ObjectiveTo observe the effectiveness and safety of modified Taohong Siwu Decoction （桃红四物汤） for patients of chronic heart failure with lower limb deep vein thrombosis in the chronic stage of blood stasis syndrome. MethodsA total of 120 patients of chronic heart failure with lower limb deep vein thrombosis in chronic stage of blood stasis syndrome were randomly divided into 60 cases each in control group and observation group. Both groups were given basic treatment of western medicine， and the observation group was additionally given modified Taohong Siwu Decoction （桃红四物汤） for oral administration， one dose per day. The treatment course for both groups lasted for 4 weeks. The total effective rate and the incidence of adverse reactions were compared between the two groups after treatment. Cardiac function indexes including left ventricular ejection fraction （LVEF）， and left ventricular end-systolic internal diameter （LVESd）， left ventricular end-diastolic internal diameter （LVEDd）， serological indexes including N-terminal natriuretic natriuretic peptide precursor （NT-proBNP）， high sensitivity C-reactive protein （hs-CRP） and vascular endothelial growth factor （VEGF）， score of traditional Chinese medicine （TCM） symptom including chest pain， swelling of the affected limb， fixed tenderness， and bruising， haemodynamics indicators including high cut whole blood viscosity， low cut whole blood viscosity， and erythrocyte pressure， and coagulation indices including activated partial thromboplastin time （APTT）， plasminogen time （PT）， and fibrinogen （FIB） levels were compared before and after treatment. ResultsDuring the study， 3 cases were excluded and 2 cases lost follow-up in the observation group， while 2 cases were excluded and 3 cases lost follow-up in the control group. A total of 110 patients completed the trial， 55 cases in each of the two groups. The total effective rate in the observation group was 92.73% （51/55）， which was significantly higher than that of the control group， 78.18% （43/55， P＜0.05）. Compared within group before treatment， LVEF， APTT and PT levels increased， LVESd， LVEDd， NT-proBNP， hs-CRP， VEGF， high cut whole blood viscosity， low cut whole blood viscosity， erythrocyte pressure volume and FIB levels decreased， chest pain， swelling of the affected limbs， stationary pressure pain and bruising score decreased in both groups after treatment， and the improvement of all above indexes was better in the observation group than that in control group （P＜0.05 or P＜0.01）. The incidence of adverse reactions was 7.27% （4/55） in the observation group and 21.82% （12/55） in the control group， and the incidence of adverse reactions in the observation group was significantly lower than that in the control group （P＜0.05）. ConclusionModified Taohong Siwu Decoction （桃红四物汤） as adjuvant treatment for patients of chronic heart failure with lower limb deep vein thrombosis in the chronic stage of blood stasis syndrome showed better clinical effectiveness when compared with western basic treatment， which can improve the clinical symptoms， cardiac function， haemodynamics， and coagulation， with good safety.

Xiang thinking is a cognitive approach that reflects the relationships between phenomena and their underlying principles by analyzing their external manifestations through methods such as analogy， reasoning， deduction， and symbolism. This article applied xiang thinking to analyze the etiology and pathogenesis of "wind， fire， phlegm， and blood stasis" in stroke， thereby exploring its impact on the principles of syndrome differentiation and treatment of this condition. Meanwhile， the article traced the construction process of xiang thinking， and interpreted the concept of "toxin pathogen" in traditional Chinese medicine from four perspectives， state， attribute， origin， and law. Furthermore， the relationship between the process of constructing xiang thinking and the origin of etiology， identification methods， pathogenesis evolution， and treatment strategies for stroke with syndrome of combined blood stasis and toxin was explored， so as to provide insights into research on the etiology and pathogenesis of stroke， as well as clinical diagnosis and treatment approaches.

ObjectiveTo investigate the effects of Scutellariae Radix combined with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） on cell proliferation， apoptosis， cancer stem cell （CSC） marker expression， and metabolism in non-small cell lung cancer （NSCLC） cells. MethodsThe anti-tumor effects of Scutellariae Radix and EGFR-TKIs （gefitinib or osimertinib） in NSCLC cells were evaluated using the cell counting kit-8 （CCK-8） and Annexin V-FITC/propidium iodide （PI） double staining apoptosis assay. The activity of Scutellariae Radix and EGFR-TKIs in three-dimensional （3D） cultures of NSCLC cells was assessed using the CellTiter-Glo® 3D cell viability assay. The mRNA and protein expression levels of CSC markers， sex determining region y box protein 2 （SOX2） and aldehyde dehydrogenase 1 family member A1 （ALDH1A1）， were detected by quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot， respectively. Changes in intracellular reactive oxygen species （ROS） levels were detected by ROS staining， and the redox ratio was detected by femtosecond laser labeling free imaging （FLI）. ResultsUnder both two-dimensional （2D） and 3D culture conditions， compared with the blank group and EGFR-TKI group， the combination group showed significantly reduced cell viability and increased apoptosis rate （P<0.05）. Compared with the EGFR-TKI group， the mRNA and protein levels of CSC markers were significantly downregulated in the combination group （P<0.05）. Additionally， the redox ratio was significantly elevated （P<0.05）， and ROS levels were also increased in the combination group compared with the EGFR-TKI group. ConclusionIn NSCLC cells， Scutellariae Radix enhances the redox ratio and increases ROS levels， thereby inhibiting the expression of CSC markers and strengthening the anti-tumor effects of EGFR-TKIs. This provides a novel molecular mechanism by which Scutellariae Radix may enhance the sensitivity of targeted therapies.

