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C-terminus of HSP70 interacting protein (CHIP) is an E3 ubiquitin ligase and HSP70 cochaperone. Mutations in the CHIP encoding gene are the cause of two neurodegenerative conditions: spinocerebellar ataxia autosomal dominant type 48 (SCA48) and autosomal recessive type 16 (SCAR16). The mechanisms underlying CHIP-associated diseases are currently unknown. Mitochondrial dysfunction, specifically dysfunction in mitochondrial autophagy (mitophagy), is increasingly implicated in neurodegenerative diseases and loss of CHIP has been demonstrated to result in mitochondrial dysfunction in multiple animal models, although how CHIP is involved in mitophagy regulation has been previously unknown. Here, we demonstrate that CHIP acts as a negative regulator of the PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy pathway, promoting the degradation of PINK1, impairing Parkin translocation to the mitochondria, and suppressing mitophagy in response to mitochondrial stress. We also show that loss of CHIP enhances neuronal mitophagy in a PINK1 and Parkin dependent manner in Caenorhabditis elegans. Furthermore, we find that multiple disease-associated mutations in CHIP dysregulate mitophagy both in vitro and in vivo in C. elegans neurons, a finding which could implicate mitophagy dysregulation in CHIP-associated diseases.
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BACKGROUND: The effect of intraoperative anesthetic regimen on pulmonary outcome after minimally invasive esophagectomy for esophageal cancer is yet undetermined. The aim of this study was to determine the effect of volatile anesthesia (sevoflurane or desflurane) compared with propofol-based intravenous anesthesia on pulmonary complications after minimally invasive esophagectomy. METHODS: Patients scheduled for minimally invasive esophagectomy were randomly assigned to 1 of 3 general anesthetic regimens (sevoflurane, desflurane, or propofol). The primary outcome was the incidence of pulmonary complications within the 7 days postoperatively, which was a collapsed composite end point, including respiratory infection, pleural effusion, pneumothorax, atelectasis, respiratory failure, bronchospasm, pulmonary embolism, and aspiration pneumonitis. The severity of pulmonary complications, surgery-related complications, and other secondary outcomes were also assessed. RESULTS: Of 647 patients assessed for eligibility, 558 were randomized, and 553 were analyzed. A total of 185 patients were assigned to the sevoflurane group, 185 in the desflurane, and 183 in the propofol group. Patients receiving a volatile anesthetic (sevoflurane or desflurane) had a significantly lower incidence (36.5% vs 47.5%; odds ratio, 0.63; 95% confidence interval, 0.44-0.91; P = .013) and lower severity grade of pulmonary complications ( P = .035) compared to the patients receiving propofol. There were no statistically significant differences in other secondary outcomes between the 2 groups. CONCLUSIONS: In patients undergoing minimally invasive esophagectomy, the use of volatile anesthesia (sevoflurane or desflurane) resulted in the reduced risk and severity of pulmonary complications within the first 7 postoperative days as compared to propofol-based intravenous anesthesia.
Assuntos
Anestesia Intravenosa , Anestésicos Inalatórios , Anestésicos Intravenosos , Desflurano , Esofagectomia , Pneumopatias , Complicações Pós-Operatórias , Propofol , Sevoflurano , Humanos , Esofagectomia/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Anestésicos Inalatórios/efeitos adversos , Anestésicos Inalatórios/administração & dosagem , Propofol/administração & dosagem , Propofol/efeitos adversos , Anestesia Intravenosa/efeitos adversos , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/efeitos adversos , Desflurano/administração & dosagem , Pneumopatias/etiologia , Sevoflurano/administração & dosagem , Sevoflurano/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Neoplasias Esofágicas/cirurgia , Anestesia por Inalação/efeitos adversosRESUMO
PURPOSE: Chemotherapy is commonly used for treatment in children over three years old with high-risk medulloblastoma(MB). However, little is currently known about the therapeutic benefits and side effects of intrathecal methotrexate(MTX), warranting further research. METHODS: In this retrospective study, patients who received intrathecal MTX during chemotherapy were included in the MTX group (n = 32), and patients that only underwent cerebrospinal fluid (CSF) cytology analysis were assigned to the control group (n = 14). RESULTS: In the MTX group, 27(84.38%) patients had metastatic disease, 3(9.38%) had diffuse anaplasia, and 3(9.38%) had residual disease greater than 1.5 cm2. Molecular subgroup classification was available for 28(87.5%) patients. In the control group, 8(57.14%) patients had metastatic disease, 3(27.27%) had diffuse anaplasia, and 6(42.86%) had residual disease greater than 1.5 cm2. Molecular subgroup classification was available for 6(42.86%) patients. The 5-year progression-free survival was 70.99% and the 5-year overall survival was 72.99% for the MTX group, and the corresponding values were 41.67% and 50% for the control group, respectively. 6 (18.75%) patients in the MTX group with group 4 disease developed MTX-related acute leukoencephalopathy and one of them died. CONCLUSIONS: Our findings support the addition of intrathecal MTX during chemotherapy as the optimal management for children with group 3 and SHH high-risk MB. However, it is not recommended for group 4 MB patients, especially in resource-limited regions. TRIAL REGISTRATION NUMBER: Retrospective registered No.(2020 - 117).
