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1.
J Biochem Mol Toxicol ; 38(10): e23832, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39267413

RESUMO

The malignant behavior and immune escape ability of cancer cells lead to therapeutic failure and poor prognosis for patients with various cancers, including colon cancer. Plexin domain containing 1 (PLXDC1) was initially identified to exert key roles in tumor by regulating angiogenesis and has recently proved to be involved in cell proliferation and migration of glioblastoma and gastric cancer cells. However, its roles in colon cancer remain unclear. In this study, the online bioinformatics databases confirmed high expression of PLXDC1 in colon cancer specimens, which was associated with cancer stages and nodal metastasis. Similarly, the increased expression of PLXDC1 was also validated in our collected samples and colon cancer cells. Moreover, patients with high expression of PLXDC1 had shorter survival, indicating that PLXDC1 might be a potential prognostic predictor for colon cancer patients. Notably, targeting PLXDC1 inhibited cancer cell viability and invasion, and enhanced cell apoptosis. Intriguingly, Tumor Immune Estimation Resource database confirmed that PLXDC1 expression was related to various tumor-infiltrating immune cells in colon adenocarcinoma including macrophages, and its expression was also correlated with M2-like macrophage markers. In vitro, colon cancer cells with PLXDC1 downregulation had a reduced ability to recruit and polarize macrophage towards M2 phenotype by decreasing the percentage of CD206+ cells and M2-like markers (CD206, CD163, arginase1, and interleukin 10 [IL-10]). Moreover, PLXDC1 knockdown attenuated M2 macrophage-mediated promotion in cancer cell viability and invasion. Mechanically, inhibition of PLXDC1 suppressed activation of the IL-6/Signal transducer and activator of transcription 3 (STAT3) signaling. Reactivating the above pathway by transfection with IL-6 plasmids reversed the suppressive effects of PLXDC1 knockdown on cancer cell malignant behaviors, macrophage recruitment and M2-like polarization. Thus, PLXDC1 downregulation may inhibit the malignancy of colon cancer cells and their ability to recruit and polarize macrophages towards M2 phenotype by blocking the IL-6/STAT3 pathway. Together, targeting PLXDC1 may attenuate the progression of colon cancer by direct roles in cancer cells and indirect roles in macrophage polarization, representing a promising therapeutic target for colon cancer patients.


Assuntos
Biomarcadores Tumorais , Neoplasias do Colo , Macrófagos , Humanos , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Prognóstico , Macrófagos/metabolismo , Macrófagos/patologia , Linhagem Celular Tumoral , Progressão da Doença , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genética , Masculino , Feminino , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica
2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(4): 519-527, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39223017

RESUMO

Objective To identify the risk factors of patients with frequent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and construct a prediction model based on the clinical data,providing a theoretical basis for the clinical prevention and treatment. Methods A total of 25 638 COPD patients admitted to the Department of Respiratory and Critical Care Medicine,the Third People's Hospital of Chengdu from January 1,2013 to May 1,2023 were selected.Among them,11 315 patients were included according to the inclusion and exclusion criteria,and their clinical characteristics were analyzed.Multivariate Logistic regression was carried out to identify the risk factors for frequent AECOPD.A nomogram model was utilized to quantify the risk of acute exacerbation,and the performance of the prediction model was assessed based on the area under the receiver operating characteristic (ROC) curve. Results In the patients with frequent AECOPD,male percentage (P<0.001),age (P<0.001),urban residence (P<0.001),smoking (P<0.001),length of stay (P<0.001),total cost (P<0.001),antibiotic cost (P<0.001),diabetes (P=0.003),respiratory failure (P<0.001),heart disease (P<0.001),application of systemic glucocorticoids (P<0.001),white blood cell count (P<0.001),neutrophil percentage (P<0.001),C-reactive protein (P<0.001),total cholesterol (P<0.001),and brain natriuretic peptide (BNP) (P<0.001) were all higher than those in the patients with infrequent AECOPD.Multivariate Logistic regression analysis revealed that age,urban residence,smoking,diabetes,heart disease,Pseudomonas aeruginosa infection,application of systemic glucocorticoids,antibiotics,respiratory failure,and elevated white blood cell count,total cholesterol,and BNP were independent risk factors for hospitalization due to frequent AECOPD.A nomogram model of hospitalization due to frequent AECOPD was constructed according to risk factors.The ROC curve was established to evaluate the performance of the model,which showed the area under the ROC curve of 0.899 (95%CI=0.892-0.905),the sensitivity of 85.30%,and the specificity of 79.80%. Conclusion Frequent AECOPD is associated with smoking,heart disease,application of systemic glucocorticoids,Pseudomonas aeruginosa infection,age,low body mass index,and elevated BNP.Predicting the risks of hospitalization due to frequent AECOPD by the established model can provide theoretical support for the treatment and risk factor management of the patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Masculino , Feminino , Fatores de Risco , Idoso , Pessoa de Meia-Idade , Modelos Logísticos , Nomogramas , Idoso de 80 Anos ou mais
3.
Clin Oral Investig ; 28(10): 529, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287813

