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1.
BMC Surg ; 24(1): 133, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702652

RESUMO

OBJECTIVES: While surgery plays a crucial role in treating papillary thyroid carcinoma (PTC), the potential effects of subsequent TSH suppression therapy on prognosis should not be overlooked. This study aims to investigate the factors that influence postoperative TSH suppression therapy in patients with PTC. METHODS: This study was a retrospective cohort study conducted at our hospital. It included 268 patients who underwent surgery and were pathologically diagnosed with PTC between February 2019 and February 2021. The selected patients received postoperative TSH suppression therapy. Based on the TSH level measured 12 months after surgery, the patients were divided into two groups: TSH level conforming group (n = 80) and non-conforming group (n = 188). We then compared the general clinical data, clinicopathological characteristics, preoperative laboratory test indicators, postoperative levothyroxine sodium tablet dosage, follow-up frequency, and thyroid function-related indicators between the two groups of patients. The correlation between the observed indicators and the success of TSH suppression therapy was further analyzed, leading to the identification of influencing factors for TSH suppression therapy. RESULTS: There were no statistically significant differences in general clinical data and clinicopathological characteristics between the two groups of patients (P > 0.05). The proportion of patients with preoperative TSH ≥ 2.0 mU/L was higher in the non-conforming group compared to the TSH level conforming group (P < 0.05), and the ROC curve analysis indicated that the area under the curve for the preoperative TSH index was 0.610 (P < 0.05). The proportion of patients in the TSH level conforming group who took oral levothyroxine sodium tablets at a dose of ≥ 1.4 µg/kg·d after surgery was higher (P < 0.05). The postoperative levels of FT3 and FT4 were higher in the TSH level conforming group (P < 0.05). The results of binary logistic regression analysis indicated that factors "Postoperative TSH level ≥ 2 mU/L", "Levothyroxine sodium tablet dose<1.4 µg/kg·d", and "Combined with Hashimoto thyroiditis" were significantly associated with an elevated risk of postoperative TSH levels failing to reach the target (P < 0.05). CONCLUSION: Optimal thyroid function in patients with PTC post-surgery is best achieved when adjusting the dose of levothyroxine sodium in a timely manner to reach the target TSH level during follow-up visits.


Assuntos
Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Tireoidectomia , Tireotropina , Tiroxina , Humanos , Estudos Retrospectivos , Masculino , Feminino , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/tratamento farmacológico , Câncer Papilífero da Tireoide/patologia , Tireotropina/sangue , Tireotropina/antagonistas & inibidores , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Pessoa de Meia-Idade , Tiroxina/uso terapêutico , Tiroxina/administração & dosagem , Adulto , Resultado do Tratamento , Período Pós-Operatório
2.
BMC Med Educ ; 24(1): 531, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38741079

RESUMO

BACKGROUND: An urgent need exists for innovative surgical video recording techniques in head and neck reconstructive surgeries, particularly in low- and middle-income countries where a surge in surgical procedures necessitates more skilled surgeons. This demand, significantly intensified by the COVID-19 pandemic, highlights the critical role of surgical videos in medical education. We aimed to identify a straightforward, high-quality approach to recording surgical videos at a low economic cost in the operating room, thereby contributing to enhanced patient care. METHODS: The recording was comprised of six head and neck flap harvesting surgeries using GoPro or two types of digital cameras. Data were extracted from the recorded videos and their subsequent editing process. Some of the participants were subsequently interviewed. RESULTS: Both cameras, set at 4 K resolution and 30 frames per second (fps), produced satisfactory results. The GoPro, worn on the surgeon's head, moves in sync with the surgeon, offering a unique first-person perspective of the operation without needing an additional assistant. Though cost-effective and efficient, it lacks a zoom feature essential for close-up views. In contrast, while requiring occasional repositioning, the digital camera captures finer anatomical details due to its superior image quality and zoom capabilities. CONCLUSION: Merging these two systems could significantly advance the field of surgical video recording. This innovation holds promise for enhancing technical communication and bolstering video-based medical education, potentially addressing the global shortage of specialized surgeons.


