This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Objective:To investigate the current trend of breast cancer neoadjuvant therapy and provide reference for the improvement of breast cancer clinical guideline in the future.Methods:Questionnaires of cross-sectional survey were sent to 110 hospitals (breast cancer surgery quantity surpassing 200) between July 2018 and September 2018. The stages and subtypes, therapeutic regimen, treatment assession, operation choice and preforming of patients underwent neoadjuvant therapy were recorded.Results:Neoadjuvant treatment has been performed in all of the 110 hospitals. The total number of breast patients underwent neoadjuvant therapy was about 14 550 (17.0% in surgical patients) in 2017. For all of the neoadjuvant patients, the proportion of stageⅡ patients was less than 30% in 81 hospitals, and the proportion of stage Ⅲ was more than 50% in 84 hospitals. The numbers of estrogen receptor (ER) (+ )/human epidermal growth factor receptor-2 (HER-2) (-), ER (-)/HER-2 (+ ) and triple negative subtype breast cancer patients were 3 550 (24.4%), 6 024 (41.4%) and 4 991 (34.3%), respectively. Patient′s scruples of relatively delayed operation and weak will of breast conservation after neoadjuvant therapy were the majority reasons for neoadjuvant therapy restriction. Anthracycline followed by taxane was the most usual neoadjuvant therapeutic regimens in 53.6% hospitals, and anthracycline plus taxane was the first choice in 42.7% hospitals. Chemotherapy with targeting therapy was recommended to HER-2 positive neoadjuvant patients in 80.9% hospitals. To assess treatment outcome of neoadjuvant treatment, 42.7% hospitals used MRI in more than 50% patients while the usage rate of MRI was less than 20% in 37.3% hospitals. The proportions of hospital using repeat-marking, tattoo and metal clip as the first method to identify the primary tumor region and lymph nodes were 60.0%, 29.1% and 10.9%, respectively. Breast-conservation rate after neoadjuvant therapy was less than 20% in 87.3% hospitals.Conclusions:Neoadjuvant therapy for breast cancer is widely performed in most hospitals in China, while the proportion of neoadjuvant treatment in patients with operable breast cancer is still low. Meanwhile, the idea of achieving de-escalation operation through neoadjuvant treatment is not promoted and the therapeutic evaluation method of neoadjuvant treatment needs further studies to improve.

Objective:To evaluate the efficacy and safety of anti-human T lymphocyte porcine immunoglobulin (P-ATG) with recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein (rhTNFR∶Fc, Etanercept) on grade Ⅲ/Ⅳ acute graft-versus-host disease (aGVHD) after allogenic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Thirty-five patients with Grade Ⅲ/Ⅳ aGVHD who received P-ATG with etanercept therapy after allo-HSCT were retrospectively analyzed. P-ATGs (5 mg·kg -1·d -1) were administrated for 3 to 5 days, and then 5mg/kg was sequentially administrated, QOD to BIW. Etanercepts were administrated 25 mg, twice a week (12.5 mg, BIW for pediatric patients) . Results:Among the 35 patients with grade Ⅲ/Ⅳ aGVHD, 21 were males and 14 females, with a median age of 10 (3-54) years. A total of 19 cases of acute myeloid leukemia, 13 of acute lymphoblastic leukemia, 1 of severe aplastic anemia, 1 of myelodysplastic syndrome, and 1 of mixed phenotypic acute leukemia were noted. The overall response (OR) rate of P-ATG with etanercept was 85.7% (30/35) , with complete response (CR) and partial response (PR) rates of 34.3% (12/35) and 51.4% (18/35) , respectively, on day 28. The OR rate of grade Ⅲ aGVHD group was higher than of grade IV aGVHD group [100% (19/19) vs. 68.8% (11/16) , P=0.004]. On day 56, the OR rate became 77.2% (27/35) , with CR and PR rates of 62.9% (22/35) and 14.3% (5/35) , respectively. The OR rate of grade Ⅲ aGVHD group was also higher than of grade Ⅳ aGVHD group [89.5% (17/19) vs. 62.5% (10/16) , P=0.009]. Thirty-five patients had no adverse effects such as fever, chills, and rash during the P-ATG infusion, and no obvious liver and kidney function damage was observed after treatment. The main treatment-related complication was infection. The reactivation rates of CMV and EBV were 77.1% (27/35) and 22.9% (8/35) , respectively, and the bacterial infection rate was 48.6% (17/35) . With a median follow-up time of 13 (1-55) months after HSCT, the 1-year and 2-year OS rates were (68.1±8.0) % and (64.3±8.4) % , respectively. The 1-year OS rate of grade Ⅲ aGVHD group was superior to grade Ⅳ aGVHD group [ (84.2±8.4) % vs. (47.6±13.1) % , χ2=3.38, P=0.05]. Conclusion:This study demonstrated that P-ATG with etanercept was effective and safe in treating grade Ⅲ-Ⅳ aGVHD after allo-HSCT.

