ObjectiveTo investigate the effect of kynurenine-3-monooxygenase （KMO） on the function of fibroblast-like synoviocytes （FLS） in rheumatoid arthritis （RA）. MethodsKMO expression in synovial tissues from RA patients and healthy controls （HC） was analyzed using bioinformatics. Synovial tissues from RA patients and HC were collected， and KMO expression in FLS within synovial tissues was detected by immunofluorescence （IF）. In vitro experiments were performed using human rheumatoid arthritis fibroblast-like synoviocytes （MH7A）. Following KMO overexpression， KMO knockdown， and KMO inhibition with the specific inhibitor Ro61-8048 in MH7A cells， Western blot， CCK-8， EdU， Transwell and ELISA assays were used to evaluate alterations in cell viability， proliferation， migration and secretory function. ResultsBioinformatic analysis revealed significantly higher KMO gene expression in RA synovial tissue compared to the HC group （P<0.001）. IF results showed increased KMO expression in FLS from RA synovial tissues relative to the HC group （P<0.01）. Overexpression of KMO led to enhanced viability， proliferation， migration， and secretory capabilities of MH7A cells （all P<0.05）， whereas knockdown or inhibition of KMO with Ro61-8048 markedly suppressed these functions （all P<0.05）. ConclusionThe expression of KMO is upregulated in the synovial tissues of RA patients and promotes the activation of RA-FLS， suggesting that KMO may serve as a potential therapeutic target for RA treatment.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

ObjectiveTo observe the clinical efficacy of modified Xiangsha Liujunzi Decoction （香砂六君子汤， XLD） in the treatment of abemaciclib-related diarrhea of spleen-stomach deficiency type， and its regulatory effect on immune function in patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative （HR+/HER2-） breast cancer. MethodsA prospective， randomized， open-label， blinded-endpoint （PROBE） study was conducted. A total of 70 patients with advanced HR+/HER2- breast cancer and abemaciclib-related diarrhea were randomly divided into two groups， with 35 cases in each group. In addition to abemaciclib， the control group was treated with oral loperamide， while the trial group was treated with oral modified XLD. Both groups received treatment for 7 days as one course. The efficacy for diarrhea after treatment was compared between groups. Traditional Chinese medicine （TCM） syndrome score， Karnofsky performance status （KPS） score， inflammatory markers including interleukin-6 （IL-6） and C-reactive protein （CRP）， and immune function indicators including CD4⁺， CD8⁺， and CD4⁺/CD8⁺ ratio were compared between groups before and after treatment. Adverse events during the study were recorded， and safety was assessed. ResultsDuring the study， 1 case in the trial group and 2 cases in the control group， were lost to follow-up leaving 34 cases in the trial group and 33 cases in the control group for final analysis. The total effective rate of diarrhea in the trial group was 94.12% （32/34）， higher than 72.73% （24/33） in the control group （P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， increased KPS scores， increased CD4⁺， CD8⁺， and CD4⁺/CD8⁺ ratio， and decreased IL-6 and CRP levels （all P＜0.05）. Compared to the control group， the trial group had higher KPS scores， CD4⁺ levels， and CD4⁺/CD8⁺ ratios， and lower TCM syndrome scores and IL-6， CRP， and CD8⁺ levels （P＜0.05）. The incidence of adverse events in the trial group was 20.59% （7/34）， with an incidence of adverse drug reactions of 14.71% （5/34） after causality assessment； in the control group， the corresponding rates were 45.45% （15/33） and 39.39% （13/33）， respectively. The incidence of adverse events in the trial group was significantly lower than that in the control group （P＜0.05）. ConclusionModified XLD can effectively alleviate abemaciclib-related diarrhea in patients with advanced HR+/HER2- breast cancer of the spleen-stomach deficiency type， reduce levels of inflammatory cytokines， and regulate immune function， with a favorable safety profile.

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 : To investigate the expression and clinical significance of kynurenine-3-monooxygenase (KMO) in peripheral blood mononuclear cells ( PBMC ) ，synovial tissue ，and fibroblastic-like synovial cells (FLS) of rheumatoid arthritis (RA) patients． Methods : Peripheral blood samples from 25 healthy control ( HC) individuals and 25 patients diagnosed with RA were collected ，and real-time fluorescence quantitative PCR and Western blot were used to detect KMO gene and protein expression in PBMC of RA and HC groups，and to analyze the correlation between the expression level of the KMO gene in the PBMC of the RA patients and the indexes of the laboratory tests．Meanwhile，immunohistochemistry and immunofluorescence were used to detect KMO expression in synovial tissue and FLS in RA and HC groups． Results : ① KMO gene and protein expression in PBMC of RA group were higher than that of HC group，and the difference was statistically significant (P＜0. 001) ．② The level of KMO gene expression in PBMC of RA group was positively correlated with disease activity index 28 score，blood sedimentation，and rheumatoid factor (rs = 0. 417，P = 0. 038 ; r = 0. 545，P = 0. 005 ; rs = 0. 433，P = 0. 031) ， and had no correlation with C-reactive protein and anti-cyclic citrullinated polypeptide antibody．③ KMO expres- sion in synovial tissue of RA group was higher than that of HC group，and the difference was statistically significant (P＜0. 01) ; KMO expression in FLS of synovial tissue of RA group was higher than that of HC group，and the difference was statistically significant (P ＜0. 001) ． Conclusion KMO expression increases in PBMC ，synovial tissue and FLS of RA patients，and the level of KMO gene expression is correlated with the disease activity of RA patients，suggesting that KMO may promote the course of RA．

