Design, synthesis, and antitumor activity evaluation of BF3-o, m, p-phenylenediamine bridged with pyrimidine-indole BF3 adduction derivatives.

Fluorescent drugs and pyrimidine-indole scaffolds have been shown to have advantages in cancer treatment. Fluorescent antitumor drugs BF3-o, m, p-phenylenediamine pyrimidine-indole derivatives (PYB1, PYB2, and PYB3) were synthesized by linking pyrimidine and indole groups with aniline through a simple step and introducing BF3. The drugs exhibit promising antitumor activity and their fluorescent properties make them useful for imaging purposes. The optical properties of the three compounds have been investigated. All of them have fluorescent properties and compound PYB2 has good fluorescent properties. Additionally, the in vitro cytotoxicity of these compounds was evaluated against the human cancer cell line HeLa and the human normal cell line L02. The inhibition rates of HeLa cells treated with PYB1, PYB2, and PYB3 at a concentration of 19.2 µg/mL were 80.91%, 77.72%, and 65.94%, respectively. These results indicate a strong inhibitory effect on cancer cells. Further through the cell imaging experiment, we can see that PYB2 can enter the cell through the cell membrane through the fluorescence scattering diagram, which has good biocompatibility. In addition, the possible interactions between the compounds and Ras protein active sites were analyzed by molecular docking. The three compounds can bind well to Ras protein through hydrogen bonding. This study provides a basis for the development and modification of pyrimidine-indole fluorescent anticancer drugs. Compound PYB2 shows potential as a fluorescent anticancer drug.

Research progress on Helicobacter pylori infection related neurological diseases.

Helicobacter pylori, a type of gram-negative bacterium, infects roughly half of the global population. It is strongly associated with gastrointestinal disorders like gastric cancer, peptic ulcers, and chronic gastritis. Moreover, numerous studies have linked this bacterium to various extra-gastric conditions, including hematologic, cardiovascular, and neurological issues. Specifically, research has shown that Helicobacter pylori interacts with the brain through the microbiota-gut-brain axis, thereby increasing the risk of neurological disorders. The inflammatory mediators released by Helicobacter pylori-induced chronic gastritis may disrupt the function of the blood-brain barrier by interfering with the transmission or direct action of neurotransmitters. This article examines the correlation between Helicobacter pylori and a range of conditions, such as hyperhomocysteinemia, schizophrenia, Alzheimer's disease, Parkinson's disease, ischemic stroke, multiple sclerosis, migraine, and Guillain-Barré syndrome.

Polymeric nanomaterials encapsulating fluorescent polyindole-nido- carborane: design, synthesis and biological evaluation.

The water-soluble nido-carborane was prepared by alkali treatment of o-carborane. A polymer PInd containing a polyindole structure was synthesized and employed to label the modified o-carborane. Subsequently, four polymeric nanomaterials were synthesized with the objective of encapsulating them in order to enhance its bioavailability. The experimental results showed that the fluorescent complex encapsulated by the pH-sensitive polymer A had the best UV absorption and fluorescence intensity, and thus A-PInd-C was chosen for subsequent experiments. The Transmission electron microscopy images revealed that the compounds exhibited a rounded internal morphology, with the layers exhibiting a tightly stacked arrangement. The AFM imaging revealed that the surface of the sample exhibited a relatively uniform and smooth appearance. In vitro release experiments conducted under acidic conditions demonstrated that A-PInd-C was released in a predominantly linear manner, with a maximum release rate of 80% observed within 48 h. Cellular imaging experiments showed that the compound could enter HeLa and HCT-116 cells and was mainly distributed around the nucleus, especially in the acidic environment. The results of the cell proliferation toxicity experiments demonstrated that A-PInd-C exhibited inhibitory effects on HeLa, PC-3 and L02 cells. Among these, the inhibitory effect on PC-3 cells was the most pronounced, reaching up to 70%. In conclusion, this paper solves the problem of poor bioavailability of carborane by improving the boron containing compounds and also makes the system have potential for Boron neutron capture therapy.

