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Vascular calcification is a significant factor contributing to the rupture of vulnerable atherosclerotic plaques, ultimately leading to cardiovascular disease. However, no effective treatments are currently available to slow the progression of vascular calcification. Notoginsenoside R1 (R1) and protocatechuic aldehyde (PCAD), primary active components extracted from Panax notoginseng and Salvia miltiorrhiza Burge, have shown potential in mitigating endothelial injury and atherosclerosis. This study investigated the effects of R1-PCAD on nitric oxide (NO) production in endothelial cells (ECs) and its role in counteracting vascular calcification and inflammation. Additionally, it explored the mechanisms underlying these effects. To simulate atherosclerotic calcification, apolipoprotein E-deficient (ApoE -/- ) mice were fed a high-fat diet and given intraperitoneal injections of vitamin D3. Treatment with the R1-PCAD combination improved endothelial function, reduced inflammation in the aorta, and lowered calcium deposition. Mechanistically, R1-PCAD enhanced eNOS-Ser1177 phosphorylation by activating the AMPKα/Akt pathway, which stimulated NO production and eNOS activation in ECs. In an in vitro co-culture model involving vascular smooth muscle cells (VSMCs) and ECs, R1-PCAD similarly reduced inflammation and calcification in VSMCs triggered by β-glycerophosphate, with these effects partially dependent on NO levels and EC functionality. Further investigation revealed that R1-PCAD facilitated NO release from ECs, which subsequently inhibited TGFβR1 activation in VSMCs. This inhibition reduced Smad2/3 activation and nuclear translocation of YAP/TAZ, thereby diminishing inflammation and calcification in VSMCs. These findings suggest that R1-PCAD alleviates vascular inflammation and calcification primarily via the NO-TGFβR1-YAP/TAZ signaling pathway. This study presents a promising new approach for treating vascular calcification by targeting intercellular signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In the chemically enhanced oil recovery (CEOR) processes, heavy components in crude oil, such as asphaltenes, adhere to reservoir rocks, significantly impeding crude oil extraction. Surfactants are frequently utilized to improve oil recovery due to their ability to reduce interfacial tension (IFT) and modify surface wettability. Nevertheless, indiscriminate surfactant usage may result in resource wastage and hinder the attainment of optimal recovery outcomes. Therefore, it is urgent to accurately and efficiently screen out optimal surfactants suitable for different oil fields. This work employs fluid density functional theory (FDFT) to investigate the competitive adsorption mechanism of surfactants and asphaltenes on rock interfaces. We examined the impact of surfactants on asphaltene adsorption and determined the optimal surfactant concentration and chain length for differing reservoir electrical properties and asphaltene compositions. Furthermore, a comprehensive assessment of surfactants was conducted, considering both performance and economic factors. The findings contribute to a deeper comprehension of the displacement effect of surfactants on asphaltenes and offer scientific screening solutions for surfactants in oil recovery processes.

Chitosan oligosaccharide (COS) can efficiently inhibit Cronobacter sakazakii (C. sakazakii) biofilm independent on antibacterial activity. However, the mechanism is still unclear. In this study, the role of out membrane protein A (OmpA) and its downstream CpxRA-mediated cellulose production pathway in COS's inhibition on C. sakazakii biofilm were explored. The spectroscopic results were shown that COS could interact with OmpA, and this changed OmpA's second structure and spatial conformation as well as cell membrane permeability and COS uptake. C. sakazakii ΔOmpA strain under COS treatment had a lower cell membrane permeability and COS uptake rate. The interaction between OmpA and COS could further initiate CpxRA system. The regulon cpxP expression level was therefore up-regulated. The deletion of the response regulator cpxR gene reduced inhibitory effect of COS on biofilm. CpxRA system inhibited expression of csgD and adrA, which coded diguanylate cyclase to generate cyclic diguanosine monophosphate (c-di-GMP). The expression of bcsAB was then down-regulated by c-di-GMP, and the cellulose production as well as biofilm were reduced. The addition of exogenous c-di-GMP could mitigate the inhibition of COS on C. sakazakii biofilm. These results not only help to elucidate biofilm inhibition mechanism of COS, but also provided a basis for developing anti-biofilm agents targeted OmpA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Estimated pulse wave velocity (ePWV) has been found to be an independent predictor of cardiovascular mortality and kidney injury, which can be estimated noninvasively. This study aimed to investigate the association between ePWV and in-hospital mortality in critically ill patients with acute kidney injury (AKI)., Methods: This study included 5960 patients with AKI from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The low and high ePWV groups were compared using a Kaplan-Meier survival curve to evaluate the differences in survival status. Cox proportional hazards models were used to explore the association between ePWV and in-hospital mortality in critically ill patients with AKI. To further examine the dose-response relationship, we used a restricted cubic spline (RCS) model. Stratification analyses were conducted to investigate the effect of ePWV on hospital mortality across various subgroups., Results: Survival analysis indicated that patients with high ePWV had a lower survival rate than those with low ePWV. Following adjustment, high ePWV demonstrated a statistically significant association with an increased risk of in-hospital mortality among AKI patients (HR = 1.53, 95% CI = 1.36-1.71, p  < 0.001). Analysis using the RCS model confirmed a linear increase in the risk of hospital mortality as the ePWV values increased ( P for nonlinearity = 0.602)., Conclusions: A high ePWV was significantly associated with an increased risk of in-hospital mortality among patients with AKI. Furthermore, ePWV was an independent predictor of in-hospital mortality in critically ill patients with AKI.

