AIM: To explore the protective effects of sinomenine (SIN) on oxidative stress and pulmonary fibrosis and its relationship with the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. METHODS: MRC-5 cells were treated with hydrogen peroxide (H2O2) to establish the oxidative stress injury model, followed by administration with SIN. Cell viability was detected using the CCK-8 method. The biochemical kits were employed to measure malondialdehyde (MDA) content and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities. The protein expression of Keap1 and Nrf2 was examined by western blot. Thirty SD rats were randomly divided into control group, bleomycin A5 (BLM) group and BLM + SIN group, with 10 animals in each group. Bleomycin A5 were intratracheally administered to the rats in BLM group and BLM+SIN group to establish the pulmonary fibrosis model. The rats in control group received the same volume of 9 g/L sodium chloride solution. The second day after model construction, the rats in BLM+SIN group were gavaged with SIN, while the rats in the other two groups were treated with 9 g/L sodium chloride solution. On day 28, all rats were sacrificed. Pulmonary tissue was isolated, and HE and Masson staining was performed to observe the pathological changes. The MDA content and SOD, GSH-Px and CAT activities in pulmonary tissue were evaluated. Western blot was used to assay pulmonary tissues Keap1 and Nrf2 protein expression. RESULTS: When compared with H2O2 group, SIN treatment increased cell viability, decreased MDA content, elevated SOD, GSH-Px and CAT activities, down-regulated Keap1 expression, and promoted nuclear translocation of Nrf2 in MRC-5 cells. In comparison with BLM group, administration of SIN decreased alveolitis and pulmonary fibrosis pathological changes and scores as well as pulmonary tissue MDA content, enhanced pulmonary tissues SOD, GSH-Px and CAT activities, down-regulated pulmonary tissues Keap1 expression, and raised Nrf2 levels in the nucleus. CONCLUSION: SIN alleviates oxidative stress and pulmonary fibrosis possibly by activating the Keap1/Nrf2 signaling pathway.

OBJECTIVE: To improve the classical 4-vessel occlusion (4VO) model established by Pulsinelli and Brierley. METHODS: Thirty-two male SD rats were randomized into sham operation group, I4VO-Con10 group, I4VO-Int10 group and I4VO-Int15 group. The sham surgery group underwent exposure of the bilateral vertebral arteries and carotid arteries without occlusion to block blood flow. The I4VO-Con10 group experienced continuous ischemia by occluding the bilateral vertebral arteries and carotid arteries for 10 minutes followed by reperfusion for 24 hours. The I4VO-Int10 and I4VO-Int15 groups were subjected to intermittent ischemia. The I4VO- Int10 group underwent 5 minutes of ischemia, followed by 5 minutes of reperfusion and another 5 minutes of ischemia, and then reperfusion for 24 hours. The I4VO-Int15 group experienced 5 minutes of ischemia followed by two cycles of 5 minutes of reperfusion and 5 minutes of ischemia, and then reperfusion for 24 hours. The regional cerebral blood flow (rCBF) was monitored with laser Doppler scanning, and survival of the rats was observed. HE staining was used to observe hippocampal pathologies to determine the optimal method for modeling. Another 48 rats were randomized into 6 groups, including a sham operation group and 5 model groups established using the optimal method. The 5 I4VO model groups were further divided based on the reperfusion time points (1, 3, 7, 14, and 28 days) into I4VO-D1, I4VO-D3, I4VO-D7, I4VO- D14, and I4VO- D28 groups. Body weight changes and survival of the rats were recorded. HE staining was used to observe morphological changes in the hippocampal, retinal and optic tract tissues. The Y-maze test and light/dark box test were used to evaluate cognitive and visual functions of the rats in I4VO-D28 group. RESULTS: Occlusion for 5 min for 3 times at the interval of 5 min was the optimal method for 4VO modeling. In the latter 48 rats, the body weight was significantly lower than that of the sham-operated rats at 1, 3, 7, 14 and 28 days after modeling without significant difference in survival rate among the groups. The rats with intermittent vessel occlusion exhibited progressive deterioration of hippocampal neuronal injury and neuronal loss. Cognitive impairment was observed in the rats in I4VO-D28 group, but no obvious ischemic injury of the retina or the optic tract was detected. CONCLUSION The improved 4VO model can successfully mimic the main pathological processes of global cerebral ischemia-reperfusion injury without causing visual impairment in rats.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Brain Ischemia ; Cerebral Infarction ; Reperfusion Injury ; Body Weight

