ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure （ALF） by observing its effect on a mouse model of ALF after prophylactic administration， and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group， model group， Jiedu Huayu granules group （JDHY group）， and farnesoid X receptor （FXR） agonist （GW4064） group using a random number table， with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling， those in the normal group and the model group were given 0.9% NaCl solution by gavage， and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling， and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin （TBil）， total bile acids （TBA）， gamma-glutamyl transferase （GGT）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in mice from each group； HE staining was used to observe liver pathological changes； RT-PCR was used to measure the mRNA expression levels of FXR， fibroblast growth factor 15 （FGF15）， fibroblast growth factor receptor 4 （FGFR4）， small heterodimer partner （SHP）， and bile salt export pump （BSEP） in mice， and Western blot was used to measure the protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP. A one-way analysis of variance was used for comparison between groups， and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in the serum levels of TBil， ALT， AST， TBA， and GGT （all P<0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil， ALT， AST， TBA， and GGT （all P <0.01）. HE staining showed that compared with the model group， the JDHY group and the GW4064 group had milder pathological injury， a reduction in the area of hepatocyte necrosis， and alleviation of cellular swelling and edema. Compared with the normal group， the model group had significant reductions in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.05）. ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.

Objective To investigate the effect of N-myc downstream regulated gene 1(NDRG1)on ferroptosis in mouse brain microvascular endothelial cells(BMVEC)induced by oxygen-glu-cose deprivation(OGD).Methods After primary BMVEC were isolated and cultured from mice,electron microscopy was used to observe the mitochondrial morphology of the cells after OGD.bEnd.3 cells were cultured and divided into six groups:control group,model group(OGD),si-NC(negative control)group,si-NDRG1(NDRG1 interference RNA)group,OGD+si-NC(negative control modeling)group,and OGD+si-NDRG1(NDRG1 interference)group(n=3).The model group,OGD+si-NC group,and OGD+si-NDRG1 group were subjected to the OGD model.Si-NC transfection was performed in the si-NC and OGD+si-NC groups,while si-NDRG1 transfection was carried out in the si-NDRG1 and OGD+si-NDRG1 groups.Cell viability,MDA,glutathione,Fe2+,lipid peroxidation levels,and protein levels of NDRG1,glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)were detected in each group.Results Compared with the control group,the model group showed a significant reduction in the number of cells adhering to the surface after OGD treatment,swollen cytoplasm and decrease in cell viability[(37.68±2.43)％vs(96.34±12.08)％,P＜0.05],down-regulation of GPX4 and up-regulation of ACSL4 and NDRG1 expression(0.78±0.02 vs 1.15±0.01,P＜0.01;1.45±0.04 vs 0.78±0.12,P＜0.01;1.22±0.01 vs 0.13±0.01,P＜0.01).In the si-NDRG1 group,the protein levels of GPX4 and NDRG1 were significantly lower,while the protein levels of ACSL4 and gluta-thione were significantly higher than the si-NC group(P＜0.05).The OGD+si-NC group showed significantly lower GPX4 expression and glutathione level,while obviously higher NDRG1,ACSL4 expression,MDA,and relative fluorescence intensities of Fe2+and oxidized lipid levels when compared to the si-NC and si-NDRG1 groups(P＜0.05).The OGD+si-NDRG1 group showed significantly lower GPX4 expression and glutathione level,and higher ACSL4 and relative fluorescence intensity of Fe2+than the si-NC group and the si-NDRG1 group,while lower NDRG1 expression than the si-NC group but higher than the si-NDRG1 group,and lower NDRG1,ACSL4,MDA,and relative fluorescence intensities of Fe2+and oxidized lipids when compared with the OGD+si-NC group(P＜0.05).Conclusion Knockdown of NDRG1 can alleviate OGD-induced ferroptosis in microvascular endothelial cells by improving iron metabolism and lipid per-oxidation.

