ObjectiveTo explore the mechanism by which Zuoguiwan improves the pancreas development in the gestational diabetes mellitus （GDM） model by observing the effects of Zuoguiwan on the expression of key regulatory factors in different stages of pancreas development. MethodsPregnant Wistar rats were randomly assigned into blank， model， insulin detemir （20 U·kg^-1） and Zuoguiwan （1.89 g·kg^-1） groups （n=18）. GDM was induced by peritoneal injection of streptozotocin on day 6.5 （E6.5d） in the embryonic stage， and the blank group was given an equal volume of sodium citrate buffer. The modeling performance was assessed by measuring the blood glucose of pregnant rats. Except the blank group and model group， pregnant rats in other groups were administrated with corresponding drugs from E9.5d to delivery. The random blood glucose of pregnant rats was monitored， and the embryos and offspring rats were measured for the length and weighed on E12.5d， E18.5d and day 21 after birth （B21d）. The Lee's index of rats on B21d was calculated. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the fasting insulin （FINS） levels of B22d rats and the Homeostasis Model Assessment for Insulin Resistance （HOMA-IR） was calculated. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total bilirubin （TBIL）， total cholesterol （CHO）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL） in E18.5d pregnant rats and B22d offspring were determined. The pathological changes in the pancreas of E12.5d， E18.5d and B22d rats were observed by hematoxylin-eosin （HE） staining. Western blot was used to determine the protein levels of pancreatic duodenal homeobox 1 （Pdx1）， pancreas-specific transcription factor 1a （Ptf1a）， and sex-determining region Y-box protein 9 （Sox9） in the pancreas of E12.5d embryos， Pdx1， Nkx2 homeobox 2 （Nkx2.2）， and hairy and enhancer of split-1 （Hes1） in the pancreas of E18.5d embryos， and Pdx1， v-maf musculoaponeurotic fibrosarcoma oncogene homolog A （Mafa）， and NK transcription factor-related homeobox gene family 6 locus 1 （Nkx6.1） in the pancreas of B22d rats. ResultsCompared with the blank group， the model group showed elevated blood glucose levels in pregnant rats on B0d， E9.5d， E12.5d， E15.5d， and E18.5d （P<0.05， P<0.01）， decreased body weight and body length （P<0.01） and increased Lee's index in the offspring. In addition， the B22d offspring showed rising levels of FBG， FINS， HOMA-IR， AST， and TG （P<0.01）， a declined level of HDL （P<0.01）， and pancreatic acinous cells with edema and loose arrangement. The pregnant rats on E18.5d exhibited raised levels of ALT， AST， and TG （P<0.05， P<0.01） in the pancreas and a declined level of HDL （P<0.05）. The E12.5d embryos showed up-regulated protein levels of Pdx1， Sox9， and Ptf1a in the pancreas （P<0.01） and the E18.5d embryos exhibited down-regulated protein levels of Pdx1， Nkx2.2， and Hes1 in the pancreas （P<0.01）. The protein levels of Pdx1， Nkx6.1， and Mafa in the pancreas of B22d offspring were down-regulated （P<0.01）. Compared with the model group， the insulin group exhibited lowered blood glucose in pregnant rats on B0d， E15.5d， and E18.5d （P<0.05， P<0.01）. The offspring in all treatment groups showcased increased body weight and body length （P<0.01） and decreased Lee's index. The B22d offspring exhibited declined levels of FBG， FINS， and HOMA-IR in the insulin group （P<0.01） and lowered levels of FBG and HOMA-IR in the Zuoguiwan group （P<0.01）. The B22d offspring in all the treatment groups showed reduced levels of ALT， AST， TBIL， CHO， TG， and LDL， a raised level of HDL， and alleviated edema of pancreatic acinous cells. The pregnant rats on E18.5d demonstrated declined levels of TG and ALT （P<0.05， P<0.01） and an elevated level of HDL （P<0.05）. The pancreas of E12.5d embryos presented down-regulated protein levels of Pdx1 and Sox9 and an up-regulated protein level of Ptf1a in the insulin group （P<0.05）. The pancreas of E12.5d embryos in the Zuoguiwan group presented down-regulated protein levels of Pdx1， Sox9， and Ptf1a （P<0.01）. All the treatment groups showed up-regulated protein levels of Pdx1， Nkx2.2， and Hes1 in the pancreas of E18.5d embryos （P<0.01） and Pdx1， Nkx6.1， and Mafa in the pancreas of B22d embryos （P<0.05， P<0.01）. ConclusionZuoguiwan can promote the growth and development and ameliorate the pathological changes in the pancreas of the offspring of GDM model by regulating the expression of Pdx1 pathway-related regulatory factors in different stages of pancreas development.

