Objective To investigate the expression of caspase-3 in colon carcinoma,colon adenoma and normal colon mucosa and its clinical significance.Methods The expression of caspase-3 was detected with immunohistochemical EnVision in 60 cases of colon carcinoma,30 cases of colon adenoma and 30 cases of normal colon mucosa.Results The positive expression rates of caspase-3 in colon carcinoma,colon adenoma and normal colorn mucosa were 18.3％(11/60),50.0％(15/30),86.7％(26/30).There was significant difference among three groups(P＜0.01).The expression of caspase-3 was closely related to Dukes clinical stage,differentiation degree,lymph node metastasis and the degree of infiltration(P＜0.01).Conclusion The low expression of caspase-3 may play an important role in the carcinogenesis of colon carcinoma and it is involved in the metastasis and infiltration.

Hepatitis B virus ; Hepatitis B, Chronic ; immunology ; virology ; Humans ; T-Lymphocytes ; immunology

Objective To investigate the effect of long-term antiviral treatment on clinical outcome and liver histology in patients with hepatitis B virus ( HBV)-related compensated cirrhosis .Methods A total of 61 patients with HBV-related compensated cirrhosis receiving antiviral therapy were enrolled from Taizhou Hospital of Zhejiang Province during September 2010 and March 2015, including 26 HBeAg-positive cases and 35 HBeAg-negative cases .Thirty-nine patients were treated with entecavir ( ETV ) and 22 were treated with adefovir dipivoxil ( ADV ) .Biochemical , serological and virological markers were examined every 3 months during treatment, and Child-Turcotte-Pugh (CTP) scores were calculated.All the patients underwent liver biopsy before and 144 weeks after antiviral treatment .Metavir scoring system was used to evaluate the liver histological activity ( A) and fibrosis score ( F) .Wilcoxon rank sum test and paired t-test were used for the evaluation of liver histopathology and liver function before and after treatment , respectively.Results After 144 weeks of antiviral treatment , HBV DNA was reduced and below the lower limit of detection in 58 patients (95.1%), HBeAg disappeared in 14 patients (14/26, 53.8%), and HBeAg seroconversion was observed in 10 patients (10/26, 38.5%); alanine aminotransferase ( ALT), aspartate amino transaminase (AST), total bilirubin (TBil) and CTP score decreased (t=7.489, 8.259, 14.000 and 6.026, all P<0.01), prothrombin time (PT) was shortened (t=9.777, P<0.01), and serum albumin (Alb) increased (t=3.446, P<0.01).Improvements in both liver histologic activity and fibrosis score were observed (Z=5.716 and 6.657, all P<0.01).Liver histological activity decreased from A1 to A0 in 16 cases, from A2 to A0 in 9 cases, from A2 to A1 in 15 cases, from A3 to A0 in 1 case, from A3 to A1 in 5 cases, and from A3 to A2 in 5 cases.Fibrosis score at the baseline was F 4 for all patients, while after treatment, there were 7 patients with F1, 22 with F2, 20 with F3, and F4 remained in rest 12 patients.Conclusion Both clinical and histological improvements can be obtained after long-term antiviral treatment for patients with HBV-related compensated cirrhosis .

In order to further investigate the mechanisms of action of berberine (Ber), we assessed the effects of Ber on the mRNA expression of nitric oxide synthases (NOS) in rat corpus cavernosum. After incubation with Ber for 1 or 3 h respectively, the levels of NOS mRNA were examined by reverse transcription polymerase chain reaction (RT-PCR). Our results showed that there were iNOS and eNOS mRNA expressions in rat corpus cavernosum. Ber enhanced eNOS mRNA expression in rat penis, but exhibited no effect on the expression of iNOS mRNA (P＞0.05). The present study indicated that the relaxation of Ber involved the NO-cGMP signal thansduction pathway. The enhancing effect of Ber on eNOS mRNA expression might associated with its relaxation of corpus cavernosum.

