Objective To investigate the expression of phosphatidylinositol 3 kinase (PI3K), phosphatase deleted on chromosome 10 (PTEN) and glycogen synthase kinase (GSK)-3β in astrocytoma and its relationship with clinicopathological features and prognosis. Methods Eighty astrocytoma tissue samples and 20 normal brain tissue samples were collected from January 2014 to December 2018,PI3K, PTEN and GSK-3βexpression in the above tissues were detected by immunohistochemistry and real-time fluorescence quantitative PCR (qPCR). The relationship between their expression and clinicopathological features and overall survival(OS) was analyzed. Spearman method was used for correlation analysis, and Cox proportional hazards regression model was used for multivariate analysis. Results Immunohistochemical staining showed that the expression of PI3K increased with the increase of astrocytoma WHO grade (P=0.109), the expression of GSK-3βand PTEN decreased with the increase of WHO grade (P=0.029, P=0.033). qPCR showed that the relative expression of PI3K mRNA increased with the increase of astrocytoma WHO grade (P=0.158), and the relative expression of PTEN mRNA and GSK-3β mRNA decreased with the increase of astrocytoma WHO grade（P=0.038,P=0.029）. PI3K was negatively correlated with PTEN and GSK-3β(r=-0.263, P=0.018; r=-0.285, P=0.010); GSK-3β was not related to the expression of PTEN (r=0.056, P=0.620). The expression of PI3K was not related to clinicopathological parameters (P>0.05); The expression of PTEN and GSK-3β was related to WHO grade and IDH-1 expression (P<0.05), but not to age, sex and the expression of GFAP and Vimentin (P>0.05). The 1-year and 2-year survival rates of PI3K positive expression group were 57.1% and 31.0%, respectively, lower than 79.0% and 71.1% of negative expression group (P=0.001); The 1-year and 2-year survival rates in GSK-3β positive expression group were 74.4% and 61.5% respectively, which were higher than 61.0% and 39.0% in negative expression group (P=0.049); The 1-year and 2-year survival rates of PTEN positive expression group were 74.9% and 62.9% respectively, which were higher than 53.3% and 23.3% of negative expression group (P=0.270). Univariate analysis showed that WHO grade, and the expression of PI3K and GSK-3β were related to OS in patients with astrocytoma (P<0.05). Cox multivariate analysis showed that PI3K expression was the independent factor affecting OS in patients with astrocytoma (P=0.001). Conclusion  The level of PI3K increases with the increase of astrocytoma WHO grade, and the level of PTEN and GSK-3β decreases with the increase of WHO grade. The prognosis of patients with PI3K positive expression, and negative expression of PTEN and GSK-3β is poor. They may be involved in the occurrence and development of astrocytoma and have a certain value in predicting the prognosis.

Objective To explore the expression of tumor necrosis factor receptor superfamily 21 (TNFRSF21) in hepatocellular carcinoma (HCC), related biological function and its relationships with prognosis and immune system. Methods The data sets of HCC cell lines were obtained from Gene Expression Omnibus (GEO) database to screen the common differentially expressed genes. The data of HCC patients were obtained from The Cancer Genome Atlas (TCGA) database, the expression of TNFRSF21 of HCC and paracancerous tissues was compared, and the relationship between TNFRSF21 and overall survival (OS), as well as clinicopathological characteristics was analyed. Moreover, expression level of TNFRSF21 in 67 patients with HCC from July 2009 to October 2010 were detected by real-time quantitative PCR (qPCR).The relationship of expression level of TNFRSF21 with OS of HCC patients was analyzed. The TNFRSF21 proteinprotein interaction network was constructed by STRING, and the biological functions and tumor-related pathways of TNFRSF21 were enriched by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). TIMER and TISIDB were used to analyze the correlation between TNFRSF21 and immune infiltrating cells in HCC. ResultsCommon differentially expressed genes TNFRSF21, CROT, APPBP2 and CPD in HepG2 and Huh7 cell lines with CSN5 knockdown, as well as HepG2 and Huh7 cell lines with COP1 knockdown were screened based on GEO database. Based on TCGA database, the median mRNA of TNFRSF21 was 3.125 in paracancerous tissues and 3.953 in 374 HCC tissues (P<0.001). TNFRSF21 mRNA in HCC tissues was 1.77±1.60, which was higher than 1.07±0.83 in paracancerous tissues (P=0.002). Survival analysis showed that only TNFRSF21 gene expression level was correlated with OS (P=0.030). In 67 HCC patients, the median OS in the high-expression group was unreached, superior to 35.0 months in the low-expression group (P=0.039). According to TCGA database, 374 HCC patients were divided into high and low expression groups based on the median TNFRSF21 expression of 2.678.It was found that TNFRSF21 expression level was significantly correlated with serum AFP level (P<0.001) and vascular invasion (P=0.029) of HCC patients. According to STRING and GO&KEGG enrichment analysis, TNFRSF21 may be involved in NF-κB and JNK signaling pathways through APP and TARDD, thus regulating the occurrence and development of tumors. TIMER analysis showed that the high expression of TNFRSF21 was associated with B cells (r=0.299,P<0.001), CD8+T cells (r=0.242, P<0.001), CD4+T cells (r=0.417, P<0.001), macrophages (r=0.527, P<0.001), neutrophils (r=0.389, P<0.001) and dendritic cells(r=0.363, P<0.001). TISIDB analysis showed that the expression of TNFRSF21 was positively correlated with the abundance of activated dendritic cells (r=0.271, P<0.001), follicular helper T cells (r=0.333, P<0.001), mast cells (r=0.270, P<0.001) and CD4+ central memory T cells (r=0.393, P<0.001). Conclusion TNFRSF21 gene is up-regulated in HCC, and related to poor prognosis. TNFRSF21 may promote the occurrence and development of HCC by inducing endothelial cell necrosis and tumor microenvironment through tumor immune infiltrating cells. TNFRSF21 can be used as a molecular marker for prognosis in HCC.

 The International Agency for Research on Cancer (IARC) estimates 36 cancer incidence rate and mortality rates in 185 countries/regions through GLOBOCAN 2020 database. Globocan2020 database shows that cervical cancer is the fourth largest tumor in women in the world, whether it is morbidity or mortality. The harm of cervical cancer to women's health and its prevention and treatment are important public health issues facing the world. This paper will summarize and compare the incidence and death prevalence of cervical cancer in the world and China from the aspects of population characteristics, regional distribution and time change trend, and combined with the reported human papillomavirus and other risk factors, primary prevention and secondary prevention strategies of cervical cancer, in order to provide scientific clues for the prevention and treatment strategies of cervical cancer in the future.

