1.Artificial intelligence-based analysis of tumor-infiltrating lymphocyte spatial distribution for colorectal cancer prognosis
Ming CAI ; Ke ZHAO ; Lin WU ; Yanqi HUANG ; Minning ZHAO ; Qingru HU ; Qicong CHEN ; Su YAO ; Zhenhui LI ; Xinjuan FAN ; Zaiyi LIU
Chinese Medical Journal 2024;137(4):421-430
Background::Artificial intelligence (AI) technology represented by deep learning has made remarkable achievements in digital pathology, enhancing the accuracy and reliability of diagnosis and prognosis evaluation. The spatial distribution of CD3 + and CD8 + T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer (CRC). This study aimed to investigate CD3 CT (CD3 + T cells density in the core of the tumor [CT]) prognostic ability in patients with CRC by using AI technology. Methods::The study involved the enrollment of 492 patients from two distinct medical centers, with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort. To facilitate tissue segmentation and T-cells quantification in whole-slide images (WSIs), a fully automated workflow based on deep learning was devised. Upon the completion of tissue segmentation and subsequent cell segmentation, a comprehensive analysis was conducted.Results::The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3 CT and CD3-CD8 (the combination of CD3 + and CD8 + T cells density within the CT and invasive margin) in predicting mortality (C-index in training cohort: 0.65 vs. 0.64; validation cohort: 0.69 vs. 0.69). The CD3 CT was confirmed as an independent prognostic factor, with high CD3 CT density associated with increased overall survival (OS) in the training cohort (hazard ratio [HR] = 0.22, 95% confidence interval [CI]: 0.12–0.38, P <0.001) and validation cohort (HR = 0.21, 95% CI: 0.05–0.92, P = 0.037). Conclusions::We quantify the spatial distribution of CD3 + and CD8 + T cells within tissue regions in WSIs using AI technology. The CD3 CT confirmed as a stage-independent predictor for OS in CRC patients. Moreover, CD3 CT shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.
2.Epidemiological characteristics of varicella in schools of Yunnan Province in 2018 - 2020
Rongbing ZHANG ; Jin HONG ; Lihua CHEN ; Xia PENG ; Jibo HE ; Zhenhui LI ; Yan LIN ; Yucheng JIA
Journal of Public Health and Preventive Medicine 2023;34(4):55-58
Objective To analyze the epidemiological characteristics of school varicella and varicella public health emergency event (PHEE) in Yunnan Province, and to provide a scientific basis for the prevention and control of varicella in schools. Methods The descriptive epidemiological method was used to analyze the reported PHEE of varicella in students and varicella in schools in Yunnan Province from 2018 to 2020. Results From 2018 to 2020, a total of 69,391 cases of varicella were reported in students in Yunnan Province, accounting for 71.48% (69 391 / 97 080) of the total cases in the province, and the annual average reported incidence rate was 255.56/100 000 (69 391/27.1522 million). The time distribution of the incidence showed double peaks, which were from May to July (26.48%) and October to January of the following year (53.88%). The incidence rates of different schools from high to low were 301.74/100 000 for primary schools (34 816/11.538 3 million), 250.43/100 000 for kindergarten (11 526/4.6024 million), 202.74/100 000 for middle school (16 779/8.276 1 million), and 119.07/100 000 for others (3 257/2.735 4 million). The age distribution was mainly concentrated in 5-9 years old, accounting for 39.81% (27 625/69 391). Varicella PHEE accounted for 25.64% (180/702)of the province's PHEE in the same period, school varicella PHEE accounted for 100% of varicella PHEE, and the attack rate was 3.38% (6 566/194 260). The sources of reported varicella PHEE were hospitals 45.40% (58/123), epidemic analysis 36.78% (44/123), schools 13.22% (15/123), and others 4.60% (6/123). Conclusion The incidence of varicella in schools in Yunnan Province is high, which is harmful to students. PHEE reported in rural schools are relatively lagging behind. On the basis of doing two doses of varicella vaccination, emergency prevention should be focused on epidemic seasons, lower grade schools and rural schools. The source of infection shall be controlled and managed in time to prevent the outbreak of the epidemic. It is recommended that varicella should be included in the management of Class C infectious diseases.
