BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

AIM: To establish individualized drug therapy strategy for patients with rejection and hyperglycemia after liver transplantation. METHODS: Clinical pharmacist collaborated with the surgeons and participated in the diagnosis and treatment of rejection and hyperglycemia after liver transplantation. Taking together liver function, therapeutic drug monitoring, drug-drug interactions between tacrolimus and wuzhi capsule, individualized drug therapy was adapted to improve the prognosis. RESULTS: The patient recovered well and survived in good health till now. CONCLUSION: It is highly suggested that clinical pharmacists actively involved in treatment of more severe and difficult-to-treat disease and design the individualized dosing regimens. This will largely contribute in reduced adverse drug reaction, improved safety and effectiveness in drug use as well as the quality of life in the "post-transplantation era".

ObjectiveTo investigate the protective effect of tanshinone I (T-I) on hepatic ischemia-reperfusion injury (HIRI) in mice. MethodsA total of 36 C57BL/6J mice were randomly divided into sham-operation group, ischemia-reperfusion (IR) group, IR+T-I (5 mg/kg) group, IR+T-I (10 mg/kg) group, IR+T-I (20 mg/kg) group, and IR+T-I (40 mg/kg) group, with 6 mice in each group. Each group was given intraperitoneal injection. The mice in the sham-operation group and the IR group were injected with an equal volume of the solvent olive oil; the mice in the IR+T-I groups were administered once a day for 7 consecutive days, a model of 70% HIRI was established at 2 hours after the last administration, and serum and liver samples were collected after 6 hours of reperfusion. Related kits were used to measure the serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the content of superoxide dismutase (SOD), malondialdehyde (MDA), caspase-3, and reduced glutathione (GSH) in liver tissue; HE staining was used to observe liver histopathology; the TUNEL method was used to measure the level of hepatocyte apoptosis; immunohistochemistry was used to measure the protein expression of caspase-3 and heme oxygenase-1 (HO-1). 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. ResultsCompared with the IR group, the IR+T-I (20mg/kg) group had significant reductions in the serum levels of ALT (192.48±23.67 U/L vs 336.90±41.52 U/L, P＜0.01) and AST (123.19±9.16 U/L vs 206.90±18.81 U/L, P＜0.01), and thus 20 mg/kg was determined as the optimal concentration. Compared with the IR group, the IR+T-I (20 mg/kg) group had significant reductions in MDA (1.34±0.21 μmol/mg vs 3.48±0.95 μmol/mg, P＜0.05) and caspase-3 (0.69±0.97 μmol/mg vs 1.04±0.35 μmol/mg, P＜0.05) and significant increases in SOD (274.47±30.53 U/mg vs 160.29±27.37 U/mg, P＜0.05) and GSH (2.12±0.27 μmol/mg vs 1.03±0.42 μmol/mg, P＜0.05). HE staining showed that the IR group had disordered structure of hepatic lobules and focal or extensive degeneration and necrosis of hepatocytes; compared with the IR group, the IR+T-I (20 mg/kg) group had a reduction in the area of hepatocyte necrosis and a basically complete structure of the liver. Immunohistochemistry showed that compared with the IR group, the IR+T-I (20 mg/kg) group had significant reductions in the number of apoptotic hepatocytes and the protein expression of caspase-3 and a significant increase in the protein expression of HO-1. ConclusionT-I exerts a protective effect against HIRI in mice by inhibiting liver oxidative stress response and hepatocyte apoptosis.

Mitochondrial dysfunction is closely related to the occurrence and development of benign and malignant diseases of the pancreas. Mitochondrial membrane of the respiratory chain electron transfer and energy transfer plays an important role in maintaining normal cellular function. When the respiratory chain was disrupted, the oxidative stress was increased in the cell, and produced a large number of oxide intermediate products which target mitochondrial protein, DNA, etc, lead to mitochondrial dysfunction finally induced acute pancreatitis, pancreatic cancer and other diseases. In addition, mitochondrial homeostasis plays an indispensable role in maintaining the normal function of islet cells. This paper reviewed the research status of mitochondrial dysfunction in pancreatic diseases.

Non-alcoholic steatohepatitis (NASH) is an important link for the progression of metabolic-related fatty liver disease to end-stage liver disease such as cirrhosis and hepatocellular carcinoma, which seriously endangers human health. NASH pathogenesis is complex, and involves the interaction between hepatic parenchymal and non-parenchymal cells (NPCs), sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and so on. Herein, the relevant research progress of NPCs in the pathogenesis of NASH is reviewed in order to further understand the role of NPCs in NASH.

