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2022 Vol. 13, No. 4

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Editorials
Trusted Artificial Intelligence for Pathology: From Theory to Practice
ZHOU Yanyan, DENG Yang, BAO Ji, BU Hong
2022, 13(4): 525-529. doi: 10.12290/xhyxzz.2022-0184
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Artificial intelligence (AI) has gradually integrated into every aspect of pathology research. However, we also encounter some problems in the practical application of pathological artificial intelligence. 1. Research institutions attach importance to the protection of data privacy, which results in the emergence of data islands and is detrimental to our training of AI models. 2. The lack of interpretability of existing AI models leads to users' incomprehension and difficulty in human-computer interaction. 3. AI models make insufficient use of multi-modal data, making it difficult to further improve their predictive effectiveness. To address the above-mentioned challenges, we propose to introduce the latest technologies of trusted artificial intelligence (TAI) into existing research of pathological AI, which is embodied as the following: 1. Securely share data. We try to break data islands on the basis of adhering to data protection. We can use federated learning methods, only provide the results of data training without uploading the data itself, and greatly increase the amount of data that can be used for training without affecting the data security. 2. Give AI interpretability. The technology of graphic neural networks is used to simulate the process of pathologists' learning pathological diagnosis, making the model itself interpretable. 3. Fuse multimodal information. Use the technology of knowledge graph to integrate and deepen the analysis of more diverse and comprehensive data sources in order to derive more accurate models. Through the above three aspects, we can achieve reliable and controllable pathological AI and clear the responsibility through trusted pathological AI technology, so as to promote the development and clinical application of pathological AI.
Nonnegligible Myocarditis: Insights from 2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure
QIU Luhong, LIU Yingxian, XU Xiqi
2022, 13(4): 530-534. doi: 10.12290/xhyxzz.2022-0077
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In September 2021, Eur Heart J published the 2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure, making important updates to the 2016 version. In the new guidelines, myocarditis is identified as a special clinical condition in heart failure that should be given more attention than before. Based on the current clinical practice of myocarditis management in China, this article aims to provide a comprehensive interpretation of the myocarditis section in the new guidelines, with the hope of improving the diagnosis and treatment of this disease.
Specialist Forum
Advances and Challenges in Applied Computational Pathology
JIAO Yiping, WANG Xiangxue, XU Jun
2022, 13(4): 535-541. doi: 10.12290/xhyxzz.2022-0287
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Computational pathology (CP) is an interdiscipline formed by pathology and informatics techniques such as artificial intelligence and computer vision. The research field of CP has been rapidly broadened from lesion detection and immunohistochemistry quantification to predictions of molecular and prognostic properties. CP models, applied intensively in clinics and research, will become an essential assistant tool for diagnosis and disease management. In this paper, we aim to review recent developments in the field of CP, and discuss major challenges and potential solutions in practice and research.
Application and Research Progress of Artificial Intelligence in Digital Pathological Image Analysis of Colorectal Cancer
LI Xiaoyan, LI Chen, CHEN Haoyuan, ZHANG Yong, ZHANG Jingdong
2022, 13(4): 542-548. doi: 10.12290/xhyxzz.2022-0074
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The artificial intelligence technology of computer science is widely used in digital pathology and develops rapidly, which is a milestone in the era of accurate diagnosis and treatment of tumors. As the gold standard of tumor diagnosis, traditional pathology is highly subjective and unrepeatable, and the work is cumbersome. Feature extraction and quantitative analysis of digital pathological images based on artificial intelligence technology are transformed into data with high fidelity and high-throughput that can be mined and analyzed. It shows unique advantages in early diagnosis, grading, and constructing the prognostic model of tumors. The development of artificial intelligence in digital pathology has brought a unique opportunity for pathology, and it is also the trend of the development of precise diagnosis and treatment in the future. In order to provide reference for clinical diagnosis and treatment, we review the current status and the value of potential application of artificial intelligence in digital pathological image analysis of colorectal cancer.
Guideline and Consensus
Clinical Practice Guideline for Primary Lung Cancer(2022 Version)
General Office of National Health Commission of the People's Republic of China
2022, 13(4): 549-570. doi: 10.12290/xhyxzz.2022-0352
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Guideline Interpretation
Interpretation on The Consensus Among Chinese Experts About Acquisition and Quality Control of Digital Pathological Images in Cervical Liquid Based Cytology
LIANG Li
2022, 13(4): 571-573. doi: 10.12290/xhyxzz.2022-0100
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In order to promote the establishment of standardized digital pathological image-database of cervical liquid-based cytology and the development and application of artificial intelligence-assisted diagnostic products, the first domestic expert consensus in the field of digital pathology namely The consensus among Chinese experts about acquisition and quality control of digital pathological images in cervical liquid-based cytology was published in 2021 and jointly formulated by the group of digital pathology and artificial intelligence of the Association of Chinese Pathologists, the Working Committee of Digital pathology and artificial intelligence of the pathological branch of the Chinese Medical Association, and the group of cell pathology of the Chinese Medical Association. Based on the key contents of the consensus, this paper interprets the relevant issues and looks forward to the future development.
