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1.
Immun Inflamm Dis ; 12(10): e70027, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39387442

RESUMEN

BACKGROUND: Endotoxic shock, particularly prevalent in intensive care units, represents a significant medical challenge. Endotoxin, upon invading the host, triggers intricate interactions with the innate immune system, particularly macrophages. This activation leads to the production of inflammatory mediators such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta, as well as aberrant activation of the nuclear factor-kappa-B and mitogen-activated protein kinase signaling pathways. OBJECTIVE: This review delves into the intricate inflammatory cascades underpinning endotoxic shock, with a particular focus on the pivotal role of macrophages. It aims to elucidate the clinical implications of these processes and offer insights into potential therapeutic strategies. RESULTS: Macrophages, central to immune regulation, manifest in two distinct subsets: M1 (classically activated subtype) macrophages and M2 (alternatively activated subtype) macrophages. The former exhibit an inflammatory phenotype, while the latter adopt an anti-inflammatory role. By modulating the inflammatory response in patients with endotoxic shock, these macrophages play a crucial role in restoring immune balance and facilitating recovery. CONCLUSION: Macrophages undergo dynamic changes within the immune system, orchestrating essential processes for maintaining tissue homeostasis. A deeper comprehension of the mechanisms governing macrophage-mediated inflammation lays the groundwork for an anti-inflammatory, targeted approach to treating endotoxic shock. This understanding can significantly contribute to the development of more effective therapeutic interventions.


Asunto(s)
Inflamación , Macrófagos , Choque Séptico , Choque Séptico/inmunología , Humanos , Macrófagos/inmunología , Macrófagos/metabolismo , Animales , Inflamación/inmunología , Activación de Macrófagos/inmunología , Transducción de Señal/inmunología , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/inmunología
2.
Clin Transl Sci ; 17(9): e70006, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39286959

RESUMEN

Venetoclax, a small molecule inhibitor of BCL-2, has demonstrated efficacy in treating acute leukemias and has been recommended as one of the first-line anti-leukemia therapies. Although venetoclax has been suggested to probably possess the ability to penetrate the central nervous system (CNS), current data to elucidate the characteristics of venetoclax in cerebrospinal fluid (CSF), bone marrow (BM), and plasma are still lacking. This study investigated the real-world characteristics of venetoclax concentrations in CSF, BM, and plasma in acute leukemia patients. Thirteen acute leukemia patients treated with venetoclax were included, with paired samples of CSF, BM, and plasma collected and venetoclax concentrations measured using LC-MS/MS. With the results, the median venetoclax concentrations were 2030 ng/mL in plasma, 16.7 ng/mL in CSF, and 1390 ng/mL in BM. The percentages of CSF/plasma and BM/plasma were 0.74% and 70.37%, respectively. While no direct correlation was observed between CSF and plasma venetoclax levels, there was a trend toward an improved CSF/plasma percentage over time following the last administration of venetoclax. In contrast, a strong correlation was found between BM and plasma levels. This study demonstrated that venetoclax could reach its effective concentration in most patients, suggesting its potential clinical utility in the management of CNS involvement in acute leukemia.


Asunto(s)
Médula Ósea , Compuestos Bicíclicos Heterocíclicos con Puentes , Sulfonamidas , Humanos , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacocinética , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/líquido cefalorraquídeo , Compuestos Bicíclicos Heterocíclicos con Puentes/sangre , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacocinética , Sulfonamidas/líquido cefalorraquídeo , Sulfonamidas/sangre , Masculino , Persona de Mediana Edad , Femenino , Anciano , Médula Ósea/efectos de los fármacos , Adulto , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/líquido cefalorraquídeo , Antineoplásicos/sangre , Espectrometría de Masas en Tándem , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/líquido cefalorraquídeo , Leucemia Mieloide Aguda/sangre , Anciano de 80 o más Años , Cromatografía Liquida , Leucemia/tratamiento farmacológico , Leucemia/líquido cefalorraquídeo , Leucemia/sangre , Adulto Joven
4.
Front Genet ; 15: 1467682, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268081

