[Bowel Sounds Detection Method Based on ResNet-BiLSTM and Attention Mechanism].

Bowel sounds can reflect the movement and health status of the gastrointestinal tract. However, the traditional manual auscultation method has subjective deviation and is time-consuming and labor-intensive. In order to better assist doctors in diagnosing bowel sounds and improve the reliability and efficiency of bowel sound detection, this study proposed a deep neural network model that combines a residual neural network (ResNet), a bidirectional long short-term memory network (BiLSTM), and an attention mechanism. Firstly, a large number of labeled clinical data was collected using the self-developed multi-channel bowel sound acquisition system, and the multi-scale wavelet decomposition and reconstruction method was used to preprocess the bowel sounds. Then, log Mel spectrogram features were extracted and sent to the network for training. Finally, the performance and effectiveness of the model were evaluated and verified by 10-fold cross-validation and an ablation experiment. The experimental results showed that the precision, recall, and F 1 score of the model reached 83%, 76%, and 79%, respectively, and it could effectively detect bowel sound segments and locate their start and end times, performing better than previous algorithms. This algorithm can not only provide auxiliary information for doctors in clinical practice but also offer technical support for further analysis and research of bowel sounds.

Jianpi-Huatan-Huoxue-Anshen formula ameliorates gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with H22 hepatocellular carcinoma.

BACKGROUND: Jianpi-Huatan-Huoxue-Anshen formula [Tzu-Chi cancer-antagonizing & life-protecting II decoction (TCCL)] is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life. However, its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear. AIM: To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC). METHODS: Ninety-six mice were inoculated subcutaneously with HCC cells. One week later, the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model. Thirty-six mice were randomly selected before administration, and feces, ileal tissue, and ileal contents were collected from each mouse. The remaining mice were randomized into normal saline, continuous chemotherapy, Yangzheng Xiaoji capsules-treated, and three TCCL-treated groups. After treatment, feces, tumors, liver, spleen, thymus, stomach, jejunum, ileum, and colon tissues, and ileal contents were collected. Morphological changes, serum levels of IL-1ß, IL-6, IL-8, IL-10, IL-22, TNF-α, and TGF-ß, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-κB, Occludin, MUC-2, Claudin-1, and IκB-α in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing. RESULTS: TCCL treatment improved thymus and spleen weight, thymus and spleen indexes, and body weight, decreased tumor volumes and tumor tissue cell density, and alleviated injury to gastric, ileal, and colonic mucosal tissues. Among proteins and genes associated with inflammation, IL-10, TGF-ß, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-κB, IL-1ß, IL-6, TNF-α, IL-22, IL-8, and IκB-α were downregulated. Additionally, TCCL increased the proportions of fecal Actinobacteria, AF12, Adlercreutzia, Clostridium, Coriobacteriaceae, and Paraprevotella in the intermediate stage of treatment, decreased the proportions of Mucipirillum, Odoribacter, RF32, YS2, and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment. Studies on ileal mucosal microbiota showed similar findings. Moreover, TCCL improved community richness, evenness, and the diversity of fecal and ileal mucosal flora. CONCLUSION: TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy.

[Treatment strategy of carotid blowout syndrome after radiotherapy for nasopharyngeal carcinoma].

Objective:To investigate the treatment of internal carotid artery rupture after radiotherapy for nasopharyngeal carcinoma. Methods:The clinical data of 7 patients with internal carotid artery rupture after radiotherapy for nasopharyngeal carcinoma from March 2020 to March 2023 were retrospectively analyzed. Results:Skull base osteonecrosis with infection occurred in 4 cases, and tumor recurrence with infection in 3 cases. DSA showed that internal carotid artery rupture was located in the internal carotid artery petrosal segment in 6 cases, and in the paravicular segment in 1 case. Balloon occlusion test（BOT） was performed in 6 patients, of which 3 passed and 3 failed. Vascular treatment included internal carotid artery embolization（4 cases）, false aneurysm embolization 1 case（rebleeding）, coated stent 1 case（rebleeding）, muscle compression during operation（1 case）. Patients with rebleeding received high-flow bypass. Three cases developed cerebral infarction after embolization without severe sequelae after treatment, and no death occurred within 90 days. After bleeding control, all 3 patients with cranial base necrosis received surgical treatment to remove the necrotic bone and tissue flap repair, and 1 patient with recurrence received gamma knife and targeted therapy, 1 patient received immune and surgical therapy, and 1 patient received immune and targeted therapy. Conclusion:Rupture and hemorrhage of internal carotid artery after radiotherapy is related to tumor invasion, tissue injury and local infection after radiotherapy. For those caused by tumor invasion, it is recommended to sacrifice the responsible vessels. For those caused by infection, emergency surgery is recommended and blood vessels preserved. Emergency vascular occlusion remains a life-saving option.

