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1.
CNS Neurosci Ther ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605602

RESUMO

AIMS: Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcomas in patients with other tumor phenotypes, but possible causal relationships between radiotherapy and induction of SGS sarcomatous components remain unexplored. Herein, we investigated the clonal origin of SGS in a patient with primary GBM progressing into SGS post-radiochemotherapy. METHODS: Somatic mutation profile in GBM and SGS was examined using whole-genome sequencing and deep-whole-exome sequencing. Mutation signatures were characterized to investigate relationships between radiochemotherapy and SGS pathogenesis. RESULTS: A mutation cluster containing two founding mutations in tumor-suppressor genes NF1 (variant allele frequency [VAF]: 50.0% in GBM and 51.1% in SGS) and TP53 (VAF: 26.7% in GBM and 50.8% in SGS) was shared in GBM and SGS. SGS exhibited an overpresented C>A (G>T) transversion (oxidative DNA damage signature) but no signature 11 mutations (alkylating-agents - exposure signature). Since radiation induces DNA lesions by generating reactive oxygen species, the mutations observed in this case of SGS were likely the result of radiotherapy rather than chemotherapy. CONCLUSIONS: Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS.

2.
J Oleo Sci ; 70(10): 1429-1435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34615829

RESUMO

Recently, the Populus yunnanensis extract has drawn the attention of most researchers, because of their anti-cancer activity. In this present research, the anti-cancer activity of the Populus yunnanensis extract was measured with Cell Counting Kit-8 (CCK-8) detection kit on the cancer cells. Then, the inhibitory activity of the Populus yunnanensis extract on the migration and invasion ability of the cancer cells was also determined in this present research with trans-well assay. Subsequently, to reveal the evolutionary genome evolution evaluation of the Populus yunnanensis and other Populus species, the high-throughput Illumina pair-end sequencing was performed and the chloroplast (cp) genome of Populus yunnanensis was determined, and the phylogenetic analysis was finished as wells. The results of the CCK-8 assay indicated that the Populus yunnanensis extract showed inhibitory effect on the cancer cell viability. Besides, the migration and invasion ability of the cancer cell was also reduced by the Populus yunnanensis extract. The complete chloroplast genome sequence results revealed that the Populus yunnanensis has a 156,505 bp circular cp genome. The phylogenetic analysis further revealed that the Populus yunnanensis has closely relationship with Populus simonii.

3.
Front Immunol ; 12: 709986, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512630

RESUMO

Background: Nowadays, researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer. However, its application against glioma is still in its infancy. In this study, the applicable candidates were excavated for mRNA vaccine treatment in the perspective of immune regulation, and suitable glioma recipients with corresponding immune subtypes were further investigated. Methods: The RNA-seq data and clinical information of 702 and 325 patients were recruited from TCGA and CGGA, separately. The genetic alteration profile was visualized and compared by cBioPortal. Then, we explored prognostic outcomes and immune correlations of the selected antigens to validate their clinical relevance. The prognostic index was measured via GEPIA2, and infiltration of antigen-presenting cells (APCs) was calculated and visualized by TIMER. Based on immune-related gene expression, immune subtypes of glioma were identified using consensus clustering analysis. Moreover, the immune landscape was visualized by graph learning-based dimensionality reduction analysis. Results: Four glioma antigens, namely ANXA5, FKBP10, MSN, and PYGL, associated with superior prognoses and infiltration of APCs were selected. Three immune subtypes IS1-IS3 were identified, which fundamentally differed in molecular, cellular, and clinical signatures. Patients in subtypes IS2 and IS3 carried immunologically cold phenotypes, whereas those in IS1 carried immunologically hot phenotype. Particularly, patients in subtypes IS3 and IS2 demonstrated better outcomes than that in IS1. Expression profiles of immune checkpoints and immunogenic cell death (ICD) modulators showed a difference among IS1-IS3 tumors. Ultimately, the immune landscape of glioma elucidated considerable heterogeneity not only between individual patients but also within the same immune subtype. Conclusions: ANXA5, FKBP10, MSN, and PYGL are identified as potential antigens for anti-glioma mRNA vaccine production, specifically for patients in immune subtypes 2 and 3. In summary, this study may shed new light on the promising approaches of immunotherapy, such as devising mRNA vaccination tailored to applicable glioma recipients.

