1.Therapeutic efficacy analysis of endoscopic combined with serological diagnosis strategy and endoscopic in G1 and G2 gastric neuroendocrine neoplasms
Wenyu LI ; Yong LIU ; Yueming ZHANG ; Lizhou DOU ; Shun HE ; Yan KE ; Xudong LIU ; Yumeng LIU ; Hairui WU ; Guiqi WANG
Chinese Journal of Oncology 2024;46(4):326-334
Objective:To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).Methods:This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment.Results:Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P<0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P<0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P<0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P<0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions:The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.
2.Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA
Siyao LIU ; Zhengqi LI ; Lizhou DOU ; Yueming ZHANG ; Yong LIU ; Yumeng LIU ; Yan KE ; Xudong LIU ; Hairui WU ; Jiangtao CHU ; Shun HE ; Guiqi WANG
Chinese Journal of Oncology 2024;46(6):549-565
Objectives:To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions.Methods:Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set ( n=284) and a validation set ( n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training ( n=243), validation ( n=105), and test ( n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results:We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression ( P<0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions:Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.
3.Therapeutic efficacy analysis of endoscopic combined with serological diagnosis strategy and endoscopic in G1 and G2 gastric neuroendocrine neoplasms
Wenyu LI ; Yong LIU ; Yueming ZHANG ; Lizhou DOU ; Shun HE ; Yan KE ; Xudong LIU ; Yumeng LIU ; Hairui WU ; Guiqi WANG
Chinese Journal of Oncology 2024;46(4):326-334
Objective:To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).Methods:This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment.Results:Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P<0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P<0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P<0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P<0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions:The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.
4.Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA
Siyao LIU ; Zhengqi LI ; Lizhou DOU ; Yueming ZHANG ; Yong LIU ; Yumeng LIU ; Yan KE ; Xudong LIU ; Hairui WU ; Jiangtao CHU ; Shun HE ; Guiqi WANG
Chinese Journal of Oncology 2024;46(6):549-565
Objectives:To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions.Methods:Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set ( n=284) and a validation set ( n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training ( n=243), validation ( n=105), and test ( n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results:We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression ( P<0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions:Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.
5.The safety and feasibility of laparoscopic indocyanine green fluorescence mapping during sentinel node navigational surgery for early gastric cancer
Chunguang GUO ; Zefeng LI ; Tongbo WANG ; Xiaojie ZHANG ; Chongyuan SUN ; Hu REN ; Yong LIU ; Lizhou DOU ; Shun HE ; Yueming ZHANG ; Guiqi WANG ; Dongbing ZHAO
Chinese Journal of General Surgery 2024;39(10):770-775
Objective:To evaluate the safety and feasibility of the laparoscopic indocyanine green (ICG) fluorescence imaging during the sentinel node navigational surgery for the early gastric cancer.Methods:Patients with <4 cm early gastric cancer were chosen. 0.5 ml ICG (2.5 mg/ml) was preoperatively injected into submucosa around the lesion in four points by the endoscopy. The sentinel lymph node basin including the stained tissue and lymph node (LN) were completely resected guided by the fluorescence mapping under ICG laparoscopy. The specimen was inspected by frozen pathology section. The radical gastrectomy was dependent on the pathology result.Result:Between 2019 and 2021, a total of 18 patients were included in the final analysis. Most tumors (16/18) located in the middle or distal stomach. Median tumor size was 2.0 cm. Lymph vessel invasion was revealed in five cases and perineural invasion in three cases. According to AJCC tumor grading system, tumor depth was classified as Tis in 2 cases, T1a in 5 cases and T1b in 11 cases. Lymph node metastasis (LNM) was revealed in four patients (4/18, 22%). Median sentinel lymph node basins per patient were 2 (range, 1-5). An average 6 (range, 2-13) LNs were harvested in each case, including 6 (1-13) ICG stained LNs and 1 (0-5) non stained LNs. All of four LNM patients were detected by sentinel node navigational surgery. The rate of the sensitivity and accuracy were 100% and 100%, respectively. The median follow-up for the entire group was 58.3 months (0.3-59.9 months), with no recurrence or metastasis observed in any patient.Conclusion:The sensitivity and accuracy of the laparoscopic indocyanine green fluorescence imaging during the sentinel node navigational surgery were satisfactory.
