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1.
Ann Vasc Surg ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964442

RESUMO

BACKGROUND: Although the popliteal vein approach is commonly used for catheter-directed thrombolysis (CDT) treatment in patients with acute lower extremity deep vein thrombosis (DVT), CDT via a new access route, the posterior tibial vein, is also used and has demonstrated good results. However, this tibial approach has not been tested in large samples. OBJECTIVE: To compare the early efficacy of CDT using the tibial and popliteal vein approaches for the treatment of acute mixed lower extremity DVT. METHODS: In this retrospective cohort study, 87 patients with acute mixed lower extremity DVT treated at the Department of Interventional Medicine of Zhuhai People's Hospital were enrolled; those with tibial vein access and popliteal vein access were included in the observation (n = 55) and control (n = 32) groups, respectively. The safety and efficacy of CDT via tibial vein access were investigated by collecting and comparing indicators such as venous patency, thrombus removal effect, thigh and calf circumference difference, swelling reduction rate of the affected limb, surgical complications, and post-discharge complication rate of the patients in the two groups. RESULTS: The postoperative thrombus clearance effect of the observation group was significantly better than that of the control group (P < 0.05), and the postoperative venous patency rate of the observation group was 83.2 ± 15.7%, which was higher than that of the control group (62.2 ± 38.2%) (P = 0.005). The swelling reduction rate of the lower extremity was 74.0 ± 33.8% in the observation group and 51.4 ± 30.0% in the control group, with a statistically significant difference (P = 0.002). However, there was no statistically significant difference (P > 0.05) in the rates of thigh swelling reduction, bleeding-related complications, or postoperative complications between the two groups of patients. CONCLUSIONS: CDT via the tibial vein approach is safe, effective, and may be a better approach for CDT access, offering superior thrombus clearance, venous patency, and lower extremity swelling reduction postoperatively.

2.
J Transl Med ; 22(1): 706, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080676

RESUMO

BACKGROUND: Drug resistance, including Adriamycin-based therapeutic resistance, remains a challenge in breast cancer (BC) treatment. Studies have revealed that macrophages could play a pivotal role in mediating the chemoresistance of cancer cells. Accumulating evidence suggests that tRNA-Derived small RNAs (tDRs) are associated the physiological and pathological processes in multiple cancers. However, the underlying mechanisms of tDRs on chemoresistance of BC in tumor-associated macrophages remain largely unknown. METHODS: The high-throughput sequencing technique was used to screen tDRs expression profile in BC cells. Gain- and loss-of-function experiments and xenograft models were performed to verify the biological function of 3'tRF-Ala-AGC in BC cells. The CIBERSORT algorithm was used to investigate immune cell infiltration in BC tissues. To explore the role of 3'tRF-Ala-AGC in macrophages, M2 macrophages transfected with 3'tRF-Ala-AGC mimic or inhibitor were co-cultured with BC cells. Effects on Nuclear factor-κb (NF-κb) pathway were investigated by NF-κb nuclear translocation assay and western blot analysis. RNA pull-down assay was performed to identify 3'tRF-Ala-AGC interacting proteins. RESULTS: A 3'tRF fragment of 3'tRF-AlaAGC was screened, which is significantly overexpressed in BC specimens and Adriamycin-resistant cells. 3'tRF-AlaAGC could promote cell malignant activity and facilitate M2 polarization of macrophages in vitro and in vivo. Higher expression of M2 macrophages were more likely to have lymph node metastasis and deeper invasion in BC patients. Mechanistically, 3'tRF-AlaAGC binds Type 1-associated death domain protein (TRADD) in BC cells, and suppression of TRADD partially abolished the enhanced effect of 3'tRF-AlaAGC mimic on phenotype of M2. The NF-κb signaling pathway was activated in BC cells co-cultured with M2 macrophages transfected with 3'tRF-AlaAGC mimic. CONCLUSIONS: 3'tRF-AlaAGC might modulate macrophage polarization via binding to TRADD and increase the effect of M2 on promoting the chemoresistance in BC cells through NF-κb signaling pathway.