Identification of the molecular subtypes and signatures to predict the prognosis, biological functions, and therapeutic response based on the anoikis-related genes in colorectal cancer.

BACKGROUND: Tumors that resist anoikis, a programmed cell death triggered by detachment from the extracellular matrix, promote metastasis; however, the role of anoikis-related genes (ARGs) in colorectal cancer (CRC) stratification, prognosis, and biological functions remains unclear. METHODS: We obtained transcriptomic profiles of CRC and 27 ARGs from The Cancer Genome Atlas, the Gene Expression Omnibus, and MSigDB databases, respectively. CRC tissue samples were classified into two clusters based on the expression pattern of ARGs, and their functional differences were explored. Hub genes were screened using weighted gene co-expression network analysis, univariate analysis, and least absolute selection and shrinkage operator analysis, and validated in cell lines, tissues, or the Human Protein Atlas database. We constructed an ARG-risk model and nomogram to predict prognosis in patients with CRC, which was validated using an external cohort. Multifaceted landscapes, including stemness, tumor microenvironment (TME), immune landscape, and drug sensitivity, between high- and low-risk groups were examined. RESULTS: Patients with CRC were divided into C1 and C2 clusters. Cluster C1 exhibited higher TME scores, whereas cluster C2 had favorable outcomes and a higher stemness index. Eight upregulated hub ARGs (TIMP1, P3H1, SPP1, HAMP, IFI30, ADAM8, ITGAX, and APOC1) were utilized to construct the risk model. The qRT-PCR, Western blotting, and immunohistochemistry results were consistent with those of the bioinformatics analysis. Patients with high risk exhibited worse overall survival (p < 0.01), increased stemness, TME, immune checkpoint expression, immune infiltration, tumor mutation burden, and drug susceptibility compared with the patients with low risk. CONCLUSION: Our results offer a novel CRC stratification based on ARGs and a risk-scoring system that could predict the prognosis, stemness, TME, immunophenotypes, and drug susceptibility of patients with CRC, thereby improving their prognosis. This stratification may facilitate personalized therapies.

Metabolic Recoding of NSUN2-Mediated m5C Modification Promotes the Progression of Colorectal Cancer via the NSUN2/YBX1/m5C-ENO1 Positive Feedback Loop.

The RNA modification, 5-methylcytosine (m5C), has recently gained prominence as a pivotal post-transcriptional regulator of gene expression, intricately intertwined with various tumorigenic processes. However, the exact mechanisms governing m5C modifications during the onset and progression of colorectal cancer (CRC) remain unclear. Here, it is determined that the m5C methyltransferase NSUN2 exhibits significantly elevated expression and exerts an oncogenic function in CRC. Mechanistically, NSUN2 and YBX1 are identified as the "writer" and "reader" of ENO1, culminating in the reprogramming of the glucose metabolism and increased production of lactic acid in an m5C-dependent manner. The accumulation of lactic acid derived from CRC cells, in turn, activates the transcription of NSUN2 through histone H3K18 lactylation (H3K18la), and induces the lactylation of NSUN2 at the Lys356 residue (K356), which is crucial for capturing target RNAs. Together, these findings reveal an intriguing positive feedback loop involving the NSUN2/YBX1/m5C-ENO1 signaling axis, thereby bridging the connection between metabolic reprogramming and epigenetic remodeling, which may shed light on the therapeutic potential of combining an NSUN2 inhibitor with immunotherapy for CRC.

A case report on a nasal and oral cavity involving large solitary fibrous tumor and comprehensive review of case literature.

Solitary fibrous tumor (SFT) represents an uncommon spindle cell sarcoma predominantly situated within soft tissue, with a notably infrequent occurrence in the nasal cavity and paranasal sinuses. In this report, we present a case involving a middle-aged male with a sizable solitary fibrous tumor affecting both the nasal and oral cavities.