6.Performance of rural practitioners of endoscopic cleaning and disinfection on the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers
Jibin LI ; Wenqiang WEI ; Yuqin LIU ; Jialin WANG ; Shangchun JIA ; Shaokai ZHANG ; Liang QIAO ; Lingbin DU ; Jinyi ZHOU ; Yongzhen ZHANG ; Liwei ZHANG ; Guiqi WANG
Chinese Journal of Digestive Endoscopy 2023;40(3):212-217
Objective:To evaluate the performance of rural practitioners of endoscopic cleaning and disinfection participating in the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers and to analyze the influencing factors.Methods:The questionnaires for skill assessment were designed based on the skill scheme and clinical practice of the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China, and the App Early diagnosis, Early treatment was used as the examination platform. The practitioners in 539 county hospitals from 25 provinces participating in the program in 2019 were assessed for techniques and skills for endoscopic cleaning and disinfection and the excellence rate was calculated. Multivariate logistic regression model was used to analyze the influencing factors for the examination. Results:A total of 1 671 endoscopic cleaning and disinfection practitioners participated in the assessment with the score of 73.41±16.60. The passing rate was 85.82%, and the excellence rate was 44.94%. Among all questions, the correct rate of "opportunistic screening flow chart" was the highest (98.21%), and that of "the evaluation index for mass screening" was the lowest (57.89%). The multivariate logistic regression analysis showed that the excellence rate was high in practitioners who had a bachelor degree or above ( OR=1.627,95% CI:1.319-2.007, P<0.001), the career for 5 to <15 years (5 to <10 years: OR=1.329,95% CI:1.045-1.689, P=0.020; 10 to <15 years: OR=1.384,95% CI:1.026-1.867, P=0.033), working in eastern and central regions (eastern regions: OR=3.476,95% CI:2.368-5.103, P<0.001;central regions: OR=4.028,95% CI:2.679-6.057, P<0.001) and with full understanding of the screening scheme ( OR=1.547,95% CI:1.246-1.921, P<0.001) . Conclusion:Practitioners on the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China have mastered the basic screening scheme and skills for endoscopic cleaning and disinfection. The education background, duration of the career, area and understanding of screening scheme are influencing factors for the excellence rate of endoscopic cleaning and disinfection.
7.Expression and prognostic significance of cell division cycle associated protein 5 in pancreatic cancer tissues
Shuzhen LI ; Xianqing ZHOU ; Wei WEI ; Yan YI ; Runyao MA ; Tong YANG ; Hailian QIN ; Guiqi YANG
Cancer Research and Clinic 2023;35(4):286-290
Objective:To analyze the expression of cell division cycle associated protein 5 (CDCA5) in pancreatic cancer tissues and its correlation with prognosis based on the bioinformatics.Methods:The RNA sequencing data (HTSeq-FPKM) and corresponding clinical information of 168 pancreatic cancer samples from January to December 2021 were downloaded from the Cancer Genome Atlas (TCGA) database, and the data of 179 pancreatic patients from January to December 2021 were downloaded from the GEPIA2 database, and 171 normal pancreatic tissues from TCGA and GTEx databases were simultaneously integrated. The relative expression level of CDCA5 mRNA in pancreatic cancer patients in GEPIA2 database and its relationship with overall survival (OS) and disease-free survival (DFS) were explored. Combined with the clinical data of the patients, univariate and multivariate Cox regression model analysis was used to analyze the factors influencing the OS of pancreatic cancer patients. Gene set enrichment analysis (GSEA) was performed to investigate the possibly involved signal pathways of CDCA5 in pancreatic cancer.Results:In the GEPIA2 database, the relative expression level of CDCA5 mRNA in pancreatic cancer tissues was higher than that in normal pancreatic tissues, and the difference was statistically significant ( P < 0.05). The pancreatic cancer patients were divided into the high CDCA5 mRNA expression group (89 cases) and the low CDCA5 mRNA expression group (89 cases) according to the median of relative expression level of CDCA5 mRNA (the case equal to the median value was not subgrouped). Survival analysis showed that patients with high CDCA5 mRNA expression had shorter OS ( P = 0.024) and DFS ( P = 0.025) compared with those with low CDCA5 mRNA expression. Multivariate Cox analysis showed that in TCGA database, N staging ( HR = 2.15, 95% CI 1.24-3.72, P = 0.006) and CDCA5 expression ( HR = 1.71, 95% CI 1.23-2.38, P = 0.001) were independent influencing factors of OS for pancreatic cancer patients. The results of GSEA enrichment analysis indicated that high CDCA5 mRNA expression was enriched in 13 biological pathways [all P < 0.05, false discovery rate (FDR) < 0.005] including cell cycle, DNA replication, homologous recombination, pyrimidine metabolism, mismatch repair, pentose phosphate pathway, glycolysis gluconeogenesis and p53. The expression of CDCA5 mRNA was positively correlated with the expressions of HK2, PKM, PGK1, ALDOA, EN01 and LDHA (all P < 0.05). Conclusions:CDCA5 is highly expressed in pancreatic cancer tissues and is associated with poor prognosis of patients, and it can be used as a prognostic marker for pancreatic cancer.
