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BACKGROUND: Hepatocellular carcinoma (HCC), a prevalent primary malignant tumor, is notorious for its high mortality rate. Despite advancements in HCC treatment, patient outcomes remain suboptimal. This study endeavors to assess the potential prognostic significance of POLH-AS1 in HCC. METHODS: In this research, we gathered RNA-Seq information from individuals with HCC in The Cancer Genome Atlas (TCGA). We analyzed the levels of POLH-AS1 expression in both HCC cells and tissues using statistical tests. Additionally, we examined various prognostic factors in HCC using advanced methodologies. Furthermore, we employed Spearman's rank correlation analysis to examine the association between POLH-AS1 expression and the tumor's immune microenvironment. Finally, the functional roles of POLH-AS1 in HCC were validated in two HCC cell lines (HEP3B and HEPG2). RESULTS: Our analysis revealed elevated POLH-AS1 expression across various cancers, including HCC, with heightened expression correlating with HCC progression. Notably, POLH-AS1 expression emerged as a potential biomarker for HCC patient survival and prognosis. Mechanistically, we identified the involvement of POLH-AS1 in tumorigenesis pathways such as herpes simplex virus 1 infection, interactions with neuroactive receptors, and the cAMP signaling pathway. Lastly, inhibition of POLH-AS1 was discovered to hinder the proliferation, invasion and migration of HEP3B and HEPG2 HCC cells. CONCLUSIONS: POLH-AS1 emerges as a promising prognostic biomarker and therapeutic target for HCC, offering potential avenues for enhanced patient management and treatment strategies.
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Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Pronóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral , Proliferación Celular , Línea Celular Tumoral , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Movimiento Celular , Células Hep G2RESUMEN
OBJECTIVE: We had previously reported endoscopic central and lateral neck dissection via breast combined with an oral approach for papillary thyroid cancer treatment. In this study, we optimized the procedure with Wu's seven steps to make the procedure quicker and easier. METHODS: Wu's seven steps for endoscopic central and lateral neck dissection via breast combined with oral approach for papillary thyroid cancer are: (1) establish the working space, (2) isolate the sternocleidomastoid and internal jugular vein, (3) dissect the thyroid via breast approach, (4) dissect the central lymph nodes via oral approach, (5) dissect the inferior board of level IV via oral approach, (6) remove the tissues of levels IV, III, and II via breast approach, and (7) wash the working space and place drainage tubes. Twelve patients were assigned to the Wu's seven steps group, and 13 patients were assigned to the contrast group. The operative procedure of the contrast group was the same as Wu's seven steps except for a few key differences, such as that the central lymph nodes were dissected via breast approach first and the internal jugular vein(IJV) was dissected from the cricoid cartilage down to the venous angle. RESULTS: The Wu's seven steps group had a short operation time and few injuries of the internal jugular vein. There were no statistical differences in other clinicopathological features or surgical complications. CONCLUSION: It appears that Wu's seven steps for endoscopic central and lateral neck dissection via breast combined with oral approach for papillary thyroid cancer are effective and safe.
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Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Disección del Cuello/métodos , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Tiroidectomía/métodos , Carcinoma Papilar/cirugía , Metástasis LinfáticaRESUMEN
In a recent clinical trial, balapiravir, a prodrug of a cytidine analog (R1479), failed to achieve efficacy (reducing viremia after treatment) in dengue patients, although the plasma trough concentration of R1479 remained above the 50% effective concentration (EC(50)). Here, we report experimental evidence to explain the discrepancy between the in vitro and in vivo results and its implication for drug development. R1479 lost its potency by 125-fold when balapiravir was used to treat primary human peripheral blood mononuclear cells (PBMCs; one of the major cells targeted for viral replication) that were preinfected with dengue virus. The elevated EC(50) was greater than the plasma trough concentration of R1479 observed in dengue patients treated with balapiravir and could possibly explain the efficacy failure. Mechanistically, dengue virus infection triggered PBMCs to generate cytokines, which decreased their efficiency of conversion of R1479 to its triphosphate form (the active antiviral ingredient), resulting in decreased antiviral potency. In contrast to the cytidine-based compound R1479, the potency of an adenosine-based inhibitor of dengue virus (NITD008) was much less affected. Taken together, our results demonstrate that viral infection in patients before treatment could significantly affect the conversion of the prodrug to its active form; such an effect should be calculated when estimating the dose efficacious for humans.
