ABSTRACT Background Colorectal cancer (CRC) is a major public health burden in Hainan Province due to its high incidence and mortality, yet region‐specific prognostic data are lacking. This study evaluates prognostic factors in postsurgical CRC patients to guide localized prevention and treatment. Methods We conducted a retrospective cohort study of 265 patients undergoing first‐time surgery for CRC between January 2015 and December 2021. Kaplan–Meier estimator and log‐rank tests were performed to analyze the overall survival rates of CRC patients. Cox proportional hazards regression and the SHAP method were performed to determine the prognostic factors of CRC. Results The study included 265 patients (mean age 63 ± 12.99 years), with 171 survivors (64.5%) and 94 deaths (35.5%). The 1‐, 3‐ and 5‐year overall survival rates of CRC patients were 93.0%, 82.1%, and 73.9%, respectively, from 2015 to 2021. In multivariable analysis, factors associated with increased mortality risk included advanced age (per 1 year increase: HR = 1.043, 95% CI: 1.018–1.069, p = 0.001), TNM stage III (HR = 11.46, 95% CI: 2.611–50.31, p = 0.001) and stage IV (HR = 15.06, 95% CI: 3.131–72.46, p = 0.001), increased tumor size (per 1 cm increase: HR = 1.267, 95% CI: 1.058–1.519, p = 0.01), positive vascular infiltration (HR = 2.399, 95% CI: 1.162–4.951, p = 0.018), elevated CEA levels (per 1 ng/mL increase: HR = 1.035, 95% CI: 1.012–1.059, p = 0.003), and increased CA125 levels (per 1 U/mL increase: HR = 1.013, 95% CI: 1.003–1.024, p = 0.014), while normal‐weight (HR = 0.385, 95% CI: 0.168–0.880, p = 0.024) was associated with a better survival. No association was found between the expression of MSH2, MDR1, and GSTπ and the survival of the patients. The SHAP beeswarm plot highlighted TNM stage and age as the primary contributors to the model's predictions. Conclusion Increased age, advanced TNM stage, larger tumor size, vascular invasion, and elevated CEA/CA125 were linked to poorer CRC prognosis, while normal BMI was protective. Further prospective studies are needed for validation.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality globally. Epigenetic regulation, especially N6-methyladenosine (m6A) RNA modification, plays a critical role in CRC development. Although molecular studies have linked m6A to CRC progression, comprehensive bibliometric assessments are scarce. We analyzed 230 publications from the Web of Science (2014–2024) using CiteSpace and VOSviewer. Highly cited studies emphasize regulators such as METTL3 and IGF2BP2 in stemness and metabolic reprogramming. A emerging trend is the integration of m6A with tumor immunotherapy, indicating a shift from basic research toward clinical translation. This evolution highlights new therapeutic opportunities in CRC.

Introduction. Traditional Chinese medicines (TCMs) may carry microbial hazards, yet conventional inspection methods often underestimate their diversity and risks. Hypothesis. Culture-based methods may overlook significant microbial diversity and potential pathogens compared with sequencing approaches. Aim. This study aimed to compare culture-based identification (VITEK-2) with 16S rRNA high-throughput sequencing for microbial detection in selected TCMs. Methodology. Thirty batches of five southern TCM samples, including Areca catechu, Alpinia oxyphylla, Eugenia caryophyllata, Pogostemon cablin and Morinda officinalis, were analysed for microbial contamination according to the 'Pharmacopoeia of the People's Republic of China' (2020 Edition). Culture-based isolates were identified using VITEK-2, and microbial communities were profiled by 16S rRNA sequencing. Results. Culture-based methods identified bile salt-resistant Gram-negative bacteria in 12 out of 30 batches (40%), comprising seven genera spanning two phyla, including Enterobacter cloacae, Pseudomonas aeruginosa, Cronobactersakazakii and Klebsiella pneumoniae. Sequencing identified 795 genera across 26 phyla, revealing far greater diversity, though DNA signatures of some cultured taxa (e.g. Enterobacter in M. officinalis and Leclercia in Areca catechu) were undetected. Microbial composition varied significantly among TCMs. Conclusion. Sequencing uncovered substantially broader microbial diversity than culture-based methods, while both approaches identified pathogenic and opportunistic microbes. These findings emphasize the critical need for more rigorous microbial surveillance and stringent quality control of TCMs to protect public health.

