ContextDrug-induced liver injury remains a major clinical challenge due to the lack of effective therapeutic options. Polygonatum odoratum extract (PO), derived from the traditional medicinal and edible plant Polygonatum odoratum (Mill.) Druce, has long been used in folk practices in forms such as herbal soups and tea infusions. However, its protective effect against acetaminophen (APAP)-induced liver injury has not yet been investigated.ObjectiveThis study evaluated the preventive effects of PO against APAP-induced acute liver injury in mice.Materials and MethodsAn APAP-induced acute liver injury model was established in C57BL/6 mice. The hepatoprotective effects of PO were validated via histopathological analysis, oxidative stress assays,and serum biomarkers Multi-omics approaches, including 16 S rDNA sequencing, transcriptomics, and network pharmacology, were integrated with molecular biology techniques and pseudo-germ-free (PGF) mouse models to elucidate the underlying mechanisms.ResultsPO significantly alleviated hepatic histopathological damage, oxidative stress, and reduced serum ALT, AST, and LDH. PO remodeling gut microbiota, mitigated colonic inflammation and oxidative stress, and improved intestinal morphology, effects abolished by microbiota depletion. Mechanistically, PO maybe inhibited hepatic ferroptosis via the gut microbiota–ceramide axis, evidenced by upregulation of GPX4 and FSP1, NRF2/KEAP1 pathway activation, downregulation of ACSL4, TFRC/TFR2, and DUOX2, restored iron homeostasis, and decreased lipid peroxidation and ROS. In vitro, PO demonstrated anti-ferroptotic effects in APAP- or RSL3-treated AML12 cells.Discussion and ConclusionPO confers hepatoprotection via the gut–liver axis, which is associated with changes in ceramide metabolism and ferroptosis-related markers.

Background Tumor cells can drive the senescence of effector T cells by unbalancing their lipid metabolism, thereby limiting adoptive T cell therapy and contributing to tumor immune evasion. Our objective is to provide a feasible strategy for enhancing T cell treatment efficacy against solid tumors.Methods In this study, liposomal arachidonyl trifluoromethyl ketone (ATK) was anchored onto the adoptive T cell surface via bioorthogonal reactions, aiming to specifically inhibit the group IVA cytosolic phospholipase A2α (cPLA2α), a key enzyme facilitating phospholipid metabolism and senescent state of T cells.Results The surface engineering exerted rare side effects on the activation and migration of T cells, but local and sustained extravasation of ATK downregulated cPLA2α expression, reprogrammed lipid metabolism, and inhibited lipid droplet accumulation. This endows T cells with delayed senescence and declined apoptosis to maintain their tumor-killing potency. Systemic administration of surface-engineered T cells resulted in superior infiltration in solid tumors and improved antitumor efficacy by enhancing the secretion of cytotoxic molecules, thereby prolonging the survival of mice bearing colorectal carcinoma and melanoma xenografts.Conclusions Lipid-metabolically remodeled T cells with delayed senescence increase efficacy in tumor microenvironment, highlighting a novel strategy for solid tumor immunotherapy.

BACKGROUND:Exosomes are specialized secreted vesicles for intercellular communication and signaling pathways as specialized secreted vesicles. Multiple studies have suggested the potential roles of hepatocyte-derived exosomes as biomarkers of liver injury and facilitators of hepatocyte proliferation and liver regeneration. METHODS:By utilizing murine models of hepatic ischemia-reperfusion injury (IRI), we examined the impact of hepatocyte-derived exosomes on mitigating hepatic IRI. RESULTS:Our experiments have demonstrated that significantly lower levels of alanine transaminase, aspartate transaminase, and lactate dehydrogenase in mice treated with hepatocyte-derived exosomes compared with mice treated with phosphate-buffered saline (PBS). Furthermore, hepatocyte-derived exosomes inhibited hepatocyte apoptosis, reduced levels of inflammatory cytokines, and suppressed the entry of inflammatory cells into the liver following hepatic IRI. Complement 3d (C3d) expression showed a notable decrease in exosome-treated mice compared with PBS-treated mice, suggesting that hepatocyte-derived exosomes effectively inhibited complement activation during hepatic IRI. Blocking the fusion of exosomes with cells using Annexin V weakened the protective effects of the exosomes against hepatic IRI. CONCLUSIONS:Our findings highlight the ability of hepatocyte-derived exosomes to mitigate hepatic IRI by inhibiting complement activation. These results reveal a novel role for exosomes in blocking complement activation, suggesting a potential new therapeutic avenue for preventing hepatic IRI.

