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Deyi Huang,1 Xingan Yang,2 Hongbiao Ruan,3 Yushui Zhuo,1 Kai Yuan,4 Bowen Ruan,1 Fang Li1 1Department of Ultrasound, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of China; 2Department of Ultrasound, Taizhou Hospital of Zhejiang Province, Linhai City, Zhejiang Province, People’s Republic of China; 3Department of Cardiology, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of China; 4Department of Clinical Laboratory, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Fang Li, Department of Ultrasound, The People’s Hospital of Yuhuan, No. 18, Changle Road, Yuhuan City, Zhejiang Province, 317600, People’s Republic of China, Tel +8613967672898, Email 3260772796@qq.comIntroduction: Chronic coronary artery disease (CAD) management often relies on myocardial contrast echocardiography (MCE), yet its effectiveness is limited by subjective interpretations and difficulty in distinguishing hibernating from necrotic myocardium. This study explores the integration of machine learning (ML) with radiomics to predict functional recovery in dyskinetic myocardial segments in CAD patients undergoing revascularization, aiming to overcome these limitations.Methods: This prospective study enrolled 55 chronic CAD patients, dividing into training (39 patients, 205 segments) and testing sets (16 patients, 68 segments). Dysfunctional myocardial segments were identified by initial wall motion scores (WMS) of ≥ 2 (hypokinesis or higher). Functional recovery was defined as a decrease of ≥ 1 grade in WMS during follow-up echocardiography. Radiomics features were extracted from dyssynergic segments in end-systolic phase MCE images across five cardiac cycles post- “flash” impulse and processed through a five-step feature selection. Four ML classifiers were trained and compared using these features and MCE parameters, to identify the optimal model for myocardial recovery prediction.Results: Functional improvement was noted in 139 out of 273 dyskinetic segments (50.9%) following revascularization. Receiver Operating Characteristic (ROC) analysis determined that myocardial blood flow (MBF) was the most precise clinical predictor of recovery, with an area under the curve (AUC) of 0.770. Approximately 1.34 million radiomics features were extracted, with nine features identified as key predictors of myocardial recovery. The random forest (RF) model, integrating MBF values and radiomics features, demonstrated superior predictive accuracy over other ML classifiers. Validation of the RF model on the testing dataset demonstrated its effectiveness, evidenced by an AUC of 0.821, along with consistent calibration and clinical utility.Conclusion: The integration of ML with radiomics from MCE effectively predicts myocardial recovery in CAD. The RF model, combining radiomics and MBF values, presents a non-invasive, precise approach, significantly enhancing CAD management.Keywords: coronary artery disease, myocardial contrast echocardiography, radiomics, machine learning, myocardial recovery prediction, random forest

Zhen Yang,1,* Xingyu Kao,1,* Na Huang,1 Kang Yuan,2 Jingli Chen,2 Mingfeng He2 1The Eighth School of Clinical Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong Province, People’s Republic of China; 2Foshan Hospital of Traditional Chinese Medicine, Foshan, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingli Chen; Mingfeng He, Email fstcmcjl@126.com; he-mingfeng@foxmail.comPurpose: Sepsis-induced lung injury (SLI) is a serious complication of sepsis. PANoptosis, a novel form of inflammatory programmed cell death that is not yet to be fully investigated in SLI. Our research aims to screen and validate the signature genes of PANoptosis in SLI by bioinformatics and in vivo experiment.Methods: SLI-related datasets were downloaded from NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) of SLI were identified and intersected with the PANoptosis gene set to obtain DEGs related to PANoptosis (SPAN_DEGs). Then, Protein–Protein Interaction (PPI) network and functional enrichment analysis were conducted based on SPAN_DEGs. SVM-REF, LASSO and RandomForest three algorithms were combined to identify the signature genes. The Nomogram and ROC curves were performed to predict diagnostic value. Immune infiltration analysis, correlation analysis and differential expression analysis were used to explore the immunological characterization, correlation and expression levels of the signature genes. Finally, H&E staining and qRT-PCR were conducted for further verification in vivo experiment.Results: Twenty-four SPAN_DEGs were identified by intersecting 675 DEGs with the 277 PANoptosis genes. Four signature genes (CD14, GSDMD, IL1β, and FAS) were identified by three machine learning algorithms, which were highly expressed in the SLI group, and had high diagnostic value in the diagnostic model. Moreover, immune infiltration analysis showed that most immune cells and immune-related functions were higher in the SLI group than those in the control group and were closely associated with the signature genes. Finally, it was confirmed that the cecum ligation and puncture (CLP) group mice showed significant pathological damage in lung tissues, and the mRNA expression levels of CD14, IL1β, and FAS were significantly higher than the sham group.Conclusion: CD14, FAS, and IL1β may be the signature genes in PANoptosis to drive the progression of SLI and involved in regulating immune processes.Keywords: sepsis, lung injury, PANoptosis, machine learning, immune infiltration analysis

