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.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective:To explore the relationship between ultrasound characteristics and invasiveness in the follicular variant of papillary thyroid carcinoma (FVPTC), and to integrate multiple ultrasound parameters for visual assessment of predictive outcomes by using Nomogram.Methods:A total of 312 FVPTC patients who were pathologically confirmed through surgery in Zhejiang Cancer Hospital and Zhejiang Provincial People′s Hospital from January 2013 to December 2023 were retrospectively collected.Based on defined criteria, FVPTC patients were categorized into high-invasion and low-invasion groups. The dataset was divided into a training set and a validation set in a ratio of 7 to 3. Clinical information and ultrasound feature parameters were collected. Univariate and multivariate Logistic regression analyses were performed on the training set. A predictive model for FVPTC invasiveness was constructed based on ultrasound features. The model′s discriminative ability and calibration were evaluated in the validation set, and a nomogram was generated.Results:The training set included a total of 218 patients with FVPTC, among which 131 were classified as high invasive.The validation set consisted of 94 patients, with 53 cases of high invasive FVPTC patients. Multivariate logistic regression analysis on the training set revealed that tumor multifocality ( OR=6.505, P=0.016), hypoechoic ( OR=3.235, P=0.103), shape ( OR=0.521, P=0.049), and microcalcifications ( OR=2.479, P=0.004) were independent influencing factors for predicting invasiveness in FVPTC. In the training set, the area under the curve (AUC) of the ultrasound predictive model was 0.704 (95% CI=0.634-0.771), and in the validation set, the AUC was 0.650 (95% CI=0.531-0.770), indicated good discriminative ability.The calibration curve showed good alignment with the ideal curve, demonstrating favorable calibration performance. Conclusions:Ultrasound features provide valuable information for assessing the invasiveness of FVPTC, and the model constructed by combining ultrasound features demonstrates good predictive efficacy for the invasiveness of FVPTC.

Objective:We investigated the efficacy of furmonertinib in the treatment of de novo small cell lung cancer (SCLC) carrying epi-dermal growth factor receptor (EGFR) sensitive mutations,and elucidated characteristics of the tumor genome,transcriptome,and immune microenvironment. Methods:We analyzed the case of a female patient initially diagnosed with extensive-stage SCLC who had an exon 19 deletion in her EGFR gene. The patient's disease progressed under first-line standard chemotherapy. She thus received the third-generation EGFR-TKI furmonertinib as her second-line treatment,achieving a partial response (PR) and 5-month progression-free survival. After furmon-ertinib treatment failed,a lung tumor biopsy was performed. Genomic,transcriptomic,and tumor immune microenvironment analyses were performed. Results:The histopathological diagnosis of SCLC was confirmed after progression on furmonertinib. Genetic testing of the treated tumor tissues showed that the patient carried an EGFR exon 19 deletion mutation. Transcriptome analysis revealed that the patient's transcriptional molecular subtype was SCLC-A. The tumor mutational burden,PD-L1 TPS,and density of tumor-infiltrating CD4+and CD8+T cells remained at a low level throughout the course of the disease,suggesting that the immune microenvironment was suppressive. Conclu-sions:Extensive-stage SCLC with EGFR-sensitive mutations exhibits a unique phenotype and tumor immune microenvironment. Furmon-ertinib could be an alternative second-line treatment for this type of tumor entity.

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 .