1.Molecular classification of head and neck squamous cell carcinoma based on hypoxia-related genes and clinical significance of STC2
ZHU Jianing ; WANG Tiantian ; ZHANG Rui ; SONG Hongquan
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(5):345-358
Objective :
To construct a molecular classification system for head and neck squamous cell carcinoma (HNSCC) utilizing hypoxia-related gene (HAG) expression profiles, and to comprehensively examine the clinicopathological significance and biological functions of the hypoxia gene stanniocalcin 2 (STC2) in HNSCC.
Methods :
Transcriptomic data and clinical information of 546 HNSCC samples were obtained from The Cancer Genome Atlas (TCGA) database, and based on the expression profiles of 200 HRGs, HNSCC was classified subclasses using non-negative matrix factorization (NMF). HNSCC was classified into three subclasses (C1, C2, and C3), and the molecular characteristics and prognostic differences of the subclasses were assessed by comparing the tumor mutation load, functional enrichment analysis, drug sensitivity, and clinical features among the subclasses. LASSO-Cox regression was used to screen prognosis-related genes and construct prognostic models. Using oral squamous cell carcinoma (OSCC)-related data in the TCGA database, we analyzed the expression differences of STC2 in OSCC and control samples, and detected the mRNA and protein expression of STC2 in oral squamous carcinoma samples using qRT-PCR and immunohistochemistry. We knocked down STC2 in CAL-27 cells and verified the knockdown efficiency by qRT-PCR and Western blot. CCK-8 assay and cell scratch assay were used to assess the effect of STC2 on cell proliferation and migration ability.
Results:
Based on HRGs expression profiles, HNSCC was categorized into three subclasses (C1, C2, and C3). Subclass C1 had moderate hypoxic activity and good prognosis; subclass C2 had the highest hypoxic activity, poor prognosis, and poor sensitivity to CTLA-4 inhibitors (P<0.05); subclass C3 had the lowest hypoxic activity and moderate prognosis, and STC2 belonged to subclass C3. The frequency of cyclin-dependent kinase inhibitor 2A (CDKN2A), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and tumor protein p53 (TP 53) mutations was higher in HNSCC. C1 genomic gain and deletion burden were significantly higher than C3 subclass (P<0.05) and C2 genomic gain than C3 subclass (P<0.05). The C2 subclass was significantly enriched in hypoxia-associated pathways, such as glycine metabolism and base excision repair (P<0.05). The C1, C2, and C3 subclasses were significantly positively correlated in terms of sex (male) (Cramer’s V=0.15), radiation exposure (Cramer’s V=0.12), medication (Cramer’s V=0.18), and pathological grading (G1/G2) (Cramer’s V=0.25) (P<0.05). Nine prognosis-related genes were screened by LASSO-Cox regression, among which high expression of STC2 was positively correlated with poorer overall survival (OS) in HNSCC patients (P<0.01). Bioinformatics analysis showed that STC2 mRNA expression was higher in OSCC than in normal controls (P<0.05). qRT-PCR and immunohistochemistry confirmed that both mRNA and protein expression of STC2 were significantly upregulated in OSCC tissues and cells (P<0.01). In vitro experiments showed that STC2 expression was knocked down to approximately 80% in CAL-27 cells (P<0.001), and the STC2 knockdown group had a reduced value-added rate (P<0.001) and a reduced percentage of scratch closure (P<0.05) compared with the control group.
Conclusion
We successfully constructed a molecular typing system for HNSCC based on the expression profiles of HRGs and categorized HNSCC into three subclasses with significant prognostic differences, among which the C2 subclass had the highest hypoxic activity and the poorest prognosis. STC2 was highly expressed in HNSCC and suggested a poor prognosis, demonstrating that it may be a potential target for HNSCC treatment.
