Li Cheng-Xu, Fei Wen-Min, Shen Chang-Bing, Wang Zi-Yi, Jing Yan, Meng Ru-Song, Cui Yong
Chinese Medical JournalVol.133,No.172020
DOI: 10.1097/CM9.0000000000001002
Abstract
Background:
Youzhi artificial intelligence (AI) software is the AI-assisted decision-making system for diagnosing skin tumors. The high diagnostic accuracy of Youzhi AI software was previously validated in specific datasets. The objective of this study was to compare the performance of diagnostic capacity between Youzhi AI software and dermatologists in real-world clinical settings.
Methods:
A total of 106 patients who underwent skin tumor resection in the Dermatology Department of China-Japan Friendship Hospital from July 2017 to June 2019 and were confirmed as skin tumors by pathological biopsy were selected. Dermoscopy and clinical images of 106 patients were diagnosed by Youzhi AI software and dermatologists at different dermoscopy diagnostic levels. The primary outcome was to compare the diagnostic accuracy of the Youzhi AI software with that of dermatologists and that measured in the laboratory using specific data sets. The secondary results included the sensitivity, specificity, positive predictive value, negative predictive value, F-measure, and Matthews correlation coefficient of Youzhi AI software in the real-world.
Results:
The diagnostic accuracy of Youzhi AI software in real-world clinical settings was lower than that of the laboratory data (P < 0.001). The output result of Youzhi AI software has good stability after several tests. Youzhi AI software diagnosed benign and malignant diseases by recognizing dermoscopic images and diagnosed disease types with higher diagnostic accuracy than by recognizing clinical images (P = 0.008, P = 0.016, respectively). Compared with dermatologists, Youzhi AI software was more accurate in the diagnosis of skin tumor types through the recognition of dermoscopic images (P = 0.01). By evaluating the diagnostic performance of dermatologists under different modes, the diagnostic accuracy of dermatologists in diagnosing disease types by matching dermoscopic and clinical images was significantly higher than that by identifying dermoscopic and clinical images in random sequence (P = 0.022). The diagnostic accuracy of dermatologists in the diagnosis of benign and malignant diseases by recognizing dermoscopic images was significantly higher than that by recognizing clinical images (P = 0.010).
Conclusion:
The diagnostic accuracy of Youzhi AI software for skin tumors in real-world clinical settings was not as high as that of using special data sets in the laboratory. However, there was no significant difference between the diagnostic capacity of Youzhi AI software and the average diagnostic capacity of dermatologists. It can provide assistant diagnostic decisions for dermatologists in the current state.
Wang Shi-Qi, Zhang Xin-Yuan, Liu Jie, Tao Cui, Zhu Chen-Yu, Shu Chang, Xu Tao, Jin Hong-Zhong
Chinese Medical JournalVol.133,No.172020
DOI: 10.1097/CM9.0000000000001023
Abstract
Background:
Diagnoses of Skin diseases are frequently delayed in China due to lack of dermatologists. A deep learning-based diagnosis supporting system can facilitate pre-screening patients to prioritize dermatologists’ efforts. We aimed to evaluate the classification sensitivity and specificity of deep learning models to classify skin tumors and psoriasis for Chinese population with a modest number of dermoscopic images.
Methods:
We developed a convolutional neural network (CNN) based on two datasets from a consecutive series of patients who underwent the dermoscopy in the clinic of the Department of Dermatology, Peking Union Medical College Hospital, between 2016 and 2018, prospectively. In order to evaluate the feasibility of the algorithm, we used two datasets. Dataset I consisted of 7192 dermoscopic images for a multi-class model to differentiate three most common skin tumors and other diseases. Dataset II consisted of 3115 dermoscopic images for a two-class model to classify psoriasis from other inflammatory diseases. We compared the performance of CNN with 164 dermatologists in a reader study with 130 dermoscopic images. The experts’ consensus was used as the reference standard except for the cases of basal cell carcinoma (BCC), which were all confirmed by histopathology.