Background: Carotid-femoral pulse wave velocity has been identified as an autonomous predictor of cardiovascular mortality and kidney injury. This important clinical parameter can be non-invasively estimated using the calculated pulse wave velocity (ePWV). The objective of this study was to examine the correlation between ePWV and in-hospital as well as one-year mortality among critically ill patients with chronic kidney disease (CKD) and atherosclerotic heart disease (ASHD)., Methods: This study included a cohort of 1173 patients diagnosed with both CKD and ASHD, sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The four groups divided into quartiles according to ePWV were compared using a Kaplan-Meier survival curve to assess variations in survival rates. Cox proportional hazards models were employed to analyze the correlation between ePWV and in-hospital as well as one-year mortality among critically ill patients with both CKD and ASHD. To further investigate the dose-response relationship, a restricted cubic splines (RCS) model was utilized. Additionally, stratification analyses were performed to examine the impact of ePWV on hospital and one-year mortality across different subgroups., Results: The survival analysis results revealed a negative correlation between higher ePWV and survival rate. After adjusting for confounding factors, higher ePWV level (ePWV > 11.90 m/s) exhibited a statistically significant association with an increased risk of both in-hospital and one-year mortality among patients diagnosed with both CKD and ASHD (HR = 4.72, 95% CI = 3.01-7.39, p  < 0.001; HR = 2.04, 95% CI = 1.31-3.19, p  = 0.002). The analysis incorporating an RCS model confirmed a linear escalation in the risk of both in-hospital and one-year mortality with rising ePWV values ( P for nonlinearity = 0.619; P for nonlinearity = 0.267)., Conclusions: The ePWV may be a potential marker for the in-hospital and one-year mortality assessment of CKD with ASHD, and elevated ePWV was strongly correlated with an elevated mortality risk in patients diagnosed with both CKD and ASHD.

Background: This study aims to investigate the short-term effects and safety of adjunct Suxiao Jiuxin Pills (SJPs) on conventional therapy in chronic coronary syndrome (CCS) patients who are intolerant to the adverse effects of long-acting nitrates., Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial. A total of 174 CCS participants from eight clinical study centers in China were included in the modified intention-to-treat analyses. Participants with CCS and intolerance to the adverse effects of long-acting nitrates were recruited and randomized to either the SJPs or the placebo group for a duration of 4 weeks., Results: Compared to the placebo group, the SJPs group showed a significant improvement in the efficacy rate after 4 weeks (OR = 2.43, 95% CI = 1.32 to 4.47, P = 0.004). Besides, individuals without a history of alcohol consumption showed a greater improvement in the SAQ summary score compared to those with a history of alcohol consumption., Conclusion: Adjunctive SJPs enhance the effectiveness of short-term conventional anti-angina treatment for patients with CCS who experience intolerance to long-acting nitrates, without significant adverse effects during application., Trial Registration: Chinese Clinical Trials Registry Platform, ChiCTR2100050066. Registered 16 August 2021, https://www.chictr.org.cn/showproj.html?proj=131470 ., (© 2024. The Author(s).)

Cardiovascular disease (CVD) is one of the leading causes of death globally, and vascular calcification (VC) has been recognized as an independent and strong predictor of global CVD and mortality. Chronic inflammation has been demonstrated to play a significant role in the progression of VC. This review aims to summarize the literature that aimed to elucidate the associations between dietary inflammation (DI) and VC as well as to explore the mechanisms underlying the association and discuss strategies (including dietary interventions) to prevent VC. Notably, diets rich in processed foods, carbohydrates with high glycemic index/load, saturated fatty acids, trans -fatty acids, cholesterol, and phosphorus were found to induce inflammatory responses and accelerate the progression of VC, indicating a close relationship between DI and VC. Moreover, we demonstrate that an imbalance in the composition of the gut microbiota caused by the intake of specific dietary choices favored the production of certain metabolites that may contribute to the progression of VC. The release of inflammatory and adhesion cytokines, activation of inflammatory pathways, oxidative stress, and metabolic disorders were noted to be the main mechanisms through which DI induced VC. To reduce and slow the progression of VC, emphasis should be placed on the intake of diets rich in omega-3 fatty acids, dietary fiber, Mg, Zn, and polyphenols, as well as the adjustment of dietary pattern to reduce the risk of VC. This review is expected to be useful for guiding future research on the interplay between DI and VC.

Purpose of Review: Our work is to establish more distinct association between specific stress and vascular smooth muscle cells (VSMCs) phenotypes to alleviate atherosclerotic plaque burden and delay atherosclerosis (AS) progression., Recent Finding: In recent years, VSMCs phenotypic transition has received significant interests. Different stresses were found to be associated with VSMCs phenotypic transition. However, the explicit correlation between VSMCs phenotype and specific stress has not been elucidated clearly yet. We discover that VSMCs phenotypic transition, which is widely involved in the progression of AS, is associated with specific stress. We discuss approaches targeting stresses to intervene VSMCs phenotypic transition, which may contribute to develop innovative therapies for AS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: It is unknown whether D2 lymphadenectomy + complete mesogastric excision for gastric cancer improves survival compared with just D2 lymphadenectomy., Methods: Between September 2014 and June 2018, patients with advanced gastric cancer were randomly assigned (1 : 1) to laparoscopic D2 lymphadenectomy or D2 lymphadenectomy + complete mesogastric excision gastrectomy. The modified intention-to-treat population was defined as patients who had pathologically confirmed gastric adenocarcinoma (pT1 N1-3 M0 and pT2-4 N0-3 M0). The primary endpoint was 3-year disease-free survival. Secondary endpoints were the recurrence pattern and overall survival., Results: The median follow-up of patients in the D2 lymphadenectomy group (169 patients) and patients in the D2 lymphadenectomy +complete mesogastric excision group (169 patients) was 55 (interquartile range 37-60) months and 51 (interquartile range 40-60) months respectively. Recurrence occurred in 50 patients in the D2 lymphadenectomy group (29.6%) versus 33 patients in the D2 lymphadenectomy + complete mesogastric excision group (19.5%) (P = 0.032). The 3-year disease-free survival was 75.5% (95% c.i. 68.3% to 81.3%) in the D2 lymphadenectomy group versus 85.0% (95% c.i. 78.7% to 89.6%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.042). The HR for recurrence in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 0.99) by Cox regression (P = 0.045). The 3-year overall survival rate was 77.5% (95% c.i. 70.4% to 83.1%) in the D2 lymphadenectomy group versus 85.8% (95% c.i. 79.6% to 90.2%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.058). The HR for death in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 1.02) (P = 0.058)., Conclusion: Compared with conventional D2 dissection, D2 lymphadenectomy + complete mesogastric excision is associated with better disease-free survival, but there is no statistically significant difference in overall survival., Registration Number: NCT01978444 (http://www.clinicaltrials.gov)., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: This study focused on circulating plasma protein profiles to identify mediators of hypertension-driven myocardial remodeling and heart failure., Methods: A Mendelian randomization design was used to investigate the causal impact of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure on 82 cardiac magnetic resonance traits and heart failure risk. Mediation analyses were also conducted to identify potential plasma proteins mediating these effects., Results: Genetically proxied higher SBP, DBP, and pulse pressure were causally associated with increased left ventricular myocardial mass and alterations in global myocardial wall thickness at end diastole. Elevated SBP and DBP were linked to increased regional myocardial radial strain of the left ventricle (basal anterior, mid, and apical walls), while higher SBP was associated with reduced circumferential strain in specific left ventricular segments (apical, mid-anteroseptal, mid-inferoseptal, and mid-inferolateral walls). Specific plasma proteins mediated the impact of blood pressure on cardiac remodeling, with FGF5 (fibroblast growth factor 5) contributing 2.96% ( P =0.024) and 4.15% ( P =0.046) to the total effect of SBP and DBP on myocardial wall thickness at end diastole in the apical anterior segment and leptin explaining 15.21% ( P =0.042) and 23.24% ( P =0.022) of the total effect of SBP and DBP on radial strain in the mid-anteroseptal segment. Additionally, FGF5 was the only mediator, explaining 4.19% ( P =0.013) and 4.54% ( P =0.032) of the total effect of SBP and DBP on heart failure susceptibility., Conclusions: This mediation Mendelian randomization study provides evidence supporting specific circulating plasma proteins as mediators of hypertension-driven cardiac remodeling and heart failure., Competing Interests: Disclosures None.

