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1.
An. bras. dermatol ; 99(4): 535-545, Jul.-Aug. 2024. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1563713

RESUMEN

Abstract Background Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. Objective This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. Methods The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. Results The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. Study limitations No animal experiments were conducted to further verify the results. Conclusion Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

2.
J. pediatr. (Rio J.) ; 100(4): 399-405, July-Aug. 2024. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1564748

RESUMEN

Abstract Objective: Ovarian torsion (OT) represents a severe gynecological emergency in female pediatric patients, necessitating immediate surgical intervention to prevent ovarian ischemia and preserve fertility. Prompt diagnosis is, therefore, paramount. This retrospective study set out to assess the utility of combined clinical, ultrasound, and laboratory features in diagnosing OT. Methods: The authors included 326 female pediatric patients aged under 14 years who underwent surgical confirmation of OT over a five-year period. Logistic regression analysis was employed to pinpoint factors linked with OT, and the authors compared clinical presentation, laboratory results, and ultrasound characteristics between patients with OT (OT group) and without OT (N-OT group). The authors conducted receiver operating characteristic (ROC) curve analysis to gauge the predictive capacity of the combined features. Results: Among 326, OTwas confirmed in 24.23 % (79 cases) of the patients. The OT group had a higher incidence of prenatal ovarian masses than the N-OT (22 cases versus 7 cases) (p < 0.0001). Similarly, the authors observed significant differences in the presence of lower abdominal pain, suspected torsion on transabdominal ultrasound, and a high neutrophil-lymphocyte ratio (NLR > 3) between the OTand non-OT groups (p < 0.05). Furthermore, when these parameters were combined, the resulting area under the curve (AUC) was 0.868, demonstrating their potential utility in OT diagnosis. Conclusion: This study demonstrates a prediction model integrating clinical, laboratory, and ultrasound findings that can support the preoperative diagnosis of ovarian torsion, thereby enhancing diagnostic precision and improving patient management. Future prospective studies should concentrate on developing clinical predictive models for OTin pediatric patients.

3.
JMIR Hum Factors ; 11: e57670, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39146009

RESUMEN

BACKGROUND: The rapid growth of web-based medical services has highlighted the significance of smart triage systems in helping patients find the most appropriate physicians. However, traditional triage methods often rely on department recommendations and are insufficient to accurately match patients' textual questions with physicians' specialties. Therefore, there is an urgent need to develop algorithms for recommending physicians. OBJECTIVE: This study aims to develop and validate a patient-physician hybrid recommendation (PPHR) model with response metrics for better triage performance. METHODS: A total of 646,383 web-based medical consultation records from the Internet Hospital of the First Affiliated Hospital of Xiamen University were collected. Semantic features representing patients and physicians were developed to identify the set of most similar questions and semantically expand the pool of recommended physician candidates, respectively. The physicians' response rate feature was designed to improve candidate rankings. These 3 characteristics combine to create the PPHR model. Overall, 5 physicians participated in the evaluation of the efficiency of the PPHR model through multiple metrics and questionnaires as well as the performance of Sentence Bidirectional Encoder Representations from Transformers and Doc2Vec in text embedding. RESULTS: The PPHR model reaches the best recommendation performance when the number of recommended physicians is 14. At this point, the model has an F1-score of 76.25%, a proportion of high-quality services of 41.05%, and a rating of 3.90. After removing physicians' characteristics and response rates from the PPHR model, the F1-score decreased by 12.05%, the proportion of high-quality services fell by 10.87%, the average hit ratio dropped by 1.06%, and the rating declined by 11.43%. According to whether those 5 physicians were recommended by the PPHR model, Sentence Bidirectional Encoder Representations from Transformers achieved an average hit ratio of 88.6%, while Doc2Vec achieved an average hit ratio of 53.4%. CONCLUSIONS: The PPHR model uses semantic features and response metrics to enable patients to accurately find the physician who best suits their needs.


