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Ulcerative colitis (UC) poses a threat to human health. The present study attempts to unravel the efficacy and potential mechanisms of paeoniflorin (PF), a naturally sourced active ingredient, for the management of UC. By establishing a DSS (dextran sulphate sodium)-induced experimental rat model of UC, this study found that PF was effective in ameliorating UC symptoms, inhibiting oxidative stress, inflammation and apoptosis, and repairing colonic epithelial damage. In addition, metabolomics revealed that PF may alleviate UC by primarily improving linoleic acid metabolism. Mechanistically, PF inhibited the CDC42/JNK signaling pathway by targeting CDC42. In particular, HuProtTM20K proteomics, molecular docking and MST revealed that PF is a novel CDC42 inhibitor. In LPS-treated Caco-2 cells, PF similarly inhibited oxidative stress, inflammation, and apoptosis and down-regulated the CDC42/JNK signaling pathway. Overall, PF inhibits oxidative stress, inflammation and apoptosis and repairs colonic epithelial damage through modulation of serum metabolites and inhibition of the CDC42/JNK signaling pathway, leading to alleviation of UC., 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.)

Objectives: This study sought to demonstrate outcomes of veno-arterial extracorporeal life support (VA-ECLS) in non-intubated ('awake') patients with cardiogenic shock, as very few studies have investigated safety and feasibility in this population., Methods: This was a retrospective review of 394 consecutive VA-ECLS patients at our institution from 2017 to 2021. We excluded patients cannulated for indications definitively associated with intubation. Patients were stratified by intubation status at time of cannulation and baseline differences were balanced by inverse probability of treatment weighting. The primary outcome was in-hospital mortality while secondary outcomes included adverse events during ECLS and destination at discharge., Results: Out of 135 patients in the final cohort, 79 were intubated and 56 were awake at time of cannulation. All awake patients underwent percutaneous femoral cannulation with technical success of 100% without intubation. Indications for VA-ECLS in awake patients included acute decompensated heart failure (64.3%), pulmonary hypertension or massive pulmonary embolism (12.5%), myocarditis (8.9%) and acute myocardial infarction (5.4%). After adjustment, awake and intubated patients had similar ECLS duration (7 vs 6 days, P = 0.19), in-hospital mortality (39.6% vs 51.7%, P = 0.28), and rates of various adverse events. Intubation status was not a significant risk factor for 90-day mortality (hazard ratio [95% confidence interval]: 1.26 [0.64, 2.45], P = 0.51) in multivariable analysis. Heart transplantation (15.1% vs 4.9%) and ventricular assist device (17.4% vs 2.2%) were more common destinations at discharge in awake patients than intubated patients (P = 0.02)., Conclusions: Awake VA-ECLS is safe and feasible with comparable outcomes as intubated counterparts in select cardiogenic shock patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Diabetic nephropathy (DN) is a prototypical chronic energy metabolism imbalance disease. The AMPK/Sirt1/PGC-1α signaling pathway plays a pivotal role in regulating energy metabolism throughout the body. Gut microbiota ferment indigestible carbohydrates to produce a variety of metabolites, particularly short-chain fatty acids (SCFAs), which exert positive effects on energy metabolism. However, the potential for SCFAs to ameliorate DN-associated renal injury via the AMPK/Sirt1/PGC-1α pathway remains a matter of debate. In this study, we investigated the effects of sodium butyrate (NaB), a SCFA, on energy metabolism in mice with spontaneous DN at two different doses. Body weight, blood glucose and lipid levels, urinary protein excretion, liver and kidney function, interleukin-6 (IL-6) levels, and the expressions of AMPK, phosphorylated AMPK (p-AMPK), mitofusin 2 (MFN2), optic atrophy 1 (OPA1), and glucagon-like peptide-1 receptor (GLP-1R) were monitored in mice. Additionally, butyrate levels, gut microbiota composition, and diversity in colonic stool were also assessed. Our findings demonstrate that exogenous NaB supplementation can improve hyperglycemia and albuminuria, reduce renal tissue inflammation, inhibit extracellular matrix accumulation and glomerular hypertrophy, and could alter the gut microbiota composition in DN. Furthermore, NaB was found to upregulate the expressions of MFN2, OPA1, p-AMPK, and GLP-1R in DN renal tissue. These results suggest that NaB could improve the composition of gut microbiota in DN, activate the AMPK/Sirt1/PGC-1α signaling pathway, and enhance mitochondrial function to regulate energy metabolism throughout the body. Collectively, our findings indicate that NaB may be a novel therapeutic agent for the treatment of DN., (© 2024. The Author(s).)

Objectives: Veno-arterial extracorporeal life support (V-A ECLS) is increasingly being utilized for postcardiotomy shock (PCS), though data describing the relationship between type of indexed operation and outcomes are limited. This study compared V-A ECLS outcomes across four major cardiovascular surgical procedures., Methods: This was a single-center retrospective study of patients who required V-A ECLS for PCS between 2015 and 2022. Patients were stratified by the type of indexed operation, which included aortic surgery (AoS), coronary artery bypass grafting (CABG), valve surgery (Valve), and combined CABG and valve surgery (CABG + Valve). Factors associated with postoperative outcomes were assessed using logistic regression., Results: Among 149 PCS patients who received V-A ECLS, there were 35 AoS patients (23.5%), 29 (19.5%) CABG patients, 59 (39.6%) Valve patients, and 26 (17.4%) CABG + Valve patients. Cardiopulmonary bypass times were longest in the AoS group ( p < 0.01). Regarding causes of PCS, AoS patients had a greater incidence of ventricular failure, while the CABG group had a higher incidence of ventricular arrhythmia ( p = 0.04). Left ventricular venting was most frequently utilized in the Valve group ( p = 0.07). In-hospital mortality was worst among CABG + Valve patients ( p < 0.01), and the incidence of acute kidney injury was highest in the AoS group ( p = 0.03). In multivariable logistic regression, CABG + Valve surgery (odds ratio (OR) 4.20, 95% confidence interval 1.30-13.6, p = 0.02) and lactate level at ECLS initiation (OR, 1.17; 95% CI, 1.06-1.29; p < 0.01) were independently associated with mortality., Conclusions: We demonstrate that indications, management, and outcomes of V-A ECLS for PCS vary by type of indexed cardiovascular surgery., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Gastric cancer (GC) is a prevalent gastrointestinal tumor characterized by high mortality and recurrence rates. Current treatments often have limitations, prompting researchers to explore novel anti-tumor substances and develop new drugs. Flavonoids, natural compounds with diverse biological activities, are gaining increasing attention in this regard. We searched from PubMed, Web of Science, SpringerLink and other databases to find the relevant literature in the last two decades. Using "gastric cancer", "stomach cancers", "flavonoid", "bioflavonoid", "2-Phenyl-Chromene" as keywords, were searched, then analyzed and summarized the mechanism of flavonoids in the treatment of GC. It was revealed that the anti-tumor mechanism of flavonoids involves inhibiting tumor growth, proliferation, invasion, and metastasis, as well as inducing cell death through various processes such as apoptosis, autophagy, ferroptosis, and pyroptosis. Additionally, combining flavonoids with other chemotherapeutic agents like 5-FU and platinum compounds can potentially reduce chemoresistance. Flavonoids have also demonstrated enhanced biological activity when used in combination with other natural products. Consequently, this review proposes innovative perspectives for the development of flavonoids as new anti-GC agents., Competing Interests: All authors declare that there are no conflicts of interest and agree to publish this paper., (© 2024 Cai et al.)