Objective To investigate the effect of N-myc downstream regulated gene 1(NDRG1)on ferroptosis in mouse brain microvascular endothelial cells(BMVEC)induced by oxygen-glu-cose deprivation(OGD).Methods After primary BMVEC were isolated and cultured from mice,electron microscopy was used to observe the mitochondrial morphology of the cells after OGD.bEnd.3 cells were cultured and divided into six groups:control group,model group(OGD),si-NC(negative control)group,si-NDRG1(NDRG1 interference RNA)group,OGD+si-NC(negative control modeling)group,and OGD+si-NDRG1(NDRG1 interference)group(n=3).The model group,OGD+si-NC group,and OGD+si-NDRG1 group were subjected to the OGD model.Si-NC transfection was performed in the si-NC and OGD+si-NC groups,while si-NDRG1 transfection was carried out in the si-NDRG1 and OGD+si-NDRG1 groups.Cell viability,MDA,glutathione,Fe2+,lipid peroxidation levels,and protein levels of NDRG1,glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)were detected in each group.Results Compared with the control group,the model group showed a significant reduction in the number of cells adhering to the surface after OGD treatment,swollen cytoplasm and decrease in cell viability[(37.68±2.43)％vs(96.34±12.08)％,P＜0.05],down-regulation of GPX4 and up-regulation of ACSL4 and NDRG1 expression(0.78±0.02 vs 1.15±0.01,P＜0.01;1.45±0.04 vs 0.78±0.12,P＜0.01;1.22±0.01 vs 0.13±0.01,P＜0.01).In the si-NDRG1 group,the protein levels of GPX4 and NDRG1 were significantly lower,while the protein levels of ACSL4 and gluta-thione were significantly higher than the si-NC group(P＜0.05).The OGD+si-NC group showed significantly lower GPX4 expression and glutathione level,while obviously higher NDRG1,ACSL4 expression,MDA,and relative fluorescence intensities of Fe2+and oxidized lipid levels when compared to the si-NC and si-NDRG1 groups(P＜0.05).The OGD+si-NDRG1 group showed significantly lower GPX4 expression and glutathione level,and higher ACSL4 and relative fluorescence intensity of Fe2+than the si-NC group and the si-NDRG1 group,while lower NDRG1 expression than the si-NC group but higher than the si-NDRG1 group,and lower NDRG1,ACSL4,MDA,and relative fluorescence intensities of Fe2+and oxidized lipids when compared with the OGD+si-NC group(P＜0.05).Conclusion Knockdown of NDRG1 can alleviate OGD-induced ferroptosis in microvascular endothelial cells by improving iron metabolism and lipid per-oxidation.

In this study, 34 deep eutectic solvents (DESs) were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes. The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis. The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30% (V/V) in DESs. AB-8 macroporous resin and ethyl acetate were used for separation and refining, and the oligomer-rich proanthocyanidin components were eventually obtained. The ultraviolet (UV) and infrared (IR) spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin. To further clarify the chemical composition of proanthocyanidin, an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins structural library and mass defect filtering (MDF) algorithm, combined with the full mass spectrometry (MS)/dd-MS² scan mode that turns on the "if idle pick others" function. By using ultra-high performance liquid chromatography and high-resolution MS (UHPLC/HRMS), the analysis used both targeted and non-targeted methods to detect proanthocyanidins. Finally, 50 oligomeric proanthocyanidin (OPC) compounds were identified, including 7 monomers, 22 dimers, 20 trimers, and 1 tetramer, most of which were procyanidins of proanthocyanidins (84%), and a small amount of prodelphinidin (14%) and other types of proanthocyanidins (2%), which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes. Meanwhile, the comparison with the grape seeds OPCs standard (United States Pharmacopeia) revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant, suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.