Yong Ling,1,* Xuejiao Hu,1,* Guansheng Zheng,1 Weitao Ye,2 Kaixuan Yuan,1 Long Ye,1 Weiye Huang,3 Benshun Tian,1 Bing Gu1 1Department of Clinical Laboratory Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510000, People’s Republic of China; 2Department of Radiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510000, People’s Republic of China; 3Department of Pathology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Benshun Tian; Bing Gu, Department of Laboratory Medicine, Guangdong Provincial People’s Hospital, 106 Zhongshan 2nd Road, Yuexiu District, Guangzhou, Guangdong, 510000, People’s Republic of China, Email tbs20161017@163.com; gb20031129@163.comAbstract: Scrub typhus is a vector-borne infectious disease caused by Orientia tsutsugamushi. Accurate and timely diagnosis at the early infection stage could save the patients’ lives. Traditional technologies were limited to rapidly and successfully detecting Orientia tsutsugamushi due to poor specificity, especially in the condition of atypical symptoms. The technology of Metagenomic next-generation sequencing (mNGS) is amenable to finding the real pathogen because it holds potential as a diagnostic platform for unbiased pathogen identification and precision medicine. Herein, we reported two clinical case reports relative to the Orientia tsutsugamushi infection diagnosed by mNGS. We hope these two cases will improve clinical diagnosis.Keywords: scrub typhus, metagenomic next-generation sequencing, Orientia tsutsugamushi

Jingzhong Ouyang,1,&ast; Zhengzheng Wang,1,&ast; Kun Yuan,2,&ast; Yi Yang,3,4 Yanzhao Zhou,1 Qingjun Li,1 Nanmu Yang,1 Haitao Zhao,5 Hong Zhao,3,4 Jinxue Zhou1 1Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 2School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 3Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Zhao, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100020, People’s Republic of China, Email zhaohong@cicams.ac.cn Jinxue Zhou, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, 450003, People’s Republic of China, Email zhoujx888@126.comPurpose: To evaluate the efficacy and safety of lenvatinib plus programmed death-1 (PD-1) antibody as postoperative adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risks of recurrence.Patients and Methods: A series of 137 patients with HCC at high risks of recurrence who underwent hepatectomy at our hospital between October 2019 and January 2022 were retrospectively analyzed. Recurrence-free survival (RFS), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. Landmark analysis was used to compare short- and long-term RFS. Univariable and multivariable analyses were used to identify prognostic factors, and subgroup analyses were performed according to high risks of recurrence.Results: A total of 85 patients underwent hepatectomy alone and 52 patients received postoperative adjuvant therapy. Compared with the hepatectomy group (HG), RFS was significantly improved in the adjuvant therapy group (ATG) (P < 0.001), but OS was not (P = 0.098). Landmark analysis revealed that RFS within 6 months of the HG was significantly different from that of the ATG (P < 0.001) but not after 6 months (P = 0.486). Multivariable analysis showed that without adjuvant therapy, high Child-Pugh classification, high alpha-fetoprotein levels, microvascular invasion, and satellite lesions were independent risk factors for recurrence within 6 months after hepatectomy. Subgroup analysis revealed that patients with MVI significantly benefited from adjuvant therapy in RFS. But for OS, adjuvant therapy was only significantly effective in patients with single tumor. The most common treatment-related adverse events during adjuvant therapy were hypertension (36.5%), rash or itching (28.8%), diarrhea (23.1%), and fatigue (21.2%).Conclusion: Postoperative adjuvant lenvatinib plus PD-1 antibody significantly improved RFS in patients with HCC at high risks of recurrence with acceptable safeties.Keywords: hepatocellular carcinoma, postoperative adjuvant therapy, lenvatinib, PD-1 antibody, efficacy, safety

Zhenshan Song,1,&ast; Fa Lin,1,&ast; Yu Chen,1 Tu Li,1 Runting Li,1 Junlin Lu,1 Heze Han,1 Ruinan Li,1 Jun Yang,1 Zhipeng Li,1 Haibin Zhang,1 Kexin Yuan,1 Ke Wang,1 Yunfan Zhou,1 Yitong Jia,1 Xiaolin Chen1– 3 1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Stroke Center, Beijing Institute for Brain Disorders, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaolin Chen, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Email chenxiaolin@bjtth.orgPurpose: Systemic inflammation plays an important role in the pathophysiology and progression of aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to investigate the association between a new biomarker, the inflammatory burden index (IBI) and the prognosis as well as in-hospital complications of aSAH patients.Patients and Methods: We analyzed data from patients with aSAH between January 2019 and September 2022 who were included in the LongTEAM (Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage) registry study. The IBI was formulated as C-reactive protein × neutrophils/lymphocytes. The unfavorable functional prognosis was assessed by the modified Rankin Scale (mRS). Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off values for IBI to distinguish the unfavorable functional prognosis. Multivariate logistic regression was applied to investigate the association between IBI and in-hospital complications. Propensity score matching was adjusted for imbalances in baseline characteristics to assess the effect of IBI on prognosis.Results: A total of 408 consecutive patients with aSAH enrolled in the study, of which 235 (57.6%) were female patients and the mean age was 55.28 years old. An IBI equal to 138.03 was identified as the best cut-off threshold to distinguish the unfavorable prognosis at 3 months (area under the curve [AUC] [95% CI] 0.637 [0.568– 0.706]). ln IBI was independently associated with 3-month functional prognosis (OR [95% CI] 1.362 [1.148– 1.615]; P< 0.001), pneumonia (OR [95% CI] 1.427 [1.227– 1.659]; P< 0.001) and deep venous thrombosis (DVT). (OR [95% CI] 1.326 [1.124– 1.564]; P=0.001). After propensity score matching (57:57), an increased proportion of patients with IBI ≥ 138.03 had a poor functional prognosis at 3 months and in-hospital complications including developed pneumonia and DVT.Conclusion: In patients with aSAH, high IBI level at admission was associated with unfavorable functional prognosis as well as pneumonia and deep vein thrombosis.Keywords: aneurysmal subarachnoid hemorrhage, inflammatory burden index, functional prognosis, complications