OBJECTIVE: To observe the therapeutic effect of electroacupuncture (EA) at five Back-Shu points on sleep, hippocampal peripheral benzodiazepine receptor (PBR) expression and hypothalamic 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β contents in insomnia rats, so as to explore its mechanisms underlying improvement of insomnia. METHODS: Forty male SD rats were randomly divided into control, model, EA and medication (Diazepam) groups (n=10 rats in each group). The insomnia model was established by intraperitoneal injection (i.p.) of para-Chlorophenylalanine (PCPA, 300 mg/kg) once daily for 2 days. EA (60 Hz, 1 mA) was applied to bilateral five Back-Shu points, i.e., Feishu (BL13), Xinshu (BL15), Ganshu (BL18), Pishu (BL20) and Shenshu (BL23) for 10 min, once daily for 6 days. Rats of the medication group were treated by gavage of Diazepam (0.92 mg/kg) once daily for 6 days. The sleep duration was recorded after i.p. of Pentobarbital Sodium (45 mg/kg). Histopathological changes of the hippocampus were displayed by H.E. staining. The contents of 5-HT, 5-HIAA, TNF-α and IL-1β in the hypothalamus were assessed by using ELISA. The expression levels of PBR mRNA and protein in the hippocampus were detected by quantitative real-time PCR, immunohistochemistry and Western blot, separately. RESULTS: Following modeling, the sleep duration was considerably shortened in rats of the model group relevant to the control group (P<0.05). After the treatment, the sleep duration was significantly increased in both EA and medication groups relevant to the model group (P<0.05). After modeling, the hippocampal neurons were obviously decreased in number, and disordered in the arrangement, the levels of hypothalamic 5-HT, 5-HIAA, TNF-α, and IL-1β were significantly down-regulated (P<0.05), and the expression of PBR mRNA and protein in hippocampus was obviously increased relevant to the control group (P<0.05). Following the treatment, the hippocampal neurons were increased in number and arranged regularly, and the contents of hypothalamic 5-HT, 5-HIAA, TNF-α, and IL-1β were considerably increased (P<0.05), and the expression of PBR mRNA and protein in hippocampus was significantly decreased in both EA and medication groups relevant to the model group (P<0.05). The therapeutic effect of EA was comparable to that of medication in increasing sleep duration, body weight, 5-HT and 5-HIAA contents (P>0.05), and significantly superior to that of the medication in increasing TNF-α and IL-1β levels (P<0.05), and considerably superior to that of medication in down-regulating PBR mRNA and protein expression (P<0.05). CONCLUSION: EA at five Back-Shu-points of the five Zang-organs can significantly improve the sleep in insomnia rats, which is closely associated with its effects in reducing the expression of PBR in hippocampus and up-regulating the levels of 5-HT, 5-HIAA, TNF-α and IL-1β in hypothalamus.

Prostate cancer (PCa) is the most common tumor in Europe and America. In recent years, the incidence rate of PCa has been increased in China. Castration-resistant prostate cancer (CRPC) is a serious difficulty in treatment of prostate cancer. The androgen receptor (AR) signal axis still plays an important role in the survival and progression of the tumor when PCa turns into CRPC. The new endocrine therapy is characterized by targeting AR signal axis, in which Abiraterone and Enzalutamide are the representatives. These two drugs can effectively inhibit the activity of AR signal axis, and prolong the survival of the patients. Although the new endocrine therapy drugs are safe and effective for CRPC, but the subsequent drug resistance can seriously affect the clinical efficacy. This paper reviews the progress on the mechanism of drug resistance of new endocrine therapy in recent years, in order to provide some references for solving the problem of drug resistance and guide the development of new drugs.