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Neoplasias Cerebelares , Meduloblastoma , Criança , Humanos , Pré-Escolar , Metotrexato/efeitos adversos , Meduloblastoma/patologia , Estudos Retrospectivos , Anaplasia/induzido quimicamente , Anaplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Cerebelares/patologiaRESUMO
Several studies have examined the functions of nucleic acids in small extracellular vesicles (sEVs). However, much less is known about the protein cargos of sEVs and their functions in recipient cells. This study demonstrates the presence of lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, in the culture medium of gastric cancer cells. We show that sEVs derived from gastric cancer cells and the plasma of patients with gastric cancer harbor LSD1. The shuttling of LSD1-containing sEVs from donor cells to recipient gastric cancer cells promotes cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2, and CD44. Additionally, sEV-delivered LSD1 suppresses oxaliplatin response of recipient cells in vitro and in vivo, whereas LSD1-depleted sEVs do not. Taken together, we demonstrate that LSD1-loaded sEVs can promote stemness and chemoresistance to oxaliplatin. These findings suggest that the LSD1 content of sEV could serve as a biomarker to predict oxaliplatin response in gastric cancer patients.
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Vesículas Extracelulares , Neoplasias Gástricas , Histona Desmetilases/genética , Humanos , Lisina , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genéticaRESUMO
Jujube (Zizyphus jujuba Mill.), a native small deciduous tree of China, is widely cultivated in China, Korea, India, Japan, Europe, and the United States (Chen et al. 2020). The fruit have been commonly consumed as healthy food supplements and traditional Chinese medicine for over 2000 years (Li et al. 2007). In August 2019, anthracnose-like leaf spot symptoms were observed on jujube plants in Xiaomenya Village, Jinan City, Shandong Province, China (36°27'39â³N, 117°3'13â³E), with over 30% leaf disease incidence. The spots were circular, sunken, brown in the center and with dark brown edges. As the spots enlarged and coalesced, it resulted in leaf perforation and early defoliation. Sometimes acervuli were observed on the lesions (Fig. S1a, b). To identify the causal agent, 20 diseased leaves were sampled, the margins of the lesions were cut into pieces (5 × 5 mm), sterilized and cultured following the protocol described previously (Wan et al. 2020) at 25 â for 5 days. Twelve monospore isolates showing identical colony morphology were obtained. Three representative isolates, JNZG11, JNZG311, JNZG313, were used for further study. When grown on PDA the colony color was initially white and then turned pale-gray to gray in 5-day-old cultures. On the reverse, colonies were brown-black with an orange pigmentation near the center. Aerial mycelium was cottony, dense, white to pale-gray. Conidia were hyaline, 1-celled, smooth-walled, subcylindrical, oblong, attenuated with slightly rounded ends, (11.1-) 12.7-13.3 (-17.8) ×(-4.4) 5.2-5.5 (-6.3) µm (n=50). Appressoria were dark-brown, oval or irregular, (7.3-) 8.6-9.2 (-9.8) ×(-5.1) 5.8-6.9 (-7.0) µm (n=50) (Fig. S1c-g). The morphology resembled those of Colletotrichum gloeosporioides species complex (Cannon et al. 2012). For accurate identification, the sequences of the ribosomal internal transcribed spacer (ITS), actin (ACT), ß-tub2 (TUB2), calmodulin (CAL), chitin synthase (CHS-1), and glyceraldehyde-3phosphate dehydrogenase (GAPDH) of the 3 isolates were sequenced (Weir et al. 2012), and deposited into GenBank (Accession Nos. see Table 1). The six loci (ITS, GAPDH, ACT, CHS-1, CAL, and TUB2) were concatenated and the aligned sequences (1904 bp) were 99.7% homologous to ex-type C. siamense ICMP18578. The sequences of 38 Colletotrichum species (44 isolates) were downloaded from GenBank for phylogenetic analyses. In the maximum likelihood phylogenetic tree generated, the highest log likelihood was -8798.90 and the three isolates were all in the C. siamense clade (bootstrap support 94 %) (Fig. S2). To complete Koch's postulates, 60 healthy, mature jujube leaves on 12 branches (5 leaves per branch) (variety 'Zhongqiuhong') were inoculated with 20 µL of spore suspension (106 conidia/mL) or sterile water as a control. The branches were placed in sterile beakers containing a small amount of sterile water sealed with plastic wrap and maintained at 28 °C, 12 h light/dark. Five days after inoculation, all treated leaves showed the typical anthracnose symptom, similar to that observed in the field (Fig. S1h). The same fungus was re-isolated from the margins of the lesions using the aforementioned methods. Whereas no fungus were isolated from the controls. Previously, C. siamense has been reported to infect Z. mauritiana in China (Shu et al. 2020). To our knowledge, this is the first report of C. siamense causing anthracnose on Z. jujuba in China. This finding provides crucial information for the effective management of this disease.
