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1.
Medicine (Baltimore) ; 98(26): e15886, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261497

RESUMO

There is limited information about the effects of corticosteroids on severe drug-induced liver injury (DILI). This study aimed to investigate the efficacy and safety of prednisone in severe DILI.Ninety patients with severe DILI were enrolled and studied retrospectively. They were divided into prednisone (n = 66) and control groups (n = 24), undergoing the same treatment regimen except that patients in the prednisone group received a median daily dose of 40 mg prednisone. The primary endpoint was severity reduction (serum total bilirubin [TBIL] <86 µmol/L).During the study, the cumulative rates of severity reduction at 4-, 8-, and 12 days were comparable between the 2 groups (prednisone versus control: 7.6%, 33.3%, and 60.6% versus 12.5%, 37.5%, and 66.7%, P = .331), and were markedly lower in the high-dose group than in the low-dose group (0%, 28.6%, and 35.7% versus 9.6%, 34.6%, and 67.3%, P = .012) or in the control group (0%, 28.6%, and 35.7% versus 12.5%, 37.5%, and 66.7%, P = .023). The 30-day overall survival rate in the prednisone group was significantly higher than in the control group (100% versus 91.7%, P = .018). Serum bilirubin and transaminase values gradually decreased in both groups, which were not significantly different mostly. Cox-regression models revealed that baseline TBIL (hazard ratio: 0.235; 95% confidence interval: 0.084-0.665; P = .006) was the only predictor for severity reduction. No severe adverse event was noted in both groups.Prednisone therapy is safe but not beneficial, and even detrimental at a daily dose > 40 mg for the treatment of severe DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Adolescente , Adulto , Idoso , Bilirrubina/sangue , Biomarcadores/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Falha de Tratamento , Adulto Jovem
2.
Acad Radiol ; 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31147236

RESUMO

RATIONALE AND OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) and partial splenic embolization (PSE) were two interventional therapies effective for the management of variceal bleeding with cirrhosis. This study aimed to investigate the effect of TIPS plus PSE for the treatment of patients with cirrhosis and recurrent variceal bleeding. MATERIAL AND METHODS: This is a single-center, nonrandomized and retrospective study that included 32 patients undergoing TIPS alone (the TIPS group) and 16 patients undergoing TIPS plus PSE (the TIPS+PSE group). RESULTS: The 5-year cumulative rates of variceal rebleeding (20.0% vs. 37.9%, p = 0.027) and shunt stenosis (35.1% vs. 55.9%, p = 0.036) in the TIPS+PSE group were significantly lower than in the TIPS group, whereas the 5-year cumulative rates of shunt blockage (12.5% vs. 25.8%, p = 0.388), and all-cause mortality (37.5% vs. 69.3%, p = 0.414) were not statistically different between the two groups. The 2-year cumulative rate of remaining free of hepatic encephalopathy was also similar between the two groups (75.0% vs. 81.3%, p = 0.704). Cox-regression analyses showed that group and reduction of portal venous pressure before and after TIPS creation were associated with both variceal rebleeding and shunt stenosis, whereas only reduction of portal venous pressure (hazard ratio 0.648, 95% confidence interval: 0.444-0.946, p = 0.025) was associated with shunt blockage. No severe adverse event was observed in the two groups. CONCLUSION: TIPS+PSE is superior to TIPS alone in control of variceal rebleeding and shunt stenosis. Further prospective studies are warranted to confirm our findings.

3.
Ying Yong Sheng Tai Xue Bao ; 30(4): 1287-1294, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30994290

RESUMO

Based on a two-year field experiment located at Shenyang Applied Ecological Experiment Station of Chinese Academy of Sciences, we examined the effects of stabilized N fertilizer combined with straw returning on rice yield and emission of N2O and CH4 in aquic brown soil. Six treatments were set up, i.e. control (CK), urea(U), urea+urease inhibitor+nitrification inhibitor (U+I), straw (S), straw+urea (S+U), straw+urea+ urease inhibitor+nitrification inhibitor (S+U+I). The results showed that urea application increased rice yield, cumulative N2O and CH4 emission, and global warming potential. The treatment of U+I significantly mitigated cumulative N2O emission. Returning rice straw to the field significantly increased cumulative N2O emission, cumulative CH4 emission, global warming potential, and greenhouse gas emission intensity. The S+U+I treatment had the highest rice yield and greenhouse gas emission intensity. U+I treatment had the the second highest rice yield and the lowest greenhouse gas emission intensity. Rice yield in the S treatment showed no significant difference with CK. Our results indicated that S+U+I and U+I are relatively better agricultural strategies compared with other treatments in paddy fields on aquic soil.