Asunto(s)
Médicos , Semántica , Humanos , Triaje/métodos , Triaje/normas , Encuestas y Cuestionarios , Algoritmos
4.
BMC Pediatr ; 24(1): 473, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39049018

RESUMEN

OBJECTIVE: Laparoscopic choledochectomy and hepatojejunostomy have been reported in children since 1995, but this procedure is technically demanding. Robotic surgical systems can simplify complex minimally invasive procedures. Currently, few reports have been made on neonates. We present the experience of 6 cases of neonatal CC(choledochal cysts). STUDY DESIGN: Between January 2022 and December 2023, 6 neonates underwent robotic resection of choledochal cyst and hepaticojejunostomy using the Da Vinci surgical system at Children's Hospital, Zhejiang University School of Medicine, a high-volume hepatobiliary disease center. demographic data of the patients and surgical outcomes were collected and analyzed. RESULTS: All 6 patients were successfully treated by robotic cystectomy and hepaticojejunostomy. The mean age was 17.3 days (range 4-25) and the mean weight was 3.6 kg (range 2.55-4.4). 5 cysts were type Ia and 1 was type Iva. The mean diameter of the cysts was 3.8 cm (range 1.25-5). The mean time to establish feeding was 4.83 days (range 4-6), and patients were discharged after a median time of 16.83 days (range 7-42) without postoperative complications. CONCLUSIONS: This procedure is safe and effective for neonates. The authors found that the use of robot-assisted surgery has ergonomic advantages in this delicate, minimally invasive procedure.


Asunto(s)
Quiste del Colédoco , Procedimientos Quirúrgicos Robotizados , Humanos , Quiste del Colédoco/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Recién Nacido , Masculino , Femenino , Yeyunostomía/métodos , Laparoscopía/métodos , Estudios Retrospectivos , Resultado del Tratamiento
5.
Paediatr Int Child Health ; 44(2): 73-78, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39066724

RESUMEN

Trichobezoars are conglomerates of hair within the gastro-intestinal tract, commonly detected in the stomach, and they can present with the Rapunzel syndrome. Isolated small-bowel trichobezoars are extremely rare. Three female patients presented with abdominal pain and bilious vomiting, and underwent various imaging examinations. Two were diagnosed with small-bowel trichobezoars with intestinal obstruction and one with intestinal obstruction only. All three underwent surgery. Two underwent laparoscopic exploration and one underwent a laparotomy. One and two patients had isolated small-bowel trichobezoars in the ileum and jejunum, respectively. Two patients were followed up by a psychiatrist, and all recovered well without recurrence. These three cases emphasise the importance of a comprehensive medical history and imaging in patients with small-bowel obstruction to determine the possibility of bezoars.


Asunto(s)
Bezoares , Obstrucción Intestinal , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Femenino , Bezoares/complicaciones , Bezoares/cirugía , Bezoares/diagnóstico por imagen , Niño , Intestino Delgado/patología , Intestino Delgado/diagnóstico por imagen , Adolescente , Laparoscopía , Laparotomía
6.
BMC Geriatr ; 24(1): 599, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997670

