1.Development and validation of a multi-modality fusion deep learning model for differentiating glioblastoma from solitary brain metastases
Shanshan SHEN ; Chunquan LI ; Yaohua FAN ; Shanfu LU ; Ziye YAN ; Hu LIU ; Haihang ZHOU ; Zijian ZHANG
Journal of Central South University(Medical Sciences) 2024;49(1):58-67
Objective:Glioblastoma(GBM)and brain metastases(BMs)are the two most common malignant brain tumors in adults.Magnetic resonance imaging(MRI)is a commonly used method for screening and evaluating the prognosis of brain tumors,but the specificity and sensitivity of conventional MRI sequences in differential diagnosis of GBM and BMs are limited.In recent years,deep neural network has shown great potential in the realization of diagnostic classification and the establishment of clinical decision support system.This study aims to apply the radiomics features extracted by deep learning techniques to explore the feasibility of accurate preoperative classification for newly diagnosed GBM and solitary brain metastases(SBMs),and to further explore the impact of multimodality data fusion on classification tasks. Methods:Standard protocol cranial MRI sequence data from 135 newly diagnosed GBM patients and 73 patients with SBMs confirmed by histopathologic or clinical diagnosis were retrospectively analyzed.First,structural T1-weight,T1C-weight,and T2-weight were selected as 3 inputs to the entire model,regions of interest(ROIs)were manually delineated on the registered three modal MR images,and multimodality radiomics features were obtained,dimensions were reduced using a random forest(RF)-based feature selection method,and the importance of each feature was further analyzed.Secondly,we used the method of contrast disentangled to find the shared features and complementary features between different modal features.Finally,the response of each sample to GBM and SBMs was predicted by fusing 2 features from different modalities. Results:The radiomics features using machine learning and the multi-modal fusion method had a good discriminatory ability for GBM and SBMs.Furthermore,compared with single-modal data,the multimodal fusion models using machine learning algorithms such as support vector machine(SVM),Logistic regression,RF,adaptive boosting(AdaBoost),and gradient boosting decision tree(GBDT)achieved significant improvements,with area under the curve(AUC)values of 0.974,0.978,0.943,0.938,and 0.947,respectively;our comparative disentangled multi-modal MR fusion method performs well,and the results of AUC,accuracy(ACC),sensitivity(SEN)and specificity(SPE)in the test set were 0.985,0.984,0.900,and 0.990,respectively.Compared with other multi-modal fusion methods,AUC,ACC,and SEN in this study all achieved the best performance.In the ablation experiment to verify the effects of each module component in this study,AUC,ACC,and SEN increased by 1.6%,10.9%and 15.0%,respectively after 3 loss functions were used simultaneously. Conclusion:A deep learning-based contrast disentangled multi-modal MR radiomics feature fusion technique helps to improve GBM and SBMs classification accuracy.
2.Study on reverse transsynaptic virus tracing targeting Shenmen (HT7) and heart in mice
Libin WU ; Fan ZHANG ; Qing YU ; Lei LIU ; Xia WEI ; Ronglin CAI ; Zijian WU ; Ling HU
Journal of Acupuncture and Tuina Science 2023;21(2):109-120
Objective: To investigate the neural connections between Shenmen (HT7)-heart and the brain by observing the tracing viruses co-labeled brain nuclear groups after injection of the pseudorabies viruses (PRV), the reverse transsynaptic virus tracer carrying different fluorescent protein genes, into the myocardium and Shenmen (HT7) point, respectively.Methods: Pseudorabies virus 531 (PRV531) carrying the green fluorescent protein gene and pseudorabies virus 724 (PRV724) carrying the red fluorescent protein gene were injected into the left ventricular wall and Shenmen (HT7) point area of the left forelimb of six C57BL/6 mice, respectively. After 120 h, whole brain tissue was extracted under 4% paraformaldehyde perfusion to prepare brain sections. Neuronal co-labeling with the tracing viruses was observed under fluorescence microscopy. Results: Co-labeled signals from the mouse ventricular wall and Shenmen (HT7) point region were found at all levels of the mouse central nervous areas, such as the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. The number of co-labeled neurons was higher in the primary motor area, the hypothalamic paraventricular nucleus, the subceruleus nucleus, and the paramedian reticular nucleus. Conclusion: There is a neural connection between Shenmen (HT7), the heart, and the brain, which may be most closely related to the autonomic nervous system.