RESUMO

OBJECTIVES: This study aims to investigate the changes in alveolar bone following the simultaneous performance of labial and lingual augmented corticotomy (LLAC) in patients with insufficient alveolar bone thickness on both the labial and lingual sides of the mandibular anterior teeth during presurgical orthodontic treatment. MATERIALS AND METHODS: Thirth-five surgical patients with skeletal Class III malocclusion were included: 19 (LLAC group) accepted LLAC surgery during presurgical orthodontic treatment, and 16 (non-surgery group, NS) accepted traditional presurgical orthodontic treatment. Cone-beam computed tomography (CBCT) scans were obtained before treatment (T0) and at the completion of presurgical orthodontic treatment (T1). The amount of vertical alveolar bone and contour area of the alveolar bone in the labial and lingual sides of mandibular incisors were measured. RESULTS: After presurgical orthodontic treatment, the contour area of the alveolar bone at each level on the lingual side and alveolar bone level on both sides decreased significantly in the NS group (P < 0.001). However, the labial and lingual bone contour area at each level and bone level increased significantly in the LLAC group (P < 0.001). The bone formation rate in the lingual apical region was the highest, significantly different from other sites (P < 0.001). CONCLUSIONS: During presurgical orthodontic treatment, LLAC can significantly increase the contour area of the labio-lingual alveolar bone in the mandibular anterior teeth to facilitate safe and effective orthodontic decompensation in skeletal Class III patients. CLINICAL RELEVANCE: This surgery has positive clinical significance in patients lacking bone thickness (< 0.5 mm) in the labial and lingual sides of the lower incisors.


Assuntos
Processo Alveolar , Tomografia Computadorizada de Feixe Cônico , Má Oclusão Classe III de Angle , Mandíbula , Humanos , Má Oclusão Classe III de Angle/cirurgia , Má Oclusão Classe III de Angle/diagnóstico por imagem , Masculino , Feminino , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/cirurgia , Adulto , Incisivo/diagnóstico por imagem , Resultado do Tratamento , Ortodontia Corretiva/métodos , Adolescente
4.
Anim Nutr ; 18: 340-355, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39290856

