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

Objective:To explore prognosis and related risk factors of patients with systemic lupus erythematosus(SLE)combined with decreased complement C3 level.Methods:A total of 173 SLE patients with decreased complement C3 level who were treated in Chongzuo People's Hospital from June 2018 to March 2022 were selected as research subjects,and divided into good progno-sis group(n=151)and poor prognosis group(n=22)according to follow-up prognostic effect.Clinical data and biochemical indicators of patients were recorded.A nomogram model was established for analysis and model validation.Results:There were statistical signifi-cance in lupus activity,C3,A/G,hs-CRP between two groups(P<0.05);lupus activity,C3,A/G,hs-CRP were independent risk factors for outcomes of SLE patients with reduced complement C3.Prediction effect of nomogram model was good,and consistency of model validation was strong.Complement C3 level was correlated with SLE(χ2=7.524,P=0.002),with a linear dose-response relation-ship(χ2=1.527,P=0.118).Conclusion:SLE patients with decreased complement C3 level have poor prognosis,who has many risk factor.Prognosis of SLE can be enhanced from aspects of lupus activity,C3,A/G and hs-CRP.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Objective:To explore the influence and mechanism of perceived school climate on life satisfaction of junior high school students.Methods:From June to September 2022, students in sixth, seventh and eighth grade of junior high school were surveyed by the perceived school climate scale, the family cumulative risk-related questionnaire, the cognitive emotion regulation strategy questionnaire and the life satisfaction scale.SPSS 25.0 software was used to process data and the macro program PROCESS 4.1 was used for model testing.Results:(1) The total scores of perceived school climate, negative cognitive emotion regulation strategy, life satisfaction and family cumulative risk were 83.00(19.00), 21.00(8.00), 23.00(9.00) and 1.00(2.00), respectively.(2) Perceived school climate was significantly and negatively correlated with negative cognitive emotion regulation strategy and family cumulative risk( r=-0.30, -0.40, both P<0.01), while significantly and positively correlated with life satisfaction ( r=0.51, P<0.01).Negative cognitive emotion regulation strategy was significantly and negatively correlated with life satisfaction ( r=-0.37, P<0.01), while significantly and positively correlated with family cumulative risk ( r=0.29, P<0.01). Family cumulative risk was significantly and negatively correlated with life satisfaction ( r=-0.45, P<0.01). (3) Negative cognitive emotion regulation strategy played a mediating role between perceived school climate and life satisfaction, and the mediating effect accounted for 13.46%(0.07/0.52) of the total effect. (4) Family cumulative risk played a moderating role in the relationship between perceived school climate and life satisfaction, and between perceived school climate and negative cognitive emotion regulation strategy. Specifically, as the level of family cumulative risk decreased, the positive predictive effect of perceived school climate on life satisfaction significantly increased ( βsimple=0.42, P<0.001). Perceived school climate significantly and negatively predicted negative cognitive emotion regulation strategy under the condition of low level family cumulative risk ( βsimple=-0.30, P<0.001). Conclusion:Under the condition of low family cumulative risk in junior high school students, the perceived positive school climate can help reduce negative cognitive emotion regulation strategy, thereby improving life satisfaction.

Chronic pain impairs functions across multiple dimensions,including physical,psychological,and social well-being.The neuro-immune mechanisms involve complex interactions between the immune system and nerve fibers at one or multiple levels of the peripheral or central nervous system.In recent years,research on the neuro-immune circuit mechanisms underlying the generation,transmission,modulation,and integration of chronic pain has advanced rapidly.However,the overall interactive dynamics of neuro-immune mechanisms remain unclear.This article systematically reviews recent advances in the neuro-immune mechanisms of chronic pain,elucidating the cascading transformation from peripheral to central sensitization.These findings provide a theoretical basis for a deeper understanding of the overall pathophysiological basis of pain chronicity and the exploration of effective clinical strategies.