3.Automated quantified tumor-stroma ratio predicts neoadjuvant chemotherapy re-sponse in gastric cancer
Wentao QIU ; Zhenhui LI ; Yiping JIAO ; Xiangxue WANG ; Shenyan ZHANG ; Lin WU ; Jun XU
Chinese Journal of Clinical Oncology 2023;50(23):1203-1210
Objective:The tumor-stroma ratio(TSR)is considered an independent prognostic factor for gastric cancer.Traditionally,TSR as-sessments have relied on the visual evaluation of surgical specimens,which is a method that lacks objectivity.This study was conducted to investigate whether the TSR in preoperative biopsy specimens can be automatically quantified using deep learning methods and whether the TSR value can be used to predict the efficacy of neoadjuvant chemotherapy(NAC)in patients with gastric cancer.Methods:In total,148 preoperative biopsy slides and 43 surgical resection slides from patients with gastric cancer who underwent NAC treatment at Yunnan Can-cer Hospital between March 2013 and March 2020 were used in the study.Tumor region segmentation and epithelial-stromal segmentation models were developed.The surgical resection slides were used to trained and evaluate the model,and the biopsy slides were used to test their predictive abilities.The TSR values were determined on the basis of the intersection of predictions from both models.The postoperat-ive pathological tumor regression grade(TRG)was used to categorize patients into good responders(TRG 0-1)and poor responders(TRG 2-3).Univariate and multivariate Logistic regression analyses were conducted to determine the correlation between the TSR value and the ef-ficacy of NAC in gastric cancer.Results:The intersection over union(IOU)value was 0.94 for the tumor tissue segmentation model and 0.88 for the epithelial-stromal segmentation model.Using cutoff values of 44.93%and 70.22%,patients were classified into low,intermediate,and high TSR groups.The proportion of good responders was significantly different among these groups(P<0.05).Multivariate Logistic re-gression analysis indicated that the TSR was an independent predictor of NAC response in gastric cancer(OR=0.10,95%CI:0.03-0.32).When the TSR three-category classification was added as a predictor of treatment response alongside conventional clinical information,the area under curve(AUC)increased from 0.71 to 0.85.Conclusions:This deep learning model is capable of automatically segmenting tumor,epi-thelial,and stromal regions based on pathological slides,accurately calculating TSR value,and predicting the efficacy of NAC on the basis of the automatically computed TSR values.
4.Epidemiological characteristics of brucellosis in Yunnan Province from 2008 to 2018 and prediction of grey GM (1, 1) model
Zhenhui LI ; Yanbo QI ; Ran LU ; Yan LIN ; Hui GUO ; Xia PENG
Chinese Journal of Endemiology 2021;40(3):225-229
Objective:To discover the epidemic characteristics of brucellosis in Yunnan Province, and establish a grey GM (1, 1) model to predict brucellosis in Yunnan Province.Methods:The epidemic data of incidence rate of brucellosis and population data in Yunnan Province from 2008 to 2018 were collected from China Disease Prevention and Control Information System and Yunnan Provincial Bureau of Statistics. Epidemiological characteristics (including time, area and population distributions) were analyzed, and grey GM (1, 1) model was used to predict the incidence of brucellosis in Yunnan Province in 2019 and 2020.Results:A total of 1 216 brucellosis cases were reported in Yunnan Province from 2008 to 2018, with an average annual incidence rate of 0.237 4/100 000, showing an increasing trend year by year (χ 2trend = 843.34, P<0.01). Case reports were mainly from March to September, accounted for 69.41% (844/1 216) of the total number of cases. The top five regions with case reports were Honghe (289 cases), Qujing (264 cases), Kunming (258 cases), Dali (160 cases), and Yuxi (134 cases), accounting for 90.87% (1 105/1 216). The occupation was mainly farmers, accounting for 79.03% (961/1 216). A grey GM (1, 1) model was established to predict the incidence of brucellosis in Yunnan Province in 2019 and 2020, which was 0.487 6/100 000 and 0.481 7/100 000, respectively. Conclusion:The incidence of brucellosis in Yunnan Province has increased compared with that of the past, and targeted prevention and control should be carried out in key areas and key populations, and the prediction results should be prospectively evaluated to gradually improve the establishment of brucellosis prediction model in Yunnan Province.