Interpretation on Clinical Guidelines for Prevention and Treatment of Type 2 Diabetes Mellitus in the Elderly in China (2022 Edition)
ZHAO Weigang
2022, 13(4): 574-580. doi: 10.12290/xhyxzz.2022-0199
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According to the data of China's seventh national population census, the elderly population (≥60 years old) accounted for 18.7% of the total population in 2020. About 30%(78.13 million)of them suffer from diabetes mellitus, among which more than 95% have type 2 diabetes mellitus. However, current prevention and treatment of type 2 diabetes mellitus in the elderly is unsatisfactory, and there is a tendency of weakening and negativity. Complications caused by poorly controlled blood glucose are the main risk factors jeopardizing the health and survival of the elderly. The Clinical Guidelines of Prevention and Treatment of Type 2 Diabetes Mellitus in the Elderly in China (2022 Edition) that summarizes the domestic and foreign relevant guidelines and research on elderly diabetic patients, aims to establish and optimize the concept of prevention and treatment in the elderly with diabetes mellitus, promote the implementation of standardized measures of prevention and treatment, and constantly improve the overall management level of diabetes mellitus in the elderly. Therefore, it is necessary to interpret its important contents.
Original Contributions
An Automatic Quantitative Analysis Method of Ki-67 Index for Breast Cancer Immunohistochemistry Based on Fusion of Spatial and Multi-scale Features
XIONG Xuechun, WU Huanwen, REN Fei, CUI Li, LIANG Zhiyong, ZHAO Ze
2022, 13(4): 581-589. doi: 10.12290/xhyxzz.2022-0158
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  Objective  To propose an intelligent quantitative analysis method of Ki-67 index for breast cancer immunohistochemical whole slide image (WSI).  Methods  The pathological sections of patients with breast cancer diagnosed and treated in Peking Union Medical College Hospital from January 2020 to December 2020 were retrospectively collected, and scanned at 40 magnification as WSI images. Manual interpretation of the Ki-67 index was conducted by 2 pathologists according to the guidelines formulated by the International Breast Cancer Ki-67 Working Group in 2019, which is considered the gold standard. According to the ratio of 5:8, WSI was randomly divided into two data sets, A and B (data set A was randomly divided into training set, validation set and test set according to a ratio of 7:1:2). After the hot spot area in WSI of the data set A was manually marked, each WSI randomly cropped 2000 512×512 pixel patches in the 40 field of view, and 50 patches of them were randomly selected to label tumor cells and calculate the Ki-67 index. The conditional random field model was used to fuse the spatial features of the image blocks, the features were extracted by the ResNet34 pre-training model to construct a hot spot recognition model, and its performance (accuracy) was evaluated in the test set. In the hot spot area, 10 fields of view were randomly selected under the high-power field of view (×40), and the model automatically completed the cell classification and calculated the average Ki-67 index. Taking the results of manual interpretation as the gold standard, the accuracy of the Ki-67 index evaluation results of the data set B by the model was calculated, and the Bland-Altman method was used to evaluate the consistency between the results of manual interpretation and model analysis.  Results  A total of 132 pathological sections of patients with breast cancer which met the inclusion and exclusion criteria were selected. There were 50 images in data set A (35, 5, and 10 images in training set, validation set, and test set, including 70 000, 10 000, and 20 000 patches, respectively), and 82 images in data set B. The average accuracy of the model for identifying hot spots in the test set was 81.5%, and the accuracy of the Ki-67 index calculation results for the B data set was 90.2%. Bland-Altman analysis showed that the Ki-67 index calculated by manual interpretation and model was in good agreement.  Conclusion  The intelligent quantitative analysis method of Ki-67 index proposed in this study has high accuracy and can assist pathologists to achieve efficient interpretation of Ki-67 index.
Computer-aided Diagnostic Methods for Medial Degeneration in Non-inflammatory Aorta Based on Multi-stained Pathological Images
WANG Hao, SUN Zhongjie, CHEN Dong, WAN Tao, LIANG Zhiyong, LIAN Guoliang, DONG Fang, GONG Shanshan, JI Junyu, QIN Cengchang
2022, 13(4): 590-596. doi: 10.12290/xhyxzz.2022-0170
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  Objective  To explore the feasibility of establishing a computer-aided diagnostic model of multi-stained pathological images in patients with non-inflammatory aortic medial degeneration(MD).  Methods  In this study, pathological sections of aortic surgical specimens for non-inflammatory lesions from patients with thoracic aortic aneurysms and dissections were retrospectively collected at the Beijing Anzhen Hospital, Capital Medical University from July to December 2018. The lesions were scanned under ×400 magnification as whole slide images(WSI) and then annotated by two pathologists. The annotated WSI images were randomly split into training and test sets in a 6:1 ratio. SE-EmbraceNet was used to train the data to construct a multi-classification model for MD of multi-stained pathology images, including intralamellar mucoid extracellular matrix accumulation (MEMA-I), translamellar mucoid extracellular matrix accumulation (MEMA-T), elastic fiber fragmentation and/or loss(EFFL) and smooth muscle cell nuclei loss (SMCNL). The classification effect of the model was evaluated based on the test set data, and the results were expressed in terms of accuracy, sensitivity, precision, and the F1 value.  Results  Totally 530 pathological slides of non-inflammatory aortic lesion surgical specimens from patients with aortic aneurysm and dissection were included. Extracted 5265 sets of images, each containing 5 stained pathological images of the same lesion site: HE staining, special staining (elastic fiber/VanGieson, Masson, Alcian blue/periodic acid Schiff) and smooth muscle actin staining. There were 4513 sets of training images, including 987 SMCNL, 2013 EFFL, 1337 MEMA-I, and 176 MEMA-T; and 752 test images including 166 SMCNL, 335 EFFL, 222 MEMA-I, and 29 MEMA-T. The overall performance of the model in the test set showed good results, with an accuracy of 96.54%(726/752). The model had the best classification performance for EFFL, with accuracy, sensitivity, precision, and F1 value all ≥98.51%. The model also had a great classification ability for SMCNL, with all evaluated indexes≥97.59%.  Conclusion  The multi-stained pathology image-based MD classification model constructed in this study has high classification accuracy and good generalization ability, which has the potential to be applied to assist in the diagnosis of the non-inflammatory aortic lesion.