RESUMEN

Introduction: The complexity of tumor cell subclonal structure has been extensively investigated in hepatocellular carcinoma. However, the role of subclonal complexity in reshaping the tumor microenvironment (TME) remains poorly understood. Methods: We integrated single-cell transcriptome sequencing data from four independent HCC cohorts, involving 30 samples, to decode the associations between tumor subclonal complexity and the TME. We proposed a robust metric to accurately quantify the degree of subclonal complexity for each sample based on discrete copy number variations (CNVs) profiles. Results: We found that tumor cells in the high-complexity group originated from the cell lineage with FGB overexpression and exhibited high levels of transcription factors associated with poor survival. In contrast, tumor cells in low-complexity patients showed activation of more hallmark signaling pathways, more active cell-cell communications within the TME and a higher immune activation status. Additionally, cytokines signaling activity analysis suggested a link between HMGB1 expressed by a specific endothelial subtype and T cell proliferation. Discussion: Our study sheds light on the intricate relationship between the complexity of subclonal structure and the TME, offering novel insights into potential therapeutic targets for HCC.

6.
Luminescence ; 39(6): e4806, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38881430

RESUMEN

As a biothiol, cysteine (Cys) is essential to both physiological and pathological processes and has been associated with many diseases, including neurological disorders, rheumatoid arthritis, and renal dysfunction. Therefore, the development of a high-performance probe for detecting Cys levels can help prevent and diagnose disease. In this study, a ratiometric fluorescent probe based on a novel fluorophore was developed for detecting Cys, and it showed high specificity and a rapid response time toward Cys. This probe demonstrates excellent biocompatibility and has been utilized effectively for the imaging of Cys in living cells.


Asunto(s)
Cisteína , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Cisteína/análisis , Cisteína/química , Humanos , Imagen Óptica , Estructura Molecular , Células HeLa
7.
Taiwan J Obstet Gynecol ; 63(3): 369-374, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38802200

RESUMEN

OBJECTIVE: To explore a precise association between tumor location and lymph node (LN) biopsy algorithm in uterine confined endometrial cancer (EC). MATERIALS AND METHODS: Patients with EC treated in the Department of Obstetrics and Gynecology, South Branch of Fujian Provincial Hospital were included in this observational retrospective study. Based on the procedure of treatment, patients were separated to stage I (2015.07-2019.09) and stage II (2019.09-2021.9). In each stage, patients were separated to high and low-risk group by the predicted results. Patients in the high-risk group received systematic lymphadenectomy in stage I and sentinel lymph node (SLN) dissection in stage II. The efficiency of lymph node metastasis (LNM) detection rates was compared between stage I and stage II cases. Precise lymph node biopsy algorithm was also constructed based on the outcomes of stage II. RESULTS: Overall, 43 patients, 28 in stage I and 15 in stage II, were included in the study. No recurrence or death cases had been found within follow-up terms. Based on the difference in the detection efficiency of LNM (p > 0.05), there was no difference between two stages. Thus, systematic lymphadenectomy and SLN biopsy provided similar success rates. The location of tumor site was also important for deciding whether pelvic or para-aortic SLN should be sampled for LNM. CONCLUSIONS: Precise SLN biopsy for EC confined to the uterus showed comparable LNM detection rate as systematic lymphadenectomy. EC location may be used to determine whether pelvic or para-aortic SLN sampling should be conducted for treatment.


Asunto(s)
Neoplasias Endometriales , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Estadificación de Neoplasias , Biopsia del Ganglio Linfático Centinela , Humanos , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Estudios Retrospectivos , Persona de Mediana Edad , Escisión del Ganglio Linfático/métodos , Metástasis Linfática/patología , Biopsia del Ganglio Linfático Centinela/métodos , Anciano , Ganglios Linfáticos/patología , Adulto , Algoritmos
8.
Surg Laparosc Endosc Percutan Tech ; 34(3): 281-289, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38533893