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Antivirales/administración & dosificación , Virus del Dengue/efectos de los fármacos , Dengue/tratamiento farmacológico , Dengue/virología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Nucleósidos/administración & dosificación , Animales , Citidina/administración & dosificación , Citidina/análogos & derivados , Citocinas/inmunología , Dengue/inmunología , Virus del Dengue/genética , Virus del Dengue/fisiología , Femenino , Humanos , Ratones , Nucleósidos/farmacología , Profármacos/administración & dosificaciónRESUMEN
Bacillus anthracis lethal toxin (LT) is a determinant of lethal anthrax. Its function in myeloid cells is required for bacterial dissemination, and LT itself can directly trigger dysfunction of the cardiovascular system. The interplay between LT and the host responses is important in the pathogenesis, but our knowledge on this interplay remains limited. Tumor necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine induced by bacterial infections. Since LT accumulates and cytokines, predominantly TNF, amass during B. anthracis infection, co-treatment of TNFâ +â LT in mice was used to mimic in vivo conditions for LT to function in inflamed hosts. Bone marrow transplantation and genetically engineered mice showed unexpectedly that the death of intestinal epithelial cells (IECs) rather than that of hematopoietic cells led to LTâ +â TNF-induced lethality. Inhibition of p38α mitogen-activated protein kinase (MAPK) signaling by LT in IECs promoted TNF-induced apoptosis and necroptosis of IECs, leading to intestinal damage and mouse death. Consistently, p38α inhibition by LT enhanced TNF-mediated cell death in human colon epithelial HT-29 cells. As intestinal damage is one of the leading causes of lethality in anthrax patients, the IEC damage caused by LTâ +â TNF would most likely be a mechanism underneath this clinical manifestation and could be a target for interventions.
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Carbunco , Bacillus anthracis , Humanos , Animales , Ratones , Factor de Necrosis Tumoral alfa , Carbunco/microbiología , Carbunco/patología , Citocinas , Transducción de SeñalRESUMEN
Procambarus clarkii is adept at using natural shelters and caves to evade attacks from predators. However, the concealment abilities and mechanisms of P. clarkii for different types of shelters under predation pressure have not yet been reported. In this study, laboratory experiments were carried out to determine the effects of different coverages (25%, 50%, and 75%) and different combinations (I-VII) of three types of shelters (PVC pipes, water grass, and stone) on the predation rhythm, behavior, and abilities of Silurus asotus on P. clarkii. The results indicated that the predation of S. asotus on P. clarkii exhibited significant rhythmicity under shelter conditions, excluding PVC pipes, 75% stone, and combination VI. Among the three types of shelters, PVC pipes provided the strongest concealment, followed by stone and water grass. With the increase in shelter coverage, the anti-predation ability of P. clarkii continued to increase, and the optimal shade rate for water grass was 50%. In the different shelter combinations, the environmental complexity had little effect on the predation activity of S. asotus on P. clarkii. These findings demonstrated that the type and abundance of shelters in the wild environment can affect the predation rhythm and activities of S. asotus on P. clarkii.
