Comparing the diagnostic accuracy of five common tumour biomarkers and CA19-9 for pancreatic cancer: a protocol for a network meta-analysis of diagnostic test accuracy

Introduction: Surgical resection is the only curative treatment for patients with resectable pancreatic cancer. Unfortunately, 80%–85% of patients present with locally advanced or metastatic unresectable pancreatic cancer at the time of diagnosis. Detection of pancreatic cancer at early stages remains a great challenge due to lack of accurate detection tests. Recommendations in existing clinical practice guidelines on early diagnosis of pancreatic cancer are inconsistent and based on limited evidence. Most of them endorse measuring serum CA19-9 as a complementary test, but also state that it is not recommended for diagnosing early pancreatic cancer. There are currently no other tumour-specific markers recommended for diagnosing early pancreatic cancer. This study aims to evaluate and compare the accuracy of five common tumour biomarkers (CA242,carcino-embryonic antigen (CEA)), CA125, microRNAs and K-ras gene mutation) and CA19-9 and their combinations for diagnosing pancreatic cancer using network meta-analysis method, and to rank these tests using a superiority index. Methods and analysis: PubMed, EMBASE and the Cochrane Central Register of Controlled Trials will be searched from inception to April 2017. The search will include the above-mentioned tumour biomarkers for diagnosing pancreatic cancer, including CA19-9. The risk of bias for each study will be independently assessed as low, moderate or high using criteria adapted from the Quality Assessment of Diagnostic Accuracy Studies 2. Network meta-analysis will be performed using STATA V.12.0 and R software V.3.4.1. The competing diagnostic tests will be ranked by a superiority index. Ethics and dissemination: Ethical approval and patient consent are not required since this study is a network meta-analysis based on published studies. The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication

The effect of metformin usage on survival outcomes for hepatocellular carcinoma patients with type 2 diabetes mellitus after curative therapy

ObjectiveMetformin has attracted more attention from researchers for its newly discovered antitumor effects. A meta-analysis was performed to reveal the efficacy of metformin on overall survival (OS) and recurrence-free survival (RFS) for HCC patients with type 2 diabetes mellitus (T2DM) after curative treatment.MethodsDatabases including PubMed, the Cochrane Library, Web of Science, CNKI, Wangfang, and Weipu Database up until 31 May 2022 were searched for relevant studies. STATA 13.0 was used to perform the meta-analysis.ResultsA total of six studies involving 5,936 patients were included in our study. The results from the current study revealed that metformin usage can significantly prolong the 3-year [odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.22–1.83, p = 0.000] and 5-year (OR = 1.88, 95% CI: 1.47–2.41, p = 0.000) OS and decrease the 1-year (OR = 1.31, 95% CI: 1.08–1.59, p = 0.007), 3-year (OR = 1.88, 95% CI: 1.48–2.37, p = 0.000), and 5-year (OR = 1.83, 95% CI: 1.40–2.40, p = 0.000) recurrence rates.ConclusionMetformin treatment significantly prolongs the OS and decreases the recurrence rate for HCC patients with T2DM after curative HCC therapy

Pharmacokinetic comparison of quercetin, isoquercitrin, and quercetin-3-O-β-D-glucuronide in rats by HPLC-MS

Background Quercetin (Qr), isoquercitrin (IQ), and quercetin-3-O-β-D-glucuronide (QG) are powerful phytochemicals that have been shown to exhibit disease prevention and health promotion properties. However, there may exist transformations between Qr, IQ, and QG in vivo. And the pharmacokinetic profiles of Qr, IQ, and QG have not been systematically compared. The pharmacokinetics study would be helpful to better understand the pharmacological actions of them. Methods Herein, we developed a reliable HPLC-MS method to compare the pharmacokinetics of Qr, IQ, and QG after separate (50 mg/kg) oral administration of them in rats, using puerarin as internal standard. The detection was performed using negative selected ion monitoring. This method was validated in terms of selectivity, linearity, precision, accuracy, extraction recovery, matrix effect, and stability; and shows reliabilities in monitoring the pharmacokinetic behaviors of these three compounds. Results Our results showed that after separate oral administration of Qr, IQ, and QG, all of the compounds could be detected in plasma. In addition, QG could be detected in the Qr group; Qr and QG could be measured in the IQ group; and Qr could be found in rat plasma after 1.5 h of QG administration. Moreover, the AUC0−t of Qr in the; Qr group (2,590.5 ± 987.9 mg/L*min), IQ group (2,212.7 ± 914.1 mg/L*min), and QG group (3,505.7 ± 1,565.0 mg/L*min) was larger than the AUC0−t of QG in the; Qr group (1,550.0 ± 454.2 mg/L*min), IQ group (669.3 ± 188.3 mg/L*min), and QG group (962.7 ± 602.3 mg/L*min). The AUC0−t of IQ was the lowest among all groups. Discussion Quercetin, IQ, and QG can all be absorbed into plasma. A mutual transformation exists between Qr and QG, and IQ can be metabolized into Qr and QG in SD rats. These results would provide a meaningful basis for understanding the pharmacological actions of these three compounds