In the progression of breast cancer, brain metastasis will occur in 15% to 30% patients. Due to the prolonged survival of breast cancer patients, the incidence of brain metastasis is gradually increasing. The incidence and characteristics of brain metastasis from breast cancer of different molecular subtypes are different. Current treatment for breast cancer brain metastasis includes local treatment and systemic treatment. In recent years, with the development of comprehensive treatment of breast cancer, the application of chemotherapy, endocrine therapy and molecular targeted therapy in breast cancer brain metastasis has received more and more attention. Many new treatment methods such as conjugated drugs, immunotherapy and other methods have also shown certain effects on breast cancer brain metastasis. This article reviews the clinical characteristics and treatment progress of different molecular subtypes of breast cancer brain metastasis, and aims to provide certain ideas and basis for the clinical diagnosis, treatment and management of breast cancer brain metastasis.

Objective To evaluate the efficacy of osimertinib as the second'line treatment for patients with epidermal growth factor receptor (EGFR)'mutant advanced non'small cell lung cancer (NSCLC), and to explore the relationship of location of metastasis before treatment and progression after drug resistance with the efficacy. Methods  From January 1, 2017 to January 1, 2019, 67 patients with advanced NSCLC who were treated with 1-2 generation EGFR'tyrosine kinase inhibitor (TKI) and 50 patients who developed drug resistance after first'line chemotherapy were included. EGFR exon T790M was mutant in all 117 patients. Osimertinib 80 mg was orally administrated once a day until the disease progressed or intolerable adverse reactions were observed. Curative effects of the whole group and different subgroups were analyzed. Results  As of October 31, 2020, 28 of 117 patients still took osimertinib, with the longest duration of 43.2 months. Eighty'nine cases progressed after treatment, and 45 cases of them died. The median progression'free survival (PFS) of the whole group was 15.2 (95% CI: 12.352'18.114) months and the median overall survival (OS) was not reached. Subgroup analysis showed that gender, the first'line treatment, and the location of the metastatic lesions before treatment had impacts on PFS (P<0.05). The first'line treatment, EGFR mutation type and primary extrafocal metastasis type before treatment were related to OS (P<0.05). The presence of intrapulmonary metastasis, pleural metastasis, pleural effusion tumor exfoliated cells, liver metastasis, lymph node metastasis and bone metastasis shortened median PFS (P<0.05), and the presence of intrapulmonary metastasis, lymph node metastasis, liver metastasis and bone metastasis shortened median OS (P<0.05). There were also differences in median PFS and death rate among patients with different location of progressive lesions, but there was no significant difference (P>0.05). The death rate of patients with bone metastasis was the highest (75.0%), while the median PFS of patients bearing adrenal metastasis was the shortest (7.1 months). Conclusion  Osimertinib showed good efficacy as the second'line treatment for advanced NSCLC bearing EGFR positive mutation. The PFS of first'line treatment with EGFR'TKI sequenced by osimertinib is longer than that of first'line chemotherapy sequenced by osimertinib. The prognosis of patients with intra'and extra'pulmonary metastasis before treatment is poor, and the influence of the location of progression on the effect is limited.

Objective To explore the expression and clinical value of microRNA (micro RNA, miR)-183 and cell cycle G1 to S phase transition 1 (GSPT1) in cervical cancer. Methods From January 2014 to December 2016，91 patients with cervical cancer who were surgically treated were enrolled. Fluorescence quantitative PCR was used to detect the expression of miR183 and GSPT1 in 91 cases of cervical cancer and adjacent tissues. The correlation between the expression of miR-183 and GSPT1 in cancer tissues were analyzed by linear correlation analysis. Bioinformatics was used to predict the site of interaction between the two. The relationship of miR-183, GSPT1 expression with clinicopathological parameters as well as prognosis were statistically analyzed. Results The expression of miR183 in cancer tissues (0.521±0.065) was lower than that in adjacent tissues (1.241±0.286), and the difference was statistically significant (P=0.000); the expression of GSPT1 in cancer tissues (2.034±0.374) was significantly higher than that in adjacent tissues (0.708±0.157) , and the difference was statistically significant (P=0.000). There was a significant negative correlation between the expression of miR-183 and GSPT1 in cancer tissues (r=-0.621, P=0.001). Bioinformatics predicted that GSPT1 mRNA between base 981 to 987 had an interaction site with miR-183.The expression of miR-183 and GSPT1 was related to FIGO stages, tumor differentiation, depth of muscle invasion and lymph node metastasis (P<0.05), but not with pathological types and age (P>0.05). The 1-, 3-, and 5-year disease-free survival rates of 91 cervical cancer patients were 86.8%, 73.6% and 61.5%, respectively. The 1-, 3- and 5-year disease-free survival rates in the high miR-183 expression group were 91.1%, 86.6% and 80.0% respectively, which were better than 82.6%, 60.9% and 43.5% in the low miR-183 expression group (P=0.012). The 1-, 3- and 5-year diseasefree survival rates in the high GSPT1 expression group were 86.0%, 60.4% and 39.5%, respectively, lower than 87.5%, 85.4% and 81.2% in the low GSPT1 expression group (P=0.007). Conclusion The expression of miR-183 in cervical cancer is decreased, and the expression of GSPT1 is increased. The two promotes the tumor progression of cervical cancer, which are expected to be prognostic markers for cervical cancer.

