1.Effect of neuromuscular electrical stimulation on quadriceps muscle strength and walking for patients after anterior cruciate ligament reconstruction
Zhijiao FAN ; Lanqi JIN ; Zhibin HUANG ; Yige LI ; Sihan YAO ; Yubao MA
Chinese Journal of Rehabilitation Theory and Practice 2025;31(2):242-248
ObjectiveTo investigate the effect of neuromuscular electrical stimulation (NMES) on quadriceps muscle strength and walking for patients after anterior cruciate ligament reconstruction (ACLR). MethodsThirty-four patients after ACLR were selected at Beijing Rehabilitation Hospital of Capital Medical University from July, 2022 to October, 2023, and randomly divided into control group (n = 17) and experimental group (n = 17). Both groups received routine rehabilitation and functional training, and the experimental group received NMES during the functional training, while the control group received sham NMES, for eight weeks. Quadriceps peak torque-to-weight ratio, single-leg support phase and plantar impulses during walking were measured before and after intervention. ResultsTwo cases in the control group and three in the experimental group dropped down. Quadriceps peak torque-to-weight ratio improved in both groups after intervention (|t| > 17.578, P < 0.001), and improved more in the experimental group than in the control group (t = 4.714, P < 0.001); while the affected single-leg support phase and the affected/unaffected single-leg support phase ratio improved in both groups (|t| > 16.882, P < 0.001), and improved more in the experimental group than in the control group (t > 3.234, P < 0.01); and plantar impulses of all zones optimized in both groups (t > 9.221, P < 0.001), and were better in the experimental group than in the control group(|t| > 2.852, P < 0.01). ConclusionNMES may further improve quadriceps muscle strength, plantar pressure distribution during walking and single-leg support in patients after ACLR.
2.Dexmedetomidine inhibits the inflammatory response mediated by microglia after traumatic brain injury in rats through the cGAS-STING pathway
Chunlei LI ; Yan LI ; Wenbin CUI ; Qiang YANG ; Zhibin JIN ; Zan LIANG
Immunological Journal 2025;41(4):224-230
Objective To investigate whether dexmedetomidine(DEX)can inhibit the inflammatory response mediated by microglia after traumatic brain injury(TBI)in rats through the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene(cGAS-STING)pathway.Methods A TBI rat model was constructed,and successfully modeled rats were randomly separated into TBI group,low and high-dose dexmedetomidine treatment groups(DEX-L,DEX-H groups),and high-dose dexmedetomidine treatment+cGAS-STING pathway activator group(DEX-H+DMXAA group),with 18 rats in each group.Additionally,18 healthy normal rats were selected as the Control group.Rats in each group were subjected to neurobehavioral scoring(mNSS).The brain water content of rats in each group was detected.Flow cytometry was used to detect Tregs in the brain tissue of each group.ELISA was applied to detect the levels of inflammatory cytokines in brain tissue.HE staining was applied to observe brain tissue injury.TUNEL staining was applied to detect neuronal apoptosis.Immunohistochemistry was applied to detect the expression of the microglial cell marker ion calcium binding adapter molecule 1(Iba1).Western blot was applied to detect the expression of apoptosis and cGAS-STING pathway related proteins.Results Compared with the Control group,the TBI group showed structural injury to brain tissue,edema,abnormal neuronal morphology,reduced number and disordered arrangement,deep staining of nuclear folds,and blurred nucleoli,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1 β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P<0.05).Compared with the TBI group,the brain tissue structure of the DEX-L and DEX-H groups was slightly injuried,edema was reduced,and the morphology of neurons was relatively normal,with a small decrease in number and relatively neat arrangement,a small amount of nuclei were wrinkled and deeply stained,and most of the nucleoli were obvious,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were reduced(P<0.05).The brain tissue structure and neuronal injury in the DEX-H+DMXAA group were more severe than the DEX-H group,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P<0.05).Conclusion Dexmedetomidine can inhibit the inflammatory response mediated by microglia after TBI in rats,and its mechanism of action is related to the inhibition of the cGAS-STING pathway.
3.Global, regional, and national prevalence and years lived with disability due to infertility, 1990-2021: Results from the Global Burden of Disease Study 2021.
