Tumor has long been a hard-nut problem in the world medical field. The effect of the conventional drugs is very limited because of the intervention of multiple micro-environmental factors during the occurrence and progression of tumors. With the characteristics of high efficiency, low toxicity and multi-targets synergistic effect, the long-circulating tumor targeted compound preparations show its unique advantages in improving tumor microenvironment and enhancing the therapeutic effect of treatment, thus it has gradually become a hotspot of studies both at home and abroad. Through consulting a great number of professional literatures at home and abroad in recent years, the authors summarized the current studies in vitro and in vive on long-circulating tumor targeted compound preparations in different carriers, in the expectation of providing new ideas and methods for the development of long-circulating tumor targeted compound preparations.
Animals ; Antineoplastic Agents ; blood ; chemistry ; therapeutic use ; Drug Compounding ; methods ; Humans ; Molecular Targeted Therapy ; methods ; Neoplasms ; blood ; drug therapy

Conus textile is a kind of highly toxic and abundantly existing conus in the South China Sea. The toxin from C.textile could act on sodium channels(δ-conotoxins)and calcium channels (ω-，ε-conotoxins), respectively. Their specific chemical structure and biological activity have attracted a lot of attention in recent years. This article briefly reviews their biochemical characteristics, isolation, gene cloning, biological and neuropharmacological activities, as well as their potential applications.

Objective：To explore the distribution of personality disorder tendency of outpatients in psychological counseling departments.Methods：Systematic sampling was used to get the sample population from Shanghai Psychological Counseling Center.The Personality Diagnostic Questionnaire(PDQ~(+4))was administered to 1402 clients to screen personality disorders.Results：The subscales for different type of personality disorder(PD)and total score of PDQ~(+4) were higher than normal sample(e.g.total score of PDQ~(+4):client(38.23±17.04)vs.normal sample(22.79±14.10),P<0.001).The score of borderline subscales in female clients were higher than that of males [borderline:female(4.25±2.48)vs.male(3.97±2.41),P<0.05],the score of antisocial,paranoid and schizotypal subscales in male clients were higher than that of females [antisocial:female(1.31)vs.male(1.71),P<0.001;paranoid:female(2.75)vs.male(3.02),P<0.01;schizotypal:female(3.31)vs.male(3.56),P<0.05].Age stratification showed that the subscales for different type of PD of PDQ~(+4) were decreased with age [e.g.,total score of PDQ~(+4):18～24 years(41.73)vs.25～34 years(39.46)vs.35～44 years(33.88)vs.≥ 45 years(30.64),Ps<0.001],the positive rate of PDQ~(+4) subscales of obsessive-compulsive(58.5%)and avoidant PDs(54.0%)were higher than others,followed by borderline PD(44.4%).Factor analysis was used for the score of PDQ~(+4),factor 1 to 3 corresponded to cluster C,B and A personality disorders respectively,and the total variance explained 67%. Conclusion：There are different rates of personality deviation between psychological counseling clients and normal sample in China.Some traits of personality disorders can be improved with the increasing of age.The abstracted factors by factor analysis are very consistent with what originally proposed in the theory of personality disorder.It should be paid attention to PD tendency of clients during psychological counseling.

AIM:To evaluate the changes of the corneal surface morphology undergoing overnight orthokeratology treatment and assess the effect of optical center deviation in controlling the development of myopia.METHODS:This was a retrospective clinical study.One hundred and thirty-four children (134 eyes) with myopia aged 10.66 ± 1.79 years were treated with overnight orthokeratology lenses.The examinations of visual acuity,axial length and corneal topography were performed before and 3,6,12,18 and 24mo after wearing orthokeratology.The results of right eye were taken as the object of this study,SPSS19.0 for statistical analysis.RESULTS:The distance of decentration about 134 children at 3,6,12,18 and 24mo after wearing orthokeratology were 0.84±0.45mm,0.77±0.40mm,0.79± 0.41 mm,0.78±0.41 mm,and 0.79±0.42mm respectively.The difference between these groups were not statistically significant (F=1.187,P=0.319).The mean distance of decentration after orthokeratology treatment was 0.79 ± 0.35mm,the growth of axial length after 24mo was 0.32± 0.30mm,the mean distance of decentration divided into 3 groups,mild (＜0.5mm) 27 eyes,medium (0.5-1.0mm)79 eyes,severe (＞ 1.0mm) 28 eyes,the growth of axial length frow 3 groups after 24mo were 0.45±0.34mm,0.32 ±0.28mm,0.23 ± 0.29mm,were statistically significant difference between each groups (F=3.825,P=0.024).By linear-regression analysis,the growth of axial length and the mean distance of decentration after 24mo was statistically significant difference (F =7.246,P =0.008),equation of linear regression was Y=0.478-0.194X.At 24mo after wearing orthokeratology,the mean distance of decentration about 18 eyes with monocular diplopia was 1.18±0.36mm,and 116 eyes without monocular was 0.73± 0.31mm,the distance of decentration were statistically significant difference (t=5.59,P＜0.01).CONCLUSION:The degree of decentration tended to be stable after 3mo of orthokeratology treatment and influenced the effect of myopia control and visual quality.

