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1.
BMC Womens Health ; 24(1): 527, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39304877

RESUMEN

BACKGROUND: Perivascular epithelioid cell tumours (PEComas) are soft tissue tumours. These neoplasms belong to the family of mesenchymal tumours, which include angiomyolipomas, clear-cell sugar tumours of the lung, and PEComas not otherwise specified (NOS). The probability of a perivascular epithelioid cell tumour (PEComa) occurring in the uterus is low, and the incidence, diagnosis, treatment, and outcomes of such tumours are still unclear. CASE PRESENTATION: A 51-year-old woman presented a 4-year history of natural menopause. An intrauterine mass was detected via ultrasound examination; the mass showed a tendency to increase but caused no symptoms. The levels of tumour markers were within the normal range. Pathological analysis of the curettage revealed perivascular epithelioid differentiation of the endometrial tumour. Consequently, a laparoscopic total hysterectomy with bilateral adnexectomy was performed. No distant metastasis was detected via whole-body positron emission computed tomography (PETCT) after the operation. Fluorescence in situ hybridization (FISH) revealed no TFE3 gene rearrangement. Next-generation sequencing of bone and soft tissue revealed negative TSC1/2 and TP53 expression. No recurrence or metastasis was observed during the 18-month follow-up period. CONCLUSION: PEComa of the gynecologic tract is a rare and challenging entity. Diffuse HMB-45 expression, TSC alterations and TFE3 rearrangement are characteristic of uterine PEComas. Surgical resection is the first choice. Genetic testing is helpful for determining the nature of the mass and for choosing targeted therapy. Further research is needed to establish treatment protocols.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Reordenamiento Génico , Neoplasias de Células Epitelioides Perivasculares , Neoplasias Uterinas , Humanos , Femenino , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/cirugía , Neoplasias de Células Epitelioides Perivasculares/patología , Persona de Mediana Edad , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/diagnóstico , Reordenamiento Génico/genética , Histerectomía/métodos
2.
J Robot Surg ; 18(1): 354, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39340614

RESUMEN

As robot-assisted laparoscopic techniques continue to advance, becoming increasingly complex and refined, there has been significant progress in the minimally invasive treatment of ureteral strictures. This abstract aims to provide an overview and description of various surgical techniques that utilize robots for repairing ureteral strictures. We have summarized the progression of these surgical methods and highlighted the latest advancements in the procedures. When compared to open surgery, robot-assisted reconstruction techniques demonstrate superior functional outcomes, fewer postoperative complications, and a faster recovery in the treatment of ureteral strictures. This abstract aims to provide an overview and description of various surgical techniques utilizing robots to repair ureteral strictures. Robotic ureteral stricture correction has emerged as a valuable therapeutic option, particularly when endoscopic procedures are not feasible. Compared to traditional open surgery, robotic methods exhibit superior therapeutic effectiveness, fewer postoperative complications, and accelerated recovery. Reconstructive procedures such as reimplantation, psoas hitch, Boari flap, ureter-to-ureter anastomosis, appendix graft, buccal mucosa graft (BMG), ileal transplantation, or kidney autotransplantation can be performed depending on the extent and location of the stricture. Robotic surgical techniques also offer advantages, such as an expanded field of vision and the incorporation of supplementary technologies such as FireflyTM, indocyanine green (ICG), and near-infrared fluorescence (NIRF) imaging. However, further long-term, multicenter investigations are necessary to validate the positive findings reported in existing case series. Compared with open surgery, robot-assisted reconstruction techniques yield superior functional outcomes, fewer postoperative complications, and accelerated recovery for the treatment of ureteral strictures.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Uréter , Obstrucción Ureteral , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Constricción Patológica/cirugía , Obstrucción Ureteral/cirugía , Uréter/cirugía , Complicaciones Posoperatorias , Procedimientos de Cirugía Plástica/métodos , Anastomosis Quirúrgica/métodos , Laparoscopía/métodos , Mucosa Bucal/cirugía , Apéndice/cirugía , Trasplante de Riñón/métodos , Íleon/cirugía , Resultado del Tratamiento , Procedimientos Quirúrgicos Urológicos/métodos , Reimplantación/métodos
3.
Transl Oncol ; 49: 102097, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39173480