5.
Orthop Surg ; 13(6): 1802-1809, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34351048

RESUMO

OBJECTIVE: To compare early clinical effects of the femoral neck system (FNS) and three cannulated screws for the treatment of patients with unstable femoral neck fractures. METHODS: A retrospective analysis with pair matching of 81 patients who received FNS or cannulated screw internal fixation for Pauwels type-3 femoral neck fracture in our hospital from January 2019 to December 2019 was conducted. Patients who received FNS were the test group, and those who received cannulated screws comprised the control group. Matching requirements were as follows: same sex, similar age, and similar body mass index (BMI). A total of 30 pairs were successfully matched at a 1:1 ratio, including 12 males and 18 females. The average age of the patients in the FNS group was 54.53 ± 6.71 years. In the cannulated screw group, the average age of the patients was 53.14 ± 7.19 years. The operation time, intraoperative blood loss, hospital stay, hospitalization cost, postoperative visual analog scale (VAS) score, time to walking without crutches, Harris score, femoral head necrosis rate, and complication rate were compared between the groups. RESULTS: Postoperative re-examination of radiographs showed satisfactory reduction in all patients, and all patients were followed up for 10-22 months. Those in the FNS group had lower postoperative VAS scores, earlier times to walking without crutches, higher Harris scores at the last follow-up, and lower complication rates (P < 0.05). VAS scores were lower in the FNS group (3.13 ± 1.07 scores) than in the cannulated screw group (3.77 ± 1.04 scores) (P = 0.018). Patients in the FNS group (5.23 ± 1.33 months) recovered to walking without crutches earlier than did those in the cannulated screw group (6.03 ± 1.45 months) (P<0.001). In addition, a statistically higher postoperative Harris score was detected in the FNS group (86.16 ± 7.26) than in the cannulated screw group (82.37 ± 7.52) (P = 0.039). Overall, a higher incidence of complications was observed in the cannulated screw group (9/30) than in the FNS group (2/30) (P = 0.042). However, intraoperative blood loss and hospitalization costs were greater in the FNS group (P < 0.05). Intraoperative blood loss was greater in the FNS group (99.73 ± 4.69) than in the cannulated screw group (30.27 ± 9.04) (P<0.001). In addition, patients in the FNS group (46976 ± 2270 ¥) spent more on hospitalization costs than did those in the cannulated screw group (15626 ± 1732 ¥) (P<0.001). No statistically significant difference in operation time, hospital stay, or femoral head necrosis rate was observed between the two groups (P > 0.05). CONCLUSION: For patients with unstable femoral neck fractures, FNS has better clinical efficacy than cannulated screws, though it is also more expensive.

6.
Biomed Res Int ; 2021: 8569921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34327238

RESUMO

Doxorubicin is a cornerstone chemotherapeutic drug widely used to treat various cancers; its dose-dependent cardiomyopathy, however, is one of the leading causes of treatment-associated mortality in cancer survivors. Patients' threshold doses leading to doxorubicin-induced cardiomyopathy (DIC) and heart failure are highly variable, mostly due to genetic variations in individuals' genomes. However, genetic susceptibility to DIC remains largely unidentified. Here, we combined a genetic approach in the zebrafish (Danio rerio) animal model with a genome-wide association study (GWAS) in humans to identify genetic susceptibility to DIC and heart failure. We firstly reported the cardiac and skeletal muscle-specific expression and sarcomeric localization of the microtubule-associated protein 7 domain-containing protein 1b (Map7d1b) in zebrafish, followed by expression validation in mice. We then revealed that disruption of the map7d1b gene function exaggerated DIC effects in adult zebrafish. Mechanistically, the exacerbated DIC are likely conveyed by impaired autophagic degradation and elevated protein aggregation. Lastly, we identified 2 MAP7D1 gene variants associated with cardiac functional decline and heart failure in cancer patients who received doxorubicin therapy. Together, this study identifies MAP7D1 as a clinically relevant susceptibility gene to DIC and heart failure, providing useful information to stratify cancer patients with a high risk of incurring severe cardiomyopathy and heart failure after receiving chemotherapy.


