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.

Objective Nude mice xenograft model with aberrant activation of the PI3K/AKT pathway was established based on PIK3CA-overexpressing non-small cell lung cancer(NSCLC)cell lines PC-9,to observe the effect of Qingkailing injection combined with gefitinib on the growth of xenograft tumor in nude mice and explore its effects on ROS levels,mTOR pathway and STAT3 pathway.Methods After the xenografttumor model of BALB/c nude mice was established successfully,the mice were randomly divided into control group,Qingkailing injection group(10 mL·kg-1),gefitinib group(2.5 mg·kg-1),and Qingkailing combined with gefitinib group,with 5 mice in each group.They were administered for 32 days and then sacrificed.The tumor weight of each group was weighed and the tumor suppression rate was calculated;the level of ROS in the tumor tissues of each group was detected by flow cytometry;the protein levels of PI3K p110α,p-AKT and p-STAT3 in the xenograft tumor tissues of each group were detected by immunohistochemistry;the protein levels of the PI3K/AKT/mTOR pathway and the STAT3 pathway in the xenografttumor tissues of each group were detected by protein western blotting.Results Compared with the control group,Qingkailing injection could slow the tumor growth,significantly reduce the tumor weight,increase the level of ROS,and could significantly down-regulate the levels of PI3K p110α,AKT,mTOR,and STAT3 proteins in the tumor tissues(P<0.05);compared with the gefitinib single-agent group,the tumor growth of the Qingkailing combined with gefitinib group was slow,the weight of the tumors was significantly lower,and it also could significantly elevate the ROS level and downregulate the levels of PI3K p110α,AKT,mTOR,and STAT3 proteins in tumor tissues(P<0.05).Conclusion Qingkailing injection combined with gefitinib inhibited the growth of gefitinib-resistant xenograft in nude mice caused by abnormal activation of the PI3K/AKT pathway.Qingkailing injection may inhibit the PI3K/AKT pathway,its downstream mTOR pathway and STAT3 signaling pathway by up-regulating ROS levels,thereby enhancing the inhibitory effect of gefitinib on the proliferation of xenograft tumors of lung cancer xenografts in nude mice.

The incidence of apoplexy remains persistently high among the older population.Based on the traditional Chinese medicine principle of"treating the elderly by focusing on the fu",this paper explores the holistic connotation of"fu".It proposes that the onset of apoplexy in the elderly is characterized by obstruction,stagnation,depression,and sluggishness,which should be treated from six fu viscera,xuanfu,and collaterals.The interconnected hierarchical network of these three systems,serving as macro-and micro-channels for qi and fluid metabolism,plays a central role in both disease development and treatment.The failure of the six fu viscera to descend and the upward invasion of turbid yin are identified as prerequisites for apoplexy onset,whereas yang qi stagnation and xuanfu blockage act as key pathogenic drivers,and the core mechanisms involve phlegm-stasis-toxin accumulation,and dysfunction of the collaterals and fu.In the treatment,acute phase requires unblocking fu viscera and restoring xuanfu patency;chronic phase focuses on dredging collaterals and opening xuanfu;and recovery phase emphasizes tonifying combined with regulating xuanfu.The understanding of"treating the elderly by focusing on the fu"emphasizes that the pathogenesis of the disease should be changed to individual conditions;"six fu viscera-xuanfu-collaterals"exhibits a pathological mechanism characterized by the transmission and reception of pathogenic factors,as well as progressive mutual involvement;in clinical practice,treatment should meticulously assess the severity and nuances of the condition,prioritizing method that emphasizes unobstructed flow;additionally,therapy should be essential to protect stomach qi and integrate therapeutic attacks within a framework of supplementation.These principles offer valuable reference for the differentiation and treatment of apoplexy.

Objective:To explore the interaction of IL-2,IL-6 factors and intestinal flora disorder in patients with rheumatoid arthritis complicated with interstitial lung disease(RA-ILD).Methods:A total of 100 RA patients diagnosed at Shijiazhuang People's Hospital from June 2021 to June 2022 were enrolled and divided into the RA-ILD group(with ILD,n=27)and RA-noILD group(with-out ILD,n=73)according to the results of pulmonary CT and clinical manifestations.Fecal samples were collected from all partici-pants,and intestinal flora levels were cultured and analyzed.Bacterial DNA was extracted from fecal samples,and the 16S rDNA gene was amplified by PCR to generate DGGE profiles of gut microbiota.The Shannon-Wiener index,evenness,and richness of intestinal bacteria were calculated.Cluster analysis was performed to compare structural differences in gut microbiota between the groups.Demo-graphic characteristics,clinical symptoms,laboratory parameters,and intestinal flora-related indicators were compared between the groups.Multivariate Logistic regression analysis was conducted to identify independent risk factors for ILD development in RA pa-tients.Spearman correlation analysis was used to evaluate relationships between serum IL-2,IL-6 levels and gut microbiota parame-ters.Cox proportional hazards regression analysis was performed to determine independent factors influencing disease progression in RA-ILD patients.Results:Smoking,age≥53.77 years old,anti-CCP antibody≥334.60 RU/ml,IL-6≥199.47 ng/ml,IL-2<3.10 ng/ml,richness<18.39,Shannon-Wiener index<2.88,Bifidobacterium<7.27 CFU/g,Bacteroides fragilis<7.75 CFU/g,Hmax<3.14 and flora uniformity<0.92 were independent factors affecting the occurrence of ILD in patients with RA.In patients with RA-ILD,serum IL-6 level was negatively correlated with richness,Shannon-Wiener index,Hmax and flora evenness,while serum IL-2 level was positively correlated with richness,Shannon-Wiener index,Hmax and flora evenness.Smoking,age,anti-CCP antibody,IL-6,IL-2,richness,Shannon-Wiener index,Bifidobacterium,Bacteroides fragilis,Hmax and flora uniformity were independent factors affecting the outcome of RA-ILD patients(P<0.05).Conclusion:Smoking,age,anti-CCP antibody,IL-6,IL-2,richness,Shannon-Wiener index,Bifido-bacterium,Bacteroides fragilis,Hmax and flora uniformity have significant diagnostic and prognostic value for RA-ILD.The changes of intestinal microbial community in patients with RA-ILD and the changes in the number and structure of intestinal bacteria may be one of the important factors of RA patients complicated with ILD.

