Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment efficacy.CD8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology.By leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy. Methods Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases.In the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T cells.Subsequently,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic model.The accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)curves.Furthermore,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic responses.Additionally,we investigated the potential underlying biological pathways that contribute to divergent treatment responses. Results We successfully developed a model capable of predicting the prognosis of patients with TNBC.The areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,respectively.Employing this risk model,we stratified the samples into high-and low-risk groups.Through KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine pathways.Furthermore,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores, Conclusion Our study demonstrates the potential of CXCL13,GBP2,and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC.These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

Objective:To investigate the efficacy and safety of chemotherapy combined with inetetamab and pyrotinib (triplet therapy group), and capecitabine combined with pyrotinib (doublet therapy group) in second-line treatment for HER2-positive metastatic breast cancer patients who have failed on trastuzumab.Methods:A retrospective analysis was conducted on 30 HER2-positive metastatic breast cancer patients who underwent second-line treatment with a regimen of chemotherapy plus inetetamab and pyrotinib at Fujian Provincial Tumor Hospital between Jan. 1, 2020 and Dec. 31, 2023, and on 28 HER2-positive metastatic breast cancer patients treated with capecitabine plus pyrotinib during the same period. The study analyzed the differences in ORR (objective response rate), CBR (clinical benefit rate), PFS (progression free survival), and OS (overall survival) between the two groups and documented any adverse reactions observed during treatment.Results:The three-drug group exhibited a higher ORR rate than the two-drug group (60.0% vs. 39.2%, P>0.05), and a higher CBR rate (83.3% vs. 57.1%, P<0.05). Univariate analysis and multivariate Logistic regression analysis showed that group (three drug group compared to two drug group) was the only independent prognostic factor affecting median PFS in patients ( P<0.05). The median PFS of the three drug group was higher than that of the two drug group (19 months vs. 11 months, P<0.05), but by the end of follow-up, neither group had reached the median OS ( P>0.05) .The three-drug group and the two-drug group demonstrated 1-year OS rates of 85% and 85%, 2-year OS rates of 74% and 63%, and 3-year OS rates of 56% and 52%, respectively. The most frequent hematological toxicities in the three-drug group were leukopenia, neutropenia, and anemia, with diarrhea being the most common non-hematological toxicity. No significant differences were observed in adverse reaction profiles between the two groups ( P>0.05) . Conclusion:In the second-line treatment of HER2 positive metastatic breast cancer, chemotherapy + inetetamab + pyrotinib significantly prolonged the median PFS and increased the CBR compared with the current domestic standard capecitabine + pyrotinib regimen, and did not increase the incidence of adverse reactions, demonstrating higher efficacy and safety.

Objective:To investigate the efficacy and safety of chemotherapy combined with inetetamab and pyrotinib (triplet therapy group), and capecitabine combined with pyrotinib (doublet therapy group) in second-line treatment for HER2-positive metastatic breast cancer patients who have failed on trastuzumab.Methods:A retrospective analysis was conducted on 30 HER2-positive metastatic breast cancer patients who underwent second-line treatment with a regimen of chemotherapy plus inetetamab and pyrotinib at Fujian Provincial Tumor Hospital between Jan. 1, 2020 and Dec. 31, 2023, and on 28 HER2-positive metastatic breast cancer patients treated with capecitabine plus pyrotinib during the same period. The study analyzed the differences in ORR (objective response rate), CBR (clinical benefit rate), PFS (progression free survival), and OS (overall survival) between the two groups and documented any adverse reactions observed during treatment.Results:The three-drug group exhibited a higher ORR rate than the two-drug group (60.0% vs. 39.2%, P>0.05), and a higher CBR rate (83.3% vs. 57.1%, P<0.05). Univariate analysis and multivariate Logistic regression analysis showed that group (three drug group compared to two drug group) was the only independent prognostic factor affecting median PFS in patients ( P<0.05). The median PFS of the three drug group was higher than that of the two drug group (19 months vs. 11 months, P<0.05), but by the end of follow-up, neither group had reached the median OS ( P>0.05) .The three-drug group and the two-drug group demonstrated 1-year OS rates of 85% and 85%, 2-year OS rates of 74% and 63%, and 3-year OS rates of 56% and 52%, respectively. The most frequent hematological toxicities in the three-drug group were leukopenia, neutropenia, and anemia, with diarrhea being the most common non-hematological toxicity. No significant differences were observed in adverse reaction profiles between the two groups ( P>0.05) . Conclusion:In the second-line treatment of HER2 positive metastatic breast cancer, chemotherapy + inetetamab + pyrotinib significantly prolonged the median PFS and increased the CBR compared with the current domestic standard capecitabine + pyrotinib regimen, and did not increase the incidence of adverse reactions, demonstrating higher efficacy and safety.

