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1.
BMC Med ; 21(1): 447, 2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974258

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease's development. There are many treatment options available to patients. We provide a comprehensive overview of the evidence on the treatment effects of several potential interventions for NAFLD with T2DM. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, Cochrane Library, and Web of Science from inception to June 30, 2023, for randomised controlled trials of treatment of NAFLD with T2DM. We performed Bayesian network meta-analyses to summarise effect estimates of comparisons between interventions. We applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks to rate all comparative outcomes' certainty in effect estimates, categorise interventions, and present the findings. This study was registered with PROSPERO, CRD42022342373. RESULTS: Four thousand three hundred and sixty-nine records were retrieved from the database and other methods, of which 24 records were eligible for studies enrolling 1589 participants. Eight clinical indicators and 14 interventions were finally in focus. Referring to the lower surface under the cumulative ranking curves (SUCRA) and the league matrix table, exenatide and liraglutide, which are also glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed excellent potential to reduce liver fat content, control glycemia, reduce body weight, and improve liver function and insulin resistance. Exenatide was more effective in reducing glycated haemoglobin (HbA1c) (mean difference (MD) 0.32, 95%CI 0.12 to 0.52), lowering BMI (MD 0.81, 95%CI 0.18 to 1.45), and lowering alanine transaminase (ALT) (MD 10.96, 95%CI 5.27 to 16.66) compared to liraglutide. However, this evidence was assessed as low certainty. Omega-3 was the only intervention that did not have a tendency to lower HbA1c, with standard-treatment (STA-TRE) as reference (MD - 0.17, 95%CI - 0.42 to 0.07). Glimepiride is the only intervention that causes an increase in ALT levels, with standard-treatment (STA-TRE) as reference (MD - 11.72, 95%CI - 17.82 to - 5.57). Based on the available evidence, the treatment effects of pioglitazone, dapagliflozin, and liraglutide have a high degree of confidence. CONCLUSIONS: The high confidence mandates the confident application of these findings as guides for clinical practice. Dapagliflozin and pioglitazone are used for glycaemic control in patients with NAFLD combined with T2DM, and liraglutide is used for weight loss therapy in patients with abdominal obesity. The available evidence does not demonstrate the credibility of the effectiveness of other interventions in reducing liver fat content, visceral fat area, ALT, and insulin resistance. Future studies should focus on the clinical application of GLP-1Ras and the long-term prognosis of patients.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Exenatida/uso terapêutico , Hipoglicemiantes/farmacologia , Liraglutida/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Metanálise em Rede , Pioglitazona/uso terapêutico , Teorema de Bayes
2.
Lancet Digit Health ; 5(11): e754-e762, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37770335

RESUMO

BACKGROUND: Hepatic echinococcosis is a severe endemic disease in some underdeveloped rural areas worldwide. Qualified physicians are in short supply in such areas, resulting in low rates of accurate diagnosis of this condition. In this study, we aimed to develop and evaluate an artificial intelligence (AI) system for automated detection and subtyping of hepatic echinococcosis using plain CT images with the goal of providing interpretable assistance to radiologists and clinicians. METHODS: We developed EDAM, an echinococcosis diagnostic AI system, to provide accurate and generalisable CT analysis for distinguishing hepatic echinococcosis from hepatic cysts and normal controls (no liver lesions), as well as subtyping hepatic echinococcosis as alveolar or cystic echinococcosis. EDAM includes a slice-level prediction model for lesion classification and segmentation and a patient-level diagnostic model for patient classification. We collected a plain CT database (n=700: 395 cystic echinococcosis, 122 alveolar echinococcosis, 130 hepatic cysts, and 53 normal controls) for developing EDAM, and two additional independent cohorts (n=156) for external validation of its performance and generalisation ability. We compared the performance of EDAM with 52 experienced radiologists in diagnosing and subtyping hepatic echinococcosis. FINDINGS: EDAM showed reliable performance in patient-level diagnosis on both the internal testing data (overall area under the receiver operating characteristic curve [AUC]: 0·974 [95% CI 0·936-0·994]; accuracy: 0·952 [0·939-0·965] for cystic echinococcosis, 0·981 [0·973-0·989] for alveolar echinococcosis; sensitivity: 0·966 [0·951-0·979] for cystic echinococcosis, 0·944 [0·908-0·970] for alveolar echinococcosis) and the external testing set (overall AUC: 0·953 [95% CI 0·840-0·973]; accuracy: 0·929 [0·915-0·947] for cystic echinococcosis, 0·936 [0·919-0·950] for alveolar echinococcosis; sensitivity: 0·913 [0·879-0·944] for cystic echinococcosis, 0·868 [0·841-0·897] for alveolar echinococcosis). The sensitivity of EDAM was robust across images from different CT manufacturers. EDAM outperformed most of the enrolled radiologists in detecting both alveolar echinococcosis and cystic echinococcosis. INTERPRETATION: EDAM is a clinically applicable AI system that can provide patient-level diagnoses with interpretable results. The accuracy and generalisation ability of EDAM demonstrates its potential for clinical use, especially in underdeveloped areas. FUNDING: Project of Qinghai Provincial Department of Science and Technology of China, National Natural Science Foundation of China, and Tsinghua-Fuzhou Institute of Data Technology Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Cistos , Aprendizado Profundo , Equinococose Hepática , Equinococose , Humanos , Equinococose Hepática/diagnóstico por imagem , Estudos Retrospectivos , Inteligência Artificial , Tomografia Computadorizada por Raios X
3.
J Minim Access Surg ; 19(4): 453-458, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37706417