Assuntos
COVID-19 , Gravação em Vídeo , Humanos , COVID-19/epidemiologia , Procedimentos de Cirurgia Plástica/educação , Retalhos Cirúrgicos , SARS-CoV-2 , Cabeça/cirurgia , Pescoço/cirurgia
3.
World J Gastrointest Surg ; 16(3): 717-730, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38577067

RESUMO

BACKGROUND: Due to the complexity and numerous comorbidities associated with Crohn's disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. AIM: To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. METHODS: A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. RESULTS: Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. CONCLUSION: Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

4.
Sci Rep ; 14(1): 8127, 2024 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-38584156

RESUMO

The traditional lecture-based learning (LBL) method is facing great challenges due to its low efficiency and single proceeding form. We designed a PRI-E learning mode that combined and modified problem-based, case-based, and evidence-based learning with a step-by-step approach. We evaluated the practical learning outcomes of using the PRI-E mode by comparing it with traditional lecture-based learning in oral and maxillofacial oncology education. "PRI-E" consists of the first letters of the English words Passion, Research, Innovation, and Education, and it means "the best Education". This prospective randomized controlled trial included 40 participants. We evenly divided the participants into the PRI-E (n = 20) and LBL group (n = 20) based on the entrance test scores. The same staff group designed and then taught the learning content with different group measures. The evaluation included the final test scores and questionnaire assessments. Without affecting the examination results, the PRI-E teaching method was more satisfactory and popular with participants in terms of ability development and classroom participation. Enacting the PRI-E teaching method required more time, but this did not affect its popularity among the participants. Compared with the LBL learning mode, the PRI-E learning mode was more organized and efficient in oral and maxillofacial oncology education without affecting academic performance. This model has a high degree of satisfaction, which is conducive to training students' comprehensive ability.


Assuntos
Aprendizagem , Aprendizagem Baseada em Problemas , Humanos , Aprendizagem Baseada em Problemas/métodos , Estudos Prospectivos , Estudantes , Avaliação Educacional
5.
Anal Chim Acta ; 1303: 342521, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38609263

RESUMO

BACKGROUND: Theranostic nanoplatforms with integrated diagnostic imaging and multiple therapeutic functions play a vital role in precise diagnosis and efficient treatment for breast cancer, but unfortunately, these nanoplatforms are usually stuck in single-site imaging and single mode of treatment, causing unsatisfactory diagnostic and therapeutic efficiency. Herein, a dual biomarkers-activatable facile hollow mesoporous MnO2 (H-MnO2)-based theranostic nanoplatform, DNAzyme@H-MnO2-MUC1 aptamer (DHMM), was constructed for the simultaneous multi-site diagnosis and multiple treatment of breast cancer. RESULTS: The DHMM acted as an integrated diagnostic and therapeutic nanoplatform that realizes multi-site fluorescence imaging-guided high-efficient photothermal/chemodynamic/gene synergistic therapy (PTT/CDT/GT) for breast cancer. The H-MnO2 exhibits high loading capacity for Cy5-MUC1 aptamer (3.05 pmoL µg-1) and FAM-DNAzyme (3.37 pmoL µg-1), and excellent quenching for the probes. In the presence of MUC1 on the cell membrane and GSH in the cytoplasm, Cy5-MUC1 aptamer and FAM-DNAzyme was activated triggering dual-channel fluorescence imaging at different sites. Moreover, the self-supplied Mn2+ was further supplied as DNAzyme cofactors to catalytic cleavage intracellular EGR-1 mRNA for high-efficient GT and stimulated the Fenton-like reaction for CDT. The H-MnO2 also showcases a favorable photothermal performance with a photothermal conversion efficiency of 44.16%, which ultimately contributes to multi-site fluorescence imaging-guided synergistic treatment with an apoptosis rate of 71.82%. SIGNIFICANCE: This dual biomarker-activatable multiple therapeutic nanoplatform was realized multi-site fluorescence imaging-guided PTT/CDT/GT combination therapy for breast cancer with higher specificity and efficiency, which provides a promising theranostic nanoplatform for the precision and efficiency of breast cancer treatment.


