Background: Elevated monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) is relevant to higher all-cause and cardiovascular mortality in patients with coronary artery disease and other comorbidities. However, the predictive values of MHR for mortality in the general population have been underutilized. This study investigated the association of MHR with all-cause and cardiovascular mortality in the adult population of the United States. Methods: This study included 34,335 participants (≥20 years) from the National Health and Nutrition Examination Survey 1999–2014 that were grouped according to MHR tertiles. Kaplan-Meier plots and long-rank tests were employed to investigate differences in survival among the groups. Moreover, the relationship of MHR with all-cause and cardiovascular mortality was further explored using multivariate Cox regression and restricted cubic spline analysis. Results: During the average follow-up of 93.5 ± 56 months, 4310 (12.6%) participants died, with 754 (2.2%) deaths attributed to cardiovascular diseases. Kaplan-Meier analysis revealed statistically obvious differences in all-cause and cardiovascular mortality among the MHR tertiles (log-rank test: all P < 0.001). In multi-adjusted models, participants in the highest tertile of MHR had an increased risk of all-cause (hazard ratio [HR] = 1.19, 95% confidence interval [CI] 1.10–1.29) and cardiovascular mortality (HR = 1.44, 95% CI 1.17–1.77), compared to those in the lowest tertile. Furthermore, the restricted cubic spline curve indicated that MHR had a non-linear association with all-cause mortality (P < 0.001), and the inflection point of MHR was 0.006. Each 2-fold change in MHR exhibited a 32% decrease (HR = 0.68, 95%CI 0.58–0.82) and a 20% increase (HR = 1.20, 95%CI 1.13–1.27) in the risk of all-cause mortality on the left and right flanks of the inflection point, respectively. Additionally, the risk of cardiovascular mortality increased by 21% per 2-fold change in MHR (HR = 1.21, 95%CI 1.07–1.36) in a linear manner. Conclusions: MHR was significantly related to all-cause and cardiovascular mortality in the general population independent of established risk factors.

Neuropathic pain is a serious clinical problem that needs to be solved urgently. ASK1 is an upstream protein of p38 and JNK which plays important roles in neuroinflammation during the induction and maintenance of chronic pain. Therefore, inhibition of ASK1 may be a novel therapeutic approach for neuropathic pain. Here, we aim to investigate the effects of paeoniflorin on ASK1 and neuropathic pain. The mechanical and thermal thresholds of rats were measured using the Von Frey test. Cell signaling was assayed using western blotting and immunohistochemistry. Chronic constrictive injury (CCI) surgery successfully decreased the mechanical and thermal thresholds of rats and decreased the phosphorylation of ASK1 in the rat spinal cord. ASK1 inhibitor NQDI1 attenuated neuropathic pain and decreased the expression of p-p38 and p-JNK. Paeoniflorin mimicked ASK1 inhibitor NQDI1 and inhibited ASK1 phosphorylation. Paeoniflorin decreased the expression of p-p38 and p-JNK, delayed the progress of neuropathic pain, and attenuated neuropathic pain. Paeoniflorin reduced the response of astrocytes and microglia to injury, decreased the expression of IL-1β and TNF-α, and downregulated the expression of CGRP induced by CCI. Paeoniflorin is an effective drug for the treatment of neuropathic pain in rats via inhibiting the phosphorylation of ASK1, suggesting it may be effective in patients with neuropathic pain.

Background: Neutrophil counts to high-density lipoprotein cholesterol ratio (NHR), a composite marker of inflammation and lipid metabolism, has been considered as a predictor of clinical outcomes in patients with acute ischemic stroke and acute myocardial infarction. However, the predictive value of NHR for all-cause and cardiovascular mortality in the general population remains unclear.Methods: Our study population comprised 34,335 adults in the United States obtained from the National Health and Nutrition Examination Survey (NHANES) (1999–2014) and were grouped in accordance with tertiles of NHR. Kaplan–Meier curves and log-rank test were used to investigate the differences of survival among groups. Multivariate Cox regression, restricted cubic spline analysis, and subgroup analysis were applied to explore the relationship of NHR with all-cause and cardiovascular mortality.Results: The mean age of the study cohort was 49.6 ± 18.2 years and 48.4% were men. During a median follow-up of 82 months, 4,310 (12.6%) all-cause deaths and 754 (2.2%) cardiovascular deaths occurred. In a fully-adjusted Cox regression model, participants in the highest tertile had 29% higher hazard of all-cause mortality than those in the lowest tertile [hazard ratio (HR) = 1.29, 95% CI: 1.19–1.41]. For cardiovascular mortality, the continuously increased HR with 95% CIs among participants in the middle and highest tertile were 1.30 (1.06–1.59) and 1.44 (1.17–1.78), respectively. The restricted cubic spline curve indicated that NHR had a non-linear association with all-cause mortality (p for non-linearity < 0.001) and a linear association with cardiovascular mortality (p for non-linearity = 0.553).Conclusion: Increased NHR was a strong and independent predictor of all-cause and cardiovascular mortality in the general population.

Hypertension is a pathological condition of persistent high blood pressure (BP) of which the underlying neural mechanisms remain obscure. Here, we show that the afferent nerves in perirenal adipose tissue (PRAT) contribute to maintain pathological high BP, without affecting physiological BP. Bilateral PRAT ablation or denervation leads to a long-term reduction of high BP in spontaneous hypertensive rats (SHR), but has no effect on normal BP in control rats. Further, gain- and loss-of-function and neuron transcriptomics studies show that augmented activities and remodeling of L1-L2 dorsal root ganglia neurons are responsible for hypertension in SHR. Moreover, we went on to show that calcitonin gene-related peptide (CGRP) is a key endogenous suppressor of hypertension that is sequestered by pro-hypertensive PRAT in SHRs. Taken together, we identify PRAT afferent nerves as a pro-hypertensive node that sustains high BP via suppressing CGRP, thereby providing a therapeutic target to tackle primary hypertension.