Communication molecules (ncRNAs) mediate tumor-associated macrophage polarization and tumor progression.

Non-coding RNAs play important roles in tumor cells and macrophages and participate in their communication as messengers. Non-coding RNAs have an impact in tumor cell proliferation, migration, and apoptosis, and they also regulate the differentiation and regulation of immune cells. In macrophages, they stimulate the polarization of macrophages into M1 or M2 by regulating proteins related to signaling pathways; in tumor cells, non-coding RNAs can enter macrophages through exosomes and affect the latter polarization. The polarization of macrophages further regulates the biological functions of cancer cells. The direction of macrophage polarization determines tumor progression, angiogenesis and drug resistance. This often creates a feedback loop. Non-coding RNAs act as bridges between tumor cells and macrophages to regulate the balance of the tumor microenvironment. We reviewed the signaling pathways related to macrophage polarization and the regulatory mechanisms of non-coding RNA in tumor-associated macrophages M1 and M2, and discussed the potential applications and prospects of exosome engineering.

Prognostic value of tumor deposits and positive lymph node ratio in stage III colorectal cancer: a retrospective cohort study.

BACKGROUND: In colorectal cancer (CRC), tumor deposits (TD) have been used to guide the N staging only in node-negative patients. It remains unknown about the prognostic value of TD in combination with positive lymph node ratio (LNR) in stage III CRC. PATIENTS AND METHODS: The authors analyzed data from 31 139 eligible patients diagnosed with stage III CRC, including 30 230 from the Surveillance, Epidemiology, and End Results (SEER) database as a training set and 909 from two Chinese hospitals as a validation set. The associations of TD and LNR with cancer-specific survival (CSS) and overall survival (OS) were evaluated using the Kaplan-Meier method and Cox regression models. RESULTS: Both TD-positive and high LNR (value ≥0.4) were associated with worse CSS in the training [multivariable hazard ratio (HR), 1.50; 95% CI: 1.43-1.58 and HR, 1.74; 95% CI: 1.62-1.86, respectively] and validation sets (HR, 1.90; 95% CI: 1.41-2.54 and HR, 2.01; 95% CI: 1.29-3.15, respectively). Compared to patients with TD-negative and low LNR (value<0.4), those with TD-positive and high LNR had a 4.09-fold risk of CRC-specific death in the training set (HR, 4.09; 95% CI: 3.54-4.72) and 4.60-fold risk in the validation set (HR, 4.60; 95% CI: 2.88-7.35). Patients with TD-positive/H-LNR CRC on the right side had the worst prognosis ( P <0.001). The combined variable of TD and LNR contributed the most to CSS prediction in the training (24.26%) and validation (32.31%) sets. A nomogram including TD and LNR showed satisfactory discriminative ability, and calibration curves indicated favorable consistency in both the training and validation sets. CONCLUSIONS: TD and LNR represent independent prognostic predictors for stage III CRC. A combination of TD and LNR could be used to identify those at high-risk of CRC deaths.