Objective: Quanzhen Yiqi decoction (QZYQ) is a traditional Chinese medicine for treating chronic obstructive pulmonary disease., Methods: Mice were exposed to cigarette smoke (CS) 6 days/week (40 cigarettes/day) for 24 weeks and then intragastrically administered QZYQ (4.72, 9.45, or 18.89 g/kg) or dexamethasone (DEX, 0.6 mg/kg) for 6 weeks. We examined the lung function and collected bronchoalveolar lavage fluid for inflammatory cell and cytokine quantification. The pathological lung changes, ROS and oxidative biomarkers were measured. We used immunohistochemistry and western blotting to evaluate the levels of Nrf2/HO-1, NLRP3/ASC/Caspase1/IL-1β/IL-18., Results: The CS group showed significant increases in the forced vital capacity, lung resistance, and chord compliance and a lower FEV50/FVC compared with the control, and QZYQ improved these changes. In addition, QZYQ effectively reduced emphysema, immune cell infiltration, and airway remodeling. QZYQ stimulated HO-1 expression and reduced oxidative stress through the Nrf2 pathway. QZYQ inhibited the production of NLRP3/ASC/Caspase-1 to inhibit IL-1β and IL-18., Conclusion: Our study suggested that QZYQ can improve the function and histology of the lungs and reduce inflammatory cell recruitment. QZYQ inhibits ROS production and NLRP3 inflammasome activation by upregulating Nrf2 to reduce lung injury. The anti-inflammatory effects of QZYQ are similar to those of DEX., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Garlic (Allium sativum) is a functional food containing multiple bioactive compounds that find widespread applications in culinary and medicinal practices. It consists of multiple chemical components, including allicin and alliin. This article offers a comprehensive review of the protective effects of garlic extracts and their active constituents on the vascular system. In vitro and in vivo experiments have shown that garlic extracts and their active ingredients possess various bioactive properties. These substances demonstrate beneficial effects on blood vessels by demonstrating anti-inflammatory and antioxidant activities, inhibiting lipid accumulation and migration, preventing lipid peroxidation, promoting angiogenesis, reducing platelet aggregation, enhancing endothelial function, and inhibiting endothelial cell apoptosis. In clinical studies, garlic and its extracts have demonstrated their efficacy in managing vascular system diseases, including atherosclerosis, diabetes, and high cholesterol levels. In summary, these studies highlight the potential therapeutic roles and underlying mechanisms of garlic and its constituents in managing conditions like diabetes, atherosclerosis, ischemic diseases, and other vascular disorders., Competing Interests: Declaration of competing interests The authors declare no conflict of interest, financial or otherwise., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Myocardial infarction (MI), an acute cardiovascular disease characterized by coronary artery blockage, inadequate blood supply, and subsequent ischemic necrosis of the myocardium, is one of the leading causes of death. The cellular, physiological, and pathological responses following MI are complex, involving multiple intertwined pathological mechanisms. Hypoxia-inducible factor-1 (HIF-1), a crucial regulator of hypoxia, plays a significant role in of the development of MI by modulating the behavior of various cells such as cardiomyocytes, endothelial cells, macrophages, and fibroblasts under hypoxic conditions. HIF-1 regulates various post-MI adaptive reactions to acute ischemia and hypoxia through various mechanisms. These mechanisms include angiogenesis, energy metabolism, oxidative stress, inflammatory response, and ventricular remodeling. With its crucial role in MI, HIF-1 is expected to significantly influence the treatment of MI. However, the drugs available for the treatment of MI targeting HIF-1 are currently limited, and most contain natural compounds. The development of precision-targeted drugs modulating HIF-1 has therapeutic potential for advancing MI treatment research and development. This study aimed to summarize the regulatory role of HIF-1 in the pathological responses of various cells following MI, the diverse mechanisms of action of HIF-1 in MI, and the potential drugs targeting HIF-1 for treating MI, thus providing the theoretical foundations for potential clinical therapeutic targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Assessing the global burden and health inequalities of Hypertension Heart Disease (HHD) during the period from 1990 to 2019., Methods: Secondary analysis of the Global Burden of Disease (GBD) study in 2019, focusing on the burden of diseases, injuries, and risk factors worldwide. Disability-Adjusted Life Years (DALYs) data related to HHD are extracted from the 2019 GBD. Inequality Slope Index (SII) and Concentration Index are calculated to assess health inequalities across regions and countries., Results: The total DALYs for HHD reached 21.51 million, demonstrating a substantial increase of 54.25% compared to the figures recorded in 1990, while the age-standardized DALY rates per 100,000 population for HHD in 2019 showed a notable decline to 268.19 (95% UI 204.57, 298.07), reflecting a significant decrease of 26.4% compared to the rates observed in 1990. The DALYs rate of hypertensive heart disease increases with age. Countries with moderate SDI accounted for 38.72% of the global burden of HHD in terms of DALYs. The highest age-standardized DALY rates (per 100,000) are predominantly concentrated in underdeveloped areas. In 1990 and 2019, the SII (per 100,000 population) for DALYs were - 121.6398 (95% CI -187.3729 to -55.90684) and - 1.592634 (95% CI -53.11027 to 49.925) respectively. The significant decline suggests a reduction in the inequality of age-standardized burden of HHD between high-income and low-income countries during this period., Conclusion: The unequal prevalence of HHD across different populations can hinder the achievement of the "health for all" objective. Persistent disparities in HHD have been observed globally over the past thirty years. It is crucial to prioritize efforts towards reducing avoidable health inequalities associated with hypertension-related heart disease, particularly in low-income and middle-income countries., (© 2024. The Author(s).)