Results:
The accuracies of multi-class and two-class models were 81.49% ± 0.88% and 77.02% ± 1.81%, respectively. In the reader study, for the multi-class tasks, the diagnosis sensitivity and specificity of 164 dermatologists were 0.770 and 0.962 for BCC, 0.807 and 0.897 for melanocytic nevus, 0.624 and 0.976 for seborrheic keratosis, 0.939 and 0.875 for the "others" group, respectively; the diagnosis sensitivity and specificity of multi-class CNN were 0.800 and 1.000 for BCC, 0.800 and 0.840 for melanocytic nevus, 0.850 and 0.940 for seborrheic keratosis, 0.750 and 0.940 for the "others" group, respectively. For the two-class tasks, the sensitivity and specificity of dermatologists and CNN for classifying psoriasis were 0.872 and 0.838, 1.000 and 0.605, respectively. Both the dermatologists and CNN achieved at least moderate consistency with the reference standard, and there was no significant difference in Kappa coefficients between them (P > 0.05).
Conclusions:
The performance of CNN developed with relatively modest number of dermoscopic images of skin tumors and psoriasis for Chinese population is comparable with 164 dermatologists. These two models could be used for screening in patients suspected with skin tumors and psoriasis respectively in primary care hospital.
Yang Yi-Fan, Feng Ling, Shi Qian, Ma Hong-Zhi, He Shi-Zhi, Hou Li-Zhen, Wang Ru, Fang Ju-Gao
Chinese Medical JournalVol.133,No.172020
DOI: 10.1097/CM9.0000000000000933
Abstract
Background:
Long non-coding RNAs (lncRNAs) play key roles in human cancers. In our previous study, we demonstrated that lncRNA FKBP prolyl isomerase 9 pseudogene 1 (FKBP9P1) was highly expressed in head and neck squamous cell cancer (HNSCC) tissues. However, its functional significance remains poorly understood. In the present study, we identify the role and potential molecular biologic mechanisms of FKBP9P1 in HNSCC.
Methods:
Quantitative real-time polymerase chain reaction was used to detect the expression of FKBP9P1 in HNSCC tissues, matched adjacent normal tissues, human HNSCC cells (FaDu, Cal-27, SCC4, and SCC9), and human immortalized keratinocytes cell HaCaT (normal control). Cal-27 and SCC9 cells were transfected with sh-FKBP9P1-1, sh-FKBP9P1-2, and normal control (sh-NC) lentivirus. Cell counting kit-8 assay, colony formation assay, wound healing assay, and trans-well assay were used to explore the biologic function of FKBP9P1 in HNSCC cells. Furthermore, western blotting was used to determine the mechanism of FKBP9P1 in HNSCC progression. Chi-squared test was performed to assess the clinical significance among FKBP9P1 high-expression and low-expression groups. Survival analyses were performed using the Kaplan-Meier method and assessed using the log-rank test. The comparison between two groups was analyzed by Student t test, and comparisons among multiple samples were performed by one-way analysis of variance and a Bonferroni post hoc test.
Results:
FKBP9P1 expression was significantly up-regulated in HNSCC tissues (tumor vs. normal, 1.914 vs. 0.957, t = 7.746, P < 0.001) and cell lines (P < 0.01 in all HNSCC cell lines). Besides, the median FKBP9P1 expression of HNSCC tissues (1.677) was considered as the threshold. High FKBP9P1 level was correlated with advanced T stage (P = 0.022), advanced N stage (P = 0.036), advanced clinical stage (P = 0.018), and poor prognosis of HNSCC patients (overall survival, P = 0.002 and disease-free survival, P < 0.001). Knockdown of FKBP9P1 led to marked repression in proliferation, migration, and invasion of HNSCC cells in vitro (P all < 0.01). Mechanistically, silencing FKBP9P1 was observed to restrain the PI3K/AKT signaling pathway.
Conclusions:
Silencing lncRNA FKBP9P1 represses HNSCC progression and inhibits PI3K/AKT (phosphatidylinositol 3 kinase/AKT Serine/Threonine Kinase) signaling in vitro. Therefore, FKBP9P1 could be a potential new target for the diagnosis and treatment of HNSCC patients.
