•A general solution is presented for RUL prediction of nonlinear deterioration process.•KPCA is selected for dimensionality reduction and nonlinear feature extraction.•GRU is presented to replace ...LSTM, which behaves better both in prediction accuracy and training time.
Remaining useful life (RUL) prediction is a key process for prognostics and health management (PHM). However, conventional model-based methods and data-driven methods for RUL prediction are bad at a very complex system with multiple components, multiple states and therefore extremely large amount of parameters. In order to solve the problem, a general two-step solution is proposed in this paper. In the first step, kernel principle component analysis (KPCA) is applied for nonlinear feature extraction. Then, a novel recurrent neural network called gated recurrent unit (GRU) is presented as the second step to predict RUL. GRU network is capable of describing a very complex system because of its specially designed structure. The effectiveness of the proposed solution for RUL prediction of a nonlinear degradation process is proved by a case study of commercial modular aero-propulsion system simulation data (C-MAPSS-Data) from NASA. Results also show that the proposed method requires less training time and has better prediction accuracy than other data-driven methods.
Oxidative stress occurs in a variety of clinical liver diseases and causes cellular damage and mitochondrial dysfunction. The clearance of damaged mitochondria by mitophagy may facilitate ...mitochondrial biogenesis and enhance cell survival. Although the supplementation of docosahexaenoic acid (DHA) has been recognized to relieve the symptoms of various liver diseases, the antioxidant effect of DHA in liver disease is still unclear. The purpose of our research was to investigate the antioxidant effect of DHA in the liver and the possible role of mitophagy in this. In vitro, H2O2-induced injury was caused in AML12 cells. The results showed that DHA repressed the level of reactive oxygen species (ROS) induced by H2O2 and stimulated the cellular antioxidation response. Most notably, DHA restored oxidative stress-impaired autophagic flux and promoted protective autophagy. In addition, PINK/Parkin-mediated mitophagy was activated by DHA in AML12 cells and alleviated mitochondrial dysfunction. The ERK1/2 signaling pathway was inhibited during oxidative stress but reactivated by DHA treatment. It was proven that the expression of ERK1/2 was involved in the regulation of mitophagy by the ERK1/2 inhibitor. We further proved these results in vivo. DHA effectively alleviated the liver oxidative damage caused by CCl4 and enhanced antioxidation capacity; intriguingly, autophagy was also activated. In summary, our data demonstrated that DHA protected hepatocytes from oxidative damage through GPR120/ERK-mediated mitophagy.
Immunotherapy shows promising therapeutic efficacy against various types of cancer, but most fail to respond. Preclinical studies have suggested that concomitant medications, such as statins, ...non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, metformin and beta-blockers, might affect clinical outcomes if used with immune checkpoint inhibitors (ICIs), but their clinical roles are conflicting. This meta-analysis investigates the effect of these concomitant medications on outcomes in patients treated with ICIs. A search was conducted for all reports published until 31 March 2021 in PubMed, Web of Science, Cochrane Library, EMBASE and conference proceedings. Studies were included if they investigated the association between the concomitant use of these medications and progression-free survival (PFS) or overall survival (OS) during ICI treatment. A total of 3331 patients from 13 eligible studies were included. Among them, five articles on statins, six studies evaluating NSAIDs, five studies employing low-dose aspirin, eight studies on metformin and four articles on beta-blockers were included. The concomitant use of statins during ICI treatment was correlated with improved OS and PFS. Low-dose aspirin was associated with better PFS instead of OS. No significant association was demonstrated between the concurrent use of NSAIDs, beta-blockers and metformin and OS or PFS. The concomitant use of statins and low-dose aspirin during ICI treatment showed a positive impact on treatment outcomes. The concurrent use of NSAIDs, beta-blockers and metformin is not significantly associated with clinical benefits. The effect of these medications in different cancer patients treated with ICI is needed to be further validated.
Background
The C‐reactive protein (CRP)/albumin (Alb) ratio (CAR) is a basic inflammatory factor that has been related to poor survival of patients with various tumors. Our research retrospectively ...examined the relationship between the CAR and the prognosis of hepatocellular carcinoma (HCC).
Methods
This study included 172 patients with HCC who were treated with transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA).
Results
The CAR was weakly related to the neutrophil/lymphocyte ratio (NLR, r = .159, P = .037) and the lymphocyte/monocyte ratio (LMR, r = −.263, P = .001). The Glasgow Prognostic Score (GPS) (0/1‐2) was related to liver cirrhosis (P = .003), tumor number (P = .02), Child‐Pugh grade (P = .001), the platelet/lymphocyte ratio (PLR, P = .006), and the LMR (P = .021). Correlation analysis demonstrated that an elevated CAR was markedly correlated with the tumor size (P = .019), alpha‐fetoprotein (AFP) level (P = .033), thrombosis of the portal vein (P = .004), the NLR (P = .036), and the LMR (P = .001). Multivariate analysis indicated that the prognosis of the CAR‐High and NLR‐High cohort (mOS = 7 months) was significantly worse than those of the CAR‐High or NLR‐High cohort (mOS = 15 months) and the CAR‐Low and NLR‐Low cohort (mOS = 26.5 months).
