Transcutaneous Auricular Vagus Nerve Stimulation Ameliorates Preeclampsia-Induced Apoptosis of Placental Trophoblastic Cells Via Inhibiting the Mitochondrial Unfolded Protein Response.

Preeclampsia is a serious obstetric complication. Currently, there is a lack of effective preventive approaches for this disease. Recent studies have identified transcutaneous auricular vagus nerve stimulation (taVNS) as a potential novel non-pharmaceutical therapeutic modality for preeclampsia. In this study, we investigated whether taVNS inhibits apoptosis of placental trophoblastic cells through ROS-induced UPRmt. Our results showed that taVNS promoted the release of acetylcholine (ACh). ACh decreased the expression of UPRmt by inhibiting the formation of mitochondrial ROS (mtROS), presumably through M3AChR. This reduced the release of pro-apoptotic proteins (cleaved caspase-3, NF-κB-p65, and cytochrome C) and helped preserve the morphological and functional integrity of mitochondria, thus reducing the apoptosis of placental trophoblasts, improving placental function, and relieving preeclampsia. Our study unravels the potential pathophysiological mechanism of preeclampsia. In-depth characterization of the UPRmt is essential for developing more effective therapeutic strategies for preeclampsia targeting mitochondrial function.

Clinical Characteristics and Epidemiological Analysis of Pneumocystis Jirovecii Pneumonia Infection in Kidney Transplant Patients with Trimethoprim-Sulfamethoxazole Dose Reduction Prophylaxis Strategy.

Background: The administration of trimethoprim-sulfamethoxazole (TMP-SMX) for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) has proven to be highly efficacious in individuals who have undergone kidney transplantation. Nevertheless, the potential for severe adverse reactions associated with this treatment cannot be overlooked, and the determination of an optimal dosage regimen continues to be a matter of investigation. The current study evaluated the effectiveness of low-dose TMP-SMX for PJP prophylaxis in kidney transplant patients and conducted an analysis of the clinical characteristics and epidemiological trends in patients with PJP infection. Methods: This retrospective analysis studied electronic medical records of 1763 kidney transplant recipients from 2017 to 2020. These patients were initially prescribed a daily half-strength TMP-SMX (40 mg/200 mg), and the efficacy of this regimen was assessed during a follow-up period of 3-51 months. Results: Under our PJP prevention and adjustment strategy, 24 patients were infected with PJP. The overall morbidity of PJP infection in our study was 1.36%, corroborates with findings from previously published studies. Among these 24 patients, up to 87.5% had their dosage adjusted due to increased creatinine or other adverse reactions, the most frequent dose was daily quarter-strength TMP-SMX (20 mg/100 mg). TMP-SMX prophylaxis successfully postponed and distributed the onset of PJP, with the mean duration from transplantation to the occurrence of PJP being 13.50±7.11 months. Conclusion: Daily administration of half-strength TMP-SMX can effectively prevent PJP, and prolonging prophylaxis with this medication may potentially reduce the incidence of infection.

Prenatal chromosomal microarray analysis and karyotyping in fetuses with isolated choroid plexus cyst: A retrospective case-control study.

OBJECTIVES: To evaluate the the diagnostic yield of chromosomal microarray analysis (CMA) in fetuses with isolated CPC (iCPC). METHODS: A total of 315 fetuses with iCPC (iCPC group) and 364 fetuses without abnormal ultrasound findings (control group) were recruited between July 2014 to March 2018. RESULTS: The overall diagnostic yield of chromosomal abnormalities by CMA and karyotyping in iCPC group was up to 4.1 %, higher than 1.4 % in the control group, p < 0.05. The detection rate of pathogenic or likely pathogenic copy number variants (CNVs) with clinical significance by CMA in iCPC group (1.3 %) was higher than in control group (0 %), p < 0.05. According to the type of chromosome abnormalities, the missed diagnosis rate of non-invasive prenatal testing (NIPT) was 1.6 % in our study. CONCLUSIONS: The presence of iCPC on ultrasound examination suggests a potential indication for genetic counseling. Karyotyping and chromosomal microarray analysis may be considered for fetuses with iCPC. It is important to be aware of the limitations of non-invasive prenatal testing, as there is a possibility of residual risk.