Assuntos
Carbocianinas , DNA Catalítico , Neoplasias , Medicina de Precisão , Compostos de Manganês , Óxidos , Imagem Óptica , Biomarcadores
6.
Parasitol Res ; 123(4): 189, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639821

RESUMO

Toxocara canis is a parasitic zoonose that is distributed worldwide and is one of the two pathogens causing toxocariasis. After infection, it causes serious public health and safety problems, which pose significant veterinary and medical challenges. To better understand the regulatory effects of T. canis infection on the host immune cells, murine macrophages (RAW264.7) were incubated with recombinant T. canis C-type lectin 4 (rTc-CTL-4) protein in vitro. The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2), receptor-interacting protein 2 (RIP2), nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) on mRNA level and protein expression level in macrophages. Our results indicated that 10 µg/mL rTc-CTL-4 protein could modulate the expression of NOD1, NOD2, and RIP2 at both the transcriptional and translational levels. The protein translation levels of NF-κB, P-p65, p38, and P-p38 in macrophages were also modulated by rTc-CTL-4 protein. Macrophages were co-incubated with rTc-CTL-4 protein after siRNA silencing of NOD1, NOD2, and RIP2. The expression levels of NF-κB, P-p65, p38, and P-p38 were significantly changed compared with the negative control groups (Neg. Ctrl.). Taken together, rTc-CTL-4 protein seemed to act on NOD1/2-RIP2-NF-κB and MAPK signaling pathways in macrophages and might activate MAPK and NF-κB signaling pathways by regulating NOD1, NOD2, and RIP2. The insights from the above studies could contribute to our understanding of immune recognition and regulatory mechanisms of T. canis infection in the host animals.


Assuntos
NF-kappa B , Toxocara canis , Animais , Camundongos , NF-kappa B/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Toxocara canis/metabolismo , Transdução de Sinais/fisiologia , Macrófagos
8.
PLoS One ; 19(4): e0300441, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38648205

RESUMO

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide, which poses a severe threat to human health. COVID-19 is a systemic ailment affecting various tissues and organs, including the lungs and liver. Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver cancer, and cancer patients are particularly at high risk of SARS-CoV-2 infection. Nonetheless, few studies have investigated the impact of COVID-19 on ICC patients. METHODS: With the methods of systems biology and bioinformatics, this study explored the link between COVID-19 and ICC, and searched for potential therapeutic drugs. RESULTS: This study identified a total of 70 common differentially expressed genes (DEGs) shared by both diseases, shedding light on their shared functionalities. Enrichment analysis pinpointed metabolism and immunity as the primary areas influenced by these common genes. Subsequently, through protein-protein interaction (PPI) network analysis, we identified SCD, ACSL5, ACAT2, HSD17B4, ALDOA, ACSS1, ACADSB, CYP51A1, PSAT1, and HKDC1 as hub genes. Additionally, 44 transcription factors (TFs) and 112 microRNAs (miRNAs) were forecasted to regulate the hub genes. Most importantly, several drug candidates (Periodate-oxidized adenosine, Desipramine, Quercetin, Perfluoroheptanoic acid, Tetrandrine, Pentadecafluorooctanoic acid, Benzo[a]pyrene, SARIN, Dorzolamide, 8-Bromo-cAMP) may prove effective in treating ICC and COVID-19. CONCLUSION: This study is expected to provide valuable references and potential drugs for future research and treatment of COVID-19 and ICC.


Assuntos
Neoplasias dos Ductos Biliares , COVID-19 , Colangiocarcinoma , Biologia Computacional , SARS-CoV-2 , Biologia de Sistemas , Colangiocarcinoma/genética , Colangiocarcinoma/virologia , Humanos , COVID-19/genética , COVID-19/virologia , SARS-CoV-2/genética , Biologia Computacional/métodos , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/virologia , Biologia de Sistemas/métodos , Mapas de Interação de Proteínas/genética , Pandemias , Infecções por Coronavirus/virologia , Infecções por Coronavirus/genética , Betacoronavirus/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes
9.
Quant Imaging Med Surg ; 14(3): 2528-2538, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38545069

