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 impact of childhood trauma on drug relapse tendency, as well as the mediating role of post-traumatic stress disorder (PTSD).Methods:From March to May 2017, a total of 403 compulsory drug rehabilitation personnel were selected for a cross-sectional study and then were investigated by the general demography scale, drug relapse risk scale, childhood trauma questionnaire (CTQ), and PTSD checklist for DSM-5(PCL-5).SPSS 27.0 software and PROCESS 4.1 macro program were used for correlation analysis, regression analysis and Bootstrap-based mediation analysis.Results:The scores of negative emotions subscale of drug relapse risk scale, emotional abuse and emotional neglect subscales of CTQ had no significant gender differences(all P>0.05).There were gender differences in relapse tendency, childhood trauma, and PTSD total scores as well as other dimensions ( t/ Z=2.08-4.67, all P<0.05).There were pairwise positive correlations among the total score of the drug relapse risk scale(31.68±9.79), CTQ(39.90±12.13), and PCL-5(11(3, 24)) for compulsory isolation and rehabilitation personnel ( r=0.28, 0.36, 0.37, P<0.05).After controlling for gender, childhood trauma could significantly and positively predict drug relapse tendency( β=0.34, t=7.24, P<0.01), and PTSD played a mediating role between childhood trauma and drug relapse tendency, with the indirect effect of 0.11(95% CI=0.06-0.16). Conclusion:Childhood trauma can affect drug relapse tendency directly, and indirectly through PTSD.

Objective:To investigate the clinical features of adherent perirenal fat (APF) in patients undergoing laparoscopic adrenal surgery through peritoneal approach, and to analyze its predictors and risk factors, so as to provide reference for clinical diagnosis and treatment.Methods:A total of 86 patients who received transabdominal approach laparoscopic adrenal surgery in the Department of Urology, the Rizhao Hospital of Traditional Chinese Medicine and the First Department of Minimally invasive Urology of Shandong Provincial Hospital from February 2021 to February 2024 were retrospectively selected as the study objects. According to whether patients developed APF during the operation, they were divided into APF group (29 cases) and non-APF group (57 cases). The Mayo Adhesive Probability (MAP) score and preoperative perirenal fat CT density were compared between the two groups. Receiver operating characteristic (ROC) curve was used to analyze the value of each index in predicting the occurrence of APF. Univariate and multivariate logistic regression models were used to analyze the influencing factors of the occurrence of APF.Results:The MAP score, CT density of perirenal fat (renal vein level, adrenal tumor level, normal adrenal gland level) and CT density score of the APF group were higher than those of the non-APF group, with statistical significance (all P<0.05). Age, body mass index (BMI), perirenal fat thickness and the proportion of diabetes mellitus and hyperlipidemia in the APF group were significantly higher than those in the non-APF group, with statistical significance (all P<0.05). The area under ROC curve predicted by MAP score, CT density of perirenal fat (renal vein level, adrenal tumor level, normal adrenal level) and CT density score for APF in patients undergoing laparoscopic adrenal surgery were 0.921, 0.655, 0.628, 0.538, and 0.912, respectively. Logistic regression model results showed that high MAP score, high CT density score, old age, high BMI, large perirenal fat thickness, and complicated diabetes were independent risk factors for APF in patients undergoing peritoneal laparoscopic adrenal surgery (all P<0.05). Conclusions:In patients with adrenal tumor treated by peritoneal laparoscopic adrenal surgery, MAP score and CT perirenal fat density examination before operation are beneficial to predict whether APF will occur, which has certain guiding significance for the formulation of surgical plan.

