1.Clinical characteristics and prognosis of brain metastasis in locally advanced rectal cancer
Ganbin LI ; Xiao ZHANG ; Chentong WANG ; Xiaoyuan QIU ; Guannan ZHANG ; Beizhan NIU ; Lai XU ; Junyang LU ; Bin WU ; Yi XIAO ; Guole LIN
Chinese Journal of Gastrointestinal Surgery 2024;27(10):1063-1068
Objective:To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC).Methods:The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan–Meier method was used for survival analysis.Results:We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4–112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2–21.8) months.Conclusion:The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.
2.Quality Control and Analysis of Treatment for Hospitalized Cancer Patients: Interview and Medical Records Study from Nine Hospitals in Beijing
Liting LU ; Yanping ZHOU ; Xiang WANG ; Xiaoyuan LI ; Xiaorong HOU ; Lidong ZHU ; Xiaohong XU ; Guibin SUN ; Ziyuan WANG ; Jieshi ZHANG ; Lin ZHAO ; Yi BA
Medical Journal of Peking Union Medical College Hospital 2024;16(2):399-405
To analyze the current quality of treatment for hospitalized cancer patients in Beijing, identify major issues in treatment practices, and propose improvements. Nine hospitals in Beijing were selected for examination. Expert on-site interviews and medical record sampling were conducted. The "Beijing Cancer Diagnosis and Treatment Quality Control Checklist" was used to assess the hardware, management, anti-cancer drug therapy, radiation therapy, and surgical treatment during cancer treatment at these hospitals from January to October 2023. The relevant problems were analyzed. Among the nine hospitals, two (22.2%) were equipped with laminar flow rooms, and three (33.3%) had intravenous drug preparation centers. In terms of institutional management, seven hospitals (77.8%) had standardized anti-cancer drug prescription authority management, eight (88.9%) had complete emergency plans, and five (55.6%) had oncology specialist pharmacists. Regarding anti-cancer drug therapy, the areas with higher completion rates included pathology diagnosis support (97.6%), routine pre-treatment examinations (96.3%), adverse reaction evaluation(92.7%), discharge summaries (95.1%), and admission records (91.5%). However, the accuracy of tumor staging before treatment (70.7%) and the evaluation of therapeutic efficacy after drug treatment (76.9%) needed improvement. The oncology specialty significantly outperformed the non-oncology specialty in terms of the accuracy rate of TNM staging (86.0% There remains significant room for improvement in the quality of cancer treatment in China. It is recommended to standardize tumor staging assessment processes, strengthen entry assessments for non-oncology departments, promote the implementation of multidisciplinary treatment models, and establish a multi-department collaborative management model.Continuous monitoring of cancer diagnosis and treatment quality indicators is essential to promote ongoing improvements in cancer treatment quality.
3.Impact of early postoperative hypocaloric parenteral nutrition on perioperative infectious complications in patients undergoing hepatectomy for primary hepatic carcinoma
Dayu CHEN ; Yao DU ; Xinhua ZHU ; Yao LU ; Xiaoyuan CHEN
International Journal of Surgery 2024;51(4):246-253
Objective:To explore the impact of early postoperative hypocaloric parenteral nutrition on perioperative infectious complications in patients undergoing hepatectomy for primary hepatic carcinoma.Methods:The data of 205 patients who underwent hepatectomy for primary hepatic carcinoma in the Division of Hepatobiliary and Transplantation Surgery at Nanjing Drum Tower Hospital between February 2020 and December 2022 were collected by a single center prospective cohort study. The patients were divided into a hypocaloric group ( n=108) and a normal calorie group ( n=97) based on whether they received hypocaloric parenteral nutrition within 72 hours postoperatively. The influence of early parenteral nutrition caloric on perioperative infectious complications was analyzed. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s) and compared using t-test. Measurement data with skewed distribution were expressed as M( Q1, Q3) and compared using the Wilcoxon rank-sum test. Comparison of categorical data was performed using the chi-square test or Fisher′s exact test. To adjust for confounding factors, patients were grouped for comparison based on whether they experienced infectious complications within the 30-day postoperative follow-up period. Factors that may influence postoperative infectious complications were first analyzed using univariate analysis, and variables with statistical significance were then included in multivariate analysis. Results:A total of 82 patients experiencing infectious complications, resulting in an incidence rate of 40.0%. Patients in the hypocaloric parenteral nutrition group had significantly lower rates of hyperglycemic events (17.6% vs 29.9%, P=0.038) and gastrointestinal reactions (12.0% vs 22.7%, P=0.043) compared to the normal calorie parenteral nutrition group, with no intergroup differences in other nutrition-related complications. Univariate analysis results revealed that hypocaloric parenteral nutrition, hepatocellular carcinoma, malnutrition assessed by the GLIM criteria, open surgery, major hepatectomy, perioperative hyperglycemic events, and the presence of pleural or ascitic fluid were potential influencing factors for the occurrence of infectious complications ( P<0.05). Multivariate analysis results suggested that malnutrition ( OR=2.707, 95% CI: 1.153-6.354, P=0.022), open surgery ( OR=2.103, 95% CI: 1.073-4.122, P=0.030), perioperative hyperglycemic events ( OR=2.630, 95% CI: 1.228-5.631, P=0.013), and the presence of pleural or ascitic fluid ( OR=2.714, 95% CI: 1.388-5.306, P=0.004) were risk factors for perioperative infectious complications in patients undergoing hepatectomy for primary hepatic carcinoma, while early postoperative hypocaloric parenteral nutrition ( OR=0.388, 95% CI: 0.199-0.757, P=0.006) was a protective factor. Conclusion:For patients undergoing hepatectomy for primary hepatic carcinoma, early postoperative hypocaloric parenteral nutrition may reduce the incidence of perioperative infectious complications compared to normal caloric parenteral nutrition, thereby improving patient clinical outcomes.
