Novel Compounds with Promising IDO1 Inhibitory Activity As New Cancer Drug Candidates: Derivatives Of N, N'-diphenylurea Linked With 1,2,3-triazole.

To explore potential indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors, we designed a series of compounds incorporating urea and 1,2,3-triazole structures. IDO1 enzymatic activity experiments with the synthesized compounds were used to verify their molecular-level activity; for instance, the half maximal inhibitory concentration value of compound 3c was 0.07 µM. Our research has yielded a series of novel IDO1 inhibitors which may be beneficial in the development of drugs targeting IDO1 for cancer treatment.

More advantages of trocar compared than steel needle in deep venipuncture catheterization.

BACKGROUND: Deep venipuncture catheterization is widely used in clinical anesthesia. However, it is worth thinking about how to improve the rate of successful catheter insertion, and relieve patients' discomfort. This paper aimed to compare the clinical advantages between trocar and steel needle. METHODS: Total 503 adult patients were recruited and randomly assigned. The control group was punctured with steel needle, and the experimental group was punctured with trocar needle. Clinical and followed-up information was recorded. Pearson's chi-squared and spearman test were performed to analyze the correlation between intervention and relative parameters. Univariate logistic regression was performed to verify the odds ratio of trocar needle compared with steel needle. RESULTS: Pearson's chi-square test and Spearman's correlation test showed a significant correlation between puncture success, puncture comfort, successful catheter insertion, puncture time, thrombosis, catheter fever, bleeding, infection and interventions (P < .05). Univariate logistic regression showed that there existed better puncture comfort (odds ratio [OR] = 6.548, 95% confidence interval [CI]: 4.320-9.925, P < .001), higher successful catheter insertion (OR = 6.060, 95% CI: 3.278-11.204, P < .001), shorter puncture time (OR = 0.147, 95% CI: 0.093-0.233, P < .001), lesser thrombosis (OR = 0.194, 95% CI: 0.121-0.312, P < .001), lesser catheter fever (OR = 0.263, 95% CI: 0.158-0.438, P < .001), lesser bleeding (OR = 0.082, 95% CI: 0.045-0.150, P < .001) and lesser infection (OR = 0.340, 95% CI: 0.202-0.571, P < .001) in trocar group compared with steel needle group. CONCLUSION: Trocar application in deep venipuncture catheterization can improve successful catheter insertion, relieve pain and discomfort of patients, reduce incidence of complications, and provide better security for patients.

Effect of Perioperative Dexmedetomidine Infusion on Postoperative Delirium in Elderly Patients Undergoing Oral and Maxillofacial Surgery: A Randomized Controlled Clinical Trial.

Purpose: The aim of the study was to determine whether perioperative dexmedetomidine administration can improve postoperative delirium in elderly patients undergoing oral and maxillofacial surgery. Patients and Methods: This was a prospective double-blind randomized controlled clinical trial conducted in Cangzhou Central Hospital from December 2021 to March 2022. Patients aged 65 and older underwent oral and maxillofacial surgery under general anesthesia. Eligible patients were randomly assigned to dexmedetomidine or control group. Dexmedetomidine was injected intravenously from 10 min before induction of anesthesia to 30 min before the end of surgery in dexmedetomidine group, while patients in the control group were given normal saline at the same rate during the same time period. The primary measurement indicators were the incidence and duration of delirium in the first five days after surgery. The secondary measurement indicators were Visual Analogue Score (VAS) for the first 24 hours following surgery, subjective sleep quality score within 24 hours postoperatively and intraoperative adverse reactions. Results: One hundred and twenty patients were randomly assigned. Baseline characteristics were similar between two groups. The incidence and duration of postoperative delirium did not differ statistically between two groups (all P > 0.05). Compared with control group, VAS scores in dexmedetomidine group were significantly lower at 6, 12, and 24 hours after surgery (all P < 0.05); moreover, Richards-Campbell Sleep Questionnaire (RCSQ) results were significantly improved 1 day after surgery in dexmedetomidine group (P < 0.05). Dexmedetomidine-related adverse reactions were similar in both groups (P > 0.05). Conclusion: Intravenous infusion of dexmedetomidine 10 min before induction of anesthesia to half an hour before the end of surgery did not improve postoperative delirium in elderly patients undergoing oral and maxillofacial surgery; however, dexmedetomidine may be associated with decreased postoperative pain and improved postoperative sleep quality.