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Background: Periostin (POSTN) is a critical extracellular matrix protein in various tumor microenvironments. However, the function of POSTN in thyroid cancer progression remains largely unknown. Methods: Postn and Rag1 knock-out mice and orthotopic mouse models were used to determine the role of POSTN on papillary thyroid tumor progression. Immunofluorescence, cell co-culture, fluorescence in situ hybridization, chromatin immunoprecipitation assay, recombinant protein and inhibitor treatment were performed to explore the underlying mechanisms of POSTN-promoted papillary thyroid tumor growth. Results: POSTN is up-regulated in papillary thyroid tumors and negatively correlates with the overall survival of patients with thyroid cancer. Cancer-associated fibroblast (CAF)-derived POSTN promotes papillary thyroid tumor growth in vivo and in vitro. POSTN deficiency in CAFs significantly impairs CAF-promoted papillary thyroid tumor growth. POSTN promotes papillary thyroid tumor cell proliferation and IL-4 expression through integrin-FAK-STAT3 signaling. In turn, tumor cell-derived IL-4 induces the activation of CAFs and stimulates POSTN expression by activating STAT6. We reveal the crucial role of CAF-derived POSTN and tumor cell-derived IL-4 in driving the development of papillary thyroid tumors through the POSTN-integrin-FAK-STAT3-IL-4 pathway in tumor cells and IL-4-STAT6-POSTN signaling in CAFs. Conclusion: Our findings underscore the significance of POSTN and IL-4 as critical molecular mediators in the dynamic interplay between CAFs and tumor cells, ultimately supporting the growth of papillary thyroid tumors.
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Fibroblastos Asociados al Cáncer , Proliferación Celular , Ratones Noqueados , Periostina , Factor de Transcripción STAT3 , Transducción de Señal , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Animales , Humanos , Ratones , Fibroblastos Asociados al Cáncer/metabolismo , Línea Celular Tumoral , Quinasa 1 de Adhesión Focal/metabolismo , Integrinas/metabolismo , Interleucina-4/metabolismo , Periostina/metabolismo , Factor de Transcripción STAT3/metabolismo , Cáncer Papilar Tiroideo/metabolismo , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/genética , Microambiente TumoralRESUMEN
Purpose: Total extraperitoneal prosthesis (TEP) is one of the most commonly used laparoscopic inguinal hernia repair procedures. This work aims to report the application of membrane anatomy to TEP and its value in intraoperative space expansion. Methods: The clinical data of 105 patients, from January 2018 to May 2020, with inguinal hernia who were treated with TEP (58 patients in the General Department of the Second Hospital of Sanming City, Fujian Province, and 47 patients in the General Department of the Zhongshan Hospital Affiliated to Xiamen University) were retrospectively analyzed. Results: All surgeries were successfully completed under the guidance of the concept of preperitoneal membrane anatomy. The operation time was 27.5 ± 9.0â min, blood loss was 5.2 ± 0.8â ml, and the peritoneum was damaged in six cases. The postoperative hospital stay was 1.5 ± 0.6 days, and five cases of postoperative seroma occurred, all self-absorbed. During the follow-up period of 7-59 months, there was no case of chronic pain and recurrence. Conclusion: The membrane anatomy at the correct level is the premise of a bloodless operation to expand the space while protecting adjacent tissues and organs to avoid complications.
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Background: Transoral endoscopic thyroidectomy vestibular approach is feasible and safe but has some unavoidable limitations, such as sensory changes in the center of the chin region. We aim to report our initial experience in performing transoral endoscopic thyroidectomy via the submental and vestibular approach for the treatment of thyroid cancer. Patients and Methods: This retrospective cohort study included patients with thyroid cancer confirmed by fine-needle aspiration who underwent endoscopic thyroidectomy and central lymph node dissection via the submental and vestibular approaches between November 2019 and January 2020. Patients' clinicopathological characteristics, operation details, and postoperative complications were analyzed. Results: Fifteen surgeries were performed successfully. The mean ± standard deviation age of the patients was 37 ± 10.8 years, the average duration of surgery was 146.5 ± 34.6â min, and the median intraoperative blood loss was 11.1 ± 6.3â mL. None of the surgeries were converted to open thyroidectomy. According to postoperative pathology, all cases involved papillary thyroid carcinoma or papillary thyroid microcarcinoma. One patient developed transient recurrent laryngeal nerve paralysis. No patient developed skin numbness at the center of the chin region. Conclusions: Transoral endoscopic thyroidectomy via the submental and vestibular approach is effective and safe in patients with thyroid cancer and does not lead to skin numbness at the center of the chin region. This technique is beneficial for surgeons less experienced in performing transoral thyroid surgery as it involves using a short and direct route to the thyroid gland, which can reduce the difficulty in establishing the first operative space to some extent.
