An extensive analysis of the prognostic and immune role of FOXO1 in various types of cancer

Forkhead Box O1 (FOXO1) has been reported to play important roles in many tumors. However, FOXO1 has not been studied in pan-cancer. The purpose of this study was to reveal the roles of FOXO1 in pan-cancer (33 cancers in this study). Through multiple public platforms, a pan-cancer analysis of FOXO1 was conducted to obtained FOXO1 expression profiles in various tumors to explore the relationship between FOXO1 expression and prognosis of these tumors and to disclose the potential mechanism of FOXO1 in these tumors. FOXO1 was associated with the prognosis of multiple tumors, especially LGG (low grade glioma), OV (ovarian carcinoma), and KIRC (kidney renal clear cell carcinoma). FOXO1 might play the role of an oncogenic gene in LGG and OV, while playing the role of a cancer suppressor gene in KIRC. FOXO1 expression had a significant correlation with the infiltration of some immune cells in LGG, OV, and KIRC. By combining FOXO1 expression and immune cell infiltration, we found that FOXO1 might influence the overall survival of LGG through the infiltration of myeloid dendritic cells or CD4+ T cells. Functional enrichment analysis and gene set enrichment analysis showed that FOXO1 might play roles in tumors through immunoregulatory interactions between a lymphoid and a non-lymphoid cell, TGF-beta signaling pathway, and transcriptional misregulation in cancer. FOXO1 was associated with the prognosis of multiple tumors, especially LGG, OV, and KIRC. In these tumors, FOXO1 might play its role via the regulation of the immune microenvironment.

Screening of UBE2S interacting protein and construction of prognostic model in hepatocellular carcinoma / 吉林大学学报(医学版)

Objective:To screen the interacting protein of ubiquitin-conjugating enzyme E2S(UBE2S)and construct the hepatocellular carcinoma(HCC)based on UBE2S interacting protein prognosis model(UIPM),and to discuss the value of UIPM in assessing the prognosis of the HCC patients.Methods:Co-immunoprecipitation(Co-IP)was used to screen the protein complexes binding to Flag-UBE2S.After validation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting methods;liquid chromatography-mass spectrometer(LC-MS)was used to identify the UBE2S interacting proteins;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted on these proteins;the prognosis-related proteins from The Cancer Genome Atlas(TCGA)were cross-referenced with UBE2S interacting proteins by survival package of R software;the key proteins were extracted through LASSO regression analysis to build the UIPM;the prognostic model risk scoring formula was established.The HCC patients in TCGA were divided into high risk group and low risk group based on median value of the risk scores.The predictive accuracy of UIPM was evaluated by receiver operating characteristic curve(ROC),and the predictive accuracy was further validated by International Cancer Genome Consortium(ICGC)Database;univariate regression analysis and multivariate Cox regression analysis were used to detect whether the UIPM risk score was an independent prognostic factor for HCC.Furthermore,the nomogram model was built.Results:A total of 97 UBE2S interacting proteins were identified through Co-IP combined with LC-MS analysis.The GO functional enrichment analysis and KEGG signaling pathway enrichment analysis results showed that the interacting proteins were closely associated with cysteine-type endopeptidase activity,oxidative stress,and cell death.The TCGA revealed 5 163 HCC prognosis-related proteins;after intersecting with UBE2S interacting proteins,40 prognosis-related interacting proteins were found.Seven key proteins were determined through LASSO regression analysis,including UBE2S,heat shock protein family A member 8(HSPA8),heterogeneous nuclear ribonucleoprotein H1(HNRNPH1),chaperonin containing TCP1 subunit 3(CCT3),eukaryotic translation initiation factor 2 subunit 1(EIF2S1),receptor for activated C kinase 1(RACK1),and actin related protein 2/3 complex subunit 4(ARPC4),and the UIPM was constructed.There was significant difference in survival rate of the patients between high risk group and low risk group(P<0.05).The ROC curve analysis results showed the area under ROC curve(AUC)values of UIPM for predicting 1-year,2-year,and 3-year survival risk scores of the HCC patients were all greater than 0.7,indicating the model had high predictive accuracy.This was also confirmed by ICGC Database data.The univariate and multivariate Cox regression analysis results showed that the UIPM risk score was an independent prognostic risk factor for the HCC patients(P<0.05).The nomogram results showed good consistency between predicted survival rate and actual survival rate of the patient.Conclusion:A total of 97 interacting proteins that interact with UBE2S may promote the occurence and devolopment of HCC through oxidative stress and dysregulation of ferroptosis pathways.The UIPM risk score is an independent risk factor for the prognosis of HCC and can be used to predict the outcomes of the patients.UBE2S,HSPA8,HNRNPH1,CCT3,EIF2S1,RACK1,and ARPC4 could be regarded as the new biomarkers and therapeutic targets for HCC.

Clinicopathologic characteristics,gene mutation profile and prognostic analysis of thyroid diffuse large B-cell lymphoma / 上海交通大学学报（医学版）

Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of thyroid diffuse large B-cell lymphoma(DLBCL).Methods·From November 2003 to December 2021,a total of 66 patients with thyroid DLBCL[23 cases(34.8%)with primary thyroid DLBCL,and 43 cases(65.2%)with secondary thyroid DLBCL]admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival and prognostic factors.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes)in 40 patients.Results·Compared to primary thyroid DLBCL,secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ(P=0.000),elevated serum lactate dehydrogenase(LDH)(P=0.043),number of affected extranodal involvement≥2(P=0.000),non-germinal center B cell(non-GCB)(P=0.030),BCL-2/MYC double expression(DE)(P=0.026),and international prognostic index(IPI)3?5-scores(P=0.000).The proportion of patients who underwent thyroid surgery(P=0.012)was lower than that of patients with primary thyroid DLBCL.The complete remission(CR)rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients(P=0.039).Fifty-five patients(83%)received rituximab combined with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)-based first-line regimen.The estimated 5-year progression free survival(PFS)rate of primary thyroid DLBCL patients was 95.0%,higher than the 49.7%of the secondary patients(P=0.010).Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.411,95%CI 1.373?14.170),elevated LDH(HR=5.500,95%CI 1.519?19.911),non-GCB(HR= 5.291,95%CI 1.667?16.788),and DE(HR=6.178,95%CI 1.813?21.058)were adverse prognostic factors of PFS in patients with thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ(HR=7.088,95%CI 0.827?60.717),elevated LDH(HR=6.982,95%CI 0.809?60.266),and DE(HR=18.079,95%CI 1.837?177.923)were adverse prognostic factors of overall survival(OS).Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.693,95%CI 1.218?18.081)and elevated LDH(HR=5.058,95%CI 1.166?21.941)were independent adverse prognostic factors of PFS in patients with thyroid DLBCL.Targeted sequencing data showed mutation frequency>20%in TET2(n=14,35%),KMT2D(n=13,32%),TP53(n=11,28%),GNA13(n=10,25%),KMT2C(n=9,22%),and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL(P=0.000).Conclusion·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ,elevated LDH,non-GCB,and DE(MYC and BCL2)are adverse prognostic factors in thyroid DLBCL.TET2,KMT2D,TP53,GNA13,and KMT2C are commonly highly mutated genes in thyroid DLBCL,and the prognosis of patients with TP53 mutations is poor.

Analysis of prognostic factors of gastric cancer patients with liver metastases and establishment of a nomogram for survival prediction / 中国现代医生

@#Objective To explore the clinical features and prognostic factors of gastric cancer patients liver metastasis.Methods Data from 7055 patients with gastric cancer were retrieved from Surveillance,Epidemiology and End Results(SEER)database between 2010 and 2015.The patients were divided into the liver metastases group(901 cases)and the non-liver metastases group(6154 cases)according to whether liver metastasis occurred.Univariate and multivariate Cox regression were used to analyze the prognostic risk factors,and the Kaplan-Meier method was used for survival analysis.Results There was a significant difference in age,gender,race,T stage,N stage,primary surgery,radiotherapy and tumor size between the two groups(P<0.05),and the median survival time of patients in the liver metastases group was 6 months,non-liver metastases group was 25 months.Cox regression analysis showed that age(P=0.009),tumor grade(P<0.001),surgery(P<0.001)and chemotherapy(P<0.001)were the main factors affecting the prognosis of gastric cancer with liver metastases.Conclusion Age,tumor grade,surgery and chemotherapy were the prognostic risk factors for gastric cancer with liver metastases.A nomogram based on age,tumor grade,surgery and chemotherapy has a good survival prediction significance for gastric cancer with liver metastases.

Bioinformatics screening and analysis of prognostic genes in breast cancer / 实用肿瘤学杂志

Objective Bioinformatics techniques were used to analyze the key genes that affect the survival of patients with breast cancer,so as to provide theoretical basis for the prognosis evaluation and targeted therapy of breast cancer.Methods The dif-ferentially expressed genes between breast cancer samples and normal breast samples were screened by TCGA database,enriched and analyzed by gene ontology(GO)and Kyoto Encyclopedia of Gene and Genome(KEGG).The protein-protein interaction network was constructed and the key genes were screened.The Kaplan-Meier method was used to find and verify the genes that might be used as potential prognostic biomarkers for breast cancer,and to explore the correlation between prognostic target genes and molecular typing and staging.The Timer database was used to analyze the correlation between prognosis-related target genes and immune cell infiltra-tion.Results A total of 1,285 differentially expressed genes were screened,including 318 up-regulated genes and 967 down-regu-lated genes(|log2FC| ≥ 1,P＜0.05).Differentially expressed genes were mainly enriched in cytokine-cytokine receptor interac-tions,PI3K-AKT signaling pathway,cAMP signaling pathway,and so on.A total of 10 key genes(AURKB,CDC20,CCNA2,NCAPG,BUB1,TOP2A,BUB1B,CCNB1,CDK1,and KIF11)were screened from the protein interaction network.Among them,the ex-pression of CCNA2,NCAPG and BUB1 in breast cancer tissues were higher than those in normal tissues.Their high expression was as-sociated with the poor prognosis of patient's overall survival(P＜0.05),and was significantly associated with the molecular typing and staging of breast cancer.The results of immune infiltration showed a significant correlation between the expression of CCNA2,NCAPG,BUB1 and the infiltration of immune cells such as B lymphocytes,CD8+T lymphocytes,neutrophils,dendritic cells and other immune cells.Conclusion CCNA2,NCAPG and BUB1 may be key genes in the occurrence and development of breast cancer,and their high expression is related to poor prognosis of breast cancer patients,which can be used as potential biomarkers for the prognosis of breast cancer.