RESUMEN

OBJECTIVES: This review aims to comprehensively summarize the differences in anticholinergic drug burden (ADB) scores between older hospitalized patients with and without delirium. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library and CINAHL EBSCOhost databases to identify prospective cohort studies exploring the relationship between ADB and the occurrence of delirium in older hospitalized patients. The primary outcome of the review was the mean ADB scores for the delirium and non-delirium groups, and the secondary outcome was the scores for the subsyndromal and non-delirium groups. The standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were incorporated using a fixed-effect method. Moreover, we performed subgroup analysis according to the admission type, age, the ADB scale type and the ADB classification. RESULTS: Nine prospective cohort studies involving 3791 older patients with a median age of 75.1 (71.6-83.9) were included. The ADB score was significantly higher in the delirium group than in the non-delirium group (SMD = 0.21, 95%CI 0.13-0.28). In subgroup analysis, the age subgroup was split into < 75 and ≥ 75 according to the median age of the older people. There were significant differences in ADB scores between older people with delirium and those without delirium in various subgroups: surgical (SMD = 0.20, 95%CI 0.12-0.28), internal medicine (SMD = 0.64, 95%CI 0.25-1.02), age < 75 (SMD = 0.17, 95%CI 0.08-0.26), age ≥ 75 (SMD = 0.27, 95%CI 0.15-0.39), ADS scale (SMD = 0.13, 95%CI 0.13-0.40), ARS scale (SMD = 0.15, 95%CI 0.03-0.26), ACB scale (SMD = 0.13, 95%CI 0.01-0.25), pre-admission ADB (SMD = 0.24, 95%CI 0.05-0.43) and ADB during hospitalization (SMD = 0.20, 95%CI 0.12-0.27). CONCLUSIONS: We found a quantitative relationship between ADB and delirium in older patients admitted for internal medicine and surgery. And this relationship remained significant in different age, ADB scale type and ADB classification subgroups. However, the actual difference in ADB scores between patients with delirium and without delirium was small. More high-quality observational studies should be conducted to explore the impact of ADB on delirium and subsyndromal delirium. CLINICAL TRIAL REGISTRATION: The protocol was published in the International Prospective Register of Systematic Reviews (PROSPERO) [Ref: CRD42022353649].


Asunto(s)
Antagonistas Colinérgicos , Delirio , Hospitalización , Humanos , Delirio/epidemiología , Antagonistas Colinérgicos/efectos adversos , Antagonistas Colinérgicos/uso terapéutico , Anciano , Estudios Prospectivos , Anciano de 80 o más Años , Estudios de Cohortes
7.
Science ; 385(6706): 295-300, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39024431

RESUMEN

The industrial catalysts utilized for propane dehydrogenation (PDH) to propylene, an important alternative to petroleum-based cracking processes, either use expensive metals or metal oxides that are environmentally unbenign. We report that a typically less-active oxide, titanium oxide (TiO2), can be combined with earth-abundant metallic nickel (Ni) to form an unconventional Ni@TiOx catalyst for efficient PDH. The catalyst demonstrates a 94% propylene selectivity at 40% propane conversion and superior stability under industrially relevant conditions. Complete encapsulation of Ni nanoparticles was allowed at elevated temperatures (>550°C). A mechanistic study suggested that the defective TiOx overlayer consisting of tetracoordinated Ti sites with oxygen vacancies is catalytically active. Subsurface metallic Ni acts as an electronic promoter to accelerate carbon-hydrogen bond activation and hydrogen (H2) desorption on the TiOx overlayer.

8.
Nat Rev Dis Primers ; 10(1): 41, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871740

RESUMEN

Acute lymphoblastic leukaemia (ALL) is a haematological malignancy characterized by the uncontrolled proliferation of immature lymphoid cells. Over past decades, significant progress has been made in understanding the biology of ALL, resulting in remarkable improvements in its diagnosis, treatment and monitoring. Since the advent of chemotherapy, ALL has been the platform to test for innovative approaches applicable to cancer in general. For example, the advent of omics medicine has led to a deeper understanding of the molecular and genetic features that underpin ALL. Innovations in genomic profiling techniques have identified specific genetic alterations and mutations that drive ALL, inspiring new therapies. Targeted agents, such as tyrosine kinase inhibitors and immunotherapies, have shown promising results in subgroups of patients while minimizing adverse effects. Furthermore, the development of chimeric antigen receptor T cell therapy represents a breakthrough in ALL treatment, resulting in remarkable responses and potential long-term remissions. Advances are not limited to treatment modalities alone. Measurable residual disease monitoring and ex vivo drug response profiling screening have provided earlier detection of disease relapse and identification of exceptional responders, enabling clinicians to adjust treatment strategies for individual patients. Decades of supportive and prophylactic care have improved the management of treatment-related complications, enhancing the quality of life for patients with ALL.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Genómica , Terapia Molecular Dirigida , Calidad de Vida , Inmunoterapia Adoptiva
9.
Dev Cell ; 59(15): 1954-1971.e7, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38776924

RESUMEN

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.