RESUMO

Background: The hand skeletal features of children and adolescents at different growth statuses and development periods, and the correlation between these skeletal features and hand asymmetric force are currently unclear. Thus, this study sought to investigate the hand skeletal features of children and adolescents at different growth statuses and at different periods of development, and the correlation between these skeletal features and asymmetric force in hands. Methods: A retrospective study was performed on subjects aged 4-20 years with good growth status (group A) or short stature (group B). Additional subjects aged 4-20, 21-40, and >40 years were enrolled in groups C, D, and E, respectively. All the subjects underwent left-hand posteroanterior X-ray radiography. Brachymesophalangia-V (BMP-V), conical epiphysis, epiphysis/metaphysis symmetry of the proximal phalanx (ESP), and the angle of the metacarpal-phalangeal axis were analyzed. Results: Of the 654 children and teenagers aged 4-20 years (median: 11 years) enrolled in the study, 432 were allocated to group A, of whom 237 (54.9%) were male and 195 (45.1%) were female, and 222 matched cases were allocated to group B, of whom 112 (50.5%) were male and 110 (49.5%) were female. The first to third ESPs were significantly (P<0.05) greater in group A than in group B, while the first to third angles of the metacarpal-phalangeal axis were significantly (P<0.05) smaller in group A than in group B. The correlation analysis revealed a highly significant (P<0.01) negative correlation between the ESP and angle of the metacarpal-phalangeal axis (r=-0.948, -0.926, -0.940, -0.885, and -0.848, respectively). The incidence of BMP-V was 15.4% in all patients, while that of conical epiphysis was 19.5%. The incidence of BMP-V and conical epiphysis was significantly (P<0.05) smaller in group A than in group B (11.1% vs. 23.8% for BMP-V and 16.6% vs. 25.2% for conical epiphysis, respectively). Additionally, 216 subjects were enrolled in group C (108 male and 108 female), 185 subjects were enrolled in in group D (93 male and 92 female), and 176 subjects were enrolled in in group E (104 male and 72 female). The second to fifth ESPs in group C were significantly (P<0.05) smaller than those in both groups D and E, while the second to fifth angles of the metacarpal-phalangeal axis were significantly (P<0.05) larger in group C than in both groups D and E. A BMP-V was present in 35 (16.2%) patients in group C, 8 (4.3%) in group D, and 2 (1.1%) in group E, and the difference among the three groups was statistically significant (P<0.05). Conclusions: The epiphyseal symmetry of the proximal phalanges is poor in short stature children and adolescents, and the angle between the metacarpal and phalangeal axes is larger in children and adolescents with short stature than those with normal height and good growth status. A negative correlation was found between the epiphyseal symmetry of the proximal phalanges and asymmetrical stress.

10.
PeerJ Comput Sci ; 10: e1751, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435550

RESUMO

Liver occupying lesions can profoundly impact an individual's health and well-being. To assist physicians in the diagnosis and treatment of abnormal areas in the liver, we propose a novel network named SEU2-Net by introducing the channel attention mechanism into U2-Net for accurate and automatic liver occupying lesion segmentation. We design the Residual U-block with Squeeze-and-Excitation (SE-RSU), which is to add the Squeeze-and-Excitation (SE) attention mechanism at the residual connections of the Residual U-blocks (RSU, the component unit of U2-Net). SEU2-Net not only retains the advantages of U2-Net in capturing contextual information at multiple scales, but can also adaptively recalibrate channel feature responses to emphasize useful feature information according to the channel attention mechanism. In addition, we present a new abdominal CT dataset for liver occupying lesion segmentation from Peking University First Hospital's clinical data (PUFH dataset). We evaluate the proposed method and compare it with eight deep learning networks on the PUFH and the Liver Tumor Segmentation Challenge (LiTS) datasets. The experimental results show that SEU2-Net has state-of-the-art performance and good robustness in liver occupying lesions segmentation.

12.
Adv Clin Exp Med ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353506

RESUMO

BACKGROUND: Oral chronic graft-versus-host disease (cGVHD) impacts quality of life of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, its precise pathogenesis remains unknown, with potential associations with differential microRNA (miRNA) expression and the TGF-â/Smad signaling pathway. OBJECTIVES: This study aims to explore miRNA expression profiles in the peripheral blood of oral cGVHD patients, focusing on miRNA-769-5p and its relationship with Smad2. MATERIAL AND METHODS: Peripheral venous blood samples were collected for RNA extraction from 8 patients with oral cGVHD, 8 patients without cGVHD and 8 participants from the healthy control group. The miRNA library was constructed using the Illumina Hiseq 2500 platform. We focused on identifying miRNAs associated with the TGF-â/Smad signaling pathway and subsequently conducted validation experiments. The oral cGVHD and without cGVHD groups were each expanded to include 15 individuals. Peripheral blood samples were subjected to polymerase chain reaction (PCR) analysis to assess miRNA levels and to evaluate Smad2 mRNA levels in peripheral blood mononuclear cells (PBMC). Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to determine the Smad2 protein levels in peripheral blood. RESULTS: The most significantly differentially expressed miRNAs among the 3 groups were miRNA-505-5p and miRNA-769-5p. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated an enrichment of the target genes of miRNA-769-5p in the TGF-â signaling pathway. It was observed that miRNA-769-5p expression was higher in patients without oral cGVHD in comparison to those with oral cGVHD. Receiver operating characteristic (ROC) analysis demonstrated that miRNA-769-5p holds diagnostic value for oral cGVHD. As a target of miRNA-769-5p, Smad2 mRNA exhibited a negative correlation with it. Moreover, both Smad2 mRNA and protein levels were higher in patients with oral cGVHD as opposed to those without cGVHD. CONCLUSIONS: Differential expression of miRNAs, particularly the downregulation of miRNA-769-5p, may influence the development of oral cGVHD by diminishing its inhibitory effect on the TGF-â/Smad signaling pathway through its interaction with Smad2.