Background: Although adverse technical events during aortic root replacement (ARR) are not uncommon and are extremely challenging, there is scant literature to help surgeons prepare for such situations. We describe our experience of outstanding technical events during ARR., Methods: This is a retrospective study of 830 consecutive ARRs at a single center from 2012 to 2022. Technical events were defined as intraoperative events that led to an unplanned cardiac procedure, need for mechanical circulatory support, or additional aortic cross-clamping. Logistic regression identified factors associated with operative mortality and technical events., Results: Technical events occurred in 90 patients (10.8%) and were attributed to bleeding (n = 26), nonischemic ventricular dysfunction (n = 23), residual valve disease (n = 20), myocardial ischemia (n = 19), and iatrogenic dissection (n = 2). Prior sternotomy (odds ratio [OR], 2.38; 95% CI, 1.36-4.19; P = .002) and complex aortic valve disease (OR, 3.09; 95% CI, 1.09-8.75; P = .03) were associated with technical events. Patients with technical events had higher rates of operative mortality (6.7% vs 2.3%, P = .03) and all major postoperative complications. Surgical indications of dissection (OR, 13.57; 95% CI, 4.95-37.23; P < .001) and complex aortic valve disease (OR, 14.09; 95% CI, 3.67-54.02; P < .001) but not adverse technical events (OR, 2.42; 95% CI, 0.81-7.26; P = .11) were associated with operative mortality., Conclusions: Adverse technical events occurred in 10.8% of ARRs and were associated with reoperative sternotomies. Technical events are associated with increased postoperative complications., Competing Interests: Disclosures Hiroo Takayama reports a relationship with Artivion, Inc, that includes: consulting or advisory; and with Edwards Lifesciences Corporation that includes: consulting or advisory. The other authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Small heterodimer partner (SHP, encoded by NR0B2) plays an important role in maintaining bile acid homeostasis. The loss of the hepatic farnesoid X receptor (FXR)/SHP signal can cause severe cholestatic liver injury (CLI). FXR and SHP have overlapping and nonoverlapping functions in bile acid homeostasis. However, the key role played by SHP in CLI is unclear., Methods: In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model was established. The effect of SHP knockout (SHP-KO) on liver and ileal pathology was evaluated. 16S rRNA gene sequencing analysis combined with untargeted metabolomics was applied to reveal the involvement of SHP in the pathogenesis of CLI., Results: The results showed that ANIT (75 mg/kg) induced cholestasis in WT mice. No significant morphological changes were found in the liver and ileal tissue of SHP-KO mice. However, the serum metabolism and intestinal flora characteristics were significantly changed. Moreover, compared with the WT + ANIT group, the serum levels of ALT and AST in the SHP-KO + ANIT group were significantly increased, and punctate necrosis in the liver tissue was more obvious. The ileum villi showed obvious shedding, thinning, and shortening. In addition, SHP-KO-associated differential intestinal flora and differential biomarkers were significantly associated., Conclusion: In this study, we elucidated the serum metabolic characteristics and intestinal flora changes related to the aggravation of CLI in SHP-KO mice induced by ANIT., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: Our objective was to analyze the development of aortic insufficiency in patients who received central aortic valve repair when undergoing continuous-flow left ventricular assist device implantation., Methods: We conducted a retrospective review of patients who underwent HeartMate II or 3 (Abbott Lab) implantation between 2004 and 2022. Ninety-four patients were excluded from analysis for history of aortic valve procedures, a bicuspid aortic valve, baseline trace aortic insufficiency, or other concomitant aortic valve procedure. Patients who had ≥ mild aortic insufficiency had concomitant aortic valve repair. Clinical characteristics, serial echocardiograms, and outcomes were determined., Results: Of the 656 patients who underwent HeartMate II or 3 implantation, 105 patients (59 HeartMate II and 46 HeartMate 3) met study criteria. Median age was 68 years [60-74 years], 91.4% [n=96] were male, 54.4% [n=56] were white, and 68.6% [n=72] received support as destination therapy. Preoperative aortic insufficiency degree was 54.3% (n=57) mild, 23.8% (n=25) mild-to-moderate, 20.0% (n=21) moderate, 1.0% (n=1) moderate-to-severe, 1.0% (n=1) severe. In hospital mortality was 5.7% [n=6]. Freedom from ≥ moderate aortic insufficiency was 96.4% (95%CI: 92.5%-100%), 93.3% (95%CI: 87.6%-99.2%), and 91.0% (95%CI: 84.1%-98.5%) at 1-year, 2-year, and 3-year post-implantation, respectively. One HeartMate II patient experienced severe aortic insufficiency and was treated with a heart transplant. Three-year survival was 63.4% [95%CI: 52.9%-75.9%]., Conclusions: Central aortic valve repair may be an effective technique to mitigate aortic insufficiency in HeartMate II and 3. A larger cohort study with longer duration of follow up is warranted to further investigate the clinical impact., (Copyright © 2024. Published by Elsevier Inc.)

Background: The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated., Purpose: This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism., Methods: The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins., Results: The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin., Conclusion: Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Chen et al.)

Redox balance plays an important role in testicular homeostasis. While lots of antioxidant molecules have been identified as widely expressed, the understanding of the critical mechanisms for redox management in male germ cells is inadequate. This study identified LanCL2 as a major male germ cell-specific antioxidant gene that is important for testicular homeostasis. Highly expressed in the brain and testis, LanCL2 expression correlates with testicular maturation and brain development. LanCL2 is enriched in spermatocytes and round spermatids of the testis. By examining LanCL2 knockout mice, we found that LanCL2 deletion did not affect postnatal brain development but injured the sperm parameters of adult mice. With histopathological analysis, we noticed that LanCL2 KO caused a pre-maturation and accelerated the self-renewal of spermatogonial stem cells in the early stage of spermatogenesis. In contrast, at the adult stage, LanCL2 KO damaged the acrosomal maturation in spermiogenesis, resulting in spermatogenic defects with a reduced number and motility of spermatozoa. Furthermore, we show that this disruption of testicular homeostasis in the LanCL2 KO testis was due to dysbalanced testicular redox homeostasis. This study demonstrates the critical role of LanCL2 in testicular homeostasis and redox balance.

Objective: Patients with congenital bicuspid aortic valve often require root replacement. This study aims to describe their long-term rates of mortality and reoperation., Methods: This is a multicenter retrospective study of 747 patients with bicuspid aortic valve who underwent aortic root replacement for aortic aneurysm between 2004 and 2020. Cumulative incidence curves for aortic valve and aortic reoperations were graphed. A Kaplan-Meier survival curve for the patient cohort was created alongside an age- and sex-matched curve for the US population. Multivariable Cox regression was used to determine characteristics associated with long-term mortality., Results: The median age of our cohort was 54 [43-64] years old, and 101 (13.5%) patients were female. In patients with bicuspid aortic valve dysfunction, 274 (36.7%) had aortic insufficiency, 187 (25.0%) had aortic stenosis, and 142 (19.0%) had both. In-hospital mortality occurred in 10 (1.3%) patients. There were 56 aortic valve reoperations and 19 aortic reoperations, with a combined cumulative incidence of 35% (95% confidence interval [CI], 23%-46%) at 15 years. In addition, there was comparable survival between the patient cohort and the age- and sex-matched US population. Age (hazard ratio [HR], 1.04; 95% CI, 1.01-1.06), concomitant CABG (HR, 2.28; 95% CI, 1.29-4.04), and bypass time (HR, 1.01; 95% CI, 1.00-1.01) were associated with increased mortality., Conclusions: Patients who undergo aortic root replacement with bicuspid aortic valve have an increased rate of aortic reoperation (35%; 95% CI, 23%-46%) while their survival appears to be comparable to the general US population (79%; 95% CI, 73%-87%) at 15 years., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

A survey of awareness and attitudes to the management of fragility fractures among the membership of the Asia Pacific Orthopaedic Association conducted in 2022 found considerable variation in care across the region. A Call to Action is proposed to improve acute care, rehabilitation and secondary fracture prevention across Asia Pacific., Purpose: Fragility fractures impose a substantial burden on older people and their families, healthcare systems and national economies. The current incidence of hip and other fragility fractures across the Asia Pacific region is enormous and set to escalate rapidly in the coming decades. This publication describes findings of a survey of awareness and attitudes to the management of fragility fractures among the membership of the Asia Pacific Orthopaedic Association (APOA) conducted in 2022., Methods: The survey was developed as a collaboration between the Asia Pacific Osteoporosis and Fragility Fracture Society and the Asia Pacific Fragility Fracture Alliance, and included questions relating to aspects of care upon presentation, during surgery and mobilisation, secondary fracture prevention, and access to specific services., Results: In total, 521 APOA members completed the survey and marked variation in delivery of care was evident. Notable findings included: Fifty-nine percent of respondents indicated that analgesia was routinely initiated in transit (by paramedics) or within 30 minutes of arrival in the Emergency Department. One-quarter of respondents stated that more than 80% of their patients underwent surgery within 48 hours of admission. One-third of respondents considered non-hip, non-vertebral fractures to merit assessment of future fracture risk. One-third of respondents reported the presence of an Orthogeriatric Service in their hospital, and less than a quarter reported the presence of a Fracture Liaison Service., Conclusion: A Call to Action for all National Orthopaedic Associations affiliated with APOA is proposed to improve the care of fragility fracture patients across the region., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Transition state (TS) on the potential energy surface (PES) plays a key role in determining the kinetics and thermodynamics of chemical reactions. Inspired by the fact that the dynamics of complex systems are always driven by rare but significant transition events, we herein propose a TS search method in accordance with the Q-learning algorithm. Appropriate reward functions are set for a given PES to optimize the reaction pathway through continuous trial and error, and then the TS can be obtained from the optimized reaction pathway. The validity of this Q-learning method with reasonable settings of Q-value table including actions, states, learning rate, greedy rate, discount rate, and so on, is exemplified in 2 two-dimensional potential functions. In the applications of the Q-learning method to two chemical reactions, it is demonstrated that the Q-learning method can predict consistent TS and reaction pathway with those by ab initio calculations. Notably, the PES must be well prepared before using the Q-learning method, and a coarse-to-fine PES scanning scheme is thus introduced to save the computational time while maintaining the accuracy of the Q-learning prediction. This work offers a simple and reliable Q-learning method to search for all possible TS and reaction pathway of a chemical reaction, which may be a new option for effectively exploring the PES in an extensive search manner., (© 2023 Wiley Periodicals LLC.)

