Objectives:To evaluate the hemodynamic impact of different bypass grafting methods on the left anterior descending(LAD)artery using computational fluid dynamics,providing a theoretical basis for optimizing coronary artery bypass grafting.Methods:A patient-specific 3D coronary model was constructed using SimVascular software,including an in-situ internal mammary artery graft(model 1)and three free grafts of varying diameters(model 2:2 mm internal mammary artery free graft;model 3 and model 4:3 mm and 4 mm great saphenous vein free grafts).The hemodynamic parameters of the native artery and grafts were compared among the four bypass grafting models.Results:All four bypass grafting models supply sufficient blood flow for the severely stenosed LAD.LAD flow was slightly lower in the model 1.Free internal mammary artery grafts showed higher flow and wall shear stress.4 mm great saphenous vein free grafts presented with maximum flow but lowest shear stress,3 mm great saphenous vein free grafts offered better hemodynamic stability.Conclusions:Computational fluid dynamics analysis indicates that free internal mammary grafts could provide superior hemodynamics,while larger grafts result in lower shear stress,which might affect long-term graft patency.These findings thus provide experimental evidences useful for optimizing LAD bypass strategies.

Objectives:To evaluate the hemodynamic impact of different bypass grafting methods on the left anterior descending(LAD)artery using computational fluid dynamics,providing a theoretical basis for optimizing coronary artery bypass grafting.Methods:A patient-specific 3D coronary model was constructed using SimVascular software,including an in-situ internal mammary artery graft(model 1)and three free grafts of varying diameters(model 2:2 mm internal mammary artery free graft;model 3 and model 4:3 mm and 4 mm great saphenous vein free grafts).The hemodynamic parameters of the native artery and grafts were compared among the four bypass grafting models.Results:All four bypass grafting models supply sufficient blood flow for the severely stenosed LAD.LAD flow was slightly lower in the model 1.Free internal mammary artery grafts showed higher flow and wall shear stress.4 mm great saphenous vein free grafts presented with maximum flow but lowest shear stress,3 mm great saphenous vein free grafts offered better hemodynamic stability.Conclusions:Computational fluid dynamics analysis indicates that free internal mammary grafts could provide superior hemodynamics,while larger grafts result in lower shear stress,which might affect long-term graft patency.These findings thus provide experimental evidences useful for optimizing LAD bypass strategies.

Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3⁺ (FOXP3⁺) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal B. fragilis was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3⁺ Tregs and curbs pro-inflammatory pathways.

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

Liver transplantation is an effective treatment for end-stage liver diseases,yet early al-lograft dysfunction(EAD)is commonly seen,and affects prognosis,thereby reducing graft and pa-tients' survival rates.Although an increasing number of patients benefit from liver transplantation,con-troversies persist regarding the associated factors and preventive strategies for EAD.This article re-viewed the research progress on liver transplantation both domestically and internationally,aiming to promote the development of liver transplantation surgery and improve treatment outcomes.

Thalidomide(THA)is renowned for its potent anti-inflammatory properties.This study aimed to eluci-date its underlying mechanisms in the context of Crohn's disease(CD)development.Mouse colitis models were established by dextran sulfate sodium(DSS)treatment.Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry,respectively.Antibiotic-treated mice served as models for microbiota depletion and transplantation.The expression of forkhead box P3+(FOXP3+)regulatory T cells(Tregs)was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort.THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile,with an increased abundance of probiotics Bacteroides fragilis,while pathogenic bacteria were depleted.In addition,THA increased beneficial metabolites bile acids and significantly restored gut barrier function.Transcriptomic profiling revealed that THA inhibited interleukin-17(IL-17),IL-1β and cell cycle signaling.Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA.Specifically,increased level of gut commensal B.fragilis was observed,correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid(7-ketolithocholic acid,7-KA)following THA treatment.This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1(FXR1)to inhibit auto-phagy.An interaction between FOXP3 and FXR1 was identified,with binding regions localized to the FOXP3 domain(aa238-335)and the FXR1 domain(aa82-222),respectively.Conclusively,THA modu-lates the gut microbiota and metabolite profiles towards a more beneficial composition,enhances gut barrier function,promotes the differentiation of FOXP3+Tregs and curbs pro-inflammatory pathways.