Objective To explore the impact of sinomenine on bleomycin A5-induced pulmonary fibrosis (PF) in rats and the underlying mechanism. Methods MRC-5 cells were cultured and treated with sinomenine to determine its optimal concentration and time through the MTT assay. Subsequently, MRC-5 cells were incubated with 80 μmol/L sinomenine for 48 hours or transfected with miR-21 mimic/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1) siRNA prior to sinomenine treatment. The expression of miR-21, ADAMTS-1, collagen type 1 (Col1) and collagen type 3 (Col3) was detected by quantitative real-time PCR (qRT-PCR) and/or Western blot analysis. Thirty SD rats were randomly divided into control group, sinomenine group and sinomenine combined with miR-21 agomir group, with 10 animals in each group. Bleomycin A5 were intratracheally administered to establish the PF model. Then, rats in control group, sinomenine group and sinomenine +miR-21 agomir group were treated with 9 g/L sodium chloride solution, sinomenine and sinomenine+miR-21 agomir, respectively. On day 28, all rats were sacrificed. HE and Masson staining was performed in pulmonary tissue. The expression of ADAMTS-1, Col1 and Col3 in pulmonary tissue were detected by qRT-PCR and/or Western blot analysis. ELISA was used to measure serum procollagen type 1 carboxyterminal propeptide (P1CP) and procollagen type 3 aminoterminal propeptide (P3NP) levels. Results Administration of sinomenine decreased miR-21 levels, up-regulated ADAMTS-1 expression, and promoted Col1 and Col3 degradation in MRC-5 cells. Importantly, interfering with the miR-21/ADAMTS-1 signaling pathway partially reversed the promotive effect of sinomenine on Col1 and Col3 degradation. Treatment of SD rats with sinomenine reduced alveolitis and PF scores, decreased serum P1CP and P3NP levels, up-regulated pulmonary ADAMTS-1 expression, and down-regulated Col1 and Col3 expression. However, these effects were reversed by miR-21 agomir. Conclusion Sinomenine promotes Col1 and Col3 degradation and inhibits PF in rats by miR-21/ADAMTS-1 pathway.
Rats ; Animals ; Pulmonary Fibrosis/genetics* ; Procollagen/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Bleomycin/adverse effects* ; Collagen Type III/metabolism* ; MicroRNAs/metabolism*

Conversion therapy has become the core in the treatment of borderline resectable or unresectable liver cancer, which provides resectable opportunities for more advanced liver cancer patients. In accordance with the first-choice treatment regimen recommended by the guidelines, the authors reported a successful case of Atezolizumab and Bevacizumab (T+A regimen) conversion therapy. The patient with initially borderline resectable advanced liver cancer was performed liver segment resection sucessfully after conversion therapy, and non-tumor recurrence was observed at postoperative 9 months. Postoperative pathological examination showed combined hepatocellular-cholangiocarcinoma, which also indicated the important value of T+A regimen in the conversion therapy of combined hepatocellular-cholangiocarcinoma.

【Objective】 To evaluate the safety and efficacy of rivaroxaban in preventing portal vein system thrombosis （PVST） in patients with liver cirrhosis after splenectomy and pericardial devascularization. 【Methods】 Totally 76 cirrhotic patients underwent splenectomy and pericardial devascularization were randomly assigned to rivaroxaban treatment group （n=38） or low-molecular weight heparin （LMWH） plus warfarin treatment group （n=38）. The experimental group was given rivaroxaban 10 mg orally， once a day， for 30 days. The control group was given subcutaneous injection of 5000 IU low molecular weight heparin （LMWH） twice a day for 5 days and warfarin （initial dose 2.5 mg） orally once a day for 30 days. Both groups were followed up for 1 year. We compared the two groups in the incidence of PVST， recovery of liver function and coagulation function， decompensation of liver function， incidence of liver cancer， and active bleeding. 【Results】 Totally 18 patients （47.4%） in rivaroxaban group developed PVST， compared with 29 patients （76.3%） in LMWH plus warfarin group （P=0.024）. The incidence of PVST during the first year after operation was significantly lower in rivaroxaban group than in LMWH plus warfarin group （F=7.852， P=0.007）. The intra-group comparisons versus baseline showed that the liver function improved from POD 21 to POM 1， and coagulation function improved from POM 2 in rivaroxaban group. In contrast， the liver function improved from POM 1 to POM 2， and coagulation function improved from POM 4 in LMWH plus warfarin group. The two groups did not significantly differ in liver function decompensation， incidence of liver cancer， or active bleeding （all P>0.05）. 【Conclusion】 The prophylactic use of rivaroxaban significantly decreases the incidence of PVST after splenectomy and pericardial devascularization in cirrhotic patients compared to LMWH plus warfarin treatment. Besides， rivaroxaban treatment is safe and effective and is associated with improved liver and coagulation functions than LMWH plus warfarin treatment.

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.

