Objective To explore the characteristics of the inhibitory effect of Evodiamine on the proliferation of activated T cells. Methods Mononuclear cells from peripheral blood (PBMCs) were obtained from healthy donors through density gradient centrifugation, and T cells were subsequently purified by using immunomagnetic bead separation. T cell activation was induced by employing anti-human CD3 and anti-human CD28 antibodies. T cells were treated with different concentrations of EVO (0.37, 1.11, 3.33, and 10)μmol/L. Flow cytometry was applied to evaluate the proliferation index, apoptosis rate, viability, CD25 expression levels, and cell cycle distribution of T cells. The expression levels of cytokines IL-2, IL-17A, IL-4, and IL-10 were quantified by using ELISA. Results 1.11, 3.33 and 10 μmol/L EVO effectively inhibited the proliferation of activated T cells, with an IC₅₀ of (1.5±0.3)μmol/L. EVO did not induce apoptosis in activated T cells and affect the survival rate of resting T cells. EVO did not affect the expression of CD25 and the secretion of IL-2 in activated T cells. EVO arrested the T cell cycle at the G2/M phase, resulting in an increase in G2/M phase cells, and exhibited a concentration-dependent effect. EVO did not affect the secretion of IL-4, IL-10 by activated T cells, but significantly inhibited the secretion of IL-17A. Conclusion EVO did not significantly affect the activation process of T cells but inhibited T cell proliferation by arresting the cell cycle at the G2/M phase and significantly suppressed the secretion of the pro-inflammatory cytokine IL-17A, which suggests that EVO has the potential to serve as a lead compound for the development of low-toxicity and high-efficiency immunosuppressants and elucidates the mechanisms underlying the anti-inflammatory and immunomodulatory effects of the traditional Chinese medicine Evodia rutaecarpa.
Humans ; Cell Proliferation/drug effects* ; Quinazolines/pharmacology* ; T-Lymphocytes/metabolism* ; Lymphocyte Activation/drug effects* ; Apoptosis/drug effects* ; Interleukin-4/metabolism* ; Interleukin-10/metabolism* ; Interleukin-2 Receptor alpha Subunit/metabolism* ; Interleukin-17/metabolism* ; Interleukin-2/metabolism* ; Cell Cycle/drug effects* ; Cells, Cultured

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objective To observe the effects of electroacupuncture at"Neiguan"and"Gongsun"on autophagy and apoptosis related indexes of interstitial cells of Cajal(ICC)in rats with functional dyspepsia(FD);To explore its possible mechanism on improving gastrointestinal motility of FD.Methods Totally 32 SPF grade SD rats were randomly divided into blank group,model group,electroacupuncture group and Western medicine group,with 8 rats in each group.An FD model was constructed using a composite etiology modeling method.The electroacupuncture group received electroacupuncture at"Neiguan"and"Gongsun",while the Western medicine group received oral administration of mosapride once a day for 7 consecutive days.The general condition,body mass and average daily intake of rats were observed every week,and gastric emptying rate and small intestine propulsion rate were detected,transmission electron microscopy was used to observe the structure of gastric antrum ICC,Western blot was used to observe the expressions of c-kit,Beclin1,LC3Ⅱ/Ⅰ,p62,Caspase-3 protein in gastric antrum tissue,qPCR was used to observe the mRNA expressions of Beclin1,LC3Ⅱ/Ⅰ,p62 and c-kit in gastric antrum tissue,TUNEL staining was used to detect the apoptosis rate of cells in gastric antrum tissue.Results Compared with the blank group,the model group rats were mentally lethargic,clustered and curled up,with reduced activity,rough and dull hair,loose and unformed feces,reduced body mass and daily food intake(P<0.05),and gastric emptying rate and small intestine propulsion rate decreased(P<0.01),ICC mitochondria swelled and dissolved,with varying degrees of vacuolar formation,rough endoplasmic reticulum dilation and destruction,and a large number of autophagosomes,the expressions of Beclin1 and LC3 Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue increased(P<0.01),the expressions of p62,c-kit protein and mRNA decreased(P<0.01),while Caspase-3 protein expression increased(P<0.01),and the apoptosis rate of gastric antral tissue cells increased(P<0.01).Compared with the model group,the condition of rats in electroacupuncture group and the Western medicine group were improved,with increased responsiveness,increased mobility,neat hair,formed feces,increased body mass and daily food intake(P<0.01),and gastric emptying rate and small intestine propulsion rate increase(P<0.01),a