Neoadjuvant chemotherapy or upfront surgery in hepatoblastoma: A multicenter retrospective study.

BACKGROUND: We retrospectively investigated the role of neoadjuvant chemotherapy in low-risk patients with hepatoblastoma (HB) who underwent curative resection between February 2009 and December 2017. We also verified the feasibility of the risk stratification system to select the optimal patients for upfront surgery. PROCEDURE: We compared 5-year overall survival (OS) and event-free survival (EFS) between the upfront surgery (n = 26) and neoadjuvant chemotherapy (n = 104) groups at three oncology centers in Beijing, China. To reduce the effect of covariate imbalance, propensity score matching (PSM) was used. We explored whether preoperative chemotherapy affected surgical outcomes and identified the risk factors for events and death, including resection margin status, PRETreatment EXTent of disease stages, age, sex, pathology classification, and α-fetoprotein levels. RESULTS: The median follow-up period was 64 (interquartile range 60-72) months. After PSM, 22 pairs of patients were identified, and the patient characteristics were similar for all variables included in PSM. In the upfront surgery group, the 5-year EFS and OS rates were 81.8% and 86.3%, respectively. In the neoadjuvant chemotherapy group, the 5-year EFS and OS rates were 81.8% and 90.9%, respectively. No significant differences in EFS or OS were observed between the groups. Pathological classification was the only risk factor for death, disease progression, tumor recurrence, other tumors found during HB diagnosis, and death from any cause (p = .007 and .032, respectively). CONCLUSIONS: Upfront surgery achieved long-term disease control in low-risk patients with resectable HB, thus reduced the cumulative toxicity of platinum-based chemotherapy drugs.

[Bowel Sounds Detection Method and Experiment Based on Multi-feature Combination].

Bowel sounds is an important indicator to monitor and reflect intestinal motor function, and traditional manual auscultation requires high professional knowledge and rich clinical experience of doctors. In addition, long-time auscultation is time-consuming and laborious， which may lead to misjudgment caused by subjective error. To solve the problem, firstly, the wavelet transform is used to preprocess the bowel sounds signal for noise reduction and enhancement. Secondly, three typical features of intestinal sound were extracted. According to the combination of these features, a three-stage decision was designed to carry out multi-parameter and multi-feature joint threshold detection. This algorithm realized the detection of bowel sound signal and the location of its start and end points, making it possible that the complete bowel sound signal was extracted effectively. In this study, a large number of clinical data and label of bowel sounds were collected, and a new effective evaluation method was proposed to verify the proposed method. The accuracy rate is 83.51%. Results of this study will provide systematic support and theoretical guarantee for the diagnosis of intestinal diseases and the monitoring of postoperative intestinal function recovery of patients.

miR-128 participates in the pathogenesis of chronic constipation by regulating the p38α/M-CSF inflammatory signaling pathway.

Chronic constipation (CC) is a gastrointestinal disorder that adversely affects the quality of life. MicroRNAs are involved in the pathogenesis of functional gastrointestinal disorders. This study aims to investigate the molecular mechanism of microRNA-128 in CC. Here, we successfully constructed a murine model of CC based on morphine and rhubarb. The expression of stem cell factor (SCF) and neuron-specific enolase (NSE) was low in the models. Using miRNA array and bioinformatic analysis, we predicted and confirmed the expression of miR-128 and its downstream target genes in CC model. Compared with the control group, CC group showed a significant downregulation of miR-128 and upregulation of p38α and macrophage colony-stimulating factors (M-CSFs). Moreover, we observed elevated inflammatory cytokine and decreased anti-inflammatory cytokine levels in colonic tissues. Furthermore, coculture assays indicated that regulating expression of miR-128 in colonic epithelial cells induced the secretion of IL-6 and TNF-α by macrophages. In conclusion, our study demonstrated that miR-128 regulated the p38α/M-CSF signaling pathway to promote chronic inflammatory responses and changes in the immune microenvironment of the colon, thereby offering potential insights into the pathogenesis of CC and therapeutic targets for its treatment.NEW & NOTEWORTHY In this study, we constructed a murine model and identified a novel signaling mechanism involved in the chronic constipation progression. Our findings on the role of miR-128/p38α/M-CSF axis provide new insights into the treatment of chronic constipation.