BACKGROUND:Effective screening for colorectal cancer (CRC) enables earlier diagnosis and intervention to improve patient survival. METHODS:In this study, we prospectively conducted a blood-based CRC screening program for community residents in Hanjiang District, Yangzhou City, and evaluated the screening efficacy of a blood-based multi-locus DNA methylation assay (ColonAiQ). The ColonAiQ-positive rate and colonoscopy participation rate of the population, detection rate of intestinal lesions, and positive predictive value (PPV) of CRC and advanced adenoma (AA) were calculated, and the associated factors were explored. RESULTS:A total of 105,285 participants were enrolled from January 2021 to December 2022, all of whom completed the ColonAiQ assay, yielding a positive rate of 6.42% (6759/105,285). The colonoscopy compliance rate was 48.56% (3282/6759). Intestinal lesions were detected in 1773 individuals (54.02%), including 63 cases of CRCs (predominately early-stage), 1195 adenomas (441 cases of AAs), 327 polyps, and 188 other benign lesions. CRC patients exhibited higher ColonAiQ scores and more positive loci compared to healthy individuals. The PPVs were 1.92% for CRC and 13.44% for AA. Among participants, 66,121 (62.8%) completed questionnaires graded by the Asia-Pacific Colorectal Screening score, with 12,139 (18.36%) classified in the high-risk tier. High-risk participants had a higher ColonAiQ-positive rate (11.07%) and PPVs for CRC (3.46%) and AA (22.18%). Factors associated with increased detection rates for CRC and AA included male gender, older age, a history of alcohol consumption, and prior polyps. CONCLUSIONS:Our study demonstrated that ColonAiQ assay effectively identifies high-risk population. These findings strongly suggest that the ColonAiQ assay represents a promising strategy for the early detection of CRC and AA in individuals at average risk. TRIAL REGISTRATION:Registered at ClinicalTrials.gov (NCT05336539).

BackgroundThe comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear.MethodsBy leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders.ResultsSCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07–1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06–1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04–1.18, p = 1.84 × 10−3).ConclusionsWe confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.

A surface-enhanced Raman scattering (SERS) detection platform was constructed based on Au nano-dodecahedrons (AuNDs) functionalized with nucleic acid aptamer-specific binding and self-assembly techniques. SERS labels were prepared by modifying Raman signaling molecules and complementary aptamer chains and were bound on the aptamer-functionalized AuNDs array. Using this protocol, the limits of detection (LODs) of miR-21 and miR-18a in the serum were 6.8 pM and 7.6 pM, respectively, and the detection time was 5 min. Additionally, miR-21 and miR-18a were detected in the serum of a mouse model of colorectal cancer. The results of this protocol were consistent with quantitative real-time polymerase chain reaction (qRT-PCR). This method provides an efficient and rapid method for the simultaneous testing of miRNAs, which has great potential clinical value for the early detection of colorectal cancer (CRC).

Purpose In order to reduce the incidence and mortality of colorectal cancer, improving the quality of colonoscopy is the top priority. At present, the adenoma detection rate is the most used index to evaluate the quality of colonoscopy. So, we further verified the relevant factors influencing the quality of colonoscopy and found out the novel quality indicators by studying the relationship between the influencing factors and the adenoma detection rate. Materials/methods The study included 3824 cases of colonoscopy from January to December 2020. We retrospectively recorded the age and sex of the subjects; the number, size, and histological features of lesions; withdrawal time and the number of images acquired during colonoscopy. We analyzed the associated factors affecting adenoma and polyp detection, and verified their effectiveness with both univariate and multivariate logistic regression analyses. Results Logistic regression analyses showed that gender, age, withdrawal time and the number of images acquired during colonoscopy could serve as independent predictors of adenoma/polyp detection rate. In addition, adenoma detection rate (25.36% vs. 14.29%) and polyp detection rate (53.99% vs. 34.42%) showed a marked increase when the number of images taken during colonoscopy was ≥29 ( P <0.001). Conclusions Gender, age, withdrawal time and the number of images acquired during colonoscopy are influencing factors for the detection of colorectal adenomas and polyps. And we can gain higher adenoma/polyp detection rate when endoscopists capture more colonoscopic images.

Abstract Background Increasing evidence suggests a vital role of the pre-metastatic niche in the formation of distant metastasis of many cancers. However, how the pre-metastatic niche is formed and promotes pulmonary metastasis of hepatocellular carcinoma (HCC) remains unknown. Methods Orthotopic liver tumor models and RNA-Seq were used to identify dysregulated genes in the pre-metastatic lung. Il1b knockout (Il1b−/−) mice and lentivirus-mediated gene knockdown/overexpression were utilized to demonstrate the role of interleukin 1 beta (IL-1β)/serum amyloid A3 (SAA3) in the pre-metastatic niche formation and pulmonary metastasis. The potential molecular mechanisms were investigated by RNA-Seq, real-time quantitative PCR (qPCR), western blotting, immunohistochemistry (IHC), flow cytometry, luciferase reporter assay, double immunofluorescent staining and H&E staining. Results Accumulation of myeloid cells and upregulation of IL-1β were observed in the pre-metastatic lung of orthotopic liver tumor models. Myeloid cells accumulation and pulmonary metastasis were suppressed in Il1b−/− mice and Il1r1-silencing mice. Mechanistically, SAA3 and matrix metallopeptidase 9 (MMP9) were identified as potential downstream targets of IL-1β. Overexpression of SAA3 in the lungs of Il1b−/− mice restored myeloid cells accumulation and pulmonary metastasis of the orthotopic HCC xenografts. Moreover, alveolar macrophages-derived IL-1β dramatically enhanced SAA3 expression in alveolar epithelial cells in an NF-κB dependent manner and increased MMP9 levels in an autocrine manner. Furthermore, SAA3 recruited myeloid cells to the lung without affecting the expression of MMP9 in myeloid cells. Conclusions Our study suggests a key role of pulmonary IL-1β and SAA3 in creating a permissive lung pre-metastatic niche by enhancing MMP9 expression and recruiting myeloid cells, respectively, thus promoting pulmonary metastasis of HCC.

Cisplatin-based chemotherapy is the main treatment option for advanced or metastatic esophageal squamous cell carcinoma (ESCC). However, most ESCC patients develop drug resistance within 2 years after receiving cisplatin chemotherapy. Ubiquitin-specific protease 10 (USP10) is abnormally expressed in a variety of cancers, but the mechanistic roles of USP10 in ESCC are still obscure. Here, the effects of USP10 on the migration and cisplatin resistance of ESCC in vivo and in vitro and the underlying mechanisms have been investigated by bioinformatics analysis, RT-PCR, western blotting, immunoprecipitation, immunohistochemistry, cell migration and MTS cell proliferation assays, deubiquitination assay, and mouse tail vein injection model. USP10 was significantly up-regulated in ESCC tissues compared with adjacent normal tissues in both public databases and clinical samples and was closely associated with overall survival. Subsequent results revealed that USP10 contributed to the migration and cisplatin resistance of ESCC cells, while knocking down USP10 in cisplatin-resistant cells exhibited opposite effects in vitro and in vivo. Further Co-IP experiments showed that integrin β1 and YAP might be targets for USP10 deubiquitination. Moreover, deficiency of USP10 significantly inhibited the migrative and chemo-resistant abilities of ESCC cells, which could be majorly reversed by integrin β1 or YAP reconstitution. Altogether, USP10 was required for migration and cisplatin resistance in ESCC through deubiquinating and stabilizing integrin β1/YAP, highlighting that inhibition of USP10 may be a potential therapeutic strategy for ESCC.

Influenza epidemics persistently threaten global health. Vaccines based on virus-like particles (VLPs), which resemble the native conformation of viruses, have emerged as vaccine candidates. However, the production of VLPs via genetic engineering remains constrained by challenges such as low yields, high costs, and being time consuming. In this study, a novel VLP platform is developed that could mimic infection and confer influenza protection through fluorination-driven self-assembly. The VLPs closely mimick the key steps in viral infection including dendritic cell (DC) attachment and pH-responsive endo-lysosomal escape, which enhances DC maturation and antigen cross-presentation. It is also observed that the VLPs migrate from the injection site to the draining lymph nodes efficiently. Immunization with VLPs triggers both Th1 and Th2 cellular responses, thereby inducing an improved CD8+ T cell response along with strong antigen-specific antibody responses. In several infected mouse models, VLP vaccines ameliorate weight loss, lung virus titers, pulmonary pathologies, and confer full protection against H1N1, H6N2, H9N2, and mixed influenza viruses. Therefore, the results support the potential of VLPs as an effective influenza vaccine with improved immune potency against infection. A methodology to generate VLPs based on fluorophilic interactions, which can be a general approach for development of pathogenic VLPs, is reported.

BACKGROUND:Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS:For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS:Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION:We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING:Science and Technology Commission of Shanghai Municipality.

Background Effective risk prediction models are lacking for personalized endoscopic screening of gastric cancer (GC). We aimed to develop, validate, and evaluate a questionnaire-based GC risk assessment tool for risk prediction and stratification in the Chinese population. Methods In this three-stage multicenter study, we first selected eligible variables by Cox regression models and constructed a GC risk score (GCRS) based on regression coefficients in 416,343 subjects (aged 40–75 years) from the China Kadoorie Biobank (CKB, development cohort). In the same age range, we validated the GCRS effectiveness in 13,982 subjects from another independent Changzhou cohort (validation cohort) as well as in 5348 subjects from an endoscopy screening program in Yangzhou. Finally, we categorized participants into low (bottom 20%), intermediate (20–80%), and high risk (top 20%) groups by the GCRS distribution in the development cohort. Results The GCRS using 11 questionnaire-based variables demonstrated a Harrell’s C-index of 0.754 (95% CI, 0.745–0.762) and 0.736 (95% CI, 0.710–0.761) in the two cohorts, respectively. In the validation cohort, the 10-year risk was 0.34%, 1.05%, and 4.32% for individuals with a low (≤ 13.6), intermediate (13.7~30.6), and high (≥ 30.7) GCRS, respectively. In the endoscopic screening program, the detection rate of GC varied from 0.00% in low-GCRS individuals, 0.27% with intermediate GCRS, to 2.59% with high GCRS. A proportion of 81.6% of all GC cases was identified from the high-GCRS group, which represented 28.9% of all the screened participants. Conclusions The GCRS can be an effective risk assessment tool for tailored endoscopic screening of GC in China. Risk Evaluation for Stomach Cancer by Yourself (RESCUE), an online tool was developed to aid the use of GCRS.

Myc is a pivotal protooncogenic transcription factor that contributes to the development of almost all Burkitt’s lymphomas and about one-third of diffuse large B-cell lymphomas. How B-cells sustain their uncontrolled proliferation due to high Myc is not yet well defined. Here, we found that Myc trans-represses the expression of murine LAPTM5, a gene coding a lysosome-associated protein, by binding to two E-boxes in the LAPTM5 promoter. While the product of intact mRNA (CDS+3′UTR) of LAPTM5 failed to suppress the growth of B-lymphomas, either the protein coded by coding sequence (CDS) itself or the non-coding 3′-untranslated region (3′UTR) mRNA was able to inhibit the growth of B-lymphomas. Moreover, Myc trans-activated miR-17-3p, which promoted tumor growth. Strikingly, LAPTM5 3′UTR contains 11 miR-17-3p-binding sites through which the LAPTM5 protein synthesis was inhibited. The functional interplay between low LAPTM5 mRNA and high miR-17-3p due to high Myc in B-lymphomas leads to further dampening of tumor-suppressive LAPTM5 protein, which promotes tumor progression. Our results indicate that Myc inhibits LAPTM5 expression in B-lymphoma cells by transcriptional and post-transcriptional modifications.

BackgroundIn China, thalidomide (THD) has been used to prevent chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC); however, there is limited evidence on the efficacy and safety of THD in this setting. The aim of this study was to evaluate the efficacy, safety, and impact on quality of life (QoL) of THD on CINV following HEC.MethodsElectronic databases were systematically searched for all randomized controlled trials (RCTs) in HEC using THD. The primary outcomes were complete response (CR) and no nausea, Secondary outcomes were the incidence of adverse events and QoL related indicators. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a fixed-effects model. In the case of heterogeneity (I2≥50%), a random-effects model was performed.ResultsA total of 3168 patients were included from 34 RCTs. In terms of CR rate, THD plus 5-HT3 receptor antagonist (5-HT3RA) with or without dexamethasone (DEX) was significantly higher than 5-HT3RA with or without DEX in the acute phase (74.4% vs 67.4%; RR 1.10), delayed phase (70.6% vs 50.4%; RR 1.53), and overall phase (68.4% vs 53.4%; RR 1.28). In terms of no nausea rate, the THD group was also significantly higher than the control group in the acute phase (61.7% vs 55.5%; RR 1.12), delayed phase (50.5% vs 30.0%; RR 1.69), and overall phase (44.6% vs 29.9%; RR 1.50). There was no statistical difference in the incidence of fatigue, headache, diarrhea, rash, hepatorenal damage, and myelosuppression between those with and without THD. The incidence of increase in KPS scores, weight gain, appetite improvement, and sleep quality improvement were significantly higher with the addition of THD.ConclusionsTHD may be effective and safe for the prevention of CINV patients treated with HEC and may improve QoL.

Background: The effect of Helicobacter pylori ( H. pylori ) status on survival for gastric cancer remains unclear. We aimed to elucidate the molecular heterogeneity of tumour-infiltrating T cells in gastric cancer with different H. pylori infection status. Methods: We conducted a prognostic analysis of 488 gastric cancer patients and performed single-cell RNA sequencing (scRNA-seq) analysis on 18,717 T cells from 6 tumour samples with or without H. pylori infection. Analysis results were validated using histological assays and bulk transcriptomic datasets. Results: We confirmed that gastric cancer patients with H . pylori infection had a significantly longer survival time compared to patients with negative H . pylori status (HR=0.74, 95% CI=0.55-0.99, P = 0.045). After unsupervised re-clustering of T cells based on scRNA-seq data, we identified ten CD4 + and twelve CD8 + clusters. Among them, four clusters in CD8 + T cells appeared to exhibit distinct distributions with different H. pylori infection status. One subgroup marked by CXCL13 , which contained mostly cells of H. pylori infection and expressed high levels of IFNG , GZMB and low level of PDCD1 , was activated by TNFRSF1A - TNF interaction. The developed gene signature was significantly associated with improved patient survival in gastric cancer. The other subgroup specifically expressed immune suppression-related genes AREG and PTGER2 , was almost exclusively populated with cells without H. pylori infection. High PTGER2 expression was significantly associated with worse prognosis with high CD8 expression. Conclusion: Our results shed light into the mechanisms underlying the target cell dependent T cell responses induced by H. pylori , which will provide assistance for precision treatment and prognosis.

Sorafenib resistance is often developed and impedes the benefits of clinical therapy in hepatocellular carcinoma (HCC) patients. However, the relationship between sorafenib resistance and tumor immune environment and adjuvant drugs for sorafenib-resistant HCC are not systemically identified. This study first analyzed the expression profiles of sorafenib-resistant HCC cells to explore immune cell infiltration levels and differentially expressed immune-related genes (DEIRGs). The prognostic value of DEIRGs was analyzed using Cox regression and Kaplan-Meier analysis based on The Cancer Genome Atlas. The primary immune cells infiltrated in sorafenib-resistant HCC mice were explored using flow cytometry (FCM). Finally, small-molecule drugs for sorafenib-resistant HCC treatment were screened and validated by experiments. The CIBERSORT algorithm and mice model showed that macrophages and neutrophils are highly infiltrated, while CD8(+) T cells are downregulated in sorafenib-resistant HCC. Totally, 34 DEIRGs were obtained from sorafenib-resistant and control groups, which were highly enriched in immune-associated biological processes and pathways. NR6A1, CXCL5, C3, and TGFB1 were further identified as prognostic markers for HCC patients. Finally, nalidixic acid was identified as a promising antagonist for sorafenib-resistant HCC treatment. Collectively, our study reveals the tumor immune microenvironment changes and explores a promising adjuvant drug to overcome sorafenib resistance in HCC.

Background Chemotherapy combined with immune checkpoints inhibitors (ICIs) has been established as a standard treatment for locally advanced, metastatic, or recurrent esophageal squamous cell cancer (ESCC). However, the optimal chemotherapy regimen in combination therapy is still unclear. Purpose To investigate the efficacy and adverse events of the fluorouracil plus platinum (FP) and taxane plus platinum (TP) regimens in ESCC patients receiving chemo-immunotherapy, we conducted this systematic review and meta-analysis. Methods Potentially eligible studies were searched from Medline, Embase, Web of Science, and the Cochrane Library. Pooled rates of overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events were compared between ICIs+TP and ICIs+FP groups in ESCC patients receiving first-line chemo-immunotherapy. Results A total of 10 clinical trials were included, of which 5 were randomized controlled trials. Compared with chemotherapy alone, chemo-immunotherapy significantly improved the OS of ESCC patients (pooled HR=0.69; 95% CI, 0.63–0.76; p<0.01). Pooled analysis revealed that ESCC patients receiving ICIs+TP had significantly higher ORR, DCR, PFS, and OS rates than those receiving ICIs+FP. No statistically significant difference in the pooled incidence rate of treatment-related death was found (2.3% vs 0.9%, P=0.08). ICIs+TP had significantly higher rates of hematologic toxicity but lower rates of gastrointestinal toxicity than ICIs+FP. Conclusions Based on the current data, the first-line treatment using ICIs+TP may be a better option than ICIs+FP in advanced, metastatic, or recurrent ESCC.