normal ICC structure,and a small amount of autophagosomes were still visible,the expressions of Beclin1,LC3Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue decreased(P<0.01),the expressions of p62,c-kit protein and mRNA increased(P<0.01),while Caspase-3 protein expression decreased(P<0.01),and the apoptosis rate of gastric antral tissue cells decreased(P<0.01).There was no statistically significant difference in various indicators between electroacupuncture group and Western medicine group(P>0.05).Conclusion Electroacupuncture at"Neiguan"and"Gongsun"can restore the number and structure of ICC and improve gastrointestinal motility,and its mechanism may be related to the inhibition of autophagy and apoptosis levels.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objective:To investigate the correlation of SERPINC1 and SERPINE1 gene polymorphisms with venous thromboembolism (VTE) in patients with malignant tumors.Methods:A retrospective case-control study was conducted. A total of 227 patients with malignant tumors in the Cancer Hospital Affiliated to Xinjiang Medical University from November 2023 to February 2024 were selected, of which 47 cases developed VTE (VTE group) and 180 cases did not develop VTE (non-VTE group). The patients' venous blood was collected, and D-dimer level was analyzed by using fully automatic coagulation analyzer; fluorescence staining was performed by using digoxin staining solution, and SERPINC1 rs2227589 locus and SERPINE1 rs1799762 locus were used as candidate genes, and fluorescence sequencing was performed by using multichannel fluorescence quantitative analyzer, and the frequencies of C, T, 4G and 5G genes were calculated.Results:There were no statistically significant differences in the age, gender, smoking, alcohol consumption, anticoagulant use, diabetes mellitus, hypertension, coronary artery disease, surgical treatment, intravenous cannulae, radiotherapy, chemotherapy, and targeted therapy between the 2 groups (all P > 0.05). The level of D-dimer in the VTE group was higher than that in the non-VTE group [(8.7±6.9) kg/m 2vs. (2.8±1.0) kg/m 2], and the difference was statistically significant ( t = 5.15, P < 0.001). The differences in C and T genotypes and gene frequencies at the SERPINC1 rs2227589 locus between the VTE group and the non-VTE group were not statistically significant (all P > 0.05). The differences in 4G and 5G genotypes and gene frequencies at the SERPINE1 rs1799762 locus between the VTE group and the non-VTE group were statistically significant (all P < 0.05), and 4G allele frequency in the VTE group was higher than that in the non-VTE group (52.13% vs. 39.72%), and the difference was statistically significant ( χ2 = 4.70, P = 0.030). Conclusions:The elevated expression of 4G allele at the SERPINE1 rs1799762 locus in patients with malignant tumors is associated with development of VTE.

Objective:To retrieve, appraise and synthesize evidence regarding the prevention and management of high-output ileostomy in post-enterostomy patients, thereby providing a scientific reference for clinical practice.Methods:A computerized search was conducted, systematically exploring national and international databases, as well as the websites of pertinent associations, to gather evidence relevant to the topic. The literature types included clinical decision-making, evidence summaries, guidelines, expert consensus, and systematic reviews. The search timeframe was established from the date of database construction until 23 August 2024. The methodological quality assessment of the literature, along with the extraction and synthesis of the evidence, was performed by two independent researchers utilizing established criteria and adhering to rigorous standards.Results:A total of 13 papers were included in the review, comprising one clinical decision, four guidelines, and eight systematic reviews. Eighteen pieces of best evidence were distilled and summarized across six key areas: diagnosis and risk identification, fluid/diet/nutrition management, medication administration, skin management, monitoring and health education, and follow-up care.Conclusions:The clinical practice rationale for the prevention and management of high-output ileostomy in post-enterostomy patients, when summarized, would offer scientific and effective evidence-based support for practice changes by clinical care staff. The practical application and translation of this evidence should thoroughly consider the nuances of clinical practice in China, as well as individual patient differences, to ensure the effective implementation of the best evidence for maximizing patient benefit.

