Objective:To investigate the application value of antegrade splenic superior region dissection first in laparoscopic total gastrectomy of obesity gastric cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 21 obesity patients with gastric cancer who underwent laparoscopic total gastrectomy in Renji Hospital of Shanghai Jiaotong University School of Medicine from July 2018 to October 2023 were collected. There were 16 males and 5 females, aged (58±13)years. All 21 patients underwent laparoscopic total gastrec-tomy with antegrade splenic superior region dissection first. Observation indicators: operation time, volume of intraoperative blood loss, laparotomy conversion, intraoperative splenic hemorrhage or gastric hemorrhage, lymph node dissection, time to postoperative first flatus, time to postoperative initial liquid food intake, duration of postoperative hospital stay, postoperative complication. Measure-ment data with normal distribution were represented as Mean± SD, and count data were expressed as absolute numbers. Results:All 21 patients underwent laparoscopic total gastrectomy success-fully, with the operation time of (283±47)minutes, time for splenogastric ligament and vascular manage-ment of (34±12)minutes, volume of intraoperative blood loss of (143±86)mL, and no laparotomy conversion. There was no intraoperative splenic hemorrhage or gastric haemorrhage. The total number of lymph node dissected in 21 patients was 375, with the number of lymph node dissected as (21±9)per case. Time to postoperative first flatus, time to postoperative initial liquid food intake and duration of postoperative hospital stay in 21 patients were (3.1±0.7)days, (4.0±0.8)days and (10.1±3.0)days, respectively. There were 2 patients with postoperative complications, including 1 case of incision infection and 1 case of lung infection. The 2 patients with postoperative com-plications were recovered and discharged after conservative treatment. There was no death during the postoperative 30 days.Conclusion:The application of antegrade splenic superior region dissec-tion first in laparoscopic total gastrectomy is safe and feasible, which can reduce surgical difficulty.

With the developing technique of the diagnosis and treatment of early gastric cancer, the quality of early gastric cancer diagnosis and treatment is coming into focus, and is crucial to improve the overall management of gastric cancer. It is necessary to establish a quality control system to ensure the quality of diagnosis and treatment for EGC. Based on the summary of the diagnosis and treatment status and technological progress of early gastric cancer, this paper proposes the quality control strategy, content and plan for the diagnosis and treatment process of EGC from the aspects of multidisciplinary diagnosis and treatment, clinical diagnosis technology, endoscopic and surgical treatment, pathological diagnosis and follow-up, with a view to expound the rationality, standardization and quality guarantee of the diagnosis and treatment process for early gastric cancer.

With the developing technique of the diagnosis and treatment of early gastric cancer, the quality of early gastric cancer diagnosis and treatment is coming into focus, and is crucial to improve the overall management of gastric cancer. It is necessary to establish a quality control system to ensure the quality of diagnosis and treatment for EGC. Based on the summary of the diagnosis and treatment status and technological progress of early gastric cancer, this paper proposes the quality control strategy, content and plan for the diagnosis and treatment process of EGC from the aspects of multidisciplinary diagnosis and treatment, clinical diagnosis technology, endoscopic and surgical treatment, pathological diagnosis and follow-up, with a view to expound the rationality, standardization and quality guarantee of the diagnosis and treatment process for early gastric cancer.

OBJECTIVE To explore the effects and potential mechanism of veratramine （VTM） on the proliferation of human glioblastoma U251 cells. METHODS The network pharmacology methods were adopted to screen the targets of ferroptosis related to the effects of VTM on glioblastoma， and to conduct gene ontology and Kyoto Encyclopedia of Genes and Genosomes enrichment analysis. Using U251 cells as the object， CCK-8 assay， the observation of cell morphological changes， DCFH-DA fluorescence probe method， FerroOrange fluorescence probe method and Western blot assay were used to validate the inhibitory effects of VTM on U251 cell proliferation and its possible mechanism. RESULTS Totally 462 targets of ferroptosis related to the effects of VTM on glioblastoma were screened out； they mainly enriched in biological processes such as oxidative stress and apoptosis， and cellular components such as cytoplasmic vesicles and mitochondrial membranes； they affected molecular functions such as iron ion （Fe2+） binding and DNA transcription processes， as well as iron death and phosphoinositide 3-kinase/protein kinase B signaling pathways. VTM with 40， 60， 80， 100， 120 and 140 μmol/L could significantly reduce the cell survival rate （P＜ 0.01）； VTM with 40， 80 and 120 μmol/L could cause cell atrophy and nuclear fragmentation， significantly inhibit the clone formation， increase the levels of intracellular reactive oxygen species （ROS） and Fe2+ levels， increase the expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2） and heme oxygenase 1 （HO-1） protein to different extents， while down-regulate the expression of glutathione peroxidase 4 （GPX4） protein （P＜0.05 or P＜0.01）. CONCLUSIONS VTM can inhibit the proliferation of U251 cells， and promote the accumulation of intracellular ROS and Fe2+， thus inducing ferroptosis； its mechanism might be related to the regulation of the Nrf2/HO-1/GPX4 signaling pathway.

Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, ORP8 has increased localization on LDs and is phosphorylated by AMPK, thereby enhancing its affinity for LC3/GABARAPs. Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride. Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice, and Osbpl8-/- mice exhibit liver lipid clearance defects. Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.
Animals ; Mice ; Lipid Droplets ; Autophagy ; Autophagosomes ; Homeostasis ; Triglycerides

Peritoneal metastasis is one of the important causes of death in patients with gastrointestinal cancer and is also a difficult point in clinical diagnosis and treatment.How to predict the occurrence of peritoneal metastasis in patients with high-risk factors,advance the threshold of diagnosis and treatment before the occurrence of peritoneal metastasis,and improve the survival benefit of patients is an unsolved problem in clinical work.In the case of low positive rate of cytology and difficulty in diagnosing occult peritoneal metastasis,new molecular markers and detection techniques for early diagnosis of peritoneal metastasis need to be verified.Peritoneal lavage fluid has the characteristics of less leukocyte-derived cell-free DNA interference,higher concentration of circulating tumor DNA(ctDNA),and direct contact with the primary lesion or potential peritoneal metastasis at physical distance,making it a unique advantage in gastrointestinal cancer.At present,the detection methods of ctDNA in peritoneal lavage fluid include digital PCR,epigenetic-based analysis,and next-generation sequencing.With the iteration of technology,the application of next-generation sequencing and personalized panels to ctDNA detection has not only shown great potential in predicting postoperative peritoneal metastasis,but also promoted the idea of preventive escalation treatment of peritoneal metastasis.This article reviews the current application of ctDNA to peritoneal lavage fluid in predicting peritoneal metastasis of gastrointestinal cancer.

This study employed the α-glucosidase inhibitory activity model as an anti-diabetic assay and implemented a bioactivity-guided isolation strategy to identify novel natural compounds with potential therapeutic properties. Hypericum sampsoniiwas investigated, leading to the isolation of two highly modified seco-polycyclic polyprenylated acylphloroglucinols (PPAPs) (1 and 2), eight phenolic derivatives (3-10), and four terpene derivatives (11-14). The structures of compounds 1 and 2, featuring an unprecedented octahydro-2H-chromen-2-one ring system, were fully characterized using extensive spectroscopic data and quantum chemistry calculations. Six compounds (1, 5-7, 9, and 14) exhibited potential inhibitory effects against α-glucosidase, with IC₅₀ values ranging from 0.050 ± 0.0016 to 366.70 ± 11.08 μg·mL^-1. Notably, compound 5 (0.050 ± 0.0016 μg·mL^-1) was identified as the most potential α-glucosidase inhibitor, with an inhibitory effect about 6900 times stronger than the positive control, acarbose (IC₅₀ = 346.63 ± 15.65 μg·mL^-1). A docking study was conducted to predict molecular interactions between two compounds (1 and 5) and α-glucosidase, and the hypothetical biosynthetic pathways of the two unprecedented seco-PPAPs were proposed.
Molecular Structure ; Hypericum/chemistry* ; alpha-Glucosidases ; Magnetic Resonance Spectroscopy ; Glycoside Hydrolase Inhibitors/pharmacology*