RESUMO

The purpose of this study was to systematically evaluate the prognosis of patients with hepatocellular carcinoma (HCC) smaller than 5 cm using microwave ablation (MWA) versus radiofrequency ablation (RFA). PubMed, Cochrane Library and Embase databases were searched for studies reporting comparisons of two interventions (MWA versus RFA) for patients with early-stage HCC published up to 31 December, 2022. The analysis evaluated the recurrence-free survival (RFS), overall survival (OS) and complications. A total of 894 patients were enrolled in six studies (two randomised controlled trials and four propensity score cohort studies). There were 446 patients in the MWA group and 448 patients in the RFA group. Compared with RFA, MWA had a significant advantage in the post-operative 1-, 2-, 3- and 5-year RFS (odds ratios [OR] = 0.58, 95% confidence interval [CI]: 0.40, 0.84; OR = 0.60, 95% CI: 0.45, 0.80; OR = 0.56, 95% CI: 0.33, 0.93; and OR = 0.44, 95% CI: 0.30, 0.65). The OS of MWA was significantly higher than that of RFA in 5 years after ablation (OR = 0.48, 95% CI: 0.34, 0.68). Moreover, MWA had an advantage in the incidence of complications (OR = 2.23, 95% CI: 1.16, 4.29). In the comparison of percutaneous MWA and RFA in the treatment of HCC with a diameter smaller than 5 cm, MWA may have more advantages in improving the prognosis.

4.
World J Gastroenterol ; 29(14): 2153-2171, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37122606

RESUMO

BACKGROUND: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a significant component of the innate immune system that plays a vital role in the development of various parasitic diseases. However, its role in hepatic alveolar echinococcosis (HAE) remains unclear. AIM: To investigate the NLRP3 inflammasome and its mechanism of activation in HAE. METHODS: We assessed the expression of NLRP3, caspase-1, interleukin (IL)-1ß, and IL-18 in the marginal zone and corresponding normal liver of 60 patients with HAE. A rat model of HAE was employed to investigate the role of the NLRP3 inflammasome in the marginal zone of HAE. Transwell experiments were conducted to investigate the effect of Echinococcus multilocularis (E. multilocularis) in stimulating Kupffer cells and hepatocytes. Furthermore, immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay were used to evaluate NLRP3, caspase-1, IL-1ß, and IL-18 expression; flow cytometry was used to detect apoptosis and reactive oxygen species (ROS). RESULTS: NLRP3 inflammasome activation was significantly associated with ROS. Inhibition of ROS production decreased NLRP3-caspase-1-IL-1ß pathway activation and mitigated hepatocyte damage and inflammation. CONCLUSION: E. multilocularis induces hepatocyte damage and inflammation by activating the ROS-mediated NLRP3-caspase-1-IL-1ß pathway in Kupffer cells, indicating that ROS may serve as a potential target for the treatment of HAE.


Assuntos
Equinococose Hepática , Inflamassomos , Animais , Ratos , Inflamassomos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Proteínas NLR , Domínio Pirina , Transdução de Sinais , Inflamação/metabolismo , Caspase 1/metabolismo , Interleucina-1beta/metabolismo
5.
Front Surg ; 10: 1089788, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36874451

