BACKGROUND:Adipose tissue-derived mesenchymal stem cells release a large amount of exosomes to participate in various pathophysiological processes,but the impact and precise mechanism of exosomes derived from adipose tissue-derived mesenchymal stem cells on autophagy of hepatic stellate cells have not been fully elucidated.OBJECTIVE:To explore the targeted regulatory effect and molecular mechanism of adipose tissue-derived mesenchymal stem cell-derived exosomes on autophagy of hepatic stellate cells through miR-15a-5p.METHODS:Adipose tissue was collected from inguinal region of 8-week male C57BL/6 mice.Adipose tissue-derived mesenchymal stem cells were extracted by collagenase digestion.Adipose tissue-derived mesenchymal stem cell-derived exosomes were extracted by ultracentrifugation.Mouse liver tissue was obtained,and hepatic stellate cells were isolated and extracted using collagenase perfusion digestion and density gradient centrifugation.The experiment was divided into two groups.In control group,hepatic stellate cells were cultured alone for 48 hours.In the exosome group,hepatic stellate cells were co-cultured with adipose tissue-derived mesenchymal stem cell-derived exosomes for 48 hours.The effects of exosomes on hepatic stellate cell proliferation,activation,autophagy,and expression of fibrosis markers were detected by western blot assay,RT-qPCR,and immunofluorescence staining.RT-qPCR and western blot assay were used to detect the effect of exosomes on the mRNA and protein expression of miR-15a-5p and the downstream signaling pathway Bcl-2,Beclin-1,and Rubicon in hepatic stellate cells.RESULTS AND CONCLUSION:(1)Compared with the control group,the ratio of autophagy markers LC3-Ⅱ expression decreased,the number of autophagosome was also significantly decreased,and the intracellular lipid droplets were regenerated,simultaneously,cell volume diminished with the weakening of proliferation in hepatic stellate cells of the exosome group,indicated that the hepatic stellate cell activation was significantly inhibited.(2)Compared with the control group,the expressions of α-smooth actin and type Ⅰ collagen were significantly decreased(P＜0.01),and the expression of miR-15a-5p was significantly increased in hepatic stellate cells of the exosome group(P＜0.01).At the same time,the expression of its downstream target gene Bcl-2 was significantly decreased(P＜0.01),while the expressions of autophagy genes Beclin-1 and Rubicon were significantly increased in hepatic stellate cells of the exosome group(P＜0.01).The results indicate that adipose tissue-derived mesenchymal stem cell-derived exosomes inhibits the expression of Bcl-2 in hepatic stellate cells by targeting miR-15a-5p and increases the expression of downstream autophagy genes Beclin-1 and Rubicon,thereby inhibiting the autophagy of hepatic stellate cells.

Objective To evaluate the clinical safety and effect of emergency gastric vein embolization(GVE)in the treatment of acute esophageal and gastric variceal bleeding(EGVB).Methods The clinical data of 72 patients with acute EGVB,who received emergency GVE at the authors' hospital from January 2018 to December 2021,were retrospectively analyzed.No TIPS,endoscopic ligature,injection of sclerosing agent,or surgery was performed in all the patients before and after GVE.The observation indicators included surgical success rate,serious complications,success rate of hemostasis,hospital stay and cost,incidence of rebleeding,and mortality of rebleeding.The endpoint of the study was the occurrence of rebleeding or death.Results In this study,the surgical success rate was 98.6％and the hemostasis success rate was 91.7％,with no serious complications.Except for 10 patients who died during hospitalization,the average hospitalization time of the 62 patients who were discharged with significant improvement in health condition was 9 days,the average hospitalization cost was 38 000 Chinese Yuan.Of the 62 patients,emergency GVE after admission was directly carried out in 36(group A),and emergency GVE was adopted after failure of the conservative treatment in 26(group B).The hospital stay in group A was shorter than that in group B,but the hospitalization costs in group A and group B were similar.In the 62 patients,the incidence of rebleeding was 37.1％within one year and 53.2％within 2 years after the treatment.The incidences of death due to rebleeding at one year and 2 years were all 14.5％.Conclusion For the treatment of acute EGBV,emergency GVE is clinically safe and effective.Early GVE treatment can reduce the risk of death and the medical cost.Therefore,GVE should be regarded as one of the conventional treatment methods for acute EGBV.The incidence of rebleeding after GVE is relatively high.GVE combined with endoscopic therapy may reduce the incidence of rebleeding,but it requires further studies to verify it.