Effects of Abdominal Wall Blocks on Postoperative Delirium in Elderly Patients Undergoing Laparoscopic Surgery: A Randomized Controlled Study.

BACKGROUND Postoperative delirium (POD) seriously affects the rapid postoperative recovery of elderly patients. We investigated the effect of abdominal wall blocks on POD in elderly patients undergoing laparoscopic radical resection of colon cancer and underlying mechanisms. MATERIAL AND METHODS A total of 100 patients undergoing laparoscopic radical resection of colon cancer were randomly assigned to group C (control) and group R (regional nerve blocks). In group R, 20 mL of local anesthesia-mixed solution was injected into the bilateral transverse abdominis muscle plane and 10 mL was injected into the bilateral posterior sheath of the rectus abdominis muscle. In group C, the same amount of saline was used for nerve block. The consumption of propofol and remifentanil during surgery was recorded. Levels of serum interleukin (IL)-6 and highly sensitive C-reactive protein (hs-CRP) during surgery were evaluated. The Confusion Assessment Method for the Intensive Care Unit Scale and the Richmond Agitation-Sedation Scale were adopted to evaluate POD. RESULTS The incidence of POD was lower in group R than in group C (P=0.048). The consumption of propofol and remifentanil was significantly reduced in group R, compared with group C (P<0.05). Compared with T0, serum IL-6 and hs-CRP levels in both groups were significantly increased at T1 and T2 (P<0.05). Moreover, serum IL-6 and hs-CRP were lower at T1 and T2 in group R compared with group C (P<0.05). CONCLUSIONS Abdominal wall blocks may alleviate POD in elderly patients undergoing laparoscopic surgery, which may be related to the reduction of anesthetic consumption and inflammatory response.

Expression of Foxp3 and its prognostic significance in colorectal cancer.

The aim of this study was to explore the expression and clinical significance of Foxp3 in colorectal tumor cells. An immunohistochemistry assay was used to detect the expression of Foxp3 in 173 cases of colorectal cancer. The relationship between the clinicopathological factors and the prognosis of colorectal cancer was analyzed. The rate of positive Foxp3 expression in tumor cells was 89.7%. There were no significant differences between cases with and without expression of Foxp3 with regard to sex, age, primary cancer sites, and distal metastasis. The expression of Foxp3 was negatively correlated with lymph node metastasis and pathological tumor, node, metastasis (pTNM) stage in tumor cells ( P < 0.05), which reflects the depth of invasion. Foxp3 expression also had a positive correlation with the degree of differentiation ( P < 0.01). A high level of Foxp3 expression was observed more often in tumor cells compared to tumor-surrounding tissues ( P = 0.003). High expression of Foxp3 was also associated with longer overall and disease-free survival ( P ⩽ 0.001). Foxp3 expression in colorectal cancer cells correlates with many clinicopathological characteristics; moreover, high expression of Foxp3 may be a promising potential prognostic factor for patients with colorectal cancer.

Colorimetric detection of microRNA based hybridization chain reaction for signal amplification and enzyme for visualization.

MicroRNAs (miRNAs) have key roles in gene expression and can be employed as biomarkers for early diagnosis of various diseases, especially cancers. Detection of miRNAs remains challenging and often requires detection platforms. Here, a horseradish peroxidase (HRP)-assisted hybridization chain reaction (HCR) for colorimetric detection of miR-155 was described. In the presence of target miRNA, the capture probe immobilized on the microplate sandwiched the target miR-155 with the 3' end of the reporter probe. Another exposed part of the RP at the 5'end triggered HCR producing double-stranded DNA polymers with multiple fluorescein isothiocyanates (FITC) for signal amplification. Finally, multiple HRP molecules were immobilized onto the long-range DNA nanostructures through FITC/anti-FITC monoclonal antibody interactions on the microplate for visualization by tetramethylbenzidine/H2O2 system and the colorless substrate turned into the blue product. To obtain accurate data, the absorbance at 450 nm was calculated by microplate reader. The detection limit was 31.8 fM (3.18 amol). Furthermore, this biosensor showed high specificity and was able to discriminate sharply between target miRNA and mismatched sequences. And this approach could be easily applied to the detection of miR-155 in serum sample, thereby ascribing it for a wide application.

Expression of Activating Protein 4 and Its Relationships with Prognosis in Gastric Cancer.