 Objective  To construct and validate a nomogram model for the prognosis of malignant meningioma based on SEER database. Methods The clinical data of patients with malignant meningioma from 1992 to 2019 were obtained from SEER database by SEER*Stat 8.4.0 software, and the screened cases were randomly divided into training set and validation set in a ratio of 8∶2. Using R 4.1.3 software, Lasso regression and multivariate Cox regression analysis were used to determine the independent prognostic factors of malignant meningioma, and the nomogram model of 1-year, 3-year and 5-year overall survival was constructed. The reliability of the nomogram was assessed by C-index, receiver operating characteristic curve (ROC), calibration curve and the risk stratification analysis. Results  A total of 717 patients were screened, including 576 in the training set and 141 in the validation set. After Lasso regression and multivariate Cox regression, age, gender, marital status and surgery were determined as independent prognostic factors for malignant meningioma（P＜0.05）. The C-index of the training set and validation set were 0.683 and 0.681, respectively. For the area under the curve (AUC) values of 1-year, 3-year and 5-year overall survival, the training set was 0.738, 0.717 and 0.747, the validation set was 0.704, 0.664 and 0.700. The calibration curve of the model showed that the predicted survival probability derived from the nomogram was in good agreement with the actual observed value. In addition, decision curve analysis (DCA) also showed that the nomogram had better benefit. After risk stratification of patients with malignant meningioma according to prognostic factors, there was a significant difference in the overall survival between the high and low risk groups (P<0.001). Conclusion  Age, gender, marital status and surgery are related to the prognosis of patients with malignant meningioma. The nomogram model constructed in this study can more accurately predict the prognosis of patients with malignant meningioma, but its wide application still needs external and prospective verify.

 

Breast cancer is the most common female malignant tumor and has become the most common cancer in the world.With the advent of targeted drugs and the improvement of systemic treatment for breast cancer, the prognosis of patients with early breast cancer has been greatly improved. However, for patients with refractory breast cancer after multi'line therapy and newly diagnosed distant metastasis, the antibodies or cytotoxic drugs alone cannot meet the therapeutic needs. Antibody-drug conjugates (ADCs) are immunoconjugates that connect cytotoxic drugs and monoclonal antibodies via the molecular linker, which can selectively deliver cytotoxic drugs to cancer cells through monoclonal antibodies targeting tumor antigens, and so they have the advantages of strong selectivity, high efficiency and low toxicity. In recent years, ADCs have played an increasingly important role in the treatment of breast cancer. This review summarizes the main mechanism of ADCs,the current status and progress of ADCs for breast cancer.

 Objective  To investigate the expression of acetyltransferase 2A (KAT2A) and survivin protein acetylation levels in esophageal cancer tissue, and to analyze the correlation and clinical significance during the onset of esophageal cancer. Methods  Seventy cases of esophageal squamous carcinoma tissues and adjacent cancer tissues were collected. The survivin and KAT2A mRNA expression was determined by reverse transcription and real-time PCR(qRT-PCR), the expression levels of survivin and KAT2A protein were detected by Immunohistochemistry and Western blotting. Fluorescence immunohistochemistry (IF) verified the location and expression of survivin and KAT2A in cancerous tissues.The survivin protein acetylation was detected by co-immunoprecipitation. The correlation between survivin protein acetylation and KAT2A, and the relationship between them and the clinicopathological characteristics of esophageal cancer were analyzed. KAT2A RNA interference sequences was constructed, then transfected into EC109 cells using liposome-mediated methods. qRT-PCR and Westrern blotting were used to detect the expression level of KAT2A mRNA and protein in esophageal cancer EC109 cells transfected with siRNA-KAT2A. The acetylation level of survivin protein was detected by co-immunoprecipitation. Results  The relative expression of survivin and KAT2A mRNA was higher in esophageal cancer tissues than that in adjacent cancer tissues（P＜0.05）. Survivin and KAT2A protein were highly expressed in esophageal cancer tissues, whereas low expressed in adjacent cancer tissues. The survivin protein was acetylated in esophageal cancer tissues. Immunofluorescence confirmed that survivin and KAT2A protein both show a high expression state in cancer tissues, which are mainly expressed in the cytoplasm, partially expressed in the nucleus, and the acetylation rate was significantly higher than that in adjacent cancer tissues（P＜0.05）. Survivin acetylation and KAT2A were related in esophageal cancer tissues, and it was positive correlation（r=0.517, P＜0.05）. Survivin protein acetylation and KAT2A are closely related to tumor TNM staging, differentiation grade and lymph node metastasis（P＜0.05）. The result of vitro experiments showed that there was no change in survivin mRNA and protein expression after downregulation of KAT2A by RNA interference（P＞0.05）, but the acetylation level of survivin protein was significantly reduced（P＜0.05）. Conclusion  Acetyltransferase KAT2A is involved in the survivin acetylation modification during the esophageal lesion. High expression of KAT2A may be an important molecular event of survivin acetylation modification and has potential value in the diagnosis and treatment of esophageal cancer.

 Soft tissue sarcomas (STS) are a rare group of mesenchymal malignancies except bone or cartilage, with a low incidence rate. Patients with advanced STS have limited treatment options, poor prognosis and high mortality. Recently, immune checkpoint inhibitors (ICIs) have made great breakthroughs in the field of tumor therapy, greatly improving the prognosis of patients with various malignancies. However, efficacy of ICIs in the treatment of STS remains unravelled. This review summarizes the role of the ICIs in various sets of advanced STS treatment and provides future research directions, hoping to serve as a reference for clinicians.

Rad51 is the central molecule of homologous recombination (HR), which assembles on ssDNA as an oligomeric nucleoprotein filament and then invades the homologous double'stranded DNA during chromosome pairing to complete the repairing of DNA damage through different downstream pathways. The role of Rad51 in malignant tumors is mainly to promote tumor development, metastasis and anticancer drug resistance, including: (1) The interactions between Rad51 and cycle checkpoint molecules play a regulatory role in related pathways to affect tumor development and metastasis. (2) The reduced expression of Rad51 leads to partial reversal of epithelial mesenchymal transformation(EMT) process to regulate EMT'related metastasis and drug resistance of tumor cells. (3)The relationship between Rad51 and drug resistance of tumor can be revealed through gene polymorphism studies. (4) A number of microRNAs and long non'coding RNAs targeting the coding region of Rad51 can regulate gene expression and ultimately regulate HR efficiency and the development of drug resistance of tumor cells. Recently, the mechanisms above have been identified by the reports of Rad51 overexpression in ovarian, breast and lung cancer, which indicates that the over'expression of Rad51 is related to metastasis and drug resistance of malignant tumor. The regulation of Rad51 expression can reverse the process of tumor drug resistance, and it is expected to become a novel target for the treatment and drug resistance of cancer.

