Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal

Objective:To investigate the interventional effect of bone marrow mesenchymal stem cell (BMMSC) transplantation with different doses of X-ray irradiation induced hepatic injury in mice.Methods:Eighteen female C57BL/6J mice were randomly divided into 0, 2, and 3 Gy irradiation groups and 0, 2, and 3 Gy transplantation groups. The irradiation group was used as the control and injected with an equal volume of culture medium. The mice in the transplantation group were irradiated with different doses of X-ray irradiation, and BMMSCs were intravenously infused into the bone marrow. The mice were sacrificed for sampling at the end of the 21st day. Mice body weight changes were recorded daily. The changes in the content of peripheral blood lymphocytes, red blood cells, platelets, and hemoglobin were detected by an automatic blood tester. The morphological changes in mice liver tissues were observed by hematoxylin-eosin staining. The serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by a biochemical analyzer. The reduced glutathione contents in liver tissue were detected by the microplate method. The malondialdehyde content in liver tissue was detected by thiobarbituric acid. The content of total superoxide dismutase (T-SOD) in liver tissue was detected by the hydroxylamine method. The expression of the F4/80 protein in liver tissue was detected by the immunohistochemistry method. The protein expression of nuclear transcription factor erythroid 2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in liver tissue was determined by the western blotting method. The mRNA expression of NLRP3, IL-6, and Nrf2 in liver tissue was detected by a real-time quantitative polymerase chain reaction. The multiple-group comparisons were analyzed by factorial analysis of variance. The inter-group comparisons were analyzed by the LSD method for statistical analysis.Results:The contents of peripheral blood lymphocytes, erythrocytes, platelets, and hemoglobin were significantly decreased in the 3 Gy irradiation group than the 0 Gy irradiation group ( P<0.05), while the activities of serum ALT and AST were significantly increased ( P<0.05). The malondialdehyde content, F4/80 protein expression level, nucleotide-binding domain and leucine-rich repeats, nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3), and interleukin 6 mRNA expression levels were significantly increased in liver tissue, while the contents of T-SOD and glutathione, Nrf2 and HO-1 protein expression levels, and Nrf2 mRNA expression level in liver tissue were significantly decreased ( P<0.05). The contents of peripheral blood lymphocytes, red blood cells, platelets, and hemoglobin were significantly increased in the 3 Gy transplantation group than the 3 Gy irradiation group ( P<0.05), while the activities of serum ALT and AST were significantly decreased ( P<0.05). The malondialdehyde content, F4/80 protein expression level, NLRP3 and interleukin-6 mRNA expression levels in liver tissue were significantly decreased ( P<0.05), while the content of T-SOD and glutathione, Nrf2 and HO-1 protein expression levels, and Nrf2 mRNA expression level in liver tissue were significantly increased ( P<0.05). Conclusion:X-ray irradiation at a dose of 3 Gy can induce liver oxidative damage in mice. BMMSC transplantation can improve X-ray irradiation-induced liver oxidative damage in mice, and its mechanism of action may be related to the regulation of the Nrf2/HO-1 pathway.

Objective:To compare and analyze the clinical efficacy of laparoscopic microwave ablation and laparoscopic hepatectomy in the treatment of hepatic hemangioma.Methods:The clinical data of 98 patients with hepatic hemangioma admitted to the Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University from June 2019 to June 2023 were retrospectively analyzed, including 20 males and 78 females, aged 24-69 years. According to the surgical method, they were divided into two groups: laparoscopic microwave ablation group (ablation group) with 34 cases, and laparoscopic hepatectomy group (resection group) with 64 cases. The differences in intraoperative and postoperative recovery related indicators, follow-up and prognosis between the two groups were compared and analyzed.Results:The operative time and blood loss in the ablation group were (90.6±21.8) min and (60.3±40.8) ml, respectively, which were lower than those in the resection group (128.7±30.0) min and (165.8±212.7) ml, and the differences were statistically significant ( t=-6.54, -2.86, P<0.001, P=0.005). There were 5 cases (14.71%) of residual lesions in the ablation group and none in the resection group, with a significant difference between the two groups ( χ2=0.01, P=0.003). The ablation group was superior to the resection group in hospital stay, drainage tube removal time and postoperative pain, with statistical significance (all P<0.05). On the 1st and 3rd day after surgery, the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin and direct bilirubin in ablation group were lower than those in resection group, and the differences were statistically significant (all P<0.05). In the ablation group, there were 14 cases of hemoglobinuria (41.2%), 2 cases of abdominal hemorrhage (5.9%), 0 cases of bile leakage and 6 cases of pleural effusion (17.7%), while in the resection group, these complications were 2 cases (3.1%), 18 cases (28.1%), 11 cases (17.2%) and 32 cases (50.0%), respectively, and there were statistical significance between the two groups (all P<0.05). In terms of prognosis, there was both one recurrence in each group (2.9% vs. 1.6%), with no significant difference ( χ2=1.00, P=0.653). Conclusion:Compared with laparoscopic hepatectomy, laparoscopic microwave ablation has obvious advantages in terms of operation time, intraoperative blood loss, hospital stay, postoperative pain and complications.