RESUMEN

BACKGROUND: Synthetic lethality (SL) emerges as a novel concept being explored to combat cancer progression and resistance to conventional therapy. Despite the efficacy of chemotherapy in select cases of colorectal cancer (CRC), a substantial proportion of patients encounter challenges, leading to an adverse prognosis of CRC patients. CRC-related SL genes offer a potential avenue for identifying therapeutic targets. METHODS: CRC-related SL genes were obtained from the SynLethDB database. The bulk RNA sequencing data, mutation data, and clinical information for treated and untreated CRC patients were enrolled from the UCSC and GEO databases. The Tumor Immunology Single Cell Center database served as the repository for collecting and analyzing single-cell RNA sequencing data. The synergistic killing effect of SL genes and chemotherapeutic drugs on resistant cells was experimentally verified. RESULTS: In the present study, pivotal SL genes associated with chemoresistance identified by using WGCNA and CRC patients categorized into two groups based on these genes. Variations between the groups were most pronounced in pathways associated with extracellular matrix remodeling. Further by integrating mutation data, five potential SL genes were discerned, which were highly expressed in the presence of TP53 or KRAS mutations, leading to a severely poor prognosis. Subsequent time series analysis revealed that the expression of GTF2H5 was gradually elevated at different stages of the transition from sensitive to resistant in CRC cells. Finally, it was preliminarily verified by experiments that GTF2H5 may play a key role in driving the drug-resistant transition within CRC cells. CONCLUSIONS: The identification of SL genes that collaboratively interact with chemotherapeutic agents could provide new insights into solving the issue of chemotherapy resistance in CRC patients. And GTF2H5 wields a fundamental influence in inducing chemoresistance in CRC, which provided a potential therapeutic target for CRC.

5.
Shanghai Kou Qiang Yi Xue ; 33(3): 332-336, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39104354

RESUMEN

PURPOSE: To evaluate the effect of standardized periodontal probing training on the teaching of periodontal clinical probing for undergraduates by using Florida probe system. METHODS: Twenty undergraduates who practiced in the Department of Periodontology of Changzhou Stomatological Hospital from May 2022 to November 2022 were selected as the study objects and randomly divided into two groups with 10 students in each group. The experimental group received standardized periodontal probing training, while the control group did not receive training. Two groups of students used the traditional probe and the Florida probe to probe the left and right half-mouth teeth of one patient. In addition, a periodontal specialist used Florida probe to conduct full oral examination of the same patient, and the results were compared with those of the two groups of students. SPSS 26.0 software package was used for statistical analysis of the obtained data. RESULTS: There was no significant difference of probing depth(PD) between undergraduates and periodontal specialist in the experimental group (P>0.05), while there was significant difference in the control group (P<0.05). In the control group, PD values in the anterior area were not statistically different from those of periodontal specialist (P>0.05), while PD values in the posterior area were statistically different (P<0.05). Both groups of patients reported that the Florida probe system was more comfortable. CONCLUSIONS: Standardized periodontal probing training is helpful to improve the clinical probing ability of undergraduates. The use of Florida probe system can not only evaluate the teaching effect, but also improve the comfort level of patients, which is worthy of further application in the teaching course of periodontal probing for undergraduates.


Asunto(s)
Periodoncia , Humanos , Periodoncia/educación , Educación en Odontología/métodos , Educación en Odontología/normas
6.
World J Gastrointest Surg ; 16(6): 1647-1659, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38983313