Tang Si-Qi, Mao Yan-Ping, Xu Cheng, Guo Rui, Li Wen-Fei, Tang Ling-Long, Sun Ying, Ma Jun
Chinese Medical JournalVol.133,No.172020
DOI: 10.1097/CM9.0000000000000978
Abstract
Background:
The classification criteria and staging groups for nasopharyngeal carcinoma described in the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system have been revised over time. This study assessed the proportion of patients whose staging and treatment strategy have changed due to revisions of the UICC/AJCC staging system over the past 10 years (ie, from the sixth edition to the eighth edition), to provide information for further refinement.
Methods:
We retrospectively reviewed 1901 patients with non-metastatic nasopharyngeal carcinoma treated in our cancer center between November 2009 and June 2012. The Akaike information criterion and Harrell concordance index were applied to evaluate the performance of the staging system.
Results:
In total, 25 (1.3%) of the 1901 patients who were staged as T2a according to the sixth edition system were downgraded to T1 in the eighth edition; 430 (22.6%) staged as N0 in the sixth edition were upgraded to N1 in the eighth edition; 106 (5.6%) staged as N1/2 in the sixth edition were upgraded to N3 in the eighth edition. In addition, 51 (2.7%) and 25 (1.3%) of the study population were upstaged from stage I to stage II and stage II to stage IVa, respectively; 10 (0.5%) was downgraded from stage II to stage I. The survival curves of adjacent N categories and staging groups defined by eighth classification system were well-separated. However, there was no significant difference in the locoregional failure-free survival (P = 0.730) and disease-free survival (P = 0.690) rates between the T2 and T3 categories in the eighth edition classification system.
Conclusions:
Modifications to the tumor-node-metastasis staging system over the past 10 years have resulted in N classification changes in numerous cases. Although the eighth edition tumor-node-metastasis staging system better predicts survival outcomes, the T classification could be simplified in future revisions.
Jin Xiao-Ying, Li Chao, Xu Wen, Liu Liu, Wei Min-Ling, Fei Hai-Yi, Li Jing, Zhou Feng, Zhang Song-Ying
Chinese Medical JournalVol.133,No.172020
DOI: 10.1097/CM9.0000000000001058
Abstract
Background:
Ectopic pregnancy (EP) is a common complication in women undergoing assisted reproductive treatment, but the underlying causes for this remain unclear. This study aimed to explore factors affecting the incidence of EP in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).
Methods:
This was a retrospective study on the incidence of EP in IVF/ICSI cycles between January 1, 2013 and December 31, 2017. Patient age, infertility diagnosis (tubal factor or not), primary or secondary infertility, type of cycle (frozen-thawed or fresh), type of embryo(s) transferred (cleavage embryo or blastocyst), number of embryos transferred (one, two, or three), previous history of EP, and endometrial combined thickness were analyzed to explore their relationships with the incidence of EP. Based on clinical typing results, the patients were divided into an EP group or a non-EP group. Categorical variables were analyzed using Chi-squared test or Fisher exact test. Logistic regression analysis was performed to explore their associations with the incidence of EP.
Results:
The percentage of patients with primary infertility in EP group was significantly lower than that in non-EP group (31.3% vs. 46.7%, χ2 = 26.032, P < 0.001). The percentage of patients with tubal infertility in EP group was also significantly higher than that in non-EP group (89.2% vs. 63.6%, χ2 = 77.410, P < 0.001). The percentages of patients with transfer of cleavage-stage embryo or blastocyst (91.4% vs. 84.4%, χ2 = 10.132, P = 0.001) and different endometrial combined thickness (ECT) (χ2 = 18.373, P < 0.001) differed significantly between EP and non-EP groups. For patients who had a previous history of one to four EPs, the percentage of patients undergoing transfer of a cleavage-stage embryo was significantly higher in EP group than that in non-EP group (92.2% vs. 77.6%, χ2 = 13.737, P < 0.001). In multivariate logistic regression analysis, tubal infertility was strongly associated with EP (adjusted odds ratio: 3.995, 95% confidence interval: 2.706-5.897, P < 0.001).
