Periodontal disease increases the severity of chronic obstructive pulmonary disease: a Mendelian randomization study.

BACKGROUND: Recent research suggests that periodontitis can increase the risk of chronic obstructive pulmonary disease (COPD). In this study, we performed two-sample Mendelian randomization (MR) and investigated the causal effect of periodontitis (PD) on the genetic prediction of COPD. The study aimed to estimate how exposures affected outcomes. METHODS: Published data from the Gene-Lifestyle Interaction in the Dental Endpoints (GLIDE) Consortium's genome-wide association studies (GWAS) for periodontitis (17,353 cases and 28,210 controls) and COPD (16,488 cases and 169,688 controls) from European ancestry were utilized. This study employed a two-sample MR analysis approach and applied several complementary methods, including weighted median, inverse variance weighted (IVW), and MR-Egger regression. Multivariable Mendelian randomization (MVMR) analysis was further conducted to mitigate the influence of smoking on COPD. RESULTS: We chose five single-nucleotide polymorphisms (SNPs) as instrumental variables for periodontitis. A strong genetically predicted causal link between periodontitis and COPD, that is, periodontitis as an independent risk factor for COPD was detected. PD (OR = 1.102951, 95% CI: 1.005-1.211, p = 0.039) MR-Egger regression and weighted median analysis results were coincident with those of the IVW method. According to the sensitivity analysis, horizontal pleiotropy's effect on causal estimations seemed unlikely. However, reverse MR analysis revealed no significant genetic causal association between COPD and periodontitis. IVW (OR = 1.048 > 1, 95%CI: 0.973-1.128, p = 0.2082) MR Egger (OR = 0.826, 95%CI:0.658-1.037, p = 0.1104) and weighted median (OR = 1.043, 95%CI: 0.941-1.156, p = 0.4239). The results of multivariable Mendelian randomization (MVMR) analysis, after adjusting for the confounding effect of smoking, suggest a potential causal relationship between periodontitis and COPD (P = 0.035). CONCLUSION: In this study, periodontitis was found to be independent of COPD and a significant risk factor, providing new insights into periodontitis-mediated mechanisms underlying COPD development.

Antioxidant Defenses Against Air Humidity Stress in Fruit Bodies of Auricularia heimuer (Agaricomycetes).

Air humidity is an important environmental factor restricting the fruit body growth of Auricularia heimuer. Low air humidity causes the fruit body to desiccate and enter dormancy. However, the survival mechanisms to low air humidity for fruit bodies before dormancy remain poorly understood. In the present study, we cultivated A. heimuer in a greenhouse and collected the fruit bodies at different air humidities (90%, 80%, 70%, 60%, and 50%) to determine the contents of malondialdehyde (MDA) and non-enzymatic antioxidants such as ascorbic acid (AsA) and glutathione (GSH); and the activities of enzymatic antioxidants including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), glutathione peroxidase (GPX) and glutathione reductase (GR). Results showed that the MDA contents tended to increase with decreasing relative air humidity. Relative air humidity below 90% caused membrane lipid peroxidation and oxidative stress (based on MDA contents) to the fruit body, which we named air humidity stress. In contrast to the control and with the degree of stress, the GSH contents and activities of SOD, CAT, GR, GPX, and APX tended to ascend, whereas AsA showed a declining trend; the POD activity only rose at 50%. The antioxidants favored the fruit body to alleviate oxidative damage and strengthened its tolerance to air humidity stress. The antioxidant defense system could be an important mechanism for the fruit body of A. heimuer in air humidity stress.

Prevention and control of ship-source pollution in the Arctic shipping routes: challenges and countermeasures.