RESUMEN

OBJECTIVE: The purpose of the current study was to statistically clarify the precise risk age in elderly patients undergoing colorectal surgery and to evaluate the safety and efficacy of laparoscopic colorectal resection in these patients. METHODS: Patients' clinical variables were extracted from the database of the Gastrointestinal Surgery Centre, Third Affiliated Hospital of Sun Yat-sen University, from 2015 to 2019. Logistic regression was conducted to identify independent risk factors of postoperative complications and ORs for each age. Curves of odds ratios (ORs) and CIs for each age were fitted by using a locally weighted scatterplot smoother, and a structural breakpoint was determined by the Chow test to identify a precise cutoff risk age for elderly patients. Comparison and subgroup analysis were conducted between surgical approach groups using the Student t test and χ 2 analysis. RESULTS: Locally weighted scatterplot smoother OR analysis manifested that patients aged 69 years old or older suffered a higher possibility of postoperative complications and should be defined as high-risk age. Comparison according to the high-risk age revealed laparoscopic colorectal surgery is better than laparotomic surgery for elderly individuals in terms of hospital stay (9.46 ± 5.96 vs 15.01 ± 6.34, P < 0.05), the incidence of intensive care unit transfer (4 vs 20, P < 0.05), and incidence of surgical site infection (15 vs 20, P < 0.05). Patients who underwent laparotomic surgery had a greater prevalence of Clavien-Dindo II/III complications ( P < 0.05). These findings remained stable even after propensity matching. Furthermore, such superiority was proved especially significant for patients who underwent left-side colorectal resection. In addition, overall survival was improved in the laparoscopic surgery group, whereas no differences were observed in disease-free survival. CONCLUSION: In our study population, age 69 or older was a cutoff point age suggests a higher possibility of postoperative morbidity after colorectal surgery. Laparoscopic colorectal resection should be regarded as a superior therapeutic choice for these elderly individuals, especially for left-side colorectal surgeries.


Asunto(s)
Neoplasias Colorrectales , Laparoscopía , Complicaciones Posoperatorias , Humanos , Laparoscopía/métodos , Laparoscopía/efectos adversos , Anciano , Masculino , Femenino , Estudios Retrospectivos , Neoplasias Colorrectales/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano de 80 o más Años , Factores de Edad , Persona de Mediana Edad , Tiempo de Internación/estadística & datos numéricos , Resultado del Tratamiento , Colectomía/métodos , Factores de Riesgo
9.
Biochem Pharmacol ; 222: 116100, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38428824

RESUMEN

V-domain containing Ig Suppressor of T cell Activation (VISTA) is predominantly expressed on myeloid cells and functions as a ligand/receptor/soluble molecule. In inflammatory responses and immune responses, VISTA regulates multiple functions of myeloid cells, such as chemotaxis, phagocytosis, T cell activation. Since inflammation and immune responses are critical in many diseases, VISTA is a promising therapeutic target. In this review, we will describe the expression and function of VISTA on different myeloid cells, including neutrophils, monocytes, macrophages, dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs). In addition, we will discuss whether the functions of VISTA on these cells impact the disease processing.


Asunto(s)
Antígenos B7 , Células Supresoras de Origen Mieloide , Humanos , Antígenos B7/genética , Células Mieloides/metabolismo , Macrófagos/metabolismo , Inflamación
10.
Am J Pathol ; 194(1): 101-120, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37827215

RESUMEN

The Wnt/ß-catenin pathway represents a promising therapeutic target for mitigating kidney fibrosis. Corin possesses the homologous ligand binding site [Frizzled-cysteine-rich domain (Fz-CRD)] similar to Frizzled proteins, which act as receptors for Wnt. The Fz-CRD has been found in eight different proteins, all of which, except for corin, are known to bind Wnt and regulate its signal transmission. We hypothesized that corin may inhibit the Wnt/ß-catenin signaling pathway and thereby reduce fibrogenesis. Reduced expression of corin along with the increased activity of Wnt/ß-catenin signaling was found in unilateral ureteral obstruction (UUO) and ureteral ischemia/reperfusion injury (UIRI) models. In vitro, corin bound to the Wnt1 through its Fz-CRDs and inhibit the Wnt1 function responsible for activating ß-catenin. Transforming growth factor-ß1 inhibited corin expression, accompanied by activation of ß-catenin; conversely, overexpression of corin attenuated the fibrotic effects of transforming growth factor-ß1. In vivo, adenovirus-mediated overexpression of corin attenuated the progression of fibrosis, which was potentially associated with the inhibition of Wnt/ß-catenin signaling and the down-regulation of its target genes after UUO and UIRI. These results suggest that corin acts as an antagonist that protects the kidney from pathogenic Wnt/ß-catenin signaling and from fibrosis following UUO and UIRI.