2.Imaging Findings of Phosphaturic Mesenchymal Tumor
Juan WANG ; Ying XIONG ; Weijia WAN ; Hongquan ZHU ; Wenzhen ZHU
Chinese Journal of Medical Imaging 2024;32(10):1058-1062
Purpose To analyze the multimodal imaging manifestations of phosphaturic mesenchymal tumor.Materials and Methods A retrospective analysis was performed on ten patients with phosphaturic mesenchymal tumor confirmed by pathology and molecular imaging from November 2012 to June 2022 in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology.The imaging features of CT in four cases,of MRI in seven cases,and of nuclear medicine in ten cases were reviewed,along with the clinical characteristics of all patients.Results The main clinical symptoms of ten patients,eight cases had pain,four cases had weakness,and nine cases had multiple fractures.Laboratory tests results:ten cases showed decreased blood phosphorus,six cases showed decreased blood 25-hydroxyvitamin D and ten cases showed elevated blood alkaline phosphatase.The lesions were heterogeneous in four cases on CT scans and in six cases on MRI scans.Calcification was common,and some had cysts and fatty components.After enhancement,seven cases showed moderate to obvious uneven enhancement.99Tcm-MDP SPECT showed increased uptake of multiple bones and joints in eight cases,18F-FDG PET/CT showed no or slight increase in lesion metabolism in eight cases,68Ga-DOTATATE PET/CT showed significantly high uptake at the lesion site in ten cases.Conclusion Phosphaturic mesenchymal tumor patients typically present with pain,fractures and hypophosphatemia.The conventional imaging features are characterized by small and concealed lesions and complex components.Particularly,68Ga-DOTATATE PET/CT imaging exhibits high sensitivity for the tumor detection.
3.To evaluate the awakening effect of high-frequency repetitive transcranial magnetic stimulation in patients with chronic consciousness disturbance after brain injury based on magnetic resonance spectroscopy
Chaoyu WU ; Yi'an OUYANG ; Zhengbiao XUE ; Jiying LAI ; Songmao OUYANG ; Shusheng WANG ; Zihui SU ; Hongquan ZHU
The Journal of Practical Medicine 2024;40(4):554-560
Objective Evaluation of the efficacy of high-frequency repetitive transcranial magnetic stimulation for chronic disturbance of consciousness after severe craniocerebral injury based on magnetic resonance spectroscopy.Methods The clinical data of 106 patients with chronic disturbance of consciousness after severe craniocerebral injury from January 2018 to December 2022 were retrospectively analyzed,and they were divided into control group(conventional rehabilitation treatment)and observation group(high frequency repetitive transcranial magnetic stimulation treatment)by propensity score matching method(1∶1),with 53 cases in each group.Both groups were examined by magnetic resonance spectroscopy(MRS)before and after treatment.The brain metabolic indexes[N-acetyl aspartate(NAA)/creatine(Cr)value,choline complex(Cho)/Cr value],Glasgow coma scale(GCS)score,electroencephalogram(EEG)grading,coma recovery scale(CRS-R)score,brainstem auditory evoked potential(BAEP)grading,upper limb sensory evoked potential(SSEP)grading and Cerebral blood flow perfusion index[cerebral blood volume(CBV),mean transit time(MTT),cerebral blood flow(CBF)]were compared between the two groups.Results After treatment,the NAA/Cr values of the thalamus and brainstem in the two groups increased,while the Cho/Cr values decreased,and the levels of brain metabolic indexes in the observation group were signifi-cantly better than those in the control group(P<0.05).The two groups'GCS score and CRS-R score increased,and the improvement of the observation group was better than that of the control group(P<0.05).The BAEP grading,EEG grading,and SSEP grading of the two groups improved,and those of the observation group were better than the control group(P<0.05).The CBF and CBV of the two groups increased,and MTT decreased,and the level of cere-bral blood perfusion index in the observation group was better than that in the control group(P<0.05).Conclusion High frequency repetitive transcranial magnetic stimulation has a significant effect on the recovery of patients with chronic consciousness disorders after severe craniocerebral injury.The mechanism may be related to improving the blood flow velocity of brain tissue and metabolism in the brain.