Assuntos
Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Macrófagos , NF-kappa B , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Macrófagos/metabolismo , Animais , Linhagem Celular Tumoral , NF-kappa B/metabolismo , Ligação Proteica/efeitos dos fármacos , RNA de Transferência/metabolismo , RNA de Transferência/genética , Polaridade Celular/efeitos dos fármacos , Camundongos , Transdução de Sinais , Camundongos Nus , Doxorrubicina/farmacologia , Camundongos Endogâmicos BALB C
3.
Orthop Surg ; 16(6): 1344-1355, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38664223

RESUMO

OBJECTIVES: Multi-planar external fixation has been used for the management of segmental tibial fractures with severe soft tissue injuries. However, fewer specialized studies have been reported. The primary aim of this study was to describe our experience of treating fractures of this type using the Taylor Spatial Frame and Ilizarov external fixation methods. METHODS: We retrospectively analyzed 33 patients with segmental tibial fracture treated at our institution between January 2016 and December 2020. The patients were divided into double Taylor Spatial Frame (D-TSF) and Ilizarov groups based on the external fixation structure. Baseline demographic data included sex, age, injury side and cause, open or closed fracture, time from injury to surgery, complications, and external frame removal and fracture healing time. The hip-knee-ankle angle (HKA) was measured from preoperative, immediate postoperative, and final follow-up full-length X-rays of bilateral lower limbs. We determined the degree of deviation in the HKA by calculating the difference between the measured angle and the ideal value of 180°; the absolute value was used to assess recovery of the lower limb force line. At the final follow-up, Johner-Wruhs tibial fracture outcome criteria (J-W TFOC) were used to classify the postoperative function of the affected limb as excellent, good, moderate, or poor. Count data were analyzed with the chi-square test or Fisher's exact test; the Mann-Whitney U test was used for rank data. RESULTS: No statistically significant differences were observed between the two groups in terms of sex, age, side of injury, cause of injury, closed or open fracture, or time between injury and surgery, which indicates that the groups were comparable (p > 0.05). A statistically significant difference was observed in external frame removal and fracture healing time between the D-TSF and Ilizarov groups (36.24 ± 8.34 vs 45.42 ± 10.21 weeks, p = 0.009; 33.33 ± 8.21 vs 42.00 ± 9.78 weeks, p = 0.011). The Johner-Wruhs criteria were used to assess the function of the affected limb, the D-TSF group performed better in correcting the lower limb force line than the Ilizarov group. A statistically significant difference in terms of excellent ratings was observed between the two groups (18/2/1/0 vs 5/5/1/1, p = 0.010). Postoperative follow-up X-rays demonstrated a significant improvement in the HKA in both groups immediately after surgery and at the final follow-up compared to the angle before surgery. At the final follow-up, a statistically significant difference was observed in the degree of deviation in the HKA between the two groups (1.58° ± 0.84° vs 2.37° ± 1.00°, p = 0.023). CONCLUSION: The D-TSF treatment is associated with minimal secondary damage to soft tissue, a straightforward and minimally invasive procedure, multiplanar stable fracture fixation, and optimization of fracture alignment and lower limb force lines, therefore, it is highly effective therapeutic option for segmental tibial fracture.


Assuntos
Fixadores Externos , Fraturas da Tíbia , Humanos , Fraturas da Tíbia/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Fixação de Fratura/métodos , Adulto Jovem , Técnica de Ilizarov/instrumentação , Idoso , Adolescente
4.
BMC Cancer ; 24(1): 393, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549044

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. METHODS: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. RESULTS: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). CONCLUSIONS: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Derrame Pleural Maligno , Humanos , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Derrame Pleural Maligno/tratamento farmacológico , Derrame Pleural Maligno/patologia , Estudos Retrospectivos , Feminino
5.
Adv Sci (Weinh) ; 11(24): e2305116, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38477559

RESUMO

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints and bone destruction. Because of systemic administration and poor targeting, traditional anti-rheumatic drugs have unsatisfactory treatment efficacy and strong side effects, including myelosuppression, liver or kidney function damage, and malignant tumors. Consequently, mesenchymal stem cells (MSCs)-involved therapy is proposed for RA therapy as a benefit of their immunosuppressive and tissue-repairing effects. This review summarizes the progress of MSCs-involved RA therapy through suppressing inflammation and promoting tissue regeneration and predicts their potential clinical application.


Assuntos
Artrite Reumatoide , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Artrite Reumatoide/terapia , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Animais
6.
Ann Vasc Surg ; 98: 301-308, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37423329