Clinical and pathological characteristics and prognostic analysis of gastric neuroendo-crine carcinoma / 中国肿瘤临床

Objective:To explore the clinical and pathological characteristics and prognostic factors of gastric neuroendocrine carcinoma(G-NEC)and gastric mixed adenoendocrine carcinoma(G-MANEC).Methods:Retrospective analysis was conducted on the clinical data of 67 patients with G-NEC and G-MANEC who underwent surgical treatment at Heping Hospital Affiliated to Changzhi Medical College from May 2015 to May 2023.The study included an analysis of the pathological characteristics distinguishing G-NEC from G-MANEC.Results:Com-pared to gastric adenocarcinoma,patients with G-NEC and G-MANEC in the stomach showed a higher incidence of gastric cancer in the male gastric cardia and were diagnosed at a later age.Tumors with larger diameters increase susceptibility to anemia,low albumin levels,and in-vasion of nerves and vasculature.Deeper tumor infiltration is associated with increased local lymph node metastases,later TNM staging,and a higher likelihood of distant metastasis post-surgery.The prognosis of G-NEC and G-MANEC is worse than that of gastric adenocarcinoma(P=0.001).However,there is no statistically significant difference in the pathological characteristics(P>0.05)and prognosis analysis(P=0.212)between G-NEC and G-MANEC.Univariate survival analysis identified age,preoperative albumin,preoperative CEA,number of lymph node metastases,TNM staging,and postoperative distant metastasis as risk factors affecting patient's overall survival(OS).In the multivariate ana-lysis,age,preoperative albumin,TNM staging,and postoperative distant metastasiswere identified as independent risk factors for OS.Con-clusions:There is a significant difference in clinical characteristics between G-NEC,G-MANEC,and gastric adenocarcinoma,often diagnosed at an advanced stage,which is prone to distant metastasis post-surgery.Poor prognosis is observed in patients aged over 60 years,with pre-operative albumin<40g/L,TNM stage Ⅱ/Ⅲ,and postoperative distant metastasis.

Analysis of efficacy and prognosis of neoadjuvant chemotherapy and （or） surgery plus radiotherapy for hypopharyngeal squamous cell carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the risk factors that affect the prognosis of patients with hypopharyngeal squamous cell carcinoma（HPSCC） and to compare the efficacy of surgical resection followed by adjuvant radiotherapy（SR） with that of neoadjuvant therapy consisting of platinum-based chemotherapy and fluorouracil combined with either cetuximab or nimotuzumab, followed by SR. The study also aimed to evaluate the overall survival（OS） of patients, their postoperative eating function, tracheostomy decannulation rate, and tumor response to the two neoadjuvant chemotherapies. Methods:A retrospective analysis was performed on the medical records of HPSCC patients who received SR or neoadjuvant therapy followed by SR treatment at the Shanghai General Hospital from 2012 to 2019 and had not undergone any prior treatment. The prognostic factors were analyzed, and the survival analysis of patients who underwent SR treatment with two neoadjuvant chemotherapy regimens was performed. Results:A total of 108 patients were included in the study. The results of the univariate analysis showed that gender（P=0.850） had no significant correlation with the survival rate of HPSCC patients who underwent SR. However, age, smoking history, alcohol consumption history, platelet-to-lymphocyte ratio（PLR）, neutrophil-to-lymphocyte ratio（NLR）, T stage, N stage, neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil, and histological grade were significantly associated with prognosis（P<0.05）. The multivariate analysis revealed that smoking history, histological grade, and neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil were independent risk factors affecting the prognosis of HPSCC（P<0.05）. Patients who received neoadjuvant therapy had longer OS than those who underwent SR only（P<0.001）. There was no significant difference in tumor response to the two neoadjuvant therapies and in OS（P>0.05）, and there was no significant difference in the rate of oral feeding and tracheostomy decannulation among the three treatment groups（P>0.05）. Conclusion:Univariate analysis showed that age at tumor onset, smoking history, alcohol consumption history, NLR, PLR, T stage, N stage, whether receiving neoadjuvant chemotherapy, and pathological grade were associated with the prognosis of HPSCC patients receiving SR treatment. Multivariate analysis showed that smoking history, pathological grade, and neoadjuvant chemotherapy were independent risk factors affecting the prognosis. Neoadjuvant chemotherapy with cetuximab or nimotuzumab can prolong the OS of patients, providing a certain basis and reference for the treatment of HPSCC.

Risk factors and prognostic analyses of acute kidney injury after heart transplantation / 中华器官移植杂志

Objective:This study aims to investigate the incidence, risk factors, and prognosis of acute kidney injury after heart transplantation.Methods:Clinical data of 180 recipients of heart transplantation at Zhengzhou Seventh People's Hospital from April 2018 to November 2022 are retrospectively analyzed. According to whether AKI occurred 7 days after surgery, the recipients are divided into a non AKI group(85 cases)and an AKI group(95 cases). The baseline data, general perioperative conditions, and clinical data of the two groups of recipients are compared using chi square test and rank sum test to identify possible influencing factors for AKI after heart transplantation.Determine independent risk factors through binary logistic regression.The Kaplan Meier method is used to draw survival curves to further clarify the impact of AKI on the survival and cumulative hospitalization of heart transplant recipients.Results:The incidence of postoperative AKI in 180 recipients of this study is 52.7%(95/180). Univariate analysis showed that there are statistically significant differences in recipient age, preoperative albumin, platelet count, graft cold ischemia time, and surgical time between the AKI group and the non AKI group(all P<0.05). Further multivariate analysis showes that recipient age( OR=1.021, 95% CI: 1.001~1.043, P=0.043), surgical time( OR=1.005, 95% CI: 1.001~1.008, P=0.005), platelet count( OR=0.995, 95% CI: 0.990~1.000, P=0.034), and donor cold ischemia time ( OR=0.996, 95% CI: 0.993~0.996, P=0.004)are independent risk factors for AKI after heart transplantation. Prognostic analysis showed that 35.7%(25 cases)of the AKI group received continuous renal replacement therapy(CRRT)after surgery, and 31.9%(23 cases) received aortic balloon counterpulsation(IABP)after surgery. Compared with 0 and 8.9%(7 cases)of the AKI group without AKI, the differences are statistically significant(all P<0.01). Compared with the non AKI group, the invasive mechanical ventilation time is 614 (504, 707) hours and 540 (460, 610) hours( P<0.01), the stay time in the intensive care unit is 12(8, 16)days and 10(6, 15)days( P=0.050), and the estimated glomerular filtration rate(eGFR)on the 7th day after surgery is 10(6, 15)ml/(min·1.73 m 2)and 68(57.5, 91.0)ml/(min·1.73 m 2)( P<0.01), with statistical significance. The cumulative survival rate of the AKI group after heart transplantation is lower than that of the non AKI group, and the cumulative hospitalization rate Is higher than the latter. The differences between the groups are statistically significant(all P<0.01). Conclusions:The incidence of AKI after heart transplantation is relatively high, and recipient age, platelet count, graft cold ischemia time, and surgical time are independent risk factors for AKI. Recipients with AKI after heart transplantation have a higher proportion of postoperative use of CRRT and IABP, longer invasive mechanical ventilation time and monitoring room stay time, and lower eGFR on the 7th day after surgery; at the same time, recipients with AKI after heart transplantation have a lower postoperative survival rate and a higher cumulative hospitalization rate.

