ObjectiveTo observe the effect of Qishao capsules on renal injury in db/db mice with diabetic kidney disease （DKD），and explore its mechanism of protecting the kidney by inhibiting podocyte apoptosis. Methodsdb/m mice （7 mice） were used as the normal group，and db/db mice （35 mice） were randomly divided into a model group，a dapagliflozin group （0.001 g·kg^-1·d^-1），and low-，medium-，and high-dose groups of Qishao capsules （0.341 3，0.682 5，and 1.365 g·kg^-1·d^-1，respectively）. Drug intervention lasted for 8 consecutive weeks. After sampling，the serum renal function indicators ［creatinine（SCr），and urea nitrogen（BUN）］，fasting blood glucose （FBG），24 h urinary protein quantification （24 h-UTP）， and other indicators of the mice were measured. The pathological tissue morphology of the kidney was observed by periodic acid-silver methenamine （PASM） and Masson's trichrome （Masson） staining. Immunohistochemical detection of cysteine-dependent aspartate-specific protease （Caspase）-3 and B-cell lymphoma 2 （Bcl-2） was performed. Western blot was used to detect the protein expression of Caspase-8，Caspase-7，Caspase-3， and other molecules. Terminal deoxynucleotidyl transferase dUTP nick End labeling （TUNEL） staining was used to observe apoptosis in renal tissue. Immunofluorescence staining of Wilms tumor suppressor gene-1 （WT-1） was used to observe podocyte injury. Real-time polymerase chain reaction （Real-time PCR） was employed to detect Caspase-8 and Caspase-3 mRNA expression in the kidneys of experimental mice. Data analysis was conducted using statistical software GraphPad Prism 10. ResultsCompared with the normal group，the model group showed significantly increased 24 h-UTP，SCr，BUN，and FBG （P<0.01）. Additionally， PASM staining of renal tissue showed increased glycogen deposition，glomerular hypertrophy，and thickening of the basement membrane. Masson staining showed collagen fiber proliferation in renal tissue. Transmission electron microscopy showed thickening of the renal tissue basement membrane and fusion or loss of foot processes in the model group. The immunohistochemical results showed that Caspase-3 in the kidneys of the mice in the model group significantly increased （P<0.01），while the Bcl-2 protein expression level decreased significantly （P<0.01）. The number of TUNEL positive cells in renal tissue significantly increased （P<0.01）. The positive expression of WT-1 in podocytes was significantly reduced （P<0.01）. Western blot analysis showed significant upregulation of Caspase-8，Caspase-7，and Caspase-3 protein expression in renal tissue （P<0.01）. The mRNA expression levels of Caspase-8 and Caspase-3 in the kidneys increased significantly （P<0.01）. Compared with the model group，the Qishao capsules groups can significantly reduce the levels of 24 h-UTP，SCr，BUN，and FBG （P<0.01）. The pathological damage of renal tissue and podocyte injury were improved to some extent. Immunohistochemistry in the kidney showed a significant decrease in Caspase-3 （P<0.01） and a significant increase in Bcl-2 protein expression level （P<0.01）. Additionally， there were a significant decrease in the number of TUNEL positive cells in renal tissue （P<0.01），a significant increase in WT-1 positive expression in podocytes （P<0.01），marked downregulation of Caspase-8，Caspase-7，and Caspase-3 protein expression in renal tissue （P<0.05，P<0.01），and a significant decrease in Caspase-8 and Caspase-3 mRNA expression levels （P<0.01）. ConclusionQishao capsules can inhibit podocyte apoptosis by regulating the expression of Caspase-8，Caspase-7， and Caspase-3，thereby improving the diabetic renal injury in db/db mice.

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.