Prognostic nomogram and epidemiological analysis for lung atypical carcinoid: A SEER database and external validation study.

PURPOSE: Our study aims to delineate the epidemiological distribution of pulmonary carcinoids, including atypical carcinoid (AC) and typical carcinoid (TC), identify independent prognostic factors, develop an integrative nomogram and examine the effects of various surgical modalities on atypical carcinoid-specific survival (ACSS). METHODS: Joinpoint regression model and age-group distribution diagram were applied to determine the epidemiological trend of the pulmonary carcinoids. Univariate and least absolute shrinkage and selection operator (LASSO)-based Cox regression models were used to identify independent factors, and a nomogram and web-based predictor were developed to evaluate prognosis of AC patients individually. We performed Kaplan-Meier survival analyses to compare the scope of various surgical interventions, with and without G-computation adjustment, utilising restricted mean survival time (RMST) to assess survival disparities. RESULTS: A total of 1132 patients were recruited from the Surveillance, Epidemiology, and End Results database (SEER) and a separate medical centre in China. The mean age of AC patients was 63.4 years and a smoking history was identified in 79.8% of AC patients. Joinpoint analysis shows rising annual rates of new AC and carcinoid cases among lung cancers. Both the proportion of pulmonary TC and AC within the total lung cancer population exhibits an L-shaped trend across successive age groups. The nomogram predicted 1, 3 and 5 years of AC with excellent accuracy and discrimination. Kaplan-Meier survival analyses, conducted both pre- and post-adjustment, demonstrated that sublobar resection's survival outcomes were not inferior to those of lobectomy in patients with stage I-II and stage III disease. CONCLUSION: This study is the first to reveal epidemiological trends in pulmonary carcinoids over the past decade and across various age cohorts. For patients with early-stage AC, sublobar resection may be a viable surgical recommendation. The established nomogram and web-based calculator demonstrated decent accuracy and practicality.

Spectral-Spatial Transformer for Hyperspectral Image Sharpening.

Convolutional neural networks (CNNs) have recently achieved outstanding performance for hyperspectral (HS) and multispectral (MS) image fusion. However, CNNs cannot explore the long-range dependence for HS and MS image fusion because of their local receptive fields. To overcome this limitation, a transformer is proposed to leverage the long-range dependence from the network inputs. Because of the ability of long-range modeling, the transformer overcomes the sole CNN on many tasks, whereas its use for HS and MS image fusion is still unexplored. In this article, we propose a spectral-spatial transformer (SST) to show the potentiality of transformers for HS and MS image fusion. We devise first two branches to extract spectral and spatial features in the HS and MS images by SST blocks, which can explore the spectral and spatial long-range dependence, respectively. Afterward, spectral and spatial features are fused feeding the result back to spectral and spatial branches for information interaction. Finally, the high-resolution (HR) HS image is reconstructed by dense links from all the fused features to make full use of them. The experimental analysis demonstrates the high performance of the proposed approach compared with some state-of-the-art (SOTA) methods.

Reclassification of Sabulilitoribacter multivorans and Sabulilitoribacter arenilitoris as Flaviramulus multivorans comb. nov. and Wocania arenilitoris comb. nov., respectively, based on genome sequence analysis.

Rapid advancements in DNA sequencing technologies are providing new approaches for bacterial taxonomy. The genus Sabulilitoribacter is a member of the family Flavobacteriaceae, which consists of more than 150 genera. In this study, genome sequence analysis was conducted to revisit the taxonomic status of Sabulilitoribacter arenilitoris and Sabulilitoribacter multivorans, the only two species of this genus. Genome sequence based phylogeny analysis showed that the genus Sabulilitoribacter was non-monophyletic: S. multivorans, the type species of genus Sabulilitoribacter, was clustered with the type species of the genus Flaviramulus, whereas S. arenilitoris formed a robust cluster with the only two species of the genus Wocania. The values of average amino acid identity, genome-wide average nucleotide identity, alignment fractions and some phenotypic features showed that S. multivorans was more closely related with the type species of the genus Flaviramulus than with S. arenilitoris, and S. arenilitoris was more closely related with the only two species of the genus Wocania than with S. multivorans. Based on these results, we consequently propose that S. multivorans and S. arenilitoris should be reclassified as Flaviramulus multivorans comb. nov. and Wocania arenilitoris comb. nov. respectively.

