Effect of Chinese quince proanthocyanidins on the inhibition of heterocyclic amines and quality of fried chicken meatballs and tofu.

Heterocyclic amines (HCAs) have potential carcinogenic and mutagenic activity and are generated in cooked protein-rich foods. Adding proanthocyanidins (PAs) to these foods before frying is an effective way to reduce HCAs. In this study, polymeric PAs (PPA) and ultrasound-assisted acid-catalyzed/catechin nucleophilic depolymerized PAs (UAPA, a type of oligomeric PA) were prepared from Chinese quince fruits (CQF). Different levels of PPA and UAPA (0.05%, 0.1%, and 0.15%) were added to chicken meatballs and tofu; then these foods were fried, and the content of HCAs in them after frying was investigated. The results showed that PPA and, particularly, UAPA significantly inhibited the formation of HCAs in fried meatballs and tofu, and this inhibition was dose-dependent. The inhibition of HCAs by both PPA and UAPA was stronger in the chicken meatballs than in fried tofu. The level of total HCAs was significantly reduced by 57.84% (from 11.93 to 5.03 ng/g) after treatment of meatballs with 0.15% UAPA, with inhibition rates of 78.94%, 50.37%, and 17.81% for norharman, harman, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), respectively. Of note, there was a negative correlation between water, lipid, protein, creatine, and glucose content and HCA content in the crust, interior, and whole (crust-plus-interior) measurements of all fried samples. Interestingly, PPA and UAPA were found more effective in inhibiting HCAs in the exterior crust than in the interior of the fried chicken meatballs. These results provide evidence that further studies on the reduction of the formation of harmful HCAs in fried foods by adding CQF PAs could be valuable to the fried food industry. PRACTICAL APPLICATION: Chinese quince proanthocyanidins treatments significantly inhibited the generation of heterocyclic amines (HCAs) in chicken meatballs and tofu when deep-fried. These results suggest that Chinese quince proanthocyanidins can be used as natural food additive for reducing HCAs in fried foods, laying the foundation for using Chinese quince fruit proanthocyanidins for HCA inhibition in the food industry.

Regulatory effect of Yinchenhao decoction on bile acid metabolism to improve the inflammatory microenvironment of hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC) is a malignant tumor with extremely high mortality. The tumor microenvironment is the "soil" of its occurrence and development, and the inflammatory microenvironment is an important part of the "soil". Bile acid is closely related to the occurrence of HCC. Bile acid metabolism disorder is not only directly involved in the occurrence and development of HCC but also affects the inflammatory microenvironment of HCC. Yinchenhao decoction, a traditional Chinese medicine formula, can regulate bile acid metabolism and may affect the inflammatory microenvironment of HCC. To determine the effect of Yinchenhao decoction on bile acid metabolism in mice with HCC and to explore the possible mechanism by which Yinchenhao decoction improves the inflammatory microenvironment of HCC by regulating bile acid metabolism, we established mice model of orthotopic transplantation of hepatocellular carcinoma. These mice were treated with three doses of Yinchenhao decoction, then liver samples were collected and tested. Yinchenhao decoction can regulate the disorder of bile acid metabolism in liver cancer mice. Besides, it can improve inflammatory reactions, reduce hepatocyte degeneration and necrosis, and even reduce liver weight and the liver index. Taurochenodeoxycholic acid, hyodeoxycholic acid, and taurohyodeoxycholic acid are important molecules in the regulation of the liver inflammatory microenvironment, laying a foundation for the regulation of the liver tumor inflammatory microenvironment based on bile acids. Yinchenhao decoction may improve the inflammatory microenvironment of mice with HCC by ameliorating hepatic bile acid metabolism.

Molecular engineering to design a bright near-infrared red photosensitizer: cellular bioimaging and phototherapy.

