1.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.
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.Application of artificial intelligence based on data enhancement and hybrid neural network to site identification during esophagogastroduodenoscopy
Shixu WANG ; Yan KE ; Jiangtao CHU ; Shun HE ; Yueming ZHANG ; Lizhou DOU ; Yong LIU ; Xudong LIU ; Yumeng LIU ; Hairui WU ; Feixiong SU ; Feng PENG ; Meiling WANG ; Fengying ZHANG ; Lin WANG ; Wei ZHANG ; Guiqi WANG
Chinese Journal of Digestive Endoscopy 2023;40(3):189-195
Objective:To evaluate artificial intelligence constructed by deep convolutional neural network (DCNN) for the site identification in upper gastrointestinal endoscopy.Methods:A total of 21 310 images of esophagogastroduodenoscopy from the Cancer Hospital of Chinese Academy of Medical Sciences from January 2019 to June 2021 were collected. A total of 19 191 images of them were used to construct site identification model, and the remaining 2 119 images were used for verification. The performance differences of two models constructed by DCCN in the identification of 30 sites of the upper digestive tract were compared. One model was the traditional ResNetV2 model constructed by Inception-ResNetV2 (ResNetV2), the other was a hybrid neural network RESENet model constructed by Inception-ResNetV2 and Squeeze-Excitation Networks (RESENet). The main indices were the accuracy, the sensitivity, the specificity, positive predictive value (PPV) and negative predictive value (NPV).Results:The accuracy, the sensitivity, the specificity, PPV and NPV of ResNetV2 model in the identification of 30 sites of the upper digestive tract were 94.62%-99.10%, 30.61%-100.00%, 96.07%-99.56%, 42.26%-86.44% and 97.13%-99.75%, respectively. The corresponding values of RESENet model were 98.08%-99.95%, 92.86%-100.00%, 98.51%-100.00%, 74.51%-100.00% and 98.85%-100.00%, respectively. The mean accuracy, mean sensitivity, mean specificity, mean PPV and mean NPV of ResNetV2 model were 97.60%, 75.58%, 98.75%, 63.44% and 98.76%, respectively. The corresponding values of RESENet model were 99.34% ( P<0.001), 99.57% ( P<0.001), 99.66% ( P<0.001), 90.20% ( P<0.001) and 99.66% ( P<0.001). Conclusion:Compared with the traditional ResNetV2 model, the artificial intelligence-assisted site identification model constructed by RESENNet, a hybrid neural network, shows significantly improved performance. This model can be used to monitor the integrity of the esophagogastroduodenoscopic procedures and is expected to become an important assistant for standardizing and improving quality of the procedures, as well as an significant tool for quality control of esophagogastroduodenoscopy.
4.Clinical effect of different plastic biliary stent indwelling methods on managing obstructive jaundice in unresectable hilar cholangiocarcinoma
Jian WANG ; Jiangtao CHU ; Yueming ZHANG ; Lizhou DOU ; Yong LIU ; Yan KE ; Xudong LIU ; Yumeng LIU ; Guiqi WANG ; Shun HE
Chinese Journal of Digestive Endoscopy 2022;39(6):441-446
Objective:To compare the clinical effect of three indwelling methods of plastic biliary stent on relieving obstructive jaundice caused by unresectable hilar cholangiocarcinoma.Methods:A retrospective study was performed on data of 61 patients with obstructive jaundice caused by unresectable hilar cholangiocarcinoma from April 2014 to December 2020 in Cancer Hospital, Chinese Academy of Medical Sciences. Plastic biliary stent placement was used to relieve jaundice, including 18 cases of intragastric indwelling at the end of biliary stent, 31 cases of duodenal papilla indwelling at the end of biliary stent, and 12 cases of horizontal portion of duodenum indwelling at the end of biliary stent. Incidence of fever within 2 weeks, perioperative mortality, 90-day obstruction rate, and median stent patency period were followed up and the results were analyzed.Results:The incidence of fever within 2 weeks of the three groups were significantly different [66.7% (12/18), 58.1% (18/31) and 16.7% (2/12), χ2=7.30, P=0.026]. There were no statistically differences in the perioperative mortality [0 (0/16), 3.2% (1/31) and 0 (0/10), χ2=1.09, P=1.000], 90-day obstruction rate [52.9% (9/17), 48.3% (14/29) and 40.0% (4/10), χ2=1.91, P=0.589], or median stent patency period (66.0 d, 91.5 d and 94.0 d, Z=4.96, P=0.084) among three groups. Conclusion:Patients with biliary plastic stents with ends placed at the horizontal portion of the duodenum show lower incidence of fever within two weeks after implantation, and similar median stent patency period, 90-day obstruction rate and perioperative mortality compared with intragastric indwelling and duodenal papilla indwelling groups. Therefore, biliary plastic stents with ends placed at the horizontal portion of the duodenum should be recommended as the preferred procedure.
