Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

This study aims to investigate the pathogenesis of precancerous lesions of gastric cancer(PLGC) and explore the potential molecular mechanism of Weifuchun Capsules(WFC) in treating PLGC via the nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. Ninety male SPF-grade Wistar rats were randomized into a normal feeding group and a modeling group. The normal feeding group received a regular diet, while the modeling group was subjected to the disease-syndrome combined modeling of PLGC. Specifically, the rats had free access to the water containing 120 μg·mL~(-1) N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and received a diet containing 0.05% ranitidine in an irregular feeding pattern(alternations between fasting and overfeeding). After 15 weeks, the rats in the normal feeding group were randomized into control, control-NF-κB activator betulinic acid(C-BA), and control-NF-κB inhibitor pyrrolidine dithiocarbamaten(C-PDTC) groups. Meanwhile, the rats in the modeling group continuously underwent the modeling procedure and were randomized into model, WFC, model-NF-κB activator(M-BA), and model-NF-κB inhibitor(M-PDTC) groups. The model group and control group were given aseptic water by intragastric administration, once a day. WFC was given at a dose(432 mg·kg~(-1)) 6 times the equivalent dose for adults(body weight: 60 kg) by gavage, once a day. The rats in the C-BA and M-BA groups were administrated with BA by intraperitoneal injection at a dose of 10 mg·kg~(-1), twice a week. The rats in the C-PDTC and M-PDTC groups were administrated with PDTC by intraperitoneal injection at a dose of 50 mg·kg~(-1), twice a week. The interventions were carried out for 4 weeks. Histopathological changes of the gastric mucosa were observed and scored by hematoxylin-eosin(HE) and alcian blue-periodic acid Sthiff(AB-PAS) staining. The levels of inflammatory cytokines including interleukin(IL)-1β, IL-6, IL-18, tumor necrosis factor-alpha(TNF-α), and IL-10 in the gastric tissue were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of proteins associated with the NF-κB/NLRP3 inflammasome in the gastric mucosa were determined by Western blot. The positive expression areas of proteins related to NF-κB/NLRP3 inflammasome in the gastric mucosa were measured by immunohistochemistry. The results showed that compared with the control group, the model, C-BA, and M-BA groups showed significantly risen scores of mucosal inflammation, degree of inflammatory activity, gland atrophy, and intestinal metaplasia, and the model and M-BA groups showed significanly risen scores of dysplasia. Compared with the model group, the WFC group demonstrated significantly declined scores of mucosal inflammation and degree of inflammatory activity, as well as declined scores of intestinal metaplasia and dysplasia. Compared with the control group, the model and C-BA groups showed significantly elevated levels of IL-1β, IL-6, IL-18, and TNF-α in the gastric tissue, and the model group showed significantly elevated level of IL-10. In addition, the model and C-BA groups showed significantly up-regulated expression of NF-κB p65, NLRP3, cysteine-aspartic acid protease 1(caspase-1), and apoptosis-associated speck-like protein containing a CARD(ASC) in the gastric mucosa and increased positive expression areas of NF-κB p65, NLRP3, and ASC. Compared with the model group, the WFC group showed significantly decreased levels of IL-1β, IL-6, IL-18, TNF-α, and IL-10 in the gastric tissue, and the M-PDTC group showed significantly lowered levels of IL-1β, IL-18, and TNF-α in the gastric mucosa. Both WFC and M-PDTC groups demonstrated significantly down-regulated expression levels of NF-κB p65, phosphorylated NF-κB p65(p-NF-κB p65), NLRP3, and caspase-1 in the gastric mucosa, along with significant decreases in the positive expression areas of NF-κB p65, NLRP3, and ASC. In conclusion, the pathogenesis of PLGC is closely related to the activation of the NF-κB/NLRP3 inflammasome signaling pathway. WFC can alleviate mucosal inflammation, inhibit glandular atrophy, partially reverse intestinal metaplasia, and reduce dysplasia to delay the process of inflammation-cancer transformation, and meanwhile it can effectively lower the levels of inflammatory cytokines and down-regulate the expression of pathway-related proteins in the stomach. Therefore, WFC may treat PLGC by inhibiting the NF-κB/NLRP3 inflammasome signaling pathway.
Animals ; Male ; NF-kappa B/genetics* ; Rats ; Rats, Wistar ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Stomach Neoplasms/pathology* ; Inflammasomes/genetics* ; Humans ; Precancerous Conditions/metabolism* ; Capsules