The Association Between Dietary Magnesium Intake and Pulmonary Function: Recent Fndings from NHANES 2007-2012.

This article aims to study the correlation between dietary magnesium intake and pulmonary function, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. This cross-sectional study examined representative samples of adults from the USA (n = 818; NHANES 2007-2012) to explore the correlation between magnesium intake and pulmonary function. We obtained the average magnesium intake over 2 days, as well as measured pulmonary function parameters, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow rate (PEF), and forced expiratory flow between 25 and 75% of FVC (FEF25-75%). Weighted multivariable linear regression was used to investigate the relationship between magnesium intake and pulmonary function. Additionally, subgroup analyses, interaction tests, and sensitivity analyses were conducted. Weighted multiple linear regression models revealed a significant positive correlation between magnesium and pulmonary function, even after adjusting for all included confounding variables. When we categorized magnesium intake into tertiles, we found that participants in the highest tertile of magnesium intake had significantly higher values for FVC (ß: 898.54, 95%CI: 211.82-1585.25), FEV1 (ß: 858.16, 95%CI: 212.41-1503.91), FEV1/FVC (ß: 0.024, 95%CI: 0.004-0.044), PEF (ß: 1324.52, 95%CI: 481.71-2167.33), and FEF25-75% (ß: 831.39, 95%CI: 84.93-1577.84). Upon stratifying the data by age and sex, it was observed that this positive correlation was particularly pronounced among men aged 40-79. At the same time, the stability of the results was further confirmed by sensitivity analyses. This study suggested that dietary magnesium intake may improve pulmonary function.

Dual-mode tunable absorber based on quasi-bound states in the continuum.

In this Letter, we propose a novel, to the best of our knowledge, dual-mode tunable absorber that utilizes quasi-bound states in the continuum (q-BIC) based on the periodically arranged silicon cylinders tetramer. By introducing asymmetry perturbation through manipulating the diameters of diagonal cylinders in the all-dielectric structure, the symmetry-protected BIC (SP-BIC) transforms into q-BIC, leading to the emergence of one transmission and one reflection Fano-like resonant mode. The relationship between the quality factor of each mode and the asymmetry parameter α is analyzed, revealing an exponential dependence with an exponent of -1.75, i.e., Q ∝ α-1.75. To explain the underlying physics, multipole decomposition analysis and Aleksandra's theory are applied. Subsequently, a monolayer graphene is introduced to the all-dielectric structure to demonstrate the application of the dual-mode tunable absorber. When the critical coupling condition is satisfied, each mode can achieve the theoretical maximum absorption, demonstrating the distinctive capability of our proposed absorber for tuning and efficient light absorption. This research provides valuable insights into light-matter interactions and opens up possibilities for optical modulation and the development of graphene-based devices.

m6A and m5C modification of GPX4 facilitates anticancer immunity via STING activation.

Cancer immunotherapy is arguably the most rapidly advancing realm of cancer treatment. Glutathione peroxidase 4 (GPX4) has emerged as the vital enzyme to prevent lipid peroxidation and maintain cellular redox homeostasis. However, the mechanism of GPX4 in the regulation of cancer immunotherapy of colon adenocarcinoma (COAD) are incompletely understood. In pan-cancer analysis, we found that GPX4 showed remarkably upregulated expression and exhibited significant association with overall survival in multiple cancer types, especially COAD. Furthermore, upregulated GPX4 expression was positively correlated with increased immune cells infiltration and enhanced expression of immunomodulators. Mechanistically, RBM15B- and IGFBP2-mediated N6-methyladenosine (m6A) modification and NSUN5-mediated 5-methylcytosine (m5C) modification of GPX4 facilitated anticancer immunity via activation of cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (STING) signaling by maintaining redox homeostasis in COAD. The risk model and nomogram model constructed based on the GPX4-derived genes further confirmed the prognostic and treatment-guiding value of GPX4. In all, our study demonstrated that m6A and m5C modification of GPX4 may be a promising target for cancer immunotherapy via activating the cGAS-STING signaling pathway in COAD.

The association between dietary approaches to stop hypertension diet and bone mineral density in US adults: evidence from the National Health and Nutrition Examination Survey (2011-2018).