Post-treatment neutrophil-lymphocyte ratio independently predicts amputation in critical limb ischemia without operation

OBJECTIVES: Limited information is available concerning the post-treatment neutrophil-lymphocyte ratio in critical limb ischemia patients who receive conservative therapy. Accordingly, this study was designed to evaluate the predictive value of the post-treatment neutrophil-lymphocyte ratio in critical limb ischemia patients without surgery. METHOD: From January 2009 to January 2011, critical limb ischemia patients were admitted to a vascular center. The demographic data, patient histories, comorbidities and risk factors were documented, and the differential cell count was determined at admission and seven days later after conservative therapy. The cutoff value of the post-treatment neutrophil-lymphocyte ratio was determined by an ROC curve. Patients were divided into groups A and B according to the cutoff value. Amputation-free survival was compared between groups. Univariate and multivariate analyses were used to identify independent risk factors. RESULT: A total of 172 patients were identified with a mean age 71.98±10.09 years; among them, 122 were male. A value of 3.8 was identified as the cutoff value of the post-treatment neutrophil-lymphocyte ratio. Groups A (post-treatment neutrophil-lymphocyte ratio ≥3.8) and B (post-treatment neutrophil-lymphocyte rati

Optimization of photovoltaic panel deployment in centralized photovoltaic power plant under multiple factors

Solar energy is one of the main renewable energy sources and has rapidly developed in many countries. However, the photovoltaic (PV) output power will be different under various meteorological and geographical conditions. Therefore, this paper presents an optimization method for the deployment of PV panels in a centralized PV power plant considering multiple factors. Firstly, the whole planning area is divided into a certain amount of sub-areas according to a given area, and fuzzy C-means algorithm is used for terrain clustering according to the geographical characteristics of the sub-areas. Secondly, the correlation analysis between each meteorological factor and PV output power is carried out separately to select the main factors affecting PV output power, and then the expected annual PV output power under the joint action of several main meteorological factors in each terrain is calculated by dual-stage attention mechanism based long short-term memory algorithm. Finally, according to the expected annual PV output of each terrain, considering the constraints including cost, area and so on, the deployment optimization of PV panels is obtained to maximize the annual PV output of the whole PV power plant and minimize the construction cost. The results of case studies show that the proposed methods effectively improve the expected PV output power of the PV power plant and reduce the construction cost

The use of blue native PAGE in the evaluation of membrane protein aggregation states for crystallization

Monodispersity obtained by the blue native PAGE (BN–PAGE) gel for membrane proteins correlates well with their propensity to crystallize. The results from BN–PAGE are more informative on the sample aggregation states in solution than other techniques such as dynamic light scattering and size exclusion chromatography. BN–PAGE is also particularly useful for efficient detergent selection for membrane protein crystallization

FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy

FBXW7 (F-box and WD repeat domain containing 7) is a critical subunit of the Skp1-Cullin1-F-box protein (SCF), acting as an E3 ubiquitin ligase by ubiquitinating targeted protein. Through degradation of its substrates, FBXW7 plays a pivotal role in drug resistance in tumor cells and shows the potential to rescue the sensitivity of cancer cells to drug treatment. This explains why patients with higher FBXW7 levels exhibit higher survival times and more favorable prognosis. Furthermore, FBXW7 has been demonstrated to enhance the efficacy of immunotherapy by targeting the degradation of specific proteins, as compared to the inactivated form of FBXW7. Additionally, other F-box proteins have also shown the ability to conquer drug resistance in certain cancers. Overall, this review aims to explore the function of FBXW7 and its specific effects on drug resistance in cancer cells