Ship-source pollution is one of the important contributors to marine environment pollution. Because the legal status of the Arctic shipping routes is not clear, there is a considerable degree of dispute in the application of the rules on the prevention and control of ship-source pollution. The increased melting of sea ice undermines the legal legitimacy of the "ice-covered areas" clause under the United Nations Convention on the Law of the Sea. The conflict between the application of the Polar Code and "ice-covered areas" will also reach an initial conclusion in the context of melting sea ice. However, the inadequacy of ship-source pollution rules in the Polar Code hampers its application, which has led to a negative impact on the more active role in the governance of pollution from Arctic shipping. For replying to the Challenges in the prevention of ship-source pollution in Arctic shipping routes, the relevant rules of the Polar Code need to be further improved, while a more binding HFO ban according to ship types needs to be applied. Therefore, a more important role in the future Arctic governance mechanism will be played by the enhanced enforcement of the Polar Code, meanwhile, the target for uniform international regulation of preventing and controlling ship-source pollution in Arctic shipping routes should be achieved.

[Evaluation of the clinical effect of acupuncture in treatment of neck pain in cervical spondylosis based on propensity score matching].

OBJECTIVE: To observe the clinical effect and safety of acupuncture in treatment of neck pain due to cervical spondylosis. METHODS: According to the patients' preference and acceptance for the interventions of neck pain induced by cervical spondylosis, an acupuncture group (221 cases) and a non-acupuncture group (251 cases) were divided. After the control of confounding factors with propensity score matching, 218 cases were included in either acupuncture group or non-acupuncture group. In the acupuncture group, acupuncture was applied to Dazhui (GV 14), Baihui (GV 20), ashi points, bilateral neck-Jiaji (EX-B 2), Fengchi (GB 20), Houxi (SI 3), Shenmai (BL 62), etc. The treatment was given once daily, one course of intervention was composed of 5 treatments and 3 courses were included. In the non-acupuncture group, the oral administration of imrecoxib tablets and cobalt tablets was prescribed for 2 weeks. Before and after treatment, the scores of Northwick Park questionnaire (NPQ) and the simplified McGill pain questionnaire (SF-MPQ) were observed, and the safety was assessed in patients of the two groups. RESULTS: After treatment completion, the scores of NPQ and SF-MPQ were all reduced when compared with those before treatment in each group (P<0.001), and the scores of NPQ and SF-MPQ in the acupuncture group were lower than those of the non-acupuncture group (P<0.001). The incidence of adverse reactions was 6.0% (13/218) in the acupuncture group and was 10.1% (22/218) in the non-acupuncture group, without statistical significance in comparison (P>0.05). CONCLUSION: Acupuncture is effective and safe in the relief of neck pain and the improvement of comprehensive quality of life in the patients with cervical spondylosis.

Simulated microgravity altered the proliferation, apoptosis, and extracellular matrix formation of L929 fibroblasts and the transforming growth factor-ß1/Smad3 signaling pathway.

Exposure to microgravity can adversely affect the fitness of astronauts. The integrity of the skin plays a crucial role in protecting against mechanical forces and infections, fluid imbalance, and thermal dysregulation. In brief, the skin wound may cause unknown challenges to the implementation of space missions. Wound healing is a physiological process that relies on the synergistic action of inflammatory cells, extracellular matrix (ECM), and various growth factors to maintain the integrity of skin after trauma. Fibroblasts are present almost throughout the entire process of wound repair, especially in the scar formation at the endpoint of wound healing. However, there is limited knowledge about the extent to which fibroblasts are affected by the lack of gravity during wound healing. In this study, we utilized the rotary cell culture system, a ground-based facility that mimics the weightless condition, to study the alterations of L929 fibroblast cells under simulated microgravity (SMG). Our results demonstrated that the SM condition exerted negative influences on the proliferation and ECM formation of the L929 fibroblast. Whereas, the apoptosis of fibroblast was significantly upregulated upon exposure to SMG conditions. Moreover, the transforming growth factor-ß1/Smad3 (TGF-ß1/smad3) signaling pathway of L929 fibroblast related to wound repair was also altered significantly under a weightless environment. Overall, our study provided evidence that fibroblasts are strongly sensitive to SMG and elucidated the potential value of the TGF-ß1/Smad3 signaling pathway modulating wound healing in the future practice of space medicine.

Autophagy in hepatic macrophages can be regulator and potential therapeutic target of liver diseases: A review.

