1.Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts
Cai XINJIA ; Zhang HEYU ; Wang YANJIN ; Zhang JIANYUN ; Li TIEJUN
International Journal of Oral Science 2024;16(2):349-358
Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence rate.OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome.Moreover,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts.Because of the different prognosis,differential diagnosis of several cysts can contribute to clinical management.We collected 519 cases,comprising a total of 2157 hematoxylin and eosin-stained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of OKC.The Inception_v3 neural network was utilized to train and test models developed from patch-level images.Finally,whole slide image-level AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms.The AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898-0.973)and prognosis(AUC=0.840,95%CI:0.751-0.930)of OKC.The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model.Furthermore,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the pathology.Here,we have developed the robust diagnostic and prognostic models for OKC.The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.
2.Transverse sinus blood flow characteristics of pulsatile tinnitus with dehiscent sigmoid plate based on 4D flow MRI
Chihang DAI ; Heyu DING ; Han LYU ; Xiaoyu QIU ; Xiaoshuai LI ; Rong ZENG ; Guopeng WANG ; Zhenghan YANG ; Shusheng GONG ; Zhenchang WANG ; Pengfei ZHAO
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(9):897-901
Objective:To investigate the hemodynamic characteristics of transverse sinus with sigmoid sinus wall dehiscence (SSWD) of pulsatile tinnitus (PT) based on 4D flow MRI.Methods:Retrospective analysis was performed on all patients admitted to Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2021 for dehiscent sigmoid plate pulsatile tinnitus. A total of 26 patients (sides) who met the criteria and underwent 4D flow MRI were included. A total of 26 subjects (46 sides), matched 1∶1 according to gender and age, were included in the normal healthy control group. Nonparametric rank sum test, Student′s t test, and ANOVA were performed by SPSS 19.0 software. Binary Logistic regression was applied to the data with statistical significance. Results:There were more patients with dominant drainage on the affected side in PT group than in control group (73.1% vs. 42.3%). The incidence of transverse with a focal intraluminal filling defect and tapered stenosis was higher than that in control group (21.7% vs. 69.2%; 17.4% vs. 42.3%). Average through-plane velocity and maximum through-plane velocity in PT group were higher than those in control group [(33.75±13.88) cm/s vs. (15.84±7.21) cm/s; (93.19±33.55) cm/s vs. (40.40±14.40) cm/s]. The middle part and proximal end of Flow avg (ml/s) in PT group were larger than those in control group [4.69 (2.87; 5.62) ml/s vs. 2.76 (1.67; 4.99) ml/s; 3.41 (2.16; 5.47) ml/s vs. 2.67 (1.68; 4.41) ml/s]. In control group, the velocity of transverse sinus changed relatively gently, while in PT group, the velocity of proximal sinus increased significantly. Binary Logistic regression showed that SSWD PT was independently correlated with proximal maximum flow velocity [ OR=1.086(1.029-1.146), P=0.003]. Conclusion:4D flow MRI showed that the dominant drainage and higher velocity at the proximal end of the transverse sinus might be an important hemodynamic characteristics of dehiscent sigmoid plate pulsatile tinnitus.
3.Genomic alterations in oral multiple primary cancers
Zhou XUAN ; Cai XINJIA ; Jing FENGYANG ; Li XUEFEN ; Zhang JIANYUN ; Zhang HEYU ; Li TIEJUN
International Journal of Oral Science 2024;16(1):145-153
Oral squamous cell carcinoma(OSCC)is the predominant type of oral cancer,while some patients may develop oral multiple primary cancers(MPCs)with unclear etiology.This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs.Clinicopathological data from patients with oral single primary carcinoma(SPC,n=202)and oral MPCs(n=34)were collected and compared.Copy number alteration(CNA)analysis was conducted to identify chromosomal-instability differences among oral MPCs,recurrent OSCC cases,and OSCC patients with lymph node metastasis.Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients.Additionally,CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients.Our findings revealed that,in contrast to oral SPC,females predominated the oral MPCs(70.59%),while smoking and alcohol use were not frequent in MPCs.Moreover,long-term survival outcomes were poorer in oral MPCs.From a CNA perspective,no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis.In addition to commonly mutated genes such as CASP8,TP53 and MUC16,in oral MPCs we also detected relatively rare mutations,such as HS3ST6 and RFPL4A.Furthermore,this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals,and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.