4.Application of 3D digital modeling combined with 3D printed model in classroom theoretical teaching of orthopedics
Hongquan SHEN ; Hongli ZHU ; Jinwei GUO ; Juan WU ; Xingyuan LIU ; Hui LU
Chinese Journal of Medical Education Research 2023;22(6):912-916
Objective:To investigate the application effect of 3D digital modeling combined with 3D printed model in assisting the classroom theoretical teaching of orthopedics in five-year undergraduate students majoring in clinical medicine.Methods:In May 2022, 33 five-year undergraduate students majoring in clinical medicine in the class of 2018 in Southwest Medical University were selected and divided into experimental group with 17 students and control group with 16 students according to the odd or even student number. The students in the experimental group were taught by traditional PPT+3D digital modeling combined with 3D printed model, and those in the control group were taught by the traditional PPT teaching method. The teaching effect was evaluated by theoretical examination and a questionnaire survey on the degree of satisfaction with teaching. SPSS 25.0 was used to perform the t-test, the Mann-Whitney U test, the rank sum test, and the chi-square test. Results:The experimental group had a significantly higher score of theoretical examination than the control group (86.24±4.16 vs. 82.50±6.06). The questionnaire survey on the degree of satisfaction with teaching showed that compared with the control group, the experimental group had a significantly higher degree of satisfaction with the understanding and learning of orthopedic diseases [3 (2, 3) vs. 2 (2, 2), P < 0.05], the improvement in learning interest [2 (2, 3) vs. 2 (1, 2), P < 0.05], classroom innovation [3 (3, 3) vs. 2 (1.5, 2), P < 0.05], and overall classroom teaching [3 (2, 3) vs. 2 (2, 2), P < 0.05]. Conclusion:In assisting the classroom theoretical teaching of orthopedics in undergraduate students majoring in clinical medicine, 3D digital modeling combined with 3D printed model can provide concrete 3D models, reduce the difficulties in learning, improve the awareness of orthopedic diseases, strengthen learning interest, and increase the degree of satisfaction with teaching and academic scores.
5.Radiomics based on three-dimensional high-resolution MR vessel wall imaging for identification of culprit plaques in symptomatic patients with middle cerebral artery atherosclerosis
Guiling ZHANG ; Jicheng FANG ; Zhenxiong WANG ; Yiran ZHOU ; Di WU ; Jun LU ; Su YAN ; Hongquan ZHU ; Shun ZHANG ; Wenzhen ZHU
Chinese Journal of Radiology 2023;57(1):27-33
Objective:To investigate the value of radiomics based on three-dimensional high resolution MR vessel wall imaging (3D HRMR-VWI) for identifying culprit plaques in symptomatic patients with middle cerebral atherosclerosis.Methods:The clinical and imaging features of 117 patients (139 middle cerebral artery plaques) with cerebrovascular diseases in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from October 2018 to October 2020 were respectively reviewed. Stratified random sampling was used to divide 139 plaques into training set (97 plaques) and validation set (42 plaque) at the ratio of 7∶3. The plaques were divided into 69 culprit plaques and 70 non-culprit plaques based on plaque MR features and clinical symptoms. The clinical and imaging characteristics of culprit plaques and non-culprit plaques were compared by independent sample t-test, Mann-Whitney U test and χ 2 test, and factors with significant difference between two groups in univariate analysis were further analyzed by multivariate logistic regression to find out the independent predictors of culprit plaques. Radiomics features were extracted, screened and radiomics model was constructed using pre-and post-contrast 3D HRMR-VWI based on the training set. The combined model was constructed by combining the independent predictors and radiomics model. Receiver operating characteristic curve and area under curve (AUC) were used to evaluate the efficacy of each model, and DeLong test was used to compare the efficacy of different models. Results:Significant difference was found in intraplaque hemorrhage, lumen area of stenosis, stenosis diameter, stenosis rate, plaque burden and enhancement rate between culprit and non-culprit plaques (all P<0.05). Multivariate logistic regression analysis confirmed that only intraplaque hemorrhage was the independent predictor for culprit plaques (OR=7.045,95%CI 1.402-35.397, P=0.018). In the validation set, the AUC of the pre-contrast 3D HRMR-VWI model was lower than that of the post-contrast 3D HRMR-VWI model ( Z=-2.01, P=0.044). The AUC of pre+post-contrast 3D HRMR-VWI model was not significantly different from that of post-contrast 3D HRMR-VWI model ( Z=0.79, P=0.427). The AUC showed no significant difference between combined model and pre+post-contrast 3D HRMR-VWI model ( Z=-0.59, P>0.05). The combined model showed the best performance in predicting culprit plaques of middle cerebral artery (AUC=0.939), with the sensitivity, specificity and accuracy of 95.24%, 76.19% and 85.71%. Conclusion:Radiomics based on 3D HRMR-VWI has potential values in identifying culprit plaques in symptomatic patients with middle cerebral atherosclerosis.
