Effect of preoperative immunonutrition on postoperative short-term clinical outcomes in patients with gastric cancer cachexia: a prospective randomized controlled trial.

BACKGROUND: Although current guidelines(ESPEN guideline: Clinical nutrition in surgery and other guidelines) recommend preoperative immunonutrition for cachectic gastric cancer patients, the strength of the recommendation is weak, and the level of evidence is low. The benefits of preoperative immunonutrition still remain controversial. PATIENTS AND METHODS: 112 patients with gastric cancer cachexia were enrolled in the study and randomly assigned in a 1:1 ratio to receive either preoperative enteral immunonutrition support (IN, n = 56) or standard enteral nutrition support (SEN, n = 56). The primary endpoint was the incidence of infectious complications, and the secondary endpoints included the nutritional indicators, inflammatory markers, immune parameters, postoperative recovery and complications and gastrointestinal intolerance reactions. RESULTS: The incidence of postoperative infectious complications(P = 0.040) and overall complications (P = 0.049)was significantly lower in the IN group compared to the SEN group. In terms of laboratory inflammatory indexes, patients in the IN group demonstrated significantly lower levels of white blood cells (WBC), C-reactive protein (CRP), and interleukin-6 (IL-6), as well as higher levels of lymphocytes (LYMPH) and immunoglobulin A (IgA), compared to patients in the SEN group, with statistically significant differences. In terms of clinical outcomes, the IN group had a shorter duration of antibiotic use (P = 0.048), shorter hospital stay (P = 0.018), and lower total hospital costs (P = 0.034) compared to the SEN group. The IN group also experienced significantly less weight loss after surgery (P = 0.043). CONCLUSION: Preoperative administration of immunonutrition formula has a positive impact on the incidence of infectious complications in patients with gastric cancer cachexia after surgery. It improves patients' inflammatory and immune status, shortens hospital stays, and reduces healthcare costs. Preoperative use of immunonutrition may contribute to the improvement of prognosis in this high-risk population.

Bioinformatics and experimental analyses of glutamate receptor and its targets genes in myocardial and cerebral ischemia.

BACKGROUND: There is a mutual hemodynamic and pathophysiological basis between the heart and brain. Glutamate (GLU) signaling plays an important role in the process of myocardial ischemia (MI) and ischemic stroke (IS). To further explore the common protective mechanism after cardiac and cerebral ischemic injuries, the relationship between GLU receptor-related genes and MI and IS were analyzed. RESULTS: A total of 25 crosstalk genes were identified, which were mainly enriched in the Toll-like receptor signaling pathway, Th17 cell differentiation, and other signaling pathways. Protein-protein interaction analysis suggested that the top six genes with the most interactions with shared genes were IL6, TLR4, IL1B, SRC, TLR2, and CCL2. Immune infiltration analysis suggested that immune cells such as myeloid-derived suppressor cells and monocytes were highly expressed in the MI and IS data. Memory B cells and Th17 cells were expressed at low levels in the MI and IS data; molecular interaction network construction suggested that genes such as JUN, FOS, and PPARA were shared genes and transcription factors; FCGR2A was a shared gene of MI and IS as well as an immune gene. Least absolute shrinkage and selection operator logistic regression analysis identified nine hub genes: IL1B, FOS, JUN, FCGR2A, IL6, AKT1, DRD4, GLUD2, and SRC. Receiver operating characteristic analysis revealed that the area under the curve of these hub genes was > 65% in MI and IS for all seven genes except IL6 and DRD4. Furthermore, clinical blood samples and cellular models showed that the expression of relevant hub genes was consistent with the bioinformatics analysis. CONCLUSIONS: In this study, we found that the GLU receptor-related genes IL1B, FOS, JUN, FCGR2A, and SRC were expressed in MI and IS with the same trend, which can be used to predict the occurrence of cardiac and cerebral ischemic diseases and provide reliable biomarkers to further explore the co-protective mechanism after cardiac and cerebral ischemic injury.

Effect of minimally invasive versus conventional aortic root replacement on transfusion and postoperative wound complications in patients: A meta-analysis.

We examined whether small incision aortic root replacement could reduce the amount of blood transfusion during operation and the risk of postoperative complications. An extensive e-review of the 4 main databases (PubMed, Cochrane, Web of Science and EMBASE) was carried out to determine all the published trials by July 2023. The search terms used were associated with partial versus full sternotomy and aortic root. This analysis only included the study articles that compared partial and full sternotomy. After excluding articles based on titles or abstracts, selected full-text articles had reference lists searched for any potential further articles. We analysed a total of 2167 subjects from 10 comparable trials. The minimally invasive aortic root graft in breastbone decreased the duration of hospitalization (MD, -2.58; 95% CI, -3.15, -2.01, p < 0.0001) and intraoperative red blood cell transfusion (MD, -1.27; 95% CI, -2.34, -0.19, p = 0.02). However, there were no significant differences in wound infection (OR, 0.88; 95% CI, 0.16, 4.93, p = 0.88), re-exploration for bleeding (OR, 0.96; 95% CI, 0.60, 1.53, p = 0.86), intraoperative blood loss (MD, -259.19; 95% CI, -615.11, 96.73, p = 0.15) and operative time (MD, -7.39; 95% CI, -19.10, 4.32, p = 0.22); the results showed that the microsternotomy did not differ significantly from that of the routine approach. Small sternotomy may be an effective and safe substitute for the treatment of the aorta root. Nevertheless, the wide variety of data indicates that larger, well-designed studies are required to back up the current limited literature evidence showing a benefit in terms of complications like postoperative wound infections or the volume of intraoperative red blood cell transfusion.