 

The use of immunecheckpoint inhibitors (ICIs) has completely changed the treatment mode of advanced cancer. At present, U.S. Food and Drug Administration (FDA) has approved various ICIs for clinical application, including cytotoxic T'lymphocyte associated antigen-4 (CTLA-4), programmed death-1 (PD-1) and its ligand (PD-L1), etc. Different from the responses of traditional chemotherapy and targeted therapy, immunotherapy is often accompanied by atypical responses, such as pseudoprogression, hyperprogression disease (HPD), dissociated responses, durable response and etc. These atypical reactions bring challenges to the evaluation of the efficacy of immunotherapy in the clinical practice. Clinicians need to regularly monitor and evaluate the treatment effect of patients, and optimize the treatment plan according to the changes of the disease. In this paper, we reviewed the atypical responses of immunotherapy at present, which provided reference for clinicians to distinguish the anti'tumor immune responses.

 

Objective To analyze the factors influencing the optimal number of lymph node detection in laparoscopic radical gastrectomy for advanced gastric cancer. Methods The data of 536 patients with advanced gastric cancer who underwent laparoscopic radical gastrectomy from January 2018 to July 2020 were reviewed, and the clinicopathological data was analyzed. The number of lymph nodes was submitted for detection after surgery, and the factors influencing the number of lymph nodes for detection were analyzed. Results Among the 536 patients, 147 had no lymph node metastasis and 389 had lymph node metastasis. In patients without lymph node metastasis, there was a statistically significant difference in tumor diameter between the group with lymph node number ≥16 and the group with lymph node number <16 (P=0.027). Receiver operator characteristic (ROC) curve analysis showed that the area under curve of the tumor diameter predicting the number of lymph nodes ≥16 for detection was 0.719 (95% CI:0.627-0.810, P<0.001), and the optimal cut'off value was 2.8 cm. In patients with lymph node metastasis, there were statistically significant differences in age and lymph node metastasis between the group with lymph node number ≥30 and the group with lymph node number<30 (P<0.05). The results of multivariate Logistic regression analysis showed that age and lymph node metastasis (N3a and N3b)were independent factors affecting lymph nodes number <30 for detection(P< 0.05). ROC curve analysis showed that the area under curve of age and lymph node metastasis predicting number of lymph node metastasis≥30 for detection were 0.575 (95% CI:0.519-0.632, P=0.008) and 0.615 (95% CI:0.559-0.672,P<0.001), respectively. The optimal cut'off values were 54 years old and 6. Conclusion Patients with tumor diameter ≤2.8 cm without lymph node metastasis were more likely to have <16 lymph nodes for detection. Patients aged >54 years and with no more than 6 metastatic lymph nodes were more likely to have <30 lymph nodes for detection. In clinical work, various influencing factors should be comprehensively considered to ensure sufficient lymph node detection, so as to formulate individualized treatment plan and improve the quality of treatment.

 Objective  To explore the expression pattern, clinical prognostic value and molecular mechanism of ubiquitin-conjugating enzyme E2C(UBE2C) in kidney renal clear cell carcinoma(KIRC). Methods  The difference of UBE2C gene expression in KIRC tissue and normal tissue was analyzed by The Cancer Genome Atlas(TCGA) and Human Protein Atlas(HPA). Combined with clinical information of KIRC patients, univariate and multivariate Cox regression analysis models were used to study the prognostic value of UBE2C gene in KIRC patients. Through gene set enrichment analysis(GSEA) of UBE2C gene, we understood the molecular mechanism of UBE2C regulating KIRC. The infiltrating immune cells content in KIRC patients were calculated, and the correlation between UBE2C gene expression level and immune cells infiltration content were evaluated. ResultsBoth gene and protein expression levels of UBE2C in KIRC tissues were higher than those in normal tissues (P<0.05). The expression of UBE2C in KIRC was correlated with tumor location, histological grade, pathological stage and TNM stage(P<0.05). Univariate and multivariate Cox regression analysis cleared that UBE2C was an independent prognostic factor for KIRC(P<0.05). GSEA results suggested that UBE2C could be involved in the regulation of cytokinecytokine receptor interactions, cell cycle checkpoints, ECM glycoproteins and other signaling pathways. The expression level of UBE2C gene was significantly correlated with the infiltration of Treg cells, T cells, Th17 cells, B cells, CD8+T cells and macrophages in the tumor microenvironment of KIRC. UBE2C was also significantly correlated with the expression levels of immune checkpoint molecules PDCD1 (PD1), CTLA4, CD27 and LAG3. Conclusion  UBE2C can serve as a risk prognostic factor for KIRC patients, and UBE2C may be a potential target for KIRC treatment.

Objective To investigate the relevant prognostic factors of malignant peripheral nerve sheath tumors (MPNST). MethodsThe data of 33 patients with MPNST from September 2010 to December 2019 were reviewed. The 33 patients included 15 males and 18 females, and the median age was 42 years (ranged from 3 to 69 years). Eleven cases were neurofibromatosis type 1(NF-1)-associated MPNST, and 22 were sporadic MPNST. The distribution of lesion location included 20 cases of extremities and 13 cases of trunk. There were 28 cases with negative surgical margin and 5 cases with positive surgical margin. All patients underwent surgery. Five patients were treated with adjuvant radiotherapy and 9 patients with adjuvant chemotherapy. One patient with ROS1 mutation received crizotinib. Progression-free survival (PFS) and overall survival (OS) were analyzed as clinical outcomes. Prognostic factors were analyzed by Cox multivariate analysis. Results The follow-up time was 6-96 months. Eight patients had local recurrence (4 of extremities, 4 of trunk),and 14 patients were companied by  metastasis (6 of extremities, 8 of trunk). The 5-year progression'free survival rate was 38.3% and 5-year overall survival rate was 53.3%. Univariate analysis showed that the tumor size, the expression of S-100 and H3K27me3, and margin status were related with PFS (P<0.05), while the expression of S-100 and H3K27me3, margin status and radiotherapy were related with OS (P<0.05). Multivariate Cox regression analysis showed that S-100 and margin status were the independent factors affecting PFS (P<0.05), while margin status was the independent prognostic factor affecting OS (P<0.05). Conclusion S-100 and surgical margin are important factors affecting the prognosis of patients with MPNST. Individualized treatment should be made according to the clinicopathological features and gene detection results of patients.