Gastric Cancer Diagnostic Model Based on Convolutional Neural Network
WANG Jixian, GUI Kun, CHEN Bingxian, RU Guoqing, ZHAO Di, CHEN Wanyuan, ZHANG Zhiyong
2022, 13(4): 597-604. doi: 10.12290/xhyxzz.2022-0021
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  Objective  To build a diagnostic model of gastric cancer based on deep learning and evaluate the performance of the model.  Methods  The pathological sections of patients diagnosed with normal gastric mucosa, chronic gastritis, high-grade intraepithelial neoplasia or gastric adenocarcinoma by endoscopic examination in Zhejiang Provincial People's Hospital from January 2015 to January 2020 were retrospectively selected. The pathology slides were scanned at ×20 magnification to generate whole slide images (WSIs). These WSIs were randomly divided into patch classification data set, slide classification training set and slide classification test set at a ratio of 2:2:1. After the lesion regions of the patch classification data set were annotated and the patches were selected, they were randomly divided into training set, test set and validation set at a ratio of 20:1:1. The deep learning model Efficientnet and ResNet were used to train and the convolutional neural network (CNN) model for cancer and non-cancer classification was constructed. Based on the patch classification test set and validation set, the performance of the model was evaluated. The results were evaluated by the patch classification accuracy and the area under the curve (AUC). This model was used for image stitching to generate the cancerous heat map of WSIs and extract the slide-level cancer and non-cancer classification features of the heat map. LightGBM slide-level classification algorithm were trained and evaluated, and the gastric cancer of WSIs were diagnosed and recognized. The results were evaluated by AUC, accuracy, sensitivity and specificity.  Results  A total of 500 pathological sections of benign gastric diseases (normal gastric mucosa, chronic gastritis) and 500 pathological sections of gastric cancer (high-grade intraepithelial neoplasia and gastric adenocarcinoma) that met the inclusion and exclusion criteria were selected. The patch classification data set, slide classification training set and slide classification test set were 400, 400 and 200, respectively. The patch classification training set, test set, validation set were 402 000, 20 000, 20 000, respectively. CNN model based on Efficientnet-b1 network structure for patch classification in test set and validation set achieved the highest accuracy[test set: 91.3% (95% CI: 88.2%-95.4%); validation set: 92.5%(95% CI: 89.0%-95.3%)]and the highest AUC[test set: 0.95(95% CI: 0.93-0.98); validation set: 0.96(95% CI: 0.92-0.98)]. The AUC of the model based on LightGBM algorithm was 0.98(95% CI: 0.89-0.98), with accuracy of 88.0%(95% CI: 81.6%-94.3%), sensitivity 100%(95% CI: 88.0%-100%), and specificity 67.0%(95% CI: 57.0%-85.0%).  Conclusion  The CNN diagnostic model based on the pathology slides of gastric biopsy can locate the cancerous tissues, classify patch-level and slide-level lesion natures accurately, identify gastric cancer accurately, which has the potential to improve the diagnosis efficiency.
Prediction of Survival Status of Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiotherapy Based on Improved Fully Convolutional Networks Model
WANG Fang, PANG Xiaolin, FAN Xinjuan
2022, 13(4): 605-612. doi: 10.12290/xhyxzz.2022-0159
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  Objective  To explore the model of using after neoadjuvant chemoradiotherapy (nCRT) imaging images of locally advanced rectal cancer (LARC) to predict whether pathological complete response (pCR) is achieved, thereby assisting physicians to develop a personalized plan.  Methods  Patients with LARC treated with nCRT at the Sixth Affiliated Hospital of Sun Yat-sen University from June 2013 to December 2018 were retrospectively included, and the treatment outcome was evaluated by total rectal mesenteric resection histopathology. The patients were divided into 2 data sets, Data A and Data B, according to the order of hospitalization time in a ratio of 1:2. Data A was used for semantic segmentation model training, and Data B was randomly divided into training and validation sets in the ratio of 7:3, which were used for pCR prediction model training and validation, respectively. The T2-weighted MRI images of Data A were collected, and the improved fully convolutional networks(FCN) model was used to semantically segment the tumor region, establish the semantic segmentation model and extract the image features in the final convolutional layer. The least absolute shrinkage and selection operator (LASSO) regression model was used to filter the extracted image features and construct a support vector machine (SVM) classifier that could predict the pCR state. The performance of the prediction model was trained on the basis of the Data B training set and further validated in the Data B validation set.  Results  A total of 304 patients with LARC who met the inclusion and exclusion criteria were enrolled, 82 patients reached pCR after nCRT, while 222 patients did not reach pCR (non-pCR). Among them, 103 patients from June 2013 to November 2015 were in Data A and 201 patients from December 2015 to December 2018 were in Data B. In Data B, 140 patients were in the training set and 61 patients in the validation set. The improved FCN model had a Dice value of 0.79(95% CI: 0.65-0.81), a sensitivity of 80%(95% CI: 77%-83%), and a specificity of 72%(95% CI: 64%-85%). A total of 512 image features in the final convolutional layer were extracted by the semantic segmentation model, and 7 were retained after LASSO regression screening for pCR state prediction. The area under the curve of the prediction model was 0.65(95% CI: 0.61-0.71) in the Data B training set and 0.69(95% CI: 0.59-0.74) in the Data B validation set for predicting pCR.  Conclusions  The improved FCN model proposed in this study has high accuracy for semantic segmentation of MRI images. The prediction model constructed based on this method is feasible to predict pCR status of LARC patients after receiving nCRT treatment.