Near-infrared red (NIR) fluorescence imaging guide phototherapeutic therapy (PDT) has the advantages of deep tissue penetration, real-time monitoring of drug treatment and disease, little damage to normal tissue, low cytotoxicity and almost no side effects, and thus, it is attracting increasing research attention and is expected to show promising potential for clinical tumor treatment. The photosensitizer (PS), light source and oxygen are the three basic and important factors to construct PDT technology, and highly efficient PSs are still being passionately pursued because they determine the PDT efficiency. Ideal PSs should have properties such as good biocompatibility, deep tissue penetration, and highly efficient reactive oxygen species (ROS) generation despite the hypoxic environment. Therefore, pure organic type I PSs with NIR fluorescence have been receiving increasing attention due to their deep penetration and hypoxia resistance. However, reported NIR-active type I PSs usually require complex synthetic procedures, which presents a challenge for mass production. In this research work, based on the molecular design ideas of introducing the heavy atom effect and intramolecular charge transfer, we prepared three NIR-active type I PSs (TNZ, TNZBr, and TNZCHO) using a very simple method with one or two synthetic steps. Clear characterizations of photophysical properties, ROS performance tests, and fluorescent imaging of human umbilical vein endothelial (HUVE) cells and PDT treatment of HepG2 cells were carried out. The results revealed that the heavy atom and intramolecular charge transfer (ICT) effects could obviously enhance the ROS efficiency, and both PSs produce only type I ROS without any type II ROS (1O2) generation. The good NIR fluorescence brightness and type I ROS efficiency ensure satisfactory bioimaging and PDT outcomes. This research provides the possibility of preparing NIR-active type I PSs via mass production.

The in vitro intestinal cell model: different co-cultured cells create different applications.

As a vitro absorption model, the Caco-2 cells originate from a human colon adenocarcinomas and can differentiate into a cell layer with enterocyte-like features. The Caco-2 cell model is popularly applied to explore drug transport mechanisms, to evaluate the permeability of drug and to predict the absorption of drugs or bioactive substances in the gut. However, there are limitations to the application of Caco-2 cell model due to lack of a mucus layer, the long culture period and the inability to accurately simulate the intestinal environment. The most frequent way to expand the Caco-2 cell model and address its limitations is by co-culturing it with other cells or substances. This article reviews the culture methods and applications of 3D and 2D co-culture cell models established around Caco-2 cells. It also concludes with a summary of model strengths and weaknesses.

Hub Genes, Possible Pathways and Predicted Drugs in Hereditary Gingival Fibromatosis by Bioinformatics Analysis.

OBJECTIVE: To explore potential pathogenic processes and possible treatments using unbiased and reliable bioinformatic tools. METHODS: Gene expression profiles of control and hepatocyte growth factor (HGF) samples were downloaded from CNP0000995. Analysis of differentially expressed genes (DEGs) was conducted using R software (version 4.2.1, R Foundation, Vienna, Austria). Functional enrichment analyses were performed using the Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) databases, then the proteinprotein interaction (PPI) network was constructed to screen the top 10 hub genes. Finally, five genes related to cell junctions were selected to build gene-miRNA interactions and predict small-molecule drugs. RESULTS: A total of 342 downregulated genes and 188 upregulated genes were detected. Candidate pathways include the extracellular matrix (ECM) receptor interaction pathway, the TGF-ß signalling pathway and the cell adhesion molecule (CAM) pathway, which were discovered through KEGG and GSEA enrichment studies. GO analyses revealed that these DEGs were significantly enriched in cell adhesion, the adherens junction and focal adhesion. Five hub genes (CDH1, SNAP25, RAC2, APOE and ITGB4) associated with cell adhesion were identified through PPI analysis. Finally, the gene-miRNA regulatory network identified three target miRNAs: hsa-miR-7110-5p, hsa-miR-149-3p and hsa-miR-1207-5p. Based on the gene expression profile, the small-molecule drugs zebularine, ecuronium and prostratin were selected for their demonstrated binding activity when docked with the mentioned molecules. CONCLUSION: This study offered some novel insights into molecular pathways and identified five hub genes associated with cell adhesion. Based on these hub genes, three potential therapeutic miRNAs and small-molecule drugs were predicted, which are expected to provide guidance for the treatment of patients with HGF.