Impact of microscopically margin-positive resection on survival in children with hepatoblastoma after hepatectomy: a retrospective cohort study.

BACKGROUND: Impact of R1 (microscopically margin-positive) resection on survival of patients with hepatoblastoma (HB) remains debatable. This study aimed to compare the long-term outcomes of R0 (microscopically margin-negative) and R1 resection for HB in children after hepatectomy. METHODS: We retrospectively reviewed files of children with HB who underwent resection at our institution between September 1, 2005, and November 30, 2017. Survival analyses and prognostic factors were evaluated using Kaplan-Meier curves and Cox regression models. RESULTS: Of 259 patients, 218 (84.2%) underwent R0 and 41 (15.8%) R1 resection. After adjusting for confounding factors, R1 resection demonstrated non-significantly lower overall survival (OS: hazard ratio [HR] = 0.75; 95% CI 0.34-1.64) and shorter event-free survival (EFS: HR = 0.97; 95% CI 0.53-1.78) rates than R0 resection. However, stratified analysis showed significantly increased risk of poor OS and EFS in patients with metastasis and mixed epithelial/mesenchymal pathologic subtype in R1 compared with R0 resection (P values for interactions < 0.05). There was no significant difference between R0 resection with metastasis and R1 resection with metastasis in the incidence of local recurrence (P = 0.494); however, a significant difference in the incidence of local recurrence was seen between R0 and R1 resection for subgroups with mixed pathologic subtypes (P = 0.035). CONCLUSIONS: With effective chemotherapy, microscopic margin status may not be associated with survival outcome in children with HB undergoing hepatectomy. However, stratified analysis showed that R1 resection might be associated with decreased survival in children with mixed epithelial/mesenchymal HB, compared with R0 resection, and not affect survival outcomes in those with an epithelial subtype and without metastasis.

Laparoscopic-assisted anorectoplasty for intermediate type rectovestibular fistula: a preliminary report.

PURPOSE: Laparoscopic-assisted anorectoplasty (LAARP) is considered to benefit the male patients with anorectal malformation (ARM). This study evaluates LAARP management for intermediate type rectovestibular fistula (IRVF) in the female patient with ARM. METHODS: Twelve patients with IRVF (aged 3-5 months) underwent LAARP from 2017 to 2019 in our institute. LAARP was performed for mobilization of the rectum, visualization and enlargement of the center of the sphincter muscle complex (SMC) from pelvic and perineal aspects, intra-fistula mucosectomy and rectal pull-through in the SMC with the fourchette and the perineal body unattached. RESULTS: LARRP was performed in all patients without conversion to open procedure. No patient suffered from wound infection, vaginal injury, recurrent fistula and anal stenosis. The parents were satisfied with the appearance of the wound. Rectal prolapse developed in one patient and needed surgical correction. The patients were followed up for a mean of 19.7 months (ranged from 12 to 35 months). CONCLUSION: Our preliminary experience shows that LAARP offers an alternative method of correction for the IRVF with good visualization of the SMC and may diminish the risks of wound dehiscence and vaginal injury.

Normal anorectal musculatures and changes in anorectal malformation.

PURPOSE: We investigated the anorectal musclulature in normal children and anorectal malformations (ARM) to evaluate its role in bowel control mechanism. METHODS: Pelves of 50 neonates died of ARM-unrelated diseases and 16 patients with anorectal malformations (8 high, 5 intermediate, and 3 low ARMs) were dissected and analyzed. RESULTS: Normal anorectal musculature was divided into three muscular tubes: the internal sphincter tube (IAST), longitudinal muscle tube (LMT) and transverse muscle tube (TMT). The LMT came from the outer longitudinal smooth muscle fiber of the rectum and the striated muscle fiber of the levator ani, and the TMT composed of the puborectalis and the external anal sphincter. However, in ARM, the IAST was absent and the LMT, the center of the sphincter muscle complex, was only from the levator ani and could be divided into the pelvic portion and the perineal portion. The former, from the upper rim of the puborectalis to the bulbar urethral, became narrowed and dislocated anteriorly near to the posterior urethra in high ARM and rectal pouch in intermediate ARM. The latter, below the bulbar urethra to the anal dimple, was fused to a column both in high and intermediate ARM. The columnar perineal LMT run downwards and then split, penetrated the superficial part of EAS and terminated at the deep aspect of the skin, to form the anal dimple, which represents the center of the perineal LMT from the perineal aspect. The length of the LMT was longer in high and intermediate ARM than the normal neonate. The columnar perineal LMT and narrowed pelvic LMT could be possibly identified by laparoscopic and perineal approaches retrospectively and widened to allow the passage of the rectum through. CONCLUSIONS: The anorectal musculature in ARM is composed of agenesic LMT and TMT and the narrowed LMT gives anatomical evidence of the center, where the neorectum should pull through.

