Autophagy is a crucial biological process in eukaryotes, which is involved in cell growth, survival and energy metabolism. It has been confirmed that autophagy mediates toxicity of anticancer drugs, especially in heart, liver and neuron. It is important to understand the function and mechanism of autophagy in anticancer drugs-induced toxicity. Given that autophagy is a double-edged sword in the maintenance of the function of heart, liver and neuron, the autophagy-mediated toxicity are very complicated in the body. We provide a review on the concept of autophagy and current status about autophagy-mediated toxicity of anticancer drugs. The knowledge is crucial in the basic study of anticancer drugs-induced toxicity, and provides some strategies for the development of alleviating the toxicity of anticancer drugs.
Antineoplastic Agents ; pharmacology ; toxicity ; Autophagy ; Humans ; Neoplasms ; drug therapy

OBJECTIVETo examine the effect and mechanism of artesunate (Art) on embryo development.

METHODSRat embryo and placental glutathione peroxidase (GSH-Px)and malondialdehyde (MDA) were identified by using DTNB (dithionitrobenzene) direct method and TBA (thiobarbituric acid). We investigated the damage of decidual cells caused by Art using cell culture techniques.

RESULTSSubcutaneous administration of Art in rats on d 6 approximate, equals d 10 of gestation induced developmental toxicity. Absorption increased when progressively increased doses were given (r=0.996,P<0.01). Twenty four hours post injection, GSH-Px in embryo decreased significantly while MDA content was significantly higher than that in the control group (P<0.05). GSH Px: study group was(43.7+/-10.7)micromol/min.mg(-1)Hb, control group was(54.5+/-10.1)micromol/min.mg(-1)Hb; MDA:study group was(230.2+/-19.8)nmol/g tissue, control group was(150.4+/-44.1)nmol/g tissue. Placental GSH-Px activity was significantly higher than that in the control group(P<0.01). After cultured human decidual cells were exposed to Art for 24 h, the LC50 was (25.2+/-3.5)mg/L.

CONCLUSIONArt may induce developmental toxicity in rat embryo and placenta by neutralizing the antioxidant defense mechanism.

Animals ; Antimalarials ; toxicity ; Artemisinins ; toxicity ; Embryo, Mammalian ; drug effects ; metabolism ; Female ; Glutathione Peroxidase ; metabolism ; Lipid Peroxidation ; drug effects ; Male ; Placenta ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sesquiterpenes ; toxicity

Aneurysm, Dissecting ; genetics ; Aortic Aneurysm ; genetics ; Diseases in Twins ; Humans ; Male ; Middle Aged

Objective To observe the sequence of fat deposit and its relationship with insulin resistance in SD rats fed by high fat diet.Methods Normal 8-week-old male SD rats were randomly divided into normal chow (NC,n=40)and high fat diet(HF,n=40)groups.Triglyceride(TG)in serum,liver and muscle were measured;glucose infusion rate(GIR)and the mRNA level of genes related to lipid metabolism in liver and muscle were determined in different stages.GIR was detected by eugiyeemic-hyperinsulinemic clamp for evaluating the insulin sensitivity.Gene expression was determined by real-time PCR.Results(1)As compared with NC group,serum TG was not increased after high fat feeding for4 and 8 weeks,it began to increase after 12 weeks [0.52(0.15-1.00) mmol/L vs O.31(0.09-0.53)retool/L, P0.05)in skeletal muscle.After 8 weeks,the expression of ACC1 in liver in HF group was increased by 20.6%,CPT-1 was decreased by 27.1%(P

OBJECTIVETo understand the genotype characteristics and its evolution of patients with poor response to initial combined treatment of Lamivudine and Adefovir dipivoxil for chronic hepatitis B.

METHODSWe detected the HBV genotypes of three patients-S1, S2, S3, who with poor response to initial treatment of Lamivudine and Adefovir dipivoxil for chronic hepatitis B over 12 months by the application of cloning and sequencing method at the time point of baseline,4 weeks after treatment, 12 weeks, 24 weeks, 48 weeks, 60 weeks. 25 clones were randomly selected to identify and sequence at each time point.

RESULTSThe total number of clones from 3 patients with poor response to initial combined treatment of Lamivudine and Adefovir dipivoxil for chronic hepatitis B at each time point was 398. About patient S1 at baseline, genotype C accounting for 8.3%, genotype B, for 91.7%, so genotype B was in dominant (22/24). But genotype C has gradually developed to 100% after treatment for 60 weeks. About patient S2 and S3, genotype B was the only type at baseline. However type B has gradually "drift" to type C during treatment. When treatment for 60 weeks, type C has taken the absolute advantage 75% for S2, and 100% for S3.