8. Effects of scacia honey on serum uric acid level and renal injury in rats
Xiuhe XU ; Xiaoli HE ; Jiashun ZHOU ; Lizhu PAN ; Zhuojun ZHOU ; Jiayue LI ; Guiqi ZHU ; Caixia WANG ; Wei YUAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(7):743-750
AIM: To observe the effect ofacacia honey (AH) on serum uric acid level and renal function in potassium oxonate modelrats after drinking AH aqueous solution. METHODS: Sixty male SD rats were selected and randomly divided into control group (CON group), potassium oxonate model group (OA model group), 10% fructose group (10% F group) and different concentration honey groups (25%, 12.5% and 6.25% AH groups). All rats were fed with normal diet.The rats in CON group were subcutaneously injected with 5% sodium carboxymethyl cellulose (CMC-Na) solution and drunk sterile water every day, while rats in other groups were injected with 100 mg / kg OA solution suspended with 5% CMC-Na subcutaneouslyand drunksterile water orfructose solution or AH solution of different concentrations every day. Before and during the 4-week test, rats were weighed and blood was taken once a week. At the end of test, urine and feces specimens or kidney tissues were collected and blood was taken from the abdominal aorta. The uric acid content in blood, urine, and feces and the levels of serum creatinine (Cre) and blood urea nitrogen (BUN) or inflammatory factors in kidney tissues were measured. Renal function and histology were evaluated. RESULTS: Compared with CON group, AH could significantly reduce the body weight of rats (P<0.05), increase the kidney organ coefficient, the levels of serum uric acid, and uric acid in urine or feces, and reduce the level of fecal uric acid (FUA) in rats. AH can down regulate the level of tumor necrosis factor alpha (TNF-a) (P< 0.05) and up regulate the expression of monocyte chemoattractant protein 1 (MCP-1) and transforming growth factor β - 1 (TGF - β1) in rats kidneys; AH can cause slight to mild dilatation of renal tubules and mild to moderate basophilic lesions of renal rubules in rat kidney in a dose dependent manner. CONCLUSION: In the doses rang of present study, AH can cause hyperuricemia, renal tubular dilatation and basophilic lesions, and lead to renal function damage in rats.
9.A content analysis of the provincial laws and regulations for voluntary blood donation
Huiying HU ; Li CHEN ; Zijia ZHANG ; Ying CHANG ; Guiqi ZHAO ; Lifen LU ; Yan ZHANG ; Qingming WANG ; Yingjia JIANG ; Hai QI ; Ming ZHU
Chinese Journal of Blood Transfusion 2022;35(8):873-877
【Objective】 To perform quantitative analysis on the sample provincial laws and regulations for voluntary blood donation, and provide reference for further revision of laws and regulations. 【Methods】 31 study samples were current provincial laws and regulations for voluntary blood donation that can be collected from open sources. The issue date and the revision date of each sample were recorded. With "The Blood Donation Law of the People’s Republic of China" as reference, 5 categories were formed and additional clauses in samples were coded and rated following content analysis procedures. Sample provinces were divided into two groups based on donation rate and their differences in evaluation scores of categories were examined using rank sum test. 【Results】 Until December, 2021, 31 sample provinces had issued and implemented provincial laws and regulation for voluntary blood donation, and 14 of which had been revised. Many detailed clauses (total score 9.32±3.09) were added in sample provincial laws and regulations, more clauses were added in the categories of 'related government agencies and their responsibilities’, 'management of clinical blood use’ and 'rewards and punishment’. Sample provinces were divided into two groups according to the donation rate per 1 000 people recommended by World Health Organization(10‰). Compared to lower donation rate group, the total score and sub score in the categories of 'basic principles’, 'management of blood collection and supply’ were significantly higher in higher donation rate group. 【Conclusion】 In revision and improvement of provincial laws and regulations, 'basic principles’ and 'management of blood collection and supply’ could be considered. This assay mainly tries to provide a new research perspective and perform quantitative analysis on content of sample provincial laws and regulation for voluntary blood donation, the actual effect of the results in this study need longer time to be examined, and we will keep following its new advances.
10.The monitoring of adverse reactions to blood donation: a multi-center analysis
Aimin REN ; Bing JU ; Yuanyuan LIU ; Lin WANG ; Qin LI ; Xiaohua YUAN ; Ling HOU ; Wen LIU ; Honghua LIU ; Zhian ZHANG ; Haibo HAN ; Guiqi ZHAO ; Juan LI ; Tao QI ; Yufeng SUN ; Tao LI ; Tianning SI ; Yang ZHANG ; Hengxin LI
Chinese Journal of Blood Transfusion 2022;35(4):365-368
【Objective】 To investigate the establishment of multi-center haemovigilance (HV) and the monitoring of adverse reactions to blood donation (ARBD), in order to provide basis for the management of blood donors. 【Methods】 The operation of HV was investigated by questionnaire. The total number of blood donations (including plateletpheresis) and ARBD cases occurred in each blood center from 2014 to 2018 were analyzed. 【Results】 Among the 24 blood centers in this survey, only nine got HV operated. The incidence of ARBD of 19 blood centers that fulfilled the questionnaire was in the range of (0.003~1.151) %. The change trend of number and incidence of ARBD cases were indeterminate. 【Conclusion】 Most blood centers did not got HV established. The incidence of ARBD varied greatly and was indeterminate. The application of HV should be further improved to strengthen ARBD management.

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