 

Objective  To investigate the value of PET/CT biphasic imaging in predicting lymph node metastasis of cervical carcinoma. Methods  We retrospectively analyzed 202 lymph nodes from January 2019 to July 2021 in 97 patients with cervical carcinoma who underwent surgery and had preoperative PET/CT for early and delayed imaging (duplex). The metabolic parameters of lymph nodes in early imaging, such as SUVmaxL1, SUVmean, SUVpeak, MTV, TLG, length-short diameter ratio (L/D), SUVmaxT of lesions, SUVmaxA of abdominal aorta, SUVmaxH of liver, and SUVmaxL2 of lymph nodes in delayed imaging were measured. The corresponding ratios, △SUVmax (SUVmaxL2-SUVmaxL1) and retention index (RI) were calculated. The differences of each parameter between lymph node metastasis group(n=42) and non-metastasis group(n=160) were compared. Multivariate regression analysis was performed in combination with traditional diagnostic criteria to establish a combined predictive diagnostic model. Receiver operating characteristic (ROC) curve was used to compare the diagnostic efficacy. Results  SUVmaxL1, SUVmean, SUVpeak, MTV, TLG, L/D, SUVmaxL2, △SUVmax, RI, SUVmaxL1/T, SUVmaxL1/A and SUVmaxL1/H were significantly different between metastasis and non-metastasis groups, and Logistic multi-factor regression analysis showed that SUVpeak, L/D, conventional PET/CT diagnostic criteria and SUVmaxL2 were independent risk factors for lymph node metastasis of cervical cancer; the area under curve (AUC) of conventional PET/CT diagnostic criteria was 0.839, with a sensitivity of 67.7 % and specificity of 87.5%; the AUC of single-temporal combined predictive diagnostic model was 0.915, with a sensitivity and specificity of 83.3% and 85.6%, respectively; the AUC of dual'temporal combined predictive diagnostic model was 0.995, with a sensitivity and specificity of 97.6% and 98.7%, respectively. The AUC of the single-temporal combined predictive diagnostic model was higher than that of the conventional PET/CT diagnostic criteria, the AUC of the dual-temporal combined predictive diagnostic model was higher than that of the conventional PET/CT diagnostic criteria, and the AUC of the dual-temporal combined predictive diagnostic model was higher than that of the single-temporal image.The difference was statistically significant (P<0.05). Conclusion The diagnostic efficacy of single-temporal and dual'temporal combined predictive diagnostic models for lymph node metastasis is higher than that of conventional diagnostic criteria, and the diagnostic efficacy of dual-temporal combined predictive diagnostic model is significantly higher than that of single-temporal combined predictive diagnostic model.

 Objective  To investigate the efficacy of simultaneous sucralfate retention enema during radiotherapy on preventing the occurrence of acute and chronic radiation proctitis in patients with cervical cancer, and to evaluate the impact on the clinical symptoms and quality of life. Methods  From January 2017 to June 2019, 208 cases of cervical cancer patients underwent radiation were enrolled in this study, and they were divided into experimental group (n=104) and control group (n=104) according to the random number table method. Patients in experimental group received simultaneous sucralfate retention enema during radiotherapy once daily. RTOG/EORTC table, simple clinical colitis activity index (SCCAI) questionnaire and inflammatory bowel diseases questionnaire (IBDQ) were used to evaluate all patients. Results  The incidences of acute radiation proctitis in experimental group and control group were 35.6% and 58.5%, respectively (P=0.000), and the occurrence of acute radiation proctitis was 21.3 days and 17.4 days (P=0.000). Grade 1, grade 2 and grade 3 acute radiation proctitis were found 19,15 and 3 cases in experimental group, and 22, 31 and 8 cases in control group. The incidences of chronic radiation proctitis in experimental group and control group were 9.6% and 22.1%, respectively (P=0.012), and and the occurrence of chronic radiation proctitis was 10.1 months and 9.2 months, respectively (P=0.235). Grade 1, grade 2, grade 3 and grade 4 chronic radiation proctitis were found 3, 4, 2, and 1 cases in experimental group and 4, 9, 8 and 2 cases in control group. Patients in experimental group had lower SCCAI scores than the control group at the end of radiotherapy, 3 months and 12 months after radiotherapy (P<0.05), while the IBDQ score was higher than that in the control group (P<0.05). Conclusion  Sucralfate retention enema during radiotherapy can effectively reduce the risk of acute and chronic radiation proctitis in patients with cervical cancer and improve the patients' clinical symptoms and quality of life.

Objective To investigate the application of ExacTrac X-ray image guidance system in position correction in craniospinal intensity modulated radiation therapy(IMRT). MethodsFrom December 2017 to March 2021, 34 patients underwent craniospinal irradiation were enrolled in this study. Each patient was treated with three target regions, including whole brain section (UP), cervical thoracic section (MID) and lumbosacral section (DOWN). The position of each section of target area was corrected by ExacTrac X'ray image guidance system before treatment, the three translation directions of left and right (Lat), head foot (Long) and ventral dorsal (Vert) axis of each target area and the three rotation directions of Pitch (rotation around Lat), Roll (rotation around Long) and Yaw (rotation around Vert) were obtained, and the positioning error before and after correction was obtained. The nonparametric Wilcoxon signed rank test was used to compare the positioning error before and after correction. ResultsTwenty treatment data were obtained from each patient, and the ExacTrac X'ray system was applied for each treatment. Among the 34 patients, each patient got 680 groups of data before and after correction. The positioning errors of UP target after correction were less than those before correction. Except for the differences in Lat, Long and Pitch directions, the differences in other directions were statistically significant (P<0.05). The positioning errors of MID target after correction were less than those before correction. Except for the differences in Lat and Yaw directions, the differences in other directions were statistically significant (P<0.05). In the DOWN target area, the positioning error after correction was less than that before correction. Except for the difference in Yaw direction, the difference in other directions was statistically significant (P<0.05). The error values before the correction of the translation direction of the target area in UP section were all distributed in (-8-8) mm, and the translation direction after the correction was all distributed in (-1-1) mm; Before the correction of rotation direction, the error value was evenly distributed in (-4-4)°, and after rotation, it was evenly distributed in (-1-1)°. The translation directions of MID section and DOWN section were distributed in (-1010) mm before correction and (-1-1) mm after correction; Before the correction of rotation direction, the error value was evenly distributed in (-4-4)°, and after rotation, it was evenly distributed in (-1-1)°. Conclusion ExacTrac X'ray image guidance system can reduce the positioning error in craniospinal IMRT, which is worthy of clinical application.