Rui LIN ; Yuan LIN ; Guangfu JIN ; Qiufen SUN ; Zhibin HU
Chinese Medical Journal 2025;138(23):3115-3123
BACKGROUND:
Infertility is a burdensome, often overlooked condition. This study aimed to investigate the global distribution and trends in the burden of infertility from 1990 to 2021.
METHODS:
We obtained data on the prevalence and years lived with disability (YLDs) related to infertility from the Global Burden of Disease 2021 study and evaluated them by calculating the estimated annual percentage change in age-standardized rates. We investigated the relationship between sociodemographic index (SDI) and the burden of infertility on the global, regional, and national levels.
RESULTS:
In 2021, there were 143,261,562 female and 55,481,380 male infertility cases worldwide, respectively. In China, female and male infertility cases accounted for 23.59% and 21.47% of the global totals, reaching 33,795,944 and 11,909,889, respectively. Compared with 2019, the global number of female and male infertility cases increased by 5,286,227 in females and 2,017,271 in males. In contrast, China saw a decline in both female and male infertility cases, with reductions of 698,735 and 154,591, respectively. From 1990 to 2021, the age-standardized prevalence rate (ASPR) and age-standardized YLDs rate (ASYR) for female infertility both increased by 0.59% annually, whereas these two corresponding indicators for male infertility increased by 0.50% annually worldwide. The burden of female infertility was consistently higher than that of male infertility and demonstrated a faster rate of increase. East Asia had the highest ASPR and ASYR for female infertility, whereas Eastern Europe had the highest metrics for male infertility. A horizontal S-shaped association was observed between the SDI and ASPR and ASYR of infertility, with a rapid decline in the infertility burden when the SDI exceeded 0.7.
CONCLUSIONS
The global burden of infertility has increased over the years, with a higher burden on women and underdeveloped regions. These findings emphasize the need to prioritize healthcare for patients with infertility to address the rising burden.
Humans
;
Female
;
Male
;
Global Burden of Disease
;
Prevalence
;
Infertility/epidemiology*
;
Adult
;
Infertility, Male/epidemiology*
;
Persons with Disabilities/statistics & numerical data*
;
Middle Aged
;
Infertility, Female/epidemiology*
;
China/epidemiology*
;
Disability-Adjusted Life Years
4.Dexmedetomidine inhibits the inflammatory response mediated by microglia after traumatic brain injury in rats through the cGAS-STING pathway
Chunlei LI ; Yan LI ; Wenbin CUI ; Qiang YANG ; Zhibin JIN ; Zan LIANG
Immunological Journal 2025;41(4):224-230
Objective To investigate whether dexmedetomidine(DEX)can inhibit the inflammatory response mediated by microglia after traumatic brain injury(TBI)in rats through the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene(cGAS-STING)pathway.Methods A TBI rat model was constructed,and successfully modeled rats were randomly separated into TBI group,low and high-dose dexmedetomidine treatment groups(DEX-L,DEX-H groups),and high-dose dexmedetomidine treatment+cGAS-STING pathway activator group(DEX-H+DMXAA group),with 18 rats in each group.Additionally,18 healthy normal rats were selected as the Control group.Rats in each group were subjected to neurobehavioral scoring(mNSS).The brain water content of rats in each group was detected.Flow cytometry was used to detect Tregs in the brain tissue of each group.ELISA was applied to detect the levels of inflammatory cytokines in brain tissue.HE staining was applied to observe brain tissue injury.TUNEL staining was applied to detect neuronal apoptosis.Immunohistochemistry was applied to detect the expression of the microglial cell marker ion calcium binding adapter molecule 1(Iba1).Western blot was applied to detect the expression of apoptosis and cGAS-STING pathway related proteins.Results Compared with the Control group,the TBI group showed structural injury to brain tissue,edema,abnormal neuronal morphology,reduced number and disordered arrangement,deep staining of nuclear folds,and blurred nucleoli,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1 β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P<0.05).Compared with the TBI group,the brain tissue structure of the DEX-L and DEX-H groups was slightly injuried,edema was reduced,and the morphology of neurons was relatively normal,with a small decrease in number and relatively neat arrangement,a small amount of nuclei were wrinkled and deeply stained,and most of the nucleoli were obvious,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were reduced(P<0.05).The brain tissue structure and neuronal injury in the DEX-H+DMXAA group were more severe than the DEX-H group,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P<0.05).Conclusion Dexmedetomidine can inhibit the inflammatory response mediated by microglia after TBI in rats,and its mechanism of action is related to the inhibition of the cGAS-STING pathway.
