Objective: Since metabolic syndrome is a significant risk factor for cardio-cerebrovascular diseases, and the relationship between metabolic syndrome (including its components) and the prognosis of stroke are controversial, this study was conducted to evaluate whether metabolic syndrome is associated with a high recurrence and mortality of stroke. Methods: This study was registered in the PROSPERO database (CRD42020177118). We searched for relevant observational cohort studies published from inception to April 23, 2020 using PubMed, Embase, and the Cochrane Library. Effect estimates with 95% CIs were pooled using the random-effects model. The primary and secondary outcomes were stroke recurrence and all-cause mortality, respectively. Leave-one-out sensitivity analyses and nonparametric trim and fill method were used to identify the stability of the results. Results: Thirteen cohort studies comprising 59,919 participants aged >60 years were included for analysis. Overall, metabolic syndrome was significantly associated with stroke recurrence (RR 1.46, 95% CI 1.07-1.97, P = 0.02). Among the metabolic syndrome components, low levels of high density lipoprotein cholesterol (HDL-C) (RR 1.32, 95% CI 1.11-1.57, P = 0.002) and number of metabolic syndrome components(≥ 2) (RR 1.68, 95% CI 1.44-1.94, P <0.001) significantly predicted stroke recurrence, whereas elevated triglyceride, elevated waist circumference, hyperglycemia, or hypertension failed to account for risk factors for stroke recurrence. Moreover, metabolic syndrome, not its components, was significantly associated with all-cause mortality (RR 1.27, 95% CI 1.18-1.36, P < 0.001). The stability of these results was further confirmed by the leave-one-out sensitivity analyses and nonparametric trim and fill method. Conclusions: The present study indicates that metabolic syndrome and some of its components (low HDL-C and number of metabolic syndrome components) seem to be risk factors for stroke recurrence. Though metabolic syndrome is also associated with all-cause mortality, the role of its components to predict all-cause mortality deserves further study.

Oxidative stress (OS) is a chemical imbalance between an oxidant and an antioxidant, causing damage to redox signaling and control or causing molecular damage. Unbalanced oxidative metabolism can produce excessive reactive oxygen species (ROS). These excess ROS can cause drastic changes in platelet metabolism and further affect platelet function. It will also lead to an increase in platelet procoagulant phenotype and cell apoptosis, which will increase the risk of thrombosis. The creation of ROS and subsequent platelet activation, adhesion, and recruitment are then further encouraged in an auto-amplifying loop by ROS produced from platelets. Meanwhile, cancer cells produce a higher concentration of ROS due to their fast metabolism and high proliferation rate. However, excessive ROS can result in damage to and modification of cellular macromolecules. The formation of cancer and its progression is strongly associated with oxidative stress and the resulting oxidative damage. In addition, platelets are an important part of the tumor microenvironment, and there is a significant cross-communication between platelets and cancer cells. Cancer cells alter the activation status of platelets, their RNA spectrum, proteome, and other properties. The "cloaking" of cancer cells by platelets providing physical protection，avoiding destruction from shear stress and the attack of immune cells, promoting tumor cell invasion.We explored the vicious circle interaction between ROS, platelets, and cancer in this review, and we believe that ROS can play a stimulative role in tumor growth and metastasis through platelets.

Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer, accounting for approximately 15% among all lung cancers. Despite the ability of chemotherapy, the first-line treatment for SCLC, to rapidly shrink tumors, nearly all patients experience recurrence and metastasis within a few months. Cancer stem cells (CSCs) are a small population of tumor cells responsible for tumorigenesis, metastasis, and recurrence after treatment, which play a crucial role in chemoresistance by promoting DNA repair and expression of drug resistance-associated proteins. Thus, targeting CSCs has been successful in certain malignancies. Tumor therapy has entered the era of immunotherapy and numerous preclinical trials have demonstrated the effectiveness of immunotherapeutic approaches targeting CSCs, such as tumor vaccines and chimeric antigen receptor (CAR) T cell, and the feasibility of combining them with chemotherapy. Therefore, a deeper understanding of the interaction between CSCs and immune system is essential to facilitate the advances of new immunotherapies approaches targeting CSCs as well as combination with standard drugs such as chemotherapy. This narrative review summarizes the mechanisms of chemoresistance of CSCs in SCLC and the latest advances in targeted therapies. Thereafter, we discuss the effects of CSCs on tumor immune microenvironment in SCLC and corresponding immunotherapeutic approaches. Eventually, we propose that the combination of immunotherapy targeting CSCs with standard drugs is a promising direction for SCLC therapies.

Metformin, one of the first-line of hypoglycemic drugs, has cardioprotective, anti-inflammatory and anticancer activities, in addition to its proven hypoglycemic effects. Furthermore, the preventive and therapeutic potential of metformin for neurodegenerative diseases has become a topic of concern. Increasing research suggests that metformin can prevent the progression of neurodegenerative diseases. In recent years, many studies have investigated the neuroprotective effect of metformin in the treatment of neurodegenerative diseases. It has been revealed that metformin can play a neuroprotective role by regulating energy metabolism, oxidative stress, inflammatory response and protein deposition of cells, and avoiding neuronal dysfunction and neuronal death. On the contrary, some have hypothesized that metformin has a two-sided effect which may accelerate the progression of neurodegenerative diseases. In this review, the results of animal experiments and clinical studies are reviewed to discuss the application prospects of metformin in neurodegenerative diseases.

Objective Accumulating evidence suggests that cancer survivors may have a relatively higher risk of stroke. The aim of this meta-analysis was to determine whether cancer survivors have a relatively higher risk of stroke than cancer-free populations on the basis of published data from population-based cohort studies. Methods PubMed, Embase, and Cochrane Library were searched from inception to February 8, 2020, for population-based cohort studies. Effect estimates with 95% confidence intervals (CIs) were pooled using the random-effects model. We conducted subgroup analyses and meta-regression to explore sources of heterogeneity and the stability of the results. Results Twenty population-based cohort studies involving 10,479,530 participants were identified. Overall, the relative risk (RR) for stroke in cancer survivors was 1.66 (95% CI 1.35–2.04; p < 0.001) compared with that in cancer-free controls; survivors of head and neck, hematologic, lung, pancreas, and stomach cancer (all p < 0.05) showed consistently significant results, whereas no significant increased risk was observed for patients with other cancer types. The effects were more prominent in cancer survivors with female sex (RR 1.38, 95% CI 1.18–1.61; p < 0.001), younger age at cancer diagnosis (<45 years) (RR 2.57, 95% CI 1.27–5.19; p = 0.009), and shorter cancer survival duration (≥1–2 years) (RR 1.69, 95% CI 1.18–2.42; p = 0.004). Moreover, cancer survivors had a significantly increased risk of ischemic stroke (RR 1.53, 95% CI 1.28–1.84; p < 0.001) compared with hemorrhagic stroke. Conclusions Cancer plays a critical role in the etiologic of stroke. Due to the existence of substantial heterogeneity among the included studies, the results should be interpreted with caution. However, early prevention and effective intervention of stroke in cancer survivors require attention from health policy makers.