CONCLUSIONSThe cloning and sequencing can represent the overall genotype level better. HBV genotype has performed the evolution trend that genotype has drifted from B to C during long-term drug pressure, which is the main reason for poor response to initial combined treatment of Lamivudine and Adefovir dipivoxil for chronic hepatitis B.

Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Drug Resistance, Viral ; Evolution, Molecular ; Female ; Genetic Drift ; Genotype ; Hepatitis B virus ; drug effects ; genetics ; isolation & purification ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Lamivudine ; therapeutic use ; Male ; Middle Aged ; Organophosphonates ; therapeutic use

OBJECTIVE: To describe the CT and MRI features of hepatic sinusoidal obstruction syndrome (HSOS) caused by herbal medicine Gynura segetum. MATERIALS AND METHODS: The CT and MRI features of 16 consecutive Gynura segetum induced HSOS cases (12 men, 4 women) were analyzed. Eight patients had CT; three patients had MRI, and the remaining five patients had both CT and MRI examinations. Based on their clinical presentations and outcomes, the patients were classified into three categories: mild, moderate, and severe. The severity of the disease was also evaluated radiologically based on the abnormal hepatic patchy enhancement in post-contrast CT or MRI images. RESULTS: Ascites, patchy liver enhancement, and main right hepatic vein narrowing or occlusion were present in all 16 cases. Hepatomegaly and gallbladder wall thickening were present in 14 cases (87.5%, 14/16). Periportal high intensity on T2-weighted images was present in 6 cases (75%, 6/8). Normal liver parenchymal enhancement surrounding the main hepatic vein forming a clover-like sign was observed in 4 cases (25%, 4/16). The extent of patchy liver enhancement was statistically associated with clinical severity classification (kappa = 0.565). CONCLUSION: Ascites, patchy liver enhancement, and the main hepatic veins narrowing were the most frequent signs of herbal medicine induced HSOS. The grade of abnormal patchy liver enhancement was associated with the clinical severity.
Adult ; Aged ; Ascites/diagnosis ; Asteraceae/chemistry ; Cholecystography ; Female ; Gallbladder/pathology ; Hepatic Veins/pathology/radiography ; Hepatic Veno-Occlusive Disease/chemically induced/*diagnosis ; Hepatomegaly/diagnosis ; Humans ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Phytotherapy/*adverse effects ; Pyrrolizidine Alkaloids/adverse effects ; Severity of Illness Index ; *Tomography, X-Ray Computed ; Young Adult

OBJECTIVETo examine the relationship between NF-kappaB signal transduction way and the sensitivity of Tca8113 carcinoma cell to Pingyangmycin chemotherapy.

METHODS2 mg/L antisense p65 oligodeoxynucle-otides (5'-GAACAGTTCGTCCATGGCCG-3') was transfected into Tca8113 cells through Lepofectin vectin, then the cells were treated with 8 mg/L Pingyangmycin. After 3 h and 6 h, the expression of p65 in nucleus was studied with immunohistochemical methods and Western blot analyses. After 48 h, the inhibitory rate of cell growth was detected with MTT assay.

RESULTSThe NF-kappaB/p65 signal transduction way in Tca8113 cells was activated after treated with Pingyangmycin. But the transfection of antisense p65 oligodeoxynucle-otides inhibited the activation of the signal transduction, the p65 expression in nucleus was decreased significantly (P < 0.05) at 6 h, and the inhibitory rate of cell growth was increased significantly (P < 0.05) at 48 h.

CONCLUSIONThe results suggested the chemotherapeutic sensitivity of Tca8113 carcinoma cell to Pingyangmycin was improved by the inhibition of NF-kappaB/p65 signal transduction.

Bleomycin ; analogs & derivatives ; Cell Line, Tumor ; Cell Proliferation ; Humans ; NF-kappa B ; Signal Transduction ; Tongue Neoplasms ; Transcription Factor RelA ; Transfection

OBJECTIVETo evaluate and compare the outcome of two kinds of diameter hollow screws for the treatment of femoral neck fractures.

METHODSFrom June 2008 to June 2013, 117 patients with femoral neck fractures were treated by closed reduction and hollow screws fixation. Among them,48 patients were fixed by 6.5 mm screw including 30 males and 18 females with an average age of (45.61 ± 11.99) years old ranging from 19 to 60 years old, involving 17 cases in Garden I/II and 31 cases in Garden III/IV; 69 patients were fixed by 8.0 mm screw including 40 males and 29 females with an average age of (45.17 ± 9.95) years old ranging from 18 to 60 years old, involving 31 cases in Garden I/II and 38 cases in Garden III/IV. The general information, operative time, hospital stay time, reduction quality, diameter of femoral head and neck, fracture healing time, the rate of fracture healing, postoperative complications were recorded and evaluated. Harris scoring was used to evaluate the hip joint function.