Asunto(s)
Enfermedades Renales , Vía de Señalización Wnt , Ratones , Animales , Vía de Señalización Wnt/fisiología , beta Catenina/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Enfermedades Renales/genética , Enfermedades Renales/prevención & control , Enfermedades Renales/metabolismo , Riñón/patología , Fibrosis , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo
11.
Bioresour Technol ; 394: 130180, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38086457

RESUMEN

As a dewatering method of high moisture solid waste sludge, biodrying still faces environmental problems such as material loss and greenhouse gas emission in the process of treatment. In this study, biochar and magnesium chloride were used to explore the synergistic effect of enhancing sludge biodrying and reducing greenhouse gas emissions. The highest temperature of biodrying was raised to 68.2 °C within 3 days, extending the longest high-temperature period to 5 days, which reduced the water content to 28.8 % in the single addition of biochar treatment. The complex addition increased the NH4+-N content of materials by 57.49 % and decreased the NO3--N content of materials by 40.62 %. The use of additives significantly reduced the emissions of CO2, CH4, and N2O compared to the no-addition treatment. The increase in dominant Actinomycetes and Chloroflexibacter was the main reason for the reduction in gas emissions.


Asunto(s)
Gases de Efecto Invernadero , Gases de Efecto Invernadero/análisis , Aguas del Alcantarillado , Carbón Orgánico , Residuos Sólidos , Óxido Nitroso/análisis , Suelo
12.
Theranostics ; 13(11): 3744-3760, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37441593

RESUMEN

Rationale: Glioblastoma (GBM) is an aggressive malignant primary brain cancer with poor survival. Hypoxia is a hallmark of GBM, which promotes tumor cells spreading (invasion) into the healthy brain tissue. Methods: To better elucidate the influence of hypoxia on GBM invasion, we proposed a data-driven modeling framework for predicting cellular hypoxia (CHPF) by integrating single cell transcriptome profiling and hypoxia gene signatures. Results: We characterized the hypoxia status landscape of GBM cells and observed that hypoxic cells were only present in the tumor core. Then, by investigating the cell-cell communication between immune cells and tumor cells, we discovered significant interaction between macrophages and tumor cells in hypoxic microenvironment. Notably, we dissected the functional heterogeneity of tumor cells and identified a hypoxic subpopulation that had highly invasive potential. By constructing cell status specific gene regulatory networks, we further identified 14 critical regulators of tumor invasion induced by hypoxic microenvironment. Finally, we confirmed that knocking down two critical regulators CEBPD and FOSL1 could reduce the invasive ability of GBM under hypoxic conditions. Additionally, we revealed the therapeutic effect of Axitinib and Entinostat through the mice model. Conclusion: Our work revealed the critical regulators in hypoxic subpopulation with high invasive potential in GBM, which may have practical implications for clinical targeted-hypoxia cancer drug therapy.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Ratones , Animales , Glioblastoma/genética , Glioblastoma/patología , Factores de Transcripción/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Hipoxia , Hipoxia de la Célula , Análisis de Secuencia de ARN , Microambiente Tumoral
13.
Front Pharmacol ; 14: 1157433, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37324464

RESUMEN

Introduction: Carboplatin (CBP) is a DNA damaging drug used to treat various cancers, including advanced melanoma. Yet we still face low response rates and short survival due to resistance. Triptolide (TPL) is considered to have multifunctional antitumor effects and has been confirmed to enhance the cytotoxic effects of chemotherapeutic drugs. Herein, we aimed to investigate the knowledge about the effects and mechanisms for the combined application of TPL and CBP against melanoma. Methods: Melanoma cell lines and xenograft mouse model were used to uncover the antitumor effects and the underlying molecular mechanisms of the alone or combined treatment of TPL and CBP in melanoma. Cell viability, migration, invasion, apoptosis, and DNA damage were detected by conventional methods. The rate-limiting proteins of the NER pathway were quantitated using PCR and Western blot. Fluorescent reporter plasmids were used to test the NER repair capacity. Results: Our results showed that the presence of TPL in CBP treatment could selectively inhibit NER pathway activity, and TPL exerts a synergistic effect with CBP to inhibit viability, migration, invasion, and induce apoptosis of A375 and B16 cells. Moreover, combined treatment with TPL and CBP significantly inhibited tumor progression in nude mice by suppressing cell proliferation and inducing apoptosis. Discussion: This study reveals the NER inhibitor TPL which has great potential in treating melanoma, either alone or in combination with CBP.

