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

This study investigated the correlation between and compared the effects of reactive oxygen species (ROS) and p38 mitogen-activated protein kinase α (p38MAPKα) in the ex vivo expanded umbilical cord blood (hUCB) CD133(+) cells. hUCB CD133(+) cells were cultured in the hematopoietic stem cells (HSCs) culture medium with N-acetylcysteine (NAC, an anti-oxidant), p38MAPKα-specific inhibitor (SB203580) or their combination. The levels of ROS and expression of phosphorylated p38MAPKα (p-p38) in CD133(+) cells were flow cytometrically detected. The efficacy of ex vivo expansion was evaluated by the density of CD133(+) cell sub-group colony-forming cells (CFC) and cobblestone area-forming cells (CAFC) assay. Our results showed decreased ROS levels in NAC, SB203580, and their combination treatment groups were almost 37%, 48%, and 85%, respectively. Furthermore, SB203580 abrogated the activation of p38MAPKα more obviously than NAC. Moreover, the CD133(+) cells in SB203580 treatment group had a 21.93±1.36-fold increase, and 14.50±1.19-fold increase in NAC treatment group, but only 10.13±0.57-fold increase in control group. In addition, SB203580 treatment led a higher level increase in the number of CFU and CAFC than NAC did. These findings suggested that, in expanded CD133(+) cells, ROS activates p38MAPKα, which, in turn, induces ROS production, and p38MAPKα might be the most suitable regulator in ROS-p38MAPKα pathway for the promotion of HSCs ex vivo expansion.

OBJECTIVETo investigate the serum levels of estradiol (E2) and progesterone (P) in patients with the auras of threatened abortion (ATA), i.e., fetal irritability and vaginal bleeding, and the relation with prognosis.

METHODSChinese medicine syndrome of 598 pregnant women with ATA consulted in authors' hospital were differentiated into 5 types, 151 patients of Shen-deficiency type; 151 of Pi-Shen deficiency type; 36 of qi-blood insufficiency type, 235 of blood-heat type, and 25 of traumatic injured type. Their serum levels of E2 and P at the 5th to 13th gestation week were monitored by competitive chemiluminescnet enzyme immunoassay. And the outcome of pregnancy, continued or defeated, was observed.

RESULTS(1) From the 7th gestation week on, serum E2 level in women with continued pregnancy (CP) increased continuously, showed a higher value than that at the previous week (P < 0.05), and was higher than that in women with defeated pregnancy (DP) of same gestation age (P < 0.05). (2) Serum P level was not different in CP women at various gestation age (P > 0.05), but from the 7th week on, it was higher in CP women than in DP women of same gestation age (P < 0.05). (3) The comparison of serum E2 in CP versus DP of women with Shen-deficiency type or Pi-Shen deficiency type was identical to that in CP versus DP of all women enrolled.

CONCLUSIONSSerum levels of E2 and P in women with ATA at 5th to 13th gestation weeks were obtained. The 7th week of pregnancy is the critical period of pregnancy development, a comparative high E2 levels and its sustained and steady elevation indicates the good-ending of pregnancy with fetal irritability and vaginal bleeding. The Chinese medicine syndrome presented in women with ATA is dominantly the Shen-deficiency type. The variation of serum E2 is one of the important material foundation in pregnancy with fetal irritability and vaginal bleeding of Shen-deficiency type.

Abortion, Threatened ; blood ; Diagnosis, Differential ; Estradiol ; blood ; Female ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Pregnancy ; Pregnancy Trimester, First ; Progesterone ; blood ; Uterine Hemorrhage

