Objective To analyze the short- and mid-term outcomes of patients undergoing reconstruction of intervalvular fibrous body (IVFB) via double valve replacement (Commando procedure) or aortic valve replacement and mitral valve repair (Hemi-Commando procedure). Methods The patients who underwent Commando or Hemi-Commando procedure between September 2014 and September 2022 in Guangdong Provincial People’s Hospital were collected. The perioperative and follow-up data were reviewed and analyzed for the assessment of short- and mid-term outcomes. Results Eleven patients received Commando procedure (a Commando group), including 4 males and 7 females with a median age of 61 (33, 68) years; 7 patients received Hemi-Commando procedure (a Hemi-Commando group), including 5 males and 2 females with a median age of 50 (36, 58) years. Two patients died in the postoperative 30 days (1 patient in the Commando group and 2 patients in the Hemi-commando group). Low cardiac output syndrome complicated with multiple organ dysfunction syndrome was the main cause of death. Fifteen patients were discharged and followed up for 13 (6, 42) months, with a survival rate of 100%. The rates of free from recurrent endocarditis or re-operation were both 100%. Conclusion Commando and Hemi-Commando procedures are effective strategies for IVFB reconstruction, and can achieve excellent mid-term outcomes if patients survive from the frailest period of early postoperative stage.

Objective To explore the mechanism of Huoxiang Zhengqi Dropping Pills in treating dampness encumbering the spleen and stomach type rats by metabolomics method based on gas chromatography-time of flight mass spectrometry(GC-TOF/MS).Methods Male SD rats were randomly divided into normal group,model group and Huoxiang Zhengqi Dropping Pills group(1 g·kg-1).The rat model of dampness encumbering the spleen and stomach was prepared by comprehensive physical modeling method combined with improper diet.Intragastric administration was performed once a day for 10 consecutive days.The macroscopic signs and behavioral indexes(body mass,body length,tail length,abdominal circumference index and spontaneous activities frequency)of rats were observed.GC-TOF/MS method was used to analyze the serum and urine metabolome of rats,identify potential biomarkers related to dampness encumbering the spleen and stomach,and analyze the metabolic pathway of Huoxiang Zhengqi Dropping Pills in rats with dampness encumbering the spleen and stomach.Results Compared with the normal group,the body mass,body length,tail length and spontaneous activities frequency of the rats in the model group were significantly reduced(P＜0.05),and the abdominal circumference index was significantly increased(P＜0.05).Compared with the model group,the body mass,body length and spontaneous activities frequency of the rats in the Huoxiang Zhengqi Dropping Pills group were significantly increased(P＜0.05),and the abdominal circumference index was significantly decreased(P＜0.05).A total of 38 and 44 potential biomarkers related to dampness encumbering the spleen and stomach were identified in rat serum and urine,respectively.Huoxiang Zhengqi Dropping Pills can effectively interfere with the serum and urine metabolic phenotypes of model rats,and can significantly reverse 17 and 13 potential biomarkers in serum and urine,involving a total of 7 metabolic pathways.Conclusion The intervention mechanism of Huoxiang Zhengqi Dropping Pills on rats with dampness encumbering the spleen and stomach syndrome may be related to the regulation of tryptophan metabolism,histidine metabolism,glutamate-glutamine metabolism,energy metabolism and intestinal flora.

Poly adenosine diphosphate ribose polymerase (PARP) inhibitors lead to synthetic lethality in homologous recombination repair-deficient (HRD) tumors by inhibiting DNA damage repair. Two PARP inhibitors, olaparib and talazoparib, have been approved for the salvage treatment of breast cancer susceptibility gene (BRCA) mutation, human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer, and adjuvant treatment of early breast cancer. PAPR inhibitor single agent shows good antitumor activity and controllable safety. A number of clinical studies on PAPR inhibitors combined with chemotherapy, radiotherapy, antiangiogenic therapy and immunotherapy are being carried out. The indications of PARP inhibitors also extend from BRCA mutation to HRD, from ovarian cancer and breast cancer to other solid tumors, promising to benefit more patients in the future.