Analysis of clinicopathological features, gene mutation characteristics and prognosis of 228 cases of primary gastrointestinal stromal tumor of small intestine / 中华消化杂志

Objective:To analyze the clinicopathological features, gene mutation characteristics, and prognostic related factors of patients with primary gastrointestinal stromal tumor (GIST) of small intestine.Methods:From January 1, 2011 to December 30, 2019, surgical resected and pathological diagnosed small intestinal GIST without preoperative adjuvant therapy, at Tianjin Medical University Cancer Institute & Hospital were retrospectively collected. The mutational status of KIT exons 9, 11, 13, and 17 and platelet-derived growth factor receptor alpha ( PDGFRA) exons 12 and 18 were detected by polymerase chain reaction and Sanger direct sequencing. Clinicopathological features and gene mutation characteristics were analyzed. Pearson chi-square test and Bonferroni continuous correction test were used to compare the categorical variables among groups. Kaplan-Meier method and log-rank test were used for univariate survival analysis. The multivariate Cox proportional hazards regression model was used for multivariate survival analysis. Results:The proportions of patients with maximum tumor diameter> 10.0 cm and high-risk GIST located in the jejunum and ileum were higher than those of patients with primary GIST located in the duodenum (18.7%, 28/150 vs. 6.4%, 5/78; 56.7%, 85/150 vs. 43.6%, 34/78), and the differences were statistically significant ( χ2=14.67 and 12.46, P=0.002 and 0.006). The results of gene detection of 58 cases of small intestinal GIST indicated that the percentage of KIT gene mutant and wild type accounted for 84.5% (49/58) and 15.5% (9/58), among which 34 cases (69.4%), 12 cases (24.5%), 2 cases (4.1%) and 1 case (2.0%) were KIT gene exons 11, 9, 13 and 17 mutations, respectively, and none of the case with PDGFRA mutation. The 3-, 5-, and 10-year progression-free survival rates of the patients with small intestinal GIST were 88.1%, 85.0%, and 68.3%, respectively, and the 3-, 5-, and 10-year overall survival rates were 96.6%, 94.5%, and 86.1%, respectively. The results of univariate survival analysis showed that the progression-free survival rate and overall survival rate of patients with very low-risk and low-risk GIST were higher than those of patients with intermediate-risk and high-risk GIST (100.0%, 49/49 vs. 72.3%, 81/112; 100.0%, 49/49 vs. 89.3%, 100/112, respectively), and the differences were statistically significant ( χ2=14.07 and 4.92, P<0.001、=0.027). The results of univariate survival analysis of patients with intermediate-risk and high-risk GIST showed that the epithelioid cell type, mitotic index >5/5 mm 2, Ki-67 proliferation index >5%, and without postoperative adjuvant therapy were all related with progression-free survival time, and the differences were statistically significant ( χ2=8.39, 5.53, 13.73 and 15.44, P=0.004、0.019、<0.001、<0.001). Without postoperative adjuvant therapy was related with poor overall survival time ( χ2=7.06, P=0.008). The results of univariate analysis in patients with intermediate-risk and high-risk GIST and without postoperative adjuvant therapy showed that the epithelioid cell type, high-risk, mitotic index >5/5 mm 2 and Ki-67 proliferation index >10% were all related with progression-free survival time, and the differences were statistically significant ( χ2=10.08, 6.51, 10.37 and 15.72, P=0.001、0.011、0.001、<0.001). The results of multivariate analysis indicated that Ki-67 proliferation index >5% ( HR=5.018, 95% confidence interval(95% CI) 1.745 to 14.430, P=0.003) and without postoperative adjuvant treatment ( HR=0.145, 95% CI 0.051 to 0.414, P<0.001) were independent risk factors of postoperative tumor progression in patients with small intestinal intermediate-risk and high-risk GIST. Ki-67 proliferation index>10% ( HR=8.381, 95% CI 1.364 to 51.487, P=0.022) was an independent risk factor of postoperative tumor progression in patients with small intestinal intermediate-risk and high-risk GIST and without postoperative adjuvant treatment. Conclusions:The most common mutation in small intestinal primary GIST is KIT mutation, followed by wild type, no case of PDGFRA gene mutation has been found. High Ki-67 proliferation index can predict poor prognosis of patients with moderate-risk and high-risk small intestinal primary GIST. Postoperative adjuvant therapy can significantly improve the prognosis of patients with small intestinal intermediate-risk and high-risk primary GIST.

