1.Intravoxel incoherent motion and dynamic contrast-enhanced MRI for assessing abnormalities of brucellosis spondylitis without conventional MRI changes
Haohua WANG ; Pengfei ZHAO ; Pengfei QIAO
Chinese Journal of Medical Imaging Technology 2024;40(8):1226-1230
Objective To observe the value of intravoxel incoherent motion(IVIM)and dynamic contrast-enhanced MRI(DCE-MRI)for assessing abnormalities of brucellosis spondylitis(BS)without conventional MRI changes.Methods Data of 36 brucellosis patients with definite spinal lesions displayed on conventional MRI(BS1 group),14 cases without brucellosis infection nor abnormal spinal signals on MRI(control group)and 36 brucellosis patients without definite spinal lesions on conventional MRI(BS2 group)were retrospectively analyzed.The values of IVIM parameters,including perfusion fraction(f),pure water diffusion coefficient(D)and pseudo-diffusion coefficient(D*),also of DCE-MRI parameters,including time-intensity curve(TIC)type,volume transport constant(Ktrans),the rate constant(Kep)and volume fraction of extravascular extracellular space per unit tissue volume(Ve)were compared among groups.Univariate and multivariate logistic regression were used to screen independent factors for discriminating BS1 and BS2.Receiver operating characteristic curves were drawn,and the areas under the curve(AUC)were calculated to evaluate the efficiency of the above parameters for discriminating BS1 and BS2.Results Among IVIM parameters,compared with control group,D*values decreased but D values increased in BS1 group,while D*values increased in BS2 group(all adjusted P<0.05).Compared with BS2 group,BS1 group had higher values of f and D and lower D*(all adjusted P<0.05).In BS1 group,the TIC types were predominantly type Ⅰ(23/36,63.89%),which were wholly or predominantly type Ⅲ in BS2 group and control group,and of the former was significantly different with latter 2(both adjusted P<0.05).Compared with control group,Ktrans increased progressively in both BS1 and BS2 groups(both adjusted P<0.05).BS1 group had lower Kep and higher Ve than BS2 and control groups(all adjusted P<0.05).Among univariate logistic regression models,the model including only f had lower capability for discriminating BS1 and BS2(AUC=0.759)than those including D,Ktrans and Ve(AUC=0.951,0.833,0.894,all P<0.05).No significant different was found among multivariate logistic regression model including f and D,model including Ktrans and Ve nor model including all above parameters(all P>0.05).Conclusion Both IVIM and DCE-MRI could be used to evaluate BS abnormality without conventional MRI changes.
2.USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer.
Dexin YANG ; Yuqin FENG ; Haohua LU ; Kelie CHEN ; Jinming XU ; Peiwei LI ; Tianru WANG ; Dajing XIA ; Yihua WU
Journal of Zhejiang University. Science. B 2023;24(2):143-156
This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‒1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‒2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48‒1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‒1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‒0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‒0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‒8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‒6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
Humans
;
Carcinoma, Non-Small-Cell Lung/genetics*
;
ErbB Receptors/genetics*
;
Extracellular Matrix Proteins/genetics*
;
Immune Checkpoint Inhibitors/therapeutic use*
;
Lung Neoplasms/genetics*
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Mutation
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Protein Kinase Inhibitors/therapeutic use*
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Proto-Oncogene Proteins p21(ras)/genetics*
;
Treatment Outcome
3.USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer
YANG DEXIN ; FENG YUQIN ; LU HAOHUA ; CHEN KELIE ; XU JINMING ; LI PEIWEI ; WANG TIANRU ; XIA DAJING ; WU YIHUA
Journal of Zhejiang University. Science. B 2023;24(2):143-156,中插1-中插9
This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01?1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49?2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48?1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39?1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A (USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32?0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38?0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75?8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88?6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12C mutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
4.Analysis of interdiscipline of medicine and engineering supported by National Natural Science Foundation in comprehensive university: Taking Xi′an Jiaotong University as an example
Yan LI ; Haohua WANG ; Yiping MOU ; Yilin CHEN ; Rongqian WU ; Yi LV ; Feng MA
Chinese Journal of Medical Science Research Management 2022;35(3):180-185
Objective:Take Xi′an Jiaotong University as an example, to analyze the funding status of the National Natural Science Foundation of the Comprehensive University in the field of medicine-Engineering integration, with a view to revealing the general picture of interdiscipline of medicine and engineering research of Xi′an Jiaotong University, and gaining a glimpse of the development of the interdiscipline of medicine and engineering research in universities.Methods:Descriptive statistics were used to analyze the basic situation of the National Natural Science Foundation of China approved in the field of medicine-Engineering integration.Results:A total number of 692 projects were funded in the field of medicine-Engineering integration, with a total funding of 420 million yuan. Funding types are mainly general projects, followed by Youth Science Foundation projects. The number of key and major projects is small, but it is of great significance to the growth of the funding amount. The Department of Medical Science and the Department of Engineering Science are the departments with the largest total number of funding projects and funding amounts. In terms of funding disciplines, the core disciplines of imaging medicine and biomedical engineering, mechanical design and manufacturing, mechanics, biomaterials, imaging and tissue engineering, optics and optoelectronics, and oncology have been formed.Conclusions:The research shows that the interdiscipline of medicine and engineering research of Xi′an Jiaotong University has continued to grow, attracting scholars in science, engineering, medicine, management and other fields to participate, forming an advantageous discipline group. For the development of the integration of medicine and engineering in domestic universities, it is recommended to strengthen the top-level design, increase support for young people, and pay attention to the advanced layout of key and major projects.