RESUMEN

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammatory indicators that can be used to predict the severity and prognosis of various diseases. We categorize acute pancreatitis by etiology into acute biliary pancreatitis (ABP) and hypertriglyceridemia-induced acute pancreatitis (HTGP). AIM: To investigate the clinical significance of NLR and PLR in assessing persistent organ failure (POF) in HTGP and ABP. METHODS: A total of 1450 patients diagnosed with acute pancreatitis (AP) for the first time at Shanxi Bethune Hospital between January 2012 and January 2023 were enrolled. The patients were categorized into two groups according to the etiology of AP: ABP in 530 patients and HTGP in 241 patients. We collected and compared the clinical data of the patients, including NLR, PLR, and AP prognostic scoring systems, within 48 h of hospital admission. RESULTS: The NLR (9.1 vs 6.9, P < 0.001) and PLR (203.1 vs 160.5, P < 0.001) were significantly higher in the ABP group than in the HTGP group. In the HTGP group, both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score ≥ 3. Likewise, in the ABP group, NLR and PLR were significantly elevated in patients with severe AP, modified computed tomography severity index score ≥ 4, Japanese Severity Score ≥ 3, and modified Marshall score ≥ 2. Moreover, NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP groups. CONCLUSION: NLR and PLR vary between ABP and HTGP, are strongly associated with AP prognostic scoring systems, and have predictive potential for the occurrence of POF in both ABP and HTGP.

7.
Appl Microbiol Biotechnol ; 108(1): 428, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39066795

RESUMEN

Acinetobacter baumannii, which is resistant to multiple drugs, is an opportunistic pathogen responsible for severe nosocomial infections. With no antibiotics available, phages have obtained clinical attention. However, since immunocompromised patients are often susceptible to infection, the appropriate timing of administration is particularly important. During this research, we obtained a lytic phage vB_AbaM_P1 that specifically targets A. baumannii. We then assessed its potential as a prophylactic treatment for lung infections caused by clinical strains. The virus experiences a period of inactivity lasting 30 min and produces approximately 788 particles during an outbreak. Transmission electron microscopy shows that vB_AbaM_P1 was similar to the Saclayvirus. Based on the analysis of high-throughput sequencing and bioinformatics, vB_AbaM_P1 consists of 107537 bases with a G + C content of 37.68%. It contains a total of 177 open reading frames and 14 tRNAs. No antibiotic genes were detected. In vivo experiments, using a cyclophosphamide-induced neutrophil deficiency model, tested the protective effect of phage on neutrophil-deficient rats by prophylactic application of phage. The use of phages resulted in a decrease in rat mortality caused by A. baumannii and a reduction in the bacterial burden in the lungs. Histologic examination of lung tissue revealed a decrease in the presence of immune cells. The presence of phage vB_AbaM_P1 had a notable impact on preventing A. baumannii infection, as evidenced by the decrease in oxidative stress in lung tissue and cytokine levels in serum. Our research offers more robust evidence for the early utilization of bacteriophages to mitigate A. baumannii infection. KEY POINTS: •A novel Saclayvirus phage infecting A. baumannii was isolated from sewage. •The whole genome was determined, analyzed, and compared to other phages. •Assaying the effect of phage in preventing infection in neutrophil-deficient models.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Genoma Viral , Acinetobacter baumannii/virología , Acinetobacter baumannii/genética , Animales , Infecciones por Acinetobacter/prevención & control , Infecciones por Acinetobacter/microbiología , Bacteriófagos/genética , Bacteriófagos/aislamiento & purificación , Bacteriófagos/fisiología , Ratas , Terapia de Fagos/métodos , Composición de Base , Modelos Animales de Enfermedad , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Pulmón/virología , Pulmón/microbiología , Neumonía/prevención & control , Neumonía/microbiología , Neumonía/virología , Masculino
8.
Environ Geochem Health ; 46(8): 270, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954122

RESUMEN

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.