BACKGROUND:Endoscopic screening is the widely accepted screening strategy for esophageal squmaous cell carcinoma (ESCC). However, massive endoscopic screening is expensive and not cost-efficient, and novel pre-endoscopy detection used as a preliminary screening method arouses new concerns. We are planning to launch an artificial intelligence (AI) assisted sponge cytology for detecting esophageal squmaous high-grade intraepithelial neoplasia (HGIN) and above lesions. The aim of this trail is to investigate the efficiency of AI-assisted sponge cytology in population-based screening of early esophageal squmaous epithelial lesions.METHODS:The study will be prospectively conducted in five regions with a high prevalence of ESCC. AI-assisted sponge cytology and endoscopic examination will be sequentially performed. Based on our previous data, at least 864 patients with esophageal HGIN and above lesions are needed to achieve enough statistical power. And, a calculated 112,500 individuals with high risks of ESCC will be recruited. In the first stage, each 24,000 participants who meet the inclusion criteria will be recruited on a voluntary basis. Setting pathological results as standard reference, diagnostic threshold and according performance of AI-assisted detection will be evaluated. A prediction model will be constructed by co-analyzing cytological results and relevant risk factors. Then, an external validation cohort will be used for validation of the model efficiency. Also, cost-efficiency analysis will be performed. This study protocol was registered on chineseclinicaltrial.gov (ChiCTR1900028524).DISCUSSION:Our study will determine whether this AI-assisted sponge cytology can be used as an effective pre-endoscopy detection tool for large-scale screening for ESCC in high-risk areas.

Background Colorectal cancer (CRC) has become the malignant tumor of the digestive tract with the highest incidence in our country, posing a serious threat to the health of our people. Early colon cancer is mostly due to the malignant transformation of colon polyps, so that early detection and resection have been shown to be effective in reducing the incidence and mortality of CRC. This study tried to investigate the related risk factors of and construct a predictive nomogram for colorectal polyps, providing meaningful guidance basis for risk stratification and screening. Methods A total of 1,799 patients who underwent colonoscopies in the Health Management Centre of the Affiliated Hospital of Yangzhou University were recruited to this study. Univariate and multivariate logistic analyses were performed to determine the risk factors for colorectal polyps, and a predictive nomogram was constructed based on the multivariable model. We determined the predictive value of the nomogram by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses (DCAs). Results The logistic regression analysis showed that age (P<0.001), gender (P<0.001), eosinophil count (P=0.005), hemoglobin level (P=0.039), and LDL-C/HDL-C ratio (LHR; P<0.001) were independent predictors of the development of colorectal polyps. The above independent risk factors were incorporated, and an individualized nomogram model was successfully established. The C-index of the nomogram was 0.679 in our model, and with the bootstrap method, the prediction curve fit well with the ideal curve, suggesting that the prediction curve constructed in this study has good predictive ability. Conclusions Age, gender, eosinophil count, hemoglobin level, and LHR are risk factors for the development of colorectal polyps. Establishing a nomogram prediction model for colorectal polyps is helpful for the early clinical screening of high-risk patients with colorectal polyps, improving the detection rate of polyps and reducing the incidence of colorectal cancer (CRC).

Objective. Thrombospondin 2 (THBS2) acts as oncogenic or tumor suppressive gene in diverse cancers. Here we studied the prognostic and immunological role of THBS2 in colorectal cancer (CRC) using bioinformatic analysis. Methods. The genetic and protein expression of THBS2 in CRC were explored across several databases, including ONCOMINE, GEPIA2, TIMER 2.0, UALCAN and HPA databases. Correlation between THBS2 expression and clinical features in CRC was assessed using UALCAN tool. Prognostic analysis was performed using GEPIA2 and PrognoScan. Immune infiltration correlation with THBS2 in CRC was investigated with TIMER 2.0 and TISIDB. THBS2 binding and correlated genes were analyzed using String, GEPIA2, and TIMER 2.0. Results. THBS2 was significantly higher in CRC across multiple databases. Age and histological subtype were correlated with THBS2 level. High THBS2 expression correlated with short overall and disease-free survival. THBS2 expression was positively correlated with immune infiltrates in CRC. Moreover, extracellular matrix structural constituent and organization, PI3K-Akt pathway, were involved in the functional mechanisms of THBS2. Conclusions. THBS2 correlates with poor prognosis and immune infiltration in CRC. THBS2 may act as a prognostic and immunological biomarker for CRC.