Cellular dysfunction caused by vesicle transport is associated with a variety of diseases.The trans-Golgi network(TGN)to endosome transport is an important pathway of vesicle transport,and its defects leading to protein balance disorders has been linked to many diseases such as cancer,neurodegenerative diseases and diabetes mellitus.Gol-gi-associated gamma-adaptin ear-containing ADP-ribosylation factor-binding protein 2(GGA2)is a crucial protein in-volved in TGN-endosomal transport.It plays a significant role in the regulation of several diseases,including cancer,Al-zheimer disease,type 2 diabetes mellitus and cerebral ischemia,by mediating protein transport with important biological significance.This article provides an overview of the molecular structure of GGA2,its role in regulating clathrin-mediated protein transport between TGN and endosomes,and its potential implications for a variety of diseases.

Liver cancer is a prevalent and highly malignant cancer worldwide,with 90％of cases being hepatocellular carcinoma,presenting a significant risk to human health.As early-stage liver cancer often lacks specific manifestations,most patients with liver cancer are already in the middle and late stage of the disease when liver cancer is diagnosed,thus,missing the opportunity for optimal radical treatment.However,the exploration of the treatment for middle and advanced primary hepatocellular carcinoma has never ceased.In recent years,transarterial chemoembolization(TACE)has been included in the standard treatment regimens for primary hepatocellular carcinoma.With the advancement of multidisciplinary comprehensive treatment,various treatment options to reduce the burden of liver cancer lesion with satisfactory therapeutic results have been reported and have been widely used in clinical practice,e.g.hepatic artery infusion chemotherapy(HAIC),targeted therapy,and immunotherapy in combination with TACE,which have significantly improved the overall survival of patients with liver cancer.This paper aims to make a comprehensive review about the latest progress of combination use of TACE and other therapies in reducing tumor burden and improving patient survival in the treatment of primary hepatocellular carcinoma,and to summarize the key issues in combination therapy that require more in-depth research.(J Intervent Radiol,2024,33:688-692)

Objective To investigate the therapeutic effect of Liangxue-jiedu decoction on acute-on-chronic liver failure(ACLF)model mice and the Toll-like receptor 4(TLR4)/c-Jun amino terminal kinase(JNK)/nuclear factor κB(NF-κB)signaling pathway.Methods An ACLF mouse model was established using combined treatment of carbon tetrachloride,lipopolysaccharide,and D-galactosamine.Biochemical analysis was performed to evaluate liver function indicators,including alanine aminotransferase,aspartate aminotransferase,and total bilirubin.Histopathological examination was conducted to assess liver tissue morphological changes.Quantitative PCR was used to detect the mRNA expression of tumor necrosis factor alpha(TNF-α),interleukin(IL)-6,IL-1 β,and TLR4 in liver tissues.A CCK8 assay was used to evaluate the optimal interventional concentration of Liangxue-jiedu decoction on Raw 264.7 cells.Enzyme-linked immunosorbent assay was used to detect the contents of TNF-α,IL-6,and IL-1βin the cell supernatant.Protein immunoblotting was performed to measure the expression of TLR4/JNK/NF-κB signaling pathway-related proteins,including TLR4,NF-κB,p-ERKl/2,ERK1/2,p-JNK,and JNK.Results Compared with the ACLF model group,the Liangxue-jiedu decoction-treated group showed reduced cell necrosis,fibrosis,and inflammatory cell infiltration in liver tissues;decreased serum levels of alanine aminotransferase,aspartate aminotransferase and total bilirubin;and lower expression of TNF-α,IL-6,IL-1β,and TLR4 mRNA.Liangxue-jiedu decoction reduced TLR4/JNK/NF-κB signaling pathway-related protein expression in liver tissues.The in vitro result also showed that Liangxue-jiedu decoction reduced TNF-α,IL-6,and IL-1 β secretion by macrophage cells and down-regulated the expression of TLR4/JNK/NF-κB signaling pathway proteins.Conclusions Liangxue-jiedu decoction effectively improved liver function in ACLF mice in a manner closely related to the downregulation of TLR4/JNK/NF-κB pathway proteins.