Clinical Application of ThinPrep Imaging System in Cervical Cytology
KONG Linghua, XIAO Xiaoping, WAN Ru, XIANG Yang
2022, 13(4): 613-619. doi: 10.12290/xhyxzz.2022-0221
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  Objective  To investigate the effectiveness of clinical application of ThinPrep Imaging System (TIS) in cervical cytology.  Methods  Manual screening results of cervical liquid-based cytology (LBC) specimens from December 2016 to May 2017 and TIS-assisted screening results of LBC specimens from December 2017 to May 2018 in the Obstetrics and Gynecology Outpatient Clinic of Peking Union Medical College Hospital were retrospectively analyzed. The diagnostic rates of abnormal cytology, histological follow-up results for abnormal cytology and high risk-human papillomavirus (Hr-HPV) positivity for abnormal cytology specimens were analyzed and compared between the two screening methods.  Results  A total of 17 407 manual screening results of cervical LBC specimens and 16 564 TIS-assisted screening results of LBC specimens were included. The overall abnormal cytology diagnostic rate was significantly higher in TIS-assisted screening than in manual screening (15.21% vs. 9.58%, P < 0.001), with the diagnostic rate of atypical squamous cells, atypical squamous cells without excluding high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, atypical glandular cells and adenocarcinoma increasing 2.77%, 0.28%, 2.08%, 0.35%, 0.08% and 0.08%, respectively. All results were statistically different (all P < 0.05). In biopsy follow-up of the patients with abnormal cytology, the histological coincidence rates of TIS-assisted screening were higher than those of manual screening, but the differences were not statistically significant (all P > 0.05). The number of abnormal glandular cells diagnosed by TIS-assisted screening was 1.89 times that of manual screening (53 cases vs. 28 cases), and the number of adenocarcinomas (confirmed by histology) in TIS-assisted screening was 2.3 times as many as that in manual screening (37 cases vs. 16 cases). The Hr-HPV positivity rates of patients with abnormal squamous epithelial cells in TIS-assisted screening and manual screening were not statistically different. Meanwhile, TIS-assisted screening was more time efficient, with 33%-50% reduction of time.  Conclusion  The use of TIS-assisted screening not only improved the detection rate of abnormal cytology and the work efficiency, but also increased histological compliance rate, which is worthy of further clinical application.
Image Compression and Storage Algorithm of Histopathology Based on Matrix Calculation
HE Ruilin, LIU Ziyu, YANG Xinyi, LI Chen, LI Xiaoyan
2022, 13(4): 620-625. doi: 10.12290/xhyxzz.2022-0127
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  Objective  To evaluate the clinical application value of the compression and storage algorithm of histopathological images based on matrix computing, and to seek the best image compression ratio.  Methods  Two classical matrix algorithms, principal component analysis (PCA) and singular value decomposition (SVD), were used to compress and reconstruct the immunohistochemical images and HE staining images of low, medium and high differentiated cervical cancer tissues. The peak signal-to-noise ratio(PSNR) and structural similarity (SSIM) were used to analyze and evaluate the quality of image reconstruction.  Results  When the compression ratio of PCA reconstruction image was 10.18 (53 principal components were retained), the mean PSNR of immunohistochemical images of low, medium and high differentiated cervical cancer tissues were 43.84±0.43, 43.27±0.25 and 43.71±0.49, respectively, and the SSIM were 0.964±0.004, 0.963±0.006 and 0.965±0.005, respectively. Meanwhile, the mean PSNR of HE staining images of low, medium and high differentiated cervical cancer tissues were 43.41±0.78, 42.95±1.03 and 43.52±0.69, respectively, and the SSIM were 0.953±0.010, 0.949±0.015 and 0.960±0.007, respectively. When the compression ratio of SVD reconstruction image was 10.00(128 singular values were retained), the mean PSNR of immunohistochemical images of low, medium and high differentiated cervical cancer tissues were 39.89±1.69, 38.20±2.19 and 40.90±0.50, respectively, and the SSIM were 0.949±0.006, 0.938±0.011 and 0.955±0.004, respectively. Meanwhile, the mean PSNR of HE staining images of low, medium and high differentiated cervical cancer tissues were 40.31±0.98, 39.46±1.59 and 40.77±1.67, respectively, and the SSIM were 0.965±0.006, 0.943±0.010 and 0.969±0.005, respectively.  Conclusions  PCA and SVD can compress and store histopathological images and obtain better image quality, which provides a solution to the problem of hospital image storage.