OBJECTIVE: The aim of this work was to investigate the expression of transcription activating protein 4 (AP-4) in gastric cancer (GC) and its impacts on prognosis. METHODS: The cancer tissues and normal tissues of 54 GC patients were sampled for the expression detection of AP-4, and the patients were followed up. RESULTS: The positive expression rate of AP-4 in the cancer tissues (68.5%) was higher than the normal tissues (22.2%; p < 0.01). The lower the tumor differentiation degree and the deeper the invasion depth, the higher the expression rate of AP-4. The median survival time of the patients with positive AP-4 expression was significantly shorter than of those without AP-4 expression (26.3/41.3 months), and the accumulative survival rate of the former was also lower than the latter (χ2 = 4.736, p = 0.03). AP-4 was expressed in GC tissues and normal gastric tissues, with the expression in the former being higher. CONCLUSIONS: The expression of AP-4 was positively related with the tumor differentiation degree, invasion depth, lymph node metastasis, and pTNM stage, while it was not related with patient gender, age, tumor size, location, or distant metastasis. AP-4 might be used as an indicator for the prognosis prediction of GC.

Association studies of ERCC1 polymorphisms with lung cancer susceptibility: a systematic review and meta-analysis.

BACKGROUND: Excision repair cross-complimentary group 1 (ERCC1) is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial. OBJECTIVES: An updated meta-analysis was conducted to explore whether lung cancer risk could be attributed to the following ERCC1 polymorphisms: rs11615 (T>C), rs3212986 (C>A), rs3212961 (A>C), rs3212948 (G>C), rs2298881 (C>A). METHODS: Several major databases (MEDLINE, EMBASE and Scopus) and the Chinese Biomedical database were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations. RESULTS: Sixteen studies with 10,106 cases and 13,238 controls were included in this meta-analysis. Pooled ORs from 11 eligible studies (8,215 cases vs. 11,402 controls) suggested a significant association of ERCC1 rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR = 1.24, 95% CI: 1.04-1.48, P = 0.02). However, such an association was disproportionately driven by a single study. Removal of that study led to null association. Moreover, initial analyses suggested that ERCC1 rs11615 exerts a more profound effect on the susceptibility of non-smokers to lung cancer than that of smokers. Moreover, no statistically significant association was found between remaining ERCC1 polymorphisms of interest and lung cancer risk, except for rs3212948 variation (heterozygous: CG vs.GG, OR = 0.78, 95% CI: 0.67-0.90, P = 0.001; dominant: CG/CC vs.GG, OR = 0.79, 95% CI: 0.69-0.91, P = 0.001). CONCLUSION: Overall, this meta-analysis suggests that ERCC1 rs3212948 G>C, but not others, is a lung cancer risk-associated polymorphism. Carefully designed studies with large sample size involving different ethnicity, smoking status, and cancer types are needed to validate these findings.

A polymorphism at the 3'-UTR region of the aromatase gene is associated with the efficacy of the aromatase inhibitor, anastrozole, in metastatic breast carcinoma.

Estrogen-related genes and the fat mass and obesity-associated (FTO) gene play a critical role in estrogen metabolism, and those polymorphisms are associated with a poor prognosis in breast cancer. However, little is known about the association between these polymorphisms and the efficacy of anastrozole. The aim was to investigate the impact of the genetic polymorphisms, CYP19A1, 17-ß-HSD-1 and FTO, on the response to anastrozole in metastatic breast carcinoma (MBC) and to evaluate the impact of those polymorphisms on various clinicopathologic features. Two-hundred seventy-two women with hormone receptor-positive MBC treated with anastrozole were identified retrospectively. DNA was extracted from peripheral blood and genotyped for five variants in three candidate genes. Time to progression was improved in patients carrying the variant alleles of rs4646 when compared to patients with the wild-type allele (16.40 months versus 13.52 months; p = 0.049). The rs4646 variant alleles were significantly associated with longer overall survival (37.3 months versus 31.6 months; p = 0.007). This relationship was not observed with the rs10046, rs2830, rs9926298 and rs9939609 polymorphisms. The findings of this study indicate that rs4646 polymorphism in the CYP19A1 gene may serve as a prognostic maker of the response to anastrozole in patients with MBC who are treated with anastrozole.

Expression of DOG1, CD117 and PDGFRA in gastrointestinal stromal tumors and correlations with clinicopathology.