Objective:To observe the application effect of skillful communication combined with pathway pain management on patients with hemorrhoids undergoing endoscopic sclerotherapy.Methods:Using the convenient sampling method, a total of 85 patients who received endoscopic sclerotherapy of internal hemorrhoids in the People's Hospital of Anyang City from September 2020 to August 2021 were selected as the research objects. They were divided into the intervention group (44 cases) and the control group (41 cases) . The control group was given routine nursing intervention, while the observation group was given skillful communication combined with pathway pain management on the basis of the control group. The pain level (VAS) before and 12, 24, 48, and 72 hours after the operation, as well as the negative emotions [anxiety (SAS) , depression (SDS) ], resilience (CD-RISC) and quality of life (WHOQOL-BREF) score of patients before and after the intervention were compared between the two groups.Results:Compared with before operation, the VAS scores of the intervention group at 12, 24, 48 and 72 h after operation were lower, and the VAS scores of the intervention group at each time point after operation were lower than those of the control group, and the differences were statistically significant ( P<0.05) . After the intervention, SAS and SDS scores of patients of the two groups were lower than those before the intervention, and SAS and SDS scores of the intervention group after the intervention were lower than those of the control group, and the differences were statistically significant ( P<0.05) . The scores of each dimension of CD-RISC after intervention in the two groups were higher than those before intervention, and the scores of each dimension of CD-RISC in the intervention group after intervention were higher than those in the control group, and the differences were statistically significant ( P<0.05) . The scores of each dimension of WHOQOL-BREF in the two groups after intervention were higher than those before intervention, and the scores of each dimension of WHOQOL-BREF in the intervention group after intervention were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Skillful communication combined with pathway pain management can reduce the pain level of patients undergoing endoscopic sclerotherapy of internal hemorrhoids, relieve the negative emotions of patients and improve their psychological resilience and quality of life, which is worthy of clinical promotion.

Objective To investigate the effect of donepezil on subventricular zone ( SVZ) neuro-genesis related neurotrophic factors after cerebral infarction. Methods Mice were randomly assigned into three groups: vehicle-treated sham group (Sham+vehicle,n=18),vehicle-treated middle cerebral artery oc-clusion (MCAO) group (MCAO + vehicle,n=30) and donepezil-treated MCAO group (MCAO+donepezil, n=30). Middle cerebral artery occlusion( MCAO) was induced by thread-occlusion method. Nissl staining was used to measure the infarct volume and the modified neurological severity score(mNSS) was used to as-sess neurologic function and brain water content was detected to assess brain edema degree. Proliferative cells and neuroblasts were labeled with 5-bromodeoxyuridine ( BrdU) and doublecortin ( DCX). The SVZ BrdU+/DCX+cells were detected by immunofluorescence. The expression of glial cell line-derived neurotro-phic factor (GDNF),brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were detec-ted by Western blot. Results The infarct volume of MCAO + donepezil group ((13. 33±4. 55)%) was sig-nificantly lower than that of MCAO + vehicle group ((31. 33±3. 93)%,t=7. 34,P<0. 05). The neurologic deficits were significantly ameliorated after donepezil treatment,and the brain water content of MCAO + done-pezil group ((71. 82±10. 18)%)was significantly less than that of MCAO + vehicle group ((85. 93± 7. 54)%,F=13. 480,P<0. 05). All differences were statistically significant (P<0. 05). The area of BrdU+/DCX+cells within SVZ of MCAO + vehicle group ((6. 16±1. 79)%) was significantly larger than that of sham + vehicle group ((2. 25±1. 09)%),and was fewer than that of MCAO+donepezil group ((16. 19± 2. 16)%,F=102. 756,P<0. 05). MCAO significantly promoted the expression of GDNF,BDNF and NGF within SVZ compared with sham operation,and donepezil increased these protein levels(F=15. 114,27. 121, 27. 398,P<0. 05). Conclusion Donepezil regulates neurogenesis via increasesing the expression of GDNF, BDNF and NGF within SVZ after cerebral infarction.

Objective To investigate the effects of cholinergic signal on neural stem cell(NSC)differenti-ation in peri-infarction region after ischemic stroke. Methods Mice were randomly assigned into sham + vehicle group,middle cerebral artery occlusion(MCAO)+ vehicle group,MCAO + donepezil group and MCAO + atro-pine group(n = 25). MCAO was induced by thread-occlusion method. Modified neurological severity score (mNSS)was used to evaluate neurological function recovery,and the brain water content was measured by dry-wet weight method. NeuN/5-bromodeoxyuridine(BrdU),CNPase/BrdU,GFAP/BrdU double-labeled cells were tested by immunofluorescence. Results Brain water content of MCAO + vehicle group was significantly higher than that of sham operation group(P < 0.05). Donepezil-treated MCAO mice had lower neurologic deficit scores and brain water content than of MCAO + vehicle group(P < 0.05). On day 14 and day 28 after MCAO,the NeuN/BrdU, CNPase/BrdU and GFAP/BrdU immune-positive cells of MCAO + vehicle group were markedly increased as com-pared with that of sham+vehicle group(P<0.05).Compared with that of MCAO+vehicle group,the number of NeuN/BrdU-positive cells,CNPase/BrdU-positive cells and GFAP/BrdU-positive cells was higher in MCAO+done-pezil group,and the number of NeuN/BrdU-positive cells and CNPase/BrdU-positive cells of MCAO + atropine group was lower(P < 0.05). Conclusions Cholinergic signal could promote NSCs differentiation in peri-infarc-tion region,a lleviate cerebral edema,and improve the brain function restoration after stroke.