Death-Associated Protein Kinase 1 Regulates Oxidative Stress in Cardiac Ischemia Reperfusion Injury.

To investigate the role of death-associated protein kinase 1 (DAPK1) in cardiac ischemia reperfusion (I/R) in vivo, and to determine whether the process is regulated by nuclear factor E2-associated factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (keap1). Western blot analysis was used to analyze the expression level of DAPK1 at different time points. The hemodynamic parameters and apoptosis of cardiac I/R injury in vivo were observed using DAPK1 knockdown lentivirus. The oxidative stress of I/R in vivo was observed. Nrf2-IN-1 was applied to determine whether the role of DAPK was regulated by Nrf2/keap1. Results show that the DAPK1 expression increased to a peak after 12 h of I/R. Moreover, the level of DAPK1 expression decreased, as determined by Western blot, after DAPK1 knockdown lentivirus administration. In addition, the hemodynamic parameters of the DAPK1-shRNA group were improved. The apoptosis level (Bax, Bcl-2, cleaved caspase-3, and TUNEL staining) increased in the I/R group, and the DAPK1 knockdown lentivirus could reverse the injury. The oxidative stress indices (CK, cTn-1, CAT, LDH, GSH-PX, MDA, and SOD) also improved in the DAPK1-shRNA group. Finally, Nrf2-IN-1 inhibited tNrf2, nNrf2, and Bcl-2 expression and boosted keap1, Bax, and cleaved caspase-3 expression after DAPK1 lentivirus administration. These findings suggest that DAPK1 may regulate the oxidative stress in cardiac I/R, and Nrf2/keap1 may be the downstream target factor of DAPK1.

Resveratrol against Cardiac Fibrosis: Research Progress in Experimental Animal Models.

Cardiac fibrosis is a heterogeneous disease, which is characterized by abundant proliferation of interstitial collagen, disordered arrangement, collagen network reconstruction, increased cardiac stiffness, and decreased systolic and diastolic functions, consequently developing into cardiac insufficiency. With several factors participating in and regulating the occurrence and development of cardiac fibrosis, a complex molecular mechanism underlies the disease. Moreover, cardiac fibrosis is closely related to hypertension, myocardial infarction, viral myocarditis, atherosclerosis, and diabetes, which can lead to serious complications such as heart failure, arrhythmia, and sudden cardiac death, thus seriously threatening human life and health. Resveratrol, with the chemical name 3,5,4'-trihydroxy-trans-stilbene, is a polyphenol abundantly present in grapes and red wine. It is known to prevent the occurrence and development of cardiovascular diseases. In addition, it may resist cardiac fibrosis through a variety of growth factors, cytokines, and several cell signaling pathways, thus exerting a protective effect on the heart.

NMDA receptor-driven calcium influx promotes ischemic human cardiomyocyte apoptosis through a p38 MAPK-mediated mechanism.

N-methyl-D-aspartate receptor (NMDAR) activity plays a key role in cerebral ischemia. Although NMDAR is also expressed in cardiomyocytes, little research has been performed on NMDAR activity in myocardial ischemia. Here, using an in vitro oxygen-glucose deprivation (OGD) cardiomyocyte model, we evaluated the effects of NMDAR activity upon calcium influx, viability, apoptosis, and investigated the roles of several key mitogen-activated protein kinases (MAPKs). Primary human neonatal cardiomyocytes were cultured under OGD conditions to mimic in vivo ischemic conditions. Enhancing NMDAR activity via NMDA significantly promoted calcium influx, decreased cell viability, increased apoptosis, and enhanced p38 MAPK phosphorylation in OGD cardiomyocytes (all P < 0.05). These effects were rescued by several calcium-channel blockers (ie, MK-801, La3+ , Gap26 peptide, 18ß-glycyrrhetinic acid) but most potently rescued via the NMDAR-specific antagonist MK-801 or removal of extracellular free calcium (all P < 0.05). Knocking-down p38 MAPK activity by small-molecule inhibition or genetic methods significantly increased cell viability and reduced apoptosis (all P < 0.05). Enhancing p38 MAPK activity abolished MK-801's apoptosis-reducing effects in a p38 MAPK-dependent manner. In conclusion, NMDAR-driven calcium influx promotes apoptosis in ischemic human cardiomyocytes, an effect which can be attributed to enhanced p38 MAPK activity.