Objective To analyze the training effect of cerebral angiography based on E-Lab surgical teaching system in neurointerventional doctors.Methods A total of 45 doctors who studied at the Neurovascular Center of The First Affiliated Hospital of Naval Medical University from September 2022 to March 2023 were selected.Fourteen doctors who met the inclusion criteria were divided into experimental group and control group,with 7 in each group.The experimental group received training through theoretical teaching and recorded cases based on E-Lab system.The control group received training through traditional theoretical teaching and clinical teaching modes.The learning outcomes of theoretical knowledge and operational skills were compared between the two groups.Results There were no significant differences in the age,professional title,the number of angiography,disease category,aortic arch anatomical type,or the number of radial artery approaches between the two groups(all P＞0.05).There were significant differences in the skill assessment scores and total scores in the final assessment between the two groups(both P＜0.05).There was no significant difference in the theoretical assessment scores between the two groups(P＞0.05).In the skill assessment,there were significant differences in wire control,catheter control,vascular superselection.operation time and proficiency level between the two groups(all P＜0.05).Conclusion E-Lab system has great efficacy and advantages in cultivating operational skills of cerebral angiography in trainees,which provides new ideas for talent cultivation for neural intervention.

In this study,34 deep eutectic solvents(DESs)were successfully prepared for the extraction of proan-thocyanidin from Rhodiolae Crenulatae Radix et Rhizomes.The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis.The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30％(V/V)in DESs.AB-8 macroporous resin and ethyl acetate were used for separation and refining,and the oligomer-rich proanthocyanidin components were eventually obtained.The ultra-violet(UV)and infrared(IR)spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin.To further clarify the chemical composition of proanthocyanidin,an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins struc-tural library and mass defect filtering(MDF)algorithm,combined with the full mass spectrometry(MS)/dd-MS2 scan mode that turns on the"if idle pick others"function.By using ultra-high performance liquid chromatography and high-resolution MS(UHPLC/HRMS),the analysis used both targeted and non-targeted methods to detect proanthocyanidins.Finally,50 oligomeric proanthocyanidin(OPC)com-pounds were identified,including 7 monomers,22 dimers,20 trimers,and 1 tetramer,most of which were procyanidins of proanthocyanidins(84％),and a small amount of prodelphinidin(14％)and other types of proanthocyanidins(2％),which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes.Meanwhile,the comparison with the grape seeds OPCs standard(United States Pharmacopeia)revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant,suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway. Methods(i)A total of 72 specific pathogen-free(SPF)grade male Sprague Dawley(SD)rats were randomly divided into six groups,with 12 rats in each group:control,model,metformin(Met,0.18 g/kg)+fluoxetine(Flu,1.8 mg/kg),and the high-,medium-,and low-ZJJF dosages(ZJJF-H,20.52 g/kg;ZJJF-M,10.26 g/kg;ZJJF-L,5.13 g/kg)groups.All groups except control group were injected once via the tail vein with streptozotocin(STZ,38 mg/kg)combined with 28 d of chronic unpredictable mild stress(CUMS)to establish diabetic rat models with de-pression.During the CUMS modeling period,treatments were administered via gavage,with control and model groups receiving an equivalent volume of distilled water for 28 d.The effi-cacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose,insulin,and glycated hemoglobin levels,along with behavioral assess-ments,including the open field test(OFT),forced swim test(FST),and sucrose preference test(SPT).Hippocampal tissue damage and neuronal apoptosis were evaluated using hema-toxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining.Apoptosis-related proteins Bax,Bcl-2,caspase-3,and the ex-pression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).