Assuntos
Agricultura/métodos , Fertilizantes , Gases de Efeito Estufa/análise , Metano/análise , Óxido Nitroso/análise , Oryza/crescimento & desenvolvimento , Solo
4.
J Biol Chem ; 294(16): 6375-6386, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30792309

RESUMO

Contactin-associated protein 1 (CASPR1 or CNTNAP1) was recently reported to be expressed in brain microvascular endothelial cells (BMECs), the major component of the blood-brain barrier. To investigate CASPR1's physiological role in BMECs, here we used CASPR1 as a bait in a yeast two-hybrid screen to identify CASPR1-interacting proteins and identified the ß3 subunit of Na+/K+-ATPase (ATP1B3) as a CASPR1-binding protein. Using recombinant and purified CASPR1, RNAi, GST-pulldown, immunofluorescence, immunoprecipitation, and Na+/K+-ATPase activity assays, we found that ATP1B3's core proteins, but not its glycosylated forms, interact with CASPR1, which was primarily located in the endoplasmic reticulum of BMECs. CASPR1 knockdown reduced ATP1B3 glycosylation and prevented its plasma membrane localization, phenotypes that were reversed by expression of full-length CASPR1. We also found that the CASPR1 knockdown reduces the plasma membrane distribution of the α1 subunit of Na+/K+-ATPase, which is the major component assembled with ATP1B3 in the complete Na+/K+-ATPase complex. The binding of CASPR1 with ATP1B3, but not the α1 subunit, indicated that CASPR1 binds with ATP1B3 to facilitate the assembly of Na+/K+-ATPase. Furthermore, the activity of Na+/K+-ATPase was reduced in CASPR1-silenced BMECs. Interestingly, shRNA-mediated CASPR1 silencing reduced glutamate efflux through the BMECs. These results demonstrate that CASPR1 binds with ATP1B3 and thereby contributes to the regulation of Na+/K+-ATPase maturation and trafficking to the plasma membrane in BMECs. We conclude that CASPR1-mediated regulation of Na+/K+-ATPase activity is important for glutamate transport across the blood-brain barrier.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Membrana Celular/metabolismo , Células Endoteliais/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Encéfalo/irrigação sanguínea , Encéfalo/citologia , Encéfalo/metabolismo , Moléculas de Adesão Celular Neuronais/genética , Membrana Celular/genética , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Células Endoteliais/citologia , Deleção de Genes , Humanos , Microvasos/citologia , Microvasos/metabolismo , Ligação Proteica/fisiologia , Transporte Proteico/fisiologia , ATPase Trocadora de Sódio-Potássio/genética
5.
Eur Radiol ; 29(9): 5032-5041, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30796573

RESUMO

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) and partial splenic embolization (PSE) were two interventional radiological treatments for the complications of cirrhosis. This study aimed to investigate the effects of concomitant PSE on the long-term shunt patency and overall survival of TIPS-treated patients. METHODS: Forty-eight patients with TIPS insertion were enrolled and studied retrospectively. They were divided into TIPS+PSE (n = 16) and TIPS groups (n = 32), undergoing combined therapy using TIPS and PSE, and monotherapy using TIPS alone, respectively. RESULTS: The 5-year cumulative primary patency rate in the TIPS+PSE group was markedly higher than in the TIPS group (56.8% vs. 32.8%, p = 0.028), whereas the 5-year cumulative secondary patency rate (93.8% vs. 87.7%, p = 0.749) and overall survival rate (62.5% vs. 30.7%, p = 0.414) were not significantly different between the two groups. Cox-regression models revealed that group (hazard ratio [HR], 0.235; 95% CI, 0.084-0.665; p = 0.006), portal venous pressure decline (HR, 0.687; 95% CI, 0.563-0.838; p = 0.000), and baseline portal vein thrombosis (HR, 3.955; 95% CI, 1.634-9.573; p = 0.002) were significant predictors for shunt dysfunction, while only ascites (HR, 2.941; 95% CI, 1.250-6.920; p = 0.013) was a significant predictor for mortality. No severe adverse event was noted in the two groups except for the potential risk of splenic abscess development in the TIPS+PSE group. CONCLUSIONS: Concomitant PSE may help increase the long-term primary shunt patency rate, but not the overall survival of TIPS-treated patients. Further prospective studies are needed to validate these retrospective findings and to investigate the potential mechanisms. KEY POINTS: • Combined therapy using TIPS and PSE is associated with higher primary patency rates than TIPS alone. • Combined therapy using TIPS and PSE is associated with similar rates of secondary patency and overall survival of patients than TIPS alone. • Group (TIPS alone or TIPS+PSE), PVD, and baseline PVT are three independent predictors for shunt dysfunction, while ascites is the only independent predictor for mortality.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30381976