RESUMO

This study was aimed to investigate the effects of dietary calcitriol or quercetin supplementation on eggshell and bone quality of laying hens. In trial 1, 72 Hy-Line Brown layers (80-week-old) with weak-shelled strength (25 to 30 N) were assigned into 4 dietary treatments with 6 replicates of 3 birds and fed a basal diet (4% calcium level) or basal diets supplemented with 0.5% calcium, 5 µg/kg calcitriol or 500 mg/kg quercetin for 4 weeks. In trial 2, 360 Hy-Line Brown layers (60-week-old) were divided into 3 groups with 8 replicates of 15 birds: control group (basal diet), calcitriol group (basal diet + 5 µg/kg calcitriol), and quercetin group (basal diet + 500 mg/kg quercetin). This trial lasted for 12 weeks. The results showed that dietary calcitriol or quercetin improved eggshell quality in both trials (P < 0.05). In trial 2, compared with the control group, both calcitriol and quercetin supplementations improved femoral bone quality, calcium retention of hens and calcium content in uterine fluid at 18.5 h post-oviposition (PO) (P < 0.05), along with enhancing uterine morphology. Compared to the control group, supplemental calcitriol or quercetin up-regulated the relative mRNA expression levels of uterine transient receptor potential cation channel, subfamily V, member 6 (TRPV6) at 8.5 h PO and plasma membrane calcium-ATPase (PMCA), vitamin D receptor (VDR), estrogen receptor alpha (ERα) at 18.5 h PO (P < 0.05), but down-regulated the uterine caspase 3 (CASP3) relative mRNA expression level at 8.5 h PO (P < 0.05). Meanwhile, the femoral relative mRNA expression levels of tartrate-resistant acid phosphatase (TRAP) (up-regulated at 8.5 and 18.5 h PO) and alkaline phosphatase (ALP) (up-regulated at 8.5 h PO but down-regulated at 18.5 h PO) were also affected by calcitriol or quercetin supplementation (P < 0.05). Compared to the calcitriol, quercetin increased hen-day egg production and femoral medullary bone volume/bone tissue volume but reduced femoral stiffness (P < 0.05), which were accompanied by increased relative mRNA expression levels of uterine TRPV6, estrogen receptor beta (ERß) at 18.5 h PO (P < 0.05). Overall, both dietary calcitriol and quercetin could improve eggshell and bone quality by modulating calcium metabolism of aged layers. Compared to calcitriol, dietary quercetin up-regulated the expression of uterine calcium transporters, without affecting eggshell quality.

5.
Eur J Surg Oncol ; 50(11): 108692, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39298871

RESUMO

BACKGROUND: The comprehensive treatment strategy, mainly cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), combined with systemic and intraperitoneal chemotherapy, is the standard treatment for malignant peritoneal mesothelioma (MPM), which can significantly prolong the survival of patients. The aim of this study is to investigate the clinical significance of postoperative normothermic intraperitoneal chemotherapy (NIPEC) in MPM patients. METHODS: Data of 152 MPM patients who underwent CRS + HIPEC and postoperative intravenous chemotherapy were retrospectively analyzed. Patients were divided into the Non-NIPEC group and the NIPEC group according to whether they received NIPEC after surgery. The baseline characteristics of the two groups were compared, and the survival outcome was analyzed in subgroups according to completeness of cytoreduction (CC) score. Multivariate survival analysis was used to determine the independent prognostic factors. RESULTS: In CC 0-1 and CC 2-3 subgroups, there was no significant difference in baseline characteristics between Non-NIPEC and NIPEC groups. Survival analysis showed that for CC 0-1 patients, there was no significant difference in overall survival (OS) between Non-NIPEC and NIPEC groups (P = 0.503). However, for CC 2-3 patients, the median OS of the NIPEC group was significantly longer than that of the Non-NIPEC group (24.5 vs. 10.3 months, P = 0.005). Pathological type, preoperative thrombosis and postoperative NIPEC (HR = 0.423, 95%CI: 0.228-0.786, P = 0.006) were independent prognostic factors for CC 2-3 patients. CONCLUSIONS: For MPM patients receiving CRS + HIPEC, postoperative intraperitoneal combined with intravenous chemotherapy may improve the survival of CC 2-3 patients, but CC 0-1 patients do not seem to derive the same benefit.

6.
Curr Mol Med ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39279704

RESUMO

BACKGROUND: Osteosarcoma (OS) is a common malignancy among adolescents and children, characterized by a high propensity for metastasis and resistance to chemotherapy. AIMS: This study aimed to investigate the role of COL12A1, a gene often overexpressed in various cancers and associated with poor prognosis, in the progression of OS and explore the underlying mechanisms. METHODS: The expression pattern and potential function of COL12A1 in OS were evaluated using bioinformatics analyses, clinical sample examination, and OS cell lines. Various assays, including transwell, CCK-8, flow cytometry, and wound healing, were performed to assess the impact of COL12A1 on OS cell growth, cell cycle progression, apoptosis, invasion, and migration. Western blot analysis was conducted to investigate markers associated with the FAK/PI3K/AKT/mTOR pathway. RESULTS: COL12A1 expression was significantly elevated in OS tissues and cells. Upregulation of COL12A1 promoted cell growth, accelerated cell cycle progression, and enhanced migration and invasion while inhibiting apoptosis. Conversely, the knockdown of COL12A1 had the opposite effect. Additionally, COL12A1 overexpression increased the phosphorylation of components in the FAK/PI3K/AKT/mTOR pathway. The FAK inhibitor Y15 mitigated the effects of COL12A1 overexpression on cell apoptosis, invasion, proliferation, and the FAK/PI3K/AKT/mTOR pathway in OS. CONCLUSION: Our findings indicated that COL12A1 enhanced OS development by activating the FAK/PI3K/AKT/mTOR pathway, suggesting that COL12A1 could serve as a valuable biomarker for the prediction and identification of OS patients.