Objective To compare the effects of endoscopic mucosal dissection(ESD)and endoscopic mucosal resection(EMR)on gastrointestinal function in patients with early gastric cancer.Methods According to different treatment methods,86 patients with early gastric cancer were divided into the ESD group and the EMR group,with 43 cases in each group.The operation duration,postoperative exhaust time and hospital stay of the two groups were observed and compared.Inflammatory factors including interleukin(IL-6)and IL-8 before surgery and 1 month after surgery were compared between the two groups of patients.Gastrointestinal hormone indexes including motilin(MTL),gastrin(GAS),apoptosis-related factors including anti-apoptotic factor(Livin)and epidermal growth factor(EGF),European Organization for Research and Treatment of Cancer(EORTC)Quality of Life Scale(QLQ-C30)score before surgery,3 months after surgery and 6 months after surgery were compared between the two groups of patients.An adverse reaction was also compared between the two groups of patients.Results The operation time,postoperative exhaust time and hospital stay were shorter in the ESD group than those of the EMR group(P＜0.05),and the intraoperative blood loss was significantly less than that of the EMR group(P＜0.05).Compared with the pre-operation,serological indexes such as IL-6,IL-8,MTL,GAS and Livin were decreased after surgery in the two groups(P＜0.05).One month after surgery,IL-6,IL-8 and Livin were decreased,and MTL and GAS were increased in the ESD group compared with those of the EMR group(P＜0.05).QLQ-C30 scores were higher at 3 months and 6 months after operation than those before operation in both groups,and the QLQ-C30 scores of the two groups were significantly higher at 6 months after operation(P＜0.05).The scale scores of the ESD group were significantly higher than those of the EMR group at 3 months and 6 months after operation(P＜0.05).The overall incidence rates of adverse reactions were(4.65%)in the ESD group and(20.93%)in the EMR group(P＜0.05).Conclusion Compared with EMR,ESD can more effectively improve the gastrointestinal function,improve the quality of life and reduce the levels of inflammation and apoptosis-related factors in patients with early gastric cancer.

Objective To compare the effects of endoscopic mucosal dissection(ESD)and endoscopic mucosal resection(EMR)on gastrointestinal function in patients with early gastric cancer.Methods According to different treatment methods,86 patients with early gastric cancer were divided into the ESD group and the EMR group,with 43 cases in each group.The operation duration,postoperative exhaust time and hospital stay of the two groups were observed and compared.Inflammatory factors including interleukin(IL-6)and IL-8 before surgery and 1 month after surgery were compared between the two groups of patients.Gastrointestinal hormone indexes including motilin(MTL),gastrin(GAS),apoptosis-related factors including anti-apoptotic factor(Livin)and epidermal growth factor(EGF),European Organization for Research and Treatment of Cancer(EORTC)Quality of Life Scale(QLQ-C30)score before surgery,3 months after surgery and 6 months after surgery were compared between the two groups of patients.An adverse reaction was also compared between the two groups of patients.Results The operation time,postoperative exhaust time and hospital stay were shorter in the ESD group than those of the EMR group(P＜0.05),and the intraoperative blood loss was significantly less than that of the EMR group(P＜0.05).Compared with the pre-operation,serological indexes such as IL-6,IL-8,MTL,GAS and Livin were decreased after surgery in the two groups(P＜0.05).One month after surgery,IL-6,IL-8 and Livin were decreased,and MTL and GAS were increased in the ESD group compared with those of the EMR group(P＜0.05).QLQ-C30 scores were higher at 3 months and 6 months after operation than those before operation in both groups,and the QLQ-C30 scores of the two groups were significantly higher at 6 months after operation(P＜0.05).The scale scores of the ESD group were significantly higher than those of the EMR group at 3 months and 6 months after operation(P＜0.05).The overall incidence rates of adverse reactions were(4.65%)in the ESD group and(20.93%)in the EMR group(P＜0.05).Conclusion Compared with EMR,ESD can more effectively improve the gastrointestinal function,improve the quality of life and reduce the levels of inflammation and apoptosis-related factors in patients with early gastric cancer.