3.Research on KBP model refining method using multi-criterion optimization technology
Mafan CAI ; Guoping ZUO ; Zhen YANG ; Ying CAO ; Zijian ZHANG ; Yongmei HU ; Xiaoyu YANG
Chinese Journal of Radiation Oncology 2022;31(9):811-816
Objective:Utilizing multi-criterion optimization (MCO) technology to improve plan design quality based on knowledge-based planning (KBP) model.Methods:Fifty-five patients with nasopharyngeal carcinoma (NPC) who had completed radiotherapy were selected, and fixed-field intensity-modulated radiotherapy (IMRT) technology was used in each case. Among them, 40 cases were randomly selected as training set 1. Then, IMRT plans in training set 1 were preprocessed by MCO technology to construct a new training set 2. With the initial training set 1 and the processed training set 2 as training samples, the traditional KBP model and the MCO-KBP model refined by MCO technology were trained, respectively. Among the remaining 15 cases, 5 cases were randomly selected as the validation set, and the remaining 10 cases were used as the test set. After verification, the test set was used to statistically analyze the plan quality of the initial manual plan and the automatic plan generated by the traditional KBP model and the MCO-KBP model.Results:The target dose (D 95%) of plans generated by the traditional KBP model and the MCO-KBP model met the clinical requirements. Conformity index (CI) and homogeneity index (HI) were almost the same ( P>0.05), and the doses of organ at risk (OAR) of the automatic plans generated by the MCO-KBP model were lower than those of the traditional KBP model. For example, compared with the traditional KBP model, the average D max of the brainstem in the automatic plans generated by the MCO-KBP model was lower by 2.13 Gy, the average D mean of the left parotid gland was lower by 1.39 Gy, the average D mean of the right parotid gland was lower by 1.59 Gy, and the average D max of the left optic nerve was lower by 1.42 Gy, the average D max of the right optic nerve was lower by 1.16 Gy, and the average D max of the pituitary gland was lower by 1.88 Gy. All of the above-mentioned dosimetry indexes were statistically significant. Conclusion:Compared with the traditional KBP model, the IMRT plans designed by the refined MCO-KBP model have obvious advantages in the protection of OAR, which proves the feasibility of utilizing MCO technology to improve the plan design quality of the KBP model.
4.Effect of moxibustion on N-methyl-D-aspartate receptor subtype 2B expression in hippocampus of rheumatoid arthritis model rats
Chuanyu PENG ; Ling HU ; Zijian WU ; Ronglin CAI ; Zhiming JIANG ; Yanping YANG
Journal of Acupuncture and Tuina Science 2022;20(3):174-180
Objective: To observe the effect of moxibustion on the expression of N-methyl-D-aspartic acid (NMDA) receptor subtype 2B (NR2B) in the hippocampus of rheumatoid arthritis (RA) rats, and to explore the analgesic mechanisms of moxibustion in RA treatment. Methods: Sixty male Sprague-Dawley rats were randomly divided into a normal group, a model group, a moxibustion group, a moxibustion + NMDA receptor antagonist (AP-5) group, and a moxibustion + NMDA receptor agonist (NMDA) group, with 12 rats in each group. Except for the normal group, rats in the other four groups were treated with complete Freund's adjuvant in a windy, cold, and damp environment to replicate RA models. Rats in the moxibustion group received suspended moxibustion with moxa sticks at Shenshu (BL23) and Zusanli (ST36), and the two points were used alternately. After intraperitoneal injection of AP-5 or NMDA, rats in the moxibustion + AP-5 group and the moxibustion + NMDA group received the same moxibustion intervention as in the moxibustion group, once a day for 15 d. The thermal withdrawal latency (TWL) of rats in each group was detected before and after modeling and after the 15-day intervention. After the 15-day intervention, hematoxylin-eosin staining was performed to observe the pathological changes in knee joints. The real-time fluorescence quantitative polymerase chain reaction method was used to detect the mRNA expression of NR2B in the hippocampus; Western blotting assay was used to detect the protein and the phosphorylated protein expression of hippocampal NR2B. Results: The synovial tissue was proliferated, the synovial lining was significantly thickened, the pannus was formed, and the cartilage and bone tissues were significantly damaged in the model group. After intervention, the pathological morphology of the knee joints in the moxibustion group, the moxibustion + AP-5 group, and the moxibustion + NMDA group was significantly improved, and the improvement in the moxibustion + AP-5 group was more notable than that in the moxibustion + NMDA group. Compared with the normal group, the TWL was significantly decreased (P<0.01), and the mRNA, protein, and phosphorylated protein expression levels of hippocampal NR2B were significantly increased in the model group (P<0.01). Compared with the model group, the TWL of each intervention group was significantly increased (P<0.01 or P<0.05), and the mRNA, protein, and phosphorylated protein expression levels of hippocampal NR2B were significantly decreased (P<0.01). Compared with the moxibustion group, the TWL was significantly increased (P<0.01), and the mRNA, protein, and phosphorylated protein expression levels of hippocampal NR2B were significantly decreased in the moxibustion + AP-5 group (P<0.01); the TWL was significantly decreased (P<0.01), and the mRNA, protein, and phosphorylated protein expression levels of hippocampal NR2B were significantly increased in the moxibustion + NMDA group (P<0.01). Conclusion: Moxibustion reduces hyperalgesia in RA inflammatory rats. The analgesic effect may be related to the decrease in the expression and phosphorylation levels of NR2B in the hippocampus.
