Objective To explore the short-term efficacy of endoscopic submucosal dissection (ESD) in the treatment of early carcinoma in the remnant stomach. Methods A retrospective study was conducted on 45 patients with early residual gastric cancer underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2014 to April 2024, with a total of 45 lesions. The patients were divided into an anastomotic group (n=15) and a non-anastomotic group (n=30) based on the location of tumor occurrence, and their clinical data, endoscopic diagnosis and treatment, and histopathological conditions were compared between the two groups. Results All 45 patients had lesions with redness and erosion. There were 9 cases of poor lifting of submucosal injection in the anastomotic group and 2 cases in the non-anastomotic group, respectively, and the difference was statistically significant (P<0.05). ESD surgery was performed on 13 lesions in the anastomotic group and 28 lesions in the non-anastomotic group, with surgery times of 80.00 (50.00, 100.00) min and 55.00 (43.75, 80.00) min, respectively. The difference in surgery time between the two groups was statistically significant (P=0.03). Among the 45 patients, ESD surgery achieved curative resection in 35 cases, including 11 cases in the anastomotic group and 24 cases in the non-anastomotic group, with no statistically significant difference. Conclusions Careful preoperative evaluation of early carcinoma in the remnant stomach is essential to prevent oversight. Lesions at anastomotic sites and suture lines present higher technical challenges for complete resection. ESD is safe and effective, with auxiliary traction technique available when necessary.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

OBJECTIVES: To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment. METHODS: LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting. RESULTS: A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups. CONCLUSIONS LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
Animals ; Female ; Cisplatin/pharmacology* ; Ovarian Neoplasms/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred BALB C ; Mice ; Rats ; Xenograft Model Antitumor Assays ; Humans ; Cell Line, Tumor ; Antineoplastic Agents/pharmacology*

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Objective:To investigate the role of ubiquitin-specific protease 21 (USP21) in enterovirus group A type 71 (EV-A71) infection.Methods:Peripheral blood mononuclear cells (PBMC) were obtained from a cohort of 24 children infected with EV-A71 and 24 healthy children. Expression of USP21 was determined by real-time fluorescence quantitative PCR (qPCR). Additionally, the impact of USP21 overexpression or knockout on EV-A71 replication was evaluated using a combination of qPCR and western blot (WB) analysis. Furthermore, WB was employed to measure the levels of EV-A71 structural protein VP1, phosphorylated interferon regulatory factor 3 (IRF3) and other key molecules in the RIG-I-like receptor (RLR) signaling pathway. Co-immunoprecipitation (Co-IP) was utilized to investigate the effects of USP21 on the ubiquitin levels of EV-A71 nonstructural protein 2A protease (2A pro). Results:In comparison to healthy children, the expression of USP21 mRNA in PBMC of children infected with EV-A71 was notably elevated. The overexpression of USP21 significantly enhanced the cytopathic effects induced by EV-A71, upregulated levels of VP1 mRNA and protein, and facilitated EV-A71 replication, leading to a decrease in cell activity with increasing levels of USP21 transfection. Following the knockout of the USP21 gene, the VP1 mRNA levels were significantly declined in comparison to the control group. Furthermore, the overexpression of USP21 was found to have no impact on the transcriptional activity of EV-A71 2A pro. However, it was observed to enhance the expression of 2A pro protein, reduce the ubiquitination of 2A pro, suppress the protein levels of mitochondrial antiviral signaling protein (MAVS) and melanoma differentiation-associated gene 5 (MDA5), as well as decrease the phosphorylation of IRF3. Additionally, the induction of IFN-β mRNA by EV-A71 infection was downregulated. Conclusions:USP21 has been shown to enhance the replication of EV-A71 through the downregulation of 2A pro ubiquitination, suppression of MAVS and MDA5 protein expression, and inhibition of the interferon signaling pathway.

