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1.
Acta Histochem ; 126(5-7): 152174, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38976933

RESUMEN

Choroidal melanoma (CM), a highly metastatic eye tumor, exhibits vasculogenic mimicry (VM) facilitated by hypoxia-induced angiogenesis. This study explored the inhibitory impact of the anti-malarial drug Artesunate (ART) on CM VM through modulation of the HIF-1α/VEGF/PDGF pathway. Immunohistochemistry (IHC) confirmed VM in CM with elevated VEGF and PDGF expression. Hypoxia promoted CM proliferation, upregulating HIF-1α, VEGF and PDGF. VEGF and PDGF enhanced CM migration, invasion and VM, with HIF-1α playing a crucial role. ART mitigated VM formation by suppressing the HIF-1α/VEGF/PDGF pathway, highlighting its potential as an anti-tumor agent in CM.

2.
Front Endocrinol (Lausanne) ; 15: 1403456, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38800479

RESUMEN

Objective: To investigate the association between blood urea nitrogen (BUN) levels and diabetic retinopathy (DR) in adults with diabetes mellitus (DM). Methods: Seven cycles of cross-sectional population information acquired from NHANES(national health and nutrition examination surveys) 2005-2018 were collected, from which a sample of diabetic adults was screened and separated into two groups based on whether or not they had DR, followed by weighted multivariate regression analysis. This study collected a complete set of demographic, biological, and sociological risk factor indicators for DR. Demographic risk factors comprised age, gender, and ethnicity, while biological risk factors included blood count, blood pressure, BMI, waist circumference, and glycated hemoglobin. Sociological risk factors included education level, deprivation index, smoking status, and alcohol consumption. Results: The multiple regression model revealed a significant connection between BUN levels and DR [odds ratio =1.04, 95% confidence interval (1.03-1.05), p-value <0.0001],accounting for numerous variables. After equating BUN levels into four groups, multiple regression modeling showed the highest quartile (BUN>20 mg/dl) was 2.22 times more likely to develop DR than the lowest quartile [odds ratio =2.22, 95% confidence interval (1.69-2.93), p- value <0.0001]. Subgroup analyses revealed that gender, race, diabetes subtype, and duration of diabetes had a regulating effect on the relationship between BUN and DR. Conclusion: BUN levels were related with an increased prevalence of DR, particularly in individuals with BUN >20 mg/dl. These findings highlight the significance of BUN level in assessing the risk of DR.


Asunto(s)
Nitrógeno de la Urea Sanguínea , Retinopatía Diabética , Encuestas Nutricionales , Humanos , Retinopatía Diabética/sangre , Retinopatía Diabética/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Estados Unidos/epidemiología , Adulto , Factores de Riesgo , Anciano , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología
3.
Ann Surg Treat Res ; 106(4): 225-230, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38586557

RESUMEN

Purpose: Whether a dilated intrahepatic bile duct (IHBD) has any effect on the prognosis of choledochal cyst (CC) remains controversial. We aimed to summarize the clinical characteristics and prognosis of CC with IHBD dilatation. Methods: One hundred ninety-two children diagnosed with CC were identified, including 127 without IHBD dilatation (group A) and 65 with IHBD dilatation (group B). A retrospective analysis was performed to explore the clinical characteristics and prognosis of CC with IHBD dilatation based on clinical indices, symptoms, and complications. Results: Compared with group A, incidences of jaundice and fever were higher in group B (P = 0.010 and P = 0.033). Preoperative total bilirubin, direct bilirubin, and indirect bilirubin were increased in group B compared to group A (P = 0.005, P < 0.001, and P = 0.014), as were preoperative ALT, AST, γ-GT, and total bile acid (P = 0.006, P = 0.025, P < 0.001, and P = 0.024). The risk of liver fibrosis or cirrhosis was significantly increased for group B compared with group A (P = 0.012) and also occurred earlier in group B (P = 0.006). In the dilated IHBDs, 95.4% (62 of 65) recovered to normal, and more than half of dilated IHBDs (37 of 65) recovered to normal in 1 week. Conclusion: Most IHBDs can recover to normal postoperatively in a short time, and proactive treatment is recommended for CC patients with IHBD dilatation for significant abnormal liver functions.

