1.Autophagy plays a role in genistein inhibiting proliferation of cervical cancer cells
Xiaoxia REN ; Yanmei YANG ; Hong WANG ; Jingquan MA ; Qian LIU ; Jiayi SHAO ; Liping TANG
Journal of Medical Postgraduates 2017;30(6):579-583
Objective For Genistein has been reported to inhibit many tumors ,we investigate the role of autophagy in the proliferation inhibition to Hela cells by Genistein and the machanism of autophagy plays in this process.Methods Human cervical cancer Hela cells were divided into control group,Genistein group and 3-MA+Genistein group,the control group were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum(FBS),Genistein group were cultured in various concentrations Genistein(25,50,100μmol/L),3-MA+Genistein group were treated with 5mmol/L 3-MA for 1h before cultured in 100μmol/L Genistein.The proliferation inhibitory rate of Hela cells was detected by MTT method.The ultrastructure changes of Hela cells was observed under transmission electronic microscope(TEM).The levels of autophagy-associated protein P62 and Beclin-1 were detected by Western blotting analysis.The expressions of autophagy-associated proteins LC3A/B in Hela cells were determined by fluorescent staining to analyse the autophagy induced by Genistein in Hela cells.Results Compared with control group ,the proliferation inhibitory rate of Hela cells was 20.9%±1.3%,33.5%±1.6% and 46.5%±3.2% when cultured in 25,50,100μmol/L Genistein(P<0.01).After treated with various concentrations Genistein for 48h, we observed a dose-dependent increase in the expression of Beclin-1 and decrease of P62.Confocal laser scanning microscopy confirmed the fluorescent density of LC3A/B expression in Hela cells treated with 100μmol/L Genistein increased significantly as compared with control group.TEM showed there are many vacuoles and double-membrane autophagosomes which involved cytoplasmic components in Hela cells treated with 100μmol/L Genistein.The proliferation inhibitory rate of Hela cells of Genistein group is decreased as compared with those in 3-MA+Genistein group[(46.5±3.2)% vs (58.2±2.2)%,P<0.01].Conclusion Genistein could inhibit Hela cells proliferation and induce autophagy.
2.Outcome of breast-conservative therapy for early-stage breast cancer: a retrospective analysis
Jiayi CHEN ; Guoliang JIANG ; Xiaoli YU ; Xizhen ZHANG ; Jiong WU ; Zhimin SHAO ; Xiaomao GUO
Chinese Journal of Radiation Oncology 2008;17(6):446-449
Objective To analyze the results of survival and local regional control of early-stage breast cancer patients treated with breast-conserving surgery and whole breast radiation therapy, and to explore the factors influencing local control. Methods From October 1995 to September 2005,335 patients with early-stage breast cancer were treated with breast conservative therapy, including 25 with post-operative radiotherapy alone( group A), 194 with sequential chemo-radiotherapy( group B) ,80 with concurrent chemoradiotherapy( group C), and 36 with chemo-radio-chemotherapy (group D). Axillary dissection was performed in 312 patients and sentinel node biopsy in 2. Adjuvant chemotherapy was given to 310 patients. Radiation of 50 Gy in 25 fractions was delivered to the whole breast in 256 patients,and to the breast and regional nodes in 79. Another 10 Gy in 5 fractions was boosted to the tumor bed. The proportion of patients with surgery-radiation interval of less than 4 weeks,4-8 weeks,8-20 weeks and over 20 weeks was 16.4%, 23.6% ,37.3% and 22.7% ,respectively. Concurrent chemo-radiation and" sandwich" modality were delivered in 80 and 36 patients,respectively. Results The median follow-up was 48(25.3-146.7) months. The 5-year local-regional control and ipsilateral breast control rates were 94.5% and 95.6%, respectively. The 5-year disease-free survival,metastasis-free survival and overall survival rates were 88.6% ,93.2% and 98.8% ,respectively. Lymph-vascular invasion and neural invasion were significant factors influencing local control in univariate analysis. No significant differences were found in local control rates among different surgery-radiation intervals or different sequencing of radiotherapy and chemotherapy. Multivariate analysis showed that lymph-vascular invasion and reexcision for positive or unknown margin were independent prognostic factors influencing local control. In group A + B, C and D, the frequency of grade Ⅲ skin toxicity was4.5%.80.0%.and 77.0%,respectively(χ2=226.00,P=0.000).Conclusiom Breast conservative therapy for early-stage breast eancer results in good local-regional control and overall survival.Lymph-vascular invasion and reexcision are independent prognostic factors for local control.Surgery-radiation interval and sequencing of radiotherapy and chemotherapy have no impact on local contr01.Grade Ⅲ skin toxicity of the concurTent radio.chemotherapy and the chemo.radio.chemotherapy group is significantly higher than that of the sequential chemotherapy-radiotherapy plus radiotherapy alone group.