5.Prediction of core genes in the treatment of colorectal cancer with naringin using bioinformatics
Zijian Song ; Jianwei Li ; Hezhi Hu
Acta Universitatis Medicinalis Anhui 2022;57(2):229-234
Objective :
To screen the mRNA core genes of naringin in the treatment of colorectal cancer (CRC) by
bioinformatics analysis , and to verify the predictive effect of mRNA core genes on CRC by survival analysis.
Methods:
The HCT116 cells of CRC were treated with DMSO solvent and naringin for 48 h and then RNA sequencing was conducted. The sequencing results were preprocessed and their differentially expressed genes were analyzed. The key lncRNAs were screened from differentially expressed genes , and the corresponding lncRNA⁃miRNA⁃mRNA regulatory network was established. With gene ontology (GO) analysis , Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and Protein⁃Protein Interaction (PPI) network analysis , the core mRNAs were obtained and verified by survival analysis method.
Results :
Ultimately , 197 differentially expressed lncRNAs , 128 differentially expressed miRNAs and 1 938 differentially expressed mRNAs were screened. Based on lncRNA⁃miRNA⁃mRNA regulatory network , 5 key lncRNAs and 117 key mRNAs were screened. The results of GO analysis and KEGG pathway analysis showed that they were mainly enriched in the functions and pathways closely related to CRC. In
the end , 6 mRNA core genes were obtained by PPI network analysis , and 3 core mRNAs (FOS , CCND2 , MXD1) were gained by survival analysis , which closely resembled CRC.
Conclusion
The molecular mechanism of naringin in the treatment of CRC is analyzed by means of bioinformatics , 3 core mRNAs with significant differences are screened out and they all have an important impact on the prognoses of patients , and the study will provide new ideas for the diagnosis , treatment and prognosis of CRC.
6.Effects of goal-oriented management of cerebral oxygen saturation on early postoperative neurocognitive impairment in elderly spinal surgery patients
Huijuan SONG ; Yuanyuan HU ; Lei TONG ; Yiran WANG ; Zijian CHENG ; Xiaoying ZHAO ; Jianxin YANG
Journal of Chinese Physician 2021;23(7):1012-1016
Objective:To observe the effect of goal-oriented management of continuous monitoring of regional cerebral oxygen saturation (rSO 2) on early postoperative neurocognitive disorders (PND) in elderly spinal surgery patients. Methods:From November 2018 to July 2019, 60 patients undergoing posterior lumbar interbody fusion in the Second Hospital of Shanxi Medical University were selected and randomly divided into control group and intervention group, 30 cases in each group. RSO 2 was recorded before anesthesia induction (T 0), 10 min after anesthesia induction (T 1), 10 min after prone position (T 2), 10 min after spinal decompression (T 3), 30 min after spinal decompression (T 4) and 10 min after extubation (T 5); The basic value of rSO 2, the minimum value of rSO 2 (rSO 2min), the average value of rSO 2 (rSO 2mean) and the maximum percentage of decrease of rSO 2 (rSO 2% max) were recorded. When rSO 2 <55% or rSO 2% max >10% and the duration was longer than 15 s, the intervention group took measures such as adjusting head position, adjusting blood pressure, increasing FiO 2 and respiratory parameters, increasing P ETCO 2 until rSO 2 returned to the required range; The control group did not interfere with the intraoperative rSO 2. Neuropsychological tests were used to evaluate the cognitive function of the two groups 7 days after operation. The patients were followed up 30 days after operation with the revised cognitive function telephone questionnaire (TICS-M). The incidence of postoperative neurocognitive impairment (PND) was recorded. The perioperative data and postoperative adverse reactions of the two groups were recorded. Results:At T 3 and T 4, the rSO 2 of the intervention group was significantly higher than that of the control group ( P<0.01), the intraoperative rSO 2min and rSO 2mean of the intervention group were higher than the control group, and the rSO 2%max was lower than the control group ( P<0.05). The incidence of PND 7 days after surgery, extubation time, postanesthesia care unit (PACU) stay time, hospital stay and postoperative adverse reactions in the intervention group were lower than those in the control group ( P<0.05). There was no significant difference in the incidence of PND 30 days after operation between the two groups ( P>0.05). Conclusions:The goal-oriented management of rSO 2 can reduce the incidence of early postoperative PND in elderly spine surgery patients, which is conducive to the rapid recovery of patients after surgery.