Single-Component Photochemical Afterglow Near-Infrared Luminescent Nano-Photosensitizers: Bioimaging and Photodynamic Therapy.

Long afterglow luminescence-guided photodynamic therapy (PDT) performs advantages of noninvasiveness, spatiotemporal controllability, and higher signal to noise ratio. Photochemical afterglow (PCA) system emitting afterglow in an aqueous environment is highly suitable for biomedical applications, but still faces the challenges of poor tissue penetration depth and responsive sensitivity. In this work, two novel compounds, Iso-TPA and ABEI-TPA, are designed and synthesized to integrate the PCA system as a single component by coupling near-infrared (NIR) photosensitizers with singlet oxygen cache units, respectively. Both compounds emit NIR afterglow based on photochemical reaction. ABEI-TPA exhibits higher photoluminescence quantum efficiency with nonconjugated linkage, while Iso-TPA with conjugated linkage possesses better reactive oxygen species generation efficiency to achieve stronger PCA and effective PDT, which is ascribed to stronger intramolecular charge transfer effect of Iso-TPA. Iso-TPA nanoparticles can achieve effective long-lasting NIR afterglow in vivo bioimaging up to 120 s with higher imaging resolution and outstanding PDT efficacy of tumor, exhibiting promising potential on bioimaging and therapy.

Modified Chinese quince oligomeric proanthocyanidin protects deep-frying oil quality by inhibiting oxidation.

Chinese quince (Chaenomeles sinensis) fruit is an underutilized resource, rich in proanthocyanidins with antioxidant ability but poor lipid solubility. In this study, a novel modified oligomeric proanthocyanidin (MOPA) was prepared, which exhibited favorable lipid solubility (354.52 mg/100 g). It showed higher radical scavenging abilities than commercial antioxidant-BHA (butylated hydroxyanisole), both at 0.4-0.5 mg/mL. The addition of MOPA (0.04 %wt.) significantly increased the oxidative stability index of the soybean oil from 5.52 to 8.03 h, which was slightly lower than that of BHA (8.35 h). Analysis of the physicochemical properties and composition of oil during deep-frying showed that MOPA demonstrated significant antioxidant effects and effectively restricted the oil oxidation. This inhibition also delays the formation of heterocyclic amines (HAs) in fried food, thereby reducing the migration of HAs from food to deep-frying oil. Therefore, MOPA is a promising novel liposoluble antioxidant for protecting the quality of deep-frying oil.

A convenient and reproducible protocol for acquisition of the hepatocyte phase for liver function-impaired patients in gadoxetic acid disodium-enhanced magnetic resonance imaging.

Background: The hepatocyte phase (HCP) in gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) plays an important role in the detection and characterization of liver lesions, treatment planning, and liver function evaluation. However, the imaging protocol is complicated and time-consuming. This cross-sectional study aimed to develop a convenient and reproducible protocol for the HCP acquisition in Gd-EOB-DTPA-enhanced MRI. Methods: A total of 107 patients were prospectively included and assigned to three groups based on Child-Pugh (CP) classification, with 37, 40, and 30 in the non-cirrhosis, CP A, and CP B groups, respectively. Dynamic HCPs were acquired every 5 min after the Gd-EOB-DTPA administration and ended in 25 min in non-cirrhosis patients and 40 min in cirrhotic patients. The HCP acquired 5 min after the initial visualization of the intrahepatic bile duct (IBD) was selected from the dynamic HCPs as the adequate HCP (HCPproposed) and the corresponding acquisition time was recorded as Timeproposed. In addition, according to the 2016 Expert Consensus (EC) on the definition of the adequate HCP from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the adequate HCPEC and the corresponding TimeEC were also determined from the dynamic HCPs. The hepatic relative enhancement ratio (RER), the contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of hepatic focal lesions in the HCPEC and HCPproposed images, as well as the TimeEC and Timeproposed were compared by the paired t-test for the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed was compared by the χ2 test. Results: The RER, CNR, and SNR showed no significant difference between the HCPEC and HCPproposed in all three groups (all P>0.05). The paired differences between TimeEC and Timeproposed were 1.08±3.56 min (P=0.07), 2.88±4.22 min (P<0.001), and 5.83±5.27 min (P<0.001) in the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed were 0.804 (86/107) and 0.962 (103/107), respectively (χ²=13.09, P=0.001). Conclusions: The adequate HCP could be acquired 5 min after the initial visualization of the IBD, which could serve as a convenient and reproducible protocol for the HCP imaging.