RESUMO

BACKGROUND: This study aimed to retrospectively compare the clinical outcomes of endovenous microwave versus radiofrequency ablation combined with foam sclerotherapy in patients with lower limb varicose veins. METHODS: We identified patients with lower limb varicose veins treated with endovenous microwave ablation or radiofrequency ablation with foam sclerotherapy between January 2018 and June 2021 at our institution. Patients were followed-up for 12 months. Clinical results, including the pre-post-Aberdeen Varicose Vein Questionnaire and post-Aberdeen Varicose Vein Questionnaire and Venous Clinical Severity Score, were compared. Complications were documented and treated accordingly. RESULTS: We included 287 cases (295 limbs total; endovenous microwave ablation + foam sclerosing agent: n = 142, 146 limbs; radiofrequency ablation + foam sclerosing agent: n = 145, 149 limbs). The operative time was shorter for endovenous microwave ablation than radiofrequency ablation (42.58 ± 15.62 min vs. 65.46 ± 24.38 min, P < 0.05); however, other procedural parameters did not differ. Furthermore, hospitalization costs for endovenous microwave ablation were lower than those for radiofrequency ablation (21,063.74 ± 850.47 yuan vs. 23,312.40 ± 1,035.86 yuan, P < 0.05). At the 12-month follow-up, the great saphenous vein closure rate was similar in both groups (endovenous microwave ablation, 97% [142/146] vs. radiofrequency ablation, 98% [146/149]; P > 0.05). Additionally, the satisfaction or incidence rates of complications were not different among the groups. In both groups, the Aberdeen Varicose Vein Questionnaire and Venous Clinical Severity Score values were significantly lower 12 months postsurgery than before surgery; however, the postoperative values did not differ. CONCLUSIONS: Endovenous microwave ablation effectively treated lower limb varicose veins, with similar short-term effects as radiofrequency ablation. Moreover, it had a shorter operative time and was less expensive than endovenous radiofrequency ablation.


Assuntos
Ablação por Cateter , Terapia a Laser , Ablação por Radiofrequência , Varizes , Insuficiência Venosa , Humanos , Soluções Esclerosantes , Micro-Ondas/efeitos adversos , Terapia a Laser/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Varizes/diagnóstico por imagem , Varizes/cirurgia , Escleroterapia/efeitos adversos , Escleroterapia/métodos , Ablação por Radiofrequência/efeitos adversos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Veia Safena/diagnóstico por imagem , Veia Safena/cirurgia , Extremidade Inferior/cirurgia , Insuficiência Venosa/cirurgia
7.
Arch Med Sci ; 19(6): 1842-1849, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38058725

RESUMO

Introduction: Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have anti-tumor activity in vitro and in vivo. HMG-CoA reductase inhibitors, called statins, are used to reduce the risk of heart disease by lowering blood cholesterol levels. Material and methods: HMG-CoA reductase activity was determined according to the method described by Takahashi et al. The structure of human HMG-COA reductase in the resolution of 2.22 Å with the X-ray diffraction method (PDB ID: 1HWK) was obtained from the PDB database. Results: In our study, the inhibitory activity of isoliquiritigenin towards HMG-CoA reductase showed a lower value of IC50 = 193.77 ±14.85 µg/ml. For a better understanding of biological activities and interactions, the molecular docking study was performed. The results of molecular docking revealed that isoliquiritigenin with a docking score of -6.740 has a strong binding affinity to HMG-COA reductase. Therefore, this compound could be considered as a potential inhibitor for the enzyme. Also, the activity of isoliquiritigenin against common human pancreatic acinar cell tumor cell lines, i.e. 266-6, TGP49, and TGP47, was evaluated. Conclusions: The cells treated with isoliquiritigenin were assessed by MTT assay for 48 h as regards the cytotoxicity and anti-human pancreatic acinar cell tumor properties in normal (HUVEC) and human pancreatic acinar cell tumor cell lines, i.e. 266-6, TGP49, and TGP47. The IC50 values of isoliquiritigenin were 262, 389, and 211 µg/ml against 266-6, TGP49, and TGP47 cell lines, respectively. The viability of the human pancreatic acinar cell tumor cell line decreased dose-dependently in the presence of isoliquiritigenin. After clinical study, isoliquiritigenin can be utilized as an efficient drug in the treatment of human pancreatic acinar cell tumor in humans.