Objective:To investigate the clinical features of adherent perirenal fat (APF) in patients undergoing laparoscopic adrenal surgery through peritoneal approach, and to analyze its predictors and risk factors, so as to provide reference for clinical diagnosis and treatment.Methods:A total of 86 patients who received transabdominal approach laparoscopic adrenal surgery in the Department of Urology, the Rizhao Hospital of Traditional Chinese Medicine and the First Department of Minimally invasive Urology of Shandong Provincial Hospital from February 2021 to February 2024 were retrospectively selected as the study objects. According to whether patients developed APF during the operation, they were divided into APF group (29 cases) and non-APF group (57 cases). The Mayo Adhesive Probability (MAP) score and preoperative perirenal fat CT density were compared between the two groups. Receiver operating characteristic (ROC) curve was used to analyze the value of each index in predicting the occurrence of APF. Univariate and multivariate logistic regression models were used to analyze the influencing factors of the occurrence of APF.Results:The MAP score, CT density of perirenal fat (renal vein level, adrenal tumor level, normal adrenal gland level) and CT density score of the APF group were higher than those of the non-APF group, with statistical significance (all P<0.05). Age, body mass index (BMI), perirenal fat thickness and the proportion of diabetes mellitus and hyperlipidemia in the APF group were significantly higher than those in the non-APF group, with statistical significance (all P<0.05). The area under ROC curve predicted by MAP score, CT density of perirenal fat (renal vein level, adrenal tumor level, normal adrenal level) and CT density score for APF in patients undergoing laparoscopic adrenal surgery were 0.921, 0.655, 0.628, 0.538, and 0.912, respectively. Logistic regression model results showed that high MAP score, high CT density score, old age, high BMI, large perirenal fat thickness, and complicated diabetes were independent risk factors for APF in patients undergoing peritoneal laparoscopic adrenal surgery (all P<0.05). Conclusions:In patients with adrenal tumor treated by peritoneal laparoscopic adrenal surgery, MAP score and CT perirenal fat density examination before operation are beneficial to predict whether APF will occur, which has certain guiding significance for the formulation of surgical plan.

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 impact of childhood trauma on drug relapse tendency, as well as the mediating role of post-traumatic stress disorder (PTSD).Methods:From March to May 2017, a total of 403 compulsory drug rehabilitation personnel were selected for a cross-sectional study and then were investigated by the general demography scale, drug relapse risk scale, childhood trauma questionnaire (CTQ), and PTSD checklist for DSM-5(PCL-5).SPSS 27.0 software and PROCESS 4.1 macro program were used for correlation analysis, regression analysis and Bootstrap-based mediation analysis.Results:The scores of negative emotions subscale of drug relapse risk scale, emotional abuse and emotional neglect subscales of CTQ had no significant gender differences(all P>0.05).There were gender differences in relapse tendency, childhood trauma, and PTSD total scores as well as other dimensions ( t/ Z=2.08-4.67, all P<0.05).There were pairwise positive correlations among the total score of the drug relapse risk scale(31.68±9.79), CTQ(39.90±12.13), and PCL-5(11(3, 24)) for compulsory isolation and rehabilitation personnel ( r=0.28, 0.36, 0.37, P<0.05).After controlling for gender, childhood trauma could significantly and positively predict drug relapse tendency( β=0.34, t=7.24, P<0.01), and PTSD played a mediating role between childhood trauma and drug relapse tendency, with the indirect effect of 0.11(95% CI=0.06-0.16). Conclusion:Childhood trauma can affect drug relapse tendency directly, and indirectly through PTSD.

Objective:To investigate the clinical efficacy of minimally invasive percutaneous internal fixation with double screws for delayed union or nonunion of scaphoid fracture.Methods:A retrospective study was conducted to analyze the 12 patients with delayed union or nonunion of scaphoid fracture who had been treated at Department of Hand and Foot Surgery, The Affiliated Hospital of Jining Medical University from March 2021 to December 2023. They were 11 males and 1 female, with an age of (29.9±13.8) years and an interval from injury to surgery of (5.1±2.6) months. They were all treated by minimally invasive percutaneous internal fixation with 2 hollow compression screws. The visual analogue scale (VAS), grip strength (percentage of the affected side to the healthy side), wrist range of motion, modified Mayo wrist score and other data were recorded and compared between pre-surgery and the last follow-up. The incidence of complications was recorded.Results:Follow-up for all patients lasted for (20.8±8.9) months. All patients achieved bony union after (10.1±3.2) weeks with no complications like infection. No post-surgery imaging revealed screw misplacement or penetration. At the last follow-up, the VAS pain score was 0 (0, 1) point, the wrist grip strength 100.6%±7.2%, the wrist flexion 88.3°±2.5°, the wrist dorsiflexion 88.5°±2.2°, and the modified Mayo wrist score (98.3±2.5) points, all significantly better than the pre-surgery values [4 (4, 5) points, 69.1%±16.0%, 61.3°±13.5°, 64.7°±9.1°, and (61.7±10.1) points] (all P < 0.05). Conclusion:In the treatment of delayed union or nonunion of scaphoid fracture, minimally invasive percutaneous internal fixation with double screws shows advantages of minimal invasion, quick fracture healing, fine functional recovery, and no need of bone grafting.