4.Clinical characteristics and prognosis of brain metastasis in locally advanced rectal cancer
Ganbin LI ; Xiao ZHANG ; Chentong WANG ; Xiaoyuan QIU ; Guannan ZHANG ; Beizhan NIU ; Lai XU ; Junyang LU ; Bin WU ; Yi XIAO ; Guole LIN
Chinese Journal of Gastrointestinal Surgery 2024;27(10):1063-1068
Objective:To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC).Methods:The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan–Meier method was used for survival analysis.Results:We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4–112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2–21.8) months.Conclusion:The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.
5.Ran-binding protein 9 targets transforming growth factor-β1 expression and induces cell apoptosis in colorectal cancer Colo320 cells
Rubo BAN ; Jielin YANG ; Xiaoyuan WANG ; Xueliang WU ; Yonggang LU
Chinese Journal of Comparative Medicine 2024;34(7):39-47
Objective To investigate the targeting of transforming growth factor β1(TGF-β1)expression by Ran-binding protein 9(RANBP9)and its effect on colorectal cancer Colo320 cell apoptosis.Methods Gene expression levels of RANBP9 were analyzed in 625 colon cancer tissues and 20 normal colon tissues in The Cancer Genome Atlas database.The relationship between RANBP9 expression and survival time of patients with colon cancer was analyzed using KMPLOT.The expression of TGF-β1 in normal colon tissues and colon cancer tissues was analyzed using the human protein immunohistochemistry database and the relationship between TGF-β1 expression and the survival of patients with colon cancer was analyzed using the UALCAN database.The relationship between RANBP9 and TGF-β1 was analyzed by dual luciferase experiments.Colo320 cells were transfected with pcDNA3.1-GFP-RANBP9 and control pcDNA3.1-GFP-RANBP9-NC plasmids,respectively,and normal control cells were established without transfection.The cells were cultured and the growth viability of each group of cells was detected by the iazolyl blue tetrazolium bromide method,apoptosis was detected by flow cytometry,the mitochondrial membrane potential was detected by JC-1 staining,and RANBP9 and TGF-β1 protein expression were detected by Western blot.Results RANBP9 expression was significantly reduced in colon cancer tissues.Compared with patients with low RANBP9 expression,patients with high RANBP9 expression had a higher survival curve and significantly higher expression of TGF-β1 in colon cancer tissue.Compared with patients with high TGF-β1 expression,patients with low TGF-β1 expression had a significantly higher survival curve(P<0.05).RANBP9 targeted the expression of TGF-β1 in colon cancer.Compared with the normal group,cell growth,mitochondrial membrane potential,and TGF-β1 expression were all significantly down-regulated and the apoptosis rate and RANBP9 expression were significantly increased in the experiment group(P<0.05).Conclusions RANBP9 can target the expression of TGF-β1,promote the growth of Colo320 colon cancer cells,decrease the mitochondrial membrane potential,and induce apoptosis.