Objective: To explore the current status and influencing factors of eating behaviors in adolescents, so as to provide a theoretical foundation for health promotion education among adolescents. Methods: Based on the database from Survey of Chinese Family Health Index (2021), by a random number table method, 1 065 teenagers were selected from the provincial capitals of 22 provinces and 5 autonomous regions in China, as well as 4 municipalities directly under the central government. A general characteristic questionnaire, Patient Health Questionnaire-9 (PHQ-9), Short Form of the Family Health Scale (FHS-SF), 10-item Short Version of the Big Five Personality(BFP-10), Content-based Media Exposure Scale (CM-E) and Sakata Eating Behavior Scale Short Form(EBS-SF) were used to collect information. Multivariate stepwise linear regression analysis was employed to identify and analyze related factors of eating behaviors among adolescents. Receiver operating characteristic was used to validate the predictive ability of the EBS-SF score for overweight and obesity among adolescents. Results: The average scores of BFI-10,C-ME, FHS-SF, PHQ-9 and EBS-SF were (33.08±4.64)(19.20±4.55)(38.48±6.65)(6.09±5.63)(16.75±4.36), respectively. Multivariate linear regression showed that family type (other types), agreeableness, conscientiousness, family health and depression were the main related factors of EBS-SF scores among adolescents( B =2.61,-0.42,0.20,-0.11,0.23, P <0.05).The analysis of receiver operating characteristic curve showed that the EBS-SF scores had a good ability in predicting obesity among male adolescents ( AUC= 0.73, P <0.01). Conclusions Family type, big five personality, family health,depression are the related factors of eating behaviors among adolescents. EBS-SF scores are predictive of obesity in adolescents, which would provide a new perspective for promoting healthy eating habits among adolescents.

Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

Objective To investigate the role of matrix GLA protein(MGP)in the pathogenesis of idiopathic calcium oxalate kidney stones(ICOS),and to find potential biomarkers for early diagnosis and disease evaluation.Methods A total of 120 patients admitted to our hospital from September 2021 to September 2023 were prospectively included,of which 60 patients with ICOS were in the calculus group and 60 patients without calculus were in the control group.Serum biochemical indexes and immunohistochemical scores of the two groups were detected,urinary MGP levels were determined by ELISA,and MGP mRNA and protein expression in renal papilla tissues were detected by qPCR and Western blot.The independent risk factors of ICOS were screened by Logistic regression analysis,and the prediction model was drawn by nomogram.Results Compared with control group,urinary MGP content in calculus group was decreased[(1 805.91±244.44)pg/ml vs.(2 014.79±252.14)pg/mnl,P＜0.05).Expression of MGP mRNA and MGP protein in renal papillae decreased(0.89±0.15 vs.1.00±0.00,P=0.001)and decreased(0.87±0.18 vs.1.00±0.00,P＜0.05).MGP immunohistochemical scores of renal tissue were decreased[4(2-6)scores vs.6(4-8)scores,P＜0.001].Multivariate analysis showed that urinary calcium(OR=1.370),urinary MGP(OR=1.127),renal papilla MGP relative expression level(OR=27.532)and renal tissue MGP immunohistochemical score(OR=1.359)were independent risk factors for ICOS.Area under ROC curve of the nomogram prediction model built based on the above factors is 0.839,indicating that the model has good differentiation ability in risk prediction.Conclusion MGP is closely related to the pathogenesis of ICOS.Urinary and renal tissue MGP levels may be potential biomarkers for early diagnosis and disease assessment of ICOS.

