1.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
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Carcinoma, Non-Small-Cell Lung/genetics*
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ErbB Receptors/genetics*
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Extracellular Matrix Proteins/genetics*
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Immune Checkpoint Inhibitors/therapeutic use*
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Lung Neoplasms/genetics*
;
Mutation
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Protein Kinase Inhibitors/therapeutic use*
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Proto-Oncogene Proteins p21(ras)/genetics*
;
Treatment Outcome
2.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.
3.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.
4.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.
5.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.
6.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.
7.New Model for Intelligent Imaging Screening of Pulmonary Nodules.
Guangyu JIN ; Shiteng SUO ; Jianxing FENG ; Xiaochen FAN ; Jingqi WEI ; Jianrong XU ; Tao YU
Chinese Journal of Medical Instrumentation 2019;43(3):226-229
The artificial intelligence based on medical aid diagnosis has been in full swing in these years. How to better and more safely utilize this new technology to improve the diagnostic efficiency and quality of doctors poses new challenges for our hospital management. This paper aims to explore relevant management problems and corresponding solutions from seven aspects:data security, system integration, technical parameters, risks, workflows and diagnosis results by introducing a new intelligent image screening system. After these management problems have been better solved, we found that the intelligent image screening system can improve the diagnostic efficiency and quality of doctors.
Artificial Intelligence
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Hospital Administration
8.The Development of Anastomat of Digestive Tract Based on the Magnetic Compressive Technique.
Hongke ZHANG ; Yi LV ; Chang LIU ; Liang YU ; Xuemin LIU ; Dinghui DONG ; Feng MA ; Haohua WANG
Chinese Journal of Medical Instrumentation 2015;39(5):331-333
A new anastomat for digestive tract operations, based on the magnetic compressive technique and mechanical transmission mechanism, is composed of a removable head and a reusable body. The head includes two parts: the proximal end can be fixed to the body, and the distal end could be used for performing a purse string suture. The procedure of anastomosis is similar to that of the stapler, and the anastomoses is established using a pair of magnetic rings. The instrument makes magnamosis more simple and feasible, and it would facilitate the clinical application. The body of the anastomat is reusable and the head could be replaced according to the clinical scenarios, these could reduce the medical cost. The magnetic rings would be excreted with the feces, and there is no foreign body response at last.
Anastomosis, Surgical
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instrumentation
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methods
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Gastrointestinal Tract
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surgery
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Humans
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Magnetics
9.Research the Expression of MDR1 Genes in Vaginal Candida Albicans Resistance to Azole Agents
Haoyan TAN ; Haohua FENG ; Yanping HE
Journal of Modern Laboratory Medicine 2015;(1):105-107,110
Objective To investigate the expression levels of MDR1 gene from azole resistant strains in vaginal Candidaalbi-cans.Methods 60 strains of Candida albicans from recurrent vagintis patients were collected and identified by CHROM agar from Aug.2011 to Aug.2012.The drug resistance was detected by disk diffusion method.According to the result of drug sensitivity test,the strains were diveded into four groups:sensitive group moderately susceptible or resistant to flucon-azole group moderately susceptible or resistant to detoconazole group and moderately susceptible or resistant to miconazole group.Each group was selected 12 strains randomly.The expression of the MDR1 gene in these 48 strains were detected by real-time RT-PCR and analysed the datas by t test statistics.Results There were 22 sensitive strains,26 strains of moder-ately susceptible or resistant to detoconazole,12 strains of moderately susceptible or resistant to fluconazole and 38 strains of moderately susceptible or resistant to miconazole in 60 strains of Candidaalbicans.The relative expression of MDR1 gene in sensitive group was 0.41±0.47,in moderately susceptible or resistant to detoconazole group fluconazole group and micon-azole group were 3.32±4.46,2.27±3.05 and 0.9±0.81 respectively.Compared with the sensitive group,t values of mod-erately susceptible or resistant to detoconazole group,fluconazole group and miconazole group were-2.177,-2.130 and-2.094.The expression level of MDR1 gene had no statistical significance between the sensitive strains and moderately sus-ceptible or resistant strains(P>0.05).Conclution The relationship between MDR1 expression and the resistance to azole agents in vaginal Candida albicans requires further study.
10.The Development of Anastomat of Digestive Tract Based on the Magnetic Compressive Technique
Hongke ZHANG ; Yi LV ; Chang LIU ; Liang YU ; Xuemin LIU ; Dinghui DONG ; Feng MA ; Haohua WANG
Chinese Journal of Medical Instrumentation 2015;(5):331-333
A new anastomat for digestive tract operations, based on the magnetic compressive technique and mechanical transmission mechanism, is composed of a removable head and a reusable body. The head includes two parts: the proximal end can be fixed to the body, and the distal end could be used for performing a purse string suture. The procedure of anastomosis is similar to that of the stapler, and the anastomoses is established using a pair of magnetic rings. The instrument makes magnamosis more simple and feasible, and it would facilitate the clinical applicaion. The body of the anastomat is reusable and the head could be replaced according to the clinical scenarios, these could reduce the medical cost. The magnetic rings would be excreted with the feces, and there is no foreign body response at last.

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