Mengdi Xie,1,&ast; Kang Yuan,2,&ast; Xinyi Zhu,2,&ast; Jingjing Chen,3 Xiaohao Zhang,4 Yi Xie,2 Min Wu,1 Zhaojun Wang,2 Rui Liu,2 Xinfeng Liu1,2,5 1Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Department of Neurology, Changhai Hospital, Navy Medical University, Shanghai, People’s Republic of China; 4Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 5Stroke Center & Department of Neurology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinfeng Liu, Department of Neurology, Jinling Hospital, Nanjing Medical University, No. 305 East Zhongshan Road, Nanjing, Jiangsu Province, 210000, People’s Republic of China, Tel +86 2584801861, Fax +86 2584805169, Email xfliu2@vip.163.com Rui Liu, Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210000, Jiangsu Province, People’s Republic of China, Tel +86 2584801861, Fax +86 2584805169, Email liurui8616@163.comBackground: Systemic immune inflammation has been investigated as a prognostic marker of different diseases. This study is designed to assess the association of systemic immune-inflammation index (SII) with long-term mortality of stroke-associated pneumonia (SAP) patients.Methods: Patients aged ≥ 18 years with SAP were selected from the Nanjing Stroke Registry Program in China. We retrospectively evaluated systemic immune-inflammation response with SII and pneumonia severity with the pneumonia severity index and the confusion, uremia, elevated respiratory rate, hypotension, and aged 65 years or older score. To explore the correlation between SII and mortality in SAP patients, multivariable Cox regressions and competing risk regressions were conducted. Mediation analysis was also performed to assess the role of pneumonia severity.Results: Among 611 patients in the SAP population, death occurred in 164 patients (26.8%) during the median follow-up of 3.0 (1.2– 4.6) years. In multivariate analysis, higher SII scores could predict increased mortality in patients with SAP (adjusted hazard ratio 2.061; 95% confidence interval, 1.256– 3.383; P = 0.004), and the association was mediated by pneumonia severity. Moreover, adding SII to traditional models improved their predictive ability for mortality.Conclusion: Our study displayed that SII was characterized in SAP patients with different prognoses. Elevated SII scores increased the risk of mortality. Further research is required for the clinical practice of the index among SAP patients.Keywords: systemic immune-inflammation index, stroke-associated pneumonia, mortality, China

Land-use and land-cover change significantly modify local land-surface characteristics and water/energy exchanges, which can lead to atmospheric circulation and regional climate changes. In particular, deforestation accounts for a large portion of global land-use changes, which transforms forests into other land cover types, such as croplands and grazing lands. Many previous efforts have focused on observing and modeling land–atmosphere–water/energy fluxes to investigate land–atmosphere coupling induced by deforestation. However, interpreting land–atmosphere–water/energy-flux responses to deforestation is often complicated by the concurrent impacts from shifts in land-surface properties versus background atmospheric forcings. In this study, we used 29 paired FLUXNET sites, to improve understanding of how deforested land surfaces drive changes in surface-energy-flux partitioning. Each paired sites included an intact forested and non-forested site that had similar background climate. We employed transfer entropy, a method based on information theory, to diagnose directional controls between coupling variables, and identify nonlinear cause–effect relationships. Transfer entropy is a powerful tool to detective causal relationships in nonlinear and asynchronous systems. The paired eddy covariance flux measurements showed consistent and strong information flows from vegetation activity (gross primary productivity (GPP)) and physical climate (e.g. shortwave radiation, air temperature) to evaporative fraction (EF) over both non-forested and forested land surfaces. More importantly, the information transfers from radiation, precipitation, and GPP to EF were significantly reduced at non-forested sites, compared to forested sites. We then applied these observationally constrained metrics as benchmarks to evaluate the Energy Exascale Earth System Model (E3SM) land model (ELM). ELM predicted vegetation controls on EF relatively well, but underpredicted climate factors on EF, indicating model deficiencies in describing the relationships between atmospheric state and surface fluxes. Moreover, changes in controls on surface energy flux partitioning due to deforestation were not detected in the model. We highlight the need for benchmarking model simulated surface-energy fluxes and the corresponding causal relationships against those of observations, to improve our understanding of model predictability on how deforestation reshapes land surface energy fluxes.

Yong Zhou,1,&ast; Yongfei Fan,1,&ast; Binzhe Qiu,1 Ming Lou,1 Xiaoshuang Liu,2 Kai Yuan,1,3 Jichun Tong1 1The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 2Nanjing Jinling Hospital: East Region Military Command General Hospital, Nanjing, People’s Republic of China; 3Heart and Lung Disease Laboratory, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jichun Tong; Kai Yuan, Email tongjichun2021@163.com; yuankai202001@163.comBackground: NSCLC (non-small cell lung cancer) has become the malignancy with the highest incidence and mortality rate worldwide. Fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a key regulator of glycolysis with both kinase and phosphatase activities. The Warburg effect, or increased glycolysis in tumors, provides the metabolic basis for cancer cell proliferation and metastasis, and the Warburg pathway enzyme PFKFB4 is a newly identified important kinase. This study aimed to elucidate the poor prognostic relevance of PFKFB4 in non-small cell lung cancer tissues and its relationship with immune cell infiltration, immune cell biomarkers, and immune checkpoints.Methods: In this study, immunohistochemical methods were used to assess PFKFB4 expression levels in 140 surgical specimens from patients with histologically confirmed non-small cell lung cancer and to investigate the relationship between PFKFB4 expression levels and the patients’ clinicopathological characteristics. The impact of PFKFB4 expression on prognosis was evaluated using Kaplan–Meier survival analysis and Cox regression analysis.Results: When compared to normal paracrine tissues, PFKFB4 expression was enhanced in lung cancer tissues, and Kaplan–Meier survival analysis revealed that patients with high PFKFB4 expression had a worse prognosis. In NSCLC, PFKFB4 was found to be associated with immune cell infiltration and immunological checkpoints.Conclusion: PFKFB4 expression may be upregulated as a sign of poor prognosis in NSCLC, and PFKFB4 may be implicated not only in the genesis and progression of NSCLC but also in its immunological control.Keywords: PFKFB4, NSCLC, prognostic marker, immune cells