5.Exploration and practice on interdisciplinary studies in universities: The case of Xi′an Jiaotong University
Yan LI ; Feng MA ; Yuan WANG ; Haohua WANG ; Yilin CHEN ; Rongqian WU ; Yi LV
Chinese Journal of Medical Science Research Management 2022;35(5):368-373
Objective:Under the background of extensive interdisciplinary studies, this article aims to provide references for other domestic universities by analyzing the current situation and exploration of universities to promote the development of interdisciplinary studies.Methods:Taking Xi′an Jiaotong University as a typical case, it was summarized from three aspects: background, specific measures, and results.Results:Measures such as strengthening top-level design, improving organizational management systems, consolidating research platforms, establishing cross-funds, and strengthening talent training modes, were adopted by Xi′an Jiaotong University to promote the development of interdisciplinary studies from all aspects of structure, system, human resources, financial resources, and incentive mechanisms. It has promoted the depth and extension of the school's science, engineering, medicine, literature, and other disciplines, improved academic influence, and serving national and regional development.Conclusions:Interdisciplinary studies is a systematic project that requires the cooperation of the government, universities, medical institutions, industry, and academia to create a policy and institutional environment for multidisciplinary collaboration, truly allowing disciplines to move from mechanical integration to knowledge fusion. Therefore, in the process of interdisciplinary development in universities, it is necessary to straighten out the guiding concepts and basic principles of interdisciplinarity, grasp the characteristics of interdisciplines, and focus on promoting the discipline structure, supporting systems, talent training, funding, and incentive mechanisms.
6.Rapidliver autotransplantation by magnetic anastomotic technique during ex situ liver resection in an animal model
Shiqi LIU ; Peng LEI ; Yi LYU ; Yulong SONG ; Haohua WANG ; Jigang BAI
Chinese Journal of Organ Transplantation 2021;42(8):485-489
Objective:To invent a set of novel magnetic anastomotic device based upon the technique of magnetic compression anastomosis(MCA)for rapid venous reconstruction during ex situ liver resection, and verify its clinical value and performance in animal models. Methods:Fiften adult mongrel dogs of either gender underwent the ex situ liver resection. The novel magnetic vessel anastomosis device for the venous reconstruction of liver autotransplantation procedure was performed on 8 mongrel dogs(MCA group), and the traditional handsewing technique was used on 5 additional dogs(THS group). Time for completing venous reconstruction and time of venous anastomosis, venous velocity, intraoperative and postoperative survival and complications were recorded. Patency was detected via color Doppler ultrasound scans and X-ray cholangiography after surgery. The changes of intestinal lumen and kidney were also observed. Results:The time required to perform IVC and PV reconstruction for liver autotransplantation was significantly shorter for the magnetic vessel anastomosis device(9.5±2.5) min than for THS(30.7±3.4) min. There was significant difference in anhepatic period( P=0.0000). After operation, except one died, other nine animals in group A survived after operation but all five cases died in the THS group during liver autotransplantation. Vascular X-ray angiography and color Doppler ultrasound found blood flow MCA group normal, and there wasn't stoma stenosis. Conclusions:MCA technique could be fast and efficacious to complete venous reconstruction for liver autotransplantation in ex situ liver resection operation, and helpful to reduce organ ischemia-reperfusion injury.