Objective To observe the activities of ChAT + neurons in subventricular zone (SVZ) after ischemic stroke and their effects on angiogenesis in peri-infarction region and related signaling pathways. Methods C57BL/6 mice were randomly assigned into sham group,middle cerebral artery occlusion (MCAO) group and atropine group. Ischemic models were made by permanent coagulation of the distal middle cerebral artery. The expression of ChAT,AChE in SVZ and VEGF,VEGFR2,pERK in peripheral regions of ischemic injury was evaluated by Western blotting and immunofluorescence. 5-bromodeoxyuridine(BrdU)/CD31 double-labeled cells were also tested by immunofluorescence. Results At 14 d after the surgery,the ratio of ChAT/AChE in SVZ increased after stroke(P < 0.05). Compared with those in Sham group,the levels of VEGF,VEGFR2 and pERK were higher in MCAO group(P<0.05)and VEGFR2-positive and BrdU/CD31-positive cells increased significantly. However,lower expression of VEGF,VEGFR2 and pERK and less VEGFR2-positive and BrdU/CD31-positive cells were found in atropine group when compared with that in MCAO group. Conclusions The activities of ChAT +neurons in SVZ are enhanced after ischemic injury and they can promote angiogenesis in peripheral region of ischemic injury via upregulating VEGF-VEGFR2 signaling pathway and improving the brain function restoration.

Objective To evaluate the feasibility and effect of sequential treatment by the heated humidified high flow nasal cannula oxygen therapy (HFNC) in mechanically ventilated patients following endotracheal tube extubation.Methods A prospective randomized controlled trial was conducted. Forty-nine patients with the sequential treatment after tracheal intubation extraction admitted to Department of Critical Care Medicine of Shanghai Tenth People's Hospital from January 1st to December 31st 2016 were enrolled. The patients were randomly divided into HFNC group (n = 25) and non-invasive positive pressure ventilation (NPPV) group (n = 24) in accordance with the random numbertable. During the study, arterial blood gas and the sputum viscosity were assessed at 12, 24, and 48 hours after NPPV or HFNC treatment, and the nasal and facial pressure ulcers within 1 week was also recorded. Receiver operating characteristic curve (ROC) was plotted, and the effect of NPPV or HFNC on oxygenation was analyzed.Results Among the 25 patients in the HFNC group, 1 patient who was re-intubated and 2 patients who were changed to NPPV were excluded, and a total of 22 patients with complete data were enrolled in HFNC group. Among the 24 patients in the NPPV group, 1 patient who gave up the treatment and 1 patient who was re-intubated were excluded, and a total of 22 patients with complete data were enrolled in NPPV group. After the sequential treatment, most patients in NPPV group showed moderate viscous sputum (12, 12 and 10 cases at 12, 24 and 48 hours, respectively), whereas the patients in HFNC group showed thin sputum (15, 16 and 15 cases at 12, 24 and 48 hours, respectively). Sputum viscosity of patients in HFNC group at each time point was significantly lower than that in NPPV group (allP < 0.01). Arterial oxygen saturation (SaO2) and arterial partial pressure of oxygen (PaO2) at 12, 24 and 48 hours in the HFNC group were significantly higher than those in the NPPV group [SaO2: 0.978±0.009 vs. 0.906±0.139 at 12 hours, 0.976±0.019 vs. 0.924±0.103 at 24 hours, 0.973±0.019 vs. 0.935±0.079 at 48 hours; PaO2 (mmHg, 1 mmHg = 0.133 kPa): 97.85±22.99 vs. 79.24±25.86 at 12 hours, 108.10±43.87 vs. 84.44±29.24 at 24 hours, 102.31±39.02 vs. 79.04±27.46 at 48 hours, allP < 0.05], however, the difference in arterial partial pressure of carbon dioxide (PaCO2) at all of the time points between the two groups was not significant. In NPPV group, 4 patients with nasal and facial pressure ulcers was found, and all with Ⅰ phase of pressure ulcers, and no nasal and facial pressure ulcers was found in HFNC group, which was significantly decreased as compared with NPPV group (χ2 = 4.400,P = 0.036). A good effect of oxygen therapy was defined as PaO2 at 48 hours after the sequential treatment was increased by 20% as compared with that before the treatment. ROC curve analysis showed that the area under the ROC curve (AUC) of HFNC on improving oxygenation was higher than that of NPPV (0.917 vs. 0.830); when PaO2 at 48 hours after HFNC treatment was 76.25 mmHg, the sensitivity was 100%, and the specificity was 75.0%.Conclusions Compared with NPPV, adoption of HFNC as sequential treatment is a feasible manner in dealing with the mechanically ventilated patients after endotracheal tube extubation, which can improve the oxygenation as well as reducing the degree of sputum viscosity and incidence of nasal and facial pressure ulcers. HFNC is a promising therapy, which may be worthy to recommend broadly in such a clinical situation.

