1.Clinicopathological features and prognosis of sporadic mismatch repair deficient colorectal cancer
Hao WANG ; Ruping HONG ; Jingci CHEN ; Jing WANG ; Zijuan ZHANG ; Xinyu REN ; Huanwen WU ; Zhiyong LIANG
Chinese Journal of Pathology 2024;53(7):702-708
Objective:To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer.Methods:A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate.Results:Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side ( P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion:For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.
2.Research progress on metabolic activation of indirect carcinogens by CYP1A1
Huanhuan WANG ; Yao WU ; Huanwen TANG ; Yuting CHEN
China Occupational Medicine 2023;50(5):596-600
Cytochrome P450 enzyme 1A1 (CYP 1A1) is one of the main members of CYP1A subfamily, which participates in metabolizing and activating a variety of indirect carcinogens. CYP1A1 can induce carcinogenesis by participating in activating exogenous compounds to produce intermediates or active metabolites that bind to specific biomolecules. CYP1A1 plays a critical role in the metabolic activation of benzo(a)pyrene e [B(a)P], and plays a key role in activating the toxic and carcinogenic effects of B(a)P. CYP1A1 involves in the metabolic activation of 7,12-dimethyl benzanthracene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and plays an important role in PhIP-induced genotoxicity. CYP1A1 is the main enzyme to metabolize and activate 7H-dibenzo[c,g]carbazole (DBC), a key factor in the carcinogenic effect of DBC. CYP1A1 is also associated with metabolic activation of indirect carcinogens such as aflatoxin B1, 3-nitrobenzene, and naphthalene. Inhibition of the catalytic activity of CYP1A1 can decrease the CYP1A1-mediated activity of carcinogens, thus playing a role in the prevention and treatment of malignant tumors.
3.Expression of small nucleolar RNA SNORD15A in acute leukemia and its clinical significance
Minjuan ZENG ; Yanquan LIU ; Shaopeng CHEN ; Jie BAO ; Hairong LIANG ; Zhongming YE ; Shuiyan LYU ; Huawen LI ; Huanwen TANG
Journal of Leukemia & Lymphoma 2023;32(4):203-209
Objective:To investigate the expression level of small nucleolar RNA SNORD15A in bone marrow of patients with acute leukemia (AL) and its relationship with clinical characteristics and prognosis of patients.Methods:Bone marrow blood samples of 53 newly treated AL patients and 29 healthy subjects without clinical diagnosis of hematologic diseases or other malignant diseases (control group) at the Affiliated Hospital of Guangdong Medical University from March 2018 to December 2021 were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression of SNORD15A in bone marrow blood mononuclear cells of the two groups. The median relative expression of SNORD15A (0.148) was used as the boundary, and AL patients were divided into low expression group (<0.148) and high expression group (≥0.148). The relationship between the expression level of SNORD15A and the clinical characteristics, clinical indicators and overall survival (OS) of AL patients was analyzed. Kaplan-Meier method was used for survival analysis and log-rank test was performed; Cox proportional hazards model was used for univariate and multivariate analyses of OS of patients.Results:The relative expression of SNORD15A was 0.148 (0.012-1.376) in newly treated AL patients and 0.921 (0.513-2.288) in the control group, and the difference was statistically significant ( Z = -6.85, P < 0.01). The differences in SNORD15A relative expression between patients with different prognostic stratification, efficacy and with or without fever and bleeding were statistically significant (all P < 0.05). The differences in platelet count, plateletcrit and albumin levels between SNORD15A low expression group and high expression group were statistically significant (all P < 0.05), and the differences in molecular biology and cytogenetic characteristics were not statistically significant (all P > 0.05). The patients in SNORD15A high expression group had better OS than the low expression group ( P < 0.05). The results of univariate Cox regression analysis showed that SNORD15A was an influencing factor for patients' OS ( HR = 0.063, 95% CI 0.005-0.766, P < 0.05); the results of multivariate Cox regression analysis showed that fatigue ( HR = 4.754, 95% CI 1.014-22.290), fever ( HR = 0.147, 95% CI 0.029-0.746) and hemoglobin ( HR = 0.970, 95% CI 0.944 -0.998) were independent influencing factors for OS (all P < 0.05). Conclusions:SNORD15A is lowly expressed in AL and may be an indicator for disease monitoring and prognostic assessment in AL patients.
