Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Objective:To analyze the breast cancer-related parameters and the ultrasonic features of positive axillary lymph nodes,to discuss the risk factors for axillary lymphnode metastatic burden,and to provide basis for preoperative evaluation of breast cancer patients.Methods:The ultrasonic and clinicopathological data of 574 breast cancer patients with axillary lymph node metastasis confirmed by surgery and pathology were retrospectively analyzed.According to the status of axillary lymphnode metastasis,the patients were divided into low nodal burden(LNB)group(n=283)and high nodal burden(HNB)group(n=291).The affected side,tumor quadrant,distance to skin,maximum diameter,internal echogenicity,shape,margin,calcification,blood supply,posterior echo,lymphnode long diameter,lymphnode short diameter,lymphnode aspect ratio,number of suspicious metastases,intranodal blood supply,lymphnode hilum morphology,age,pathological type,histological grade,molecular subtype,and the expressions of estrogen receptor(ER),progesterone receptor(PR),Ki-67,human epidermal growth factor receptor 2(HER2),and P53 were compared between two groups.Logistic regression was used to analyze the risk factors for axillary lymph node metastatic burden in the breast cancer patients;receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate the predictive value.Results:The univariate analysis results showed that there were statistically significant differences in tumor quadrant,distance to skin,molecular subtype,HER2 positive expression,lymphnode long diameter,lymph node short diameter,lymph node aspect ratio,number of suspicious metastases,and lymphnode hilum morphology between two groups(P<0.05).The multivariate Logistic regression analysis results showed that tumor located in the upper outer quadrant(OR=0.648,P=0.021),distance to skin<5 mm(OR=0.283,P=0.016),Luminal A(OR=1.564,P=0.044),lymphnode long diameter≥20 mm(OR=2.050,P<0.01),lymphnode short diameter≥8.6 mm(OR=2.430,P<0.01),lymph node aspect ratio<2(OR=1.585,P<0.01),and indistinct lymphnode hilum structure(OR=2.092,P<0.01)were the independent risk factors for axillary lymphnode metastatic burden.The ROC curve analysis results showed that compared with the ultrasonic features of positive axillary lymph nodes,the AUC of the combination of breast cancer-related parameters and ultrasonic features of positive axillary lymphnodes was larger(Z=2.72,P=0.006 5),and it had higher predictive value for axillary lymphnode metastatic burden.Conclusion:The tumor quadrant,distance to skin,molecular subtype,lymphnode long diameter,lymph node short diameter,lymphnode aspect ratio,and lymphnode hilum structure are the independent risk factors for axillary lymphnode metastatic burden,and they have certain predictive value for axillary lymphnode metastatic burden.

Objective To construct a training program for retuming to work after delivery based on Morrison's job adaptation theory in operating room nurses and to explore its application effect.Methods On the basis of literature research and Delphi expert consultation method,a training program of postpartum return of operating room nurses was constructed.From August 2021 to December 2022,the preliminary application of this research program was carried out,with 6 cases in an experimental group and 5 cases in a control group.The differences between the 2 groups were compared by Job Adaptation Scale,Psychological Resilience Scale and satisfaction evaluation,and the application effect was evaluated.Results After 2 rounds of correspondence,a training program for postpartum return of operating room nurses was formed,which included 4 first-level indicators(role adaptation,task adaptation,environment adaptation and cultural adaptation),and 32 second-level indicators.The authority coefficients of the 2 rounds of correspondence consultation were 0.908 and 0.917,and the Kendall W coefficients were 0.224 and 0.206,respectively(both P＜0.001).The preliminary application results showed that there were statistically significant differences in job adaptation and satisfaction evaluation between the 2 groups(both P＜0.05).There was no significant difference in psychological resilience score between groups(P＞0.05).Conclusion The postpartum retum training program for operating room nurses established in this study is scientific and practical to a certain extent.In the future,samples can be expanded and multi-center studies can be carried out to further test the practicability and effectiveness of the program.

