Triple-negative breast cancer(TNBC)is a highly aggressive and prognostically unfavorable subtype.Tertiary lymphoid structure(TLS)within the tumor microenvironment,comprising dendritic cells,B cells,T cells,and other immune cells,modulate the tumor immune response.The heterogeneity of TLS in TNBC,such as density,structural maturity,and molecular expression patterns,affects the tumor immune microenvironment and,consequently,treatment responses and clinical outcomes.Studies indicate a positive correlation between the density and maturity of TLS and the pathological complete response(pCR)of TNBC patients,with TLS enhancing the quantity of tumor-infiltrating immune cells and improving anti-tumor immune responses,thereby increasing sensitivity to chemotherapy and immunotherapy.Recent research has found that mature TLS are associated with effective immune responses,becoming significant predictors of treatment response.The combination of TLS with immune checkpoint inhibitors has shown promising prospects.Research demonstrates that promoting the formation or enhancing the functionality of TLS can improve anti-tumor immune effects and enhance treatment outcomes for TNBC patients.Targeting TLS may reduce immune evasion and increase the sensitivity to immunotherapy.However,clinical application of TLS still faces challenges,particularly the impact of their heterogeneity on treatment response.Current assessment methods for TLS are not standardized,lacking a uniform standard and diagnostic system,which limits their widespread application.Future research should focus on resolving these issues by developing standardized assessment tools and further exploring the role of TLS in immune escape and resistance mechanisms.This review aimed to summarize and analyze the existing research progress on TLS in TNBC,in order to provide new ideas for the development of personalized immunotherapy strategies.

Triple-negative breast cancer(TNBC)is a highly aggressive and prognostically unfavorable subtype.Tertiary lymphoid structure(TLS)within the tumor microenvironment,comprising dendritic cells,B cells,T cells,and other immune cells,modulate the tumor immune response.The heterogeneity of TLS in TNBC,such as density,structural maturity,and molecular expression patterns,affects the tumor immune microenvironment and,consequently,treatment responses and clinical outcomes.Studies indicate a positive correlation between the density and maturity of TLS and the pathological complete response(pCR)of TNBC patients,with TLS enhancing the quantity of tumor-infiltrating immune cells and improving anti-tumor immune responses,thereby increasing sensitivity to chemotherapy and immunotherapy.Recent research has found that mature TLS are associated with effective immune responses,becoming significant predictors of treatment response.The combination of TLS with immune checkpoint inhibitors has shown promising prospects.Research demonstrates that promoting the formation or enhancing the functionality of TLS can improve anti-tumor immune effects and enhance treatment outcomes for TNBC patients.Targeting TLS may reduce immune evasion and increase the sensitivity to immunotherapy.However,clinical application of TLS still faces challenges,particularly the impact of their heterogeneity on treatment response.Current assessment methods for TLS are not standardized,lacking a uniform standard and diagnostic system,which limits their widespread application.Future research should focus on resolving these issues by developing standardized assessment tools and further exploring the role of TLS in immune escape and resistance mechanisms.This review aimed to summarize and analyze the existing research progress on TLS in TNBC,in order to provide new ideas for the development of personalized immunotherapy strategies.

Since the beginning of the 21st century, with the continuous development of anti-HER2-targeted drugs, more treatment options have been provided for patients with HER2-positive breast cancer and the survival prognosis has been significantly improved. At present, anti-HER2 targeted drugs mainly include monoclonal antibody drugs such as trastuzumab and pertuzumab, small molecule tyrosine kinase inhibitors such as lapatinib and neratinib, and antibody-drug conjugates such as TDM1 and T-DXd, which play an extremely important role in different disease processes. The treatment of HER2-positive breast cancer is based on targeted therapy with trastuzumab. Early-stage patients with high risk factors can be treated with intensive targeted therapy to further improve the prognosis, while advanced patients need a reasonable arrangement of targeted therapy to overcome drug resistance and prolong survival. This article will review the current status, the latest research progress and the future prospects of anti-HER2 targeted therapy in different stages of the disease.