This study aimed to investigate the relationship between the dietary approaches to stop hypertension (DASH) dietary patterns and bone mineral density (BMD) in adults residing in the United States. To achieve this, data from the National Health and Nutrition Examination Survey (NHANES) database for 2011-2018 were utilized. This study utilized the NHANES database from 2011 to 2018, with a sample size of 8,486 US adults, to investigate the relationship between the DASH diet and BMD. The DASH diet was assessed based on nine target nutrients: total fat, saturated fat, protein, fiber, cholesterol, calcium, magnesium, sodium and potassium. The primary outcome measures were BMD values at the total BMD, thoracic spine, lumbar spine, and pelvis. Multivariable linear models were employed to analyze the association between the DASH diet and BMD. Interaction tests, subgroup, and sensitivity analysis were also followed. A negative correlation was observed between the DASH diet and total BMD (OR: - 0.003 [95%CI: - 0.005, - 0.001), pelvic (OR: - 0.005 [95%CI: - 0.007, - 0.002]), and thoracic BMD (OR: - 0.003 [95%CI: - 0.005, - 0.001]). However, the DASH diet does not appear to have a particular effect on lumbar spine BMD (OR: - 0.002 [95%CI: - 0.004, 0.001]). Similarly, when the DASH diet was categorized into tertiles groups, the relationship with total BMD, pelvic BMD, thoracic BMD, and lumbar spine BMD remained consistent. Furthermore, we performed a sensitivity analysis by converting BMD to Z-scores, and the results remained unchanged. Subgroup analyses and interaction tests indicated no significant dependence of BMI, gender, smoking, hypertension, and diabetes on the observed association (all p for interactions > 0.05). The DASH diet has been identified as potentially reducing total BMD, while specifically impacting thoracic and pelvic BMD. However, it appears to have no significant effect on lumbar spine BMD.

Surgical treatment of carotid blowout syndrome after radiotherapy for head and neck malignant tumors: a single-center experience.

To explore the treatments for and manifestations of carotid blowout syndrome (CBS) and to further explore the critical role of high-flow bypass combined with parent artery isolation. The clinical data of nine patients with radiotherapy-related CBS who were admitted to our hospital from March 2020 to March 2023 were retrospectively analyzed. Relevant literature was reviewed. From March 2020 to March 2023, nine CBS patients were admitted to Tianjin Huanhu Hospital, including eight males and one female. Digital subtraction angiography was performed for all the patients; all the pseudoaneurysms were located at the petrous segment of the internal carotid artery. A balloon occlusion test was performed on four patients, which was tolerated by all patients. CT and MRI scans showed seven cases of osteonecrosis combined with infection and two cases of tumor recurrence. Emergency permanent parent artery occlusion was performed on six patients, aneurysm embolization was completed in one case, covered stent implantation was performed in one patient, and three cases were treated by cerebral bypass surgery (including two patients with failed interventional treatment). Rebleeding was found in two patients, and no rebleeding was found in the bypass group. Paralysis was found in three patients, and asymptomatic cerebral infarction without permanent neurologic impairment was found in three patients. Two patients died due to tumor progression. Emergency occlusion surgery is lifesaving in the acute phase of CBS. Endovascular therapy cannot prevent the progression of pseudoaneurysms or lower the recurrence rate of bleeding events. High-flow bypass combined with parent artery isolation is a safe and effective method that may facilitate further surgical treatment. Further research is warranted.

CRISPR/Cas9: a powerful tool in colorectal cancer research.

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide and seriously threatens human health. The clustered regulatory interspaced short palindromic repeat/CRISPR-associate nuclease 9 (CRISPR/Cas9) system is an adaptive immune system of bacteria or archaea. Since its introduction, research into various aspects of treatment approaches for CRC has been accelerated, including investigation of the oncogenes, tumor suppressor genes (TSGs), drug resistance genes, target genes, mouse model construction, and especially in genome-wide library screening. Furthermore, the CRISPR/Cas9 system can be utilized for gene therapy for CRC, specifically involving in the molecular targeted drug delivery or targeted knockout in vivo. In this review, we elucidate the mechanism of the CRISPR/Cas9 system and its comprehensive applications in CRC. Additionally, we discussed the issue of off-target effects associated with CRISPR/Cas9, which serves to restrict its practical application. Future research on CRC should in-depth and systematically utilize the CRISPR/Cas9 system thereby achieving clinical practice.

Screening and validation of the optimal panel of reference genes in colonic epithelium and relative cancer cell lines.