7.
Clin Chem ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39288005

RESUMO

BACKGROUND: Due to the diversity of the immune repertoire (IR), reconstructing full-length IR using traditional short-read sequencing has proven challenging. METHODS: A full-length IR sequencing (FLIRseq) work flow was developed with linear rolling circle amplification and nanopore sequencing. Its accuracy and quantification ability were verified by plasmid mixtures and commercial B-cell receptor/T-cell receptor sequencing (BCR/TCR-seq) based on short reads. IRs in tissues and the peripheral blood from 8 patients with acute lymphoblastic leukemia, 3 patients with allergic diseases, 4 patients with psoriasis, and 5 patients with prostate cancer were analyzed using FLIRseq. RESULTS: FLIRseq reads had lower mismatch rates and gap rates, and higher identify rates than nanopore reads (all P < 2.2 × -16). The relative quantification of components by FLIRseq was consistent with the actual quantification (P > 0.05). FLIRseq had superiority over BCR/TCR-seq, providing the long complementarity-determining region 3, B-cell isotype, and the rarely used V gene sequence. FLIRseq observed an increase in clonotype diversity (P < 0.05) and a decrease in the percentage of abnormal BCRs/TCRs in patients with leukemia in remission. For patients with allergic diseases or psoriasis, FLIRseq provided direct insights into V(D)J recombination and specific immunoglobulin classes. Compared with that in prostate cancer tissues, the full-length V segment of the biased T-cell receptor ß chain from lymphocytes in psoriatic tissues showed a more consistent AlphaFold2-predicted protein structure (P < 0.05). CONCLUSIONS: FLIRseq enables unbiased and comprehensive analyses of direct V(D)J recombination and immunoglobulin classes, thereby contributing to characterizing pathogenic mechanisms, monitoring minimal residual disease, and customizing adoptive cell therapy.

8.
Int J Mol Sci ; 25(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39273123

RESUMO

Notch signaling is a conserved pathway crucial for nervous system development. Disruptions in this pathway are linked to neurodevelopmental disorders, neurodegenerative diseases, and brain tumors. Hairy/E(spl) (HES) genes, major downstream targets of Notch, are commonly used as markers for Notch activation. However, these genes can be activated, inhibited, or function independently of Notch signaling, and their response to Notch disruption varies across tissues and developmental stages. MIB1/Mib1 is an E3 ubiquitin ligase that enables Notch receptor activation by processing ligands like Delta and Serrate. We investigated Notch signaling disruption using the zebrafish Mib1 mutant line, mib1ta52b, focusing on changes in the expression of Hairy/E(spl) (her) genes. Our findings reveal significant variability in her gene expression across different neural cell types, regions, and developmental stages following Notch disruption. This variability questions the reliability of Hairy/E(spl) genes as universal markers for Notch activation, as their response is highly context-dependent. This study highlights the complex and context-specific nature of Notch signaling regulation. It underscores the need for a nuanced approach when using Hairy/E(spl) genes as markers for Notch activity. Additionally, it provides new insights into Mib1's role in Notch signaling, contributing to a better understanding of its involvement in Notch signaling-related disorders.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Receptores Notch , Transdução de Sinais , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Receptores Notch/metabolismo , Receptores Notch/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neurogênese/genética
9.
Artigo em Inglês | MEDLINE | ID: mdl-39327069