Bioinformatics analysis of expression of reduced folate carrier(RFC1) in colorectum, related signaling pathways and its relationship with patient prognosis / 国际生物医学工程杂志

Objective:To investigate the expression and related signaling pathways of reduced folate carrier 1 (RFC1) in colorectal cancer (CRC) and its relationship with the prognosis of patients.Methods:The expression of RFC1 gene in various solid tumors and CRC was analyzed in the Cancer Genome Atlas(TCGA) database. The RFC1 protein-protein interaction network was established using the search tool for the retrieval of interacting genes (STRING). The differences in survival rate between patients with high and low expression of RFC1 were compared using the Gene Expression Profile Interaction Analysis (GEPIA) database. Differentially expressed genes were subjected to Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using the Annotation, Visualization and Integrated Discovery (DAVID) database. The immunohistochemical expression level and location of RFC1 in CRC tissues and adjacent normal tissues were analyzed.Results:The expression difference of RFC1 mRNA in various human solid tumors was not obvious. In CRC tissues, the expression level of RFC1 was higher than that in adjacent normal tissues, but the expression level of RFC1 was not related to the tumor stage of the CRC patients. The correlation index between RFC1 proteins was 119, and the average inter-protein region clustering coefficient was 0.836. There was significant protein network enrichment between RFC1 and its interacting genes ( P<0.05). The biological processes of RFC1 are mainly enriched in DNA replication, semi-conservative replication to maintain telomere activity, DNA metabolism, error-free translation synthesis, DNA synthesis involved in DNA repair, etc. The cellular components are mainly enriched in replication forks, chromosomes, nucleoplasm, DNA replication factor C complex, Ctf18 RFC complex, etc. The molecular functions are mainly enriched in DNA binding nucleic acid binding, impaired DNA binding, DNA activity, catalytic activity, etc. For the KEGG signaling pathway, RFC1 is mainly enriched in DNA replication, nucleotide excision repair, mismatch repair, and malignant tumorigenesis. The disease-free survival rate and overall survival rate of CRC patients with high expression of RFC1 were lower than those of low expression group, and the difference in overall survival rate between the two was statistically significant ( P<0.05). The RFC1 protein was mainly expressed in the cytoplasm, and the positive expression was yellow-brown granular and evenly distributed in the cells. Most of the RFC1 proteins were highly or moderately expressed in colorectal cancer tissues, but low in normal intestinal epithelium. Conclusions:The expression of RFC1 is increased in CRC tissues, and its high expression is related to the decreased overall survival rate of CRC patients. RFC1 can be used as a molecular marker of poor prognosis in CRC and may become a potential target for CRC therapy.

Epidemiological investigation of 201 emergency adult sudden death patients and analysis of the influence of leukocyte count and lactic acid concentration on prognosis / 中国综合临床

Objective:To investigate the clinical situation of 201 emergency adult sudden death patients, and analyze the influence of white blood cell count and arterial blood lactate level on prognosis.Methods:The clinical data of 201 patients diagnosed with sudden death in the emergency department of Medical College of Cangzhou people's Hospital from January 2017 to January 2021 were retrospectively analyzed. The gender, age, disease composition and etiology of the patients were statistically analyzed. The independent sample t-test was used to compare the measurement data with normal distribution, the χ 2 test or Fisher exact probability method was used to compare the counting data between groups, and the logistic regression model was used to screen the risk factors of emergency death, and the impact of white blood cell count and arterial blood lactate level on the prognosis was analyzed. Results:After active rescue, 11.44% (23/201) of the patients were successfully rescued, and 88.56% (178/201) of the patients were ineffective; ≥46-≤65 years old was the age group with high incidence of sudden death (55.22%(111/201)). The proportion of male (43.28% (87/201), 23.38% (42/201)) in the age group of ≥46-≤65 years old and the age group over 65 years old were higher than that of female (11.94% (24/201), 14.43% (29/201)), with a statistically significant difference (χ 2=4.801, 9.209; P=0.028, 0.002). In the past history of sudden death patients, the proportion of cardiovascular disease (53.23% (107/201)) was the highest; the proportion of patients may have inducements before sudden death was 74.13% (149/201), the proportion of patients have premonitory symptoms before sudden death was 67.66% (136/201), and sudden cardiac death was the first cause. Logistic regression analysis showed that white blood cell count ( OR=4.442,95% CI: 1.898-10.395), arterial blood lactic acid concentration ( OR=4.272,95% CI: 2.024-9.016), and albumin concentration ( OR=2.657,95% CI: 1.302-5.422) were independent risk factors affecting emergency sudden death patients ( P values were 0.001, <0.001, 0.007, respectively). Conclusions:There are some differences in gender, age and past history of adult sudden death patients. Most of them have premonitory symptoms and inducements. Sudden cardiac death is the primary cause. The increases of white blood cell count and lactic acid level, the decrease of albumin level are the risk factors of sudden death.

The expression of CD27 on T cells in microenvironment and its correlationship to the prognosis of multiple myeloma / 中华检验医学杂志