Risk factors for recurrence of common bile duct stones after surgical treatment and effect of ursodeoxycholic acid intervention.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an accurate diagnostic method for choledocholithiasis and treatment option for stone removal. Additionally, ursodeoxycholic acid (UDCA) can dissolve cholesterol stones and prevent their development and reappearance by lowering the cholesterol concentration in bile. Despite these treatment options, there are still patients who experience stone recurrence. AIM: To analyze the risk factors for choledocholithiasis recurrence after ERCP retrograde cholangiopancreatography and the effect of UDCA intervention. METHODS: The clinical data of 100 patients with choledochal stones who were hospitalized at the Yixing People's Hospital and underwent ERCP for successful stone extraction between June 2020 and December 2022 were retrospectively collected. According to the post-ERCP treatment plan, 100 patients were classified into UDCA (n = 47) and control (n = 53) groups. We aimed to assess the clinical efficacy and rate of relapse in the two patient populations. We then collected information (basic demographic data, clinical characteristics, and serum biochemical indicators) and determined the factors contributing to relapse using logistic regression analysis. Our secondary goal was to determine the effects of UDCA on liver function after ERCP. RESULTS: Compared to the control group, the UDCA group demonstrated a higher clinical effectiveness rate of 92.45% vs 78.72% (P < 0.05). No significant differences were observed in liver function indices, including total bilirubin, direct bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase, between the two groups before treatment. After treatment, all liver function indices were significantly reduced. Comparing the control vs UDCA groups, the UDCA group exhibited significantly lower levels of all indices (55.39 ± 6.53 vs 77.31 ± 8.52, 32.10 ± 4.62 vs 45.39 ± 5.69, 142.32 ± 14.21 vs 189.63 ± 16.87, 112.52 ± 14.25 vs 149.36 ± 15.36, 122.61 ± 16.00 vs 171.33 ± 22.09, 96.98 ± 10.44 vs 121.35 ± 11.57, respectively, all P < 0.05). The stone recurrence rate was lower in the UDCA group (13.21%) in contrast with the control group (44.68%). Periampullary diverticula (OR: 6.00, 95%CI: 1.69-21.30), maximum stone diameter (OR: 1.69, 95%CI: 1.01-2.85), stone quantity >3 (OR: 4.23, 95%CI: 1.17-15.26), and positive bile culture (OR: 7.61, 95%CI: 2.07-27.91) were independent factors that influenced the relapse of common bile duct stones after ERCP (P < 0.05). Furthermore, postoperative UDCA was identified as a preventive factor (OR: 0.07; 95%CI: 0.08-0.09). CONCLUSION: The intervention effect of UDCA after ERCP for common bile duct stones is adequate, providing new research directions and references for the prevention and treatment of stone recurrence.

Helicobacter pylori upregulates circPGD and promotes development of gastric cancer.

PURPOSE: Helicobacter pylori (H. pylori) has unique biochemical traits and pathogenic mechanisms, which make it a substantial cause of gastrointestinal cancers. Circular RNAs (circRNAs) have concurrently been identified as an important participating factor in the pathophysiology of several different cancers. However, the underlying processes and putative interactions between H. pylori and circRNAs have received very little attention. To address this issue, we explored the interaction between H. pylori and circRNAs to investigate how they might jointly contribute to the occurrence and development of gastric cancer. METHODS: Changes in circPGD expression in H. pylori were detected using qRT-PCR. Cell proliferation and migration changes were assayed by colony formation, the CCK-8 assay and the transwell assay. Apoptosis was measured by flow cytometry. Western blot was conducted to detect changes in cell migration, apoptosis, proliferation and inflammation-associated proteins. QRT-PCR was used to measure changes in circPGD and inflammation-associated factors. RESULTS: We found that H. pylori induced increased circPGD expression in infected human cells and facilitated gastric cancer progression in three ways by promoting cell proliferation and migration, enhancing the inflammatory response, and inhibiting apoptosis. CONCLUSIONS: CircPGD appears to play a role in H. pylori-related gastric cancer and may thus be a viable, novel target for therapeutic intervention.

Multi-center verification of the influence of data ratio of training sets on test results of an AI system for detecting early gastric cancer based on the YOLO-v4 algorithm.

Objective: Convolutional Neural Network(CNN) is increasingly being applied in the diagnosis of gastric cancer. However, the impact of proportion of internal data in the training set on test results has not been sufficiently studied. Here, we constructed an artificial intelligence (AI) system called EGC-YOLOV4 using the YOLO-v4 algorithm to explore the optimal ratio of training set with the power to diagnose early gastric cancer. Design: A total of 22,0918 gastroscopic images from Yixing People's Hospital were collected. 7 training set models were established to identify 4 test sets. Respective sensitivity, specificity, Youden index, accuracy, and corresponding thresholds were tested, and ROC curves were plotted. Results: 1. The EGC-YOLOV4 system completes all tests at an average reading speed of about 15 ms/sheet; 2. The AUC values in training set 1 model were 0.8325, 0.8307, 0.8706, and 0.8279, in training set 2 model were 0.8674, 0.8635, 0.9056, and 0.9249, in training set 3 model were 0.8544, 0.8881, 0.9072, and 0.9237, in training set 4 model were 0.8271, 0.9020, 0.9102, and 0.9316, in training set 5 model were 0.8249, 0.8484, 0.8796, and 0.8931, in training set 6 model were 0.8235, 0.8539, 0.9002, and 0.9051, in training set 7 model were 0.7581, 0.8082, 0.8803, and 0.8763. Conclusion: EGC-YOLOV4 can quickly and accurately identify the early gastric cancer lesions in gastroscopic images, and has good generalization.The proportion of positive and negative samples in the training set will affect the overall diagnostic performance of AI.In this study, the optimal ratio of positive samples to negative samples in the training set is 1:1~ 1:2.