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 To investigate the value of geometric parameters of vertebrobasilar artery(VBA)for judging whether vertebral artery(VA)provide cross blood supply of posterior cerebral artery(PCA)blood supply area.Methods MR T2-fluid attenuated inversion recovery(FLAIR),3D time of flight(TOF)MR angiography(MRA)and territorial arterial spin labeling(t-ASL)images of 244 healthy adults were prospectively acquired.The angles between left VA(LVA)or right VA(RVA)and basilar artery(BA)were measured,and the sum and difference between the two angles were calculated(referred to as the sum of VA angles and the difference of VA angles),and the differences of diameters of LVA and RVA were measured and calculated(referred to as the difference of VA diameters).VA perfusion distribution type in PCA blood supply area were observed,and those with type Ⅲ or Ⅵ were enrolled in cross group,while those with type Ⅱ or Ⅴ were enrolled in non-cross group,respectively.The geometric parameters of VBA were compared between groups.Receiver operating characteristic(ROC)curve of parameters being significant different between groups were drawn,and the efficacy of these parameters for judging whether VA provide cross blood supply of PCA area were evaluated.Results There were 34 subjects in cross group and 75 in non-cross group.The sum of VA angles and the difference of VA angles in cross group were both larger than those in non-cross group(both P＜0.05),while the difference of VA diameters were not significantly different between groups(P＞0.05).The AUC of the difference of VA angles for judging whether VA provide cross blood supply of PCA area was 0.676(P＜0.05),while of the sum of VA angles was 0.598(P=0.103).Conclusion The angle differences of LVA and RVA with BA had certain application value for judging whether VA provide cross blood supply of PCA area.

Objective To explore the perfusion distribution of vertebral arteries(VA)in healthy adults,and to observe the impact of VA diameter on perfusion distribution based on territorial arterial spin labeling(t-ASL)technique.Methods A total of 228 healthy adult volunteers were prospectively recruited.t-ASL imaging was utilized to analyze VA perfusion patterns in supratentorial region.Bilateral VA diameters,absolute inter-side VA diameter differences,as well as perfusion volumes(PV)supplied by each VA to supratentorial,cerebellar and their combined were recorded.Pearson correlation analysis was performed to analyze the correlations of VA diameters with PVsupratentorial,PVcerebellar and PVsupratentorial+cerebellar.Results Five patterns of distinct perfusion distribution were identified in supratentorial region,leading to participant stratification into 5 groups.Significant differences of absolute inter-side VA diameter differences was found among groups(P＜0.001).The mean bilateral VA diameter,PVsupratentorial,PVcerebellar and PVsupratentorial+cerebellar was(1.94±0.49)mm,(91.77±49.34)cm3,(74.72±27.68)cm3 and(166.49±59.53)cm3,respectively.VA diameter showed low-moderate positive correlations with PVsupratentorial,PVcerebellar and PVsupratentorial+cerebellar(r=0.483,0.179,0.484,all P＜0.001).Conclusion Perfusion imaging of t-ASL could visualize various perfusion distribution forms of VA in supratentorial region.Diameter of VA had certain impact on both spatial distribution characteristics and quantitative perfusion volumes.

Objective To explore the sleep quality and mental fatigue level in elderly patients with cerebrovascular small disease(CSVD).Methods A total of 222 patients aged over 65 years old hospitalized due to chronic diseases in Department of Neurology of the Affiliated Jiangning Hospi-tal of Nanjing Medical University from August 2022 to June 2024 were recruited prospectively and continuously.According to the CSVD score,they were divided into a CSVD group(CSVD score≥1,148 cases)and a non-CSVD group(CSVD score=0,74 cases).All the patients were evaluated by sleep quality,fatigue and neuropsychological scale when they were fully cooperated and in good condition.Subsequently,the patients in the CSVD group were further assigned into a good sleep subgroup(117 cases)and a poor sleep subgroup(31 patients).Results The CSVD group had significantly higher total score of Pittsburgh sleep quality index(PSQI),sleep quality score,sleep disturbance score,total score of self-rating fatigue,and mental fatigue score than the non-CSVD group(P＜0.01).The sleep quality score,sleep disturbance score,and mental fatigue score were risk factors for CSVD(P＜0.05).The mental fatigue score was significantly higher in the CSVD patients with poor sleep than those with good sleep(4.13±1.15 vs 2.50±1.92,P＜0.01).Conclusion Elderly CSVD patients were more likely to have decreased sleep quality and mental fatigue,and among them,those with poor sleep quality are prone to having mental fatigue than those with good sleep.