6.Feasibility of a Clinical-Radiomics Model to Predict the Outcomes of Acute Ischemic Stroke
Yiran ZHOU ; Di WU ; Su YAN ; Yan XIE ; Shun ZHANG ; Wenzhi LV ; Yuanyuan QIN ; Yufei LIU ; Chengxia LIU ; Jun LU ; Jia LI ; Hongquan ZHU ; Weiyin Vivian LIU ; Huan LIU ; Guiling ZHANG ; Wenzhen ZHU
Korean Journal of Radiology 2022;23(8):811-820
Objective:
To develop a model incorporating radiomic features and clinical factors to accurately predict acute ischemic stroke (AIS) outcomes.
Materials and Methods:
Data from 522 AIS patients (382 male [73.2%]; mean age ± standard deviation, 58.9 ± 11.5 years) were randomly divided into the training (n = 311) and validation cohorts (n = 211). According to the modified Rankin Scale (mRS) at 6 months after hospital discharge, prognosis was dichotomized into good (mRS ≤ 2) and poor (mRS > 2); 1310 radiomics features were extracted from diffusion-weighted imaging and apparent diffusion coefficient maps. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator logistic regression method were implemented to select the features and establish a radiomics model. Univariable and multivariable logistic regression analyses were performed to identify the clinical factors and construct a clinical model. Ultimately, a multivariable logistic regression analysis incorporating independent clinical factors and radiomics score was implemented to establish the final combined prediction model using a backward step-down selection procedure, and a clinical-radiomics nomogram was developed. The models were evaluated using calibration, receiver operating characteristic (ROC), and decision curve analyses.
Results:
Age, sex, stroke history, diabetes, baseline mRS, baseline National Institutes of Health Stroke Scale score, and radiomics score were independent predictors of AIS outcomes. The area under the ROC curve of the clinical-radiomics model was 0.868 (95% confidence interval, 0.825–0.910) in the training cohort and 0.890 (0.844–0.936) in the validation cohort, which was significantly larger than that of the clinical or radiomics models. The clinical radiomics nomogram was well calibrated (p > 0.05). The decision curve analysis indicated its clinical usefulness.
Conclusion
The clinical-radiomics model outperformed individual clinical or radiomics models and achieved satisfactory performance in predicting AIS outcomes.
7. Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV
Yudong PENG ; Kai MENG ; Hongquan GUAN ; Liang LENG ; Ruirui ZHU ; Boyuan WANG ; Meian HE ; Longxian CHENG ; Kai HUANG ; Qiutang ZENG
Chinese Journal of Cardiology 2020;48(0):E004-E004
Objective:
To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease (CVD).
Methods:
A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU,
8.The role of the hamstrings in stabilizing a knee with ACL deficit
Yi WANG ; Qirong DONG ; Jianming XU ; Hongquan PANG ; Zhigao JING ; Jianbing ZHU ; Jinjie TIAN
Chinese Journal of Physical Medicine and Rehabilitation 2020;42(7):623-627
Objective:To investigate the effect of enhancing the strength of the hamstring on the stability of the knee joint.Methods:Thirty patients with anterior cruciate ligament (ACL) tears were randomly divided into a training group ( n=15) and a control group ( n=15). After the injury′s edema stage, all of the subjects received the standard 6-stage rehabilitation training for ACL injury, including isokinetic exercise, isometric tension and contraction exercise, single or bipedal jumping, proprioception exercises and cardiovascular exercise. On the basis of that standard training, additional hamstring strengthening training was given to the training group. It involved three sessions of weight-bearing flexion of the knee joint six to eight times, at least five times a week for three months. All of the subjects underwent the passive relaxation test (PRT), knee function scoring (Lysholm scores) and weight-bearing MRI before and within 1 month after the training. Anterior shift of the tibia (TAS) was measured using weight-bearing magnetic resonance imaging (MRI). Results:Before the training there were no significant differences between the groups in terms of average PRT or Lysholm scores. After the training, the average PRT score in neither group had improved significantly. The average Lysholm scores of the training and control groups were not significantly different either, though both groups′ averages had improved significantly compared with before the training. The average tibial shifts were also significantly smaller than before the training, with the training group′s average significantly smaller than that of the control group.Conclusion:Increasing hamstring muscle strength can reduce tibial anteversion in the weight-bearing upright position and improve the stability of the knee joint after ACL injury.
