1.Retrospective study of role of neoadjuvant rectal scores in evaluating the 10-year disease-free survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy followed by surgery
Weili ZHANG ; Chi ZHOU ; Weifeng WANG ; Weihao LI ; Jiahua HE ; Zhenhai LU ; Xiaojun WU ; Junzhong LIN ; Jianhong PENG
Chinese Journal of Gastrointestinal Surgery 2024;27(6):608-614
Objective:To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy.Methods:Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores.Results:Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46–63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44–58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1–2 in 246 patients (50.5%) and 3–4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8–16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7–133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8–16, and >16 were 85.1%, 80.5%, and 66.4%, respectively ( P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408–0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559–4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer ( P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62–0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49–0.60). The two scores differed significantly in accuracy ( Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion:The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.
2.Retrospective study of role of neoadjuvant rectal scores in evaluating the 10-year disease-free survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy followed by surgery
Weili ZHANG ; Chi ZHOU ; Weifeng WANG ; Weihao LI ; Jiahua HE ; Zhenhai LU ; Xiaojun WU ; Junzhong LIN ; Jianhong PENG
Chinese Journal of Gastrointestinal Surgery 2024;27(6):608-614
Objective:To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy.Methods:Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores.Results:Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46–63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44–58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1–2 in 246 patients (50.5%) and 3–4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8–16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7–133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8–16, and >16 were 85.1%, 80.5%, and 66.4%, respectively ( P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408–0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559–4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer ( P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62–0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49–0.60). The two scores differed significantly in accuracy ( Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion:The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.
3.A novel bakuchiol aminoguanidine derivative induces apoptosis in human triple-negative breast cancer cells
Zhenhai ZHANG ; Jing ZHU ; Jian'an WANG ; Jie CHEN ; Yingying PANG ; Chengzhu WU
Journal of Zhejiang University. Medical sciences 2024;53(4):509-518
Objective:To synthesize new bakuchiol aminoguanidine derivatives and test their effect on viability and apoptosis of human triple-negative breast cancer(TNBC)cells.Methods:Two bakuchiol derivatives 1 and 2 were obtained by formylation and Shiff base reaction of bakuchol.The structures of derivatives 1 and 2 were identified by 1H-NMR,13C-NMR,and high-resolution electrospray ionization mass spectrometry(HR-ESI-MS)analysis.Human TNBC MDA-MB-231 cells were treated with bakuchiol and its derivatives and cell viability was measured by MTT assay.Apoptosis was detected by fluorescence microscopy and flow cytometry with Annexin V-FITC/PI staining.The expressions of apoptosis-related proteins were analyzed with Western blotting.The JC-1 and reactive oxygen species(ROS)assay kits were used to determine the effect of new bakuchiol derivatives on mitochondrial function.Results:Based on spectroscopic analysis,a new bakuchiol schiff base derivative was elucidated as 2-{(E)-5-[(S,E)-3,7-dimethyl-3-vinylocta-1,6-dien-1-yl]-2-hydroxylbenzylidene}hydrazine-1-carboximidamide(derivative 2).Bakuchiol and its derivatives 1 and 2 all showed cytotoxic activity against the MDA-MB-231 cells.Derivative 2 exhibited the most potent cytotoxic activity to MDA-MB-231 cell with IC50 of(13.11±1.09),(6.91±1.78),and(2.23±1.32)μmol/L after 24,48,and 72 h.It had low toxicity to normal mouse liver(AML-12)cells with IC50 of(31.23±1.58)μmol/L at 72 h.Fluorescence microscopy and flow cytometry demonstrated apoptosis in breast cancer cells after treating with derivative 2 in a concentration dependent manner.Western blotting showed that after derivative 2 treatment,the expression of apoptosis-related proteins cytochrome C,cleaving caspase-3 and Bax/Bcl-2 radio in MDA-MB-231 cells increased;in addition,apoptosis was associated with the decreased mitochondrial membrane potential and increased reactive oxygen species accumulation.Conclusion:The novel bakuchiol aminoguanidine derivative(derivative 2)is capable of inducing apoptosis in MDA-MB-231 cells,but has low toxicity to normal liver cells,suggesting that it may be used as a lead compound for an anti-TNBC agent.
4.Chlorella sp.-ameliorated undesirable microenvironment promotes diabetic wound healing.