5.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
6.Evaluation of current status in implementation of WS 582-2017 Specifications for testing of quality control in X and γ ray stereotactic radiotherapy system
Wei CHEN ; Jinxin JU ; Zhibin ZHANG ; Qiao MA ; Xingjiang CAO ; Xiangyong FAN ; Xindi WEI ; Zihao ZHANG ; Lanlan TIAN ; Tianyuan QIU ; Jin WANG
Chinese Journal of Radiological Medicine and Protection 2024;44(12):1043-1048
Objective:To investigate WS 582-2017 Specifications for testing of quality control in X and γ ray stereotactic radiotherapy system (hereinafter referred to as WS 582-2017) with respect to its current status, existing problems and evaluation since its implementation in Beijing, Chongqing, Jiangsu and Sichuan. Methods:The evaluation of this standard was carried out by means of field survey, questionnaire survey and expert seminar. In accordance with the WS 582-2017 implementation assessment programme, a total of 153 professionals involved in the implementation of WS 582-2017 from 80 radiological health technical service institutions, health supervision institutions and medical institutions of two municipalities and two provinces were surveyed in 2023. The investigation was carried out by using a combination of cluster sampling and stratified sampling and through sampling professionals with of different institution characteristics and different technical titles. The general survey method was used for Jiangsu province, while the cluster sampling method was used for others, with 153 individulas from 80 institutions being sampled for the investigation.Results:The awareness rate of WS 582-2017 was 80.39%, of which 90.85% considered it to be scientific and rigorous, 81.05% considered it to be operational and 97.39% considered it to be in consistency with the relevant regulatory standards, 90.20% considerd it to have played an important role in promoting radiological protection optimization for radiotherapy, 90.85% considered the implementation of it to have played a significant role in the quality control of standarded testing of radiotherapy equipment, and 86.93% considered the implementation of it to have played a significant role in enhancing the professional competence of relevant technicians.Conclusions:The overall implementation of WS 582-2017 in two municipalities and two provinces is good, with scientific and operable technical contents and the remarkable effect achieved in its implementation. However, the WS 582-2017 needs to be further improved in some areas, and training on the standard needs to be strengthened to improve the awareness rate of it.
7.Evaluation of current status in implementation of WS 582-2017 Specifications for testing of quality control in X and γ ray stereotactic radiotherapy system
Wei CHEN ; Jinxin JU ; Zhibin ZHANG ; Qiao MA ; Xingjiang CAO ; Xiangyong FAN ; Xindi WEI ; Zihao ZHANG ; Lanlan TIAN ; Tianyuan QIU ; Jin WANG
Chinese Journal of Radiological Medicine and Protection 2024;44(12):1043-1048
Objective:To investigate WS 582-2017 Specifications for testing of quality control in X and γ ray stereotactic radiotherapy system (hereinafter referred to as WS 582-2017) with respect to its current status, existing problems and evaluation since its implementation in Beijing, Chongqing, Jiangsu and Sichuan. Methods:The evaluation of this standard was carried out by means of field survey, questionnaire survey and expert seminar. In accordance with the WS 582-2017 implementation assessment programme, a total of 153 professionals involved in the implementation of WS 582-2017 from 80 radiological health technical service institutions, health supervision institutions and medical institutions of two municipalities and two provinces were surveyed in 2023. The investigation was carried out by using a combination of cluster sampling and stratified sampling and through sampling professionals with of different institution characteristics and different technical titles. The general survey method was used for Jiangsu province, while the cluster sampling method was used for others, with 153 individulas from 80 institutions being sampled for the investigation.Results:The awareness rate of WS 582-2017 was 80.39%, of which 90.85% considered it to be scientific and rigorous, 81.05% considered it to be operational and 97.39% considered it to be in consistency with the relevant regulatory standards, 90.20% considerd it to have played an important role in promoting radiological protection optimization for radiotherapy, 90.85% considered the implementation of it to have played a significant role in the quality control of standarded testing of radiotherapy equipment, and 86.93% considered the implementation of it to have played a significant role in enhancing the professional competence of relevant technicians.Conclusions:The overall implementation of WS 582-2017 in two municipalities and two provinces is good, with scientific and operable technical contents and the remarkable effect achieved in its implementation. However, the WS 582-2017 needs to be further improved in some areas, and training on the standard needs to be strengthened to improve the awareness rate of it.