N-Methyl-D-Aspartate Receptor-Driven Calcium Influx Potentiates the Adverse Effects of Myocardial Ischemia-Reperfusion Injury Ex Vivo.

BACKGROUND: Despite the adverse effects of N-methyl-D-aspartate receptor (NMDAR) activity in cardiomyocytes, no study has yet examined the effects of NMDAR activity under ex vivo ischemic-reperfusion (I/R) conditions. Therefore, our aim was to comprehensively evaluate the effects of NMDAR activity through an ex vivo myocardial I/R rat model. METHODS: Isolated rat hearts were randomly segregated into 6 groups (n = 20 in each group): (1) an untreated control group; (2) a NMDA-treated control group; (3) an untreated I/R group; (4) an I/R+NMDA group treated with NMDA; (5) an I/R+NMDA+MK-801 group treated with NMDA and the NMDAR inhibitor MK-801; and (6) an I/R+NMDA+[Ca]-free group treated with NMDA and [Ca]-free buffer. The 4 I/R groups underwent 30 minutes of ischemia followed by 50 minutes of reperfusion. Left ventricular pressure signals were analyzed to assess cardiac performance. Myocardial intracellular calcium levels ([Ca]i) were assessed in isolated ventricular cardiomyocytes. Creatine kinase, creatine kinase isoenzyme MB, lactate dehydrogenase, cardiac troponin I, and cardiac troponin T were assayed from coronary effluents. TTC and TUNEL staining were used to measure generalized myocardial necrosis and apoptosis levels, respectively. Western blotting was applied to assess the phosphorylation of PKC-δ, PKC-ε, Akt, and extracellular signal-regulated kinase. RESULTS: Enhanced NMDAR activity under control conditions had no significant effects on the foregoing variables. In contrast, enhanced NMDAR activity under I/R conditions produced significant increases in [Ca]i levels (∼1.2% increase), significant losses in left ventricular function (∼5.4% decrease), significant multi-fold increases in creatine kinase, creatine kinase isoenzyme MB, lactate dehydrogenase, cardiac troponin I, and cardiac troponin T, significant increases in generalized myocardial necrosis (∼36% increase) and apoptosis (∼150% increase), and significant multi-fold increases in PKC-δ, PKC-ε, Akt, and extracellular signal-regulated kinase phosphorylation (all P < 0.05). These adverse effects were rescued by the NMDAR inhibitor MK-801 or [Ca]-free buffer (all P < 0.05). CONCLUSIONS: NMDAR-driven calcium influx potentiates the adverse effects of myocardial I/R injury ex vivo.

EEG components of inhibitory control ability in internet gaming disorder: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Inhibitory control ability is a crucial cognitive function that enables individuals to regulate their impulses and behaviors in a goal-directed manner. However, with the increasing prevalence of internet gaming disorder (IGD), there has been growing concern about the impact of excessive gaming on inhibitory control ability. Despite the accumulating evidence on this topic, the research conclusion on whether people with IGD have worse inhibition control ability than healthy controls remains inconsistent, and the lack of effective electroencephalography prediction indicators further complicates this issue. To address this research gap, the present study aimed to investigate whether N2 event-related potential (ERP) and P3 ERP components could serve as reliable indicators of inhibitory control ability in individuals with IGD. METHODS: To achieve this goal, a systematic literature search was conducted in several databases, including Web of Science, ScienceDirect (EBSCO), SpringerLink, PubMed, and Wiley Online Library. The inclusion criteria were strictly implemented to ensure the quality of the studies included in the meta-analysis. In the end, a total of 5 studies, with 139 participants diagnosed with IGD and 139 healthy controls, were included in the analysis. RESULTS: Meta-analysis revealed large effect sizes of N2 and P3 amplitudes in individuals with IGD, indicating that these two ERP components could be potential indicators of inhibitory control ability. Specifically, the N2 and P3 amplitude was significantly larger in individuals with IGD than in the healthy control group, suggesting deficits in inhibitory control function and increased impulsivity in the IGD group. In the inhibition control task, the IGD group required more cognitive resources to suppress impulsive responses. CONCLUSION: Overall, the findings of this meta-analysis shed light on the potential use of N2 and P3 amplitudes as reliable indicators of inhibitory control ability in individuals with IGD. The results provide crucial insights into the neural mechanisms underlying inhibitory control impairment in IGD, which could inform the development of effective interventions for this condition. Further research is needed to explore the functional significance of these ERP components and their potential clinical applications in the diagnosis and treatment of IGD.

Modified aortic root anastomosis and the frozen elephant trunk technique using an integrated tetra-furcate graft to repair type A aortic dissection.

