Objective:To screen differentially expressed genes (DEGs) associated with liver cancer by bioinformatics analysis method, and to investigate the mechanism of the minichromosome maintenance protein 2 ( MCM2) and replication factor C subunit 4 ( RFC4) genes in liver cancer in vitro. Methods:Gene expression profiling data of 80 and 36 hepatocellular carcinoma tissues and 307 and 13 cirrhotic tissues were obtained from the GSE25097 and GSE98620 datasets of the gene expression analysis (GEO) database, respectively. Gene expression profiling data of 374 liver cancer tissues and 50 normal liver tissues were downloaded from the cancer genome atlas (TCGA) database. Limma and DESeqs R software were used to process the gene expression profiling data, construct protein-protein interaction networks, and analysis the relevance of these genes to survival. Weighted gene co-expression network analysis was performed to screen out the core genes. Liver cancer SMMC7721 cells were transfected with MCM2 blank plasmid (MCM2 control group), MCM2 overexpression plasmid [MCM2 WT1 group, MCM2 WT2 (2-fold WT1) group], RFC4 blank plasmid (RFC4 control group), and RFC4 overexpression plasmid [RFC4 WT1 group, RFC4 WT2 (2-fold WT1) group], respectively. The expression of MCM2 and RFC4 in liver cancer cell lines and their transfection levels were detected by real-time fluorescence quantitative reverse transcription PCR and Western blotting. The effects of MCM2 and RFC4 on the proliferation of hepatocellular carcinoma cells were detected by MTT assay and cell cloning assay, respectively. The effects of MCM2 and RFC4 on the migration of liver cancer cells were determined by the scratch assay. The effects of MCM2 and RFC4 on liver cancer cell invasion were detected by Transwell assay.Results:By bioinformatic analysis, 9 HCC DEGs were selected, including ubiquitin conjugating enzyme E2 T ( UBE2T), aurora kinase A ( AURKA), targeting protein for Xklp2 ( TPX2), MCM2, RFC4, ribonucleoside-diphosphate reductase subunit M2 ( RRM2), serine peptidase inhibitory factor Kazal type 1 ( SPINK1), collagen type XV alpha 1 chain ( COL15A1) and C-C motif chemokine 25 ( CCL25). Among the six genes associated with clinical stages, the MCM2 and RFC4 genes were found to be strongly associated with prognosis in liver cancer. The relative protein expression of MCM2 and RFC4 in HepG2 cells (1.83±0.07, 1.44±0.09) and SMMC7721 cells (1.74±0.05, 1.43±0.08) was higher than that in MIHA cells (1.00±0.02, 1.00±0.03), and all the differences were statistically significant (all P<0.05). The relative gene expression of MCM2 and RFC4 in HepG2 cells (14.30±0.12, 5.10±0.18) and SMMC7721 cells (10.60±0.11, 7.60±0.07) was higher than that in MIHA cells (1.00±0.05, 1.00±0.03), and all the differences were statistically significant (all P<0.05). Compared with the MCM2 control group, the absorbance values [(0.28±0.01 and 0.21±0.01) vs 0.18±0.03], the number of clonal cells [(717±12 and 782±29) cells vs (389±17) cells], the percentage migration [(0.43±0.02 and 0.68±0.01) vs 0.15±0.06], and the number of cellular invasions [(933±21 and 821±11) cells vs (409±16) cells] were higher in the MCM2 WT1 and MCM2 WT2 groups, and the differences were all statistically significant (all P<0.05). Compared with the RFC4 control group, the absorbance values [(0.30±0.02 and 0.21±0.01) vs 0.17±0.02], the number of cloned cells [(571±11 and 728±9) cells vs (373±23) cells], the percentage migration [(0.75±0.11 and 0.67±0.04) vs 0.34±0.07], and the number of cell invasion [(835±26 and 818±18) cells vs (629±12) cells] were higher in the RFC4 WT1 and the RFC4 WT2 groups, and the differences were statistically significant (all P<0.05). Conclusions:MCM2 and R FC4 genes play a role in promoting tumorigenesis and growth in hepatocellular carcinoma.