Asunto(s)
Fructosa , Humanos , Animales , Ratones , Fructosa/metabolismo , Cromatina/metabolismo , Aldehído Reductasa/metabolismo , Aldehído Reductasa/genética , Leucemia/metabolismo , Leucemia/patología , Leucemia/genética , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Ensamble y Desensamble de Cromatina , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinogénesis/genética , Línea Celular Tumoral , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Adenosina Trifosfatasas
10.
Sci Total Environ ; 931: 172924, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38697550

RESUMEN

The water quality in the drinking water reservoir directly affects people's quality of life and health. When external pollution input is effectively controlled, endogenous release is considered the main cause of water quality deterioration. As the major nitrogen (N) and phosphorus (P) sources in reservoirs, sediment plays a vital role in affecting the water quality. To understand the spatial and temporal variation of N and P in the sediment, this study analyzed the current characteristics and cumulative effects of a semi-humid reservoir, Yuqiao Reservoir, in North China. The N and P concentrations in the reservoir sediment were decreased along the flow direction, while the minimum values were recorded at the central sediment profile. External input and algal deposition were the main factors leading to higher sediment concentrations in the east (Re-E) and west (Re-W) areas of reservoir sediment profiles. According to the long-term datasets, the peaks of both sediment total nitrogen content and deposition rate were observed in the 2010s, which has increased about three times and six times than in the1990s, respectively. Therefore, the increase in phosphorus concentration may be the main reason for eutrophication in water in recent years. The mineralization of organic matter has a significant promoting effect on releasing N and P from sediments, which will intensify eutrophication in water dominated by P and bring huge challenges to water environment management. This study highlights that the current imbalance in N and P inputs into reservoirs and the endogenous P release from sediment will have a significant impact on water quality.

11.
Arch Dermatol Res ; 316(6): 299, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38819446

RESUMEN

Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor originating from epidermal or appendageal keratinocytes, with a rising incidence in recent years. Understanding the molecular mechanism driving its development is crucial. This study aims to investigate whether miR-34a-5p is involved in the pathogenesis of cSCC by targeting Sirtuin 6 (SIRT6).The expression levels of miR-34a-5p and SIRT6 were determined in 15 cSCC tissue specimens, 15 normal tissue specimens and cultured cells via real-time polymerase chain reaction (RT-qPCR). Pearson's correlation analysis was conducted to evaluate the relationship between miR-34a-5p and SIRT6 expression levels in cSCC tissues. A431 and SCL-1 cells were transfected with miR-34a-5p mimic, negative control or miR-34a-5p mimic together with recombinant plasmids containing SIRT6 gene. Cell counting kit-8, clone formation assay, wound healing assay, and flow cytometry were employed to assess the effects of these transfections on proliferation, migration, and apoptosis, respectively. The interaction between miR-34a-5p and SIRT6 was characterized using a dual-luciferase reporter assay.MiR-34a-5p expression was down-regulated in cSCC tissues significantly, while the SIRT6 expression was the opposite. A negative correlation was observed between the expression of miR-34a-5p and SIRT6 in cSCC tissues. Furthermore, overexpression of miR-34a-5p led to a significant reduction in the proliferation and migration abilities of A431 and SCL-1 cells, accompanied by an increase in apoptosis levels and a decrease in SIRT6 expression levels. MiR-34a-5p was identified as a direct target of SIRT6. Importantly, overexpression of SIRT6 effectively counteracted the inhibitory effect mediated by miR-34a-5p in cSCC cells.Our findings suggest that miR-34a-5p functions as a tumor suppressor in cSCC cells by targeting SIRT6.


