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1.
Br J Haematol ; 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38639167

The dysregulation of the Janus family tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) is closely related to acute lymphoblastic leukaemia (ALL), whereas the clinical value of phosphorylated STAT5 (pSTAT5) remains elusive. Herein we performed a prospective study on clinical significance of flow cytometry-based pSTAT5 in adult B-ALL patients. A total of 184 patients were enrolled in the Precision-Classification-Directed-Target-Total-Therapy (PDT)-ALL-2016 cohort between January 2018 and December 2021, and STAT5 phosphorylation was detected by flow cytometry at diagnosis. Based on flow-pSTAT5, the population was classified into pSTAT5low (113/184, 61.1%) and pSTAT5high (71/184, 38.9%). Overall survival (OS) and event-free survival (EFS) were inferior in pSTAT5high patients than in those with pSTAT5low (OS, 44.8% vs. 65.2%, p = 0.004; EFS, 23.5% vs. 52.1%, p < 0.001), which was further confirmed in an external validation cohort. Furthermore, pSTAT5 plus flow-based minimal residual disease (MRD) postinduction defines a novel risk classification as being high risk (HR, pSTAT5high + MRD+), standard risk (SR, pSTAT5low + MRD-) and others as moderate-risk group. Three identified patient subgroups are distinguishable with disparate survival curves (3-year OS rates, 36.5%, 56.7% and 76.3%, p < 0.001), which was confirmed on multivariate analysis (hazard ratio 3.53, p = 0.003). Collectively, our study proposed a novel, simple and flow-based risk classification by integrating pSTAT5 and MRD in favour of risk-guided treatment for B-ALL.

2.
Endocr Pract ; 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38679386

BACKGROUND: The association between obesity, metabolic dysregulation, and the aggressive pathological traits of papillary thyroid carcinoma (PTC) continues to be a contentious issue. To date, no investigations have examined the impact of metabolic status on the malignant pathological features of PTC in relation to obesity. METHODS: This research involved 855 adult PTC patients from Shandong Provincial Hospital, classified into four groups based on metabolic and obesity status: metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). We employed logistic regression to investigate the relationship between these metabolic obesity phenotypes and PTC's pathological characteristics. Mediation analysis was also performed to determine metabolic abnormalities' mediating role in the nexus between obesity and these characteristics. RESULTS: Relative to MHNO individuals, the MUO group was significantly associated with an elevated risk of larger tumor sizes and a greater number of tumor foci in PTC. Mediation analysis indicated that obesity directly influences tumor size, whereas its effect on tumor multifocality is mediated through metabolic dysfunctions. Specifically, HDL-C levels were notably associated with tumor multifocality within obese subjects, serving as a mediator in obesity's impact on this trait. CONCLUSION: The concurrent presence of obesity and metabolic dysregulation is often connected to more aggressive pathological features in PTC. The mediation analysis suggests obesity directly affects tumor size and indirectly influences tumor multifocality via low HDL-C levels.

3.
Ecotoxicol Environ Saf ; 277: 116343, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38657456

Curcumin (CUR) is a compound extracted from turmeric that has a variety of functions including antioxidant and anti-inflammatory. As an estrogen-like mycotoxin, zearalenone (ZEN) not only attacks the reproductive system, but also has toxic effects on the liver. However, whether CUR can alleviate ZEN-induced liver injury remains unclear. This paper aims to investigate the protective effect of CUR against ZEN-induced liver injury in mice and explore the molecular mechanism involved. BALB/c mice were randomly divided into control (CON) group, CUR group (200 mg/kg b. w. CUR), ZEN group (40 mg/kg b. w. ZEN) and CUR+ZEN group (200 mg/kg b. w. CUR+40 mg/kg b. w. ZEN). 28 d after ZEN exposure and CUR treatment, blood and liver samples were collected for subsequent testing. The results showed that CUR reversed ZEN-induced hepatocyte swelling and necrosis in mice. It significantly reduced the serum alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice (p < 0.05). In addition, CUR significantly reduced hepatic ROS, malondialdehyde, hydrogen peroxide and apoptosis levels in mice (p < 0.05). Quantitative RT-PCR and Western blot results showed that CUR significantly reduced the expression of Bax and Caspase3, and reversed the increase of Nrf2, HO-1 and NQO1 expression in the liver of mice induced by ZEN (p < 0.05). In conclusion, CUR alleviated ZEN-induced liver injury in mice by scavenging ROS and inhibiting the mitochondrial apoptotic pathway.