BACKGROUND:Adipose tissue-derived mesenchymal stem cells release a large amount of exosomes to participate in various pathophysiological processes,but the impact and precise mechanism of exosomes derived from adipose tissue-derived mesenchymal stem cells on autophagy of hepatic stellate cells have not been fully elucidated.OBJECTIVE:To explore the targeted regulatory effect and molecular mechanism of adipose tissue-derived mesenchymal stem cell-derived exosomes on autophagy of hepatic stellate cells through miR-15a-5p.METHODS:Adipose tissue was collected from inguinal region of 8-week male C57BL/6 mice.Adipose tissue-derived mesenchymal stem cells were extracted by collagenase digestion.Adipose tissue-derived mesenchymal stem cell-derived exosomes were extracted by ultracentrifugation.Mouse liver tissue was obtained,and hepatic stellate cells were isolated and extracted using collagenase perfusion digestion and density gradient centrifugation.The experiment was divided into two groups.In control group,hepatic stellate cells were cultured alone for 48 hours.In the exosome group,hepatic stellate cells were co-cultured with adipose tissue-derived mesenchymal stem cell-derived exosomes for 48 hours.The effects of exosomes on hepatic stellate cell proliferation,activation,autophagy,and expression of fibrosis markers were detected by western blot assay,RT-qPCR,and immunofluorescence staining.RT-qPCR and western blot assay were used to detect the effect of exosomes on the mRNA and protein expression of miR-15a-5p and the downstream signaling pathway Bcl-2,Beclin-1,and Rubicon in hepatic stellate cells.RESULTS AND CONCLUSION:(1)Compared with the control group,the ratio of autophagy markers LC3-Ⅱ expression decreased,the number of autophagosome was also significantly decreased,and the intracellular lipid droplets were regenerated,simultaneously,cell volume diminished with the weakening of proliferation in hepatic stellate cells of the exosome group,indicated that the hepatic stellate cell activation was significantly inhibited.(2)Compared with the control group,the expressions of α-smooth actin and type Ⅰ collagen were significantly decreased(P＜0.01),and the expression of miR-15a-5p was significantly increased in hepatic stellate cells of the exosome group(P＜0.01).At the same time,the expression of its downstream target gene Bcl-2 was significantly decreased(P＜0.01),while the expressions of autophagy genes Beclin-1 and Rubicon were significantly increased in hepatic stellate cells of the exosome group(P＜0.01).The results indicate that adipose tissue-derived mesenchymal stem cell-derived exosomes inhibits the expression of Bcl-2 in hepatic stellate cells by targeting miR-15a-5p and increases the expression of downstream autophagy genes Beclin-1 and Rubicon,thereby inhibiting the autophagy of hepatic stellate cells.

Objective To investigate the role of matrix GLA protein(MGP)in the pathogenesis of idiopathic calcium oxalate kidney stones(ICOS),and to find potential biomarkers for early diagnosis and disease evaluation.Methods A total of 120 patients admitted to our hospital from September 2021 to September 2023 were prospectively included,of which 60 patients with ICOS were in the calculus group and 60 patients without calculus were in the control group.Serum biochemical indexes and immunohistochemical scores of the two groups were detected,urinary MGP levels were determined by ELISA,and MGP mRNA and protein expression in renal papilla tissues were detected by qPCR and Western blot.The independent risk factors of ICOS were screened by Logistic regression analysis,and the prediction model was drawn by nomogram.Results Compared with control group,urinary MGP content in calculus group was decreased[(1 805.91±244.44)pg/ml vs.(2 014.79±252.14)pg/mnl,P＜0.05).Expression of MGP mRNA and MGP protein in renal papillae decreased(0.89±0.15 vs.1.00±0.00,P=0.001)and decreased(0.87±0.18 vs.1.00±0.00,P＜0.05).MGP immunohistochemical scores of renal tissue were decreased[4(2-6)scores vs.6(4-8)scores,P＜0.001].Multivariate analysis showed that urinary calcium(OR=1.370),urinary MGP(OR=1.127),renal papilla MGP relative expression level(OR=27.532)and renal tissue MGP immunohistochemical score(OR=1.359)were independent risk factors for ICOS.Area under ROC curve of the nomogram prediction model built based on the above factors is 0.839,indicating that the model has good differentiation ability in risk prediction.Conclusion MGP is closely related to the pathogenesis of ICOS.Urinary and renal tissue MGP levels may be potential biomarkers for early diagnosis and disease assessment of ICOS.