This study aims to investigate the pharmacological effects and mechanisms of Yougui Yin in treating glucocorticoid-induced osteonecrosis. A rat model of glucocorticoid-associated osteonecrosis of the femoral head(GA-ONFH) was established by intramuscular injection of dexamethasone at 20 mg·kg~(-1) every other day for 8 weeks. Rats were randomly allocated into control, model, and low-and high-dose(1.5 and 3.0 g·kg~(-1), respectively) Yougui Yin groups. After modeling, rats in Yougui Yin groups were administrated with Yougui Yin via gavage, which was followed by femoral specimen collection. Hematoxylin-eosin staining was employed to observe femoral head repair, and immunofluorescence was employed to assess adipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs) within the femoral head. Cell experiments were carried out with dexamethasone(1 μmol·L~(-1))-treated BMSCs to evaluate the effects of Yougui Yin-medicated serum on adipogenic differentiation. Animal experiments demonstrated that compared with the model group, Yougui Yin at both high and low doses significantly improved bone mineral density(BMD), bone volume/total volume(BV/TV) ratio, and trabecular thickness(Tb.Th) in the femoral head. Additionally, Yougui Yin alleviated necrosis-like changes and adipocyte infiltration and significantly reduced the expression level of peroxisome proliferator-activated receptor γ(PPARγ) in the femoral head, thereby suppressing the adipogenic differentiation of BMSCs in GA-ONFH rats. The cell experiments revealed that Yougui Yin-medicated serum markedly inhibited dexamethasone-induced adipogenic differentiation of BMSCs and down-regulated the level of PPARγ. The overexpression of PPARγ attenuated the inhibitory effect of Yougui Yin-medicated serum on the adipogenic differentiation of BMSCs, indicating the critical role of PPARγ in Yougui Yin-mediated suppression of adipogenic differentiation of BMSCs. In conclusion, Yougui Yin exerts therapeutic effects on glucocorticoid-induced osteonecrosis by down-regulating PPARγ expression and inhibiting adipogenic differentiation of BMSCs.
Animals ; Mesenchymal Stem Cells/metabolism* ; PPAR gamma/genetics* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Glucocorticoids/adverse effects* ; Rats, Sprague-Dawley ; Adipogenesis/drug effects* ; Osteonecrosis/genetics* ; Cell Differentiation/drug effects* ; Bone Marrow Cells/metabolism* ; Femur Head Necrosis/chemically induced* ; Humans

The zebrafish model has attracted much attention due to its strong reproductive ability, short research cycle, and ease of maintenance. It has always been an important vertebrate model system, often used to carry out human disease research. Its motor behavior features have the advantages of being simpler, more intuitive, and quantifiable. In recent years, it has received widespread attention in the study of traditional Chinese medicine(TCM)for the treatment of sleep disorders, neurodegenerative diseases, fatigue, epilepsy, and other diseases. This paper reviews the characteristics of zebrafish motor behavior and its applications in the pharmacodynamic verification and mechanism research of TCM extracts, active ingredients, and TCM compounds, as well as in active ingredient screening and safety evaluation. The paper also analyzes its advantages and disadvantages, with the aim of improving the breadth and depth of zebrafish and its motor behavior applications in the field of TCM research.
Zebrafish/physiology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Drug Evaluation, Preclinical/methods* ; Animals ; Sleep Wake Disorders/physiopathology* ; Epilepsy/physiopathology* ; Neurodegenerative Diseases/physiopathology* ; Fatigue/physiopathology* ; Behavior, Animal/physiology* ; Motor Activity/physiology*

OBJECTIVE: To investigate the factors affecting ferric chloride (FeCl₃) - induced carotid artery thrombosis model experiment. METHODS: After the common carotid artery was damaged by FeCl₃, the injured vessels were dissected for fixation, embedding, frozen section, and then processed HE staining. The carotid thrombus area ratio was calculated. We examined the effect of FeCl₃ concentration (5%, 10% and 15%), reaction time (2, 4 and 6 min), and recipient mouse age (4-5, 6-8 and 10 weeks) on the formation and stability of arterial thrombosis model. The model was injected through the post-glomus venous plexus of mouse eyeball with 0.075 μg/g and 0.1 μg/g R300 to verify the accuracy of the FeCl₃-induced model on thrombus formation by adjusting the platelet number. RESULTS: HE staining showed that thrombus formation induced by 10% and 15% FeCl₃ was more stable, dense and larger than 5% FeCl₃-induced thrombosis. 10% FeCl₃ induced the formation of dense and large thrombosis after 4 and 6 minutes of vascular endothelium injury, while the thrombosis induced for 2 minutes were looser and smaller in area. Mouse age can not affect thrombus formation and stability, because there were no significant differences in the formation of dense thrombus and thrombus area induced by 10% FeCl₃ among three different age groups of mice. CONCLUSION Many factors affect the formation and stability of arterial thrombosis model induced by FeCl₃. This optimal experimental conditions for construction of a stable carotid artery thrombosis model are 10% FeCl₃, 4 minutes for injury, and 6-8 week old mice.
Animals ; Mice ; Ferric Compounds/adverse effects* ; Chlorides ; Disease Models, Animal ; Carotid Artery Thrombosis/chemically induced* ; Male