Real-time quantitative polymerase chain reaction (RT-qPCR) is the most common method to determine mRNA expression, and Minimum Information for Publication of RT-qPCR Experiments (MIQE) proposes that a panel of reference genes for RT-qPCR is conducive to obtaining accurate results. This study aimed to screen and verify the optimal panel of reference genes in colorectal cancer (CRC) and normal colonic cell lines. In the study, eight candidate reference genes (GAPDH, ACTB, 18S, PPIA, B2M, SDHA, GUSB, and YWHAZ) were selected for RT-qPCR to detect their expression in NCM460, HT29, HCT116, SW480, SW620, DLD-1, LOVO and RKO cell lines. The stability of reference genes and the optimal panel were evaluated by geNorm, NormFinder, and BestKeeper software. As results, the expression levels of candidate reference genes differed in the colonic epithelial cell lines, and the number of optimal panel of reference genes is two. B2M and YWHAZ were the two most stable reference genes for NCM460, HCT116, SW620, LOVO, and RKO cell lines, while only one of B2M and YWHAZ was most stable in HT29 and SW480 cells. In DLD-1 cells, the stability of B2M and YWHAZ ranked 3rd and 6th, PPIA and GUSB were the most stable two. Furthermore, the YWHZA + B2M performed smaller intragroup differences than other panel or single reference gene. In conclusion, this study indicates the optimal panel of reference genes is YWHZA + B2M for the NCM460, HCT116, SW620, LOVO, RKO, SW480, and HT29 cell lines, but it is PPIA + GUSB in DLD-1 cell lines.

[A case of sinonasal inverted papilloma with malignant transformation and distant metastasis: a 10-year follow-up report].

Sinonasal inverted papilloma（SNIP） is a kind of benign tumor originating from the nasal cavity and paranasal sinuses, accounting for 70% of papillomas. The incidence of the disease is more common in males, with an average age of 50-60 years. It is most likely to occur in unilateral maxillary sinus and ethmoid sinus, followed by sphenoid sinus and frontal sinus.It has the characteristics of local invasion, high recurrence rate and malignant tendency, and most malignant transformation into squamous cell carcinoma. Endoscopic nasal resection and appropriate adjuvant therapy can help to reduce the recurrence rate and inhibit further deterioration. We report the results of a 10-year follow-up of a SNIP patient, including the clinical manifestations, recurrence course and treatment plan during the 10 years. The patient underwent multiple nasal endoscopic surgeries, and had a recurrence of multiple focal attachment pattern, and finally had direct invasion and distant metastasis. Tumor recurrence and further deterioration persisted despite the use of a comprehensive treatment.

Topological plasmons in stacked graphene nanoribbons.

In this Letter, we theoretically study the topological plasmons in Su-Schrieffer-Heeger (SSH) model-based graphene nanoribbon (GNR) layers. We find that for the one-dimensional (1D) stacked case, only two topological modes with the field localized in the top or bottom layer are predicted to exist by the Zak phase. When we further expand the stacked 1D GNR layers to two-dimensional (2D) arrays in the in-plane direction, the topology is then characterized by the 2D Zak phase, which predicts the emergence of three kinds of topological modes: topological edge, surface, and corner modes. For a 2D ribbon array with Nx × Ny units, there are 4(Ny - 1), 4(Nx - 1), and 4 topological edge, surface, and corner modes, and the field is highly localized at the edge/surface/corner ribbons. This work offers a platform to realize topological modes in GNRs and could be important for the design of topological photonic devices such as lasers and sensors.

Etiology and clinical characteristics of primary epistaxis.

