Background: Necroptosis, a recently discovered programmed cell death, has been pathologically linked to various diseases and is thus a promising target for treating diseases. However, a comprehensive and objective report on the current status of entire necroptosis research is lacking. Therefore, this study aims to conduct a bibliometric analysis to quantify and identify the status quo and trending issues of necroptosis research in the last decade.Methods: Articles were acquired from the Web of Science Core Collection database. We used two bibliometric tools (CiteSpace and VOSviewer) to quantify and identify the individual impact and cooperation information by analyzing annual publications, journals, co-cited journals, countries/regions, institutions, authors, and co-cited authors. Afterwards, we identified the trending research areas of necroptosis by analyzing the co-occurrence and burst of keywords and co-cited references.Results: From 2012 to 2021, a total of 3,111 research articles on necroptosis were published in 786 academic journals by 19,687 authors in 885 institutions from 82 countries/regions. The majority of publications were from China and the United States, of which the United States maintained the dominant position in necroptosis research; meanwhile, the Chinese Academy of Sciences and Ghent University were the most active institutions. Peter Vandenabeele published the most papers, while Alexei Degterev had the most co-citations.Cell Death & Diseasepublished the most papers on necroptosis, whileCellwas the top 1 co-cited journal, and the major area of these publications was molecular, biology, and immunology. High-frequency keywords mainly included those that are molecularly related (MLKL, TNF-alpha, NF-κB, RIPK3, RIPK1), pathological process related (cell-death, apoptosis, necroptosis, necrosis, inflammation), and disease related (cancer, ischemia/reperfusion injury, infection, carcinoma, Alzheimer’s disease).Conclusion: Necroptosis research had a stable stepwise growth in the past decade. Current necroptosis studies focused on its cross-talk with other types of cell death, potential applications in disease treatment, and further mechanisms. Among them, the synergy with ferroptosis, further RIPK1/RIPK3/MLKL studies, its association with inflammation and oxidative stress and translational applications, and the therapeutic potential to treat cancer and neurodegenerative diseases are the trending research area. These might provide ideas for further research in the necroptosis field.

Purpose: Excessive daytime sleepiness is highly prevalent and has been associated with increased risk of cardiovascular diseases, but evidence for its association with cardiovascular mortality is limited and inconsistent. We aimed to determine whether excessive daytime sleepiness is independently associated with cardiovascular mortality in general adult population. Patients and Methods: A prospective study of 10,330 adult participants (aged ≥ 20 years) from National Health and Nutrition Examination Survey (NHANES) 2005– 2006 and 2007– 2008 was followed up until December 31st, 2015. Excessive daytime sleepiness was defined as the self-reported feeling of being overly sleepy often or always during the day. Cox proportional hazard ratios (HRs) with 95% confidence interval (CI) were estimated to assess risk for cardiovascular mortality. Results: A total of 10,330 participants with mean age of 47.3 years (95% CI, 46.0 to 48.1) were included in this analysis. Approximately, 18.5% of US adults reported excessive daytime sleepiness. Over a mean follow-up of 8.3 years, 262 cardiovascular deaths occurred. Participants with excessive daytime sleepiness had 2.85-times greater risk (95% CI, 1.33– 6.09) of cardiovascular death than those without daytime sleepiness in multivariable analysis corrected for sociodemographic factors, comorbidities and cardiovascular risk factors including depression. Further adjustment for self-reported sleep disorders and sleep duration only slightly attenuated this association (HR, 2.55; 95% CI, 1.23– 5.27). No interactions between excessive daytime sleepiness and age, sex or cardiovascular disease at study entry were observed (all Ps> 0.05). Conclusion: Excessive daytime sleepiness is highly prevalent among US adults and is independently associated with an approximately two-and-a-half-fold increased risk of cardiovascular mortality in a large national sample. Screening for excessive daytime sleepiness may be a simple and cost-effective tool for identifying individuals at high risk of cardiovascular death.

Objective: To evaluate the association between dietary inflammatory index (DII) and Atherosclerotic cardiovascular disease (ASCVD) among U.S. adults.Methods: We collected data from National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. Adults who reported complete information to diagnose ASCVD and calculate DII were included. We used three models to differentially adjust the covariates, including age, sex, race or ethnicity, education level, smoking status, poverty, insurance, body mass index, hyperlipemia, hypertension, and diabetes. Logistic regression was used to estimate the Odds Ratio (OR) and 95% confidence interval (95% CI) for ASCVD grouped by DII deciles. We additionally conducted spline smoothing with the generalized additive model (GAM) and the log-likelihood ratio to examine the non-linear relationship between DII and ASCVD. If exists, the segmented linear regression will be used to detect the cutoff point. The subgroup analyses were stratified by various atherosclerotic cardiovascular diseases (i.e., CHD, angina, heart attack, and stroke) and sex.Results: A total of 48,733 participants (mean age, 47.13 ± 0.19 years) with 51.91% women were enrolled, of which 5,011 were diagnosed with ASCVD. In the crude model, participants in the five highest deciles (D6, 7, 8, 9, and 10) of DII score had a significantly higher risk of having ASCVD compared to those in the first decile. In the fully adjusted model, those in the tenth decile [OR = 1.47, 95% CI = (1.18,1.84)] of DII had a significantly increased risk of ASCVD compared to the first decile. Notably, when DII is above 3, the ASCVD risk increased by 41% for each one increase in DII [OR = 1.41, 95% CI = (1.15,1.73)]. This relationship was more pronounced in females.Conclusion: Our study revealed a positive and non-linearly association between DII and ASCVD in U.S. adults. This relationship was more pronounced in females. The findings provide a reference for future research and diet recommendations.