Changes of MicroRNA Expression and Apoptosis in Endometrial Glandular Epithelial Cells under Hypoxic
WANG Hanbi, DOU Shuaijie, LIU Simiao, ZHANG Wanyu, LIU Meizhi, DENG Chengyan
2022, 13(4): 626-631. doi: 10.12290/xhyxzz.2022-0095
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  Objective  To explore the changes in the transcription levels of microRNAs(miRNAs) in endometrial glandular epithelial cells (EECs) under hypoxia and their effects on apoptosis.  Methods  EECs were seeded into six-well plates in logarithmic growth phase(1×105 cells/well), and divided into two groups: hypoxia group and control group. The cells in both hypoxia group and the control group were placed in a hypoxic environment (the volume ratio of O2∶N2∶CO2 was 1∶94∶5) and cultured in normoxic environment (O2∶CO2 volume ratio of 95∶5). All cells were collected after they were cultured 4 h, and Trizol was added into the cells and total RNAs were extracted. High-throughput sequencing was used to detect the changes of miRNAs expression profiles in the two groups of EECs. Subsequently, realtime fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the gene expression of miR-7704 and miR-7974. Flow cytometry was used to detect the apoptosis of EECs. The protein expression changes of p53 and apoptosis-related proteins were detected by Western blot.  Results  High-throughput sequencing detected the expression levels of 21 common miRNAs. Compared with the control group, 16 miRNAs were up-regulated and 5 miRNAs were down-regulated in the EECs of the hypoxia group; the expression of miR-7704 and miR-7974 decreased most significantly in the hypoxia group(all P < 0.05). RT-PCR results showed that compared with the control group, the relative expression levels of miR-7704 and miR-7974 in EECs of the hypoxia group decreased by 20% and 80%, respectively. The results of flow cytometry showed that the ratio of early apoptotic cells and late apoptotic cells in the hypoxia group was higher than that in the control group (all P < 0.001). The results of Western blot showed that the expression of p53 in EECs in the hypoxia group increased, and the expression of the anti-apoptotic protein B-cell lymphoma-2 decreased compared with the control group(all P < 0.05).  Conclusions  Hypoxic environment can induce changes in the expression profile of miRNAs in EECs, among which the down-regulation of miR-7974 is the most significant. p53 may be the target protein of miR-7974, and hypoxia-induced EEC apoptosis may be achieved by down-regulating the level of miR-7974 and promoting the expression of p53.
The Value of Insulin-like Growth Factor 2 in Urinary Exosomes of Bladder Urothelial Carcinoma
YANG Tingkai, WEN Jin, JI Zhigang
2022, 13(4): 632-636. doi: 10.12290/xhyxzz.2021-0446
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  Objective  To explore the expression of insulin-like growth factor 2 (IGF2) in urinary exosomes of patients with bladder urothelial carcinoma, and to evaluate its clinical value in the diagnosis of bladder urothelial carcinoma.  Methods  Patients with bladder urothelial carcinoma or non-urothelial carcinoma diagnosed and treated by Peking Union Medical College Hospital from September to December 2020 were prospectively selected as the research subjects. Fluorescence quantitative reverse transcription PCR was used to detect the expression levels of IGF2 in the urine exosomes of the two groups. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of IGF2 in urinary exosomes for diagnosing bladder urothelial carcinoma were calculated, using pathological results as the gold standard.  Results  A total of 35 patients with bladder urothelial carcinoma and 60 non-urothelial carcinoma patients who met the inclusion and exclusion criteria were selected. The positive expression rate of IGF2 in urinary exosomes in patients with bladder urothelial carcinoma was significantly higher than that in patients with non-urothelial carcinoma (71.4% vs. 10.0%, P=0.000). The sensitivity of IGF2 in urinary exosomes for diagnosing bladder urothelial carcinoma was 71.43% (95% CI: 53.48%-84.76%), the specificity was 90.00% (95% CI: 78.83%-95.87%), the positive likelihood ratio was 7.14 (95% CI: 3.25-15.70), the negative likelihood ratio was 0.32 (95% CI: 0.19-0.54).  Conclusions  IGF2 is highly expressed in urinary exosomes of patients with bladder urothelial carcinoma, which has high diagnostic specificity for bladder urothelial carcinoma, but a slightly lower sensitivity. IGF2 is expected to be used as a primary screening index for bladder urothelial carcinoma.
Reviews
Research Advances of Hyperlipidemic Pancreatitis
ZHAO Huijia, WU Dong, WU Wenming
2022, 13(4): 637-643. doi: 10.12290/xhyxzz.2021-0760
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Hyperlipidemic pancreatitis (HLP) is one of the most important causes of acute pancreatitis. The pathogenesis is associated with the accumulation of free fatty acids which can activate the inflammatory response. Compared with other causes, HLP is more likely to have the clinical features characterized by more severe symptoms, more complications, and higher likelihood of persistent organ failure. The HLP patients always need lipid lowering therapy such as apheresis or insulin therapy to reduce serum triglyceride rapidly. Assessment of the presence of hyperlipidemia in patients of acute pancreatitis and prompt management are crucial for the prognosis and the prevention of recurrence. This article reviews the etiology, pathogenesis, clinical features, and treatment of hypertriglyceridemia-induced acute pancreatitis.