In the recent years, the damage of the spleen has been increased due to trauma or neoplastic diseases. Traditional view holds the point that the damaged spleen should be completely removed, but with the development of spleen surgery, the important physiological function of the spleen has been widely recognized, and partial splenectomy has been well recognized by the surgeons. This paper summarized the clinical experience in partial splenectomy and raised some technical points.

OBJECTIVETo compare the efficacy difference between's flying acupuncture combined with conventional treatment and conventional treatment alone on acute cerebral infarction hemiplegia.

METHODSA total of 120 patients were randomly divided into an observation group and a control group, 60 cases in each one. The control group was treated with conventional treatment, including anti-platelet aggregation, lipid-lowering, formula of traditional Chinese medicine which could promote circulation and remove stasis, neurotrophic medication and symptomatic treatment; mannitol was used for cerebral infarction with large area or increased intracranial pressure. Based on the conventional treatment applied in the control group, the observation group was treated with flying acupuncture at the affected Jianyu (LI 15), Quchi (LI 11), Shousanli (LI 10), Waiguan (TE 5), Hegu (LI 4), Huantiao (GB 30), Biguan (ST 31), Futu (ST 32), Zusanli (ST 36), etc. The treatment was given once a day, six days per week, for totally 2 weeks. The simplified Fugl-Meyer score, National Institute of Health Stroke Scale (NIHSS) and ADL-Bathel index (BI) score were evaluated before and after treatment in the two groups.

RESULTSAfter the treatment, the simplified Fugl-Meyer and BI were significantly increased in both groups (all<0.05), which was significantly higher in the observation group (both<0.05); after the treatment, the NIHSS was significantly lowered in both groups (both<0.05), which was significantly lower in the observation group (<0.05).

CONCLUSION 's flying acupuncture combined with conventional treatment were effective for acute cerebral infarction hemiplegia, which have better efficacy than conventional treatment on improving motor function, neurological deficit and daily living ability, and the pain is mild.

Objective To investigate the consensus and controversies on the delineation of radiotherapy target volume for patients with locally advanced non-small cell lung cancer (LA-NSCLC).Methods Questionnaires including 15 questions on the delineation of radiotherapy target volume of NSCLC were sent to 12 radiation departments in China in November 2015.A patient with LA-NSCLC was selected by Fudan University Shanghai Cancer Center, and simulation CT images and medical history data were sent to the 12 radiation departments.Twelve radiation oncologists from the 12 radiation departments showed and explained the delineation of radiotherapy target volume of their own, and the patient was discussed by all experts in the sixth multidisciplinary summit forum of precise radiotherapy and chemotherapy for tumor and lung cancer.Results All receivers of the questionnaire answered the questions.The standard lung window width/level for the delineation of lung cancer was 800-1600/-600 to-750 HU, and the mediastinum window was 350-400/20-40 HU.Respiratory movement was measured by stimulator, 4D-CT, and stimulator+4D-CT with 2-5 mm expansion based on experience.The primary clinical target volume (CTV) was defined as gross target volume (GTV) plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma.The metastatic lesion of mediastinal lymph nodes was delineated as 5 mm plus primary lesion in 6 departments and as primary lesion in another 6 departments.Of the 12 departments, 10 applied 5 mm of set-up error, 1 applied 3 mm, and 1 applied 4-6 mm.For V20 of the lungs, 10 departments defined it as<30%, 1 as<35%, and 1 as 28%.Nine departments defined the radiation dose of concurrent chemoradiotherapy (CCRT) for LA-NSCLC as 60 Gy in 30 fractions, 62.7 Gy in 33 fractions in 1 department, 50-60 Gy in 25-30 fractions in 1 department, and 60-70 Gy in 25-30 fractions in 1 department.For the delineation of target volume for the LA-NSCLC patient treated with CCRT, the primary planning target volume (PTV) was defined as GTV plus organ movement (IGTV) and set-up error (GTV→IGTV→PTV) in 3 departments, as CTV plus organ movement (ITV) and set-up error (GTV→CTV→ITV→PTV) in 8 departments, and as CTV plus set-up error/IGTV plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma (CTV) and set-up error (GTV→CTV→PTV/GTV→IGTV→CTV→PTV) in 1 department.For the delineation of PTV in the mediastinal lymph node, GTV→IGTV→PTV was performed in 3 departments, GTV→CTV→ITV→PTV in 8 departments, and GTV→CTV→PTV in 1 department.For 10%-100% patients with LA-NSCLC, the radiation field needed to be replanned when 38-50 Gy was completed.There was no unified standard for the optimal standardized uptake value (SUV) of positron emission tomography (PET)-computed tomography (CT) simulation and delineation.Seven departments had applied magnetic resonance imaging (MRI) simulation and 10 departments had applied stereotactic body radiation therapy (SBRT) for the treatment of early-stage NSCLC.For the delineation of PTV for early-stage NSCLC (T1-2N0M0), GTV→IGTV→PTV was performed in 5 departments, IGTV→PTV in 3 departments, and GTV→CTV→ITV→PTV in 2 departments.In all the 12 departments, peripheral early-stage NSCLC was given 6.0-12.5 Gy/fraction, 3-12 fractions and central early-stage NSCLC was given 4.6-10.0 Gy/fraction, 5-10 fractions.The results of discussion on the delineation of target volume for the patient were as follows:respiratory movements should be measured by 4D-CT or simulator;the lung window width/level is 1600/-600 HU and the mediastinal window width/level is 400/20 HU;the primary controversy is whether the involved-field irradiation or elective nodal irradiation should be used for the delineation of CTVnd in the mediastinal lymph node.Conclusions Basic consensus is reached for the delineation of target volume in LANSCLC in these aspects:lung window width/level, respiratory movements and set-up error, primary lesion delineation, the radiation dose in CCRT, and the optimal time for replanning the radiation field.There are controversies on the optimal SUV in the delineation of target volume based on PET-CT simulation, the optimal dose fractionation in SBRT for early-stage NSCLC, and the delineation of CTVnd.