Nanostructured TiO2 Arrays for Energy Storage.

Because of their extensive specific surface area, excellent charge transfer rate, superior chemical stability, low cost, and Earth abundance, nanostructured titanium dioxide (TiO2) arrays have been thoroughly explored during the past few decades. The synthesis methods for TiO2 nanoarrays, which mainly include hydrothermal/solvothermal processes, vapor-based approaches, templated growth, and top-down fabrication techniques, are summarized, and the mechanisms are also discussed. In order to improve their electrochemical performance, several attempts have been conducted to produce TiO2 nanoarrays with morphologies and sizes that show tremendous promise for energy storage. This paper provides an overview of current developments in the research of TiO2 nanostructured arrays. Initially, the morphological engineering of TiO2 materials is discussed, with an emphasis on the various synthetic techniques and associated chemical and physical characteristics. We then give a brief overview of the most recent uses of TiO2 nanoarrays in the manufacture of batteries and supercapacitors. This paper also highlights the emerging tendencies and difficulties of TiO2 nanoarrays in different applications.

[Clinical analysis of monochorionic-diamniotic twins with genetic discordance].

OBJECTIVE: To explore the genetic etiology of 5 cases of monochorionic-diamniotic (MCDA) with genetic discordance. METHODS: 148 cases of MCDA twins who were diagnosed by amniocentesis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region from January 2016 to June 2020 were selected as the study subjects. Relevant clinical data of the pregnant women were collected, and amniotic fluid samples of the twins were collected separately. Chromosomal karyotyping analysis and single nucleotide polymorphism array (SNP array) assay were carried out. RESULTS: The results of chromosomal karyotyping analysis showed that 5 of the MCDA twins had inconsistent chromosome karyotypes, with an incidence of 3.4% (5/148). SNP array assay showed that 3 fetuses were mosaics. CONCLUSION: Genetic discordance occurs among MCDA twins, and prenatal counseling for such cases should be given by doctors with experience in medical genetics and fetal medicine, and personalized clinical management should be recommended.

pH-Responsive Hydrogel as a Potential Oral Delivery System of Baicalin for Prolonging Gastroprotective Activity.

Gastric ulcer is one of the most common gastrointestinal diseases, and natural products have obvious advantages in the treatment of gastrointestinal diseases. Baicalin (Bai) extracted from scutellaria baicalensis exhibits anti-inflammatory, antioxidant, and anti-apoptotic activities. Herein, a pH-responsive sodium alginate/polyaspartate/CaCO3 (SA/PASP@CaCO3) in situ hydrogel was established for the oral delivery of Bai. In this study, we detected the gelling properties, mechanical strength, in vitro erosion, and in vitro release behavior of the hydrogels. Meanwhile, the efficiency of Bai/SA/PASP@CaCO3 hydrogel on ethanol-induced acute gastric ulcers, acetic acid-induced chronic gastric ulcers, and H2O2-stimulated human gastric epithelial GES-1 cells was explored. The pathological examination revealed that Bai-loaded hydrogel alleviated acute and chronic gastric ulcers. In vivo and in vitro results further confirmed that Bai/SA/PASP@CaCO3 in situ hydrogels significantly relieved oxidative stress injury. Moreover, through Western blot assay, Bai/SA/PASP@CaCO3 hydrogel was also found to dramatically increase the proteins levels of NRF2, HO-1, and Bcl2, and reduce levels of p-JNK, cleaved-caspase-3 and Bax; through flow cytometry, it was observed to significantly inhibit the H2O2-induced apoptosis of GES-1 cells. Importantly, the Bai/SA/PASP@CaCO3 in situ hydrogel system showed better anti-gastric ulcer efficiency than free drug, and could serve as a potential drug delivery system for the clinical treatment of gastric ulcers.

Inflammation promotes resistance to immune checkpoint inhibitors in high microsatellite instability colorectal cancer.

