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Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population:a two-sample bidirectional Mendelian randomization study

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Journal of geriatric Cardiology 2024年第1期21卷 64-80页

作者： Xiong-Bin MA Yong-Ming LIU Yan-Lin LV Lin QIAN The First Clinical Medical College of Lanzhou University LanzhouGansuChina geriatric Cardiovascular department and Gansu Clinical Research Center for geriatric Diseases First Hospital of Lanzhou UniversityGansuChina

BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is uncertain.This Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction population.METHODS Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association studies.Individuals without myocardial infarction history,HF,or LV ejection fraction(LVEF)<50%(n=16,923)in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome dataset.The dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the results.RESULTS In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni adjustment.Conversely,no significant relationships were observed between other iron and LV parameters.After Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the analysis.CONCLUSIONS We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.

关键词： fraction function parameters

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Identification of tumor-suppressor genes in lung squamous cell carcinoma through integrated bioinformatics analyses

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Oncology Research 2024年第1期32卷 187-197页

作者： HENG LI YOUMING LEI GAOFENG LI YUNCHAO HUANG The 2nd department of Thoracic surgery The Third Affiliated Hospital of Kunming Medical UniversityYunnan Tumor HospitalKunming650118China The 1st department of Thoracic surgery The Third Affiliated Hospital of Kunming Medical UniversityYunnan Tumor HospitalKunming650118China department of geriatric Thoracic surgery The First Affiliated Hospital of Kunming Medical UniversityKunming650032China

Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management.In this study,we aim to identify a panel of signature genes closely associated with LUSC,which can provide novel insights into the progression of LUSC.Gene expression profiles were retrieved from public resources including gene expression omnibus(GEO)and the cancer genome atlas(TCGA)database.Differentially expressed genes(DEGs)between LUSC specimens and normal lung tissues were identified by bioinformatics analyses.A total of 66 DEGs were identified based on two cohorts of data.CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN,ABI3BP,MAMDC2,FGF7,FAM107A,SPARCL1,DCN,COL14A1,and MFAP4 and CHRDL1,which showed significant downregulation in LUSC.Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment.Together,our data revealed novel candidate tumor-suppressor genes in LUSC,suggesting previously unappreciated mechanisms in the progression of LUSC.

关键词： LUSC DEGs WGCNA PPI network Tumor-suppressor

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GLI1 and PTTG1 expression in colorectal carcinoma patients undergoing radical surgery and their correlation with lymph node metastasis

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World Journal of Gastrointestinal surgery 2024年第5期16卷 1328-1335页

作者： Feng Cao Yang-Yan Chen Hong-Cheng Wang department of Care Section Beijing Geriatric HospitalBeijing 100095China Research department Shanghai Zhangjiang Institute of Medical InnovationShanghai 200000China Care department Beijing Geriatric HospitalBeijing 100095China

BACKGROUND Few studies have investigated the expression of GLI1 and PTTG1 in patients undergoing radical surgery for colorectal carcinoma(CRC)and their association with lymph node metastasis(LNM).Therefore,more relevant studies and analyses need to be conducted.AIM To explore GLI1 and PTTG1 expression in patients undergoing radical surgery for CRC and their correlation with LNM.METHODS This study selected 103 patients with CRC admitted to our hospital between April 2020 and April 2023.Sample specimens of CRC and adjacent tissues were collected to determine the positive rates and expression levels of GLI1 and PTTG1.The correlation of the two genes with patients’clinicopathological data(e.g.,LNM)was explored,and differences in GLI1 and PTTG1 expression between patients with LNM and those without were analyzed.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive potential of the two genes for LNM in patients with CRC.RESULTS Significantly higher positive rates and expression levels of GLI1 and PTTG1 wereobserved in CRC tissue samples compared with adjacent tissues.GLI1 and PTTG1 were strongly linked to LNM in patients undergoing radical surgery for CRC,with higher GLI1 and PTTG1 levels found in patients with LNM than in those without.The areas under the ROC curve of GLI1 and PTTG1 in assessing LNM in patients with CRC were 0.824 and 0.811,respectively.CONCLUSION GLI1 and PTTG1 expression was upregulated in patients undergoing radical surgery for CRC and are significantly related to LNM in these patients.Moreover,high GLI1 and PTTG1 expression can indicate LNM in patients with CRC undergoing radical surgery.The expression of both genes has certain diagnostic and therapeutic significance.