OBJECTIVE To explore the clinical efficacy of the Yushen Yangluan Formula in treating diminished ovarian reserve(DOR)with kidney essence deficiency based on mitochondrial energy metabolism and oxidative stress.METHODS A total of 70 pa-tients diagnosed with DOR due to kidney essence deficiency,who visited the gynecology department of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine from September 2023 to June 2024,were selected.The patients were randomly divided into two groups according to the random number table method.The treatment group(35 cases)received the Yushen Yangluan Formula,while the control group(35 cases)received a Chinese herbal placebo,with treatment lasting for 3 months,and during the treatment pe-riod,one case dropped out from each group.Antral follicle count(AFC),traditional Chinese medicine(TCM)syndrome scores,and serum levels of anti-Mullerian hormone(AMH),follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),re-active oxygen species(ROS),and adenosine triphosphate(ATP)levels were compared between the two groups.RESULTS After treatment,the TCM syndrome scores for kidney deficiency in both groups decreased compared to before treatment(P<0.05,P<0.01),with the experimental group showing greater improvement than the control group(P<0.01).Following treatment,the FSH levels in the experimental group decreased compared to before treatment(P<0.05),while AMH levels increased(P<0.05),and the antral follicle count(AFC)also increased significantly(P<0.01),with the experimental group outperforming the control group(P<0.05,P<0.01).After treatment,serum ROS levels in the experimental group decreased(P<0.01),and ATP levels increased(P<0.01),with the experimental group showing superior results compared to the control group(P<0.01).CONCLUSION Yushen Yangluan Formu-la can improve the ovarian function and TCM syndrome score of patients with DOR of kidney essence deficiency type,which may be re-lated to improving mitochondrial energy metabolism and reducing oxidative stress.

Objective:To investigate the change trend in the burden of 5 common malignant tumors of digestive system (esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer) in the Chinese population from 1990 to 2021.Methods:The descriptive epidemio-logic method was conducted. The number of new cases, crude incidence rate, age-standardized incidence rate, the number of deaths, crude mortality rate and age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021 of the Global Burden of Disease were collected. The age-standardized rate was calculated based on the standardized demographics of the whole world in the Global Burden of Disease for the year 2021. Observation indicators: (1) The incidence of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (2) the mortality of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (3) the change trend of age-standardized incidence rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (4) the change trend of age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The Joinpoint regression model was constructed for trend analysis, specifically to calculate the annual percentage change, average annual percentage change (AAPC), and their 95% confidence interval ( CI) for age-standardized incidence and mortality rates for each cancer type at different time periods. Results:(1) The incidence of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The number of new cases of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer in the Chinese population changed from 207 495, 407 471, 158 389, 37 818 and 96 434 in 1990 to 320 805, 611 799, 658 321, 118 665 and 196 637 in 2021. The crude incidence rates of the above cancer types changed from 17.64/100 000, 34.64/100 000, 13.46/100 000, 3.21/100 000, 8.20/100 000 in 1990 to 22.55/100 000, 43.00/100 000, 46.27/100 000, 8.34/100 000, 13.82/100 000 in 2021. The new cases of esophageal cancer, stomach cancer, colorectal cancer, pancreatic cancer, and liver cancer all showed an increasing trend, with absolute changes of 54.61%, 50.15%, 315.64%, 213.78%, and 103.91%, respectively. (2) The mortality of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The number of deaths of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer in the Chinese population changed from 210 821, 374 066, 119 303, 38 883 and 94 937 in 1990 to 296 443, 445 013, 275 129, 119 602 and 172 068 in 2021. The crude death rates of the above cancer types changed from 17.92/100 000, 31.80/100 000, 10.14/100 000, 3.31/100 000, 8.07/100 000 in 1990 to 20.84/100 000, 31.28/100 000, 19.34/100 000, 8.41/100 000, 12.09/100 000 in 2021. Death cases of esophageal cancer, stomach cancer, colorectal cancer, pancreatic cancer, and liver cancer all showed an increa-sing trend, with absolute changes of 40.61%, 18.97%, 130.61%,207.59%, and 81.24%, respectively. (3) The change trend of age-standardized incidence rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The change trends of age-standardized incidence rates of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer, and liver cancer in the Chinese population were divided into 5, 5, 4, 5, and 5 periods, respectively, and the AAPCs of age-standardized incidence rates of the above cancer types were -1.60% (95% CI as -1.78% to -1.42%), -1.60% (95% CI as -1.78% to -1.43%), 1.66% (95% CI as 1.39% to 1.94%), 0.72% (95% CI as 0.36% to 1.08%), and -0.31% (95% CI as -0.39% to -0.23%). (4) The change trend of age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The change trend of age-standardized mortality rates of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer, and liver cancer in the Chinese population were divided into 5, 5, 4, 5, and 4 periods, respectively, and the AAPC of age-standardized mortality rates for each of the above mentioned cancer types were -1.96% (95% CI as -2.03% to -1.90%), -2.44% (95% CI as -2.50% to -2.38%), -0.49% (95% CI as -0.58% to -0.41%), 0.56% (95% CI as 0.48% to 0.63%), and -0.68% (95% CI as -0.89% to -0.52%). Conclusions:From 1990 to 2021, the disease burden of esophageal cancer, gastric cancer and liver cancer in the Chinese population show a downward trend. The standardized incidence of colorectal cancer shows an upward trend, and the standardized mortality rate shows a downward trend. The disease burden of pancreatic cancer shows an upward trend.