13.
Plants (Basel) ; 13(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38256750

RESUMO

Flavanone 3-hydroxylase (F3H) catalyzes trihydroxyflavanone formation into dihydroflavonols in the anthocyanin biosynthesis pathway, serving as precursors for anthocyanin synthesis. To investigate the CsF3Ha promoter's regulation in the 'Zijuan' tea plant, we cloned the CsF3Ha gene from this plant. It was up-regulated under various visible light conditions (blue, red, and ultraviolet (UV)) and using plant growth regulators (PGRs), including abscisic acid (ABA), gibberellic acid (GA3), salicylic acid (SA), ethephon, and methyl jasmonate (MeJA). The 1691 bp promoter sequence was cloned. The full-length promoter P1 (1691 bp) and its two deletion derivatives, P2 (890 bp) and P3 (467 bp), were fused with the ß-glucuronidase (GUS) reporter gene, and were introduced into tobacco via Agrobacterium-mediated transformation. GUS staining, activity analysis, and relative expression showed that visible light and PGRs responded to promoter fragments. The anthocyanin content analysis revealed a significant increase due to visible light and PGRs. These findings suggest that diverse treatments indirectly enhance anthocyanin accumulation in 'Zijuan' tea plant leaves, establishing a foundation for further research on CsF3Ha promoter activity and its regulatory role in anthocyanin accumulation.

14.
J Vasc Surg Venous Lymphat Disord ; 12(2): 101727, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38043681

RESUMO

OBJECTIVE: Thrombi in the axial calf veins have quite different anatomical and physiological characteristics from that in the muscular calf veins, but their treatment was usually addressed in the same manner. We performed a meta-analysis of randomized and cohort studies to compare clinical outcomes among patients with isolated axial vs muscular calf deep vein thrombosis (DVT). METHODS: Recurrent venous thromboembolism (VTE) was selected as the primary outcome. Resolution, proximal propagation of calf DVT, pulmonary embolism (PE), major bleeds, and clinically relevant non-major bleeds were separately analyzed as secondary outcomes. Data were pooled and compared with risk ratio (RR) and 95% confidence interval (CI). RESULTS: Thirteen studies, consisting of 4889 patients, met the inclusion criteria and were included for analysis. A greater rate of recurrent VTE (FE model: RR, 1.23; 95% CI, 1.00-1.53; I2 = 29%), resolution (FE model: RR, 1.32; 95% CI, 1.01-1.72; I2 = 31%), proximal propagation (FE model: RR, 1.63; 95% CI, 1.10-2.41; I2 = 40%), and PE (FE model: RR, 2.79; 95% CI, 1.31-5.95; I2 = 0%) in the axial group compared with the muscular group. There was no difference in the pooled estimates for major bleeds (FE model: RR, 1.09; 95% CI, 0.61-1.95; I2 = 0%), and clinically relevant non-major bleeds (FE model: RR, 1.80; 95% CI, 0.93-3.48) in the axial and muscular arms. CONCLUSIONS: Patients with calf DVT limited to muscular veins might have a lower rate of recurrent VTE, resolution, proximal propagation, and PE vs those with axial calf vein involvement and exhibited similar safety outcomes.


