Objective To elucidate the causal relationships between colorectal cancer (CRC) and prevalent psychiatric disorders through a two-sample Mendelian randomization approach. Methods Utilizing publicly available genome-wide association study data, we explored the connections between CRC and various psychiatric disorders, including depression, anxiety, bipolar disorder, and schizophrenia. We applied three statistical analyses: inverse variance weighting, MR-Egger, and median weighting. Sensitivity analyses were conducted to ensure the reliability and validity of the results. Results Inverse variance weighting analysis showed no significant links between CRC and depression (P=0.090), anxiety (P=0.099), or schizophrenia (P=0.899). Conversely, a significant inverse relationship was found with bipolar disorder (P=0.010). Conclusion No causal connection exists between CRC and the psychiatric conditions of depression, anxiety, or schizophrenia. However, CRC may have a causal association with a reduced risk of bipolar disorder, further supporting the existence of the gut-brain axis.

Oral squamous cell carcinoma (OSCC) is a malignant tumor that seriously threatens human health. Its typical biological characteristics include strong local invasiveness, high lymph node metastasis rate, and high recurrence rate after treatment. Hepatocyte growth factor (HGF), cellular-mesenchymal to epithelial transition factor (c-Met), and the HGF/c-Met signaling pathway are involved in the regulation of the occurrence and development of OSCC. HGF and c-Met proteins are overexpressed in OSCC, and multiple studies have suggested that they are significantly associated with the malignant characteristics of tumors and poor prognosis. Furthermore, the abnormal activation of the HGF/c-Met signaling pathway (driven by HGF-dependent autocrine/paracrine or non-dependent mechanisms such as MET gene mutations, amplification, fusion, and protein overexpression) can synergistically promote tumor cell invasion, metastasis, and angiogenesis by activating downstream signaling pathways. However, HGF/c-Met can also mediate immune escape by promoting lactate secretion increase, inducing programmed death ligand 1 (PD-L1) expression upregulation, activating and expanding myeloid-derived suppressor cells, and promoting the proliferation of regulatory T cells (Tregs). In addition, the crosstalk between the HGF/c-Met signaling pathway and key pathways such as phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT), epidermal growth factor receptor (EGFR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT3), and non-coding RNAs can also promote tumor progression. Currently, three types of targeted drugs have been developed targeting the HGF/c-Met pathway: HGF monoclonal antibody, c-Met monoclonal antibody, and tyrosine kinase inhibitors. Some of these drugs have entered clinical trials. However, the emergence of drug resistance during treatment, especially the bidirectional compensatory activation of alternative signaling pathways such as EGFR, has become a major challenge in clinical practice. This article aims to provide an in-depth analysis of the mechanism of action of the HGF/c-Met pathway in OSCC and its interaction with other pathways, and to review the current research status of existing therapeutic drugs. The aim is to provide an important theoretical basis for developing more effective combined treatment strategies and achieving individualized precise treatment, ultimately improving the clinical prognosis and quality of life of patients.