4.Biomarkers of malignant transformation in oral leukoplakia: from bench to bedside.
Xinjia CAI ; Jianyun ZHANG ; Heyu ZHANG ; Tiejun LI
Journal of Zhejiang University. Science. B 2023;():1-15
Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma, which indicates a high potential of malignancy. The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life; however, it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management. As a major problem in the field of head and neck pathologies, it is imperative to identify biomarkers of malignant transformation in oral leukoplakia. In this review, we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside. Although no single biomarker has yet been applied in the clinical setting, profiling for genomic instability might be a promising adjunct.
5.Effect of the sonic hedgehog inhibitor GDC-0449 on an in vitro isogenic cellular model simulating odontogenic keratocysts.
Jiemei ZHAI ; Heyu ZHANG ; Jianyun ZHANG ; Ran ZHANG ; Yingying HONG ; Jiafei QU ; Feng CHEN ; Tiejun LI
International Journal of Oral Science 2019;11(1):4-4
Odontogenic keratocysts (OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome (NBCCS). OKCs are locally aggressive, cause marked destruction of the jaw bones and have a propensity to recur. PTCH1 mutations (at ∼80%) are frequently detected in the epithelia of both NBCCS-related and sporadic OKCs, suggesting that PTCH1 inactivation might constitutively activate sonic hedgehog (SHH) signalling and play a major role in disease pathogenesis. Thus, small molecule inhibitors of SHH signalling might represent a new treatment strategy for OKCs. However, studies on the molecular mechanisms associated with OKCs have been hampered by limited epithelial cell yields during OKC explant culture. Here, we constructed an isogenic PTCH1 cellular model of PTCH1 inactivation by introducing a heterozygous mutation, namely, c.403C>T (p.R135X), which has been identified in OKC patients, into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. This was followed by the induction of epithelial differentiation. Using this in vitro isogenic cellular model, we verified that the PTCH1 heterozygous mutation causes ligand-independent activation of SHH signalling due to PTCH1 haploinsufficiency. This activation was found to be downregulated in a dose-dependent manner by the SHH pathway inhibitor GDC-0449. In addition, through inhibition of activated SHH signalling, the enhanced proliferation observed in these induced cells was suppressed, suggesting that GDC-0449 might represent an effective inhibitor of the SHH pathway for use during OKC treatment.
Anilides
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pharmacology
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Basal Cell Nevus Syndrome
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Hedgehog Proteins
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genetics
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pharmacology
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Humans
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Molecular Targeted Therapy
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Odontogenic Cysts
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genetics
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physiopathology
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therapy
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Odontogenic Tumors
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genetics
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physiopathology
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therapy
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Pyridines
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pharmacology
6.Establishment and application of multidisciplinary chain management model based on information technology in surgical patient handover
Xinglian GAO ; Jiaohua YU ; Heyu WU ; Wenjing YU ; Jianhui SHEN ; Qiong MA ; Suyun LI
Chinese Journal of Modern Nursing 2019;25(17):2210-2212
Objective? To explore the clinical application of information technology in the multidisciplinary chain management of surgical patient handover, in order to reduce the safety hazard in the process of surgical patient handover. Methods? In the contemporary controlled study, 300 patients were selected as the control group from February to July 2017 by cluster sampling, and 303 patients were selected as experimental group from February to July 2018. Traditional sectional handover method was adopted in the control group, to managed the patients' handover from each section. In the experimental group, based on the information communication platform between the surgery room and relevant clinical departments, by clinical electronic documents chain transfer method, quality inspection and supervision information feedback technology, to achieve shared decision and improvement of patients handover problems, we built the multidisciplinary management pattern. The two groups were compared for statistical difference from six aspects:the rate of acceptance specification, the accuracy of identity verification method, the rate of operation labeling verification, the accuracy of inventory of items, the evaluation of pipeline patency, and the evaluation of skin condition at the compression site. Results? The rate of standard delivery of surgical patient handover increased from 49.33% to 92.08% in the two groups. The experimental group was better than the control group in the rate of correct delivery of handover from the following five aspects: identity recognition, indication of surgical site, inventory of articles carried, unobstructed pipeline and skin state of the pressure site with statistical significance (P< 0.01). Conclusions? The multidisciplinary chain management model of surgical patient handover supported by information technology is effective in clinical application, which can significantly reduce the risk of hazard in patient handover and is worthy of clinical promotion.