Objective:To treat the chronic non-atrophic gastritis patients induced by Helicobacter pylori with Qingweizhitong Weiwan combined with standard triple therapy,and to detect the differential expression of related immflammation genes with PCR array,and to clarify its mechanism.Methods: Ten patients with chronic non-atrophic gastritis complicated with Helicobacter pylori infection were used as treatment group and 10 health people were used as health control group. The patients in treatment group were treated with Qingweizhitong Weiwan combined with standard triple therapy for 14 d. The blood samples of the subjects in treatment group and health control group were collected before and after treatment,and QIAGEN human antibacterial response PCR array was performed to test the total RNA inperipheral blood and to analyze the differential expressions of 84 inflammation-related genes.Results:The differential expressions of 20 inflammation-related genes were found.Compared with health control group,the expression levels of 20 genes in treatment group before treatment were up-regulated (Fold-change>2);after treatment,the expression levels of 20 genes were down-regulated,and 11 of them were similar to the level in health control group (Fold-change< 2).More specifically,part of 20 genes was related to NLRP3 inflammasome.Compared with health control group,the gene expression levels of CASP1,IL1B,NLRP3,and PYCARD in treatment group before treatment were up-regulated (P <0.05).Compared with before treatment,the expression levels of CASP1,IL1B,NLRP3,and PYCARD in treatment group after treatment were down-regulated (P <0.05).Conclusion:The mechanism of Qingweizhitong Weiwan combined with standard triple therapy in the treatment of chronic non-atrophic gastritis patients induced by Helicobacter pylori may be related to inhibiting the expressions of NLRP3 inflammasome-related genes and interfering the antimicrobial innate immune response.

Objective To investigate the hemostatic function of biological glue in renal trauma.Methods Establishment of rab-bit kidney scratch,partial nephrectomy and renal injury penetrating wound models were available with a biological glue and hemo-static powder processing,observed and recorded the amount of bleeding and bleeding time.Tissue sample were transected from the wound of kidneys in each group after a month,and the renal wound healing condition was observed by pathological examination.Re-sults The hemostatic function of biological glue was better than styptic powder,the amount of bleeding in biological glue group and hemostatic powder group of kidney scratched model were(1.39±0.09)mL,(1.77±0.44)mL,the difference was not statistically significant(P =0.115);the bleeding time were(5.02 ±0.23)s,(66.40± 7.35)s,the difference was statistically significant(P <0.01);the amount of bleeding in two models of partial nephrectomy and renal penetrating wound were(2.07±0.25)mL,(11.42± 1.33)mL;(2.01 ± 0.36)mL,(3.95 ± 0.39)mL and bleeding time were(6.16 ± 0.69)s,(139.38 ± 8.97)s;(7.68 ± 0.80)s, (144.26±9.27)s,the differences were statistically significant(P <0.01).Pathology results showed that the wounds healed well. Conclusion The hemostatic function of biological glue in renal trauma were remarkable and stable,and was worth to be further promoted.

Objective To explore the feasibility of making cystoscope training model with rapid prototyping technology and its training method in cystoscope operation. Methods Constructed a cystoscope training model, and designed a set of corresponding training methods ac-cording to the process and behavioral essentials of cystoscope operation. Selected 20 students who have never learned cystoscope operation and trained them with the new designed cystoscope training mode and training methods, and the training results were verified. Results Compared before and after the training, the operation time of all the trainees were significantly shortened, and their operation steps and skills were more proficient. Conclusion Cystoscope training model can help beginners to grasp the theoretical basis of cystoscopy, operation steps, and behavioral essentials, so as to shorten the learning curve of the cystoscope operation.

Objective The purification methods of the exosomes derived form T cells were established in order to get high quan-tity exosomes .Methods Exosomes from T cells culture supernatants were purified by ExoQuick Precipitation ,ultrafiltration and sucrose gradient centrifugation ,differential ultracentrifugation ,and confirmed via using transmission electron microscopy .The pro-tein expression of the exosomes were analyzed by SDS-PAGE electrophoresis .Western blotting was used to test the expression of IL-2 .Results The protein concentration of the exosomes purified through ExoQuick Precipitation ,ultrafiltration and sucrose gradi-ent centrifugation were higher than through differential ultracentrifugation (P<0 .05) .SDS-PAGE displayed the difference among the exosome purified by three methods .Three kinds of exosomes all expressed IL-2 .Conclusion ExoQuick Precipitation ,ultrafiltra-tion and sucrose gradient centrifugation technique can obtain high purity and complete exosome sample .