Comparative Study on the Clinical Effects of Different Surgical Methods in the Treatment of Gastrointestinal Stromal Tumors.

Objective: The objective is to compare the clinical efficacy of laparoscopic resection (LAP), endoscopic full-thickness resection (EFR), and endoscopic submucosal dissection (ESD) in the treatment of gastrointestinal stromal tumors. Methods: The clinical data of 105 patients who were treated in our hospital and diagnosed with GIST by pathology after surgery from March 2019 to March 2021 were collected. Patients were divided into the LAP group, EFR group, and ESD group according to different surgical methods. The clinical data, surgical conditions, complications, and postoperative conditions of the patients were recorded retrospectively. Patients were followed up closely after surgery. Results: The operation time of the EFR group and ESD group was shorter than that of the LAP group, and the operation time of the EFR group was shorter than that of the ESD group (P < 0.05). The amount of intraoperative blood loss in the EFR group and ESD group was lower than that in the LAP group (P < 0.05). There was no significant difference in the complete resection rate among the three groups (P > 0.05). There was no significant difference in the total incidence of complications among the three groups (P > 0.05). The postoperative abdominal pain time, postoperative hospital stay, and total hospitalization costs of the EFR group and ESD group were lower than those of the LAP group (P < 0.05). No recurrence or metastasis cases were found in the three groups during the follow-up period, and there were no GIST-related deaths in the three groups. Conclusion: LAP, EFR, and ESD have good curative effect, good safety, and good prognosis in the treatment of GIST. But compared with LAP, EFR and ESD have the advantages of less trauma, faster recovery, shorter hospitalization time, and lower hospitalization cost.

Construction and Multicenter Diagnostic Verification of Intelligent Recognition System for Endoscopic Images From Early Gastric Cancer Based on YOLO-V3 Algorithm.

INTRODUCTION: Endoscopy is an important tool for the diagnosis of early gastric cancer. Therefore, a combination of artificial intelligence and endoscopy has the ability to increase the speed and efficiency of early gastric cancer diagnosis. YOU ONLY LOOK ONCE (YOLO) is an advanced object detection depth neural network algorithm that has not been widely used in gastrointestinal image recognition. OBJECTIVE: We developed an artificial intelligence system herein referred to as "EGC-YOLO" for the rapid and accurate diagnosis of endoscopic images from early gastric cancer. METHODS: More than 40000 gastroscopic images from 1653 patients in Yixing people's Hospital were used as the training set for the system, while endoscopic images from the other two hospitals were used as external validation test sets. The sensitivity, specificity, positive predictive value, Youden index and ROC curve were analyzed to evaluate detection efficiencies for EGC-YOLO. RESULTS: EGC-YOLO was able to diagnose early gastric cancer in the two test sets with a high superiority and efficiency. The accuracy, sensitivity, specificity and positive predictive value for Test Sets 1 and 2 were 85.15% and 86.02%, 85.36% and 83.02%, 84.41% and 92.21%, and 95.22% and 95.65%, respectively. In Test Sets 1 and 2, the corresponding Threshold-values were 0.02, 0.16 and 0.17 at the maximum of the Youden index. An increase in Threshold-values was associated with a downward trend in sensitivity and accuracy, while specificity remained relatively stable at more than 80%. CONCLUSIONS: The EGC-YOLO system is superior for the efficient, accurate and rapid detection of early gastric cancer lesions. For different data sets, it is important to select the appropriate threshold-value in advance to achieve the best performance of the EGC-YOLO system.