8.
Redox Rep ; 28(1): 2279813, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38010093

RESUMO

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with severity of pneumonia; however, the mechanism by which OSA promotes lung cancer progression is unclear. METHODS: Twenty-five lung cancer patients were recruited to investigate the relationship between OSA and cancer-associated fibroblast (CAFs) activation. Lung cancer cells (A549) and WI38 fibroblast cells were used to explore the hypoxia-induced TGFß expression using qPCR, Western blot, and ELISA. Wound healing and transwell assays were performed to evaluate cancer cell migration and invasion. A549 or A549-Luc + WI38 xenograft mouse models were established to detect the intermittent hypoxia (IH) associated with lung tumor growth and epithelial-mesenchymal transition (EMT) in vivo. RESULTS: OSA promotes CAF activation and enrichment in lung cancer patients. Hypoxia (OSA-like treatment) activated TGFß signaling in both lung cancer cells and fibroblasts, which promoted cancer cell migration and invasion, and enriched CAFs. IH promoted the progression and EMT process of lung cancer xenograft tumor. Co-inoculation of lung cancer cells and fibroblast cells could further promote lung cancer progression. CONCLUSIONS: IH promotes lung cancer progression by upregulating TGFß signaling, promoting lung cancer cell migration, and increasing the CAF activation and proportion of lung tumors.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Pulmonares , Apneia Obstrutiva do Sono , Humanos , Animais , Camundongos , Neoplasias Pulmonares/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Fator de Crescimento Transformador beta/metabolismo , Invasividade Neoplásica/patologia , Hipóxia , Linhagem Celular Tumoral
9.
Vasa ; 52(6): 355-365, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37779391

RESUMO

Insufficiency of the small saphenous vein causes 15% of varicose veins in the lower extremities. Endovenous ablation for the treatment of small saphenous vein varices has become a trend, and an increasing number of studies have reported the effects of different types of endovenous ablation in patients with small saphenous varicose veins. The purpose of this systematic review is to summarize the results of existing studies on endovenous ablation for the treatment of small saphenous varicose veins, compare its role and efficacy, and provide insights into the future development of endovenous ablation for treating small saphenous varicose veins. A systematic review of literature published from January 1, 2002 to January 1, 2022 was conducted from PubMed, Embase, and China Academic Journals full-text databases. The pre-determined inclusion criteria were clinical literature of endovenous ablation for treating small saphenous varicose veins. Keywords included "ablation", "small saphenous vein", "lesser saphenous vein", "short saphenous vein", "xiaoyinjingmai" and "xiaorong". Of the 506 articles screened, 33 articles were included in this review: 19 articles were related to endovenous laser ablation, five were related to mechanochemical ablation, seven were related to radiofrequency ablation, and two were related to both endovenous laser ablation and radiofrequency ablation. The anatomical success rate of endovenous laser ablation, radiofrequency ablation, and mechanochemical ablation were 94.3%, 96.0%, and 88.1%, respectively, and the heterogeneities were all moderate. Most of the current studies are of a low-quality level of research. Hence, long-term follow-up studies and large-scale randomized controlled trials are required to obtain high-quality evidence. Although the gold standard for the treatment of small saphenous vein insufficiency remains unclear, endovenous ablation is still the recommended method.


Assuntos
Terapia a Laser , Varizes , Insuficiência Venosa , Humanos , Veia Safena/diagnóstico por imagem , Veia Safena/cirurgia , Varizes/diagnóstico por imagem , Varizes/cirurgia , Escleroterapia/efeitos adversos , Escleroterapia/métodos , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , China , Resultado do Tratamento , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/cirurgia
10.
Adv Healthc Mater ; 12(28): e2301413, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37657182

RESUMO

The development of smart theranostic nanoplatforms has gained great interest in effective cancer treatment against the complex tumor microenvironment (TME), including weak acidity, hypoxia, and glutathione (GSH) overexpression. Herein, a TME-responsive nanoplatform named PMICApt /ICG, based on PB:Mn&Ir@CaCO3 Aptamer /ICG, is designed for the competent synergistic photothermal therapy and photodynamic therapy (PDT) under the guidance of photothermal and magnetic resonance imaging. The nanoplatform's aptamer modification targeting the transferrin receptor and the epithelial cell adhesion molecule on breast cancer cells, and the acid degradable CaCO3 shell allow for effective tumor accumulation and TME-responsive payload release in situ. The nanoplatform also exhibits excellent PDT properties due to its ability to generate O2 and consume antioxidant GSH in tumors. Additionally, the synergistic therapy is achieved by a single wavelength of near-infrared laser. RNA sequencing is performed to identify differentially expressed genes, which show that the expressions of proliferation and migration-associated genes are inhibited, while the apoptosis and immune response gene expressions are upregulated after the synergistic treatments. This multifunctional nanoplatform that responds to the TME to realize the on-demand payload release and enhance PDT induced by TME modulation holds great promise for clinical applications in tumor therapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Verde de Indocianina/farmacologia , Verde de Indocianina/uso terapêutico , Fotoquimioterapia/métodos , Microambiente Tumoral , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Glutationa/farmacologia , Linhagem Celular Tumoral
12.
Gastric Cancer ; 26(6): 904-917, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37572185