5.Construction of sepsis-associated competing endogenous RNA network based on Gene Expression Omnibus datasets and bioinformatic analysis
Junrong MO ; Zhenhui ZHANG ; Meiting CHEN ; Haifeng MAO ; Yongcheng ZHU ; Yanling LI ; Huilin JIANG ; Peiyi LIN ; Xiaohui CHEN
Chinese Critical Care Medicine 2021;33(4):427-432
Objective:To analyze the sepsis related long non-coding RNA (lncRNA) and mRNA expression profiles based on Gene Expression Omnibus (GEO) datasets and bioinformatic analysis, and to analyze the sepsis-associated competing endogenous RNA (ceRNA) network based on microRNA (miRNA) database.Methods:The sepsis-related lncRNA dataset was downloaded from the GEO database, and the differential expression analysis was conducted by Bioconductor on the sepsis dataset to obtain differentially expressed lncRNA (DElncRNA) and differentially expressed mRNA (DEmRNA), and cluster heat map was drawn. miRNA combined with DElncRNA were predicted by miRcode. mRNA targeted by miRNA was simultaneously met by three databases: TargetScan, miRDB, and mirTarBase. The interaction relationship of lncRNA-miRNA-mRNA was obtained. The regulatory network visualization software CytoScape was used to draw ceRNA networks. DEmRNA in the ceRNA networks were imported into the Search Tool for the Retrieval of Interacting Genes Database (STRING) online database to draw the protein-protein interaction (PPI) map. The gene ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEmRNA were performed.Results:Dataset GSE89376 and GSE145227 were found from GEO database. Difference analysis showed there were 14 DElncRNA and 359 DEmRNA in the elderly group of GSE89376; 8 DElncRNA and 153 DEmRNA in the adult group of GSE89376; 1 232 DElncRNA and 1 224 DEmRNA in the children group of GSE145227. Clustering heatmap showed that there were significant differences in the expression of lncRNA and mRNA between the sepsis group and the control group. The ceRNA networks were constructed with miRNA. Several DElncRNA and multiple DEmRNA participated in the ceRNA network of sepsis. The PPI diagram demonstrated that several genes encoding proteins interacted with each other and form a multi-node interaction network with multiple genes encoding proteins. Functional annotation and enrichment analysis demonstrated that there might be a crosstalk mechanism on functionally related genes such as nuclear receptor activity, ligand-activated transcription factor activity, and steroid hormone receptor activity, and played a role in the occurrence and development of diseases through forkhead box transcription factor O (FoxO) signaling pathway, Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway, p53 signaling pathway, and phosphateidylinositol 3-kinase (PI3K)/Akt signaling pathway.Conclusion:Through sepsis-related lncRNA-miRNA-mRNA ceRNA network and combining with KEGG pathway analysis, there were several lncRNA and mRNA participating in the ceRNA network related sepsis, which played an important role in several signal pathways.
7.Multi-slice Spiral CT Manifestations of Celiac Artery Compression of Median Arcuate Ligament
Wanjun LI ; Hai XU ; Xiupeng LIN ; Meixian WU ; Jialiang SHEN ; Zhenhui LAI
Chinese Journal of Medical Imaging 2016;24(1):40-42
Purpose Median arcuate ligament (MAL) compression is the most common reason for celiac artery stenosis or occlusion, celiac artery compression of asymptomatic MAL is often misdiagnosed. This study aims to evaluate the multi-slice spiral CT manifestations of the celiac artery compression of median arcuate ligament. Materials and Methods CT features of 26 patients with celiac artery compression of median arcuate ligament were retrospectively studied. Eleven cases were symptomatic and fifteen cases were asymptomatic. Results In 14 cases (53.8%), the location of compression was at the level of superior 1/3 of the L1 vertebral body. There was statistic difference in location of the origin of compression between the celiac artery narrowing group and the non-narrowing group (P<0.05). CT manifestations included: narrowing of the celiac artery were observed in 26 patients on sagittal reformatted images with hollow on the anterior wall; a characteristic hooked appearance was observed. Narrowed celiac artery on the transverse images was seen in 21 patients, and a soft-tissue band extending across the anterior aspect of artery in 12 of them. Poststenotic dilatation was revealed in 20 patients. Collateral circulation was seen in 8 patients. Conclusion Multi-slice spiral CT can be helpful in demonstrating the location of celiac artery compression of median arcuate ligament and tell the characteristic imaging features.