Objective:To explore the influence and mechanism of perceived school climate on life satisfaction of junior high school students.Methods:From June to September 2022, students in sixth, seventh and eighth grade of junior high school were surveyed by the perceived school climate scale, the family cumulative risk-related questionnaire, the cognitive emotion regulation strategy questionnaire and the life satisfaction scale.SPSS 25.0 software was used to process data and the macro program PROCESS 4.1 was used for model testing.Results:(1) The total scores of perceived school climate, negative cognitive emotion regulation strategy, life satisfaction and family cumulative risk were 83.00(19.00), 21.00(8.00), 23.00(9.00) and 1.00(2.00), respectively.(2) Perceived school climate was significantly and negatively correlated with negative cognitive emotion regulation strategy and family cumulative risk( r=-0.30, -0.40, both P<0.01), while significantly and positively correlated with life satisfaction ( r=0.51, P<0.01).Negative cognitive emotion regulation strategy was significantly and negatively correlated with life satisfaction ( r=-0.37, P<0.01), while significantly and positively correlated with family cumulative risk ( r=0.29, P<0.01). Family cumulative risk was significantly and negatively correlated with life satisfaction ( r=-0.45, P<0.01). (3) Negative cognitive emotion regulation strategy played a mediating role between perceived school climate and life satisfaction, and the mediating effect accounted for 13.46%(0.07/0.52) of the total effect. (4) Family cumulative risk played a moderating role in the relationship between perceived school climate and life satisfaction, and between perceived school climate and negative cognitive emotion regulation strategy. Specifically, as the level of family cumulative risk decreased, the positive predictive effect of perceived school climate on life satisfaction significantly increased ( βsimple=0.42, P<0.001). Perceived school climate significantly and negatively predicted negative cognitive emotion regulation strategy under the condition of low level family cumulative risk ( βsimple=-0.30, P<0.001). Conclusion:Under the condition of low family cumulative risk in junior high school students, the perceived positive school climate can help reduce negative cognitive emotion regulation strategy, thereby improving life satisfaction.

Chronic pain impairs functions across multiple dimensions,including physical,psychological,and social well-being.The neuro-immune mechanisms involve complex interactions between the immune system and nerve fibers at one or multiple levels of the peripheral or central nervous system.In recent years,research on the neuro-immune circuit mechanisms underlying the generation,transmission,modulation,and integration of chronic pain has advanced rapidly.However,the overall interactive dynamics of neuro-immune mechanisms remain unclear.This article systematically reviews recent advances in the neuro-immune mechanisms of chronic pain,elucidating the cascading transformation from peripheral to central sensitization.These findings provide a theoretical basis for a deeper understanding of the overall pathophysiological basis of pain chronicity and the exploration of effective clinical strategies.

Objective:To explore prognosis and related risk factors of patients with systemic lupus erythematosus(SLE)combined with decreased complement C3 level.Methods:A total of 173 SLE patients with decreased complement C3 level who were treated in Chongzuo People's Hospital from June 2018 to March 2022 were selected as research subjects,and divided into good progno-sis group(n=151)and poor prognosis group(n=22)according to follow-up prognostic effect.Clinical data and biochemical indicators of patients were recorded.A nomogram model was established for analysis and model validation.Results:There were statistical signifi-cance in lupus activity,C3,A/G,hs-CRP between two groups(P<0.05);lupus activity,C3,A/G,hs-CRP were independent risk factors for outcomes of SLE patients with reduced complement C3.Prediction effect of nomogram model was good,and consistency of model validation was strong.Complement C3 level was correlated with SLE(χ2=7.524,P=0.002),with a linear dose-response relation-ship(χ2=1.527,P=0.118).Conclusion:SLE patients with decreased complement C3 level have poor prognosis,who has many risk factor.Prognosis of SLE can be enhanced from aspects of lupus activity,C3,A/G and hs-CRP.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Objective:To explore the locations of the lumbosacral nerve roots by use of the magnetic stimulation.Methods:Thirty healthy subjects were studied. The projections of the right L 2 to S 1 intervertebral foramina on their body surfaces were determined manually with ultrasound assistance. Magnetic stimulation was applied to different nerve root segments to induce compound muscle action potentials (CMAP) in the vastus medialis, tibialis anterior, and gastrocnemius muscles of the lower limbs. The changes in latency, amplitude, and motor threshold were observed. Results:Magnetic stimulation on the L 2-L 3 segment resulted in a significant direct excitation of the vastus medialis. That on the L 5-S 1 segment evoked a significant direct excitatory effect on the tibialis anterior and gastrocnemius, with a motor threshold below 40%, an amplitude exceeding 1mV, and many effective responses. However, during the magnetic stimulation on the L 4 segment, the amplitude of the vastus medialis was above 1mV, with no significant differences in the number of effective responses among the muscle groups. Moreover, there was a stepwise change in the latency of effective muscle responses to magnetic stimulation at different segments. The CMAP latencies of 12+ ms for the tibialis anterior and 13+ ms for the gastrocnemius indicated activation of the L 5 and L 4 nerve roots, respectively, while those of 6+ ms, 7+ ms, and 8+ ms for the vastus medialis suggested activation of the L 4, L 3, and L 2 nerve roots, respectively. Conclusions:Based on the responses (CMAP latency, amplitude and motor threshold) of the vastus medialis, tibialis anterior and gastrocnemius to magnetic stimulation at different L 2 to S 1 segments, the spinal nerve root segments responsible for innervation can be inferred.