Assuntos
Cardiomiopatias/induzido quimicamente , Cardiomiopatias/genética , Doxorrubicina/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Apoptose , Autofagia , Elementos de DNA Transponíveis/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Insuficiência Cardíaca/fisiopatologia , Modelos Biológicos , Músculo Esquelético/metabolismo , Mutação/genética , Miocárdio/metabolismo , Miócitos Cardíacos/patologia , Polimorfismo de Nucleotídeo Único/genética , Agregados Proteicos , Fatores de Risco , Estresse Fisiológico
7.
Biochem Genet ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34327615

RESUMO

The present study established a necroptosis model in vitro and investigated the role of HMGB1 in cell necroptosis. A combination of tumor necrosis factor-α and z-VAD-fmk was used to induce necroptosis in L929 cells with necroptosis inhibitor necrostatin-1 applied as an intervention. Flow cytometry and transmission electron microscopy (TEM) were used to measure cell necroptosis. Western blotting assay was applied to detect the expression of receptor-interacting serine/threonine-protein kinase 3 (RIPK3), mixed lineage kinase domain-like pseudokinase (MLKL) and HMGB1. Co-immunoprecipitation (Co-IP) assay was used to confirm the interaction between HMGB1 and RIPK3. Our study demonstrated that HMGB1 migrated from the nucleus to the cytoplasm at the onset of necroptosis and was subsequently released passively to the extracellular matrix. Further experiments determined that the binding of HMGB1 with RIPK3 in the cytoplasm was loose during necroptosis. By contrast, when necroptosis was inhibited, the interaction in the cytoplasm was tight suggesting that this association between HMGB1 and RIPK3 might affect its occurrence. In conclusion, the transfer of HMGB1 from nucleus to cytoplasm, and its interaction with RIPK3 might be potentially involved in necroptosis.

8.
Acta Pharmacol Sin ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294886

RESUMO

Inhibition of autophagy has been accepted as a promising therapeutic strategy in cancer, but its clinical application is hindered by lack of effective and specific autophagy inhibitors. We previously identified cepharanthine (CEP) as a novel autophagy inhibitor, which inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. In this study we investigated whether and how inhibition of autophagy/mitophagy by cepharanthine affected the efficacy of chemotherapeutic agent epirubicin in triple negative breast cancer (TNBC) cells in vitro and in vivo. In human breast cancer MDA-MB-231 and BT549 cells, application of CEP (2 µM) greatly enhanced cepharanthine-induced inhibition on cell viability and colony formation. CEP interacted with epirubicin synergistically to induce apoptosis in TNBC cells via the mitochondrial pathway. We demonstrated that co-administration of CEP and epirubicin induced mitochondrial fission in MDA-MB-231 cells, and the production of mitochondrial superoxide was correlated with mitochondrial fission and apoptosis induced by the combination. Moreover, we revealed that co-administration of CEP and epirubicin markedly increased the generation of mitochondrial superoxide, resulting in oxidation of the actin-remodeling protein cofilin, which promoted formation of an intramolecular disulfide bridge between Cys39 and Cys80 as well as Ser3 dephosphorylation, leading to mitochondria translocation of cofilin, thus causing mitochondrial fission and apoptosis. Finally, in mice bearing MDA-MB-231 cell xenografts, co-administration of CEP (12 mg/kg, ip, once every other day for 36 days) greatly enhanced the therapeutic efficacy of epirubicin (2 mg/kg) as compared with administration of either drug alone. Taken together, our results implicate that a combination of cepharanthine with chemotherapeutic agents could represent a novel therapeutic strategy for the treatment of breast cancer.

