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 explore the application of bridge-in, objective, pre-assessment, participatory learning, post-assessment, and summary (BOPPPS) combined with knowledge point auction-based learning in the internship teaching of pediatric general surgery nursing students.Methods:Ninety nursing students completing internships in the General Surgery Department of Children's Hospital, Zhejiang University School of Medicine from July 2022 to April 2024 were selected as the research subjects. According to the order of admission, they were divided into control group (July 2022 to May 2023) and experimental group (June 2023 to April 2024), with 45 students in each group. The control group received conventional teaching, while the experimental group received BOPPPS teaching combined with knowledge point auction-based learning. Theoretical and practical training assessment scores were compared between the two groups. Additionally, a survey on the degree of satisfaction with the teaching was administered upon internship completion . Data were analyzed using t-tests with SPSS 26.0. Results:The theoretical scores of nursing students in the experimental group were higher than those in the control group, and the difference was statistically significant; The performance of the experimental group's nursing students in practical training assessment was higher than that of the control group [peripheral venous puncture catheterization: (27.62±2.10) vs. (22.41±3.80)]; Gastrointestinal decompression technique: (22.82±1.70) vs. (18.21±2.91); Rescue of anaphylactic shock: (16.52±3.13) vs. (21.32±2.41); There was a statistically significant difference in the evaluation of teacher guidance ability between the two groups of nursing students in terms of intestinal fistula nursing (14.11±2.70) vs. (17.90±1.93). However, there was no statistically significant difference in the satisfaction score of the experimental group nursing students in other aspects of teaching compared to the control group, and the difference was statistically significant.Conclusions:BOPPPS combined with knowledge point auction-based learning improves knowledge mastery in clinical teaching for pediatric general surgery interns, enhance operational confidence, and is readily accepted by students.

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 explore the application of bridge-in, objective, pre-assessment, participatory learning, post-assessment, and summary (BOPPPS) combined with knowledge point auction-based learning in the internship teaching of pediatric general surgery nursing students.Methods:Ninety nursing students completing internships in the General Surgery Department of Children's Hospital, Zhejiang University School of Medicine from July 2022 to April 2024 were selected as the research subjects. According to the order of admission, they were divided into control group (July 2022 to May 2023) and experimental group (June 2023 to April 2024), with 45 students in each group. The control group received conventional teaching, while the experimental group received BOPPPS teaching combined with knowledge point auction-based learning. Theoretical and practical training assessment scores were compared between the two groups. Additionally, a survey on the degree of satisfaction with the teaching was administered upon internship completion . Data were analyzed using t-tests with SPSS 26.0. Results:The theoretical scores of nursing students in the experimental group were higher than those in the control group, and the difference was statistically significant; The performance of the experimental group's nursing students in practical training assessment was higher than that of the control group [peripheral venous puncture catheterization: (27.62±2.10) vs. (22.41±3.80)]; Gastrointestinal decompression technique: (22.82±1.70) vs. (18.21±2.91); Rescue of anaphylactic shock: (16.52±3.13) vs. (21.32±2.41); There was a statistically significant difference in the evaluation of teacher guidance ability between the two groups of nursing students in terms of intestinal fistula nursing (14.11±2.70) vs. (17.90±1.93). However, there was no statistically significant difference in the satisfaction score of the experimental group nursing students in other aspects of teaching compared to the control group, and the difference was statistically significant.Conclusions:BOPPPS combined with knowledge point auction-based learning improves knowledge mastery in clinical teaching for pediatric general surgery interns, enhance operational confidence, and is readily accepted by students.