Transalveolar technique for sinus floor elevation(TSFE)offers the advantages of minimal invasiveness,reduced postoperative reaction,and shorter operative time for vertical bone augmentation in the maxillary posterior region.The clinical data of one patient with severe deficiency of residual bone height(RBH)in the maxillary posterior region,a blood vessel visible in the lateral wall of the maxillary sinus and a visible septum at the floor of the maxillary sinus were reported,and two-stage flexible TSFE was used to improve the vertical bone height of the operated area while reducing trauma,the risk of Schneiderian membrane rupture and maxillary sinus infection,etc.,and the relevant literatures were reviewed.The patient,male,26 years old,complained of missing left maxillary posterior teeth for more than 1 year and requested restoration.The patient had 27 missing teeth,normal keratinized gingiva,full alveolar ridge,no elongation of the opposing teeth,fair width of the proximal and normal occlusal distance.The results of cone beam CT(CBCT)showed that the distance between the sinus crests at the site of the 27 teeth was about 3 mm,the width of the alveolar bone was about 12.8 mm,the bone density was normal,and there were no residual roots or other abnormalities;no cyst-like lesions were seen in the walls of the maxillary sinuses bilaterally,and separation was seen at the floor of the maxillary sinus on the left side and a blood vessel was seen in the lateral wall of the maxillary sinus.A diagnosis of Kennedy class Ⅱ maxillary tooth defects was made.After two stages of TSFE,the Schneiderian membrane was intact and the bone height of the implant area was elevated to 9.6 mm from 3 mm preoperatively after the completion of the restoration,with stable bone augmentation,good osseointegration,and restoration of normal occlusal function.For the patients with severe bone height deficiency in the maxillary posterior region,flexible two-stage TSFE should be considered,which can help to reduce the risk of maxillary sinus infection and Schneiderian membrane rupture while minimizing the damage and obtaining the ideal bone augmentation results.

Objective:To investigate the clinical efficacy of minimally invasive percutaneous internal fixation with double screws for delayed union or nonunion of scaphoid fracture.Methods:A retrospective study was conducted to analyze the 12 patients with delayed union or nonunion of scaphoid fracture who had been treated at Department of Hand and Foot Surgery, The Affiliated Hospital of Jining Medical University from March 2021 to December 2023. They were 11 males and 1 female, with an age of (29.9±13.8) years and an interval from injury to surgery of (5.1±2.6) months. They were all treated by minimally invasive percutaneous internal fixation with 2 hollow compression screws. The visual analogue scale (VAS), grip strength (percentage of the affected side to the healthy side), wrist range of motion, modified Mayo wrist score and other data were recorded and compared between pre-surgery and the last follow-up. The incidence of complications was recorded.Results:Follow-up for all patients lasted for (20.8±8.9) months. All patients achieved bony union after (10.1±3.2) weeks with no complications like infection. No post-surgery imaging revealed screw misplacement or penetration. At the last follow-up, the VAS pain score was 0 (0, 1) point, the wrist grip strength 100.6%±7.2%, the wrist flexion 88.3°±2.5°, the wrist dorsiflexion 88.5°±2.2°, and the modified Mayo wrist score (98.3±2.5) points, all significantly better than the pre-surgery values [4 (4, 5) points, 69.1%±16.0%, 61.3°±13.5°, 64.7°±9.1°, and (61.7±10.1) points] (all P < 0.05). Conclusion:In the treatment of delayed union or nonunion of scaphoid fracture, minimally invasive percutaneous internal fixation with double screws shows advantages of minimal invasion, quick fracture healing, fine functional recovery, and no need of bone grafting.