Lipid nanoparticle (LNP) delivery systems are widely used in the delivery of small-molecule drugs and nucleic acids. In this study, we prepared LNP-miR-155 by lipid nanomaterial technology and investigated the effects of LNP-miR-155 on β-catenin/transcription factor 4 (TCF4)/solute carrier family 31 member 1/copper transporter 1 (SLC31A1/CTR1) signaling and copper transport in colorectal cancer. For this, we used an LNP-miR-155 cy5 inhibitor and LNP-miR-155 cy5 mimics for the transfection of HT-29/SW480 cells. The transfection efficiency and uptake efficiency were detected by immunofluorescence. Relevant cell assays confirmed that the LNP-miR-155 cy5 inhibitor mediates the regulation of copper transport through the β-catenin/TCF4/SLC31A1 axis. The LNP-miR-155 cy5 inhibitor reduced cell proliferation, migration, and colony formation and promoted cell apoptosis. We also confirmed that miR-155 downregulates HMG box-containing protein 1 (HBP1) and adenomatous polyposis coli (APC) in cells and activates the function of β-catenin/TCF4 signaling. In addition, we found that the copper transporter, SLC31A1, is highly expressed in colorectal cancer cells. Furthermore, we also found that the complex β-catenin/TCF4 promotes the transcription of SLC31A1 by binding to its promoter region, which sustains the transport of copper from the extracellular region to the intracellular region and increases the activities of Cu2+-ATPase and superoxide dismutase (SOD). In summary, the LNP-miR-155 cy5 inhibitor regulates β-catenin/TCF4 by downregulating SLC31A1-mediated copper transport and intracellular copper homeostasis.

Mitogen-activated protein kinases (MAPK), specifically the c-Jun N-terminal kinase (JNK)–MAPK subfamily, play a crucial role in the development of various cancers, including hepatocellular carcinoma (HCC). However, the specific roles of JNK1/2 and their upstream regulators, MKK4/7, in HCC carcinogenesis remain unclear. In this study, we performed differential expression analysis of JNK–MAPK components at both the transcriptome and protein levels using TCGA and HPA databases. We utilized Kaplan–Meier survival plots and receiver operating characteristic (ROC) curve analysis to evaluate the prognostic performance of a risk scoring model based on these components in the TCGA-HCC cohort. Additionally, we conducted immunoblotting, apoptosis analysis with FACS and soft agar assays to investigate the response of JNK–MAPK pathway components to various death stimuli (TRAIL, TNF-α, anisomycin, and etoposide) in HCC cell lines. JNK1/2 and MKK7 levels were significantly upregulated in HCC samples compared to paracarcinoma tissues, whereas MKK4 was downregulated. ROC analyses suggested that JNK2 and MKK7 may serve as suitable diagnostic genes for HCC, and high JNK2 expression correlated with significantly poorer overall survival. Knockdown of JNK1 enhanced TRAIL-induced apoptosis in hepatoma cells, while JNK2 knockdown reduced TNF-α/cycloheximide (CHX)—and anisomycin-induced apoptosis. Neither JNK1 nor JNK2 knockdown affected etoposide-induced apoptosis. Furthermore, MKK7 knockdown augmented TNF-α/CHX- and TRAIL-induced apoptosis and inhibited colony formation in hepatoma cells. Targeting MKK7, rather than JNK1/2 or MKK4, may be a promising therapeutic strategy to inhibit the JNK–MAPK pathway in HCC therapy.

Background: The purpose of this study was to analyze and evaluate the effect of astaxanthin on clinical indicators related to cardiovascular disease. Methods: Fives databases include PUBMED, CNKI, WEIPU, WAN FANG and ClinicalTrials were searched up to January 31, 2022, and the random-effects model was used to calculate the summary risk. A total of 14 epidemiological studies were included in this meta-analysis. Results: The overall study showed no significant dose-response association of astaxanthin (AST) with diastolic blood pressure, DBP (weighted mean difference, WND:-0.186, 95%confidence interval, CI:-0.374 to 0.002, P =0.052) and body mass index, BMI ( WND:0.095, 95%CI: -0.164 to 0.354, P =0.473).However, the results revealed that astaxanthin can significantly reduce the concentrations of total cholesterol (WND:-0.310, 95% CI:-0.541 to -0.168, P =0.000), the concentrations of low-density lipoprotein cholesterol, LDL-C (WND: -0.207, 95% CI: -0.396 to -0.019, P =0.031), the concentrations of triglyceride (WND:-0.603, 95% CI:-1.028 to -0.179, P =0.005), the concentrations of glucose (WND: -0.353, 95% CI:-0.596 to -0.110, P =0.004) and systolic blood pressure, SBP(WND:-0.258, 95% CI:-0.495 to -0.021, P =0.033). Moreover, astaxanthin could increase the concentrations of high-density lipoprotein cholesterol, HDL-C (WND: -0.294, 95% CI:-0.515 to -0.072, P =0.009). Conclusions: This meta-analysis indicates that astaxanthin has a protection role on the cardiovascular system. Further studies need to be conducted to verify the findings.