Yongfei Fan,1 Yong Zhou,1 Ming Lou,1 Xinwei Li,2 Xudong Zhu,1 Kai Yuan1,3 1Department of Thoracic Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 2Department of Gastroenterology, Affiliated Cancer Hospital of Bengbu Medical College, Bengbu, People’s Republic of China; 3Heart and Lung Disease Laboratory, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of ChinaCorrespondence: Kai Yuan, Department of Thoracic Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, No. 29 Xinglong Lane, Changzhou, 213003, Jiangsu Province, People’s Republic of China, Tel +86-13915890721, Email yuankai1978@163.comPurpose: The role of RNA N6-methyladenosine (m6A) modification in the progression of multiple tumours and the tumour microenvironment (TME) has been progressively demonstrated and promises a new direction for tumour therapy. However, there have been no reports on systematic analyses of RNA m6A modification in TME in non-small cell lung cancer (NSCLC).Patients and Methods: In this study, we used unsupervised cluster analysis to identify three m6A modification patterns of 28 m6A regulators and three m6A gene signature subgroups of commonly differentially expressed genes (co-DEGs) in the three m6A modification patterns. Quantifying these subtypes using the ssGSEA and ESTIMATE algorithms to characterise the tumour immune microenvironment (TIME) in NSCLC. Based on the principal component analysis (PCA), we used co-DEGs to construct m6A scores to analyse the characteristics of m6A modifications in individual patients and assessed the practical clinical utility of m6A scores using a nomogram for survival prediction.Results: A total of 28 m6A regulators in 1210 NSCLC samples were mainly enriched in RNA modification and metabolic biological processes. The three following m6A modification patterns were identified based on the role of the 28 m6A regulators in TME: immune inflammation, immune evasion and immune desert. The m6A scores calculated based on co-DEGs in these modification patterns were significantly positively correlated with immune infiltration and significantly negatively correlated with tumour mutational burden (TMB). Survival was significantly better in the high-m6A-score group than in the low-m6A-score group, and the m6A score could be used as an independent favourable prognostic factor. In addition, assessment of both immune checkpoint inhibitors (ICIs) and immunophenoscore (IPS) revealed a better immunotherapeutic effect in the high-m6A-score group.Conclusion: The modification characteristics of 28 m6A regulators in the TIME of NSCLC were analysed from a comprehensive to an individual basis, which may facilitate the development of more effective clinical immunotherapeutic strategies.Graphical Abstract: Keywords: immunophenotype, immunotherapy, m6A modification, non-small cell lung cancer, tumour microenvironment

Kaisheng Yuan, Ruiqi Zeng, Pengteng Deng, Aiping Zhang, Huiqian Liu, Ning Wang, Yongxi Tang, Zhikang Yin, Hang Liu Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Hang Liu, Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Tel +86-185-8030-9681, Email liuhang723@163.comPurpose: Adrenocortical carcinoma (ACC) is an endocrine malignant tumor with poor prognosis. The study aimed to construct ACC immune-related gene prognostic signature and verify the efficacy of prognostic signature.Methods: ACC RNA-seq data and clinical information are downloaded from TCGA databases and GEO databases. We used single sample gene set enrichment analysis (ssGSEA) to assess immune cell infiltration in ACC patients and ACC patients were divided into high- and low-immune cell infiltration clusters. The validity of ssGSEA grouping was verified using the ESTIMATE algorithm. A total of 275 differentially expressed immune-related genes (IRGs) were obtained from the intersection of IRGs and differentially expressed genes (DEGs) in high and low immune cell infiltration clusters. LASSO analysis was used to identify 13 IRGs that regulate the prognosis of ACC patients through immune infiltration. Kaplan–Meier analysis, ROC curve, univariate and multivariate Cox regression further confirmed that these 13 immune-related gene signatures were innovative and significant prognostic factors, which were independent of clinical features. Finally, ACC prognostic nomogram was constructed, ROC curve and calibration curve were drawn to evaluate the accuracy of the prognostic nomogram.Results: LASSO regression analysis was used to screen out ACC survival-related genes. Univariate and multivariate Cox proportional risk regression models were used to analyze and construct the ACC prognosis nomogram. The AUC for predicting 1-, 3- and 5-year overall survival rate of ACC patients was 0.799, 0.966 and 0.969, suggesting good prediction accuracy. The calibration curve shows that the predicted results of the prognostic nomogram are in good agreement with the actual situation.Conclusion: ssGSEA technique plays an important role in the construction of ACC prognostic model. Based on IRGs associated with survival independently predicted ACC prognosis, we identified thirteen immune-related genes as prognostic signature for ACC.Keywords: immune, prognostic, adrenocortical carcinoma, ACC, single sample gene set enrichment analysis, ssGSEA, risk score