关键词： Colorectal carcinoma GLI1 PTTG1 Radical resection Lymph node metastasis

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Association of prealbumin with short-term and long-term outcomes in patients with acute ST-segment elevation myocardial infarction

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Journal of geriatric Cardiology 2024年第4期21卷 421-430页

作者： Jing TAN Jin SI Ke-Ling XIAO Ying-Hua ZHANG Qi HUA Jing LI department of Cardiology Xuanwu Hospital Capital Medical UniversityBeijingChina department of geriatric Medicine Xuanwu Hospital Capital Medical UniversityNational Clinical Research Center for Geriatric DiseasesBeijingChina

BACKGROUND Prealbumin is considered to be a useful indicator of nutritional status. Furthermore, it has been found to be associated with severities and prognosis of a range of diseases. However, limited data on the association of baseline prealbumin level with outcomes of patients with acute ST-segment elevation myocardial infarction(STEMI) are available.METHODS We analyzed 2313 patients admitted for acute STEMI between October 2013 and December 2020. In-hospital outcomes and mortality during the 49 months(interquartile range: 26–73 months) follow-up period were compared between patients with the low prealbumin level(< 170 mg/L) and those with the high prealbumin level(≥ 170 mg/L).RESULTS A total of 114 patients(4.9%) died during hospitalization. After propensity score matching, patients with the low prealbumin level than those with the high prealbumin level experienced higher incidences of heart failure with Killip class Ⅲ(9.9%vs. 4.4%, P = 0.034), cardiovascular death(8.4% vs. 3.4%, P = 0.035) and the composite of major adverse cardiovascular events(19.2%vs. 10.3%, P = 0.012). Multivariate logistic regression analysis identified that the low prealbumin level(< 170 mg/L) was an independent predictor of in-hospital major adverse cardiovascular events(odds ratio = 1.918, 95% CI: 1.250–2.942, P = 0.003). The cutoff value of prealbumin level for predicting in-hospital death was 170 mg/L(area under the curve = 0.703, 95% CI: 0.651–0.754, P< 0.001;sensitivity = 0.544, specificity = 0.794). However, after multivariate adjustment of possible confounders, baseline prealbumin level(170 mg/L) was no longer independently associated with 49-month cardiovascular death. After propensity score matching, Kaplan-Meier survival curves revealed consistent results.CONCLUSIONS Decreased prealbumin level closely related to unfavorable short-term outcomes. However, after multivariate adjustment and controlling for baseline differences, baseline prealbumin level was not independently associated with an increased risk of long-term cardio

关键词： patients admitted infarction

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Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model

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Neural Regeneration Research 2024年第3期19卷 687-696页

作者： Longqing Zhang Xi Tan Fanhe Song Danyang Li Jiayi Wu Shaojie Gao Jia Sun Daiqiang Liu Yaqun Zhou Wei Mei department of Anesthesiology Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Healthand Wuhan Clinical Research Center for Geriatric AnesthesiaTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Activated G-protein-coupled receptor 39(GPR39)has been shown to attenuate inflammation by interacting with sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α).However,whether GPR39 attenuates neuropathic pain remains unclear.In this study,we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated rats.Intrathecal injection of TC-G 1008,a specific agonist of GPR39,significantly alleviated mechanical allodynia in the rats with spared nerve injury,improved spinal cord mitochondrial biogenesis,and alleviated neuroinflammation.These changes were abolished by GPR39 small interfering RNA(siRNA),Ex-527(SIRT1 inhibitor),and PGC-1αsiRNA.Taken together,these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1αpathway in rats with spared nerve injury.

关键词： G-protein-coupled receptor 39(GPR39) neuroinflammation neuropathic pain nuclear respiratory factor 1(NRF1) peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α) sirtuin 1(SIRT1) spinal cord mitochondrial transcription factor A(TFAM)

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ALKBH5 suppresses autophagic flux via N6-methyladenosine demethylation of ZKSCAN3 mRNA in acute pancreatitis

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World Journal of Gastroenterology 2024年第12期30卷 1764-1776页

作者： Tao Zhang Shuai Zhu Geng-Wen Huang department of General surgery Xiangya HospitalCentral South UniversityChangsha 410005HunanChina. National Clinical Research Center for geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410005HunanChina.

BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.

关键词： Acute pancreatitis Autophagy ZKSCAN3 N6-methyladenosine ALKBH5

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TRIANGLE operation,combined with adequate adjuvant chemotherapy,can improve the prognosis of pancreatic head cancer:A retrospective study

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1773-1786页

作者： Jia-Hao Chen Li-Yong Zhu Zhi-Wei Cai Xiao Hu Abousalam Abdoulkader Ahmed Jie-Qiong Ge Xiao-Yan Tang Chun-Jing Li Yun-Long Pu Chong-Yi Jiang department of Hepato-Biliary-Pancreatic surgery Huadong Hospital Affiliated to Fudan UniversityShanghai 200040China Shanghai Key Laboratory of Clinical geriatric Medicine Fudan UniversityShanghai 200040China department of Nursing Huadong Hospital Affiliated to Fudan UniversityShanghai 200040China