5.Prevalence and risk factors of Blastocystis hominis infection in inpatients in Jiangjin District, Chongqing City
Ji-Ming KANG ; Yi-Ting LI ; Rui CHEN ; Ying-Fang YU ; Xi-Tong LI ; Xiu-Ping WU ; Yan-Hong CHU ; Jia-Xu CHEN ; Shun-Xian ZHANG ; Li-Guang TIAN
Chinese Journal of Schistosomiasis Control 2019;31(5):479-485
Objective To understand the prevalence and risk factors of Blastocystis hominis infection in inpatients in Jiangjin District, Chongqing City. Methods A cross-sectional study was conducted in a community hospital in Jiangjin District, Chongqing City, and the inpatients were surveyed by questionnaires. After obtaining the informed consent from the inpatients or legal guardians, the stool and blood samples were collected and examined by microscopy and PCR from April 17 to May 1, 2018. The univariate analysis and logistic regression analysis were used to analyze the risk factors of the B. hominis infection. Results A total of 198 hospitalized patients were investigated, and the infection rate of B. hominis was 10.61% (21/198), and the infection rate of the females (12.10%) was higher than that of the males (8.11%), but the difference was not statistically significant. The highest rate of infection was 19.23% in the age group of 10 to 20 years, followed by 17.74% in the age group of 60 years and above, and the lowest rate was 2.38% in the age group of 20 to 40 years. The difference in infection rates of B. hominis among the different age groups was statistically significant (P < 0.05). The infection rate of B. hominis in the people who used dry pail latrines was 33.30%, which was higher than that of the people who used water flush toilets (9.10%) (P < 0.05). The genotypes of B. hominis were ST1, ST3, ST6 and ST7, and ST6 and ST3 being the most predominant genotypes which accounted for 47.62% (10/21) and 38.10% (8/21) respectively, and among the infected males, the genotypes were only ST3 and ST6. The multiple logistic regression analysis showed that among the factors affecting B. hominis infection, only keeping pets was a risk factor [OR = 3.798, 95% CI (1.245, 11.581), P < 0.05]. Conclusion A high prevalence of B. hominis infection is found in the inpatients in Jiangjin District, Chongqing City, the predominant genotypes are ST6 and ST3, and keeping pets may be one of the main risk factors.
6.Epidemiological characteristics and risk factors of Blastocystis hominis infection among patients with HIV/AIDS in Fuyang City Anhui Province
Shun-Xian ZHANG ; Ying-Fang YU ; Xiu-Ping WU ; Yan-Hong CHU ; Xue-Jiao TENG ; Feng-Feng WANG ; Jia-Xu CHEN ; Li-Guang TIAN
Chinese Journal of Schistosomiasis Control 2019;31(5):498-503
Objective To investigate the prevalence and risk factors of Blastocystis hominis infections among patients with HIV/AIDS in Fuyang City, Anhui Province. Methods A cross-sectional study was conducted in Fuyang City, Anhui Province in 2016. The demographic and socioeconomic status, and the lifestyle and production style were collected using a questionnaire survey. B. hominis DNA was detected in subjects’stool samples using a PCR assay, and the CD4+ T lymphocyte count and HIV viral load were measured in the subjects’ blood samples. The risk factors of B. hominis infections among patients with HIV/AIDS were identified using univariate and multivariate logistic regression analyses. Results A total of 398 HIV/AIDS patients were enrolled in this study, with a mean age of 49.3 years, a mean body weight of 55.9 kg and a mean height of 164.4 cm. The prevalence of B. hominis infection was 6.78% in the study subjects, and no gender- (χ2 = 1.589, P = 0.207), education level- (χ2 =0.508, P = 0.776), marital status- (χ2 = 0.419, P = 0.811) or occupation-specific prevalence (χ2 = 2.744, P = 0.615) was detected. Among the patients with HIV/AIDS, there were no significant differences in the age (t = 0.370, P = 0.712), height (t = 1.587, P =0.113), body weight (t = 0.516, P = 0.606), CD4+ T lymphocyte count (t = 1.187, P = 0.230) or HIV viral load (t = 0.193, P =0.496) between B. hominis-infected and uninfected individuals. Dinking non-tap water [OR = 6.554, 95% CI: (1.876 to 22.903)] and keeping dogs [OR = 5.895, 95% CI: (2.017 to 17.225)] were identified as risk factors for B. hominis infection in patients with HIV/AIDS. Conclusion The prevalence of B. hominis infection is high in HIV/AIDS patients, and drinking non-tap water and keeping dogs are risk factors for B. hominis infection among HIV/AIDS patients.