Yubin Tian,1,2,&ast; Yong Zhou,2,&ast; Junhui Liu,1,2 Lei Yi,2 Zhaojia Gao,2,3 Kai Yuan,1,3 Jichun Tong2,3 1School of Medical, Dalian Medical University, Dalian, People’s Republic of China; 2The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 3Heart and Lung Disease Laboratory, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Yuan; Jichun Tong, Email yuankai202001@163.com; tongjichun2012@163.comPurpose: To investigate the expression profile of systemic RNA interference deficient-1 transmembrane family member 1 (SIDT1) in patients with non-small cell lung cancer (NSCLC) and assess its prognostic value and immune infiltration.Materials and Methods: A tissue microarray (TMA) was purchased containing 60 paired NSCLC tissues and matched para-tumor tissues, and another TMA was constructed comprising 140 NSCLC tissues. Then, immunohistochemical staining and scoring were performed. Finally, we evaluated the expression profiles and prognostic values of SIDT1 in NSCLC. Correlation between SIDT1 gene expression and the immune microenvironment of NSCLC was investigated using the ESTIMATE and CIBERSORT algorithms.Results: SIDT1 was mainly detected in the cytoplasm and the cell membrane. SIDT1 expression was significantly higher in tumor tissues than in para-tumor tissues. High expression of SIDT1 was correlated with the NSCLC stage. High SIDT1 expression signals worsening overall survival (OS) in NSCLC patients, especially in stage I. In LUSC, high SIDT1 expression is an independent prognostic factor for worsening OS.Conclusion: High SIDT1 expression predicted a low survival rate in LUSC patients, suggesting it may be a potential target for prognostic assessment of NSCLC patients.Keywords: NSCLC, prognosis, TMA, immune infiltration, SIDT1

Zhong Wang,1,&ast; Kai Yuan,1,&ast; Yan-Bin Ji,2,&ast; Su-Xia Li,3 Le Shi,1 Zhe Wang,1 Xin-Yu Zhou,4 Yan-Ping Bao,3 Wen Xie,5 Ying Han,3 Jie Shi,3 Lin Lu,1,3,6 Wei Yan,1 Wen-Hao Chen1 1Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University, Beijing, 100191, People’s Republic of China; 2Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, 250012, People’s Republic of China; 3National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, 100191, People’s Republic of China; 4Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 5Mental Health Center of Anhui Province, Hefei, 230032, People’s Republic of China; 6Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen-Hao Chen; Wei Yan Peking University Sixth Hospital/Peking University Institute of Mental Health, 51 Huayuanbei Road, Haidian District, Beijing, 100191, People’s Republic of ChinaTel +86-10-82801342; Tel +86-10-62723704Email chenwenhao@bjmu.edu.cn; weiyan@bjmu.edu.cnIntroduction: Accumulating evidence suggests that both sleep loss and gut dysbiosis can lead to metabolic disorders. However, less is known about the impact of total sleep deprivation (SD) and sleep recovery on the composition, function, and metabolic dynamics of the gut microbiota.Methods: Specific-pathogen free Sprague–Dawley rats were subjected to 48 h of SD with gentle handling and then allowed to recover for 1 week. Taxonomic profiles of fecal microbiota were obtained at baseline, 24 h of SD, 48 h of SD, and 1 week of recovery. We used 16S rRNA gene sequencing to analyze the gut microbial composition and function and further characterize microbiota-derived metabolites in rats.Results: The microbiota composition analysis revealed that gut microbial composition and metabolites did not change in the rats after 24 h of SD but were significantly altered after 48 h of SD. These changes were reversible after 1 week of sleep recovery. A functional analysis was performed based on Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations, indicating that 19 KEGG pathways were significantly altered in the gut microbiota in SD rats. These functional changes occurred within 24 h of SD, were more apparent after 48 h of SD, and did not fully recover after 1 week of sleep recovery.Conclusion: These results indicate that acute total SD leads to significant compositional and functional changes in the gut microbiota, and these changes are reversible.Keywords: gut microbiota, sleep deprivation, short-chain fatty acid, function prediction

Weihong Chen,1 Mengjiu Zhang,1 Yan Guo,1 Zhen Wang,1 Qingqing Liu,1 Runze Yan,1 Yi Wang,1 Qiaoru Wu,1 Kai Yuan,2 Weiwei Sun1 1Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China; 2School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of ChinaCorrespondence: Kai Yuan; Weiwei Sun Email yuankai@bucm.edu.cn; sunweitcm@163.comIntroduction: Dysbiosis of gut microbiota impairs the homeostasis of immune and metabolic systems. Although previous studies have revealed the correlation between gut microbiota and various diseases, the function between gut microbiota and diabetic nephropathy (DN) has not been discovered distinctly. In this study, we tried to investigate the profile and function of gut microbiota in DN.Methods: A total of 100 people were enrolled in this study. Twenty were healthy people, 20 were diabetes patients, and 60 were DN patients. The DN patients were divided into three stages including stage III, IV, and V. We conducted taxonomic analyses in different groups. The distributions of phyla, classes, orders, families, and genera in different groups and samples were investigated. We also evaluated the correlations between clinical parameters and gut microbiota in 60 DN patients.Results: The gut microbiota in the healthy group, diabetes group, and DN group had 1764 operational taxonomic units (OTUs) in total. The healthy group had 1034 OTUs, the diabetes group had 899 OTUs, and the DN group had 1602 OTUs. The diversity of gut microbiota in the stage III DN group was smaller than that in the other groups. 24-h urinary protein was positively correlated with Alistipes and Subdoligranulum, cholesterol was positively correlated with Bacteroides and Lachnoclostridium, and estimated glomerular filtration rate was negatively correlated with Ruminococcus torques group.Discussion: The gut microbiota might play an important role in the development and pathogenesis of DN. A change in gut microbiota diversity is correlated with disease progression. Some kinds of gut microbiota including Alistipes, Bacteroides, Subdoligranulum, Lachnoclostridium, and Ruminococcus torques group might be detrimental factors in DN.Keywords: diabetic nephropathy, gut microbiota, genus, progression