BACKGROUND: Surgery is the preferred treatment for acute Stanford type A aortic dissection (STAAD); however, due to the complexity of the procedure, cardiac ischaemia and cardiopulmonary bypass (CPB) time are longer than general heart surgery, leading to complications. In this present study, we used an integrated tetra-furcate graft for both modified aortic root and distal arch anastomoses (frozen elephant trunk technique, [FET]), and investigated postoperative outcomes associated with this technique in patients with STAAD. METHODS: We included a total of 140 patients who underwent total arch replacement and FET between January 2019 and June 2022 in the present study, 41 patients who underwent the modified technique, and 99 who underwent the graft eversion technique. We subsequently analyzed the perioperative outcomes to compare the differences between the two techniques. RESULTS: There were no statistically significant differences between the two groups in regards to the preoperative characteristics; however, the intraoperative CPB, cardiac ischaemia, and operation times of the modified technique group were significantly shorter than those of the eversion technique group (P = 0.02, P = 0.01, and P = 0.04, respectively), as were postoperative hypoxaemia, intensive care unit (ICU) stay, and ventilation times (P = 0.04, P = 0.03, and P = 0.04, respectively). Additionally, the degree of postoperative bilirubin elevation was milder in the modified technique group (P = 0.002 for direct bilirubin and P = 0.01 for indirect bilirubin). CONCLUSIONS: The modified anastomosis technique can significantly shorten CPB, cardiac ischemia, and operation times, and reduce the intraoperative FFP transfusion and postoperative hypoxemia times. This modified technique, therefore, is worth utilizing for patients with STAAD.

The association and clinicopathological significance of Integrin alphavbeta6 and Rac1 expression in gastric carcinoma.

Background: The present study investigate the expression and correlation of ITGB6 and Rac1 proteins in gastric cancer tissues. By exploring the clinical significance and functions of these proteins, we aimed to gain further insights into the mechanisms underlying gastric cancer development. Patients and methods: In this study, a total of 198 patients diagnosed with gastric cancer and who underwent gastrectomy between July 2010 to October 2012 were included. The median follow-up time was 52.00 months. To evaluate the factors influencing overall survival, Kaplan-Meier survival curve analysis and Cox regression analysis were conducted. Furthermore, an independent prognostic factor-based nomogram was constructed and validated to predict survival outcomes in gastric cancer patients. In addition, in vitro experiments including CCK8 and Transwell assays were conducted to explore the roles of ITGB6 and Rac1 in gastric cancer. Results: The expression levels of ITGB6 and Rac1 in gastric cancerous and paraneoplastic tissues were detected by immunohistochemistry. The correlation and clinical significance of the two proteins were also investigated. ITGB6 expression showed significant associations with tumor size (P=0.030), pathological grading (P=0.013), location (P=0.031), N stage (P=0.002), and clinical stage (P=0.002). Additionally, we found that tumor size (P=0.013), tumor's anatomical location (P=0.031), N stage (P=0.002), clinical stage (P=0.035), and survival status (P<0.001) were significantly associated with the expression of Rac1. ITGB6 was moderately correlated with Rac1 (r=0.285, P<0.001). Both the Kaplan-Meier survival analysis and Cox regression model analysis demonstrated that the presence of positive expression of ITGB6 and Rac1 proteins served as independent prognostic factors for gastric cancer. These findings highlight the potential of ITGB6 and Rac1 as valuable markers for predicting the prognosis of gastric cancer patients (HR=2.212 P<0.001 and HR=2.073 P=0.001), with a significant poorer trend for 5-year survival (P<0.0001, respectively, the log-rank test). Additionally, subsequent in vitro experiments preliminarily demonstrated that ITGB6 and Rac1 promoted the proliferation, migration and invasion of gastric cancer cells, and ITGB6 may functions via targeting Rac1. Conclusion: ITGB6 and Rac1 are indicators of poor prognosis and tumor progression in gastric cancer patients. The potential signaling pathways associated with both may provide useful targets for the prevention and treatment of gastric cancer.

Enhancing milk quality and modulating rectal microbiota of dairy goats in starch-rich diet: the role of bile acid supplementation.

BACKGROUND: Diets rich in starch have been shown to increase a risk of reducing milk fat content in dairy goats. While bile acids (BAs) have been used as a lipid emulsifier in monogastric and aquatic animals, their effect on ruminants is not well understood. This study aimed to investigate the impact of BAs supplementation on various aspects of dairy goat physiology, including milk composition, rumen fermentation, gut microbiota, and BA metabolism. RESULTS: We randomly divided eighteen healthy primiparity lactating dairy goats (days in milk = 100 ± 6 d) into two groups and supplemented them with 0 or 4 g/d of BAs undergoing 5 weeks of feeding on a starch-rich diet. The results showed that BAs supplementation positively influenced milk yield and improved the quality of fatty acids in goat milk. BAs supplementation led to a reduction in saturated fatty acids (C16:0) and an increase in monounsaturated fatty acids (cis-9 C18:1), resulting in a healthier milk fatty acid profile. We observed a significant increase in plasma total bile acid concentration while the proportion of rumen short-chain fatty acids was not affected. Furthermore, BAs supplementation induced significant changes in the composition of the gut microbiota, favoring the enrichment of specific bacterial groups and altering the balance of microbial populations. Correlation analysis revealed associations between specific bacterial groups (Bacillus and Christensenellaceae R-7 group) and BA types, suggesting a role for the gut microbiota in BA metabolism. Functional prediction analysis revealed notable changes in pathways associated with lipid metabolism, suggesting that BAs supplementation has the potential to modulate lipid-related processes. CONCLUSION: These findings highlight the potential benefits of BAs supplementation in enhancing milk production, improving milk quality, and influencing metabolic pathways in dairy goats. Further research is warranted to elucidate the underlying mechanisms and explore the broader implications of these findings.