Cardiovascular toxicities following the use of tyrosine kinase inhibitors in hepatocellular cancer patients: a retrospective, pharmacovigilance study.

BACKGROUND: Cardiac adverse events (AEs) are common in tyrosine kinase inhibitors(TKIs). This study explored the cardiac AEs of TKIs through the Food and Drug Administration's Adverse Event Reporting System (FAERS). METHODS: Disproportionality analysis and Bayesian analysis were utilized for data mining of the suspected cardiac AEs of TKIs, based on FAERS data from January 2004 to December 2021. RESULTS: A total of 4708 cardiac AEs reports of sorafenib, regorafenib, lenvatinib, and cabozantinib were identified. Hypertension accounts for the most reported cardiac AE. Lenvatinib appears to induce cardiac failure with the highest signals strength [ROR = 7.7 (3.46,17.17)]. Acute myocardial infarction was detected in lenvatinib [ROR = 7.91 (5.64,11.09)] and sorafenib [ROR = 2.22 (1.74, 2.84)]. Acute coronary syndrome was detected in lenvatinib [ROR = 11.57 (6.84, 19.58)] and sorafenib [ROR = 2.81 (1.87,4.24)]. Atrial fibrillation was detected in sorafenib [ROR = 1.82 (1.55,2.14)] and regorafenib [ROR = 1.36 (1.03,1.81)]. Meanwhile, aortic dissections were detected in sorafenib [ROR = 5.08 (3.31,7.8)] and regorafenib [ROR = 3.39 (1.52,7.56)]. Most patients developed hypertension and cardiac failure within 30 days of initiating TKI treatments. Patients taking lenvatinib had an increased incidence of developing acute coronary syndrome after 180 days of treatment. CONCLUSION: Analysis of FAERS data provides a precise profile on the characteristics of cardiac AEs associated with different TKI regimens. Distinct monitoring and appropriate management are needed in the care of TKI recipients.

Recent advances in aggregation-induced emission-active type I photosensitizers with near-infrared fluorescence: From materials design to therapeutic platform fabrication.

Near-infrared (NIR) fluorescence imaging-guided photodynamic therapy (PDT) technology plays an important role in treating various diseases and still attracts increasing research interests for developing novel photosensitizers (PSs) with outstanding performances. Conventional PSs such as porphyrin and rhodamine derivatives have easy self-aggregation properties in the physiological environment due to their inherent hydrophobic nature caused by their rigid molecular structure that induces strong intermolecular stacking π-π interaction, leading to serious fluorescence quenching and cytotoxic reactive oxygen species (ROS) reduction. Meanwhile, hypoxia is an inherent barrier in the microenvironment of solid tumors, seriously restricting the therapeutic outcome of conventional PDT. Aforementioned disadvantages should be overcome urgently to enhance the therapeutic effect of PSs. Novel NIR fluorescence-guided type I PSs with aggregation-induced emission (AIE), which features the advantages of improving fluorescent intensity and ROS generation efficiency at aggregation as well as outstanding oxygen tolerance, bring hope for resolving aforementioned problems simultaneously. At present, plenty of research works fully demonstrates the advancement of AIE-active PDT based on type I PSs. In this review, cutting-edge advances focusing on AIE-active NIR type I PSs that include the aspects of the photochemical mechanism of type I ROS generation, various molecular structures of reported type I PSs with NIR fluorescence and their design strategies, and typical anticancer applications are summarized. Finally, a brief conclusion is obtained, and the underlying challenges and prospects of AIE-active type I PSs are proposed.

Effect of Socioeconomic Disparities on Suicide Risk in Patients With Prostate Cancer During 2005 to 2020: A Population Study.