Min Wu,1,&ast; Xiaohao Zhang,2,&ast; Jingjing Chen,3,&ast; Mingming Zha,4 Kang Yuan,5 Kangmo Huang,2 Yi Xie,2 Jianzhong Xue,6 Xinfeng Liu1,2,7 1Department of Neurology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, 210002, People’s Republic of China; 2Department of Neurology, Jinling Hospital, Affiliated Medical School of Nanjing University, Nanjing, 210002, People’s Republic of China; 3Department of Neurology, Changhai Hospital, Navy Medical University, Shanghai, 200433, People’s Republic of China; 4Department of Neurology, Jinling Hospital, Medical School of Southeast University, Nanjing, 210002, People’s Republic of China; 5Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 6Department of Neurology, Changshu No.2 People’s Hospital, Changshu, People’s Republic of China; 7Stroke Center & Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinfeng LiuDepartment of Neurology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, No. 305 Zhongshan East Road, Xuanwu District, Nanjing, Jiangsu Province, 210002, People’s Republic of ChinaTel +86 138 13835114Email xfliu2@vip.163.comJianzhong XueDepartment of Neurology, Changshu No.2 People’s Hospital, No. 18 Taishan Road, Changshu, Jiangsu Province, People’s Republic of ChinaTel +86 13506247572Email xjz2021@sina.comBackground and Purpose: The impact of low-grade inflammation (LGI) on stroke recurrence has not been well studied yet. We aimed to evaluate the association between LGI and stroke recurrence in patients with ischemic stroke.Methods: Patients with first-ever ischemic stroke diagnosed within 72 hours of symptoms onset were consecutively recruited from the Nanjing Stroke Registry Program. C-reactive protein (CRP) level, white blood cell (WBC) count, platelet (PLT) count, and neutrophil-to-lymphocyte ratio (NLR) were conceived as low-grade inflammation biomarkers and combined into a standardized LGI score. The association of LGI score with the risk of stroke recurrence was analyzed with multivariate Cox regression models. Analyses accounting for the competing risk of stroke recurrence and death were also performed.Results: Of the 1214 patients studied (median age, 61 years; male, 71.6%), 177 (14.6%) patients experienced a recurrent stroke with a median follow-up of 23.0 (interquartile ranges, 14.5– 34.0) months. Patients with stroke recurrence had a higher LGI score (median, 3 versus − 2; P < 0.001) than those without recurrence. The univariate analysis indicated that patients with LGI scores in the fourth quartile were more likely to have a stroke recurrence (hazard ratios [HR], 4.312; 95% confidence interval [CI], 2.675– 6.952; P < 0.001). After adjusting for potential confounders, the association remained significant in the multivariate Cox regression model (HR, 4.080; 95% CI, 2.420– 6.879; P < 0.001). Competing risks model and sensitivity analysis further confirmed this conclusion.Conclusion: This study showed that an elevated LGI score was associated with a higher risk of stroke recurrence, independent of other vascular risk factors.Keywords: low-grade inflammation, stroke recurrence, ischemic stroke, predictor

Xiuqun Gong,1,&ast; Zeyu Lu,2,&ast; Xiwu Feng,3,&ast; Kang Yuan,4 Mei Zhang,1 Xiaosi Cheng,1 Min Xue,1 Liang Yu,1 Jun Lu,5,6 Chuanqing Yu1 1Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, People’s Republic of China; 2College of Medicine, Anhui University of Science and Technology, Huainan, People’s Republic of China; 3Department of Cardiothoracic Surgery, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, People’s Republic of China; 4Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 5Department of Medical Laboratory, College of Medicine, Anhui University of Science and Technology, Huainan, People’s Republic of China; 6Department of Clinical Laboratory, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun LuDepartment of Medical Laboratory, College of Medicine, Anhui University of Science and Technology, 168 Taifeng Road, Huainan, 232001, Anhui Province, People’s Republic of ChinaTel + 86- 13855453149Email cfdxlujun@126.comChuanqing YuDepartment of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, 203 Huaibin Road, Huainan, 232007, Anhui Province, People’s Republic of ChinaTel +86- 18949669880Email yuchuanqin1967@163.comObjective: Increased level of serum uric acid (UA) is often considered a risk factor for ischemic stroke. However, there are limited data on the association between UA and intracerebral hemorrhage (ICH). This study aimed to examine the connection between UA and early neurological deterioration (END) in patients with ICH.Methods: This is a prospective observational study. Patients with ICH were enrolled from January 2017 to December 2020. END was diagnosed as the Canadian Stroke Scale (CSS) score decreased ≥ 1 points between admission and 48 hours. UA was measured at admission. Multivariable logistic regression analysis was performed to explore the relationship between serum UA and END.Results: Of the 498 enrolled patients, 132 (26.5%) were developed with END. Patients with END had a significantly higher level of serum UA (332 vs 270 μmol/L, P < 0.001). Univariate logistic regression analysis indicated that patients with the highest quartile of UA level had an OR of 3.256 (95% CI: 1.849– 5.734, P < 0.001) for END compared with those with the lowest quartile of UA level. After adjusting for major confounders, the highest UA quartile remained as an independent predictor for END (OR = 2.282, 95% CI: 1.112– 4.685, P = 0.013).Conclusion: Higher serum UA level was independently associated with END in patients with ICH; therefore, intervention to lower UA level may be worth considering.Keywords: early neurological deterioration, intracerebral hemorrhage, uric acid