Objective:To investigate the learning curve for a five-step procedure, namely, a transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 66 patients with Siewert type II adenocarcinoma of the esophagogastric junction who had undergone the five-step procedure performed by the same surgeon in the Gastrointestinal Surgery Department of Guangdong Provincial Hospital of Chinese Medicine from May 2017 to April 2023. The learning curve were plotted using cumulative summation analysis and selected indicators, including intraoperative blood loss, duration of surgery, time to first flatus, time to first tolerance of liquid food, length of hospital stay, and incidence of perioperative complications at different stages were compared. The data were analyzed using SPSS 24.0 statistical software. Numerical data are presented as cases (%) and data were analyzed using the χ 2 test or Fisher's exact test. Normally distributed measurement data are presented as x±s, and independent sample t-testing was performed for inter group comparison. Non-normally distributed measurement data are presented as M( Q1, Q3) and the Mann–Whitney U test was used for inter group comparison. Results:The five-step procedure had been successfully completed without switching to open surgery in all 66 study patients. There were no perioperative deaths, blood loss was 100 (50, 200) mL and duration of surgery 329.4±87.3 minutes. The equation of optimal fit for the duration of surgery was y=0.031x 3-4.4757x 2+164.97x-264.4 ( P<0.001, R2=0.9797). The cumulative summation learning curve reached a vertex when 25 surgical procedures had accumulated. Using 25 cases as the cut-off, we divided the learning curves into learning and proficiency periods and patients into learning (25) and proficiency period groups (41). There were no statistically significant differences between the two groups of patients in sex, age, body mass index, American Society of Anesthesiologists score, history of abdominal surgery, comorbidities, preoperative neoadjuvant therapy, maximum tumor diameter, surgical procedure, or T and N stage of tumor ( P>0.05). The following factors differed significantly (all P<0.05) between the learning and proficiency stages: in the latter there was less intraoperative blood loss (100 [50, 100] ml vs. 200 [100, 200] ml, U=-3.940, P<0.001), shorter duration of surgery ([289.8±50.7] minutes vs. [394.4±96.0] minutes, t=5.034, P<0.001), more mediastinal lymph nodes removed (5 [2, 8] vs. 2 [1, 5], U=-2.518, P=0.012), earlier time to first flatus (2 [2, 3] days vs. 4 [3, 6] days, U=-4.016, P<0.001), earlier time to first tolerance of liquid food (5 [4, 6] days vs. 7 [6, 8] days, U=-2.922, P=0.003), shorter duration of hospital stay (8 [8, 10] vs. 10 [9, 12] days, U=-2.028, P=0.043). The incidence of surgical complications did not differ significantly between the two groups ( P=0.238). Conclusion:Satisfactory results can be achieved with the five-step procedure for patients with Siewert type II adenocarcinoma of the esophagogastric junction once 25 procedures have been performed.