4.
World J Gastroenterol ; 30(10): 1420-1430, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38596496

RESUMEN

BACKGROUND: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research. AIM: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs. METHODS: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues. RESULTS: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues. CONCLUSION: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC.


Asunto(s)
Quiste del Colédoco , Humanos , Femenino , Ratas , Animales , Quiste del Colédoco/cirugía , Reproducibilidad de los Resultados , Ratas Sprague-Dawley , Modelos Animales , Dilatación Patológica , Bilirrubina , Modelos Animales de Enfermedad
5.
J Cancer Res Clin Oncol ; 150(4): 202, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38630320

RESUMEN

PURPOSE: Choroidal melanoma (CM), a kind of malignant tumor, is the main type of Uveal melanoma and one half of CM patients develop metastases. As a member of Eph/ephrin pathway that plays vital role in tumors, EphrinA3 (EFNA3) has been proved to promote tumorigenesis in many tumors. But the effect of EFNA3 in CM has not been studied yet. Through inhibiting angiogenesis, inducing apoptosis and autophagy and so on, Artesunate (ART) plays a key anti-tumor role in many tumors, including CM. However, the exact mechanisms of anti-tumor in CM remain unclear. METHODS: The UALCAN and TIMER v2.0 database analyzed the role of EFNA3 in CM patients. Quantitative real time polymerase chain reaction (qPCR) and Western blot were used to detect the expression of EFNA3 in CM. The growth ability of CM was tested by clonogenic assay and Cell counting kit-8 assay, and the migration ability using Transwell assay. RESULTS: Our results found EFNA3 boosted CM cells' growth and migration through activating Stat3/Akt signaling pathway, while ART inhibited the tumor promoting effect of CM via downregulating EFNA3. In xenograft tumor model, EFNA3 knockdown and ART significantly inhibited tumor growth. CONCLUSION: EFNA3 could be a valuable prognostic factor in CM.


Asunto(s)
Melanoma , Neoplasias de la Úvea , Humanos , Animales , Melanoma/tratamiento farmacológico , Melanoma/genética , Artesunato/farmacología , Proteínas Proto-Oncogénicas c-akt , Carcinogénesis , Transformación Celular Neoplásica , Modelos Animales de Enfermedad , Transducción de Señal
6.
J Colloid Interface Sci ; 662: 857-869, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38382370

RESUMEN

Copper-based nanomaterials show considerable potential in the chemodynamic therapy of cancers. However, their clinical application is restricted by low catalytic activity in tumor microenvironment and copper-induced tumor angiogenesis. Herein, a novel copper-doxorubicin-anlotinib (CDA) nanoconjugate was constructed by the combination of copper-hydrazide coordination, hydrazone linkage and Schiff base bond. The CDA nanoconjugate consists of a copper-3,3'-dithiobis(propionohydrazide)-doxorubicin core and an anlotinib-hyaluronan shell. Benefiting from hyaluronan camouflage and abundant disulfide bonds and Cu2+, the CDA nanoconjugate possessed excellent tumor-targeting and glutathione-depleting abilities and enhanced chemodynamic efficacy. Released doxorubicin significantly improved copper-mediated chemodynamic therapy by upregulating nicotinamide adenine dinucleotide phosphate oxidase 4 expression to increase intracellular H2O2 level. Furthermore, the nanoconjugate produced excessive •OH to induce lipid peroxidation and mitochondrial dysfunction, thus greatly elevating doxorubicin-mediated chemotherapy. Importantly, anlotinib effectively inhibited the angiogenic potential of copper ions. In a word, the CDA nanoconjugate is successfully constructed by combined coordination and pH-responsive linkages, and displays the great potential of copper-drug conjugate for targeted synergistic chemo/chemodynamic/antiangiogenic triple therapy against cancers.