Assuntos
Isquemia Mesentérica , Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Humanos , Anticoagulantes/efeitos adversos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/terapia , Tromboembolia Venosa/induzido quimicamente , Isquemia Mesentérica/complicações , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia , Embolia Pulmonar/terapia , Embolia Pulmonar/complicações , Hemorragia/induzido quimicamente
15.
Nat Cancer ; 5(1): 66-84, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38151625

RESUMO

Chromosomal instability (CIN) is a hallmark of cancer, caused by persistent errors in chromosome segregation during mitosis. Aggressive cancers like high-grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC) have a high frequency of CIN and TP53 mutations. Here, we show that inhibitors of the KIF18A motor protein activate the mitotic checkpoint and selectively kill chromosomally unstable cancer cells. Sensitivity to KIF18A inhibition is enriched in TP53-mutant HGSOC and TNBC cell lines with CIN features, including in a subset of CCNE1-amplified, CDK4-CDK6-inhibitor-resistant and BRCA1-altered cell line models. Our KIF18A inhibitors have minimal detrimental effects on human bone marrow cells in culture, distinct from other anti-mitotic agents. In mice, inhibition of KIF18A leads to robust anti-cancer effects with tumor regression observed in human HGSOC and TNBC models at well-tolerated doses. Collectively, our results provide a rational therapeutic strategy for selective targeting of CIN cancers via KIF18A inhibition.


Assuntos
Cinesinas , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Cinesinas/genética , Cinesinas/metabolismo , Mitose/genética , Linhagem Celular , Pontos de Checagem da Fase M do Ciclo Celular
16.
Asian J Androl ; 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38156805

RESUMO

RING finger 187 (RNF187), a ubiquitin-ligating (E3) enzyme, plays a crucial role in the proliferation of cancer cells. However, it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells. To investigate the potential involvement of RNF187 in germ cell development, we conducted interference and overexpression assays using GC-2 cells, a mouse spermatocyte-derived cell line. Our findings reveal that the interaction between RNF187 and histone H3 increases the viability, proliferation, and migratory capacity of GC-2 cells. Moreover, we provide evidence demonstrating that RNF187 interacts with H3 and mediates the ubiquitination of H3 at lysine 57 (K57) or lysine 80 (K80), directly or indirectly resulting in increased cellular transcription. This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediating histone H3 ubiquitination, thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of gene transcription. These discoveries provide a new theoretical foundation for further comprehensive investigations into the function of RNF187 in the reproductive system.

17.
Cell Death Dis ; 14(10): 696, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875515

RESUMO

As a common malignant tumor among women, ovarian cancer poses a serious threat to their health. This study demonstrates that long non-coding RNA NRSN2-AS1 is over-expressed in ovarian cancer tissues using patient sample and tissue microarrays. In addition, NRSN2-AS1 is shown to promote ovarian cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, NRSN2-AS1 stabilizes protein tyrosine kinase 2 (PTK2) to activate the ß-catenin pathway via repressing MG-53-mediated ubiquitinated degradation of PTK2, thereby facilitating ovarian cancer progression. Rescue experiments verify the function of the NRSN2-AS1/PTK2/ß-catenin axis and the effects of MG53 on this axis in ovarian cancer cells. In conclusion, this study demonstrates the key role of the NRSN2-AS1/PTK2/ß-catenin axis for the first time and explores its potential clinical applications in ovarian cancer.


Assuntos
Neoplasias Ovarianas , RNA Longo não Codificante , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Cateninas/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Wnt/genética , Movimento Celular/genética , Quinase 1 de Adesão Focal/metabolismo
18.
Invest New Drugs ; 41(6): 834-841, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897650

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal adverse reaction to pembrolizumab. The clinical characteristics of pembrolizumab induced HLH are unknown. Exploring the clinical features of pembrolizumab induced HLH is crucial for the treatment and prevention of immune checkpoint inhibitor-induced HLH. METHODS: The literature related to pembrolizumab induced HLH was collected for retrospective analysis by searching the Chinese and English databases from inception until August 31, 2023. RESULTS: A total of 24 patients were included, including 17 men (70.8%) with a median age of 61 years (41,80). The time between the last infusion and the start of HLH ranged from 2 to 46 days, with a median time of 14 days. Fever (100%) was the most common symptom, accompanied by splenomegaly (14 cases, 58.3%) and hepatomegaly (6 cases, 25.0%). Laboratory examination revealed revealed anemia (18 cases, 75.0%), leukopenia (12 cases, 50.0%), thrombocytopenia (20 cases, 83.3%), hypertriglyceridemia (11 cases, 45.8%), hypofibrinogenemia (11 cases, 45.8%). decreased natural killer cell function (7 cases, 29.2%), and elevated soluble CD25(15 cases, 62.5%). All patients developed hyperferriinemia, with a median of 30,808 ng/mL (range 1303 ~ 100,000). Bone marrow biopsy showed hemophagocytosis (15 cases, 62.5%). After discontinuation of pembrolizumab and treatment with steroids, etoposide, intravenous immunoglobulin, cytokine blocking, and immunosuppression, 17 patients recovered or improved, and 5 patients eventually died. CONCLUSION: HLH should be suspected when unexplained fever, cytopenia, splenomegaly, and elevated aminotransferase occur in patients using pembrolizumab. Screening for risk factors before treatment with pembrolizumab may be necessary to prevent HLH.