Apoptosis , Chemical and Drug Induced Liver Injury , Curcumin , Mice, Inbred BALB C , Reactive Oxygen Species , Zearalenone , Animals , Zearalenone/toxicity , Curcumin/pharmacology , Apoptosis/drug effects , Reactive Oxygen Species/metabolism , Mice , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/drug therapy , Mitochondria/drug effects , Liver/drug effects , Liver/pathology , Liver/metabolism , Male , Oxidative Stress/drug effects , Antioxidants/pharmacology
4.
J Am Chem Soc ; 146(11): 7210-7215, 2024 Mar 20.
Article En | MEDLINE | ID: mdl-38437461

Transition metal-catalyzed reductive cross-couplings to build C-C/Si bonds have been developed, but the reductive cross-coupling to create the C(sp2)-B bond has not been explored. Herein, we describe a nickel-catalyzed reductive cross-coupling between aryl halides and bromoboranes to construct a C(sp2)-B bond. This protocol offers a convenient approach for the synthesis of a wide range of aryl boronate esters, using readily available starting materials. Mechanistic studies indicate that the key to the success of the reaction is the activation of the B-Br bond of bromoboranes with a Lewis base such as 2-MeO-py. The activation ensures that bromoboranes will react with the active nickel(I) catalyst prior to aryl halides, which is different from the sequence of the general nickel-catalyzed reductive C(sp2)-C/Si cross-coupling, where the oxidative addition of an aryl halide proceeds first. Notably, this approach minimizes the production of undesired homocoupling byproduct without the requirement of excessive quantities of either substrate.

5.
Inorg Chem ; 63(13): 6067-6074, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38489513

The first examples of alkali metal selenite sulfates, namely, Na8(SeO3)(SO4)3 (1), Na2(H2SeO3)(SO4) (2), and K4(H2SeO3)(HSO4)2(SO4) (3), were successfully synthesized by hydrothermal reactions. Their structures display three different zero-dimensional configurations composed of isolated sulfate tetrahedra and selenite groups separated by alkali metals. Na8(SeO3)(SO4)3 (1) features a noncentrosymmetric structure, while Na2(H2SeO3)(SO4) (2) and K4(H2SeO3)(HSO4)2(SO4) (3) are centrosymmetric. Powder second-harmonic-generation measurements revealed that Na8(SeO3)(SO4)3 (1) shows a phase-matchable SHG intensity about 1.2 times that of KDP. UV-vis-NIR diffuse reflectance spectroscopic analysis indicated that Na8(SeO3)(SO4)3 (1) has a short UV cutoff edge and a large optical band gap, which makes it a possible UV nonlinear optical material. Theoretical calculations revealed that the birefringence of Na8(SeO3)(SO4)3 (1) is 0.041 at 532 nm, which is suitable for phase-matching condition. This work provides a good experimental foundation for the exploration of new UV nonlinear crystals in an alkali metal selenite sulfate system.

6.
Ann Hematol ; 2024 Mar 07.
Article En | MEDLINE | ID: mdl-38451293

Epigenetic modifier (EM) genes play important roles in the occurrence and progression of acute lymphoblastic leukemia (ALL). However, the prognostic significance of EM mutations in ALL has not yet been thoroughly investigated. This retrospective study included 205 adult patients with ALL engaged in a pediatric-type regimen. Based on targeted next-generation sequencing, they were divided into EM mutation group (EM-mut, n = 75) and EM wild-type group (EM-wt, n = 130). The EM-mut group showed a higher positive rate of minimal residual disease (MRD) on treatment day24 and before consolidation therapy (P = 0.026, 0.020). Multivariate Cox regression analysis showed that EM-mut was an independent adverse factor for overall survival (OS) and event-free survival (EFS) (HR = 2.123, 1.742; P = 0.009, 0.007). Survival analysis revealed that the OS and EFS rates were significantly lower in the EM-mut group than in the EM-wt group (3-year OS rate, 45.8% vs. 65.0%, P = 0.0041; 3-year EFS rate, 36.7% vs. 53.2%, P = 0.011). In conclusion, EM was frequently mutated in adult ALL and was characterized by poor response to induction therapy and inferior clinical outcomes.