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 observe the clinical efficacy of filiform needle combined with fire needles for cervical radiculopathy(CR)due to wind-cold obstructing the meridians. Methods:A total of 60 patients with CR due to wind-cold obstructing the meridians were randomized into an observation group and a control group,with 30 cases in each group.The control group was treated with filiform needle treatment,and the observation group was treated with additional fire needle point-pricking treatment.The visual analog scale(VAS)and 20-point scale of CR developed by Yasuhisa TANAKA(YT-20)were scored before treatment and after 1,2,3,and 4 weeks of treatments.The tenderness threshold was measured.The local skin temperature was measured by an infrared thermal imager.A safety evaluation was performed after treatment. Results:After treatment,the VAS score in the observation group at each time point was lower than that in the control group(P<0.05).The YT-20 score,tenderness threshold,and local skin temperature in the observation group were all higher than those in the control group(P<0.05).The VAS score in the observation group at each time point after treatment was lower than that before treatment(P<0.05),and the YT-20 score,tenderness threshold,and local skin temperature at each time point were higher than those before treatment(P<0.05).After 3 and 4 weeks of treatments,the VAS score in the control group was lower than that before treatment(P<0.05),and the YT-20 score,tenderness threshold,and local skin temperature were higher than those before treatment(P<0.05).The group factor effects of VAS and YT-20 scores,tenderness threshold,and local skin temperature between the two groups were statistically significant(P<0.05).There was no significant difference in the time effect and the interaction effect between time and group(P>0.05). Conclusion:Filiform needle combined with fire needle or applied alone both can relieve neck pain in patients with CR due to wind-cold obstructing the meridians,and improve the temperature of the neck.The combination of filiform needle and fire needle works more quickly and has better efficacy.

Objective To investigate the predictive value of combined serum levels of N-terminal pro-B-type natriuretic peptide(NT-proBNP)and lipoprotein(a)[Lp(a)]and coagulation function indicators for occurrence of deep venous thrombosis(DVT)in elderly patients with chronic heart failure(CHF).Methods A total of 230 elderly CHF patients admitted in Hengshui People's Hos-pital from January 25 to December 25,2022 were enrolled,and divided into a DVT group(76 ca-ses)and a non-DVT group(154 cases)based on the presence of DVT or not.And another 100 healthy individuals taking physical examination during the same period were included and served as the control group.The general information,clinical data,and coagulation indicators of each group were collected.Serum NT-proBNP and Lp(a)levels were measured with ELISA.Logistic regression analysis was used to determine the independent risk factors,and ROC curve was used to determine the predictive values of single and combined detection.Results The incidence of lower limb arteriosclerosis was significantly higher in the DVT group than that in the non-DVT group(P＜0.05),but there were no statistical differences in other data(P＞0.05).Platelet count and LDL in DVT group were higher than those in non-DVT group,and HDL was lower than those in non-DVT group(P＜0.05).The DVT group had notably shorter activated partial throm-boplastin time(aPTT),prothrombin time(PT)and thrombin time(TT),and remarkably higher FIB,D-dimer,NT-proBNP and Lp(a)levels when compared with the non-DVT group(P＜0.05).Logistic regression analysis showed that HDL,aPTT,FIB,D-dimer,NT-proBNP and Lp(a)were independent risk factors for DVT in elderly CHF patients(P＜0.05,P＜0.01).The obtained lo-gistic regression model was:Logit(P)=0.933X3+0.744X8+0.812X11+0.681X12+0.774X13+0.684X14.The combined regression model had an AUC value of 0.948(95％CI:0.918-0.977),a sensitivity of 89.47％and a specificity of 89.61％.Conclusion NT-proBNP,Lp(a),and coagula-tion function indicators are independent risk factors for DVT in elderly CHF patients,and com-bined detection has high predictive value.

