Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

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

ObjectiveTo explore the possible mechanism of the treatment of dry eye with liver-meridian constraint-heat syndrome by Runmu Xiaoyao Powder （润目逍遥散） by miR-146a-5p and interleukin-1 receptor-associated kinase 1/tumour necrosis factor receptor associated factor 6/nuclear factor-κB （IRAK1/TRAF6/NF-κB） signalling pathway. MethodsEighty C57BL/6J mice were randomly divided into normal group， model group， agonist group， inhibitor group， sodium hyaluronate group， and Runmu Xiaoyao Powder high-， medium-， and low-dose groups， with 10 mice in each group. Except for the normal group， the mice of dry eye with liver-meridian constraint-heat syndrome were modeled by using benzalkonium chloride solution eye drops combined with chronic pain stimulation. Beginning on the 30th day of modelling， mice in Runmu Xiaoyao Powder high-， medium-， and low-dose groups were given 29， 14.5， and 7.25 g/kg of Runmu Xiaoyao Powder respectively twice daily by gavage； mice in sodium hyaluronate group were given 5 μl of sodium hyaluronate drops twice daily； mice in the agonist group were given 2 nmol of agomir-146a-5p drops in each eye at a time， and those in the inhibitor group were given 5 nmol of antagomir-146a-5p drops in each eye， with every other day， 3 times per week； mice in the normal and model groups were gavaged with deionised water at 1 ml/（100 g·d）. The intervention was continued for 14 days in each group， and mice in each group were examined for tear secretion， tear film rupture time， corneal fluorescein staining， and irritability scores on the day following the last intervention； HE staining was used to observe the pathological conditions of the cornea and lacrimal glands in each group； corneal and lacrimal gland inflammatory factors， such as interleukin 1β （IL-1β）， tumour necrosis factor α （TNF-α）， miR-146a-5p expression， were examined； matrix metalloproteinase 3 （MMP-3） and matrix metalloproteinase 9 （MMP-9） expression in cornea， IRAK1， TRAF6， nuclear factor κB p65 （NF-κB p65） protein and mRNA expression in cornea and lacrimal gland， and phosphorylated nuclear factor κB p65 （p-NF-κB p65） protein expression were detected. ResultsCompared with the normal group， mice in the model group showed reduced tear secretion， shorter tear film rupture time， higher irritability score （P＜0.05）， and pathological examination showed staining in the centre of the cornea， obvious corneal damage， increased volume of lacrimal gland follicular cells， disordered arrangement， a large number of inflammatory cell infiltration， and increased neovascularisation； corneal and lacrimal gland tissues showed elevated expression of IL-1β and TNF-α， decreased expression of miR -146a-5p， elevated expression of IRAK1， TRAF6， NF-κB p65， p-NF-κB p65 protein and IRAK1， TRAF6， NF-κB p65 mRNA， and elevated expression of MMP-3， MMP-9 protein in the cornea （P＜0.05）. Compared with the model group， all of the above indexes were significantly improved in high-dose group of Runmu Xiaoyao Powder， while some indexes were improved in the sodium hyaluronate group and the middle- and low-dose Runmu Xiaoyao Powder groups （P＜0.05）. Compared with the model group， corneal and lacrimal IRAK1 and TRAF6 mRNA and IRAK1， TRAF6 and p-NF-κB p65 protein expression decreased in the agonist group； compared with the inhibitor group， IRAK1， TRAF6， NF-κB p65 mRNA and protein expression in the cornea and lacrimal gland in the Runmu Xiaoyao Powder groups decreased （P＜0.05）. ConclusionRunmu Xiaoyao Powder can negatively regulate the IRAK1/TRAF6/NF-κB signalling pathway in the cornea and lacrimal gland of mice with dry eye of liver-meridian constraint-heat syndrome by up-regulation of miR-146a-5p， so as to inhibit inflammatory response and reduce the damage of the ocular surface tissues， and the high doses group showed the best effect.

OBJECTIVE To explore the application effects of the multi-disciplinary treatment （MDT）-based continuous pharmaceutical care system in patients undergoing anti-infection treatment. METHODS This research team innovatively developed an MDT continuous pharmaceutical care system， which was applied to cases of anti-infection treatment following MDT due to infection， aiming to innovate the continuous medication supervision model. A retrospective analysis method was used to collect data from 150 patients in the intensive care unit who underwent conventional anti-infection MDT consultations from January to October 2021 in Banan Hospital Affiliated to Chongqing Medical University， serving as the control group， and 130 patients in the intensive care unit who were under the MDT continuous pharmaceutical care system from January to October 2022 were selected as the intervention group. The general information of the patients， the information continuous tracking management， the outcomes of anti- infection treatment， adverse drug reactions， antibacterial drug management indicators， and the degree of satisfaction of relevant medical staff with the clinical pharmacists’ pharmaceutical services were compared between the two groups. RESULTS Comparison of general information between the two groups showed no statistically significant differences （P＞0.05）. The proportion of continuous tracking management in the intervention group was significantly higher than in the control group （P＜0.01）， and the differences in the initiators and reasons for continuous tracking management between the two groups were statistically significant （P＜0.05）. The intervention group had better outcomes in anti-infection treatment compared to the control group （P＜0.05）. The antibacterial drug management indicators （total length of hospital stay， duration of antibacterial drug use， total drug costs， and amount of antibacterial drugs used） in the intervention group were significantly lower than in the control group， while overall degree of satisfaction among medical staff was significantly higher in the intervention group than in the control group （P＜0.05）. No statistically significant differences were found in adverse reaction occurrence and antibacterial drug costs between the two groups （P＞0.05）. CONCLUSIONS The application of this system in patients who underwent anti-infection treatment after MDT can achieve continuous multi-disciplinary tracking management with clinical pharmacists at the core， which is beneficial for promoting the follow-up efficiency of the MDT team， raising the quality of clinical pharmacists’ pharmaceutical services， strengthening treatment outcomes， and promoting the rational use of antibacterial drugs in clinical practice.

Objective:To explore the current situation of synergistic allocation of factors of production in China's medical research institutes,sort out the focuses and deficiencies of the existing policies,so as to provide references for the optimization of production factor and the new quality productivity formation in medical institutions.Methods:Based on the two-factor productivity theory,the index evaluation system is constructed,and the composite system synergy model is used to analyze the degree of order of production factors and the degree of synergy of the composite system,and explore the change of synergy degree of each sequential covariate;and the macro model of the health system is used in conjunction with the content analysis method to carry out the frequency counting of the policies to promote the enhancement of the capacity of each production factor of the main body of innovation of the medical scientific research institutes.Results:The synergistic degree of the production factors and the composite system of medical research institutions showed a non-synergistic development trend,with the worst synergistic level in 2021;number of personnel,number of institutions,building floor space,production factors and sequential coefficients were weakly synergized and in a state of non-synergistic development.Among the 43 policy texts,the internal submodular policy tools were used more,the external submodular policy tools were used less,and the use of internal and external policy tools is unbalanced.Conclusion:The number of personnel,institutions and building area of medical research institutions are constraints on the synergistic development of innovative entities.It is recommended to increase the training of innovative talents in medical research institutions,improve the construction of new institutions,coordinate the layout of large scientific devices and functional housing,introduce targeted systematic planning,improve the market of factors of production,and consolidate the technological foundation for future development.