OBJECTIVE To investigate the components and metabolites of leaves of Cyclocarya paliurus in rats plasma. METHODS UHPLC-Q/TOF-MS method was applied to identify the components and metabolites of rat plasma. The prototype components and metabolites were analyzed in rats plasma of leaves of Cyclocarya paliurus water extract after intragastric administration by comparing the chromatograms of Cyclocarya paliurus, blank serum and drug-containing serum. RESULTS A total of 15 compounds including 6 prototype components and 9 metabolites were identified. The main prototype components in blood were caffeylquinic acid, flavonoids and saponins, and the metabolic pathways were methylation and hydroxylation. CONCLUSION This experiment showes that the prototype components absorbed into blood may be the potential bioactive components in leaves of Cyclocarya paliurus, providing a scientific basis for clarifying its material basis in pharmacodynamics.

Objective To establish a rapid prediction method of the antioxidant activity in aqueous extract solutions of Melastoma dodecandrum based on ultraviolet spectroscopy and partial least squares regression algorithm. Methods The DPPH free radical scavenging effect was used to characterize the antioxidant activity of aqueous extract solutions of Melastoma dodecandrum. The ultraviolet spectra of 190-600 nm were collected. The partial least squares regression model of antioxidant activity was established after optimizing the wavelength range and preprocessing method. The software was devised using Visual Basic as the integrated development environment to provide a convenient tool for the rapid determination of antioxidant activity. Results The optimal partial least squares regression model was established based on 200-290 nm as wavelength range and unit variance scaling as preprocessing method. The correlation coefficient of calibration, root mean square error of estimation, root mean square error of cross-validation was 0.887, 2.20% and 2.17%, respectively. The correlation coefficient of validation, root mean square error of prediction was 0.868, 2.08%. The average predicted recovery was 100.1±2.3%. With the predictive function in the software, the antioxidant activity of aqueous extract solution of Melastoma dodecandrum can be calculated automatically within 2 s after collecting the ultraviolet spectra. Conclusions This study provides a rapid method for the prediction of antioxidant activity in aqueous extract solutions of Melastoma dodecandrum.

Objective To explore the delayed discount and personality characteristics of impulsive and premeditated male prisoners and their correlation.Methods A total of 120 male prisoners with aggressive behaviors were tested by Self-made General Situation Questionnaire,Impulsive / Premeditated Aggression Scale (IPAS),NEO Five-Factor Inventory (NEO-FFI),Delay Discount Task (DDT).The effective participants were ninety,including 51 in impulsive group and 39 in premeditated group.Analyzed the difference of delayed discount and personality characteristics between the two group.Results (1) In the delayed discount task,the delay discount rat (K) of the impulsive violence group (0.0278 ± 0.0555) was significantly higher than that of the premeditated violence group (0.0042±0.0078).The difference was statistically significant (t=3.004,P =0.004).(2) The scores of agreeableness (35.84 ± 4.08) and conscientiousness (37.04±4.83) in impulsive violence group were lower than that in premeditated violence group(38.46±5.53,42.31±5.96),and the difference was statistically significant (t=-2.587,P=0.011;t =-4.634,P＜0.01).(3) Correlation analysis showed that K value was not significantly correlated with all dimensions of the big five personality(P＞0.05).Conclusion Male impulsive prisoners have faster tendency to delay discounting compared with male premeditated prisoners.Lower agreeableness and conscientiousness are the personality characteristics of male impulsive prisoners.

Objective To explore the intertemporal decision-making function in geriatric depressive patients and it's correlation with impulsive personality traits.Methods Forty patients with geriatric depression(GD group) and Forty demographic characteristic matched health controls (HC group) were recruited.The delay discounting task was used to measure the decision-making function,and the barratt impulsiveness scale was used to measure the impulsive traits.The delay discounting rate (k) transformed to common logarithm lgk.Results Lgk and the scores of barratt impulsiveness scale,attention impulsiveness subscale,motor impulsiveness subscale in GD group((-2.00±0.81),(42.67±8.51),(46.50± 16.84),(43.50± 10.45)) were more larger than those in HC group ((-2.31±0.51),(32.27±6.18),(34.81±8.15),(26.88±7.65),and the differences were statistically significant (t=2.060,P=0.043;t=6.252,P＜0.01;t=3.951,P＜0.01;t =8.117,P＜0.01).In addition,lgk had positive correlation with the scores of motor impulsiveness factor in GD group(r=0.408,P=0.009).Conclusion The delayed discounting ability is impaired and correlated with the motor impulsiveness in GD patients.

OBJECTIVETo establish homozygous transgenic mouse strain expressing human tau isoform with P301L mutation.

METHODSFive transgenic mice expressing human tau isoform with P301L mutation were obtained by microinjection into male nuclei. Homozygote and hemizygote were identified by PCR and real-time fluorescent quantitative PCR.

RESULTSNinety five homozygous transgenic mice were selected, and the results indicated that homozygous transgenic mice were superior to hemizygote in simulating the changes of biological characteristics.

CONCLUSIONExogenous gene tau is able to stably transmit to next generation and the combination of SYBR Green real-time fluorescent quantitative PCR with the traditional mating is a fast, reliable and economical way to screen homozygous and hemizygous transgenic mice.

Animals ; Female ; Homozygote ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microinjections ; Mutation ; tau Proteins ; genetics