LILRB4 knockdown inhibits aortic dissection development by regulating pyroptosis and the JAK2/STAT3 signaling pathway.

Aortic dissection (AD) is a life-threatening condition with a high mortality rate and without effective pharmacological therapies. Our previous study illustrated that leukocyte immunoglobulin-like receptor B4 (LILRB4) knockdown promoted the contractile phenotypic switch and apoptosis of AD cells. This study aimed to further investigate the role of LILRB4 in animal models of AD and elucidate its underlying molecular mechanisms. Animal models of AD were established using 0.1% beta-aminopropionitrile and angiotensin II and an in vitro model was developed using platelet-derived growth factor BB (PDGF-BB). The effects of LILRB4 knockdown on histopathological changes, pyroptosis, phenotype transition, extracellular matrix (ECM), and Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) pathways were assessed using a series of in vivo and in vitro assays. The effects of the JAK2 inhibitor AG490 on AD cell function, phenotypic transition, and ECM were explored. LILRB4 was highly expressed in AD and its knockdown increased survival rate, reduced AD incidence, and alleviated histopathological changes in the AD mouse model. Furthermore, LILRB4 knockdown promoted contractile phenotype switch, stabilized the ECM, and inhibited pyroptosis. Mechanistically, LILRB4 knockdown inhibited the JAK2/STAT3 signaling pathway. JAK2 inhibitor AG490 inhibited cell viability and migration, enhanced apoptosis, induced G0/G1 cell cycle arrest, and suppressed S-phase progression in PDGF-BB-stimulated human aortic smooth muscle cells. LILRB4 knockdown suppresses AD development by inhibiting pyroptosis and the JAK2/STAT3 signaling pathway.

Case report: Surgery combined with extracorporeal membrane oxygenation for a patient with type A aortic dissection complicated with myocardial infarction after percutaneous coronary intervention.

Background: Aortic dissection (AD) is a severe cardiovascular disease characterized by aortic rupture, aortic valve insufficiency, aortic branch lumen stenosis, and occlusion. Acute ST-segment elevation myocardial infarction may be the primary manifestation when aortic dissection affects the coronary artery, leading to delayed or missed diagnosis of aortic dissection, and preventing patients from receiving timely and comprehensive treatment. Simultaneous aortic repair and coronary artery bypass grafting surgery are controversial because of their high mortality rates. Personalized and optimal treatment plans for patients should be taken seriously based on their different conditions and treatment options. Case presentation: A 42-year-old man who experienced 1 h of persistent precordialgia was admitted to a local second-level hospital for emergency treatment. Electrocardiogram (ECG) showed evidence of ST-segment elevation, and myocardial enzyme levels were CK-MB 18.35 ng/ml and troponin 0.42 ng/ml. The patient was treated for acute myocardial infarction (AMI) and urgently sent to the interventional catheter room. Coronary angiography showed stenosis of the starting part of the right coronary artery trunk. Thus, stent implantation was performed, and the stenosis section recovered patency; however, postoperative precordialgia was not alleviated. Computed tomography angiography (CTA) revealed a type A AD. The patient was immediately transferred to a higher-level hospital, underwent emergency surgery with cardiopulmonary bypass (CPB) ascending aorta replacement, SUN's procedure (total arch replacement and stented elephant trunk implantation), and simultaneous implantation of extracorporeal membrane oxygenation (ECMO), and regained consciousness within intensive care unit care. ECMO was discontinued when hemodynamics stabilized. The patient ultimately recovered well and was discharged. Conclusion: This case demonstrated that precordialgia is not limited to myocardial infarction but may also be accompanied by aortic dissection. Percutaneous coronary intervention (PCI) can timely and effectively restore coronary artery perfusion, strive for the opportunity of aortic repair surgery, and can overcome pump failure caused by myocardial infarction, cardiopulmonary bypass, heart block time, and myocardial ischemia-reperfusion injury. Personalized treatment is crucial for patients with complex type A aortic dissection.

Rumen bacterial cluster identification and its influence on rumen metabolites and growth performance of young goats.

