OBJECTIVE To investigate the improvement effects and mechanism of Xiangsha yiwei tang on gastric mucosal injury in rats with chronic atrophic gastritis （CAG）. METHODS Rats were randomly assigned into normal control group， model group， Xiangsha yiwei tang low-， medium- and high-dose groups （6， 12， 18 g/kg， calculated by crude drug）， and high-dose group of Xiangsha yiwei tang+740 Y-P [Xiangsha yiwei tang 18 g/kg+transforming growth factor β1/phosphatidyl inositol 3 kinase/ protein kinase B（TGF-β1/PI3K/Akt） pathway activator group 740 Y-P 10 mg/kg]， with 18 rats in each group. Rats in each group were administered the corresponding drugs via oral gavage or injection， once daily， for 4 consecutive weeks. Gastric mucosal blood flow， the levels of serum gastrointestinal hormones [including motilin （MTL）， gastrin （GAS）， and pepsinogen （PP）]， as well as inflammatory cytokines [including tumor necrosis factor- α （TNF- α）， interleukin-1β （IL-1β）， IL-6] in rats were measured. Pathological damage to gastric mucosal tissue was observed in rats； the apoptotic rate of gastric mucosal cells was detected. The expressions of TGF-β1/PI3K/Akt signaling pathway-related proteins and apoptosis-related proteins [including B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）] in the gastric mucosal tissues of rats were assessed. RESULTS Compared with normal control group， model group had abnormal gastric mucosal tissue structure， with shedding of gastric mucosal epithelial cells， and prominent infiltration of inflammatory cells. Gastric mucosal blood flow， the serum levels of MTL， GAS， PP， and Bcl-2 protein expression were lowered significantly， while serum levels of TNF-α， IL-1β and IL-6， apoptosis rate， protein expressions of Bax and TGF-β1， the phosphorylations of PI3K and Akt were increased significantly （P＜0.05）. Compared with model group， Xiangsha yiwei decoction groups exhibited attenuated histopathological injuries in gastric mucosal tissues， reduced inflammatory cell infiltration， and significant improvements in the aforementioned quantitative parameters （P＜0.05）. Compared with high-dose group of Xiangsha yiwei tang， high-dose group of Xiangsha yiwei decoction combined with 740 Y-P exhibited significantly aggravated histopathological injuries in gastric mucosal tissues， and the aforementioned quantitative parameters were markedly reversed （P＜0.05）. CONCLUSIONS Xiangsha yiwei tang can alleviate gastric mucosal damage in CAG rats， and its mechanism of action is related to the inhibition of TGF-β1/PI3K/Akt signaling pathway.

OBJECTIVES: To study the mechanism mediating the protective effect of asiaticoside (AS) against myocardial ischemia-reperfusion injury (MIRI) in rats. METHODS: Fifty SD rats were randomized into sham-operated group, MIRI model group and AS treatment group. AS treatment was administered at low, moderate and high doses by daily gavage for 2 weeks before MIRI modeling (n=10). Serum levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), interleukin-18 (IL-18) and IL-1β, the volume of myocardial infarction and ischemia, and myocardial pathologies of the rats were determined or observed. The protein expression levels of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the myocardial tissues were detected using Western blotting. The changes in the expression levels of these proteins were also detected in H9C2 cells with AS pretreatment prior to hypoxia-reoxygenation (H/R) injury. RESULTS: The rats models of MIRI exhibited significant myocardial infarction and ischemia with increased serum levels of LDH and CK-MB and myocardial expressions of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18. AS pretreatment effectively reduced myocardial infarction volume in the rat models and significantly reduced serum LDH and CK-MB levels and the protein levels in the myocardial tissue in a dose-dependent manner. In the H9C2 cell model of H/R injury, AS pretreatment significantly suppressed the elevation of the protein expressions of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18. Molecular docking studies showed that AS had a strong binding affinity with NLRP3. CONCLUSIONS Asiaticoside can alleviate MIRI in rats possibly by inhibiting NLRP3 inflammasome-mediated pyroptosis.
Animals ; Myocardial Reperfusion Injury/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Inflammasomes/metabolism* ; Triterpenes/pharmacology* ; Interleukin-18/metabolism* ; Male ; Interleukin-1beta/metabolism* ; Caspase 1/metabolism*

The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C₁₈ column and a conventional C₁₈ column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H₂O₂ measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H₂O₂ clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.

Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

Sepsis refers to a life-threatening organ dysfunction caused by a dysregulated host response to infection,with persistently high morbidity and mortality,posing a significant healthcare burden.As integral components of innate and adaptive immunity,macrophages exhibit high plasticity and can differentiate into distinct phenotypes(M1 pro-inflammatory and M2 anti-inflammatory)in response to various environmental stimuli,playing crucial roles in both the hyperinflammatory phase and late immunosuppressive phase of sepsis.The metabolic profile of M2 macrophages has gradually become a research focus,and it is regulated by a variety of enzymes and signaling pathways,including adenosine 5'-monophosphate-activated protein kinase,peroxisome proliferator-activated receptor and protein kinase RNA-like ER kinase pathways.These pivotal signaling pathways and enzymes can promote the polarization of M2 macrophages and enhance their anti-inflammatory functions by modulating the metabolism of glucose,lipid,and amino acid,thereby conferring protective effects against sepsis and providing new ideas for the targeted treatment.

Integrated medical curriculum is an important direction for the development of medical education. While integrated theoretical courses have been practiced for many years, integrated experiments are still in the exploratory stage. Taking the integrated experiments of medical microbiology and immunology in Xi'an Jiaotong University as an example, this article introduces the design concept, implementation details, effectiveness evaluation, improvements, and prospects of integrated experiments established based on clinical practice principles, so as to provide a reference for further optimization of integrated experiments in the future.