RESUMO

The 2014 Ebola outbreak in West Africa had brought great threat to the public health worldwide. There were no approved anti-viral therapy and vaccine available to control the disease at that time. Several kinds of Ebola vaccines were under development urgently in the world, among which the novel recombinant adenovirus type-5 vector-based Ebola vaccine( Ad5-EBOV)-the first Ebola vaccine based on the 2014 Zaire Guinea epidemic strain was developed in China and its safety and immunogenicity were demonstrated in China and SierraLeone. The license for marketing was approved on Oct 19.2017by Chinese Food and Drug Administration (CFDA).In order to standardize the test on the virus titer of Ad5-EBOV, China's national standard substance for virus titer of Ad5-EBOV was established according to the recommendations for the preparation, characterization and establishment of international and other biological reference standards from WHO and Chinese Pharmacopoeia, 3rd edition. Standard for virus titer of Ad5-EBOV was prepared with volume of 0.5ml per ampoule in lyophilized form. The samples of the standard designated as A, B, C, D with different aims were blinded and distributed to five labs to be collaboratively calibrated. The virus titer of this standard was determined with antibody staining method according to the instructions of Adeno-X™ Rapid Titer Kit. The homogeneity and stability of the standard substance were also satisfied. The virus titer value of standard was 8.54LgIFU/ml, 95% confidence interval was between 7.94LgIFU/ml and 9.14LgIFU/ml. This standard was approved by the Chinese national committee, and available in NIFDC(www.nifdc.org.cn), lot No. is 250019-201501.

7.
Clin Transl Gastroenterol ; 9(11): 202, 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30416197

RESUMO

BACKGROUND: Acute-on-chronic liver failure (ACLF) can be caused by reactivation of chronic hepatitis B virus (HBV) infection (HBV-ACLF). It's unclear whether HBV genotypes affect the clinical and therapeutical outcomes of patients with HBV-ACLF. This study was to investigate the short-term antiviral response and overall survival in HBV-ACLF patients treated by tenofovir or entecavir. METHODS: Seventy-three consecutive patients with HBV-ACLF were stratified into genotype B group (n = 33) and C group (n = 40). They were prospectively followed-up. RESULTS: At 2 weeks, the genotype B group had significantly lower HBV-DNA load (P = 0.005), greater HBV-DNA decline (P = 0.026), higher proportion of patients with HBV-DNA < 500 IU/ml (P = 0.007), improved Child-Turcotte-Pugh (CTP; P = 0.032) and model for end-stage liver disease (MELD; P = 0.039) scores compared to the genotype C group. At three months, survivors in both groups had undetectable HBV-DNA loads, comparable CTP (P = 0.850) and MELD (P = 0.861) scores; the genotype C group had markedly lower overall survival rate than the B group (P = 0.013). The genotype (hazard ratio [HR]: 2.138; 95% confidence interval [CI]: 1.034-4.143; P = 0.041), MELD score (HR:1.664, 95%CI: 1.077-2.571; P = 0.022) and HBV-DNA decline (HR: 0.225, 95% CI: 0.067-0.758; P = 0.016) at 2 weeks were significantly associated with mortality at 3 months. No severe adverse event was noted. CONCLUSIONS: Genotype B was associated with better short-term antiviral response and clinical outcome compared to genotype C in patients with HBV-ACLF.

8.
Chemosphere ; 208: 808-817, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29906755

RESUMO

Chinese cooking fume is one of the sources of volatile organic compounds (VOCs) in the air. An innovative control technology combining photocatalytic degradation and ozone oxidation (UV/TiO2+O3) was developed to decompose VOCs in the cooking fume. Fiberglass filter (FGF) coated with TiO2 was prepared by an impregnation procedure. A continuous-flow reaction system was self-designed by combining photocatalysis with advanced ozone oxidation technique. By passing the simulated cooking fume through the FGF, the VOC decomposition efficiency in the cooking fume could be increased by about 10%. The decomposition efficiency of VOCs in the cooking fume increased and then decreased with the inlet VOC concentration. A maximum VOC decomposition efficiency of 64% was obtained at 100 ppm. Similar trend was observed for reaction temperature with the VOC decomposition efficiencies ranging from 64 to 68%. Moreover, inlet ozone concentration had a positive effect on the decomposition of VOCs in the cooking fume for inlet ozone≤1000 ppm and leveled off for inlet ozone>1000 ppm. 34% of VOC decomposition efficiency was achieved solely by ozone oxidation with or without near-UV irradiation. A maximum of 75% and 94% VOC decomposition efficiency could be achieved by O3+UV/TiO2 and UV/TiO2+O3 techniques, respectively. The maximum decomposition efficiencies of VOCs decreased to 79% for using UV/TiO2+O3 technique with adding water in the oil fume. Comparing the chromatographical species of VOCs in the oil fume before and after the decomposition of VOCs by using UV/TiO2+O3technique, we found that both TVOC and VOC species in the oil fume were effectively decomposed.