RESUMO

Objective: To summarize the single-centre experience of Ex vivo Liver Resection and Autotransplantation (ELRA) to treat end-stage hepatic alveolar echinococcosis (HAE). Methods: Retrospective analysis of clinical data and follow-up data of 13 patients admitted to the Affiliated Hospital of Qinghai University from January 2015 to December 1, 2020, with the Ex vivo Liver Resection and Autotransplantation for hepatic alveolar echinococcosis. Result: 13 patients underwent successful total/ semi-ex-vivo liver resection combined with Ex vivo Liver Resection and Autotransplantation with no intra-operative deaths. the median standard liver volume was 1,118 ml (1,085-1,206.5 ml); the median residual liver volume was 634 ml (526.5-1,338 ml); The median weight of the autograft was 845.8 g (619.5-1,020.5 g), the median operation time was 14.5 h (11.5-16.15 h); the median anhepatic period time was 290 min (257-312.5 min). The median intraoperative blood loss was 1,900 ml (1,300-3,500 ml); the median number of erythrocyte suspensions entered was 7.5 u (6-9u). The median length of hospital stay was 32 days (24-40 days). Postoperative complications occurred in 9 patients during hospitalization,with 7 patients graded at grade III or higher by Clavien-Dindo; 4 patients died postoperatively. 1 patient had recurrent abdominal distension with massive thoracoabdominal fluid and coagulation dysfunction 8 months after surgery and was considered to have small liver syndrome. 1 patient developed HAE recurrence during the follow-up, which was considered intraoperative incisional implantation. Conclusion: ELRA is one of the most valuable therapeutic measures for the treatment of end-stage complicated hepatic alveolar echinococcosis. Precise preoperative assessment of liver function, individualized intraoperative duct reconstruction, and precise management of the postoperative disease can achieve better treatment results.

6.
Front Oncol ; 12: 961194, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465396

RESUMO

Objective: This study aimed to investigate the clinical characteristics and risk factors of patients with hepatocellular carcinoma (HCC) with extrahepatic metastases (EHM) and to establish an effective predictive nomogram. Methods: Clinical and pathological data from 607 patients with hepatocellular carcinoma admitted to the Affiliated Hospital of Qinghai University between 1 January 2015 and 31 May 2018 were documented, as well as demographics, clinical pathological characteristics, and tumor-related parameters to clarify clinical risk factors for HCC EHM. These risks were selected to build an R-based clinical prediction model. The predictive accuracy and discriminating ability of the model were determined by the concordance index (C-index) and the calibration curve. The results were validated with a bootstrap resample and 151 patients from 1 June 2018 to 31 December 2019 at the same facility. Results: In multivariate analysis, independent factors for EHM were neutrophils, prothrombin time, tumor number, and size, all of which were selected in the model. The C-index in the EHM prediction model was 0.672 and in the validation cohort was 0.694. In the training cohort and the validation cohort, the calibration curve for the probability of EHM showed good agreement between the nomogram prediction and the actual observation. Conclusion: The extrahepatic metastasis prediction model of hepatocellular carcinoma constructed in this study has some evaluation capability.

7.
Front Oncol ; 12: 849047, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402272

RESUMO

Echinococcosis is a human-animal parasitic disease caused by Echinococcosis tapeworm larvae in humans. From a global perspective, it is mainly prevalent in the mid-high latitudes of the Northern Hemisphere, and it is a widespread infectious disease. Its form, host and release areas are slightly different. In clinical practice, Echinococcus granulosus (hepatic cystic echinococcosis) is the most common. Its growth mode is swelling growth and its metastasis is more common in implanted metastasis; However, hepatic alveolar echinococcosis (HAE) is rare. It has been reported that HAE can metastasize through the blood or lymph nodes, and its invasive growth pattern is known as "carcinoma". At this time, it may be accompanied by invasion of the portal vein and inferior vena cava(IVC)or metastasis to distant organs outside the liver (such as lung, brain, lymph nodes). Most patients are in the middle or late stages, making treatment complicated. World Health Organization guidelines recommend radical resection of HAE; However, there is no consensus on lymph node dissection. To date, there have been no reports of cases of HAE accompanied by inferior vena cava-para-abdominal aortic suspected lymph node metastasis and infection. This article reports a clinical case of a complex HAE treated by the surgical method of "middle liver resection + abdominal enlarged lymph node resection + inferior vena cava repair", and histological examination was performed to illustrate the differences in microscopic pathology of alveolar echinococcosis invading the liver and lymph nodes at different magnifications. This article reviews the relevant literature on HAE and derives the latest treatment methods for HAE to provide a reference for future clinical cases of similar alveolar echinococcosis and maximize the benefits of patients.