Asunto(s)
Radioisótopos de Cesio , Minería , Contaminantes Radiactivos del Suelo , Medición de Riesgo , China , Contaminantes Radiactivos del Suelo/análisis , Radioisótopos de Cesio/análisis , Humanos , Radioisótopos de Estroncio/análisis , Cesio/análisis , Ciudades , Suelo/química , Método de Montecarlo , Monitoreo de Radiación
9.
bioRxiv ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38826355

RESUMEN

An "induced PARP inhibitor (PARPi) sensitivity by epigenetic modulation" strategy is being evaluated in the clinic to sensitize homologous recombination (HR)-proficient tumors to PARPi treatments. To expand its clinical applications and identify more efficient combinations, we performed a drug screen by combining PARPi with 74 well-characterized epigenetic modulators that target five major classes of epigenetic enzymes. Both type I PRMT inhibitor and PRMT5 inhibitor exhibit high combination and clinical priority scores in our screen. PRMT inhibition significantly enhances PARPi treatment-induced DNA damage in HR-proficient ovarian and breast cancer cells. Mechanistically, PRMTs maintain the expression of genes associated with DNA damage repair and BRCAness and regulate intrinsic innate immune pathways in cancer cells. Analyzing large-scale genomic and functional profiles from TCGA and DepMap further confirms that PRMT1, PRMT4, and PRMT5 are potential therapeutic targets in oncology. Finally, PRMT1 and PRMT5 inhibition act synergistically to enhance PARPi sensitivity. Our studies provide a strong rationale for the clinical application of a combination of PRMT and PARP inhibitors in patients with HR-proficient ovarian or breast cancer.

10.
Int Immunopharmacol ; 137: 112487, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38889513

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is the third most malignant tumor in the world. 5-fluorouracil (5­FU) -based chemotherapy is the first-line chemotherapy scheme for CRC, whereas acquired drug resistance poses a huge obstacle to curing CRC patients and the mechanism is still obscure. Therefore, identification of genes associated with 5­FU chemotherapy and seeking second-line treatment are necessary means to improve survival and prognosis of patients with CRC. METHODS: The Cancer Therapeutics Response Portal (CTRP) database and Genomics of Drug Sensitivity in Cancer (GDSC) database were used to identify CRC-related genes and potential second-line therapies for 5-FU-resistant CRC. The single-cell RNA sequencing data for CRC tissues were obtained from a GEO dataset. The relationship between ITGA2 and 5-FU-resistant was investigated in vitro and in vivo models. RESULTS: ACOX1 and ITGA2 were identified as risk biomarkers associated with 5-FU-resistance. We developed a risk signature, consisting of ACOX1 and ITGA2, that was able to distinguish well between 5-FU-resistance and 5-FU-sensitive. The single-cell sequencing data showed that ITGA2 was mainly enriched in malignant cells. ITGA2 was negatively correlated with IC50 values of most small molecule inhibitors, of which selumetinib had the highest negative correlation. Finally, knocking down ITGA2 can make 5-FU-resistant CRC cells sensitive to 5-FU and combining with selumetinib can improve the therapeutic effect of 5-FU resistant cells. CONCLUSION: In summary, our findings demonstrated the critical role of ITGA2 in enhancing chemotherapy resistance in CRC cells and suggested that selumetinib can restore the sensitivity of chemotherapy-resistant CRC cells to 5-FU by inhibiting ITGA2 expression.


Asunto(s)
Bencimidazoles , Neoplasias Colorrectales , Resistencia a Antineoplásicos , Fluorouracilo , Integrina alfa2 , Humanos , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Fluorouracilo/uso terapéutico , Fluorouracilo/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Integrina alfa2/genética , Integrina alfa2/metabolismo , Animales , Bencimidazoles/uso terapéutico , Bencimidazoles/farmacología , Línea Celular Tumoral , Ratones , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C
11.
J Virol ; 98(7): e0046724, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38864621