Background Sacubitril/valsartan (S/V) demonstrated significant effects in improving left ventricular performance and remodeling in patients with heart failure with reduced ejection fraction. However, its effects on the right ventricle remain unclear. This systematic review and meta‐analysis aimed to assess the impact of S/V on right ventricular function and pulmonary hypertension. Methods and Results We searched PubMed, Embase, Cochrane Library, and Web of Science from January 2010 to April 2021 for studies reporting right ventricular and pulmonary pressure indexes following S/V treatment. The quality of included studies was assessed using the Newcastle‐Ottawa scale. Variables were pooled using a random‐effects model to estimate weighted mean differences with 95% CIs. We identified 10 eligible studies comprising 875 patients with heart failure with reduced ejection fraction (mean age, 62.2 years; 74.0% men), all of which were observational. Significant improvements on right ventricular function and pulmonary hypertension after S/V initiation were observed, including tricuspid annular plane systolic excursion (weighted mean difference, 1.26 mm; 95% CI, 0.33–2.18 mm; P =0.008), tricuspid annular peak systolic velocity (weighted mean difference, 0.85 cm/s; 95% CI, 0.25–1.45 cm/s; P =0.005), and systolic pulmonary arterial pressure (weighted mean difference, 7.21 mm Hg; 95% CI, 5.38–9.03 mm Hg; P <0.001). Besides, S/V had a significant beneficial impact on left heart function, which was consistent with previous studies. The quadratic regression model revealed a certain correlation between tricuspid annular plane systolic excursion and left ventricular ejection fraction after excluding the inappropriate data ( P =0.026). Conclusions This meta‐analysis verified that S/V could improve right ventricular performance and pulmonary hypertension in heart failure with reduced ejection fraction, which did not seem to be fully dependent on the reverse remodeling of left ventricle. Registration URL: https://www.crd.york.ac.uk/prospero ; Unique identifier: CRD42021247970.

ObjectivesThis study aimed to investigate whether there are sex differences in clinical characteristics and prognosis in patients with primary thrombotic antiphospholipid syndrome (ptAPS).MethodsFrom January 2013 to July 2021, 154 consecutive patients diagnosed with ptAPS were prospectively recruited. Multivariable Cox regression was used to evaluate the association between gender and the composite endpoint including thromboembolic recurrence or all-cause death during follow-up.ResultsTotally, 80 (52%) male and 74 (48%) female patients with ptAPS were included, and men had a higher percentage of smokers/ex-smokers [50 (62%) vs. 6 (8%), p < 0.001] and hyperhomocysteinemia [26 (32%) vs. 9 (12%), p = 0.003]. The baseline thromboembolic events were similar in two genders, except for limb ischemia [15 (19%) in men vs. 1 (1%) in women, p < 0.001]. During a median follow-up of 42 months, the composite endpoint occurred in 30 (38%) male and 15 (20%) female patients (p = 0.019). Male gender [HR 2.499, 95% CI (1.316, 4.743), p = 0.005] and warfarin administration [HR 0.482, 95% CI (0.257, 0.905), p = 0.023] remained independent risk factors for the composite endpoint. Male gender [HR 3.699, 95% CI (1.699, 8.246), p = 0.001] and isolated lupus anticoagulant positivity [HR 2.236, 95% CI (1.039, 4.811), p = 0.040] were independent risk factors for thromboembolic recurrence.ConclusionThere are sex disparities in the clinical characteristics in patients with ptAPS and the male gender is an independent risk factor for the poor prognosis. Male patients with isolated lupus anticoagulant (LA) positivity have the highest risk of thromboembolic recurrence.

Colorectal cancer (CRC) is a malignant tumor with a high incidence and mortality worldwide. Currently, the underlying molecular mechanisms of CRC are still unclear. Zinc finger protein 3 (ZNF3) is a zinc-finger transcription factor that has been reported as a candidate for breast cancer prognosis, suggesting its involvement in the regulation of tumorigenesis. However, the association between ZNF3 and CRC remains unknown. To investigate the role of ZNF3 in CRC, we first analyze the correlation between ZNF3 expression and CRC, and the results demonstrate that ZNF3 is highly expressed in CRC tissue and cells, which is associated with the age of CRC patients. In vitro studies show that ZNF3 overexpression promotes CRC cell migration. Compared to control cells, knockdown of ZNF3 markedly suppresses CRC cell proliferation, migration and invasion and promotes G0/G1 phase cell cycle arrest. The expressions of the EMT-related markers TWIST and MMP1 are significantly decreased when ZNF3 is silenced. Additionally, overexpression of MMP1 and TWIST exacerbates CRC cell proliferation, accelerates the S phase cell cycle in ZNF3-knockdown SW480 cells, and increases cell migration and invasion through Transwell chambers. These data suggest that ZNF3 is involved in cellular proliferation, migration and invasion by regulating MMP1 and TWIST in CRC cells.