Linc00441 interacts with DNMT1 to regulate RB1 gene methylation and expression in gastric cancer.

Recent studies revealed that several Long noncoding RNAs (LncRNAs) are associated with progression of gastric cancer (GC), while the functional role and molecular mechanism of many GC-associated lncRNAs remain undetermined. The tumor suppressor-gene retinoblastoma gene (RB1) was decreased in several human cancers including gastric cancer (GC). In this study, we investigated whether Linc00441 was involved in the suppression of RB1. Our findings showed that the up-regulated Linc00441 was inversely correlated with RB1 expression in human GC tumor samples. The gain- and loss-of-function investigation revealed that Linc00441 could promote the proliferation of GC cells. Furthermore, RNA pull down and RIP assays demonstrated that Linc00441 could recruit DNMT1 to the RB1 promoter and suppressed RB1 expression in GC cells. In conclusion, our findings revealed that Linc00441 played crucial role in GC progression and suggested that Linc00441 was potentially an effective target for GC therapy in the future.

A118G Polymorphism in µ-Opioid Receptor Gene and Interactions with Smoking and Drinking on Risk of Oesophageal Squamous Cell Carcinoma.

AIM: To investigate the single nucleotide polymorphism (SNP) of A118G and its interaction with smoking and drinking on oesophageal squamous cell carcinoma (ESCC) risk. METHODS: A total of 960 subjects (545 males and 415 females) with a mean age of 58.1 ± 13.4 years were selected, including 490 ESCC patients and 470 normal control subjects. A logistic regression model was used to examine the association between A118G and ESCC and its interaction with A118G and current smoking and drinking. The odds ratio (OR) and 95% confident interval (95%CI) were calculated. RESULTS: The frequency for the A allele of A118G was significantly higher in ESCC cases, OR (95%CI) = 1.22 (1.08-1.59). Logistic regression analysis showed a significant association between the A allele in A118G and increased ESCC risk. The ESCC risk was significantly higher in carriers of the A allele of the A118G polymorphism than those with GG (AG + AA vs. GG, adjusted OR (95%CI) = 1.20 (1.05-1.53)). We found that current smokers with AG or AA of the A118G genotype have the highest ESCC risk compared with never smokers with a GG genotype; the OR (95%CI) was 2.57 (1.66-3.33). Current drinkers with AG or AA of the A118G genotype have the highest ESCC risk compared with not currently drinking subjects with the GG genotype, OR (95%CI) = 2.36 (1.47-3.25), after adjusting for covariates. CONCLUSION: The A allele of A118G and ESCC and additional interaction between the A allele of A118G and smoking or drinking were associated with increased ESCC risk.

Prediction rule for estimating advanced colorectal neoplasm risk in average-risk populations in southern Jiangsu Province.

OBJECTIVE: The aim of this study was to establish the risk scoring system towards the advanced colorectal neoplasm (CN) risk in the average-risk populations in the southern Jiangsu Province, and to evaluate the screening efficacy. METHODS: Totally 905 cases of the average-risk populations who received the colonoscopy were selected as the objective. The multivariate logistic regression analysis method was used to establish the scoring system towards the occurrence risk of the advanced tumor, and its screening efficacy was evaluated through the prediction consistency, distinguishing ability and screening accuracy. RESULTS: The scoring system consisted of five variables, namely age, gender, coronary heart disease, egg intake and stool frequency. The results revealed that it had good prediction consistency (P=0.205) and distinguishing ability [the area under the receiver operating characteristic (ROC) curve was 0.75, with 95% confidence interval (95% CI) of 0.69-0.82]. Thus, 2.5 points was set as the screening cutoff value, and its sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 93.8%, 47.6%, 50.1%, 9.1%, 99.3%, 1.79 and 0.13, respectively. CONCLUSIONS: The established scoring system had good screening efficacy, and can be used as the screening tool applying to the CN screening within the average-risk populations in the southern Jiangsu Province.