RESUMO

In human life and production, excessive oily wastewaters containing detergents are produced and discharged, causing severe environmental pollution and water resource problems. A metal-organic framework (MOF)-based membrane is an economical and environmentally friendly tool for emulsion separation but is limited by a complex preparation process and poor flexibility. Herein, we developed a simple method to synthesize a MOF-based mixed-matrix membrane (MMM) by spray and fabricated the membrane on poly(vinylidene fluoride) (PVDF) fibers via postdeposition and in situ growth manners. The prepared ZIF-8/PVA MMMs have uniform distribution of ZIF-8 particles and poly(vinyl alcohol) (PVA) on the PVDF fibers. PVA improved the adhesion between the ZIF-8 particles and between the MOF layer and PVDF fiber, endowing the separation membrane with high flexibility and bendability. The prepared ZIF-8/PVA membrane exhibited hydrophilicity and underwater superoleophobicity, which showed high separation efficiency and considerable water flux for emulsions, emulsion containing dye, and surfactant-stabilized emulsion. In addition, the fabricated ZIF-8/PVA/PVDF fibers exhibited good antifouling property and flexibility and can maintain stable separation efficiency after working several times and even under bending, demonstrating the stability and potentiality of the ZIF-8/PVA/PVDF fibers in practical applications. This work paves a new avenue for the synthesis and application of MOF-based MMMs.

10.
Int J Biol Macromol ; 280(Pt 3): 135972, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39322139

RESUMO

Lung cancer remains a major driver of global morbidity and mortality, and diagnosing lung tumors early in their development is vital to maximizing treatment efficacy and patient survival. Several biomarkers, including CYFRA 21-1, NSE, ProGRP, CEA, and miRNA, have been identified as reliable indicators for early lung cancer detection and monitoring treatment progress. However, the minute changes in the levels of these biomarkers during the early stages of disease necessitate advanced detection platforms. In this space, electrochemical biosensors have currently emerged as robust tools for early lung cancer screening and diagnosis owing to their low costs, rapid responses, and superior sensitivity and selectivity. This review provides an up-to-date overview of the application of electrochemiluminescence, photoelectrochemical, and other electrochemical analytical strategies for detecting lung cancer-associated protein biomarkers, and miRNA. This review compares these techniques to provide a concise overview of the principles underlying these electrochemical analytical methods, the preparation of their components, and the performance of the resulting biosensors. Lastly, a discussion of the challenges and opportunities associated with electrochemical biosensors detection of lung cancer-associated biomarkers are provided.

14.
Front Endocrinol (Lausanne) ; 15: 1217250, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104815

RESUMO

Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass. Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS). Results: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor. Conclusion: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.


Assuntos
Carcinoma Neuroendócrino , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/diagnóstico , Idoso , Adulto , Estudos Retrospectivos , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Taxa de Sobrevida
15.
Materials (Basel) ; 17(16)2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39203342

RESUMO

The processes of hemp bast fiber retting, forming, and drying offer the opportunity for value-added products such as natural fiber-reinforced composites. A new process for the retting of raw bast fibers through enzyme-triggered self-cultured bacterial retting was developed in the lab-scale setup. This study focused on comparing the energy consumption and environmental impacts of this bacterial retting process with the thermochemical retting process currently widely used to obtain lignocellulosic fibers for composites. The gate-to-gate life cycle assessment (LCA) models of the two retting processes were constructed to run a comparison analysis using the TRACI (the tool for the reduction and assessment of chemical and other environmental impacts) method for environmental impacts and the cumulative energy demand (CED) method for energy consumptions. This work has demonstrated the advantages of the bacterial retting method from an environmental standpoint. The result of our research shows about a 24% gate-to-gate reduction in CED for bacterial retting and 20-25% lower environmental impacts relating to global warming, smog formation, acidification, carcinogenics, non-carcinogenics, respiratory effects, ecotoxicity, and fossil fuel depletion when compared to that of thermochemical retting.