RESUMEN

Acinetobacter baumannii, an opportunistic pathogen, poses a significant threat in intensive care units, leading to severe nosocomial infections. The rise of multi-drug-resistant strains, particularly carbapenem-resistant A. baumannii, has created formidable challenges for effective treatment. Given the prolonged development cycle and high costs associated with antibiotics, phages have garnered clinical attention as an alternative for combating infections caused by drug-resistant bacteria. However, the utilization of phage therapy encounters notable challenges, including the narrow host spectrum, where each phage targets a limited subset of bacteria, increasing the risk of phage resistance development. Additionally, uncertainties in immune system dynamics during treatment hinder tailoring symptomatic interventions based on patient-specific states. In this study, we isolated two A. baumannii phages from wastewater and conducted a comprehensive assessment of their potential applications. This evaluation included sequencing analysis, genome classification, pH and temperature stability assessments, and in vitro bacterial inhibition assays. Further investigations involved analyzing histological and cytokine alterations in rats undergoing phage cocktail treatment for pneumonia. The therapeutic efficacy of the phages was validated, and transcriptomic studies of rat lung tissue during phage treatment revealed crucial changes in the immune system. The findings from our study underscore the potential of phages for future development as a treatment strategy and offer compelling evidence regarding immune system dynamics throughout the treatment process.IMPORTANCEDue to the growing problem of multi-drug-resistant bacteria, the use of phages is being considered as an alternative to antibiotics, and the genetic safety and application stability of phages determine the potential of phage application. The absence of drug resistance genes and virulence genes in the phage genome can ensure the safety of phage application, and the fact that phage can remain active in a wide range of temperatures and pH is also necessary for application. In addition, the effect evaluation of preclinical studies is especially important for clinical application. By simulating the immune response situation during the treatment process through mammalian models, the changes in animal immunity can be observed, and the effect of phage therapy can be further evaluated. Our study provides compelling evidence that phages hold promise for further development as therapeutic agents for Acinetobacter baumannii infections.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Carbapenémicos , Modelos Animales de Enfermedad , Terapia de Fagos , Acinetobacter baumannii/virología , Acinetobacter baumannii/efectos de los fármacos , Animales , Infecciones por Acinetobacter/terapia , Infecciones por Acinetobacter/microbiología , Ratas , Terapia de Fagos/métodos , Carbapenémicos/farmacología , Bacteriófagos/fisiología , Bacteriófagos/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Masculino , Genoma Viral , Aguas Residuales , Neumonía/terapia , Neumonía/microbiología , Neumonía/virología
13.
Int Immunopharmacol ; 134: 112197, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38733826

RESUMEN

BACKGROUND: In China, CRC incidence is escalating. The main hurdles are heterogeneity and drug resistance. This research delves into cellular senescence in CRC, aiming to devise a prognostic model and pinpoint mechanisms impacting drug resistance. METHODS: Mendelian randomization (MR) analysis confirmed the association between CRC and cellular aging. The Cancer Genome Atlas (TCGA)-CRC data served as the training set, with GSE38832 and GSE39582 as validation sets. Various bioinformatics methods were employed to construct and validate a risk model. CRC cells with NADPH Oxidase 4 (NOX4) knockout were generated using CRISPR-Cas9 technology. Protein blotting and colony formation assays elucidated the role of NOX4 in CRC cell aging and drug resistance. RESULTS: A prognostic model, derived from dataset analysis, uncovered a link between high-risk groups and cancer progression. Notable differences in the tumor microenvironment were observed between risk groups. Finally, NOX4 was found to be linked with aging and drug resistance in CRC. CONCLUSION: This research presents a novel senescence-based CRC prognosis model. It identifies NOX4's role in CRC drug resistance, suggesting it is a potential treatment target.


Asunto(s)
Senescencia Celular , Neoplasias Colorrectales , Resistencia a Antineoplásicos , NADPH Oxidasa 4 , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , NADPH Oxidasa 4/metabolismo , NADPH Oxidasa 4/genética , Pronóstico , Microambiente Tumoral , Línea Celular Tumoral , Masculino , Femenino
14.
J Hazard Mater ; 470: 134161, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38569338