Asunto(s)
Apoptosis , Carcinoma de Células Escamosas , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , MicroARNs , Sirtuinas , Neoplasias Cutáneas , Humanos , Sirtuinas/genética , Sirtuinas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Apoptosis/genética , Movimiento Celular/genética , Proliferación Celular/genética , Línea Celular Tumoral , Progresión de la Enfermedad , Masculino , Regulación hacia Abajo , Femenino , Persona de Mediana Edad
12.
Nat Commun ; 15(1): 4636, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38821951

RESUMEN

The catalytic partial oxidation of methane (POM) presents a promising technology for synthesizing syngas. However, it faces severe over-oxidation over catalyst surface. Attempts to modify metal surfaces by incorporating a secondary metal towards C-H bond activation of CH4 with moderate O* adsorption have remained the subject of intense research yet challenging. Herein, we report that high catalytic performance for POM can be achieved by the regulation of O* occupation in the atomically dispersed (AD) MoNi alloy, with over 95% CH4 conversion and 97% syngas selectivity at 800 °C. The combination of ex-situ/in-situ characterizations, kinetic analysis and DFT (density functional theory) calculations reveal that Mo-Ni dual sites in AD MoNi alloy afford the declined O2 poisoning on Ni sites with rarely weaken CH4 activation for partial oxidation pathway following the combustion reforming reaction (CRR) mechanism. These results underscore the effectiveness of CH4 turnovers by the design of atomically dispersed alloys with tunable O* adsorption.

13.
Clin Nutr ; 43(7): 1675-1682, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38815493

RESUMEN

OBJECTIVE: This study aimed to investigate the potential association between dietary live microbe intake and sarcopenia. METHODS: Data from 5368 participants were gathered from the National Health and Nutrition Examination Survey (NHANES). Dietary information was assessed using a self-report questionnaire. The participants were categorized into low, medium, and high dietary live microbe groups. Sarcopenia was defined according to the National Institutes of Health (NIH) definition (appendicular skeletal muscle mass/body mass index <0.789 for men and <0.512 for women). Multivariate regression analysis and stratified analyses were performed. RESULTS: After adjusting for potential confounding factors, individuals in the high dietary live microbe group exhibited a lower prevalence of sarcopenia compared to those in the low dietary live microbe group. The adjusted odds ratio (with 95% confidence intervals) was 0.63 (0.44-0.89) (p for trend <0.05). Subgroup analyses indicated a potential difference in the impact of dietary live microbe intake on sarcopenia between individuals with and without diabetes (p for interaction = 0.094). CONCLUSION: Higher dietary live microbe intake was associated with a lower risk of sarcopenia.


Asunto(s)
Dieta , Encuestas Nutricionales , Sarcopenia , Humanos , Sarcopenia/epidemiología , Sarcopenia/prevención & control , Masculino , Femenino , Persona de Mediana Edad , Dieta/métodos , Dieta/estadística & datos numéricos , Anciano , Estudios Transversales , Factores de Riesgo , Prevalencia , Adulto , Índice de Masa Corporal
14.
J Pediatr (Rio J) ; 100(4): 399-405, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38582497