3.Research progress on the mechanism of CDK4/6 inhibitors promoting antitumor immunity by regulating the immune microenvironment of triple negative breast cancer
Jiayi WU ; Keyu CHEN ; Xiying SHAO ; Xiaojia WANG
Journal of International Oncology 2022;49(6):362-365
Triple negative breast cancer is a subtype of breast cancer with poor prognosis and lack of effective treatment. Cyclin dependent kinase (CDK) 4/6 inhibitors promote antitumor immunity by influencing the triple negative breast cancer immune microenvironment, such as increasing the tumor cell surface pragrammed death-ligand 1 protein expression, enhancing T cell activation and antigen presentation, changing the proportion of T cell subgroup and inducing lymphocyte infiltration. The change of immune microenvironment is related to tumor progression, but its mechanism is extremely complex. Exploring the mechanism of CDK4/6 inhibitor affecting immune microenvironment and its biomarkers can provide a new direction for the diagnosis and treatment of triple negative breast cancer.
4.Role of Cytokines and Related Signaling Pathways in Intervention of Chinese Medicine in Radiation-induced Lung Injury: A Review
Jiayi SHAO ; Mianhua WU ; Yanxia MA ; Zequn JIANG ; Hongyi XU ; Muhan LI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):244-253
Radiation-induced lung injury (RILI), one of the common complications caused by radiotherapy, encompasses two phases: an early phase known as radiation pneumonitis (RP) and a late phase called radiation fibrosis (RF), threatening the life and life quality of patients, with poor prognosis. Accumulating evidence has shown that the occurrence of RILI is related to a variety of cytokines and signaling pathways. This paper summarized the research on the effects of Chinese medicine on RILI from the perspective of cytokines and signaling pathways. Cytokines include transforming growth factor-β1 (TGF-β1), interleukins (ILs), tumor necrosis factor-α (TNF-α), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and high mobility group box-1 (HMGB1). Related signaling pathways are phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, Wnt/β-catenin signaling pathway, Notch1/Jagged1 signaling pathway, and nuclear factor-E2-related factor2/antioxidant response element (Nrf2/ARE) signaling pathway. Cytokines may interfere with RILI progression by initiating various downstream signaling pathways, such as TGF-β1/Smads signaling pathway, TGF-β1/VEGF signaling pathway, TNF-α/nuclear factor-κB (NF-κB) signaling pathway, and HMGB1/Toll-like receptor 4 (TLR4) signaling pathway. In recent years, many scholars have attempted to delay RILI progression by down-regulating the expression of cytokines, antagonizing the effect of cytokines or regulating signaling pathways. It has been verified that many Chinese medicines, Chinese medicine monomers, and compound Chinese medicine prescriptions can inhibit the release of some cytokines or regulate some signaling pathways to reduce the incidence/severity of RILI, with satisfactory therapeutic effects, which have attracted the interest of scholars.
5.Radiographic evaluation of femoral acetabular impingement
Xin ZHANG ; Gang YANG ; Yan XU ; Hongjie HUANG ; Jiayi SHAO ; Jianquan WANG ; Dingge LIU ; Kaiping LIU
Chinese Journal of Orthopaedics 2023;43(23):1621-1630
Femoral acetabular impingement (FAI) is a condition characterized by abnormal anatomical structures of the femoral head and/or acetabulum, leading to impingement between the proximal femur and the rim of the acetabulum during hip movement. This impingement causes damage to the acetabular cartilage, labrum, chronic hip pain, and limited range of motion. The diagnosis of this condition requires evaluation based on symptoms, physical signs, and imaging examinations. Among these, imaging plays a crucial role in assessing the pathology of FAI. In recent years, imaging techniques have contributed to a deeper understanding of the mechanisms underlying FAI and the development of hip-preserving surgeries. The purpose of this paper is to provide a reference for the imaging-related diagnosis and measurement of FAI. X-ray films include pelvic anteroposterior view, false-profile view and 45°Dunn view. Doctors can understand the anatomical morphology of the femur and acetabulum by measuring relevant indicators in the X-ray films. For example, the α Angle of the femur >50°-60 ° in the pelvic anteroposterior view can indicate CAM-type FAI. However, the crisscross sign, posterior wall sign and LCE Angle >40° suggest Pincer type FAI. The ACE Angle, which reflects the anterior coverage of the acetabulum, was mainly measured on the false-profile view. The ACE Angle <20° is considered as insufficient anterior acetabular coverage, and acetabular dysplasia may be present.If it >40° is the anterior acetabular overcoverage, suggesting pincer-type FAI. The 45°Dunn view is mainly used to show the femoral head and neck deformity at 3 o'clock, where the femoroacetabular impingement is obvious. This position has a good indication effect for CAM-type FAI. CT can show the shape of the hip joint more intuitively by three-dimensional reconstruction of the patient's hip joint, which is convenient for surgical planning and postoperative evaluation. In addition, CT can also be used for the differential diagnosis of external hip impingement, such as ischiofemoral impingement, anterior inferior iliac spine impingement and greatertrochanteric impingement. MR Has excellent soft tissue imaging ability and can show other lesions that are difficult to be found by X-ray and CT, such as acetabular labrum and cartilage injury. It is essential for preoperative evaluation. Appropriate imaging examination plays a key role in the diagnosis and treatment of FAI.