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The present study was aimed to explore the involvement of dopamine D1 receptor of the anterior cingulate cortex (ACC) in the regulation of chronic inflammatory pain-related emotion. On the first day, the rats were acclimated to the environment and the baseline indices were measured. On the second day, the rats were administered with the dopamine D1 receptor antagonist SCH-23390 or agonist SKF38393 in the ACC, and then they were subcutaneously injected with complete Freund's adjuvant (CFA, 0.08 mL) in the left hind paw to establish conditioned place avoidance (CPA) response after pairing with specific environment. On the third day, the CPA response and the firing frequency of ACC neurons were observed synchronously, and the open-field behavior, mechanical pain behavior and paw withdrawal latency (PWL) tests were also observed subsequently. In other experiments, rats were given subcutaneous injection of normal saline (NS) on the left hind paw after SCH-23390 or SKF-38393 was administered in the ACC, and then the same observations were performed. The results showed that: (1) Compared with the control group, the PWL and mechanical pain thresholds of rats injected with CFA on the left hind paw were significantly decreased (P < 0.05); (2) The residence time of rats injected with CFA in the "pain environment" and open field center was significantly shortened (P < 0.05); (3) Pre-injection of antagonist SCH-23390 in ACC (10 µg) alleviated the anxiety-like negative behavior response induced by CFA (P < 0.05) and reversed CFA-induced increases of discharge frequency of ACC neurons (P < 0.05); (4) Pre-injection of agonist SKF-38393 in the ACC (10 µg) induced CPA-like behavioral response in rats injected with NS in the left hind paw, and increased the firing frequency of ACC neurons (P < 0.05); (5) Immunofluorescence detection showed that dopamine D1 receptor and NMDA receptor were co-expressed in the same neuron. These results suggest that inhibition of dopamine D1 receptor in ACC can alleviate the negative emotional response induced by persistent pain.
Assuntos
Dor Crônica , Giro do Cíngulo , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/efeitos adversos , Animais , Ansiedade , Hiperalgesia , Ratos , Receptores de Dopamina D1/metabolismoRESUMO
BACKGROUND: Currently, no available coherent management protocol exists for pediatric cancers associated with pleural effusion, ascites, and pericardial effusion. This study aimed to retrospectively present our experience in treating pediatric cancer patients with pleural effusion, ascites, and pericardial effusion using interleukin-2 (IL-2) and dexamethasone (DEX) intracavitary injections. METHODS: Between January 1st, 2008 and December 31st, 2020, medical reports of patients diagnosed with solid tumors or lymphoma were checked to identify patients diagnosed with > 2 cm pleural effusion, and/or more than grade 1 ascites, and/or more than small pericardial effusion. Patients diagnosed with effusions and treated with IL-2 and DEX were identified as being in the effusion group. Meanwhile, patients with the same primary tumors and effusions but did not receive interleukin 2 and DEX injection were reviewed and classified as the control group. RESULTS: Forty patients with solid tumors and 66 patients with lymphoma were further diagnosed with pleural effusion, ascites, or pericardial effusion. A total of 85 patients received IL-2 and DEX injection while the remaining 21 did not. The Kaplan Meier analysis revealed a significant difference between the two groups, with p < 0.01 for event free survival (EFS) and p < 0.01 for overall survival (OS), both of which had p < 0.01. Hazard ratio was found to be 0.344 for OS and 0.352 for EFS. CONCLUSIONS: This retrospective study illustrates that thoracic, intraperitoneal, or pericardial intracavitary injection of DEX plus IL-2 can be an effective and safe treatment for pediatric cancers with pleural effusion, ascites, and pericardial effusion.