Obesity and its related metabolic diseases have become a global public health challenge. Traditional weight loss methods have limited efficacy in patients with moderate to severe obesity, while bariatric surgery, although effective, carries a relatively high risk. Endoscopic weight loss techniques, due to their minimally invasive nature, safety, and reversibility, have gradually become an important supplement to obesity treatment. This article systematically reviews the research progress of gastric and small intestine-related endoscopic bariatric procedures, including intragastric balloon therapy, endoscopic sleeve gastroplasty, gastric bypass stents, and duodenal mucosal resurfacing.The authors believe that gastric-related procedures are suitable for patients whose primary goal is weight loss. Among these, the adjustable intragastric balloon offers the highest flexibility, being non-invasive and reversible with good short-term weight loss effects, making it suitable for bridging to bariatric surgery in patients with severe obesity. Endoscopic sleeve gastroplasty achieves weight loss effects closest to those of bariatric surgery, with favorable long-term weight loss outcomes, and is suitable for weight loss treatment in patients with contraindications to bariatric surgery. Gastric drainage procedures result in poor patient experience due to issues related to fistula tubes; moreover, the small sample size of studies on gastric-related endoscopic procedures means they are not considered representative. In contrast, small intestine-related procedures are more suitable for patients focusing on the improvement of metabolic diseases. Overall, endoscopic techniques exhibit significant short-term efficacy, but their long-term efficacy and standardization still require further research. In the future, it will be necessary to integrate artificial intelligence-assisted operations and individualized treatment strategies to optimize efficacy and expand clinical application.

Objective:To construct a symptom network for type 2 diabetes mellitus (T2DM) patients, identify bridging symptoms and core symptoms, and explore influencing factors, providing references for precise and efficient symptom management.Methods:A convenience sampling method was used to select 340 T2DM patients hospitalized in the Endocrinology Department of Affiliated Hospital of North Sichuan Medical College from December 2023 to February 2024. A general information survey and the Chinese version of Diabetes Symptom Checklist-Revised were used to collect data. Multiple linear regression analysis was performed to explore the influencing factors of T2DM patients' lack of vitality. Network analysis was used to identify core symptoms and bridging symptoms among symptom clusters. A total of 340 questionnaires were distributed, and 336 valid questionnaires were returned, resulting in a valid response rate of 98.8% (336/340) .Results:The most common symptoms in T2DM patients included thirst and dry mouth, foamy urine, and overall fatigue. The most troublesome symptoms were overall fatigue, lack of vitality, and thirst and dry mouth. In the symptom network, lack of vitality had the highest intensity ( rs=7.980) and closeness centrality ( rc=0.014), followed by overall fatigue ( rs=7.940) and feeling down ( rs=7.200). Overall fatigue ( rbs=7.190, rbc=0.380) was identified as the strongest bridging symptom in the network. Univariate analysis showed that age, education level, diabetes duration, diabetes complications, and regular blood glucose monitoring were significant factors affecting lack of vitality in T2DM patients ( P<0.05). Multiple linear regression analysis indicated that education level, regular blood glucose monitoring, and diabetes complications were significant factors affecting lack of vitality ( P<0.05) . Conclusions:Lack of vitality is the core symptom in T2DM patients, and overall fatigue is the bridging symptom connecting different symptom clusters. The lack of vitality is influenced by factors such as education level, regular blood glucose monitoring, and diabetes complications. Healthcare providers should use symptom network analysis to timely identify core symptoms, bridging symptoms, and their influencing factors, and develop precise and efficient interventions to improve symptom management and reduce the symptom burden in T2DM patients.