[摘 要] 正常细胞及肿瘤细胞在发生凋亡或受到某些信号刺激时均可释放出直径为0.1~1 μm的膜状囊泡。肿瘤细胞受到信号刺激后骨架改变，导致细胞质膜包裹细胞内容物并向膜外侧起泡形成囊状小体，称为肿瘤囊泡，其不仅影响肿瘤细胞的生物学特性，对肿瘤免疫微环境也产生深刻的影响。除生物学效应外肿瘤囊泡还可作为一种天然的药物载体将治疗药物递送到肿瘤细胞，发挥抗肿瘤作用。研究证实，载药的肿瘤囊泡在天然免疫和获得性免疫反应中均体现良好的抗肿瘤激活效应，目前载药肿瘤囊泡已经进入临床应用阶段，在胆管癌、恶性胸腔积液的治疗中展现了良好的应用前景。

To investigate the changes in neurological symptoms and signs, as well as serum copper, serum ceruloplasmin after hepatic transplantation in patients with Wilson's disease, neurological symptoms and signs, serum copper, serum ceruloplasmin before and after hepatic transplantation in 18 patients with Wilson's disease were observed, and those changes were followed up in 20 non-operative controls treated with penicillamine. Our results showed that the neurological symptoms and signs, serum copper and serum ceruloplasmin were improved in the operative group but deteriorated in the non-operative control group. Our study showed that hepatic transplantation is better than penicillamine in the treatment of Wilson's disease.
Adolescent ; Adult ; Ceruloplasmin ; metabolism ; Child ; Copper ; blood ; Female ; Follow-Up Studies ; Hepatolenticular Degeneration ; blood ; surgery ; Humans ; Liver Transplantation ; Male ; Treatment Outcome

The mutation of AT gene (ATM) leads to the AT disease (ataxia telangiectasis), the cancer incidence of AT patients and its carriers are significantly higher than the normal persons. And they are easy to have lymphoid tumors, including the lymphoma and leukemia et al. These indicate the ATM play a important role in the cancers pathogenesis mechanism. The ATM gene locate in the human chromosome 11q22-23, and the ATM is a kind of nuclear protein, its major functional domain is P13K (phosphatidylinositol 3-kinase), locates on the carboxy terminus. ATM protein plays a critical role in the signal transduction of cell cycle checkpoint, the repair of damaged DNA and the apoptosis. The mutation of the ATM gene leads to the functional and structural change of ATM protein in the AT patient, then leads to the abnormality of cell cycle checkpoint and the DNA damage repair, the apoptosis sensitivity increase. So the AT patients and their cells are radiosensitive, the characteristic of AT patient suggests the ATM gene is valuable in the cancer's gene therapy
Ataxia Telangiectasia ; complications ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins ; DNA-Binding Proteins ; Genetic Predisposition to Disease ; Humans ; Leukemia ; epidemiology ; etiology ; genetics ; Lymphoma ; epidemiology ; etiology ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Signal Transduction ; Tumor Suppressor Proteins

OBJECTIVETo explore the significance of combined therapy of arsenic trioxide (As2O3) and all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL).

METHODSRetrospective study of 80 APL patients was performed and the complete remission (CR), the recovery time of peripheral hemoglobin and platelet, the early mortality, and the adverse reaction rates were analyzed between the ATRA group and the ATRA combined As2O3 group (combined group).

RESULTSCR rate of the combined group and the ATRA group was 91.7% and 87.5% respectively, which showed no significant difference; time of reaching CR, hemoglobin recovery, and platelet recovery for the combined group were 28.0 +/- 7.8 days, 22.36 +/- 8.72 days and 19.38 +/- 9.52 days respectively, while those were 47.7 +/- 10.9 days, 28.40 +/- 8.95 days and 28.03 +/- 7.29 days for the ATRA group, which suggested a significantly shorter period of the combined group of achieving recovery. With 7.1% compared to 13.2%, the early mortality of the combined group seemed lower than that of the ATRA group but with no significance observed (P>0.05). The adverse reaction rates of the two groups also lacked any significant difference (P>0.05).

CONCLUSIONCompared with using ATRA alone, the combined therapy of AS2O3 and ATRA was dominant in achieving CR and recovery for APL. Besides, the combined therapy carries the promise of reducing the early mortality with no aggravation of the adverse reaction.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; Child ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Oxides ; administration & dosage ; Remission Induction ; Retrospective Studies ; Tretinoin ; administration & dosage ; Young Adult