Inflammation is a common medical complication in colorectal cancer (CRC) patients, which plays significant roles in tumor progression and immunosuppression. However, the influence of inflammatory conditions on the tumor response to immune checkpoint inhibitors (ICI) is incompletely understood. Here we show that in a patient with high microsatellite instability (MSI-H) CRC and a local inflammatory condition, the primary tumor progresses but its liver metastasis regresses upon Pembrolizumab treatment. In silico investigation prompted by this observation confirms correlation between inflammatory conditions and poor tumor response to PD-1 blockade in MSI-H CRCs, which is further validated in a cohort of 62 patients retrospectively enrolled to our study. Inhibition of local but not systemic immune response is verified in cultures of paired T cells and organoid cells from patients. Single-cell RNA sequencing suggests involvement of neutrophil leukocytes via CD80/CD86-CTLA4 signaling in the suppressive immune microenvironment. In concordance with this finding, elevated neutrophil-to-lymphocyte ratio indicates inhibited immune status and poor tumor response to ICIs. Receiver operating characteristic curve further demonstrates that both inflammatory conditions and a high NLR could predict a poor response to ICIs in MSI- CRCs, and the predictive value could be further increased when these two predictors are combined. Our study thus suggests that inflammatory conditions in MSI-H CRCs correlate with resistance to ICIs through neutrophil leukocyte associated immunosuppression and proposes both inflammatory conditions and high neutrophil-to-lymphocyte ratio as clinical features for poor ICI response.

A Single Vaccination of Chimeric Bivalent Virus-Like Particle Vaccine Confers Protection Against H9N2 and H3N2 Avian Influenza in Commercial Broilers and Allows a Strategy of Differentiating Infected from Vaccinated Animals.

H9N2 and H3N2 are the two most important subtypes of low pathogenic avian influenza viruses (LPAIV) because of their ongoing threat to the global poultry industry and public health. Although commercially available inactivated H9N2 vaccines are widely used in the affected countries, endemic H9N2 avian influenza remains uncontrolled. In addition, there is no available avian H3N2 vaccine. Influenza virus-like particles (VLPs) are one of the most promising vaccine alternatives to traditional egg-based vaccines. In this study, to increase the immunogenic content of VLPs to reduce production costs, we developed chimeric bivalent VLPs (cbVLPs) co-displaying hemagglutinin (HA) and neuraminidase (NA) of H9N2 and H3N2 viruses with the Gag protein of bovine immunodeficiency virus (BIV) as the inner core using the Bac-to-Bac baculovirus expression system. The results showed that a single immunization of chickens with 40µg/0.3mL cbVLPs elicited an effective immune response and provided complete protection against H9N2 and H3N2 viruses. More importantly, cbVLPs with accompanying serological assays can successfully accomplish the strategy of differentiating infected animals from vaccinated animals (DIVA), making virus surveillance easier. Therefore, this cbVLP vaccine candidate would be a promising alternative to conventional vaccines, showing great potential for commercial development.

RIOK1 mediates p53 degradation and radioresistance in colorectal cancer through phosphorylation of G3BP2.

RIO Kinase 1 (RIOK1) is involved in various pathologies, including cancer. However, the role of RIOK1 in radioresistance of colorectal cancer (CRC) remains largely unknown. In this study, we reported that RIOK1 was overexpressed in rectal cancer tissue with weaker tumor regression after neoadjuvant chemoradiotherapy (neoCRT). Moreover, higher RIOK1 expression predicted a poor prognosis in patients with rectal cancer. Blockade of RIOK1 using Toyocamycin, a pharmacological inhibitor of RIOK1, or by knocking down its expression, decreased the resistance of CRC cells to radiotherapy in vitro and in vivo. A mechanistic study revealed that RIOK1 regulates radioresistance by suppressing the p53 signaling pathway. Furthermore, we found that RIOK1 and Ras-GAP SH3 domain binding protein 2 (G3BP2) interact with each other. RIOK1 phosphorylates G3BP2 at Thr226, which increases the activity of G3BP2. RIOK1-mediated phosphorylation of G3BP2 facilitated ubiquitination of p53 by murine double minute 2 protein (MDM2). Altogether, our study revealed the clinical significance of RIOK1 in CRC, and therapies targeting RIOK1 might alleviate the CRC tumor burden in patients.

Novel and recurrent ASPM mutations of founder effect in Chinese population.