BACKGROUND The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein,celiac axis-common hepatic artery,and superior mesenteric artery to improve patient prognosis.Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma(PDAC),data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy(PD).AIM To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC.METHODS This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023,with or without the TRIANGLE operation.Patients were divided into the PD_(TRIANGLE)and PD_(non-TRIANGLE)groups.Surgical and survival outcomes were compared between the two groups.Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy≥6 months.RESULTS The PD_(TRIANGLE)and PD_(non-TRIANGLE) groups included 52 and 55 patients,respectively.There were no significant differences in the baseline characteristics or perioperative indexes between the two groups.Furthermore,the recurrence rate was lower in the PD_(TRIANGLE) group than in the PD_(non-TRIANGLE) group(48.1%vs 81.8%,P<0.001),and the local recurrence rate of PDAC decreased from 37.8%to 16.0%.Multivariate Cox regression analysis revealed that PD_(TRIANGLE)(HR=0.424;95%CI:0.256-0.702;P=0.001),adequate adjuvant chemotherapy≥6 months(HR=0.370;95%CI:0.222-0.618;P<0.001)and margin status(HR=2.255;95%CI:1.252-4.064;P=0.007)were found to be independent factors for the recurrence rate.CONCLUSION The TRIANGLE operation is safe for PDAC patients undergoing PD.Moreover,it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

关键词： TRIANGLE operation Pancreatic ductal adenocarcinoma Heidelberg triangle Adjuvant chemotherapy Prognosis Pancreaticoduodenectomy

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Early Quality Life Impairment in Alzheimer Disease’s Patients in geriatric department: About 214 Cases in Pitié Salpêtrière Hospital of Paris (France)

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Open Journal of Internal Medicine 2024年第1期14卷 30-42页

作者： Andia Abdoulkader Audrey Rouet Benedicte Dieudonné Jacque Boaddert Charlotte Tomeo Sandrine Greffard Marc Verny department of geriatric of Pitie Salpetrière Hospital 47-83 Boulevard de l’H&ocircpital Paris France

Alzheimer’s disease (AD) is the most common neurodegenerative disease causing an alteration of life quality in the terminal stage. The purpose was to report 14 years of experience about the early impact on the quality of life of patients with AD. Methodology: Descriptive retrospective study over 14 years in the geriatric department of Pitié Salpêtrière Hospital, using the activity of daily living, Instrumental activity of daily living, neuropsychological inventory and Hoen Yahr scale evaluated at the time of diagnosis of AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer Disease’s and Related Disorders Association diagnostic criteria. Results: A total of 214 exploitable files had been listed. At the moment of diagnosis, the mean age was 82.1 years with extremes 68 to 95 with sex ratio 1.6 in women’s favor. The mean socio-cultural level was 4.9 with extremes about 0 to 7. There was poly pathology with a mean Cumulative Illness Rate Scale = 4.6 with extremes 0 to 16. the mean cognitive status was moderate = 22.5 with extremes 0 to 30. Quality life showed moderate impairment of IADL = 9.2 with extreme 3 to 11 compared to activity of daily living. The activity of daily living was more affected in 68 - 80-year-olds, while poly pathology impacted more on IADL in men. The cognitive impairment was more deficient in IADL when the MMSE test was low. The common disorders at the NPI were psychological, behavioral and psychotic. Conclusion: At the early diagnosis of Alzheimer’s Disease cognitive deficiencies were predominant and influenced on global Instrumental activity and psychological, behavioral disorders.

关键词： Alzheimer’s Disease IADL ADL NPI Paris France

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Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration Research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang department of Pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing geriatric Medical Research Center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

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Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis

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Chinese Journal of Cancer Research 2024年第3期36卷 282-303页

作者： Yifei Wang Yidan Ma Lei He Jun Du Xiaoguang Li Peng Jiao Xiaonan Wu Xiaomao Xu Wei Zhou Li Yang Jing Di Changbin Zhu Liming Xu Tianlin Sun Lin Li Dongge Liu Zheng Wang department of Pathology Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences department of Minimally Invasive Tumor Therapies Center Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences department of Thoracic surgery Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences department of Oncology Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences department of Respiratory and Critical Care Medicine Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences Amoy Diagnostics Co. Ltd.

Objective: The clinical significance of homologous recombination deficiency(HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer(NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods: A total of 355 treatment-na?ve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score(GSS), with a score of ≥50 considered HRD-positive. Genomic,transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed.Results: Of the patients, 25.1%(89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair(HRR) mutations, higher tumor mutation burden(TMB)(P<0.001), and fewer driver gene mutations(P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK) mutant NSCLC, and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-Ⅱ, interferon(IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival(PFS) to targeted therapy(first- and third-generation EGFR-TKIs)(P=0.042). Additionally, HRD-positive, EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions: Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-posit

关键词： Non-small cell lung cancer homologous recombination deficiency genetic alterations transcriptional analysis tumor microenvironment prognosis

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