Objective To investigate the influencing factors for spontaneous bacterial peritonitis (SBP) in patients with acute-on-chronic liver failure (ACLF),and to provide a reference for clinical diagnosis and prognosis evaluation.Methods A retrospective analysis was performed for the clinical data of 667 patients with ACLF who were hospitalized and treated in our hospital from January 2009 to December 2014,and according to the presence or absence of SBP,they were divided into ACLF group(n =232) and ACLF-SBP group(n =435).The general information,laboratory markers,and incidence of complications were compared between the two groups.The t-test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups,and a logistic regression analysis was used to identify independent risk factors for ACLF complicated by SBP.Results The comparison of laboratory markers and comorbidities showed that there were significant differences between the two groups in albumin (Alb) (t =-4.110,P ＜ 0.001),alanine aminotransferase (U =-6.653,P ＜ 0.001),aspartate aminotransferase (t =-8.045,P ＜ 0.001),blood sodium (t =-2.879,P =0.006),prothrombin time activity (t =-2.140,P =0.037),international normalized ratio (t =1.453,P =0.042),hemoglobin (t =-3.446,P =0.001),upper gastrointestinal bleeding (x2 =48.252,P =0.002),hepatorenal syndrome (x2 =16.244,P =0.031),and pulmonary infection (x2 =13.564,P ＜ 0.001).The multivariate logistic regression analysis showed that there were significant differences in Alb (OR =1.119,95 ％ CI:1.052 ～ 1.189),platelet count (PLT) (OR =1.035,95 ％ CI:0.755 ～ 1.084),upper gastrointestinal bleeding (OR =1.117,95 ％ C1:0.072 ～ 1.135),and pulmonary infection (OR =2.275,95 ％ CI:0.978 ～ 5.292) (P =0.002,0.038,0.022,and 0.036).Conclusion In the treatment of ACLF patients,risk factors including low Alb,low PLT,upper gastrointestinal bleeding,and pulmonary infection should be prevented,and early diagnosis and intervention of these risk factors helps to reduce the incidence of SBP.

Objective To investigate the role of Src signaling pathway in neurogenesis promoted by choline acetyltransferase (CHAT) + neurons in the subventricular zone (SVZ) after ischemic stroke.Methods The eighty-four mice were randomly assigned into four groups:sham-operated mice treated with vehicle (Sham+vehicle,n=18),middle cerebral artery occlusion (MCAO)-operated mice treated with vehicle (MCAO+vehicle,n=22),MCAO mice treated with donepezil (MCAO+donepezil,n=21),MCAO mice treated with donepezil and Src inhibitor KX2-391 (MCAO+donepezil+KX2-391,n=23).Mice were subjected to the temporary MCAO model of ischemic stroke.Modified neurological severity score (mNSS) was used to assess neurologic function of the mice.Proliferative cells were labeled with Ki67,and neuroblasts with doublecortin (DCX).The expression of Ki67+/DCX+ in the SVZ was detected by immunofluorescence.The expression of Ki67,phospho-epidermal growth factor receptor (p-EGFR),p-Raf,Src and p-Akt in the SVZ were quantified by Western blot.Results MCAO+donepezil+KX2-391 group showed worse performance in the mNSS test than MCAO+donepezil group (P＜0.05).Ten days after MCAO,the number of Ki67+/DCX+ cells in the SVZ of MCAO+donepezil group was 125.33± 13.71/area,which was 71.67± 18.35/area in MCAO+ donepezil+KX2-391 group (P＜0.05).What's more,the expression of proteins Ki67,p-EGFR,p-Raf,Src and p-Akt in mice of MCAO+donepezil group was markedly increased,which was (1.39±0.23),(1.42±0.19),(0.88±0.13),(1.14±0.19),(1.04±0.18) and it was decreased in MCAO+donepezil+KX2-391 group,which was 0.84±0.26,0.94±0.26,0.73±0.15,0.71±0.18,0.81±0.19(P＜0.05).Conclusion CHAT+ neurons in SVZ may promote neurogenesis after stroke via Src-epidermal growth factor receptor (EGFR) signaling pathway.