Conclusions:
In IVF/ICSI cycles, transfer of a blastocyst-stage embryo, especially for patients with a previous history of EP, reduced the rate of EP. Tubal infertility was strongly associated with EP.
Jing Hao, Tian Yuan, Tang Yu, Wang Shu-Lian, Jin Jing, Song Yong-Wen, Liu Yue-Ping, Fang Hui, Chen Bo, Qi Shu-Nan, et al.
Chinese Medical JournalVol.133,No.172020
DOI: 10.1097/CM9.0000000000001025
Abstract
Background:
The effects of oral contrast agents (OCAs) on dosimetry have not been studied in detail. Therefore, this study aimed to examine the influence of OCAs on dose calculation in volumetric-modulated arc therapy plans for rectal cancer.
Methods:
From 2008 to 2016, computed tomography (CT) images were obtained from 33 rectal cancer patients administered OCA with or without intravenous contrast agent (ICA) and 14 patients who received no contrast agent. CT numbers of organs at risk were recorded and converted to electronic densities. Volumetric-modulated arc therapy plans were designed before and after the original densities were replaced with non-enhanced densities. Doses to the planned target volume (PTV) and organs at risk were compared between the plans.
Results:
OCA significantly increased the mean and maximum densities of the bowels, while the effects of ICA on these parameters depended on the blood supply of the organs. With OCA, the actual doses for PTV were significantly higher than planned and doses to the bowel increased significantly although moderately. However, the increase in the volume receiving a high-range doses was substantial (the absolute change of intestine volume receiving ≥52 Gy: 1.46 [0.05-3.99, cubic centimeter range: -6.74 to 128.12], the absolute change of colon volume receiving ≥50 Gy: 0.34 [0.01-1.53 cc, range: -0.08 to 3.80 cc]. Dose changes due to ICA were insignificant. Pearson correlation showed that dose changes were significantly correlated with a high intestinal volume within or near the PTV (ρ > 0.5, P < 0.05) and with the density of enhanced intestine (ρ > 0.3, P < 0.05).
Conclusions:
Contrast agents applied in simulation cause underestimation of doses in actual treatment. The overdose due to ICA was slight, while that due to OCA was moderate. The bowel volume receiving ≥50Gy was dramatically increased when OCA within the bowel was absent. Physicians should be aware of these issues if the original plan is barely within clinical tolerance or if a considerable volume of enhanced intestine is within or near the PTV.
Kang Xi, Guo Ting, Liu Lyu, Ding Shui-Zi, Lei Cheng, Luo Hong
Chinese Medical JournalVol.133,No.172020
DOI: 10.1097/CM9.0000000000000858
Abstract
Background:
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Genome-wide association studies in non-Asian population revealed a link between COPD and mutations in the PTCH1 gene encoding Patched1, a receptor in the Hedgehog signaling pathway important for lung morphogenesis and pulmonary function. The aim of this study was to investigate the association between PTCH1 polymorphisms and the COPD risk in the Chinese Han population.
Methods:
We performed a case-control study including 296 patients with COPD and 300 healthy individuals. Single-nucleotide polymorphisms in the PTCH1 gene were identified and genotyped based on the linkage disequilibrium analysis in all participants. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression analysis after adjustment for age, gender, and smoking.
Results:
In total, 28 single-nucleotide polymorphisms were identified in patients with COPD. Among them, "A" allele of rs28491365 (OR: 1.388, 95% CI: 1.055-1.827, P = 0.018), and "G" alleles of rs10512248 (OR: 1.299, 95% CI: 1.021-1.653, P = 0.033) and rs28705285 (OR: 1.359, 95% CI: 1.024-1.803, P = 0.033; respectively) were significantly associated with an increased COPD risk. Genetic model analysis revealed that the "T/T" genotype of rs34695652 was associated with a decreased COPD risk under the recessive model (OR: 0.490, 95% CI: 0.270-0.880, P = 0.010), whereas rs28504650/rs10512248 haplotype CG was significantly associated with an increased COPD risk after adjustment for age, gender, and smoking status (OR: 6.364, 95% CI: 1.220-33.292, P = 0.028).