RESUMO

BACKGROUND: Peroxisome proliferator-activated receptor delta (PPARδ) promotes inflammation and carcinogenesis in many organs, but the underlying mechanisms remains elusive. In stomachs, PPARδ significantly increases chemokine Ccl20 expression in gastric epithelial cells while inducing gastric adenocarcinoma (GAC). CCR6 is the sole receptor of CCL20. Here, we examine the role of PPARδ-mediated Ccl20/Ccr6 signaling in GAC carcinogenesis and investigate the underlying mechanisms. METHODS: The effects of PPARδ inhibition by its specific antagonist GSK3787 on GAC were examined in the mice with villin-promoter-driven PPARδ overexpression (PpardTG). RNAscope Duplex Assays were used to measure Ccl20 and Ccr6 levels in stomachs and spleens. Subsets of stomach-infiltrating immune cells were measured via flow cytometry or immunostaining in PpardTG mice fed GSK3787 or control diet. A panel of 13 optimized proinflammatory chemokines in mouse sera were quantified by an enzyme-linked immunosorbent assay. RESULTS: GSK3787 significantly suppressed GAC carcinogenesis in PpardTG mice. PPARδ increased Ccl20 level to chemoattract Ccr6+ immunosuppressive cells, including tumor-associated macrophages, myeloid-derived suppressor cells and T regulatory cells, but decreased CD8+ T cells in gastric tissues. GSK3787 suppressed PPARδ-induced gastric immunosuppression by inhibiting Ccl20/Ccr6 axis. Furthermore, Ccl20 protein levels increased in sera of PpardTG mice starting at the age preceding gastric tumor development and further increased with GAC progression as the mice aged. GSK3787 decreased the PPARδ-upregulated Ccl20 levels in sera of the mice. CONCLUSIONS: PPARδ dysregulation of Ccl20/Ccr6 axis promotes GAC carcinogenesis by remodeling gastric tumor microenvironment. CCL20 might be a potential biomarker for the early detection and progression of GAC.


Assuntos
Adenocarcinoma , PPAR delta , Neoplasias Gástricas , Humanos , Animais , Camundongos , Quimiocina CCL20/genética , Quimiocina CCL20/metabolismo , PPAR delta/genética , Linfócitos T CD8-Positivos , Microambiente Tumoral , Carcinogênese , Receptores CCR6/genética , Receptores CCR6/metabolismo
13.
Int Immunopharmacol ; 122: 110652, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37478668

RESUMO

Accumulating evidence has shown an increased tumor incidence and reduced survival rate in cancer patients with obstructive sleep apnea (OSA). Although intermittent hypoxia is known to play a crucial role, the molecular mechanism by which intermittent hypoxia accelerates lung cancer progression remains to be elucidated.A lung cancer xenograft mouse model was established by subcutaneously injecting LLC cells into C57BL/6 mice. The tumor-bearing mice were exposed to either normoxia or intermittent hypoxia and received either IgG2a, anti-programmed death ligand-1 (PD-L1), PX-478, or anti-PD-L1 + PX-478 treatment.A significant upregulation of tumor associated macrophages (TAMs) papulation and PD-L1 levels was observed in lung adenocarcinoma patients with OSA. We further confirmed that hypoxia-inducible factor-1 alpha (HIF-1α) regulates PD-L1 at transcriptional levels, mainly through binding to the hypoxia response element 4. Using a lung cancer xenograft mouse model, we observed that intermittent hypoxia exposed tumors grew faster and bigger with upregulated HIF-1α and PD-L1 expression, enhanced TAMs and Treg populations, and reduced cytotoxic T cells and cytokine secretion. Finally, we found a combination of PX-478 and anti-PD-L1 exerted an encouraging tumor inhibition effect compared to single treatment. Combination therapies based on HIF-1α and PD-L1 blockade might serve as a promising strategy to treat lung cancer patients with OSA.


Assuntos
Neoplasias Pulmonares , Apneia Obstrutiva do Sono , Humanos , Animais , Camundongos , Macrófagos Associados a Tumor/metabolismo , Camundongos Endogâmicos C57BL , Neoplasias Pulmonares/patologia , Antígeno B7-H1/metabolismo , Hipóxia/metabolismo , Imunidade
14.
Oncol Lett ; 26(2): 325, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37415626