Objectives: The decision to undergo aortic aneurysm repair balances the risk of operation with the risk of aortic complications. The surgical risk is typically represented by perioperative mortality, while the aneurysmal risk relates to the 1-year risk of aortic events. We investigate the difference in 30-day and 1-year mortality after total arch replacement for aortic aneurysm., Methods: This was an international two-centre study of 456 patients who underwent total aortic arch replacement for aneurysm between 2006 and 2020. Our primary end-point of interest was 1-year mortality. Our secondary analysis determined which variables were associated with 1-year mortality., Results: The median age of patients was 65.4 years (interquartile range 55.1-71.1) and 118 (25.9%) were female. Concomitantly, 91 (20.0%) patients had either an aortic root replacement or aortic valve procedure. There was a drop in 1-year (81%, 95% confidence interval (CI) 78-85%) survival probability compared to 30-day (92%, 95% CI 90-95%) survival probability. Risk hazards regression showed the greatest risk of mortality in the first 4 months after discharge. Stroke [hazard ratio (HR) 2.54, 95% CI (1.16-5.58)], renal failure [HR 3.59 (1.78-7.25)], respiratory failure [HR 3.65 (1.79-7.42)] and reoperation for bleeding [HR 2.97 (1.36-6.46)] were associated with 1-year mortality in patients who survived 30 days., Conclusions: There is an increase in mortality up to 1 year after aortic arch replacement. This increase is prominent in the first 4 months and is associated with postoperative complications, implying the influence of surgical insult. Mortality beyond the short term may be considered in assessing surgical risk in patients who are undergoing total arch replacement., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Sophorolipids (SLs) are surface active compounds that have excellent surface-lowering properties. SLs were produced by Starmerella bombicola (CGMCC1576) yeast with sunflower seed oil, fried waste oil, cooked tung oil and raw tung oil used as hydrophobic carbon sources. The results showed that the strain could use sunflower seed oil and fried waste oil as hydrophobic carbon sources to produce SLs, and the yields were 44.52 and 39.09 gl-1. It could not be used as cooked tung oil and raw tung oil. The analysis by high-performance liquid chromatography/high resolution mass spectrometry (HPLC-MS/MS) showed that the main composition and structure of SLs produced by fermentation using fried waste oil were similar to that of sunflower seed oil as hydrophobic carbon source. The yield of SLs was the highest when the fried waste oil was used as hydrophobic carbon source, glucose (8%), waste oil (6%) and yeast (0.3%). When fried waste oil was used as a hydrophobic carbon source in a parallel 4-strand fermentation tank (FT), the combination with the largest yield and the most cost saving was that 3% of fried waste oil was added into the initial medium, and another 3% was again added after 72 h of fermentation. The total yield of SLs was 121.28 gl-1, and the yield of lactone SLs was 48.07 gl-1., (© 2024 The Author(s).)

Background: Alcohol septal ablation (ASA) and septal myectomy (SM) are 2 options for septal reduction therapy (SRT) to treat medication-resistant symptomatic obstructive hypertrophic cardiomyopathy (HCM). Because differences in mortality rates after these different SRT methods have not been extensively investigated in real-world settings, in this study compared the 1-year mortality rates after ASA and SM using population-based database. Methods and Results: Utilizing New York Statewide Planning and Research Cooperative System (SPARCS) data from 2005 to 2016, we performed a comparative effectiveness study of ASA vs. SM in patients with HCM. The outcome was all-cause death up to 360 days after SRT. We constructed a multivariable logistic regression model and performed sensitivity analysis with propensity score (PS)-matching and inverse probability of treatment weighting (IPTW) methods. We identified 755 patients with HCM who underwent SRT: 348 with ASA and 407 with SM. The multivariable analysis showed that all-cause deaths were significantly fewer in the ASA group at 360 days after SRT (adjusted odds ratio=0.34; 95% confidence interval [CI] 0.13-0.84; P=0.02). The PS-matching and IPTW methods also supported a lower mortality rate in the ASA group at 360 days post-SRT. Conclusions: In this population-based study of patients with HCM who underwent SRT in a real-world setting, the 1-year all-cause mortality rate was significantly lower in patients who underwent ASA compared with SM., Competing Interests: None declared., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

The current study aims to develop and validate machine learning (ML) models for the prediction of cancer status by the non-invasive urinary proteomic in a population-based cohort. In this retrospective study, urinary proteome profiles in 804 cases from the FLEMENGHO cohort were measured by mass spectrometry. After feature selection by LASSO on both clinical variables and urinary proteome profile, benchmark models by clinical variables were built with six different ML algorithms. Proteome-based models and combined models were built and compared with the benchmark models. The models' performance, i.e. area under the curve (AUC) was compared by Delong method. The 95% confidence interval was estimated by the bootstrapping method. The best-performing model was explained by Shapley Additive Explanations (SHAP) method. The predictive role of proteome biomarkers in longitudinal cancer diagnosis was also explored. A clinical model, based on age, blood sugar and blood lipid profile, yielded the best AUC of 0.75 (0.68-0.82), with 0.80 (0.72-0.91) for the proteome model based on 13 selected biomarkers and 0.83 (0.77-0.90) for the combined model ( P =0.01 for comparison with clinical model). SHAP on the support vector machine in the combined setting showed that except for age, proteome biomarkers contribute to the final prediction of the model. After adjusting with clinical factors, three proteome biomarkers are independent risk factors for longitudinal cancer development. Urinary proteome profiling, together with fine-tuned machine learning algorithms, demonstrates the predictive potential for cancer diagnosis transparently., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Although postoperative follow-up after aortic surgery is recommended by guidelines, its clinical utility is not well documented. We hypothesized that structured follow-up imaging by an aortic program would improve outcomes. We then documented radiologic findings on asymptomatic postoperative imaging., Methods: All patients who survived to discharge after open thoracic aortic surgery between January 2017 and July 2021 were included, excluding endocarditis. Patients who followed at our center and received scheduled imaging were compared with patients who did not. Survival was analyzed by the method of Kaplan-Meier, and reintervention was assessed using the Fine-Gray subhazard function. Routine imaging was reviewed for aortic growth, pseudoaneurysm, and perigraft density., Results: After aortic surgery, the cumulative incidence of follow-up was 38.6% at 3 years postoperatively. Patients with follow-up were more likely to have a dissection and fewer comorbidities but were similar in regards to socioeconomic factors and distance to hospital. After matching and accounting for immortal time bias, patients with follow-up had a greater reintervention rate (26.0% vs 9.0%) with similar survival (98.7% vs 95.2%, P = .110) at 4 years. The cumulative incidence of pseudoaneurysm, significant perigraft density, and growth ≥3 mm/year on routine imaging was 49.7% at 3 years., Conclusions: Implementation of structured follow-up imaging by an aortic program resulted in low clinical compliance. Follow-up was associated with increased rates of aortic reintervention. Clinically relevant radiologic findings were common on asymptomatic imaging and increased throughout 5-year follow-up rather than plateauing in the early postoperative period., Competing Interests: Conflict of Interest Statement H.T. reported consultant for Artivion and speaker with Terumo. M.C. reported consulting fees from Artivion and Terumo. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the influence of intraoperative factors relative to preoperative risk factors on recovery after aortic root replacement (ARR)., Methods: Retrospective review of baseline and intraoperative characteristics was performed of 822 patients at our Aortic Center from 2005 to 2019. Inclusion criteria were all patients age 18 and older who underwent ARR at our institution from 2005 to 2019. The primary endpoint was the aggregate outcome of "failure to achieve uneventful recovery (FUR)," as previously defined., Results: In total, 207 (25%) patients experienced FUR. The following preoperative and intraoperative variables were significantly associated with FUR in the multivariable analysis: cardiopulmonary bypass time (OR 1.01, 95% CI 1.01-1.02) open chest management (OR 5.67, 95% CI 2.65-12.1), ejection fraction (OR 1.03, 95% CI 1.01-1.04), chronic kidney disease > stage 3a (OR 2.37, 95% CI 1.54-3.63), bicuspid aortic valve (OR 1.54, 95% CI 1.21-1.96), and female sex (OR 1.30, 95% CI 1.06-1.61). Cardiopulmonary bypass time and open chest management were among the top three partial R 2 contributors to the logistic regression model variance., Conclusions: These findings suggest efficacy in using intraoperative parameters to predict postoperative outcomes after ARR., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Ethnopharmacological Relevance: Tetradium ruticarpum (A.Juss.) T.G.Hartley, a traditional Chinese medicine with thousands of years of medicinal history, has been employed to address issues such as indigestion, abdominal pain, and vomiting. Dehydroevodiamine (DHE) is a quinazoline alkaloid extracted from traditional Chinese medicine Tetradium ruticarpum (A.Juss.) T.G.Hartley. Previous studies have shown that DHE has anti-inflammatory, analgesic, and antioxidant activities. However, it is still unclear whether DHE has an effect on ethanol-induced gastric ulcers., Aim of the Study: The objective of this study is to investigate the therapeutic efficacy and underlying mechanisms of action of DHE on ethanol-induced gastric ulcers using network pharmacology and metabolomics strategies., Methods: In this study, we used ethanol-induced rats as a model to assess the efficacy of DHE by biochemical indicator assays and pathological tissue detection. The integration of network pharmacology and metabolomics was used to explore possible mechanisms and was validated by western blot experiments. Finally, molecular docking was used to analyze the binding energy between DHE and the targets of PIK3CG and PLA2G2A., Results: DHE was able to reverse ethanol-induced abnormalities in biochemical indicators and improve pathological tissue. Network pharmacology results indicated that DHE may be involved in the regulation of gastric ulcers by modulating 79 targets, and metabolomics results showed that a total of 13 metabolites were changed before and after DHE administration. Integrating network pharmacology and metabolomics, PIK3CG and PLA2G2A were identified as possible targets to exert therapeutic effects. In addition, the MAPKs pathway may also be involved in the regulation of ethanol-induced gastric ulcers. Finally, molecular docking results showed that DHE had low binding energies with both PIK3CG and PLA2G2A., Conclusions: These findings suggest that DHE was able to exert a protective effect against ethanol-induced gastric ulcers by modulating multiple metabolites with multiple targets. This study provides a valuable reference for the development of antiulcer drugs., Competing Interests: Declaration of competing interest There were no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Gastric ulcers (GUs) are prevalent digestive disorders worldwide. Wuzhuyu Decoction (WZYT) is a traditional Chinese medicine that has been employed for centuries to alleviate digestive ailments like indigestion and vomiting. This study aims to explore the potential effects and underlying mechanisms of WZYT on alcohol induced gastric ulcer treatment. Methods: We employed macroscopic assessment to evaluate the gastric ulcer index (UI), while the enzyme-linked immunosorbent assay (ELISA) was utilized for detecting biochemical indicators. Pathological tissue analysis involved hematoxylin-eosin (H&E) staining and Periodic Acid-Schiff (PAS) staining to assess gastric tissue damage. Additionally, the integration of network analysis and metabolomics facilitated the prediction of potential targets. Validation was conducted using Western blotting. Results: The research revealed that WZYT treatment significantly reduced the gastric ulcer index (UI) and regulation of alcohol-induced biochemical indicators levels. Additionally, improvements were observed in pathological tissue. Network analysis results indicated that 62 compounds contained in WZYT modulate alcohol-induced gastric ulcers by regulating 183 genes. The serum metabolomics indicated significant changes in the content of 19 metabolites after WZYT treatment. Two pivotal targets, heme oxygenase 1 (HMOX1) and albumin (ALB), are believed to assume a significant role in the treatment of gastric ulcers by the construction of "compounds-target-metabolite" networks. Western blot analysis confirmed that WZYT has the capacity to elevate the expression of HMOX1 and ALB targets. Conclusion: The integration of network analysis and metabolomics provides a scientific basis to propel the clinical use of WZYT for GUs. Our study provides a theoretical basis for the use of Wuzhuyu decoction in the treatment of gastric ulcers., 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 © 2024 Wang, Chen, Chang, He, He, Wang, Wei, Jing, Zhou, Li and Zhao.)