8.Osteoporosis-related factors in patients with knee osteoarthritis before total knee arthroplasty
Zhishuai REN ; Zhaojun CHENG ; Hejun SUN ; Zhenhui SUN ; Zijian CUI ; Lilong ZHANG ; Yongzhi LIN ; Renzan ZHANG ; Bing PENG ; Xueli ZHANG
Chinese Journal of Tissue Engineering Research 2016;20(22):3212-3218
BACKGROUND:The greatest risk of osteoporosis in total knee arthroplastyisperioperative and long-term periprosthetic fractures. However, limited by the traditional concept of osteoarthritis patientswhousualy not associated with osteoporosis, domestic clinical trials have not given enough attention to the osteoporosis before total knee arthroplasty.
OBJECTIVE:To analyze the osteoporosis and its relative factors in osteoarthritis patients before total knee arthroplasty.
METHODS:Data of 81 cases (81 knees) of knee osteoarthritiswhounderwenttotal knee arthroplasty in the Department of Joint Surgery of Tianjin People’s Hospital from January 2012 to November 2014 were retrospectively analyzed. They received lumbar spine and hip bone mineral density examination before surgery. The correlation of bone mineral density with age, body mass index, knee motion range,and knee deformity was analyzed before surgery. The independent risk factors for osteoporosis before replacement were analyzed.
RESULTS AND CONCLUSION:(1) Of 81 patients, there were normal bone mineral density in 25 cases (31%), osteopenia in 35 cases (43%),andosteoporosis in 21 cases (26%). Al 10 males had no osteoporosis and 21 in 71 female cases suffered osteoporosis (30%). Theincidence of osteoporosis in females was significantly higher than in male patients (P=0.046). (2) There was a linear correlation of bone mineral density with age and body mass index (correlation coefficientr=-0.230, 0.225). (3) The age of≥65 years and body mass index≥25 kg/m2were independent risk factors of osteoporosis before replacement (P< 0.05). (4) Patients with knee osteoarthritis had higher incidence of osteopenia and osteoporosis before total knee arthroplasty. The degree of osteoporosis was negatively correlated with age, but positively correlated with body mass index. The age of≥65 years and body mass index < 25 kg/m2were independent risk factors for preoperative osteoporosis. Thus, bone mineral density examination is essential for those patients before total knee arthroplasty.
9.The regulatory effect of miR-101 and miR-125a-5p on autophagy in lipopolysaccharide derived THP-1 macrophages
Jieling XU ; Zhenhui ZHANG ; Huilin JIANG ; Peiyi LIN ; Xiaohui CHEN
Chinese Critical Care Medicine 2016;28(4):334-338
Objective To investigate the role of micro-RNAs (miR-101 and miR-125a-5p) in autophagy of lipopolysaccharide (LPS) derived human THP-1 macrophages.Methods Human monocytic leukemia cell line THP-1 was cultured in vitro,and it was differentiated into macrophages after being induced with phorbol (50 μg/L) for 48 hours.THP-1 macrophages were stimulated with LPS in 0,250,500,1 000 μg/L respectively for 12 hours,miR-mimic was transfected into THP-1 macrophages as induced by Lipofectamine RNAiMAX,and the transfection efficiency of miRNA was determined with fluorescence microscopy.Enzyme linked immunosorbent assay (ELISA) was used to determine the levels of tumor necrosis factor-α (TNF-α) and monocyte chemotaxis protein-1 (MCP-1) in the supernatants of culture.Western Blot was used to detect the protein expressions of autophagy proteins ATG4D,Beclin1,and LC3 Ⅱ.The expression levels of miR-101 and miR-125a-5p were determined by quantitative reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results ① The releasing levels of TNF-α and MCP-1 induced by LPS with 250,500,1 000 μg/L were significantly increased as compared the cells without LPS stimulation [TNF-α (ng/L):1 336.1 ± 18.5,1 340.6±24.8,1 364.5± 14.9 vs.47.6±4.4;MCP-1 (ng/L):996.3 ±51.3,934.6±84.3,974.2±69.5 vs.21.3±6.5,all P < 0.01],but no significant differences