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Purpose: Complete lymph node dissection is essential for the management of papillary thyroid carcinoma (PTC) with lymph node metastasis (LNM). This work aimed to describe the feasibility of endoscopic lateral neck dissection via the breast and transoral approach (ELNDBTOA) in PTC patients and the necessity of the addition of the transoral approach. Methods: We included 13 patients with PTC and suspected lateral LNM who underwent ELNDBTOA at the Zhongshan Hospital, Xiamen University. Total thyroidectomy, ipsilateral central lymph node dissection, and selective neck dissection (levels IIA, IIB, III, and IV) were performed endoscopically via the breast approach. Residual lymph nodes were further dissected via the transoral approach. Results: The mean operation time was 362.1 ± 73.5â min. In the lateral neck compartments, the mean number of retrieved lymph nodes was 36.6 ± 23.8, and the mean number of positive lymph nodes was 6.8 ± 4.7. In further dissection via the transoral approach, lymph nodes in the lateral neck compartment were obtained in nine patients (9/13, 69.2%), and three patients (3/13, 23.1%) had confirmed lateral neck metastases. Transient hypocalcemia occurred in two patients (2/13, 15.4%), and three patients (3/13, 23.1%) developed transient skin numbness in the mandibular area. No other major complications were observed. There was no evidence of local recurrence or distant metastasis during the follow-up period (range, 24-87 months). All patients were satisfied with the good cosmetic outcome. Conclusion: ELNDBTOA is an option with proven feasibility for select PTC patients with LNM, and the addition of the transoral approach is necessary to ensure complete dissection.
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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global crisis due to strong infectivity and fast transmission speed. Some patients with Coronavirus Disease 2019 (COVID-19) progress rapidly and may develop fatal complications, which brings serious challenges in disease assessment and treatment. Recent progress in the understanding of the molecular biology of SARS-CoV-2 has led to the identification of a variety of laboratory biomarkers that could be potentially applied to clinical practice for the diagnosis, treatment, and prognosis of patients with COVID-19. In this review we summarize the updated status on the identification of COVID-19 related laboratory markers, and propose further direction on the application of these markers to clinical diagnosis and management of patients with COVID-19.
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COVID-19 , Biomarcadores , Humanos , Laboratorios , SARS-CoV-2RESUMEN
On 12 May 2008, the Wenchuan earthquake struck in Sichuan, China. Within 1 month after the earthquake, 98 injured children were admitted to the Children's Hospital of Chongqing Medical University. According to clinical manifestations, 50 children were diagnosed with wound infections. Wound secretions were cultured for bacteria. Pathogen distribution and drug resistance were analyzed. A total of 99 pathogens were isolated; 16 (16%) were Gram-positive bacteria and 81 (82%) were Gram-negative bacteria. The distribution of pathogens isolated within 1 month after the earthquake was different to the distribution of pathogens in 546 general hospitalized cases in the y before the earthquake. The pathogens most frequently isolated 1 month after the earthquake were Acinetobacter baumannii (27%), Enterobacter cloacae (18%) and Pseudomonas aeruginosa (13%). The pathogens most frequently isolated in the y prior to the earthquake were Escherichia coli (27%), Staphylococcus aureus (23%) and coagulase-negative staphylococci (9%). The rate of isolated drug-resistant bacteria was higher in the earthquake cases than in the general hospitalized cases. In the cases injured in the earthquake, the rates of isolation of methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing E. cloacae, E. coli and Klebsiella pneumoniae were higher than in the cases from before the earthquake. Multidrug-resistant and pandrug-resistant A. baumannii were isolated at a higher rate in cases after the earthquake than in those before the earthquake. These changes in the spectrum of pathogens and in the drug resistance of the pathogens isolated following an earthquake will provide the basis for emergency treatment after earthquakes.