7.Effect of the sonic hedgehog inhibitor GDC-0449 on an in vitro isogenic cellular model simulating odontogenic keratocysts
Zhai JIEMEI ; Zhang HEYU ; Zhang JIANYUN ; Zhang RAN ; Hong YINGYING ; Qu JIAFEI ; Chen FENG ; Li TIEJUN
International Journal of Oral Science 2019;11(1):33-41
Odontogenic keratocysts (OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome (NBCCS).OKCs are locally aggressive,cause marked destruction of the jaw bones and have a propensity to recur.PTCH1 mutations (at ~80%) are frequently detected in the epithelia of both NBCCS-related and sporadic OKCs,suggesting that PTCH1 inactivation might constitutively activate sonic hedgehog (SHH) signalling and play a major role in disease pathogenesis.Thus,small molecule inhibitors of SHH signalling might represent a new treatment strategy for OKCs.However,studies on the molecular mechanisms associated with OKCs have been hampered by limited epithelial cell yields during OKC explant culture.Here,we constructed an isogenic PTCH1R135X/+ cellular model of PTCH1 inactivation by introducing a heterozygous mutation,namely,c.403C>T (p.R135X),which has been identified in OKC patients,into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Casg) system.This was followed by the induction of epithelial differentiation.Using this in vitro isogenic cellular model,we verified that the PTCH1R135X/+ heterozygous mutation causes ligand-independent activation of SHH signalling due to PTCH1 haploinsufficiency.This activation was found to be downregulated in a dose-dependent manner by the SHH pathway inhibitor GDC-0449.In addition,through inhibition of activated SHH signalling,the enhanced proliferation observed in these induced cells was suppressed,suggesting that GDC-0449 might represent an effective inhibitor of the SHH pathway for use during OKC treatment.
8.A study on risk factors of perforation in acute appendicitis
Chinese Journal of Postgraduates of Medicine 2018;41(12):1057-1060
Objective To identify risk factors of perforation in acute appendicitis. Methods Patients with acute appendicitis who underwent surgical treatment from 2016 January to 2017 December were retrospectively reviewed. According to clinical and pathological records, patients were divided into perforation group (including 150 patients) and non-perforation group (including 157 patients). The progress of disease, duration from occurrence to surgery, preoperative highest temperature and pulse rate, and a series of indicators including WBC, NCP, LCP, HCT, CRP, TP through blood routine or biochemical assays. Logistic regression analysis was adopted to analyze the risk factors of perforation were compared. Results Preoperative highest temperature, pulse rate, WBC, NCP, LCP and CRP in perforation and non-perforation group were (37.98 ± 0.54) ℃ vs. (37.58 ± 0.52) ℃, (94.94 ± 20.74) times/min vs. (87.41 ± 15.35) times/min, (15.25 ± 4.71)×109/L vs. (11.04 ± 4.29)×109/L, (83.06 ± 9.84)% vs. (75.27 ± 13.71)%, (11.76 ± 3.73)% vs. (18.23 ± 5.72)%, (89.35 ± 23.10) mg/L vs. (52.16 ± 18.46) mg/L, respectively. There existed significant differences between the two groups (P<0.05). Logistic regression analysis showed that WBC ( OR=1.185, 95% CI 1.090-1.280), CRP( OR=2.043, 95% CI 1.243-2.843), the preoperative highest temperature ( OR=2.007, 95% CI 1.114-3.616), and pulse rate ( OR=1.160, 95% CI 1.124-1.196) were risk factors of perforation in patients with acute appendicitis (P<0.05). The Hosmer-Lemeshow test proved that the predictive accuracy rate of the Logistic model was up to 79.1%. Conclusions WBC, CRP, the preoperative highest temperature and pulse rate are risk factors, which contributes to predict the risk of perforation in patients with acute appendicitis.