Objective: Although postoperative atrial fibrillation has been shown to be associated with worse survival after thoracic aortic surgery, its effect on outcomes independently from other postoperative complications is not well understood., Methods: This is a single-center retrospective study of patients who underwent open thoracic aortic aneurysm repair between March 2005 and March 2021. Postoperative atrial fibrillation was defined as new-onset atrial fibrillation that developed during the index hospital stay. Patients with preoperative atrial fibrillation were excluded. Postoperative major complications included reoperation for bleeding, respiratory failure, acute renal failure, and stroke. Variables associated with postoperative atrial fibrillation were analyzed with multivariable regression. Survival of patients without major complications was compared between patients without atrial fibrillation and patients with postoperative atrial fibrillation after propensity score matching for baseline and intraoperative characteristics., Results: Of 1454 patients, 520 (35.8%) were observed to have postoperative atrial fibrillation. Patients with postoperative atrial fibrillation had a higher rate of postoperative major complications than those without atrial fibrillation (20.2% vs 12.2%, P < .001). Ten-year survival was 82.0% in patients with postoperative atrial fibrillation and 87.0% in patients without atrial fibrillation (P = .008). In the cohort of patients without complications, 10-year survival was similar between patients with and without postoperative atrial fibrillation after propensity score matching (83.6% vs 83.8%, P = .75)., Conclusions: Postoperative atrial fibrillation is common after open proximal thoracic aortic aneurysm repair. Although development of major postoperative complications is associated with postoperative atrial fibrillation and decreased long-term survival, isolated postoperative atrial fibrillation does not appear to influence long-term survival., Competing Interests: Conflict of Interest Statement H.T. is a consultant for Artivion and speaker for Terumo. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Coronavirus disease 2019 (COVID-19) is a lifethreatening disease worldwide due to its high infection and serious outcomes resulting from acute lung injury. Qingwen Baidu decoction (QBD), a well-known herbal prescription, has shown significant efficacy in patients with Coronavirus disease 2019. Hence, this study aims to uncover the molecular mechanism of QBD in treating COVID-19-related lung injury., Methods: Traditional Chinese Medicine Systems Pharmacology database (TCMSP), DrugBanks database, and Chinese Knowledge Infrastructure Project (CNKI) were used to retrieve the active ingredients of QBD. Drug and disease targets were collected using UniProt and Online Mendelian Inheritance in Man databases (OMIM). The core targets of QBD for pneumonia were analyzed by the Protein-Protein Interaction Network (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to reveal the underlying molecular mechanisms. The analysis of key targets using molecular docking and animal experiments was also validated., Results: A compound-direct-acting target network mainly containing 171 compounds and 110 corresponding direct targets was constructed. The key targets included STAT3, c-JUN, TNF-α, MAPK3, MAPK1, FOS, PPARG, MAPK8, IFNG, NFκB1, etc. Moreover, 117 signaling pathways mainly involved in cytokine storm, inflammatory response, immune stress, oxidative stress and glucose metabolism were found by KEGG. The molecular docking results showed that the quercetin, alanine, and kaempferol in QBD demonstrated the strongest affinity to STAT3, c- JUN, and TNF-α. Experimental results displayed that QBD could effectively reduce the pathological damage to lung tissue by LPS and significantly alleviate the expression levels of the three key targets, thus playing a potential therapeutic role in COVID-19., Conclusion: QBD might be a promising therapeutic agent for COVID-19 via ameliorating STAT3-related signals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet on hepatic diseases. It discusses the molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly in liver injury, liver fibrosis, NAFLD/NASH, and HCC. In the regulation of liver injury, polyphenols exhibit anti-inflammatory and antioxidant effects, primarily targeting the TGF-β, NF-κB/TLR4, PI3K/AKT, and Nrf2/HO-1 signaling pathways. In the regulation of liver fibrosis, polyphenolic compounds effectively reverse the fibrotic process by inhibiting the activation of hepatic stellate cells (HSC). Furthermore, polyphenolic compounds show efficacy against NAFLD/NASH by inhibiting lipid oxidation and accumulation, mediated through the AMPK, SIRT, and PPARγ pathways. Moreover, several polyphenolic compounds exhibit anti-HCC activity by suppressing tumor cell proliferation and metastasis. This inhibition primarily involves blocking Akt and Wnt signaling, as well as inhibiting the epithelial-mesenchymal transition (EMT). Additionally, clinical trials and nutritional evidence support the notion that certain polyphenols can improve liver disease and associated metabolic disorders. However, further fundamental research and clinical trials are warranted to validate the efficacy of dietary polyphenols., (© 2023 John Wiley & Sons Ltd.)

F-type ATP synthase (F-ATPase) and vacuolar ATP hydrolase (V-ATPase) are well-known biomolecular motors, which play significant catalytic roles in ATP synthesis and ATP hydrolysis reactions. Their rotational torques are important factors involved in their rotational behavior that can be measured experimentally but with considerable difficulty. To overcome this difficulty and thereby provide an in-depth understanding of their operation mechanism, we herein carry out simple and fast computer modelling to study the two proteins, using our torque approach that relies on interatomic forces and coordinates of unequilibrated configurations taken from brief molecular dynamics (MD) simulations. As predicted by the torque approach, F-ATPase is demonstrated to be a random rotor, but it prefers to rotate in clockwise direction (as seen from the membrane toward the protein) for ATP synthesis, owing to the predominantly negative angle-averaged torques. By contrast, V-ATPase tends to rotate only in counterclockwise direction for ATP hydrolysis, due to the almost uniform averaged positive torques generated by the unidirectional rotation near the three catalytic sites. The rotational behaviors of both proteins are also affected by the surrounding solvent which can promote or hinder the internal rotation. By combining the torque approach with classic force-field MD simulations, the torques of two biomolecular motors can be calculated economically, and are found to agree with previous experiments and theoretical calculations. This work demonstrates that our torque approach can be extended to the field of biology and can help gain a deeper insight into the mechanistic rotation of biomolecular motors with modest computation time.Communicated by Ramaswamy H. Sarma.

