AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.

AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.

Background and Aims:Laparoscopic hiatal hernia repair(LHHR)is the gold-standard surgical treatment for hiatal hernia(HH),but postoperative recurrence remains a challenge due to hiatal enlargement and disruption of the phrenoesophageal ligament.This study aimed to assess the feasibility,safety,and short-term efficacy of a novel three-dimensional small intestinal submucosa(3D-SIS)patch designed for circumferential crural reinforcement and ligament-like reconstruction in a porcine LHHR model.Methods:Twelve healthy pigs(35-40 kg)were equally randomized into non-mesh group,SIS flat patch group,and 3D-SIS patch group.All animals underwent LHHR and Nissen fundoplication under general anesthesia.In the non-mesh group,the hiatal defect was closed with interrupted sutures.In the SIS flat patch group,a U-shaped SIS patch was placed posterior to the esophagus to reinforce the crura and fixed with medical glue.In the 3D-SIS patch group,an intraoperatively assembled three-dimensional patch was applied,consisting of an upper keyhole-shaped layer for circumferential diaphragmatic reinforcement,a tubular middle part encircling the abdominal esophagus,and a lower small keyhole-shaped patch covering the gastroesophageal junction,all fixed with medical glue.After 3 months,laparotomy was performed to assess recurrence,patch integration,and complications,followed by biomechanical and histological evaluations.Results:All procedures were completed successfully with no deaths or major complications.Operative time was slightly longer in the patch groups,while blood loss was similar.No hernia recurrence or patch migration was observed at 3 months.Biomechanical testing revealed higher ultimate load and Young's modulus in both SIS groups than in the non-mesh group.Histological analysis demonstrated neovascularization and collagen deposition in the patch groups,with the 3D-SIS patch showing more complete circumferential integration and ligament-like tissue formation.Conclusion:The 3D-SIS patch is feasible and safe in porcine LHHR.It provides circumferential diaphragmatic reinforcement and promotes phrenoesophageal ligament-like regeneration,offering a new concept for reducing postoperative recurrence and reconstructing the anti-reflux barrier.

Background and Aims:Laparoscopic hiatal hernia repair(LHHR)is the gold-standard surgical treatment for hiatal hernia(HH),but postoperative recurrence remains a challenge due to hiatal enlargement and disruption of the phrenoesophageal ligament.This study aimed to assess the feasibility,safety,and short-term efficacy of a novel three-dimensional small intestinal submucosa(3D-SIS)patch designed for circumferential crural reinforcement and ligament-like reconstruction in a porcine LHHR model.Methods:Twelve healthy pigs(35-40 kg)were equally randomized into non-mesh group,SIS flat patch group,and 3D-SIS patch group.All animals underwent LHHR and Nissen fundoplication under general anesthesia.In the non-mesh group,the hiatal defect was closed with interrupted sutures.In the SIS flat patch group,a U-shaped SIS patch was placed posterior to the esophagus to reinforce the crura and fixed with medical glue.In the 3D-SIS patch group,an intraoperatively assembled three-dimensional patch was applied,consisting of an upper keyhole-shaped layer for circumferential diaphragmatic reinforcement,a tubular middle part encircling the abdominal esophagus,and a lower small keyhole-shaped patch covering the gastroesophageal junction,all fixed with medical glue.After 3 months,laparotomy was performed to assess recurrence,patch integration,and complications,followed by biomechanical and histological evaluations.Results:All procedures were completed successfully with no deaths or major complications.Operative time was slightly longer in the patch groups,while blood loss was similar.No hernia recurrence or patch migration was observed at 3 months.Biomechanical testing revealed higher ultimate load and Young's modulus in both SIS groups than in the non-mesh group.Histological analysis demonstrated neovascularization and collagen deposition in the patch groups,with the 3D-SIS patch showing more complete circumferential integration and ligament-like tissue formation.Conclusion:The 3D-SIS patch is feasible and safe in porcine LHHR.It provides circumferential diaphragmatic reinforcement and promotes phrenoesophageal ligament-like regeneration,offering a new concept for reducing postoperative recurrence and reconstructing the anti-reflux barrier.

Multimorbidity has emerged as a critical global public health challenge, necessitating effective management strategies. In Heilongjiang Province, a cold north region in China with a high prevalence of multimorbidity, healthcare disparities, uneven resource distribution, and inadequate chronic disease control remain pressing issues. Driven by national policies on family physician contracting and regional demands for chronic disease management, this study established a "hospital-community general practitioner co-management" model utilizing a mobile-based digital platform. This model integrates hospital-based general practitioners into primary care teams to optimize resource allocation and enhance multimorbidity management. The initiative aims to explore pathways for improving healthcare system reform and strengthening the chronic disease prevention framework in the region.