PURPOSE: Mutations in ASPM are the most common causes of primary microcephaly (MCPH), which is a rare brain developmental disorder with few studies in Chinese population so far. This study aimed to identify the common pathogenic variants of ASPM and estimated the incidence of MCPH5 in Guangxi population. METHODS: We ascertained six MCPH cases caused by ASPM mutations in Guangxi Zhuang Autonomous Region, Whole-exome sequencing (WES) was performed to uncover the causal variants. The haplotype analysis was used to estimate the age of the recurrent variation. RESULTS: Five different pathogenic variants were identified in this batch of MCPH5 cases, including two novel variants p.Ser842fs*9 and p.Lys1340Argfs*29. An rarely reported pathogenic variant, c.1789C>T/p.Arg597* was found to be a founder mutation in local population. We evaluated all ASPM variants detected among 2674 non-microcephalic individuals and estimated the MCPH5 incidence to be 5.03/1,000,000 in Guangxi population. CONCLUSIONS: We reported the first case series of Chinese MCPH cases with ASPM mutation and revealed a highly recurrent founder mutation in this local population. MCPH5 may be the major type of congenital microcephaly in Chinese population.

Altering Ligand Fields in Single-Atom Sites through Second-Shell Anion Modulation Boosts the Oxygen Reduction Reaction.

Single-atom catalysts based on metal-N4 moieties and anchored on carbon supports (defined as M-N-C) are promising for oxygen reduction reaction (ORR). Among those, M-N-C catalysts with 4d and 5d transition metal (TM4d,5d) centers are much more durable and not susceptible to the undesirable Fenton reaction, especially compared with 3d transition metal based ones. However, the ORR activity of these TM4d,5d-N-C catalysts is still far from satisfactory; thus far, there are few discussions about how to accurately tune the ligand fields of single-atom TM4d,5d sites in order to improve their catalytic properties. Herein, we leverage single-atom Ru-N-C as a model system and report an S-anion coordination strategy to modulate the catalyst's structure and ORR performance. The S anions are identified to bond with N atoms in the second coordination shell of Ru centers, which allows us to manipulate the electronic configuration of central Ru sites. The S-anion-coordinated Ru-N-C catalyst delivers not only promising ORR activity but also outstanding long-term durability, superior to those of commercial Pt/C and most of the near-term single-atom catalysts. DFT calculations reveal that the high ORR activity is attributed to the lower adsorption energy of ORR intermediates at Ru sites. Metal-air batteries using this catalyst in the cathode side also exhibit fast kinetics and excellent stability.

RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases.

Introduction: Regulator of chromatin condensation 1 (RCC1) is a major guanine-nucleotide exchange factor for Ran GTPase, and it plays key roles in various biological processes. Previous studies have found that RCC1 may play a role in the development of tumors, but little is known about the relationship between RCC1 and colorectal liver oligometastases (CLOs). Methods: One hundred and twenty-nine pairs of matched human CLO samples, including both primary tumor and its liver metastasis specimens, were subjected to immunohistochemistry to determine the location and expression levels of RCC1. Associations between RCC1 and survival as well as gene expression profiling were explored. Results: In this study, we first observed that RCC1 was mildly increased in CLO tumor tissues compared with normal tissues, and the localization was primarily nuclear. In addition, our study found that high RCC1 expression in liver oligometastases was an independent prognostic marker for unfavorable recurrence-free survival and overall survival (p = 0.036 and p = 0.016). Gene expression profiles generated from microarray analysis showed that RCC1 was involved in pathways including "Myc targets," "E2F targets" and "DNA repair" pathways. Conclusion: Our data indicated that RCC1 was expressed mainly in the nucleus, and strong and significant associations were found between RCC1 expression levels and the survival of CLO patients. These findings indicated that RCC1 may play a role in CLO development.

Prognostic Value of the C-Reactive Protein/Albumin Ratio and Systemic Immune-Inflammation Index for Patients With Colorectal Liver Metastasis Undergoing Curative Resection.