7.Immunomagnetic Nanosphere-based Strategy for Rapid, Efficient and Accurate Detection of Lymphnode Metastatic Carcinoma Cells
Yan Xu MA ; Hui Yin QIN ; Bo Chu QI ; Ling Ling WU ; Ling Zhi ZHANG ; Shun He XIA ; Wen Dai PANG
Chinese Journal of Analytical Chemistry 2017;45(12):1874-1881
A strategy based on immunomagnetic nanospheres ( IMNs ) for rapid, efficient and accurate detection of lymphnode metastasis carcinoma cells ( LNMCCs ) was developed in this study. First, IMNs processing magnetism and biological targeting were fabricated by the approach developed by our group previously. Then, LNMCCs in lymph node fine needle aspiration ( LNFNA) specimens were separated and enriched by the immunomagnetic isolation using IMNs. At last, the captured cells were identified with Wright's staining and immunocytochemistry ( ICC) . The separation and enrichment of LNMCCs with immunomagnetic isolation could reduce the background interference of LNFNA specimens effectively; the identification with Wright ' s staining and ICC offered more reliable information for accurate diagnosis, so the sensitivity, specificity and overall diagnostic accuracy had an obvious improvement compared with the conventional cytologic diagnosis. Besides, the simple and rapid incubation of LNFNA specimens with IMNs needed just 5 min, so the cytomorphology of captured LNMCCs could be intactly retained, which enabled to provide important basis for classifying lymphnode metastasis carcinoma ( LNMC ) and the subsequent pathological study. Moreover, the specific capture of epithelial carcinoma cells in LNFNA specimens with IMNs could make a definite diagnosis of the captured cells as LNMCCs, thus realizing the differentiated diagnosis of LNMC and malignant lymphoma. Additionally, this strategy exhibited successful LNMCCs detection in LNFNA specimens from 110 patients and had higher sensitivity ( 98 . 0%) , specificity ( 100 . 0%) , and overall diagnostic accuracy (98. 2%) than the conventional cytologic diagnosis. Therefore, it was a new attempt to use IMNs for detection of LNMCCs in LNFNA specimens from LNMC patients, and offered new ideas for LNMC diagnosis and study.
8.Experience in reducing intraoperative blood loss in radical retropubic prostatectomy.
Ding-Yi LIU ; Qi TANG ; Wei-Mu XIA ; Ming-Wei WANG ; Jian WANG ; Yan-Feng ZHOU ; Jia-Shun YU ; Chen-Long CHU ; Chong-Yu ZHANG ; Zhou-Jun SHEN ; Wen-Long ZHOU
National Journal of Andrology 2012;18(11):994-998
OBJECTIVETo search for an effective method of reducing intraoperative blood loss in radical retropubic prostatectomy (RRP).
METHODSWe performed RRP for 100 patients with prostate cancer, 50 (group A) with the Walsh or Poor method for handling the dorsal venous complex (DVC), and the other 50 (group B) through the following three additional procedures for hemostasis: first placing a #7 prophylactic suture in the distal position of DVC, then ligating the vascular bundle of the prostatic apex with continuous 4-0 Vicryl sutures, and lastly placing a 4-0 absorbable suture followed by freeing the neurovascular bundle (NVB) or freeing NVB before suturing the remained levator ani myofascia and the deep layer of Denovilliers' fascia above the rectal serosa with 4-0 Vicryl. We assessed the effects of the three hemostatic methods in RRP by comparing the volumes of intraoperative blood loss and transfusion, operation time and perioperative levels of hemoglobin.
RESULTSThere were no significant differences between groups A and B in age, PSA, Gleason score, clinical stage, prostate volume, operation time and perioperative hemoglobin levels (P>0.05). The volumes of intraoperative blood loss and transfusion were markedly higher in group A ([1103.00 +/- 528.03] ml and [482.00 +/- 364.60] ml) than in B ([528.00 +/- 258.96] ml and [140.00 +/- 266.28] ml) (P<0.05).
CONCLUSIONIntraoperative blood loss in RRP could be significantly decreased by placing a prophylactic hemostatic suture in the distal position of DVC, continuous suture of the vascular bundle of the prostatic apex after cutting off the urethra, and placing a fine absorbable suture above NVB or continuous suture of the remained levator ani mony fascia and the deep layer of Denovilliers'fascia above the rectal serosa with absorbable sutures after freeing NVB.