4.Investigation and comparative study on death cognition and hospice care attitude of the graduate students of clinical medicine
Yanquan LIU ; Xiaomei HONG ; Tao HUANG ; Jinlong HUANG ; Yue YIN ; Xinyi LIU ; Yuting CHEN ; Hui YANG ; Huanwen TANG
Chinese Journal of Medical Education Research 2023;22(4):512-518
Objective:To investigate and analyze the status quo of death cognition and hospice care attitude of clinical medical graduate students, to compare the differences between the two groups, and to explore the correlation between death cognition and hospice care attitude, so as to provide the reference for the reform and construction of death cognition and hospice care education in medical colleges and universities in China.Methods:A survey was carried out on 496 doctoral and postgraduate students majoring in clinical medicine by using the "Questionnaire of General Sociology Survey", the Chinese version of the "Death Attitude Profile Revised Scale", and the Chinese version of the "Frommelt Attitudes Toward Care of the Dying Scale Form B (FATCOD-B)" to investigate the death cognition and hospice care attitude of 496 doctoral and postgraduate students majoring in clinical medicine, and classified and compared the survey results of the two groups. The results of this study were statistically analyzed by t-test, Pearson correlation analysis and other statistical methods. Results:A total of 469 valid questionnaires were recovered after excluding 27 unqualified questionnaires. Statistical analysis showed that the scores of each dimension in the death attitude description scale of doctoral students were ranked as follows: approach acceptance (4.28±0.53), neutral acceptance (3.99±0.41), death avoidance (2.74±0.63), fear of death (2.65±0.57) and escape acceptance (2.47±0.69) the scores of postgraduates were ranked as neutral acceptance (3.96±0.52), approach acceptance (2.84±0.61), fear of death (2.78±0.65), death escape (2.62±0.73), escape acceptance (2.39±0.77). At the same time, the scores of hospice care attitude in the doctoral group were higher than those in the master group [(110.63±8.96) vs. (106.78±6.52)], and the difference was statistically significant ( P<0.001). In addition, the scores of "fear of death" and the scores of hospice care attitudes were negatively correlated with the scores of doctoral and master students ( r=-0.25, r=-0.21), while the scores of hospice care attitudes were positively correlated with the scores of "neutral acceptance" in death cognition ( r=0.50, r=0.32). However, the hospice care attitude scores of doctoral students were negatively correlated with the "death avoidance" scores in death cognition ( r=-0.27). Conclusion:Doctoral and postgraduate students have a certain awareness of hospice care, while their death cognition and hospice care attitude still need to be improved and strengthened from sociology, psychology, ethics and other perspectives. The above will promote the harmony between doctors and patients while meeting the needs of an aging society in China.
5.Application and effectiveness of narrative medicine in clinical internship: with department of thoracic surgery as an example
Chinese Journal of Medical Education Research 2023;22(8):1201-1205
Objective:To investigate the effect of narrative medicine teaching on the academic performance and empathy ability of clinical interns in department of thoracic surgery.Methods:A total of 74 interns in the department of thoracic surgery, with the "5+3" integration major of clinical medicine in Chongqing Medical University, were divided into observation group and control group, with 37 interns in each group. The interns in the control group received traditional teaching, and those in the observation group received narrative medicine teaching in addition to traditional teaching. The two groups were compared in terms of department examination score, level of humanistic concern, empathy level, ability to handle doctor-patient relationship, degree of satisfaction with teaching, discipline interest, and job intention after graduation. SPSS 21.0 was used to perform the t-test and chi-square test. Results:Compared with the control group, the observation group had significantly better theoretical score [(85.16±10.04) vs. (79.73±8.27)], operational skill score [(85.32±8.77) vs. (79.70±7.56)], level of humanistic concern [(3.78±0.95) vs. (3.24±1.04)], empathy scale score [(104.89±12.90) vs. (96.57±11.00)], results of the questionnaire on doctor-patient communication skills, confidence in professional practice, and doctor-patient orientation [(52.59±10.15) vs. (72.59±5.86)], degree of satisfaction with teaching (89.2% vs. 64.8% in the control group), discipline interest [(3.86±1.08) vs. (3.05±1.12)], and job intention after graduation (29.7% vs. 8.1%).Conclusion:Narrative medicine introduced into clinical practice teaching can improve the effectiveness of teaching, the empathy ability of students, and the degree of satisfaction with teaching.