Hangyi WU ; Pei YANG ; Aiqin LI ; Xin JIN ; Zhenhai ZHANG ; HuiXia LV
Acta Pharmaceutica Sinica B 2023;13(1):410-424
Chronic diabetic wound remains a critical challenge suffering from the complicated negative microenvironments, such as high-glucose, excessive reactive oxygen species (ROS), hypoxia and malnutrition. Unfortunately, few strategies have been developed to ameliorate the multiple microenvironments simultaneously. In this study, Chlorella sp. (Chlorella) hydrogels were prepared against diabetic wounds. In vitro experiments demonstrated that living Chlorella could produce dissolved oxygen by photosynthesis, actively consume glucose and deplete ROS with the inherent antioxidants, during the daytime. At night, Chlorella was inactivated in situ by chlorine dioxide with human-body harmless concentration to utilize its abundant contents. It was verified in vitro that the inactivated-Chlorella could supply nutrition, relieve inflammation and terminate the oxygen-consumption of Chlorella-respiration. The advantages of living Chlorella and its contents were integrated ingeniously. The abovementioned functions were proven to accelerate cell proliferation, migration and angiogenesis in vitro. Then, streptozotocin-induced diabetic mice were employed for further validation. The in vivo outcomes confirmed that Chlorella could ameliorate the undesirable microenvironments, including hypoxia, high-glucose, excessive-ROS and chronic inflammation, thereby synergistically promoting tissue regeneration. Given the results above, Chlorella is considered as a tailor-made therapeutic strategy for diabetic wound healing.
5.Correction to: Potentiating CD8+ T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling.
Juanjuan YUAN ; Ting CAI ; Xiaojun ZHENG ; Yangzi REN ; Jingwen QI ; Xiaofei LU ; Huihui CHEN ; Huizhen LIN ; Zijie CHEN ; Mengnan LIU ; Shangwen HE ; Qijun CHEN ; Siyang FENG ; Yingjun WU ; Zhenhai ZHANG ; Yanqing DING ; Wei YANG
Protein & Cell 2022;13(9):694-700
6.Analysis on infection risk in secondary close contacts of COVID-19 patients.
Bo YI ; Yan Ru CHU ; Yi CHEN ; Dong Liang ZHANG ; Yan Wu ZHANG ; Song LEI ; Lu HONG ; Qiao Fang LI ; Xiao Min GU ; Xu Ying LAO ; Hai Bo WANG ; Jun Fen LIN ; Guozhang XU
Chinese Journal of Epidemiology 2022;43(8):1237-1240
Objective: To study the infection rate of secondary close contacts of COVID-19 patients, and assess the infection risk in the contacts. Methods: COVID-19 patients' close contacts (with a clear exposure time to index case) with negative nucleic acid test results and secondary close contacts were surveyed in continuous isolation and medical observation in this prospective study. The dynamic nucleic acid test results of the close contacts and secondary contacts of COVID-19 patients were collected to assess their risk of infection. Results: A total of 4 533 close contacts were surveyed, in whom 14 were confirmed as COVID-19 patients with overall secondary attack rate of 0.31%, and 4 201 secondary contacts were tracked, in whom no subsequent infections occurred. Conclusion: Close contacts of COVID-19 patients entered in centralized isolation for medical observation with negative nucleic acid tese results,the secondary close contacts of COVID-19 patients have no risk of infection.