Kai Yuan,1,2 Jin Long Zhang,2 Jie Yu Yan,2 Bing Yuan,1 Jin Xin Fu,2 Yan Wang,2 Xue Dong Sun,3 Yang Guan,2 Feng Duan,2 Mao Qiang Wang1,2 1Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 2Department of Interventional Radiology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of ChinaCorrespondence: Mao Qiang WangDepartment of Interventional Radiology, The Fifth Medical Center, Chinese PLA General Hospital, 28 Fu-Xing Road, Beijing, 100853, People’s Republic of ChinaTel +86 10-66937190Email wangmq@vip.sina.comPurpose: To assess the long-term outcome of performing uterine artery embolization (UAE) using small particles in women with symptomatic adenomyosis (AD).Methods: Twenty-seven consecutive women (median age 42 years, range 29– 53 years) with AD, in eight cases AD combined with fibroids, who underwent UAE between February 2015 and January 2019, were retrospectively analyzed. The embolization was performed using small-sized polyvinyl alcohol particles (100 μm and 300 μm). The patients completed the Uterine Fibroid Symptom and Quality of Life questionnaire at baseline and at a 42-month follow-up (range 24– 71). The junction zone (JZ) thickness and uterine volume were also calculated at baseline and at a three-month follow-up.Results: The total symptom severity score (SSS) decreased from a median of 59 (range 34– 78) at baseline to a median of 9 (range 3– 47) at the end of this study; the health-related quality of life score (HRQOL) increased from a median of 38 (range 23– 49) at baseline to a median of 84 (range 46– 97) at 42 months. Twenty of the 27 patients were asymptomatic. The clinical response of the remaining seven women was little improvement in their symptoms, and one of the seven women underwent a hysterectomy at 35 months. Twenty-six of the 27 (96%) patients had a preserved uterus at the 42-month follow-up. There was no difference after UAE in SSS, HRQOL, junction zone (JZ) thickness, and uterus volume between patients with pure AD and those with AD combined with fibroids (p = 0.729, 0.710, 0.973, and > 0.99). There was no difference in the JZ thickness and uterus volume at baseline between the asymptomatic women and the women with an insufficient response (p = 0.854 and 0.253), and there were no major complications afterwards.Conclusion: From the long-term follow-ups, it could be seen that UAE using small particles is safe and effective in treating AD, especially in preserving the uterus. There is no relationship between the clinical outcomes and the initial presence of AD, with or without fibroids, and the JZ thickness at baseline does not seem to be a predictor for the long-term outcome of UAE.Keywords: adenomyosis, uterine artery embolization, UFS–QoL, interventional radiology

Wen Shen,1,* Zhiyin Weng,2,* Minjuan Fan,1 Shukun Wang,1 Ruili Wang,1 Yang Zhang,1 Hong Tian,1 Xi Wang,1 Xin Wu,1 Xiaolei Yang,1 Wei Wei,1 Kaifen Yuan1 1Respiratory Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2School of Pharmaceutical Science, Kunming Medical University, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kaifen YuanRespiratory Department, The Second Affiliated Hospital of Kunming Medical University, No. 374 Dianmian Road, Kunming 650101, Yunnan Province, People’s Republic of ChinaTel +86-13888320577Email yuankaifen@kmmu.edu.cnBackground: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible expiratory airflow obstruction, and its chronic course is worsened by recurrent acute exacerbations. Our previous microarray assay identified microRNA (miR)-301a-5p as being associated with progression of acute exacerbation of COPD (AE-COPD); however, the mechanism underlying COPD pathogenesis remains unknown.Methods: Samples of serum and peripheral blood mononuclear cells (PBMCs) were isolated from healthy control subjects and patients with stable COPD (R-COPD) or with an acute exacerbation of COPD (AE-COPD). Human HULEC-5a and human bronchial epithelial (HBE) cells were transfected with methyl-CpG-binding domain protein 2 (MBD2), sh-MBD2, miR-301a-5p mimics or an inhibitor, and then stimulated with cigarette smoke extract (CSE). Conditioned medium co-culture assays were performed by adding the supernatant of medium derived from HULEC-5a cells transfected with miR-301a-5p mimics or inhibitor into wells containing si-c-x-c motif chemokine receptor 4 (CXCR4)-transfected-lung fibroblasts or human leukemic THP-1 cell line macrophages. Transwell assays were performed to analyze cell migration.Results: Our analysis of clinical samples showed that decreased miR-301a-5p levels in patients with AE-COPD were positively correlated with levels of MBD2 expression, but negatively correlated with levels of chemokine ligand C-X-C motif chemokine ligand 12 (CXCL12) expression. MBD2 overexpression significantly promoted miR-301a-5p production, but suppressed CXCL12 production in HULEC-5a and HBE cells. CXCL12 was confirmed to be a direct target of miR-301a-5p. CXCR4 knockdown significantly enhanced the suppressive effect of miR-301a-5p mimics and attenuated the promotional effects of the miR-301a-5p inhibitor on the migration of circulating fibroblasts and macrophages, as well as the expression levels of phospho-mitogen-activated protein kinase (p-MEK) and phospho-protein kinase B (p-AKT).Conclusion: In summary, the MBD2/miR-301a-5p/CXCL12/CXCR4 pathway was shown to affect the migration of lung fibroblasts and monocyte-derived macrophages, which may play an important role during COPD exacerbations.Keywords: chronic obstructive pulmonary disease, microRNA-301a-5p, inflammatory chemokine, cell recruitment