 Objective  To explore the value of ultrasonic strain elastography (SE) combined with supermicro blood flow imaging (SMI) in the identification of thyroid nodules. Methods  The imaging and clinical data of 80 patients with thyroid nodules who were examined from May 2019 to August 2020 were selected, and pathological examination results were used as the gold standard, and patients were divided into benign group (n=34) and malignant group (n=46), SE and SMI were performed in both groups. The ultrasound elasticity scoring standard was used to evaluate the results of SE detection of thyroid nodules, the results of SMI detection of thyroid nodules were evaluated according to Alder blood flow classification, and receiver operating characteristic curve (ROC)was used to analyze the diagnostic efficiency of SE and SMI alone and in combination in the diagnosis of thyroid nodules. ResultsThe ultrasonic elastic score of malignant thyroid nodules detected by SE was significantly higher than that of benign nodules (P=0.000). A total of 38 cases of malignant nodules were detected, including 5 cases in benign group and 33 cases in malignant group. Taking 4 points as the cut-off value, the malignant rate of 1-3 points was 31.0% (13/42), and the malignant rate of 4-5 points was 86.8% (33/38). The Alder blood flow grade of malignant thyroid nodules detected by SMI was significantly higher than that of benign nodules (P = 0.000). A total of 39 cases of malignant nodules were detected, including 7 cases in benign group and 32 cases in malignant group. Taking grade 2 as the cut-off value, the malignant rate of grade 0-1 was 34.1% (14/41), and the malignant rate of grade 2-3 was 82.1% (32/39). In the diagnosis of benign and malignant thyroid nodules, the sensitivity of SE, SMI and their combination were 0.690, 0.659 and 0.871 respectively, the specificity were 0.868, 0.821 and 0.857 respectively, the accuracy were 0.775, 0.738 and 0.863 respectively, and the areas under the ROC curve were 0.785, 0.745 and 0.854 respectively. Conclusion  Compared with separate diagnosis, the combined diagnosis of SE and SMI can effectively improve the diagnostic efficiency of benign and malignant thyroid nodules, and has a higher reference value.

【Abstract】Objective  To screen ncRNAs involved in the development of small cell lung cancer（SCLC） and predicted potential targets for its diagnosis and treatment. Methods Differential gene analysis was performed on the expression profile microarray data obtained from Gene Expression Omnibus (GEO), ceRNA network was constructed, and functional enrichment analysis and PPI network construction were performed. A total of 7 patients with surgically treated small cell lung cancer were collected, and some differential genes (lncRNA, mRNA and miRNA) were validated in clinical samples using qPCR. Results A total of 99 lncRNAs, 46 miRNAs and 73 mRNA molecules were involved in the construction of the regulatory network. GO and KEGG analyses indicated that the dysregulated mRNAs were mainly involved in cellular cancerization, proliferation and metastasis in small cell lung cancer. According to the PPI network analysis, 46 genes were considered hub genes. qPCR Results  showed that compared to adjacent normal tissues, lnc-ENST00000430027.3 showed relatively high expression (P＜0.001), hsa-miR-143-5p showed relatively low expression (P＜0.01) and FANCA showed relatively high expression (P＜0.01) in small cell lung cancer tissues. Conclusion Combined with the validation of clinical specimens for some genes, it provides a new basis for the molecular biology study of small cell lung cancer diagnosis and treatment.

【Abstract】Objective To investigate the relationship between serum exosome hsa_circ_0004390 and chemotherapy resistance and adverse prognosis in patients with epithelial ovarian cancer (EOC). Methods From January to December 2017, the cancer tissue and serum samples of 87 patients with primary EOC were collected from the First Department of Oncology of Qidong People’s Hospital (QidongHospital affiliated to Nantong University), and 85 healthy female volunteers were recruited to obtain control serum samples. The patients who were ineffective in adjuvant chemotherapy or had disease progression within 6 months were included in the drug resistance group (n=30), and the other patients were included in the sensitive group (n=57). Tissue samples from 10 patients undergoing radical surgery were used for next generation sequencing (NGS) to screen the circRNA gene spectrum. The expression level of candidate circRNAs gene was verified by real-time fluorescent quantitative PCR (qPCR).Results Among the circRNA genes identified by NGS, a total of 285 circrnas expressed differently in the EOC tissues of the drug-resistant group and the sensitive group (P＜0.05). After verification, the relative expression levels of hsa_circ_0004390 (P＝0.004) and hsa_circ_0006276 (P＝0.045) in the EOC tissue of the 5 patients in the drug-resistant group were higher than sensitive group, so we chose these two genes for further analysis. q-PCR showed that compared with the control group, the relative expression of serum exosomalhsa_circ_0004390 [2.57 (1.47, 2.99) vs. 0.94 (0.61, 1.35), P＜0.001] and hsa_circ_0006276 [1.26 (1.03, 1.46) vs. 0.87 (0.67, 1.39), P＝0.001] in EOC group were significantly increased. Further analysis of the working characteristic curve of the subjects found that the serum exosomalhsa_circ_0004390 was more effective in the diagnosis of EOC. In addition, the expression of serum exosomalhsa_circ_0004390 in patients with drug resistance was significantly higher than that in patients with sensitivity group [3.07 (2.66, 3.66) vs. 1.69 (1.23, 2.59), P＜0.001]. However, serum exosomalhsa_circ_0006276 was not associated with platinum chemotherapy reaction (P＞0.05). After further adjusting the Objective  interference factors, it was found that the serum exosomalhsa_circ_0004390 was an independent risk factor affecting the platinum chemotherapy response in EOC patients (P＜0.05). In addition, patients with low level of serum exosomalhsa_circ_0004390 expression (＜2.57) and patients with high level (≥2.57) of OS were better (P＝0.005).Conclusion Serum exosome hsa_circ_0004390 contribute to predict the chemotherapeutic response and survival prognosis of Platinum-based EOC patients, which may provide a new target for EOC treatment.