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

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.

Objective Nude mice xenograft model with aberrant activation of the PI3K/AKT pathway was established based on PIK3CA-overexpressing non-small cell lung cancer(NSCLC)cell lines PC-9,to observe the effect of Qingkailing injection combined with gefitinib on the growth of xenograft tumor in nude mice and explore its effects on ROS levels,mTOR pathway and STAT3 pathway.Methods After the xenografttumor model of BALB/c nude mice was established successfully,the mice were randomly divided into control group,Qingkailing injection group(10 mL·kg-1),gefitinib group(2.5 mg·kg-1),and Qingkailing combined with gefitinib group,with 5 mice in each group.They were administered for 32 days and then sacrificed.The tumor weight of each group was weighed and the tumor suppression rate was calculated;the level of ROS in the tumor tissues of each group was detected by flow cytometry;the protein levels of PI3K p110α,p-AKT and p-STAT3 in the xenograft tumor tissues of each group were detected by immunohistochemistry;the protein levels of the PI3K/AKT/mTOR pathway and the STAT3 pathway in the xenografttumor tissues of each group were detected by protein western blotting.Results Compared with the control group,Qingkailing injection could slow the tumor growth,significantly reduce the tumor weight,increase the level of ROS,and could significantly down-regulate the levels of PI3K p110α,AKT,mTOR,and STAT3 proteins in the tumor tissues(P<0.05);compared with the gefitinib single-agent group,the tumor growth of the Qingkailing combined with gefitinib group was slow,the weight of the tumors was significantly lower,and it also could significantly elevate the ROS level and downregulate the levels of PI3K p110α,AKT,mTOR,and STAT3 proteins in tumor tissues(P<0.05).Conclusion Qingkailing injection combined with gefitinib inhibited the growth of gefitinib-resistant xenograft in nude mice caused by abnormal activation of the PI3K/AKT pathway.Qingkailing injection may inhibit the PI3K/AKT pathway,its downstream mTOR pathway and STAT3 signaling pathway by up-regulating ROS levels,thereby enhancing the inhibitory effect of gefitinib on the proliferation of xenograft tumors of lung cancer xenografts in nude mice.

Over the past four decades,respiratory imaging has achieved a leapfrogging development from conventional morphological assessment to precision medicine.Beginning with conventional X-ray that laid the foundation,followed by CT technological breakthroughs,MRI explorations,and advances in nuclear medicine and molecular imaging,this review outlined the key technologies and clinical translation achievements at each stage,analyzed current research hotspots such as artificial intelligence and radiomics,radiation protection in low-dose CT,and integration of functional and molecular imaging,prospected the future trends in early diagnosis,treatment monitoring,and synergy with targeted therapy,emphasizing the paradigm shift in this field from empirical diagnosis to data-driven precise evaluation,as well as its core supportive role in diagnosis and management of respiratory diseases.

Objective:To evaluate the efficacy of peritoneal dialysis (PD) in the treatment of acute kidney injury (AKI) in critically ill neonates.Methods:It was a retrospective study. The baseline characteristic data, PD protocols, PD catheter placement methods and clinical outcomes of AKI neonates who underwent PD in the General Hospital of Ningxia Medical University between July 2015 and December 2024 were collected and analyzed.Results:(1) Among the 8 neonates with AKI, gestational age was (30.38±6.02) weeks, and birth weight was 1 397.5 (839.0, 2 312.5) g, with 6 premature infants. The time from birth to AKI onset was 144 (48, 294) hours. The leading cause of AKI was sepsis (6/8). The treatment time of PD was (93.12±37.20) hours. (2) Renal function recovery: After PD treatment, urine output was significantly increased ( Z=-3.29, P<0.001), and serum creatinine was significantly decreased ( t=2.66, P=0.032). (3) Hyperkalemia: Six out of 8 patients presented with hyperkalemia, which significantly decreased after PD treatment ( t=3.37, P=0.008). (4) Acid-base balance:Five out of 8 neonates had metabolic acidosis, and 3 of 5 neonates achieved basically complete correction (including lactic acidosis). There was no statistically significant difference in acid-base balance indicators before and after PD treatment (all P>0.05). (5) PD-related complications: Two out of 8 patients experienced peritoneal dialysate leakage, and no other PD-related complications occurred. (6) Outcomes: The hospital stay was 27.0 (8.0, 57.5) days. Four out of 8 neonates survived, while the other 4 neonates died after withdrawal of treatment. The primary cause was multiple organ failure. Conclusions:PD is a safe and effective treatment for neonatal AKI, facilitating early renal recovery and correction of electrolyte and acid-base imbalances.