RESUMEN

BACKGROUND: Exposure to PM2.5 has been linked to neurodegenerative diseases, with limited understanding of constituent-specific contributions. OBJECTIVES: To explore the associations between long-term exposure to PM2.5 constituents and neurodegenerative diseases. METHODS: We recruited 148,274 individuals aged ≥ 60 from four cities in the Pearl River Delta region, China (2020 to 2021). We calculated twenty-year average air pollutant concentrations (PM2.5 mass, black carbon (BC), organic matter (OM), ammonium (NH4+), nitrate (NO3-) and sulfate (SO42-)) at the individuals' home addresses. Neurodegenerative diseases were determined by self-reported doctor-diagnosed Alzheimer's disease (AD) and Parkinson's disease (PD). Generalized linear mixed models were employed to explore associations between pollutants and neurodegenerative disease prevalence. RESULTS: PM2.5 and all five constituents were significantly associated with a higher prevalence of AD and PD. The observed associations generally exhibited a non-linear pattern. For example, compared with the lowest quartile, higher quartiles of BC were associated with greater odds for AD prevalence (i.e., the adjusted odds ratios were 1.81; 95% CI, 1.45-2.27; 1.78; 95% CI, 1.37-2.32; and 1.99; 95% CI, 1.54-2.57 for the second, third, and fourth quartiles, respectively). CONCLUSIONS: Long-term exposure to PM2.5 and its constituents, particularly combustion-related BC, OM, and SO42-, was significantly associated with higher prevalence of AD and PD in Chinese individuals. ENVIRONMENTAL IMPLICATION: PM2.5 is a routinely regulated mixture of multiple hazardous constituents that can lead to diverse adverse health outcomes. However, current evidence on the specific contributions of PM2.5 constituents to health effects is scarce. This study firstly investigated the association between PM2.5 constituents and neurodegenerative diseases in the moderately to highly polluted Pearl River Delta region in China, and identified hazardous constituents within PM2.5 that have significant impacts. This study provides important implications for the development of targeted PM2.5 prevention and control policies to reduce specific hazardous PM2.5 constituents.


Asunto(s)
Contaminantes Atmosféricos , Exposición a Riesgos Ambientales , Material Particulado , Material Particulado/análisis , China/epidemiología , Humanos , Anciano , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/inducido químicamente , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/inducido químicamente , Anciano de 80 o más Años , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/etiología , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Prevalencia
15.
Intern Emerg Med ; 19(4): 983-991, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38480612

RESUMEN

Sepsis-associated encephalopathy (SAE) is defined as a dysfunction of the central nervous system experienced during sepsis with variable clinical features. The study aims to identify the prognostic role of urinary ketone bodies in relation to clinical outcomes in patients with SAE. The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to conduct a retrospective cohort study. We recruited 427 patients with SAE admitted to the intensive care unit (ICU) from the MIMIC-III database. Patients with SAE were divided into a survival group (380 patients) and a non-survival group (47 patients). We used the Wilcoxon signed-rank test and the multivariate logistic regression analysis to analyze the relationship between the level of urinary ketone bodies and the clinical prognosis in patients with SAE. The primary outcome was the relationship between urinary ketone body levels and 28-day mortality of SAE. The secondary outcomes were the relationship between urinary ketone body levels and length of ICU stays, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment (SOFA), Glasgow Coma Scale, mechanical ventilation, renal replacement therapy, and the use of vasopressors. The 28-day mortality of patients with SAE was 11.0%. Urinary ketone body levels were not significantly associated with the 28-day mortality of patients with SAE. Urinary ketone body levels were associated with SOFA score and the use of vasopressors in patients with SAE. The SOFA score was an independent risk factor for the 28-day mortality in patients with SAE. Urinary ketone body levels were significantly associated with SOFA score and the use of vasopressors in patients with SAE. Furthermore, the SOFA score can predict the prognosis of short-term outcomes of patients with SAE. Therefore, we should closely monitor the changes of urinary ketone bodies and SOFA score and intervene in time.