Sporadic colorectal cancer (sCRC) is one of the leading causes of cancer death worldwide. As a highly heterogeneous complex disease, the currently reported classical genetic markers for sCRC, including APC, KRAS, BRAF, and TP53 gene mutations and epigenetic alterations, can explain only some sCRC patients. Here, we first reported a deleterious c.551C>T mutation in SARDH in sCRC. SARDH was identified as a novel tumor suppressor gene and was abnormally decreased in sCRC at both the transcriptional and the translational level. SARDH mRNA levels were also down-regulated in oesophageal cancer, lung cancer, liver cancer, and pancreatic cancer in the TCGA database. SARDH overexpression inhibited the proliferation, migration, and invasion of CRC cell lines, whereas its depletion improved these processes. SARDH overexpression was down-regulated in multiple pathways, especially in the chemokine pathway. The SARDH transcript level was positively correlated with the methylation states of CXCL1 and CCL20. Therefore, we concluded that SARDH depletion is involved in the development of sCRC.

Mutations in transforming growth factor beta receptor II (TGFBR2) are detected in up to 30% of overall colorectal cancer (CRC). Dysregulation of some microRNAs participated in the CRC pathogenesis. In this study, we used the gene ontology analyses, the Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene set enrichment analysis to indicate that miR-3191 was involved in the regulation of transforming growth factor beta (TGF-BETA) signal pathway in CRC. These bioinformatics results were supported by data obtained from CRC samples and experiments in vitro. The luciferase reporter assay was used to confirm that miR-3191 modulates TGF-BETA signal pathway by targeting TGFBR2. By transwell migration and invasion assays, we showed that miR-3191 promoted CRC cell migration and invasion by downregulating TGFBR2. And it may serve as a novel therapeutic strategy for treating CRC patients.

The aim of this study was to evaluate the role of vimentin expression in the prognosis and progression of CRC. Meta-analysis was conducted to investigate the correlations between vimentin and prognosis and clinicopathological features in CRC. Literatures were searched by PubMed, Embase, ClinicalKey, CNKI, VIP, and WanFang databases. The Cancer Genome Atlas (TCGA) database was used to assess the association of vimentin expression with survival rate in CRC. Eleven reports with 1969 cases were included in the meta-analysis. The results showed that positive vimentin expression predicted a poor overall survival (OS) in the univariate analysis (HR: 2.087, 95%CI: 1.660-2.625) and multivariate analysis (HR: 1.633, 95%CI: 1.223-2.181). Vimentin overexpression also conferred worse disease-free survival (DFS) in the univariate analysis (HR: 2.069, 95%CI: 1.024-4.179) and multivariate analysis (HR: 2.802, 95%CI: 1.421-5.527). Moreover, upregulated vimentin is related to lymph node metastasis (OR: 2.288, 95%CI: 1.159-4.517), TNM stages (OR: 1.957, 95%CI: 1.333-2.873), and N stage (OR: 2.316, 95%CI: 1.482-3.620). Analysis of TCGA database indicated that elevated vimentin predicated a shorter OS (p=0.033). Our findings reveal that upregulated vimentin contributes to the progression and poor prognosis of CRC. Vimentin may be a prognostic biomarker and therapeutic target in patients with CRC.