9.Mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence
Hui WANG ; Xiaoxia WEI ; Zhimin MA ; Mengmeng JI ; Yanqian HUANG ; Jing ZHANG ; Meng ZHU ; Juncheng DAI ; Guangfu JIN ; Hongxia MA ; Zhibin HU ; Hongbing SHEN
Chinese Journal of Epidemiology 2022;43(12):1875-1880
Objective:To evaluate the possible mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence.Methods:After excluding individuals with missing educational levels and cancer information at baseline, 446?772 participants in the UK Biobank (UKB) prospective cohort study were included. Cox regression models were used to investigate the associations of educational level and smoking and healthy diet score with the incidence of lung cancer. Mediating effect analysis was conducted to analyze the mediating effect of smoking and healthy diet score on the correlation between educational level and lung cancer.Results:During a median follow-up of 7.13 years, 1?994 new- onset lung cancer cases were observed. Per 1 standard deviation (5 years) increase in educational level was associated with a 12% lower risk of lung cancer ( HR=0.88, 95% CI: 0.84-0.92). The corresponding level 1-5 in the International Standard Classification for Education (ISCED) were mapped to UKB self‐report highest qualification to estimate the educational level. A higher rank means a higher educational level. Compared with level ISCED-1, the HR(95% CI) of level ISCED-2, ISCED-3, ISCED-4 and ISCED-5 were respectively 0.83 (0.72-0.94), 0.67 (0.53-0.85), 0.76 (0.65-0.89) and 0.72 (0.64-0.80) for lung cancer. Education years were negatively correlated with smoking, with β coefficients (95% CI) being -0.079 (-0.081- -0.077), but positively correlated with healthy diet score ( β=0.042, 95% CI: 0.039-0.045). Analysis of mediating effect indicated that the association of educational level with lung cancer risk was mediated by smoking and healthy diet score, the proportions of mediating effect were 38.952% (95% CI: 31.802%-51.659%) and 1.784% (95% CI: 0.405%-3.713%), respectively. Conclusion:Smoking and healthy diet score might mediate the effect of educational level on the incidence of lung cancer, indicating that improving the level of education can reduce the risk of lung cancer by changing lifestyles such as smoking and diet.
10.Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma.
Na QIN ; Yuancheng LI ; Cheng WANG ; Meng ZHU ; Juncheng DAI ; Tongtong HONG ; Demetrius ALBANES ; Stephen LAM ; Adonina TARDON ; Chu CHEN ; Gary GOODMAN ; Stig E BOJESEN ; Maria Teresa LANDI ; Mattias JOHANSSON ; Angela RISCH ; H-Erich WICHMANN ; Heike BICKEBOLLER ; Gadi RENNERT ; Susanne ARNOLD ; Paul BRENNAN ; John K FIELD ; Sanjay SHETE ; Loic LE MARCHAND ; Olle MELANDER ; Hans BRUNNSTROM ; Geoffrey LIU ; Rayjean J HUNG ; Angeline ANDREW ; Lambertus A KIEMENEY ; Shan ZIENOLDDINY ; Kjell GRANKVIST ; Mikael JOHANSSON ; Neil CAPORASO ; Penella WOLL ; Philip LAZARUS ; Matthew B SCHABATH ; Melinda C ALDRICH ; Victoria L STEVENS ; Guangfu JIN ; David C CHRISTIANI ; Zhibin HU ; Christopher I AMOS ; Hongxia MA ; Hongbing SHEN
Frontiers of Medicine 2021;15(2):275-291
Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Adenocarcinoma of Lung/genetics*
;
Carcinoma, Non-Small-Cell Lung/genetics*
;
Carcinoma, Squamous Cell/genetics*
;
Genetic Heterogeneity
;
Genetic Predisposition to Disease
;
Genome-Wide Association Study
;
Humans
;
Lung Neoplasms/genetics*
;
Polymorphism, Single Nucleotide

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