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Antibacterianos/farmacología , Bacterias/clasificación , Bacterias/efectos de los fármacos , Infecciones Bacterianas/microbiología , Terremotos , Infección de Heridas/microbiología , Heridas y Lesiones/complicaciones , Adolescente , Bacterias/aislamiento & purificación , Niño , Preescolar , China , Farmacorresistencia Bacteriana , Femenino , Hospitales de Enseñanza , Humanos , Masculino , Pruebas de Sensibilidad MicrobianaRESUMEN
Purpose: Transoral endoscopic thyroidectomy via vestibular approach (TOETVA), with its excellent cosmetic effect, has become increasingly popular worldwide. Nonetheless, anatomic obstacles have limited its development to a certain extent. Here, we present our preliminary outcomes of transoral endoscopic thyroidectomy via submental and vestibular approach (TOETSMVA), which can overcome those limitations. Methods: From November 2019 to March 2020, we performed TOETSMVA in 21 consecutive patients with thyroid carcinoma at Zhongshan Hospital, Xiamen University. A 1.5-cm lateral incision was made at two fingers below the mandible; two 5-mm incisions were made in the vestibule near the first molars; TOETSMVA was completed through these incisions. The demographic data and surgical outcomes of the patients were retrospectively reviewed. Results: Twenty-one patients with a mean age of 37.5 ± 10.4 years were incorporated into this study. Fourteen patients had papillary thyroid micro-carcinomas, two had papillary thyroid carcinomas, and five had benign nodules. Eight patients had lymph node metastases. All surgeries were performed successfully without conversion to open thyroidectomy. The mean operation time was 138.8 ± 33.2 min; the average hospital stay was 3.3 ± 0.8 days. No patients developed cutaneous paralysis in the midline chin region. Transient recurrent laryngeal nerve paralysis was observed in one patient. There was no evidence of postoperative bleeding, infection, tetany, or other complications. Conclusion: TOETSMVA was shown to be a safe and advisable alternative for selected patients. This approach can overcome the limitations of TOETVA without sacrificing cosmetic results.
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Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials.
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Neoplasias Encefálicas/diagnóstico por imagen , Colina/análogos & derivados , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Radiofármacos , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Glioblastoma/diagnóstico por imagen , Xenoinjertos , Humanos , Procesamiento de Imagen Asistido por Computador , Mediciones Luminiscentes/métodos , RatonesRESUMEN
Dengue fever is the most important arthropod-transmitted viral disease affecting humans. It is a blood-borne disease characterized by persistent fever and joint pain. In the blood, primary peripheral blood mononuclear cells (PBMCs), in particular monocytes, are the main target of the dengue virus (DENV). These cells are poorly permissive for in vitro dengue virus infection and their infectivity varies from donor to donor. To overcome this barrier, an anti-dengue antibody was used to improve the infectivity of DENV-2 clinical isolates to PBMCs, the monocytic leukemia cell line, THP-1 and the granulocyte cell line, KU812. A higher throughput 96-well-format assay based on a fluorescent-activated cell sorter could potentially be developed to evaluate the antiviral potency of compounds in DENV-infected PBMCs in vitro. The results correlate well with data obtained by a standard plaque assay. Altogether, an assay has been developed that enables evaluation of the antiviral activity of test compounds in a physiologically-relevant cell system (PBMCs). These screening processes are urgently needed for dengue drug discovery.