8.
J Parasitol ; 108(2): 159-165, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35353187

RESUMO

The serum ferritin (SF) levels of patients with hepatic alveolar echinococcosis (HAE) were compared to the laboratory reference value, and the correlation between SF and associated parameters in patients with HAE was assessed. Hematological and imaging data of 245 patients with HAE were collected. Patients were classified into the LSF group (SF ≤ 204 ng/ml) or HSF group (SF > 204 ng/ml) according to the level of SF. There was no significant difference in the serum iron level between groups (P > 0.05). Significant differences in unsaturated iron-binding capacity (UIBC), liver function, blood coagulation, lipid, blood cell count, and lesion characteristics were observed (P < 0.05). Correlation analysis showed that SF was related to UIBC, γ-glutamyl transferase, total bilirubin (TBIL), direct bilirubin (DBIL), fibrinogen (FIB), neutrophil count, and maximal lesion diameter (all absolute rs ≥ 0.4). The correlation coefficient between SF and UIBC showed the highest absolute value (rs = -0.556, P < 0.001). Single-factor linear regression analysis showed that TBIL and DBIL showed the R2 values were 0.221 and 0.220, and the R2 values of UIBC, FIB, and maximal lesion diameter were 0.157, 0.174, and 0.167, respectively, and those of the remaining indicators were <0.1. Multi-factor binary logistic regression analysis showed that UIBC (P < 0.001, OR = 0.909), FIB (P = 0.020, OR = 1.662), hemoglobin (HGB) (P = 0.002, OR = 1.029), and maximal lesion diameter (P = 0.002, OR = 1.146) were significant factors influencing SF abnormalities. SF levels in some patients with HAE were higher than the laboratory reference value. Correlation and regression analysis of SF suggested that the UIBC, FIB, HGB, and maximal lesion diameter were related to SF and affected the SF level. These results may be helpful for the diagnosis and severity assessment of HAE in the future.


Assuntos
Equinococose Hepática , Equinococose Hepática/diagnóstico por imagem , Ferritinas , Humanos
9.
BMC Med Imaging ; 22(1): 27, 2022 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-35151256

RESUMO

BACKGROUND: Microwave ablation (MWA) is a popular therapy for liver malignant tumor in recent years. Few studies have been conducted on its use in the treatment of hepatic alveolar echinococcosis (HAE). The study aims to evaluate the efficacy and safety of MWA in the treatment of HAE. METHODS: This study analyzed the data of 45 patients (mean age, 38 ± 2 years; 24 males) diagnosed with HAE and underwent MWA treatment between June 2014 to December 2019. The patients after MWA were examined by CT or MRI [follow-up: 32 months (IQR 23-48.5)] to determine whether the lesions were relapsed and to evaluate the therapeutic effect of MWA. The safety of MWA was evaluated by monitoring postoperative complications. Clinical data, such as patient demographics, imaging features of the lesions, relevant findings of laboratory tests before and after ablation, and information related to ablation, were collected and analyzed. Paired-sample t tests and paired-sample Wilcoxon signed-rank tests were used to compare relevant laboratory indicators before and after MWA. RESULTS: MWA was applied to 57 HAE lesions in 45 patients. The median size of lesions was 3.42 cm (IQR2.85-4.41). The rate of complete ablation was 100% (57/57). The median follow-up time was 32 months (IQR 23-48.5). The recurrence rate was 13% (6/45), and the median time of recurrence was 22 months. The rate of minor complications was 11.1% (5/45), and there were no major complications and deaths. Compared to preoperative, ALB, RBC, HBG, and PLT were decreased (p < 0.001); ALT, TB, DB, and WBC were increased (p < 0.001); and no statistically difference in PT, APTT, and INR (p > 0.05). CONCLUSIONS: MWA might be a safe and effective way to cure HAE. Meanwhile, it provides a new option and a new way of thinking about treatment for patients with HAE.


Assuntos
Ablação por Cateter/métodos , Equinococose Hepática/cirurgia , Ultrassonografia de Intervenção , Adulto , Ablação por Cateter/efeitos adversos , Equinococose Hepática/diagnóstico por imagem , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/cirurgia , Masculino , Micro-Ondas
11.
Technol Health Care ; 30(4): 799-814, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35068426

RESUMO

BACKGROUND: Alveolar echinococcosis is an epidemic disease caused by the parasitism of Echinococcus multilocularis (Em) larvae in the intermediate or final host. OBJECTIVE: To identify and analyze B-cell and T-cell (Th1, Th2, and Th17) epitopes of the Em antigen protein thrombospondin 3 (TSP3). METHODS: The amino acid sequence of TSP3 was obtained, and the secondary structural characteristics of TSP3 were predicted using bioinformatics software to further predict its potential T-cell and B-cell epitopes. The spleen lymphocytes of BALB/c mice, which were immunized with the TSP3 protein, were collected for co-culture with B-cell and T-cell antigen small peptides. The B-cell epitopes and T-cell epitope subtypes Th1, Th2, and Th17 were identified as having good immunogenicity. RESULTS: After identification, it was found that the predominant epitopes of B cells existing in TSP3 were T18-33, T45-55, and T110-122. Furthermore, the predominant epitopes of T cells existing in TSP3 were T33-42, T45-55, T80-90, and T110-122 in the T1 subtype, T45-55, T68-77, and T92-104 in the Th2 subtype, and T53-63 and T80-90 in the Th17 subtype. CONCLUSIONS: Six T-cell and eight B-cell dominant epitopes of the TSP3 antigen were revealed; these results may be applied in the development of a dominant epitope vaccine.