COVID-19/epidemiology*
;
Contact Tracing
;
Humans
;
Incidence
;
Nucleic Acids
;
Prospective Studies
;
SARS-CoV-2
7.China Health and Retirement Longitudinal Study: depressive symptoms of middle-aged and elderly disabled people and its related factors
Jia LIU ; Hongye PENG ; Zaofang YAN ; Kailin HUANG ; Miyuan WANG ; Qiyuan MAO ; Xin WU ; Zhenhai ZHAO
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(3):273-278
Objective:To explore the status of depression symptoms and related factors of depressive symptoms in middle-aged and elderly disabled people in China and provide references on the preventive cares of depression.Methods:Research data were obtained from the 2018 follow-up data of China Health and Retirement Longitudinal Study(CHARLS).Disabled people were selected as the research object. The scores of center for epidemiological studies depression scale(CES-D) were used to evaluate depressive symptoms. Fourteen variables derived from the 3 dimensions of demographic characteristics, health status, and health related behaviors were utilized in this study.SAS 9.4 were used for descriptive analysis, univariate analysis and Logistic regression analysis.Results:A total of 1 708 middle-aged and elderly disabled people were included, among whom 932(54.5%)were diagnosed with depressive symptoms, and the score of CES-D was (11.45±7.19).Self-rated poor health, self-rated poor memory, life dissatisfaction, physical pain were the risk factors of depressive symptoms ( OR=1.87, 4.22, 1.83, 5.30, 1.75). Male, educational level (middle-high school, high school or above), sleeping duration (6-9 h) were the protective factors of depressive symptoms( OR=0.74, 0.72, 0.10, 0.56). Conclusion:Middle-aged and elderly disabled people in China have a high detection rate of depressive symptoms. Female, lower education background, inadequate amount of sleep, self-rated unsatisfactory healthy, self-rated poor memory, dissatisfaction towards life and suffering from physical pain may be more likely to have depressive symptoms in middle-aged and elderly people with disabilities.
8.Potentiating CD8
Juanjuan YUAN ; Ting CAI ; Xiaojun ZHENG ; Yangzi REN ; Jingwen QI ; Xiaofei LU ; Huihui CHEN ; Huizhen LIN ; Zijie CHEN ; Mengnan LIU ; Shangwen HE ; Qijun CHEN ; Siyang FENG ; Yingjun WU ; Zhenhai ZHANG ; Yanqing DING ; Wei YANG
Protein & Cell 2021;12(4):240-260
Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8
9.Role of pre-suture craniotomy combined with controlled decompression under intracranial pressure monitoring in surgery for posttraumatic acute diffuse brain swelling
Jianguo YANG ; Xingming ZHONG ; Yiqi WANG ; Zhaohui ZHAO ; Yong CAI ; Zhenhai FEI ; Lei ZHANG ; Hua GU ; Tao YANG ; Liping WU
Chinese Journal of Neuromedicine 2021;20(3):288-293
Objective:To investigate the application value of pre-suture craniotomy combined with intracranial pressure monitoring in surgery for posttraumatic acute diffuse brain swelling (PADBS).Methods:One hundred and fifty-seven patients with PADBS admitted to our hospital from February 2015 to December 2019 were chosen in our study; 68 patients (control group), admitted to our hospital from February 2015 to June 2017, underwent controlled decompression under intracranial pressure monitoring; and 89 patients (treatment group), admitted to our hospital from June 2017 to December 2019, were performed pre-suture craniotomy combined with controlled decompression under intracranial pressure monitoring. The craniotomy time, brain tissue exposure time, cranial closure time, incidence of acute encephalocele, and Glasgow outcome scale (GOS) scores at 6 months after injury were retrospectively analyzed and compared between the two groups.Results:As compared with those in the control group, the patients in the treatment group had significantly longer intraoperative craniotomy time ([19.2±1.6] min vs. [15.4±1.4] min), significantly shorter exposure time of brain tissues ([18.5±2.4] min vs. [26.3±2.2] min), significantly shorter time of cranial closure ([11.2±1.5] min vs. [18.3±2.1] min), and statistically lower incidence of acute encephalocele (22.5% vs. 38.2%), P<0.05). The good prognosis rate of the treatment group (70.8%) was significantly higher than that of the control group (50.0%), and the mortality rate (6.7%) was statistically lower than that of the control group (17.6%, P<0.05). Conclusion:Pre-suture craniotomy combined with controlled decompression under intracranial pressure monitoring can shorten the time of cranial closure and brain tissue exposure, reduce the incidence of acute encephalocele, and ultimately improve the prognosis of patients with posttraumatic acute diffuse brain swelling.
10. Clinicopathological features and prognosis of breast cancer patients under 20 years old - report of 3 cases and literature review
Chao LIU ; Fangming LIU ; Yonglin ZHANG ; Xinyi GAO ; Yushuang HE ; Jierong WU ; Zhenhai MA
Chinese Journal of Endocrine Surgery 2019;13(6):522-524
This article reports the clinical data, diagnosis and treatment plan and prognosis of 3 patients with breast cancer under 20 years old. The clinical pathological features, treatment and prognosis were discussed in the literature, and compared with the biological characteristics of young (under 35 years old) breast cancer patients, providing a reference for the clinical individualized treatment of the disease.

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