Objective:To explore the efficacy and safety of mitotane in adrenal cortical carcinoma (ACC) at high risk of recurrence.Methods:A prospective observational study was designed from September 2022 to November 2023. ACC patients undergoing surgery with high recurrence risk (positive margin or Ki-67 index >10% or capsule rupture or large size or high-grade ACC) in Peking Union Medical College Hospital were enrolled in this study. All patients started mitotane treatment within 3 months after surgery, with a dose of 1.5 g/d, increased by 0.5 g per week. Once the dose reached 3 g/day, adjustments were made based on blood concentration levels. All patients received mitotane therapy for at least 1 year, and CT was performed every 12 weeks to evaluate the efficacy. The primary endpoint was 1-year progression-free survival (PFS) and safety. The efficacy was analyzed by Kaplan-Meier method for survival, and the occurrence of treatment-related adverse events was summarized.Results:A total of 12 ACC patients at high risk of recurrence were screened, comprising 6 males and 6 females. Tumors were located on the left side in 8 patients, on the right in 3, and bilaterally in 1. Five patients were classified as ENSAT stageⅡ, while 7 were classified as ENSAT stage Ⅲ. The maximum diameter of tumor was (9.07 ± 2.86) cm; the median age at diagnosis was 48 (35, 51) years, and the median Ki-67 index was (28.9 ± 16.1)%. The median time from surgery to initiation of mitotane therapy was 31 (23.0, 43.2) days, and 9 patients had blood drug concentrations of 14-20 mg/L. The median follow-up time was 16.7 (12.4, 25.2) months. At 1 year after mitotane therapy, 10 (83.8%) patients were still in disease-free survival state, with a median mitotane PFS of 27.6 months (95% CI 16.4-not reached). All ACC patients experienced 1-2 grade adverse events after taking mitotane. One patient (8.3%) experienced grade 3 adverse event, including the increasing of alanine aminotransferase and aspartate aminotransferase, as well as anorexia. No grade 4-5 adverse events occurred. The most common adverse events were gastrointestinal symptoms (10 cases), including nausea, vomiting, anorexia, and diarrhea, followed by liver function damage(9 cases) and neurotoxicity(4 cases). Conclusions:Mitotane has shown the prospect of improving the prognosis of ACC patients at high risk of recurrence after surgery. Because of its serious toxic and side effects, it is necessary to monitor its blood concentration to adjust the dosage, and take measures for adverse reactions to ensure the safety of patients.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective:To investigate the impact of high-density lipoprotein (HDL) subfraction cholesterol, measured by the vertical auto profile (VAP) technique based on vertical density gradient ultracentrifugation, on the occurrence and progression of coronary heart disease.Methods:This retrospective case-control study consecutively enrolled 94 inpatients diagnosed with coronary artery disease (CAD) by percutaneous coronary angiography at Ningbo University Affiliated First Hospital between June 2023 and June 2024 (CAD group), and 48 outpatients from the cardiology department without carotid or coronary atherosclerosis(non-CAD group). The VAP technique was employed to measure HDL subfraction cholesterol levels (HDL 3-C and HDL 2-C) and their subtypes (HDL 2a-C, HDL 2b-C, HDL 2c-C; HDL 3a-C, HDL 3b-C, HDL 3c-C, HDL 3d-C). Logistic regression analysis was performed to assess the association between HDL subfraction composition and CAD. CAD patients were further stratified by the number of affected coronary vessels (left anterior descending artery, left circumflex artery, and right coronary artery): 44 with single-vessel disease, 22 with double-vessel disease, and 28 with triple-vessel disease for correlation analysis. All CAD patients underwent 6-month clinical and telephone follow-up to record major adverse cardiovascular events (MACE), including acute myocardial infarction, stroke, and repeat revascularization. Using the median HDL 3d-C level (0.064 mmol/L) as cutoff, CAD patients were divided into high-level ( n=48) and low-level ( n=46) subgroups for Kaplan-Meier survival analysis with log-rank testing. Results:Compared with non-CAD controls, CAD patients showed significantly higher HDL 3d-C [0.064 (0.041, 0.095) mmol/L vs 0.055 (0.038, 0.067) mmol/L] and HDL 3b-C [0.031 (0.001, 0.054) mmol/L vs 0.007 (0.004, 0.029) mmol/L], lower HDL 3c-C (0.220±0.080 mmol/L vs 0.254±0.062 mmol/L) and HDL 3a-C [0.282 (0.224, 0.351) mmol/L vs 0.334 (0.269, 0.433) mmol/L] (all P<0.05). Logistic regression revealed that HDL2b-C was a protective factor against atherosclerosis severity ( OR=0.914, 95% CI 0.896-0.987, P<0.001); HDL 3d-C served as both a CAD risk factor ( OR=2.303,95% CI 1.740-3.047, P<0.001) and disease progression indicator ( OR=1.224, 95% CI 1.123-1.335, P=0.025). MACE patients ( n=6) had elevated HDL3d-C versus non-MACE cases ( n=88) [0.120 (0.083, 0.173) mmol/L vs 0.061 (0.037, 0.092) mmol/L, P<0.05]. The high HDL 3d-C subgroup demonstrated significantly lower 6-month survival (χ2=4.777, P=0.029). Conclusion:Contrary to conventional understanding, our study reveals that HDL2b serves as a protective factor against coronary artery disease progression, whereas HDL 3d-C acts not only as a pathogenic factor for CAD but also as a critical determinant of CAD-related adverse events.