PURPOSE: To determine whether socioeconomic disparities have an impact on the likelihood of suicide among prostate cancer patients. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with malignant prostate cancer between 2005 and 2020. The socioeconomic disparities of the patients were evaluated by median household income (MHI) and ethnicity. Ethnicity included Spanish-Hispanic-Latino and non-Spanish-Hispanic-Latino. A Cox proportional risk model was utilized. Using the Kaplan-Meier approach, the cumulative incidence of suicide mortality was measured. RESULTS: A total of 857,418 US population with prostate cancer were included. In the multivariate analysis, individuals with MHI over $75,000 had a lower risk of suicide mortality than those with MHI between $54,999 and $74,999 in all patients (aHRs: 0.693, 95 CI%: 0.603-0.797). Spanish-Hispanic-Latino displayed lower overall suicide mortality in all patients (aHRs: 0.426, 95% CI: 0.323-0.561). In the subgroup analysis of different ages, individuals with MHI over $75,000 had a lower risk of suicide than those with MHI between $54,999 and $74,999 in patients 60 to 79 years (aHRs: 0.668, 95% CI: 0.562-0.794) and individuals with MHI below $54,999 had higher suicide risk than those with MHI between $54,999 and $74,999 in patients 80+ years (aHRs: 1.786, 95% CI: 1.100-2.902). Hispanic-Latino individuals had lower overall suicide mortality in 00 to 59 years (aHRs: 0.420, 95% CI: 0.240-0.734), 60 to 79 years (aHRs: 0.445, 95% CI: 0.319-0.621), 80+ years (aHRs: 0.363, 95% CI: 0.133-0.988). CONCLUSION: Socioeconomic disparities, including MHI and ethnicity, are important factors strongly related to suicide risk in prostate cancer patients. The lower MHI individuals and non-Spanish-Hispanic-Latino individuals were associated with higher suicide risk.

Estimating the economic burden of colorectal cancer in China, 2019-2030: A population-level prevalence-based analysis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Comprehensive data on the economic burden of CRC at a population-level is critical in informing policymaking, but such data are currently limited in China. METHODS: From a societal perspective, the economic burden of CRC in 2019 was estimated, including direct medical and nonmedical expenditure, disability, and premature-death-related indirect expenditure. Data on disease burden was taken from the GBD 2019 and analyzed using a prevalence-based approach. The per-person direct expenditure and work loss days were from a multicenter study; the premature-death-related expenditure was estimated using a human capital approach. Projections were conducted in different simulated scenarios. All expenditure data were in Chinese Yuan (CNY) and discounted to 2019. RESULTS: In 2019, the estimated overall economic burden of CRC in China was CNY170.5 billion (0.189% of the local GDP). The direct expenditure was CNY106.4 billion (62.4% of the total economic burden), 91.4% of which was a direct medical expenditure. The indirect expenditure was CNY64.1 billion, of which 63.7% was related to premature death. The predicted burden would reach CNY560.0 billion in 2030 given constant trends for disease burden; however, it would be alternatively reduced to

The connection between six common air pollution particles and adult brain tumors: a meta-analysis of 26,217,930 individuals.

Environmental air pollutants (black carbon (BC), nitrogen oxides (NOx), particulate matter with diameter < 2.5 µm (PM2.5), nitrogen dioxide (NO2), particulate matter with diameter <10 µm (PM10), and ozone (O3)) are one of the major menaces to mankind's health globally. This analysis reviews the association between exposure to these air pollutants and the chance of developing brain tumors in adults (total brain tumors, malignant brain tumors, and benign brain tumors). Studies published by April 2022 were searched. Raw effect sizes were converted to standardized effect sizes per 10 µg/m3 increase. Random effect models were applied to calculate combined effect size and 95% confidence intervals (CIs) were computed. A total of 8 articles were included for meta-analysis. The pooled effect size (ES) for per 10 µg/m3 BC intake was 1.67 (95% CI: 1.25, 2.22), P = 0.449. For every 10 µg/m3 rise in NO2 concentration, ES was 1.03 (95% CI: 1.01, 1.05), P = 0.319. Meanwhile, there was a boundary association between NOx and adult brain tumors (ES and 95% CI: 1.01; 1.00, 1.01/10 µg/m3; P = 0.716). While there was no conjunction between PM2.5, PM10, O3 (PM2.5: ES and 95% CI: 1.04; 0.99, 1.08/10 µg/m3; P = 0.834; PM10: ES and 95% CI: 1.01; 0.97, 1.04/10 µg/m3; P = 0.627; O3: ES and 95% CI: 0.97; 0.94, 1.00/10 µg/m3; P = 0.253). This research shows testimony of a significant link between air pollutants and brain tumors in adults, especially when exposed to BC, NO2, and NOx. This evidence emphasizes the importance of improving air quality as part of a comprehensive approach to prevent the occurrence and deterioration of brain tumors.