Objective To observe the effects of hemoperfusion(HP)combined with hemodialysis on cholinesterase(ChE)activity and inflammatory factors in patients with acute organophosphorus pesticide poisoning(AOPP).Methods A retrospective cohort study was conducted.Seventy-three AOPP patients admitted to the department of emergency of Yingshang People's Hospital from January 2020 to December 2022 were enrolled.The patients were divided into HP group(31 cases)and HP+continuous renal replacement therapy(CRRT)group(42 cases)according to different treatment regimens.All patients were given supportive treatment according to the standard protocol after admission.HP was given to the patients as soon as possible after admission,and the treatment time was between 2 hours and 3 hours,with an interval of 24 hours.Patients in HP+CRRT group were treated with continuous veno-venous hemodiafiltration(CVVHDF)after HP.The serum ChE,tumor necrosis factor-α(TNF-α),and interleukins(IL-1,IL-6)levels were compared between the two groups after admission(T0),at the end of the first HP/HP+CRRT(T1),at the end of the second HP/HP+CRRT(T2),and at the end of the third HP/HP+CRRT(T3).The ChE recovery time,the incidence of intermediate syndrome(IMS),the length of hospital stay,and the rate of admission to ICU were also compared.Results With the extension of treatment time,the ChE activity at T1,T2,and T3 in the two groups was significantly higher than that at T0,and the levels of TNF-α,IL-1,and IL-6 were significantly lower than those at T0,reaching the trough value at T3,and the changes in HP+CRRT group were more significant than those in HP group[ChE activity(U/L):2 903.26±164.43 vs.2 292.98±350.96,TNF-α(ng/L):78.24±10.75 vs.100.55±15.58,IL-1(ng/L):95.98±22.56 vs.127.94±18.74,IL-6(ng/L):34.36±8.66 vs.58.74±10.46,all P<0.05].The recovery time of ChE activity and length of hospital stay in HP+CRRT group were significantly shorter than those in HP group[ChE activity recovery time(days):4.42±1.17 vs.7.31±1.46,length of hospital stay(days):9.25±2.14 vs.12.75±2.30,both P<0.05],the incidence of IMS and ICU admission rate were significantly lower than those in HP group[the incidence of IMS:33.33%(14/42)vs.61.29%(19/31),ICU admission rate:9.52%(4/42)vs.29.03%(9/31),both P<0.05].Conclusion For AOPP patients,HP+CRRT is superior to HP alone in the clearance of inflammatory factors,restoring ChE activity,reducing the incidence of IMS,and shortening the length of hospital stay,making it a valuable option for clinical application.

Objective : To investigate the role of early inhibition of Toll⁃like receptor 4 (TLR4) in regulating hippampal neuroimmune responseto adolescent ratsafter neonatal hypoxic⁃ischemic brain damage(HIBD) . Methods: Postnatal day 7 rats were randomized into controlgroup , hypoxic ischemia (HI) group , and HI + TAK⁃242( the specific inhibitor of TLR4)(TAK⁃242) group. The expression of TLR4 in rat hippocampus was detected by immunohistochemistry at 3 days after HI. Immunofluorescence were used to determine the number of Iba⁃1 + , GFAP + , CD161 + , MPO + and CD3 + cells in the hippocampus at 21 days after HI. Immunohistochemistry was used to detect ICAM⁃1 and C3a expression in the hippocampal CA1 region ; and Western blot was used to detect tumor necrosis factor interleukin IL⁃1β , TNF⁃α and IL⁃10 expression. Results : Compared with control group , significantly raised TLR4 expression was observed in the left hippocampal CA1 , CA3 and DG regions(P < 0. 01 or P < 0. 05) , while the expression in the TAK⁃242 group lowered compared to the HI group (P < 0. 05) . The number of GFAP + cells in the CA1 area of the hippocampus in the TAK⁃242 group of neonatal rats decreased compared to which in the HI group at 21 days after HI(P < 0. 05) , but the number of CD3 + T lymphocytes in the hippocampal CA1 area of new born rats in the HI group increased compared to which in the Control group (P < 0. 05) , but the difference between TAK⁃242 and the Control group was not statistically significant. The number of Iba⁃1 + cells , MPO + cells , CD161 + cells , the expression of ICAM⁃1 and C3a in hippocampal CA1 region , and the expression of TNF⁃α , IL⁃1β and IL⁃10 in hippocampus of rats were not different among groups at 21 days after HIBD. Conclusion Early inhibition of TLR4 may ameliorate adolescent neuroimmune disorders by reducing the increase of hippocampal astrocytesafter neonatal HIBD.

The 8th Japan-China Hepato-Pancreato-Biliary Symposium was held in Tokyo,Japan from 22nd to 23rd November 2018.The meeting was convened coincidently with the 80th Annual Congress of Japanese Surgical Association,which attracted the participation of Chinese and Japanese hepatobiliary and pancreatic surgeons.The symposium aimed to explore the latest achievements and clinical issues of diagnosis and treatment for hepato-pancreato-biliary diseases.In this article,authors reviewed the up-to-date research information in order to share the experience,achievements and new information in the field of hepatobiliary and pancreatic diseases with colleagues.