Purpose: The prevalence of frailty in individuals with cardiometabolic disease (CMD) has become a growing concern in public health. The purpose of this study was to investigate the association between estimated pulse wave velocity (ePWV) and frailty in middle-aged and older adults with CMD., Methods: We analyzed data from 23,313 non-institutionalized adults with CMD from the National Health and Nutrition Examination Survey 2003-2018. Frailty status was determined using the frailty index, and logistic regression models were used to assess the association of ePWV with frailty risk. Multivariable logistic regression and propensity-score matching (PSM) were used to adjust for potential confounders. The restricted cubic spline regression model was used to evaluate the non-linear association between ePWV and frailty risk., Results: After adjusting for potential confounding factors, we found that each one m/s increase in ePWV was associated with a 15% higher risk of frailty (odds ratio [OR] = 1.15, 95% confidence interval [CI] 1.12 to 1.18, P < 0.001). After PSM, the association remained significant (OR = 1.05, 95% CI 1.03 to 1.08, P < 0.001). The logistic models with restricted cubic splines showed a non-linear dose-response association, with the risk of frailty increasing more rapidly when ePWV exceeded 9.5 m/s., Conclusions: The findings of this study suggest that a higher level of ePWV is associated with an increased risk of frailty in middle-aged and older adults with CMD, and may serve as a viable alternative to directly measured cfPWV., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Recent insights suggest that remnant cholesterol (RC) plays a role in cellular senescence, yet its specific contribution to frailty remains indeterminate. Through the integration of observational and mendelian randomization (MR) studies, this research explores the impact of elevated serum RC levels on frailty susceptibility., Methods: A dual-method approach, combining an observational study with an MR study, was employed to investigate the connection between RC and frailty. The observational study included 11,838 participants from the National Health and Nutrition Examination Survey. Multivariable logistic regression and propensity score matching were employed to control for potential confounders. The non-linear relationship was assessed using restricted cubic splines. To circumvent observational study limitations, a two-sample MR analysis was conducted using the inverse-variance weighted method, leveraging genome-wide association studies (GWAS) data., Results: After adjusting for potential confounding variables, the observational study identified a significant association between high serum RC levels and frailty in middle-aged and older adults (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.20 to 2.33, P = 0.003), exhibiting a non-linear dose-response correlation (non-linear P = 0.011). This association persisted after propensity score matching (OR = 1.53, 95% CI = 1.14 to 2.06, P = 0.005). The MR study echoed these results, demonstrating a causal association of RC with the frailty index (β = 0.059, 95% CI = 0.033 to 0.085, P = 1.05E-05), consistent with the observational findings (β = 0.017, 95% CI = 0.008 to 0.026, P = 4.51E-04)., Conclusion: This study provides evidence that higher RC levels amplify frailty risk in middle-aged and older adults, implying that the reduction of RC levels may present a promising strategy for frailty prevention and management., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Chronic obstructive pulmonary disease (COPD) is a serious chronic lung disease. Schisandrin A (SchA) is one of the most important active ingredients in Schisandra chinensis and has been used to treat various lung diseases in several countries. Here, we studied the pharmacological effect of SchA on airway inflammation induced by cigarette smoke (CS) and explored the therapeutic mechanism of SchA in COPD model mice. Our results showed that SchA treatment significantly improved the lung function of CS-induced COPD model mice and reduced the recruitment of leukocytes and hypersecretion of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF). H&E staining showed that SchA treatment could effectively reduce emphysema, immune cell infiltration and airway wall destruction. In addition, we found that SchA treatment can stimulate the expression of heme oxygenase-1 (HO-1) through the nuclear factor-erythroid 2-related factor (Nrf2) pathway, significantly reduce oxidative stress, increase catalase (CAT) and superoxide dismutase (SOD) levels, and suppress the level of malondialdehyde (MDA) in COPD model mice. Moreover, SchA treatment suppressed the generation of the NLRP3/ASC/Caspase1 inflammasome complex to inhibit the inflammatory response caused by IL-1β and IL-18 and pyroptosis caused by GSDMD. In conclusion, our study shows that SchA treatment can inhibit the production of ROS and the activation of the NLRP3 inflammasome by upregulating Nrf-2, thereby producing anti-inflammatory effects and reducing lung injury in COPD model mice. More importantly, SchA exhibited similar anti-inflammatory effects to dexamethasone in COPD model mice, and we did not observe substantial side effects of SchA treatment. The high safety of SchA makes it a potential candidate drug for the treatment of COPD., (© 2023. The Author(s).)