Assuntos
Culinária , Filtração/instrumentação , Ozônio/química , Titânio/química , Compostos Orgânicos Voláteis/isolamento & purificação , Poluentes Atmosféricos/análise , Catálise , Oxirredução , Processos Fotoquímicos , Raios Ultravioleta , Compostos Orgânicos Voláteis/análise
9.
Acad Radiol ; 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29934023

RESUMO

RATIONALE AND OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) placement using the same-diameter covered stents can lead to differed declines of portal venous pressure declines (PVDs). This study aimed to compare the long-term shunt patency and clinical efficacy of TIPS placement that caused low PVDs (≤9 mmHg) and high PVDs (>9 mmHg). MATERIALS AND METHODS: A total of 129 patients treated by TIPS placement with 8 mm-diameter polytetrafluoroethylene covered stents were included and analyzed retrospectively. They were stratified into group A with low PVDs (n = 69) and group B with high PVDs (n = 60). RESULTS: The 6-year actuarial probabilities of remaining free of shunt dysfunction (47.2% vs 64.6%; p = 0.007) and variceal rebleeding (48.3% vs 63.9%; p = 0.038) were significantly lower in group A than in group B. The 6-year actuarial probability of remaining free of hepatic encephalopathy was significantly higher in group A than in group B (44.5% vs 32.5%; p = 0.010), though the 6-year cumulative survival rate was similar in both groups (A vs B: 65.5% vs 56.0%; p = 0.240). The baseline portal vein thrombosis (hazard ratio [HR]: 6.045, 95% confidence interval [CI]: 2.762-13.233; p = 0.000) and stent type (HR: 4.447, 95%CI: 1.711-11.559, p = 0.002) were associated with shunt dysfunction, whereas only ascites was associated with mortality (HR: 1.373, 95%CI: 1.114-3.215; p = 0.024). CONCLUSION: High PVDs (>9 mmHg) were associated with higher shunt patency, lower incidence of variceal rebleeding, but higher frequency of hepatic encephalopathy and similar survival rate than low PVDs (≤9 mmHg) after TIPS placement.

10.
Am J Forensic Med Pathol ; 39(3): 218-222, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29851656

RESUMO

Long QT syndrome (LQTS) is known to be involved in some sudden unexplained death (SUD) cases. To make clear whether the pathogenic genes of LQTS are involved in SUD in Yunnan province, southwest of China, we examined 4 mutation hotspot segments of KCNQ1, KCNH2, and SCN5A genes in 83 SUD cases using polymerase chain reaction and direct DNA sequencing. Genomic DNA was extracted from paraffin-embedded tissues in 83 cases of sudden cardiac death. One novel homozygous missense variant was identified in exon 3 of KCNQ1, c. 575G>T (p.R192L) in one case. One novel heterozygous missense variant was identified in exon 7 of KCNH2, c.1789T>A (p.Y597N) in 1 case. One novel heterozygous missense variant was identified in exon 7 of KCNH2, c.1800C>A (p.S600R) in 9 cases. In addition, 18 individuals were found to have heterozygous missense variant in exon 7 of KCNH2, c.1801G>A (p.G601S). Our study suggests that some SUDs in Yunnan province may be related with the pathogenic genes of LQTS.


Assuntos
Morte Súbita Cardíaca/etiologia , Canal de Potássio ERG1/genética , Canal de Potássio KCNQ1/genética , Mutação de Sentido Incorreto , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , China , Éxons , Feminino , Genética Forense , Heterozigoto , Humanos , Síndrome do QT Longo/genética , Masculino , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
11.
J Clin Gastroenterol ; 2018 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-29659382