Hepatolenticular degeneration is a rare disease,and the number of cases of primary liver cancer occurring on the basis of liver cirrhosis caused by hepatolenticular degeneration is very small.This paper reports a case of hepatolenticular degeneration with primary liver cancer,and then reviews and summarizes current cases of this disease both domestically and internationally.
Humans ; Hepatolenticular Degeneration/complications* ; Liver Neoplasms/complications*

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

Objective: To investigate the impact of childhood traumatic experiences on individual risktaking decisions in early adulthood using functional nearinfrared spectroscopy (fNIRS), so as to provide the reference for clarifying the brain mechanisms underlying the impact of childhood trauma on individual risky decision. Methods: From December 2023 to March 2024, 28 children with childhood trauma experiences (trauma group) and 32 healthy college students (control group) were selected from Jining Medical University by a combination of stratified descent and convenient sampling methods. All subjects participated in the Iowa Game task fNIRS scanning. The brain activation, functional connectivity, graph theory properties (degree centrality, betweenness centrality, and local efficiency), and Receiver Operating Characteristic (ROC) analysis were performed by using preprocessing fNIRS data. Results: Compared with control group, trauma group showed significantly fewer choice times in the inferior deck (Z=-0.88), and showed significantly decreased activation levels in the right frontalpolar (Z=-2.59), as well as showed significant decreased functional connectivity between left dorsolateral prefrontal and in right dorsolateral prefrontal (Z=-3.78), and between left dorsolateral prefrontal cortex and the right frontal pole (Z=-3.68)(P<0.05). The central index of right inferior frontal gyrus in the trauma group was higher than that in the control group, while the central index of left and right dorsolateral frontal lobes was lower than that in the control group (Z=2.13, -2.53, -2.12, P<0.05). The centrality index of the right inferior frontal gyrus in the trauma group was higher than that in the control group (Z=2.47, P<0.05). The local efficiency indicators of the right inferior frontal gyrus, left and right frontal pole in the trauma group were higher than those in the control group (Z=2.51, 2.17, 2.53, P<0.05). The results of the ROC curve analysis showed that the local efficiency achieved the highest area under the curve (AUC=0.68). Conclusions Young adults with childhood trauma experience tend to choose lower loss, and the frontal pole shows a lack of activation in the whole process of risk decision performance. The abnormalities in the brain connectivity and network properties might be the neural basis of excessive defense mechanisms that childhood trauma leads to risky decisions.

Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

Objective:To investigate how reactive oxygen species(ROS)regulates the signal transduction of platelet activation and apoptosis,and to explore the relationship between platelet activation and apoptosis.Methods:Platelets were directly stimulated with thrombin or pretreated with ROS inhibitor N-acetylcysteine(NAC)before being stimulated with thrombin,and then flow cytometry was used to detect the effects of thrombin and NAC on P-selectin expression,αⅡbβ3 activation,mitochondrial membrane potential depolarization,phosphatidylserine(PS)externalization,ROS expression and platelet aggregation.Results:Thrombin could induce the production of ROS in platelets in a concentration-and time-dependent manner.0.01 U thrombin induced ROS-dependent high degree of integrin αⅡbβ3 activation,P-selectin expression,and platelet aggregation.The platelets induced by different concentration gradients of thrombin exhibited ROS-dependent mitochondrial membrane potential depolarization and PS externalization in platelets.After induction with thrombin for 30 min,the activation of integrin αⅡbβ3 in platelets reached its maximum level,and after 60 minutes,the depolarization of mitochondrial membrane potential in platelets reached its maximum level.However,the expression of P-selectin,depolarization of mitochondrial membrane potential,and platelet aggregation function were all inhibited to a certain extent when the platelets were pretreated with ROS inhibitor NAC and then induced with thrombin.Conclusion:When platelets are induced by thrombin,ROS first regulates the activation of platelets,and then regulates the apoptosis of platelets.Both platelet activation and apoptosis depend on the production of ROS in platelets,and the signals of activation and apoptosis occur orderly.Inhibiting the ROS signal in platelets can effectively inhibit the activation and apoptosis of platelets.