Purpose: Gain insight into the impact of B vitamins, including vitamin B1, vitamin B2, niacin, vitamin B6, total folate, and vitamin B12 on the risk of frailty in patients with chronic obstructive pulmonary disease (COPD)., Methods: This study was an American population-based cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES). A total of 1201 COPD patients were included in the analysis. Of these, the intake of B vitamins was determined by the two 24-h recall interviews. We followed the method constructed by Hakeem et al. to calculate the frailty index (FI), which is used as a reliable tool to assess the debilitating status of patients with COPD. Missing data were imputed by the MissForest method based on random forests. Multivariate logistic regression model and inverse probability weighted based on propensity scores were used to correct for confoundings., Results: Logistic regression models showed that vitamin B6 intake was negatively correlated with frailty risk in COPD patients, while other B vitamins including B1, B2, niacin (vitamin B3), total folic acid and vitamin B12 were not. After adjusting for covariates, the association between vitamin B6 and frailty risk (adjusted OR = 0.80, 95%CI = 0.66-0.95, P = 0.013) remained significant. At the same time, sensitivity analysis proves the robustness of the results., Conclusion: COPD patients with lower vitamin B6 intake have a higher risk of frailty. However, intake of vitamin B1, B2, niacin, total folic acid, and vitamin B12 was not associated with frailty risk in COPD patients., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background/aim: Depression has become a multiple disease worldwide, and is closely related to the systemic inflammatory response., Methods: Based on the data of the National Health and Nutrition Examination Survey (NHANES), this study included 2,514 depressive and 26,487 non-depressive adults. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were used to quantify systemic inflammation. The multivariate logistic regression and inverse probability weighting methods were used to analyze the effect size of SII and SIRI on the risk of depression., Results: After adjusting for all confounders, the above associations of SII and SIRI with depression risk remained significant (SII, OR = 1.02, 95% CI = 1.01 to 1.02, p = 0.001; SIRI, OR = 1.06, 95% CI = 1.01 to 1.10, p = 0.016). Each 100-unit increase in SII was associated with a 2% increase in the risk of depression, while each one-unit increase in SIRI was associated with a 6% increase in the risk of depression., Conclusion: Systemic inflammatory biomarkers (SII and SIRI) significantly affected the risk of depression. SII or SIRI can serve as a biomarker of anti-inflammation treatment for depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Huan, Lin and Hu.)

Lung adenocarcinoma (LUAD) is a highly heterogeneous disease with complex pathogenesis, high mortality, and poor prognosis. Cuproptosis is a new type of programmed cell death triggered by copper accumulation that may play an important role in cancer. LncRNAs are becoming valuable prognostic factors in cancer patients. The effect of cuproptosis-related lncRNAs (CRlncRNAs) on LUAD has not been clarified. Based on the Cancer Genome Atlas database, CRlncRNAs were screened by co-expression analysis of cuproptosis- related genes and lncRNAs. Using CRlncRNAs, Cox and LASSO regression analyses constructed a risk prognostic model. The predictive efficacy of the model was assessed and validated using survival analysis, receiver operating characteristic curve, univariate and multifactor Cox regression analysis, and principal component analysis. A nomogram was constructed and calibration curves were applied to enhance the predictive efficacy of the model. Tumor Mutational Burden analysis and chemotherapeutic drug sensitivity prediction were performed to assess the clinical feasibility of the risk model. The novel prognostic signature consisted of 5 potentially high-risk CRlncRNAs, MAP3K20-AS1, CRIM1-DT, AC006213.3, AC008035.1, and NR2F2-AS1, and 5 potentially protective CRlncRNAs, AC090948.1, AL356481.1, AC011477.2, AL031600.2, and AC026355.2, which had accurate and robust predictive power for LUAD patients. Collectively, the novel prognostic signature constructed based on CRlncRNAs can effectively assess and predict the prognosis of patients and provide a new perspective for the diagnosis and treatment of LUAD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background/aim: Optimized dietary patterns have been considered an important determinant of delaying aging in cardiometabolic disease (CMD). Dietary pattern with high-level dietary inflammatory potential is a key risk factor for cardiometabolic disease, and has drawn increasing attention. The aim of this study was to investigate whether dietary pattern with high dietary inflammatory potential was associated with aging acceleration in cardiometabolic disease., Materials and Methods: We analyzed the cross-sectional data from six survey cycles (1999-2000, 2001-2002, 2003-2004, 2005-2006, 2007-2008, and 2009-2010) of the National Health and Nutritional Examination Surveys (NHANES). A total of 16,681 non-institutionalized adults and non-pregnant females with CMD were included in this study. Dietary inflammatory index (DII) was used to assess the dietary inflammatory potential. The two age acceleration biomarkers were calculated by the residuals from regressing chronologic age on Klemera-Doubal method biological age (KDM BioAge) or Phenotypic Age (PhenoAge), termed "KDMAccel" and "PhenoAgeAccel." A multivariable linear regression accounting for multistage survey design and sampling weights was used in different models to investigate the association between DII and aging acceleration. Four sensitivity analyses were used to ensure the robustness of our results. Besides, we also analyzed the anti-aging effects of DASH-type dietary pattern and "Life's Simple 7"., Results: For 16,681 participants with CMD, compared with the first tertile of DII after adjusting for all potential confounders, the patients with second tertile of DII showed a 1.02-years increase in KDMAccel and 0.63-years increase in PhenoAgeAccel (KDMAccel, β = 1.02, 95% CI = 0.64 to 1.41, P < 0.001; PhenoAgeAccel, β = 0.63, 95% CI = 0.44 to 0.82, P < 0.001), while the patients with the third tertile of DII showed a 1.48-years increase in KDMAccel and 1.22-years increase in PhenoAgeAccel (KDMAccel, β = 1.48, 95% CI = 1.02 to 1.94, P < 0.001; PhenoAgeAccel, β = 1.22, 95% CI = 1.01 to 1.43, P < 0.001). In addition, DASH-type dietary pattern was associated with a 0.57-years reduction in KDMAccel (β = -0.57, 95% CI = -1.08 to -0.06, P = 0.031) and a 0.54-years reduction in PhenoAgeAccel (β = -0.54, 95% CI = -0.80 to -0.28, P < 0.001). The each one-unit increase in CVH score was associated with a 1.58-years decrease in KDMAccel (β = -1.58, 95% CI = -1.68 to -1.49, P < 0.001) and a 0.36-years in PhenoAgeAccel (β = -0.36, 95% CI = -0.41 to -0.31, P < 0.001)., Conclusion: Among CMD, the dietary pattern with high dietary inflammatory potential was association with aging acceleration, and the anti-aging potential of DASH-type dietary pattern and "Life's Simple 7" should also be given attention, but these observations require future prospective validation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Wang, Huan, Zhang, Lin, Li and Li.)