RESUMEN

OBJECTIVE: Ovarian torsion (OT) represents a severe gynecological emergency in female pediatric patients, necessitating immediate surgical intervention to prevent ovarian ischemia and preserve fertility. Prompt diagnosis is, therefore, paramount. This retrospective study set out to assess the utility of combined clinical, ultrasound, and laboratory features in diagnosing OT. METHODS: The authors included 326 female pediatric patients aged under 14 years who underwent surgical confirmation of OT over a five-year period. Logistic regression analysis was employed to pinpoint factors linked with OT, and the authors compared clinical presentation, laboratory results, and ultrasound characteristics between patients with OT (OT group) and without OT (N-OT group). The authors conducted receiver operating characteristic (ROC) curve analysis to gauge the predictive capacity of the combined features. RESULTS: Among 326, OT was confirmed in 24.23 % (79 cases) of the patients. The OT group had a higher incidence of prenatal ovarian masses than the N-OT (22 cases versus 7 cases) (p < 0.0001). Similarly, the authors observed significant differences in the presence of lower abdominal pain, suspected torsion on transabdominal ultrasound, and a high neutrophil-lymphocyte ratio (NLR > 3) between the OT and non-OT groups (p ˂ 0.05). Furthermore, when these parameters were combined, the resulting area under the curve (AUC) was 0.868, demonstrating their potential utility in OT diagnosis. CONCLUSION: This study demonstrates a prediction model integrating clinical, laboratory, and ultrasound findings that can support the preoperative diagnosis of ovarian torsion, thereby enhancing diagnostic precision and improving patient management. Future prospective studies should concentrate on developing clinical predictive models for OT in pediatric patients.


Asunto(s)
Torsión Ovárica , Ultrasonografía , Humanos , Femenino , Torsión Ovárica/diagnóstico , Niño , Estudios Retrospectivos , Adolescente , Preescolar , Curva ROC , Lactante , Valor Predictivo de las Pruebas , Modelos Logísticos , Anomalía Torsional/diagnóstico , Anomalía Torsional/diagnóstico por imagen
15.
J Hematol Oncol ; 17(1): 23, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38659046

RESUMEN

BACKGROUND: The autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up. METHODS: Participants received an average dose of 0.5 × 106 cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated. RESULTS: Seventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes. CONCLUSIONS: These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma. TRIAL REGISTRATION: LEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.


Asunto(s)
Antígeno de Maduración de Linfocitos B , Inmunoterapia Adoptiva , Mieloma Múltiple , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antígeno de Maduración de Linfocitos B/inmunología , Estudios de Seguimiento , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Mieloma Múltiple/terapia , Mieloma Múltiple/mortalidad , Receptores Quiméricos de Antígenos/uso terapéutico , Receptores Quiméricos de Antígenos/inmunología , Inducción de Remisión , Tasa de Supervivencia
16.
J Cancer Res Clin Oncol ; 150(4): 189, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605258

RESUMEN

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).


Asunto(s)
Antineoplásicos , Arsénico , Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Antineoplásicos/efectos adversos , Arsénico/uso terapéutico , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Pandemias , Resultado del Tratamiento
17.
J Environ Sci (China) ; 143: 1-11, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38644008

RESUMEN

Potential health risks related to environmental endocrine disruptors (EEDs) have aroused research hotspots at the forefront of water treatment technologies. Herein, nitrogen-doped titanium dioxide/schwertmannite nanocomposites (N-TiO2/SCH) have been successfully developed as heterogeneous catalysts for the degradation of typical EEDs via photo-Fenton processes. Due to the sustainable Fe(III)/Fe(II) conversion induced by photoelectrons, as-prepared N-TiO2/SCH nanocomposites exhibit much enhanced efficiency for the degradation of bisphenol A (BPA; ca. 100% within 60 min under visible irradiation) in a wide pH range of 3.0-7.8, which is significantly higher than that of the pristine schwertmannite (ca. 74.5%) or N-TiO2 (ca. 10.8%). In this photo-Fenton system, the efficient degradation of BPA is mainly attributed to the oxidation by hydroxyl radical (•OH) and singlet oxygen (1O2). Moreover, the possible catalytic mechanisms and reaction pathway of BPA degradation are systematically investigated based on analytical and photoelectrochemical analyses. This work not only provides a feasible means for the development of novel heterogeneous photo-Fenton catalysts, but also lays a theoretical foundation for the potential application of mineral-based materials in wastewater treatment.