Objective:To determine national trends for breast conserving surgery and to explore the factors affecting the scale of breast conserving surgery in China.Methods:A questionnaire survey was mailed to 110 hospitals with an year′s volume of more than 200 breast cancer surgeries in each center in China concerning hospital variations and percentage of breast conserving surgery.Results:The overall proportion of breast conserving surgery is 21.9% for operable breast cancer in China. There is a significant positive correlation between local Gross Domestic Product (GDP) and the rate of breast conserving surgery ( P=0.001). Hospitals with higher annual operation volume have higher breast-conserving ratios( P=0.042). Compared with non-teaching hospitals, more patients with stage I breast cancer underwent breast conserving surgery in teaching hospitals ( P=0.021). After breast-conserving surgery, the proportion of positive margins needing reoperation had a lower percentage and in cancer hospitals it was the lowest ( P=0.023). The method of pathological evaluation and the remedy strategy for positive margin was not related to per capita GDP and hospital category ( P>0.05). Conclusions:This survey demonstrates the current practices of breast conserving surgery in China. Local GDP, hospital category and tumor stage were factors influencing breast conserving surgery. Breast conserving surgery in China is still at a low level compared with developed countries.

Objective:To investigate the current trend of breast cancer neoadjuvant therapy and provide reference for the improvement of breast cancer clinical guideline in the future.Methods:Questionnaires of cross-sectional survey were sent to 110 hospitals (breast cancer surgery quantity surpassing 200) between July 2018 and September 2018. The stages and subtypes, therapeutic regimen, treatment assession, operation choice and preforming of patients underwent neoadjuvant therapy were recorded.Results:Neoadjuvant treatment has been performed in all of the 110 hospitals. The total number of breast patients underwent neoadjuvant therapy was about 14 550 (17.0% in surgical patients) in 2017. For all of the neoadjuvant patients, the proportion of stageⅡ patients was less than 30% in 81 hospitals, and the proportion of stage Ⅲ was more than 50% in 84 hospitals. The numbers of estrogen receptor (ER) (+ )/human epidermal growth factor receptor-2 (HER-2) (-), ER (-)/HER-2 (+ ) and triple negative subtype breast cancer patients were 3 550 (24.4%), 6 024 (41.4%) and 4 991 (34.3%), respectively. Patient′s scruples of relatively delayed operation and weak will of breast conservation after neoadjuvant therapy were the majority reasons for neoadjuvant therapy restriction. Anthracycline followed by taxane was the most usual neoadjuvant therapeutic regimens in 53.6% hospitals, and anthracycline plus taxane was the first choice in 42.7% hospitals. Chemotherapy with targeting therapy was recommended to HER-2 positive neoadjuvant patients in 80.9% hospitals. To assess treatment outcome of neoadjuvant treatment, 42.7% hospitals used MRI in more than 50% patients while the usage rate of MRI was less than 20% in 37.3% hospitals. The proportions of hospital using repeat-marking, tattoo and metal clip as the first method to identify the primary tumor region and lymph nodes were 60.0%, 29.1% and 10.9%, respectively. Breast-conservation rate after neoadjuvant therapy was less than 20% in 87.3% hospitals.Conclusions:Neoadjuvant therapy for breast cancer is widely performed in most hospitals in China, while the proportion of neoadjuvant treatment in patients with operable breast cancer is still low. Meanwhile, the idea of achieving de-escalation operation through neoadjuvant treatment is not promoted and the therapeutic evaluation method of neoadjuvant treatment needs further studies to improve.