6.Expression and clinical significance of Flap endonuclease 1 in acute myeloid leukemia
Yanquan LIU ; Minjuan ZENG ; Yue YIN ; Yuting CHEN ; Huanwen TANG
Cancer Research and Clinic 2023;35(4):246-251
Objective:To investigate the expression level of flap endonuclease 1 (FEN1) in bone marrow mononuclear cells of patients with acute myeloid leukemia (AML) and its relationship with clinicopathologic features and therapeutic effect, so as to provide a new direction for disease monitoring and targeted therapy in AML patients.Methods:The data of 57 newly treated AML patients and 26 healthy individuals (the healthy control) from the First Clinical College of Guangdong Medical University and Fujian Medical University Union Hospital from November 2018 to December 2020 were retrospectively analyzed. Bone marrow samples of all subjects were collected. Quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) was used to detect FEN1 mRNA expression in bone marrow mononuclear cells of all subjects. Bone marrow samples from 9 newly-diagnosed AML patients and 4 healthy controls were collected, and FEN1 protein expression level was detected by using Western blotting. Differences in FEN1 mRNA expression in AML patients achieving different therapeutic effects were compared among AML patients whose data with evaluable efficacy. AML patients were divided into high FEN1 expression group (≥ critical value) and low FEN1 expression group (< critical value), taking the median relative expression level of FEN1 mRNA as the critical value. The correlation of FEN1 expression level with clinicopathologic features, laboratory indicators, cellular and molecular genetic changes in AML patients at initial diagnosis was analyzed.Results:The median relative expression of FEN1 mRNA in newly treated AML patients was higher than that in healthy controls [0.696 (0.025-3.661) vs. 0.246 (0.013-1.237), Z = 1.75, P = 0.041]. Western blotting showed that the expression level of FEN1 protein in AML patients was higher than that in healthy controls. The relative expression of FEN1 mRNA in 15 recurrent AML patients was higher than that in 19 patients patients achieving complete remission (CR) [1.153 (0.047-4.172) vs. 0.259 (0.023-1.148), Z = 2.71, P = 0.009]. The proportion of patients with French-American-British(FAB) type M 5, fever at initial diagnosis and lymph node enlargement in FEN1 high expression group (32 cases) was higher than that in FEN1 low expression group (25 cases) (all P < 0.05). There were no significant differences in the proportion of gender, age, fatigue, pale skin mucosa and large liver and spleen of patients between the two groups (all P > 0.05). At initial diagnosis, the white blood cell count, lactate dehydrogenase, C-reactive protein and bone marrow primitive cell proportion in FEN1 high expression group were higher than those in FEN1 low expression group (all P < 0.05), and the hemoglobin and platelet count in FEN1 high expression group were lower than those in FEN1 low expression group (all P < 0.05). There were no significant differences in procalcitonin level, the proportion of chromosome karyotype, cytogenetic prognosis grade and patients with or without gene mutation between the two groups (all P > 0.05). Conclusions:FEN1 expression is up-regulated in AML patients and further increased in relapsed patients. FEN1 expression in AML patients is associated with adverse clinicopathological features and poor detection results of laboratory indicators, which may become indicators for disease monitoring in AML patients.
7.Diagnostic value of multi-parametric cardiac magnetic resonance in acute rejection after heart transplantion
Xiaobing ZHOU ; Tingyu LI ; Yijin WU ; Yuelong YANG ; Rui CHEN ; Xiaodan LI ; Huanwen XU ; Xinyi WU ; Huimin WANG ; Chang LIU ; Min WU ; Hui LIU
Chinese Journal of Organ Transplantation 2022;43(12):736-742
Objective:To evaluate the diagnostic value of multiparametric cardiac magnetic resonance(CMR)or detecting the occurrence of acute rejection(AR)after heart transplantation(HT).Methods:From 2019 to 2021, 44 HT recipients are prospectively recruited from Guangdong Provincial People's Hospital.Another 51 healthy volunteers are recruited from a local community as healthy controls.CMR studies are performed for obtaining baseline parameters.According to the clinicopathological diagnostic criteria of AR by the consensus of International Society for Heart and Lung Transplantation, 81 CMR studies of 44 HT recipients are further divided into two groups of AR (18 cases)and non-AR(71 cases). CMR parameters includ global ventricular structure/function, T2, T1, extracellular volume(ECV)and late gadolinium enhancement(LGE). A combined model is established by binary Logistic regression and receiver operator characteristic curve(ROC)constructed.Results:The age range is(41.8±16.8)years in 44 HT recipients and(41.8±9.7)years in 51 healthy controls.T1 mapping indicated that myocardial global ECV of left ventricle is significantly higher in AR patients than non-AR controls(32.4%±6.0% vs 28.5%±2.4%; P<0.001 9). Global native T1 is higher in AR group than that in non-AR group(49.8±3.1 vs 47.5±2.8 ms, P=0.009)and the difference is statistically significant.The cutoff value of global ECV is 30.62% with a sensitivity of 61% and a specificity of 86% for detecting AR.And T2 mapping reveale that T2 value of global left ventricle is significantly higher in AR group than that in non-AR group(49.8±3.1 vs 47.5±2.8 ms, P=0.009). LGE extent is significantly higher in AR group than those in non-AR group( P=0.004). Through including global native T1 and ECV into a logistic regression model, multiparametric CMR can yield an area under curve(AUC)of 0.794.It hints at the potential of CMR for detecting AR. Conclusions:Multiparametric cardiac magnetic resonance offers an excellent predictive capacity for a noninvasive detection of AR.