RESUMO

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) can be triggered by reactivation of chronic hepatitis B (CHB). Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are now the most potent antiviral agents for CHB. This study aimed to compare the short-term safety and efficacy of TDF with ETV in the treatment of ACLF due to reactivation of CHB [hepatitis B virus (HBV)-ACLF]. PATIENTS AND METHODS: In total, 67 consecutive patients with HBV-ACLF were divided into TDF group (n=32) receiving daily TDF (300 mg/d) and ETV group (n=35) receiving daily ETV (0.5 mg/d). They were prospectively followed-up and the primary endpoint was overall survival at 3 months. RESULTS: At 2 weeks, the TDF group had significantly higher HBV-DNA reduction (P=0.003), lower HBV-DNA level (P=0.001), higher rate of HBV-DNA undetectbility (P=0.007), lower Child-Turcotte-Pugh (CTP; P=0.003), and model for end-stage liver disease (P=0.002) scores than the ETV group. At 3 months, HBV-DNA was undetectable in all survived patients; CTP (P=0.970) and model for end-stage liver disease (P=0.192) scores were comparable between the 2 groups, but markedly lower than at baseline (P<0.01); the TDF group had significantly higher cumulative survival rate than the ETV group (P=0.025). The white blood cell count (hazard ratio, 2.726; 95% confidence interval, 2.691-7.897; P=0.000), and HBV-DNA reduction (hazard ratio, 0.266; 95% confidence interval, 0.033-0.629; P=0.013) at 2 weeks were independent predictors for mortality. Both drugs were well tolerated. CONCLUSIONS: The short-term efficacy of TDF was superior to ETV for the treatment of HBV-ACLF. The white blood cell count and HBV-DNA reduction at 2 weeks were independent predictors for mortality at 3 months.

12.
World J Surg Oncol ; 16(1): 72, 2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29587787

RESUMO

BACKGROUND: We aimed to evaluate the clinical and imaging presentations of Langerhans cell histiocytosis (LCH) in the pediatric temporal bone. METHODS: This retrospective study included 27 pediatric cases with pathological confirmed LCH of the temporal bone. The clinical and imaging features of the cases were analyzed. The involvement of ossicular chain and otic capsule was also evaluated. RESULTS: A total of 38 lesions (27 cases) with 11 bilateral involvement were identified. For the 27 cases, the most common complaint was periauricular swelling (12/27, 44.4%), followed by otorrhea (9/27, 33.3%) and otalgia (5/27, 18.2%). The mastoid process was the most common involved subsite (31/38, 81.6%) among the 38 lesions. Ten (26.3%, 10/38) lesions belonged to the group of the diffuse involvement, 22 (57.9%, 22/38) were divided into the group of partial involvement and six (15.8%,6/38) localized lesions with punched-out appearance. Erosion of ossicular chains and otic capsule were found in three and seven lesions respectively. CONCLUSION: The results indicate that the most common subsite for LCH of the pediatric temporal bone was the mastoid process. The location and extent of pediatric LCH of the temporal bone varied a lot between each other. The ossicular chains usually remain intact and the erosion of otic capsule can occur in some lesions.


Assuntos
Histiocitose de Células de Langerhans/patologia , Processamento de Imagem Assistida por Computador/métodos , Osso Temporal/patologia , Tomografia Computadorizada por Raios X/métodos , Pré-Escolar , Feminino , Seguimentos , Histiocitose de Células de Langerhans/diagnóstico por imagem , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Osso Temporal/diagnóstico por imagem
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 83-90, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29397823

RESUMO

OBJECTIVE: The study was to investigate the effect of silencing Eps8 gene expression on proliferation and apoptosis of human leukemia K562 cells and its molecular mechanism. METHODS: The expetriments were divided into 3 groups, including blank control group(K562 cells without treatment), K562-shRNA group(K562 cells transfected by specific Eps8-shRNA lenticiral vector) and K562-NC group(K562 cells transfected by negtive control lenticiral vector). K562 cells with stably-silenced Eps8 gene were constucted by lentibirus-mediated RNA technology. The efficacy of transfection was observed by fluorescence microscopy and the changes of Eps8 mRNA and protein level were detected by RT-PCR and Western blot respectively. Cell proliferation was confirmed by typan blue exclusion and MTT method. The apoptosis rate of cells was analysed by the flow cytometry, and colony forming was detected by methylcellulose colony forming assay. The protein level change of phosphrylated-AKT were detected by Western blot. RESULTS: Stably-silenced Eps8 gene K562 cells and the negative control cells were successfully constructed. Compared with the blank control group and the K562-NC group, the proliferation of K562-shRNA cells were siginificantly inhibited(P<0.05); the apoptosis of K562-shRNA cells increased(P<0.05). In addition, the methylcellulose colony forming assay showed that the colony forming was dramatically suppressed in K562-shRNA cells (P<0.05). Furthermore, knocking down Eps8 gene reduced the protein level of AKT phosphrylation at both residue Ser437 and Thr308(P<0.05), while there was no obvious change in the level of total-AKT(P>0.05). Knocking down Eps8 gene reduced the protein level of m-TOR phosphrylation and PRAS40 phosphrylation (P<0.05), while there was no obvious change in the level of total-mTOR and PRAS40 (P>0.05). CONCLUSION: Silencing Eps8 gene through lentvirus can inhibit the cell proliferation and promote the apoptosis of human leukemia K562 cells, which possibly relates with the inhibition of AKT/mTOR activation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose , Proliferação de Células , Inativação Gênica , Humanos , Células K562 , Leucemia , RNA Interferente Pequeno , Transfecção
14.
Acad Radiol ; 25(7): 925-934, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29373208

