ObjectiveTo investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

OBJECTIVES: To investigate the therapeutic effects of cimifugin on Crohn's disease (CD)-like colitis in mice and its possible mechanism. METHODS: Thirty adult male C57BL/6 mice were randomized equally into control group, 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced CD-like colitis model group, and cimifugin treatment (daily gavage at 12.5 mg/kg) group. The therapeutic effect of cimifugin was evaluated by observing changes in body weight, disease activity index (DAI) scores, colon length, histopathological inflammation scores, and inflammatory cytokine levels in the colonic mucosa. Intestinal barrier integrity in the mice was assessed using immunofluorescence assay and Western blotting for claudin-1 and ZO-1; T-helper (Th) cell subset ratios in the mesenteric lymph nodes were analyzed with flow cytometry. Network pharmacology, KEGG enrichment analysis and molecular docking were used to predict the targets of cimifugin and analyze the key pathways and cimifugin-MAPK protein interactions, which were validated by Western blotting in the mouse models. RESULTS: In mice with TNBS-induced colitis, cimifugin treatment significantly attenuated body weight loss and colon shortening, lowered DAI and histopathological scores, decreased IFN-γ and IL-17 levels, and increased IL-4 and IL-10 levels in the colonic mucosa. Cimifugin treatment also significantly improved TNBS-induced claudin-1 dislocation and reduction of goblet cells, upregulated claudin-1 and ZO-1 expressions, reduced Th1 and Th17 cell percentages, and increased Th2 and Treg cell percentages in the colonic mucosa of the mice. KEGG analysis suggested a possible connection between the effect of cimifugin and MAPK signaling, and molecular docking showed strong binding affinity between cimifugin and MAPK core proteins. Western blotting demonstrated significantly decreased phosphorylation levels of JNK, ERK, and p38 in the colonic mucosa of cimifugin-treated mouse models. CONCLUSIONS Cimifugin alleviates TNBS-induced CD-like colitis by repairing intestinal barrier damage and restoring Th1/Th2 and Th17/Treg balance via suppressing MAPK pathway activation.
Animals ; Mice, Inbred C57BL ; Male ; Mice ; Crohn Disease/immunology* ; Colitis/immunology* ; MAP Kinase Signaling System/drug effects* ; Trinitrobenzenesulfonic Acid ; T-Lymphocytes, Helper-Inducer/drug effects* ; Intestinal Mucosa ; Disease Models, Animal

As one of the core theories of spleen governing transportation and transformation in the traditional Chinese medicine visceral manifestation theory,the modern biological basis of"spleen qi disperses essence"has not been fully elucidated.Lipids are one of the three major nutrients in the body,which are derived from exogenous absorption or endogenous transformation,and belong to the category of"grease"and"essence"substances in traditional Chinese medicine.Because of their hydrophobic nature,lipids require apolipoproteins to be transported in the bloodstream and used by the body;similarly,essence also needs spleen qi transformation to be distributed throughout the body and exert their nourishing effects,revealing a certain degree of inherent unity between the two.When the spleen qi functions properly,essence dispersal is orderly and lipid metabolism remains in homeostatic balance;if spleen deficient leads to impaired transportation,the essence will not be distributed,and the lipid turbidity will accumulate,causing disease.Classic strengthening spleen prescriptions such as Zexie Decoction,can reshape lipid homeostasis by regulating apolipoproteins.Based on apolipoprotein-mediated lipid metabolism,this paper explores the modern molecular biology basis of the theory of"spleen qi disperses essence,"which provides novel insights for enriching the modern research of traditional Chinese medicine visceral manifestation theory,and lays the foundation for clinical practice and theoretical innovation in the treatment of metabolic diseases from the spleen.

As one of the core theories of spleen governing transportation and transformation in the traditional Chinese medicine visceral manifestation theory,the modern biological basis of"spleen qi disperses essence"has not been fully elucidated.Lipids are one of the three major nutrients in the body,which are derived from exogenous absorption or endogenous transformation,and belong to the category of"grease"and"essence"substances in traditional Chinese medicine.Because of their hydrophobic nature,lipids require apolipoproteins to be transported in the bloodstream and used by the body;similarly,essence also needs spleen qi transformation to be distributed throughout the body and exert their nourishing effects,revealing a certain degree of inherent unity between the two.When the spleen qi functions properly,essence dispersal is orderly and lipid metabolism remains in homeostatic balance;if spleen deficient leads to impaired transportation,the essence will not be distributed,and the lipid turbidity will accumulate,causing disease.Classic strengthening spleen prescriptions such as Zexie Decoction,can reshape lipid homeostasis by regulating apolipoproteins.Based on apolipoprotein-mediated lipid metabolism,this paper explores the modern molecular biology basis of the theory of"spleen qi disperses essence,"which provides novel insights for enriching the modern research of traditional Chinese medicine visceral manifestation theory,and lays the foundation for clinical practice and theoretical innovation in the treatment of metabolic diseases from the spleen.