7.The effect and mechanism of short-chain fatty acid regulate tacrolimus-related hyperglycemia in mice
Zijian ZHANG ; Wenjiao JIAO ; Yue XU ; Lian GONG ; Weixun ZHANG ; Xiaopeng HU
Chinese Journal of Urology 2021;42(11):856-861
Objective:To investigate the effect and mechanism of short-chain fatty acids (SCFAs) on the side-effect of tacrolimus on blood glucose.Methods:The C57BL/6 mice were treated with tacrolimus orally (10 mg/kg, tacrolimus group), tacrolimus plus 150 mmol/L sodium butyrate and isovalerate mixed solution (SCFAs group), broad-spectrum antibiotics (antibiotic group), and tacrolimus plus broad-spectrum antibiotics (tac&abx group). After 8 weeks intervention, the fasting blood glucose (FBG), oral glucose tolerance test (OGTT), hemoglobin A1C (HbA1c) were tested as indicators of glucose metabolism, and the gut microbiota, SCFAs concentration in the ileocecal, serum glucagon-like peptide-1 (GLP-1), fasting serum insulin, and GLP-1 expression in intestinal mucosa were performed for intestinal-glucose metabolism mechanism.Results:The FBG and HbA1c were significantly increased in tacrolimus group[(7.31±0.97)mmol/L, (8.34±1.12)%] than control group [(5.23±0.30)mmol/L, (4.32±0.80)%, all P<0.05], which remained normal in antibiotic group [(4.92±0.31)mmol/L, (5.61±0.98)%)], tac&abx group[(5.95±0.37)mmol/L, (4.56±0.26)%] and SCFAs groups [(5.87±0.68)mmol/L, (5.07±1.79)%]. The OGTT in the tacrolimus group showed glucose tolerance impairment, while other groups remained normal. The ileocecal butyric acid and isovaleric acid concentrations in the tacrolimus group were (722.3±262.2) μg/g and (10.0±5.1)μg/g, lower than the control group[ (1 321.3±165.5) μg/g, (19.7±3.6)μg/g, P<0.05]. The above acids in the SCFAs group remained normal as in the control group [(1 375.7±451.6) μg/g, (24.5±11.5)μg/g)]. The fasting serum insulin in the tacrolimus group decreased significantly to (3.2 ± 0.6)mIU/L, compared with control[ (4.4±0.9) mIU/L]and SCFAs groups [(7.0±1.1) mIU/L]. The GLP-1 test indicated a significant decrease in the tacrolimus group[ (4.7±2.9)pg/ml, P<0.05] compared with the SCFAs group and control group [(42.5±19.9) pg/ml, (33.1±9.1) pg/ml]. Conclusions:Tacrolimus affects glucose metabolism through the SCFAs-associated GLP-1 pathway in the intestine, and oral supplementation with mixed SCFAs provides a new insight for the prevention and treatment of tacrolimus-induced hyperglycemia in transplant recipients.