Background: Acute respiratory failure (ARF) is a common cause of admission to the intensive care unit (ICU) for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). There is still a lack of effective interventions and treatments. ACE inhibitors (ACEI)/ angiotensin II receptor blockers (ARB) were effective in COPD patients. We aimed to study the effect of ACEI/ARB use on AECOPD combined with ARF and evaluate the effect of in-hospital continuation of medication., Methods: We included patients with AECOPD and ARF from the Medical Information Bank for Intensive Care (MIMIC-III) database. MIMIC III is a large cohort database from Boston, USA. Patients were divided into two groups according to the use of ACEI/ARB before admission. Propensity score matching (PSM) was used to reduce potential bias between the two groups. Cox regression and Kaplan-Meier curves compared 30-day mortality in ACEI/ARB users and non-users. We also defined and analyzed the use of in-hospital ACEI/ARB. Multiple models were used to ensure the robustness of the findings. Subgroup analysis was used to analyze the variability between groups., Results: A total of 544 patients were included in the original study. After PSM, 256 patients were included in the matched cohort. Multivariate Cox regression showed 30-day mortality was significantly lower in ACEI/ARB users compared with controls (HR = 0.50, 95% CI: 0.29-0.86, p = 0.013). In PSM and inverse probability-weighted models, the results are stable Continued in-hospital use of ACEI/ARB remains effective (HR 0.40, 95% CI 0.22-0.74, p = 0.003). Kaplan-Meier showed a significant difference in survival between the two groups., Conclusion: This study found that pre-hospital ACEI/ARB use was associated with reduced mortality in patients with AECOPD and ARF., Competing Interests: The authors declare that they have no competing interests., (© 2022 Ruan et al.)

Background: Tripartite motif-containing protein 44 ( TRIM44 ) was recently identified as a novel oncogene that is overexpressed in several types of human cancers. However, the biological functions of TRIM44 in epithelial ovarian cancer (EOC) remain unclear. Here, we aimed to investigate the role of TRIM44 in EOC and its clinical implications., Methods: TRIM44 was knocked down using shRNA transfection. In vitro proliferation, invasion, migration and apoptosis of ovarian cancer (OC) cells were detected by CCK8, colony formation assay, Transwell inserts and flow cytometry analysis. The growth ability of xenograft tumors was examined in vivo in a nude mouse metastatic tumor model. Finally, we performed gene chip analysis and ingenuity pathway analysis (IPA) to analyze the potential gene network., Results: High expression of TRIM44 was observed in EOC tissues. Knockdown of TRIM44 expression substantially suppressed the proliferation, migration, invasion and colony-forming ability of EOC cells in vitro and attenuated tumor growth in vivo . Mechanistic studies revealed that silencing TRIM44 dramatically downregulated the expression of FOXM1 , EZH2 , CCNE2 , CCND3 and BIRC5 in EOC cells, at least in part through inactivation of the FOXM1-EZH2 signaling pathway., Conclusions: Collectively, these data suggest that downregulation of TRIM44 inhibits the progression of EOC through suppression of the FOXM1-EZH2 signaling pathway. These results provide novel insight into the role of TRIM44 in tumorigenesis and suggest that it could be a potential therapeutic target for ovarian carcinoma., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-21-2915/coif). All authors report that this work was supported by grants of Heilongjiang Provincial Natural Science Foundation of China (No. LH2020H124); the Liande Wu Science Foundation for Young Scholars of Harbin Medical University Cancer Hospital (No. WLD-QN1705); the Jingying Foundation of the Harbin Medical University Cancer Hospital (No. JY2015-04); The Medical Award Foundation Project of Beijing (No. YXJL-2021-0577-0421); and The Science and Technology Innovation Medical Development Foundation Project of Beijing (No. KC2021-JF-0055-01). The authors have no other conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Introduction: Acute pulmonary embolism (APE) is a typical cardiovascular emergency worldwide. Mean hemoglobin concentration (MCHC) is a standard indicator of anemia. Studies on the association between MCHC and APE are scarce. We aimed to investigate the relationship between MCHC and APE., Methods: Clinical data were extracted from the Medical Information Bank for Intensive Care (MIMIC)-III. Adult (≥18 years) patients with APE admitted for the first time were included in this study. An analysis was conducted to evaluate the association between MCHC and the prognosis of patients by the Cox regression analysis, generalized additives models and Kaplan-Meier survival curves. The primary outcome was 30-day mortality, and the secondary outcomes were 1-year and 3-year mortality., Results: A total of 813 patients who met the selection criteria were enrolled, of whom 130 (16.0%) died within 30 days of admission. Univariate Cox regression indicated that MCHC was significantly associated with mortality (30-day: HR = 0.74, 95% CI = 0.66-0.82, P  < 0.001; 1-year: HR = 0.80, 95% CI = 0.74-0.86, P  < 0.001; 3-year: HR = 0.82, 95% CI = 0.77-0.88, P  < 0.001). MCHC remains stable after adjusting multiple models. Kaplan-Meier survival curves showed that patients with lower MCHC had a poorer 30-day prognosis., Conclusions: Lower MCHC is an independent risk factor for increased mortality in patients with APE. As an inexpensive biomarker, MCHC should receive more attention.