Assuntos
Equinococose , Echinococcus multilocularis , Animais , Equinococose/prevenção & controle , Epitopos de Linfócito B , Camundongos , Trombospondinas
12.
Acta Trop ; 228: 106307, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35016884

RESUMO

BACKGROUND: To explore the efficacy of microwave ablation (MWA) in the treatment of hepatic alveolar echinococcosis (HAE) with a diameter of ≤5 cm. METHOD: From June 2014 to January 2020, patients diagnosed with HAE were retrospectively analyzed. After balancing the confounding factors by propensity score matching (PSM) , the patients were divided into MWA group (n = 20) and radical operation group (n = 20) by 1:1 matching. The safety and effectiveness of MWA were assessed by comparing the differences between the two groups in terms of postoperative general laboratory indices, grading of postoperative complications, length of postoperative hospitalization, the outcome of treatment, and disease recurrence. RESULT: After PSM, all confounders were not statistically different (P>0.05) . Compared with the radical surgery group, patients in the MWA group had lower postoperative ALT and WBC elevations (P<0.001) , shorter postoperative hospital stay (P<0.001) ) , lower hospital costs (P<0.001) . The effective rate of the two groups was 100%. There was no statistical difference in the incidence of postoperative complications and recurrence rate (P>0.05). CONCLUSION: MWA is a safe and effective means of treating HAE ≤ 5 cm in diameter.


Assuntos
Equinococose Hepática , Neoplasias Hepáticas , Ablação por Radiofrequência , Equinococose Hepática/cirurgia , Humanos , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
14.
Comput Math Methods Med ; 2021: 3422393, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34845413

RESUMO

BACKGROUND: To analyze the expression of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and cognitive impairment, explore the relationship between the expression of VEGF family genes and prognosis of patients with HCC, and evaluate the predictive ability of VEGF in cognitive impairment using computerized methods. METHODS: VEGF expression in liver cancer tissues and normal tissues was analyzed using bioinformatics methods. The Kaplan-Meier survival analysis method was also used to analyze the relationship between VEGF expression and the prognosis of patients with HCC. Furthermore, immune infiltration assessment and gene set enrichment analysis were performed. Meanwhile, the differential expression of VEGF family genes between patients with Alzheimer's disease (AD) and healthy controls was also checked. RESULTS: Based on The Cancer Genome Atlas (TCGA) database, the VEGF family genes (VEFGA, VEGFB, VEGFC, and VEGFD) were highly expressed in cancer tissues and were significantly associated with poor prognosis in HCC. In HCC, the VEGF family genes showed significant heterogeneity in their functional and immune infiltration characteristics. Finally, VEGF family genes were identified as prognostic biomarkers in AD and risk prediction markers in HCC. CONCLUSIONS: VEGF is highly expressed in patients with HCC and lowly expressed in patients with AD. VEGF has opposite opposing roles in the treatment of tumors and cognitive impairment.


Assuntos
Doença de Alzheimer/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fatores de Crescimento do Endotélio Vascular/genética , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Biologia Computacional , Bases de Dados Genéticas , Expressão Gênica , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Marcadores Genéticos , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Fatores de Risco , Fator B de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/genética , Fator D de Crescimento do Endotélio Vascular/genética
15.
Biochem Biophys Res Commun ; 577: 45-51, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34507064

RESUMO

Liver cancer is one of the most common malignancies that is difficult to treat due to late diagnosis and chemo-resistance. In the present study, we developed and validated a cell based split nanoLuc biosensor to monitor the Apaf1-Apaf1 interactions in response to apoptosis-inducing drugs such as cisplatin. We showed that the activity of split nanoLuc is reconstituted only in response to apoptotic inducer, cisplatin and in a dose-dependent manner. Apaf1 mutants which were unable to oligomerize failed to recover nanoLuc activity while constitutively active variant increased the nanoLuc activity. Generation of Apaf1 knockout HepG2 and treatment with cisplatin showed dramatic reduction in cell death suggesting that cisplatin mainly targets liver cancer cells through apoptosis. As the natural products are potent sources of compounds for adjuvant therapy, we screened a collection of natural products and identified lentinan as an inducer of apoptosome formation, a key step for induction of apoptosis. Lentinan is a polysaccharide with antitumor, pro-apoptotic properties that functions with poorly understood mechanisms. Lentinan was shown to have cytotoxic effects with the IC50 of 650 µM. Sub-lethal lentinan concentration doubled the nanoLuc activity when co-treated with cisplatin. We also showed that lentinan hugely reduced the dose of cisplatin to induce certain amount of death and that lentinan co-treatment with cisplatin enhanced the Apaf1 transcription in HepG2 cells while lentinan or cisplatin alone failed to alter the transcription. In addition, lentinan and cisplatin co-treatment induced mitochondrial depolarization. This suggested that lentinan combinatorial therapy with cisplatin engaged a different signalling pathway to kill the liver cancer cells and that adjuvant therapy with lentinan can reduce the dose of cisplatin and thus reduce the possibility of chemo-resistance.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Técnicas Biossensoriais/métodos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Apoptose/genética , Fator Apoptótico 1 Ativador de Proteases/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Cisplatino/administração & dosagem , Sinergismo Farmacológico , Células Hep G2 , Humanos , Lentinano/administração & dosagem , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Mutação
16.
Front Immunol ; 12: 691364, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248983