ObjectiveTo investigate the association between the risk of increase in total cholesterol （TC） and the risk of cholelithiasis by using bidirectional Mendelian randomization （MR）. MethodsThe open gwas public database was used to obtain the single nucleotide polymorphism data associated with TC and cholelithiasis， and a secondary data analysis was performed for all summary data of genome-wide association studies. The genetic loci closely associated with TC or cholelithiasis were selected as exposure or outcome variables， and the bidirectional MR analysis was performed using the methods such as Egger regression， Weighted median， IVW random effects model， and IVW fixed effects model， with odds ratio （OR） values for evaluating the causal relationship between TC and cholelithiasis. ResultsWith TC as the exposure and cholelithiasis as the outcome， TC-cholelithiasis had an overall OR value of 0.91 （95% confidence interval ［CI］： 0.85‍ ‍—‍ ‍0.97） before elimination of heterogeneity and 0.93 （95%CI： 0.89‍ ‍—‍ ‍0.97） after elimination of heterogeneity. With cholelithiasis as the exposure and TC as the outcome， TC-cholelithiasis had an overall OR value of 0.20 （95%CI： 0.06‍ ‍—‍ ‍0.65） before elimination of heterogeneity and 0.28 （95%CI： 0.10‍ ‍—‍ ‍0.83） after elimination of heterogeneity. There was a bidirectional causal relationship between genetically predicted TC and cholelithiasis. ConclusionThis study confirms the bidirectional causal relationship between TC and cholelithiasis. The risk of cholelithiasis decreases with the increase in alleles associated with the elevation of TC level； on the contrary， the risk of elevated TC level decreases with the increase in alleles associated with the onset of cholelithiasis.

Objective:To investigate the relationship between the visceral adiposity index(VAI) and cognitive decline.Methods:A cross-sectional study was conducted.Between October 2020 and March 2023, 483 elderly residents living in communities in Hefei were recruited and divided into four groups based on VAI scores, Q1(VAI ≤ 1.14), Q2(VAI>1.15 and ≤1.85), Q3(VAI>1.86 and ≤2.81) and Q4(VAI>2.82).General cognitive function was assessed by(MMSE)and(MoCA).Attention and working memory were tested by forward and backward digit span tasks.Logistic regression was utilized to analyze the relationship between different VAI scores and insulin resistance.The correlation between different VAI scores and cognitive function domains was analyzed by partial correlation.Results:The values of BMI, fasting plasma glucose, fasting insulin, HbA1c, high-sensitivity C-reactive protein, HOMA-IR and HOMA-β increased with increasing VAI scores(all P<0.01).VAI was significantly correlated with insulin sensitivity after adjusting for confounding factors including sex.The risk of insulin resistance in Q4 was 7.40 times that in Q1( OR=7.40, 95% CI: 4.30-12.74, P<0.05).In addition, the correlation coefficients between VAI and forward digital span and between VAI and backward digital span were -0.116 and -0.105, respectively(both P<0.05), but there was no correlation between VAI and MMSE or MoCA. Conclusions:VAI is closely related to insulin resistance and also associated with early cognitive decline in elderly people with visceral obesity.

The incidence of psycho-cardiological diseases， i.e.， cardiovascular diseases combined with psychological disorders， is increasing year by year. Brain-derived neurotrophic factor （BDNF） plays a role in the pathogenesis of such diseases. According to the theory of collateral diseases， our team innovates the concept of regulating mental activity by dredging collaterals in the treatment of psycho-cardiological diseases and summarizes the concepts of "heart of Qi and collaterals" and "heart of vessels and collaterals". We believe that obstructed collaterals and disturbed mental activity run through the whole course of psycho-cardiological diseases， being the core pathogenesis. BDNF closely related to the core pathogenesis can regulate nerve and vascular inflammation， alleviate oxidative stress， and mediate a variety of signaling pathways， thereby promoting the survival and repair of nerve cells and vascular endothelial cells to regulate emotion and protect the heart. Therefore， BDNF is one of the potential biomarkers for clinical treatment of psycho-cardiological diseases. Collateral obstruction caused by blood stasis is specifically manifested as collateral deficiency， blood stasis， and Qi stagnation in collaterals. It can easily lead to inflammation， free radical generation， and antioxidant system changes in the patients with psycho-cardiological diseases， which can cause oxidative stress damage， affect the BDNF level， and result in mental disorders， such as anxiety and depression. Disturbed mental activity is mainly caused by the disturbance in the heart of Qi and collaterals， which is specifically manifested as the disturbance of the mind and liver soul. It is prone to cause anxiety or depression symptoms， which is closely related to the BDNF-mediated abnormal activation of neural circuits， nerve injury， and inflammation. This article elaborates on the theoretical connotation and pathological mechanism of regulating mental activity by dredging collaterals in the treatment of psycho-cardiological diseases from the perspective of BDNF， aiming to provide new ideas for the prevention and treatment of psycho-cardiological diseases and collateral diseases.