9.
Clin Neurol Neurosurg ; 207: 106711, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34102421

RESUMO

STUDY DESIGN: A prospective study and technique description. OBJECTIVE: This study introduced a method for posterior cervical pedicle screw placement by using the bilateral posterior lamina nutrient foramens as the entry point. METHODS: Firstly, 30 dry C3-C7 vertebrae specimens were harvested for measurement. The lamina nutrient foramens were used as the entry points for posterior cervical pedicle screw placement and four linear and two angle parameters were obtained from a computed tomography scan(CT). Then, 60 patients who underwent C3-C7 pedicle screw fixation using this method were included, linear and angle parameters were obtained from a postoperative CT. RESULTS: The average incidences of lamina nutrient foramen on the C3-C7 specimens were 88.3%, 90.0%, 95.0%, 95.0%, and 96.7%, respectively. The distances from the entry point to the pedicle screw tip (OD), the pedicle transverse angles (α), and the pedicle sagittal angles (ß) measure for the entry points from C3-C7 were 28.74 ± 3.45-30.15 ± 2.01 mm, 26.88 ± 6.89° to 32.72 ± 5.91°, and 12.48 ± 9.31° to 19.71 ± 8.45°, respectively, with no significant differences between the left and right sides. In the 60 patients who underwent surgery, the lengths of the pedicle screws (PL) were 28.34 ± 2.25-30.15 ± 2.31 mm, the pedicle transverse angles (α) were 26.89 ± 6.86° to 32.36 ± 5.65°, and the pedicle sagittal angles (ß) were 12.49 ± 9.11° to 20.06 ± 8.91°. The new method had a 96.8% (454/469) success rate among these patients, with no screws penetrating the spinal canal or signs of vertebral artery injury. CONCLUSION: Entry at the bilateral lamina nutrient foramen represents an alternative posterior cervical pedicle screw placement technique that is feasible and safe.

10.
CNS Neurosci Ther ; 27(8): 951-962, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33960680

RESUMO

AIMS: High immune cell infiltration in gliomas establishes an immunosuppressive tumor microenvironment, which in turn promotes resistance to immunotherapy. Hence, it is important to identify novel targets associated with high immune cell infiltration in gliomas. Our previous study showed that serum levels of beta-2 microglobulin (B2M) in lower-grade glioma patients were lower than those in glioblastoma patients. In the present study, we focused on exploring the roles of B2M in glioma immune infiltration. METHODS: A large cohort of patients with gliomas from the TCGA, CGGA, and Gravendeel databases was included to explore differential expression patterns and potential roles of B2M in gliomas. A total of 103 glioma tissue samples were collected to determine the distributions of B2M protein levels by immunofluorescent assays. Kaplan-Meier survival analysis and meta-analysis were used for survival analysis. GO(Gene-ontology) enrichment analysis, co-expression analysis, KEGG(Kyoto Encyclopedia of Genes and Genomes) pathway analysis, and immune infiltration analysis were performed to explore roles and related mechanisms of B2M in glioma. RESULTS: We found that both B2M mRNA and protein levels were abnormally upregulated in glioma samples compared with those from normal brain tissue. B2M expression was correlated with tumor grade and was downregulated in IDH1 mutant samples. Furthermore, B2M was a moderately sensitive indicator for predicting the mesenchymal molecular subtype of gliomas. Interestingly, glioma patients with lower B2M expression had remarkably longer survival times than those with higher B2M expression. Moreover, meta-analysis showed that B2M was an independent predictive marker in glioma patients. The results of GO enrichment analysis revealed that B2M contributed to immune cell infiltration in glioma patients. In addition, results of KEGG pathway analysis and co-expression analysis suggested that B2M may mediate glioma immune infiltration via chemokines. CONCLUSIONS: We conclude that B2M levels are critical for the survival times of glioma patients, at least in part due to mediating high immune infiltration.