14.
J Environ Manage ; 335: 117492, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36863149

RESUMEN

Mobile genetic elements (MGEs) mediated horizontal gene transfer is the primary reason for the propagation of antibiotic resistance genes in environment. The behavior of MGEs under magnetic biochar pressure in sludge anaerobic digestion (AD) is still unknown. This study evaluated the effects of different dosage magnetic biochar on the MGEs in AD reactors. The results showed that the biogas yield was highest (106.68 ± 1.16 mL g-1 VSadded) with adding optimal dosage of magnetic biochar (25 mg g-1 TSadded), due to it increased the microorganism's abundance involved in hydrolysis and methanogenesis. While, the total absolute abundance of MGEs in the reactors with magnetic biochar addition increased by 11.58%-77.37% compared with the blank reactor. When the dosage of magnetic biochar was 12.5 mg g-1 TSadded, the relative abundance of most MGEs was the highest. The enrichment effect on ISCR1 was the most significant, and the enrichment rate reached 158.90-214.16%. Only the intI1 abundance was reduced and the removal rates yield 14.38-40.00%, which was inversely proportional to the dosage of magnetic biochar. Co-occurrence network explored that Proteobacteria (35.64%), Firmicutes (19.80%) and Actinobacteriota (15.84%) were the main potential host of MGEs. Magnetic biochar changed MGEs abundance by affecting the potential MGEs-host community structure and abundance. Redundancy analysis and variation partitioning analysis showed that the combined effect of polysaccharides, protein and sCOD exhibited the greatest contribution (accounted for 34.08%) on MGEs variation. These findings demonstrated that magnetic biochar increases the risk of MGEs proliferation in AD system.


Asunto(s)
Genes Bacterianos , Aguas del Alcantarillado , Anaerobiosis , Antibacterianos/farmacología , Secuencias Repetitivas Esparcidas , Fenómenos Magnéticos , Estiércol/microbiología
15.
Biochem Pharmacol ; 210: 115492, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36898416

RESUMEN

Tumor cells can evade the innate and adaptive immune systems, which play important roles in tumor recurrence and metastasis. Malignant tumors that recur after chemotherapy are more aggressiveciscis, suggesting an increased ability of the surviving tumor cells to evade innate and adaptive immunity. Therefore, in order to reduce patient mortality, it is important to discover the mechanisms by which tumor cells develop resistance to chemotherapeutics. In the present study we focused on the tumor cells that survived chemotherapy. We found that chemotherapy could promote the expression of VISTA in tumor cells, and that this change was mediated by HIF-2α. In addition, VISTA overexpression on melanoma cells promoted immune evasion, and the application of the VISTA-blocking antibody 13F3 enhanced the therapeutic effect of carboplatin. These results offer an insight into the immune evasion of chemotherapy-resistant tumors, and provide a theoretical basis for the combined application of chemotherapy drugs and VISTA inhibitors to treat tumors.


Asunto(s)
Inmunidad Adaptativa , Recurrencia Local de Neoplasia , Humanos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo
16.
Pathol Oncol Res ; 29: 1610874, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36910015

RESUMEN

Objectives: We aimed to explore reasonable lymph node classification strategies for left-sided colon cancer (LCC) patients. Methods: 48,425 LCC patients from 2010 to 2015 were identified in the US Surveillance, Epidemiology, and End Results database. We proposed an innovative revised nodal (rN) staging of the 8th American Joint Committee on Cancer (AJCC) Tumor/Node/Metastasis (TNM) classification based on the cut-off value of retrieved lymph nodes and survival analyses in patients with LCC. Log odds of positive lymph nodes (LODDS) stage is a numerical classification strategy obtained by a formula that incorporates the numbers of retrieved and positive lymph nodes. To develop the TrN or TLODDS classification, patients with similar survival rates were grouped by combining T and rN or LODDS stage. The TrN or TLODDS classification was further evaluated in a validation set of 12,436 LCC patients from 2016 to 2017 in the same database and a Chinese application set of 958 LCC patients. Results: We developed novel TrN and TLODDS classifications for LCC patients that incorporated 7 stages with reference to the AJCC staging system. In comparison to the 8th AJCC TNM and TrN classifications, TLODDS classification demonstrated significantly better discrimination (area under the receiver operating characteristic curve, 0.650 vs. 0.656 vs. 0.661, p < 0.001), better model-fitting (Akaike information criteria, 309,287 vs. 308,767 vs. 308,467), and superior net benefits. The predictive performance of the TrN and TLODDS classifications was further verified in the validation and application sets. Conclusion: Both the TrN and TLODDS classifications have better discriminatory ability, model-fitting, and net benefits than the existing TNM classification, and represent an alternative to the current TNM classification for LCC patients.