OBJECTIVE: To discuss the significance of DOG1, CD117 and PDGFRA in the diagnosis of gastrointestinal stromal tumors (GISTs), and analyze their correlations with clinicopathological features and risk ranking. METHOD: DOG1, CD117 and PDGFRA were detected with IHC Envision ldpe-g-nvp in 63 GISTs and 43 cases of non-GISTs, and analyzed for relations with clinicopathological factors (gender, age, location, tumor size, mitotic phase, histology) and risk degree. RESULTS: The positive expression rate of DOG1, CD117 and PDGFRA in GISTs was 84.1% (53/63), 90.5% (57/63), 53.2% (33/63), respectively. Among the 6 CD117 negative cases, all were DOG1 positive and 5 were PDGFRA positive. Rates in patients with non-GISTs was 11.6%, 16.3%, 6.98%, respectively. Expression of DOG1 and PDGFRA demonstrated no significant variation with gender, age, position, tumor size, mitotic phase, histology, and risk rank. However, CD117 was related with position and histology (P=0.008 and P=0.045), those in the mesentery having a higher positive rate than those derived from stomach, small intestine, colon and rectum (50.0% vs 94.7%, P=0.008). Furthermore CD117 was also highly expressed in spindle and epithele types. CONCLUSIONS: DOG1 had a good sensitivity and specificity as a kind of newly discovered marker, especially for KIT negative GISTs. However, DOG1, CD117 and PDGFRA cannot be used for assessing the rish of patients.

Comparisons of multiple characteristics between young and old lung cancer patients.

BACKGROUND: Risk factors that contribute to younger patients with lung cancer are still relatively unknown. The aim of this study was to compare the clinical characteristics, histological types, stages at diagnosis, treatment modalities and survival rates between young and old patients with lung cancer. METHODS: The study was designed as a retrospective review of all lung cancer patients admitted to the Third Affiliated Hospital of Harbin Medical University from 1998 to 2008. Survival analyses using univariate and multivariate approaches were performed to compare the survival rates between different age groups and to discover potential prognostic factors. RESULTS: This research included 3320 patients with primary lung cancer, of whom 626 (18.8%) were 45 years old or younger at the time of diagnosis. The percentage of smokers and the male to female ratios between the young and old patient groups were 51.27% vs. 70.6% (P < 0.001) and 1.99 vs. 2.13 (P = 0.4801), respectively. The young patient group had a higher incidence of adenocarcinoma and fewer surgeries. The 1-year, 3-year and 5-year survival rates in the young patient group were generally lower than those of the old patient group, with significant differences (P = 0.0232). The clinical stage of the tumor was a prognostic factor for both non-small cell lung cancer patients (P < 0.0001) and small cell lung cancer patients (P = 0.0002). Symptoms, diagnostic method, histology, smoking, treatment modality and body mass index were shown to have significant relationships with the survival of lung cancer patients (P < 0.05). CONCLUSIONS: Patients with lung cancer who are younger than 45 years old might have a significantly poorer prognosis than that of older patients. Symptoms, diagnosis method, histology, smoking, treatment modality and body mass index can be independent prognostic factors for lung cancer.

Icariin induces mouse embryonic stem cell differentiation into beating functional cardiomyocytes.

Icariin, the primary active component of Epimedium extracts, has recently been shown to induce cardiomyocyte differentiation of murine embryonic stem (mES) cells in vitro. However, as these cardiomyocytes were not functionally characterized, the potential application of icariin-induced cardiomyocytes in clinical practice remains unclear. Therefore, in this study, we characterized the structure and function of icariin-induced cardiomyocytes to evaluate their potential application in transplantation for cardiac failure treatment. mES cells were cultured as embryoid bodies (EBs) via the direct suspension method in the presence of icariin. The protein expression profiles and ultrastructural characteristics of mES cell-derived cardiomyocytes were then characterized by immunofluorescence and transmission electron microscopy, respectively. In addition, the expression of cardiac-specific and calcium handling genes was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Cardiomyocytes induced by icariin treatment expressed the cardiac-specific proteins myosin light chain-1v (MLC1v), atrial natriuretic polypeptide (ANP), and cardiac troponin I (cTnI). Furthermore, these cells appeared to possess myofibrils organized into mature sarcomeres that had formed A and I bands. In addition, icariin treatment upregulated the mRNA levels of MLC1v, ANP, cTnI, calsequestrin (CSQ), and sodium-calcium exchanger (NCX) in these cells. Icariin induces the differentiation of mES cells into beating cardiomyocytes with normal structure and function. Therefore, these cells may have promising applications in cardiac cell therapy or tissue engineering.