Clinical Diagnosis and Treatment of Tardive Dyskinesia
WANG Xixi, WAN Xinhua
2022, 13(4): 644-651. doi: 10.12290/xhyxzz.2021-0717
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Tardive dyskinesia(TD) is a kind of disabling movement disorder characterized by involuntary movements of the face, neck, extremities or trunk that results from long-term use of dopamine receptor blocking agents.The most common reason is the use of antipsychotic drug(APD). Identified risk factors include the type, dose, as well as the duration of APD. Age, sex, genetics also play a role. CYP2D6, DRD2, DRD3, HTR2A, HTR2C, VMAT2, MnSOD, HSPG2 gene may be involved. The pathogenesis is not clear. Three hypotheses are proposed: dopamine receptor super-sensitivity, oxidative stress and maladaptive synaptic plasticity. TD is quite hard to cure, prevention is of vital importance. This article reviews the clinical diagnosis and treatment of TD, so as to further deepen medical staff's understanding of TD.
Advances in Urinary Tumor Markers of Prostate Cancer
WANG Shijun, LI Yingjie, WEN Jin
2022, 13(4): 652-657. doi: 10.12290/xhyxzz.2021-0774
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Prostate cancer (PCa) is currently the second most common cancer in men worldwide.The current gold standard for diagnosing PCa relies on ultrasound-guided systematic core needle biopsy after detection changes in a digital rectal examination and elevated prostate-specific antigen(PSA) level in the blood serum. Yet, serum PSA cannot reliably discriminate between benign pathologies and clinically significant forms of PCa. A common problem caused by the low specificity of this marker is over diagnosis, which leads to unnecessary biopsies and over treatment. This may be associated with various treatment complications (such as bleeding or infection) and generate unnecessary costs. Therefore, there is an urgent need for more specific and predictive biomarkers to effectively discriminate between aggressive and nonaggressive tumors and to avoid unnecessary prostate biopsies. Biomarkers derived from prostate cancer cells are released into prostatic fluids and then into urine. Urine after manipulation of the prostate is enriched with PCa biomarkers, including prostate cancer cells, DNAs, RNAs, proteins and other small molecules. In recent years, several non-invasive, cost-effective, high-accuracy urinary diagnostic biomarkers such as PSA, PCA3, MALAT1 and microRNA have been developed. This article reviews the biomarkers for the non-invasive testing of PCa in urine.
Complicated and Rare Disease
Nutcracker Syndrome with Varicocele Treated with Left Gonadal Vein-inferior Vena Cava Transposition and High Ligation of Spermatic Vein: A Case Report
HUANG Mengju, DI Xiao, XU Weifeng, WANG Xuan, CHEN Yuexin, ZHENG Yuehong
2022, 13(4): 658-663. doi: 10.12290/xhyxzz.2021-0503
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Nutcracker syndrome (NCS) is a rare disease that may cause proteinuria, renal dysfunction and varicose of genital veins. Traditional open surgery prefers left renal vein transposition, but this surgical method is more traumatic and patients often have more postoperative short-term and long-term complications affecting the quality of life. This article reports a case of a young male patient with NCS complicated with left varicocele. He was treated with left gonadal vein-inferior vena cava transposition and high ligation of spermatic vein, which achieved good results after surgery. This surgical method provides a new treatment idea for patients with NCS and varicocele, which is worthy of clinical reference.
Clinical Biobank
Construction and Management of Biobank Information System for Multi-center Colorectal Cancer Clinical Research
KONG Weiming, LYU Wenwen, JIANG Jiayuan, FENG Tienan, YU Zhangsheng
2022, 13(4): 664-669. doi: 10.12290/xhyxzz.2021-0763
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In recent years, the incidence of colorectal cancer in China has increased significantly. With the in-depth exploration of the mechanisms of colorectal cancer recurrence and metastasis, a biobank information system that can provide comprehensive biological information is becoming more and more important. This paper expounds on the construction of a multi-center colorectal cancer clinical research biobank information system that includes three subsystems as follows: a clinical electronic data acquisition system, a biological sample management system, and a biological information data platform using the micro-service architecture. This paper explains how these subsystems are used in the multi-center management module and their characteristic functions in clinical research. Data quality and interconnection are supported through standardized data management solutions such as unified coding rules, structured clinical information, standardized sample circulation information, and standardized data storage. Thereby, this system provides comprehensive biomedical information for the promotion of translational medicine research and the development of precision medicine.
Clinical Practice Guidelines
Initiative to Promote the Development of Patient and Public Versions of Guidelines in China
2022, 13(4): 670-672. doi: 10.12290/xhyxzz.2022-0378
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Abstract:
As a health education tool, the patient and public versions of guidelines intend to improve the medical literacy of patients and the public, facilitate doctor-patient communication, and share decision-making in healthcare. At present, patient and public versions of guidelines are at an early stage in China, and there are problems such as immature methodologies and low awareness among stakeholders. Therefore, this paper proposes five initiatives to facilitate high-quality development of the patient and public versions of guidelines in China.