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Antivirales/aislamiento & purificación , Virus del Dengue/efectos de los fármacos , Dengue/virología , Evaluación Preclínica de Medicamentos/métodos , Citometría de Flujo/métodos , Granulocitos/virología , Monocitos/virología , Antivirales/farmacología , Línea Celular , HumanosRESUMEN
Dengue virus (DENV) infection could lead to dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The disease outcome is controlled by both viral and host factors. Inflammation mediators from DENV-infected cells could contribute to increased vascular permeability, leading to severe DHF/DSS. Therefore, suppression of inflammation could be a potential therapeutic approach for treatment of dengue patients. In this context, p38 MAPK (mitogen-activated protein kinase) is a key enzyme that modulates the initiation of stress and inflammatory responses. Here we show that SB203580, a p38 MAPK inhibitor, suppressed the over production of DENV-induced pro-inflammatory mediators such as TNF-α, IL-8, and RANTES from human PBMCs, monocytic THP-1, and granulocyte KU812 cell lines. Oral administration of SB203580 in DENV-infected AG129 mice prevented hematocrit rise and lymphopenia, limited the development of inflammation and pathology (including intestine leakage), and significantly improved survival. These results, for the first time, have provided experimental evidence to imply that a short term inhibition of p38 MAPK may be beneficial to reduce disease symptoms in dengue patients.
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Dengue/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Imidazoles/uso terapéutico , Inflamación/tratamiento farmacológico , Piridinas/uso terapéutico , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Permeabilidad Capilar/efectos de los fármacos , Línea Celular , Quimiocina CCL5/biosíntesis , Cricetinae , Culicidae , Dengue/virología , Virus del Dengue/patogenicidad , Inhibidores Enzimáticos/farmacología , Hematócrito , Humanos , Imidazoles/farmacología , Interleucina-8/biosíntesis , Linfopenia/prevención & control , Ratones , Piridinas/farmacología , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
This work presents a modified method, namely coaxial electrohydrodynamic atomization, for the preparation of microspheres with distinct core/shell structures. This allows the encapsulation of two drugs with different characteristics in hydrophilic properties in one single step. Variation of ratios between outer flow and inner flow produces polymer microspheres with different core/shell ratios, and consequently results in variable release rates of drugs. Significant changes in release patterns were demonstrated when the distributions of the two drugs in microspheres were swapped. Moreover, cell culture experiments and animal experiments have been carried out to testify the performances of different microspheres in cytotoxicity, cellular apoptosis in vitro and tumor inhibition against subcutaneous U87 glioma xenograft in BALB/c nude mice. These findings present the advantages and possible application of this kind of multi-drug release system in treating brain tumors. Moreover, the release rates and characteristic sequences of multi-drugs can be tailored and tuned according to treatment necessity and applied in treating other kinds of tumors.
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Neoplasias Encefálicas/tratamiento farmacológico , Microesferas , Paclitaxel/uso terapéutico , Suramina/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Bioensayo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Mediciones Luminiscentes , Masculino , Ratones , Ratones Desnudos , Microscopía Electrónica de Rastreo , Paclitaxel/farmacología , Tejido Subcutáneo/patología , Suramina/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Pharmacokinetics and therapeutic efficacy of submicron/nanoscale, intracranial implants were evaluated for treating malignant glioblastoma in mice. 9.1% (w/w) paclitaxel-loaded polylactide-co-glycolide (PLGA) nanofiber discs (F3) were fabricated and characterized for morphology and size distribution. Along with F3, three other formulations, 9.1% (w/w) paclitaxel-loaded PLGA submicron-fiber discs (F2), 16.7% (w/w) paclitaxel-loaded PLGA microspheres entrapped in hydrogel matrices (H80 and M80) were intracranially implanted in BALB/c mice and the coronal brain sections were analyzed for bio-distribution of paclitaxel on 14, 28 and 42 days post-implantation. BALB/c nude mice with intracranial human glioblastoma (U87 MG-luc2) were used in the therapeutic efficacy study. Animals were randomized to intracranial implantation of F3 and H80 with paclitaxel dose of 10mg/kg, placebo F3, placebo H80, weekly intratumoral injection of Taxol (10mg/kg) or no treatment and the treatment response was analyzed by bioluminescence imaging and histological (H&E, Ki-67) examinations. Enhanced, therapeutic paclitaxel penetration (approximately 1 microm) in the mouse brain up to 5mm from the implant site even after 42 days post-implantation from F3 and H80 was confirmed and deduced to be diffusion/elimination controlled. F3 and H80 demonstrated significant (approximately 30 fold) tumor inhibition and significantly low tumor proliferation index after 41 days of treatment in comparison to sham and placebo controls. The submicron/nanoscale implants are able to demonstrate optimal paclitaxel pharmacokinetics in the brain/tumor with significant tumor inhibition in a glioblastoma xenograft model in mice and hence could be potentially useful to treat highly recurrent GBM.