Asunto(s)
Carcinoma Hepatocelular , Indoles , Neoplasias Hepáticas , Nanopartículas , Neoplasias , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Cobre , Ácido Hialurónico , Nanoconjugados , Peróxido de Hidrógeno , Neoplasias Hepáticas/tratamiento farmacológico , Doxorrubicina/farmacología , Glutatión , Línea Celular Tumoral , Microambiente Tumoral
8.
J Laparoendosc Adv Surg Tech A ; 34(6): 541-545, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38190306

RESUMEN

Background: To explore the safety, efficacy, advantages, and disadvantages of robotic-assisted splenectomy (RS) in children by analyzing and comparing the clinical data of RS and laparoscopic splenectomy (LS). Methods: The clinical data of 35 children who underwent laparoscopic or RS or partial splenectomy from February 2010 to October 2022 were included. A retrospective analysis based on general information, clinical data, and prognosis were performed. Results: Among 35 cases, 14 cases, and 21 cases underwent RS and LS, respectively. The average operation time was 167 (120-224) minutes in the RS group and 176 (166-188) minutes in the LS group. The intraoperative blood loss was significantly larger in LS group than RS group (P = .0009). The length of hospital stay was significantly longer in LS group than RS group (P = .0015), and the hospitalization cost was significantly higher in RS group than LS group (P < .0001). There were no cases of conversion to laparotomy in the RS group, but two cases in the LS group. In terms of postoperative complications, there were one and three cases in the RS and LS groups, respectively. Conclusion: The Robotic Surgical System was safe and feasible in pediatric splenectomy or partial splenectomy which was an alternative to laparoscopic surgery.


Asunto(s)
Laparoscopía , Procedimientos Quirúrgicos Robotizados , Esplenectomía , Humanos , Esplenectomía/métodos , Laparoscopía/métodos , Masculino , Femenino , Procedimientos Quirúrgicos Robotizados/métodos , Niño , Estudios Retrospectivos , Adolescente , Tiempo de Internación/estadística & datos numéricos , Tempo Operativo , Preescolar , Complicaciones Posoperatorias/epidemiología , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Resultado del Tratamiento
9.
Asian J Surg ; 47(1): 269-273, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37648540

RESUMEN

OBJECTIVE: To study the diagnosis, management strategies, and outcomes of pediatric patients with blunt pancreatic injury. METHODS: The clinical data of patients with blunt pancreatic injury at Children's Hospital, Zhejiang University School of Medicine from January 2011 to September 2022 were collected and analyzed retrospectively. RESULTS: A total of 51 patients were enrolled. According to the American Association for the Surgery of Trauma (AAST) classification of pancreatic injury, 41 patients were categorized in the low-grade and nine in the high-grade groups. On admission, serum amylase and lipase levels in the high-grade group were significantly higher than in the low-grade group (P = 0.025 and P = 0.021, respectively). The peak levels of serum amylase and lipase in the high-grade group were considerably higher than in the low-grade group (P = 0.017 and P = 0.038, respectively). Two patients received surgical treatment, but none experienced pancreatectomy. The remaining 49 patients were successfully treated with conservative methods. The incidence of pancreatic pseudocysts in patients was 47.1% (24/51), and half required external drainage. CONCLUSION: Conservative management is safe for most children with blunt pancreatic injury, surgical intervention should be adopted in patients with hemodynamic instability or multiple organ failure.


Asunto(s)
Traumatismos Abdominales , Heridas no Penetrantes , Humanos , Niño , Estudios Retrospectivos , Resultado del Tratamiento , Páncreas/cirugía , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/cirugía , Traumatismos Abdominales/diagnóstico , Traumatismos Abdominales/epidemiología , Traumatismos Abdominales/cirugía , Lipasa , Amilasas
10.
Int J Surg ; 110(2): 859-863, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37995094