The main purpose of this study was to perform a meta-analysis to assess the interaction between smoking and nine genes (GSTM1, GSTT1, GSTP1, CYP1A1, NAT2, SULT1A1, hOGG1, XRCC1 and p53) on colorectal cancer, gastric cancer, liver cancer and oesophageal cancer. Published articles from the PubMed, ISI and EMBASE databases were retrieved. A total of 67 case-control studies or nested case-control studies were identified for the analysis. The pooled jodds ratio (OR) with 95% confidence interval (CI) was calculated using the random effect model. The overall study showed that the GSTM1 polymorphism was associated with the risk of the four digestive cancers among Asian population (OR 1.284, 95% CI: 1.122-1.470, p: 0). Subgroup analyses by cancer site showed that GSTM1 null genotype increased the gastric cancer risk in total population (OR 1.335, 95% CI: 1.145-1.556, p: 0). However, the association of GSTM1 null genotype with the oesophageal cancer risk was found in smokers (OR 1.382, 95% CI: 1.009-1.894, p:0.044), but not in non-smokers (OR 1.250, 95% CI: 0.826-1.891, p:0.290). Moreover, smokers with the CYP1A1 IIe462Val polymorphism were at an increased cancer risk in Asian population (OR=1.585, 95% CI 1.029-2.442, p: 0.037). None of the other gene-smoking interactions was observed in the above cancers. This meta-analysis reveals two potential gene-smoking interactions, one is between smoking and GSTM1 on oesophageal cancer, and the other is between smoking and CYP1A1 IIe462Val on the four cancers in Asian population. Future studies need to be conducted to verify the conclusions.

Background Although the genetic spectrum of human colorectal cancer (CRC) is mainly characterized by APC , KRAS and TP53 mutations, driver genes in tumor initiation have not been conclusively demonstrated. In this study, we aimed to identify novel markers for CRC. Methods We performed exome analysis of sporadic colorectal cancer (sCRC) coding regions to screen loss of function (LoF) mutation genes, and carried out systems-level approaches to confirm top rank gene in this study. Results We identified loss of BMP5 is an early event in CRC . Deep sequencing identified BMP5 was mutated in 7.7% (8/104) of sCRC samples, with 37.5% truncating mutation frequency. Notably, BMP5 negative expression and its prognostic value is uniquely significant in sCRC but not in other tumor types. Furthermore, BMP5 expression was positively correlated with E-cadherin in CRC patients and its dysregulation play a vital role in epithelial-mesenchymal transition (EMT), thus triggering tumor initiation and development. RNA sequencing identified, independent of BMP/Smads pathway, BMP5 signaled though Jak-Stat pathways to inhibit the activation of oncogene EPSTI1 . Conclusions Our result support a novel concept that the importance of BMP5 in sCRC. The tumor suppressor role of BMP5 highlights its crucial role in CRC initiation and development.

Ras-association domain family protein 6 (RASSF6) is a member of tumor suppressor RASSFs family with a wide range of function from RAS interaction, Hippo signaling involvement to cell cycle and apoptosis regulation. RASSF6 is reported inactivated in various types of cancer. However, whether RASSF6 is associated with colorectal cancer and the underlying mechanisms have yet to be investigated. In our previous exome sequencing study, we found a somatic loss-of-function (LoF) mutation in RASSF6 in one sporadic colorectal cancer (sCRC) patient, and two missense mutations in deep sequencing group of sCRC samples, implying the possibility that RASSF6 may be involved in the pathogenesis of sCRC. In this study, we demonstrate that RASSF6 acts as a tumor suppressor in colon cancer cells. Decreased level of RASSF6 was observed in adenocarcinoma compared to normal tissues, especially in advanced tumor cases. Further experiments showed exogenous introduction of RASSF6 into LoVo cells suppressed cell proliferation, migration, invasion, and induced apoptosis in vitro as well as tumor growth in vivo. In contrast, knockdown of RASSF6 in HT-29 cells showed the opposite effects. Taken together, our results suggest, in addition to epigenetics changes, functional somatic mutations may also contribute to the downregulation of RASSF6 and further participate in the pathogenesis of sCRC. RASSF6 may serve as a novel candidate against tumor growth for sCRC.

Although numerous in vitro studies and animal model data have suggested that flavan-3-ols, the most common subclass of flavonoids in the diet, may exert protective effects against cancer, epidemiologic studies have reported inconclusive results for the association between flavan-3-ols intake and cancer risk. Therefore, we conducted this meta-analysis of epidemiologic studies to investigate the preventive effects of flavan-3-ols on various types of cancers. A total of 43 epidemiologic studies, consisting of 25 case-control and 18 prospective cohort studies, were included. A significant inverse association was shown between flavan-3-ols intake and the risk of overall cancer (relative risk (RR) 0.935, 95%CI: 0.891-0.981). When cancer types were separately analyzed, a statistically significant protective effect of flavan-3-ols consumption was observed in rectal cancer (RR 0.838, 95%CI: 0.733-0.958), oropharyngeal and laryngeal cancer (RR 0.759, 95%CI: 0.581-0.993), breast (RR 0.885, 95%CI: 0.790-0.991) in case-control studies and stomach cancer in women (RR 0.633, 95%CI: 0.468-0.858). Our analysis indicates the potential benefits of flavan-3-ols in cancer prevention.