[Purpose]To analyze the trends of disease burden for lung cancer worldwide and in China from 1990 to 2021.[Methods]Data of the disease burden of lung cancer and population demographics in 1990 and 2021 stratified by sex and age groups for global,five SDI quintiles re-gions,and eight countries including China,Japan,Republic of Korea,United Kingdom,France,United States,Canada,and Australia were extracted from the Global Burden of Disease Study 2021(GBD 2021)database.The age-standardized mortality rate(ASMR)and age-standard-ized disability-adjusted life year rate(ASDR)of lung cancer attributable to 7 level-3 risk factors in China for 1990 and 2021 were also extracted.Counterfactual analysis was used to decompose changes in lung cancer deaths and DALY from 1990 to 2021 into four contributing factors:popu-lation size,population structure,age-standardized incidence or prevalence,and lung cancer case fatality or disease severity.The percentage changes in lung cancer deaths and DALY attributed to these four factors were calculated respectively.[Results]In 2021,there were 934 704 new cases and 814 364 deaths of lung cancer in China.From 1990 to 2021,the incidence,preva-lence,mortality,and DALY rates of lung cancer in China increased faster than those worldwide and in high-middle SDI regions,which was similar to Japan and Republic of Korea.In contrast,the mortality rates of lung cancer decreased in United States and United Kingdom;and the DALY rates of lung cancer decreased in United States,United Kingdom,Canada and Australia.From 1990 to 2021,the age-related lung cancer deaths and DALY in China increased by 193.91％and 146.20％,respectively.The primary contributor to the increase in lung cancer deaths was population aging(102.82％)among men and rising age-standardized incidence(119.00％)among women,while the primary contributor to the increase in DALY was rising age-standardized prevalence for both men(153.12％)and women(218.77％).In 2021,the top three risk factors contributing to lung cancer ASMR and ASDR in China were smoking,particulate matter pollution and occupational carcinogen exposure.Compared with 1990,the ASMR of lung cancer and its proportion at-tributable to particulate matter pollution and low dietary fruits were decreased,while the propor-tions in ASDR of lung cancer attributable to smoking and secondhand smoke increased.[Conclu-sion]Lung cancer is a major public health challenge in China.Compared with worldwide,high-middle SDI regions and certain developed countries,China has experienced faster growth in the incidence,prevalence,mortality and DALY of lung cancer,especially among women.To reduce disease burden,sustained efforts on lung cancer prevention and control are urgently required in China.

Objective To observe the value of body mass and body mass index(BMI)for calculating size specific dose estimate(SSDE)value of chest and abdominal CT in children.Methods Totally 486 children who underwent chest and abdominal CT scanning were retrospectively enrolled,including 201 underwent chest and 285 underwent abdominal CT scanning.SSDE value was calculated with software,body mass and BMI and recorded as SSDEstandard,SSDEweight and SSDEBMI,respectively,and the correlation and consistency between the former and the latter two were analyzed.Results SSDEweight(chest r=0.974,abdomen r=0.972)and SSDEBMI(chest r=0.933,abdomen r=0.950)were both highly correlated with SSDEstandard(all P＜0.01)and had good consistency.The root mean square error between SSDEweight and SSDEstandard of chest and abdominal CT was 0.245 and 0.249,between SSDEBMI and SSDEstandard was 0.653 and 0.956,respectively.Conclusion Body mass and BMI could be used to conveniently calculate SSDE value of chest and abdominal CT scanning in children,and the results had good consistency with that based on software.