RESUMO

Lung adenocarcinoma (LUAD) represents the most prevalent subtype of lung cancer and typically has high incidence and fatality rates. Motor neuron and pancreas homeobox 1 (MNX1) and coiled-coil domain-containing 34 (CCDC34) serve as oncogenes in multiple types of cancer. However, their role in LUAD remains to be elucidated. In the present study, bioinformatics analysis and LUAD cell lines were adopted to examine the expression of MNX1 and CCDC34. The proliferation, migration and invasion abilities of A549 cells were determined using Cell Counting Kit-8, colony formation, wound-healing and Transwell assay, and flow cytometry was conducted to assess cell cycle distribution and apoptosis. The interaction between MNX1 and CCDC34 was verified by luciferase reporter and chromatin immunoprecipitation assays. In addition, an in vivo animal model of LUAD was established for validation. The results demonstrated that both MNX1 and CCDC34 were upregulated in LUAD cell lines. MNX1 knockdown significantly suppressed cell proliferation, migration and invasion, hindered cell cycle progression and promoted cell apoptosis in vitro and inhibited tumor growth in vivo. However, the antitumor effect of MNX1 knockdown was weakened by simultaneous CCDC34 overexpression in vitro. In terms of mechanism, MNX1 was demonstrated to directly bind to the CCDC34 promoter and transcriptionally activate CCDC34 expression. In conclusion, the present study highlighted a critical role of the MNX1/CCDC34 axis in regulating LUAD progression, providing novel therapeutic targets for LUAD treatment.

15.
Pathol Oncol Res ; 29: 1610897, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37334172

RESUMO

Objective: This study aimed to develop a novel scoring system, named the integrated oxidative stress score (IOSS), based on oxidative stress indices to predict the prognosis in stage III gastric cancer. Methods: Retrospective analysis of stage III gastric cancer patients who were operated on between January 2014 and December 2016 were enrolled into this research. IOSS is a comprehensive index based on an achievable oxidative stress index, comprising albumin, blood urea nitrogen, and direct bilirubin. The patients were divided according to receiver operating characteristic curve into two groups of low IOSS (IOSS ≤ 2.00) and high IOSS (IOSS > 2.00). The grouping variable was performed by Chi-square test or Fisher's precision probability test. The continuous variables were evaluated by t-test. The disease free survival (DFS) and overall survival (OS) were performed by Kaplan-Meier and Log-Rank tests. Univariate Cox proportional hazards regression models and stepwise multivariate Cox proportional hazards regression analysis were determined to appraise the potential prognostic factors for DFS and OS. A nomogram of the potential prognostic factors by the multivariate analysis for DFS and OS was established with R software. In order to assess the accuracy of the nomogram in forecasting prognosis, the calibration curve and decision curve analysis were produced, contrasting the observed outcomes with the predicted outcomes. Results: The IOSS was significantly correlated with the DFS and OS, and was a potential prognostic factor in patients with stage III gastric cancer. Patients with low IOSS had longer survival (DFS: χ2 = 6.632, p = 0.010; OS: χ2 = 6.519, p = 0.011), and higher survival rates. According to the univariate and multivariate analyses, the IOSS was a potential prognostic factor. The nomograms were conducted on the potential prognostic factors to improve the correctness of survival prediction and evaluate the prognosis in stage III gastric cancer patients. The calibration curve indicated a good agreement in 1-, 3-, 5-year lifetime rates. The decision curve analysis indicated that the nomogram's predictive clinical utility for clinical decision was better than IOSS. Conclusion: IOSS is a nonspecific tumor predictor based on available oxidative stress index, and low IOSS is found to be a vigorous factor of better prognosis in stage III gastric cancer.


Assuntos
Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Prognóstico , Nomogramas , Intervalo Livre de Doença
16.
Ann Vasc Surg ; 96: 374-381, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37230316

RESUMO

BACKGROUND: In the last decade, the microwave ablation catheter specifically for treating lower extremity varicose veins has become popular. However, imited data is available on the efficacy, analysis, and evaluation of endovenous microwave ablation (EMWA) in treating SSV insufficiency. Our objective is to evaluated the feasibility, safety, and 1-year outcomes of EMWA and concomitant foam sclerotherapy of primary small saphenous vein (SSV) insufficiency. METHODS: Our team carried out a single-center, retrospective analysis of 24 patients treated with EMWAand concomitant foam sclerotherapy for primary SSV insufficiency. All operations were performed using a MWA catheter and polidocanol for the trunk and branches of the SSV, respectively. The SSV occlusion rate was assessed at the 6- and 12-month follow-up examinations using duplex ultrasound. Secondary outcomes included the Clinical, Etiological, Anatomical, Pathophysiological (CEAP) clinical class; Venous Clinical Severity Score (VCSS); Aberdeen Varicose Vein Questionnaire (AVVQ); periprocedural pain; and complications. RESULTS: 100% of the cases have been technically successful. At the 6-month follow-up, all treated SSVs were occluded. The 12-month assessment duplex doppler showed anatomical success in patients with 95.8% (95% confidence interval, 0.756-0.994). The CEAP clinical class, VCSS, and the AVVQ had decreased significantly at the 6- and 12-month follow-up, respectively. CONCLUSIONS: EMWA and concomitant foam sclerotherapy is a feasible and effective technique for treating SSV insufficiency.