11.
J Orthop Surg Res ; 16(1): 334, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34020675

RESUMO

BACKGROUND: Osteoporosis is a common disease in aging populations. However, osteoporosis treatment is still challenging. Here, we aimed to investigate the role of neohesperidin (NEO) in osteoporosis progression and the potential mechanism. METHODS: Bone mesenchymal stem cells (BMSCs) were isolated and treated with different concentrations of NEO (0, 10, 30, 100 µM). Cell proliferation was analyzed by cell count kit-8 (CCK-8) assay. RNA-sequencing was performed on the isolated BMSCs with control and NEO treatment. Differentially expressed genes were obtained by R software. Alkaline phosphatase (ALP) staining and Alizarin red staining (ARS) were performed to assess the osteogenic capacity of the NEO. qRT-PCR was used to detect the expression of osteoblast markers. Western blot was used to evaluate the protein levels in BMSCs. RESULTS: NEO treatment significantly improved hBMSC proliferation at different time points, particularly when cells were incubated with 30 µM NEO (P < 0.05). NEO dose-dependently increased the ALP activity and calcium deposition than the control group (P < 0.05). A total of 855 differentially expressed genes were identified according to the significance criteria of log2 (fold change) > 1 and adj P < 0.05. DKK1 partially reversed the promotion effects of NEO on osteogenic differentiation of BMSCs. NEO increased levels of the ß-catenin protein in BMSCs. CONCLUSION: NEO plays a positive role in promoting osteogenic differentiation of BMSCs, which was related with activation of Wnt/ß-catenin pathway.

12.
Drug Des Devel Ther ; 15: 1641-1652, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33907383

RESUMO

Background: Gut microbiota is associated with the progression of brain tumors. However, the alterations in gut microbiota observed during glioma growth and temozolomide (TMZ) therapy remain poorly understood. Methods: C57BL/6 male mice were implanted with GL261 glioma cells. TMZ/sodium carboxymethyl cellulose (SCC) was administered through gavage for five consecutive days (from 8 to 12 days after implantation). Fecal samples were collected before (T0) and on days 7 (T1), 14 (T2), and 28 (T3) after implantation. The gut microbiota was analyzed using 16S ribosomal DNA sequencing followed by absolute and relative quantitation analyses. Results: Nineteen genera were altered during glioma progression with the most dramatic changes in Firmicutes and Bacteroidetes phyla. During glioma growth, Lactobacillus abundance decreased in the early stage (T1) and then gradually increased (T2, T3); Intestinimonas abundance exhibited a persistent increase; Anaerotruncus showed a transient increase (T2) and then a subsequent decrease (T3). Similar longitudinal changes in Intestinimonas and Anaerotruncus abundance were observed in TMZ-treated mice, but the decrease of Anaerotruncus at T3 in the TMZ-treated group was less than that in the vehicle-treated group. No significant change in Lactobacillus was observed after TMZ treatment. Additionally, compared to vehicle control, TMZ treatment led to an enrichment in Akkermansia and Bifidobacterium. Conclusion: Glioma development and progression altered the composition of gut microbiota. Induction of Akkermansia and Bifidobacterium as well as the prevention of the reduction in Anaerotruncus may contribute to the anti-tumor effect of TMZ. This study helps to reveal the association between levels of specific microbial species in the gut and the anti-tumor effect of TMZ.