AIM:To explore the potential mecha-nism of arecoline in promoting oral submucous fi-brosis based on key factors of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)pathway.METHODS:SD rats were randomly divided into arecoline low-dose group,arecoline medium-dose group,and are-coline high-dose group(5,10,and 15 mg/mL).The oral buccal mucosa was injected with the corre-sponding concentration of arecoline(ANE)solution to induce the establishment of oral submucous fi-brosis(OSF)models,with 8 rats in each group.An-other 8 unmodeled rats were selected as the blank group,and the changes in mouth opening of the rats were detected after 8 weeks of grouping and intervention.HE and Masson staining were used to observe the pathological changes of oral buccal mucosa,measure the length of epithelial staple process and calculate collagen volume fraction.Western blot and qRT-PCR were used to detect the expression of collagen-Ⅰ(COL-Ⅰ),E-cadherin,fibro-nectin(FN)and PI3K/Akt/mTOR signaling pathway-related proteins and mRNA in rat oral buccal muco-sa.The levels of tumor necrosis factor(TNF)-α,in-terleukin(IL)-1β and transforming growth factor(TGF)-β1 in rat serum were detected by ELISA.Hu-man immortalized keratinocytes(HaCaT cell line)were cultured in vitro,and the effects of different concentrations of arecoline,PI3K activator,and PI3K inhibitor on the survival rate of HaCaT cells were investigated by CCK-8 method.According to the results of CCK-8,the concentration of arecoline 75 μg/mL,the concentration of PI3K activator 10μmol/L,and the concentration of PI3K inhibitor 2μmol/L were selected as the subsequent experi-mental concentrations.The cells were set as blank group,arecoline group,PI3K activator group,PI3K inhibitor group,and arecoline+PI3K inhibitor group.The mRNA expression levels of COL-Ⅰ,E-cad-herin,FN,PI3K,Akt,and mTOR in each group of cells were detected by qRT-PCR.The levels of TNF-α,IL-1β and TGF-β1 in each group of cells were de-tected by ELISA.RESULTS:Compared with the blank group,the arecoline low-dose group,the are-coline medium-dose group,and the arecoline high-dose group significantly reduced the mouth open-ing,significantly shortened the length of the epi-thelial staple process,significantly increased the collagen volume fraction,inflammatory cell infiltra-tion,and severe pathological damage.The protein expression levels of COL-Ⅰ,FN,p-PI3K,p-Akt,and p-mTOR were up-regulated,and the protein expres-sion levels of E-cadherin were down-regulated.The mRNA expressions of COL-Ⅰ,FN,PI3K,Akt,and mTOR were significantly increased.The mRNA ex-pression of E-cadherin was significantly reduced,and the levels of TNF-α,IL-1β,and TGF-β1 were sig-nificantly increased(all P＜0.05 or P＜0.01).Com-pared with the blank group,the mRNA expression levels of COL-Ⅰ,FN,PI3K,Akt,and mTOR in the cells of the arecoline group and the PI3K activator group were up-regulated,and the mRNA expression lev-els of E-cadherin were down-regulated.Compared with the blank group,the mRNA expression levels of COL-Ⅰ,FN,PI3K,Akt,and mTOR in the cells of the PI3K inhibitor group were down-regulated,and the mRNA expression levels of E-cadherin were up-regulated.Compared with the PI3K inhibitor group,the mRNA expression levels of COL-Ⅰ,FN,PI3K,Akt,and mTOR in the cells of the arecoline+PI3K inhibi-tor group were up-regulated,the mRNA expression levels of E-cadherin were down-regulated,and the levels of TNF-α,IL-1β,and TGF-β1 were significant-ly increased(all P＜0.05 or P＜0.01).CONCLUSION:Arecoline can significantly promote oral submucous fibrosis,which may play a pro-fibrotic role by up-regulating the PI3K/Akt/mTOR signaling pathway.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism* ; Arthritis, Rheumatoid/immunology* ; Animals ; Dendritic Cells/metabolism* ; Paroxetine/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Lymphocyte Activation/drug effects* ; Female ; T-Lymphocytes/metabolism* ; Middle Aged