To investigate the current trends of breast reconstruction ( BR ) after mastectomy in China. Methods A list of hospitals with more than 200 cases of breast cancer surgery per year nationwide was obtained, and 110 institutions were selected according to the geographical distribution. The research was conducted in the form of a questionnaire survey, and 92.3%(169／183) of the questions were single?choice questions. Information such as demographics of surgeons and hospitals, number of mastectomy and BR, type and timing of BR was included in the survey. Survey formal notification letter was issued by the China Anti?Cancer Association Breast Cancer Committee and Chinese College of Surgeons, Committee of Mammary Surgeons. Questionnaires were sent to the respondents of each center by email. The survey time range was from January 1, 2017 to December 31, 2017. All data were completely collected before September 7, 2018.Results A total of 110 units participated in the survey.In total, 87.3%(96／110) of the hospitals have conducted BR surgery. The BR after mastectomy was 10.7%( 6 534／61 099), among this, implant BR accounted for 65.7%(4 296／6 534), autologous BR accounted for 20.1%(1 312／6 534), and autologous combined implant BR accounted for 14.2%( 927／6 534 ). Immediate reconstruction accounted for 67.6%(4 417／6 534) of BR, while delayed BR accounted for 32.4%(2 097／6 534). In 2017, 77.8%( 35／45) of the plastic surgery departments cooperated with general surgery departments. General BR could be conducted after mastectomy accounted for 83.6%( 92／110 ). The proportion of reconstruction was positively correlated with the gross domestic product ( GDP) per capita ( r＝0.311, P＝0.002). The one?step implant?based BR(IBBR) was the most preferred type in immediate BR. Two?step IBBR was the most preferred method in delayed BR. Hospitals that routinely evaluated aesthetics after BR accounted for 64.6%( 62／96), while only 16.7%( 16／96) of hospitals used patient?reported outcome measure (PROM). The most commonly used PROM tool was BREAST?Q. Conclusions The overall BR in China is on upward trend, but gap between China and the developed countries still exists. Breast surgery departments should strengthen further cooperation with plastic surgery departments. Simultaneously, the aesthetics evaluation and PROM after BR should be put a high premium.

Objective: To investigate the current trends of breast reconstruction(BR) after mastectomy in China. Methods: A list of hospitals with more than 200 cases of breast cancer surgery per year nationwide was obtained, and 110 institutions were selected according to the geographical distribution. The research was conducted in the form of a questionnaire survey, and 92.3% (169/183) of the questions were single-choice questions. Information such as demographics of surgeons and hospitals, number of mastectomy and BR, type and timing of BR was included in the survey. Survey formal notification letter was issued by the China Anti-Cancer Association Breast Cancer Committee and Chinese College of Surgeons, Committee of Mammary Surgeons. Questionnaires were sent to the respondents of each center by email. The survey time range was from January 1, 2017 to December 31, 2017. All data were completely collected before September 7, 2018. Results: A total of 110 units participated in the survey. In total, 87.3% (96/110) of the hospitals have conducted BR surgery. The BR after mastectomy was 10.7% (6 534/61 099), among this, implant BR accounted for 65.7%(4 296/6 534), autologous BR accounted for 20.1% (1 312/6 534), and autologous combined implant BR accounted for 14.2% (927/6 534). Immediate reconstruction accounted for 67.6% (4 417/6 534) of BR, while delayed BR accounted for 32.4% (2 097/6 534). In 2017, 77.8% (35/45) of the plastic surgery departments cooperated with general surgery departments. General BR could be conducted after mastectomy accounted for 83.6% (92/110). The proportion of reconstruction was positively correlated with the gross domestic product (GDP) per capita (r=0.311, P=0.002). The one-step implant-based BR(IBBR) was the most preferred type in immediate BR. Two-step IBBR was the most preferred method in delayed BR. Hospitals that routinely evaluated aesthetics after BR accounted for 64.6% (62/96), while only 16.7% (16/96) of hospitals used patient-reported outcome measure (PROM). The most commonly used PROM tool was BREAST-Q. Conclusions The overall BR in China is on upward trend, but gap between China and the developed countries still exists. Breast surgery departments should strengthen further cooperation with plastic surgery departments. Simultaneously, the aesthetics evaluation and PROM after BR should be put a high premium.

Objective: To explore the current clinical practice of implant-based breast reconstruction (IBBR) in China. Methods: The current survey was sponsored by Chinese Anti-Cancer Association, Committee of Breast Cancer Society and Chinese Society of Breast Surgeons. A survey was mailed to 110 hospitals in China, which have more than 200 breast cancer operations performed in 2017. The survey mainly included questions on the clinical practice of IBBR, sociodemographic and geographical factors associated with IBBR practice, reasons and concerns for selecting IBBR, type and timing of breast reconstruction, and the complications of IBBR. Data were analyzed using χ² test, Fisher′s exact test or Kruskal-Wallis rank sum test. Results: IBBR was available in 86.4% (95/110) included hospitals. It was predominantly performed breast reconstruction surgery, the proportion of IBBR in all the breast reconstruction was 65.75% (4 296/6 534). However, the rate of IBBR in all the patients received mastectomy was only 7.06% (4 296/60 877). Among all the included hospitals, the number of implant reconstructions performed in 2017 was 24 (57.5) cases (M(Q_R), range: 2-565 cases). Factors associated with the performance of IBBR including regional per capita gross domestic product (H=10.47, P=0.005) and annual surgery volume (H=8.30, P=0.016). The main reasons for choosing IBBR were relatively simple surgical procedure, short learning curve and short operation time. The effects of adjuvant radiotherapy on prosthesis, postoperative complications and patient satisfaction were the main concerns for implant reconstruction. Compared with delay reconstruction, a higher proportion of IBBR was observed in immediate reconstruction (83.1% vs. 62.0%, χ²=12.522, P=0.000). In all, 10.5% (10/95) hospitals reported more than 10% grade Ⅲ to Ⅳ capsular contracture. The incidence of infections need surgical intervention was reported between 10% and 20% by 4.2% (4/95) hospitals. Hospitals with 6% to 10% implant rupture and 6% to 15% implant removal were 1.1% (1/95) and 4.2% (4/95) respectively. Conclusions IBBR was the most common used surgery in breast reconstruction after mastectomy. However, the proportion of IBBR in patients after mastectomy was still low. Reginal economy, surgery volume of hospitals, lack of specialty training program and the concern about complications and patient′s satisfaction were the factors affecting the development of IBBR.