13.
Zhongguo Zhong Yao Za Zhi ; 46(2): 298-305, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645115

RESUMO

The differences of the active ingredients in Dendrobium huoshanense of different growth years and their protective effects on acute liver injury were studied to provide evidence for optimizing harvest time. The contents of polysaccharides, total flavonoids and total alkaloids in D. huoshanense of different growth years were determined by UV spectrophotometry, and the contents of gigantol in D. huoshanense were determined by HPLC. C57 BL/6 mice were randomly divided into blank control group(saline), modeling group(saline), high-dose(7.5 g·kg~(-1)) and low-dose(1.25 g·kg~(-1)) groups of D. huoshanense of different growth years. Each group was intragastrically administered every day for 2 weeks. 500 mg·kg~(-1) paracetamol was injected intraperitoneally 2 h after last treatment except the control group. After 12 hours, the serum and liver tissues were collected to detect the activities of ALT and AST, and the levels of SOD and MDA. The hepatic histopathological examination was performed. The results showed that the chemical constituents of D. huo-shanense of different growth years were significantly different(P<0.05). The contents of polysaccharide and gigantol of D. huoshanense of 2 growth years were the highest. The contents of flavonoids and alkaloids of D. huoshanense of 3 growth years were the hig-hest, followed by the D. huoshanense of 2 growth years, and the lowest were that of 1 growth year. Compared with the modeling group, D. huoshanense of different growth years could decrease the activities of ALT and AST in serum. Meanwhile, the levels of MDA reduced significantly, while those of SOD increased markedly. Histopathological results suggested that all D. huoshanense samples were effective in the reduction of the necrosis of hepatocytes in different degrees. The results of the multi-component SPSS paired tests showed that polysaccharide and gigantol probably played a leading role in the liver protection effects, while D. huoshanense of 2 growth years showed the best efficacy. The optimal harvesting time of D. huoshanense is 2 growth years.


Assuntos
Alcaloides , Dendrobium , Animais , Cromatografia Líquida de Alta Pressão , Fígado , Camundongos , Polissacarídeos
14.
Cancer Med ; 10(8): 2802-2811, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33709570

RESUMO

OBJECTIVES: This study aimed to establish a machine learning prediction model that can be used to predict bone metastasis (BM) in patients with newly diagnosed thyroid cancer (TC). METHODS: Demographic and clinicopathologic variables of TC patients in the Surveillance, Epidemiology, and End Results database from 2010 to 2016 were retrospectively analyzed. On this basis, we developed a random forest (RF) algorithm model based on machine-learning. The area under receiver operating characteristic curve (AUC), accuracy score, recall rate, and specificity are used to evaluate and compare the prediction performance of the RF model and the other model. RESULTS: A total of 17,138 patients were included in the study, with 166 (0.97%) developed bone metastases. Grade, T stage, histology, race, sex, age, and N stage were the important prediction features of BM. The RF model has better predictive performance than the other model (AUC: 0.917, accuracy: 0.904, recall rate: 0.833, and specificity: 0.905). CONCLUSIONS: The RF model constructed in this study could accurately predict bone metastases in TC patients, which may provide clinicians with more personalized clinical decision-making recommendations. Machine learning technology has the potential to improve the development of BM prediction models in TC patients.


Assuntos
Neoplasias Ósseas/secundário , Aprendizado de Máquina , Neoplasias da Glândula Tireoide/patologia , Área Sob a Curva , Tomada de Decisões Assistida por Computador , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Fatores de Risco , Programa de SEER
15.
Int J Gynecol Cancer ; 31(4): 512-517, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33608452

RESUMO

BACKGROUND: Villoglandular adenocarcinoma is a rare sub-type of cervical adenocarcinoma. OBJECTIVE: To analyze the clinicopathological features and evaluate the prognosis of patients with villoglandular adenocarcinoma of the cervix. METHODS: Patient characteristics, procedure, pathology, and surgical outcomes were retrospectively reviewed in patients with villoglandular adenocarcinoma between November 2006 and June 2019 from multiple centers in China. In order to explore the difference between villoglandular adenocarcinoma and routine adenocarcinoma, patients (FIGO 2009 stage IA1-IB2) who had complete data during the same time period were included. RESULTS: A total of 60 patients with villoglandular adenocarcinoma and 104 with standard adenocarcinoma were included. The median age of the patients with villoglandular adenocarcinoma was 42 years (range 27-68). The most common 2009 FIGO stage was IB1 in 39 (65%) patients with villoglandular adenocarcinoma. A total of 23 patients underwent laparoscopic surgery (two total hysterectomies, 21 radical hysterectomies) and the other 37 patients underwent laparotomy (three total hysterectomies, 34 radical hysterectomies). A total of 56 patients underwent lymphadenectomy and three (5.4%) had positive lymph nodes. Fifteen (25%) patients had one or both ovaries preserved. Seven patients were lost to follow-up. The median follow-up time for the entire group was 50.2 months (range 5.1-154.6). No deaths or recurrences occurred. Excluding six patients with FIGO 2009 stage II, the 5-year disease-free survival of the 47 patients with villoglandular adenocarcinoma with FIGO 2009 stage I for whom there was follow-up, was significantly higher than that of the 104 patients with standard cervical adenocarcinoma (100% vs 92.2%, log-rank p=0.039). However, the 5-year overall survival of the two groups did not differ (100% vs 95.7%, log-rank p=0.11). CONCLUSION: Villoglandular adenocarcinoma has a favorable prognosis. Further studies are needed to provide more details of treatment strategies and prognosis.