RESUMO

RATIONALE AND OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is an established method for portal hypertension. This study was to investigate the long-term safety, technical success, and patency of TIPS, and to determine the risk factors and clinical impacts of shunt dysfunction. MATERIALS AND METHODS: A total of 154 consecutive patients undergoing embolotherapy of gastric coronary vein and/or short gastric vein and TIPS creation were prospectively studied. Follow-up data included technical success, patency and revision of TIPS, and overall survival of patients. RESULTS: During the study, the primary and secondary technical success rates were 98.7% and 100%, respectively. Sixty-three patients developed shunt dysfunction, 30 with shunt stenosis and 33 with shunt occlusion. The cumulative 60-month primary, primary assisted, and secondary patency rates were 19.6%, 43.0%, and 93.4%, respectively. The cumulative 60-month overall survival rates were similar between the TIPS dysfunction group and the TIPS non-dysfunction group (68.6% vs. 58.6%, P = .096). Baseline portal vein thrombosis (P < .001), use of bare stents (P = .018), and portal pressure gradient (PPG) (P = .020) were independent predictors for shunt dysfunction, hepatocellular carcinoma (P < .001), and ascites (P = .003) for overall survival. The accuracy of PPG for shunt dysfunction was statistically significant (P < .001), and a cutoff value of 8.5 had 77.8% sensitivity and 64.8% specificity. CONCLUSIONS: The long-term safety, technical success, and patency of TIPS were good; baseline portal vein thrombosis, use of bare stents, and PPG were significantly associated with shunt dysfunction; shunt dysfunction has little impact on patients' long-term survival because of high secondary patency rates.

15.
Integr Cancer Ther ; 17(2): 477-485, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29108428

RESUMO

BACKGROUND: The outcome of patients with intermediate stage hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) remains poor. Search for a more effective therapy is still necessary. OBJECTIVE: This study aimed to investigate the effect of combining TACE with Kang'ai (KA) injection for treating patients with intermediate stage HCC. METHODS: A total of 89 patients with intermediate stage HCC were enrolled and divided into TACE +KA group (n = 48) receiving repeated TACE plus KA injection, and TACE group (n = 41) receiving repeated TACE alone. All patients were prospectively studied. Primary endpoints were overall survival (OS) and time to radiologic progression (TTP). RESULTS: The TACE + KA group had significantly longer median OS (27.0 vs 21.0 months, P = .038) and TTP (12.0 vs 10.0 months, P = .028) than TACE group. The 1-, 2-, and 3-year OS rates in the TACE + KA group were markedly higher than in TACE group (88.5%, 58.8%, and 20.8% vs 81.3%, 44.9%, and 6.7%, respectively, P = .038), while the 1- and 2-year TTP rates in the TACE + KA group were significantly lower than in TACE group (49.3% and 86.9% vs 75.3% and 100%, P = .028). TACE + KA group displayed significantly lower incidences of intrahepatic and extrahepatic metastases, as well as postembolization syndrome than TACE group ( P < .05). Multivariate analyses revealed group ( P = .023), maximum tumor size ( P = .019), and tumor number ( P = .034) as significant predictors for OS, and group ( P = .046), maximum tumor size ( P = .002) and α-fetoprotein level ( P = .020) as significant predictors for TTP. Both TACE and KA injection were well tolerated. CONCLUSION: TACE plus KA injection is more effective than TACE alone for treating patients with intermediate stage HCC in this nonrandomized study. Further research is warranted.

16.
Clin Appl Thromb Hemost ; 24(3): 462-470, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28110540

RESUMO

Portal vein thrombosis (PVT) is a common complication in cirrhosis. The aim of this study was to determine risk factors for PVT, assess the efficacy of anticoagulant therapy, and evaluate the effects of PVT on patients with cirrhosis undergoing elective transjugular intrahepatic portosystemic shunt (TIPSS). A total of 101 patients with cirrhosis undergoing elective TIPSS were prospectively studied. After TIPSS, all patients received preventive therapy for PVT and were followed up at 3, 6, 12, and 24 months. Clinical outcomes were compared between patients who developed PVT after TIPSS and those who did not. Multivariate analysis showed that white blood cell count (relative risk [RR]: 0.377; 95% confidence interval [CI]: 0.132-0.579; P = .001), Child-Turcotte-Pugh score (RR: 1.547; 95% CI: 1.029-2.365; P = .032), and ascites (RR: 1.264; 95% CI: 1.019-1.742; P = .040) were independent predictors for PVT. Warfarin treatment within 12 months achieved significantly higher rates of complete recanalization than aspirin or clopidogrel in patients with PVT (54.5% vs 31.3%; P = .013), although adverse events were similar between the 2 groups ( P > .05). Patients without PVT had significantly lower 2-year cumulative rates of variceal rebleeding (15.9% vs 36.6%; P = .023), shunt dysfunction (27.0% vs 46.8%; P = .039), hepatic encephalopathy (24.1% vs 42.6%; P = .045), and hepatocellular carcinoma (11.4% vs 31.2%; P = .024) and markedly higher 2-year cumulative survival rates (89.8% vs 72.9%; P = .041) than those with PVT. The PVT is associated with poorer clinical outcomes in TIPSS-treated patients, and warfarin is both safe and more effective in recanalizing PVT than aspirin or clopidogrel.