Objective To investigate the expression of the circular RNA circ-PHC3 in cervical cancer tissues and its regulatory mechanisms in the proliferation,migration,and invasion of cervical cancer cells.Methods The expression levels of circ-PHC3 in cervical cancer tissues and adjacent non-tumor tissues were analyzed using the GEO database.The correlation between circ-PHC3 expression and the clinical stage as well as prognosis of cervical cancer patients was also evaluated.The expression of circ-PHC3 in cervical cancer cell lines HCC94,C33A,HeLa,HCC1106,and SiHa was detected by real-time quantitative polymerase chain reaction(qRT-PCR).The cell line with the highest circ-PHC3 expression was selected for transfection with a circ-PHC3 inhibitor.The interaction between circ-PHC3 and miR-1179 was validated using a dual luciferase reporter gene assay.The expression levels of miR-1179 in transfected cells were further assessed by qRT-PCR.Functional assays,including colony formation,flow cytometry,wound healing,and Transwell assays,were conducted to evaluate cell proliferation,cell cycle progression,migration,and invasion,respectively.Western blot analysis was performed to determine the expression of key proteins associated with proliferation,migration,and invasion in circ-PHC3-modulated cells.Finally,in vivo experiments were carried out to investigate the impact of circ-PHC3 silencing on the growth and metastasis of cervical cancer cells in animal models.Results The expression level of circ-PHC3 in cervical cancer tissues was significantly higher than that in adjacent normal tissues(P<0.01).Furthermore,circ-PHC3 expression was significantly associated with the clinical stage of cervical cancer(P<0.01).Patients with high circ-PHC3 expression exhibited a notably lower survival rate compared to those with low circ-PHC3 expression(P<0.01).In cervical cancer cell lines including HCC94,C33A,HeLa,HCC1106,and SiHa,circ-PHC3 expression was markedly upregulated(all P<0.01),with the highest expression observed in HCC1106 cells(P<0.01).Circ-PHC3 was found to directly interact with miR-1179(P<0.01),and silencing circ-PHC3 significantly increased miR-1179 expression(P<0.01).Transfection of HCC1106 cells with a circ-PHC3 inhibitor significantly suppressed cell proliferation,migration,and invasion(all P<0.01),and induced cell cycle arrest(P<0.01);these effects were partially reversed by co-transfection with a miR-1179 inhibitor(all P<0.05).In HCC1106 cells with circ-PHC3 knockdown,the expression levels of key proteins associated with proliferation,migration,and invasion—Cyclin E,CDK2,MMP-9,and N-cadherin—were significantly reduced(all P<0.01),and this reduction was partially attenuated by miR-1179 inhibition(all P<0.01).In vivo experiments further demonstrated that circ-PHC3 knockdown significantly inhibited tumor growth and metastasis of HCC1106 cells(all P<0.01).Conclusions Circ-PHC3 is highly expressed in cervical cancer tissues,and its overexpression is significantly correlated with poor prognosis in patients with cervical cancer.Knockdown of circ-PHC3 upregulates the expression of miR-1179 and suppresses the proliferation,migration,and invasion of cervical cancer cells.

Objective To investigate the expression of the circular RNA circ-PHC3 in cervical cancer tissues and its regulatory mechanisms in the proliferation,migration,and invasion of cervical cancer cells.Methods The expression levels of circ-PHC3 in cervical cancer tissues and adjacent non-tumor tissues were analyzed using the GEO database.The correlation between circ-PHC3 expression and the clinical stage as well as prognosis of cervical cancer patients was also evaluated.The expression of circ-PHC3 in cervical cancer cell lines HCC94,C33A,HeLa,HCC1106,and SiHa was detected by real-time quantitative polymerase chain reaction(qRT-PCR).The cell line with the highest circ-PHC3 expression was selected for transfection with a circ-PHC3 inhibitor.The interaction between circ-PHC3 and miR-1179 was validated using a dual luciferase reporter gene assay.The expression levels of miR-1179 in transfected cells were further assessed by qRT-PCR.Functional assays,including colony formation,flow cytometry,wound healing,and Transwell assays,were conducted to evaluate cell proliferation,cell cycle progression,migration,and invasion,respectively.Western blot analysis was performed to determine the expression of key proteins associated with proliferation,migration,and invasion in circ-PHC3-modulated cells.Finally,in vivo experiments were carried out to investigate the impact of circ-PHC3 silencing on the growth and metastasis of cervical cancer cells in animal models.Results The expression level of circ-PHC3 in cervical cancer tissues was significantly higher than that in adjacent normal tissues(P<0.01).Furthermore,circ-PHC3 expression was significantly associated with the clinical stage of cervical cancer(P<0.01).Patients with high circ-PHC3 expression exhibited a notably lower survival rate compared to those with low circ-PHC3 expression(P<0.01).In cervical cancer cell lines including HCC94,C33A,HeLa,HCC1106,and SiHa,circ-PHC3 expression was markedly upregulated(all P<0.01),with the highest expression observed in HCC1106 cells(P<0.01).Circ-PHC3 was found to directly interact with miR-1179(P<0.01),and silencing circ-PHC3 significantly increased miR-1179 expression(P<0.01).Transfection of HCC1106 cells with a circ-PHC3 inhibitor significantly suppressed cell proliferation,migration,and invasion(all P<0.01),and induced cell cycle arrest(P<0.01);these effects were partially reversed by co-transfection with a miR-1179 inhibitor(all P<0.05).In HCC1106 cells with circ-PHC3 knockdown,the expression levels of key proteins associated with proliferation,migration,and invasion—Cyclin E,CDK2,MMP-9,and N-cadherin—were significantly reduced(all P<0.01),and this reduction was partially attenuated by miR-1179 inhibition(all P<0.01).In vivo experiments further demonstrated that circ-PHC3 knockdown significantly inhibited tumor growth and metastasis of HCC1106 cells(all P<0.01).Conclusions Circ-PHC3 is highly expressed in cervical cancer tissues,and its overexpression is significantly correlated with poor prognosis in patients with cervical cancer.Knockdown of circ-PHC3 upregulates the expression of miR-1179 and suppresses the proliferation,migration,and invasion of cervical cancer cells.