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Dexametasona/uso terapêutico , Interleucina-2/metabolismo , Linfoma/tratamento farmacológico , Derrame Pleural Maligno/tratamento farmacológico , Criança , Pré-Escolar , Estudos de Coortes , Dexametasona/farmacologia , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
Cornus hongkongensis (Hemsl.) is an excellent ornamental tree species in China and elsewhere. In 2019, C. hongkongensis anthracnose was firstly observed at the campus of Jiangxi Agricultural University (JXAU) (28°45'56â³N, 115°50'21â³E), then found in parks, Nanchang, China. In early August, the disease appeared and lasted until the leaves dropped (November). The disease incidence was above 60%, and the diseased leaf rate was above 70%. The lesions mostly appeared along the leaf edges. Some small round to irregular lesions also developed in other parts of the leaves. These diseased leaves had circular or irregularly shaped spots with gray-white color in the center and dark brown on the edge of the lesions. Later, the lesions became necrotic and shriveled. As the disease progressed, the spots coalesced so that affected leaves appeared blighted (Supplementary Figure 1 A-C). To identify the pathogen, leaves with typical symptoms from the campus of JXAU were collected and small pieces (5 × 5 mm) from the lesion borders were surfaced sterilized in 70% ethanol for 30 s, followed by 1 min in 3% NaOCl, and then rinsed with sterile distilled water three times. Leaf pieces were placed on potato dextrose agar (PDA) and incubated at 25 °C under a 12-h light/dark cycle (3000 lx). Pure cultures were obtained from individual conidia by single spore isolates. For studies of microscopic morphology, a representative isolate JX-S4 was subcultured on PDA. The colony of JX-S4 was white and turning gray and light gray on the reverse side, producing dark-green pigmentation near the center (Supplementary Figure 1 D). The conidia were one-celled, straight, hyaline, subcylindrical with rounded ends and 16.9 ± 1.6 × 6.0 ± 0.6 µm (n = 50) in size. Appressoria were one-celled, pale brown, thick-walled, ellipsoidal, and measured 8.7 ± 1.7 × 6.4 ± 0.8 µm (n = 50) (Supplementary Figure 1 E, F). The morphological characteristics of JX-S4 matched those of the Colletotrichum siamense species (Weir et al. 2012). For accurate identification, the internal transcribed spacer (ITS) and the genes encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH), chitin synthase (CHS-I), beta-tubulin 2 (TUB2), and calmodulin (CAL) were respectively amplified with primers ITS1/ITS4, GDF/GDR, CHS-79F/CHS-345R, ßt2a/ßt2b, and CL1/CL2. The sequences were deposited in GenBank (Accession nos. MT587807, MT628710, MT628709, MT628711, and MT628708). Phylogenetic analysis was calculated with concatenated sequences (ITS, GAPDH, CHS-I, CAL, and TUB2) using MEGA 7. In the maximum likelihood phylogenetic tree, Isolate JX-S4 was clustered with C. siamense with 93% bootstrap support (Supplementary Figure 2). Based on the morphological characteristics and phylogenetic analysis, JX-S4 was identified as C. siamense. Pathogenicity test of JX-S4 was verified on 45 attached healthy leaves from three C. hongkongensis plants (10-year-old) at the campus of JXAU inoculated with mycelial plugs (φ=5 mm) from the culture edge (6-day-old) on PDA. And an additional 45 healthy leaves were inoculated with PDA plugs as controls. The leaves were wounded with a red-hot needle (φ=0.5 mm). All treatment and control leaves were wrapped up with black plastic bags to keep them moist for 2 days. The pathogenicity tests were repeated twice. Within 7 days, all the inoculated leaves developed the lesions, which were similar to those observed in the field. Control leaves were asymptomatic (Supplementary Figure 1 G, H). The same fungus was re-isolated from the symptomatic tissues, fulfilling Koch's postulates. To our knowledge, this is the first report of C. siamense causing C. hongkongensis anthracnose. This finding provides crucial information for managing this disease. For example, when diagnosing Cornus anthracnose, C. siamense needs to be looked out for and appropriate control measures implemented.