16.
J Hepatocell Carcinoma ; 11: 1607-1622, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206422

RESUMO

Purpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib and tislelizumab (TACE-Len-T) versus TACE plus lenvatinib (TACE-Len) as the first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC). Patients and Methods: This retrospective study included 136 uHCC patients treated with TACE-Len-T or TACE-Len from January 1, 2021, to June 30, 2023. Clinical outcomes including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs) were compared between the two groups. The risk factors affecting OS and PFS were also analyzed. Results: The median OS and PFS of the TACE-Len-T group were significantly longer than those of the TACE-Len group (Median OS: not reached vs 13.8 months, P<0.001; Median PFS: 13.0 months vs 2.7 months, P<0.001). The best overall objective response rate (ORR) was also better with TACE-Len-T treatment (ORR: 72.1% vs 29.4%, P<0.001), and the disease control rate (DCR) significantly increased in the TACE-Len-T group (88.2% vs 48.5%, P<0.001). Multivariate analyses revealed that TACE-Len treatment, tumor number >3, and cTACE were independent risk factors for OS, whereas TACE-Len treatment was the only independent risk factor for PFS. The frequency and severity of AEs in the TACE-Len-T group were comparable to those in the TACE-Len group (any grade: 92.6% vs 91.2%, P=0.753; grade 3 or 4: 33.8% vs 32.3%, P=0.855). Conclusion: TACE-Len-T treatment significantly improved OS, PFS, ORR, and DCR over TACE-Len treatment, with a manageable safety profile in uHCC.

17.
J Laparoendosc Adv Surg Tech A ; 34(8): 682-690, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39110618

RESUMO

Background: Celiac axis stenosis can potentially lead to insufficient blood supply to vital organs, such as the liver, spleen, pancreas, and stomach. This condition result in the development of collateral circulation between the superior mesenteric artery and the hepatic artery. However, these collateral circulations are often disrupted during pancreaticoduodenectomy (PD), which may increase the risk of postoperative complications. Methods: A retrospective analysis was conducted on patients who underwent laparoscopic pancreaticoduodenectomy (LPD) from April 2015 to April 2023. Celiac trunk stenosis is classified according to the degree of stenosis: no stenosis (<30%), grade A (30%-<50%), grade B (50%-≤80%), and grade C (>80%). The incidence of postoperative complications was evaluated, and both univariate and multivariate risk analyses were conducted. Results: A total of 997 patients were included in the study, with mild celiac axis stenosis present in 23 (2.3%) patients, moderate stenosis in 18 (1.8%) patients, and severe stenosis in 10 (1.0%) patients. Independent risk factors for the development of bile leakage, as identified by both univariate and multivariate analyses, included body mass index (BMI) (HR = 1.108, 95% CI = 1.008-1.218, P = .033), intra-abdominal infection (HR = 2.607, 95% CI = 1.308-5.196, P = .006), postoperative hemorrhage (HR = 4.510, 95% CI = 2.048-9.930, P = <0.001), and celiac axis stenosis (50%-≤80%, HR = 4.235, 95% CI = 1.153-15.558, P = .030), and (>80%, HR = 4.728, 95% CI = .882-25.341, P = .047). Celiac axis stenosis, however, was not determined to be an independent risk factor for pancreatic fistula (P > 0.05). Additionally, the presence of an aberrant hepatic artery did not significantly increase the risk of postoperative complications when compared with celiac axis stenosis alone. Conclusion: Severe celiac axis stenosis is an independent risk factor for postoperative bile leakage following LPD.


Assuntos
Artéria Celíaca , Laparoscopia , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Humanos , Estudos Retrospectivos , Pancreaticoduodenectomia/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Laparoscopia/efeitos adversos , Idoso , Constrição Patológica/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Bile
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1097-1105, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39192404