Asunto(s)
Compuestos de Bencidrilo , Compuestos de Hierro , Nanocompuestos , Nitrógeno , Fenoles , Titanio , Contaminantes Químicos del Agua , Titanio/química , Compuestos de Bencidrilo/química , Fenoles/química , Nanocompuestos/química , Contaminantes Químicos del Agua/química , Nitrógeno/química , Catálisis , Hierro/química , Peróxido de Hidrógeno/química , Disruptores Endocrinos/química , Purificación del Agua/métodos
18.
Sci Total Environ ; 923: 171417, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38447725

RESUMEN

The water-level fluctuations zones (WLFZs) are crucial transitional interfaces within river-reservoir systems, serving as hotspots for N2O emission. However, the comprehension of response patterns and mechanisms governing N2O emission under hydrological fluctuation remains limited, especially in karstic canyon reservoirs, which introduces significant uncertainty to N2O flux assessments. Soil samples were collected from the WLFZs of the Hongjiadu (HJD) Reservoir along the water flow direction from transition zone (T1 and T2) to lacustrine zone (T3, T4 and T5) at three elevations for each site. These soil columns were used to conduct simulation experiments under various water-filled pore space gradients (WFPSs) to investigate the potential N2O flux pattern and elucidate the underlying mechanism. Our results showed that nutrient distribution and N2O flux pattern differed significantly between two zones, with the highest N2O fluxes in the transition zone sites and lacustrine zone sites were found at 75 % and 95 % WFPS, respectively. Soil nutrient loss in lower elevation areas is influenced by prolonged impoundment durations. The higher N2O fluxes in the lacustrine zone can be attributed to increased nutrient levels resulting from anthropogenic activities. Furthermore, correlation analysis revealed that soil bulk density significantly impacted N2O fluxes across all sites, while NO3-and SOC facilitated N2O emissions in T1-T2 and T4-T5, respectively. It was evident that N2O production primarily contributed to nitrification in the transition zone and was constrained by the mineralization process, whereas denitrification dominated in the lacustrine zone. Notably, the annual N2O efflux from WLFZs accounted for 27 % of that from the water-air interface in HJD Reservoir, indicating a considerably lower contribution than anticipated. Nevertheless, this study highlights the significance of WLFZs as a vital potential source of N2O emission, particularly under the influence of anthropogenic activities and high WFPS gradient.

19.
Chem Rev ; 124(6): 2955-3012, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38478971

RESUMEN

The structure of catalysts determines the performance of catalytic processes. Intrinsically, the electronic and geometric structures influence the interaction between active species and the surface of the catalyst, which subsequently regulates the adsorption, reaction, and desorption behaviors. In recent decades, the development of catalysts with complex structures, including bulk, interfacial, encapsulated, and atomically dispersed structures, can potentially affect the electronic and geometric structures of catalysts and lead to further control of the transport and reaction of molecules. This review describes comprehensive understandings on the influence of electronic and geometric properties and complex catalyst structures on the performance of relevant heterogeneous catalytic processes, especially for the transport and reaction over structured catalysts for the conversions of light alkanes and small molecules. The recent research progress of the electronic and geometric properties over the active sites, specifically for theoretical descriptors developed in the recent decades, is discussed at the atomic level. The designs and properties of catalysts with specific structures are summarized. The transport phenomena and reactions over structured catalysts for the conversions of light alkanes and small molecules are analyzed. At the end of this review, we present our perspectives on the challenges for the further development of structured catalysts and heterogeneous catalytic processes.

20.
An Bras Dermatol ; 99(4): 535-545, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38548549

RESUMEN

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. OBJECTIVE: This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. METHODS: The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. RESULTS: The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. STUDY LIMITATIONS: No animal experiments were conducted to further verify the results. CONCLUSION: Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.


Asunto(s)
Apoptosis , Carcinoma de Células Escamosas , Proliferación Celular , Sirtuinas , Neoplasias Cutáneas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Western Blotting , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/genética , Ciclo Celular/fisiología , Línea Celular Tumoral , Movimiento Celular , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Inmunohistoquímica , Sirtuinas/genética , Sirtuinas/metabolismo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/genética
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