BACKGROUND:In recent years,the treatment of anterior cruciate ligament injury has become more and more mature.However,there are still disputes about the timing of surgery,the choice of surgical methods,the choice of grafts,and the methods to promote graft healing after anterior cruciate ligament injury. OBJECTIVE:To summarize the latest research progress of surgical timing,surgical methods,graft selection and methods to promote graft healing after anterior cruciate ligament injury,and to find new treatment directions for anterior cruciate ligament injury. METHODS:Relevant articles concerning anterior cruciate ligament injury were retrieved from PubMed,CNKI,WanFang Date,VIP,SinoMed,ScienceDirect,Springer and Cochrane Library.After the screening,72 related articles were finally included. RESULTS AND CONCLUSION:(1)Surgical timing:Compared with delayed anterior cruciate ligament reconstruction,early reconstruction can reduce meniscus injury,elevate quality of life,and improve functional recovery.However,it is still uncertain whether the different operation timing will accelerate cartilage injury.(2)Surgical methods:Arthroscopic anterior cruciate ligament reconstruction is a common surgical method for anterior cruciate ligament injury.Dynamic internal stabilization repair of anterior cruciate ligament can bring similar results to traditional anterior cruciate ligament reconstruction in short-term and long-term effects.(3)Graft selection:Autogenous hamstring tendon is the first choice of anterior cruciate ligament graft,while bone-patellar tendon-bone grafts and allografts are the secondary choices.(4)Among the methods to promote graft healing,suture band strengthening can increase knee joint stability and ensure graft healing.Stem cells promote the tendon-bone healing of grafts through anti-inflammatory action,angiogenesis,inhibition of osteolysis and promotion of chondrocyte differentiation.Preserving the residual end of the anterior cruciate ligament can maintain the stability of the knee joint,promote the recovery of proprioception,and provide a prerequisite for the healing of the graft.The effectiveness of platelet-rich plasma in promoting graft healing remains to be discussed.However,biomaterials,gene therapy,stem cell application and other methods to promote tendon healing remain in the stage of molecular and animal researches.Clinical transformation is also needed in the future.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Objective:This study sought to investigate the feasibility, anatomical indications and operating points of transcatheter aortic valve replacement (TAVR) procedure in the treatment of pure aortic regurgitation (AR).Methods:The medical records of 4 elderly patients with pure AR who were treated in the cardiology department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2020 to March 2021 were retrospectively analyzed. All patients were implanted with self-expandable valve stents via peripheral artery approach for TAVR treatment. The feasibility, anatomical indications and key points of TAVR were analyzed.Results:The 4 patients with pure AR who were carefully screened had an average age of 66 years, and all achieved TAVR treatment success without serious perioperative complications and death. Postoperative examination and follow-up data showed that cardiac functions and cardiac remodeling indexes were significantly improved.Conclusions:This exploratory study shows that TAVR is technically feasible and effective treatment option for selected elderly patients with native pure AR, which is worthy of further study.