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BACKGROUND: There is no consensus about how to manage pulmonary metastasis in patients with hepatoblastoma. We reviewed a treatment with a combination of oxaliplatin, vincristine, and topotecan (OVT) paired with radiofrequency ablation (RFA) of 12 patients with multiple refractory / recurrent pulmonary hepatoblastoma. METHODS: The medical records from patients with ≤21 years of age presenting with multiple deposits (≥2) of refractory / recurrent pulmonary hepatoblastoma were reviewed. The following data were extracted from each patient: age, gender, histological subtyping, cycles of OVT, tumor size, biomarkers, chemotherapy regimen and dosage, RFA details, treatment response, follow up, and patient outcomes. The primary outcome measure was the complete response (CR) of pulmonary diseases, and secondary outcomes were event-free survival rate and overall survival rate. RESULTS: Of 12 assessable patients, three (25%) (95% CI, 46.3-104) patients achieved PR (partial resopnse) after they finished OVT. After RFA, five (41.7%) (95% CI, 8.95-74.4) patients achieved CR (complete response). The 2 year event-free survival rate was 33% (95% CI, 20.5-64.6). The 2 year overall survival for the study group was 41.7% (95% CI, 8.9-74.4). All toxicity events were handled satisfactorily and no toxic related deaths were observed. CONCLUSIONS: Our review report shows that OVT combined with RFA can be a successful treatment modality for previously heavily treated refractory / recurrent pulmonary metastatic lesions from hepatoblastoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Hepatoblastoma/terapia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Ablação por Radiofrequência/métodos , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Hepatoblastoma/mortalidade , Hepatoblastoma/secundário , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/mortalidade , Masculino , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Oxaliplatina/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Topotecan/administração & dosagem , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
Capillary leak syndrome (CLS) is a rare but fatal disease, which has been reported following the infusions of interleukin-2, tumor necrosis factor, granulocyte-colony stimulating factor, certain monoclonal antibodies, and gemcitabine, suggesting that drugs can also cause CLS. In this study, seven Wilm's tumor cases with CLS had been presented, which was suggested to be caused following administration of vincristine (VCR). From January 1st, 2014 to December 31st, 2016, medical records from Wilm's tumor patients were reviewed to identify those diagnosed with CLS. Moreover, the following data were extracted for each patient, including age, gender, histological subtyping, tumor stage, risk group, biomarkers, chemotherapy regimen and dosage, surgery details, clinical manifestation of CLS, treatment regimen of CLS, and patient outcomes. From January 1st, 2014 to December 31st, 2016, a total of seven patients with Wilms tumor were identified with a diagnosis of VCR-associated CLS. Typically, for these seven cases in our study, the predominant features of CLS included interstitial pneumonia and pulmonary edema. Moreover, steroid therapy was demonstrated as the most effective therapy in our study. The clinical features of VCR-induced CLS are distinct, and pediatric oncologists should be aware of CLS that manifests as interstitial pneumonia and pulmonary edema during the VCR treatment for patients with Wilm's tumor.
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Síndrome de Vazamento Capilar/induzido quimicamente , Vincristina/efeitos adversos , Tumor de Wilms/tratamento farmacológico , Feminino , Humanos , Lactente , MasculinoRESUMO
With the evolution of medical techniques and technology, an increasing number of infants, neonates, and fetuses are exposed to general anesthesia for clinical diagnostic and therapeutic process. The neurotoxic effects of general anesthetics on developing brain have been a subject of concern and considerable research interest. Population-based study confirmed that single short-term general anesthetic exposure does not affect nervous system function, but multiple exposures to general anesthesia could damage cognitive function. Animal studies further discovered the underlying mechanisms. Nervous system is most susceptible to general anesthetics during the brain growth spurt. The time-point is more critical than the duration of exposure to general anesthetics. General anesthetics can induce intracellular calcium overload, disturb energy metabolism, promote cell apoptosis and lead to cell loss. General anesthetics can damage synaptic structure, transmission and plasticity, and impair brain function. High throughput omics technologies have been used to screen the differentially expressed genes induced by general anesthetics, which provide further understanding of the mechanism of general anesthetics affecting cognitive function. This review provides an update on the pathophysiologic mechanisms underlying the anesthesia-neurotoxicity, which will be helpful to provide instructions for the clinical use of general anesthesia in children.