Investigation and Evaluation of Chinese Clinical Practice Guidelines Published in Medical Journals in 2019: Analysis on Dissemination and Implementation
LYU Meng, LUO Xufei, LIU Yunlan, REN Mengjuan, LIU Xiao, SHI Qianling, WANG Zijun, LU Shuya, LIU Hui, LI Qiu, CHEN Yaolong
2022, 13(4): 673-678. doi: 10.12290/xhyxzz.2022-0028
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Abstract:
  Objective  To analyze the status of dissemination and implementation of Chinese clinical practice guidelines published in medical journals in 2019, and to propose suggestions on promoting the dissemination and implementation of Chinese guidelines in the future.  Methods  We analyzed Chinese guidelines published in 2019 on the following aspects: reporting the dissemination and implementation; being published in multiple journals, editions and languages. Besides, we also searched published interpretation reports related to 2019 Chinese guidelines so as to understand the status of dissemination and implementation of guidelines in China.  Results  A total of 226 Chinese guidelines published in medical journals in 2019 were identified. Only 5.8% (13/226) reported the information on dissemination and implementation with 12 different strategies. Dissemination and implementation by academic conferences and social media were mostly mentioned and reported in 8 guidelines. As for the application of the strategies of dissemination and implementation, 12.4% (28/226) published in different journals; 9.3% (21/226) published different editions; 8.4% (19/226) published both English and Chinese versions. After search and screening, we included 48 interpretation reports, which interpreted 30 (13.3%, 30/226) Chinese guidelines. The median interval of publication time between the guideline and interpretation study was 5.5 months.  Conclusions  The reporting rate of dissemination and implementation and the application of related strategies of Chinese guidelines published in 2019 were relatively low. We suggest that guideline developers should develop specific and detailed strategies on guideline dissemination and implementation, and follow the reporting guidance.
Drug Therapy for Tumors
Pharmacological Effects and Clinical Evaluation of PD-1 Inhibitor of Tislelizumab in the Treatment of Advanced Malignant Tumors
LUO Xiangchong, WANG Zhouqing, LI Qiongyan, MAO Guibing, AN Le, ZHU Jiahong, TAO E'hong, SUN Lifei, WANG Shengfei, LI Gaofeng
2022, 13(4): 679-686. doi: 10.12290/xhyxzz.2021-0691
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Abstract:
In recent years, immunotherapy has made breakthroughs in the field of malignant tumors, and more and more novel immune checkpoint inhibitors have been developed, revolutionizing the first-line, second-line and post-line treatment options for malignant tumors. Tislelizumab is a domestically developed inhibitor of programmed death-1 (PD-1). The drug has shown good antitumor potential and safety in classical Hodgkin's lymphoma, uroepithelial carcinoma, non-small cell lung cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma and gastric cancer/gastroesophageal junction carcinoma. In this review, the structure and mechanism of action, pharmacodynamics and pharmacokinetics, clinical research and adverse reactions of tislelizumab are reviewed to provide reference for clinical application.
Medical Supports to Tibet & Xinjiang
Analysis of Disease Spectrum of Testicular and Adnexal Lesions in Tibetan Population of Tibet
LUO Hanhuan, WANG Qian, DA Zhen, DUOBU La, CIREN Quzhen, HUO Zhen
2022, 13(4): 687-692. doi: 10.12290/xhyxzz.2021-0349
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Abstract:
  Objective  To summarize and analyze the disease spectrum of testicular and adnexal lesions in Tibetan patients in Tibet Autonomous Region.  Methods  The relevant data of all Tibetan patients with testicular and adnexal lesions diagnosed by pathology in Tibet Autonomous Region People's Hospital from January 2012 to March 2021 were collected retrospectively, including age, clinical manifestations, general manifestations of diseased tissues, and diagnostic results.  Results  There were 317 cases of testicular and adnexal lesions diagnosed by pathology, with the mean age of (38.72±19.74) years and the clinical manifestations mainly characterized by swelling and pain in the scrotum area (88.01%, 279/317). There were 85 cases of neoplastic diseases (26.81%, 85/317), in which malignant tumors accounted for 96.47%, with an average age of (38.09±14.52) years. There were 232 cases of non-neoplastic diseases (73.19%, 232/317), with an average age of (38.94±21.36) years. The gross manifestations of the lesions were as follows: the lesions of the neoplastic disease were 2-17 cm in diameter and were nodular or lobulated, the sections were solid or cystic-solid, and bleeding or necrosis could be seen in some areas; the lesions of non-neoplastic diseases were 0.6-8 cm in diameter and were mostly cystic with smooth cystic wall, and some lesions were solid nodules. Among neoplastic diseases, the tumor types were germ cell tumors (88.24%, 75/85), lymphohematopoietic tumors (4.71%, 4/85), mesenchymal tumors (4.71%, 4/85), leyding cell tumor(1.18%, 1/85), and papillary cystadenoma of the epididymis (1.18%, 1/85). Among germ cell tumors, seminoma were mainly type (66.67%, 50/75), followed by mixed germ cell tumor (14.67%, 11/75), embryonal carcinoma (12.00%, 9/75). All 4 cases of lymphohematopoietic tumor were diffuse large B-cell lymphoma. Among non-neoplastic diseases, hydrocele accounted for 56.03% (130/232), followed by inflammatory diseases (31.03%, 72/232) and testicular dysplasia (8.62%, 20/232), testicular torsion/infarction (3.88%, 9/232) and testicular adnexal cyst (0.43%, 1/232) accounted for a lower proportion. Testicular and epididymal tuberculosis (77.78%, 56/72) was the main type of inflammatory diseases.  Conclusions  Testicular and adnexal lesions in Tibetan people maybe more common among middle-aged people, with a complex and diverse disease spectrum, dominated by non-neoplastic disease. Hydrocele and tuberculosis are the most common non-neoplastic diseases. About 1/4 of the lesions are neoplastic diseases, and germ cell tumors are the dominant type.