Enterotypes, which are defined as bacterial clusters in the gut microbiome, have been found to have a close relationship to host metabolism and health. However, this concept has never been used in the rumen, and little is known about the complex biological relationships between ruminants and their rumen bacterial clusters. In this study, we used young goats (n = 99) as a model, fed them the same diet, and analyzed their rumen microbiome and corresponding bacterial clusters. The relationships between the bacterial clusters and rumen fermentation and growth performance in the goats were further investigated. Two bacterial clusters were identified in all goats: the P-cluster (dominated by genus Prevotella, n = 38) and R-cluster (dominated by Ruminococcus, n = 61). Compared with P-cluster goats, R-cluster goats had greater growth rates, concentrations of propionate, butyrate, and 18 free amino acids¸ and proportion of unsaturated fatty acids, but lower acetate molar percentage, acetate to propionate ratio, and several odd and branched chain and saturated fatty acids in rumen fluid (P < 0.05). Several members of Firmicutes, including Ruminococcus, Oscillospiraceae NK4A214 group, and Christensenellaceae R-7 group were significantly higher in the R-cluster, whereas Prevotellaceae members, such as Prevotella and Prevotellaceae UCG-003, were significantly higher in P-cluster (P < 0.01). Co-occurrence networks showed that R-cluster enriched bacteria had significant negative correlations with P-cluster enriched bacteria (P < 0.05). Moreover, we found the concentrations of propionate, butyrate and free amino acids, and the proportions of unsaturated fatty acids were positively correlated with R-cluster enriched bacteria (P < 0.05). The concentrations of acetate, acetate to propionate ratio, and the proportion of odd and branched chain and saturated fatty acids were positively correlated with P-cluster enriched bacteria (P < 0.05). Overall, our results indicated that rumen bacterial clusters can influence rumen fermentation and growth performance of young goats, which may shed light on modulating the rumen microbiome in early life to improve the growth performance of ruminant animals.

Litter size influences rumen microbiota and fermentation efficiency, thus determining host early growth in goats.

Introduction: Multiple litters are accompanied by low birth weight, low survival rates, and growth rates in goats during early life. Regulating rumen microbiota structure can indirectly or directly affect host metabolism and animal growth. However, the relationship between high litter size and rumen microbiome, rumen fermentation, and growth performance in goat kids is unclear. Methods: In the present study, thirty 6-month-old, female goats were investigated, of which 10 goats were randomly chosen from single, twin and triplet goats respectively, and their birth weight was recorded. From birth, all goats were subjected to the same feed and management practices. Individual weaning and youth body weight were measured, and the rumen fluid samples were collected to characterize the bacterial communities and to determine the ruminal volatile fatty acids (VFA), free amino acids (AA), and free fatty acids (FA) concentration of those young goats. Results and Discussion: Compared with the single and twin goats, triplet goats have lower weaning and youth body weight and average daily gain (ADG). Ruminal propionate, butyrate, and total VFA were decreased in triplet goats. Meanwhile, ruminal AA, such as branched chain amino acids (BCAA), essential amino acids (EAA), unsaturated fatty acids (UFA), and monounsaturated fatty acids (MUFA) were decreased, while saturated fatty acids (SFA) and odd and branched chain fatty acids (OBCFA) were increased in triplet goats. Our results also revealed that litter size significantly affected the rumen bacterial communities, and triplet goats had a lower the Firmicutes: Bacteroidota ratio, the abundance of Firmicutes phylum, Rikenellaceae family, and Rikenellaceae RC9 gut group, and had a higher proportion of Prevotellaceae family, and several genera of Prevotellaceae, such as Prevotella, and unclassified f Prevotellaceae. Furthermore, Spearman's correlation network analysis showed that the changes in the rumen bacteria were associated with changes in rumen metabolites. In conclusion, this study revealed that high litter size could bring disturbances to the microbial communities and decrease the rumen fermentation efficiency and growth performance, which can be utilized to better understand variation in microbial ecology that will improve growth performance in triplet goats.

Microbial Enterotypes Shape the Divergence in Gut Fermentation, Host Metabolism, and Growth Rate of Young Goats.