Aged ; Blood Loss, Surgical ; prevention & control ; Hemostatic Techniques ; Humans ; Male ; Middle Aged ; Prostatectomy ; methods ; Prostatic Neoplasms ; surgery
9.Study on dysmetabolism in patients with non-alcoholic fatty liver disease and its different combinations.
Jing LIANG ; Yu-shun CHU ; Tao HAN ; Yan LI ; Yan-ying JIANG
Chinese Journal of Hepatology 2011;19(11):865-867
Aged
;
Fatty Liver
;
complications
;
metabolism
;
Female
;
Humans
;
Insulin Resistance
;
Lipids
;
Liver
;
metabolism
;
Male
;
Metabolic Diseases
;
metabolism
;
Middle Aged
;
Non-alcoholic Fatty Liver Disease
10.The biomechanics study of rabbit osteoporosis models treated by 99Tc-MDP combined with GuKang Ling
Ke-jia, GAO ; Guo-ding, ZHAO ; Zhi-wei, YE ; Xiao-gang, MEI ; Ying-min, TIAN ; Chu-shun, YAN ; Wei, WANG ; Wei, LI ; Zheng-yu, CAI ; Hai-ping, SONG
Chinese Journal of Nuclear Medicine 2011;31(5):328-333
Objective To study the bone biomechanics of the rabbit osteoporosis models induced by dexamethasone sodium phosphate injection (DX) using a combined treatment modality of 99Tc-MDP and GuKangLing.Methods Rabbits were intramuscularly injected with DX (2 mg/kg) twice a week for 6 weeks.The animal osteoporosis model group (Group C) and normal group (Group A) were compared to confirm the model was available.Another control group (Group B),the osteoporosis control group (Group D) were set for the comparison at the end of the experiment.The 99Tc-MDP therapy group (Group E),GuKangLing therapy group (Group F) and 99Tc-MDP plus GuKangLing therapy group (Group G) were included in the study.The treatment lasted for 16 weeks.The bone biomechanics,cytopathology bone histomorphology,bone mineral density (BMD),X-ray,CT,bone scintigraphy and serum bone alkaline phosphatase (BALP)and P (bone gla protein) were chosen as the markers or methods to evaluate the treatment results (excellent,effective and invalid).The analysis of variance (ANOVA) and t-test were used for group comparison analysis.Results Cytopathology result indicated that there was no bone trabecula destruction in Group A.However,there was distinct bone destruction in Group C.The bone biomechanics (left femur head (265.914 ±52.773) N,L4(369.671 ±94.919) N),BMD(left femur (0.238 ±0.016) g/cm2,L4(0.236 ±0.016) g/cm2)and bone histomorphology ( (66.230 ± 10.848) % ) in Group C reduced clearly as compared with Group A ((405.343±55.410) N,(750.870±53.718) N,(0.294±0.017) g/cm2,(0.302±0.023) g/cm2,( 131.500 ± 21.846) % ) ( t ≥4.550,all P < 0.01 ).Radionuclide bone scan also showed that the uptake of tracers was higher by the main arthrosis in Group C than that in Group A.Vertebra was not clearly visualized on bone scan image.There were significant differences between Group A and Group C in serum BALP and P ((45.000±7.303) vs (12.485 ±1.512) U/L,(0.168±0.018) vs (0.115 ±0.017) μg/L,t =4.126,5.476,both P < 0.01 ),which indicated that the animal osteoporosis model was available.The pathological results showed an improved recovery of bone structure and trabecular in Groups E and G,but a worse recovery in Group F.Biomechanics result in Groups E and G (left femur head (386.457 ±77.077) N and (432.771 ± 17.525) N,L4(649.550 ± 126.859) N and (655.443 ±76.555) N) improved apparently,which were similar to Group B.The radiotracer uptake in Group F was lower than that in group D.The bone biomechanics,bone histomorphology,BMD,serum BALP and P after the treatment showed significant differences in Groups E,F and G (F:8.556 - 31.608,all P<0.01 ),and the bone biomechanics result in Group G was a little better than that in Group E (t =2.625,P < 0.05 ).The results of Group G and E were considered as excellent,and Group F was considered as effective.Conclusions The treatment of 99Tc-MDP combined with GuKangLing could improve the bone biomechanics of rabbit osteoporosis models and may be a potential method to increase the bone strength for resisting external force.

Result Analysis
Print
Save
E-mail