Objectives: We aim to investigate the association between parameters surrounding circulatory arrest and postoperative acute kidney injury in aortic surgery., Methods: This is a single-center retrospective study of 1118 adult patients who underwent aortic repair with median sternotomy between January 2010 and May 2019. Acute kidney injury was defined on the basis of a modified version of the 2012 Kidney Disease Improving Global Outcomes Scale that excluded urine output. The primary outcome of interest was any stage of acute kidney injury., Results: Circulatory arrest was required in 369 patients, and 307 patients (27.5%) developed acute kidney injury: stage 1 in 241 patients, stage 2 in 38 patients, and stage 3 in 28 patients. Lower-body ischemia (the period during circulatory arrest without blood flow to kidneys) duration was not associated with acute kidney injury after multivariable logistic regression (1-40 minutes, odds ratio, 0.67; 95% confidence interval, 0.43-1.04; P = .075; >40 minutes, odds ratio, 0.67; 95% confidence interval, 0.29-1.55; P = .356). Hypertension (odds ratio, 1.65; 95% confidence interval, 1.09-2.54; P = .020), preoperative estimated glomerular filtration rate (odds ratio, 0.99; 95% confidence interval, 0.98-1.00; P = .010), packed red blood cell transfusion volume (odds ratio, 1.00; 95% confidence interval, 1.00-1.00; P = .028), and nadir temperature (odds ratio, 0.93; 95% confidence interval, 0.88-0.99; P = .013) were independently associated with acute kidney injury after multivariable analysis. Although there was a positive association between lower-body ischemia duration and development of acute kidney injury with univariable cubic spline, the positive curve was flattened after adjustment for the described variables., Conclusions: Within the range of our clinical practice, prolonged lower-body ischemia duration was not independently associated with postoperative acute kidney injury, whereas nadir temperature was., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

The Spontaneous combustion problem poses a significant threat to the coal waste dumps after reclamation. Spontaneous combustion alters the soil environment and further affects vegetation growth. Therefore, it is essential to understand the response of vegetation and soil to spontaneous combustion for ensuring vegetation restoration. Here, taking the reclaimed plant type, Medicago sativa L. (alfalfa), as an indicator, this study carried out a field survey in a typical spontaneous combustion area (study area) of a coal waste dump after reclamation. A total of 41 soil and 70 vegetation sampling points were investigated in the field survey, including soil environmental factors (soil temperature, ST; soil water content, SWC; soil organic carbon, SOC; total nitrogen, TN; available phosphorus, AP; available potassium, AK; bulk density, BD; pH) and alfalfa growth indicator (above-ground biomass, AGB). The spatial variation of alfalfa AGB reached 69.9 %, and all soil environmental factors showed moderate variation (12.28-35.03 %) except for BD and pH. ST was found to have a strong explanatory ability on the variation of AGB in the entire study area (q = 0.62, p < 0.01), but the ability weakened with the improvement of the health grades of alfalfa (Grades A, B, C, and D). From Grade D to Grade A, the q-value gradually reduced from 0.71 (p < 0.01) to 0.05 (no significance). The interaction effects of soil environmental factors showed mostly bilinear and non-linear enhancement. In regions with severe vegetation degradation (Grade C and Grade D of alfalfa), the interaction of ST with BD, AP, AK, and TN played a dominant role in the spatial variation of alfalfa AGB (44.8-86.15 %). However, in the regions of Grade A and Grade B, the spatial variation of alfalfa AGB was mainly affected by the interaction effects of AK, TN, AP, and SOC (60.13-84.77 %). As a simple analysis method, Geodetector can help researchers to better understand the complex response mechanism of vegetation-soil under spontaneous combustion of coal waste dump. This study provides a theoretical reference for vegetation restoration of coal waste dumps., Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Chronic non-atrophic gastritis (CNAG) is a common clinical gastrointestinal disease with a long and recurrent course. In China, Wuzhuyu decoction (WZYD) has been used for centuries to treat gastrointestinal disorders. To unravel the efficacy and mechanism of WZYD for CNAG, a clinical study was conducted. And metabolomics was used to explore the mechanism of WZYD for CNAG patients., Methods: Twenty patients in total were recruited in this study (Nos. ChiCTR2200062296) and the protocol was approved by the Ethics Committee (Approval number: KY-2022-2-6-1) and complied with the Declaration of Helsinki. The formula granule of WZYD were assessed by UHPLC-QQQ-TOF to discern the main potential active compounds. The endoscopy evaluation and histopathological changes were detected as effective indicators. Serum samples from patients were used for metabolomics. Inflammatory factors in patients' serum were determined by ELISA. Metabolomics revealed a series of differential metabolites and signaling pathways., Results: WZYD was capable to prevent CNAG by ameliorating score of endoscopy evaluation including erosion, hemorrhage, as well as chronic inflammation and active chronic inflammation score after treatment were decreased. The results indicated that 10 core metabolic components were associated with the treatment of WZYD. Moreover, these metabolic components proved that pyrimidine metabolism and thiamine metabolism were critically responsible for CNAG. In addition, WZYD treatment effectively reduced serum levels of TNF-α, IL-10, and COX-2., Conclusion: Altogether, WZYD can effectively alleviate CNAG by inhibiting inflammation and regulating related metabolic processes, which might be the molecular mechanism of WZYD treatment of CNAG. More studies are warranted to be conducted in this area., Trial Registration: ChiCTR, ChiCTR2200062296. Registered 1 August 2022, https://www.chictr.org.cn/com/25/showprojen.aspx?proj=174027., 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., (© 2023 Hu et al.)

Background: Gastric precancerous lesions (GPLs) are omens for gastric cancer (GC), which developing with a series of pathological changes of gastric mucosa. Reversing epithelial-mesenchymal transition (EMT) in gastric mucosa is the main approach to restrain GPLs from evolving into cancer. Tanshinone I (Tan-I), the active ingredients of traditional Chinese herb Salvia miltiorrhiza, has exhibited anticancer effect., Purpose: To investigate the effect and mechanism of Tan-I in intervening GPLs, and provide a new therapeutic strategy for prevention of GC., Methods: Gastric mucosal epithelial cells were treated with the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) to construct MNNG-induced cell (MC cell) of gastric mucosa that undergoing EMT process. Then, this study explored the effect and mechanism of Tan-I in vitro. Subsequently, this study constructed GPL mice to clarify the exact efficacy and mechanism of Tan-I on GPLs., Results: Tan-I inhibited MC cell proliferation, invasion and migration. Simultaneously, the aberrant expression of E-cadherin and N-cadherin were reversed. Tan-I attenuated inflammation by reducing the release of nitric oxide, TNFα and IL-1β. Tan-I reversed the EMT and inflammatory processes by regulating p38 and STAT3., Conclusion: This study showed that Tan-I inhibited the progression of GPLs by reversing the EMT process and reducing inflammation by restraining the p38/STAT3 signaling pathway., 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.)