6.User's guide to international calibration protocol TRS-398V7 for absorbed dose to water
Zhipeng WANG ; Kun WANG ; Sunjun JIN ; Han WU ; Jiale HAN ; Gang LU ; Xiaoyuan YANG
Chinese Journal of Medical Physics 2024;41(11):1327-1336
To fulfill the calibration requirements for absorbed dose to water in external beam radiotherapy,the summary offers a streamlined calibration procedure and recommendations in accordance with TRS-398(version 7)published by International Atomic Energy Agency in 2024.It addresses various considerations for reference measurement conditions in external beam radiotherapy and defines the appropriate scope for ionization chambers.In terms of ionization chamber measurements,it elaborates on the methods for measuring various correction factors and provides a table of beam quality conversion factors.The calibration uncertainty is examined by comparing the contributions of different factors before and after the update.The results demonstrate that using IBA FC65-G ionization chamber to calibrate high-energy photon beams,high-energy electron beams,proton beams and light ion beams results in relative deviations of-0.4%,0.5%,-1.7%and-1.3%as compared with the earlier versions,with relative standard uncertainties of 1.0%,1.1%,1.7%and 2.6%,respectively.The guideline which is tailored to the national radiotherapy dose calibration standards and practices presents an optimized calibration approach for TRS-398,allowing clinicians to conduct absolute dose calibration more efficiently and accurately.
7.Targeted Inhibition of p21 Promotes the Growth of Breast Cancer Cells and Impairs the Tumor-Killing Effect of the Vaccinia Virus
Xiaoyuan JIA ; Yujia ZHAO ; Qiang LI ; Xiaming LU ; Xiaoyan WANG ; Hui WANG ; Ziyi SHI ; Yipeng XU ; Biao HUANG ; Fang HUANG ; Yigang WANG
Journal of Breast Cancer 2024;27(5):293-304
Purpose:
Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus.
Methods:
p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts.
Results:
p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells.
Conclusion
Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.
8.Targeted Inhibition of p21 Promotes the Growth of Breast Cancer Cells and Impairs the Tumor-Killing Effect of the Vaccinia Virus
Xiaoyuan JIA ; Yujia ZHAO ; Qiang LI ; Xiaming LU ; Xiaoyan WANG ; Hui WANG ; Ziyi SHI ; Yipeng XU ; Biao HUANG ; Fang HUANG ; Yigang WANG
Journal of Breast Cancer 2024;27(5):293-304
Purpose:
Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus.
Methods:
p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts.
Results:
p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells.
Conclusion
Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.
9.Targeted Inhibition of p21 Promotes the Growth of Breast Cancer Cells and Impairs the Tumor-Killing Effect of the Vaccinia Virus
Xiaoyuan JIA ; Yujia ZHAO ; Qiang LI ; Xiaming LU ; Xiaoyan WANG ; Hui WANG ; Ziyi SHI ; Yipeng XU ; Biao HUANG ; Fang HUANG ; Yigang WANG
Journal of Breast Cancer 2024;27(5):293-304
Purpose:
Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus.
Methods:
p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts.
Results:
p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells.
Conclusion
Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.
10.Influencing factors for direct-acting antiviral therapy failure in treatment of hepatitis C
Yuqing YANG ; Jia SHANG ; Chengzhen LU ; Song YANG ; Hongyu CHEN ; Jiali PAN ; Yifan HAN ; Hongli XI ; Qian KANG ; Ning TAN ; Xiaoyuan XU
Journal of Clinical Hepatology 2022;38(5):1059-1063
Objective To investigate the influencing factors for direct-acting antiviral agent (DAA) therapy failure in the treatment of hepatitis C by comparing baseline clinical data and resistance-associated substitution (RAS) in sequencing data between the patients with HCV RNA reactivation after DAA therapy and the patients with successful DAA treatment. Methods A total of 13 patients from multiple centers who failed DAA therapy from November 2019 to October 2021 were enrolled as treatment failure group, and sequencing was performed for their positive serum samples. A total of 51 patients with successful DAA treatment were enrolled as control group, and baseline clinical data and sequencing results were compared between the treatment failure group and the control group. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; univariate and multivariate logistic regression analyses were performed to calculate odds ratio ( OR ) and investigate the influencing factors for treatment failure. Results All 12 patients with complete treatment data experienced recurrence within 1 year after the end of medication. The male patients with treatment failure had significantly higher baseline total bilirubin, direct bilirubin, and creatinine than their female counterparts ( Z =-2.517, -2.440, and -2.132, P =0.010, 0.010, and 0.038), and the patients with an age of ≤55 years ( OR =5.152, 95% confidence interval [ CI ]: 1.116-23.790, P =0.036) or genotype 3b ( OR =9.726, 95% CI : 1.325-71.398, P =0.025) had a higher probability of treatment failure. There were differences in the incidence rates of major RAS mutations on three gene fragments between the treatment failure group and the treatment success group, and the common RAS mutations detected in the treatment failure group were not detected in the treatment success group. Conclusion Age, genotype, and RAS in serum virus gene sequence are influencing factors for DAA treatment failure.

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