Objective:To explore the expression and clinical significance of fibrinogen-like protein 2(FGL2)in gastrointesti-nal stromal tumor(GIST).Methods:Immunohistochemical EnVision two-step method was used to detect expression of FGL2 protein in 158 GIST patients,and correlation between FGL2 protein and clinicopathological parameters was analyzed,and relationship be-tween FGL2 protein and the count of CD3+T,CD8+T,CD20+T and CD68+T of tumor-infiltrating lymphocytes(TILs)in GIST was inves-tigated.Results:Expression of FGL2 protein in GIST was negatively correlated with tumor size,NIH risk grade,necrosis and mitotic image count(P<0.05),there was no significant difference in gender and tumor location(P>0.05).FGL2 expression was associated with low CD3+T cell counts in GIST(P<0.05),while there was no significantly difference with CD8+T,CD20+T and CD68+T cell counts(P>0.05).Conclusion:FGL2 protein is involved in occurrence and development of GIST,which expression level is partly pre-dictive of the malignant potential of GIST.FGL2 protein may participate in occurrence and development of GIST by regulating tumor microenvironment.

Objective:To evaluate the autogenous arteriovenous fistula(AVF) insufficiency by ultrasound monitoring of brachial artery resistance index(RI).Methods:The brachial artery RI and blood flow volume(FV) data of 828 patients who underwent color-Doppler ultrasound detection after AVF in the General Hospital of Western Theater Command from January 2019 to June 2021 were retrospectively analyzed. The patients were grouped according to the adequacy of clinical dialysis, including 668 patients in the group with normal AVF function and 160 patients in the group with insufficient AVF function. The general information and ultrasonic measurement parameters were compared between the two groups. The correlation between brachial artery FV and RI was analyzed. The evaluation of brachial artery flow RI for AVF insufficiency was analyzed by ROC curve.Results:There were statistically significant differences between the two groups in brachial artery RI and FV(both P<0.001). The results of Pearson correlation analysis showed that brachial artery FV was negatively correlated to RI ( r=-0.657, P<0.001). The area under ROC curve for assessing AVF function by brachial artery RI was 0.970, with 95% CI was 0.955-0.986, the optimal cut-off value was 0.665, and the sensitivity and specificity were 0.888 and 0.955, respectively. Conclusions:Brachial artery RI in patients with AVF insufficiency is significantly higher than that in patients with normal AVF function. The optimal cutoff value of brachial artery RI can be used as an evaluation parameter for rapid screening of AVF function.

Background: Colorectal cancer is one of the most commonly diagnosed cancer and leading causes of cancer death worldwide. Fibrinogen-like protein 2 (FGL2), a member of the fibrinogen family, has been demonstrated as a regulator of immune cell functions in tumor microenvironment and might facilitate tumor progression. Aims: To study the expression and clinical significance of FGL2 in colon cancer. Methods: One hundred and fifty colon cancer patients diagnosed from January 2018 to January 2022 at the Second Hospital of Tianjin Medical University were enrolled in this study. The paraffin-embedded tissues were collected for detection of FGL2 protein and the surface markers of tumor infiltrating immune cells (TIICs), including CD4, CD8, CD20, CD68, and CD56 by using immunohistochemistry. The correlations of FGL2 expression level with the clinicopathological parameters and TIICs counting were analyzed. Results: Expression of FGL2 was upregulated in 68.7% of the colon cancer cases. Its expression level was correlated positively with the tumor size and TNM staging (all P<0.05), while no correlations were found between FGL2 expression level and gender, age, tumor differentiation, and presence of vascular invasion (all P>0.05). Meanwhile, the expression level of FGL2 was associated with the cell counting of CD4

Autophagy is a special cellular process, which can participate in regulating cell survival, growth, differentiation and homeostasis maintenance by transporting damaged organelles and macromolecular substances to lysosomes for degradation. Autophagy plays a very important role in all aspects of life process. Research results show that autophagy plays an important role in tumor occurrence, development and metastasis. The synergistic effect of autophagy and vascular endothelial growth factor promotes tumor angiogenesis and cell repair, and may play an important role in the development of tumor resistance to anti-vascular drug therapy. Targeted therapy with autophagy as the target may be a new direction for anti-tumor molecular targeted therapy in the future, aiming to provide multi-target collaborative therapy to benefit patients.