Objective:To investigate the learning curve for a five-step procedure, namely, a transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 66 patients with Siewert type II adenocarcinoma of the esophagogastric junction who had undergone the five-step procedure performed by the same surgeon in the Gastrointestinal Surgery Department of Guangdong Provincial Hospital of Chinese Medicine from May 2017 to April 2023. The learning curve were plotted using cumulative summation analysis and selected indicators, including intraoperative blood loss, duration of surgery, time to first flatus, time to first tolerance of liquid food, length of hospital stay, and incidence of perioperative complications at different stages were compared. The data were analyzed using SPSS 24.0 statistical software. Numerical data are presented as cases (%) and data were analyzed using the χ 2 test or Fisher's exact test. Normally distributed measurement data are presented as x±s, and independent sample t-testing was performed for inter group comparison. Non-normally distributed measurement data are presented as M( Q1, Q3) and the Mann–Whitney U test was used for inter group comparison. Results:The five-step procedure had been successfully completed without switching to open surgery in all 66 study patients. There were no perioperative deaths, blood loss was 100 (50, 200) mL and duration of surgery 329.4±87.3 minutes. The equation of optimal fit for the duration of surgery was y=0.031x 3-4.4757x 2+164.97x-264.4 ( P<0.001, R2=0.9797). The cumulative summation learning curve reached a vertex when 25 surgical procedures had accumulated. Using 25 cases as the cut-off, we divided the learning curves into learning and proficiency periods and patients into learning (25) and proficiency period groups (41). There were no statistically significant differences between the two groups of patients in sex, age, body mass index, American Society of Anesthesiologists score, history of abdominal surgery, comorbidities, preoperative neoadjuvant therapy, maximum tumor diameter, surgical procedure, or T and N stage of tumor ( P>0.05). The following factors differed significantly (all P<0.05) between the learning and proficiency stages: in the latter there was less intraoperative blood loss (100 [50, 100] ml vs. 200 [100, 200] ml, U=-3.940, P<0.001), shorter duration of surgery ([289.8±50.7] minutes vs. [394.4±96.0] minutes, t=5.034, P<0.001), more mediastinal lymph nodes removed (5 [2, 8] vs. 2 [1, 5], U=-2.518, P=0.012), earlier time to first flatus (2 [2, 3] days vs. 4 [3, 6] days, U=-4.016, P<0.001), earlier time to first tolerance of liquid food (5 [4, 6] days vs. 7 [6, 8] days, U=-2.922, P=0.003), shorter duration of hospital stay (8 [8, 10] vs. 10 [9, 12] days, U=-2.028, P=0.043). The incidence of surgical complications did not differ significantly between the two groups ( P=0.238). Conclusion:Satisfactory results can be achieved with the five-step procedure for patients with Siewert type II adenocarcinoma of the esophagogastric junction once 25 procedures have been performed.

Objective:To explore the effect and its mechanism of nalbuphine on pruritus/paresthesia induced by fospropofol disodium under general anesthesia.Methods:The study was designed as a prospective, single-center, randomized, double-blind controlled trial. Patients scheduled for surgery under general anesthesia in Xijing Hospital, Air Force Medical University from April to May 2022 were entered and randomly divided into nalbuphine group and control group using the random sequence table method. Patients of both groups were given general anesthesia with fospropofol disodium. Thirty minutes before the end of the surgery, patients in the nalbuphine group received intravenous injection of nalbuphine 0.2 mg/kg (0.1 ml/kg), while those in the control group received intravenous injection of an equal volume of 0.9% sodium chloride injection. Venous blood samples of patients in the 2 groups were collected 5 minutes before anesthesia induction and 5 minutes after awakening to detect levels of serum interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and S-100 calcium binding protein β (S-100β). The primary indicator of the study was the incidence of pruritus/paresthesia within 30 minutes after extubation; the secondary indicators included time to eye opening upon calling, the maximum pruritus/paresthesia score within 30 minutes after extubation, nausea/ vomiting score, pain score, the incidence of pruritus/paresthesia within 24 hours after operation, the score of patient satisfaction to anesthesia, and the levels of postoperative serum inflammatory markers.Results:A total of 98 patients enrolled the study, 49 in each group. There were no statistically significant differences in gender, age, body mass index, American Society of Anesthesiologists grade, operation type, operation time, or anesthesia time of patients between the 2 groups (all P>0.05). The incidence of pruritus/paresthesia and the score of pruritus/paresthesia 30 minutes after extubation were lower in the nalbuphine group than those in the control group, with statistically significant differences [24.5% (12/49) vs. 61.2% (30/49), P<0.001; 4 (2, 5) vs. 6 (5, 7), P=0.031]. At 24 hours of postoperation, the score of patient satisfaction to anesthesia in the nalbuphine group was higher than that in the control group, with a statistically significant difference [8 (7, 9) vs. 6 (3, 7), P=0.042]. Compared with the control group, the postoperative serum IL-6 in patients of the nalbuphine group was significantly lower [(329.5±105.5) ng/L vs. (398.5±102.6) ng/L, P=0.033], while differences in levels of TNF-α and S-100 β were not statistically significant (all P>0.05). Conclusion:Nalbuphine can significantly reduce the incidence of pruritus/paresthesia induced by fospropofol disodium under general anesthesia and improve the patient satisfaction to anesthesia, and its mechanism may involve the inhibition of inflammatory response by nalbuphine.