8.Correlation between dietary approaches to stop hypertension pattern and central obesity affected by PM2.5 exposure
Huanwen ZHANG ; Tingting QIAO ; Zhen CHEN ; Tao LUO ; Zewen ZHANG ; Lu WANG ; Jianghong DAI
Journal of Environmental and Occupational Medicine 2022;39(11):1262-1268
Background There is a lack of evidence on whether exposure to PM2.5 and its constituents would affect the relationship between the dietary approaches to stop hypertension (DASH) and central obesity. Objective To investigate the effect of exposure to PM2.5 and its constituents on the correlation between the DASH dietary pattern and the prevalence of central obesity. Methods The data were obtained from the baseline survey of the "Xinjiang Multi-Ethnic Natural Population Cohort Construction and Health Follow-Up Study" in Urumqi. A DASH score was calculated according to intake frequency of 8 food groups, and summed from intake frequency of recommended food groups scored from 1 to 5 from low to high, and intake frequency of restricted food groups scored from 1 to 5 from high to low. A higher DASH score indicates better compliance with the DASH dietary pattern. We estimated exposure using satellite-derived PM2.5 and a chemical transport model (GEOS-Chem) for its constituents, including organic carbon (OC), black carbon (BC), sulfate (SO42−), nitrate (NO3−), ammonium (NH4+), and soil dust. Central obesity was defined by waist circumference: ≥90 cm for men or ≥85 cm for women according to Criteria of weight for adults (WS/T 428—2013). A logistic regression model was used to analyze the effects of the DASH dietary pattern as well as PM2.5 and its constituents on central obesity, and a stratified analysis was used to explore the effects of PM2.5 and its constituents on the association between the DASH dietary pattern and central obesity. Results The study included 9 565 urban residents, aged (62.30±9.42) years, with a central obesity prevalence rate of 60.75%. After adjusting for selected confounders, the DASH score Q5 group had a 17.5% lower risk of central obesity than the Q1 group (OR=0.825, 95%CI: 0.720-0.947). PM2.5 and its constituents OC, BC, SO42−, NH4+, and soil dust were positively associated with the prevalence of central obesity, but no association was observed between constituent NO3− exposure and central obesity. The stratified analysis revealed that the prevalence of central obesity was reduced in the DASH score Q5 group in participants exposed to low concentrations of PM2.5 and its constituents NO3−, NH4+, and soil dust, while the protective effect of the DASH pattern on central obesity disappeared in subjects exposed to high concentrations of PM2.5 and its constituents NO3−, NH4+, and soil dust. Conclusion Exposure to PM2.5 and its constituents NO3−, NH4+, and soil dust could attenuate the protective effect of the DASH pattern on central obesity.
9.Construction of clinical medical examination question bank based on virtual reality technology
Yanquan LIU ; Yaling LIN ; Yue YIN ; Langhui ZHANG ; Jianzhen SHEN ; Yuting CHEN ; Huanwen TANG
Chinese Journal of Medical Education Research 2022;21(10):1288-1292
Using novel virtual reality (VR) technology to carry out the construction of clinical medical examination question bank, while deepening the reform of clinical medical course examination, it continues to innovate the medical professional evaluation system and improve the flexibility, diversity and scientificity of clinical medicine in teaching and assessment. It is of great and far-reaching significance to improve the teaching level and the quality of medical education in medical colleges and universities. This paper analyzes and discusses the necessity and feasibility of building a clinical medical examination question bank, and the advantages and prospects of integrating VR technology to carry out the construction of clinical medical examination question bank. At the same time, the exploration and practice of the examination question bank construction based on VR technology disscussed in detail would provide innovative thinking and reference for the clinical medical teaching and evaluation, medical personnel training and other aspects in China.
10.Evaluation of CBL application effect in clinical practice teaching of cardiothoracic surgery
Chinese Journal of Medical Education Research 2021;20(1):63-65
Objective:To investigate the application effect of case-based learning (CBL) in clinical practice teaching of cardiothoracic surgery.Methods:A total of 86 interns who rotated in our department from February to November 2019 were randomized into observation group ( n = 43) and control group ( n = 43) by drawing lots. The control group used traditional teaching method, and the observation group used CBL teaching method. The differences between the two groups in professional theoretical performance, clinical skill achievement and teaching satisfaction were compared. Results:The professional theoretical scores, clinical skills scores, and teaching satisfaction of the observation group were better than those of the control group, with statistical differences ( P < 0.05). Conclusion:The CBL teaching method can effectively help interns master professional theoretical knowledge and clinical practice skills of cardiothoracic surgery, which has obtained satisfactory teaching results and is worthy of promotion.

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