Socioeconomic status on survival outcomes in patients with colorectal cancer: a cross-sectional study.

BACKGROUND: Colorectal cancer (CRC) is widely acknowledged as a prevalent malignancy and the second most common cause of cancer-related mortality worldwide. The aim of this study was to examine the independent impact of Median Household Income (MHI) on prognosis and survival outcomes in patients with CRC. METHODS: Data from 17 cancer registries of the United States Surveillance, Epidemiology, and End Results program, with follow-up extended until November 2022 was analyzed. A Cox proportional hazards regression analysis was conducted to evaluate the influence of different levels of MHI on survival outcomes among patients with CRC. A total of 761,697 CRC patient records were retrieved from the SEER database. RESULTS: The Cox regression analysis results indicated that patients with higher MHI exhibited improved overall survival outcomes when compared to those with lower MHI (MMHI: P < 0.001; HMHI: P < 0.001). Regardless of the specific tumor location, gender, stage of CRC, or treatment method, higher MHI is consistently linked to improved survival outcomes. However, this association was not found to be statistically significant among American Indian/Alaska Native (MMHI: P = 0.017; HMHI: P = 0.081), Asian or Pacific Islander (MMHI: P = 0.223; HMHI: P = 0.002) and unmarried or domestic partner patients (MMHI: P = 0.311; HMHI: P = 0.011). CONCLUSION: These results emphasize the importance of considering socioeconomic factors, such as income level, in understanding and addressing disparities in survival outcomes of CRC patients.

High myopia control is comparable between multifocal rigid gas-permeable lenses and spectacles.

Purpose: Ocular pathology may be reduced by slowing myopia progression. The purpose of this study was to evaluate the potential of a novel custom-designed rigid gas permeable (RGP) contact lens to control high myopia by comparing the efficacy of multifocal RGP lenses and single-vision spectacles for high myopia control. Methods: The medical records of children fitted with spectacles or multifocal rigid gas-permeable lenses between January 2018 and May 2020 were retrospectively reviewed. Children (5-17 years) with non-cycloplegic spherical equivalent refraction of ≤ -6.00 D or spherical equivalent refraction > - 6.00 D with baseline axial length ≥ 26.5 mm, and astigmatism of ≥ -2.00 D were included. Axial length and refraction were measured at baseline, before fitting the participants with multifocal rigid gas-permeable lenses or spectacles, and at 1- and 2-year follow-up visits. Changes in axial length were compared between the groups. Results: Among the 77 children with 1-year follow-up data, the mean axial elongation was 0.20 ± 0.17 mm and 0.21 ± 0.14 mm in the multifocal rigid gas-permeable and control groups, respectively, without significant differences between groups (F = 0.004, p = 0.835). Among the 41 patients who completed 2 years of follow-up, the mean axial elongation values in the multifocal rigid gas-permeable and control groups were 0.21 ± 0.15 mm and 0.24 ± 0.13 mm, respectively, at the 1-year follow-up, and 0.37 ± 0.27 mm and 0.43 ± 0.23 mm, respectively, at the 2-year follow-up, without significant between-group differences at either time point (p = 0.224). Conclusion: Axial length increased at a similar rate in both the control (spectacles) and multifocal rigid gas-permeable lens groups, suggesting that multifocal rigid gas-permeable lenses have no significant impact on controlling high myopia progression compared with spectacles.