Background/Aim: Several observational studies showed a significant association between elevated iron status biomarkers levels and sepsis with the unclear direction of causality. A two-sample bidirectional mendelian randomization (MR) study was designed to identify the causal direction between seven iron status traits and sepsis. Methods: Seven iron status traits were studied, including serum iron, ferritin, transferrin saturation, transferrin, hemoglobin, erythrocyte count, and reticulocyte count. MR analysis was first performed to estimate the causal effect of iron status on the risk of sepsis and then performed in the opposite direction. The multiplicative random-effects and fixed-effects inverse-variance weighted, weighted median-based method and MR-Egger were applied. MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran's Q statistic methods were used to assess heterogeneity and pleiotropy. Results: Genetically predicted high levels of serum iron (OR = 1.21, 95%CI = 1.13-1.29, p = 3.16 × 10 -4 ), ferritin (OR = 1.32, 95%CI = 1.07-1.62, p =0.009) and transferrin saturation (OR = 1.14, 95%CI = 1.06-1.23, p = 5.43 × 10 -4 ) were associated with an increased risk of sepsis. No significant causal relationships between sepsis and other four iron status biomarkers were observed. Conclusions: This present bidirectional MR analysis suggested the causal association of the high iron status with sepsis susceptibility, while the reverse causality hypothesis did not hold. The levels of transferrin, hemoglobin, erythrocytes, and reticulocytes were not significantly associated with sepsis. Further studies will be required to confirm the potential clinical value of such a prevention and treatment strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hu, Cheng, Mao, Chen, Cui and Qiu.)

Purpose: This study aimed to identify the COPD molecular subtypes reflecting pulmonary function damage on the basis of metabolism-related gene expression, which provided the opportunity to study the metabolic heterogeneity and the association of metabolic pathways with pulmonary function damage., Methods: Univariate linear regression and the Boruta algorithm were used to select metabolism-related genes associated with forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC) in the Evaluation of COPD to Longitudinally Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. COPD subtypes were further identified by consensus clustering with best-fit. Then, we analyzed the differences in the clinical characteristics, metabolic pathways, immune cell characteristics, and transcription features among the subtypes., Results: This study identified two subtypes (C1 and C2). C1 exhibited higher levels of lower pulmonary function and innate immunity than C2. Ten metabolic pathways were confirmed as key metabolic pathways. The pathways related to N-glycan, hexosamine, purine, alanine, aspartate and glutamate tended to be positively associated with the abundance of adaptive immune cells and negatively associated with the abundance of innate immune cells. In addition, other pathways had opposite trends. All results were verified in Genetic Epidemiology of COPD (COPDGene) datasets., Conclusion: The two subtypes reflect the pulmonary function damage and help to further understand the metabolic mechanism of pulmonary function in COPD. Further studies are needed to prove the prognostic and therapeutic value of the subtypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Yuanlong Hu and Xiaomeng Cheng are Co-first authors., (© 2021 Hu et al.)

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a disease with high heterogeneity, which is a major challenge in clinical individualized treatment. A mucus phenotype is one of the main characteristics of COPD. MATERIAL AND METHODS Gene expression profiles of lung tissue samples were from the Lung Genomics Research Consortium. MUC5B-associated gene signatures were obtained based on a nonlinear feature screening algorithm. These signatures were used to fit a latent profile analysis (LPA) model to identify COPD molecular subtypes and build a subtype classifier to verify the subtypes. Then, we explored the characteristics of cilium assembly and beating signatures, transcriptome features, immune infiltration among the 3 subtypes by xCell, single-sample gene set enrichment analysis, network perturbation amplitude, and weighted gene co-expression network analysis algorithms. An external dataset was used to verify the above COPD subtypes. RESULTS Three subtypes associated with mucus were identified by LPA and verified in an external dataset. Subtype 1 displayed higher T helper type 1 (Th1) and basophil infiltration, higher Th17/regulatory T cells (Tregs) ratio, a higher level of cilium assembly and beating, and lower mast cell and Treg infiltration. The subtypes 2 and 3 demonstrated higher macrophage M2 infiltration in lung tissue, while subtype 3 had higher neutrophil and eosinophil infiltration than subtype 2. CONCLUSIONS Overall, this work identified 3 mucus-associated molecular subtypes related to MUC5B expression, which deepens the understanding of airway mucus secretion in COPD and potentially provides valuable information for precision therapy.

Implementation of complete mesogastric excision in gastric cancer surgery, named D2 lymphadenectomy plus complete mesogastric excision (D2+CME), has recently been proposed as an optimal procedure. However, the safety and efficacy of D2+CME remain uncertain. In this randomized controlled trial, patients receiving D2+CME exhibit less intraoperative blood loss, more lymph node harvesting, and earlier postoperative flatus than patients receiving conventional D2 radical surgery. Univariate Cox regression analysis reveals that the risk ratio for postoperative flatus in D2+CME group is 1.247 (p = 0.044). Overall postoperative complications are comparable between the two groups, but complications are significantly less severe in the D2+CME group than the D2 group (Clavien-Dindo classification grade ≥ IIIa: 4 D2+CME patients [11.8%] versus 9 D2 patients [33.3%]; p = 0.041). In conclusion, our work shows that D2+CME is associated with better short-term outcomes and surgical safety than conventional D2 dissection for patients with advanced gastric cancer., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Background: Although radical gastrectomy with D2 lymph node dissection has become the standard surgical approach for locally advanced gastric cancer, patients still have a poor prognosis after operation. Previously, we proposed laparoscopic distal gastrectomy (D2 lymphadenectomy plus complete mesogastrium excision [D2 + CME]) as an optimized surgical procedure for locally advanced gastric cancer. By dissection along the boundary of the mesogastrium, D2 + CME resected proximal segments of the dorsal mesogastrium completely with less blood loss, and it improved the short-term surgical outcome. However, the oncologic therapeutic effect of D2 + CME has not yet been confirmed., Methods/design: A single-center, prospective, parallel-group, randomized controlled trial of laparoscopic distal gastrectomy with D2 + CME versus conventional D2 was conducted for patients with locally advanced gastric cancer at Tongji Hospital, Wuhan, China. In total, 336 patients who met the following eligibly criteria were included and were randomized to receive either the D2 + CME or D2 procedure: (1) pathologically proven adenocarcinoma; (2) 18 to 75 years old; cT2-4, N0-3, M0 at preoperative evaluation; (3) expected curative resection via laparoscopic distal gastrectomy; (4) no history of other cancer, chemotherapy, or radiotherapy; (5) no history of upper abdominal operation; and (6) perioperative American Society of Anesthesiologists class I, II, or III. The primary endpoint is 3 years of disease-free survival. The secondary endpoints are overall survival, recurrence pattern, mortality, morbidity, postoperative recovery course, and other parameters., Discussion: Previous studies have demonstrated the safety and feasibility of D2 + CME for locally advanced gastric cancer; however, there is still a lack of evidence to support its therapeutic effect. Thus, we performed this randomized trial to investigate whether D2 + CME can improve oncologic outcomes of patients with locally advanced gastric cancer. The findings from this trial may potentially optimize the surgical procedure and may improve the prognosis of patients with locally advanced gastric cancer., Trial Registration: ClinicalTrials.gov, NCT01978444 . Registered on October 31, 2013.

