Expression of Fascin-1 and its diagnostic value in liver cancer.

Although some studies have reported on the expression and clinical significance of Fascin-1 (FSCN1) in liver cancer, the clinical application and differential diagnosis value of FSCN1 in liver cancer are still unclear. The aim of this study was to analyze the expression level of FSCN1 protein in liver cancer tissues and explore its diagnostic and application value in differentiating between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The immunehistochemical analysis was used to detect the expression of FSCN1 in 108 cases of HCC, 26 cases of ICC, 23 cases of liver cirrhosis, and 11 cases of normal liver tissues. The differences in the positive expression rate and strong positive expression rate of FSCN1 among different groups were analyzed. The positive rate of FSCN1 in normal liver tissues, liver cirrhosis, HCC, and ICC tissues was 0.0% (0/11), 0.0% (0/23), 13.9% (15/108), and 92.3% (24/26), respectively, while the strong positive rate was 0.0% (0/11), 0.0% (0/23), 0.9% (1/108), and 69.2% (18/26), respectively. Both the positive rate and strong positive rate of FSCN1 in ICC tissues were significantly higher than those in HCC, liver cirrhosis, and normal liver tissues. Additionally, the positive rate of FSCN1 in moderately to poorly differentiated HCC tissues was 18.8% (15/80), significantly higher than in well-differentiated HCC (0.0%, 0/28) (P = 0.031). In liver cancer, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FSCN1 positive prediction for ICC were 92.3%, 86.1%, 61.5%, and 97.9%, respectively, whereas the sensitivity, specificity, PPV, and NPV of FSCN1 strong positive prediction for ICC were 69.2%, 99.1%, 94.7%, and 93.0%, respectively. These results suggest that FSCN1 may play an important role in the occurrence and progression of liver cancer, and it can be used as a novel diagnostic marker for ICC.

The real-world treatment characteristic and efficacy of immune checkpoint inhibitors in non-small cell lung cancer: Data from a retrospective cohort study.

BACKGROUND: The efficacy and prognosis of immune checkpoint inhibitors (ICIs) remain unresolved issues. Here, we assessed the treatment characteristics and efficacy of ICIs in non-small cell lung cancer (NSCLC) using real-world data and evaluated the predictive value of factors, including programmed death-ligand 1 (PD-L1) expression, for the clinical outcome of ICIs in NSCLC. METHODS: Analyzed data was collected from hospitalized patients in the West China Hospital of Sichuan University between January 2017 and March 2023. The Kaplan-Meier method was utilized for analyzing real-world progression-free survival (rwPFS), while Cox regression models was employed to access the correlation between the efficacy of immunotherapy and sociodemographic characteristics, disease information, and characteristics of ICI treatment. RESULTS: A total of 545 patients were included in the retrospective study and characteristics of immunotherapy varied significantly among PD-L1 expression groups. The median rwPFS for the entire population was 9.76 months. Subgroup analyses revealed that patients with high PD-L1 expression, early TNM stage, first-line immunotherapy, EGFR wild-type and those who have not received radiotherapy and targeted therapy previously were more likely to have better rwPFS. Furthermore, multivariate Cox regression analyses identified PD-L1 expression, EGFR mutation status and previous radiotherapy as the most influential predictors of the response to ICI treatment. CONCLUSIONS: This study presents the real-world experience of Chinese NSCLC patients undergoing ICI treatment, offering guidance for clinical decision-making based on various patient conditions, preferences, and indications for ICIs, through the evaluation of immunotherapy efficacy and predictors in NSCLC patients.

Preoperative Prediction of Metastatic Lymph Nodes Posterior to the Right Recurrent Laryngeal Nerve in cN0 Papillary Thyroid Carcinoma.

