Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Objective To construct the K64 capsule depolymerase recombinant protein,Dep44,and investigate its potential application against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Methods The de-polymerase-encoding phage vB_Kpn_HF1013(GenBank:PP803128)was isolated and genomically analyzed to screen for candidate depolymerases.The recombinant protein Dep44 was constructed and functionally verified for depolymerase activity.Dep44 sensitive range was validated and Dep44 antimicrobial activity was assessed by bio-film disruption and serum sterilization assays.Results The tail spike protein of phage vB_Kpn_HF1013 exhibited depolymerase activity and recombinant protein Dep44 specifically degraded K64 CRKP capsule.Biofilm eradication assays demonstrated that recombinant Dep44 at both 2 μg/mL and 10 μg/mL significantly disrupted bacterial bio-films relative to the control.Serum bactericidal assays showed that Dep44 exhibited synergistic activity with serum,dependent on the complement system,as Dep44 alone lacked bactericidal properties.Conclusion Dep44 effec-tively targets and degrades K64 CRKP capsule,disrupts biofilms,and enhances serum bactericidal activity,high-lighting its potential for managing K64 CRKP infections and clearing biofilms from medical devices.

Objective:To observe the tumor control and the degree of radiation-induced lung injury (RILI) between FLASH irradiation and conventional dose rate (CONV) irradiation, and compare the changes in plasma proteomic profiles of mice following whole-lung FLASH and CONV irradiation using proteomics method.Methods:A mouse model with metastatic lung cancer was established. After whole-lung irradiation, changes in normal lung capacity were monitored using CT scans. Then, a RILI model was constructed to examine pathological alterations in lung tissues following whole-lung CONV and FLASH irradiation. Plasma samples were collected from mice receiving whole-lung CONV irradiation ( n = 5) and whole-lung FLASH irradiation ( n = 5), followed by comparison with samples from the control group of healthy mice (also referred to as the healthy control group). These plasma samples were analyzed using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics, followed by the screening and identification of differentially expressed proteins using high-throughput bioinformatics. Moreover, protein-protein interaction (PPI) network analysis was conducted to identify hub genes using the STRING database and Cytoscape software. Results:Whole-lung FLASH and CONV irradiation produced consistent tumor control, with the former significantly reducing RILI compared to the latter. A total of 609 proteins were identified through proteomic analysis. Among them, 89 differentially expressed proteins were detected in the whole-lung FLASH group. Gene Ontology (GO) enrichment analysis indicated that up-regulated genes were primarily associated with stress and inflammatory responses, whereas down-regulated genes were related to ATP metabolism and angiogenesis regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that up-regulated genes were predominantly enriched in unfolded protein response pathways, while down-regulated genes were mainly involved in metabolic pathways and oxidative phosphorylation. Integrated PPI analysis and subsequent validation via reverse transcription-polymerase chain reaction (RT-PCR) revealed four key genes.Conclusions:Compared to the whole-lung CONV irradiation, whole-lung FLASH irradiation reduces the RILI of normal lung tissues while maintaining equivalent tumor control in metastatic lung cancer. Proteomic analysis of differentially expressed proteins in plasma after whole-lung FLASH and CONV irradiation provides valuable insights into the molecular mechanisms underlying the FLASH effect.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Objective:To understand the status of intestinal helminth infections in Lunan area of Shandong Province (Jining City, Rizhao City, Linyi City, Heze City, and Zaozhuang City), and provide scientific basis for formulating parasitic disease prevention and control strategies.Methods:From 2016 to 2023, a stratified sampling method was used to conduct surveillance in 33 counties (cities, districts, hereinafter referred to as counties) in Lunan area of Shandong Province. Each county was divided into five areas (east, south, west, north, and center), with one administrative village (community) selected from each area. And ≥200 permanent residents (aged ≥3 years old, having lived locally for ≥6 months) were sampled from each village (community), and one stool sample was collected from each participant. The Kato-Katz method (two slides per sample) was used for parasite detection, and the results were analyzed.Results:From 2016 to 2023, a total of 49 436 people were surveyed, including 23 861 males and 25 575 females, with an age range of 3 - 105 years old. The testing identified 687 intestinal helminth infections, with an overall infection rate of 1.39%. The predominant infection was whipworm (582 cases), with an infection rate of 1.18%; followed by roundworm and hookworm, with infection rates of 0.13% (62 cases) and 0.05% (23 cases) respectively; other types of helminths ( Clonorchis sinensis and pinworm) totaled 20 cases, with an infection rate of 0.04%. From 2016 to 2023, the annual intestinal helminth infection rates were 2.76% (201/7 292), 0.90% (56/6 327), 0.84% (52/6 200), 1.70% (124/7 282), 1.23% (88/7 133), 1.45% (104/7 150), 0.34% (17/5 058), and 1.46% (45/3 084), showing an overall downward trend (χ 2trend = 42.40, P < 0.001). The ≥60 age group had the highest intestinal helminth infection rate (2.39%, 323/13 489), while the 30 - 39 age group had the lowest rate (0.68%, 48/7 016). There was statistically significant difference in infection rates among different age groups (χ 2 = 172.25, P < 0.001). There was no statistically significant difference in infection rates between genders (χ 2 = 0.03, P = 0.862). Farmers had the highest infection rate (1.69%, 560/33 118), with statistically significant differences among different occupational groups (χ 2 = 64.88, P < 0.001). Those with primary school education or below had the highest infection rate (1.82%, 445/24 469), with statistically significant differences among different education levels (χ 2 = 64.93, P < 0.001). Conclusions:In Lunan area of Shandong Province, whipworm is the predominant intestinal helminth infection, with elderly people being the high-risk group. Although the intestinal helminth infection rate in this region remains at a low level, there is still a risk of transmission. Continuous surveillance is needed, along with strengthened prevention and control measures for key populations.