Procyanidin C1 inhibits tumor growth and metastasis in colon cancer via modulating miR-501-3p/HIGD1A axis.

INTRODUCTION: Although colon (COAD) and rectal adenocarcinoma (READ) combined to refer to colorectal cancer (CRC), substantial clinical evidence urged that CRC should be treated as two different cancers due to compared with READ, COAD showed higher morbidity and worse 5-year survival. OBJECTIVES: This study has tried to screen for the crucial gene that caused the worse prognosis and investigate its mechanism for mediating tumor growth and metastases in COAD. Meanwhile, the potential anti-COAD compound implicated in this mechanism was identified and testified from 1,855 food-borne chemical kits. This study aims to bring a new perspective to the development of new anti-COAD drugs and personalized medicine for patients with COAD. METHODS AND RESULTS: The survival-related hub genes in COAD and READ were screened out from The Cancer Genome Atlas (TCGA) database and the results showed that HIGD1A, lower expressed in COAD than in READ, was associated with poor prognosis in COAD patients, but not in READ. Over-expressed HIGD1A suppressed CRC cell proliferation, invasion, and migration in vitro and in vivo. Meanwhile, the different expressed microRNA profiles between COAD and READ showed that miR-501-3p was highly expressed in COAD and inhibited HIGD1A expression by targeting 3'UTR of HIGD1A. MiR-501-3p mimics promoted cell proliferation and metastasis in CRC cells. In addition, Procyanidin C1 (PCC1), a kind of natural polyphenol has been verified as a potential miR-501-3p inhibitor. In vitro and in vivo, PCC1 promoted HIGD1A expression by suppressing miR-501-3p and resulted in inhibited tumor growth and metastasis. CONCLUSION: The present study verified that miR-501-3p/HIGD1A axis mediated tumor growth and metastasis in COAD. PCC1, a flavonoid that riched in food exerts anti-COAD effects by inhibiting miR-501-3p and results in the latter losing the ability to suppress HIGD1A expression. Subsequently, unfettered HIGD1A inhibited tumor growth and metastasis in COAD.

[Effects of electroacupuncture on NLRP3/Caspase-1/GSDMD axis and neurological function in rats with cerebral ischemic reperfusion].

OBJECTIVE: To investigate the neuroprotective effect of electroacupuncture (EA) at "Quchi" (LI 11) and "Zusanli" (ST 36) in the rats with cerebral ischemic reperfusion and the potential mechanism of microglia pyroptosis. METHODS: Sixty SD rats were randomly divided into a sham-operation group, a model group and an EA group, with 20 rats in each group. The Zea Longa method was employed to establish the rat model of the middle cerebral artery occlusion and reperfusion (MACO/R) in the left brain. In the EA group, since the 2nd day of modeling, EA was given at "Quchi" (LI 11) and "Zusanli" (ST 36) of right side with disperse-dense wave, 4 Hz/20 Hz in frequency and 0.2 mA in current intensity, 30 min each time, once a day for lasting 7 consecutive days. The reduction rate of cerebral blood flow was measured with laser Doppler flowmetry during operation. The neurological function of rats was observed using Zea Longa neurobehavioral score. The cerebral infarction volume was detected by TTC staining method. The microglia positive expression in the ischemic side of the cortex was detected with the immunofluorescence method. Under transmission electron microscope, the ultrastructure of cell in the ischemic cortex was observed. The mRNA expression levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1) and gasdermin D (GSDMD) in the ischemic cortex were detected using real-time PCR. RESULTS: Compared with the sham-operation group, in the model group, the reduction rate of cerebral blood flow was increased during operation (P<0.001); Zea Longa neurobehavional score and the percentage of cerebral infarction volume were increased (P<0.001), the numbers of M1-type microglia marked by CD68+ and M2-type microglia marked by TMEM119+ were elevated in the ischemic cortex (P<0.001), the mRNA expression of NLRP3, ASC, Caspase-1 and GSDMD was increased (P<0.001, P<0.01); the cytomembrane structure was destroyed, with more cell membrane pores formed in the ischemic cortex. Compared with the model group, after intervention, Zea Longa neurobehavioral score and the percentage of cerebral infarction volume were reduced (P<0.05), the number of M1-type microglia marked by CD68+ was reduced (P<0.05) and the number of M2-type microglia marked by TMEM119+ was increased (P<0.05); and the mRNA expression of NLRP3, ASC, Caspase-1 and GSDMD was decreased (P<0.01, P<0.05) in the EA group. Even though the cytomembrane structure was incomplete, there were less membrane pores presented in the ischemic cortex in the EA group after intervention. CONCLUSION: The intervention with EA attenuates the neurological dysfunction and reduces the volume of cerebral infarction in the rats with cerebral ischemic reperfusion. The underlying mechanism is related to the inhibition of microglia pyroptosis through modulating NLRP3/Caspase-1/GSDMD axis.