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Anestésicos Gerais/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Cognição , Anestesia Geral/efeitos adversos , Animais , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologiaRESUMO
This study aims to investigate the effect of microRNA-129 (miR-129) on proliferation and apoptosis of hippocampal neurons in epilepsy rats by targeting c-Fos via the MAPK signaling pathway. Thirty rats were equally classified into a model group (successfully established as chronic epilepsy models) and a normal group. Expression of miR-129, c-Fos, bax, and MAPK was detected by RT-qPCR and Western blotting. Hippocampal neurons were assigned into normal, blank, negative control (NC), miR-129 mimic, miR-129 inhibitor, siRNA-c-Fos, miR-129 inhibitor+siRNA-c-Fos groups. The targeting relationship between miR-129 and c-Fos was predicted and verified by bioinformatics websites and dual-luciferase reporter gene assay. Cell proliferation after transfection was measured by MTT assay, and cell cycle and apoptosis by flow cytometry. c-Fos is a potential target gene of miR-129. Compared with the normal group, the other six groups showed a decreased miR-129 expression; increased expression of expression of c-Fos, Bax, and MAPK; decreased proliferation; accelerated apoptosis; more cells arrested in the G1 phase; and fewer cells arrested in the S phase. Compared with the blank and NC groups, the miR-129 mimic group and the siRNA-c-Fos group showed decreased expression of c-Fos, Bax, and MAPK, increased cells proliferation, and decreased cell apoptosis, fewer cells arrested in the G1 phase and more cells arrested in the S phase. However, the miR-129 inhibitor groups showed reverse consequences. This study suggests that miR-129 could inhibit the occurrence and development of epilepsy by repressing c-Fos expression through inhibiting the MAPK signaling pathway.
Assuntos
Apoptose/genética , Proliferação de Células/genética , Hipocampo/patologia , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/genética , Neurônios/patologia , Proteínas Proto-Oncogênicas c-fos/genética , Animais , Linhagem Celular Tumoral , Epilepsia/genética , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/genéticaRESUMO
PURPOSE: This study was to determine the efficacy of vincristine and irinotecan in children with relapsed hepatoblastoma (HB). METHODS: A total of 10 patients with relapsed HB were enrolled. Three patients were excluded. Patients received irinotecan 50 mg/m(2)/day, day 1-5 and vincristine 1.5 mg/m(2)/day, day 1, repeated every 3 weeks. The maximum cycles were eight. Reevaluation of tumor was performed every two cycles. The primary outcome was the rate of complete resection. Secondary outcomes were event-free survival (EFS) and overall survival (OS). RESULTS: Of the seven patients assessable for response, one patient with normal AFP level showed a progressive disease and withdrew. He finally died 6 months later. Four had PR, all of them underwent a second surgery and achieved complete resection. Two patients had SD, one patient relapsed 6 months after orthotopic liver transplantation and died, the other one undergoing surgery had micro margin positive, he relapsed again but alive. The rate of complete resection was 71.4% (including orthotopic liver transplantation). The 2-year EFS and OS for the whole group were 57.1% (95% CI, 12.7% to 34.2%) and 71.4% (95% CI, 16.39% to 37.4%), respectively. CONCLUSIONS: The combination of irinotecan and vincristine has a significant antitumor activity and acceptable toxicity in children with relapsed HB.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Hepatoblastoma , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Pré-Escolar , Intervalo Livre de Doença , Hepatoblastoma/mortalidade , Hepatoblastoma/terapia , Humanos , Lactente , Irinotecano , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Transplante de Fígado , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Taxa de Sobrevida , Fatores de Tempo , Vincristina/administração & dosagemRESUMO
PURPOSE: The use of neoadjuvant chemotherapy has improved the survival of patients with hepatoblastoma (HB). However, an increased number of treatment complications and toxic deaths, particularly from heart failure, have been observed with doxorubicin treatment. We have applied cisplatin as a single agent to treat children with high-risk HB to improve event-free survival (EFS). METHODS: Between 2007 and 2009, 14 patients with untreated high-risk HB were enrolled in this study. All the patients received a single-agent treatment of cisplatin. The initial cisplatin cycle was administered in a continuous intravenous 24-hour infusion of 80 mg/m/24 h. The primary outcome was the rate of complete resection. Secondary outcomes were EFS and overall survival (OS). RESULTS: Eleven patients (78.6%) had an overall partial response. Two patients (14.3%) had stable disease. One patient experienced (7.1%) progression. Of the 4 patients who presented with lung metastases initially, 1 patient achieved complete response, 2 patients achieved partial response, and 1 patient experienced progression during preoperative chemotherapy. The complete resection rate was 78.6% (95% CI, 49%-95%). The Kaplan-Meier estimates of 2-year EFS and OS for the whole group were 64.3% (95% CI, 35%-87%) and 85.7% (95% CI, 57%-98%), respectively. The 2-year EFS and OS rates of patients who achieved complete resection were 81.8% (95% CI, 48%-98%) and 100% (95% CI, 62%-100%), respectively. CONCLUSIONS: The single-agent cisplatin had less toxicity than cisplatin plus doxorubicin and achieved an equal rate of complete resection in high-risk HB compared with conventional multiagent chemotherapy.