6.Clinical outcomes of hip arthroscopic surgery in treating femoral acetabular impingement for athletes
Jiayi SHAO ; Fan YANG ; Yan XU ; Jianquan WANG ; Xiaodong JU
Chinese Journal of Orthopaedics 2024;44(2):79-86
Objective:To investigate the clinical efficacy of arthroscopic surgery for the treatment of femoral acetabular impingement (FAI) in athletes.Methods:A total of 18 FAI athletes (athlete group) who underwent hip arthroscopy in the Department of Sports Medicine, Peking University Third Hospital from April 2014 to June 2021 were retrospectively analyzed, including 12 males and 6 females, aged 20.44±3.45 years (range, 15-27 years). According to gender, age, body mass index and follow-up time, 36 non-athlete FAI patients (non-athlete group) were matched at a ratio of 1∶2 by propensity score matching method. There were 18 males and 18 females, aged 20.81±4.68 years (range 14-31 years). The hip pain visual analogue scale (VAS), modified Harris hip score (mHHS), hip outcome score-activity of daily living scale (HOS-ADL) and hip outcome score-sports scale (HOS-SS) scores were compared between the two groups before and after surgery. The minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) were also compared between the two groups.Results:All patients successfully completed the surgery and were followed up for 33.56±19.20 months (range, 24-77 months). The VAS score at the last follow-up decreased from 6.22±1.52 points before surgery to 1.28±1.67 points in the athletes group, and decreased from 6.28±1.37 points before surgery to 1.67±1.69 points in the non-athletes group. There was no significant difference between the two groups ( P>0.05). The mHHS score at the last follow-up increased from 65.53±12.90 points before surgery to 92.28±13.59 points in the athletes group, and increased from 61.01±11.96 points before surgery to 86.82±11.98 points in the non-athletes group. There was no significant difference between the two groups ( P>0.05). The HOS-ADL score at the last follow-up increased from 72.77±18.86 points before surgery to 94.00±11.36 points in the athletes group, and increased from 70.35±13.12 points before surgery to 90.78±9.36 points in non-athletes group. There was no significant difference between the two groups ( P>0.05). The HOS-SS score at the last follow-up increased from 49.77±22.93 points before surgery to 87.28±17.62 points in the athletes group, and increased from 44.08±19.66 before surgery to 72.57±20.16 in the non-athletes group. The HOS-SS scores in the athletes group at the last follow-up were higher than those in the non-athletes group ( P<0.05). Furthermore, 61% (11/18) in the athletes group achieved MCID in HOS-ADL after surgery, which was lower than the non-athletes group's 81% (31/36), with a statistically significant difference (χ 2=4.339, P=0.037). Conclusion:Hip arthroscopy in the treatment of FAI in athletes can achieve satisfactory pain relief and motor function.
7.Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases
Xuheng SUN ; Yijun WANG ; Wei ZHANG ; Yajun GENG ; Yongsheng LI ; Tai REN ; Maolan LI ; Xu'an WANG ; Xiangsong WU ; Wenguang WU ; Wei CHEN ; Tao CHEN ; Min HE ; Hui WANG ; Linhua YANG ; Lu ZOU ; Peng PU ; Mingjie YANG ; Zhaonan LIU ; Wenqi TAO ; Jiayi FENG ; Ziheng JIA ; Zhiyuan ZHENG ; Lijing ZHONG ; Yuanying QIAN ; Ping DONG ; Xuefeng WANG ; Jun GU ; Lianxin LIU ; Yeben QIAN ; Jianfeng GU ; Yong LIU ; Yunfu CUI ; Bei SUN ; Bing LI ; Chenghao SHAO ; Xiaoqing JIANG ; Qiang MA ; Jinfang ZHENG ; Changjun LIU ; Hong CAO ; Xiaoliang CHEN ; Qiyun LI ; Lin WANG ; Kunhua WANG ; Lei ZHANG ; Linhui ZHENG ; Chunfu ZHU ; Hongyu CAI ; Jingyu CAO ; Haihong ZHU ; Jun LIU ; Xueyi DANG ; Jiansheng LIU ; Xueli ZHANG ; Junming XU ; Zhewei FEI ; Xiaoping YANG ; Jiahua YANG ; Zaiyang ZHANG ; Xulin WANG ; Yi WANG ; Jihui HAO ; Qiyu ZHANG ; Huihan JIN ; Chang LIU ; Wei HAN ; Jun YAN ; Buqiang WU ; Chaoliu DAI ; Wencai LYU ; Zhiwei QUAN ; Shuyou PENG ; Wei GONG ; Yingbin LIU
Chinese Journal of Digestive Surgery 2022;21(1):114-128
Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.