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Multimorbidity has emerged as a critical global public health challenge, necessitating effective management strategies. In Heilongjiang Province, a cold north region in China with a high prevalence of multimorbidity, healthcare disparities, uneven resource distribution, and inadequate chronic disease control remain pressing issues. Driven by national policies on family physician contracting and regional demands for chronic disease management, this study established a "hospital-community general practitioner co-management" model utilizing a mobile-based digital platform. This model integrates hospital-based general practitioners into primary care teams to optimize resource allocation and enhance multimorbidity management. The initiative aims to explore pathways for improving healthcare system reform and strengthening the chronic disease prevention framework in the region.

Objective:To investigate the quality of life (QoL) and its related influencing factors of patients undergoing laparoscopic hiatal hernia repair (LHHR).Methods:The retrospec-tive cohort study was conducted. The clinical data of 215 patients undergoing LHHR in Beijing Chaoyang Hospital of Capital Medical University from August 2020 to April 2022 were collected. There were 90 males and 125 females, aged (62±14)years. All patients underwent symptom scoring and quality of life assessment 6 months after LHHR. Measurement data with normal distribution were represented as Mean± SD, and comparison before and after operation within the group was conducted using the paired t test. Measurement data with skewed distribution were represented as M(range). Stepwise linear regression analysis was used for influencing factors analysis. Optimal model was selected based on Akaike information criterion. Results:(1) Treatment. Of 215 patients, 162 cases underwent LHHR+gastric fundus folding surgery (Dor surgery), and 53 cases underwent LHHR+reconstruction of HIS angle. The score of visual analogue scale (VAS) of heartburn symptoms in 215 patients 6 months after surgery was 0(range, 0-4), with the score of VAS of acid reflux symptoms was 0(range, 0-9), the score of VAS of belching symptoms was 0(range, 0-9), the score of VAS of chest pain symptoms was 0(range, 0-9), the score of VAS of early satiety symptoms was 0(range, 0-9), respectively. (2) Assessment of QoL before and after surgery. The score of MOS item short from health survey (SF-36) of physiological function in 215 patients before and after LHHR was 80±24 and 87±18, with the score of SF-36 of physiological functionality before and after LHHR was 49±45 and 68±38, the score of SF-36 of body pain before and after LHHR was 65±23 and 74±19, the score of SF-36 of general health condition before and after LHHR was 46±7 and 51±9, the score of SF-36 of vigour before and after LHHR was 67±19 and 75±17, the score of SF-36 of social function before and after LHHR was 71±24 and 81±18, the score of SF-36 of emotional function before and after LHHR was 60±45 and 77±33, the score of SF-36 of emotional health before and after LHHR was 68±19 and 76±17, the score of SF-36 of health change before and after LHHR was 33±19 and 57±28. There were significant differences in the above indicators before and after surgery ( t=-7.82, -8.73, -8.20, -10.08, -9.75, -8.83, -8.00, -9.88, -12.95, P<0.05). (3) Factors influencing physical compo-nent summary (PCS) and mental component summary (MCS) 6 months after LHHR. Results of multi-variate analysis showed that gender, age, mental disease, cerebral infarction, hypoproteinemia, score of VAS of acid reflux 6 month after surgery and score of VAS of chest pain 6 month after surgery were independent factors influencing PCS 6 months after LHHR ( P<0.05), and mental disease, malignant tumor, hypoproteinemia, score of VAS of heartburn 6 month after surgery and score of VAS of belching 6 month after surgery were independent factors influencing MCS 6 months after LHHR ( P<0.05). Conclusions:LHHR can improve patients′ QoL. Gender, age, mental disease, cerebral infarc-tion, hypoproteinemia, score of VAS of acid reflux 6 month after surgery and score of VAS of chest pain 6 month after surgery are independent factors influencing PCS 6 months after LHHR, and mental disease, malignant tumor, hypoproteinemia, score of VAS of heartburn 6 month after surgery and score of VAS of belching 6 month after surgery are independent factors influencing MCS 6 months after LHHR.