Objective To investigate the role of the piriformcortex in regulating attentional behavior in mice.Methods Adult male C57BL/6J mice were subjected to a 5-choice serial reaction time task(5-CSRTT).Immunofluorescence staining was performed to detect expressions of cellular FBJ murine osteosarcoma viral oncogene homolog protein(c-Fos)in the piriform cortex.The changes of attentional behavior in the 5-CSRTT test were explored following either stereotactic injection of diphtheria toxin A virus to specifically damage piriform cortex neurons or chemogenetical inhibition of the neuronal activity inthe piriform cortex.Results It was found that the expression of c-Fos in the 5-CSRTT-tested mice was significantly increased compared to the control.Both lesion and chemogenetic inhibition of piriform cortex neuronsreduced the accuracy of attention,but omission rates and premature responses remained unaffected in the 5-CSRTT test.Conclusion Piriform cortex neuronsmay play a critical role in modulating attentional processes in mice.

Drug repurposing offers a promising alternative to traditional drug development and significantly reduces costs and timelines by identifying new therapeutic uses for existing drugs. However, the current approaches often rely on limited data sources and simplistic hypotheses, which restrict their ability to capture the multi-faceted nature of biological systems. This study introduces adaptive multi-view learning (AMVL), a novel methodology that integrates chemical-induced transcriptional profiles (CTPs), knowledge graph (KG) embeddings, and large language model (LLM) representations, to enhance drug repurposing predictions. AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning (MVL), matrix factorization, and ensemble optimization techniques to integrate heterogeneous multi-source data. Comprehensive evaluations on benchmark datasets (Fdataset, Cdataset, and Ydataset) and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art (SOTA) methods, achieving superior accuracy in predicting drug-disease associations across multiple metrics. Literature-based validation further confirmed the model's predictive capabilities, with seven out of the top ten predictions corroborated by post-2011 evidence. To promote transparency and reproducibility, all data and codes used in this study were open-sourced, providing resources for processing CTPs, KG, and LLM-based similarity calculations, along with the complete AMVL algorithm and benchmarking procedures. By unifying diverse data modalities, AMVL offers a robust and scalable solution for accelerating drug discovery, fostering advancements in translational medicine and integrating multi-omics data. We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.

Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.

Objective: To analyze the association between different sleep statuses and overweight/obesity among primary school students, so as to provide a basis for the development of childhood overweight and obesity prevention and control strategies. Methods: In November 2023, a total of 3 391 primary school students of grade 1-6 from seven schools in Baoan District, Shenzhen, were surveyed by questionnaires and physical examinations by using multistage cluster sampling. The Logistic regression analysis was used to explore the association between primary school students sleep status and overweight/obesity. Results: The detection rate of overweight/obesity in primary school students was 22.59%, the detection rate of overweight/obesity in boys (27.04%) was higher than that in girls (17.44%), the only child (25.81%) had higher rates than nononly child (21.76%), and the differences were statistically significant (χ2=51.48, 5.98, P＜0.05). Multivariate Logistic regression analysis showed that, after controlling for confounders, primary school students weekend nighttime sleep duration (OR=0.83, 95%CI=0.75-0.91), weekly average nighttime sleep duration (OR=0.76,95%CI=0.64-0.89), and weekend compensated sleep duration (OR=0.89,95%CI=0.81-0.97) were negatively associated with the risk of developing overweight/obesity (P＜0.05). Compared with to primary school students with school days nap durations <0.5 h, those whose napped for 0.5-＜1 h and ≥1 h on school days had a 20% (OR=1.20, 95%CI=1.02-1.42) and 37% (OR=1.37, 95%CI=1.02-1.83) increased risk of overweight/obesity, respectively (P＜0.05). Conclusions Increasing weekend nighttime sleep duration, average weekly nighttime sleep duration, and weekend compensatory sleep duration can reduce the risk of overweight and obesity in primary school students. School days nap duration is a risk factor for overweight/obesity among primary school students.