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.

Objective To construct the K64 capsule depolymerase recombinant protein,Dep44,and investigate its potential application against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Methods The de-polymerase-encoding phage vB_Kpn_HF1013(GenBank:PP803128)was isolated and genomically analyzed to screen for candidate depolymerases.The recombinant protein Dep44 was constructed and functionally verified for depolymerase activity.Dep44 sensitive range was validated and Dep44 antimicrobial activity was assessed by bio-film disruption and serum sterilization assays.Results The tail spike protein of phage vB_Kpn_HF1013 exhibited depolymerase activity and recombinant protein Dep44 specifically degraded K64 CRKP capsule.Biofilm eradication assays demonstrated that recombinant Dep44 at both 2 μg/mL and 10 μg/mL significantly disrupted bacterial bio-films relative to the control.Serum bactericidal assays showed that Dep44 exhibited synergistic activity with serum,dependent on the complement system,as Dep44 alone lacked bactericidal properties.Conclusion Dep44 effec-tively targets and degrades K64 CRKP capsule,disrupts biofilms,and enhances serum bactericidal activity,high-lighting its potential for managing K64 CRKP infections and clearing biofilms from medical devices.

Objective To investigate the effects of Echinococcus multilocularis infection on levels of memory T (Tm) cells and their subsets in lymph nodes of mice at different stages of infection, so as to provide new insights into immunotherapy for alveolarechinococcosis. MethodsTwenty-four C57BL/6J mice aged 6 to 9 weeks were randomly divided into the infection group and the control group, of 12 mice in each group. Mice in the infection group were administered with 3 000 E. multilocularis protoscoleces via portal venous injection, while animals in the control group were administered with an equal volume of physiological saline. Three mice from each group were sacrificed 4, 12 weeks and 24 weeks post-infection, and lymph nodes were sampled and stained with hematoxylin and eosin (HE) to investigate the histopathological changes of mouse lymph nodes in the infection group. The expression and localization of T lymphocyte surface markers CD3, CD4, and CD8 were observed in mouse lymph nodes using immunohistochemical staining. In addition, lymphocyte suspensions were prepared from mouse lymph nodes in both groups at different time points post-infection, and the levels of Tm cell subsets and their secreted cytokines were detected using flow cytometry. Results HE staining showed diffuse structural alterations in the subcapsular cortical and paracortical regions of mouse lymph nodes in the infection group 4 weeks post-infection with E. multilocularis. Immunohistochemical staining detected CD3, CD4 and CD8 expression in mouse lymph nodes in both groups. Flow cytometry revealed higher proportions of CD4⁺ Tm cells [(55.3 ± 4.8)% vs. (38.8 ± 6.1)%; t = -4.259, P < 0.05] and CD4⁺ tissue-resident Tm (Trm) cells [(57.7 ± 3.7)% vs. (34.1 ± 11.2)%; t = -3.990, P < 0.05] in mouse lymph nodes in the infection group than in the control group 4 weeks post-infection, and higher proportions of CD4⁺ Tm cells [(34.6 ± 3.2)% vs. (23.3 ± 7.5)%; t = -2.764, P < 0.05] and CD4⁺ Trm cells [(44.0 ± 1.9)% vs. (31.2 ± 1.5)%; t = -4.039, P < 0.05] in mouse lymph nodes in the infection group than in the control group 24 weeks post-infection. The proportions of CD8⁺ Tm cells were higher in the infection group than in the control group 4 weeks [(56.8 ± 2.7)% vs. (43.9 ± 5.2)%; t = -4.416, P < 0.01] and 12 weeks post-infection [(25.4 ± 2.7)% vs. (12.0 ± 2.6)%; t = -2.552, P < 0.05], while the proportions of tumor necrosis factor (TNF)-α⁺ CD4⁺ T cells [(15.7 ± 5.0)% vs. (49.4 ± 6.4)%; t = 7.150, P < 0.01], TNF-α⁺CD8⁺ T cells [(20.7 ± 5.5)% vs. (57.5 ± 8.4)%; t = -6.694, P < 0.01], and TNF-α⁺ CD8⁺ Tm cells [7.0% (1.0%) vs. 31.0% (11.0%); Z = -2.236, P < 0.05] were lower in the infection group than in the control group 24 weeks post-infection. Conclusions Tm cells levels are consistently increased in lymph nodes of mice at different stages of E. multilocularis infection, with Trm cells as the predominantly elevated subset. The impaired capacity of CD8⁺ Tm cells to secrete the effector molecule TNF-α in mouse lymph nodes at the late-stage infection may facilitate chronic parasitism of E. multilocularis.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.