Objective To study the partial mechanism of astragalosides(ASTs)against biliary fibrosis through inhibiting ductular reaction.Methods Rats were randomly divided into sham operation group,bile duct ligation(BDL)group and ASTs group(n=8 in each group).On the first day of the second week after BDL,the rats in ASTs group were given intragastric administration of ASTs for 3 weeks(160 mg·kg-1·d-1,once a day).Rats in sham operation group and BDL group were given the same volume of water.At the end of the fourth week,all rats were euthanasia.HE staining and sirius red staining were used to observe the pathological changes and collagen deposition.The degree of liver fibrosis was evaluated by semi-quantitative analysis of positive area of sirius red staining and the content of hydroxyproline.The expression changes of α smooth muscle actin(α-SMA),Desmin,cytokeratin(CK)19,CK7,epithelial cell adhesion molecule(Epcam),OV6 and lysyl oxidase(LOX)family proteins in liver tissue were detected by immunohistochemistry,Western blot,and real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).In vitro,hepatic progenitor cell line WB-F344 cells were induced by sodium butyrate to differentiate into biliary epithelial cells,intervented of ASTs,and collected after 4 days.The expression changes of CK19,LOXL1 and LOXL2 of cells were detected by qRT-PCR.Results Compared with BDL group,serum ALT and AST activities in ASTs group were significantly decreased(P<0.01).Histopathological injury of liver tissue was significantly reduced,Hyp content and percentage of positive area of sirius red were significantly decreased(P<0.01).Immunohistochemical staining showed that the positive expressions of α-SMA,Desmin,CK19,CK7,Epcam and OV6 were significantly decreased in the ASTs group.The mRNA expressions of α-SMA,CK7,LOX and LOXL1 were significantly decreased.The protein expressions of Epcam and LOXL1 were significantly reduced.In vitro results showed that the gene expressions of CK19,LOXL1 and LOXL2 were significantly increased after sodium butyrate induction(P<0.01).Compared with sodium butyrate group,the gene expressions of CK19,LOXL1 and LOXL2 were significantly decreased in ASTs group(P<0.01).Conclusion ASTs improved biliary fibrosis by inhibiting ductular reaction,and the mechanism may be related to the down-regulation of LOXL1.

Objective To investigate the intervention effect of GDC-0449, a hedgehog signaling pathway inhibitor, on rats with liver fibrosis induced by carbon tetrachloride (CCl 4 ) combined with 2-acetylaminofluorene (2-AAF). Methods A total of 18 female Fisher344 rats were randomly divided into normal group, CCl 4 /2-AAF group, and GDC-0449 group, with 6 rats in each group. The rats in the CCl 4 /2-AAF group and the GDC-0449 group were given subcutaneously injected 30% CCl 4 -olive oil solution at a dose of 2 mL/kg twice a week for 6 weeks to induce liver fibrosis; since week 7, in addition to the injection of CCl 4 -olive oil solution, the rats in these two groups were given 2-AAF (100 mg/kg/d) by gavage, and the rats in the GDC-0449 group were given GDC-0449 (25 mg/kg/d) by gavage, while those in the normal group were given an equal volume of olive oil solution by injection and normal saline by gavage. All rats were sacrificed at the end of week 9, and related samples were collected. HE staining and sirius red (SR) staining were used to observe the changes in liver histopathology and collagen deposition, and the semi-quantitative analysis of SR-positive area and Ishak score were used to evaluate fibrosis degree; the alkaline hydrolysis method was used to measure the level of hydroxyproline (Hyp) in liver tissue; immunohistochemistry, Western blot, and qRT-PCR were used to measure the expression of α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col-Ⅰ), type Ⅳ collagen (Col-Ⅳ), cytokeratin 19 (CK19), cytokeratin 7 (CK7), the epithelial cell adhesion molecule Epcam, and the hedgehog signaling pathway in liver tissue; double immunofluorescence staining was used to observe the colocalization of CK19 and the oval cell marker OV6. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the CCl 4 /2-AAF group had marked inflammatory cell aggregation and collagen deposition in liver tissue, with the formation of a pseudolobular structure, as well as significant increases in Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Col-Ⅰ, Col-Ⅳ, Epcam, CK19, CK7, the transmembrane transporter Smoothened (Smo), Hedgehog ligand Desert Hedgehog (Dhh), the Indian Hedgehog membrane-binding receptor Patched (Ptch2), and glioma-related oncogenes Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed that CK19-positive cells also expressed OV6 in the liver tissue of rats in the CCl 4 /2-AAF group, with a significant increase compared with the normal group. Compared with the CCl 4 /2-AAF group, the GDC-0449 group had significant reductions in inflammatory cell aggregation and collagen deposition in liver tissue, Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Epcam, CK19, CK7, Smo, Ptch2, Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed a significant reduction in the number of cells with co-expression of OV6 and CK19 in liver tissue. Conclusion The Hedgehog signaling pathway inhibitor GDC-0449 can significantly inhibit the progression of liver fibrosis induced by CCl 4 /2-AAF in rats, possibly by inhibiting hepatic stellate cell activation, collagen deposition, activation and proliferation of hepatic progenitor cells, and differentiation of hepatic progenitor cells into biliary epithelial cells.