Conclusions:
The study provides a new insight into the role of PTCH1 polymorphisms in the susceptibility to COPD in the Chinese Han population.
Wang Bin-Shuai, Li You-Zhao, Fang Yang-Yi, Zhang Shu-Dong, Ma Lu-Lin
Chinese Medical JournalVol.133,No.172020
DOI: 10.1097/CM9.0000000000000828
Abstract
Background:
Renal cell carcinoma (RCC) has the propensity to lead to venous tumor thrombus (VTT). Nephrectomy with tumor thrombectomy is an effective treatment option but is a technically challenging surgical procedure that is accompanied by a high rate of complications. The aims of this study were to investigate pre-operative imaging parameters for the assessment of inferior vena cava (IVC) wall invasion due to a tumor thrombus in patients with RCC and to identify predictors from the intra-operative findings.
Methods:
Clinical and imaging data were collected from 110 patients who underwent nephrectomy with IVC tumor thrombectomy (levels I-IV) for RCC and IVC tumor thrombus at the Peking University Third Hospital between May 2015 and March 2018. Univariable and multivariable logistic regression and receiver operating characteristic curves were used to assess the correlations between pre-operative imaging features and intra-operative macroscopic invasions of the IVC wall by tumor thrombus.
Results:
Among the 110 patients, 41 underwent partial or segmental resection of IVC. There were univariate associations of pre-operative imaging parameters that could be used to predict the need for IVC resection, including those of the Mayo classification, maximum anterior-posterior (AP) diameter of the renal vein at the renal vein ostium (RVo), maximum AP diameter of the VTT at the RVo and IVC occlusion. For the multivariable analysis, the AP diameter of the VTT at the RVo and IVC occlusion were associated with a significantly increased risk of invasion of the IVC wall by tumor thrombus. The optimum imaging thresholds included an AP diameter of the VTT at the RVo larger than 17.0 mm and the presence of IVC occlusion, with which we predicted invasions of the IVC wall requiring IVC resection. The probabilities of intra-operative IVC resection for patients without both independent factors, with an AP diameter of the VTT at the RVo larger than 17.0 mm, with IVC occlusion, and with both concurrent factors were 5%, 23%, 56%, and 66%, respectively.
Conclusion:
An increase in the AP VTT diameter at the RVo and the presence of complete occlusion of the IVC are independent risk factors for a high probability of IVC wall invasion by tumor thrombus.
Zhao Yan-Hui, Wang Zhi, Zhang Na, Cui Tao, Zhang Yan-Hui
Chinese Medical JournalVol.133,No.172020
DOI: 10.1097/CM9.0000000000000867
Abstract
Background:
Circular RNA ciRS-7 has been reported to be involved in the progression of various cancers. However, ciRS-7 expression and its role in clear cell renal cell carcinoma (ccRCC) progression remains unclear. This study aimed to investigate the effect of ciRS-7 expression on ccRCC and the related signaling pathway.
Methods:
ciRS-7 expression was analyzed using quantitative reverse transcription polymerase chain reaction in 87 pairs of ccRCC and matched adjacent normal tissues. The role of ciRS-7 in ccRCC cell proliferation and invasion was determined using the cell counting kit-8 and invasion assays, respectively. Potential mechanisms underlying the role of ciRS-7 in promoting ccRCC progression were explored by Western blotting. The relationship between the expression of ciRS-7 and features of ccRCC was analyzed by the Chi-square test and progression-free survival was determined using a Kaplan-Meier plot.