Objective To explore the effect of Ferroprotin 1 expression on tumorigenesis,invasiveness and survival of breast cancer.Methods In this study,100 breast cancer patients were enrolled.IHC SP was used to detect the expression of Ferroprotinl in paraffin-embedded tissues.The `association of Ferroprotin 1 expression and clinico-pathological parameters was evaluated by chi-square test.Survival analysis was calculated by Kaplan-Meier model and Log-rank test.Results The expression of Ferroprotin 1 was significantly higher in para-cancerous normal tissues (37/100,37％ ) than that in breast cancer tissues (24/100,24％ ;P =0.046 ).In these with positive axillary LN,there were more with low expression level of Ferroprotin 1 ( 36/40,90％ ) than those with high expression level ( 4/40,10％ ),P =0.007.More patients with low Ferroprotin1 were at advanced stage than those with high ferroprotin1 [Ⅲ 44/57 (77.2％) ;Ⅳ 17/18 ( 94.4％ )]( P =0.05 ).No significant association was found between ferroprotin1 and tumor grade,histology type,ER/PR,HER2,tumor size (P＞0.05).Ferroprotin1 has no significant effect on breast cancer survival ( P =0.591 ) by Kaplan-Meier curve and Log-rank test.Conclusions Low Ferroprotin 1 may lead to the tumorigenesis of breast cancer.Downregulated Ferroprotin1 promotes the LN involvement of breast cancer and accompanies with more advanced disease.However Ferroprotinl might not play an important role in the survival of breast cancer.

Objective To investigate the potential role of miR-34a on breast cancer recurrence and prognosis.Methods In this study,88 breast cancer patients underwent mastectomy with detailed clinical follow-up information.Extracting RNA from the formalin-fixed paraffin embedded samples,miR-34a levels were quantified by quantitative real-time polymerase chain reaction (qRT-PCR).miR-34a levels among clinico-pathological variables were accessed by Mann Whitney-U test.RFS and OS survival curves were derived from Kaplan-Meier estimates and the curves were compared by Log-rank tests.All statistical tests were two-sided.Results Significantly lower miR-34a level was found in tumor tissue compared to paired normal tissue (P =0.000).A potential relationship between miR-34a levels and existing clinico-pathological parameters of breast cancer,such as menstrual status,tumor size,nodal involvement,stage of disease,hormone receptor status,HER2 status,or tumor subtype was investigated.No statistically significant difference were identified for these features (P ＞ 0.05).miR-34a level was significant lower among G3 group than G1 + 2 group (P =0.024).Down-regulated miR-34a level was observed in breast cancer with later relapse compared to patients without relapse (P =0.008).When considering 2-△Ct =0.117 (median level)as cut-off value,patients with miR-34a up-regulation showed a positive association towards a longer survival,either RFS(P=0.026,Log-rank test) or OS(P =0.019,Log-rank test).Conclusions miR-34a,as a tumor suppressor,promotes differentiation and contributes to relapse when down-regulated.miR-34a has the potential as prognostic factor for breast cancer.

Objective The present study was to explore association of PvuⅡand XbaⅠpolymorphism in ER-?gene with genetic susceptibility for breast cancer without BRCAl/2 gene mutation. Methods 113 BRCA1/2 negative hereditary breast cancer patients from independent families and 113 agematched healthy control subjects were analyzed. Genotype analysis was conducted by polymerase chain reaction (PCR) and then DNA direct sequencing. The odd-ratios (OR) and 95% confidence intervals (CI) was calculated by unconditional logistic regression model. Results The frequency of PvuⅡpolymorphism CC(PP) ,CT(Pp) ,TT(pp) genotype in patients was found in 16 cases(14.2% ), 58 cases(51. 3% ) , and 39 cases (34. 5% ). The distribution of AA (xx) , AG (Xx) , GG (XX) genotype of XbaⅠpolymorphism were found in 76 cases ( 67. 2% ) , 34 cases ( 30. 1% ), and 3 cases ( 2. 7% ) among patients. Among premenopausal women, CT genotype of PvuⅡconfered a significantly increased risk for breast cancer compared with CC genotype ( adjusted OR = 2. 07; 95% CI, 0. 68 - 6. 30) ; Carriers of GG of XbaⅠhad a decreased risk for breast cancer (adjusted OR =0. 11; 95 % CI, 0. 01 - 1. 27) compared with AA genotype. Furthermore, combined analysis of two polymorphisms indicated individuals carrying PvuⅡCT and XbaⅠAA genotype were at increased risk for breast cancer as compared with those with PvuⅡCC and XbaⅠGG genotype (Oft = 11.43, 95% CI, 1.12-116.7) among premenopausal women. Conclusions PvuⅡand XbaⅠpolymorphisms in ER-?gene could be a candidate locus for low penetrance breast cancer susceptibility in Chinese population, especially among premenopausal women.