Laparoscopic surgical technique to enhance the management of anorectal malformations: 330 cases' experience in a single center.

PURPOSE: Laparoscopic-assisted anorectoplasty (LAARP) is considered to benefit the patients with vesico-prostatic fistula. The aim of this study is to present the details of our LAARP technique for improving the short- and long-term outcomes in the patients with high and intermediate types of anorectal malformations (ARMs). METHODS: 330 patients with high-type (174 cases) and intermediate-type (156 cases) anorectal malformation (aged 8 days to 15 years) underwent LAARP from 2001 to 2019. LAARP was performed for full mobilization and resection of the dilated rectum, intra-rectal closure of the fistula, visualization, and enlargement of the center of the longitudinal muscle tube (LMT) from pelvic and perineal aspects. RESULTS: LAARP was performed in all patients and no patient was converted to open procedure. The urethral diverticulum was found in three patients (1.02%, 3/294) according to postoperative protocol voiding cystourethrogram but was not associated with any symptoms such as urinary tract infection and dysuria. Rectal prolapse requiring surgical intervention developed in 25 (7.6%) of 330 patients. Anal stricture occurred in three patients and re-do anoplasty was performed 5 months after LAARP. Anal retraction occurred in two patients and re-pull-through was conducted at 5 and 6 days, respectively, after LAARP. 228 patients who were older than 3 years were followed up. The median follow-up period was 5.8 years (range 3-15 years). 217 patients (95.2%) had voluntary bowel movements; 202 patients (88.6%) were free from soiling or with grade 1 soiling; 30 patients (13.6%) and 25 patients (11.3%) suffered from grade 1 and grade 2 constipation, respectively, while no patient had grade 3 constipation. CONCLUSION: Our experience demonstrates that the LAARP has advantages on rectal mobilization and resection, intra-rectal fistula closure and accurate tunnel formation in the LMT with minimal trauma. The improvement of the short-term and long-term outcomes after LAARP has been shown not only for high-type ARM but also for intermediate-type ARM.

Results of surgical resections with positive margins for children with hepatoblastoma: Case series from a single Asian center.

The influence of margin status on the survival of patients with hepatoblastoma (HB) remains controversial. Here, we report long-term follow-up outcomes of 26 patients with HB who underwent hepatectomy with positive microscopic margins. Although these patients had microscopic residuals, the 5-year overall survival and event-free survival rates of those who had no metastases or macrovascular involvement (MVI) were 86.7% and 80.8%, respectively. This may support the hypothesis that patients with HB who undergo hepatectomy with positive microscopic residuals but without MVI or metastases can also achieve satisfactory survival rate. Further studies in this field are required.

Single-incision laparoscopic-assisted anorectoplasty for treating children with intermediate-type anorectal malformations and rectobulbar fistula: a comparative study.

PURPOSE: Single-incision laparoscopic-assisted anorectoplasty (SILAARP) was compared to posterior sagittal anorectoplasty (PSARP) for treating intermediate-type anorectal malformations (ARMs) with rectobulbar fistula. METHODS: Between December 2011 and January 2016, 48 children with intermediate-type ARMS were treated with SILAARP (n = 34) or PSARP (n = 14) in our centre. Data including demographics, complications, and long-term outcomes were retrospectively compared. RESULTS: No significant difference was observed between both groups in terms of median operative time and complications. The length of postoperative hospital stay was shorter in the SILAARP group than in the PSARP group (6.15 ± 1.10 vs 9.64 ± 4.13 days; p = 0.008). After a mean follow-up of 59.38 ± 13.68 months, the rates of voluntary bowel movements, soiling, and constipation were similar in both groups. Anorectal manometry was performed in 15 and 7 children from the SILAARP and PSARP groups, respectively. Although there were no significant differences in the presence of rectoanal relaxation reflex and high-pressure-zone length, anal canal resting pressure was higher in the SILAARP group than in the PSARP group (33.35 ± 12.95 vs 23.06 ± 8.40 mmHg; p = 0.039). CONCLUSIONS: Both SILAARP and PSARP seemed feasible and effective for treating intermediate-type ARMs with rectobulbar fistula in children. However, SILAARP significantly reduced the length of postoperative hospital stay and improved anal canal resting pressure.