8.
J Bone Oncol ; 44: 100525, 2024 Feb.
Article En | MEDLINE | ID: mdl-38314324

Objective: This study was designed to delve into the complexities involved in diagnosing of benign and malignant bone tumors and to assess the potential of AI technologies like ChatGPT in improving diagnostic accuracy and efficiency. The study also explores the few-shot learning as a method to optimize ChatGPT's performance in specialized medical domains such as benign and malignant bone tumors diagnosis. Methods: A total of 1366 benign and malignant bone tumors-related imaging reports were collected and diagnosed by 25 experienced physicians. The gold standard of diagnosis was established by combining clinical, imaging and pathological principles.These reports were then input into the ChatGPT model which underwent a few-shot learning method to generate diagnostic results. The diagnostic results of the physicians and the AI model were compared to evaluate the performance of ChatGPT. An experiment was conducted to assess the influence of different radiologist's reporting styles on the model's diagnostic performance. Furthermore, in-depth analysis of misdiagnosed cases was carried out, categorizing diagnostic errors and exploring possible causes. Results: The diagnostic results generated by ChatGPT showed an accuracy of 0.73, sensitivity of 0.95, and specificity of 0.58. After few-shot learning, ChatGPT demonstrated significant improvement, achieving an accuracy of 0.87, sensitivity of 0.99, and specificity of 0.73, bringing it much closer to the level of physician diagnostics. In an experiment analyzing the influence of the radiologist's reporting style, the model demonstrated higher sensitivity when interpreting reports written by high-level radiologists. In 56 benign cases, ChatGPT misdiagnosed them as malignant. Among these, 35 benign lesions- fibrous dysplasia and osteofibrous dysplasia- were incorrectly identified as metastatic tumors or osteosarcomas; 8 cases of myositis ossificans were wrongly diagnosed as extraosseous osteosarcoma. 7 cases of giant cell tumor of bone at the end of long bone were misdiagnosed as osteosarcoma by intermediate doctors. Chondroblastoma was misdiagnosed as malignant tumor in 6 cases -2 osteosarcoma and 4 chondrosarcoma-In this study, 23 osteosarcoma cases were misdiagnosed by ChatGPT as osteomyelitis; Chondrosarcoma was misdiagnosed as fibrous dysplasia or aneurysmal bone cyst in 8 cases. Four cases of spinal chordoma were misdiagnosed as spinal tuberculosis. Conclusion: Our findings highlight the potential of ChatGPT in the diagnosis of benign and malignant bone tumors, offering advantages like enhanced efficiency and a reduction in missed diagnoses. However, the necessity of collaborative interactions between physicians and ChatGPT in practical settings was underscored. With an examination into AI's capacity in benign and malignant bone tumors diagnosis, this study lays the groundwork for future AI advancements in medicine. Additionally, the benefits of few-shot learning in fine-tuning ChatGPT applications in specialized fields were also demonstrated.