Objective:This study aimed to observe whether the treatment-free remission (TFR) of second-generation tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) is better than imatinib (IM) .Methods:The clinical data of 274 CML patients who discontinued treatment and with complete clinical data were retrospectively studied from June 2013 to March 2021. Using both univariate and multivariate Cox proportional hazards regression models, risk factors influencing TFR outcomes after drug withdrawal in CML patients were assessed.Results:A total of 274 patients were enrolled, 140 patients were women (51.1%) , with a median age of 48 (9-84) years at the time of TKI discontinuation. Prior to TKI discontinuation, 172 (62.8%) patients were treated with IM, and 102 (37.2%) had received second-generation TKI treatment, including 73 patients who had shifted from IM to a second-generation TKI and 29 patients who used second-generation TKI as the first-line treatment. The rationale for converting to a second-generation TKI are as follows: 37 patients aimed deep molecular response (DMR) to achieve TFR, seven patients changed due to IM intolerance, and 29 patients changed because of failure to achieve the optimal treatment response. The use of the last type of TKI included 96 patients (94.1%) with nilotinib, three patients (2.9%) with dasatinib, and two patients (2%) with flumatinib, including one patient who changed to IM due to second-generation TKI intolerance. No statistical differences were found in the median age at diagnosis and TKI discontinuation, sex, Sokal score, IFN treatment before TKI, median time of TKI treatment to achieve DMR, and the reasons for TKI discontinuation between the second TKI and IM ( P>0.05) .The median cumulative treatment time of TKI (71.5 months vs 88 months, P<0.001) , the last TKI median treatment time (60 months vs 88 months, P<0.001) , and the median duration of DMR (58 months vs 66 months, P=0.002) were significantly shorter in the second-generation TKI compared with IM. In the median follow-up of 22 (6-118) months after TKI discontinuation, 88 patients (32.1%) had lost their MMR at a median of 6 (1-91) months; of the 53 patients (60.2%) who lost MMR within 6 months, the overall TFR rate was 67.9%, and the cumulative TFR rates at 12 and 24 months were 70.5% and 67.5%, respectively. Withdrawal syndrome occurred in 26 patients (9.5%) . For patients who restarted TKI treatment, 72 patients (83.7%) achieved DMR again at a median treatment of 4 (1 to 18) months. The univariate analysis showed that the TFR rate of patients treated with second-generation TKI was significantly higher than those who were treated with IM (77.5% vs 62.2%, P=0.041) . A further subgroup analysis found that the TFR rate of the second-generation TKI patients was significantly higher than those treated with IM (80.8% vs 62.2%, P=0.026) . No significant difference was found in the second-generation TKI used as the first line treatment compared with those who were treated with IM (69.0% vs 62.2%, P=0.599) . The multivariate analysis results showed that second-generation TKI treatment was an independent prognostic factor affecting TFR in patients who discontinued TKI ( RR=1.827, 95% CI 1.015-3.288, P=0.044) . Conclusion:In the clinical setting, more CML patients rapidly achieved TFR using second-generation TKI than IM treatment.

End-stage liver disease is the late stage of various acute and chronic liver diseases with high mortality and seriously threatens people's health. Liver transplantation is currently an effective treatment method for this disease, but its clinical application is greatly limited by the factors such as shortage of donors and high costs. In recent years, clinical and basic studies have shown that bone marrow mesenchymal stem cell and its exosomes have good clinical application prospects in the treatment of end-stage liver disease. This article reviews the mechanism of action and clinical application of bone marrow mesenchymal stem cell and its exosomes in the treatment of end-stage liver disease, so as to provide a reference for further research.

