RESUMEN
The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 system, a groundbreaking innovation in genetic engineering, has revolutionized our approach to surmounting complex diseases, culminating in CASGEVY™ approved for sickle cell anemia. Derived from a microbial immune defense mechanism, CRISPR/Cas9, characterized as precision, maneuverability and universality in gene editing, has been harnessed as a versatile tool for precisely manipulating DNA in mammals. In the process of applying it to practice, the consecutive exploitation of novel orthologs and variants never ceases. It's conducive to understanding the essentialities of diseases, particularly cancer, which is crucial for diagnosis, prevention, and treatment. CRISPR/Cas9 is used not only to investigate tumorous genes functioning but also to model disparate cancers, providing valuable insights into tumor biology, resistance, and immune evasion. Upon cancer therapy, CRISPR/Cas9 is instrumental in developing individual and precise cancer therapies that can selectively activate or deactivate genes within tumor cells, aiming to cripple tumor growth and invasion and sensitize cancer cells to treatments. Furthermore, it facilitates the development of innovative treatments, enhancing the targeting efficiency of reprogrammed immune cells, exemplified by advancements in CAR-T regimen. Beyond therapy, it is a potent tool for screening susceptible genes, offering the possibility of intervening before the tumor initiative or progresses. However, despite its vast potential, the application of CRISPR/Cas9 in cancer research and therapy is accompanied by significant efficacy, efficiency, technical, and safety considerations. Escalating technology innovations are warranted to address these issues. The CRISPR/Cas9 system is revolutionizing cancer research and treatment, opening up new avenues for advancements in our understanding and management of cancers. The integration of this evolving technology into clinical practice promises a new era of precision oncology, with targeted, personalized, and potentially curative therapies for cancer patients.
Asunto(s)
Sistemas CRISPR-Cas , Neoplasias , Medicina de Precisión , Humanos , Sistemas CRISPR-Cas/genética , Medicina de Precisión/métodos , Neoplasias/genética , Neoplasias/terapia , Edición Génica/métodos , Animales , Oncología Médica/métodos , Oncología Médica/tendenciasRESUMEN
To investigate the expression of Bax and Bcl2 protein in peripheral blood mononuclear cells (PBMC) of patients with chronic heart failure (CHF), and to analyze their value for predicting major adverse cardiovascular event (MACE) in CHF patients. A total of 154 fasting venous blood samples from CHF patients were collected in our hospital from January 2017 to June 2019, and they were divided into 2 group according to whether MACE occurred during 3 years follow-up, MACE group and No-MACE group. Levels of Bax and Bcl2 protein expression in PBMC of CHF patients using enzyme-linked immunosorbent assay (ELISA), and then evaluated the predictive power of Bax and Bcl2 expression for MACE using logistic regression analysis and ROC curve. 62 (40.26%) of 154 CHF patients occurred MACE during follow-up, and there were significant differences in age, diabetes, LVEF, LDL-C and NYHA grade between MACE group and No-MACE group. Levels of Bax protein expression in PBMC of CHF patients in MACE group were significantly higher than those in No-MACE group, while levels of Bcl2 protein expression were significantly lower than those in No-MACE group, and Bax and Bcl2 protein levels increased and decreased with NYHA grades in MACE group and No-MACE group, respectively. Results of univariate and multivariate logistic regression analysis showed that Bax (OR, 1.026; 95% CI, 1.003-1.049; Pâ =â .027) and Bcl2 levels (OR, 0.952; 95% CI, 0.908-0.998; Pâ =â .041) were independent predictive factors for MACE in CHF patients. In addition, Bax and Bcl2 levels could be used to differentiate CHF patients at risk for MACE with an AUC of 0.744 (95% CI: 0.660-0.827) and an AUC of 0.743 (95% CI: 0.667-0.819), respectively. Levels of Bax and Bcl2 protein in PBMC could be used as independent predictive factors for MACE in CHF patients.
Asunto(s)
Insuficiencia Cardíaca , Leucocitos Mononucleares , Humanos , Proteína X Asociada a bcl-2 , Leucocitos Mononucleares/metabolismo , PronósticoRESUMEN
Public transit, especially urban rail systems, plays a vital role in shaping commuting patterns. Compared with census data and survey data, large-scale and real-time big data can track the impacts of urban policy implementations at finer spatial and temporal scales. Therefore, this study proposed a multi-level analytical framework using transit smartcard data to examine urban commuting dynamics in response to rail transit upgrades. The study area was Shenzhen, one of the most highly urbanized and densely populated cities in China, which provides the opportunity to examine the effects of rail transit upgrades on commuting patterns in a rapidly developing urban context. Changes in commuting patterns were examined at three levels: city, region, and individual. At the city level, we considered the average commuting time, commuting speed, and commuting distance across the whole city. At the region level, we analyzed changes in the job accessibility of residential zones. Finally, this study evaluated the potential effects of rail transit upgrades on the jobs-housing relationship at the individual level. Difference-in-difference models were used for causal inference between rail transit upgrades and commuting patterns. In the very short term, the opening of new rail transit lines resulted in no significant changes in overall commuting patterns across the whole city; however, two effects of rail transit upgrades on commuting patterns were identified. First, rail transit upgrades enhanced regional connectivity between residential zones and employment centers, thus improving job accessibility. Second, rail transit improvement increased the commuting distances of individuals and contributed to the separation of workplaces and residences. This study provides meaningful insights into the effects of rail transit upgrades on commuting patterns.