Assuntos
Fibrose/complicações , Veia Porta/patologia , Derivação Portossistêmica Transjugular Intra-Hepática , Trombose Venosa/etiologia , Varfarina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , Clopidogrel , Procedimentos Cirúrgicos Eletivos , Feminino , Fibrose/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Resultado do Tratamento
17.
Medicine (Baltimore) ; 96(45): e8498, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29137043

RESUMO

Portal vein thrombosis (PVT) is common in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS). This study had 3-fold aims: to assess risk factors for PVT; to determine the efficacy of anticoagulant therapy; to investigate the impact of PVT on clinical outcomes in TIPS-treated cirrhosis.Between June 2012 and February 2016, 126 TIPS-treated patients with cirrhosis were enrolled and studied prospectively. Enrolled patients were screened for PVT before TIPS and at 3, 6, 12, and 24 months post-TIPS. All patients received warfarin (1.5-3.0 mg/day) or aspirin (100 mg/day) or clopidogrel (75 mg/day) post-TIPS. Results of patients with and without PVT (baseline and de novo) were compared.White blood cell (WBC) counts (odds ratio (OR): 0.430, 95% confidence interval (CI): 0.251-0.739, P = .002) and Child-Turcotte-Pugh (CTP) score (OR: 2.377, 95% CI: 1.045-5.409, P = .039) were significant baseline predictors for PVT in TIPS-treated patients with cirrhosis. Warfarin resulted in markedly greater rates of complete recanalization than aspirin or clopidogrel (P < .05) in patients with PVT. Patients with PVT had markedly higher 2-year cumulative rates of variceal rebleeding, shunt dysfunction, hepatic encephalopathy, and hepatocellular carcinoma, and prominently lower overall survival than those without PVT (P < .05).In TIPS-treated patients with cirrhosis, lower WBC count and higher CTP score were independent baseline predictors for PVT; patients with PVT had worse clinical outcomes than those without; warfarin may be more effective in recanalizing PVT than aspirin or clopidogrel.


Assuntos
Anticoagulantes/administração & dosagem , Cirrose Hepática/cirurgia , Veia Porta/patologia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/administração & dosagem , Clopidogrel , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Transjugular Intra-Hepática/mortalidade , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Ticlopidina/administração & dosagem , Ticlopidina/análogos & derivados , Varfarina/administração & dosagem
18.
Int J Mol Sci ; 18(7)2017 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-28640193

RESUMO

The epidermis of swollen storage roots in purple cultivars of turnip "Tsuda" (Brassica rapa) accumulates anthocyanin in a light-dependent manner, especially in response to UV-A light, of which the mechanism is unclear. In this study, we mutagenized 15,000 seeds by 0.5% (v/v) ethyl methane sulfonate (EMS) and obtained 14 mutants with abnormal anthocyanin production in their epidermis of swollen storage roots. These mutants were classified into two groups: the red mutants with constitutive anthocyanin accumulation in their epidermis of storage roots even in underground parts in darkness and the white mutants without anthocyanin accumulation in the epidermis of storage roots in aboveground parts exposed to sunlight. Test cross analysis demonstrated that w9, w68, w204, r15, r21, r30 and r57 contained different mutations responsible for their phenotypic variations. Further genetic analysis of four target mutants (w9, w68, w204 and r15) indicated that each of them was controlled by a different recessive gene. Intriguingly, the expression profiles of anthocyanin biosynthesis genes, including structural and regulatory genes, coincided with their anthocyanin levels in the epidermis of storage roots in the four target mutants. We proposed that potential genes responsible for the mutations should be upstream factors of the anthocyanin biosynthesis pathway in turnips, which provided resources to further investigate the mechanisms of light-induced anthocyanin accumulation.