8.Long non-coding RNA ARHGAP5-AS1 inhibits the proliferation, migration and invasion of breast cancer cells
HU Caixia ; ZHANG Xiufen ; FANG Kai ; GUO Zijian ; LI Lihua
Chinese Journal of Cancer Biotherapy 2020;27(11):1255-1263
[摘 要] 目的:检测长链非编码RNA(long non-coding RNA,lncRNA)ARHGAP5-AS1在乳腺癌组织及细胞中的表达,分析其表达与患者临床病理参数及预后的相关性,并初步探讨其对乳腺癌细胞体外增殖、迁移和侵袭的影响。方法:通过对TCGA数据库中乳腺癌相关数据集的生物信息学分析,筛选出在乳腺癌中低表达且与患者不良预后相关的lncRNA ARHGAP5-AS1,采用qPCR方法在江南大学附属医院肿瘤科从2010年4月至2016年10月收集的乳腺癌组织中验证其表达。采用χ2检验分析ARHGAP5-AS1表达与乳腺癌患者临床病理参数之间的关系,Kaplan-Meier生存分析构建生存曲线,比较高、低表达组的总生存期和无复发生存期。CCK-8实验、划痕实验和Transwell实验分别检测ARHGAP5-AS1敲低对乳腺癌细胞MDA-MB-231和BT-549的增殖、迁移和侵袭的影响。结果:TCGA数据库分析结果显示,ARHGAP5-AS1在乳腺癌组织中的表达水平显著低于正常乳腺组织(P<0.01),其低表达与较大肿瘤直径(T3)、远处转移(M1)、ER和PR阴性以及较短的总生存期显著相关(均P<0.05)。乳腺癌组织中ARHGAP5-AS1表达水平显著低于癌旁组织(P<0.05),其低表达与较大的肿瘤直径和淋巴结转移相关(均P<0.05)。同样,ARHGAP5-AS1在6株人乳腺癌细胞系(MDA-MB-231、BT-549、MDA-MB-468、MCF-7、HCC1937、Hs578T)中的表达水平也显著低于正常乳腺上皮细胞系(MCF-10A)(均P<0.05)。细胞功能实验显示,ARHGAP5-AS1敲低促进MDA-MB-231和BT-549细胞的增殖、迁移和侵袭(均P<0.05)。结论:ARHGAP5-AS1异常低表达可能通过促进乳腺癌细胞的增殖、迁移和侵袭影响乳腺癌的发生发展。
9.Contribution of by to moxibustion.
Zijian WU ; Huangan WU ; Ling HU ; Qing YU ; Jie WANG
Chinese Acupuncture & Moxibustion 2018;38(5):5493-5452
Mr. was a famous acupuncturist in China. He succeeded the acupuncture from his family in childhood, and practiced acupuncture strictly with insightful and original perspective. The , one of his magnum opus, proposed innovative ideas in the theory and clinical practice of moxibustion, such as revival of moxibustion, three phases of moxibustion sensation, moxibustion for heat syndromes. In this article, the contribution of to moxibustion was discussed from background of compiling this book, poem and medical cases, explanation on moxibustion theory and practice and its effects on later ages.
Acupuncture
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history
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China
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History, 20th Century
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History, 21st Century
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Humans
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Moxibustion
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history
10.Establishment of orthotopic colorectal cancer model by colonoscopy with submucosal injection in living mice
Zhengchun WU ; Lingxiang WANG ; Xiongying MIAO ; Zhulin YANG ; Kang CHEN ; Kunpeng WANG ; Wenhao CHEN ; Zijian ZHANG ; Kai DENG ; Junjiao HU ; Xibin YANG ; Yu WEN ; Li XIONG
International Journal of Biomedical Engineering 2018;41(3):250-256
Objective To set up a living mice colonoscopy platform to establish an orthotopic model of colorectal cancer in mice under direct vision,and to observe its biological behavior such as metastasis.Methods Eighteen-week-old male C57/BL mice were anesthetized,and the intestinal lumen of the mice was examined by a self-developed living mice colonoscopy and Olympus URF-P5 ureteroscopy,respectively.The imaging effects of the two methods were compared.Human colon cancer HT-29 cells were injected into the colonic mucosa of BALB/c-nu mice under direct vision.The colonoscopy was performed on the 3rd,7th and 15th day after the injection to observe the tumor formation in the intestinal lumen.The mice were sacrificed when the body weight decreased significantly or cachexia appeared,and then the abdominal cavity was examined including the tumor formation and metastasis.Results The self-developed living mice colonoscopy platform can provide clear vision of enteric cavity,and no mice died in the colonoscopy examination.In vivo subcutaneous injection of HT-29 cells in mice was performed with a perforation rate of 15%,a mortality rate of 33.3%,a tumor formation rate of 62.5%,an abdominal metastasis rate of 60%,a liver metastasis rate of 25%,and an abdominal wall transfer rate of 25%.Conclusion The self-developed mice colonoscopy platform can be used for the study of colorectum in living mice.The imaging effect is no less than that of Olympus URF-P5 ureteroscopy.In addition,an orthotopic colorectal cancer model can be established by this platform combing with submucosal injection technology.


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