Long-term outcomes after cholecystocolostomy for progressive familial intrahepatic cholestasis.

AIM: To evaluate the long-term efficacy of cholecystocolostomy surgery for progressive familial intrahepatic cholestasis (PFIC). METHODS: From August 2003 to November 2014, 34 clinically diagnosed children, including 11 with familial intrahepatic cholestasis-1 (FIC1), 13 with bile salt export pump (BSEP) disease, five with low γ-glutamyl transpeptidase (GGT) disease (levels <100 U/L), and five with multidrug resistance class III (MDR3) disease with high GGT (>100 U/L), were identified in our center. Data were collected retrospectively from individuals who collectively had 36 surgical operations and two orthotopic liver transplantations (OLT). RESULTS: Serum total bilirubin (0 = 163.54 ± 106.02, 36 months = 23.38 ± 17.66 µmol/L) and bile acid (0 = 325.83 ± 153.09, 36 months = 48.36 ± 79.71 µmol/L) decreased after cholecystocolostomy in PFIC patients (P < 0.001). All patients experienced decreased severity of pruritus (88.2% vs. 16.1%, P < 0.001) and a greater freedom from growth retardation after cholecystocolostomy (-3.35 vs. -1.03, P < 0.001). Defecation frequency increased in PFIC patients after cholecystocolostomy (P = 0.002). Four patients (three with FIC1 and one with BSEP) experienced recurrence of cholestasis and two underwent reoperation. Two BSEP patients underwent OLT. One patient with BSEP and one patient with MDR3 died due to severe diarrhea and dehydration; one BSEP patient died of intractable constipation. CONCLUSIONS: This is the first long-term, large-scale analysis of cholecystocolostomy approaches for PFIC. Approaches single and well tolerated, and generally result in improvement of pruritus and cholestasis.

CRISPR/Cas9 screening: unraveling cancer immunotherapy's 'Rosetta Stone'.

Clustered regularly interspaced palindromic repeats (CRISPR)-based technology, a powerful toolset for the unbiased functional genomic screening of biological processes, has facilitated several scientific breakthroughs in the biomedical field. Cancer immunotherapy has advanced the treatment of numerous malignancies that previously had restricted treatment options or unfavorable outcomes. In the realm of cancer immunotherapy, the application of CRISPR/CRISPR-associated protein 9 (Cas9)-based genetic perturbation screening has enabled the identification of genes, biomarkers, and signaling pathways that govern various cancer immunoreactivities, as well as the development of effective immunotherapeutic targets. In this review, we summarize the advances in CRISPR/Cas9-based screening for cancer immunotherapy and outline the immunotherapeutic targets identified via CRISPR screening based on cancer-type classification.

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.

Degree of transverse colon ptosis: an alternative surrogate for evaluation of slow transit constipation.

Background: Although transverse colon ptosis (TCP) is commonly diagnosed in patients with constipation, it has not attracted significant attention in the evaluation of constipation. Herein, we assessed the correlation between TCP-related radiological parameters and the severity of slow transit constipation (STC). Methods: This study was a single-center retrospective cohort study, with participants enrolled between 2012 and 2020 in Zhongnan Hospital of Wuhan University, China. STC was diagnosed according to Rome IV criteria and results of colonic transit test (CTT); healthy volunteers were also recruited as controls. All participants were examined using abdominal X-rays (AXRs) to acquire the radiological parameters related to TCP. Among these parameters, the degree of TCP (DTCP) was defined as the vertical distance from the top of the splenic flexure to the lowest point of the reverse colon. The Wexner Constipation Score and Hospital Anxiety and Depression Scale were used to assess clinical severity. After multivariable linear regression, the correlations between radiological parameters and severity of STC were investigated. We also explored the differences in radiological parameters between the operation and the conservative group. Results: The study included 139 patients with STC and 125 healthy people in as the normal control (NC). Patients with STC probably had larger DTCPs than those in the NC group (242.27±25.86 vs. 93.00±32.57 mm; P<0.001). Pearson correlation analysis showed that TCP-related parameters were consistent with the symptom severity of STC [e.g., parameter DTCP was strongly correlated with Wexner Constipation Score, with a ß coefficient (95% CI) of 8.63 (8.24-9.02), P<0.001]. Multivariable linear regression models showed that patients with a larger DTCP were more likely to undergo surgery (23.67; 95% CI: 1.40-45.94; P=0.04). Conclusions: TCP-related parameters, especially the DTCP, may serve as novel and feasible alternative indices for the assessment of STC. However, the potential value of DTCP in assisting the evaluation of STC needs to be confirmed in study with a larger sample size.