Objective: To investigate the current status of breast reconstruction surgery in China and analyze the specific views of Chinese doctors on the relationship between radiotherapy and breast reconstruction surgery. Methods: A total of 110 medical institutions nationwide with more than 200 cases of breast cancer surgery yearly were selected into this questionnaire survey. The questionnaire survey included basic information of the surgeons and their hospitals, information of breast cancer surgeries in 2017, types of reconstruction surgery and specific views on the relationship between radiotherapy and reconstruction surgery. Results: In total, 110 hospitals participated in the survey, 96(87.3%) had undergone breast reconstruction surgery. Reconstruction with implants accounted for 65.7% of the total reconstruction surgery and the proportion of autologous reconstruction was 20.1%. For patients who probably required postoperative radiotherapy, the preferred surgical procedure in the surveyed hospitals was implant based reconstruction surgery. For those who were confirmed to receive postoperative radiotherapy or had undergone radiotherapy after total mastectomy, autologous tissue reconstruction was recommended. Postoperative radiotherapy was a negative factor for immediate breast reconstruction, and most hospitals believed that radiotherapy exerted slight effect on surgery. The proportion of delay-immediate breast reconstruction reached 66% and 86% of hospitals preferred to replace with the prosthesis at 6 months after radiotherapy. Patients with local recurrence after breast-conserving surgery could also receive immediate reconstruction and implant reconstruction was the preferred surgical procedure. Conclusions The proportion of breast reconstruction in China is relatively low and Chinese doctors still lack of technical mastery. In the face of conflict with radiotherapy, the regime selected by Chinese doctors is not in accordance with those recommended by the guideline and consensus, prompting that more professional training should be delivered for Chinese doctors to further promote the development of breast reconstruction in China.

To investigate the current trends of breast reconstruction ( BR ) after mastectomy in China. Methods A list of hospitals with more than 200 cases of breast cancer surgery per year nationwide was obtained, and 110 institutions were selected according to the geographical distribution. The research was conducted in the form of a questionnaire survey, and 92.3%(169／183) of the questions were single?choice questions. Information such as demographics of surgeons and hospitals, number of mastectomy and BR, type and timing of BR was included in the survey. Survey formal notification letter was issued by the China Anti?Cancer Association Breast Cancer Committee and Chinese College of Surgeons, Committee of Mammary Surgeons. Questionnaires were sent to the respondents of each center by email. The survey time range was from January 1, 2017 to December 31, 2017. All data were completely collected before September 7, 2018.Results A total of 110 units participated in the survey.In total, 87.3%(96／110) of the hospitals have conducted BR surgery. The BR after mastectomy was 10.7%( 6 534／61 099), among this, implant BR accounted for 65.7%(4 296／6 534), autologous BR accounted for 20.1%(1 312／6 534), and autologous combined implant BR accounted for 14.2%( 927／6 534 ). Immediate reconstruction accounted for 67.6%(4 417／6 534) of BR, while delayed BR accounted for 32.4%(2 097／6 534). In 2017, 77.8%( 35／45) of the plastic surgery departments cooperated with general surgery departments. General BR could be conducted after mastectomy accounted for 83.6%( 92／110 ). The proportion of reconstruction was positively correlated with the gross domestic product ( GDP) per capita ( r＝0.311, P＝0.002). The one?step implant?based BR(IBBR) was the most preferred type in immediate BR. Two?step IBBR was the most preferred method in delayed BR. Hospitals that routinely evaluated aesthetics after BR accounted for 64.6%( 62／96), while only 16.7%( 16／96) of hospitals used patient?reported outcome measure (PROM). The most commonly used PROM tool was BREAST?Q. Conclusions The overall BR in China is on upward trend, but gap between China and the developed countries still exists. Breast surgery departments should strengthen further cooperation with plastic surgery departments. Simultaneously, the aesthetics evaluation and PROM after BR should be put a high premium.