Purpose: This study aimed to investigate the changes in microRNA-130a (miR-130a) and its correlation with cardiotoxicity during epirubicin/cyclophosphamide followed by docetaxel plus trastuzumab (EC-D+T) adjuvant chemotherapy in human epidermal growth factor receptor-2-positive (HER2+) breast cancer patients. Methods: A total of 72 HER2+ breast cancer patients who underwent resection and were scheduled to receive EC-D+T adjuvant therapy were consecutively enrolled. The expression of miR-130a and cardiotoxicity (defined as any of the following situations: 1) absolute decline of left ventricular ejection fraction (LVEF) ≥ 10% and LVEF < 53%; 2) heart failure; 3) acute coronary artery syndromes; and 4) fatal arrhythmia) were assessed every 3 months throughout the 15-month EC-D+T treatment. Results: The accumulating cardiotoxicity rate was 12 (16.7%), of which the incidence of heart failure, acute coronary syndrome, life-threatening arrhythmias, ΔLVEF ≥ 10%, and LVEF < 53% was 0 (0.0%), 1 (1.4%), 0 (0.0%), and 12 (16.7%), respectively. Baseline miR-130a expression was negatively correlated with LVEF (%) and positively correlated with cardiac troponin I. The expression of miR-130a gradually increased in both cardiotoxicity and noncardiotoxicity patients during EC-D+T treatment, while the increment of miR-130a was more obvious in cardiotoxicity patients compared with non-cardiotoxicity patients. Further logistic regression and receiver operating characteristic curve analysis indicated that miR-130a was an independent predictive factor for increased cardiotoxicity risk. Conclusion MiR-130a increases constantly and predicts high cardiotoxicity risk during ECD+T adjuvant chemotherapy in HER2+ breast cancer patients.

Purpose: This study aimed to investigate the changes in microRNA-130a (miR-130a) and its correlation with cardiotoxicity during epirubicin/cyclophosphamide followed by docetaxel plus trastuzumab (EC-D+T) adjuvant chemotherapy in human epidermal growth factor receptor-2-positive (HER2+) breast cancer patients. Methods: A total of 72 HER2+ breast cancer patients who underwent resection and were scheduled to receive EC-D+T adjuvant therapy were consecutively enrolled. The expression of miR-130a and cardiotoxicity (defined as any of the following situations: 1) absolute decline of left ventricular ejection fraction (LVEF) ≥ 10% and LVEF < 53%; 2) heart failure; 3) acute coronary artery syndromes; and 4) fatal arrhythmia) were assessed every 3 months throughout the 15-month EC-D+T treatment. Results: The accumulating cardiotoxicity rate was 12 (16.7%), of which the incidence of heart failure, acute coronary syndrome, life-threatening arrhythmias, ΔLVEF ≥ 10%, and LVEF < 53% was 0 (0.0%), 1 (1.4%), 0 (0.0%), and 12 (16.7%), respectively. Baseline miR-130a expression was negatively correlated with LVEF (%) and positively correlated with cardiac troponin I. The expression of miR-130a gradually increased in both cardiotoxicity and noncardiotoxicity patients during EC-D+T treatment, while the increment of miR-130a was more obvious in cardiotoxicity patients compared with non-cardiotoxicity patients. Further logistic regression and receiver operating characteristic curve analysis indicated that miR-130a was an independent predictive factor for increased cardiotoxicity risk. Conclusion MiR-130a increases constantly and predicts high cardiotoxicity risk during ECD+T adjuvant chemotherapy in HER2+ breast cancer patients.

Objective The inhibitory effect of the PARP inhibitor olaparib on human acute myeloid leukemia HL-60 cells was studied. Methods The HL-60 cells in logarithmic growth phase were treated with different concentrations(1. 25,2. 5,5 and 10 μmol/L) of olaparib for different time. The CCK-8 assay was used to detect the inhibitory effect of olaparib on HL-60 cells. The apoptotic level of HL-60 cells was detected by Annexin-V/PI double staining method,and the expression of related signal proteins ( PARP-1 and caspase-3)in HL-60 cells was detected by Western blot. Results HL-60 cells were inhibited by olaparib at dif-ferent concentrations(1. 25,2. 5,5 and 10 μmol/L) for 48 h,and the inhibition rate gradually increased with the prolongation of the action time;at the same time,the apoptotic rate was increased in HL-60 cells after olaparib treatment for 48 h,showing a dose-de-pendent manner;the PARP activity was inhibited and caspase-3 was activated in HL-60 cells treated with olaparib. Conclusion The PARP inhibitor olaparib not only inhibits proliferation of HL-60 cells,but it also promotes apoptosis of HL-60 cells by inhibi-ting PARP activity and activating caspase-3.