RESUMO

Background: To explore the relationship between the preoperative immune inflammation index (SII) and the prognostic nutritional index (PNI) and the overall survival rate (OS) of patients with alveolar hydatid disease. Methods: The clinical data of patients with hepatic alveolar echinococcosis treated by surgery in the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Qinghai University from January 2015 to January 2019 were analyzed retrospectively, and the SII, PNI, PLR and NLR were calculated. Spearman correlation analysis was utilized to analyze the correlation among SII, PNI, PLR and NLR. Receiver operating characteristic curve (ROC) was utilized to determine the best intercept values of SII, PNI, PLR and NLR, and Chi-square test was used to evaluate the relationship between SII, PNI and various clinicopathological features in patients with hepatic alveolar echinococcosis. The kaplan-Meier method was used to draw survival curves and analyze the relationship between them and the total survival time of patients. A cox regression model was used to analyze the relationship between SII, PNI and the prognosis of patients with hepatic alveolar echinococcosis. Finally, ROC curve was used to estimate the predictive efficacy of SII, PNI and COSII-PNI for the prognosis of patients with hepatic alveolar echinococcosis. Results: A total of 242 patients were included, including 96 males and 146 females, aged 11.0-67.0 (36.6 ± 11.7) years. The values of SII, PNI, PLR and NLR are calculated, and the best truncation values of SII, PNI, PLR and NLR are given in ROC curve. The kaplan-Meier survival curve was used to analyze the relationship between SII, PNI, PLR, NLR and the overall survival time of patients with hepatic alveolar echinococcosis. The results showed that the median follow-up time was 45 months (95%CI: 39.484-50.516), and the average survival time was 49 months (95%CI: 47.300-51.931), which was low p<0.001); The 5-year OS rate of low PNI was significantly lower than that of high PNI group (37.7% vs 71.6%; p<0.001); The 5-year OS rate in low PLR group was significantly higher than that in high PLR group (70.4% vs 24.3%; p<0.001); The 5-year OS rate in low NLR group was significantly higher than that in high NLR group (67.2% vs 28.8%; p<0.001). Cox unifoliate analysis showed that SII, PNI, PLR and NLR were important prognostic factors related to OS. Cox multivariate analysis showed that SII(HR=4.678, 95% CI: 2.581-8.480, P<0.001) and PNI(HR=0.530, 95%CI: 0.305-0.920, P<0.05) were identified as independent risk indicators of OS, while NL was identified as independent risk indicators of OS ROC curve analysis showed that AUC of SII, PNI, PLR, NLR and COSII-PNI were 0.670(95%CI: 0.601-0.738), 0.638(95%CI: 0.561-0.716) and 0.618(95% CI: 0.541-0.694), respectively COSII-PNI is superior to SII and PNI in evaluating prognosis (P < 0.05). Conclusions: SII and PNI can be regarded as independent risk factors reflecting the prognosis of patients with hepatic alveolar echinococcosis. The lower SII and the higher PNI before operation, the better the prognosis of patients, and the combined application of SII and PNI before operation can improve the accuracy of prediction.


