The pretreatment RDW showed a U-shaped relationship with the risk of overall survival (OS, P = 0.047). The low RDW (< 12.6) and high RDW (> 13.4) groups showed significantly worse OS (P < 0.05) and progression-free survival (PFS; P < 0.05) than the median group (13.4 > RDW > 12.6) in the discovery and validation cohort, respectively. RDW could predict the clinical outcomes successfully. In the discovery cohort, RDW achieved the area under the receiver operating characteristic curve (AUC) of 0.9206 in predicting the clinical outcomes, and the predictive value (AUC = 0.7177) of RDW was verified in the validation cohort. In addition, RDW combined with MSKCC predictive model can distinguish clinical outcomes with the AUC of 0.8348 for OS and 0.8125 for PFS. Compared with the RDW and MSKCC prognosis variables, the RDW combined with MSKCC scores better identified a subgroup of patients with favorable long-term survival in the validation cohort (P < 0.001). RDW combined MSKCC score remained to be independently associated with clinical outcomes by multivariable analysis. Conclusions: Based on the pretreatment RDW and MSKCC scores, a novel predictive tool was established to stratify PCNS-DLBCL patients with different prognosis effectively. The predictive model developed accordingly is promising to judge the response of PCNS-DLBCL to methotrexate-based combination immunochemotherapy treatment. Thus, hematologists and oncologists could tailor and adjust therapeutic modalities by monitoring RDW in a prospective rather than the reactive manner, which could save medical expenditures and is a key concept in 3PM. In brief, RDW combined with MSKCC model could serve as an important tool for predicting the response to different treatment and the clinical outcomes for PCNS-DLBCL, which could conform with the principles of predictive, preventive, and personalized medicine. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00290-5.

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