9.Evaluation of endovascular optical coherence tomography in carotid atherosclerotic stenosis: comparison between symptomatic and asymptomatic patients
Rui LIU ; Qingwen YANG ; Xuan SHI ; Xiaohui XU ; Hongquan GUO ; Wusheng ZHU ; Xinfeng LIU
International Journal of Cerebrovascular Diseases 2020;28(6):426-432
Objective:To explore the value of intravascular optical coherence tomography (OCT) in evaluating carotid atherosclerotic stenosis, and compare the morphological characteristics of symptomatic and asymptomatic carotid atherosclerotic plaques.Methods:Patients diagnosed as carotid atherosclerotic stenosis and performed OCT in the Department of Neurology, Jinling Hospital, Medical School of Nanjing University from January 2017 to November 2019 were enrolled retrospectively. Digital subtraction angiography (DSA) and OCT were used to determine the degree of stenosis of the diseased vessels, and the plaque characteristics observed by OCT were recorded. Symptomatic carotid atherosclerotic stenosis is defined as a history of transient ischemic attack, amaurosis fugax, or stroke related to the blood supply area of the diseased vessel within 6 months before the carotid artery examination. The baseline clinical and imaging data of the symptomatic group and the asymptomatic group were compared. Multivariate logistic regression analysis was used to determine the independent risk factors for symptomatic carotid atherosclerotic stenosis. Results:A total of 56 patients were enrolled. DSA and OCT had good consistency in carotid artery diameter measurement ( r=0.93, P<0.001). When the OCT technique was used to evaluate the plaque properties, the consistency of inter-observer ( κ=0.96, P<0.001) and intra-observer ( κ=0.96, P<0.001) was higher. The proportions of patients with type Ⅵ plaque (66.7% vs. 34.5%; P=0.016) and macrophage infiltration (51.9% vs. 24.1%; P=0.032) in the symptomatic group were significantly higher than those in the asymptomatic group, while the proportion of patients with fibrotic plaque was significantly lower than that in the asymptomatic group (40.7% vs. 69.0%; P=0.034). Multivariate logistic regression analysis suggested that type Ⅵ plaques (odds ratio 13.798, 95% confidence interval 1.38-137.675; P=0.025) and macrophage infiltration (odds ratio 5.856, 95% confidence interval 1.405-24.406; P=0.015) were the independent risk factors for symptomatic carotid atherosclerotic stenosis. Conclusions:OCT can be used to evaluate the degree of vascular stenosis and plaque characteristics in patients with carotid atherosclerotic stenosis. The detection rate of complex plaques in patients with symptomatic carotid atherosclerotic stenosis is significantly higher. Type Ⅵ plaque and macrophage infiltration are the independent risk factors for symptomatic carotid atherosclerotic stenosis.
10.Correction to: Increasing targeting scope of adenosine base editors in mouse and rat embryos through fusion of TadA deaminase with Cas9 variants.
Lei YANG ; Xiaohui ZHANG ; Liren WANG ; Shuming YIN ; Biyun ZHU ; Ling XIE ; Qiuhui DUAN ; Huiqiong HU ; Rui ZHENG ; Yu WEI ; Liangyue PENG ; Honghui HAN ; Jiqin ZHANG ; Wenjuan QIU ; Hongquan GENG ; Stefan SIWKO ; Xueli ZHANG ; Mingyao LIU ; Dali LI
Protein & Cell 2019;10(9):700-700
In the original publication the grant number is incorrectly published. The correct grant number should be read as "17140901600". The corrected contents are provided in this correction article. This work was partially supported by grants from the National Natural Science Foundation of China (Nos. 81670470 and 81600149), a grant from the Shanghai Municipal Commission for Science and Technology (17140901600, 18411953500 and 15JC1400201) and a grant from National Key Research and Development Program (2016YFC0905100).


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