were found among the three LPS stimulation groups.The protein expressions of ATG4D,Beclin1 and LC3 1Ⅱ were up-regulated in the presence of different LPS concentrations (0,250,500,1 000 μg/L) for 12 hours in THP-1 macrophages (when compared with the cells without LPS stimulation,t value of ATG4D was 8.103,38.410,52.020,P value was 0.015,0.001,< 0.001;t value of Beclin1 was 3.026,5.328,3.482,P value was 0.047,0.034,0.037;t value of LC3 Ⅱ was 3.836,6.200,4.665,P value was 0.018,0.003,0.010),and the optimal concentration was 500 tg/L LPS.When THP-1 macrophages were stimulated with 500 μg/L LPS for 12 hours,the expression levels of miR-101 and miR-125a-5p were down-regulated significantly as compared with the cells without LPS stimulation [miR-101 (2-△ △Ct):0.68 ± 0.08 vs.1.95 ±0.26,t =8.047,P =0.001;miR-125a-5p (2-△ △Ct):0.23 ± 0.06 vs.1.69± 0.42,t =5.975,P =0.004].② The higher transfection efficiency was showed under fluorescence microscope.Westem Blot results showed the protein expressions of ATG4D,Beclin1 and LC3 Ⅱ were down-regulated as induced by an over-expression of miR-101 or miR-125a-5p in THP-1 macrophages,and more obviously down regulated by co-transfected with miR-101 and miR-125a-5p (compared with negative control group,t value was 14.550,5.855,14.180,P value was 0.005,0.014,< 0.001).Conclusion miR-101 and miR-125a-5p can inhibit the autophagy in LPS challenged THP-1 macrophages,and the potential mechanism might be related to target regulation of ATG4D.
10.Changes of plasma intermedin during head-up tilt test in children with postural tachycardia syndrome and its significance.
Hongxia LI ; Ying LIAO ; Zhenhui HAN ; Yuli WANG ; Ping LIU ; Qingyou ZHANG ; Jing LIN ; Chaoshu TANG ; Hongfang JIN ; Junbao DU
Chinese Journal of Pediatrics 2015;53(5):375-378
OBJECTIVETo explore possible mechanisms of postural tachycardia syndrome (POTS) by comparing plasma intermedin (IMD) during head-up tilt test (HUTT) in children with POTS.
METHODThe study subjects were divided into two groups: POTS group and control group. The POTS group consisted of twenty-nine children (male 14, female 15) with POTS, the mean age (12.4 ±3.1) years old, admitted into Peking University First Hospital from November 2013 to June 2014. The control group consisted of 32 healthy children (male 17, female 15). Their mean age was (11.6±2.2) years old, who were confirmed as healthy by physical examination and HUTT. Finapres Medical System was used to continuously monitor heart rate and blood pressure during HUTT, and electrocadiogram was performed. Supine systolic and diastolic blood pressure, mean arterial pressure (MAP), ΔMAP (standing mean arterial pressure-supine MAP), supine heart rate and ΔHR (standing HR-supine HR) were compared between POTS group and control group. Sandwich immunoluminescence assay was used to test plasma IMD. The plasma IMD level was compared in supine between POTS and control group. The plasma IMD level in supine was compared with HUTT in POTS group.
RESULTNo significant differences were found in age, height, weight, supine systolic and diastolic blood pressure, MAP, ΔMAP and supine heart rate between POTS group and control group (P>0.05). ΔHR in POTS group was significantly higher than that of control group ((48±10) vs. (22±7) beats /min, t=9.797, P<0.05). The plasma IMD level in POTS group was lower than that of control group in supine position ((497±61)×10(-6) vs. (529±58)×10(-6) mg/L, t=2.117, P<0.05). But, it was higher during HUTT than supine IMD in POTS group ((537±57) ×10(-6) vs. (497±61)×10(-6) mg/L, t=-2.464, P<0.05). The plasma delta IMD level (HUTT vs. supine) was positively correlated with delta HR in POTS group (r=0.435, P<0.05).
CONCLUSIONThe excessively high heart rate during HUTT have a positive correlation with plasma IMD, which may play a role in the pathogenesis of POTS in children.


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