Enterotypes can be useful tools for studying the gut microbial community landscape, which is thought to play a crucial role in animal performance. However, few studies have been carried out to identify enterotypes and their associations with growth performance in young goats. In this study, two enterotypes were categorized in 76 goats: cluster 1 (n = 39) and cluster 2 (n = 37). Compared to cluster 2, cluster 1 had greater growth rates, the concentrations of acetate, propionate, valerate, and total volatile fatty acids (VFA) in the gut. Several serum glycolipid metabolism parameters, including glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were also increased in cluster 1, while serum IgG was decreased in cluster 1. Using α-diversity analysis, we found a microbiome with lower richness and diversity in cluster 1. Some gut bacteria, including Succinivibrio and several members of the Prevotellaceae family, were enriched in cluster 1, while Christensenellaceae R-7 group, Romboutsia, and Clostridium sensu stricto 1 were enriched in cluster 2. A co-occurrence network analysis revealed that the differential interaction patterns existed in two enterotypes, and microbial function prediction suggested that some nutrient metabolism-related pathways, including amino acid biosynthesis and starch and sucrose metabolism, were enriched in cluster 1. Furthermore, a correlation analysis showed that enterotype-related bacteria were closely correlated with gut fermentation, serum biochemistry, and growth rate. Overall, our data provide a new perspective for understanding enterotype characteristics in goats, offering insights into important microbial interaction mechanisms for improving the growth performance of ruminant animals. IMPORTANCE The intricate relationships between a host animal and its resident gut microbiomes provide opportunities for dealing with energy efficiency and production challenges in the livestock industry. Here, we applied the enterotype concept to the gut microbiome in young goats and found that it can be classified into two enterotypes which are apparently associated with divergences in gut fermentation, blood biochemistry, and goat growth rates. The microbial co-occurrence networks and function predictions differed between the two enterotypes, suggesting that the formation of host phenotype may be modified by different bacterial features and complex bacterial interactions. The characteristics of enterotypes related to growth performance in young goats may enable us to improve long-term production performance in goat industry by modulating the gut microbiome during early life.

Aortic arch branch-prioritized reconstruction for type A aortic dissection surgery.

Background: Acute Stanford type A aortic dissection (STAAD) is a fatal condition requiring urgent surgical intervention. Owing to the complexity of the surgical process, various complications, such as neurological disorders, are common. In this study, we prioritized the reconstruction of aortic arch branches during surgery and investigated the association between prioritizing the branches and the postoperative outcomes of patients with STAAD. Methods: Ninety-seven patients were included in the observational study and underwent total arch replacement and frozen elephant trunk technique between January 2018 and June 2021. Of these, 35 patients underwent the branch-priority technique, and 62 patients underwent the classic technique. By analyzing the perioperative outcomes, we compared the differences between the two techniques. Results: The branch priority group had significantly shorter cardiopulmonary bypass and ventilator times and earlier postoperative wake-up times than the classic group. Additionally, the ICU stay time was shorter, with a significant decrease in neurological complications and 24 h drainage in the branch priority group compared to the classic group. Conclusion: The branch priority technique can effectively provide better brain protection, resulting in earlier awakening of patients after surgery, reduced neurological complications, shorter ventilation time and decreased ICU hospitalization time. Therefore, it is recommended for use in aortic dissection surgeries.

Multi-omics revealed the long-term effect of ruminal keystone bacteria and the microbial metabolome on lactation performance in adult dairy goats.

BACKGROUND: The increased growth rate of young animals can lead to higher lactation performance in adult goats; however, the effects of the ruminal microbiome on the growth of young goats, and the contribution of the early-life rumen microbiome to lifelong growth and lactation performance in goats has not yet been well defined. Hence, this study assessed the rumen microbiome in young goats with different average daily gains (ADG) and evaluated its contribution to growth and lactation performance during the first lactation period. RESULTS: Based on monitoring of a cohort of 99 goats from youth to first lactation, the 15 highest ADG (HADG) goats and 15 lowest ADG (LADG) goats were subjected to rumen fluid microbiome and metabolome profiling. The comparison of the rumen metagenome of HADG and LADG goats revealed that ruminal carbohydrate metabolism and amino acid metabolism function were enhanced in HADG goats, suggesting that the rumen fluid microbiome of HADG goats has higher feed fermentation ability. Co-occurrence network and correlation analysis revealed that Streptococcus, Candidatus Saccharimonans, and Succinivibrionaceae UCG-001 were significantly positively correlated with young goats' growth rates and some HADG-enriched carbohydrate and protein metabolites, such as propionate, butyrate, maltoriose, and amino acids, while several genera and species of Prevotella and Methanogens exhibited a negative relationship with young goats' growth rates and correlated with LADG-enriched metabolites, such as rumen acetate as well as methane. Additionally, some functional keystone bacterial taxa, such as Prevotella, in the rumen of young goats were significantly correlated with the same taxa in the rumen of adult lactation goats. Prevotella also enriched the rumen of LADG lactating goats and had a negative effect on rumen fermentation efficiency in lactating goats. Additional analysis using random forest machine learning showed that rumen fluid microbiota and their metabolites of young goats, such as Prevotellaceae UCG-003, acetate to propionate ratio could be potential microbial markers that can potentially classify high or low ADG goats with an accuracy of prediction of > 81.3%. Similarly, the abundance of Streptococcus in the rumen of young goats could be predictive of milk yield in adult goats with high accuracy (area under the curve 91.7%). CONCLUSIONS: This study identified the keystone bacterial taxa that influence carbohydrate and amino acid metabolic functions and shape the rumen fluid microbiota in the rumen of adult animals. Keystone bacteria and their effects on rumen fluid microbiota and metabolome composition during early life can lead to higher lactation performance in adult ruminants. These findings suggest that the rumen microbiome together with their metabolites in young ruminants have long-term effect on feed efficiency and animal performance. The fundamental knowledge may allow us to develop advanced methods to manipulate the rumen microbiome and improve production efficiency of ruminants. Video Abstract.