Kai Yuan,1,* Jingtian Mei,1,* Dandan Shao,2 Feng Zhou,1 Han Qiao,1 Yakun Liang,3 Kai Li,2 Tingting Tang1 1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China; 2Key Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People’s Republic of China; 3Shanghai Institute of Precision Medicine, Shanghai 200125, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tingting TangShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery,Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Room 701, No. 3 Building, 639 Zhizaoju Road, Shanghai 200011, People’s Republic of ChinaTel/Fax +86 21 6313 7020Email ttt@sjtu.edu.cnKai LiKey Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, People’s Republic of ChinaTel/Fax +86 21-52413903Email likai@mail.sic.ac.cnBackground: Cerium oxide nanoparticles (CeO2NPs) are potent scavengers of cellular reactive oxygen species (ROS). Their antioxidant properties make CeO2NPs promising therapeutic agents for bone diseases and bone tissue engineering. However, the effects of CeO2NPs on intracellular ROS production in osteoclasts (OCs) are still unclear. Numerous studies have reported that intracellular ROS are essential for osteoclastogenesis. The aim of this study was to explore the effects of CeO2NPs on osteoclast differentiation and the potential underlying mechanisms.Methods: The bidirectional modulation of osteoclast differentiation by CeO2NPs was explored by different methods, such as fluorescence microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. The cytotoxic and proapoptotic effects of CeO2NPs were detected by cell counting kit (CCK-8) assay, TdT-mediated dUTP nick-end labeling (TUNEL) assay, and flow cytometry.Results: The results of this study demonstrated that although CeO2NPs were capable of scavenging ROS in acellular environments, they facilitated the production of ROS in the acidic cellular environment during receptor activator of nuclear factor kappa-&Bgr; ligand (RANKL)-dependent osteoclast differentiation of bone marrow-derived macrophages (BMMs). CeO2NPs at lower concentrations (4.0 μg/mL to 8.0 μg/mL) promoted osteoclast formation, as shown by increased expression of Nfatc1 and C-Fos, F-actin ring formation and bone resorption. However, at higher concentrations (greater than 16.0 μg/mL), CeO2NPs inhibited osteoclast differentiation and promoted apoptosis of BMMs by reducing Bcl2 expression and increasing the expression of cleaved caspase-3, which may be due to the overproduction of ROS.Conclusion: This study demonstrates that CeO2NPs facilitate osteoclast formation at lower concentrations while inhibiting osteoclastogenesis in vitro by inducing the apoptosis of BMMs at higher concentrations by modulating cellular ROS levels.Keywords: cerium oxide nanoparticles, osteoclast, osteoclastogenesis, ROS, apoptosis

Peixian Zhang,* Lan Shi,* Linjing Song, Yi Long, Kehua Yuan, Wanbao Ding, Lei Deng Department of Oncology, Yan’an Hospital of Kunming City & Yan’an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, People’s Republic of China *These authors contributed equally to this workCorrespondence: Lei Deng; Wanbao DingDepartment of Oncology, Yan’an Affiliated Hospital of Kunming Medical University. No. 245 East of Renmin Road, Kunming, Yunnan 650051, People’s Republic of ChinaEmail leidengkm@163.com; wabading@163.comPurpose: Synchronous colorectal liver metastasis (SCLM) had limited availability of tools to predict survival and tumor recurrence. LncRNA CRNDE and lncRNA SNHG7 have been proven to be closely related to cancer progression. However, the predictive value of lncRNA CRNDE and lncRNA SNHG7 in cancer prognosis is still unclear. The purpose of this study was to investigate whether lncRNA CRNDE and lncRNA SNHG7 could be used as promising biomarkers for prognosis prediction of SCLM patients who underwent hepatectomy.Methods: The expression profile of lncRNA CRNDE and lncRNA SNHG7 in serum of SCLM patients was examined by qRT-PCR. The relationship between lncRNA expression and clinicopathological characteristics was analyzed. The Cox proportional-hazards regression model and Kaplan-Meier analysis were performed to analyze the association between lncRNA expression and overall survival (OS) and tumor recurrence of SCLM patients.Results: Levels of lncRNA CRNDE and lncRNA SNHG7 in patients who underwent recurrence or death were significantly higher than that of patients with recurrence-free or survival (P< 0.01). Both lncRNA CRNDE high level and lncRNA SNHG7 high level showed a significant correlation with differentiation of primary tumor, invasion depth of primary focus, lymph node metastases, number of liver metastases, and liver metastasis grade. High levels of lncRNA CRNDE or lncRNA SNHG7 predicted shorter recurrence time, shorter OS time, higher recurrence rate and lower OS rate. Furthermore, lncRNA CRNDE and lncRNA SNHG7 were independent risk factors for high recurrence and poor OS in SCLM underwent hepatectomy.Conclusion: Taken together, lncRNA CRNDE and lncRNA SNHG7 could be promising biomarkers for prediction of OS and tumor recurrence in SCLM underwent hepatectomy.Keywords: lncRNA CRNDE, lncRNA SNHG7, prognosis, recurrence, synchronous colorectal liver metastasis, SCLM

The boundary between the lithosphere and asthenosphere is associated with a platewide high-seismic velocity "lid" overlying lowered velocities, consistent with thermal models. Seismic body waves also intermittently detect a sharp velocity reduction at similar depths, the Gutenberg (G) discontinuity, which cannot be explained by temperature alone. We compared an anisotropic tomography model with detections of the G to evaluate their context and relation to the lithosphere-asthenosphere boundary (LAB). We find that the G is primarily associated with vertical changes in azimuthal anisotropy and lies above a thermally controlled LAB, implying that the two are not equivalent interfaces. The origin of the G is a result of frozen-in lithospheric structures, regional compositional variations of the mantle, or dynamically perturbed LAB.