Conclusions
Combination of the NLR and the CAR represents a convenient, quick, and noninvasive biological marker that could improve prognostic prediction in patients with HCC.
Pyroptosis is a novel type of programmed cell death associated with the pathogenesis of many inflammatory diseases. Docosahexaenoic acid (DHA) and Arachidonic acid (AA) is widely involved in ...inflammatory pathological processes. However, the effect and mechanism of DHA and AA on pyroptosis in Kupffer cells are poorly understood. The present study demonstrated that DHA and AA ameliorated lipopolysaccharide (LPS)-induced Kupffer cells pyroptosis by reversing the increased expression of NLRP3 inflammasome complex, GSDMD, IL-1β, IL-18, and PI-stained positive rate. Next, the study revealed that GPR120 silencing eliminated the anti-pyroptosis of DHA and AA in LPS-induced Kupffer cells, suggesting that DHA and AA exerted their effect through GPR120 signaling. Importantly, GPR120 endocytose and binds to NLRP3 under LPS stimulation. Furthermore, co-immunoprecipitation showed that DHA and AA promoted the interaction between GPR120 and NLRP3 in LPS-exposed Kupffer cells, thus inhibiting the self-assembly of NLRP3 inflammasome complex. Finally, the study verified that DHA and AA alleviated hepatic injury through inhibiting Kupffer cells pyroptosis in vivo. The findings indicated that DHA and AA alleviated LPS-induced Kupffer cells pyroptosis via GPR120 interaction with NLRP3, it might become a potential therapeutic approach hepatic injury.
The combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic agents has shown promising efficacy in unresectable hepatocellular carcinoma (HCC), but until now no clinical prognostic ...models or predictive biomarkers have been established.
From 2016 to 2021, a total of 258 HCCs treated with ICIs and tyrosine kinase inhibitors (TKIs) were retrospectively enrolled, as the study cohort. Patients' baseline data was extracted by least absolute and shrinkage selection operator (LASSO) and Cox regression. Finally, a prognostic model in the form of nomogram was developed. Model performance was assessed in terms of discrimination, calibration, and clinical utility. A 5-fold cross-validation was used to evaluate the internal repeatability of the model. In addition, the patient cohort was divided into three subgroups according to nomogram scores. Their survivals were estimated by Kaplan-Meier methods and the differences were analyzed using log-rank tests.
Seven clinical parameters were selected: Eastern Cooperative Oncology Group performance status (ECOG PS), combination of transarterial chemoembolization (TACE), extrahepatic metastasis (EHM), platelet to lymphocyte ratio (PLR), alanine aminotransferase (ALT), alpha-fetoprotein (AFP), and Child-Pugh score. The model had an area under the curve (AUC) of 0.777 at 1 year and 0.772 at 2 years. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) showed that the discrimination, consistency and applicability of the model were good. In addition, cross-validation validated the discrimination of the model, and the C index value of the model is 0.7405. The median overall survival (OS) of the high-, medium- and low-risk subgroups was 7.58, 17.50 and 53.17 months, respectively, with a significant difference between the groups (P < 0.0001).
We developed a comprehensive and simple prognostic model for the combination of ICIs plus TKIs. And it may predict the efficacy of the combination regimen for unresectable HCC.
Emerging evidences suggest that cognitive deficits in individuals with mild cognitive impairment (MCI) are associated with disruptions in brain functional connectivity (FC). This systematic review ...and meta‐analysis aimed to comprehensively evaluate alterations in FC between MCI individuals and healthy control (HC) using functional near‐infrared spectroscopy (fNIRS). Thirteen studies were included in qualitative analysis, with two studies synthesized for quantitative meta‐analysis. Overall, MCI patients exhibited reduced resting‐state FC, predominantly in the prefrontal, parietal, and occipital cortex. Meta‐analysis of two studies revealed a significant reduction in resting‐state FC from the right prefrontal to right occipital cortex (standardized mean difference SMD = −.56; p < .001), left prefrontal to left occipital cortex (SMD = −.68; p < .001), and right prefrontal to left occipital cortex (SMD = −.53; p < .001) in MCI patients compared to HC. During naming animal‐walking task, MCI patients exhibited enhanced FC in the prefrontal, motor, and occipital cortex, whereas a decrease in FC was observed in the right prefrontal to left prefrontal cortex during calculating‐walking task. In working memory tasks, MCI predominantly showed increased FC in the medial and left prefrontal cortex. However, a decreased in prefrontal FC and a shifted in distribution from the left to the right prefrontal cortex were noted in MCI patients during a verbal frequency task. In conclusion, fNIRS effectively identified abnormalities in FC between MCI and HC, indicating disrupted FC as potential markers for the early detection of MCI. Future studies should investigate the use of task‐ and region‐specific FC alterations as a sensitive biomarker for MCI.