Assuntos
Terapia a Laser , Varizes , Insuficiência Venosa , Humanos , Escleroterapia/efeitos adversos , Escleroterapia/métodos , Seguimentos , Veia Safena/cirurgia , Estudos Retrospectivos , Micro-Ondas/efeitos adversos , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/terapia , Terapia a Laser/efeitos adversos , Resultado do Tratamento , Ultrassonografia de Intervenção , Varizes/diagnóstico por imagem , Varizes/terapia , Varizes/complicações
17.
World J Surg Oncol ; 21(1): 136, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37098553

RESUMO

BACKGROUND: To compare the clinical efficacy of two alimentary tract reconstruction methods-"P"-shape jejunal interposition (PJI) and Roux-en-Y anastomosis after total gastrectomy. METHOD: The following search phrases were utilized to search PubMed, Cochrane Library, Embase, China Academic Journals Network Full-text Database (CNKI), and Wanfang Database as of April 2022: "gastrectomy," "Roux-en-Y," "interposition," "total gastrectomy," and "jejunal interposition." Meta-analysis of the operation time, intraoperative blood loss, complication rate, and postoperative nutritional status of patients was performed using RevMan 5.4 software. RESULTS: A total of 24 studies and 1887 patients were included in the study. Among patients who received a total gastrectomy, the operation time in the PJI group was substantially longer than that in the Roux-en-Y group (WMD = 19.77, 95% CI: 5.84-33.70, P = 0.005). The incidence of postoperative reflux esophagitis in the PJI group was considerably reduced than that in the Roux-en-Y group (OR = 0.39, 95% CI: 0.28-0.56, P < 0.01). The probability of postoperative dumping syndrome in the PJI group was significantly lower than that in the Roux-en-Y group (OR = 0.27, 95% CI: 0.17-0.43, P < 0.01), and the postoperative body mass changes were significantly lower in the PJI group than in the Roux-en-Y group (WMD = 3.94, 95% CI: 2.24-5.64, P < 0.01). The PJI group had substantially higher postoperative hemoglobin, albumin, and total protein levels than the Roux-en-Y group (WMD = 13.94, 95% CI: 7.77-19.20, P < 0.01; WMD = 3.97, 95% CI: 2.58-5.37, P < 0.01; WMD = 5.31, 95% CI: 3.45-7.16, P < 0.01). The prognostic nutritional index was higher in the PJI group than in the Roux-en-Y group (WMD = 9.25, 95% CI: 7.37-11.13, P < 0.01). CONCLUSION: PJI is a safe and effective reconstruction method and is superior to Roux-en-Y anastomosis in the prevention and treatment of postoperative complications and postoperative nutritional recovery in patients after total gastrectomy.


Assuntos
Anastomose em-Y de Roux , Neoplasias Gástricas , Humanos , Anastomose em-Y de Roux/efeitos adversos , Anastomose em-Y de Roux/métodos , Neoplasias Gástricas/complicações , Anastomose Cirúrgica/efeitos adversos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Jejuno/cirurgia
18.
Med Sci Monit ; 29: e938912, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36922715

RESUMO

BACKGROUND This study aimed to evaluate the safety and efficacy of portal vein puncture with a new guidance system using double C-arm digital subtraction angiography (DSA) during transjugular intrahepatic portosystemic shunt (TIPS) placement. MATERIAL AND METHODS The procedure details of TIPS placements performed on 39 patients in our center between January and December 2021 were retrospectively analyzed. The procedure was performed under double C-arm DSA guidance (study group) and C-arm DSA (control group) in 18 and 21 patients, respectively. We analyzed the procedure's technical success, duration of the overall procedure, portal vein puncture, fluoroscopy, radiation exposure, complications, and mortality and morbidity rates 30 days after the procedure. RESULTS TIPS placement was performed successfully in all patients. The mean portal vein puncture time in the study group (9±5.7 min) was significantly shorter than in the control group (33±14.9 min, p=0.02). The complete mean dose area product of the procedure showed no significant differences (study group, 126±53 Gy/cm²; control group. 142±66 Gy/cm²; p=0.42). The intraprocedural complication rates were 0% and 19% in the study and control groups, respectively (p=0.04). The 30-day post-procedural mortality rate in the control group was 4.8% (1/21), with no deaths from technical complications. CONCLUSIONS Double C-arm DSA guidance is a safe and effective method to assist TIPS placement. This approach may result in shorter portal vein puncture time and lower intraprocedural complication rates.