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Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Hepatoblastoma/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adolescente , Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Hepatoblastoma/mortalidade , Hepatoblastoma/patologia , Humanos , Lactente , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The study of bacterial community diversity and metabolic function in lake water is of great significance to the healthy development of the urban landscape lake water environment. In this study, Hancheng Lake, Nanhu Lake, Xingqing Lake, and Taohuatan Lake were selected as the study area. Illumina Nova high-throughput sequencing technology was used to study the composition and structure of bacterial communities in four different types of lakes. The correlation between bacterial communities and environmental factors was analyzed using the RDA method. Tax4Fun was used to predict the metabolic function of bacterial communities. The results showed that the diversity of bacterial communities was different in different lakes. The α diversity of Taohuatan Lake was the highest, and that of Xingqing Lake was the lowest. The bacterial community structure of the same lake had a trend of aggregation. The dominant phyla of bacteria in the four lakes were similar, mainly Proteobacteria, Bacteroidetes, and Actinobacteria. The difference was only in the proportion of bacteria. Additionally, the distribution of bacterial communities at the genus level in the four lakes was quite different. The physical and chemical properties of lakes were significantly correlated with bacterial community, and the most critical factor was nitrogen and phosphorus nutrients(P<0.05). Tax4Fun function prediction showed that the metabolic function of bacterial communities in the four lakes was similar, and the relative abundance of amino acid metabolism and carbohydrate metabolism was the highest. In addition, the potential drug-resistant bacterial pollution and the possibility of human infectious diseases were higher. These results are helpful for understanding the current situation of bacteria in urban lakes in Xi'an and providing a theoretical basis for the management and sustainable development of urban lakes.
Assuntos
Bactérias , Lagos , Humanos , Lagos/química , Bactérias/genética , Proteobactérias , Bacteroidetes , Água , China , RNA Ribossômico 16SRESUMO
Net primary productivity (NPP) is an indicator to reflect the production capacity of terrestrial ecosystems, as well as a key indicator for ecological quality. NPP at large scale is difficult to be measured. At present, most of the assessment of ecosystem quality uses NPP products with low resolution, which cannot capture the detailed characteristics of the ecosystem and is not conducive to the assessment of ecosystem quality at small-scale. The establishment of a rapid and efficient assessment method for small-scale ecosystem quality will greatly promote the protection and restoration of ecosystems in China. We focused on the calculation method of ecosystem quality assessment and NPP, and optimized the calculation process of the NPP, and obtained NPP by remote sensing without ground observation data. We established a regression model for remote sensing inversion of leaf area index, and estimated the vegetation coverage by using dimidiate pixel model, developed a set of methods for rapid assessment of ecosystem quality by remote sensing. Taking Nanwenghe National Nature Reserve as an example, we evaluated the change of ecosystem quality from 2001 to 2022. The results showed that from 2001 to 2022, the ecosystem qua-lity of the reserve was good as a whole, and that the area with good and excellent quality accounted for more than 85% in 2022. High vegetation coverage was the backbone of the sustainable good ecosystem quality of the reserve. From 2001 to 2022, ecosystem quality of the reserve showed a trend of first decreasing and then increasing, with the lowest point of ecosystem quality in 2013. This method had achieved good results in the evaluation of ecosystem quality in Nanwenghe National Nature Reserve. The index optimization method proposed in this study could facilitate the rapid and accurate assessment of ecosystem quality in small-scale regions, and thus provides technical reference for the precise improvement of ecosystem quality.