9.
Quant Imaging Med Surg ; 14(2): 1602-1615, 2024 Feb 01.
Article En | MEDLINE | ID: mdl-38415150

Background: As artificial intelligence (AI) becomes increasingly prevalent in the medical field, the effectiveness of AI-generated medical reports in disease diagnosis remains to be evaluated. ChatGPT is a large language model developed by open AI with a notable capacity for text abstraction and comprehension. This study aimed to explore the capabilities, limitations, and potential of Generative Pre-trained Transformer (GPT)-4 in analyzing thyroid cancer ultrasound reports, providing diagnoses, and recommending treatment plans. Methods: Using 109 diverse thyroid cancer cases, we evaluated GPT-4's performance by comparing its generated reports to those from doctors with various levels of experience. We also conducted a Turing Test and a consistency analysis. To enhance the interpretability of the model, we applied the Chain of Thought (CoT) method to deconstruct the decision-making chain of the GPT model. Results: GPT-4 demonstrated proficiency in report structuring, professional terminology, and clarity of expression, but showed limitations in diagnostic accuracy. In addition, our consistency analysis highlighted certain discrepancies in the AI's performance. The CoT method effectively enhanced the interpretability of the AI's decision-making process. Conclusions: GPT-4 exhibits potential as a supplementary tool in healthcare, especially for generating thyroid gland diagnostic reports. Our proposed online platform, "ThyroAIGuide", alongside the CoT method, underscores the potential of AI to augment diagnostic processes, elevate healthcare accessibility, and advance patient education. However, the journey towards fully integrating AI into healthcare is ongoing, requiring continuous research, development, and careful monitoring by medical professionals to ensure patient safety and quality of care.

10.
Foods ; 13(4)2024 Feb 13.
Article En | MEDLINE | ID: mdl-38397543

Cottonseed meal (CSM) is the major by-product of the cottonseed oil extraction process with high protein content. However, the presence of free gossypol (FG) in CSM severely restricts its utilization in the food and animal feed industries. The development of a biological strategy for the effective removal of FG in CSM has become an urgent need. In this study, three bacterial laccases including CotA from Bacillus licheniformis, CueO from Escherichia coli, and LcLac from Loigolactobacillus coryniformis were heterologously expressed and investigated for their FG degradation ability. The results showed that CotA laccase displayed the highest FG-degrading capacity among the three laccases, achieving 100% FG degradation at 37 °C and pH 7.0 in 1 h without the addition of a redox mediator. Moreover, in vitro and in vivo studies confirmed that the hepatotoxicity of FG was effectively eliminated after oxidative degradation by CotA laccase. Furthermore, the addition of CotA laccase could achieve 87% to 98% FG degradation in defatted CSM within 2 h. In conclusion, CotA laccase can be developed as an effective biocatalyst for the detoxification of FG in CSM.

11.
Chemistry ; 30(18): e202303857, 2024 Mar 25.
Article En | MEDLINE | ID: mdl-38205617

The methods for the cross-coupling of aryl(trialkyl)silanes are long-standing challenges due to the extreme inertness of C-Si(R3) bond, though the reaction is environmentally friendly and highly regioselective to synthesize biaryls. Herein, we report a copper-catalyzed cross-coupling of aryl(trialkyl)silanes and aryl via a radical mechanism. The reaction proceeds efficiently with aryl sulfonium salts as limiting reagents, exhibits broad substrate scope, and provides an important synthetic strategy to acquire biaryls, exemplified by unsymmetrical fluorescence probes and late-stage functionalization of drugs. Of note, the experimental and theoretical mechanistic studies revealed a radical mechanism where the copper catalyst and CsF play critical roles on the radical generation and desilylation process.

12.
Br J Haematol ; 204(4): 1393-1401, 2024 Apr.
Article En | MEDLINE | ID: mdl-38168845

Cytomegalovirus (CMV) DNAemia and disease are common complications in patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). Few studies have compared the efficacy and safety of the HSCT donor and third-party CMV-specific cytotoxic T lymphocytes (CMV-CTLs) in the treatment of CMV DNAemia and disease. In this study, we retrospectively compared the efficacy and safety of HSCT donor and third-party CMV-CTLs in patients with refractory CMV DNAemia or disease after allo-HSCT at our centre from January 2017 to September 2021. Fifty-three patients who received CMV-CTL therapy were enrolled, including 40 in the donor group and 13 in the third-party group, and they were adults aged 18 years or older. Within 6 weeks of treatment, 26 (65.0%) and 9 (69.2%) patients achieved complete response in the donor and third-party groups (p = 1.000). The 2-year overall survival was 59.6% (95% CI 46.1%-77.1%) and 53.8% (32.6%-89.1%) in the donor and third-party groups (p = 0.860). Four (10.0%) patients in the donor group and two (15.4%) patients in the third-party group developed acute graft-versus-host disease within 3 months after CMV-CTL infusions. In conclusion, our data suggest that donor and third-party CMV-CTLs have comparable efficacy and safety for refractory CMV DNAemia and disease.


Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation , Adult , Humans , Cytomegalovirus , T-Lymphocytes, Cytotoxic , Cytomegalovirus Infections/therapy , Cytomegalovirus Infections/complications , Retrospective Studies , Transplantation, Homologous/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects
13.
Nat Mater ; 23(5): 695-702, 2024 May.
Article En | MEDLINE | ID: mdl-38287128

π-Conjugated polymers (CPs) have broad applications in high-performance optoelectronics, energy storage, sensors and biomedicine. However, developing green and efficient methods to precisely synthesize alternating CP structures on a large scale remains challenging and critical for their industrialization. Here a room-temperature, scalable and homogeneous Suzuki-Miyaura-type polymerization reaction is developed with broad generality validated for 24 CPs including donor-donor, donor-acceptor and acceptor-acceptor connectivities, yielding device-quality polymers with high molecular masses. Furthermore, the polymerization protocol significantly reduces homocoupling structural defects, yielding more structurally regular and higher-performance electronic materials and optoelectronic devices than conventional thermally activated polymerizations. Experimental and theoretical studies reveal that a borate transmetalation process plays a key role in suppressing protodeboronation, which is critical for large-scale structural regularity. Thus, these results provide a general polymerization tool for the scalable production of device-quality CPs with alternating structural regularity.

14.
J Spinal Cord Med ; 47(1): 6-14, 2024 Jan.
Article En | MEDLINE | ID: mdl-36972206

CONTEXT: Robot-assisted gait training (RAGT) has been increasingly adopted in many rehabilitation facilities for walking function and activity in individuals with spinal cord injury (SCI). However, the effectiveness of RAGT on lower extremity strength and cardiopulmonary function, especially static pulmonary function, have not been clearly outlined. OBJECTIVE: Determine the effect of RAGT on cardiopulmonary function and lower extremity strength in SCI survivors. METHODS: Eight databases were systematically searched for randomized controlled trials comparing RAGT with conventional physical therapy or other non-robotic therapies for survivors with SCI. Study selection required lower extremity strength decline after SCI at baseline. The overall effects of RAGT were calculated using a meta-analytic method. Begg's test was used to assess the risk of publication bias. RESULTS: The pooled analysis demonstrated that RAGT may have a positive effect for individuals with SCI on lower extremity strength enhancing (n = 408; standardized mean difference [SMD] = 0.81; 95% confidence interval [CI] = 0.14-1.48) and cardiopulmonary endurance(n = 104; standardized mean difference [SMD] = 2.24; 95% confidence interval [CI] = 0.28-4.19). However, no significant effect was established on static pulmonary function. No publication bias was observed according to the Begg's test. CONCLUSIONS: RAGT may be a useful technique for improving lower limb strength and cardiovascular endurance in SCI survivors. The usefulness of RAGT in enhancing static pulmonary function was not demonstrated by the study. However, these results should be interpreted with caution, given the low number of selected studies and subjects. Clinical studies with large sample sizes will be necessary in the future.


Exercise Therapy , Robotics , Spinal Cord Injuries , Humans , Exercise Therapy/methods , Gait , Lower Extremity , Spinal Cord Injuries/complications , Spinal Cord Injuries/rehabilitation , Walking
15.
Br J Haematol ; 204(2): 628-637, 2024 02.
Article En | MEDLINE | ID: mdl-38050437