Background: Proteins related to sperm motility and sperm morphology have an important impact on sperm function such as metabolism, motility and fertilisation etc. An understanding of the key proteins related to semen quality in Niangya yaks would help to provide support for breeding. However, the key proteins that affect semen quality in Niangya yaks remain unclear., Methods: Herein, we applied tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC‒MS/MS) to analyze the expression levels of sperm proteins in groups of high- and low-quality semen from Niangya yaks. And fifteen differentially expressed proteins (DEPs) were randomly selected for expression level validation by parallel reaction monitoring (PRM)., Results: Of the 2,092 quantified proteins, 280 were identified as DEPs in the high-quality group versus the low-quality group. Gene Ontology (GO) analysis revealed that in terms of biological pathways, the DEPs were mainly involved in metabolic processes, cell transformation processes, and single organism metabolic processes. In terms of cell composition, the DEPs were mainly located in the cell membrane, organelle, molecular complex. In terms of molecular functions, the most abundant functions of the DEPs were catalytic activity, binding activity, transport activity, and enzyme regulation activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the DEPs were mainly involved in the cytokine and cytokine receptor interaction, notch signaling pathway, lysine biosynthesis, renal function-related protein and proteasome pathway. From protein-protein interaction (PPI) analysis of DEPs involved in important pathways, 6 related proteins affecting the semen quality of Niangya yaks were identified. And the results of the PRM and TMT analysis were consistent., Conclusions: The differential sperm proteomic analysis of high- and low-quality semen from Niangya yaks, revealed 6 proteins (PSMC5, PSMD8, PSMB3, HSP90AA1, UGP2 and HSPB1), were mainly concentrated in energy production and metabolism, might play important roles in semen quality, which could serve as candidates for the selection and breeding of Niangya yaks., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In Chinese medicine, the primary considerations revolve around toxicity and effect. The clinical goal is to achieve maximize effect while minimizing toxicity. Nevertheless, both clinical and experimental research has revealed a distinct relationship between these two patterns of action in toxic Traditional Chinese Medicines (TCM). These TCM often exhibit characteristic "double-sided" or "multi-faceted" features under varying pathological conditions, transitioning between effective and toxic roles. This complexity adds a layer of challenge to unraveling the ultimate objectives of Traditional Chinese medicine. To address this complexity, various hypotheses have been proposed to explain the toxicity and effect of Traditional Chinese Medicines. These hypotheses encompass the magic shrapnel theory for effect, the adverse outcome pathway framework, and the indirect toxic theory for toxicity. This review primarily focuses on high-, medium-, and low-toxicity Traditional Chinese Medicines as listed in Chinese Pharmacopoeia. It aims to elucidate the essential intrinsic mechanisms and elements contributing to their toxicity and effectiveness. The critical factors influencing the mechanisms of toxicity and effect are the optimal dosage and duration of TCM administration. However, unraveling the toxic-effect relationships in TCM presents a formidable challenge due to its multi-target and multi-pathway mechanisms of action. We propose the integration of multi-omics technology to comprehensively analyze the fundamental metabolites, mechanisms of action, and toxic effects of TCM. This comprehensive approach can provide valuable insights into the intricate relationship between the effect and toxicity of these TCM., 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, Deng, Xiong, Hu, Chen, Zhang, Ma and Zhao.)

Objectives: Lateral thoracotomy (LT) approach may preserve the right ventricular (RV) function after left ventricular assist device (LVAD) implantation. This study evaluated the short- and long-term RV function using echocardiography after LVAD implantation via LT or median sternotomy (sternotomy)., Methods: The patients who underwent HeartMate 3 implantation were retrospectively reviewed. The RV function was assessed before and 1 month and 1 year after LVAD implantation. The primary and secondary outcomes were all-cause mortality and a composite of death or readmission due to RV failure, respectively., Results: Of the 195 patients, 55 (28%) underwent LT and 140 (72%) underwent sternotomy. There were no significant differences in the preoperative RV geometry or function. One month after the LVAD implantation, the LT group had a smaller RV end-diastolic dimension [42 (29-48) vs 47 (42-52) mm; P = 0.003] and RV end-diastolic area [25 (21-28) vs 29 (24-36) cm2; P < 0.001] and a greater RV fractional area change [30 (25-34)% vs 28 (23-31)%; P = 0.04] and peak systolic tissue velocity [8 (7-9) vs 7 (6-8) cm/s; P = 0.01]. Twenty-four patients died and 46 met the composite end point. Kaplan-Meier curve analysis did not reveal significant differences between LT and sternotomy in the 2-year survival (93% vs 83%; log-rank test, P = 0.28) and adverse event rate (76% vs 71%; log-rank test, P = 0.65)., Conclusions: LT approach yielded a better-preserved RV function at 1 month; however, there were no significant differences in the 2-year survival and adverse event rates., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: Existing aortic graft complicates the surgical management of prosthetic valve endocarditis (PVE); yet, its impact has not been well studied. We compared outcomes of patients with prior aortic valve replacement (AVR) versus aortic surgery plus AVR, who underwent reoperative aortic root replacement (ARR) for PVE of the aortic valve., Methods: All patients who underwent reoperative ARR for PVE between 2004 and 2021 from 2 aortic centres were included. Two groups were formed based on the presence/absence of aortic graft: prior aortic surgery (AO) and prior AVR (AV) alone. Inverse propensity treatment weighting matched the groups. The Kaplan-Meier method was used to analyse long-term survival, and Fine and Gray model was used to compare the cumulative incidence of reoperation., Results: A total of 130 patients were included (AO n = 59; AV n = 71). After matching, AO patients had increased stroke incidence (12.4% vs 0.9%) and renal failure requiring dialysis (11.5% vs 2.5%). In-hospital mortality was comparable (21.5% AO and 18.6% AV). Survival over 5 years was 68.9% (56.6-83.8%) in AO and 62.7% (48.1-81.7%) in AV (P = 0.70). The cumulative incidence of reoperation was similar [AO 6.3% (0.0-13.2%) vs AV 6.1% (0.0-15.1%), P = 0.69]., Conclusions: Reoperative ARRs for prosthetic valve/graft endocarditis are high-risk procedures. AO patients had higher incidence of postoperative morbidity versus AV patients. For all patients surviving operative intervention, survival and reoperation rates over 5 years were comparable between groups., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Chronic gastritis (CG) is a common clinical digestive system disease, which is not easyily cured and is prone to recurrence. Traditional Chinese medicine (TCM) plays a significant role in the treatment of CG and has attracted increasing attention for clinical applications. In recent years, a large number of reports have shown that TCM has good therapeutic effect on CG. The aim of this paper is to investigate the pharmacological activities and mechanism of action of TCM in the treatment of CAG. Therefore, by searching the databases of Pubmed, China National Knowledge Infrastructure, Wanfang, and Baidu academic databases, this paper has summarized the molecular mechanisms of TCM in improving CG. The results show that the improvement of GC by TCM is closely related to a variety of molecular mechanisms, including the inhibition of Helicobacter pylori (Hp) infection, alleviation of oxidative stress, improvement of gastric function, repair of gastric mucosa, inhibition of inflammatory response, and apoptosis. More importantly, IRF8-IFN-γ, IL-4-STAT6, Hedgehog, pERK1/2, MAPK, PI3K-Akt, NF-κB, TNFR-c-Src-ERK1/2-c-Fos, Nrf2/HO-1, and HIF-1α/VEGF signaling pathways are considered as important molecular targets for TCM in the treatment of GC. These important findings will provide a direction and a basis for further exploring the pathogenesis of GC and tapping the potential of TCM in clinical treatment. This review also puts forward a bright prospect for future research of TCM in the treatment of CG.

Introduction: Thalassemia is the most common monogenic disease in South and Southeast Asia. An accurate assessment of the relative frequency and composition of thalassemia mutations is important for the design of appropriate strategies to prevent the disease. In this study, we aimed to decode the molecular characterization of thalassemia mutations in Zhuhai region of southern China., Methods: A total of 8048 individuals who were potential thalassemia carriers were enrolled. Gap-polymerase chain reaction (Gap-PCR) and reverse dot-blot (RDB) hybridization methods were employed to detect common deletional and non-deletional thalassemia mutations. Multiplex ligation dependent probe amplification (MLPA) and Sanger sequencing were used to analyze and verify rare and complex mutations., Results: We diagnosed 3433 individuals as thalassemia carriers or patients. Of these, 2395 (69.76%) individuals with α-thalassemia harbored 13 α-globin gene mutations. The three most common α-thalassemia mutations were -- SEA (60.08%), -α 3.7 (20.62%) and -α 4.2 (9.25%). We diagnosed 903 (26.30%) individuals with β-thalassemia and identified 20 β-globin gene mutations, of which the three most frequent were CD41/42 (-TCTT) (38.10%), IVS-II-654 (C>T) (23.69%) and TATAbox-28 (A>G) (15.18%). In addition, we identified 15 rare thalassemia variants. We also summarized the association between the thalassemia genotype and hematological parameters, which demonstrated the broad phenotypic heterogeneity caused by globin gene mutations., Conclusion: This is the first survey of thalassemia molecular epidemiology and hematological phenotype in Zhuhai region. It uncovered a high prevalence and complex molecular spectrum of thalassemia. These findings can be used as a basis for thalassemia diagnosis, counseling and prevention management., (© 2023 John Wiley & Sons Ltd.)