9.SMN1 gene deletion analysis using mid-trimester amniotic fluid cells by real-time PCR
Heyu HU ; Xingli FU ; Jing YU ; Bei ZHANG ; Zhenhua TANG ; Huifen CHEN ; Li ZHANG ; Bo GONG
Chinese Journal of Laboratory Medicine 2016;39(6):418-422
Objectives To investigate the prenatal diagnosis method of spinal muscular atrophy with amniotic fluid sample.Methods Totally 1 064 amniotic fluid samples from mid-trimester pregnant women were enrolled during January 2015 and January 2016 in 4 hospitals.Genetic analysis was performed for detecting potential contamination of maternal tissue by a genetic technique based on short tandem repeat ( STR) markers.Deletion of SMN1 gene was detected in 1 062 uncontaminated amniotic fluid samples by real-time PCR and multiplex ligation-dependent probe amplification ( MLPA) respectively.Results Two contaminated amniotic fluid samples were detected within 1 064 mid-trimester pregnant women by STR genotyping.The other 1 062 uncontaminated amniotic fluid samples were tested by real-time PCR.There were 37 samples with heterozygous deletion of Exon 7 of SMN1 gene ( 3.67%) , 34 samples with heterozygous deletion of Exon 8 of SMN1 gene (3.2%) and two samples with homozygous deletion of Exon 7 and Exon8 of SMN1 gene ( 0.19%) respectively , while other samples observed with no deletion of Exon 7 and Exon8 in SMN1 gene.Totally 41 samples with heterozygous or homozygous deletion of SMN 1 gene and 55 samples with undetected deletion of SMN 1 gene were confirmed by MLPA and the results showed 100%consistence with that of real-time PCR.Conclusions Both real-time PCR and MLPA are suitable for detecting the deletion of SMN 1 gene with amniotic fluid sample . Real-time PCR exhibits less sample requirement and time compared with MLPA .
10.Warming nursing to severe traumatic patients with hypothermia and nursing measures
Heyu WU ; Li WU ; Ling JIAN ; Ping WANG ; Hong LIU ; Ling YE
Modern Clinical Nursing 2016;15(11):31-35
Objective To investigate the causes of hypothermia in severe trauma patients as well as the effects of warming nursing.Methods Toally 100 severe trauma patients with hypothermia were engaged in the study during January to December 2014.Their temperature was monitored and recorded,the causes analyzed so that the warming nursing measures were done to them.Results Among the 100 patients,59 contracted hypothermia,with the rate of 59.0% before operation,28 contracted hypothermia during operation,with the incidence rate of 28.0%.The causes of hypothermia included injury,anaesthesia,exposure and fluid resuscitation.The nursing measures included pre-treatment before anaesthesia,avoidance of more exposure and intraoperative warming.Conclusions For the patients with severe trauma,the hypothermia during the operation can be caused by injury,anaesthesia,exposure and fluid resuscitation.The warming nursing can reduce the incidence of hypothermia so as to increase their survival rate.

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