Objective:To investigate the quality of life (QoL) and its related influencing factors of patients undergoing laparoscopic hiatal hernia repair (LHHR).Methods:The retrospec-tive cohort study was conducted. The clinical data of 215 patients undergoing LHHR in Beijing Chaoyang Hospital of Capital Medical University from August 2020 to April 2022 were collected. There were 90 males and 125 females, aged (62±14)years. All patients underwent symptom scoring and quality of life assessment 6 months after LHHR. Measurement data with normal distribution were represented as Mean± SD, and comparison before and after operation within the group was conducted using the paired t test. Measurement data with skewed distribution were represented as M(range). Stepwise linear regression analysis was used for influencing factors analysis. Optimal model was selected based on Akaike information criterion. Results:(1) Treatment. Of 215 patients, 162 cases underwent LHHR+gastric fundus folding surgery (Dor surgery), and 53 cases underwent LHHR+reconstruction of HIS angle. The score of visual analogue scale (VAS) of heartburn symptoms in 215 patients 6 months after surgery was 0(range, 0-4), with the score of VAS of acid reflux symptoms was 0(range, 0-9), the score of VAS of belching symptoms was 0(range, 0-9), the score of VAS of chest pain symptoms was 0(range, 0-9), the score of VAS of early satiety symptoms was 0(range, 0-9), respectively. (2) Assessment of QoL before and after surgery. The score of MOS item short from health survey (SF-36) of physiological function in 215 patients before and after LHHR was 80±24 and 87±18, with the score of SF-36 of physiological functionality before and after LHHR was 49±45 and 68±38, the score of SF-36 of body pain before and after LHHR was 65±23 and 74±19, the score of SF-36 of general health condition before and after LHHR was 46±7 and 51±9, the score of SF-36 of vigour before and after LHHR was 67±19 and 75±17, the score of SF-36 of social function before and after LHHR was 71±24 and 81±18, the score of SF-36 of emotional function before and after LHHR was 60±45 and 77±33, the score of SF-36 of emotional health before and after LHHR was 68±19 and 76±17, the score of SF-36 of health change before and after LHHR was 33±19 and 57±28. There were significant differences in the above indicators before and after surgery ( t=-7.82, -8.73, -8.20, -10.08, -9.75, -8.83, -8.00, -9.88, -12.95, P<0.05). (3) Factors influencing physical compo-nent summary (PCS) and mental component summary (MCS) 6 months after LHHR. Results of multi-variate analysis showed that gender, age, mental disease, cerebral infarction, hypoproteinemia, score of VAS of acid reflux 6 month after surgery and score of VAS of chest pain 6 month after surgery were independent factors influencing PCS 6 months after LHHR ( P<0.05), and mental disease, malignant tumor, hypoproteinemia, score of VAS of heartburn 6 month after surgery and score of VAS of belching 6 month after surgery were independent factors influencing MCS 6 months after LHHR ( P<0.05). Conclusions:LHHR can improve patients′ QoL. Gender, age, mental disease, cerebral infarc-tion, hypoproteinemia, score of VAS of acid reflux 6 month after surgery and score of VAS of chest pain 6 month after surgery are independent factors influencing PCS 6 months after LHHR, and mental disease, malignant tumor, hypoproteinemia, score of VAS of heartburn 6 month after surgery and score of VAS of belching 6 month after surgery are independent factors influencing MCS 6 months after LHHR.

Objective:To evaluate the feasibility and safety of laparoscopic surgery of hiatal hernia with gastric volvulus.Methods:A retrospective study was conducted to analyze the clinical data of 29 cases of hiatal hernia with gastric volvulus undergoing laparoscopic mesh repair and fundoplication at Beijing Chao-Yang Hospital from Jun 2021 to Dec 2022. Fundoplication was performed according to esophageal motility. The general data, operation times, intraoperative blood loss, percentage of intrathoracic stomach, hernia and gastric volvulus classification, conversion to open surgery, post-operative hospital stay and complications, symptom improvement rate, post-operative satisfaction were analyzed.Results:Chronic obstruction symptoms were the most common complaint among the 29 patients. All the operations were done laparoscopicaly with no conversion case,19(65%) cases with type Ⅲ hiatal hernia, 20(70%)　cases with organoaxial gastric volvulus, average operating time was (110.2±33.3)min, average blood loss was (12.6±7.0)ml, percentage of intrathoracic stomach 75.9%±15.8%, length of hernia defect was (6.6±1.2)cm, width of hernia defect was (5.0±1.1)cm .Average post-operative hospital stay was (6.4±1.7) days, perioperative complications were pneumonia(7%) ,atelectasis(7%) and gastric motility disorder(3%). All the patients were followed up for 15 to 32 months, without report of patch infection, long-term chronic pain, intestinal obstruction and hernia recurrence. Postoperative symptom improvement rate was 90%,postoperative satisfaction rate was 90%.Conclusion:Laparoscopic surgery of hiatal hernia with gastric volvulus is a safe, feasible and effective method with satisfactory results.