Hepatic macrophages are a complex population of cells that play an important role in the normal functioning of the liver and in liver diseases. Autophagy, as a maintainer of cellular homeostasis, is closely connected to many liver diseases. And its roles are not always beneficial, but manifesting as a double-edged sword. The polarization of macrophages and the activation of inflammasomes are mediated by intracellular and extracellular signals, respectively, and are important ways for macrophages to take part in a variety of liver diseases. More attention should be paid to autophagy of hepatic macrophages in liver diseases. In this review, we focus on the regulatory role of hepatic macrophages' autophagy in a variety of liver diseases; especially on the upstream regulator of polarization and inflammasomes activation of the hepatic macrophages. We believe that the autophagy of hepatic macrophages can become a potential therapeutic target for management of liver diseases.

Regeneration of the heart: from molecular mechanisms to clinical therapeutics.

Heart injury such as myocardial infarction leads to cardiomyocyte loss, fibrotic tissue deposition, and scar formation. These changes reduce cardiac contractility, resulting in heart failure, which causes a huge public health burden. Military personnel, compared with civilians, is exposed to more stress, a risk factor for heart diseases, making cardiovascular health management and treatment innovation an important topic for military medicine. So far, medical intervention can slow down cardiovascular disease progression, but not yet induce heart regeneration. In the past decades, studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury. Insights have emerged from studies in animal models and early clinical trials. Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease. In this review, we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

Estimation of the bio-accessibility of methylmercury from aquatic foods using a PBTK model with an approximate Bayesian computation method in Chinese pregnant women.

BACKGROUND: Fish are the primary source of protein and docosahexaenoic acid (DHA) for pregnant women and children, but methylmercury (MeHg) pollution is the potential hazard of fish consumption. In risk assessments, the bio-accessibility of MeHg is usually assumed to be 100%, which could lead to overestimation of dietary exposure. METHOD: An existing PBTK model was adapted to estimate parameters of the bio-accessibility based on MeHg exposure data from a cohort of 397 Chinese pregnant women. The posterior distributions of parameters were determined by using the ABC - MCMC. RMSEP and Spearman's rank correlation coefficients (Rho) were calculated to determine the goodness of model fitting. The Monte Carlo analysis was performed for the parameter distributions to estimate the model variability. RESULT: The median of daily MeHg intake and maternal MeHg levels were 0.018 µg/kg bw and 3.01 µg/kg in the early and middle terms of pregnancy. The estimated bio-accessibility of freshwater fish, marine fish and others were 46.1, 17.3 and 58.2%, separately. The RMSEP improved from 11.18 to 2.54 and the Rho improved from 0.19 to 0.22 after bio-accessibility optimization. The model variability was estimated to be 2.6. CONCLUSION: The bio-accessibility estimated in this study was comparable to that determined in previous in vitro studies. The optimized model could improve the prediction performance on the MeHg body burden by dietary exposure.

Association between prenatal exposure to ambient air pollutants and postpartum depressive symptoms: A multi-city cohort study.

BACKGROUND: Women are vulnerable to depression during postpartum period. While several studies have shown associations between ambient air pollution exposure and depression in general population, there was few studies focused on the effect of various air pollutants on postpartum depression (PPD). OBJECTIVE: This study is designed to explore the association between prenatal exposure to air pollutants and PPD, and to reveal the potential vulnerable exposure time point. METHODS: The study enrolled 10,209 pregnant women who delivered between October 2019 and February 2021 in 5 participating hospitals from 3 cities in China. Edinburgh Postnatal Depression Scale (EPDS) was administered at 6 weeks postpartum to identify PPD symptoms. Associations between PPD symptoms and exposure levels in PM2.5, PM10, SO2, CO, NO2, and O3 averaged over the whole pregnancy and each trimester were estimated using logistic regression models after adjusting for potential confounding factors. Distributed lag models (DLMs) were used to determine the relevant associations in each gestational week. RESULTS: The risk for developing PPD symptoms was significant following a 10 µg/m3 increase in PM10 (aOR = 1.47, 95%CI:1.36-1.59), NO2 (aOR = 1.63, 95%CI:1.44-1.85), and 0.1 mg/m3 increase in CO (aOR = 2.31, 95%CI: 1.99-2.69) during the whole pregnancy. Similar results were also found in exposure during each trimester of pregnancy. Besides, SO2 exposure during the second trimester was a major risk factor for developing PPD symptoms (aOR = 1.10, 95%CI:1.03-1.18). Consistent effects were also observed in DLMs, except for PM2.5 and O3, which showed no significant sensitive windows throughout pregnancy period. CONCLUSION: Exposure to PM10, CO, NO2, and SO2 in pregnancy is associated with increased risks of developing depression at 6 weeks postpartum. Our findings reveal the importance of air pollution control for preventing maternal mental health disorders among the public.