Objective:To explore the spatial support capacity and its influence in osteogenic effect of composite biofilm based on poly(propylene carbonate)(PPC)/poly(butylene succinate)(PBS)in rabbit tibial bone defect models,and to clarify its barrier functional reliability and osteogenetic effect in vivo.Methods:The composite biofilms of PPC/PBS and PPC/PBS/collegen type Ⅰ(Col-Ⅰ)(PPC/PBS/Co)were prepared.Eighteen Japanese big-ear rabbits were selected and two bone defects were prepared on each side of the tibia of the rabbits.Six rabbits were randomly selected to place PPC/PBS composite biofilm on the bone defects,2 rabbits were executed at 2,4,8 and 12 weeks after operation,and the surface microstructures of PPC/PBS composite biofilm in the rabhit bone defect area were observed by scanning electron microscope(SEM).The experiment was divided into blank control group,PPC/PBS composite biofilm group,BME-10X collagen membrane group,and PPC/PBS/Co composite biofilm group.The above biofilms were placed on the corresponding bone defects of rabbits by operation,while no biofilm was placed in the rabbits in blank control group.Three rabbits were killed at 2,4,8 and 12 weeks after operation respectively,and the gray values of regenerated bone in the bone defect areas of the rabbits in varrous groups were detected by soft X-ray;the fluorescence intensities of regenerated bone tissue in the bone defect areas of the rabbits in various groups were observed by laser scanning confocal microscope after fluorescence labeling.The pathomorphology of regenerated bone tissue in the bone defect areas of the rabbits in various groups were observed by HE staining and modified Gomori staining,and the expression levels of bone morphogenetic protein 2(BMP-2)and osteopontin(OPN)in the regenerated bone tissue in bone defect areas of the rabbits in various groups were detected by immunohistochemical staining.Results:In general,the PPC/PBS composite biofilm was tightly covered in the bone defect area without displacement and collapse.The SEM results showed that the porous surface of PPC/PBS composite biofilm appeared micropore structure and the number of micropores was increased with the prolongation of time,while the smooth surface of biofilm basically did not form the micropore-like structure.The results of soft X-ray detection showed that the gray values of regenerated bone tissue in bone defect areas of the rabbits in various groups were increased with the prolongation of time,and the gray value of regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group was significantly higher than those in other groups(P＜0.05).The confocal micrscope results showed that the fluorescence intensity of regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group was similar to those in blank control group at 4,8,and 12 weeks;compared with PPC/PBS composite biofilm group and BME-10X collagen membrane group,the fluoresence intensity of regenerated bone tissue in bone defect areas of the rabbits in PPC/PB/Co composite biofilm group at 4 weeks was increased(P＜0.05),and the fluoresence intensity of regenerated bone tissue in bone defect areas of the rabbits at 8 and 12 weeks were decreased(P＜0.05).The results of HE staining and modified Gomori staining showed that compared with PPC/PBS composite biofilm group and BME-10X collagen membrane group,the new bone formed faster in PPC/PBS/Co composite biofilm group and blank control group at 2 and 4 weeks,and the lamellar bone mineralization was higher at 12 weeks.The immunohistochemical staining results showed that compared with blank control group,PPC/PBS composite biofilm group and BME-10X collagen membrane group,the expression levels of BMP-2 and OPN proteins in the regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group at 2 and 4 weeks were increased(P＜0.05 or P＜0.01);compared with blank control group and PPC/PBS composite biofilm group,the expression levels of BMP-2 and OPN proteins in the regenerated bone tissue in bone defect areas of the rabbits in BME-10X collage membrane group were decreased(P＜0.05 or P＜0.01).Conclusion:PPC/PBS composite biofilm has excellent spatial support capacity and reliable physical barrier function.The PPC/PBS/Co composite biofilm has a good effect in guiding bone regeneration in vivo.