RESUMEN

BACKGROUND: Robot-assisted surgery is increasingly used in children. While robot-assisted surgery in children has been proved to be safe and feasible, use in infants is controversial. The purpose of this study was to present a study of robot-assisted abdominal surgery in children less than5 months of age. MATERIALS AND METHODS: A retrospective analysis of 111 patients less than 5 months of age who underwent abdominal surgery from April 2020 to December 2022 in our hospital. The data included clinical information, operative details, and postoperative outcomes. RESULTS: Among these 111 patients, 67 underwent robot-assisted surgery and 44 underwent laparoscopic-assisted surgery, the robot-assisted group includes 40 patients with Hirschsprung disease, 20 patients with choledochal cysts, and 7 patients with intestinal duplication, the laparoscopic-assisted group includes 26 patients with Hirschsprung disease, 9 patients with choledochal cysts, and 9 patients with intestinal duplication. For Hirschsprung disease, the operation time was significantly longer ( P =0.013) and the intraoperative bleeding was significantly less ( P =0.000) in the robot-assisted group than the laparoscopic assisted group. For choledochal cysts, the median operation time of 180 mins for the robot-assisted group was not significantly longer than the laparoscopic assisted surgery group at 160 mins ( P =0.153). For intestinal duplication, the operation time was significantly longer ( P =0.002) in the robot-assisted group than the laparoscopic assisted group. For these three diseases, the hospitalization expense was significantly higher ( P <0.05) in the robot-assisted group than the laparoscopic assisted group, there were no significant differences in complications, and postoperative fasting time between two groups ( P >0.05). CONCLUSION: Robot-assisted abdominal surgery in children less than 5 months of age is safe and feasible. This study showed that the surgical indications for the Da Vinci robot system in children can be extended to infants.


Asunto(s)
Quiste del Colédoco , Enfermedad de Hirschsprung , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Robótica , Niño , Lactante , Humanos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Estudios Retrospectivos , Enfermedad de Hirschsprung/cirugía , Laparoscopía/efectos adversos , Resultado del Tratamiento
11.
BMC Surg ; 23(1): 294, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37752449

RESUMEN

BACKGROUND: There are few studies comparing robotic-assisted surgery (RAS) and laparoscopic-assisted surgery (LAS) in Hirschsprung's disease (HSCR). This study aimed to compare intraoperative and postoperative outcomes between RAS and LAS performed during the same period. METHODS: All consecutive 75 patients with pathologically diagnosed as HSCR who underwent Swenson pull-through surgery from April 2020 to Nov 2022, were included. Patients were divided into RAS group and LAS group and a retrospective analysis was performed based on clinical indexes and prognosis. RESULTS: A total of 75 patients were included, among which, 31 patients received RAS and 44 received LAS. The RAS and LAS groups had similar ages, sex, weight, postoperative hospital stays, and fasting times. Compared with LAS, blood loss (p = 0.002) and the incidence of Hirschsprung-associated enterocolitis (p = 0.046) were significantly lower in the RAS group. The first onset of Hirschsprung-associated enterocolitis in patients younger than 3 months occurred significantly earlier (p = 0.043). Two patients experienced anastomotic leakage in the LAS group and one patient experienced incisional hernia in the RAS group. The cost of RAS was significantly higher than that of LAS (p < 0.0001). CONCLUSIONS: RAS is a safe and effective alternative for HSCR children, and a delaying primary surgery until later in infancy (> 3 months) may improve outcomes.


Asunto(s)
Enterocolitis , Enfermedad de Hirschsprung , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Humanos , Niño , Lactante , Enfermedad de Hirschsprung/cirugía , Enfermedad de Hirschsprung/complicaciones , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Laparoscopía/efectos adversos , Enterocolitis/etiología , Enterocolitis/cirugía , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento
12.
Optom Vis Sci ; 100(10): 721-725, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37639550

RESUMEN

PURPOSE: We present a rare case of Streptococcus constellatus -induced odontogenic orbital cellulitis. METHODS: An 8-year-old boy presented to an outpatient clinic with complaints of right-sided toothache, right eye swelling, and decreased visual acuity. He was referred to a pediatric critical care department for further management. Comprehensive diagnostic assessments, such as ophthalmic examination, blood tests, computed tomography, and MRI, were performed. RESULTS: On presentation, the best-corrected visual acuities were 20/250 and 20/20 in the right and left eyes, respectively. Examination revealed grade 2+ eyelid edema and erythema and grade 4+ chemosis and exophthalmos in the right eye. The patient displayed restricted eye movements in all directions. Blood tests revealed a total white blood cell count of 12,100 cells/µL. Axial and coronal computed tomography revealed right-sided maxillary sinus, ethmoidal sinus, and orbital abscesses. Therefore, the patient was diagnosed with septicemia, orbital cellulitis, and orbital apex syndrome in the right eye. Intravenous antibiotics were administered; paracentesis of the orbital abscess was performed under local anesthesia. However, the patient's condition worsened, resulting in a complete loss of light perception in the right eye. Accordingly, surgery was performed under general anesthesia within 24 hours of admission; the surgery involved drainage of the orbital abscess through an inferior intraorbital incision, as well as drainage of the ethmoid sinus and maxillary sinus abscesses via nasal endoscopy. A culture obtained from the orbital abscess yielded S. constellatus . The infection was managed by a combination of surgical intervention, antibiotics, steroids, and hyperbaric oxygen therapy. However, because of optic nerve injury, vision in the affected eye partially recovered to 20/200. CONCLUSIONS: Streptococcus constellatus -induced pediatric orbital cellulitis can result in significant morbidity. The significant improvement in vision, from no light perception to 20/200, emphasizes the importance of timely diagnosis and treatment in patients who present with acute orbital cellulitis and vision loss symptoms.