Objective:To analyze the expression of CD27 on T lymphocytes in the microenvironment of multiple myeloma (MM), and explore whether CD27 level or the CD27-/CD27+ ratio of T-cell affect the prognosis of MM patients.Methods:A total number of 103 newly-diagnosed MM patients from January 2016 to June 2019 were enrolled in the Affiliated Cancer Hospital of Harbin Medical University. All patients received bortezomib-based three-drugs combination regimen. The expression of CD27 on T lymphocytes in bone marrow aspirate samples was detected by flow cytometry before any treatment. MM patients were divided into two groups according to the CD27 level: CD27-high expression group (CD27 expression on T-cells ≥20%) and CD27-low expression group (CD27 expression on T-cells <20%). The clinical characteristics, treatment response and prognosis of patients between the two groups were analyzed using χ 2-test. The survival and clinical information of patients were compared using Kaplan-Meier method, and the related factors related to the survival of MM were analyzed using Cox proportional risk model. Results:Among 103 MM patients, 68 cases (66.0%) were included in CD27 high expression group, and 35 cases (34.0%) were included in low expression group. The percentage of bone marrow plasma cells and β2-MG level in CD27 high expression group were higher than those in CD27 low expression group significantly (54.4% [37/68] vs 22.9% [8/35], χ2=9.352, P=0.002;58.8% [40/68] vs 37.1% [13/35], χ2=4.348, P=0.037), and the proportion of ISS stage Ⅱ-Ⅲ in CD27 high expression group was higher than the counterpart (79.4% [54/68] vs 60% [21/35], χ2=4.399, P=0.036). After 4 cycles of three-drug combination therapy, the overall response rate ( ORR=stringent complete response+complete response+very good partial response+partial response) of the low CD27 expression group was higher than the high expression group (82.9% [29/35] vs 38.2% [26/68], χ2=18.489, P<0.01). The deep response rate to treatment (stringent complete response+complete response+very good partial response) was higher (48.6% [17/35] vs 27.9% [19/68], χ2=4.326, P=0.038), and the progression, free surviva (PFS) was longer (21months vs.14.1months, t=18.655, P<0.001) in the low expression group compared with CD27-high group. Univariate analysis showed that CD27-/CD27+T lymphocyte ratio, ISS stage Ⅱ-Ⅲ, age ≥65 years, β2-Mg ≥3.5 mg/L, and plasma cell proportion ≥30% were associated with the poor prognosis of MM patients, and the differences were significant statistically ( P<0.05). Multivariate analysis showed that CD27-/CD27+T lymphocyte ratio was an independent prognostic factor for 2-year overall survival (OS)( HR=2.425, 95% CI 1.216-4.835, P=0.012) and 2-year PFS ( HR=1.881, 95% CI 1.085-3.260, P=0.024) in MM patients. Conclusions:The expression of CD27 in T lymphocytes is correlated with the prognosis, treatment response and progression-free survival of MM. The ratio of CD27-/CD27+T lymphocytes is an independent prognostic indicator.

Value of lymphocyte subsets in assessing the prognosis of adult hemophagocytic syndrome / 中华检验医学杂志

Objective:To explore the prognostic value of lymphocyte subsets in adult hemophagocytic syndrome (HPS).Methods:A total of 172 adult HPS patients diagnosed in 8 medical centers from January 2013 to August 2020 were selected for the study, of whom 87 were male (50.6%, 87/172), and 85 were female (49.4%, 85/172), with 68 survivors and 104 deaths. The clinical data were summarized, and variables such as lymphocyte subsets, immunoglobulin characteristics and fibrinogen were retrospectively analyzed, and the correlation between the mentioned variables and patient prognosis was analyzed. The optimal cut-off values of continuous variables were calculated by MaxStat, and the prognostic factors of HPS patients were screened based on the Cox proportional hazard regression model.Results:The median age of HPS patients was 56 (42, 66) years old, and the 5-year cumulative survival rate was 37.4% (37.4/100). The median age, platelet and albumin were 48 (27, 63) years, 84×10 9/L and 32.3 g/L in the survival group, and 59 years, 45.5×10 9/L, and 27.3 g/L in the death group, respectively. The differences between the two groups was statistically significant ( Z=?3.368, P=0.001; Z=?3.156, P=0.002; Z=?3.431, P=0.001). Patients with differentiated cluster 8+(CD8+)<11.1%, CD3+<64.9%, CD4+>51%, and CD4/CD8 ratio>2.18 had poor prognosis (χ 2=7.498, P=0.023; χ 2=4.169, P=0.041; χ 2=4.316, P=0.038; χ 2=9.372, P=0.002). Multivariable analysis showed that CD4/CD8 ratio, age, fibrinogen and hemoglobin were independent prognostic factors in HPS patients ( HR=2.435, P=0.027; HR=5.790, P<0.001; HR=0.432, P=0.018; HR=0.427, P=0.018). Conclusion:Peripheral blood lymphocyte subsets can be used to evaluate the prognosis of patients with HPS; CD4/CD8 ratio, age, fibrinogen, and hemoglobin are independent prognostic factors in HPS patients.

Effects of radical radiotherapy combined with different regimens of chemotherapy on radiation intestinal injury in patients with non-metastatic anal squamous cell carcinoma / 中华胃肠外科杂志