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Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Nanoestructuras/administración & dosificación , Nanoestructuras/química , Paclitaxel/administración & dosificación , Paclitaxel/farmacocinética , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacocinética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Implantes de Medicamentos/administración & dosificación , Implantes de Medicamentos/química , Implantes de Medicamentos/farmacocinética , Glioblastoma/patología , Masculino , Tasa de Depuración Metabólica , Ratones , Ratones Endogámicos BALB C , Paclitaxel/química , Resultado del TratamientoRESUMEN
OBJECTIVE: To analyze the factors affecting the occurrence and severity of crush syndrome (CS) after crush injury (CI) in pediatric trauma victims in the Wenchuan earthquake. METHODS: Medical records of 98 patients who were transferred to our hospital were retrospectively reviewed. The risk factors, such as age, gender, time being besieged, type of injury, wound infection, hemodialysis, etc., which were assessed with T-test/chi(2)/Fisher's exact tests and logistic regression analysis for the occurrence of crush syndrome after crush injury. Possible risk factors influencing CS severity were analyzed. RESULTS: There were 15 patients with CS, and all these cases were from 59 patients with extremities crush injury. The incidence of CS reached 15.3% in pediatric trauma victims after earthquake and 25.4% in extremities crush injury. Six risk factors were assessed with logistic regression analysis for three outcomes relating to crush syndrome, they are age, time being szeged and closed CI, whose log-odds ratio (log-OR) respectively was 1.049, 1.221, and 0.068 (P < 0.05 for all). And no correlation was found between CS and gender, upper or lower limbs injury or wound infection. There was no significant difference in wounds infection rate between patients with open injury and those who underwent CS fasciotomy (P = 0.754), but there was significant difference between those patients who underwent CS fasciotomy and those who underwent other operative incisions (P < 0.05). Wound infection had a significant association with severity of CS (P = 0.041) as compared with other factors such as age, gender, and time being szeged. CONCLUSION: The occurrence of crush syndrome is mainly because of extremities crush injury and also has significant relations with age, time being szeged and closed crush injury in children. Infection of incisional wound after CS fasciotomy is a risk factor for aggravation of CS.