Asunto(s)
Exoftalmia , Celulitis Orbitaria , Streptococcus constellatus , Masculino , Humanos , Niño , Celulitis Orbitaria/diagnóstico , Celulitis Orbitaria/terapia , Celulitis Orbitaria/etiología , Absceso/diagnóstico , Absceso/terapia , Absceso/complicaciones , Trastornos de la Visión/etiología , Exoftalmia/tratamiento farmacológico , Antibacterianos/uso terapéutico
13.
Front Pediatr ; 11: 1162236, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37404555

RESUMEN

Background: The emergence of the robotic surgery system has assisted the further development of minimally invasive surgery by facilitating more delicate and precise complex procedures. The purpose of this study was to present a study of robot-assisted resection of the choledochal cyst and to discuss the technical points. Methods: In total, 133 patients who were diagnosed with a choledochal cyst and underwent surgery from April 2020 to February 2022 in the Children's Hospital, Zhejiang University School of Medicine, were retrospectively analyzed. The data were collected including the clinical information of the patients, operative details, and postoperative outcomes. Results: Among these 133 patients, 99 underwent robot-assisted surgery and 34 underwent laparoscopic assisted surgery. The median operation time was 180 min, with an interquartile range (IQR) of 170-210 min for the robot-assisted group and 180 min with an IQR of 157.5-220 min in the laparoscopic assisted group (P = 0.290). The detection rate of 82.5% for the distal opening of the cystic type of choledochal cyst was higher in the robot-assisted group than that in the laparoscopic assisted group at 34.8% (P = 0.000). The postoperative hospital stay was shorter (P = 0.009) and the hospitalization expense was higher (P = 0.000) in the robot-assisted group than that of the laparoscopic assisted group. There was no significant difference between the two groups in terms of complications, postoperative indwelling days of the abdominal drainage tube, intraoperative blood loss, and postoperative fasting time (P > 0.05). Conclusions: Robot-assisted resection of choledochal cyst is safe and feasible, it is ideal for the patient requiring a meticulous operation, and its postoperative recovery was shorter than for traditional laparoscopy.

14.
Int J Biol Macromol ; 224: 797-809, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36283555

RESUMEN

Recently, it was newly revealed that the DNA damage induced by cis­platinum (Cis-Pt) mediated chemotherapy was significantly impaired by the highly expressed programmed death ligand-1 (PD-L1) in tumor cells. Besides, the efficacy of Cis-Pt was also limited due to its severe side effects, especially enhanced drug efflux induced by multidrug resistance protein 1 (MDR-1) and increased tumor metastasis. Up to now, few drugs or carbohydrates could simultaneously solve these defects of Cis-Pt mediated chemotherapy. Here, we newly found that metformin-modified chitosan (Ch-Met) possessed ideal selective mitochondria accumulation capacity, leading to the further disrupted mitochondrial function, which then effectively inhibited the upregulated PD-L1 expression to inhibit DNA damage repair in tumor cells, as well as impaired drug efflux and lowered tumor metastasis. Therefore, it was demonstrated that Ch-Met could sensitize the chemotherapy efficacy of Cis-Pt.