Objectives: To determine the role of adding open distal anastomosis to proximal aortic aneurysm repairs in bicuspid aortic valve (BAV) patients., Methods: Retrospective review was performed of 1132 patients at our Aortic Center between 2005 and 2019. Inclusion criteria were all patients diagnosed with a BAV who underwent proximal aortic aneurysm repair with open or clamped distal anastomosis. Exclusion criteria were patients without a BAV, age < 18 years, aortic arch diameter ≥ 4.5 cm, type A aortic dissection, previous ascending aortic replacement, ruptured aneurysm, and endocarditis. Propensity score matching in a 2:1 ratio (220 clamped: 121 open repairs) on 18 variables was performed., Results: Median follow-up time was 45.6 months (range 7.2-143.4 months). In the matched groups, no significant differences were observed between the respective open and clamped distal anastomosis groups for Kaplan Meier 10-year survival (86.9% vs. 92.9%; p = 0.05) and landmark survival analysis after 1 year (90.6%; vs. 93.3%; p = 0.39). Overall incidence of aortic arch-related reintervention was low (n = 3 total events). In-hospital complications were not significantly different in the open with respect to the clamped repair group, including in-hospital mortality (2.5% vs. 0.5%; p = 0.13) and stroke (0% vs. 0.9%; p = 0.54). In multivariable analysis, open distal anastomosis repair was not associated with long-term mortality (Hazard Ratio (HR) 1.98; p = 0.06)., Conclusion: We found no significant inter-group differences in survival, reintervention, or in-hospital complication rates, with low rates of mortality, and aortic arch-related reintervention, suggesting adding open distal anastomosis may not provide benefit in BAV patients undergoing proximal aortic aneurysm repairs., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Aims: Prior studies have suggested causal relationships between obesity and acute cardiovascular events. It has been also known that the risk of acute cardiovascular events is reduced by bariatric surgery. However, little is known about whether bariatric surgery lowers the risk of acute cardiovascular events in patients with obesity and hypertrophic cardiomyopathy (HCM). In this context, we aimed to investigate whether bariatric surgery is associated with a reduced risk of cardiovascular-related acute care use in patients with HCM., Methods and Results: In this population-based study, the bariatric surgery group consisted of patients with HCM who underwent bariatric surgery from January 2004 to December 2014. The control group included those who have obesity and HCM and received non-bariatric elective intra-abdominal surgery during the same period. The outcome was cardiovascular-related acute care use (i.e. emergency department (ED) visits or unplanned hospitalizations for cardiovascular disease) during a 1-year post-surgery period. We used the SPARCS database, a population-based ED and inpatient database in New York State. We constructed logistic regression models with generalized estimating equations to compare the risk of the outcome events during sequential 6-month post-surgery periods. We adjusted for age, sex, number of ED visits and hospitalizations for cardiovascular disease within 2 years before the index surgery, and the Elixhauser co-morbidity measures. We also performed propensity score (PS)-matching and inverse probability treatment weighting analyses using these variables. The analytic cohort consisted of 207 adults with obesity and HCM, including 147 patients who underwent bariatric surgery and 60 in the control group. The risk was not significantly different in the 1-6 months post-surgery period. By contrast, in the 7-12 months post-surgery period, the risk of cardiovascular-related acute care use was significantly lower in the bariatric surgery group (adjusted odds ratio 0.23; 95% CI 0.068-0.71; P = 0.01) compared with the control group. In the PS-matched cohort, there were no significant differences in the baseline characteristics. The PS-matched analysis demonstrated lower risk of the outcome event in the bariatric surgery group in the 7-12 months post-surgery period. The inverse probability treatment weighting analysis replicated the findings., Conclusions: Bariatric surgery was associated with a lower risk of cardiovascular-related acute care use in the 7-12 months post-surgery period in this population-based study., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Although the unique risks of implanting a prosthetic valve after aortic valve (AV) surgery in young patients are well established, studies of aortic root replacement (ARR) are lacking. We investigated long-term outcomes after valve-sparing root replacement (VSRR) versus the use of a composite valve graft with bioprosthesis (b-CVG) in patients age <50 years., Methods: A total of 543 patients age <50 years underwent VSRR (n = 335) or b-CVG (n = 208) between 2004 and 2021 from 2 aortic centers, excluding those with dissection or endocarditis. Endpoints included mortality over time, reoperative aortic valve replacement (AVR), and development of greater than moderate aortic insufficiency (AI) or aortic stenosis (AS). Fine and Gray competing risk regression was used to compare the risk of reintervention. Propensity score matching (PSM) balanced patient comorbidities, and landmark analysis isolated outcomes beginning 4 years postoperatively., Results: Compared with VSRR, b-CVG was associated with lower 12-year survival (88.6% vs 92.9%; P = .036) and a higher rate of AV reintervention (37.6% vs 12.0%; P = .018). After PSM, survival was similar in the 2 arms (93.4% for b-CVG vs 93.0% for VSRR; P = .72). However, both Fine and Gray multivariable risk regression and PSM showed that b-CVG was independently associated with AV reintervention at >4 years postoperatively (Fine and Gray: subdistribution hazard ratio, 4.3 [95% confidence interval, 1.8-10.2; P = .001]; PSM: 35.7% for b-CVG versus 14.3% for VSRR; P = .024]). PSM rates of greater than moderate AI/AS at 10 years were more than 2-fold greater in the b-CVG arm compared with the VSRR arm (37.1% vs 15.9%; P = .571)., Conclusions: b-CVG in young patients is associated with early valvular degeneration, with increasing rates of reoperative AVR occurring even within 10 years. In contrast, VSRR is durable with excellent survival. In eligible young patients, every effort should be made to retain the native AV., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Primary biliary cirrhosis (PBC) is a chronic cholestatic immune liver disease characterized by persistent cholestasis, interlobular bile duct damage, portal inflammation, liver fibrosis, eventual cirrhosis, and death. Existing clinical and animal studies have made a good progress in bile acid metabolism, intestinal flora disorder inflammatory response, bile duct cell damage, and autoimmune response mechanisms. However, the pathogenesis of PBC has not been clearly elucidated. We focus on the pathological mechanism and new drug research and development of PBC in clinical and laboratory in the recent 20 years, to discuss the latest understanding of the pathological mechanism, treatment options, and drug discovery of PBC. Current clinical treatment mode and symptomatic drug support obviously cannot meet the urgent demand of patients with PBC, especially for the patients who do not respond to the current treatment drugs. New treatment methods are urgently needed. Drug candidates targeting reported targets or signals of PBC are emerging, albeit with some success and some failure. Single-target drugs cannot achieve ideal clinical efficacy. Multitarget drugs are the trend of future research and development of PBC drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Wei, Chen, Zhou and Ma.)

Gastric cancer (GC) is one of the most serious gastrointestinal malignancies with high morbidity and mortality. The complexity of GC process lies in the multi-phenotypic linkage regulation, in which regulatory cell death (RCD) is the core link, which largely dominates the fate of GC cells and becomes a key determinant of GC development and prognosis. In recent years, increasing evidence has been reported that natural products can prevent and inhibit the development of GC by regulating RCDs, showing great therapeutic potential. In order to further clarify its key regulatory characteristics, this review focused on specific expressions of RCDs, combined with a variety of signaling pathways and their crosstalk characteristics, sorted out the key targets and action rules of natural products targeting RCD. It is highlighted that a variety of core biological pathways and core targets are involved in the decision of GC cell fate, including the PI3K/Akt signaling pathway, MAPK-related signaling pathways, p53 signaling pathway, ER stress, Caspase-8, gasdermin D (GSDMD), and so on. Moreover, natural products target the crosstalk of different RCDs by modulating above signaling pathways. Taken together, these findings suggest that targeting various RCDs in GC with natural products is a promising strategy, providing a reference for further clarifying the molecular mechanism of natural products treating GC, which warrants further investigations in this area., (© 2023 John Wiley & Sons Ltd.)

Hereditary cholestatic liver disease caused by a class of autosomal gene mutations results in jaundice, which involves the abnormality of the synthesis, secretion, and other disorders of bile acids metabolism. Due to the existence of a variety of gene mutations, the clinical manifestations of children are also diverse. There is no unified standard for diagnosis and single detection method, which seriously hinders the development of clinical treatment. Therefore, the mutated genes of hereditary intrahepatic cholestasis were systematically described in this review., 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 Xie, Wei, Ma, Wang, He, Zhang, Yang, Wang, Chang, Jing, Li, Zhou and Zhao.)

Background: Farnesoid X receptor (FXR) is a key metabolic target of bile acids (BAs) and is also a target for drugs against several liver diseases. However, the contribution of FXR in the pathogenesis of cholestasis is still not fully understood. The purpose of this study is to provide a comprehensive insight into the metabolic properties of FXR-involved cholestasis in mice. Materials and methods: In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model and FXR -/- mice were established to investigate the effect of FXR on cholestasis. The effect of FXR on liver and ileal pathology was evaluated. Simultaneously, Untargeted metabolomics combined with 16s rRNA gene sequencing analysis was applied to reveal the involvement of FXR in the pathogenesis of cholestasis. Results: The results showed that ANIT (75 mg/kg) induced marked cholestasis in WT and FXR -/- mice. It is noteworthy that FXR -/- mice developed spontaneous cholestasis. Compared with WT mice, significant liver and ileal tissue damage were found. In addition, 16s rRNA gene sequencing analysis revealed gut microbiota dysbiosis in FXR-/- mice and ANIT-induced cholestasis mice. Differential biomarkers associated with the pathogenesis of cholestasis caused by FXR knockout were screened using untargeted metabolomics. Notably, Lactobacillus &#95; johnsonii &#95;FI9785 has a high correlation with the differential biomarkers associated with the pathogenesis and progression of cholestasis caused by FXR knockout. Conclusion: Our results implied that the disorder of the intestinal flora caused by FXR knockout can also interfere with the metabolism. This study provides novel insights into the FXR-related mechanisms of cholestasis., 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 Wei, He, Zhao, Jing, Li, Chen, Zheng and Zhao.)