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.

Trans-Anastomotic Drainage Tube Placement After Hand-Sewn Anastomosis in Patients Undergoing Intersphincteric Resection for Low Rectal Cancer: An Alternative Drainage Method.

Anastomotic leakage (AL) is a common complication after intersphincteric resection (ISR). It significantly reduces quality of life and causes great distress to patients. Although traditional drainage (e.g., anal and pelvic catheters) may reduce the impact of AL to some extent, their role in reducing the incidence of AL remains controversial. In this study, we developed a novel drainage technique involving the placement of drainage tubes through the gap between sutures during handsewn anastomosis, to reduce the occurrence of anastomotic leakage. We retrospectively analyzed 34 consecutive patients who underwent intersphincteric resection requiring handsewn anastomosis between February 1, 2017, and January 1, 2021. Patients were classified into the trans-anastomotic drainage tube group (TADT, n = 14) and the non-TADT group (n = 20) based on whether trans-anastomotic tube placement was performed. The incidence of postoperative complications, such as AL, was compared between the two groups, and anal function of patients at 1-year post-ISR was evaluated. Six cases of AL occurred in the non-TADT group, while none occurred in the TADT group; this difference was statistically significant (p=0.031). The TADT group also had a shorter hospital stay (p=0.007). There were no other significant intergroup differences in operation time, blood loss, pain score, anastomotic stenosis, intestinal obstruction, or incidence of wound infection. In the 30 patients (88.2%) evaluated for anal function, there were no significant intergroup differences in stool frequency, urgency, daytime/nocturnal soiling, Wexner incontinence score, or Kirwan grading. Taken together, trans-anastomotic tube placement is a novel drainage method that may reduce AL after ISR requiring handsewn anastomosis and without adversely affecting anal function.

Characterization of Circular RNA Expression Profiles in Colon Specimens of Patients with Slow Transit Constipation.

Background: Slow transit constipation (STC) is a clinical syndrome characterized by a decreased urge to defecate and delayed colonic transit. Circular RNAs (circRNAs) are a recently discovered class of regulatory RNAs that have emerged as critical biomarkers and regulators of various diseases. However, the expression profiles and mechanisms underlying circRNA regulation in human STC tissues have not been explored. Methods: High-throughput RNA sequencing technology was used to compare the differences in circRNA expression profiles in colon samples taken from patients with STC or controls. Bioinformatics analyses were performed on the host genes of the differentially expressed circRNAs (DE-circRNAs), a competing endogenous RNA network was constructed, and the expression levels of some DE-circRNAs were verified using quantitative real-time polymerase chain reactions (qRT-PCR). Results: There were 190 DE-circRNAs identified in the STC group. Bioinformatics analysis predicted that the DE-circRNAs were enriched in the relaxation of smooth muscle, actin binding, actin cytoskeleton organization, dilated cardiomyopathy, and cardiac muscle contraction. These results suggest that muscle diseases may be related to the pathogenesis of STC. The expression levels of the 12 most differentially expressed circRNAs were verified using qRT-PCR. In addition, circRNA-microRNA-mRNA regulatory networks were constructed using the 8 most significant circRNAs. Some mRNAs predicted to be closely related to smooth muscle function were found in these networks. Conclusions: This study provides a helpful blueprint for researchers to select candidate circRNAs for further study of the pathogenesis of STC and screen potential biomarkers or targets for use in the diagnosis and treatment of STC.

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.