This PASS-ALL study was designed to explore the effect of paediatric-inspired versus adult chemotherapy regimens on survival of adolescents and young adults (AYA) with high-risk Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia (HR PH-ve B-cell ALL) eligible for allogeneic haematopoietic stem cell transplantation (allo-HSCT). The PASS-ALL study is a multicentre, observational cohort study, and 143 patients with HR B-cell PH-ve ALL were enrolled from five centres-77 patients allocated in the paediatric-inspired cohort and 66 in the adult cohort with comparable baseline characteristics. Of the 143 patients, 128 cases underwent allo-HSCT. Three-year leukaemia-free survival (LFS) in the paediatric-inspired cohort was 72.2% (95% CI 60.8%-83.6%) compared with 44.6% (95% CI 31.9%-57.3%; p = 0.001). Furthermore, time-to-positive minimal residual disease (TTP-MRD) post-HSCT was marked different, 3-year cumulative incidence of relapse was 25.9% (95% CI 15.8%-37.2%) in paediatric cohort and 45.4% (95% CI 40.0%-57.9%) in adult cohort (p = 0.026). Finally, the 3-year OS rate was 75.3% (95% CI 64.9%-85.7%) for the paediatric-inspired cohort and 64.1% (95% CI 51.8%-76.4%) for the adult cohort (p = 0.074). On a multivariate analysis, paediatric-inspired regimen is a predictive factor for LFS (HR = 2.540, 95% CI 1.327-4.862, p = 0.005). Collectively, our data suggest that paediatric-inspired chemotherapy pre-HSCT results in deeper and durable MRD response reduces relapse post-HSCT and improves survival in HR B-cell PH-ve ALL patients with allo-HSCT.


Burkitt Lymphoma , Hematopoietic Stem Cell Transplantation , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adolescent , Young Adult , Humans , Child , Philadelphia Chromosome , Neoplasm Recurrence, Local , Hematopoietic Stem Cell Transplantation/methods , Recurrence , Retrospective Studies
16.
Angew Chem Int Ed Engl ; 63(4): e202314228, 2024 Jan 22.
Article En | MEDLINE | ID: mdl-38019184

Axially chiral diaryl ethers are present in numerous natural products and bioactive molecules. However, only few catalytic enantioselective approaches have been established to access diaryl ether atropisomers. Herein, we report the N-heterocyclic carbene-catalyzed enantioselective synthesis of axially chiral diaryl ethers via desymmetrization of prochiral 2-aryloxyisophthalaldehydes with aliphatic alcohols, phenol derivatives, and heteroaromatic amines. This reaction features mild reaction conditions, good functional group tolerance, broad substrate scope and excellent enantioselectivity. The utility of this methodology is illustrated by late-stage functionalization, gram-scale synthesis, and diverse enantioretentive transformations. Control experiments and DFT calculations support the association of NHC-catalyzed desymmetrization with following kinetic resolution to enhance the enantioselectivity.

17.
Leuk Lymphoma ; 65(2): 219-227, 2024 Feb.
Article En | MEDLINE | ID: mdl-37938093

The prognostic impact of TP53 mutations (TP53mut) in adult acute lymphoblastic leukemia (ALL) remains debatable. Herein, we determined the clinical significance of TP53mut in 283 adult ALL patients treated with a pediatric-type regimen. TP53mut were found in 11.0% (31) of patients, including 19 cases in adolescent and young adult (AYA) patients and 12 cases in non-AYA patients. Patients with TP53mut had poorer overall survival (OS) and event-free survival (EFS) in the non-AYA subgroup (n = 64) (3-year OS, 18.2% vs 50.9%, p = .0033; 3-year EFS, 0 vs 45.3%, p = .00028). however, this had to be taken cautiously due to a limited number of patients. In the AYA subgroup (n = 219), TP53mut did not impact OS or EFS (3-year OS, 60.6%vs71.0%, p = .55; 3-year EFS, 52.5%vs59.6%, p = .57). Collectively, our data reveal that the pediatric-type regimen eliminated the poor prognostic impact of TP53mut in AYA ALL. However, in non-AYA ALL patients, TP53mut remain a potential biomarker associated with poor outcomes.


Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adolescent , Young Adult , Humans , Child , Prognosis , Mutation , Biomarkers , Progression-Free Survival , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Tumor Suppressor Protein p53/genetics
18.
Breast J ; 2023: 6282654, 2023.
Article En | MEDLINE | ID: mdl-38075552

Breast cancer is considered the most prevalent malignancy due to its high incidence rate, recurrence, and metastasis in women that makes it one of the deadliest cancers. The current study aimed to predict the genes associated with the recurrence and metastasis of breast cancer and to validate their effect on MDA-MB-231 cells. Through the bioinformatics analysis, the transcription factor 7 cofactor (MLLT11) as the target gene was obtained. MLLT11-specific siRNA was synthesized and transfected into MDA-MB-231 cells. The results demonstrated that the siRNA significantly reduced the MLLT11 mRNA levels. Moreover, cell migration and invasion, as well as the protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, matrix metalloproteinase (MMP) 2, and MMP9, were significantly lower in the groups treated with siRNA while the apoptosis was augmented. Collectively, MLLT11 siRNA elicited ameliorative properties on breast cancer cells, possibly via the inhibition of the PI3K/AKT signaling pathway.


Breast Neoplasms , Female , Humans , Apoptosis , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation , MDA-MB-231 Cells , Neoplasm Invasiveness/pathology , Neoplasm Proteins/pharmacology , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Transcription Factors
19.
Cancer Metab ; 11(1): 24, 2023 Dec 06.
Article En | MEDLINE | ID: mdl-38057929

BACKGROUND: The relationship between obesity and non-Hodgkin's lymphoma (NHL) was controversial, which may be due to the crudeness definition of obesity based on body mass index (BMI). As obesity and metabolic abnormalities often coexist, we aimed to explore whether the classification of obesity based on metabolic status can help to evaluate the real impact of obesity on the readmission of NHL. METHODS: In this retrospective cohort study, utilizing the 2018 Nationwide Readmissions Database, we identified NHL-related index hospitalizations and followed them for non-elective readmission. The patients with NHL were classified as metabolically healthy non-obese (MHNO) and obese (MHO) and metabolically unhealthy non-obese (MUNO) and obese (MUO). Readmission rates for each phenotype were calculated at 30-day intervals. Multiple COX regression was used to analyze the association of metabolic-defined obesity with 30-day, 90-day, and 180-day readmission rates in patients with NHL. RESULTS: There were 22,086 index hospitalizations with NHL included. In the multivariate COX regression, MUNO was associated with increased 30-day (HR = 1.113, 95% CI 1.036-1.195), 90-day (HR = 1.148, 95% CI 1.087-1.213), and 180-day readmission rates (HR = 1.132, 95% CI 1.077-1.189), and MUO was associated with increased 30-day (HR=1.219, 95% CI: 1.081-1.374), 90-day (HR = 1.228, 95% CI 1.118-1.348), and 180-day readmission rates (HR = 1.223, 95% CI 1.124-1.33), while MHO had no associations with readmission rates. CONCLUSIONS: The presence of metabolic abnormalities with or without obesity increased the risk of non-selective readmission in patients with NHL. However, obesity alone had no associations with the risk of non-selective readmission, suggesting that interventions for metabolic abnormalities may be more important in reducing readmissions of NHL patients.

20.
Int J Med Robot ; : e2604, 2023 Dec 19.
Article En | MEDLINE | ID: mdl-38115728

BACKGROUND: Ureteral injury is common during gynaecological laparoscopic surgery. Real-time auto-segmentation can assist gynaecologists in identifying the ureter and reduce intraoperative injury risk. METHODS: A deep learning segmentation model was crafted for ureter recognition in surgical videos, utilising 3368 frames from 11 laparoscopic surgeries. Class activation maps enhanced the model's interpretability, showing its areas. The model's clinical relevance was validated through an End-User Turing test and verified by three gynaecological surgeons. RESULTS: The model registered a Dice score of 0.86, a Hausdorff 95 distance of 22.60, and processed images in 0.008 s on average. In complex surgeries, it pinpointed the ureter's position in real-time. Fifty five surgeons across eight institutions found the model's accuracy, specificity, and sensitivity comparable to human performance. Yet, artificial intelligence experience influenced some subjective ratings. CONCLUSIONS: The model offers precise real-time ureter segmentation in laparoscopic surgery and can be a significant tool for gynaecologists to mitigate ureteral injuries.

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