Objective:To investigate the clinical characteristics and risk factors of alcoholic liver disease (ALD) combined with type 2 diabetes mellitus (T2DM).Methods:The clinical data of 70 patients with ALD combined with T2DM (ALD + T2DM group) who received treatment from March 2015 to March 2020 in the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. The clinical data of 69 patients with ALD (ALD group) and 69 patients with T2DM (T2DM group) who concurrently received treatment were also analyzed. Sex, age, body mass index, drinking habits and other basic information in the three groups were collected. The risk factors of ALD combined with T2DM were evaluated by logistic regression analysis.Results:The daily alcohol intake and years of drinking in the ALD + T2DM group were (110.97 ± 79.78) g/d and (25.17 ± 10.05) years, respectively, which were significantly higher than (91.48 ± 64.26) g/d and (21.78 ± 8.91) years respectively in the ALD group ( t = 1.699, 2.102, both P < 0.05). The incidence of metabolic syndrome in the ALD + T2DM group was 34.3% (24/70), which was significantly higher than 15.9% (11/69) in the ALD group ( χ2 = 6.210, P < 0.05). The activity ratio of aspartate aminotransferase/alanine aminotransferase, total bilirubin level, gamma glutamyl transpeptidase activity in the ALD + T2DM group were 1.59 ± 0.93, (64.73 ± 39.90) μmol/L, (522.93 ± 353.66) U/L, respectively, which were significantly higher than (1.04 ± 0.53), (10.37 ± 4.51) μmol/L, (35.73 ± 23.99) U/L, respectively in the T2DM group ( t = 4.280, 3.780, 5.045, all P < 0.05). Triacylglycerol level in the ALD + T2DM group was significantly higher than that in the ALD group [(1.69 ± 1.04) mmol/L vs. (1.28 ± 0.87) mmol/L, t = 2.523, P < 0.05). Prothrombin time and lactate dehydrogenase activity in the ALD + T2DM group were (13.13 ± 2.79) s and (226.17 ± 79.93) U/L, respectively, which were significantly higher than (10.41 ± 0.84) s, (172.63 ± 39.34) U/L, respectively in the T2DM group ( t = 7.715, 4.969, both P < 0.05). Multivariate Logistic regression analysis showed that prothrombin time, triacylglycerol level, years of drinking, gamma glutamyl transpeptidase activity, and amount of drinking were the main risk factors for ALD combined with T2DM ( OR = 2.010, 3.270, 1.230, 1.060, 1.006, all P < 0.05). Conclusion:Patients with ALD combined with T2DM are prone to metabolic syndrome and lipid disorders, which may aggravate the disease. Prothrombin time, triacylglycerol level, years of drinking play an important role in the development of ALD combined with T2DM.