Objective: To investigate the effects of radical radiotherapy combined with different chemotherapy regimens (fluorouracil-based versus docetaxel plus cisplatin) on the incidence of radiation intestinal injury and the prognosis in patients with non-metastatic anal squamous cell carcinoma. Methods: A retrospective cohort study was conducted to recruit non-metastatic anal squamous cell carcinoma patients who underwent chemoradiotherapy in the Sixth Affiliated Hospital of Sun Yat-sen University and Nanfang Hospital from July 2013 to January 2021. Inclusion criteria: (1) newly diagnosed anal and perianal squamous cell carcinoma; (2) completed radical radiotherapy combined with concurrent chemotherapy; (3) tumor could be evaluated before radiotherapy. Exclusion criteria: (1) no imaging evaluation before treatment, or the tumor stage could not be determined; (2) patients undergoing local or radical resection before radiotherapy; (3) distant metastasis occurred before or during treatment; (4) recurrent anal squamous cell carcinoma. A total of 55 patients (48 from the Sixth Affiliated Hospital of Sun Yat-sen University and 7 from Nanfang Hospital) were given fluorouracil (the 5-FU group, n=34) or docetaxel combined with the cisplatin (the TP group, n=21). The evaluation of radiation intestinal injury, hematological toxicity and 3-year disease-free survival (DFS) rate were compared between the two groups. The effects of chemotherapy regimen and other clinicopathological factors on the incidence and severity of acute and chronic radiation intestinal injury were analyzed. The assessment of radiation intestinal injury was based on the American Cancer Radiotherapy Cooperation Group (RTOG) criteria. Results: During radiotherapy and within 3 months after radiotherapy, a total of 45 patients developed acute radiation intestinal injury, including 18 cases of grade 1 (32.7%), 22 cases of grade 2 (40.0%) and 5 cases of grade 3 (9.1%). No patient developed chronic radiation intestinal injury. Among the 34 patients in the 5-FU group, 21 had grade 2-3 radiation intestinal injury (21/34, 61.8%), which was significantly higher than that in the TP group (6/21, 28.6%) (χ(2)=5.723, P=0.017). Multivariate analysis showed that 5-FU chemotherapy regimen was an independent risk factor for radiation intestinal injury (HR=4.038, 95% CI: 1.250-13.045, P=0.020). With a median follow-up period of 26 (5-94) months, the 3-year DFS rate of patients in TP group and 5-FU group was 66.8% and 77.9%, respectively, whose difference was not significant (P=0.478). Univariate analysis showed that the DFS rate was associated with sex, age, tumor location, T stage, N stage, and induction chemotherapy (all P<0.05), while the DFS rate was not associated with chemotherapy regimen or radiation intestinal injury (both P>0.05). Multivariate analysis revealed that age ≥ 50 years old was an independent risk factor affecting the prognosis of patients (HR=8.301, 95% CI: 1.130-60.996, P=0.038). Conclusions: For patients with non-metastatic anal squamous cell carcinoma, radical radiotherapy combined with TP chemotherapy regimen can significantly reduce the incidence of radiation intestinal injury as compared to 5-FU regimen. However, due to the short follow-up time, the effect of different chemotherapy regimens on the prognosis is not yet clear.

Current Situation of Clinical Feature and Gene Phenotype of Young Adult Lung Cancer / 中国肺癌杂志

Young adult lung cancer is defined as a group of patients refers to whose onset age is less than 40 years old and ≥18 years old. Compare with elder lung cancer, the clinical symptoms of them are not typical, the stage is usually late at the time of discovery, and most of them have regional lymphatic metastasis or distant metastasis. Current study found that young adult lung cancer has a relatively unique genetic background, the abundance of tumor-driving genes is high, and it is closely related to its clinical manifestation and prognosis. Young adult lung cancer is the focus of attention in the field of cancer in recent years. This article reviewed the literature on the clinical features, gene phenotypic characteristics and prognosis of young adult lung cancer in order to provide provide some references and clues for the study on young adult lung cancer.

Analysis for screening and prognostic value of differentially expressed genes in cervical cancer / 临床检验杂志

Objective@#To identify the pivotal differentially expressed genes in cervical cancer based on data mining from GEO database. @*Methods@#The cervical cancer-related gene expression data (GSE9750 and GSE63514) was downloaded from GEO database and the differentially expressed genes were screened and identified by GEO2R tool. GO and KEGG enrichment pathways were analyzed by using DAVID online tool. The results were verified using the data from GSE7803, GSE39001 and TCGA. @*Results@#A total of 176 differentially expressed cervical cancer-related genes were screened, including 41 up-regulated genes and 135 down-regulated genes. Among them, INHBA was highly expressed in cervical cancer tissues and negatively correlated with overall survival ( HR =2.5, P ＜ 0.01 ) and disease-free survival ( HR =2.7, P ＜0.01). @*Conclusion@#We obtained multiple genes related to the pathogenesis of cervical cancer by data mining of the gene chip in GEO database. INHBA could be used as a new potential molecular marker for tumor diagnosis and prognosis evaluation.

Effect of different liver function Child-Pugh classification on clinical prognosis of hepatocellular carcinoma recipients after liver transplantation / 器官移植

Objective To evaluate the effect of the different Child-Pugh classification on the recurrence and survival of hepatocellular carcinoma (HCC) recipients after liver transplantation. Methods Clinical data of 125 HCC recipients undergoing liver transplantation were retrospectively analyzed. The 3-year disease-free survival (DFS) and overall survival (OS) rates were calculated by Kaplan-Meier survival curve. The independent risk factors probably affecting the recurrence and survival of HCC recipients after liver transplantation were identified by using Cox's proportional hazards regression model. Results The median follow-up time was 25.6 months. The 3-year DFS and OS rates were 68.4% and 65.7% for all patients. The 3-year DFS and OS rates in 113 patients with Child-Pugh class A/B HCC were 68.6% and 66.2%, whereas 66.7% and 65.6% for 12 patients with Child-Pugh class C HCC with no statistical significance (all P>0.05). Cox's proportional hazards regression model demonstrated that vascular invasion (P=0.001)and the number of tumors>3 (P=0.025) were the independent risk factors for the postoperative recurrence of HCC in recipients undergoing liver transplantation. Alpha fetoprotein (AFP)>400μg/L (P=0.035), vascular invasion (P=0.031) and number of tumors>3 (P=0.008) were the independent risk factors affecting the survival of HCC patients. Conclusions The postoperative prognosis does not significantly differ between Child-Pugh class C and A/B HCC patients after liver transplantation. AFP, vascular invasion and number of tumors are the risk factors affecting the clinical prognosis of HCC patients after liver transplantation. Liver transplantation is an efficacious treatment for HCC patients with Child-Pugh class C.