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Síndrome de Aplastamiento , Desastres , Terremotos , Puntaje de Gravedad del Traumatismo , Adolescente , Niño , Preescolar , China , Femenino , Humanos , Masculino , Factores de RiesgoRESUMEN
OBJECTIVE: To investigate the distribution and the drug resistance pattern of pathogenic bacteria isolated from pediatric cases suffering from wounds infection following the Wenchuan earthquake. METHODS: Of the ninety-eight injured children, 50 had wound infection diagnosed by clinical examination. Specimens for culture were collected from the fifty injured children and the results of bacterial identification and antibiotic resistance were retrospectively reviewed. RESULTS: In the fifty injured children with wound infection, microbial growth was detected in 31 (62.0%) and 21 children suffered from mixed infections (the infection rate was 67.7%). Ninety-nine pathogens were isolated, gram positive bacteria accounted for 16.16% (16 strains), Gram negative bacteria accounted for 81.82% (81 strains), and fungus 2.02% (2 strains). Staphylococcus aureus (5 strains, 5.05%), Enterococcus faecalis (3 strains, 3.03%) and Enterococcus faecium (2 strains, 2.02%) were the primary Gram-positive bacteria identified and Gram-negative infections typically included Acinetobacter baumanii (27 strains, 27.27%), Enterobacter cloacae (18 strains, 18.18%) and Pseudomonas aeruginosa (13 strains, 13.13%). Acinetobacter baumanii was the most common organism isolated from wounds. Duration of being szeged and complications had a significant association with wound infection with Acinetobacter baumanii. Drug sensitivity tests displayed that the isolated bacteria were highly resistant to common antibiotics. One strain of Acinetobacter baumanii-calcoaceticus complex and six strains of Acinetobacter baumanii were resistant to all common antibiotics including imipenem/cilastatin. Vancomycin-resistant Gram-positive bacteria were not identified. CONCLUSION: Following the Wenchuan earthquake disaster, wound infection profiles of pediatric patients were significantly different, Acinetobacter baumanii was the main common organism isolated from wounds in contrast to the previous low isolation rate. The isolated bacteria were highly and multiple drug resistant and it was difficult to treat. Knowing the distribution and the drug resistance pattern of pathogen is of paramount importance in guiding the clinical treatment.
Asunto(s)
Desastres , Farmacorresistencia Bacteriana , Terremotos , Heridas y Lesiones/microbiología , Adolescente , Niño , Preescolar , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/aislamiento & purificación , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Infección de Heridas/microbiologíaRESUMEN
In this study, the cardioprotective effects of nitric oxide (NO)-aspirin, the nitroderivative of aspirin, were compared with those of aspirin in an anesthetized rat model of myocardial ischemia-reperfusion. Rats were given aspirin or NO-aspirin orally for 7 consecutive days preceding 25 min of myocardial ischemia followed by 48 h of reperfusion (MI/R). Treatment groups included vehicle (Tween 80), aspirin (30 mg.kg(-1).day(-1)), and NO-aspirin (56 mg.kg(-1).day(-1)). NO-aspirin, compared with aspirin, displayed remarkable cardioprotection in rats subjected to MI/R as determined by the mortality rate and infarct size. Mortality rates for vehicle (n = 23), aspirin (n = 22), and NO-aspirin groups (n = 22) were 34.8, 27.3, and 18.2%, respectively. Infarct size of the vehicle group was 44.5 +/- 2.7% of the left ventricle (LV). In contrast, infarct size of the LV decreased in the aspirin- and NO-aspirin-pretreated groups, 36.7 +/- 1.8 and 22.9 +/- 4.3%, respectively (both P < 0.05 compared with vehicle group; P < 0.05, NO-aspirin vs. aspirin ). Moreover, NO-aspirin also improved ischemia-reperfusion-induced myocardial contractile dysfunction on postischemic LV developed pressure. In addition, NO-aspirin downregulated inducible NO synthase (iNOS; 0.37-fold, P < 0.01) and cyclooxygenase-2 (COX-2; 0.61-fold, P < 0.05) gene expression compared with the vehicle group after 48 h of reperfusion. Treatment with N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg), a nonselective NOS inhibitor, aggravated myocardial damage in terms of mortality and infarct size but attenuated effects when coadministered with NO-aspirin. L-NAME administration did not alter the increase in iNOS and COX-2 expression but did reverse the NO-aspirin-induced inhibition of expression of the two genes. The beneficial effects of NO-aspirin appeared to be derived largely from the NO moiety, which attenuated myocardial injury to limit infarct size and better recovery of LV function following ischemia and reperfusion.