16.
Pancreas ; 50(2): 227-234, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33565800

RESUMO

OBJECTIVES: Elucidation of the regulatory mechanisms of gemcitabine sensitivity is needed to improve the therapeutic effects of this drug in pancreatic cancer. METHODS: PANC-1 cells were transfected with small hairpin RNA against PVT1 or microRNA (miR)-143 mimics or inhibitor. The gemcitabine sensitivity of pancreatic cancer was evaluated. Autophagosomes were analyzed with an immunofluorescence assay. Cell viability and proliferation were examined with MTT assays. Quantitative reverse transcription-polymerase chain reaction and Western blotting were used to analyze the expression of PVT1, miR-143, HIF-1α, VMP1, LC3I/II, p62, and Beclin-1. The interactions of PVT1/miR-143 and miR-143/HIF-1α were assessed by dual-luciferase reporter assays. RESULTS: PVT1 was upregulated while miR-143 was downregulated in pancreatic cancer. Both PVT1 knockdown and miR-143 overexpression suppressed autophagy and improved gemcitabine sensitivity in pancreatic cancer. PVT1 directly sponged miR-143 to regulate HIF-1α expression. MiR-143 inhibitor reversed the effect of PVT1 knockdown on autophagy and gemcitabine sensitivity. CONCLUSIONS: PVT1 knockdown inhibited autophagy and improved gemcitabine sensitivity via the miR-143/HIF-1α/VMP1 axis in pancreatic cancer. Our investigation elucidated a novel regulatory mechanism of gemcitabine sensitivity and may contribute to improve the therapeutic effects of chemotherapy drugs on pancreatic cancer.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33433250

RESUMO

PURPOSE: To evaluate the efficacy of stent-in-stent (SIS) and side-by-side (SBS) bilateral stenting for treating malignant hilar biliary obstruction (MHBO). MATERIAL AND METHODS: Relevant studies in Pubmed, Embase, and Cochrane Library were identified through June 2020. This meta-analysis was conducted using RevMan v5.3, using relevant endpoint data relating to clinical and technical success, complications, stent dysfunction, and overall survival (OS) rates extracted from these studies. RESULTS: We identified six relevant studies which included 315 MHBO patients treated with either SBS (n = 161) or SIS bilateral (n = 154) stenting. We saw no significant difference between these two groups with respect to clinical success (OR: 1.07; 95% CI: 0.46, 2.49, p = .87), complication (HR: 0.12; 95% CI: -0.04, 0.27, p = .15), stent dysfunction (OR: 0.68; 95% CI: 0.42, 1.10, p = .11), or OS (HR: 0.97; 95% CI: 0.82, 1.16, p = .74). However, the SBS group exhibited significantly lower technical success rates (OR: 6.55; 95% CI: 1.10, 38.83, p = .04). Significant heterogeneity was only detected for the endpoint of complication rates (I2 = 60%). CONCLUSION: These results suggest that SIS bilateral stenting yields better rates of technical success than does SBS bilateral stenting in MHBO patients.