Background: We evaluated the prognostic value of C-reactive protein/albumin (CAR) and systemic immune-inflammation index (SII), which we calculated as neutrophil × platelet/lymphocyte) in patients with colorectal liver metastasis (CRLM) after curative resection. Methods: We retrospectively enrolled 283 consecutive patients with CRLM who underwent curative resection between 2006 and 2016. We determined the optimal cutoff values of CAR and SII using receiver operating curve (ROC) analysis. Overall survival (OS)- and recurrence-free survival (RFS)-related to CAR and SII were analyzed using the log-rank test and multivariate Cox regression methods. Results: We found that a high CAR was significantly associated with poor OS (P < 0.001) and RFS (P = 0.008) rates compared with a low CAR; a high SII was significantly associated with poor RFS (P = 0.003) rates compared with a low SII. The multivariate analysis indicated that CAR was an independent predictor of OS (hazard ratio [HR] = 2.220; 95% confidence interval [CI] = 1.387-3.550; P = 0.001) and RFS (HR = 1.494; 95% CI = 1.086-2.056; P = 0.014). The SII was an independent predictor of RFS (HR = 1.973; 95% CI = 1.230-3.162; P = 0.005) in patients with CRLM. Conclusion: We proved that CAR was an independent predictor of OS and RFS in patients with CRLM who underwent curative resection, and that the prognostic value of CAR was superior to that of SII.

TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability.

Resistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

Formulation optimization of solid self-microemulsifying pellets for enhanced oral bioavailability of curcumin.

Solidification of self-microemulsifying drug delivery systems (SMEDDS) is one of the major trends to promote the transformation of self-microemulsion technology into industrialization. Here, a preliminary curcumin SMEDDS formulation was constructed to improve the druggability of curcumin, through the determination of equilibrium solubility determination, self-emulsifying grading assessment, and pseudo-ternary phase diagrams drafting. Furthermore, the optimal curcumin SMEDDS formulation consisted of 10% Ethyl oleate, 57.82% Cremophor RH 40, and 32.18% Transcutol P was obtained by the simplex lattice design. Besides, curcumin solid self-microemulsifying drug delivery system (S-SMEDDS) was developed by the extrusion and spheronization process to achieve the solidification of SMEDDS. The formulation of curcumin S-SMEDDS pellets was screened by the single factor experiment and the process parameters were investigated using the orthogonal optimization method. Subsequently, curcumin S-SMEDDS pellets were evaluated by apparent morphology characterization, redispersibility study, drug release behavior, and pharmacokinetic evaluation. Results from the pharmacokinetic study in rabbits showed that the AUC0-τ of the curcumin S-SMEDDS pellets and curcumin suspension were 5.91 ± 0.28 µg/mL·h and 2.05 ± 0.04 µg/mL·h, while the relative bioavailability was 289.30%. These studies demonstrated that S-SMEDDS pellets can be a promising strategy for curcumin industrialized outputs.

Voltage-gated sodium channel Nav1.5 promotes tumor progression and enhances chemosensitivity to 5-fluorouracil in colorectal cancer.

Nav1.5, encoded by SCN5A, has been associated with metastasis in colorectal cancer (CRC). Here, we investigated the mechanism by which Nav1.5 regulates tumor progression and whether Nav1.5 influences chemosensitivity to 5-fluorouracil (5-FU) in CRCs. CRC cases were evaluated for Nav1.5 expression. Elevated Nav1.5 expression was associated with poor prognosis in CRCs, whereas stage II/III patients with upregulated SCN5A expression could have better survival after receiving 5-FU-based adjuvant chemotherapy. In CRC cells, SCN5A knockdown reduced the proliferation, migration and invasion. According to RNA sequencing, SCN5A knockdown inhibited both the cell cycle and epithelial-mesenchymal transition. In addition, Nav1.5 stabilized the KRas-calmodulin complex to modulate Ras signaling, promoting Ca2+ influx through the Na+-Ca2+ exchanger and Ca2+ release-activated calcium channel. Meanwhile, SCN5A knockdown increased the 50% inhibitory concentration to 5-FU by upregulating 5-FU-stimulated apoptosis in CRCs. In conclusion, Nav1.5 could progress to proliferation and metastasis through Ca2+/calmodulin-dependent Ras signaling in CRC, and it could also enhance 5-FU-stimulated apoptosis. Clinically, patients with stage II/III CRCs with elevated SCN5A expression demonstrated poor prognosis, yet those patients could benefit more from 5-FU-based chemotherapy than patients with lower SCN5A expression.