Asunto(s)
Neoplasias del Colon , Ganglios Linfáticos , Humanos , Estadificación de Neoplasias , Pronóstico , Ganglios Linfáticos/patología , Neoplasias del Colon/patología , Análisis de Supervivencia , Estudios Retrospectivos
17.
Cells ; 12(3)2023 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-36766710

RESUMEN

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with different molecular subtypes. Although progress has been made, the identification of TNBC subtype-associated biomarkers is still hindered by traditional RNA-seq or array technologies, since bulk data detected by them usually have some non-disease tissue samples, or they are confined to measure the averaged properties of whole tissues. To overcome these constraints and discover TNBC subtype-specific prognosis signatures (TSPSigs), we proposed a single-cell RNA-seq-based bioinformatics approach for identifying TSPSigs. Notably, the TSPSigs we developed mostly were found to be disease-related and involved in cancer development through investigating their enrichment analysis results. In addition, the prognostic power of TSPSigs was successfully confirmed in four independent validation datasets. The multivariate analysis results showed that TSPSigs in two TNBC subtypes-BL1 and LAR, were two independent prognostic factors. Further, analysis results of the TNBC cell lines revealed that the TSPSigs expressions and drug sensitivities had significant associations. Based on the preceding data, we concluded that TSPSigs could be exploited as novel candidate prognostic markers for TNBC patients and applied to individualized treatment in the future.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/metabolismo , Análisis de Expresión Génica de una Sola Célula , Biomarcadores de Tumor/genética , Análisis Multivariante , Biología Computacional
18.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 37(1): 31-36, 2023 Jan 15.
Artículo en Chino | MEDLINE | ID: mdl-36708112

RESUMEN

Objective: By comparing with traditional L-shaped plate, to explore the effectiveness of new Pilon plate in the treatment of type C Pilon fracture. Methods: A clinical data of 57 patients with type C Pilon fractures who met the selection criteria between May 2018 and January 2020 was analyzed retrospectively. Thirty-two patients were treated with new Pilon plate (trial group) and 25 patients with traditional L-shaped plate (control group). There was no significant difference in gender, age, cause of injury, fracture side and type, the interval between injury and operation between the two groups (P>0.05). The operation time and complications of the two groups were recorded. X-ray films were taken after operation to assess the quality of fracture reduction according to the Burwell-Charnley classification and fracture healing. Ankle function was evaluated according to Johner-Wruhs scoring standard and American Orthopaedic Foot and Ankle Society (AOFAS) score. Results: The operations of the two groups were completed successfully, and the operation time of the trial group was significantly shorter than that of the control group (t=-3.025, P=0.005). After operation, the incision necrosis occurred in 2 cases of the control group, and the incisions of other patients in both groups healed by first intention. All patients were followed up 8-16 months, with an average of 10.1 months. There was no significant difference in follow-up time between the two groups (t=0.433, P=0.667). X-ray films showed that the ankle reduction of the trial group was rated as excellent in 28 cases and good in 4 cases, with an excellent and good rate of 100%, while in the control group, the ankle reduction was rated as excellent in 15 cases, good in 5 cases, and fair in 5 cases, with an excellent and good rate of 80.0%. There was a significant difference in the excellent and good rate of fracture reduction between the two groups (Z=-2.565,P=0.010). The fracture healed in both groups, and the healing time was (16.59±3.78) weeks in the trial group and (17.80±3.81) weeks in the control group, and there was no significant difference between the two groups (t=-1.191, P=0.239). At last follow-up, according to Johner-Wruhs scoring standard, the ankle joint function in the trial group was evaluated as excellent in 25 cases and good in 7 cases, with an excellent and good rate of 100%; the AOFAS score was 90.9±4.5. In the control group, 16 cases were excellent, 5 cases were good, and 4 cases were fair, and the excellent and good rate was 84.0%; the AOFAS score was 85.2±10.0. The ankle function scores of the trial group was superior to that of the control group (P<0.05). During follow-up, except for 1 case of ankle traumatic arthritis in the control group, there was no complication such as ankle malunion, plate loosening and fracture, or fracture reduction loss in both groups. Conclusion: Compared with the traditional L-shaped plate, the new Pilon plate in the treatment of type C Pilon fracture has the advantages of high reduction quality, reliable fixation, less irritation to soft tissue, high fracture healing rate, and satisfactory functional recovery of ankle joint.