Intraoperative performance and outcomes of robotic and laparoscopic total gastrectomy for gastric cancer: A high-volume center retrospective propensity score matching study.

BACKGROUND: Studies on robotic total gastrectomy (RTG) are currently limited. This study aimed to compare the intraoperative performance as well as short- and long-term outcomes of RTG and laparoscopic total gastrectomy (LTG). METHODS: A total of 969 patients underwent robotic (n = 161) or laparoscopic (n = 636) total gastrectomy between October 2014 and October 2021. The two groups of patients were matched 1:3 using the propensity score matching (PSM) method. The intraoperative performance as well as short- and long-term outcomes of the robotic (n = 147) and the laparoscopic (n = 371) groups were compared. RESULTS: After matching, the estimated intraoperative blood loss was lower (80.51 ± 68.77 vs. 89.89 ± 66.12, p = 0.008), and the total number of lymph node dissections was higher (34.74 ± 12.44 vs. 29.83 ± 12.22, p < 0.001) in the RTG group compared with the LTG group. More lymph node dissections at the upper edge of the pancreas were performed in the RTG group than in the LTG (12.59 ± 4.18 vs. 10.33 ± 4.58, p = 0.001). Additionally, postoperative recovery indicators and laboratory data were greater in the RTG group than those in the LTG group, while postoperative complications were comparable between the two groups (19.0% vs. 18.9%, p = 0.962). For overweight or obese patients with body mass indexes (BMIs) ≥25, certain clinical outcomes of the RTG remained advantageous, and no significant differences in three-year overall survival (OS) or relapse-free survival (RFS) were observed. CONCLUSIONS: Robotic total gastrectomy demonstrated better intraoperative performance, could improve the short-term clinical outcomes of patients, and was more conducive to patient recovery. However, the long-term efficacies of the two approaches were similar. Robotic surgical systems may reduce surgical stress responses in patients, allowing them to receive postoperative chemotherapy sooner.

TAK-242 protects against oxygen-glucose deprivation and reoxygenation-induced injury in brain microvascular endothelial cells and alters the expression pattern of lncRNAs.

Background: Deep hypothermic circulatory arrest (DHCA) is a technique used during the surgical treatment of aneurysms of the thoracic aorta in adult patients, and complex congenital heart disease in neonates. And brain microvascular endothelial cells (BMECs) are essential components of the cerebrovascular network and participate in maintaining the blood-brain barrier (BBB) and brain function. In our previous study, we found that oxygen-glucose deprivation and reoxygenation (OGD/R) activated Toll-like receptor 4 (TLR4) signaling in BMECs, and induced pyroptosis and inflammation. In this study, we further investigated the potential mechanism of ethyl(6R)-6-[N-(2-Chloro-4-fluorophenyl) sulfamoyl] cyclohex-1-ene-1-carboxylate (TAK-242) on BMECs under OGD/R, as in patients with sepsis, the TAK-242 was tested in clinical trials. Methods: To confirm the function of TAK-242 on BMECs under OGD/R, cell viability, inflammatory factors, inflammation-associated pyroptosis, and nuclear factor-κB (NF-κB) signaling were determined using Cell Counting Kit-8 (CCK-8) assay, enzyme-linked immunosorbent assay (ELISA), and western blotting, respectively. To investigate the lncRNAs associated with TLR4 during OGD/R, long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression patterns were profiled with RNA deep sequencing. Moreover, to confirm whether lncRNA-encoded short peptides, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used. Results: Relative control group, OGD/R inhibited the cell viability, increased the section of inflammatory factors secretion, including IL-1ß, IL-6, and TNF-α, and promoted the pathways of TLR4/NLRP3/Caspase-1 and TLR4/NF-κB. However, TAK-242 + OGD/R group promoted OGD/R cell viability, decreased OGD/R-induced inflammatory factors secretion, and inhibited the pathways of TLR4/NLRP3/Caspase-1 and TLR4/NF-κB. In addition, AABR07000411.1, AABR070006957.1, and AABR070008256.1 were decreased in OGD/R cells compared with controls, but TAK-242 restored their expression under OGD/R condition. AABR07000473.1, AC130862.4, and LOC10254972.6 were induced by OGD/R, but were suppressed in TAK-242 + OGD/R cells compared with OGD/R. Moreover, AABR07049961.1, AC127076.2, AABR07066020.1, and AABR07025303.1-encoded short peptides were dysregulated in OGD/R cells, and TAK-242 attenuated the dysregulation of AABR07049961.1, AC127076.2, and AABR07066020.1-encoded short peptides. Conclusions: TAK-242 alters the expression pattern of lncRNAs in OGD/R cells, and differently expressed lncRNAs may exert a protective effect against OGD/R injury through a mechanism of competing endogenous RNA (ceRNA) and encoding short peptides. These findings maybe provide a new theory basis for the treatment of DHCA.