Background: The advantages of the dissecting the metastatic lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) remain a great deal of controversies in papillary thyroid carcinoma (PTC) patients without clinical evidence. The purpose of our retrospective research was to investigate the predictive factors of the LN-prRLN in cN0 PTC patients. Methods and Materials: Altogether 251 consecutive cN0 PTC participants accepted unilateral or bilateral thyroidectomy accompanied with LN-prRLN dissection between June 2020 and May 2023 were included in the research. Then, univariate and multivariate logical regression analysis were conducted to analyze the relationship between the LN-prRLN and these predictive factors, and a predictive model was also developed. Surgical complications of LN-prRLN dissection were also presented. Results: The rate of LN-prRLN was 17.9% (45/251) in cN0 PTC patients after the analysis of postoperative histology. The age <55 years, multifocality, microcalcification, and BRAFV600E mutation were identified to be predictive factors of LN-prRLN in cN0 PTC patients. The risk score for LN-prRLN was calculated: risk score = 1.192 × (if age <55 years) + 0.808 × (if multifocality) + 1.196 × (if microcalcification in nodule) + 0.918 × (if BRAFV600E mutation in nodule). The rates of the transient hypoparathyroidism and hoarseness were 1.2% (3/251) and 2.0% (5/251), respectively. Conclusion: The age <55 years, multifocality, microcalcification, and BRAFV600E mutation are independent predictors of the LN-prRLN in cN0 PTC patients. An effective predictive model was established for predicting the LN-prRLN in cN0 PTC patients, with the aim to better guide the surgical treatment of PTC. A thorough inspection of the lateral compartment is recommended in PTC patients with risk factors. The multicenter research with long-term follow-up should be carried out to ascertain the optimal surgical approach for patients with PTC.

Rhein suppresses esophageal cancer development by regulating cell cycle through DNMT3B gene.

The mechanism by which DNMT3B facilitates esophageal cancer (ESCA) progression is currently unknown, despite its association with adverse prognoses in several cancer types. To investigate the potential therapeutic effects of the Chinese herbal medicine rhubarb on esophageal cancer (ESCA), we adopted an integrated bioinformatics approach. Gene Set Enrichment Analysis (GSEA) was first utilized to screen active anti-ESCA components in rhubarb. We then employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key molecular modules and targets related to the active components and ESCA pathogenesis. This system-level strategy integrating multi-omics data provides a powerful means to unravel the molecular mechanisms underlying the anticancer activities of natural products, like rhubarb. To investigate module gene functional enrichment, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In addition, we evaluated the predictive impact of DNMT3B expression on ESCA patients utilizing the Kaplan-Meier method. Finally, we conducted experiments on cell proliferation and the cell cycle to explore the biological roles of DNMT3B. In this study, we identified Rhein as the main active ingredient of rhubarb that exhibited significant anti-ESCA activity. Rhein markedly suppressed ESCA cell proliferation. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we determined that the blue module was associated with Rhein target genes and the cell cycle. Additionally, DNMT3B was identified as a Rhein target gene. Analysis of The Cancer Genome Atlas (TCGA) database revealed that higher DNMT3B levels were associated with poor prognosis in ESCA patients. Furthermore, Rhein partially reversed the overexpression of DNMT3B to inhibit ESCA cell proliferation. In vitro studies demonstrated that Rhein and DNMT3B inhibition disrupted the S phase of the cell cycle and affected the production of cell cycle-related proteins. In this study, we found that Rhein exerts its anti-proliferative effects in ESCA cells by targeting DNMT3B and regulating the cell cycle.

Imprinted gene detection effectively improves the diagnostic accuracy for papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most frequent histological type of thyroid carcinoma. Although an increasing number of diagnostic methods have recently been developed, the diagnosis of a few nodules is still unsatisfactory. Therefore, the present study aimed to develop and validate a comprehensive prediction model to optimize the diagnosis of PTC. METHODS: A total of 152 thyroid nodules that were evaluated by postoperative pathological examination were included in the development and validation cohorts recruited from two centres between August 2019 and February 2022. Patient data, including general information, cytopathology, imprinted gene detection, and ultrasound features, were obtained to establish a prediction model for PTC. Multivariate logistic regression analysis with a bidirectional elimination approach was performed to identify the predictors and develop the model. RESULTS: A comprehensive prediction model with predictors, such as component, microcalcification, imprinted gene detection, and cytopathology, was developed. The area under the curve (AUC), sensitivity, specificity, and accuracy of the developed model were 0.98, 97.0%, 89.5%, and 94.4%, respectively. The prediction model also showed satisfactory performance in both internal and external validations. Moreover, the novel method (imprinted gene detection) was demonstrated to play a role in improving the diagnosis of PTC. CONCLUSION: The present study developed and validated a comprehensive prediction model for PTC, and a visualized nomogram based on the prediction model was provided for clinical application. The prediction model with imprinted gene detection effectively improves the diagnosis of PTCs that are undetermined by the current means.