Objective:To investigate the short-term efficacy of laparoscopic total gastrec-tomy with hand-sewn esophagojejunostomy versus Roux-en-Y anastomosis.Methods:The propen-sity score matching and retrospective cohort study was conducted. The clinicopathological data of 159 patients who underwent laparoscopic total gastrectomy in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to July 2021 were collected. There were 107 males and 52 females, aged 63(range, 28?79)years. Of 159 patients, 71 cases undergoing totally laparoscopic total gastrectomy with hand-sewn esophagojejunostomy were allocated into totally laparoscopic group and 88 cases undergoing laparoscopic-assisted total gastrectomy with Roux-en-Y anastomosis were allocated into laparoscopic-assisted group, respectively. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and postoperative conditions; (3) perioperative complications. Propensity score matching was done by the 1:1 nearest neighbor matching method. Measurement data with normal distribution were expressed as Mean± SD, and t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(range), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher's exact probability method. The rank sum test was used for comparison of ordinal data. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 159 patients, 112 cases were successfully matched, including 56 cases in the totally laparoscopic group and 56 cases in the laparoscopic-assisted group. Before propensity score matching, age, cases with tumor located in cardia or gastric body in the totally laparoscopic group were 61(range, 30?76)years, 26, 45, respectively. The above indicators in the laparoscopic-assisted group were 65(range, 28?79)years, 50, 38, respectively. There were significant differences in the above indicators between the two groups ( Z=?2.89, χ2=6.43, P<0.05). After propensity score matching, the males and females, age, body mass index, cases of American Society of Anesthesiologists classification Ⅰ, Ⅱ, Ⅲ and Ⅳ, tumor diameter, cases with tumor located in cardia or gastric body, cases in TNM stage Ⅰ, Ⅱ and Ⅲ of patients in the totally laparoscopic group were 40, 16, (62±9)years, (22.7±2.8)kg/m 2, 22, 26, 7, 1, 3.5(range, 0.6?17.0)cm, 24, 32, 22, 9, 25. The above indicators of patients in the laparoscopic-assisted group were 38, 18, (62±10)years, (22.7±3.2)kg/m 2, 19, 32, 5, 0, 4.0(range, 0.6?15.0)cm, 23, 33, 21, 7, 28, respectively. There was no significant difference in the above indicators between the two groups ( χ2=0.17, t=?0.09, ?0.04, Z=?0.12, ?0.82, χ2=0.04, Z=?0.42, P>0.05). The elimination of age and tumor location confounding bias ensured comparability between the two groups. (2) Intraoperative and postoperative conditions: after propensity score matching, the total operation time, time of esophagojejunostomy, postopera-tive 24-hour pain numerical score and time to first out-off bed activities were (310±49)minutes, (37±10)minutes, 2.3±0.8 and (2.4±0.7)days for patients in the totally laparoscopic group, versus (344±77)minutes, (44±12)minutes, 3.1±1.2 and (2.9±1.0)days in the laparoscopic-assisted group, showing significant differences between the two groups ( t=?2.85, ?3.05, ?4.20, ?3.10, P<0.05). (3) Perioperative complications: after propensity score matching, 6 cases of the patients in the totally laparoscopic group had Clavien-Dindo grade 2 or higher complications, including 2 cases of anas-tomotic leak, 1 case of anastomotic stenosis, 1 case of pleural effusion, 1 case of abdominal infection and 1 case of intestinal obstruction. The incidence of Clavien-Dindo grade 2 or higher complications was 10.7%(6/56). In the laparoscopic-assisted group, 5 patients had Clavien-Dindo grade 2 or higher complications, including 2 cases of anastomotic leak, 1 case of abdominal infection, 1 case of intestinal obstruction and 1 case of cholangitis. The incidence of Clavien-Dindo grade 2 or higher complications was 8.9%(5/56). There was no significant difference in the incidence of Clavien-Dindo grade 2 or higher complications between the two groups ( χ2=0.10, P>0.05). Patients with anas-tomotic leak were improved after puncture and drainage, secondary surgery and conservative treat-ment, and other complications were improved after symptomatic treatment. Conclusions:Com-pared with Roux-en-Y anastomosis in laparoscopic total gastrectomy, the time of hand-sewn esophagojejunostomy and esophago-jejunal anastomosis are shorter, patients have less postopera-tive pain and faster postoperative recovery. Both methods have good peri-operative safety.

Objective:To preliminarily analyze the expression of angiotensin-converting enzyme 2 (ACE2) and to investigate its potential regulatory mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP).Methods:Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from February 2020 to May 2021 were selected, including 17 males and 6 females, aging from 23 to 66 years old. Expression of ACE2 was evaluated via immunohistochemical staining in controls with non-chronic rhinosinusitis, non-eosinophilic CRSwNP (non-ECRSwNP), and eosinophilic CRSwNP (ECRSwNP) tissue, respectively. Correlations between ACE2 and the indicated Th1/Th2-related cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-25, IL-33, TSLP and periostin) were analyzed based on GSE72713 dataset. Protein-protein interaction (PPI) network was constructed via string database, immune infiltration of GSE72713 dataset was evaluated using cibersort algorithm. ACE2 was comprehensively analyzed by microRNA regulatory network, gene set enrichment analysis (GSEA) and pharmacological analysis. Statistical analysis was performed using GraphPad 7.0 and SPSS 20.0 software.Results:ACE2 was up-regulated in non-ECRSwNP compared with ECRSwNP. Microarray analysis showed that ACE2 was positively correlated with IFN-γ while inversely correlated with IL-5, IL-13 and periostin significantly. Analysis of immune infiltration suggested that ACE2 expression correlated positively with the number of M1 macrophage while negatively with M2 macrophage. GSEA demonstrated that interferon-related signaling pathways were up-regulated in non-ECRSwNP, and miRNA-200B/miRNA-200C/miRNA-429 pathways targeting ACE2 were enriched in ECRSwNP. Results of pharmacological analysis indicated that ampicillin was able to promote the expression of ACE2 whereas acetaminophen could down regulated the expression of ACE2.Conclusion:Expression pattern of ACE2 is varied in non-ECRSwNP and ECRSwNP, which may be related to the different infiltration of indicated cytokines and different regulatory pathways of miRNA.