Objective To compare methimazole and propylthiouracil affecting liver function by treating hyperthyroidism.Methods Total 80 patients with hyperthyroidism were randomly divided into two groups.Group A (41 cases) was given methimazole,group B (39 cases) was given propylthiouracil.The effect of methimazole and propylthiouracil affecting liver function by treating hyperthyroidism was evaluated by the indexes of thyroid function,liver function,liver damage,and adverse reaction during treatment.Results Before treatment,there were no statistical significance on FT3 and FT4 between two groups.After treatment,the FT3and FT4 were decreased and TSH was increased in two groups (P ＜ 0.05).But there were no statistical significance between two groups.Before treatment,there was no statistical significance on ALT,AST,and GGT between two groups.After treatment,the ALT,AST,and GGT increased in group B and higher than that of group A (P ＜ 0.05).The ALT,AST,and GGT had no change before and after treatment in the group A.During treatment,there were five cases of liver injury in group A and 14 cases in group B.The liver injury rate of group B was higher than that of group A (P ＜ 0.05) and injury time of group B was later than that of group A.During treatment,there was no statistical significance on adverse reaction rate between two groups.Conclusion The efficacy of methimazole was equal to propylthiouracil in treating hyperthyroidism.Compared with propylthiouracil,the methimazole had less injury on liver but induce the liver injury in earlier.It is suggested that the patients should check the liver function regularly during treatment.

Objective To investigate the association between Has‐miRNA‐149 polymorphism and susceptibility of digestive tract cancer .Methods A systematic search of Pubmed ,EMBASE and Web of Science ,CNKI ,Wanfang was conducted for relevant studies .The odds ratios(OR) and 95% confidence intervals(95% CI) calculated by Stata12 .0 software were used to assess the asso‐ciation between Has‐miRNA‐149 polymorphism and risk of digestive tract cancer .The Q test ,I2 value and funnel plot were conduc‐ted to examine heterogeneity and publication bias ,respectively .Results A total of thirteen eligible studies containing 4 424 cases and 5 290 controls were included in this Meta analysis .There were significant relationships between Hsa‐miRNA‐149 polymorphism and susceptibility of digestive tract cancer (Domina model CT+CC vs .TT ,OR=0 .915 ,95% CI:0 .840-0 .996 ,P=0 .040 ;Hetero‐zygous model CT vs .TT ,OR=0 .880 ,95% CI:0 .803 -0 .965 ,P=0 .007) .In the stratified analysis ,it was found that the risk of colorectal cancer decreased in patients carrying CC/CT genotypes(OR=0 .834 ,95% CI:0 .715-0 .972 ,P=0 .021) ,especially in A‐sians (CT+CC vs .TT ,OR=0 .894 ,95% CI:0 .818-0 .977 ,P=0 .013) ,while that was not found in the Caucasoids .Conclusion Has‐miRNA‐149 polymorphism is associated with the susceptibility of digestive tract cancer .The CC/CT genotypes may decrease the risk of digestive tract cancer ,especially in Asians .