Objective To investigate the clinical significance of bone marrow immunopathogenesis in the diagnosis and staging of lymphoma. Methods Clinical data of 266 patients with newly diagnosed lymphoma admitted to Department of Hematology in the First Hospital of Jilin University from August 2015 to December 2017 were retrospectively analyzed. The results of lymphoma diagnosis and staging in different bone marrow detection methods were compared, SPSS 22.0 software was used to make statistical analysis and χ2 test was used to compare the positive rates of lymphoma bone marrow infiltration in different methods. Results In the 266 patients, 64 cases (24.1 %) were diagnosed with lymphoma by using bone marrow detection on the condition that no lymph node pathology was available and all the immunophenotypes of 64 cases were identified by bone marrow immunopathology. Bone marrow infiltration was identified in 121 patients (45.5 %), among which the rate of bone marrow infiltration was 0 (0/12) in Hodgkin lymphoma (HL) and 47.6 % (121/254) in non-Hodgkin lymphoma (NHL). The rate of bone marrow infiltration was 50.0 % (105/210) and 36.4 % (16/44) in B type and T type NHL respectively. The positive rate of bone marrow infiltration detected by bone marrow smear, bone marrow biopsy, bone marrow flow cytometry and bone marrow immunopathology were 78.5 % (95/121), 87.6 % (106/121), 89.3 % (108/121), 96.7 % (117/121) respectively. Bone marrow immunopathology was more advantageous than any other methods, and there was a statistical difference (χ2＝18.38, 9.09, 3.76; all P < 0.05). Among 121 patients who were identified with bone marrow infiltration by bone marrow detection, the staging of 42 patients (34.7 %) were amended, including the staging of 39 amended patients (32.2 %) through bone marrow immunopathologic detection. Conclusion Bone marrow immunopathology can be used for the diagnosis and classification of lymphoma, which has an obvious advantage in detecting bone marrow infiltration of lymphoma compared with bone marrow smear, bone marrow biopsy, bone marrow flow cytometry, and it can be used to amend the clinical staging.

Objective:To explore cardiac repair effect of AKT gene transfected amniotic fluid mesenchymal stem cells (AFMSC) transplantation on ischemic reperfusion injured myocardium in rabbit model . Methods :AKT overex‐pressed lentiviral vector was established to transfect AFMSC ;New Zealand rabbits were randomly divided into low glucose DMEM (L‐DMEM) group (group A) ,AFMSC group (group B) and AKT transfected AFMSC group (AKT‐AFMSC group ,group C) .Then rabbit myocardial ischemia reperfusion injury model was established .Before reper‐fusion ,0.2ml L‐DMEM ,AFMSC and AKT‐AFMSC was directly injected into infarct area and surrounding myocar‐dial epicardium in corresponding group . On 21 days after operation , left ventricular end‐diastolic dimension (LVEDd) ,left ventricular shortening fraction (LVFS) ,left ventricular ejection fraction (LVEF) ,infarct size and pathological changes were compared among three groups .Results:Compared with L‐DMEM group and AF‐MSC group ,there was significant reductions in LVEDd [ (16.37 ± 0.84) mm ,(15.06 ± 1.01) mm vs .(13.51 ± 0.85) mm] and infarct size [ (37.3 ± 2.1)% ,(26.6 ± 0.7)% vs .(18.1 ± 1.2)% ] ,and significant rise in LVFS [ (29.18 ± 2.36)% ,(33.65 ± 2.81)% vs .(36.89 ± 3.02)% ] and LVEF [ (58.62 ± 3.47)% ,(67.42 ± 3.03)% vs .(72.02 ± 2.89)% ] , P< 0.05 or < 0.01. Pathological injury significantly relieved in AKT‐AFMSC group than those of group A and group B .Conclusion:Compared with amniotic fluid mesenchymal stem cells ,AKT‐transfected amniotic fluid mesenchymal stem cells possesses better effects of repairing injured myocardium and improving myocardial function in ischemic reperfusion injured myocardium .

Purpose Protein is the main influencing factors for diffusion weighted imaging (DWI) signals and apparent diffusion coefficient (ADC), it results in hyperintensity on DWI and low ADC, but not fully matched in clinic. This paper aims to investigate the effect of protein type and concentration on the signal intensity (SI) and ADC of DWI. Materials and Methods Different concentrations of albumin, globulin solution and the mixed solution were created in vitro. DWI was performed on GE 1.5T superconducting nuclear MRI system. Results ① There was a linear negative correlation between the ADC value and the concentrations of protein solution (at 37℃, ra= - 0.849, Pa<0.05; rg= - 0.843, Pg<0.05; at 40℃, ra= - 0.894, Pa<0.05; rg= - 0.819, Pg<0.05);there was a linear positive correlation between the SI of DWI and the concentrations of the albumin solution (at 37℃, r=0.753, P<0.05; at 40℃, r=0.845, P<0.05). There was no correlation between the SI of DWI and the concentrations of the globulin solution (at 37℃, r= - 0.222, P>0.05; at 40℃ , r= - 0.270, P>0.05). ② SI of the albumin solution was significantly higher than the globulin solution at the same concentration and temperature (t=3.96, P<0.001); the ADC values were not statistically different between the albumin and the globulin solution (t=0.61, P>0.05). Conclusion The nature of the cystic fluid can be understood preliminarily through quantitative analysis of the cystic fluid DWI and ADC values, so as to provide theoretical basis for the qualitative diagnosis of cystic lesions in vivo.