Assuntos
Derivação Portossistêmica Transjugular Intra-Hepática , Humanos , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Angiografia Digital , Estudos Retrospectivos , Veia Porta/cirurgia , Punções , Resultado do Tratamento
19.
Sci Bull (Beijing) ; 68(3): 284-294, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36732117

RESUMO

The chirality of bioactive molecules is closely related to their functions. D-amino acids commonly distributed in the bacterial cell walls trigger a robust anti-infective immune response. Inspired by that, two kinds of chiral polypeptides, poly(L-phenylalanine)-block-poly(L-lysine) (PL-K) and poly(L-phenylalanine)-block-poly(D-lysine) (PD-K), were synthesized and used as nanoadjuvants of nanovaccines for cancer prevention and therapy. The amphiphilic polypeptides self-assembled into nanoparticles with a diameter of about 30 nm during ultrasonic-assisted dissolution in phosphate-buffered saline. The nanovaccines PL-K-OVA and PD-K-OVA were easily prepared by mixing solutions of PL-K or PD-K and the model antigen chicken ovalbumin (OVA), respectively, with loading efficiencies of almost 100%. Compared to PL-K-OVA, PD-K-OVA more robustly induced dendritic cell maturation, antigen cross-presentation, and adaptive immune response. More importantly, it effectively prevented and treated the OVA-expressed B16-OVA melanoma model. PD-K-OVA achieved a tumor inhibition rate of 94.9% and even 97.0% by combining with anti-PD-1 antibody. Therefore, the chiral polypeptide nanoparticles represent simple, efficient, and extensively applicable nanoadjuvants for various nanovaccines.


Assuntos
Melanoma Experimental , Nanopartículas , Animais , Peptídeos/química , Nanopartículas/química , Ovalbumina/química , Apresentação de Antígeno , Antígenos
20.
Orthop Surg ; 15(2): 423-431, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36448261

RESUMO

OBJECTIVE: To compare the effectiveness of a six-month home-based telerehabilitation based on the Internet-based rehabilitation management system coupled with conventional outpatient care in elderly patients with hip fractures following total hip replacement (THR). METHODS: Elderly patients (aged over 65 years) with first hip fractures who underwent THR between March 2018 and September 2018 in Tianjin Hospital were enrolled in this study. Patients were divided into two groups: telerehabilitation group (n = 43) and telephone group (n = 42). A Internet-based telerehabilitation management system was established and applied on patients in the telerehabilitation group. For patients in the telephone group, the rehabilitation intervention was administered through conventional outpatient care (telephone along with outpatient follow-up). Data from the Harris hip scale (HHS), functional independence measure (FIM), self-rating anxiety scale (SAS), and postoperative complications at 1, 3, and 6 months after surgery were collected and compared between the two groups. RESULTS: A total of 85 elderly patients completed the 6-month follow-up assessment. Results showed that the HHS score was significantly higher in the telerehabilitation group than in the telephone group at 1 month (66.35 ± 4.63 vs 63.48 ± 4.49), 3 months (76.33 ± 4.52 vs 71.81 ± 3.84), and 6 months (84.23 ± 3.13 vs 77.29 ± 4.95) after surgery (P < 0.001). The FIM score was significantly higher in the telerehabilitation group than in the telephone group at 1 month (89.00 ± 5.63 vs 73.35 ± 8.70), 3 months (100.16 ± 4.56 vs 92.81 ± 5.17), and 6 months (111.70 ± 3.13 vs 98.64 ± 5.12) after surgery (P < 0.001). The SAS score was significantly lower in the telerehabilitation group than in the telephone group at 1 month (42.40 ± 3.07 vs 46.21 ± 3.53), 3 months (36.77 ± 2.26 vs 40.24 ± 1.66), and 6 months (29.26 ± 1.63 vs 33.81 ± 2.62) after surgery (P < 0.001). The overall complication rate was significantly lower in the telerehabilitation group than in the telephone group (14% vs 40.5%) (P < 0.05). CONCLUSION: Internet-based rehabilitation management system can not only promote the physical rehabilitation of patients, but also play a positive role in psychological rehabilitation and the prevention of complications, which provides new ideas and methods for clinical rehabilitation.


Assuntos
Artroplastia de Quadril , Fraturas do Quadril , Telerreabilitação , Idoso , Humanos , Artroplastia de Quadril/reabilitação , Telerreabilitação/métodos , Recuperação de Função Fisiológica , Resultado do Tratamento , Fraturas do Quadril/cirurgia
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