Asunto(s)
Antineoplásicos , Quitosano , Metformina , Neoplasias , Humanos , Cisplatino/farmacología , Antígeno B7-H1/metabolismo , Metformina/farmacología , Adyuvantes Inmunológicos/farmacología , Línea Celular Tumoral , Antineoplásicos/farmacología , Resistencia a Antineoplásicos
16.
Acta Pharm Sin B ; 12(11): 4204-4223, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36386474

RESUMEN

As a promising modality for cancer therapy, photodynamic therapy (PDT) still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment. To ameliorate such a situation, we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles via hydrophilic and hydrophobic self-assembly strategy by using near-infrared photodynamic dye MHI148 chemically modified bovine serum albumin (BSA-MHI148) and multi-kinase inhibitor Sorafenib (SRF) as a novel tumor oxygen and immune microenvironment regulation drug. Benefiting from the accumulation of SRF in tumors, BSA-MHI148@SRF nanoparticles dramatically enhanced the PDT efficacy by promoting cascade two-stage tumor re-oxygenation mechanisms: (i) SRF decreased tumor oxygen consumption via inhibiting mitochondria respiratory. (ii) SRF increased the oxygen supply via inducing tumor vessel normalization. Meanwhile, the immunosuppression micro-environment was also obviously reversed by two-stage immune re-sensitization as follows: (i) Enhanced immunogenic cell death (ICD) production amplified by BSA-MHI148@SRF induced reactive oxygen species (ROS) generation enhanced T cell infiltration and improve its tumor cell killing ability. (ii) BSA-MHI148@SRF amplified tumor vessel normalization by VEGF inhibition also obviously reversed the tumor immune-suppression microenvironment. Finally, the growth of solid tumors was significantly depressed by such well-designed BSA-MHI148@SRF nanoparticles, which could be potential for clinical cancer therapy.

17.
Front Pediatr ; 10: 921853, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36046482

RESUMEN

Background: Choledochal cyst perforation is extremely rare, and early diagnosis or prediction is important for the immediate therapeutic intervention of perforations. This study aimed to define the predictor(s) of an impending or complete spontaneous perforation of choledochal cyst and establish the optimal operative timing. Methods: All 429 consecutive choledochal cyst patients from January 2015 to December 2021, were included. A retrospective study was performed based on Kaplan-Meier analysis, and Cox univariate and multivariate analyses. Results: A total of 429 patients were included, among which, 21 had choledochal cyst perforations (group A), and 408 did not (group B). Compared to group B, the serum alanine aminotransferase, aspartate aminotransferase, direct bilirubin, gamma-glutamyl transpeptidase, indirect bilirubin, total bilirubin, and alkaline phosphatase were significantly higher in group A (p = 0.025, 0.006, < 0.0001, 0.0001, 0.001, < 0.0001, and 0.033). High serum gamma-glutamyl transpeptidase was negatively associated with perforation-free preoperative survival, and multivariate Cox regression revealed that serum gamma-glutamyl transpeptidase was an independent predictive factor for an impending or complete perforation (p = 0.042). Conclusions: A gamma-glutamyl transpeptidase level ≥ 346.5 U/L accompanied with significantly elevated liver enzymes and bilirubin levels was indicative of the possibility of an impending or complete choledochal cyst perforation, and a proactive surgical approach should be considered.

18.
Carbohydr Polym ; 295: 119878, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-35989018

RESUMEN

At present, the tumor's poor oxygen perfusion and limited tumor drug permeation are the major bottlenecks that limit the therapeutic effectiveness of the oxygen-sensitive antitumor therapies, like doxorubicin (Dox)-mediated chemotherapy and photodynamic therapy (PDT). To our best knowledge, the abnormal tumor mitochondria oxidative phosphorylation (OXPHOS) was the vital cause of such phenomenon, which induced the hypoxia tumor microenvironment and enhanced drug efflux from tumor cells via enhanced multidrug resistance protein 1 (MDR-1) expression. In this study, it was newly revealed that biguanide-modified chitosan (Bi-Ch) possessed ideal mitochondria depression capacity, leading to the following decreased dosage needed to disrupt mitochondrial function to reverse tumor hypoxia and depress MDR-1 expression. By doing this, Bi-Ch effectively enhanced Dox accumulation in tumor cells and amplified its cytotoxicity owing to the amplified ROS generation by Dox. Therefore, Bi-Ch could be used to improve the efficacy of oxygen-sensitive tumor therapies in vitro.