18.
World J Biol Psychiatry ; : 1-9, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33143498

RESUMO

OBJECTIVES: Environmental and genetic factors play important roles in the development of schizophrenia (SCZ), bipolar disorder (BPD) or major depressive disorder (MDD). Some risk loci are identified with shared genetic effects on major psychiatric disorders. To investigate whether SNX29 gene played a significant role in these psychiatric disorders in the Han Chinese population. METHODS: We focussed on 11 single-nucleotide polymorphisms (SNPs) harbouring SNX29 gene and carried out case-control studies in patients with SCZ (n = 1248), BPD (n = 1344), or MDD (n = 1056), and 1248 healthy controls (HC) recruited from the Han Chinese population. We constructed weighted gene co-expression network analysis (WGCNA) and extracted significant modules by R package. RESULTS: We found that rs3743592 was significantly associated with MDD and rs6498263 with BPD in both allele and genotype distributions. Before correction, rs3743592 showed allelic and genotypic significance with SCZ, rs6498263 showed allelic significance with SCZ. WGCNA identified top 10 modules of co-expressed genes. Gene Ontology (GO) and pathway analysis were used to examine the functions of SNX29, which revealed that SNX29 was involved in the regulation of a number of biological processes, such as TGF-beta, ErbB, and Wnt signalling pathway, etc. CONCLUSIONS: Our results supported common risk factors in SNX29 might share among these three mental disorders in the Han Chinese population.

19.
Br J Neurosurg ; : 1-11, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33252289

RESUMO

PURPOSE: Cranioplasty (CP) after decompressive craniectomy (DC) is routinely performed for reconstructive purposes and improves rehabilitation. However, the optimal timing of CP remains controversial. This study aimed to assess differences in clinical outcomes following different timings of CP in patients with traumatic brain injury. MATERIALS AND METHODS: Patients with traumatic brain injury who underwent CP after DC in Zhongnan Hospital of Wuhan University from 1 January 2010 to 1 May 2017, and in Affiliated Hospital of Guizhou Medical University from 1 January 2015, to 1 May 2017, were retrospectively reviewed. According to the timing of CP, patients were divided into an 'early group' (3-6 months) and a 'late group' (6-12 months). The clinical characteristics of patients and postoperative complications occurred within 1-year follow-up were analysed. The neurological function was assessed with Barthel Index (BI). RESULTS: A total of 100 patients (58 cases in early group and 42 cases in late group) were included. The median interval between DC and CP was 135 days and 225 days in the early and late CP groups, respectively. The overall complication rate after CP was 16%, and no significant difference in complication rate was observed between the early and late CP groups (17.2% vs.14.3%, p = 0.69). The neurological function was improved in early CP group (pre-CP 85.77 ± 11.61 vs. post-CP 95.34 ± 9.02, p < 0.001, but not in late CP group (pre-CP 82.74 ± 22.82 vs. post-CP 88.93 ± 22.86, p = 0.22). In addition, a significantly higher proportion of patients in the early CP group showed neurological functional improvement in comparison with the late CP group (early vs. late: 74.1% vs. 57.1%, p = 0.04). Multivariate analysis further demonstrated that the timing of CP is an independent predictor for neurological outcomes (OR = 0.32, 95% CI 0.13-0.82, p = 0.02). CONCLUSION: Early CP (3-6 months) following posttraumatic DC was associated with better neurological outcomes than late CP (>6 months).

20.
Nanoscale Res Lett ; 15(1): 211, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33170390

RESUMO

A 13.5 kV 4H-SiC PiN rectifier with a considerable active area of 0.1 cm2 is fabricated in this paper. Charge-field-modulated junction termination extension (CFM-JTE) has been proposed for satisfying the requirement of ultra-high reverse voltage, which enlarges the JTE dose tolerance window, making it approximately 2.8 times that of the conventional two-zone JTE. Besides, the CFM-JTE can be implemented through the conventional two-zone JTE process. The measured forward current is up to 100 A @ VF = 5.2 V in the absence of carrier lifetime enhancement technology. The CFM-JTE structure accomplishes 96% of the theoretical breakdown voltage of the parallel plane junction with a relatively small terminal area of 400 µm, which contributes to achieving the Baliga's figure of merit of 58.8 GW/cm2.

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