RESUMO

OBJECTIVE: To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma (SI-DLBCL), in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology. METHODS: The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted, the clinical and pathological features, diagnosis, treatment and prognosis were analyzed. Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors. RESULTS: Among the 138 patients with SI-DLBCL included in this study, 85 (61.59%) were male, 53 (38.41%) were female, the median age of onset was 59.5 (16-84) years, the clinical manifestations lacked specificity, the first-line treatment regimen was mainly chemotherapy (67.39%), 94 cases (68.12%) received chemotherapy alone, 40 cases (28.98%) were treated with chemotherapy combined with surgery, and 4 cases (2.90%) were treated with surgery alone. The median follow-up time was 72 (1-148) months. Among the 138 patients with SI-DLBCL, 79 (57.25%) survived, 34 (24.64%) died, 25 cases (18.12%) lost to follow-up, the PFS rates of 1-year, 3-year and 5-year were 57.97%, 49.28% and 32.61%, and the OS rates of 1-year, 3-year and 5-year were 60.14%, 54.35% and 34.06%, respectively. The results of univariate Cox regression analysis showed that age, Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients, and age, Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients. The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients. CONCLUSION: Patients with SI-DLBCL are more common in middle-aged and elderly men, and the early clinical manifestations lack specificity, and the first-line treatment regimen is mainly R-CHOP chemotherapy, and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Idoso de 80 Anos ou mais , Adolescente , Adulto , Neoplasias Intestinais/terapia , Neoplasias Intestinais/diagnóstico , Fatores de Risco , Adulto Jovem , Modelos de Riscos Proporcionais
19.
J Surg Oncol ; 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39183488

RESUMO

BACKGROUND: To explore the most effective adjuvant chemotherapy regimen for malignant peritoneal mesothelioma (MPM) through patient derived tumor-like cell clusters (PTC) drug sensitivity test. METHODS: PTC were cultured in vitro with intraoperative specimens, and drug sensitivity test was performed to calculate the most effective chemotherapy regimen for MPM. The patients were divided into conventional and individualized chemotherapy group according to whether they received PTC drug testing. Univariate and multivariate analyses were conducted to identify independent prognostic factors. RESULTS: Among 186 MPM patients included, 63 underwent PTC culture and drug sensitivity test. The results showed that the most effective chemotherapy regimen was oxaliplatin + gemcitabine. After propensity score matching, a total of 64 patients were enrolled in the following study, including 32 patients receiving individualized chemotherapy guided by PTC drug results as group 1 and 32 patients receiving conventional chemotherapy as group 2. Survival analysis showed that the median OS of group 1 was not reached, significantly longer than that of group 2 (23.5 months) (p < 0.05). CONCLUSIONS: Compared with conventional chemotherapy, individualized chemotherapy guided by PTC drug sensitivity tests can prolong patient survival, and oxaliplatin + gemcitabine + apatinib could be the optimal adjuvant treatment regimen for MPM.

20.
Medicine (Baltimore) ; 103(29): e38985, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39029009

RESUMO

RATIONALE: Patients with relapsed and refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with the T315I mutation are at higher risk of relapse and have shorter overall survival. PATIENT CONCERNS: A 31-year-old man presented to the hematology department with intermittent fever and pancytopenia. He was diagnosed with Ph+ acute lymphoblastic leukemia and experienced 2 relapses during treatment. A drug-resistant T315I mutation was detected in the ABL kinase region during review. DIAGNOSES: Morphological examination of the bone marrow revealed approximately 93.5% lymphoid blast. Flow cytometric analysis confirmed the diagnosis of common B-cell ALL with the following phenotype: CD34, CD45dim, CD19, CD10, cCD79a, CD58dim, CD81dim, cTdT, HLA-DR, CD22dim, CXCR4, CD33dim, CD20, CD25, CD13, CD123. The examination of the ABL kinase region mutation suggested a T315I mutation. INTERVENTIONS: Olverembatinib, a third-generation TKI drug, was administered in combination with inotuzumab ozogamicin to treat the disease. OUTCOMES: The patient achieved morphological remission with a negative flow cytometry MRD test, and the quantification of BCR-ABL transcripts was 0% after 1 cycle of therapy. LESSONS: The third-generation TKI olverembatinib has been proven to be effective in CML patients with the T315I mutation, and it may also be effective in Ph+ acute lymphoblastic leukemia. Some new immune drugs have also shown improvement in the remission rate. Combination therapy with olverembatinib and Ino can achieve a complete molecular response in patients with relapsed and refractory Ph+ ALL with the T315I mutation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Inotuzumab Ozogamicina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Masculino , Adulto , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromossomo Filadélfia , Mutação
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