PurposeNumerous studies have reported the prognostic significance of lymphocyte-to-monocyte ratio (LMR) in malignancies, but its prognostic value among lung cancer remains controversial. This meta-analysis aimed to explore the prognostic significance of LMR in lung cancer patients.ResultsEight studies including 3954 patients were included in this meta-analysis. Pooled results indicated that low LMR was significantly associated with poorer progression-free survival (hazard ratio (HR): 1.431, 95% confidence interval (CI): 1.294–1.582, p < 0.001) and overall survival (OS) (HR: 1.651, 95% CI: 1.306–2.086, p < 0.001), compared with high LMR. Similar results were observed in subgroups regardless of treatment, LMR cut-off value, or districts. However, no significant correlation between the LMR and OS was observed in the small cell lung cancer (SCLC) subgroup (HR = 1.262, 95% CI: 0.864–1.841, p = 0.229).Materials and MethodsIdentified literatures were extracted and retrieved from PubMed, Embase, Web of Science, and the Cochrane Library databases; All eligible studies focused on the association between LMR and the prognosis of lung cancer.ConclusionsLow LMR is associated with poor outcomes among lung cancer patients. Further studies are needed to discuss the correlation between LMR and lung cancer prognosis.

No consensus has been reached on the association between the b2-adrenergic receptor polymorphisms A46G and C79G and essential hypertension risk. We performed a meta-analysis to confirm the possible association. After reviewing 303 reports in PubMed and 359 reports in Embase, we included in our meta-analysis 18 articles (20 studies) that met our inclusion criteria. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. There was no statistical association between A46G and hypertension risk in all subjects, Asians or Caucasians. However, an association was observed in the dominant genetic model (AA vs. (AG+GG)) (P¼0.04, odds ratio (OR)¼1.38, 95% confidence interval (CI) 1.01-1.87, P heterogeneity ¼0.98, fixed-effects model) in the subgroup of mixed Africans. No overall statistical association could be found between C79G and hypertension risk or any ethnic subgroup. In the research conducted on severe hypertension (systolic blood pressure X160 mm Hg and/or diastolic blood pressure X95 mm Hg hypertensive population), significant association was found in the dominant genetic model (CC vs. (CG+GG)) (P¼0.04, OR¼1.38, 95% CI 1.02-1.86, P heterogeneity ¼0.03, random-effects model), and there was also a borderline significance between the C79 allele and severe hypertension (P¼0.05, OR¼1.26, 95% CI 1.00-1.57, P heterogeneity ¼0.04, random-effects model). No association could be found in this study between the two polymorphisms and stage 2 hypertension. More studies stratified for different ethnicities and different stages of hypertension should be performed in the future.

Background: Genetic variation is thought to contribute to the etiology of hypertension, and E-selectin is a candidate essential hypertension-associated gene. This study thus sought to investigate possible genetic associations between the T1880C, C602A and T1559C polymorphisms of E-selectin and essential hypertension.

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Superoxide dismutase (SOD) is one of the major antioxidants in vivo and is expected to play critical roles on the defense against reactive oxygen species (ROS)-mediated damages, such as ionizing radiation damages. Herein, inspired by the function and structure of natural SODs and cerium oxide nanozymes, two monovalent cerium-based metal organic frameworks (Ce-MOFs), CeIIIBTC and CeIVBTC, were designed for superoxide radical (O2 •–) elimination and ionizing radiation protection. These two Ce-MOFs selectively scavenge O2 •– and are excellent SOD mimics. Like natural SODs and cerium oxide nanozymes, the SOD-like catalytic mechanism of Ce-MOFs involves a cycle between Ce(IV) and Ce(III). Furthermore, by constructing monovalent Ce-MOFs, we found that high-valent CeIVBTC are more effective SOD-like nanozymes compared to CeIIIBTC. With smaller size, better monodispersity, and more effective SOD-like activity, CeIVBTC nanozymes were further applied for ionizing radiation protection. Both in vitro and in vivo results demonstrated that CeIVBTC nanozymes could efficiently scavenge ROS, prevent cells from γ-ray radiation-induced cell viability decrease and DNA damages, and improve the survival rate of irradiated mice by recovering the bone marrow DNA damage and alleviating oxidative stress of tissues. The protective effect and good biocompatibility of CeIVBTC nanozymes will enable the development of Ce-MOFs-based radioprotectants and facilitate treatment of other ROS-related diseases.