Asunto(s)
Quitosano , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Biguanidas/farmacología , Biguanidas/uso terapéutico , Línea Celular Tumoral , Quitosano/metabolismo , Quitosano/farmacología , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos , Mitocondrias/metabolismo , Oxígeno
19.
PeerJ ; 10: e13745, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35860042

RESUMEN

Recent evidence indicates that cancer stem cells (CSCs) are the origin of cancers. Scientists have identified CSCs in various tumors and have suggested the existence of a variety of states of CSCs. The existence of epithelial-mesenchymal transition (EMT)-like CSCs has been confirmed in vitro, but they have not been identified in vivo. Tumor budding was defined as single cell or clusters of ≤ 5 cells at the invasive front of cancers. Such tumor budding is hypothesized to be closely related to EMT and linked to CSCs, especially to those migrating at the invasive front. Therefore, tumor budding has been proposed to represent EMT-like stem cells. However, this hypothesis has not yet been proven. Thus, we studied the expression of EMT markers, certain CSC markers of tumor budding, and the tumor center of cervical squamous cell carcinoma (CxSCC). We performed tissue chip analyses of 95 primary CxSCCs from patients. Expression of EMT and CSC markers (E-cadherin, ß-catenin, vimentin, Ki67, CD44, SOX2 , and ALDH1A1) in a set of tumor samples on tissue chips (87 cases of tumor budding/the main tumor body) were evaluated by immunohistochemistry. We found that the cell-membranous expression of ß-catenin was stronger in the main tumor body than in tumor buds. Compared with the main tumor body, tumor buds had reduced proliferative activity as measured by Ki67. Moreover, vimentin expression was high and E-cadherin expression was low in tumor buds. Expression of EMT-related markers suggested that tumor buds were correlated with EMT. We noted that CxSCC tumor buds had a CD44negative/low/SOX2high/ALDH1A1high staining pattern, indicating that tumor buds of CxSCC present CSC-like immunophenotypic features. Taken together, our data indicate that tumor buds in CxSCC may represent EMT-like CSCs in vivo.


Asunto(s)
Carcinoma de Células Escamosas , Transición Epitelial-Mesenquimal , Neoplasias del Cuello Uterino , Femenino , Humanos , beta Catenina/metabolismo , Cadherinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Antígeno Ki-67/metabolismo , Células Madre Neoplásicas/metabolismo , Vimentina/metabolismo , Neoplasias del Cuello Uterino/metabolismo
20.
Int J Ophthalmol ; 15(3): 489-494, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35310055

RESUMEN

AIM: To observe the best-corrected visual acuity (BCVA) and central foveal thickness (CFT) repeatedly after the intravitreal injection of conbercept (IVC) for treating cystoid macular edema (CME) in branch retinal vein occlusion (BRVO) and explore the relationship between the duration of CME and visual outcome. METHODS: Subgroup analysis was performed to compare short-term (within 90d of CME onset) and long-term (over 90d of CME onset) macular edema in BRVO. After an initial IVC, a pro re nata (PRN) strategy was performed according to the recurrence of CFT or decrease of BCVA. Analysis of variance using repeated measurements, statistical analysis following indicators including BCVA and CFT collected at baseline and 1, 3, and 6mo after IVC. RESULTS: Among the 60 cases included in this retrospective study, 36 were short-term CME, and 24 were long-term CME. There were statistical significances between and within groups of the BCVAs at different time points (P<0.001). The interaction was found between group and time (P=0.006), indicating the difference in the speed of BCVA improvement between groups. In particular, the improvement speed of BCVA in the short-term CME group was faster than that in the long-term CME group. There were significant differences between and with groups of the CFT at different time points (P<0.001). However, the interaction between group and time in relation to CFT had no significant differences (P=0.59). CONCLUSION: IVC treatment for CME following BRVO is effective and safe. The duration of CME before treatment is a significant predictor of the visual outcomes of patients with BRVO. The improvement of vision might be faster with early IVC treatment than with delayed treatment.

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