Objective:To explore mechanism of regulation of proliferation,migration,invasion and expressions of immune factors of ovarian cancer SKOV3 cells by circSKA3/miR-3163/disintegrin-metalloproteinase 9(ADAM9)gene axis.Methods:qRT-PCR was used to detect circSKA3 and miR-3163 expressions in ovarian cancer tissues and paracancerous tissues.Western blot was used to detect ADAM9 protein level in tissues.SKOV3 cells were selected for cell experiment in vitro,and divided into sh-NC group,sh-circSKA3 group,miR-NC group,miR-3163 group,sh-circSKA3+anti-miR-3163 group,sh-circSKA3+pcDNA-ADAM9 group.circSKA3 and miR-3163 expressions in SKOV3 cells were detected by qRT-PCR.CCK-8,scratch test and Transwell were used to detect cell proliferation activity,migration and invasion ability.ELISA was used to detect expressions of TNF-α,IL-6 and IL-10.Double luciferase report experiment verified targeting relationship between circSKA3 with miR-3163,miR-3163 and ADAM9.Western blot was used to detect levels of ADAM9,matrix metalloproteinase-2(MMP-2)and MMP-9 in SKOV3 cells.Results:Com-pared with paracancerous tissues,circ-SKA3 and ADAM9 expressions were increased,and miR-3163 expression was decreased in ovarian cancer tissues(P<0.05).Compared with sh-NC group/miR-NC group,sh-circSKA3 group/miR-3163 group showed decreased cell proliferative activity and healing rate,decreased number of invasive cells,MMP-2,MMP-9 proteins and TNF-α and IL-6 expres-sions were decreased,expression of IL-10 was increased(P<0.05).circSKA3 could targeting regulate expression of miR-3163,and miR-3163 could targeting bind to ADAM9(P<0.05).Compared with sh-circSKA3 group,cell proliferation activity and scratch healing rate in sh-circSKA3+anti-miR-3163 and sh-circSKA3+pcDNA-ADAM9 groups were increased,number of invasive cells was in-creased,MMP-2,MMP-9 protein and TNF-α,IL-6 expressions were increased,while expression of IL-10 was decreased(P<0.05).Conclusion:Silencing circSKA3 expression can reduce expression of ADAM9 by up-regulating miR-3163 expression,inhibit ovarian cancer cell proliferation,migration and invasion,and regulate immune factor expression.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Objective: To explore the changes in root volume and root resorption in incisor arteries from adult patients with skeletal class Ⅲ malocclusion before and after camouflaged orthodontic treatment and to provide a reference for the clinic. Methods : Thirty permanent dentition adult patients with skeletal class Ⅲ malocclusion were included from the Orthodontic Department. CBCT data of each patient at pretreatment and posttreatment were acquired, and 3D digital root models were reconstructed. The whole and segmented root volumes (cervical part, bodily part and apical part) of the right incisors were calculated. Results: The root volumes (whole, cervical part, bodily part and apical part) posttreatment were smaller than those pretreatment (P<0.001). Maxillary central incisors and lateral incisors showed similar resorption in the cervical root and bodily root and more changes in the apical root, but there was no significant difference (P>0.05). Mandibular central incisors and lateral incisors showed more root resorption in the apical root than in the cervical root and bodily root (P<0.01). The absorption ratio of all segmented roots in each incisor showed a significant difference (P<0.001), and apical absorption was the most obvious. There were no significant differences in root volume change amounts or the absorption ratio of the whole, cervical part and bodily part in all incisors (P>0.05). The absorption ratio showed a significant difference in the mandibular lateral incisors (P = 0.028). Conclusion After camouflaged orthodontic treatment of adult skeletal class Ⅲ malocclusion, incisor root resorption occurred mainly in the apical part, but the cervical and bodily parts should also be considered. There was a high risk of root resorption in the mandibular incisors.