The existing eligible randomized controlled trials (RCTs) were critically appraised for the effectiveness and safety of Chinese herbal medicine Dengzhan Shenmai for ischemic stroke. Systematic review and meta-analysis (CRD42016042914, http://www.crd.york.ac.uk/PROSPERO). Six electronic databases were searched from inception to May 2016. Risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI) were used as effect estimates using RevMan 5.3. Meta-analysis was performed where data were available. A summary of finding table was generated by the GRADEpro (version 3.6). We identified 14 RCTs involving 5206 participants. Majority of the included trials were of high risk of bias in methodological quality. For acute ischemic stroke, adding DZSM capsule to conventional therapy achieved higher Barthel Index scores (MD 22.37, 95% CI 21.34-23.40), lower neurological function deficit scores (MD - 3.73, 95% CI -5.27 to -2.19) and lower recurrence rate (RR 0.22, 95% CI 0.10, 0.46). For patients in their convalescence (or sequelae) stage of ischemic stroke, DZSM capsule was superior in improving quality of life (MD 28.8, 95% CI 7.10-50.50) and recurrence rate (RR 0.71, 95% CI 0.51-0.99) compared to placebo. No trials reported serious adverse events. DZSM capsule appears to improve neurological function, quality of life, and reduce recurrence rate based on conventional therapy for ischemic stroke. DZSM capsule seems generally safe for clinical application. However, the findings of benefit are inconclusive due to generally weak evidence, and further large, rigorous trials are still warranted.

Background: The prevalence of obesity continues to increase in spite of substantial efforts towards its prevention, posing a major threat to health globally. Circadian disruption has been associated with a wide range of preclinical and clinical disorders, including obesity. However, whether rest-activity rhythm (RAR), an expression of the endogenous circadian rhythm, is associated with excess adiposity is poorly understood. Here we aimed to assess the association of RAR with general and abdominal obesity.Methods: Non-institutionalized adults aged ≥20 years participating in the US National Health and Nutrition Examination Survey (NHANES) 2011-2014 who wore accelerometers for at least four 24-hour periods were included (N=7,838). Amplitude, mesor, acrophase and pseudo-F statistic of RAR were estimated using extended cosinor model, and interdaily stability (IS) and intradaily variability (IV) were computed by nonparametric methods. We tested the association between rest-activity rhythm and general obesity defined by body mass index and abdominal obesity by waist circumference. Waist-to-height ratio, sagittal abdominal diameter, and total and trunk fat percentages measured by imaging methods were also analyzed.Results: In multivariable analysis, low amplitude (magnitude of the rhythm), mesor (rhythm-corrected average activity level), pseudo-F statistic (robustness of the rhythm), IS (day-to-day rhythm stability), or high IV (rhythm fragmentation) were independently associated with higher likelihood of general or abdominal obesity (all Ps<.05). Consistently, RAR metrics were similarly associated with all adiposity measures (all Ps<.01). Delayed phase of RAR (later acrophase) was only significantly related to general and abdominal obesity in women.Conclusions: Aberrant RAR is independently associated with anthropometric and imaging measures of general and abdominal obesity. Longitudinal studies assessing whether RAR metrics can predict weight gain and incident obesity are warranted.

Background: Dyslipidemia is a critical driver in the development of coronary heart disease (CHD), which further exacerbates the risk of major adverse cardiovascular events (MACEs). Chinese herbal medicine (CHM) plays an important role in the regulation of lipid levels and improvement of prognosis. However, few systematic reviews report whether the efficacy of CHM therapy for regulating lipid levels and lowering cardiovascular events is associated with baseline lipid levels.Methods: Randomized controlled trials assessing efficacy of CHM for lipid profiles and MACEs among patients with CHD were searched in six databases. Two authors independently extracted studies according to a predesigned form. Cochrane risk of bias tool and Grading of Recommendations Assessment, Development, and Evaluation system were used to assess the methodological quality of the included studies. The primary outcomes were blood lipid levels and MACEs including cardiovascular mortality, non-fatal myocardial infarction, revascularization, angina pectoris, heart failure, and non-fatal stroke across baseline lipid levels. The secondary outcomes were individual components of the primary outcomes.Results: A total of 23 trials with 7,316 participants were included in this study. Altogether 377 cardiovascular events occurred in 3,670 patients in the CHM group, while 717 events occurred in 3,646 patients in the Western medicine–alone group. Compared with the Western medicine alone, additional CHM significantly lowered low-density lipoprotein cholesterol (LDL-C) [MD = −0.46, 95% CI (−0.60 to −0.32), P < 0.00001, I² = 96%]. The risk reduction in MACEs associated with CHM vs. Western medicine therapy was 0.52 [95% CI (0.47–0.58), P < 0.00001, I² = 0%], but varied by baseline LDL-C level (P = 0.03 for interaction). Triglycerides (TG) level was also significantly lowered by additional CHM vs. Western medicine alone [MD = −0.27, 95% CI (−0.34 to −0.20), P < 0.00001, I² = 81%], and risk reduction for MACEs also varied with baseline TG, with greater risk reduction in higher baseline TG subgroups (P = 0.03 for interaction). Similar results were observed with total cholesterol and high-density lipoprotein cholesterol.Conclusion: Compared with Western medicine alone, additional CHM was associated with lower risk of cardiovascular events and improvement of lipid profiles. Risk reduction for cardiovascular events was associated with baseline LDL-C and TG levels.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023425791.