Five new flavonoid derivatives, cajavolubones A-E (1-5), along with six known analogues (6-11) were isolated from Cajanus volubilis, and their structures were elucidated by spectroscopic analysis and quantum chemical calculations. Cajavolubones A and B (1 and 2) were identified as two geranylated chalcones. Cajavolubone C (3) was a prenylated flavone, while cajavolubones D and E (4 and 5) were two prenylated isoflavanones. Compounds 3, 8, 9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.
Flavonoids/chemistry* ; Cajanus ; Molecular Structure ; Chalcones/chemistry*

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.

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 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.

Objective To evaluate the influence factors on surgical methods in DCIS (Ductal carcinoma in situ) patients,and the prognosis of different surgical methods in a 10-year single-center retrospective study.Methods We retrospectively included 1557 DCIS patients who received treatments in our center from Jan.2006 to Nov.2016.T tests,Chi-square analysis and logistic regression analysis were used to analyze influence factors on surgical methods.Kaplan-Meier and Log-rank analysis were used to evaluate recurrence-free survival(RFS) and loco-regional recurrence-free survival (LRRFS) in patients with different surgical methods.Results Of the enrolled 1557 DCIS patients,surgical methods included modified radical mastectomy,simple mastectomy (with or without axillary evaluation) and breast conservation surgery (with or without axillary evaluation).The number of DCIS cases in our center increased (P＜0.001),so did the percentage of DCIS in annual malignant surgery cases (P=-0.026).Significant decrease was found in modified radical mastectomy (P=0.012).More than half of the patients received simple mastectomy after 2010,and more than one fifth of the patients received breast conservation surgery after 2008.About 13.99％ patients who received mastectomy had breast reconstruction.The independent influence factors of refusing breast conservation surgery were age ≥ 50(P＜0.001),medium nuclear grade (P=0.044),tumor size ＞ 15mm (P＜0.001) and spontaneous discharge (P＜0.001).Patients with smaller tumor size (≤ 15mm) and no spontaneous discharge had 4.18-fold and 7.04-fold greater preference for breast conservation surgery,respectively(OR=0.232,P＜0.001;OR=0.144,P＜0.001).There were no significant differences in RFS and LRRFS in patients with different surgical methods.Conclusion The evaluation in trends and influence factors of different surgical methods provides basis on surgical precision medicine in DCIS patients.

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.

Objectives: To examine the influence factors on axillary evaluation in ductal carcinoma in situ (DCIS) patients, and the prognosis of different choices of axillary evaluation in a single-center retrospective study. Methods: Totally 1 557 DCIS patients admitted in Department of Breast Surgery, Fudan University Shanghai Cancer Center from January 2006 to November 2016 were retrospectively enrolled. All patients were female. The median age was 49 years (range: 21 to 85 years). Surgical methods included modified radical mastectomy, simple mastectomy (with or without axillary evaluation) and breast conservation surgery (with or without axillary evaluation). Axillary evaluation included axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB). T tests, χ² test and Logistic regression analysis was used to analyze influence factors on axillary evaluation, respectively. Kaplan-Meier curve and Log-rank analysis were used to evaluate recurrence-free survival (RFS) and loco-regional recurrence-free survival (LRRFS) in patients with different surgical methods. Results: Among the 1 557 DCIS patients, there were 1 226 cases received axillary evaluation, while 331 cases not received axillary evaluation. Patients were separated into 3 groups by different axillary evaluation choices: SLNB group (957 cases, 61.46%), ALND group (197 cases, 12.65%) and no evaluation group (403 cases, 25.88%). The patients in SLNB group increased significantly (P=0.000), from 3.85% (60/1 557) in 2006 to 75.19% (1 170/1 557) in 2016. The independent influence factors of receiving axillary evaluation were high nuclear grade (OR=3.191, 95%CI: 1.722 to 5.912, P=0.001) and tumor size>15 mm (OR=1.698, 95%CI: 1.120 to 2.573, P=0.012). Also, patients received breast conservation surgery were more likely to refuse axillary evaluation (OR=0.155, 95%CI: 0.103 to 0.233, P=0.000). There were no significant differences in RFS and LRRFS in patients with different axillary evaluation choices. Conclusions The investigation in trends and influence factors of different axillary evaluation choices provided basis on surgical precision medicine in DCIS patients. Patients received SLNB increased significantly. The independent influence factors of axillary evaluation were nuclear grade, tumor size and surgical methods. There was no significant differences in prognosis among the groups receiving different axillary evaluations.