Assuntos
Equinococose , Hepatopatias , Adolescente , Adulto , Idoso , Criança , Equinococose/imunologia , Equinococose/mortalidade , Equinococose/cirurgia , Equinococose/terapia , Feminino , Humanos , Inflamação/imunologia , Inflamação/mortalidade , Inflamação/cirurgia , Inflamação/terapia , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Fígado/cirurgia , Hepatopatias/imunologia , Hepatopatias/mortalidade , Hepatopatias/cirurgia , Hepatopatias/terapia , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Cuidados Paliativos , Contagem de Plaquetas , Período Pré-Operatório , Prognóstico , Adulto Jovem
17.
Clin Infect Dis ; 73(1): e246-e251, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33146713

RESUMO

BACKGROUND: Alveolar echinococcosis (AE) is a serious parasitic disease caused by the larvae of Echinococcus multilocularis. It is the less common but substantially more deadly of the 2 major echinococcosis diseases that can occur globally but are concentrated in central Asia. METHODS: We analyzed parasite circulating cell-free DNA (cfDNA) in 149 plasma samples using a DNA sequencing-based method (105 AE, 16 cystic echinococcosis, 4 liver cancer, 4 gallstones, and 20 healthy volunteers). After identifying the Echinococcus-specific cfDNA (Em-cfDNA) sequences in the samples, we determined whether Em-cfDNA could be used for AE diagnosis and as a potential indicator of the effectiveness of surgical treatment. We also examined potential associations between Em-cfDNA levels and clinical features of AE patients. RESULTS: Our work demonstrates that varying reads of Em-cfDNA were detectable in the plasma of 100% of preoperative AE patients and that all of the non-AE patients and healthy volunteers were negative. Em-cfDNA has good sensitivity and specificity for the diagnosis of AE. We also found that Em-cfDNA levels apparently have reference value for evaluating the therapeutic efficacy of surgery interventions for AE lesions. Finally, our analysis revealed that Em-cfDNA levels can reflect meaningful information about lesion size in preoperative AE patients. CONCLUSIONS: We demonstrate that sequencing-based monitoring of Em-cfDNA can be used in the clinic as a powerful diagnostic indicator for AE. We also note that there is a strong potential for use of this liquid-biopsy method to monitor ongoing disease status in postintervention AE patients.


Assuntos
Ácidos Nucleicos Livres , Equinococose , Echinococcus multilocularis , Parasitos , Animais , Equinococose/diagnóstico , Echinococcus multilocularis/genética , Humanos
18.
Parasite ; 27: 74, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33357363

RESUMO

BACKGROUND: Echinococcosis is a chronic consumptive liver disease. Little research has been carried out on the nutritional status of infected patients, though liver diseases are often associated with malnutrition. Our study investigated four different nutrition screening tools, to assess nutritional risks of hospitalized patients with echinococcosis. METHODS: Nutritional Risk Screening 2002 (NRS 2002), Short Form of Mini Nutritional Assessment (MNA-SF), Malnutrition Universal Screening Tool (MUST), and the Nutrition Risk Index (NRI) were used to assess 164 patients with alveolar echinococcosis (AE) and 232 with cystic echinococcosis (CE). Results were then compared with European Society for Clinical Nutrition and Metabolism (ESPEN) criteria for malnutrition diagnosis. RESULTS: According to ESPEN standards for malnutrition diagnosis, 29.2% of CE patients and 31.1% of AE patients were malnourished. The malnutrition risk rates for CE and AE patients were as follows: NRS 2002 - 40.3% and 30.7%; MUST - 51.5% and 50.9%; MNA-SF - 46.8% and 44.1%; and NRI - 51.1% and 67.4%. In patients with CE, MNA-SF and NRS 2002 results correlated well with ESPEN results (k = 0.515, 0.496). Area-under-the-curve (AUC) values of MNA-SF and NRS 2002 were 0.803 and 0.776, respectively. For patients with AE, NRS 2002 and MNA-SF results correlated well with ESPEN (k = 0.555, 0.493). AUC values of NRS 2002 and MNA-SF were 0.776 and 0.792, respectively. CONCLUSION: This study is the first to analyze hospitalized echinococcosis patients based on these nutritional screening tools. Our results suggest that NRS 2002 and MNA-SF are suitable tools for nutritional screening of inpatients with echinococcosis.