Assuntos
Ecossistema , Modelos Teóricos , Tecnologia de Sensoriamento Remoto , China , Mudança ClimáticaRESUMO
BACKGROUND: Sirtuin 1, a nicotinamide adenine dinucleotide-dependent deacetylase that is highly expressed in the hippocampus and anterior cortex tissues related to Alzheimer's Disease pathology, can cross the blood-brain barrier and is a promising biomarker. METHODS: A 1:1:1 case-control study was conducted and serum fasting blood glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, SIRT1, IL-6, Aß1-42, T-tau and P-tau-181 levels were evaluated in blood samples of 26 patients form the Alzheimer's Disease group, 26 patients form the mild cognitive impairment group, and 26 individuals form the normal control group. Receiver operator characteristic curves were used to evaluate the diagnostic significance. RESULTS: Serum SIRT1 level was significantly down-regulated in the mild cognitive impairment patients and Alzheimer's Disease patients compared with that in the normal control group (P<0.05). ROC curve analysis demonstrated that SIRT1 was a promising biomarker to distinguish Alzheimer's Disease patients from the mild cognitive impairment patients and the normal control group. In addition, SIRT1 was estimated to perform well in the diagnosis of Alzheimer's Disease ([AUC] = 0.742). CONCLUSIONS: In summary, the present study suggested that serum SIRT1 might be an early promising diagnostic biomarker for Alzheimer's Disease.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/patologia , Sirtuína 1 , Estudos de Casos e Controles , Disfunção Cognitiva/patologia , Biomarcadores , Diagnóstico Precoce , Colesterol , Proteínas tau , Peptídeos beta-AmiloidesRESUMO
Purpose: This work aimed to report our experience with ultrasound-guided instillation for the treatment of lymphangiomas in children, so as to determine whether the combined use of bleomycin and dexamethasone achieved a higher response rate and a lower side effect rate. Methods: The medical records from patients with lymphangiomas between January 1st, 2013 and September 31st, 2020, were reviewed. Patients who received bleomycin combined with dexamethasone sclerotherapy were classified as the dexamethasone group, while those receiving bleomycin without dexamethasone were classified as the control group. Results: Altogether one hundred and twenty-seven patients were diagnosed with lymphangiomas. Among them, one hundred and five patients received bleomycin combined with dexamethasone injection, while the remaining twenty-two received bleomycin injection alone. The excellent rates were 89.52% [95% confidence interval (CI), 81.64-94.40%] in the dexamethasone group and 72.73% (95% CI, 52.51-92.94%) in the control group (p < 0.05). Additionally, the recurrence rates were 3.81% (95% CI, 1.22-10.03%) in the dexamethasone group and 13.64% (95% CI, 3.6-36.0%) in the control group (p > 0.05). After comparison between the two groups, the following risk factors were identified. These include >10 sacs at the initial stage of diagnosis, larger size after all injections, and response to the first injection. Conclusions: Although there was no significant difference in the recurrence rate between the two groups, this retrospective study demonstrated that the excellent response rates were dramatically improved between the two groups, suggesting that bleomycin combined with DEX was an effective and highly safe treatment for all types of pediatric lymphangiomas. Moreover, this study also identified three novel features as the significant risk factors for recurrence.
RESUMO
PURPOSE: To evaluate the clinical characteristics and treatment outcomes of Chinese children with advanced stage anaplastic large cell lymphoma (ALCL) who were treated with the low-intensity APO regimen. METHODS: Clinical data from children newly diagnosed with advanced stage ALCL and treated with the APO regimen were reviewed. RESULTS: Altogether 22 eligible patients with advanced stage ALCL were recruited in this study. 18 (81%) patients achieved complete response (CR) after the initial induction, and 4 experienced relapse. Among patients with relapsed or refractory ALCL, CR was achieved in 3 (50%) who received the BFM95 R3/R4 regimen. Besides, 2 patients received the targeted therapy with crizotinib and were still alive. The 5-year OS and EFS rates were 82 ± 8.7% and 68.2 ± 9.4%%, respectively. According to our results, the elevated LDH level and bone marrow involvement were identified as the poor prognostic factors for EFS (p=0.035 and 0.048, respectively). During APO treatment, only 23% patients experienced grade 3-4 hematologic toxicity. CONCLUSIONS: In this study, bone marrow involvement and elevated serum LDH levels were identified as the poor prognostic factors for EFS. In resource-limited regions, patients with advanced stage ALCL can also achieve comparable outcomes to those in high-income regions, and the BFM95 R3/R4 regimen can take the role of salvage treatment for patients with relapsed or refractory disease. Nonetheless, new therapeutic strategy is still needed.