Asunto(s)
Cuerpos Cetónicos , Encefalopatía Asociada a la Sepsis , Humanos , Estudios Retrospectivos , Femenino , Masculino , Cuerpos Cetónicos/orina , Pronóstico , Persona de Mediana Edad , Anciano , Encefalopatía Asociada a la Sepsis/orina , Encefalopatía Asociada a la Sepsis/fisiopatología , Encefalopatía Asociada a la Sepsis/complicaciones , Unidades de Cuidados Intensivos/estadística & datos numéricos , Estudios de Cohortes , Puntuaciones en la Disfunción de Órganos , Biomarcadores/orina
16.
Cell Signal ; 118: 111134, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38484942

RESUMEN

Colorectal cancer (CRC) is one of the most common malignant tumors with complex molecular regulatory mechanisms. Alternative splicing (AS), a fundamental regulatory process of gene expression, plays an important role in the occurrence and development of CRC. This study analyzed AS Percent Spliced In (PSI) values from 49 pairs of CRC and normal samples in the TCGA SpliceSeq database. Using Lasso and SVM, AS features that can differentiate colorectal cancer from normal were screened. Univariate COX regression analysis identified prognosis-related AS events. A risk model was constructed and validated using machine learning, Kaplan-Meier analysis, and Decision Curve Analysis. The regulatory effect of protein arginine methyltransferase 5 (PRMT5) on poly(RC) binding protein 1 (PCBP1) was verified by immunoprecipitation experiments, and the effect of PCBP1 on the AS of Obscurin (OBSCN) was verified by PCR. Five AS events, including HNF4A.59461.AP and HNF4A.59462.AP, were identified, which can distinguish CRC from normal tissue. A machine learning model using 21 key AS events accurately predicted CRC prognosis. High-risk patients had significantly shorter survival times. PRMT5 was found to regulate PCBP1 function and then influence OBSCN AS, which may drive CRC progression. The study concluded that some AS events is significantly different in CRC and normal tissues, and some of these AS events are related to the prognosis of CRC. In addition, PRMT family-driven arginine modifications play an important role in CRC-specific AS events.


Asunto(s)
Empalme Alternativo , Neoplasias Colorrectales , Humanos , Empalme Alternativo/genética , Arginina , Estimación de Kaplan-Meier , Metiltransferasas , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , Proteína-Arginina N-Metiltransferasas/genética
17.
Cell Death Dis ; 15(2): 153, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378679

RESUMEN

Breast cancer (BC) is the most commonly diagnosed malignant tumour in females worldwide. Although remarkable advances in early detection and treatment strategies have led to decreased mortality, recurrence and metastasis remain the major causes of cancer death in BC patients. Increasing evidence has demonstrated that circular RNAs (circRNAs) play critical roles in cancer progression. However, the detailed biological functions and molecular mechanisms of circRNAs in BC are unclear. The aim of this study was to investigate the possible role of circRNAs in the progression of BC. Differentially expressed circRNAs in BC were identified by integrating breast tumour-associated somatic CNV data and circRNA high-throughput sequencing. Aberrant hsa_circ_0007990 expression and host gene copy number were detected in BC cell lines via quantitative polymerase chain reaction (qPCR). The expression level of hsa_circ_0007990 in BC tissues was validated by in situ hybridization (ISH). Loss- and gain-of-function experiments were performed in vitro and in vivo, respectively, to explore the potential biological function of hsa_circ_0007990 in BC. The underlying mechanisms of hsa_circ_0007990 were investigated through MS2 RNA pull-down, RNA immunoprecipitation, RNA fluorescence in situ hybridization, immunofluorescence, chromatin immunoprecipitation and luciferase reporter assays. The levels of hsa_circ_0007990 were elevated in BC tissues and cell lines, an effect that was partly due to host gene copy number gains. Functional assays showed that hsa_circ_0007990 promoted BC cell growth. Mechanistically, hsa_circ_0007990 could bind to YBX1 and inhibit its degradation by preventing ubiquitin/proteasome-dependent degradation, thus enhancing the expression of the cell cycle-associated gene E2F1. Rescue experiments suggested that hsa_circ_0007990 promoted BC progression through YBX1. In general, our study demonstrated that hsa_circ_0007990 modulates the ubiquitination and degradation of YBX1 protein and further regulates E2F1 expression to promote BC progression. We explored the possible function and molecular mechanism of hsa_circ_0007990 in BC and identified a novel candidate target for the treatment of BC.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Femenino , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Neoplasias de la Mama/patología , Proteolisis , Hibridación Fluorescente in Situ , Línea Celular Tumoral , Proliferación Celular/genética , ARN/genética , MicroARNs/genética , Regulación Neoplásica de la Expresión Génica/genética , Proteína 1 de Unión a la Caja Y/genética , Proteína 1 de Unión a la Caja Y/metabolismo , Factor de Transcripción E2F1/metabolismo
18.
Opt Express ; 31(16): 26301-26313, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37710493