Identification and effective regulation of scarb1 gene involved in pigmentation change in autotetraploid Carassius auratus.

The autotetraploid Carassius auratus (4nRR, 4 n=200, RRRR) is derived from whole-genome duplication of Carassius auratus red var. (RCC, 2 n=100, RR). In the current study, we demonstrated that chromatophores and pigment changes directly caused the coloration and variation of 4nRR skin (red in RCC, brownish-yellow in 4nRR). To further explore the molecular mechanisms underlying coloration formation and variation in 4nRR, we performed transcriptome profiling and molecular functional verification in RCC and 4nRR. Results revealed that scarb1, associated with carotenoid metabolism, underwent significant down-regulation in 4nRR. Efficient editing of this candidate pigment gene provided clear evidence of its significant role in RCC coloration. Subsequently, we identified four divergent scarb1 homeologs in 4nRR: two original scarb1 homeologs from RCC and two duplicated ones. Notably, three of these homeologs possessed two highly conserved alleles, exhibiting biased and allele-specific expression in the skin. Remarkably, after precise editing of both the original and duplicated scarb1 homeologs and/or alleles, 4nRR individuals, whether singly or multiply mutated, displayed a transition from brownish-yellow skin to a cyan-gray phenotype. Concurrently, the proportional areas of the cyan-gray regions displayed a gene-dose correlation. These findings illustrate the subfunctionalization of duplicated scarb1, with all scarb1 genes synergistically and equally contributing to the pigmentation of 4nRR. This is the first report concerning the functional differentiation of duplicated homeologs in an autopolyploid fish, substantially enriching our understanding of coloration formation and change within this group of organisms.

Relationship between chorioamnionitis or funisitis and lung injury among preterm infants: meta-analysis involved 16 observational studies with 68,397 participants.

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

Telemedicine-Enhanced Lung Cancer Screening Using Mobile Computed Tomography Unit with Remote Artificial Intelligence Assistance in Underserved Communities: Initial Results of a Population Cohort Study in Western China.

Introduction: Lung cancer is a leading cause of cancer deaths globally. Despite favorable recommendations, low-dose computed tomography (LDCT) lung screening adoption remains low in China. Barriers such as limited infrastructure, costs, distance, and personnel shortages restrict screening access in disadvantaged regions. We initiated a telemedicine-enabled lung cancer screening (LCS) program in a medical consortium to serve people at risk in underserved communities. The objective of this study was to describe the implementation and initial results of the program. Methods: From 2020 to 2021, individuals aged 40-80 years were invited to take LCS by mobile computed tomography (CT) units in three underserved areas in Western China. Numerous CT scans were remotely reported by radiologists aided by artificial intelligence (AI) diagnostic systems. Abnormal cases were tracked through an integrated hospital network for follow-up. A retrospective cohort study documented participant demographics, health history, LDCT results, and outcomes. Descriptive analysis was conducted to report baseline characteristics and first-year follow-up results. Results: Of the 28,728 individuals registered in the program, 19,517 (67.94%) participated in the screening. The study identified 2.68% of participants with high-risk pulmonary nodules and diagnosed 0.55% with lung cancer after a 1-year follow-up. The majority of high-risk participants received timely treatment in hospitals. Conclusions: This study demonstrated mobile CT units with remote AI assistance improved access to LCS in underserved areas, with high participation and early detection rates. Our implementation supports the feasibility of deploying telemedicine-enabled LCS to increase access to a large scale of basic radiology and diagnostic services in resource-limited settings. Clinical Trial Registration Number: ChiCTR1900024623.

Optimizing robotic thyroid surgery: lessons learned from an retrospective analysis of 104 cases.

Background: Robotic assistance in thyroidectomy is a developing field that promises enhanced surgical precision and improved patient outcomes. This study investigates the impact of the da Vinci Surgical System on operative efficiency, learning curve, and postoperative outcomes in thyroid surgery. Methods: We conducted a retrospective cohort study of 104 patients who underwent robotic thyroidectomy between March 2018 and January 2022. We evaluated the learning curve using the Cumulative Sum (CUSUM) analysis and analyzed operative times, complication rates, and postoperative recovery metrics. Results: The cohort had a mean age of 36 years, predominantly female (68.3%). The average body mass index (BMI) was within the normal range. A significant reduction in operative times was observed as the series progressed, with no permanent hypoparathyroidism or recurrent laryngeal nerve injuries reported. The learning curve plateaued after the 37th case. Postoperative recovery was consistent, with no significant difference in hospital stay duration. Complications were minimal, with a noted decrease in transient vocal cord palsy as experience with the robotic system increased. Conclusion: Robotic thyroidectomy using the da Vinci system has demonstrated a significant improvement in operative efficiency without compromising safety. The learning curve is steep but manageable, and once overcome, it leads to improved surgical outcomes and high patient satisfaction. Further research with larger datasets and longer follow-up is necessary to establish the long-term benefits of robotic thyroidectomy.

Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study.

OBJECTIVE: This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). PATIENTS AND METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety. RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs. CONCLUSION: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.

Intraoperative AI-assisted early prediction of parathyroid and ischemia alert in endoscopic thyroid surgery.

BACKGROUND: The preservation of parathyroid glands is crucial in endoscopic thyroid surgery to prevent hypocalcemia and related complications. However, current methods for identifying and protecting these glands have limitations. We propose a novel technique that has the potential to improve the safety and efficacy of endoscopic thyroid surgery. PURPOSE: Our study aims to develop a deep learning model called PTAIR 2.0 (Parathyroid gland Artificial Intelligence Recognition) to enhance parathyroid gland recognition during endoscopic thyroidectomy. We compare its performance against traditional surgeon-based identification methods. MATERIALS AND METHODS: Parathyroid tissues were annotated in 32 428 images extracted from 838 endoscopic thyroidectomy videos, forming the internal training cohort. An external validation cohort comprised 54 full-length videos. Six candidate algorithms were evaluated to select the optimal one. We assessed the model's performance in terms of initial recognition time, identification duration, and recognition rate and compared it with the performance of surgeons. RESULTS: Utilizing the YOLOX algorithm, we developed PTAIR 2.0, which demonstrated superior performance with an AP50 score of 92.1%. The YOLOX algorithm achieved a frame rate of 25.14 Hz, meeting real-time requirements. In the internal training cohort, PTAIR 2.0 achieved AP50 values of 94.1%, 98.9%, and 92.1% for parathyroid gland early prediction, identification, and ischemia alert, respectively. Additionally, in the external validation cohort, PTAIR outperformed both junior and senior surgeons in identifying and tracking parathyroid glands (p < 0.001). CONCLUSION: The AI-driven PTAIR 2.0 model significantly outperforms both senior and junior surgeons in parathyroid gland identification and ischemia alert during endoscopic thyroid surgery, offering potential for enhanced surgical precision and patient outcomes.

MiR-548t-5p regulates pancreatic ductal adenocarcinoma metastasis through an IL-33-dependent crosstalk between cancer cells and M2 macrophages.

IL-33 has been associated with pro- and anticancer functions in cancer. However, its role in pancreatic cancer metastasis remains unknown. This study aimed to explore the role of miR-548t-5p/IL-33 axis in the metastasis of pancreatic cancer. Luciferase activity assay, qRT-PCR, Western blot and ELISA were performed to prove whether IL-33 is the target of miR-548t-5p. In vivo metastasis assay and cellular transwell assay were performed to explore the role of miR-548t-5p/IL-33 axis in the invasion and metastasis of pancreatic cancer. Co-culture experiments and immunohistochemistry were performed to observe whether IL-33 affects cell invasion and metastasis dependent on the involvement of M2 macrophages. THP-1 cell induction experiment and flow cytometry were performed to explore the effect of IL-33 on macrophage polarization. CCK-8, colony formation, cell apoptosis, cell cycle, cell wound healing and transwell assay were performed to investigate the effect of IL-33 induced M2 macrophages on cell malignant biological behavior by coculturing pancreatic cancer cells with the conditioned medium (CM) from macrophages. We found that miR-548t-5p regulated the expression and secretion of IL-33 in pancreatic cancer cells by directly targeting IL-33 mRNA. IL-33 secreted by cancer cells promoted the recruitment and activation of macrophages to a M2-like phenotype. In turn, IL-33 induced M2 macrophages promoted the migration and invasion of cancer cells. Moreover, IL-33 affected pancreatic cancer cell invasion dependent on the involvement of M2 macrophages in the co-culture system. Thus, our study suggested that manipulation of this IL-33-dependent crosstalk has a therapeutic potential for the treatment of pancreatic cancer metastasis.

Dynamic Analysis of the Impact of Micropapillary Component on Different Recurrence Patterns of Pathological Stage IA3 Lung Adenocarcinoma: A Multicenter, Retrospective Study.

BACKGROUND: This study aimed to evaluate the dynamic impact of the micropapillary (MIP) component on local recurrence (LR), distant metastasis (DM), and multiple recurrence (MR) of pathological stage IA3 lung adenocarcinoma. METHODS: Between July 2012 and July 2020, a total of 351 patients at two medical institutions were enrolled in this study. Cumulative incidence of curves, dynamic risk curves, and time-dependent multivariate analysis was performed to evaluate the effect of the MIP component on patients. RESULTS: The 5-year cumulative incidence of total recurrence with or without an MIP component was 34.2% and 12.3%, respectively (p = 0.001). In three recurrence patterns, our findings revealed that the 5-year cumulative incidence of LR (p = 0.048) and DM (p = 0.005) was higher in the 'MIP-present' group than in the 'MIP-absent' group. In the dynamic recurrence curve, the risk of the three recurrence patterns was different and varied over time between the two groups, especially in DM. Moreover, the dynamic cumulative event curve showed that after 1, 2, and 3 years of survival, the cumulative incidence of DM in the group with MIP continued to be higher than that in the group without MIP (all p < 0.05). Time-dependent Cox regression analysis indicated that the MIP component continued to be an independent risk factor for the cumulative incidence of DM in patients with 3-year survival. CONCLUSIONS: Of the three recurrence patterns, the MIP component mainly aggravated the risk of DM in patients with pathological stage IA3 lung adenocarcinoma, which persisted for 3 years.

Comparing Sleep Patterns and Clinical Features between Preschool and School-Age Children with OSA.

OBJECTIVE: This study aimed to evaluate sleep patterns and investigate differences in clinical features among young individuals with snoring and obstructive sleep apnea (OSA). METHODS: Data from 213 children and adolescents who underwent polysomnography (PSG) for primary snoring or OSA were collected between July 2017 and December 2021. To analyze differences in sleep architecture, hypoxia levels, and other clinical features, the participants were divided into two age groups: a preschool group and a school-age group. RESULTS: The school-age group had significantly higher apnea-hypopnea index, obstructive apnea index, oxygen desaturation index, and body mass index than the preschool group. Both the lowest and average oxygen saturation levels were lower in the school-age group. Adenoid hypertrophy was more prevalent in the preschool group. The rate of overweight or obesity was 35.6% in the preschool group and even 94.2% in the school-age group. There were higher percentages of N1 and N2 sleep stages, and lower percentages of N3 and REM sleep stages in the school-age group. The groups exhibiting moderate to severe OSA demonstrated significant alterations in the difference between sleeping and waking diastolic blood pressure. CONCLUSION: There is a higher frequency of respiratory events among school-age children compared with their preschool peers. Moreover, alterations in sleep structure are more prominent in the school-age group. Adenoid hypertrophy may serve as the primary instigator of OSA in preschool children, whereas the predominant causes in school-age children may be obesity or excessive weight. LEVEL OF EVIDENCE: Retrospective chart review, 3 Laryngoscope, 134:1472-1478, 2024.

Response of cholangiocarcinoma with epigastric metastasis to lenvatinib plus sintilimab: A case report and review of literature.

BACKGROUND: Cholangiocarcinoma (CCA) poses a significant clinical challenge due to its low radical resection rate and a propensity for high postoperative recurrence, resulting in a poor dismal. Although the combination of targeted therapy and immunotherapy has demonstrated notable efficacy in several solid tumors recently, however, its application in CCA remains underexplored and poorly documented. CASE SUMMARY: This case report describes a patient diagnosed with stage IV CCA, accompanied by liver and abdominal wall metastases, who underwent palliative surgery. Subsequently, the patient received two cycles of treatment combining lenvatinib with sintilimab, which resulted in a reduction in abdominal wall metastasis, while intrahepatic metastasis displayed progression. This unexpected observation illustrates different responses of intrahepatic and extrahepatic metastases to the same therapy. CONCLUSION: Lenvatinib combined with sintilimab shows promise as a potential treatment strategy for advanced CCA. Genetic testing for related driver and/or passenger mutations, as well as an analysis of tumor immune microenvironment analysis, is crucial for optimizing drug combinations and eventually addressing the issue of non-response in specific metastatic sites.

Advances in research on molecular markers in immune checkpoint inhibitor-associated myocarditis.

Immune checkpoint inhibitors (ICIs) play a crucial role in the immunotherapy of malignant tumors, preventing immune evasion by tumor cells and activating autoimmune cells to eliminate the tumor. Despite their proven effectiveness in antitumor therapy, potential immune-related adverse effects must be recognized, particularly ICI-associated myocarditis (ICIAM). ICIAM is the most lethal form of organ immunotoxicity, with a significant impact on short-term mortality. However, ICIAM is predominantly asymptomatic or mildly nonspecific. It is difficult to diagnose, especially due to the lack of unique molecular markers. This article aims to provide a comprehensive overview of the progress made in identifying molecular markers for ICIAM.

Intelligent prognosis evaluation system for stage I-III resected non-small-cell lung cancer patients on CT images: a multi-center study.

Background: Prognosis is crucial for personalized treatment and surveillance suggestion of the resected non-small-cell lung cancer (NSCLC) patients in stage I-III. Although the tumor-node-metastasis (TNM) staging system is a powerful predictor, it is not perfect enough to accurately distinguish all the patients, especially within the same TNM stage. In this study, we developed an intelligent prognosis evaluation system (IPES) using pre-therapy CT images to assist the traditional TNM staging system for more accurate prognosis prediction of resected NSCLC patients. Methods: 20,333 CT images of 6371 patients from June 12, 2009 to March 24, 2022 in West China Hospital of Sichuan University, Mianzhu People's Hospital, Peking University People's Hospital, Chengdu Shangjin Nanfu Hospital and Guangan Peoples' Hospital were included in this retrospective study. We developed the IPES based on self-supervised pre-training and multi-task learning, which aimed to predict an overall survival (OS) risk for each patient. We further evaluated the prognostic accuracy of the IPES and its ability to stratify NSCLC patients with the same TNM stage and with the same EGFR genotype. Findings: The IPES was able to predict OS risk for stage I-III resected NSCLC patients in the training set (C-index 0.806; 95% CI: 0.744-0.846), internal validation set (0.783; 95% CI: 0.744-0.825) and external validation set (0.817; 95% CI: 0.786-0.849). In addition, IPES performed well in early-stage (stage I) and EGFR genotype prediction. Furthermore, by adopting IPES-based survival score (IPES-score), resected NSCLC patients in the same stage or with the same EGFR genotype could be divided into low- and high-risk subgroups with good and poor prognosis, respectively (p < 0.05 for all). Interpretation: The IPES provided a non-invasive way to obtain prognosis-related information from patients. The identification of IPES for resected NSCLC patients with low and high prognostic risk in the same TNM stage or with the same EGFR genotype suggests that IPES have potential to offer more personalized treatment and surveillance suggestion for NSCLC patients. Funding: This study was funded by the National Natural Science Foundation of China (grant 62272055, 92259303, 92059203), New Cornerstone Science Foundation through the XPLORER PRIZE, Young Elite Scientists Sponsorship Program by CAST (2021QNRC001), Clinical Medicine Plus X - Young Scholars Project, Peking University, the Fundamental Research Funds for the Central Universities (K.C.), Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences (2021RU002), BUPT Excellent Ph.D. Students Foundation (CX2022104).

Relevance and mechanism of STAT3/miR-221-3p/Fascin-1 axis in EGFR TKI resistance of triple-negative breast cancer.

The epidermal growth factor receptor 1 (EGFR) plays a crucial role in the progression of various malignant tumors and is considered a potential target for treating triple-negative breast cancer (TNBC). However, the effectiveness of representative tyrosine kinase inhibitors (TKIs) used in EGFR-targeted therapy is limited in TNBC patients. In our study, we observed that the TNBC cell lines MDA-MB-231 and MDA-MB-468 exhibited resistance to Gefitinib. Treatment with Gefitinib caused an upregulation of Fascin-1 (FSCN1) protein expression and a downregulation of miR-221-3p in these cell lines. However, sensitivity to Gefitinib was significantly improved in both cell lines with either inhibition of FSCN1 expression or overexpression of miR-221-3p. Our luciferase reporter assay confirmed that FSCN1 is a target of miR-221-3p. Moreover, Gefitinib treatment resulted in an upregulation of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in MDA-MB-231 cells. Using Stattic, a small-molecule inhibitor of STAT3, we observed a significant enhancement in the inhibitory effect of Gefitinib on the growth, migration, and invasion of MDA-MB-231 cells. Additionally, Stattic treatment upregulated miR-221-3p expression and downregulated FSCN1 mRNA and protein expression. A strong positive correlation was noted between the expression of STAT3 and FSCN1 in breast cancer tissues. Furthermore, patients with high expression levels of both STAT3 and FSCN1 had a worse prognosis. Our findings suggest that elevated FSCN1 expression is linked to primary resistance to EGFR TKIs in TNBC. Moreover, we propose that STAT3 regulates the expression of miR-221-3p/FSCN1 and therefore modulates resistance to EGFR TKI therapy in TNBC. Combining EGFR TKI therapy with inhibition of FSCN1 or STAT3 may offer a promising new therapeutic option for TNBC.

Establishment of a Prognostic Nomogram for Cancer-Specific Survival in Patients With Base-of-Tongue Squamous Cell Carcinoma: A Retrospective Study Based on the SEER Database.

BACKGROUND: The aim of this retrospective study was to construct and clinically apply a nomogram for cancer-specific survival (CSS) in patients diagnosed with base-of-tongue squamous cell carcinoma (BOTSCC) to predict their survival prognosis. METHODS: We collected 8448 patients diagnosed with BOTSCC during 2004-2015 from the Surveillance, Epidemiology, and End Results (SEER) database and divided 30% and 70% of them into validation and training cohorts, respectively. We utilized backward stepwise regression in the Cox model to select variables. Predictive variables were subsequently identified from the variables selected above by using multivariate Cox regression. The new survival model was compared with the American Joint Committee on Cancer (AJCC) prognosis model using the following variables: calibration curve, time-dependent area under the receiver operating characteristic curve (AUC), concordance index (C-index), integrated discrimination improvement (IDI), decision-curve analysis (DCA), and net reclassification improvement (NRI). RESULTS: A nomogram was established for predicting the CSS probability in patients with BOTSCC. Factors including sex, race, age at diagnosis, marital status, radiotherapy status, chemotherapy status, TNM AJCC stage, surgery status, tumor size, and months from diagnosis to treatment were selected through multivariate Cox regression as independent predictors of CSS. Calibration plots indicated that the model we established had satisfactory calibration ability. The AUC, C-index, IDI, DCA, and NRI results illustrated that the nomogram performed explicit prognoses more accurately than did the AJCC system alone. CONCLUSION: We identified the relevant factors affecting the survival of BOTSCC patients and analyzed the data on patients suffering from BOTSCC in the SEER database. These factors were used to construct a new nomogram to give clinical staff a more-visual prediction model for the 3-, 5-, and 8-year probabilities of CSS for patients newly diagnosed with BOTSCC, thereby aiding clinical decision making.