【Abstract】Objective To investigate the relationship between Ki-67 expression and the clinicopathologic features and prognosis of patients with carcinoembryonic antigen (CEA) and gastric cancer after surgery. Methods Retrospective analysis of clinical and follow-up data of patients who underwent radical gastrectomy for cancer at the Jiangsu Oncology Hospital between January 2015 and December 2016. The serum CEA expression was detected by electrochemiluminescence within 1 week before operation, the expression of Ki-67 was detected by immunohistochemistry. Correlation between Ki-67, CEA expression, and clinicopathologic characteristics was analyzed using the Pearson chi-square test. Kaplan-Meier analysis method, Log-rank test, and Cox regression model were used to analyze the prognostic impact of Ki-67 or combined CEA. Results Of 798 patients with postoperative gastric cancer, 368(46.1%) had Ki-67 high expression. Ki-67 expression was associated with age (P＜0.01), TNM stage (Ⅲ vs. Ⅰ, P＝0.036), T stage (T₄ vs. T1-T3, P＜0.001) and CEA (P＝0.01), but not N stage (P>0.05). CEA correlates with clinical stage (stage Ⅰ-Ⅲ , P＝0.003). The 5-year overall survival (OS) rate for all patients was 68.4%. Cox regression analysis showed that age (P＜0.001), TNM stage (P＜0.001), Ki-67 (P＝0.04), and CEA (P＝0.006) were independent predictors of survival after gastric cancer surgery. The 5-year OS rate of patients with stage Ⅲ with Ki-67-L and CEA-normal-expression (CEA-N) was higher than that of patients with high expression (59.8% vs. 48.9%,P＝0.003;60.4% vs.43.8%,P＝0.003), but no correlation was found in patients with stage Ⅰ and Ⅱ. Statistically significant differences in 5-year OS were observed between low-risk (Ki-67-L + CEA-N) group, intermediate-risk (Ki-67-H or CEA-H) group, and high-risk (Ki-67-H + CEA-H) groups (76.3% vs. 66.7% vs. 55.1%, P＜0.001) group. In patients with stage Ⅱ and Ⅲ, the 5-year OS rate was higher in low-risk group than in the intermediate-risk or high-risk group (78.4% vs. 79.1% vs. 61.4%, P＝0.008;68.2% vs. 47.3% vs. 46.3%, P＜0.001). Conclusion Ki-67 may affect survival in patients with gastric cancer after surgery, combined detection of Ki-67 and CEA contributes to improved predicting prognosis in patients with stage Ⅱ and Ⅲ gastric cancer.

【Abstract】Objective  To investigate the expression and clinical significance of exosomal microRNAs (miR-133a) in clear cell renal cell carcinoma (ccRCC). Methods Serum samples were collected from 293 patients with ccRCC who underwent radical nephrectomy in our hospital from September 2015 to January 2019, and another 200 healthy people were collected as control group. Total RNA was extracted from serum and tissue exosomes, and differentially expressed mirnas were identified by TaqMan low-density microarray (TLDA), and verified by real-time fluorescence quantitative PCR (qPCR). Overall survival (OS) and disease-free survival (DFS) were followed up. Results Compared with healthy control group serum and adjacent normal tissue, three miRNAs (miR-133a, miR-210, miR-7-1) were differentially expressed in serum exosomes and tumor tissues of ccRCC patients by TLDA screening. The expression of exosomes miR-133a was significantly down-regulated in ccRCC patients by qPCR (P＜0.001). The expression of exosome miR-133a in ccRCC patients was positively correlated with that in tumor tissues (r=0.467, P＜0.001). Receiver operating characteristic (ROC) curves confirmed that the area under the ccRCC curve (AUC) for the diagnosis of serum exosome miR-133a was 0.78 (95%CI: 0.747-0.729). The expression of preoperative serum exosome miR-133a was correlated with TNM stage and Fuhrman grade (P＜0.05), but not renal function index (P>0.05). The DFS and OS of patients with high expression of serum exosome miR-133a before surgery were both longer than those with low expression (P＜0.001). Cox proportional regression analysis showed that serum exosome miR-133a was an independent prognostic factor for OS in patients with ccRCC [HR=0.486 (95CI: 0.226-1.043); P＝0.034]. Conclusion Serum exosome miR-133a is closely related to the occurrence, development and prognosis of ccRCC, and may be a biomarker to predict the prognosis of patients with ccRCC.

【Abstract】Objective To analyze the expression levels of platelet membrane glycoprotein Ⅱb/Ⅲa fibrinogen receptor (PAC-1), platelet P-selectin (CD62P) and SLC7A11 on platelet surface and their clinical significance in elderly patients with laryngeal squamous cell carcinoma. Methods Eighty-seven elderly patients with laryngeal squamous cell carcinoma admitted to our hospital from January 2016 to January 2021 (laryngeal cancer group) were collected, and 87 patients with vocal cord polyp admitted to our hospital during the same period (control group) were selected. Blood and pathological specimens were collected from the patients, and the positive rate of specific fluorescent antibody binding platelets was determined by flow cytometry using monoclonal immunofluorescence labeling, PAC-1 and CD62P were detected, and expression of SLC7A11 was detected by immunohistochemical SP method. The relationship between the expressions of PAC-1, CD62P and SLC7A11 and the prognosis of patients was analyzed. Results The positive expression rate of PAC-1 and CD62P in laryngeal cancer group was higher than that in control group, and the high expression rate of SLC7A11 (62.07%) was lower than that in control group (28.74%), the difference was statistically significant (P＜0.05). Among the 87 patients with good prognosis, 69 patients had good prognosis, and 18 patients had poor prognosis. The positive expression rate of PAC-1 and CD62P in the poor prognosis group was higher than that in the good prognosis group, and the high expression rate of SLC7A11 (94.44%) was higher than that in the good prognosis group (53.62%) (P＜0.05). The proportion of clinical stage and cervical lymph node metastasis in patients with poor prognosis was significantly higher than that in the control group (P＜0.05), but there were no differences in age, gender and degree of differentiation between the two groups (P>0.05). Multivariate Logistic regression analysis with clinical stage, cervical lymph node metastasis, PAC-1, CD62P and SLC7A11 as independent variables showed that clinical stage, cervical lymph node metastasis, PAC-1, CD62P and SLC7A11 were independent risk for recurrence (P＜0.001). Conclusion PAC-1, CD62P and SLC7A11 are highly expressed in elderly patients with laryngeal squamous cell carcinoma, and are closely related to the prognosis of patients, which may be used as a reference indicator for prognosis evaluation.