Background: Primary epistaxis (rupture of nasal artery vessels) is a common emergency, but the related factors are still controversial. This study collected the data on primary epistaxis patients and healthy people undergoing a physical examination at the same center to explore and classify primary epistaxis by its characteristics. Methods: Primary epistaxis was divided into septal epistaxis and non-septal epistaxis, and logistic regression was performed to determine the risk factors. Results: In total, 196 cases of septal epistaxis and 127 cases of non-septal epistaxis, and the control group was 182 healthy subjects. There were significant differences in sex, drinking history, hypertension history and hyperlipidemia between the bleeding group and the control group, but no correlation with smoking, diabetes, cardiovascular and cerebrovascular events, or anticoagulant drug use. In the age group of 26-40 years it was related to alcohol consumption and hypertension, for those aged 41-55 years it was related to hypertension, in the age group of 56-70 years it was related to hypertension, high triglyceride and high apolipoprotein B levels, and no related factors were found in the age group >70 years. The risk factors for non-septal cases were increased low-density lipoprotein (LDL) [P=0.035; odds ratio (OR), 2.450; 95% confidence interval (CI): 1.067-5.624], male sex (P=0.002; OR, 3.136; 95% CI: 1.501-6.554), and younger age (P=0.000; OR, 0.941; 95%CI: 0.920-0.962). All patients with nosebleed underwent nasal endoscopy and the bleeding site was successfully located and treated with electrocoagulation. No further bleeding or serious complications occurred after 6 months of follow-up. Conclusions: Primary epistaxis is more common in males and is related to alcohol consumption, hypertension, and hyperlipidemia. In the young age groups, male sex, and increased LDL were high risk factors for non-septal hemorrhage in winter and spring. Nasal endoscopy and electrocoagulation are safe and effective.

Cumulative effects of temperature on blood pressure during pregnancy: A cohort study of differing effects in three trimesters.

BACKGROUND: Little is known about the non-linear cumulative effects of temperature on blood pressure (BP) during pregnancy. We investigated the differing effects of daily ambient temperature on BP for up to 30 days in three trimesters. METHODS: The first, second, and third trimester analyses included 2547, 2299, and 2011 pregnant women, respectively, from a prospective cohort in Nanjing from January 2017 to January 2020. BP was measured at each follow-up visit. The individual daily temperature exposures were calculated for 30 days prior to the follow-up date. The Distributed Lag Non-linear Model was used to investigate the relationship between temperature and BP in each trimester. RESULTS: Temperatures under 15 °C elevate systolic, diastolic BP, and mean arterial pressure (SBP, DBP, and MAP) in the first trimester, while temperatures above 15 °C reduce SBP in the second and third trimesters. By using Distributed Lag Linear Models, we estimated that with a 1 °C decrease in daily temperature, the SBP and DBP increased by 0.32 (95 % CI: 0.12, 0.52) and 0.23 (95 % CI: 0.07, 0.39) mmHg, respectively, in the first trimester with a 20-day cumulative lag, while with a 1 °C increase in daily temperature, the SBP decreased by 0.23 (0.35, 0.10) mmHg in the third trimester with a 30-day cumulative lag. The significant effects of temperature mainly manifested between 2 and 4 weeks of exposure. CONCLUSIONS: Temperature has different effects on BP over three trimesters. Protective measures to reduce cold-related BP rise will help reduce the risk of hypertensive disorders of pregnancy.

m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine.

Background: The RNA modification 5-methylcytosine (m5C) is one of the most prevalent post-transcriptional modifications, with increasing evidence demonstrating its extensive involvement in the tumorigenesis and progression of various cancers. Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related deaths worldwide. However, the role of m5C modulators in shaping tumor microenvironment (TME) heterogeneity and regulating immune cell infiltration in CRC requires further clarification. Results: The transcriptomic sequencing data of 18 m5C regulators and clinical data of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and systematically evaluated. We found that 16 m5C regulators were differentially expressed between CRC and normal tissues. Unsupervised cluster analysis was then performed and revealed two distinct m5C modification patterns that yielded different clinical prognoses and biological functions in CRC. We demonstrated that the m5C score constructed from eight m5C-related genes showed excellent prognostic performance, with a subsequent independent analysis confirming its predictive ability in the CRC cohort. Then we developed a nomogram containing five clinical risk factors and the m5C risk score and found that the m5C score exhibited high prognostic prediction accuracy and favorable clinical applicability. Moreover, the CRC patients with low m5C score were characterized by "hot" TME exhibiting increased immune cell infiltration and higher immune checkpoint expression. These characteristics were highlighted as potential identifiers of suitable candidates for anticancer immunotherapy. Although the high m5C score represented the non-inflammatory phenotype, the CRC patients in this group exhibited high level of sensitivity to molecular-targeted therapy. Conclusion: Our comprehensive analysis indicated that the novel m5C clusters and scoring system accurately reflected the distinct prognostic signature, clinicopathological characteristics, immunological phenotypes, and stratifying therapeutic opportunities of CRC. Our findings, therefore, offer valuable insights into factors that may be targeted in the development of precision medicine-based therapeutic strategies for CRC.