A novel gene called LAPTM4B (lysosome-associated protein transmembrane 4 beta) plays several crucial roles in carcinogenesis. In this case-control study, we investigated the relationship between LAPTM4B gene polymorphism and susceptibility to endometrial carcinoma (EC). In an adjusted multivariate logistic regression analyses, subjects with the LAPTM4B*1/2 and *2/2 genotypes respectively exhibited 1.572-fold (95% confidence interval (CI) = 1.041-2.375) and 2.335-fold (95% CI = 1.365-3.995) increases in the risk of developing EC relative to those carrying LAPTM4B*1/1. Patients with LAPTM4B *2 had both significantly shorter overall survival (OS) and shorter disease-free survival (DFS) (both p < 0.001). Multivariate analysis showed that LAPTM4B genotype is an independent prognostic factor for OS and DFS (both p < 0.001). These results suggest that LAPTM4B polymorphisms might play an important role in the aetiology of EC.

Astrocyte elevated gene-1 (AEG-1) plays an important role in tumor progression including transformation, evasion of apoptosis, invasion, metastasis, and chemoresistance. However, the expression of AEG-1 in ovarian carcinoma and its significance are still unclear. The aim of this study was to examine the expression of AEG-1 in ovarian carcinoma. Immunohistochemistry was performed to determine the expression of AEG-1 in 81 ovarian carcinoma specimens. The correlation of AEG-1 expression with clinicopathological parameters was assessed using χ2 analysis. Patient survival was analyzed using the Kaplan-Meier and log-rank tests. Cox regression was used for the multivariate analysis of prognostic factors. High expression of AEG-1 was detected in 66.67% of the ovarian carcinomas and was significantly associated with the International Federation of Gynecology and Obstetrics stage, histological grade, presence of residual tumor after primary surgery, and tumor recurrence. Patients with high AEG-1 expression had significantly poorer overall survival and disease-free survival (both P<0.001) when compared with patients with low expression of AEG-1. The multivariate Cox analysis showed that AEG-1 was an independent factor for both overall survival and disease-free survival (both P<0.001). These results showed that high AEG-1 expression was associated with progression and prognosis of ovarian carcinoma.

Lysosome-associated protein transmembrane 4β-35 (LAPTM4B-35) is a member of the mammalian 4-tetratransmembrane spanning protein superfamily, which is overexpressed in several solid malignancies. However, the expression of LAPTM4B-35 and its role in the progression of cervical carcinoma is unknown. The aim of this study was to determine the level of expression of LAPTM4B-35 in cervical carcinoma. Immunohistochemistry was used to determine the expression of LAPTM4B-35 protein in 53 cervical intraepithelial neoplasias (CINs) and 113 cervical carcinomas in comparison with 20 normal cervical specimens. The correlation between the expression of the LAPTM4B-35 protein and the clinicopathologic characteristics of patients with cervical carcinoma was analyzed. Statistical analysis showed that LAPTM4B-35 expression was significantly elevated in CINII/III and cervical carcinoma but not in CINI compared with the normal controls (P=0.002, P<0.001 and P=0.289, respectively). In addition, the LAPTM4B-35 expression was significantly higher in both the CINII/III and cervical carcinoma cases than in the CINI cases (P=0.021 and P=0.002, respectively). High LAPTM4B-35 staining was present in 72.57% (82 of 113) of all the cases with cervical carcinoma. The overexpression of LAPTM4B-35 was significantly associated with the International Federation of Gynecology and Obstetrics stage (P=0.014), tumor histologic grade (P=0.033), lymph node metastasis (P=0.045), and recurrence (P=0.010). The Kaplan-Meier survival analysis showed that the high expression of LAPTM4B-35 was related to the poor overall survival and disease-free survival of patients with cervical carcinoma (P=0.004 and P=0.005, respectively). Multivariate Cox analysis showed that LAPTM4B-35 was an independent factor for both overall survival and disease-free survival (P=0.015 and P=0.016, respectively). Overexpression of LAPTM4B-35 may be associated with tumor progression in cervical carcinoma and thus may serve as a new molecular marker to predict the prognosis of cervical carcinoma patients.

During boreal summer, much of the water vapor and CO entering the global tropical stratosphere is transported over the Asian monsoon/Tibetan Plateau (TP) region. Studies have suggested that most of this transport is carried out either by tropical convection over the South Asian monsoon region or by extratropical convection over southern China. By using measurements from the newly available National Aeronautics and Space Administration Aura Microwave Limb Sounder, along with observations from the Aqua and Tropical Rainfall-Measuring Mission satellites, we establish that the TP provides the main pathway for cross-tropopause transport in this region. Tropospheric moist convection driven by elevated surface heating over the TP is deeper and detrains more water vapor, CO, and ice at the tropopause than over the monsoon area. Warmer tropopause temperatures and slower-falling, smaller cirrus cloud particles in less saturated ambient air at the tropopause also allow more water vapor to travel into the lower stratosphere over the TP, effectively short-circuiting the slower ascent of water vapor across the cold tropical tropopause over the monsoon area. Air that is high in water vapor and CO over the Asian monsoon/TP region enters the lower stratosphere primarily over the TP, and it is then transported toward the Asian monsoon area and disperses into the large-scale upward motion of the global stratospheric circulation. Thus, hydration of the global stratosphere could be especially sensitive to changes of convection over the TP.