Objective To explore the correlation of contrast-enhanced ultrasound(CEUS)parameters of adenomyoma before and after MR-guided focused ultrasound surgery(MRgFUS)with the therapeutic efficacy.Methods Uterine ultrasound and CEUS data of 26 patients with adenomyoma before and 24 h,1 and 6 months after MRgFUS,as well as MRI before and immediately after MRgFUS were retrospectively analyzed.The lesion volume shown on CEUS and MRI before MRgFUS,the non perfusion volume(NPV)of adenomyoma on MRI immediately after and CEUS 24 h after MRgFUS were compared.The ablation rate of lesions was calculated based on CEUS 24 h after MRgFUS.The focal blood flow score before,24 h after MRgFUS and the sum of the two,also the numerical rating scale(NRS)score before and 1,6 months after MRgFUS and the change rate were analyzed.The correlations of CEUS parameters with the efficacy of MRgFUS for treating adenomyoma were observed.Results No significant difference of lesion volume nor NPV on CEUS or MRI was found(both P＞0.05).The ablation rate of lesions 24 h after treatment was(58.11±24.92)%.The focal blood flow score before,24 h after MRgFUS and the sum of the two was 2.00(2.00,2.00),1.00(1.00,1.00)and 3.50(3.00,3.50),respectively,with significant difference between before and 24 h after MRgFUS(Z=-4.463,P＜0.001).NRS score was 5.00(4.00,6.00),3.00(2.00,4.00)and 2.00(1.00,3.00)before treatment,1 and 6 months after treatment,respectively,with significant differences at different time points(all P＜0.01).The change rate of NRS score 1 and 6 months after treatment was 35.42%(23.75%,50.00%)and 60.00%(50.00%,77.08%),respectively.The lesion blood flow score before and 24 h after MRgFUS and the sum of the two were all negatively correlated with ablation rate(rs=-0.552,-0.820,-0.745),while positively correlated with NRS scores 6 months after treatment(rs=0.513,0.552,0.496)but negatively correlated with the change rate of NRS scores 6 months after treatment(rs=-0.525,-0.479,-0.531).The ablation rate 24 h after treatment was negatively correlated with NRS scores(rs=-0.462)while positively correlated with the change rate of NRS scores 6 months after treatment(rs=0.500).Conclusion CEUS parameters before and after treatment were correlated with the therapeutic efficacy of MRgFUS for treating adenomyoma.

As a special role in the nursing team,the staff in nursing department plays a very important role in the con-struction and development of the nursing team.This paper discusses the post characteristics and the quality and ability require-ments of the staff in nursing department,and sorts out and summarizes the methods and strategies in improving their post compe-tence including the abilities of professional knowledge,coordination and execution,language expression,observation and think-ing,scientific research innovation,communication,service and resisting pressure.These will provide reference for the staff in nursing department to grow into excellent key-members of nursing management.

Objective:To explore characteristics of intestinal flora in patients with rheumatoid arthritis complicated with inter-stitial lung disease(RA-ILD),to analyze its influencing factors,and to explore improvement of intestinal flora in patients with RA-ILD by different treatment methods.Methods:A total of 100 patients with RA-ILD who visited Shijiazhuang People's Hospital from June 2021 to June 2022 were selected as research objects,and 100 healthy patients in Shijiazhuang People's Hospital during same pe-riod were selected as healthy group.High throughput sequencing was performed on intestinal flora of two groups,OTU flora abundance and α-Diversity,β-diversity,flora distribution and LEfSe difference were analyzed.Another 100 patients with RA-ILD were randomly divided into group A(n=50)and group B(n=50).Group A was treated with leflunomide+nidanib or pifenidone,and group B was treated with leflunomide+nidanib or pifenidone+bifidobacterium triad.Improvement of intestinal flora in two groups after treatment was analyzed.Correlation analysis was used to determine correlation between changes of intestinal flora and clinical characteristics and indicators in RA-ILD patients.Results:OTU flora abundance,α-diversity and β-diversity in RA-ILD patients were lower than that of healthy people.Abundance of Intestinibacter in RA-ILD group was higher than that in healthy group,and abundance of Lactobacillus,Escherichia coli,Klebsiella,Candidatus saccharimonas,Odoribacter and Enterococcus in RA-ILD group were lower than that in healthy group.After treatment,flora structure of group A and group B was improved.Group B was closer to healthy population,and cu-rative effect was significantly better than that of group A.Integinibacter bacteria level was positively correlated with age,RA course,DAS28,CRP,RF and KL-6(P<0.05),and negatively correlated with DLCO(P<0.05).Lactobacillus level was negatively correlated with course of RA,DAS28,CRP,RF,IL-6(P<0.05),and positively correlated with VC(P<0.05);Shigella coli level was negtively correlatied with RA course,ILD course,DAS28,ESR,RF,TNF-α(P<0.05).Klebsiella level was positively correlated with VC and DLCO(P<0.05);Bacterial level of Candida saccharimonas was negatively correlated with DAS28,ESR,CRP,RF,IL-6,TNF-α(P<0.05)and positive correlated with DLCO(P<0.05);Odoribacter bacteria level was negatively correlated with DAS28,CRP,RF,IL-6 and KL-6(P<0.05),and positively correlated with VC(P<0.05);Enterococcus level was negatively correlated with course of RA,ILD,DAS28,ESR,RF and KL-6(P<0.05),while positively correlated with DLCO(P<0.05).Conclusion:Intestinal microflora abundance of RA-ILD patients is significantly lower than that of healthy people,and there aree significant differences in some microflora,which are closely related to clinical characteristics and indicators.Using of bifidobacterium triad in clinical treatment is helpful to improve intestinal flora of RA-ILD patients.