TITLE: État nutritionnel et outils de dépistage pour détecter le risque nutritionnel chez les patients hospitalisés atteints d'échinococcose hépatique. ABSTRACT: Contexte : L'échinococcose est une maladie hépatique consommatrice chronique. Il existe peu de recherches sur l'état nutritionnel des patients infectés, bien que les maladies du foie soient souvent associées à la malnutrition. Notre étude a examiné quatre différents outils de dépistage nutritionnel, pour évaluer les risques nutritionnels des patients hospitalisés atteints d'échinococcose. Méthodes : Les méthodes Nutritional Risk Screening 2002 (NRS 2002), Short Form of Mini Nutritional Assessment (MNA-SF), Malnutrition Universal Screening Tool (MUST) et Nutrition Risk Index (NRI) ont été utilisées pour évaluer 164 patients atteints d'échinococcose alvéolaire (EA) et 232 avec échinococcose kystique (EK). Les résultats ont ensuite été comparés aux critères de la Société européenne pour la nutrition clinique et le métabolisme (ESPEN) pour le diagnostic de la malnutrition. Résultats : Selon les normes ESPEN pour le diagnostic de la malnutrition, 29,2 % des patients avec EK et 31,1 % des patients avec EA étaient malnutris. Les taux de risque de malnutrition pour les patients EK et EA étaient, respectivement : NRS 2002 - 40,3 % et 30,7 % ; MUST - 51,5 % et 50,9 % ; MNA-SF - 46,8 % et 44,1 % ; NRI - 51,1 % et 67,4 %. Chez les patients atteints d'EK, les résultats de MNA-SF et NRS 2002 étaient bien corrélés aux résultats ESPEN (k = 0,515, 0,496), et les valeurs de l'aire sous la courbe (ASC) du MNA-SF et du NRS 2002 étaient respectivement de 0,803 et 0,776. Pour les patients atteints d'EA, les résultats NRS 2002 et MNA-SF étaient bien corrélés avec ESPEN (k = 0,555, 0,493), et les valeurs de l'ASC du NRS 2002 et du MNA-SF étaient respectivement de 0,776 et 0,792. Conclusion : Cette étude est la première à analyser les patients hospitalisés atteints d'échinococcose à partir de ces outils de dépistage nutritionnel. Nos résultats suggèrent que les méthodes NRS 2002 et MNA-SF sont des outils appropriés pour le dépistage nutritionnel des patients hospitalisés atteints d'échinococcose.


Assuntos
Equinococose Hepática , Desnutrição , Estado Nutricional , Medição de Risco , Adulto , China/epidemiologia , Equinococose Hepática/complicações , Equinococose Hepática/diagnóstico , Equinococose Hepática/epidemiologia , Feminino , Humanos , Masculino , Desnutrição/complicações , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Avaliação Nutricional , Medição de Risco/métodos , Fatores de Risco
19.
World J Surg ; 44(11): 3884-3892, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32647987

RESUMO

PURPOSE: Biliary leakage caused by cystobiliary communication (CBC) is a common clinical concern. This study sought to identify predictors of CBC in hepatic cystic echinococcosis (HCE) patients undergoing hydatid liver cyst surgery and establish nomograms to predict CBC. METHODS: A predictive model was established in a training cohort of 310 HCE patients diagnosed between January 2013 and May 2017. Upon revision of the records of clinical parameters and imaging features of these patients, the lasso regression model was used to optimize feature selection for the CBC risk model. Combined with feature selection, a CBC nomogram was developed with multivariable logistic regression. C-index and calibration plots were used to analyze and evaluate the discrimination and calibration. The net benefit and predictive accuracy of the nomogram were performed via decision curve analysis (DCA) and receiver operating characteristic (ROC) curve. An independent validation cohort of 132 patients recruited from June 2017 to May 2019 was used to evaluate the practicability of the nomogram. RESULTS: Predictors contained four features, namely alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), cyst size and cyst location. The C-index of the nomogram is 0.791 (95% CI, 0.736-0.845), while the C-index verified by bootstrap is 0.746, indicating high prediction accuracy. The area under the curve (AUC) of the CBC in training was 0.766. ROC curve analysis demonstrated high sensitivity and specificity. Decision curve analysis confirmed the CBC nomogram was clinically useful when the intervention was determined at the non-adherence possibility threshold of 8%. CONCLUSION: The nomogram developed using the ALP, GGT, cyst size and cyst location could be used to facilitate the CBC risk prediction in HCE patients.


Assuntos
Cistos , Equinococose Hepática , Comunicação , Equinococose Hepática/cirurgia , Humanos , Nomogramas , Curva ROC , Fatores de Risco
20.
Iran J Parasitol ; 15(1): 138-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32489386

RESUMO

There is no direct evidence to support the existence of regional lymph node metastatic routes in hepatic alveolar echinococcosis, and only a few literature have been reported. There was a case of hepatic alveolar echinococcosis suspected of metastasis of regional lymph node in Clinical Center for Hydatidosis, Qinghai Province, China. The patient was a 24-yr-old male from pastoral area of Seda County, Sichuan Province, China in 2018. He was admitted to the hospital for physical examination and had no special discomfort. Preoperative examination showed liver occupancy and regional lymph node enlargement in the space between liver and stomach. Hepatectomy and lymph node resections were performed. Postoperative pathological results showed that both primary and metastatic lesion were of alveolar echinococcosis. Recovery of patient was good without complications and recurrence. In this case, metastasis was considered because the liver lesion was not directly connected to the lymph node. However, the case was still suspected due to the lack of pathological examination of other lymph nodes in the lymphatic return pathway. Regional lymph node metastasis may be one of the metastatic ways of alveolar echinococcosis.

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