Objective To explore the prognostic values of telomerase reverse transcriptase promoter (TERTp) mutation and 1p/19q co-deletion in newly-diagnosed O6-methylguanine-DNA methyltransferase (MGMT) promoter un-methylated/isocitrate dehydrogenase (IDH) wild-type glioblastoma multiform (GBM). Methods A total of 82 patients pathologically newly-diagnosed MGMT promoter un-methylated/IDH wild-type GBM, admitted to our hospitals from March 2016 to November 2018, were included in this study. TERTp mutations (TERTp wild-type and TERTp mutation [C228 mutation and C250 mutation]) in GBM specimens were detected by PCR sequencing, 1p/19q co-deletion in GBM specimens was detected by fluorescence in situ hybridization (FISH), and clinical data, adverse reactions and prognoses of patients with different molecular typing were compared. Results There were 33 patients in the TERTp wild type group with mean age of 48 years, and 49 patients in the TERTp mutation group with mean age of 59 years; the difference of age was significant (P<0.05); there were no statistical differences in gender distribution, Karnofsky performance status (KPS) scores, tumor sites and surgical resection degrees between the two groups (P>0.05). There were 8 patients with 1p/19q co-deletion and 74 patients without 1p/19q co-deletion; no significant differences in above clinical parameters were noted between the two groups. There were no statistically significant differences in the incidences of bone marrow suppression, digestive tract response and fatigue, disease progression rate, or survival rate between patients from TERTp wild type group and TERTp mutation group, and between patients with 1p/19q co-deletion and patients without 1p/19q co-deletion (P>0.05). No significant differences in above clinical parameters, disease progression rate, and survival rate were noted between patients with C228 mutation and C250 mutation (P>0.05). Conclusion TERTp typing and 1p/19q co-deletion status do not have prognostic value in newly-diagnosed MGMT un-methylated/IDH wild-type GBM patients; patients with TERTp mutations have older age than wild-type patients; patients with C250 mutation trend to have higher survival rate than those with C228 mutation.

Objective To explore the prognostic value of ADC tot of diffusion-weighted magnetic resonance imaging with multiple diffusion gradient factor ( b) values ( Mb DWI) in predicting overall survival (OS) of patients with locally advanced pancreatic cancer (LAPC) undergoing CyberKnife and sequential S-1. Methods Forty-one LAPC patients were enrolled (28 male and 13 female), who had routine pancreatic MRI and multiple b value DWI (Mb DWI, b value =0, 25, 50, 75, 100, 150, 200, 400, 600, 800 and 1000 s/mm2) scan (3.0 T) prior to radiotherapy.ADCtot value was calculated using single index model .Two independent radiologists on abdominal radiology manually drew the target area of interest and measured ADC tot at 1-month interval, and the interclass correlation coefficient (ICC) was calculated.The median ADCtot was used as a standard to divided the data into high value and low value .The survival was analyzed by Kaplan-Meier method and compared by log rank test .Cox proportional hazard model was employed to identify predictive factors for OS.Results The median ADCtot value by two independent radiologists was (1.54 ±0.27) ×10 -3 and(1.55 ±0.28) ×10 -3 mm2/s, respectively.The ICC was 0.994, and the consistency was good.Pre-treatment ADC tot value was the independent prognostic factor for the OS of patients who received CyberKnife and S-1 (HR: 1.083, 95％CI 1.083-12.554,P=0.0368), indicating that the mortality increased by 1.083 times as ADCtot increased by 1 unit.Similarly, CyberKnife combined with S-1 was also the independent prognostic factor for the OS (HR:0.329, 95％CI 0.142-0.765, P=0.0098), indicating that the mortality of patients treated by CyberKnife and S-1 was 0.329 times of that of patients who did not take S-1. Conclusions The pre-treatment ADC tot was an independent predictor for OS of LAPC patients treated by CyberKnife and sequential S-1, which had a certain prognostic value .

The activation of p21 kinase 2 (PAK2) has a certain value in cancer research, since its participation in a series of intracellular biological activities. There is a relatively little research on its relationship with the development of tumors. PAK2 can be activated by a variety of upstream signals, especially small G protein Rho family of Rac and Cdc42, and it participates in a variety of important signaling pathways and cell function regulation. Abnormal expression of PAK 2 has been reported in various tumors, which involves in cytoskeletal remodeling, cell motility, apoptosis, signal transduction, gene transcription, translation and angiogenesis. Therefore, PAK2 plays an important role in tumor occurrence and development. The study on PAK2 and the targeting therapy for anti-PAK2 provides a new sight on the treatment and prevention of tumor.