ObjectiveTo investigate the therapeutic effect of Lycopi Herba extract on chronic prostatitis （CNP） and explore the underlying action mechanism via the inflammasome NOD-like receptor protein 3 （NLRP3） pathway. MethodNormal human prostatic stromal cells， namely WPMY-1 were induced by lipopolysaccharide （LPS） of 5 mg·L^-1， and the effects of Lycopi Herba extract of 3.125， 6.25， 12.5， 25， 50， and 100 mg·L^-1 on interleukin-6 （IL-6） level released by LPS-induced WPMY-1 cells were detected by enzyme-linked immunosorbent assay （ELISA）. The half-maximal inhibitory concentration （IC₅₀） was calculated. The expression of key proteins in the NLRP3 pathway was detected by western blot after Lycopi Herba extract of 50， 75， and 100 mg·L^-1 was administered to WPMY-1 cells. The rat model of CNP was established by injecting carrageenan salt solution into the abdominal lobe of the prostate gland. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the prostate gland in rats. The prostate organ index of rats was measured. The level of 5α-dihydrotestosterone （5α-DHT） in serum， as well as the levels of IL-6， tumor necrosis factor-α （TNF-α）， transforming growth factor-β₁ （TGF-β₁）， cyclooxygenase-2 （COX-2）， prostaglandin E₂ （PGE₂）， and inducible nitric oxide synthase （iNOS） in prostate tissue were detected by ELISA. The key protein expressions of COX-2， TGF-β₁， and NLRP3 pathway in prostate tissue were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expressions of COX-2， IL-1β， TGF-β₁， and TNF-α mRNA in prostate tissue. ResultCompared with the normal group， the level of IL-6 and the protein expression levels of NLRP3， ASC， Caspase-1， and IL-1β of WPMY-1 cells in the model group were increased （P<0.05， P<0.01）. Compared with the model group， Lycopi Herba extract could inhibit the levels of IL-6 （P<0.01） released by LPS-induced WPMY-1 cells， with IC₅₀ of 38.26 mg·L^-1. The protein expression levels of NLRP3， ASC， and IL-1β in the low-， medium-， and high-dose groups of Lycopi Herba extract were significantly down-regulated （P<0.05， P<0.01）. The expression levels of Caspase-1 protein in medium- and high-dose groups of Lycopi Herba extract were significantly down-regulated （P<0.05， P<0.01）. Compared with the sham operation group， the prostate organ index of rats in the model group was significantly increased （P<0.01）， a large number of inflammatory cells were infiltrated in the prostate tissue， and the histopathological score was significantly increased （P<0.05）； the levels of 5α-DHT in serum， the levels of TNF-α， PGE₂， IL-6， TGF-β₁， NOS₂/iNOS， and COX-2 in prostate tissue， and expression levels of COX-2， IL-1β， and TGF-β₁ were significantly increased （P<0.05， P<0.01）. The mRNA expression levels of COX-2， TGF-β₁， NLRP3， Caspase-1， ASC， and IL-1β in prostate tissue were significantly up-regulated （P<0.05， P<0.01）. Compared with model group， the low and high doses of Lycopi Herba extract could alleviate the pathological changes in prostate tissue induced by carrageenan， significantly reduce the level of 5α-DHT in serum， levels of TNF-α， PGE₂， TGF-β₁， and iNOS in prostate tissue （P<0.05， P<0.01）， and mRNA expression levels of COX-2， IL-1β， and TGF-β₁ （P<0.05， P<0.01）. The protein expression levels of COX-2， Caspase-1， ASC， and NLRP3 in prostate tissue were significantly down-regulated （P<0.05， P<0.01）. The prostate organ index of the low-dose group of Lycopi Herba extract was significantly decreased （P<0.01）. The level of COX-2 in prostate tissue of the high-dose group of Lycopi Herba extract was significantly decreased， and the protein expression levels of TGF-β₁ and IL-1β were significantly down-regulated （P<0.05）. ConclusionLycopi Herba extract has an obvious therapeutic effect on CNP and may reduce inflammation by inhibiting the activation of the inflammasome NLRP3 signaling pathway.