RESULTSAll patients were followed up for 19.6 months (18 to 24 months). The difference of operative time, duration of hospitalization, quality of reduction were not statistically significant (P > 0.05). There was no difference between two groups about the average diameter of the femoral head and neck, the fracture healing time, the rate of healing and the postoperative complications (P > 0.05). There were no difference between two groups about Harris scale. There were significant difference between Garden III/IV and I /II (P > 0.05).

CONCLUSIONClosed reduction and internal fixation with hollow screw in treating the young adult patients with femoral neck fracture is the first choice, both different diameters hollow screws could meet the requirements of fixation of femoral neck fracture, and not affect on fracture healing time and postoperative complications.

Adult ; Bone Screws ; Female ; Femoral Neck Fractures ; surgery ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Middle Aged

OBJECTIVEThe purpose of this study is to investigate whether low-dose spiral chest CT scan can replace standard-dose CT scan in detecting pulmonary metastases for patients with gestational trophoblastic tumor (GTT).

METHODSTotally, 34 GTT patients underwent 56 chest CT scans for the assessment of pulmonary metastasis. All patients received CT examination both at standard-dose (120 KV, 150 mAs, pitch 1, and a standard reconstruction algorithm) and low-dose CT (120 KV, 40 mAs, pitch 2, and a bone reconstruction algorithm) simultaneously each time. The images were interpreted by two radiologists independently. A metastasis by CT image was defined as a nodule within lung parenchyma that could not be attributed to a pulmonary vessel. The number of lesions detected at each dose protocol was recorded. The size of each lesion was measured and categorized as < 5 mm, 5 - 10 mm or > or = 10 mm. The differences in detection of the lesions between the standard- and low-dose CT protocols were compared using Wilconxon signed rank test.

RESULTS1417 lesions were detected at the standard-dose, whereas 1214 lesions were found by low-dose CT. Lesions < 5 mm detected by low-dose CT were fewer than that detected by standard-dose CT (Z = -3.368, P = 0.000), though there was no statistically significant difference between the standard- and low-dose CT in detecting lesion > or = 5 mm (Z = -0.055, P = 0.957). Moreover, the risk score of the patients was not affected either. The sensitivity of low-dose CT was 69.16% for all size of lesions, 58.50% for < 5 mm, 87.07% for 5 - 10 mm, and 97.01% for > or = 10 mm. The positive predictive value for different sizes of lesion was 80.71% (all sizes), 73.82% (5 mm), 88.86% (5 - 10 mm), and 98.48% (> or = 10 mm), respectively.

CONCLUSIONLow-dose chest CT can replace the standard-dose chest CT as a screening and follow-up examination to assess the change in pulmonary metastasis for patients with gestational trophoblastic tumor.

Adult ; Female ; Gestational Trophoblastic Disease ; diagnostic imaging ; secondary ; Humans ; Lung Neoplasms ; diagnostic imaging ; secondary ; Middle Aged ; Pregnancy ; Radiation Dosage ; Tomography, Spiral Computed ; methods ; Uterine Neoplasms ; pathology

OBJECTIVETo investigate the effect of extract of ginkgo biloba leaf (EGb) during the formation of HBV-related hepatocellular carcinoma (HCC).

METHODS99 HBV transgenic mice were randomly divided into control group, high-dose group, low-dose group. High-dose group and low-dose group were intraperitoneal injected 35mg/(kg x d) and 17.5 mg/(kg x d) of the shuxuening injection. Control group without special treatment. The serological markers and immunohistochemical markers in liver tissue will be done at the first 12 months and 18 months.

RESULTS(1) HBV transgenic mice can be found HCC at the 18 months. The incidence of HCC was lower in high-dose group and low-dose group, there was statistically different among the three groups. (2) The semi-quantitative scoring of liver HBx expression was highest in the control group at the 12 months. The semi-quantitative scoring of liver HBx, p53 and Bcl-2 expression was highest in the control group at the 18 months. They all appeared statistically different among the three groups. (3) Spearman correlation analysis showed that HCC incidence and liver tissue HBx, p53, Bcl-2 expression was a certain degree of positive correlation, r was 0.536, 0.487 and 0.403, P < 0.05.

CONCLUSIONEGb can reduced the incidence of the HCC with HBV transgenic mice. The reason may be that the EGb can reduce liver HBx, p53, Bcl-2 protein expression in the HBV transgenic mice.

Animals ; Carcinoma, Hepatocellular ; drug therapy ; etiology ; genetics ; prevention & control ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Gene Expression Regulation, Neoplastic ; drug effects ; Ginkgo biloba ; chemistry ; Hepatitis B ; complications ; drug therapy ; Humans ; Liver Neoplasms ; drug therapy ; etiology ; genetics ; prevention & control ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic