Objective·To systematically evaluate the changing trends of appendicitis disease burden among the children in China from 1990 to 2023, analyze the driving factors underlying burden changes, and predict the disease burden trends from 2024 to 2050.Methods·Based on the data from Global Burden of Disease Study 2023 (GBD 2023), indicators including incidence, mortality, and disability-adjusted life years (DALYs) of appendicitis in Chinese children aged 0‒14 years were extracted. Age-standardized indicators were adopted to assess the level of disease burden; the estimated annual percentage change (EAPC) was used to evaluate temporal trends, and differences by gender and age were explored were explored. The Das Gupta decomposition method was applied to quantify the independent contributions of population growth, population age structure, and epidemiological factors to changes in disease burden. The Bayesian age-period-cohort (BAPC) model was employed to predict the trends of core indicators from 2024 to 2050.Results·From 1990 to 2023, the number of incident appendicitis cases among Chinese children decreased from 260 374 (95% UI 166 444‒396 374) to 187 216 (95% UI 118 429‒289 624), with a slight decline in the age-standardized incidence rate (ASIR) (EAPC=-0.72%). The number of deaths fell from 285 (95% UI 116‒464) to 36 (95% UI 20‒60), and DALYs dropped from 26 708 (95% UI 13 092‒41 742) to 5 124 (95% UI 3 417‒7 345). The age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) decreased significantly, with EAPCs of -6.48% and -4.88%, respectively. The ASIR was highest among children aged 10‒14 years, while the ASMR was relatively higher among children under 10 years old. The ASIR was consistently higher in boys than in girls. The ASMR in boys was lower than that in girls before 2009 but exceeded that in girls thereafter; similarly, the ASDR in boys was lower than that in girls before 2006 but became higher thereafter. Decomposition analysis showed that the decline in incidence burden was driven by population growth and epidemiological changes, while the reductions in mortality and disability burden were mainly driven by epidemiological improvements. The BAPC model predicted that the ASIR, ASMR, and ASDR would continue to decline from 2024 to 2050, but a slight rebound might occur after 2045.Conclusion·Between 1990 and 2023, the mortality and disability burden of appendicitis among Chinese children was significantly reduced, whereas the decline in incidence burden was relatively limited. Differences in disease burden existed across age groups and genders, and the overall disease burden may rise slightly in the future.
Objective·To investigate the regulatory role of the selenoprotein SELENOI (ethanolamine phosphotransferase 1, EPT1) in the proliferation, migration and invasion of gastric cancer cells, as well as its molecular mechanism.Methods·The expression levels of SELENOI in gastric mucosal epithelial cells and gastric cancer cell lines were detected using Western blotting and quantitative real-time PCR (qPCR). The clinical pathological data of 100 patients who underwent surgery at the Department of Gastrointestinal Surgery of Renji Hospital, Shanghai Jiao Tong University School of Medicine, from 2010 to 2015 were collected, and the association between SELENOI expression levels and patient prognosis was analyzed. The expression of SELENOI in gastric adenocarcinoma tumor tissues and normal tissues was analyzed based on The Cancer Genome Atlas (TCGA) database. The differentially expressed genes between the SELENOI high- and low-expression groups were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to select SELENOI-related signaling pathways. The regulatory association of SELENOI with this pathway was verified by qPCR and Western blotting. HGC-27 and NUGC-3 gastric cancer cells were treated with SELENOI-targeted small interfering RNA (siRNA), SELENOI overexpression plasmid alone, or in combination with the mechanistic target of rapamycin (mTOR) inhibitor rapamycin. The cell proliferation ability was detected by CCK-8 assay, and cell migration and invasion abilities were detected by Transwell assay.Results·Bioinformatics analysis revealed that SELENOI was significantly highly expressed in gastric cancer tissues (P<0.05). Kaplan-Meier survival analysis of 100 patients with gastric adenocarcinoma showed that patients with high SELENOI expression had worse prognosis (P=0.022). qPCR and Western blotting results confirmed that the expression levels of SELENOI in HGC-27, NUGC-3, AGS, and MKN45 gastric cancer cell lines were significantly higher than those in gastric mucosal epithelial cells GES-1 (all P<0.05). KEGG pathway enrichment analysis and subsequent molecular validation experiments confirmed that SELENOI promoted the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mTOR signaling pathway in gastric cancer. CCK-8 and Transwell assay results showed that SELENOI enhanced the proliferation, migration and invasion abilities of gastric cancer cells by activating the PI3K/AKT/mTOR signaling pathway, and rapamycin significantly reversed this tumor-promoting effect.Conclusion·SELENOI is highly expressed in gastric cancer tissues and cells. SELENOI can promote the proliferation, migration and invasion of gastric cancer cells by activating the PI3K/AKT/mTOR signaling pathway.
Objective·To systematically assess the expression characteristics and prognostic significance of syndecan-binding protein (SDCBP) across various cancers, as well as its associations with the tumor immune microenvironment, tumor mutational burden (TMB), and drug sensitivity, and to validate the biological functions and underlying mechanisms of SDCBP in gastric cancer through in vitro experiments.Methods·This study conducted comprehensive multi-omics analyses to examine the differential expression, prognostic indicators, immune infiltration, immune checkpoints, TMB/microsatellite instability (MSI), and drug sensitivity associated with SDCBP by integrating data from various bioinformatics databases. In addition, Western blotting, cell counting kit-8 (CCK-8) assay, wound healing assay, and Transwell assay were utilized to assess the impact of SDCBP on the proliferation and migration of gastric cancer cells, and to elucidate its regulatory roles in epithelial-mesenchymal transition (EMT)-related proteins and the TGF-β/Smad signaling pathway.Results·SDCBP expression was significantly upregulated in various malignant tumors, including gastric cancer, and its high expression was closely associated with poor prognosis (all P<0.05). Additionally, SDCBP expression levels exhibited a positive correlation with diverse immune-infiltrating cells, immune regulatory factors, and major histocompatibility complex (MHC) molecules. Furthermore, in certain tumors, SDCBP expression was significantly associated with TMB or MSI (all P<0.05). Drug sensitivity analysis revealed that elevated SDCBP expression was positively correlated with tumor drug resistance, and in specific cancer types, negatively correlated with intratumoral microbial abundance (all P<0.05). In vitro experiments provided further evidence that SDCBP was highly expressed in gastric cancer tissues and cell lines. SDCBP expression was significantly reduced in patients older than 65 years (P<0.05). Furthermore, SDCBP expression levels differed significantly across TNM stages (Ⅰ‒Ⅳ), with stage Ⅲ exhibiting the highest expression (P<0.05). According to Lauren classification, diffuse-type tumors exhibited significantly higher SDCBP expression compared to intestinal-type and mixed-type tumors (P<0.05). Furthermore, molecular subtype analysis indicated that SDCBP expression was significantly greater in the invasive subtype than in other subtypes (P<0.001).The silencing of SDCBP inhibited the viability and migration of gastric cancer cells, whereas its overexpression facilitated the malignant phenotypes of these cells (P<0.05). Mechanistic investigations suggested that SDCBP may advance the progression of gastric cancer by modulating the expression of EMT-related proteins, including N-cadherin, Vimentin, and Snail1 (P<0.05), and by activating the TGF-β/Smad signaling pathway.Conclusion·SDCBP has important clinical relevance across pan-cancer types and may serve as a key molecule promoting gastric cancer progression, providing theoretical support for its potential role as a prognostic biomarker and therapeutic target.
Objective·To investigate the auxiliary diagnostic value of serum gastrin-17 (G-17) and pepsinogen Ⅰ(PGⅠ) as biomarkers for autoimmune gastritis (AIG).Methods·A total of 100 patients suspected of AIG based on endoscopic screening were retrospectively enrolled. Clinical data were collected, including laboratory parameters such as parietal cell antibody (PCA) and intrinsic factor antibody (IFA). Based on serum antibody results, patients positive for either PCA or IFA were assigned to the confirmed AIG group (n=82), and those negative for both antibodies were assigned to the suspected AIG group (n=18). Serological parameters, including G-17, PGⅠ, PGⅡ, and vitamin B12, were compared between the two groups. Multivariable Logistic regression was employed to identify independent predictors of AIG. The diagnostic performance of serological markers and their combinations was assessed using receiver operating characteristic (ROC) curve analysis.Results·Serological analysis revealed significantly higher G-17 levels and significantly lower PG Ⅰlevels, PG Ⅰ/Ⅱ ratio, and vitamin B12 levels in the confirmed AIG group (all P<0.05). Multivariable Logistic analysis identified G-17 as an independent predictor of AIG (OR=1.09, 95% CI 1.02‒1.16, P=0.009). ROC analysis showed that the combination of G-17>17.84 pmol/L and PGⅠ<12.69 ng/mL yielded the best diagnostic performance, with an area under the curve (AUC) of 0.883 (95% CI 0.800‒0.967), sensitivity of 79.3%, and specificity of 83.3%. Among patients in the confirmed AIG group, 34.1% (28/82) were IFA-positive. Age was identified as an independent predictor of IFA positivity (OR=1.05‒1.06, P<0.05),with age >55.5 years identified as an important risk threshold. A predictive model incorporating age (>55.5 years), G-17, and PG Ⅰ/Ⅱ ratio showed good predictive performance for IFA positivity, with an AUC of 0.72 (95% CI 0.598‒0.835), sensitivity of 67.9%, and specificity of 70.4%.Conclusion·In settings where specific antibody (PCA/IFA) testing is unavailable, the combination of serum G-17 and PG Ⅰ measurements may serve as an effective auxiliary tool for diagnosing AIG. For AIG patients aged >55.5 years, attention to changes in G-17 levels and the PG Ⅰ/Ⅱ ratio may help identify individuals at high risk of IFA positivity.
Objective·To evaluate the diagnostic performance and application value of a domestically developed microfluidic technology-based nucleic acid detection system for gastrointestinal pathogens.Methods·A total of 534 fecal samples were collected from Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, between April 5th, 2024 and October 6th, 2025. Based on the purpose of testing, the samples were divided into three independent cohorts. Cohort A included 15 samples confirmed positive for Clostridium difficile by the Xpert Clostridium difficile assay (Xpert C. difficile), which were used to evaluate the performance of the gastrointestinal pathogen detection panel (high definition gastrointestinal panel, HD GI panel) for detecting Clostridium difficile. Cohort B included 167 samples from patients requiring comprehensive gastrointestinal pathogen screening and was used to compare the multi-pathogen detection performance of the HD GI panel with the FilmArray gastrointestinal panel (FilmArray GI panel). Cohort C consisted of 352 fecal samples from children with clinically suspected gastrointestinal infections who were admitted to the pediatric intensive care unit (PICU), and was used to analyze the epidemiological characteristics of gastrointestinal pathogens in critically ill children and the clinical application value of the HD GI panel. Sociodemographic and baseline clinical data of children in Cohort C were collected. The Kappa test assessed the agreement between the two detection methods. The McNemar test was used to compare the differences in positive detection rates between the two methods. Pearson correlation analysis was used to evaluate the correlation CT values obtained by the two methods. Using the results of the FilmArray GI panel as the reference standard, the sensitivity, specificity, positive predictive value, and negative predictive value of the HD GI panel, along with their 95% confidence intervals, were calculated. Multivariate Logistic regression analysis was used to identify factors affecting the detection accuracy.Results·The detection results for Clostridium difficile obtained with the HD GI panel and the Xpert C. difficile assay were consistent, and the CT values showed a moderate positive correlation (r=0.594, P=0.019). The overall compliance between the HD GI panel and the FilmArray GI panel was 92.22%, and the Kappa test indicated good consistency between the two methods (κ=0.823, P<0.001). Compared with the FilmArray GI panel, the HD GI panel achieved a sensitivity of 88.89%, a specificity of 93.81%, a positive predictive value of 87.27%, and a negative predictive value of 94.64%. Among critically ill children, the overall positivity rate detected by the HD GI panel was 39.77%. Norovirus GⅡ, rotavirus A, and adenovirus were the predominant viral pathogens, whereas enteroaggregative Escherichia coli (EAEC), Clostridium difficile, and Salmonella were the main bacterial pathogens. Co-infections accounted for 30.00%. Compared with clinical diagnosis, the HD GI panel demonstrated a sensitivity and a negative predictive value of 100.00%, with a diagnostic accuracy of 93.60%. The Kappa test showed a high level of agreement between the two methods (κ=0.860, P<0.001). Multivariate Logistic regression analysis further revealed that the presence of underlying diseases was an independent factor associated with detection accuracy (OR=0.051, 95%CI 0.014‒0.141, P<0.001).Conclusion·The HD GI panel demonstrates diagnostic performance comparable to that of mainstream platforms for gastrointestinal pathogen detection, offering advantages such as simple operation, rapid turnaround, and a pathogen spectrum consistent with the characteristics of pediatric gastrointestinal infections in China. It is well suited for use in primary hospitals and high-throughput testing settings.
Objective·To investigate the role and molecular mechanism of lysine demethylase 4B (KDM4B) in anti-tumor immunity of colorectal cancer (CRC).Methods·KDM4B expression levels in tumor and para-tumor tissues from a CRC tissue microarray were assessed by immunohistochemistry (IHC) staining. Transcriptomic sequencing datasets from the Gene Expression Omnibus (GEO) database were utilized to analyze the correlations of KDM4B mRNA expression with patient prognosis and intratumoral CD8⁺ T cell infiltration in CRC. Gene Set Enrichment Analysis (GSEA) was conducted on CRC samples with high and low KDM4B expression to identify KDM4B-related biological processes. KDM4B-related biological processes were examined in CRC cells subjected to KDM4B knockdown or B3 treatment using quantitative real-time PCR (qPCR), immunofluorescence (IF) staining, and Western blotting. Mouse subcutaneous tumor models were employed to evaluate the impact of Kdm4b knockdown or B3 treatment on CT26 tumor growth, as well as intratumoral CD8⁺ T cell infiltration and cytotoxicity in vivo. Additionally, the anti-tumor efficacy of B3 treatment, anti-programmed cell death protein-1 (PD-1) antibody therapy, and their combination (B3+anti-PD-1) was compared in CT26 subcutaneous tumor models.Results·IHC staining results revealed that KDM4B expression was significantly higher in CRC tissues than in para-tumor tissues (P<0.001). Analysis of transcriptomic datasets from the GEO database showed that CRC patients in the KDM4B-low expression group exhibited longer overall survival and increased intratumoral CD8⁺ T cell infiltration (both P<0.05). GSEA results indicated that low KDM4B expression was significantly correlated with typeⅠ interferon response and Th1-type cytotoxic response. qPCR, IF staining, and Western blotting results showed that KDM4B knockdown or B3 treatment promoted DNA double-strand breaks, activated the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, and increased the expression of type Ⅰ interferons and Th1-type chemokines in CRC cells (all P<0.05). In vivo experiments demonstrated that Kdm4b knockdown or B3 treatment suppressed CT26 tumor growth, and enhanced intratumoral CD8⁺ T cells infiltration and granzyme B expression (all P<0.05). Moreover, compared with B3 or anti-PD-1 antibody monotherapy, the combination of B3 and anti-PD-1 antibody exhibited stronger anti-tumor effects against mouse CT26 subcutaneous tumors (all P<0.05).Conclusion·KDM4B knockdown or B3 treatment enhances the expression of type Ⅰinterferons and Th1-type chemokines in CRC cells, promotes CD8⁺ T cell-mediated anti-tumor immunity in vivo, and sensitizes CRC to anti-PD-1 antibody therapy.
As a novel in vitro three-dimensional culture model, organoids, with their high self-organizing ability, can recapitulate the morphological structures, pathophysiological functions, genetic variation profiles, and drug treatment responsiveness of their parental tissues. Compared with traditional animal models, organoids have the characteristics of short preparation cycle, low cost, less ethical controversy and high throughput. They are currently widely applied in biomedical research. Patient-derived organoid models retain the heterogeneity of their tissues of origin, can be continuously expanded and passaged in vitro over the long term, and maintain cell viability after cryopreservation and resuscitation. These characteristics provide a valuable platform for human disease modeling and demonstrate significant application value in exploring pathogenesis, screening novel drugs, and predicting drug sensitivity. The intervention of artificial intelligence (AI) has further enhanced the automation and standardization in the construction and application of organoids. This article systematically summarizes the research progress of organoids related to benign and malignant diseases of the digestive system, with particular emphasis on optimization strategies for constructing organoids derived from different organs and tissues. The paper also introduces the collection methods for digestive system tumor samples and the impact of neoadjuvant therapy on organoid construction. In addition, the article summarizes the advances of AI algorithms in organoid construction and applications, including AI-assisted organoid morphological characterization, cell viability assessment, drug sensitivity prediction, and the development of AI-integrated automated organoid platforms. In the future, AI will play a significant role in organoid construction for digestive system disease organoids and their diverse application scenarios, providing strong support for translational applications such as disease modeling, molecular target discovery, drug screening, and elucidation of drug resistance mechanisms.
Objective·To evaluate the safety and feasibility of robot-assisted left hemicolectomy for colon cancer (R-LCC) in patients with left-sided colon cancer requiring left colic flexure mobilization.Methods·A total of 105 patients with colon cancer who underwent R-LCC in the Department of Gastrointestinal Surgery, the First Affiliated Hospital of Nanchang University, between September 2015 and June 2023 were retrospectively enrolled. Clinical and pathological data of all patients were collected. The incidence of postoperative complications was analyzed, and postoperative prognostic follow-up was conducted for all patients.Results·Among the 105 patients with colon cancer who underwent R-LCC, one patient converted to open surgery due to intraoperative bleeding. The median operative time was 165 min. All patients achieved R0 resection, with no cases of positive resection margins. The ulcerative type was the most common gross tumor type, accounting for 69.5% of all cases. The maximum tumor diameter was (4.67±1.97) cm. The total number of harvested lymph nodes was 14 (1‒42), and the number of metastatic lymph nodes was 0 (0‒13). The overall incidence of postoperative complications within 30 d was 16.2%. Surgical site infection was the most common postoperative complication, with an incidence rate of 6.7%. The 1- and 3-year cumulative survival rates were 91.4% and 85.1%, respectively.Conclusion·Patients undergoing R-LCC with left colic flexure mobilization have a low incidence of intraoperative complications and favorable survival outcomes. These findings confirm that robotic surgery is safe and feasible for this procedure.
Objective·To explore the latent profiles of resilience among young and middle-aged patients with gastrointestinal cancer undergoing chemotherapy, and analyze the factors associated with these profiles.Methods·From October 2024 to August 2025, a purposive sampling method was adopted to enroll young and middle-aged patients (18‒59 years old) with gastrointestinal cancer who received standardized chemotherapy in the Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine. A cross-sectional survey was conducted using the General Information Questionnaire, Resilience Scale, Emotion Regulation Questionnaire, Social Support Rating Scale, and Hospital Anxiety and Depression Scale. Mplus 8.3 software was used for latent profile analysis. With each item score of resilience as the indicator variable, the latent categories of resilience in young and middle-aged patients with gastrointestinal cancer undergoing chemotherapy were identified. Subsequently, multivariate Logistic regression analysis was performed to identify factors associated with the latent profiles, with the profile category as the dependent variable.Results·A total of 393 valid patients were included, and the total resilience score of patients was 65.72±13.54. The model fitting results showed that the three-profile model was optimal. According to the characteristics of item scores, the three profiles were named as the passive vulnerability group (21.4%), stable adaptation group (51.1%), and active growth group (27.5%). Multivariate Logistic regression analysis revealed that, with the active growth group as the reference, patients who were male, had no religious belief, had a monthly income of less than 3 000 yuan, had a higher depression level, and obtained lower scores of subjective support and cognitive reappraisal were more likely to be classified into the passive vulnerability group. Patients who had no religious belief, had a monthly income of less than 10 000 yuan, and had lower scores of subjective support and cognitive reappraisal were more likely to be classified into the stable adaptation group.Conclusion·Resilience among young and middle-aged patients with gastrointestinal cancer undergoing chemotherapy exhibits heterogeneity and can be divided into three categories: the passive vulnerable group, stable adaptive group, and active growth group. Patients who are male, have no religious belief, have a lower monthly income, have a higher depression level, have lower subjective support, and use cognitive reappraisal strategies less frequently tend to have lower resilience levels.
Primary malignant melanoma of the esophagus (PMME) is an extremely rare malignant tumor. To investigate its clinicopathological characteristics, this study reports the clinicopathological features, immunophenotypes, and prognostic information of two cases. The patients were a 74-year-old female and a 64-year-old male, who presented with a foreign body sensation during swallowing and abdominal distension, respectively, with no history of primary melanoma in the skin or other sites. The lesions were located in the upper and lower esophagus, and appeared grossly as a large ulcer and a slightly elevated nodule, respectively. Microscopic examination revealed localized loss of the surface squamous epithelium in both cases, with in situ melanoma components observed within the residual epithelium. Immunohistochemical analysis demonstrated that tumor cells in both cases strongly expressed melanoma antigen recognized by T-cells 1 (MelanA) and SRY-box transcription factor 10 (Sox-10), with partial expression of S100 calcium-binding protein (S100) and microphthalmia-associated transcription factor (MiTF). This study indicates that PMME is a rare primary esophageal tumor whose endoscopic appearance can easily be confused with those of other primary esophageal malignancies. Therefore, pathological diagnosis plays a crucial role in establishing the diagnosis of this disease.
Objective·To investigate the expression characteristics and clinical prognostic value of the deubiquitinating enzyme ubiquitin-specific peptidase 38(USP38)in gastric cancer,as well as its pro-oncogenic molecular mechanism,and to identify the downstream key target RNA-binding motif protein 14(RBM14).Methods·Tumor and adjacent non-tumor tissue specimens were collected from 50 patients with gastric cancer who underwent surgical treatment at the Department of Gastrointestinal Surgery,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine.Quantitative real-time PCR and Western blotting were used to verify the expression of USP38 in gastric cancer,and data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)were used to analyze the correlation between the clinical characteristics of patients with gastric cancer and USP38 expression levels.Gene Set Enrichment Analysis(GSEA),Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed to predict USP38-related signaling pathways.Potential substrates of USP38 were screened by combining published literature with the results of Pearson correlation analysis.The effects of USP38 on the proliferation and migration of AGS and HGC-27 gastric cancer cells were assessed using the cell counting kit-8(CCK-8),5-ethynyl-2'-deoxyuridine(EdU)assay,colony formation assay,and wound healing assay.A stable knockdown cell line was constructed using lentiviral vectors carrying short hairpin RNA(shRNA)targeting USP38,and functional rescue experiments were performed to validate the biological function of the USP38-RBM14 regulatory axis.Results·TCGA data analysis showed that USP38 was significantly highly expressed in gastric cancer tissues(P<0.001),and its expression level was positively correlated with shorter overall survival(log-rank P<0.001,HR=1.36)and pathological stage(P=0.017).GSEA analysis revealed that the high-USP38-expression group was significantly enriched in the G2/M checkpoint,early 2 factor(E2F)targets,nuclear speckles,and DNA damage repair pathways(all adjusted P value<0.001),and knockdown of USP38 downregulated the expression of proliferation-and mesenchymal-related markers.Functional experiments confirmed that USP38 knockdown significantly inhibited the proliferation and migration of gastric cancer cells(P<0.05).Pearson correlation analysis revealed that the expression levels of USP38 and its potential binding protein RBM14 were significantly positively correlated(R=0.22,P<0.001).Further studies revealed that USP38 knockdown decreased RBM14 protein levels,and experiments with a proteasome inhibitor and cycloheximide(CHX)indicated that USP38 stabilized RBM14 at the post-translational level.Functional rescue experiments showed that RBM14 overexpression partially reversed the inhibitory effect of USP38 knockdown on gastric cancer cells,confirming that USP38 promoted gastric cancer progression by stabilizing RBM14 protein.Conclusion·USP38 is highly expressed in gastric cancer and is associated with poor patient prognosis;knocking down USP38 can inhibit the proliferation and migration of gastric cancer cells.USP38 exerts an oncogenic effect by stabilizing the RBM14 protein.
Objective·To evaluate and compare the efficacy of three types of radical esophagectomy for esophageal cancer.Methods·The clinical data of 298 patients who underwent radical esophagectomy were retrospectively analyzed. The patients were divided into three groups based on the surgical approach: the synchronous insufflation mediastinoscopy with laparoscopy esophagectomy (SIMLE) group, the combined insufflation mediastinoscopy-laparoscopy esophagectomy (CIMLE) group, and the McKeown group. Propensity score matching (PSM) was performed at a 1∶1 ratio for pairwise stratification matching between groups. Differences among the groups were analyzed in terms of preoperative baseline data, operative time, intraoperative blood loss, indicators of internal homeostasis, postoperative complications, number of lymph nodes dissected, and postoperative recovery status.Results·After PSM, 75 pairs were matched between the SIMLE and CIMLE groups, and 88 pairs between the SIMLE and McKeown groups. Operative time and intraoperative blood loss in the SIMLE group were significantly lower than those in the CIMLE and McKeown groups (all P<0.001). At the end of anesthesia induction, indicators of internal homeostasis, including pH value, glucose, base excess, and lactate levels, in the SIMLE group were superior to those in the CIMLE and McKeown groups (all P<0.05). The SIMLE group also showed better outcomes than the other two groups in terms of complications such as anastomotic leakage and anastomotic stricture (P<0.05). The postoperative hospital stay in the SIMLE group was shorter than that in the CIMLE and McKeown groups (both P<0.001). At 7 days postoperatively, levels of interleukin-6, tumor necrosis factor-ɑ, and C-reactive protein in the SIMLE group were significantly lower than those in the CIMLE and McKeown groups (all P<0.05). At 14 days postoperatively, recovery of prealbumin and albumin levels was better in the SIMLE group (all P<0.05). Within 1 month after surgery, the SIMLE group had significantly higher scores on the 15-item Quality of Recovery-15 (QoR-15) scale compared to the CIMLE and McKeown groups (all P<0.05).Conclusion·The SIMLE procedure, through synchronous operation using mediastinoscopy and laparoscopy, can shorten operative time, reduce surgical stress, and accelerate postoperative recovery, providing a new minimally invasive treatment option for patients with esophageal cancer.
Objective·To evaluate the efficacy of statins combined with glucocorticoids in preventing esophageal stricture after large-area endoscopic submucosal dissection (ESD).Methods·This was a retrospective cohort study. Patients who underwent ESD for early-stage esophageal carcinoma and precancerous lesions with a surgical wound covering ≥3/4 of the circumference in the Department of Gastroenterology, Hebei Medical University Third Hospital, from January 2015 to January 2023 were enrolled. Patient baseline data, surgery-related information, and postoperative follow-up data were collected. All patients received oral prednisone acetate postoperatively. Patients were categorized into two groups based on statin administration: an oral glucocorticoid group and an oral glucocorticoid plus statin group. The two groups were compared in terms of the incidence of postoperative esophageal stricture, time to first stricture onset, number of balloon dilations after stricture formation, and adverse reactions. Multivariate Logistic regression analysis was employed to identify risk factors associated with esophageal stricture.Results·A total of 53 patients were enrolled, including 32 in the oral glucocorticoid group and 21 in the oral glucocorticoid plus statin group. There were significant differences in the prevalence of coronary heart disease, cerebral infarction, and hyperlipidemia between the two groups (all P<0.05). However, no significant differences were observed in gender, age, body mass index (BMI), smoking history, drinking history, history of hypertension or diabetes, esophageal lesion location, lesion invasion depth, postoperative pathological results, and longitudinal length of resected mucosa. A total of 16 patients developed postoperative esophageal stricture in the 53 patients, with an overall stenosis rate of 30.2%. The oral glucocorticoid group exhibited a higher stricture rate compared with the oral glucocorticoid plus statin group (37.5% vs 19.0%), though this difference was not statistically significant (P=0.152). After esophageal stricture occurred, the number of balloon dilations was significantly lower in the oral glucocorticoid plus statin group than in the oral glucocorticoid group [(1.50±0.58) times vs (2.33±0.65) times, P=0.040]. There were no significant differences in the time to first stricture onset between the two groups (P=0.368). Multivariate Logistic regression analysis identified circumferential wound involvement as a significant risk factor for esophageal stricture (OR=35.266, 95% CI 5.600‒222.103, P<0.001). However, the use of statins showed no statistically significant association with esophageal stricture (OR=0.216, 95% CI 0.033‒1.393, P=0.107).Conclusion·The combination of glucocorticoids and statins can safely and effectively reduce the number of balloon dilatations and alleviate the severity of esophageal stricture in patients developing esophageal stricture after ESD.
Objective·To compare and analyze the short-term effect of the Da Vinci robotic system and laparoscopy for the resection of mesenteric cyst in children.Methods·A retrospective analysis was conducted on the clinical data of 71 children who underwent Da Vinci robotic-assisted or laparoscopic-assisted mesenteric cyst resection in the Department of General Surgery, Children's Hospital, Zhejiang University School of Medicine between January 2020 and August 2025. Patients were divided into the Da Vinci group (n=33) and the laparoscopic group (n=38) based on surgical approach. Comparative analysis of baseline characteristics, operative time, intraoperative blood loss, mode of surgical completion, cyst location, maximum cyst diameter, postoperative fasting time, postoperative hospital stay, and postoperative complications was performed to evaluate the advantages and disadvantages of the two approaches.Results·Baseline characteristics showed no statistically significant differences between the two groups in gender, age, weight, clinical symptoms, cyst location, or maximum cyst diameter (all P>0.05). Regarding the mode of surgical completion, all 33 patients (100%) in the Da Vinci group underwent complete intracavitary cyst dissection or bowel resection and anastomosis; only 3 patients (7.9%) in the laparoscopic group completed all procedures via an intracavitary approach, while the remaining patients required extraperitoneal completion of the procedure. The distribution of surgical completion modes differed significantly between the two groups (P<0.001). There were no statistically significant differences in operative time or postoperative fasting time between the two groups (both P>0.05). Intraoperative blood loss was significantly lower in the Da Vinci group than in the laparoscopic group [5 (2, 5) mL vs 6 (5, 10) mL, P<0.001], and postoperative hospital stay was also significantly shorter in the Da Vinci group [9 (7,11) d vs 10.5 (8,13) d, P=0.033]. No complications were observed in the Da Vinci group. In the laparoscopic group, one patient experienced intraoperative ureteral injury, and one developed postoperative chylous fistula. All patients were followed up for 6 months after discharge and achieved favorable recovery without cyst recurrence.Conclusion·Compared with laparoscopic surgery, the Da Vinci robotic approach for pediatric mesenteric cyst resection markedly increases the rate of complete intracavitary procedures, with the merits of less intraoperative hemorrhage and faster postoperative recovery. It demonstrates reliable short-term efficacy and favorable safety.
Safety and precision are the core pursuits driving the sustainable development of minimally invasive surgery. With advantages including high-definition three-dimensional visualization, stable and flexible instrument manipulation, and highly precise operations, robotic surgery is highly consistent with the developmental concepts of modern minimally invasive surgery. As an important branch of robotic surgery, robotic gastrectomy has undergone more than two decades of clinical exploration and iterative evolution, with its technical system becoming increasingly mature and achieving large-scale clinical application. Clinical studies have confirmed that robotic gastrectomy yields superior short-term outcomes compared with laparoscopic gastrectomy; it can effectively reduce intraoperative blood loss and the incidence of postoperative complications, and also exhibits prominent advantages in key procedures such as dissection of lymph nodes and totally intracorporeal gastrointestinal reconstruction. The clinical application scenarios of robotic gastrectomy have been further expanded with the rapid development of domestically manufactured surgical robots, continuous innovation of single-port robotic systems and vigorous advancement of 5G-based remote robotic surgery. However, consensus has not yet been reached regarding its long-term oncological benefits, high-quality prospective evidence-based medical evidence remains relatively insufficient, and challenges such as prolonged operative time and high treatment costs have, to some extent, restricted its widespread adoption in primary-level hospitals. This review integrates clinical studies and cutting-edge advances in robotic gastrectomy from domestic and international perspectives, systematically elaborates the technical evolution, current clinical application status, predominant existing challenges, and future development directions of this surgical approach. The study aims to provide a theoretical reference for the standardized and high-quality development of domestic robotic gastric surgery in China and drive the continuous advancement of minimally invasive gastric cancer surgery toward precision, intelligence and affordability.
Objective·To explore the inhibitory effect of bardoxolone methyl (CDDO-Me) on ubiquitin-specific protease 48 (USP48) and its mechanisms against colorectal cancer.Methods·In vitro enzyme activity assays, thermal shift analysis (TSA), and molecular docking techniques were employed to verify the binding ability of CDDO-Me to USP48 and its inhibitory effect on USP48 enzymatic activity. The cellular thermal shift assay (CETSA) was used to confirm the targeted binding of CDDO-Me to USP48 in colorectal cancer cells. Western blotting was utilized to detect the impact of CDDO-Me on the expression levels and ubiquitination modifications of the USP48 substrates high mobility group AT-hook 2 (HMGA2) and nuclear factor NF-κB p65 subunit (RelA/p65). Wound-healing assay and cell counting kit-8 (CCK-8) assay were adopted to examine the effects of CDDO-Me on the migration and proliferative activities of colorectal cancer cells, and the USP48 overexpression experiments were carried out to verify its target specificity. Subcutaneous xenograft and lung metastasis models of MC38 colorectal cancer were established in mice to investigate the in vivo anti-tumor effects of CDDO-Me, and immunohistochemistry was used to detect the expression levels of cell proliferation nuclear antigen Ki-67, terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL), HMGA2, and p65 in tumor tissues.Results·CDDO-Me directly bound to USP48 in vitro and significantly inhibited its deubiquitinating activity. CETSA experiment confirmed that CDDO-Me specifically interacted with USP48 in colorectal cancer cells. By inhibiting USP48, CDDO-Me enhanced K48-linked ubiquitination of HMGA2, promoted its proteasomal degradation, and down-regulated the protein expression levels of HMGA2 and p65 in colorectal cancer cells in a dose-dependent manner. CDDO-Me significantly inhibited the migration and proliferative activities of colorectal cancer cells, and USP48 overexpression reversed these effects. In vivo experiments indicated that CDDO-Me significantly inhibited the growth and lung metastasis of MC38 colorectal cancer subcutaneous xenografts in mice, decreased the expression levels of Ki-67, HMGA2, and p65 in tumor tissues, and increased the number of TUNEL-positive cells.Conclusion·CDDO-Me is a novel USP48 inhibitor. It can promote the ubiquitination-mediated degradation of the oncogenic substrate HMGA2 by targeting and inhibiting USP48, thereby suppressing the proliferation and migration of colorectal cancer cells, as well as tumor growth and metastasis in vivo.
Objective·To explore the function and potential mechanism of circular RNA (circRNA) hsa_circ_0001900 in Wilms tumor.Methods·Lentivirus was used to construct cell lines with stable overexpression of hsa_circ_0001900 (WIT-49, WT-CLS1, and SK-NEP-1), and specific small interfering RNA (siRNA) was used to transiently silence this molecule. Transcriptome sequencing was performed on hsa_circ_0001900-overexpressing and control cell lines, and its potential biological functions were preliminarily explored based on enrichment analysis of differentially expressed genes. cell counting kit-8 (CCK-8) assay, wound-healing assay, Transwell assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were used to evaluate the effects of hsa_circ_0001900 on the proliferation, migration, invasion, and apoptosis of Wilms tumor cells. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were further adopted to screen Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways potentially regulated by hsa_circ_0001900. Finally, flow cytometry was used to detect cell cycle distribution and apoptosis to verify the related pathways experimentally.Results·PCR assays confirmed that the expression of hsa_circ_0001900 was significantly upregulated in Wilms tumor cell lines (WIT-49, WT-CLS1, and SK-NEP-1) compared with normal human embryonic kidney HEK-293T cells. Cell lines with stable overexpression and transient silencing were successfully constructed using lentivirus and siRNA, respectively. Enrichment analysis of transcriptomic data showed that differentially expressed genes were mainly enriched in pathways associated with cell proliferation, cell cycle regulation, migration, and apoptosis. In vitro experiments further confirmed that overexpression of hsa_circ_0001900 promoted the proliferation, migration, and invasion of Wilms tumor cells, while silencing this molecule significantly inhibited the above malignant biological behaviors and induced cell apoptosis. Mechanistically, enrichment analysis centered on hsa_circ_0001900 revealed that GSEA and GSVA jointly enriched the cell cycle signaling pathway. Flow cytometry detection showed that stable overexpression of hsa_circ_0001900 markedly shortened the G1 phase and prolonged the S phase in WIT-49, WT-CLS1, and SK-NEP-1 cells, suggesting that this molecule may drive the malignant progression of Wilms tumor by facilitating G1/S phase transition.Conclusion·hsa_circ_0001900 is specifically highly expressed in Wilms tumor cells. This molecule promotes the proliferation, migration, and invasion of Wilms tumor cells and inhibits cell apoptosis by accelerating the G1/S cell cycle transition.
The corneal nerve density-sensation-reflex axis plays an important role in maintaining the physiological homeostasis of the ocular surface. An in-depth understanding of the function of this axis is essential for the prevention and treatment of neurotrophic keratitis and the protection of visual function. Neurotrophic keratitis is one of the typical pathological models of axis imbalance. It is caused by trigeminal nerve injury, which leads to a reduction in corneal nerve density and corneal innervation, resulting in decreased corneal sensation and impairment of the protective blink reflex. This article reviews the anatomical and physiological basis of this axis and summarizes the quantitative evidence and molecular mechanisms underlying the effects of reduced nerve density on axis function. In addition, the assessment methods of axis function are discussed, including the quantification of corneal nerve parameters by in vivo confocal microscopy, the evaluation of corneal sensation using the Cochet-Bonnet esthesiometer, and the assessment of blink function by the corneal reflex test. In terms of therapeutic strategies, this article summarizes interventions targeting axis function, including epithelial trophic support and sensory restoration as well as corneal reinnervation. Furthermore, potential novel therapeutic approaches and therapeutic targets for the restoration of axis function are discussed.
Objective·To investigate the effect of the degree of maxillary sinus pneumatization(MSP)on total bone thickness(BT)and cortical bone thickness(CBT)along the insertion path of miniscrew implants(MIs)placed in the infrazygomatic crest(IZC)region.Methods·Young adult orthodontic patients aged 18-34 years were included.Cone-beam computed tomography(CBCT)data collected at the initial visit were analyzed.Based on the distance from the apex of the mesiobuccal root of the maxillary first molar to the sinus floor(sinus floor-apex distance,SFA),the samples were divided into three groups:high sinus floor group(HS group,SFA≥3 mm),middle sinus floor group(MS group,0 mm≤SFA<3 mm),and low sinus floor group(LS group,SFA<0 mm).MIs were placed at angles of 50° or 60° relative to the palatal plane at the apex levels of the mesiobuccal root of the maxillary first molar(U6M),the distobuccal root of the maxillary first molar(U6D),and the mesiobuccal root of the maxillary second molar(U7M),as well as 2 mm cranial to these apex levels.BT and CBT along the insertion path were measured and compared.Results·A total of 87 patients were included:HS group(n=33)with an SFA of(4.88±1.32)mm,MS group(n=27)with an SFA of(1.57±0.76)mm,and LS group(n=27)with an SFA of(-1.82±0.96)mm.At the U6M and U6D insertion sites,BT and CBT in all groups decreased as the degree of MSP increased.At U7M,no statistically significant differences in BT and CBT were found between the HS and MS groups,but both were greater than those in the LS group(all P<0.05).No statistically significant differences in BT were observed between the MS and LS groups at different sagittal sites.In the HS group,BT gradually decreased in the distal direction.All groups showed a trend toward thinner BT in the more cranial direction.In the HS group,at the apex level,a 50° insertion angle resulted in greater BT than a 60° insertion angle;at 2 mm cranial to the apex,no significant difference in BT was found between the 50° and 60° insertion angles.In the MS group,at both the apex level and 2 mm cranial to the apex,a 60° insertion angle provided greater BT than a 50° insertion angle.In the LS group,at 2 mm cranial to the apex,a 60° insertion angle provided greater BT than a 50° insertion angle;however,regardless of whether a 50° or 60° insertion angle was used,sufficient BT could not be obtained in the LS group.Conclusion·BT and CBT decreased significantly with increasing MSP in the IZC region.For HS patients,MI placement in the IZC region is generally safe.For MS patients,MI placement at the apex level is relatively safe.For LS patients,MI placement in the IZC region is not recommended.
Objective·To analyze the three-dimensional structure of the human histone methyltransferase SUV39H1 in complex with heterochromatin protein 1α bound to the endogenous nucleosome core particle (NCPendo) through cryo-electron microscopy (cryo-EM).Methods·The human SUV39H1 gene was cloned into the pMLink vector with an N-terminal 6×His-3×Flag tag, and the human HP1α gene was cloned into the pMLink vector with an N-terminal 2×HA tag. The SUV39H1-HP1α complex was co-expressed in Expi293F mammalian suspension cells through transient transfection using polyethylenimine. The expressed complex was sequentially purified by affinity chromatography with anti-DYKDDDDK resin and glycerol gradient ultracentrifugation combined with chemical cross-linking. Subsequently, cryo-EM data collection and single-particle reconstruction were performed to obtain the three-dimensional electron density map of the SUV39H1-HP1α-NCPendo complex. AlphaFold2-predicted models were docked into the EM density using UCSF Chimera.Results·The SUV39H1-HP1α-NCPendo complex was successfully obtained with high purity by affinity chromatography and glycerol density gradient ultracentrifugation. Cryo-EM single-particle reconstruction yielded a preliminary density map of the SUV39H1-HP1α-NCPendo complex at a resolution of approximately 3.6 Å (1 Å=10-10 m). In addition to the nucleosome core particle, an extra discontinuous peripheral density was observed. Based on its size and spatial distribution, preliminary structural fitting suggested that this density may correspond to the SET domain of SUV39H1.Conclusion·The density map of the SUV39H1-HP1α-NCPendo complex was obtained by cryo-EM and single-particle reconstruction. Although the peripheral density is discontinuous and does not support reliable atomic modeling, its size and spatial features are consistent with the SET domain (including pre-SET, SET, and post-SET sub-modules) of SUV39H1. In addition, the chromo domain (CD) of SUV39H1 and HP1α were not been clearly resolved, suggesting that these regions may exhibit conformational dynamics within this complex.