The β1-adrenoceptor (ADRB1) gene Arg389Gly polymorphism has been extensively studied as a candidate gene in essential hypertension (EH), but no consensus has been reached on the relationship between this polymorphism and EH risk. To systematically explore their possible association, a meta-analysis was conducted. All relevant case-control trials in English-language publications before 1 June 2012 were identified by searching the PubMed and Embase databases. Finally, eight articles met our inclusion criteria, including a total of 5,088 patients with EH and 6,515 controls. No evidence of publication bias was found. Fixed-effects model and random-effects model were applied for dichotomous outcomes to combine results from individual studies. Overall, the Gly allelic frequency of Arg389Gly polymorphism was significantly lower in EH subjects than that in controls (Gly versus Arg: P = 0.04, OR = 0.89, 95 % CI [0.80-1.00], P heterogeneity = 0.03, I (2) = 52 %, random-effects model; GlyGly + ArgGly versus ArgArg: P = 0.02, OR = 0.86, 95 % CI [0.76-0.97], P heterogeneity = 0.08 and I (2) = 42 %, random-effect model). Subgroup analysis by ethnicity detected this association only in East Asians. In sensitivity analysis, the study by Bengtsson K was recognized as the main cause of heterogeneity, which was the only one study with the diagnostic standard for EH as systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg. We concluded that the Gly allele of ADRB1 Arg389Gly polymorphism might confer lower risk for EH, especially in East Asians.

The genetic causes of atrial fibrillation (AF) with slow conduction are unknown. Eight kindreds with familial AF and slow conduction, including a family affected by early‐onset AF, heart block, and incompletely penetrant nonischemic dilated cardiomyopathy (DCM) underwent whole exome sequencing. A known pathogenic mutation in the desmin (DES) gene resulting in p.S13F substitution (NM_001927.3:c.38C>T) at a PKC phosphorylation site was identified in all four members of the kindred with early‐onset AF and heart block, while only two developed DCM. Higher penetrance for AF and heart block prompted a genetic screening for DES modifier(s). A deleterious mutation in the phosphodiesterase‐4D‐interacting‐protein (PDE4DIP) gene resulting in p.A123T substitution (NM_001002811:c.367G>A) was identified that segregated with early‐onset AF, heart block, and the DES mutation. Three additional novel deleterious PDE4DIP mutations were identified in four other unrelated kindreds. Characterization of PDE4DIPA123T in vitro suggested impaired compartmentalization of PKA and PDE4D characterized by reduced colocalization with PDE4D, increased cAMP activation leading to higher PKA phosphorylation of the β2‐adrenergic‐receptor, and decreased PKA phosphorylation of desmin after isoproterenol stimulation. Our findings identify PDE4DIP as a novel gene for slow AF and unravel its epistatic interaction with DES mutations in development of conduction disease and arrhythmia.

Untethered mobile micro-/nanomotors (MNMs), as newly-emerging attractive and versatile nanotechnologies, are expected to be the next-generation disease treatment tools, for breaking through the limitations of conventional passive drug delivery manner. However, the advances in these fascinating platforms have been hampered by the complexity of the biological environment and the particularity of disease microenvironment. Consequently, specific design strategies and clinical imaging techniques are essential to ensure the high-efficiency of biomedical MNMs on actuation, targeting, localization, and therapy when performing assigned in vivo tasks. This review thus comprehensively addresses three aspects of biomedical MNMs, including design, imaging, and disease treatment, highlighting the intelligent MNMs with biomimetic functionality and chemotactic capability, emphasizing the applicability of different imaging techniques, and focusing on various proofof-concept studies based on physiological characteristics for the treatment of major diseases. In addition, the key challenges and limitations of current biomedical MNMs are addressed, which may inspire future research and facilitate translation toward clinical treatment.