Assuntos
Antocianinas/genética , Vias Biossintéticas , Brassica rapa/genética , Mutação , Antocianinas/metabolismo , Brassica rapa/metabolismo , Brassica rapa/efeitos da radiação , Metanossulfonato de Etila/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Mutagênese , Mutagênicos/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Sementes/genética , Sementes/metabolismo , Luz Solar , Raios Ultravioleta
19.
J Immunother ; 40(5): 164-174, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28452850

RESUMO

Multitargeted tyrosine kinase inhibitors (MTKIs) have been shown to combine with natural killer (NK) cell adoptive transfer for the treatment in various cancers. MTKIs sensitize cancer cells to NK cell therapy through upregulation of nature killer group 2 member D ligands (NKG2DLs) on tumor cells. However, the molecular mechanism of MTKIs-mediated upregulation of NKG2DLs is still unknown. In this study, we confirmed sunitinib induced downregulation of its targets, such as vascular endothelial growth factor, platelet-derived growth factor, and c-kit in multiple-drug-resistant nasopharyngeal carcinoma cell line CNE2/DDP and hepatoma cell line HepG2. Then, we further showed sunitinib induced cell proliferation inhibition, apoptosis, and DNA damage in CNE2/DDP and HepG2 cells. Coculture experiments showed that sunitinib-treated CNE2/DDP and HepG2 cells were able to increase the activation and cytotoxicity of NK cells. Quantitative polymerase chain reaction results showed that sunitinib upregulated NKG2DLs, apoptotic genes, DNA damage repair genes, and nuclear factor (NF)-κß family genes. Silencing of NF-κß1, NF-κß2, or RelB (NF-κß pathway) inhibited sunitinib-induced upregulation of NKG2DLs. Taken together, we concluded that sunitinib upregulated NKG2DLs through NF-κß signaling noncanonical pathway which might mediate higher cytotoxic sensitivity of CNE2/DDP and HepG2 cells to NK cells.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Carcinoma/metabolismo , Vigilância Imunológica/efeitos dos fármacos , Indóis/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/biossíntese , Neoplasias Nasofaríngeas/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Pirróis/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma/terapia , Carcinoma Hepatocelular/terapia , Técnicas de Cocultura , Terapia Combinada , Citotoxicidade Imunológica/efeitos dos fármacos , Expressão Gênica , Células Hep G2 , Humanos , Imunoterapia Adotiva , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/transplante , Ligantes , Neoplasias Hepáticas/terapia , NF-kappa B/genética , NF-kappa B/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/agonistas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/terapia , RNA Interferente Pequeno/genética , Transdução de Sinais , Sunitinibe
20.
J Clin Apher ; 32(6): 453-461, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28304106

RESUMO

BACKGROUND: Therapeutic plasma exchange (TPE) and double plasma molecular absorption system (DPMAS) were two extracorporeal liver support systems. Few studies compared their efficacy profile. OBJECTIVE: This study was to compare the efficacy of TPE and DPMAS on acute-on-chronic liver failure (ACLF) caused by hepatitis B virus (HBV-ACLF). METHODS: 60 HBV-ACLF patients were enrolled and prospectively studied. All patients received entecavir therapy, and were assigned to TPE group (n = 33) and DPMAS group (n = 27). Primary end-points were the effects of TPE and DPMAS on liver function and serum inflammatory markers. RESULTS: Serum procalcitonin, interleukin (IL)-6, and high sensitive C-reactive protein (hsCRP) were significantly elevated in patients with HBV-ACLF. TPE achieved significantly higher removal rates of total bilirubin (TBIL, P = .002), direct bilirubin (DBIL, P = .006), and hsCRP (P = .010) than DPMAS, but DPMAS displayed lower loss rate of albumin (P = .000). TPE and DPMAS resulted in similarly increased serum IL-6 levels and comparable 12-week survivals (P > .05). Multivariate analysis showed that hospital stay (Relative Risk [RR]: 1.062, 95% Confidence Interval [CI]: 1.011-1.115, P = .016), prothrombin time (RR: 1.346, 95% CI: 1.077-1.726, P = .010), and international normalized ratio (RR: 0.013, 95% CI: 0.006-0.788, P = .041) were independent predictors for 12-week survival. Both TPE and DPMAS treatments were well-tolerated. CONCLUSION: Compared to DPMAS, TPE was more efficient in eliminating TBIL, DBIL, and hsCRP, but it was associated with higher loss rate of albumin. TPE and DPMAS were similar in improving 12-week survivals in HBV-ACLF.


Assuntos
Absorção Fisico-Química , Insuficiência Hepática Crônica Agudizada/tratamento farmacológico , Guanina/análogos & derivados , Vírus da Hepatite B , Troca Plasmática , Insuficiência Hepática Crônica Agudizada/terapia , Insuficiência Hepática Crônica Agudizada/virologia , Adulto , Antivirais , Bilirrubina/isolamento & purificação , Proteína C-Reativa/isolamento & purificação , Feminino , Guanina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida
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