Assuntos
Anemia , Linfo-Histiocitose Hemofagocítica , Masculino , Humanos , Pessoa de Meia-Idade , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/complicações , Estudos Retrospectivos , Esplenomegalia/complicações , Anticorpos Monoclonais Humanizados/efeitos adversos
19.
Int J Ophthalmol ; 16(9): 1527-1534, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37724286

RESUMO

AIM: To evaluate the trends and changes in the number and rates of disability-adjusted life years (DALYs) and prevalence of cataract in China between 1990 and 2019, and to predict the trends of cataract burden from 2020 to 2030. METHODS: The Global Burden of Diseases (GBD) database was employed to collect the data on DALYs and the prevalence of cataract in China, which was distinguished by age and sex during the past three decades from 1990 to 2019, and then changes in the number and rates of cataract from 2020 to 2030 were predicted. All data were analyzed by the R program (version 4.2.2) and GraphPad Prism 9.0 statistics software. RESULTS: The number of DALYs of cataract increased from 449 322.84 in 1990 to 1 087 987.61 in 2019, number of cataract cases increased from 5 607 600.94 in 1990 to 18 142 568.96 in 2019. The age-standardized DALY rates (ASDR) generally increased slightly [estimated annual percentage change (EAPC=0.1; 95%CI: -0.24 to 0.45), age-standardized prevalence rates (ASPR) also increased (EAPC=0.88; 95%CI: 0.6 to 1.15). Cataract burden increased with age and female gender. Among the causes of cataract, air pollution was the most important, followed by smoking, high fasting plasma glucose, and high body mass index (BMI). The burden of cataract is predicted to grow persistently from 2020 to 2030, the number of DALYs and prevalence for cataract will rise to 2 336 431 and 43 698 620 respectively by 2030, the ASDR is predicted to be 85/100 000 and ASPR will be 1586/100 000 in 2030, females will still be at greater risk of suffering from cataract than males. CONCLUSION: The burden of cataract in China kept rising from 1990 to 2019. Increasing age and female gender are risk factors for cataract. Air pollution, smoking, high fasting plasma glucose, and high BMI are associated with cataract. The burden of cataract in China will gradually increase from 2020 to 2030, the elderly women in particular need attention. Our results may be of help for providing reference strategies to reduce cataract burden in the near future.

20.
Int J Ophthalmol ; 16(8): 1317-1325, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37602344

RESUMO

AIM: To evaluate the efficacy and safety of ultrasound cycloplasty (UCP) for glaucoma. METHODS: A comprehensive search of PubMed, Embase, Web of Science, and Google Scholar databases was used to select studies met the inclusion criteria. Meta-analysis was performed by Review Manager and StataCorp LLC. RESULTS: A total of 19 articles met the inclusion criteria. Overall, UCP is effective and safe in the glaucoma treatment, the risk ratio (RR) of the success rate was 2.28 (95%CI, 1.82-2.84). After UCP, patients had a significant reduction in intraocular pressure (IOP; mm Hg), the weighted mean difference (WMD) was 11.39 (95%CI, 9.88-12.90). In addition, UCP brings fewer postoperative complications with RR of 0.30 (95%CI, 0.19-0.49). Most of the complications were short-term and mild. Postoperatively, patients' use of IOP-lowering medications reduced, the standardized mean difference (SMD) was 0.78 (95%CI, 0.40-1.17). However, best corrected visual acuity (BCVA; logMAR) did not have obvious improvement after UCP, the WMD was 0.01 (95%CI, -0.06-0.09). This procedure does provide painfulness relief, with RR of 3.06 (95%CI, 1.95-4.81). CONCLUSION: UCP is effective and safe for suitable glaucoma. It can effectively decrease IOP in glaucoma patients, reduce the patients' dependence on IOP-lowering medications after surgery, relief the painfulness and has fewer long-term or severe postoperative complications, but the BCVA did not improve much.

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