Objective:To investigate the prognostic factors of Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG) after radical resection with different surgical approaches.Methods:The retrospective case-control study was conducted. The clinicopathological data of 442 patients who were admitted to Tianjin Medical University Cancer Institute and Hospital from February 2003 to July 2011 were collected. There were 362 males and 80 females, aged from 21 to 85 years, with a median age of 64 years. Patients underwent radical resection of AEG. Observation indicators: (1) surgical situations; (2) follow-up; (3) progrostic factors analysis of AEG after radical resection; (4) survival of patients after radical resection of AEG via abdominal approach; (5) survival of patients after radical resection of AEG via thoracoabdominal approach; (6) survival of patients after radical resection of Siewert type Ⅱ type AEG; (7) survival of patients after radical resection of Siewert type Ⅲ AEG. Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival of patients up to June 2018. Measurement data with skewed distribution were described as M (range). Count data were expressed as absolute numbers or percentages. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-rank test was used for survival analysis. Univariate analysis was conducted using the Kaplan-Meier method. Multivariate analysis was conducted using the COX proportional hazard model. Results:(1) Surgical situations: 442 patients underwent radical resection of AEG, including 204 via abdominal approach and 238 via thoracoabdominal approach. There were 391 patients with D 2 lymphadenectomy and 51 with D 2+ lymphadenectomy. (2) Follow-up: 442 patients were followed up for 8-162 months, with a median follow-up time of 37 months. All the 442 patients survived for 2-156 months, with a median survival time of 31 months. The 1-, 3-, 5-year overall survival rates were 79.2%, 42.0%, 30.0%, respectively. (3) Prognostic factors analysis of AEG after radical resection: results of univariate analysis showed that tumor diameter, Lauren type, pathological T staging, pathological N staging, pathological TNM staging, lymphatic vessel invasion, and soft tissue infiltration were related factors for prognosis of patients after radical resection of Siewert type Ⅱ and Ⅲ AEG ( χ2=4.028, 4.885, 19.435, 17.014, 34.449, 9.707, 11.866, P<0.05). Results of multivariate analysis showed that pathological TNM staging, lymphatic vessel invasion, and soft tissue infiltration were independent influencing fators for prognosis of patients after radical resection of Siewert type Ⅱ and Ⅲ AEG ( hazard ratio=1.255, 0.486, 1.454, 95% confidence interval: 1.024-1.539, 0.325-0.728, 1.096-1.928, P<0.05). (4) Survival of patients after radical resection of AEG via abdominal approach: of the 204 patients undergoing radical resection of AEG via abdominal approach, the 1-, 3-, 5-year survival rates were 83.6%, 50.4%, 37.8% for 121 patients with Siewert type Ⅱ AEG, respectively, versus 72.0%, 39.3%, 31.8% for 83 patients with Siewert type Ⅲ AEG, showing no significant difference in the survival between the two groups ( χ2=1.854, P>0.05). (5) Survival of patients after radical resection of AEG via thoracoabdominal approach: of the 238 patients undergoing radical resection of AEG via thoracoabdominal approach, the 1-, 3-, 5-year survival rates were 79.6%, 38.8%, 23.8% for 183 patients with Siewert type Ⅱ AEG, respectively, versus 79.1%, 37.6%, 29.3% for 55 patients with Siewert type Ⅲ AEG, showing no significant difference in the survival between the two groups ( χ2=0.215, P>0.05). (6) Survival of patients after radical resection of Siewert type Ⅱ AEG: of the 304 patients with Siewert typeⅡAEG, the postoperative 1-, 3-, 5-year survival rates were 83.6%, 50.4%, 37.8% for 121 patients undergoing radical resection of AEG via abdominal approach, respectively, versus 79.6%, 38.8%, 23.8% for 183 patients undergoing radical resection of AEG via thoracoabdominal approach, showing no significant difference in the survival between the two groups ( χ2=2.406, P>0.05). (7) Survival of patients after radical resection of Siewert type Ⅲ AEG: of the 138 patients with Siewert type Ⅲ AEG, the postoperative 1-, 3-, 5-year survival rates were 72.0%, 39.3%, 31.8% for 83 patients undergoing radical resection of AEG via abdominal approach, respectively, versus 79.1%, 37.6%, 29.3% for 55 patients undergoing radical resection of AEG via thoracoabdominal approach, showing no significant difference in the survival between the two groups ( χ2=0.640, P>0.05). Conclusions:Pathological TNM staging, lymphatic vessel invasion, and soft tissue infiltration are independent fators for prognosis of patients after radical resection of Siewert type Ⅱ and Ⅲ AEG. Siewert types and surgical approach are not related factors for prognosis of patients after radical resection of AEG. There is no significant difference in the survival between patients with different Siewert types of AEG undergoing radical resection via different surgical approaches.