Results:
ciRS-7 was overexpressed in ccRCC tissues compared with that in matched adjacent normal tissues. In addition, ciRS-7 up-regulation was closely associated with tumor diameter (P = 0.050), clinical stage (P = 0.009), and distant metastasis (P = 0.007). ciRS-7 knockdown in 786O and 769P cells markedly inhibited their proliferative and invasive abilities. In addition, ciRS-7 inhibition reduced phosphorylated epidermal growth factor receptor (p-EGFR) and phosphorylated serine/threonine kinase (p-Akt) levels.
Conclusions:
ciRS-7 up-regulation could promote ccRCC cell proliferation and invasion, which may be related with the EGFR/Akt signaling pathway. ciRS-7 might be a potential ccRCC therapeutic target.
Zhang Yan-Ru, Yu Zhen, Xiong Wen-Jie, Liu Xu-Xiang, Liu Hui-Min, Cui Rui, Wang Qi, Chen Wen-Ming, Qiu Lu-Gui, Yi Shu-Hua
Chinese Medical JournalVol.133,No.172020
DOI: 10.1097/CM9.0000000000000999
Abstract
Background:
TOSO, also named Fas inhibitory molecule 3 (FAIM3), has recently been identified as an immunoglobulin M (IgM) Fc receptor (FcμR). Previous studies have shown that TOSO is specifically over-expressed in chronic lymphocytic leukemia (CLL). However, the functions of TOSO in CLL remain unknown. The B-cell receptor (BCR) signaling pathway has been reported to be constitutively activated in CLL. Here, we aimed to investigate the functions of TOSO in the BCR signaling pathway and the pathogenesis of CLL.
Methods:
We over-expressed TOSO in B-cell lymphoma cell lines (Granta-519 and Z138) by lentiviral transduction and knocked down TOSO by siRNA in primary CLL cells. The over-expression and knockdown of TOSO were confirmed at the RNA level by polymerase chain reaction and protein level by Western blotting. Co-immunoprecipitation with TOSO antibody followed by liquid chromatography coupled with tandem mass spectrometry (IP/LCMS) was used to identify TOSO interacting proteins. Western blotting was performed to detect the activation status of BCR signaling pathways as well as B-cell lymphoma 2 (BCL-2). Flow cytometry was used to examine the apoptosis of TOSO-over-expressing B lymphoma cell lines and TOSO-down-regulated CLL cells via the staining of Annexin V and 7-AAD. One-way analyses of variance were used for intergroup comparisons, while independent samples t tests were used for two-sample comparisons.
Results:
From IP/LCMS, we identified spleen tyrosine kinase (SYK) as a crucial candidate of TOSO-interacting protein and confirmed it by co-immunoprecipitation. After stimulation with anti-IgM, TOSO over-expression increased the phosphorylation of SYK, and subsequently activated the BCR signaling pathway, which could be reversed by a SYK inhibitor. TOSO knockdown in primary CLL cells resulted in reduced SYK phosphorylation as well as attenuated BCR signaling pathway. The apoptosis rates of the Granta-519 and Z138 cells expressing TOSO were (8.46 ± 2.90)% and (4.20 ± 1.21)%, respectively, significantly lower than the rates of the control groups, which were (25.20 ± 4.60)% and (19.72 ± 1.10)%, respectively (P < 0.05 for both). The apoptosis rate was reduced after knocking down TOSO in the primary CLL cells. In addition, we also found that TOSO down-regulation in primary cells from CLL patients led to decreased expression of BCL-2 as well as lower apoptosis, and vice versa in the cell line.
Conclusions:
TOSO might be involved in the pathogenesis of CLL by interacting with SYK, enhancing the BCR signaling pathway, and inducing apoptosis resistance.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has been changing for nearly 20 years. GOLD has moved from single assessment using spirometry to a more comprehensive assessment of chronic obstructive pulmonary disease using spirometry, symptoms and exacerbation history. And subsequently, a new assessment system for chronic obstructive pulmonary disease separated spirometric grades from the old assessment system, and classified patients only according to their symptoms and history of exacerbation. The distribution, clinical characteristics, treatment, and prognosis of the new subgroups were different from the old ones. In this review, we will present a brief profile of changes made to the disease assessment method of GOLD, based on the relevant existing literature.