Objective To investigate the effects of miR-129-5p on the proliferation and migration of osteosarcoma cells and the regulation of HMGB1 gene. Methods The expression of miR-129-5p and HMGB1 in osteosarcoma cell line MG-63, Saos-2 and osteoblast hFOB1.19 were detected by RT-PCR and Western blot. Bioinformatics methods were used to predict whether there were binding sites between mir-129-5p and HMGB1 gene. Double luciferase reporter gene system was used to verify the interaction between miR-129-5p and the target gene HMGB1. miR-129-5p mimic and inhibitor were transfected into osteosarcoma cell lines with low and high miR-129-5p expression, respectively, and the transfection efficiency was detected by RT-PCR. After successful transfection, the proliferation and migration of osteosarcoma cell lines were detected by CCK-8 assay, scratch assay and Transwell migration assay, respectively, and Western blot was used to detect the expression of HMGB1 in the transfected osteosarcoma cell lines. Results Expression of miR-129-5p in osteosarcoma cells was lower than that in normal osteoblasts (P < 0.05), and the expression of HMGB1 in osteosarcoma cell lines was higher than that in normal osteoblasts (P < 0.05). There were binding sites between miR-129-5p and HMGB1 genes, and the luciferase activity of HMGB1-WT plasmid group was down-regulated after transfection with miR-129-5p mimic (P < 0.05). Transfection of miR-129-5p mimic significantly increased the expression of miR-129-5p in MG-63 cells (P < 0.05), inhibited the proliferation and migration of MG-63 cells (P < 0.05), and decreased the expression level of HMGB1. After transfection with miR-129-5p inhibitor, the expression of miR-129-5p in Saos-2 cells was significantly decreased (P < 0.05), the proliferation and migration abilities of Saos-2 cells were enhanced (P < 0.05), and the expression level of HMGB1 was also increased. Conclusion miR-129-5p may inhibit the proliferation and migration of osteosarcoma cells through HMGB1 gene.

Objective To study the degradation behavior and mechanical properties of magnesium alloy plate on treatment of tibial fracture in New Zealand rabbits. Methods Thirty-six adult New Zealand rabbits were randomly divided into experimental group (magnesium alloy bone plate group, n=18) and control group (titanium alloy bone plate group, n=18). Tibial fractures in experimental group and control group were fixed with magnesium alloy bone plate and titanium alloy bone plate, respectively. After operation, X-ray, scanning electron microscopy, energy spectrum analysis, weight loss test and four-point bending test were performed in each group to analyze the degradation behavior and mechanical properties of magnesium alloy plate after tibial fracture treatment. Results Magnesium alloy bone plate could be degraded gradually in vivo. The degradation of magnesium alloy bone plate was deepened gradually with the implantation time, and the surface was corroded uniformly. The mechanical properties of magnesium alloy bone plate decreased gradually with the degradation in vivo. Conclusions Magnesium alloy bone plate can degrade gradually with fracture healing in vivo, and its mechanical properties gradually decline, but it can still meet the requirements of fracture internal fixation, and is a kind of good new degradable orthopedic implant material.

Objective:To investigate the clinicopathologic features, treatment, and prognosis in patients with Castleman disease (CD) .Methods:We retrospectively analyzed the clinicopathologic data of 59 patients for whom a diagnosis of Castleman disease was confirmed using pathological examination from October 2011 to October 2019 at the Henan Cancer Hospital. The patients were divided into the following two groups as per the following clinical classifications: unicentric CD (UCD, n=47) and multicentric CD (MCD, n=12) . Data on clinical manifestations, laboratory findings, treatment, and prognosis were analyzed. Results:There was no significant difference in the median age and the ratio of male to female between the UCD and MCD. UCD was characterized by asymptomatic enlargement of the single lymph node. The main pathological type was hyaline vascular histopathology (83.0%) . Of these, 44 patients chose surgical resection, and their prognosis was good. Treatment. MCD was characterized by multiple enlarged superficial and/or deep lymph nodes with B symptoms, weakness, and hepatosplenomegaly. Anemia, hypoproteinemia, and globulin level were increased on laboratory examinations. Plasmacyte histopathology was the main pathological type and was present in about 50.0% of the subjects. Only chemotherapy was performed for these MCD patients, followed by chemotherapy or chemotherapy followed by radiotherapy, and the efficient was 58.3% (7/12) .Conclusions:UCD, characterized by asymptomatic enlargement of the single lymph node, shows good postoperative prognosis. MCD has relatively complex clinical manifestations and poor prognosis, and optimal treatment is yet to be established.