Objective To investigate the permeability of brain microvascular endothelial cells under the condition of high glucose exposure. Methods The bEnd.3 cell line was chosen to detect the value of trans- endothelial electrical resistance (TEER), the activity of alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT).Hence, the characteristics of blood-brain barrier in cell model were identified.The permeability of brain microvascular endothelial cells on high glucose exposure was evaluated by cell morphology, cell viability, intracellular lactate dehydrogenase activity and relative expression of ZO-1 and Occludin genes. Results The value of TEER, the activity of ALP and γ-GT increased gradually with increasing incubation time.The observation of cell morphology showed that the number of cells decreased significantly under high glucose exposure, and the adherence was unstable.Cell viability decreased with higher concentration of glucose or longer exposure time under high glucose exposure.The activity of lactate dehydrogenase was also decreased, and there were significant differences among the dose groups (P < 0.05).In addition, the expression levels of tight junction protein ZO-1 and Occludin were further detected.It was found that high glucose exposure inhibited the expression of ZO-1 and Occludin genes in a dose-dependent manner. Conclusion The bEnd.3 cell line has the characteristics of blood-brain barrier.High glucose exposure inhibited the expression of tight junction protein ZO-1 and Occludin. The results might be related to the change of the permeability in brain microvascular endothelial cells

Objective To assess the changes on the whole night polysomnography (PSG) in patients with chronic fatigue syndrome(CFS). Methods The whole night PSGs were recorded from 24 patients with CFS and 33 normal subjects. Results Compared with normal subjects, patients with CFS showed significantly reduced total sleep duration ([488.7?21.7]min vs [515.9?31.7]min, P

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 evaluate the results of manipulative reduction and percutaneous pin fixation for the treatment of severely displaced proximal humeru fracturess in children.

METHODSFrom January 2006 to December 2010, 43 patients with severely displaced proximal humeru fractures were treated with manipulative reduction and percutaneous pin fixation. There were 28 boys and 15 girls,ranging in age from 3 to 17 years,with an average of 11.1 years. Preoperative diagnoses were confirmed by the X-ray films as Neer-Horwitz type III or IV fractures. All the patients were close fractures without nerve or vascular injuries. Under C-arm X-ray machine, anatomical reduction was achieved by manipulative reduction according to the bone fracture type. The fractures were fixed by percutaneous pinning. Postoperative X-ray confirmed anatomical reduction. Follow-up index were recorded: intra-operative and postoperative complications, postoperative radiographic examination, upper extremity length and range of shoulder motion. Neer score system was used to evaluate shoulder function.

RESULTSAll the patients were followed up, and the duration ranged from 3 to 37 months with an average of 20.4 months. The mean Neer score of the injured side was (95.0 +/- 4.3) (ranged, 85 to 100). Thirty-eight patients got an excellent result, 5 good. The X-ray showed all the fractures healed without shortening deformity or epiphyseal arrest at early stage. All the patients could participate in the normal physical activities and had a normal range of motion and excellent strength of the shoulder joint.

CONCLUSIONThe method of manipulative reduction and percutaneous pin fixation is relatively reliable treatment for severely displaced proximal humerus fractures in children.

Adolescent ; Child ; Child, Preschool ; Female ; Fracture Fixation, Internal ; instrumentation ; methods ; Humans ; Humeral Fractures ; surgery ; Internal Fixators ; Male ; Treatment Outcome

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

OBJECTIVETo examine the correlation between p65 expression and the metastasis and prognosis in tongue carcinoma.

METHODSThe immunohistochemical expression of p65 was examined in 50 cases of tongue carcinoma, and the clinical and histopathologic records were retrospectively analyzed.

RESULTSOverexpression of p65 in cytoplasma and nucleus was found in 64% cases of tongue carcinoma. There was significant difference of p65 expression among different TNM stages, and the higher expression rate of p65 was found in higher stages. Overexpression of p65 was also related to lymph node metastasis. Significantly greater increase in expression levels of p65 was found in the metastatic cases (n = 22) compared to the nonmetastatic cases (n = 10). However, there was no significant difference of p65 expression among different histopathologic grading. The 5-year survival rate of p65 positive and negative group was 59.3% and 88.9% respectively, and there was significant difference in Kaplan-Meier survival curve (chi2 = 5.6, P < 0.05).

CONCLUSIONThe results suggest that the expression of p65 was important to predict the metastasis and prognosis in tongue carcinoma.

Adult ; Aged ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Tongue Neoplasms ; Transcription Factor RelA