MDT Case from PUMCH
Menstrual Disturbance, Edema of the Lower Limb and Acute Kidney Injury: A Rare Event of "Tumor Embolism" in Malignant Pelvic Tumor
GAO Xuehan, DI Xiao, FENG Fengzhi, ZHOU Na, ZHOU Weixun, LI Yuan, ZHU A'fang, HE Lei, QIAO Yi, SUN Mengqing, JIANG Xin, CHEN Yuexin, ZHENG Yuehong
2022, 13(4): 693-701. doi: 10.12290/xhyxzz.2021-0640
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Abstract:
Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine malignancy, accounting for less than 1% of all uterine malignancies. And there is no literature reporting about acute obstruction of inferior vena cava (IVC) caused by LG-ESS. In November 2021, A patient diagnosed with LG-ESS was admitted to our hospital, presenting with pitting edema of the right lower limb, menstrual disturbance, nausea, oliguria andincreased serum creatinine. Imaging suggested complete obstruction of IVC cava. This difficult case was successfully treated with staging surgery combined with endocrine therapy by a cooperative multidisciplinary team (MDT). The important role of MDT in the treatment process of such a difficult and serious case was demonstrated.
Teaching and Research
Exploration on the Training and Evaluation Mode of Clinical Postdoctoral Trainees in Radiology Department Based on Core Competence
CHEN Yu, XUE Huadan, ZHANG Daming, SHI Yuxi, SUN Hao, DING Ning, SU Tong, ZHU Huijuan, JIN Zhengyu, ZHANG Shuyang
2022, 13(4): 702-708. doi: 10.12290/xhyxzz.2021-0800
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Abstract:
The postdoctoral training program of clinical medicine explores a new form of medical elite education in China. As one of the first pilot departments of the clinical postdoctoral program of Peking Union Medical College Hospital, Radiology Department has established a clinical postdoctoral training system and optimized the evaluation and feedback system, taking into account the work characteristics and based on the six core competence objectives proposed by the consensus of the resident core competence framework of China Resident Training Elite Teaching Hospital Alliance. This program has thus become a post-graduation education project for training Chinese compound radiology elites, which can in turn provide reference for the implementation of similar projects in other teaching hospitals.
Policy and Regulation
Research on 58 Crimes of Illegally Organizing Blood Trade in Beijing
ZHAO Zhiquan
2022, 13(4): 709-712. doi: 10.12290/xhyxzz.2021-0052
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Abstract:
  Objective  Summarize the characteristics of criminal cases of illegal blood trade, and provide a reference for combating such incidents.  Methods  On November 18, 2020, the official website of Judgmental Documents of China was searched for judgmental documents about the crime of illegal organization of blood trade from 2013 to 2019 in Beijing with the keywords "Beijing" and "crime of blood trade by illegal organizations". The case data involved in the judgmental documents, including the criminal's personal information, judgment results, time and location of the crime, etc., were classified and summarized.  Results  A total of 58 judgmental documents were retrieved about the crime of illegally organizing blood trade, involving 58 cases, 115 criminals, 638 people, and 13 600 mL of illegally traded blood. Among the 115 criminals, 99 were male (86.1%) and 16 were female (13.9%); the ages were 18 to 61 years old (with an average age of 33 years). Ten were sentenced to detention, suspended sentence and fined; 8 were sentenced to fixed-term imprisonment, suspended sentence and fined; 97 were sentenced to fixed-term imprisonment and fined. From 2013 to 2019, the frequency of blood-trading crime by illegal organizations in Beijing showed a trend of fluctuating and declining. Among them, there was a big rebound in 2015, with the highest frequency of cases (34.5%, 20/58), and the lowest frequency was in 2018 (0). Based on the statistics on the month in which the crime of blood trade happened, it was found that the frequency of cases was the highest (32.8%, 19/58) in January, followed by June (15.5%, 9/58) and there were no illegal blood trade in April and May. The 58 cases of illegal blood trade involved 8 urban areas in Beijing, of which Haidian District accounted for the highest proportion (62.1%, 36/58), followed by Fangshan District (22.4%, 13/58). About 55.2% (32/58) of the cases took place in hospitals, and 44.8% (26/58) in blood centers (including blood collection stations).  Conclusions  From 2013 to 2019, the crime of blood trade by illegal organizations in Beijing showed a general downward trend. Summarizing the characteristics of the crime of blood trade by illegal organizations is helpful for accurate prevention of crime.
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