A comprehensive clinical evaluation of first-line drugs for ALK-positive advanced non-small cell lung cancer.

Background: Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are mainly used in the treatment of ALK-positive advanced non-small cell lung cancer (NSCLC), but a comprehensive clinical evaluation of ALK-TKIs is lacking. Hence, a comparison of ALK-TKIs for first-line treatment of ALK-positive advanced NSCLC is essential to provide rational drug use and a basis for improving national policies and systems. Methods: According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs (2021) and the Technical Guideline for the Clinical Comprehensive Evaluation of Antitumor Drugs (2022), a comprehensive clinical evaluation index system of first-line treatment drugs for ALK-positive advanced NSCLC was established by literature review and expert interviews. We conducted a systematic literature review, meta-analysis, and other relevant data analyses, combined with an indicator system, to establish a quantitative and qualitative integration analysis for each indicator and each dimension of crizotinib, ceritinib, alectinib, ensartinib, brigatinib, and lorlatinib. Results: The comprehensive clinical evaluation results of all dimensions were as follows: in terms of safety, alectinib had a lower incidence of grade 3 and above adverse reactions; for effectiveness, alectinib, brigatinib, ensartinib, and lorlatinib showed better clinical efficacy, and alectinib and brigatinib have been recommended by several clinical guidelines; in terms of economy, second-generation ALK-TKIs have more cost-utility advantages, and both alectinib and ceritinib have been recommended by the UK and Canadian Health Technology Assessment (HTA) agencies; for suitability, accessibility, and innovation, alectinib has a higher degree of physician recommendations and patient compliance. Except for brigatinib and lorlatinib, all other ALK-TKIs have been admitted to the medical insurance directory; the accessibility of crizotinib, ceritinib, and alectinib is good, meeting the needs of patients. Second- and third-generation ALK-TKIs have higher blood-brain barrier permeability, stronger inhibition ability, and innovation than first-generation ALK-TKIs. Conclusions: Compared with other ALK-TKIs, alectinib performs better across six dimensions and has a higher comprehensive clinical value. The results provide better drug choice and rational use for patients with ALK-positive advanced NSCLC.

Development and validation of a Cancer Patient Suicidal Ideation Scale.

Aim: To develop a Cancer Patient Suicidal Ideation Scale (CAPASIS) and test its reliability and validity. Patients & methods: An initial CAPASIS was developed. Clinical assessment was conducted using an adjusted initial scale with 239 cancer patients for item reduction and 253 for scale validation. Results: Item selection analyses resulted in 22 items. The revised model fits were acceptable (normal chi-square [χ2/df] = 1.919; standardized root mean residual  = 0.057; root mean square error of approximation = 0.060; goodness fit index = 0.882; adjusted goodness fit index [AGFI] = 0.844; Tucker-Lewis index = 0.898; comparative fit index  = 0.915; incremental fit index  = 0.917). The Cronbach's alpha coefficient was 0.911. Conclusion: The CAPASIS has good validity and reliability, with a six-factor structure of 'entrapment', 'defeat', 'isolation', 'hopelessness', 'burdensomeness' and 'humiliation', which can help identify patients with suicidal ideation.