Astrocyte activation is key in neurodegenerative diseases. Hydrogen sulfide (H 2 S) exhibits neuroprotective effects on astrocytes, although the underlying molecular mechanism remains unclear. Here, we explored the effects of H 2 S on lipopolysaccharide (LPS)-induced astrocyte activation and astrocyte-mediated neuroinflammation. After inducing primary astrocytes via LPS exposure, H 2 S levels were altered. The generation and secretion of inflammatory mediators by astrocytes and their interrelation with P-glycoprotein (P-gp), an important transporter belonging to the ABC transporter family, were assessed. Activated astrocytes showed upregulated glial fibrillary acidic protein (GFAP) mRNA expression, and significantly increased proinflammatory factor mRNA/protein expression and release. The secretory capacity of astrocytes was reduced, with significantly decreased proinflammatory factor levels in culture supernatant after P-gp inhibitor verapamil pretreatment. The increase in the intracellular H 2 S level inhibited LPS-induced GFAP expression and P65 nuclear entry in astrocytes. mRNA expression and release of proinflammatory factors were reduced significantly, with no significant changes in cytoplasmic protein expression. S-sulfhydration levels increased significantly with the increased concentration of sodium hydrosulfide or S-adenosyl-L-methionine addition, with only moderate changes in astrocyte P-gp expression. H 2 S regulates NF-κB activation, leads to S-sulfhydration of P-gp, and inhibits the biosynthesis and secretion of proinflammatory factors by astrocytes. The regulatory effects of H 2 S on astrocytes may have clinical value for exploring new therapeutic strategies against neurodegenerative diseases., (© 2022. The Author(s).)

Objectives: Outcomes beyond 10 years for David V valve-sparing aortic root replacement (VSARR) in bicuspid aortic valve (BAV) patients have yet to be explored. We investigated long-term outcomes after BAV VSARR compared to VSARR for tricuspid aortic valve (TAV) patients., Methods: A total of 677 patients with BAV (n = 171) and TAV (n = 506) underwent VSARR between 2005 and 2020 from 2 aortic centres, excluding those with dissection, endocarditis, stenosis or prior aortic valve (AV) surgery. Multivariable Cox regression compared adjusted survival over a 12-year period. Fine and Gray competing risk regression compared risk and cumulative incidence of reoperation/reintervention. Propensity score matching created balanced groups, and landmark analysis isolated outcomes beginning 4 years postoperatively. Finally, longitudinal mixed modelling assessed AV deterioration on echocardiogram., Results: No difference was observed in 12-year survival of BAV versus TAV (propensity score matching 92.0% vs 89.9%, P = 0.97; multivariable hazard ratio 0.76, 95% confidence interval 0.34-1.69, P = 0.51). Adjusted 12-year cumulative incidence and risk of AV and/or proximal aorta reoperation/reintervention were not observed to be different (15.7% BAV vs 5.7% TAV, P = 0.37; subdistribution hazard ratio 1.54, 95% confidence interval 0.60-3.94, P = 0.36); however, landmark analysis showed increased incidence of late reoperation/reintervention in BAV versus TAV (11.7% vs 0.0%, P = 0.04). BAV was not associated with AV deterioration over time (BAV coefficient ± standard error: 0 ± 0.30, P = 1)., Conclusions: VSARR for BAV patients has excellent 12-year survival and low reoperation/reintervention rates, which were not observed to be different from TAV patients. However, higher incidence of reoperation/reintervention was observed in the late years after BAV VSARR. Our study provides key information for surgical consultation of patients with bicuspid aortopathy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Diabetic nephropathy (DN) is one of the most severe complications of diabetes. However, due to its complex pathological mechanisms, no effective therapeutic methods (other than ACEIs and ARBs) have been applied, which have been used for many years in clinical practice. Recent studies have shown that emerging therapeutics, including novel target-based pharmacotherapy, cell therapies, and dietary regulation, are leading to new hopes for DN management. This review aims to shed new light on the treatment of DN by describing the important pathological mechanisms of DN and by analysing recent advances in clinical treatment, including drug therapy, cell therapy, and dietary regulation. In pathological mechanisms, RAAS activation, AGE accumulation, and EMT are involved in inflammation, cellular stress, apoptosis, pyroptosis, and autophagy. In pharmacotherapy, several new therapeutics, including SGLT2 inhibitors, GLP-1 agonists, and MRAs, are receiving public attention. In addition, stem cell therapies and dietary regulation are also being emphasized. Herein, we highlight the importance of combining therapy and dietary regulation in the treatment of DN and anticipate more basic research or clinical trials to verify novel strategies., Competing Interests: Declaration of competing interest 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Co 3 ZnC can efficiently boost the activity of Co@N, O co-doped carbons for hydrogen evolution. The results show that moderate Co 3 ZnC plays key roles in achieving an appropriate weighted Co 3d band centre, enhancing charger transfer and thus optimizing the electrochemical active surface area. Thus, a low overpotential of ∼219 mV can drive a high current density of 1000 mA cm -2 under the favourable condition of moderate Co 3 ZnC.

Diabetic nephropathy is one of the most common complications in diabetes. It has been shown to be the leading cause of end-stage renal disease. However, due to their complex pathological mechanisms, effective therapeutic drugs other than angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which have been used for 20 years, have not been developed so far. Recent studies have shown that diabetic nephropathy is characterized by multiple signalling pathways and multiple targets, including inflammation, apoptosis, pyroptosis, autophagy, oxidative stress, endoplasmic reticulum stress and their interactions. It definitely exacerbates the difficulty of therapy, but at the same time it also brings out the chance for natural products treatment. In the most recent two decades, a large number of natural products have displayed their potential in preclinical studies and a few compounds are under invetigation in clinical trials. Hence, many compounds targeting these singals have been emerged as a comprehensive blueprint for treating strategy of diabetic nephropathy. This review focuses on the cellular and molecular mechanisms of natural prouducts that alleviate this condition, including preclinical studies and clinical trials, which will provide new insights into the treatment of diabetic nephropathy and suggest novel ideas for new drug development., Competing Interests: Declaration of Competing Interest All authors declare that there are no interest conflicts and agree to publish this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Dialysis is a well-established risk factor for morbidity and mortality after cardiovascular procedures. However, little is known regarding the outcomes of proximal aortic surgery in this high-risk cohort., Methods: Perioperative (in-hospital or 30-day mortality) and 10-year outcomes were analyzed for all the patients who underwent open proximal aortic repair with the diagnosis of nonruptured thoracic aortic aneurysm (aneurysm, n = 325) or type A aortic dissection (dissection, n = 461) from 1987 to 2015 using the US Renal Data System database., Results: In patients with aneurysm, perioperative mortality was 12.6%. The 10-year mortality was 81% ± 3%. Age 65 years or more (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.03 to 1.78; P = .03), chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.01-2.82; P = .047), and Black race (HR, 1.46; 95% CI, 1.09-1.97; P = .01) were independently associated with worse 10-year mortality. In patients with dissection, perioperative mortality was 24.3% and 10-year mortality was 87.9% ± 2.2%. Age 65 years or more (HR, 1.49; 95% CI, 1.19-1.86; P < .001), congestive heart failure (HR, 1.39; 95% CI, 1.11-2.57; P = .004), and diabetes mellitus as the cause of dialysis (HR, 1.75; 95% CI, 1.2-2.57; P = .004) were independently associated with worse 10-year mortality. Black race (HR, 0.74; 95% CI, 0.6-0.92; P = .008) was associated with a better outcome., Conclusions: We described challenging perioperative and 10-year outcomes for dialysis patients undergoing proximal aortic repair. The present study suggests the need for careful patient selection in the elective repair of proximal aortic aneurysm for dialysis-dependent patients, whereas it affirms the feasibility of emergency surgery for acute type A aortic dissections., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Surgical treatment for congenitally corrected transposition of the great arteries is widely debated, with both physiologic repair and anatomic repair holding advantages and disadvantages. This meta-analysis, which includes 44 total studies consisting of 1857 patients, compares mortality at different time points (operative, in-hospital, and post-discharge), reoperation rates, and postoperative ventricular dysfunction between these two categories of procedures. Although anatomic and physiologic repair had similar operative and in-hospital mortality, anatomic repair patients had significantly less post-discharge mortality (6.1% vs 9.7%; P  = .006), lower reoperation rates (17.9% vs 20.6%; P  < .001), and less postoperative ventricular dysfunction (16% vs 43%; P  < .001). When anatomic repair patients were subdivided into those who had atrial and arterial switch versus those who had atrial switch with Rastelli, the double switch group had significantly lower in-hospital mortality (4.3% vs 7.6%; P  = .026) and reoperation rates (15.6% vs 25.9%; P  < .001). The results of this meta-analysis suggest a protective benefit of favoring anatomic repair over physiologic repair.