【Abstract】Objective  To investigate whether circDUSP16 can be used as a potential biomarker to predict the efficacy and prognosis of adjuvant chemotherapy for resectable gastric cancer (GC). Methods Serum samples were collected from 226 GC patients who underwent radical gastrectomy in our hospital from January 2017 to May 2021. In addition, the serum samples of 209 healthy people in our hospital were selected as control. The expression level of circDUSP16 in serum was detected by real-time quantitative PCR (qPCR). Patients with recurrence or metastasis within 6 months after the end of chemotherapy were included in the chemotherapy insensitive group, while others were included in the chemotherapy sensitive group. Results Serum circDUSP16 level in GC group was significantly higher than that in non-cancer control group (P＜0.001). The area under ROC curve (AUC) of serum circDUSP16 for GC diagnosis was 0.874 (95%CI: 0.843-0.906). 95 patients (42.0%) with GC relapsed within 6 months after the end of chemotherapy. The expression level of circDUSP16 in serum of chemotherapy insensitive group was significantly higher than that of chemotherapy sensitive group (P＜0.001). The AUC of serum circDUSP16 predicted chemotherapy sensitivity was 0.898 (95%CI: 0.854-0.941), and the specificity and sensitivity were 89.8% and 80.8%, respectively, at the optimal cut-off value of 1.870. Multivariate Logistic regression analysis showed that serum circDUSP16 was an independent factor for chemotherapy sensitivity in GC patients (P＜0.001). According to the median value of circDUSP16 in serum of GC patients, the patients were divided into low expression group (< 1.64) and high expression group (≥1.64). The overall survival rate of baseline GC patients in the low and high circDUSP16 expression groups was 69.9% and 14.2%, respectively, and the median OS stage was longer in the low expression group (P＜0.001). Multivariate Cox proportional regression analysis showed that serum circDUSP16 was an independent prognostic factor for GC patients (P＜0.001). Conclusion High serum circDUSP16 expression was associated with drug resistance and poor survival prognosis of GC adjuvant chemotherapy, which is promising as a potential predictor of GC adjuvant chemotherapy efficacy and poor prognosis.

【Abstract】Objective  To investigate the clinical significance of miR-204 promoter methylation in colorectal cancer (CRC). Methods From January 2018 to March 2020，the blood samples, tumor tissue samples and paracarcinoma normal colon mucosal tissue samples were collected from 69 CRC patients admitted to the department of gastroenterology of our hospital. Another 68 healthy volunteers were recruited as the normal control group. The plasma samples were collected. Methylation levels of CpG sites identified in tumor and normal tissue were analyzed using the Tumor Gene Atlas Project (TCGA) database and gene-on-a-chip data (Methyl450K). The gene expression and promoter methylation status of miR-204 were detected by quantitative methylation-specific PCR (qMSP) and quantitative real-time PCR (qPCR). Results The TCGA data indicated that the expression of miR-204 was coordinately down-regulated with the expression of host gene TRPM3, and two CpG islands around the miR-204 promoter were identified. Compared with the paracancer tissues, the miR-204 promoter methylation reference percentage (PMR) was increased in CRC tissues[1.78 (0.35, 16.61) vs. 1.51 (0.45, 2.98), P＜0.001]. And the methylation level of miR-204 promoter was negatively correlated with the expression level of miR-204 (r=-0.324, P＝0.007), and positively correlated with DNA methyltransferase 1 mRNA (r=0.502, P＜0.001). Moreover, compared with the normal control group, the PMR of miR-204 promoter was significantly higher in plasma cfDNA of CRC patients[6.57 (0.76, 12.45) vs. 1.60 (0.59, 3.4), P＝0.015]. And PMR of miR-204 promoter in plasma cfDNA of CRC patients was positively correlated with PMR of miR-204 promoter in CRC tissues (r=0.418, P＜0.001).The area under receiver operating characteristic curve of PMR of miR-204 promoter in plasma cfDNA for CRC diagnosis was 0.701 (95%CI: 0.610-0.791), the sensitivity and specificity were 56.5% and 94.1%. In addition, further stratified analysis was conducted according to clinical stage and differentiation degree, there was no significant correlation between the hypermethylation of miR-204 promoter and the main clinical characteristics of CRC patients (P＞0.05). Conclusion miR-204 promoter methylation is significantly correlated with CRC, and the status of miR-204 promoter methylation in plasma cfDNA may be used as potential biomarkers for CRC diagnosis and monitoring.

【Abstract】Objective To analyze the relationship between saliva miR-15b and cleaved caspase-3 expression and prognosis in oral squamous cell carcinoma (OSCC). Methods One hundred and fifty-four patients with OSCC admitted to our hospital from May 2016 to June 2020 (OSCC group) were collected, and 103 healthy volunteers were collected as control group. The levels of miR-15b in saliva and cleaved caspase-3 expression in tissues were detected by quantitative real-time PCR(qPCR) and immunohistochemical staining, respectively. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of saliva miR-15b expression in OSCC. The relationship between miR-15b expression in saliva and clinicopathologic features of oral squamous cell carcinoma was analyzed. Multivariate Cox regression was used to analyze the prognostic factors of OSCC. Results The level of miR-15b in saliva of OSCC patients was significantly lower than that of control group (0.72±0.33 vs. 1.00±0.23, P＜0.001). The area under the ROC curve of saliva miR-15b to diagnose OSCC was 0.760 (0.703-0.817). Expression levels of caspase-3 and cleaved caspase-3 protein were significantly higher in OSCC than in paracancer tissue (P＜0.001). Spearman correlation analysis showed that saliva miR-15b levels in OSCC patients were negatively correlated with cleaved caspase-3 protein expression (r=-0.321, P＜0.001). Salivary miR-15b expression was associated with tumor diameter and prognosis (P＜0.05). The 5-year DFS rate and 5-year OS rate in the low expression group were 28.57% and 44.16%, respectively, while the 5-year DFS rate and 5-year OS rate in the high expression group were 62.34% and 81.82%, respectively, and the difference was statistically significant (P＜0.001). Multivariate Cox proportional regression model showed that TNM stage, radical surgery, and saliva miR-15b level were independent prognostic factors affecting OS in OSCC patients (P＜0.05). Conclusion The level of miR-15b in saliva of OSCC patients is correlated with cleaved caspase-3, which can be used as a biomarker to predict the prognosis of OSCC patients.