Integrated medical curriculum is an important direction for the development of medical education. While integrated theoretical courses have been practiced for many years, integrated experiments are still in the exploratory stage. Taking the integrated experiments of medical microbiology and immunology in Xi'an Jiaotong University as an example, this article introduces the design concept, implementation details, effectiveness evaluation, improvements, and prospects of integrated experiments established based on clinical practice principles, so as to provide a reference for further optimization of integrated experiments in the future.

Objective:To report the therapeutic effectiveness of Mindfulness-Based Cognitive Therapy(MBCT)for one outpatient with depression.Methods:A pre-and post-intervention design was used to evaluate a 10-week online MBCT intervention for case W.The Symptom Check List-90(SCL-90),Defense Style Question-naire(DSQ),Mindful Attention Awareness Scale(MAAS),Self-Acceptance Questionnaire(SAQ),and NEO-Five Factor Inventory(NEO-FFI)were conducted one week before MBCT(baseline),five weeks during MBCT,one week after the end of MBCT,and two years after the end of MBCT.A semi-structured interview was conducted with W five months after the end of MBCT.Results:Quantitative results showed that no matter one week or 2 years after the end of MBCT,W's depression,anxiety,immature defense mechanisms,mindfulness levels,self-acceptance levels,and extroversion/agreeableness all showed reliable improvement compared to baseline(|RCI|＞1.96).Qualitative analysis showed that in W's narrative,psychiatric drugs,enhancing awareness,avoiding thinking biases,promoting self-acceptance and care,and stable treatment alliances were the factors that W could benefit from MBCT.Conclusion:Online MBCT could effectively improve the symptoms and psychological function of this out-patient with depression.

Objective:To report the therapeutic effectiveness of Mindfulness-Based Cognitive Therapy(MBCT)for one outpatient with depression.Methods:A pre-and post-intervention design was used to evaluate a 10-week online MBCT intervention for case W.The Symptom Check List-90(SCL-90),Defense Style Question-naire(DSQ),Mindful Attention Awareness Scale(MAAS),Self-Acceptance Questionnaire(SAQ),and NEO-Five Factor Inventory(NEO-FFI)were conducted one week before MBCT(baseline),five weeks during MBCT,one week after the end of MBCT,and two years after the end of MBCT.A semi-structured interview was conducted with W five months after the end of MBCT.Results:Quantitative results showed that no matter one week or 2 years after the end of MBCT,W's depression,anxiety,immature defense mechanisms,mindfulness levels,self-acceptance levels,and extroversion/agreeableness all showed reliable improvement compared to baseline(|RCI|＞1.96).Qualitative analysis showed that in W's narrative,psychiatric drugs,enhancing awareness,avoiding thinking biases,promoting self-acceptance and care,and stable treatment alliances were the factors that W could benefit from MBCT.Conclusion:Online MBCT could effectively improve the symptoms and psychological function of this out-patient with depression.

Objective:To compare the effectiveness and safety profile of centrifugal and membrane plasma separation model in artificial liver therapy with a dual plasma molecular adsorption system (DPMAS).Method:A retrospective study was conducted. Data of inpatients with liver failure who were treated with DPMAS therapy in the Liver Disease Center of Nanfang Hospital, Southern Medical University, from October 2022 to June 2024 were included. Clinical data such as demographic characteristics, etiology, DPMAS treatment-related indicators (including plasma separation method, vascular access, frequency of treatment, treatment duration, type of anticoagulant drugs, and membrane rupture condition), and laboratory test indicators before and after DPMAS treatment were collected. Categorical variables were compared by the χ2 test. Continuous variables were compared using a t-test or a non-parametric test between groups. Result:Data of 232 cases with liver failure who received artificial liver therapy with DPMAS were included. A total of 473 times DPMAS treatment was given. The average age was 50 years old, and males accounted for 82.3%. Centrifugal plasma separation was the initial DPMAS treatment in 176 (75.9%) cases, while membrane plasma separation was used in 56 cases (24.1%). The most common vascular access for DPMAS treatment was the internal jugular vein. The most commonly used anticoagulant was unfractionated heparin. The treatment duration of DPMAS was significantly higher with centrifugal separation than that with membrane separation ( P<0.001). Hemoglobin levels (mean before and after treatment in the centrifugal: 112.8 g/L vs. 106.3 g/L, P<0.001; mean before and after treatment in the membrane group: 108.4 g/L vs. 103.3 g/L, P<0.001), red blood cell count (mean before and after treatment in the centrifugal group: 3.7×10 9/L vs. 3.5×10 9/L, P<0.001; mean before and after treatment in the membrane group: 3.5×10 9/L vs. 3.3×10 9/L, P<0.001) and platelet count (mean before and after treatment in the centrifugal group: 134.5×10 9/L vs. 119.6×10 9/L, P<0.001; mean before and after treatment in the membrane group: 120.7 ×10 9/L vs. 97.3 ×10 9/L, P<0.001) were slightly decreased following initial DPMAS treatment in both groups. The decrease in platelets was significantly lower in centrifugal separation than that in membrane separation (median: 10.4% vs. 17.0%; P=0.003). There was no statistically significant difference observed in the proportion of puncture site bleeding in terms of plasma separation-related adverse events between the two groups, but plasma separator membrane rupture occurred two times in the DPMAS treatment. Conclusion:Centrifugal and membrane separation, both with DPMAS therapy, can cause a slight decrease in hemoglobin, red blood cell count, and platelets in patients with liver failure. Membrane separation causes a larger drop in platelets than centrifugal plasma separation. The operational convenience of medical personnel, the risk of membrane rupture, the coagulation markers, the patient's vascular condition, and other factors should be comprehensively considered when choosing the plasma separation model.