7.Localization of small pulmonary nodules with magnetic beads: An animal experiment
Lu LV ; Aihua SHI ; Xiaopeng YAN ; Zhixuan ZHANG ; Guxiang ZHOU ; Junke FU ; Feng MA ; Haohua WANG ; Yi LV ; Yong ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(11):1360-1364
Objective To investigate the feasibility of using magnetic beads to locate small pulmonary nodules. Methods Twelve rabbits were randomly divided into two groups, 6 in each group. One group underwent thoracotomy after anesthesia and the other group underwent percutaneous puncture under the guidance of X-ray. One and two cylindrical tracer magnets (magnetic beads) with a diameter of 1 mm and a height of 3 mm were injected adjacent to the imaginary pulmonary nodules in left lung in each group. The magnetic beads beside the imaginary nodules were attracted by a pursuit magnet with a diameter of 9 mm and a height of 19 mm. The effectiveness of localization by magnetic beads were determined by attraction between tracer and pursuit magnets. Results All processes were uneven in 12 rabbits. There was micro hemorrhage and no hematoma in the lung tissue at the injection site of the magnetic beads. When tracked with the pursuit magnets, there was one bead divorce in cases that one bead was injected, but no migration or divorce of the magnetic beads in cases that two magnetic beads were simultaneously injected to localize the small pulmonary nodules. Conclusion The feasibility of using magnetic beads to locate small pulmonary nodules has been preliminarily verified.
8.Application of magnetic surgery technique in thoracic surgery
ZHANG Yong ; YAN Xiaopeng ; SHI Aihua ; WANG Haohua ; MA Feng ; LIU Shiqi ; LU Yi ; FU Junke
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(03):336-342
The earliest research of magnetic surgery was the application of magnetic anastomotic device to anastomose the blood vessels. Now, it has been widely used for anastomosis of blood vessels, gastrointestinal tract and biliary tract. The concept of "magnetic surgery" was named firstly by LU Yi in 2010 and magnetic surgery was classified into magnetic anchoring technique, magnetic navigation technique, magnetic compression technique, magnetic tracing technique, and magnetic suspension technique. The applications of magnetic surgery in the field of thoracic surgery mainly include magnetic compression technique, magnetic anchoring technique and magnetic navigation technique. This paper summarizes the application of magnetic surgery in thoracic surgery and prospects its future development in the field of thoracic surgery.
9.Hexokinase-Ⅱ role in tumor growth and targeting therapy
Haohua WANG ; Xiuxing CHEN ; Guifang GUO
Journal of International Oncology 2017;44(3):213-216
The energy for tumor cells mainly derives from the aerobic glycolysis,that is,the Warburg effect,which also provides a large amount of precursor substances for the growth of tumor cells.Hexokinase-Ⅱ (HK-Ⅱ),highly expressed in tumor tissue,is the rate-limiting enzyme of glycolysis and closely related to the energy metabolism of tumor.Recent studies have showed that HK-Ⅱ not only mediates Warburg effect,but also promotes tumor proliferation by inhibiting tumor cell apoptosis and regulating autophagy.It has been confirmed that blocking HK-Ⅱ gene expression and inhibiting HK-Ⅱ with small molecule inhibitor can kill tumor cells in many kinds of cancer.Agent targeting HK-Ⅱ may become a new generation of targeted drugs.
10.Effect of Ligustrazine on the Expression of Caspase-3 and ABR Threshold in Guinea Pig Cochlea after Gentamicin Ototoxicity
Zhengdao YANG ; Jifang ZHANG ; Haohua HOU ; Zhangmin WANG ; Yueqiu NI
Journal of Shenyang Medical College 2016;18(5):403-406,409
Objective:To investigate the effects of Ligustrazine (TMP) on the expression of caspase-3 and ABR threshold in guinea pig cochlea after gentamicin (GM) ototoxicity. Methods:A total of 80 guinea pigs were randomly divided into saline group, GM group, GM+TMP group and TMP group. The duration of treatment was lasted 10 d continuously in all groups. The dose was decided by their weight. The ABR threshold were measured before and after administration of 10 d. SABC immunohistochemical method was used to detect the expression of caspase-3 in the spiral ganglion,cochlea hair cells,and stria vascularis of guinea pigs. Results:(1) The average gray value in the spiral ganglion cells, stria vascularis and hair cells in GM group had significant difference with those in the same position of control group (P<0.05) .The average gray value in the spiral ganglion cells and hair cells in GM+TMP group had no difference with those in the same position of control group (P>0.05), but in stria vascularis (P<0.05) . Meanwhile the average gray value in spiral ganglion, hair cells, stria vascularis in TMP+GM group had significant difference with those in GM group (P<0.05) . (2) The ABR threshold had no significant differences before treatment (P>0.05) . After administration of 10 d, the ABR threshold of GM group was significantly changed (P<0.05) . The ABR thresholds in GM group was significantly higher than that in control group (P<0.05) . The ABR threshold in TMP+GM group was lower than that in GM group (P<0.05) . Conclusion:TMP participates in preventing the process of cochlea injury caused by GM,through blocking the expression of caspase-3 in cochlea tissue of GM ototoxicosis probably,which achieve the protection of GM deafness eventually.

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