RESUMEN

We have developed a simple time-bin phase encoding quantum key distribution system, using the optical injection locking technique. This setup incorporates both the merits of simplicity and stability in encoding, and immunity to channel disturbance. We have demonstrated the field implementation of quantum key distribution over long-distance deployed aerial fiber automatically. During the 70-day field test, we achieved approximately a 1.0 kbps secure key rate with stable performance. Our work takes an important step toward widespread implementation of QKD systems in diverse and complex real-life scenarios.

19.
Opt Express ; 31(16): 26335-26343, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37710496

RESUMEN

In this work, we present a new time-bin phase-encoding quantum key distribution (QKD), where the transmitter utilizes an inherently stable Sagnac-type interferometer, and has comparable electrical requirements to existing polarization or phase encoding schemes. This approach does not require intensity calibration and is insensitive to environmental disturbances, making it both flexible and high-performing. We conducted experiments with a compact QKD system to demonstrate the stability and secure key rate performance of the presented scheme. The results show a typical secure key rate of 6.2 kbps@20 dB and 0.4 kbps@30 dB with channel loss emulated by variable optical attenuators. A continuous test of 120-km fiber spool shows a stable quantum bit error rate of the time-bin basis within 0.4%∼0.6% over a consecutive 9-day period without any adjustment. This intrinsically stable and compatible scheme of time-bin phase encoding is extensively applicable in various QKD experiments, including BB84 and measurement-device-independent QKD.

20.
J Pain Res ; 16: 2619-2632, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37533560

RESUMEN

Background: Neuropathic pain (NP) is a common and severe problem following spinal cord injury (SCI). However, its relationship with functional outcome remains unclear. Methods: A retrospective explorative analysis was performed on SCI patients admitted to a tertiary academic medical center between January 2018 and June 2022. The candidate predictor variables, including demographics, clinical characteristics and complications, were analyzed with logistic and linear regression. Spinal Cord Independence Measure (SCIM) scores at discharge and mean relative functional gain (mRFG) of SCIM were as outcome parameters. Results: A total of 140 SCI patients included for the final analysis. Among them, 44 (31.43%) patients were tetraplegics, and 96 (68.57%) patients were paraplegics; 68 (48.57%) patients developed NP, and 72 (51.43%) patients did not. Logistic and linear regression analyses of SCIM at discharge both showed that NP [OR=3.10, 95% CI (1.29,7.45), P=0.01; unstandardized ß=11.47, 95% CI (4.95,17.99), P<0.01; respectively] was significantly independent predictors for a favorable outcome (SCIM at discharge ≥ 50, logistic regression results) and higher SCIM total score at discharge (linear regression results). Besides, NP [unstandardized ß=15.67, 95% CI (8.94,22.41), P<0.01] was also independently associated with higher mRFG of SCIM scores. Furthermore, the NP group had significantly higher mRFG, SCIM total scores and subscales (self-care, respiration and sphincter management, and mobility) at discharge compared to the non-NP group. However, there were no significant differences in mRFG, SCIM total score or subscales at discharge among the NP subgroups in terms of locations (at level pain, below level pain, and both) or timing of occurrence (within and after one month after SCI). This study also showed that incomplete injury, lumbar-sacral injury level and non-anemia were significantly independent predictors for a favorable outcome, and higher mRFG of SCIM scores (except for non-anemia). Conclusion: NP appears independently associated with better functional recovery in SCI patients, suggesting the bright side of this undesirable complication. These findings may help to alleviate the psychological burden of NP patients and ultimately restore their confidence in rehabilitation.

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