This meta‐analysis was performed to assess the relationship between Lenvatinib use for malignancy and hypertension (HTN). A total of 2483 patients met inclusion criteria. The relative risk (RR) for ...all‐grade and high‐grade (≧3) HTN were 2.61 (p ≦ .001) and 3.35 (p≦ .001), respectively, for Lenvatinib compared with other multitarget tyrosine kinase inhibitors or placebo. The cumulative incidence of all‐grade and high‐grade HTN was 70% and 34%, respectively. The studies with median treatment duration (TD) longer than 7.4 months demonstrated a higher incidence of high‐grade HTN than studies with shorter TD (34% vs 28%). The incidence of all levels of HTN increased with TD (68% vs 49%). Trials with median progression‐free survival (PFS) longer than nine months had a higher incidence of both all‐grade (37% vs 28%) and high‐grade (71% vs 48%) HTN. Lenvatinib, a drug commonly used in cancer treatment, is a risk factor for the development of HTN. A longer duration of Lenvatinib treatment was associated with higher frequency of HTN. Further investigation for Lenvatinib of the association between the occurrence of HTN and prognosis will be warranted.
Objective To describe and analyze the predictive models of the prognosis of patients with hepatocellular carcinoma (HCC) undergoing systemic treatment. Design Systematic review. Data sources PubMed ...and Embase until December 2020 and manually searched references from eligible articles. Eligibility criteria for study selection The development, validation, or updating of prognostic models of patients with HCC after systemic treatment. Results The systematic search yielded 42 eligible articles: 28 articles described the development of 28 prognostic models of patients with HCC treated with systemic therapy, and 14 articles described the external validation of 32 existing prognostic models of patients with HCC undergoing systemic treatment. Among the 28 prognostic models, six were developed based on genes, of which five were expressed in full equations; the other 22 prognostic models were developed based on common clinical factors. Of the 28 prognostic models, 11 were validated both internally and externally, nine were validated only internally, two were validated only externally, and the remaining six models did not undergo any type of validation. Among the 28 prognostic models, the most common systemic treatment was sorafenib (n = 19); the most prevalent endpoint was overall survival (n = 28); and the most commonly used predictors were alpha-fetoprotein (n = 15), bilirubin (n = 8), albumin (n = 8), Child-Pugh score (n = 8), extrahepatic metastasis (n = 7), and tumor size (n = 7). Further, among 32 externally validated prognostic models, 12 were externally validated > 3 times. Conclusions This study describes and analyzes the prognostic models developed and validated for patients with HCC who have undergone systemic treatment. The results show that there are some methodological flaws in the model development process, and that external validation is rarely performed. Future research should focus on validating and updating existing models, and evaluating the effects of these models in clinical practice. Systematic review registration PROSPERO CRD42020200187. Keywords: Hepatocellular carcinoma, Systemic treatment, Prognostic models, Review and critical appraisal
Objective: We assessed the efficacy and safety of transarterial chemoembolization (TACE) in combination with lenvatinib plus programmed death receptor-1 (PD-1) signaling inhibitors (camrelizumab or ...sintilimab) in unresectable hepatocellular carcinoma (uHCC). Methods: In this retrospective study, patients with uHCC were pretreated with lenvatinib for 1 to 2 weeks before TACE. Camrelizumab or sintilimab were initially administered intravenously in 1 week after TACE of a 21-day cycle. Primary objectives were objective response rate (ORR) and disease control rate (DCR) by modified Response Evaluation Criteria in Solid Tumors (mRECIST). The secondary endpoints included the progression-free survival (PFS), overall survival (OS), and toxicity. Results: Between March 5, 2019 and February 30, 2021, 53 patients were screened for eligibility. At data cutoff, 35.8% of patients remained on treatment. Median follow-up was 15.4 months. Confirmed ORR in the 51 evaluable patients was 54.9% (95% CI 41.4%-67.7%). DCR was 84.3% (95% CI 72.0%-91.8%). Median PFS was 8.5 months (95% CI 6.4 to 10.6 months). The median OS was not estimable. Grade ≥3 treatment-related adverse events occurred in 32.1% of patients. No new safety signals were identified. Conclusion: TACE in combination with lenvatinib plus anti-PD-1 inhibitors may have promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals.
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