Proteomic analysis of the effects of simulated microgravity in human gastric mucosal cells.

Microgravity is an ecological factor that affects the environment of the body. In this study, quantitative isobaric labeling (tandem mass tag) method was used to study the changes in human gastric mucosal cells under simulated microgravity for the first time. Comparative proteomic analysis identified 394 (202 upregulated and 192 downregulated) and 542 (286 upregulated and 256 downregulated) proteins differentially regulated by simulated microgravity after 3 and 7 days, respectively. Then the identified proteins were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for further exploration. The results of the analysis showed that the ribosomes of gastric mucosal cells were significantly impacted after exposure to simulated microgravity for 3 days, and the cells appeared to be in a state of stress and inflammation. Exposure to simulated microgravity for 7 days significantly affected the mitochondria of the cells, oxidative stress became more evident, while inflammation and weakened connections were observed in the cells. The results of this study highlighted the temporal response trend of gastric mucosal cells to the stressor of microgravity at the two time points of 3 and 7 days. These findings will provide insights into the development of methods to protect the gastric mucosa during space flight.

Autophagy in Gastric Mucosa: The Dual Role and Potential Therapeutic Target.

The incidence of stomach diseases is very high, which has a significant impact on human health. Damaged gastric mucosa is more vulnerable to injury, leading to bleeding and perforation, which eventually aggravates the primary disease. Therefore, the protection of gastric mucosa is crucial. However, existing drugs that protect gastric mucosa can cause nonnegligible side effects, such as hepatic inflammation, nephritis, hypoacidity, impotence, osteoporotic bone fracture, and hypergastrinemia. Autophagy, as a major intracellular lysosome-dependent degradation process, plays a key role in maintaining intracellular homeostasis and resisting environmental pressure, which may be a potential therapeutic target for protecting gastric mucosa. Recent studies have demonstrated that autophagy played a dual role when gastric mucosa exposed to biological and chemical factors. More indepth studies are needed on the protective effect of autophagy in gastric mucosa. In this review, we focus on the mechanisms and the dual role of various biological and chemical factors regulating autophagy, such as Helicobacter pylori, virus, and nonsteroidal anti-inflammatory drugs. And we summarize the pathophysiological properties and pharmacological strategies for the protection of gastric mucosa through autophagy.

Modes of Transport to School and Their Associations with Weight Status: A Cross-Sectional Survey of Students in Shanghai, China.

Background: Over the past two decades, both transport modes as well as overweight/obesity have changed dramatically among students in China, but their relationships are not clear. This study aimed to investigate modes of transport to school and their associations with the weight status of Chinese students. Methods: A cross-sectional study was conducted with non-resident students aged 6 to 17 years from all 16 districts across Shanghai, China in October and November 2019. Information about sociodemographic characteristics and the models of travel to school among students was investigated using an online, self-administered, structured questionnaire (or those assisted by their parents). Weight and height were measured by school health workers, and the Chinese standard age adjusted BMI (weight/height2) was used to classify students' weight status. Cumulative logistic regression modelling was used to examine the relationships. Results: The main mode of transport to school was an active mode (46.5%, defined as walking, bicycling, or public transport), followed by an inactive mode of transport (30.5%, defined as a car or bicycle as a passenger), and a combination of both modes (23%). About one-third of the students were overweight or obese and 5% were underweight. No statistically significant association between transport modes and weight status was found in this study. Conclusions: In Shanghai, close to one-third of children travel to school by an inactive mode of transport. The findings of this study did not support the notion that an active mode to school could be beneficial for preventing overweight/obesity in students in China.

Prognostic Significance of Relative Hyperglycemia after Percutaneous Coronary Intervention in Patients with and without Recognized Diabetes.

BACKGROUND: The research on the association between the relative glycemic level postpercutaneous coronary intervention (PCI) and adverse prognosis in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients is relatively inadequate. OBJECTIVE: The study aimed to identify whether the glycemic level post-PCI predicts adverse prognosis in NSTE-ACS patients. METHODS: Patients (n=2465) admitted with NSTE-ACS who underwent PCI were enrolled. The relative glycemic level post-procedure was calculated as blood glucose level post-PCI divided by HbA1c level, which was named post-procedural glycemic index (PGI). The primary observational outcome of this study was major adverse cardiovascular events (MACE) [defined as a composite of all-cause death, non-fatal myocardial infarction (MI) and any revascularization]. RESULTS: The association between PGI and MACE rate is presented as a U-shape curve. Higher PGIs [hazard ratio (HR): 1.669 (95% confidence interval (CI): 1.244-2.238) for the third quartile (Q3) and 2.076 (1.566-2.753) for the fourth quartile (Q4), p<0.001], adjusted for confounding factors, were considered to be one of the independent predictors of MACE. The association between the PGI and the risk of MACE was more prominent in the non-diabetic population [HR (95%CI) of 2.356 (1.456-3.812) for Q3 and 3.628 (2.265-5.812) for Q4, p<0.001]. There were no significant differences in MACE risk between PGI groups in the diabetic population. CONCLUSION: Higher PGI was a significant and independent predictor of MACE in NSTE-ACS patients treated with PCI. The prognostic effect of the PGI is more remarkable in subsets without pre-existing diabetes than in the overall population. The predictive value of PGI was not identified in the subgroup with diabetes.

Triglyceride-Glucose Index as a Surrogate Marker of Insulin Resistance for Predicting Cardiovascular Outcomes in Nondiabetic Patients with Non-ST-Segment Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

AIM: The triglyceride-glucose index (TyG index) is proposed as a surrogate parameter for insulin resistance (IR) and, when elevated, is related to increased cardiovascular risks. Whether the TyG index is of great value in predicting adverse prognosis for individuals diagnosed with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), who received elective percutaneous coronary intervention (PCI), and without recognized diabetes remains unclear. METHODS: Overall, 1,510 subjects diagnosed with NSTE-ACS, who received elective PCI, and without recognized diabetes were enrolled in the current study. All participants received a routine follow-up after discharge. The TyG index was obtained from the following equation: napierian logarithmic (ln) [fasting triglyceride (TG, mg/dL)×fasting blood glucose (FBG, mg/dL)/2]. Adverse cardiovascular events included all-cause death, nonfatal myocardial infarction (MI), nonfatal ischemic stroke, and ischemia-driven revascularization, composite of which was defined as the primary endpoint. RESULTS: Overall, 316 (20.9%) endpoint events were documented during a 48-month follow-up. Despite adjusting for confounding variates, the TyG index remains to be a significant risk predictor for the primary endpoint, with a hazard ratio (HR) [95% confidence interval (CI)] of 2.433 (1.853-3.196) (P＜0.001). A significant enhancement on the predictive performance for the primary endpoint emerged when adding the TyG index into a baseline model [area under the receiver-operating characteristic (ROC) curve (AUC), 0.835 for baseline model vs. 0.853 for baseline model＋TyG index, P＜0.001; net reclassification improvement (NRI), 0.194, P＜0.001; integrated discrimination improvement (IDI), 0.023, P=0.007]. CONCLUSIONS: The TyG index is an independent risk predictor for adverse cardiovascular events in nondiabetic subjects diagnosed with NSTE-ACS and who received elective PCI. Further prospective studies are needed to verify these findings.

Prognostic impact of estimated remnant-like particle cholesterol in patients with differing glycometabolic status: an observational cohort study from China.

BACKGROUND: It is uncertain whether estimated remnant-like particle cholesterol (RLP-C) could predict residual risk in patients with different glycometabolic status. This study aimed to evaluate the relationship between estimated RLP-C and adverse prognosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) treated with percutaneous coronary intervention (PCI) and to identify the potential impact of glycometabolism on the predictive value of estimated RLP-C. METHODS: The study assessed 2419 participants with NSTE-ACS undergoing PCI at Beijing Anzhen Hospital from January to December 2015. Estimated RLP-C was calculated as follows: total cholesterol (TC) minus low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The adverse events included all-cause death, non-fatal myocardial infarction (MI), and ischemia-driven revascularization. RESULTS: Estimated RLP-C was prominently associated with adverse prognosis in the total population [hazard ratio (HR) 1.291 per 1-SD increase, 95% confidence interval (CI) 1.119-1.490, P <  0.001], independent of confounding risk factors. However, subgroup analysis showed that increasing estimated RLP-C was related to a higher risk of adverse events in the diabetic population only [HR 1.385 per 1-SD increase, 95% CI 1.183-1.620, P <  0.001]. Estimated RLP-C failed to be a significant determinant of adverse prognosis in non-diabetic and pre-diabetic subgroups. The addition of estimated RLP-C to a baseline model including traditional risk factors enhanced the predictive performance both in total and diabetic populations. CONCLUSIONS: High estimated RLP-C level is a significant predictor for recurrent adverse events in patients with diabetes and NSTE-ACS treated with PCI.

Impacts of triglyceride-glucose index on prognosis of patients with type 2 diabetes mellitus and non-ST-segment elevation acute coronary syndrome: results from an observational cohort study in China.

BACKGROUND: The relationship between triglyceride-glucose index (TyG index) and the prevalence and prognosis of cardiovascular disease has been confirmed by former studies. However, it remains uncertain whether TyG index has a prognostic impact in patients with type 2 diabetes mellitus (T2DM) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS: The study retrospectively enrolled 798 patients (mean age: 60.9 ± 8.3 years; 68.3% men) with T2DM and NSTE-ACS who underwent PCI at Beijing Anzhen Hospital from January to December 2015. TyG index was calculated as previously reported: ln [fasting TGs (mg/dL) * FBG (mg/dL)/2]. The primary endpoint was a composite of adverse events as follows: all-cause death, non-fatal myocardial infarction (MI) and ischemia-driven revascularization. RESULTS: TyG index was significantly higher in patients with a primary endpoint event compared with those without. Multivariate Cox proportional hazards analysis showed that 1-unit increase of TyG index was independently associated with higher risk of primary endpoint, independent of other risk factors [hazard ratio (HR) 3.208 per 1-unit increase, 95% confidence interval (CI) 2.400-4.289, P < 0.001]. The addition of TyG index to a baseline risk model had an incremental effect on the predictive value for adverse prognosis [AUC: baseline risk model, 0.800 vs. baseline risk model + TyG index, 0.856, P for comparison < 0.001; category-free net reclassification improvement (NRI) 0.346, P < 0.001; integrated discrimination improvement (IDI) 0.087, P < 0.001]. CONCLUSIONS: Increased TyG index is a significant predictor of adverse prognosis in patients with T2DM and NSTE-ACS undergoing PCI. Further studies need to be performed to determine whether interventions for TyG index have a positive impact on improving clinical prognosis.

Impacts of geriatric nutritional risk index on prognosis of patients with non-ST-segment elevation acute coronary syndrome: Results from an observational cohort study in China.

BACKGROUND AND AIMS: It is recognized that malnutrition increases risk of worse prognosis in patients with various diseases. The present study investigated if poor nutritional status predicts adverse outcomes in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: The study enrolled 2299 patients (mean age: 60.01 ± 8.95 years; 71.8% male) with NSTE-ACS who underwent PCI at Beijing Anzhen Hospital from January to December 2015. The entire cohort was divided into training set (n = 1519) and testing set (n = 780) at a ratio of approximate 2 : 1. Nutritional status was assessed by geriatric nutritional risk index (GNRI). The primary endpoint was a composite of adverse events as follows: all-cause death, non-fatal myocardial infarction (MI) and any revascularization. Multivariate Cox analysis showed that GNRI significantly associated with primary endpoint, independent of other risk factors [hazard ratio (HR) 1.159 per 1-point decrease of GNRI, 95% confidence interval (CI) 1.130-1.189, p < 0.001]. The addition of GNRI to a baseline model had an incremental effect on the predictive value for adverse prognosis in training set [AUC: from 0.821 to 0.873, p < 0.001; category-free net reclassification improvement (NRI): 0.313, p < 0.001; integrated discrimination improvement (IDI): 0.108, p < 0.001]. The incremental effect of GNRI was further validated and confirmed in testing set. CONCLUSION: Lower GNRI is a significant predictor of adverse prognosis in patients with NSTE-ACS undergoing PCI. Further studies need to be performed to determine whether nutritional interventions have a positive impact on improving clinical prognosis.

Correction to: Simulated microgravity significantly altered metabolism in epidermal stem cells.

The affiliation given for Yan Cui in this article is not correct. The following is the correction affiliation.

Melatonin attenuates vascular calcification by inhibiting mitochondria fission via an AMPK/Drp1 signalling pathway.

Mitochondrial fission plays a role in cardiovascular calcification. Melatonin has previously been shown to protect against cardiovascular disease, so this study sought to explore whether it attenuates vascular calcification by regulating mitochondrial fission via the AMP-activated protein kinase/dynamin-related protein 1 (AMPK/Drp1) signalling pathway. The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin red staining, while calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure the expression of runt-related transcription factor 2 (Runx2), Drp1 and cleaved caspase 3. Melatonin markedly reduced calcium deposition and ALP activity. Runx2 and cleaved caspase 3 were down-regulated, Drp1 was reduced in response to melatonin, and this was accompanied by decreased apoptosis. Melatonin also reduced levels of mitochondrial superoxide, reversed ß-glycerophosphate (ß-GP)-induced ΔΨm dissipation and decreased mitochondrial fragmentation. The effects of melatonin in ß-GP-treated VSMCs were similar to those of mitochondrial division inhibitor 1. Melatonin significantly activated the expression of AMPK and decreased Drp1 expression. Treatment with compound C ablated the observed benefits of melatonin treatment. These findings indicate that melatonin protects VSMCs against calcification by inhibiting mitochondrial fission via the AMPK/Drp1 pathway.

Melatonin Attenuates Calcium Deposition from Vascular Smooth Muscle Cells by Activating Mitochondrial Fusion and Mitophagy via an AMPK/OPA1 Signaling Pathway.

Mitochondrial fusion/mitophagy plays a role in cardiovascular calcification. Melatonin has been shown to protect against cardiovascular disease. This study sought to explore whether melatonin attenuates vascular calcification by regulating mitochondrial fusion/mitophagy via the AMP-activated protein kinase/optic atrophy 1 (AMPK/OPA1) signaling pathway. The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin Red S staining, while calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure expression of runt-related transcription factor 2 (Runx2), mitofusin 2 (Mfn2), mito-light chain 3 (mito-LC3) II, and cleaved caspase 3. Melatonin markedly reduced calcium deposition and ALP activity. Runx2 and cleaved caspase 3 were downregulated in response to melatonin, whereas Mfn2 and mito-LC3II were enhanced and accompanied by decreased mitochondrial superoxide levels. Melatonin also maintained mitochondrial function and promoted mitochondrial fusion/mitophagy via the OPA1 pathway. However, OPA1 deletion abolished the protective effects of melatonin on VSMC calcification. Melatonin treatment significantly increased p-AMPK and OPA1 protein expression, whereas treatment with compound C ablated the observed benefits of melatonin treatment. Collectively, our results demonstrate that melatonin protects VSMCs against calcification by promoting mitochondrial fusion/mitophagy via the AMPK/OPA1 pathway.