Objective:To explore the germline mutation frequency of genetic susceptibility genes and clinical characteristics in early-onset breast cancer (onset age ≤35 years) in China.Methods:Clinical information and peripheral blood of 150 patients aged 35 and younger diagnosed with breast cancer in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to December 31, 2019 were collected. Then DNA was extracted to detect germline mutations in breast cancer susceptibility gene (BRCA) 1, BRCA2, ataxia telangiectasia mutated (ATM) , partner and localizer of BRCA2 (PALB2) , tumor protein 53 (TP53) and cell cycle checkpoint kinase 2 (CHEK2) genes. Mutations were interpreted as pathogenic, likely pathogenic, uncertain significance, likely benign and benign according to the classification criteria and guidelines for genetic variation. Patients were divided into mutation group ( n=18) and non-mutation group ( n=132) according to the presence or absence of pathogenic or probable pathogenic germline mutations, and the χ2 test was used to analyze the relationships between genetic susceptibility gene mutations and clinicopathological characteristics. Results:Eighteen pathogenic or likely pathogenic germline mutations were detected in 150 patients with early-onset breast cancer, for an overall mutation frequency of 12.0%. Among them, there were 8 (5.3%) BRCA2 mutation, 7 (4.7%) BRCA1 mutation, 1 (0.7%) PALB2 mutation, and 2 (1.3%) TP53 mutation. There were no pathogenic or likely pathogenic variants in ATM and CHEK2 genes. The mutation type was dominated by frameshift mutation (9/18, 50.0%) , followed by nonsense mutation (7/18, 38.9%) , missense mutation (1/18, 5.6%) and splice acceptor mutation (1/18, 5.6%) . Among the molecular subtypes of 18 mutation carriers, 9 cases were Luminal B, 6 cases were triple negative breast cancer (TNBC) , 2 cases were Luminal A, and only 1 case was human epidermal growth factor receptor-2 (HER-2) amplification. Among them, 8 BRCA2 mutation carriers were Luminal type, and 6 of 7 BRCA1 mutation carriers were TNBC type. There were no statistical differences in family history of breast cancer ( P=0.343) , estrogen receptor (ER) status ( χ2=0.16, P=0.688) , HER-2 status ( χ2=2.89, P=0.089) , molecular subtype ( χ2=1.99, P=0.575) , and initial diagnosis TNM stage ( χ2=2.49, P=0.115) between the mutation group and the non-mutation group. Conclusion:The patients with early-onset breast cancer have high frequency of germline mutations. It is recommended that patients with early-onset breast cancer undergo genetic counseling and multigene testing.

Breast cancer screening is an economical, effective, and simple screening measure for asymptomatic people to achieve the goals of early detection, early diagnosis and early treatment. Existing screening methods are mainly based on breast cancer X-rays and ultrasound, which are less sensitive to early lesions and cannot assess the risk of breast cancer in asymptomatic people. Breast cancer susceptibility genes, DNA methylation, microRNAs and circulating tumor cells, as blood biomarkers for breast cancer screening and early diagnosis, can identify high-risk breast cancer populations and improve the early diagnosis rate of breast cancer.

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.
Antineoplastic Agents/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Breast Neoplasms/drug therapy* ; Female ; Humans ; Immunoconjugates/therapeutic use* ; Receptor, ErbB-2

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) composed of trastuzumab, a linker, and a microtubule inhibitor. T-DM1 combines the highly effective targeting of antibody with the high anti-tumor activity of cytotoxic drugs, while reduces the off-target toxic side effects of cytotoxic drugs. T-DM1 has been applied in neoadjuvant therapy of HER2-positive breast cancer and rescue treatment of advanced breast cancer, greatly improves the prognosis of breast cancer patients. More and more clinical trials of T-DM1 for HER2 breast cancer and other solid tumors are ongoing, and more positive results are expected.

Objective:To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies.Methods:A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed.Results:The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old ( OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC ( OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein ( OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position ( OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level ( OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions:The CRT problem can′t be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) composed of trastuzumab, a linker, and a microtubule inhibitor. T-DM1 combines the highly effective targeting of antibody with the high anti-tumor activity of cytotoxic drugs, while reduces the off-target toxic side effects of cytotoxic drugs. T-DM1 has been applied in neoadjuvant therapy of HER2-positive breast cancer and rescue treatment of advanced breast cancer, greatly improves the prognosis of breast cancer patients. More and more clinical trials of T-DM1 for HER2 breast cancer and other solid tumors are ongoing, and more positive results are expected.

Objective:To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies.Methods:A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed.Results:The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old ( OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC ( OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein ( OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position ( OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level ( OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions:The CRT problem can′t be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.