Prognosis of the complete transposition of great arteries with left ventricular outflow tract obstruction after intraventricular repair / 中国胸心血管外科临床杂志

@#Objective     To compare the clinical characteristics and prognosis of patients who received two different intraventricular repair. Methods     We retrospectively analyzed the clinical data of 24 complete transposition of the great arteries (TGA)/left ventricular outflow tract obstruction (LVOTO) patients who all received intraventricular repair. The patients were allocated into two groups including a REV group and a Rastelli group. There were 13 patients with 9 males and 4 females at median age of 25.2 (6, 72) months in the REV group. There were 11 patients with 10 males and 1 female at median age of 47.9 (14, 144) months in the Rastelli group. Results     The age at operation (P=0.041), pulmonary valve Z value (P=0.002), and LVOT gradient (P=0.004), rate of multiphase operation between the REV group and the Rastelli group was statistically different. The mean follow-up time was 17.3 months. And during the follow-up, 1 patient had early mortality, 2 patients had early reintervention, 7 patients had postoperative RVOTO, and received Rastelli and larger VSD inner diameter were associated with postoperative RVOTO. Conclusion     As the traditional surgery for TGA/LVOTO patients, the intraventricular repair has a low early mortality and low early reintervention. Modified REV is associated with postoperative peripheral pulmonary vein isolation (PVIS). Patients who received Rastelli operation and with larger VSD inner diameter are more likely to have postoperative RVOTO, but the reintervention for PVI and   RVOTO during follow up is very low.

A study on the prognosis of different surgical procedures for severe jejunoileal atresia / 中国新生儿科杂志

Objective To compare the prognosis of different surgical procedures and to find the relatively safe and effective treatment for severe jejunoileal atresia(sJA).Method From January 2007 to June 2018,children with sJA receiving different surgical procedures in our hospital were retrospectively reviewed.Their clinical data were analyzed,including the survival rate,complication rate,unplanned re-operation rate and postoperative nutritional status.Result A total of 130 patients were enrolled in this study.According to the different types of surgical procedures,the patients were assigned into primary anastomosis group (58 cases,44.6％),Mikulicz double barrel ileostomy group (17 cases,13.1％) and Bishop-Koop anastomosis group (55 cases,42.3％).The overall mortality rate was 6.2％ (8/130).No significant differences existed in mortality rates among the three groups (P＞0.05).The incidences of gastrointestinal complications in primary anastomosis group (70.6％,12/17) and Mikulicz group (70.6％,12/17) were both higher Bishop-Koop group (34.5％,19/55),the differences were statistically significant (P＜0.05).The unplanned re-operation rates were 34.5％ (20/58) in the primary anastomosis group and 17.6％ (3/17) in the Mikulicz group,both higher than the Bishop-Koop group (3.6％,2/55),the differences were also statistically significant (P＜0.05).Multivariate analysis showed that the risk of complications in the primary anastomosis group (OR=3.434,95％CI 1.392～8.471) and Mikulicz group (OR=5.933,95％CI 1.467～23.991) were higher than the Bishop-Koop group.The risk of unplanned re-operation in the primary anastomosis group was 12.422 times as the Bishop-Koop group (95％CI 2.535～60.877).No significant differences existed between the Mikulicz group and the Bishop-Koop group in the risk of unplanned re-operation (P＞0.05).The weight for age (Z-score) in the Bishop-Koop group (-1.4,95％CI-2.0～-0.8) at the stoma closure time was better than the Mikulicz group (-3.2,95％CI-4.4～-2.0),the difference was statistically significant (P＜0.01).Conclusion Bishop-Koop anastomosis has lower complication rate and lower unplanned re-operation rate in the treatment of sJA.The nutritional status of children who received Bishop-Koop anastomosis is better than Mikulicz double barrel ileostomy at the stoma closure time.Bishop-Koop anastomosis is relatively safe and effective for sJA patients.

Risk and prognostic factor analysis of bloodstream infection in intensive care unit / 中国感染与化疗杂志

Objective To investigate the risk factors and prognostic factors of bloodstream infection in intensive care unit(ICU). Methods The data of patients with bloodstream infection in ICU of Harrison International Peace Hospital from October 2014 to October 2017 were retrospectively analyzed and 210 patients with negative blood culture were selected. The physiological and laboratory parameters were compared between patients with positive blood culture and those with negative blood culture. Multivariate logistic regression analysis was used to screen the risk factors of bloodstream infection. Overall, 189 patients with bloodstream infection were classified into survival group(n=121)and death group(n=68)according to the survival status within 30 days after blood culture. The risk factors related to 30-day patient outcome following bloodstream infection were analyzed. Results A total of 189 cases of bloodstream infection were identified in the ICU during the 3-year period, including 118 cases due to gram-negative bacilli, 65 cases caused by gram-positive cocci, and 6 cases due to fungi. Univariate analysis showed that prior use of carbapenem or third generation cephalosporins, central venous catheterization, length of hospital stay≥2 weeks, and mechanical ventilation were the risk factors of bloodstream infection(P<0.05). Multivariate logistic regression analysis showed that prior use of carbapenems or third-generation cephalosporins(OR=20.15), central venous catheterization(OR=25.34), and mechanical ventilation(OR=18.26)were independent risk factors for bloodstream infection in ICU patients. Univariate analysis showed that prior use of carbapenem or third generation cephalosporins, mixed infection or septic shock, multi-drug resistant bacterial infection, and high APACHE Ⅱ(acute physiological and chronic health evaluation system Ⅱ)score were significant risk factors for 30-day mortality following bloodstream infection(P<0.05). Multivariate logistic regression analysis showed mixed infection or septic shock(OR=15.30), multi-drug resistant bacterial infection(OR=10.75)and high APACHE Ⅱ score(OR=13.70)were independent risk factors for 30-day mortality following bloodstream infection. Conclusions Prior use of carbapenem or third generation cephalosporins, central venous catheterization and mechanical ventilation are independent risk factors for bloodstream infection in ICU patients. Mixed infection or septic shock, multi-drug resistant bacterial infection, and high APACHE Ⅱ score are independent risk factors for 30-day mortality following bloodstream infection.