Asunto(s)
Fracturas de Tobillo , Fracturas de la Tibia , Humanos , Fracturas de Tobillo/diagnóstico por imagen , Fracturas de Tobillo/cirugía , Fijación Interna de Fracturas , Curación de Fractura , Estudios Retrospectivos , Fracturas de la Tibia/cirugía , Resultado del Tratamiento , Ensayos Clínicos Controlados como Asunto
19.
Int J Mol Sci ; 24(2)2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36674577

RESUMEN

SNAI2 (Snai2) is a zinc-finger transcriptional repressor that belongs to the Snail family. The accumulated evidence suggests that SNAI2 exhibits biphasic effects on regulating a stem-like phenotype in various types of cells, both normal and malignant. In this study, by exogenously expressing SNAI2 in SiHa cells, SNAI2 exhibited the capacity to inhibit a stem-like phenotype in cervical cancer cells. The SNAI2-overexpressing cells inhibited cell growth, tumorsphere formation, tumor growth, enhanced sensitivity to cisplatin, reduced stem cell-related factors' expression, and lowered tumor initiating frequency. In addition, the EPCAMhigh cells sorted from SiHa cells exhibited an enhanced capacity to maintain a stem-like phenotype. Further study demonstrated that the trans-suppression of EPCAM expression by SNAI2 led to blockage of the nuclear translocation of ß-catenin, as well as reduction in SOX2 and c-Myc expression in SiHa and HeLa cells, but induction in SNAI2 knockdown cells (CaSki), which would be responsible for the attenuation of the stem-like phenotype in cervical cancer cells mediated by SNAI2. All of these results demonstrated that SNAI2 could attenuate the stem-like phenotype in cervical cancer cells through the EPCAM/ß-catenin axis.


Asunto(s)
Neoplasias del Cuello Uterino , beta Catenina , Humanos , Femenino , beta Catenina/metabolismo , Neoplasias del Cuello Uterino/patología , Molécula de Adhesión Celular Epitelial/genética , Células HeLa , Factores de Transcripción de la Familia Snail/genética , Línea Celular Tumoral , Fenotipo
20.
Rev Cardiovasc Med ; 24(9): 267, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39076388

RESUMEN

Background: Hypertrophic obstructive cardiomyopathy (HOCM) patients are reported to have a potential risk of sudden cardiac death (SCD); however, HCM with left ventricular outflow tract (LVOT) obstruction, which is regarded as a risk indicator of SCD, is doubtful since the LVOT gradient is dynamic and may be confounded by various environmental factors and routine activities. The purpose of this study was to explore the clinical prognosis of HOCM through a multicenter cohort study with data-driven propensity score matching (PSM) analysis. Methods: The cohort included 2268 patients with HCM from 1996 to 2021 in 13 tertiary hospitals. In the present study, we excluded 458 patients who underwent alcohol septal ablation (ASA) and septal myectomy (SM) surgery so 1810 HCM patients were eventually included. We developed a data-driven propensity score using 24 demographic and clinical variables to create 1:1 propensity-matched cohorts. A Cox proportional hazard regression model was constructed to assess the effect of HOCM on mortality. Results: After logit-matching, there were no significant differences in all-cause mortality (log-rank χ 2 = 1.509, p = 0.22), cardiovascular mortality/cardiac transplantation (log-rank χ 2 = 0.020, p = 0.89) or SCD (log-rank χ 2 = 0.503, p = 0.48) between patients with HOCM and hypertrophic nonobstructive cardiomyopathy (HNCM), and according to the Cox proportional hazard regression model, LVOT obstruction was not a risk predictor in patients with HCM. Conclusions: In both matched and unmatched cohorts, there were no significant differences in clinical prognosis between HOCM and HNCM patients, and LVOT obstruction was not an independent risk predictor of prognosis in patients with HCM. Clinical Trial Registration: ChiCTR1800017330.

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