Drug repurposing offers a promising alternative to traditional drug development and significantly re-duces costs and timelines by identifying new therapeutic uses for existing drugs.However,the current approaches often rely on limited data sources and simplistic hypotheses,which restrict their ability to capture the multi-faceted nature of biological systems.This study introduces adaptive multi-view learning(AMVL),a novel methodology that integrates chemical-induced transcriptional profiles(CTPs),knowledge graph(KG)embeddings,and large language model(LLM)representations,to enhance drug repurposing predictions.AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning(MVL),matrix factorization,and ensemble optimization techniques to integrate heterogeneous multi-source data.Comprehensive evaluations on benchmark datasets(Fdata-set,Cdataset,and Ydataset)and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art(SOTA)methods,achieving superior accuracy in predicting drug-disease associations across multiple metrics.Literature-based validation further confirmed the model's predictive capabilities,with seven out of the top ten predictions corroborated by post-2011 evidence.To promote transparency and reproducibility,all data and codes used in this study were open-sourced,providing resources for pro-cessing CTPs,KG,and LLM-based similarity calculations,along with the complete AMVL algorithm and benchmarking procedures.By unifying diverse data modalities,AMVL offers a robust and scalable so-lution for accelerating drug discovery,fostering advancements in translational medicine and integrating multi-omics data.We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.

Objective:To compare the efficacies of endovascular therapy (EVT) and standard medical therapy in acute ischemic stroke (AIS) patients aged ≥85 years, and analyze the independent influencing factors for poor prognosis of AIS patients after EVT.Methods:Sixty-nine AIS patients aged ≥85 years admitted to Department of Neurology, Xi'an Third Hospital from January 2018 to April 2024, including 40 accepted EVT and 28 accepted standard medicinal therapy, were enrolled. Modified Rankin scale (mRS) was used to evaluate the prognosis of the patients 90 days after onset. General data, prognosis and complications between the EVT group and standard medical therapy group were compared. General data, treatment processes and complications between patients with good prognosis and poor prognosis in the EVT group were compared. Multivariate Logistic regression was used to analyze the independent influencing factors for poor prognosis in AIS patients after EVT.Results:Compared with the standard medical therapy, the EVT group had significantly lower NIHSS score at discharge, greater improvement in NIHSS score (NIHSS score at admission-NIHSS score at discharge), lower mRS score 90 days after onset, higher good prognosis rate, lower mortality rate within 90 days of onset, and longer hospital stay ( P<0.05). In the EVT group, 11 patients (27.5%) had good prognosis and 29 patients (72.5%) had poor prognosis 90 days after onset. Compared with the good prognosis group, the poor prognosis group had significantly higher blood glucose level and lower Alberta Stroke Program Early CT Score (ASPECT) on admission ( P<0.05). Multivariate Logistic regression analysis showed that blood glucose on admission ( OR=2.363, 95% CI: 1.134-4.928, P=0.022) and ASPECT score on admission ( OR=0.273, 95% CI: 0.088-0.854, P=0.026) were independent influencing factors for poor prognosis in AIS patients after EVT. Conclusion:AIS patients aged ≥85 years received EVT have better prognosis compared with those accepted standard medical therapy; these patients with high glucose level and low ASPECT score on admission have poor prognosis.