(ii)To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological ef-fects of ZJJF,an additional 50 SPF grade male SD rats were randomly divided into five groups,with 10 rats in each group:control,model,SP600125(SP6,a JNK antagonist,10 mg/kg),ZJJF(20.52 g/kg),and ZJJF(20.52 g/kg)+Anisomycin(Aniso,a JNK agonist,15 mg/kg)groups.Ex-cept for control group,all groups were established as diabetic rat models with depression,and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period.Behavioral changes in rats were evaluated through the OFT,FST,and SPT,and hippocampal neuron damage and apoptosis were ob-served using HE staining,Nissl staining,TUNEL staining,and transmission electron mi-croscopy(TEM).Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed. Results(i)ZJJF significantly reduced the high blood glucose,insulin,and glycated he-moglobin levels in model rats(P<0.01).It increased autonomous activity and decreased de-spair-like behaviors(P<0.01),improved the pathological damage of hippocampal neurons,increased the number of neuronal nuclei(P<0.01),and reduced the number of mechanocytes,vacuolar cells,and apoptotic neurons(P<0.05,P<0.01,and P<0.01,respec-tively).ZJJF down-regulated the expression levels of pro-apoptotic proteins Bax and caspase-3(P<0.01),up-regulated the anti-apoptotic protein Bcl-2(P<0.01),and significantly inhibit-ed the overexpression of phosphorylated JNK(p-JNK),Elk-1,and c-fos(P<0.01).(ii)SP6 in-creased autonomous activity and reduced despair time in model rats(P<0.05),although it had no significant effects on sucrose preference(P>0.05).It increased the number of Nissl bodies in hippocampal neurons(P<0.01),reduced the protein expression levels of Bax(P<0.01)and caspase-3(P<0.05),and decreased the number of apoptotic neurons(P<0.05).SP6 also increased the expression level of Bcl-2(P<0.01),and inhibited the high expression levels of p-JNK,Elk-1,and c-fos(P<0.01,P<0.01,and P<0.05,respectively),suggesting that hip-pocampal neuronal apoptosis in diabetic rats with depression is associated with abnormal ac-tivation of JNK signaling pathway.Compared with ZJJF group,ZJJF+Aniso group showed a decrease in sucrose preference(P<0.05)and an increase in despair time(P<0.01)with more notable hippocampal neuronal damage.This group also exhibited a decrease in expression level(P<0.01)Bcl-2 and an increase in expression levels of Bax,caspase-3,p-JNK,Elk-1,and c-fos(P<0.01,P<0.05,P<0.05,P<0.01,and P<0.05,respectively),indicating that the antidepressant effects of ZJJF,its improvement of neuronal apoptosis,and regulation of JNK signaling molecules could all be reversed by a specific JNK agonist. Conclusion ZJJF exerts a significant hypoglycemic effect and ameliorates the apoptosis of hippocampal neurons by inhibiting the activation of JNK signaling pathway,which is a promising formula for the treatment of diabetic depression in clinical settings.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective To investigate the relationship between brain structural networks and gut micro-biota in patients with mild cognitive impairment associated with Parkinson's disease(PD-MCI),and the impact on cognitive function by neuroimaging and intestinal microbiology techniques.Methods 29 cases of patients with PD-MCI and 17 cases of PD patients with normal cognitive function(PD-NC)were enrolled.MRI T1-weighted and diffusion tensor imaging were collected for graph theory analysis,and fecal samples were analyzed using 16s DNA sequencing.Partial correlation analysis assessed relationships among differential bacteria,structural network prop-erties,and cognitive scale scores,finally followed by mediation effect analysis.Results In PD patients,the abundance of Prevotellaceae,Alloprevotella,and UCG-10 bacteria was positively correlated with language and memory cognitive domains,while the abundance of UCG-010 showed a negative correlation with executive function.Additionally,the gut microbiota also was associated with several distinct brain structural network node characteristics.Mediation analysis indicated that Prevotellaceae's effect on logical memory was mediated by the node degree in the right opercular inferior frontal gyrus(IE=0.074,95%CI:0.21～0.001,P=0.046).Conclusions PD-MCI patients showed distinct gut microbiota and brain network features compared to PD-NC patients.The association and the me-diation analysis of gut microbiota with brain networks and cognitive impairment suggests a role for Prevotellaceae in brain network alterations related to MCI,highlighting the gut-brain axis's potential influence on cognition.