Objective:To explore the effect path of death attitude and purpose in life on attitude toward hospice care of undergraduate intern nursing students.Methods:This study was a cross-sectional study. Using the convenient sampling method, a total of 229 undergraduate intern nursing students from two schools in Hefei, Anhui Province were selected as the research objects from October to December 2022. General data questionnaire, Chinese Version of Frommelt Attitudes Toward Care of the Dying Scale Form B (FATCOD-B-C), Chinese Version of Death Attitude Profile-Revised (DAP-R) Scale and Chinese Version of Purpose in Life Test (PIL-C) were used to investigate. Pearson correlation analysis was used to explore the correlation between death attitudes, purpose in life and attitude toward hospice care among undergraduate intern nursing students. Structural equation model was used to examine the path relationship between attitude towards death and purpose in life on attitude toward hospice care.Results:A total of 229 questionnaires were sent out in this study, and 214 were effectively recovered, with an effective recovery rate of 93.45% (214/229). Among 214 undergraduate intern nursing students, the scores of FATCOD-B-C, Chinese Version DAP-R Scale, and PIL-C were (101.06±8.16), (91.21±12.13) and (94.45±11.90), respectively. The results of Pearson correlation analysis showed that the purpose in life was positively correlated with attitude toward hospice care ( r=0.290, P<0.01), while the attitude to death was negatively correlated with attitude toward hospice care ( r=-0244, P<0.01). The results of structural equation model path analysis showed that the purpose in life (life goal, life attitude) can affect attitude toward hospice care through death attitude (escape acceptance, natural acceptance, fear of death) . Conclusions:Effective interventions on purpose in life and attitude towards death of undergraduate intern nursing students can improve their attitudes toward hospice care .

Objective:To explore the effect and possible mechanism of Zexie Tang(ZXT)regulate the balance of M1/M2 polarization in macrophage cells.Methods:Lipid metabolism disorder mouse model was induced by Western diet(WD)in vivo,RAW264.7 cell M1/M2 macrophage model was induced by LPS/IL-4 in vitro,set up blank group,model group and ZXT group.The flu-orescence intensity of M1 and M2 macrophage markers in adipose tissue and RAW264.7 cells was observed by immunofluorescence staining;protein levels of p-AKT,AKT and COX-2 were measured by Western blot;levels of macrophage marker gene mRNAs of M1 and M2 were analysed by qPCR;IL-1β and IL-10 were measured by ELISA;content of NO was detected by Griess;binding of active components of Alismatis Rhizoma and Atractylodes Macrocephala with PI3K protein was analyzed by Docking.Results:Compared with WD group,expression of CD11c was significantly decreased in ZXT group,while expression of CD206 was significantly up-regulated;ZXT reversed LPS-induced increased in CD80 expression,down-regulated mRNA levels of M1 macrophage marker gene iNOS,etc,decreased the expression of COX-2 protein,and inhibited the secretion of IL-1β(P<0.001);ZXT promoted IL-4-induced CD206 expression,up-regulation of M2 macrophage marker gene Arg-1 and other mRNAs levels and secretion of IL-10;ZXT reversed the LPS-induced increased in NO release;p-AKT/AKT protein level increased in vivo and in vitro after ZXT administration;Docking re-sults show that many active ingredients in Alismatis Rhizoma and Atractylodes Macrocephala could form hydrogen bonds stably with PI3K protein.Conclusion:ZXT regulates the M1/M2 polarization balance of macrophages,and its mechanism may be related to the regulation of PI3K/AKT pathway.

Signal transducer and activator of transcription 3(STAT3)is known to modulate the expression of genes related to cell transformation,proliferation,and survival,making it a significant target for cancer therapy.Recent research has also highlighted the crucial involvement of aberrant STAT3 activation in the pathogenesis of diabetic kidney disease(DKD).Accordingly,this article focuses on the therapeutic potential of targeting STAT3 in DKD.The structure of STAT3,its mechanisms of activity regulation,mechanisms of abnormal STAT3 activation in DKD,and a summary of the current research is provided.The review aims provide a reference for research into the pathogenesis of DKD and the development of new drugs.

Objective To investigate the changes and clinical significance of plasminogen activator inhibi-tor-1(PAI-1),transforming growth factor-β(TGF-β),vascular endothelial growth factor(VEGF),and inter-leukin-6(IL-6)in patients with tuberculous pleurisy and pleural fibrosis.Methods A total of 103 patients with tuberculous pleurisy and pleural fibrosis who were treated in a hospital from July 2020 to July 2023 were selected as the research subjects.After 2 weeks of treatment,they were divided into a significant effect group and a non-significant effect group based on the therapeutic efficacy of glucocorticoid treatment.The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion were compared before treatment,after 1 and 2 weeks of treatment.The correlation between the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion and the therapeutic efficacy was analyzed by Spearman correlation analysis.Pearson correlation analy-sis was used to analyze the correlation between the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleu-ral effusion and the levels of these indicators in pleural effusion after 2 weeks of treatment.A receiver operat-ing characteristic curve was drawn to analyze the predictive value of the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion for the efficacy of tuberculous pleurisy and pleural fibrosis patients after 1 and 2 weeks of treatment.Results The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 1 and 2 weeks of treatment in both groups were lower than those before treatment,and the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 1 and 2 weeks of treatment in the significant effect group were lower than those in the non-significant effect group,with statistically significant differences(P＜0.05).The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 1 and 2 weeks of treatment were negatively correlated with the efficacy(P＜0.05).The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 2 weeks of treatment were positively correlated(r=0.761,0.783,0.812,0.741,all P＜0.05).The area under the curve(AUC)of combined detection of serum and pleural effusion in-dicators after 1 and 2 weeks of treatment was greater than the AUC of individual indicators(P＜0.05).Con-clusion The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion of patients with tubercu-lous pleurisy and pleural fibrosis are related to the efficacy of treatment.The combined detection of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion has good predictive value and can provide reference for clinical intervention.