AIM: To discuss the relationship between prostate specific membrane antigen(PSMA) and prostate cancer and to seek a target for diagnosis and therapy of prostate cancer.METHODS: A pair of primers was designed according to the published PSMA mRNA sequence.Total RNA was extracted from prostate cancer tissues and was reversely transcribed into cDNA,which was used as a template for PCR to amplify the PSMA gene.The recombinant was sequenced and the result was analyzed by BLAST.The PSMA5 gene specific primers were designed to identify its expression in different cells and prostate tissues.RESULTS: A new alternatively spliced variant of PSMA named PSMA5 was discovered when sequencing the recombinant.PSMA5 showed well pathological tissue-specificity,and its expression rate in prostate cancer,benign prostatic hyperplasia of prostate,and normal prostate tissue were 92.6%,78.8% and 10.0%,respectively.It expressed specifically in Pca cell line LNCaP,not in cell lines of PC3,bladder carcinoma,renal carcinoma,or hepatoma.CONCLUSION: A new alternative spliced variant of PSMA named PSMA5 was discovered,which was well correlated with prostate cancer and benign prostatic hyperplasia.This finding may give a new clue to the evolution of prostate cancer and may provide a target for the diagnosis and therapy of prostate cancer.

AIM: To find out the gene structure and diversity of protate specific membrane antigen(PSMA) alternative spliced variants, and probe into the pathogenesis of prostate cancer.METHODS: 5'-RACE and 3'-RACE methods were used to amplify the 5' and 3'end of alternative spliced variant and then those viariants were sequenced for analyzing the gene stucture and diversity of PSMA alternative spliced variants of prostate cancer tissues.RESULTS: Four new alternative spliced variants of PSMA were discovered from prostate cancer tissues.Compared with reported PSMA alternative spliced variants,different insertions and deletions existed in different sites of those new variants.CONCLUSION: The discovery of the new variants confirms the diversity of PSMA spliced variants and provides the clues for seeking the target of diagnosis and therapy of prostate cancer.

OBJECTIVETo investigate the effects of Bushen Huoxue Fang (BSHX) on the apoptosis of epithelial cells in the prostatic ductal system of rats with benign prostatic hyperplasia (BPH) and its possible action mechanism.

METHODSOne hundred 3- month-old male Wistar rats were randomly divided into four groups of equal number (control, castrated, BPH model, and BSHX). BPH models were made by subcutaneous injection of testosterone following castration; the rats in the BSHX group were treated intragastrically with BSHX at 2.34 g/ml after modeling, while those in the other two groups with equal volume of saline, all for 37 days. On the 38th day, all the rats were sacrificed and their prostates harvested for detection of the distribution of TGF-beta1 and alpha-actin and the count of positive cells in the prostatic ductal system by immunohistochemical staining. The apoptosis rate of epithelial cells in the prostatic ductal system was determined by TUNEL assay.

RESULTSThe expression of TGF-beta1 was significantly increased in the rats of the BSHX group as compared with the BPH models in both the proximal prostatic duct ([15.28 +/- 4.30]% vs [36.42 +/- 8.10]%, P < 0.01) and the distal prostatic duct ([4.42 +/- 2.07]% vs [8.71 +/- 2.28 ]%, P < 0.05), while the expression of alpha-actin in the proximal duct was remarkably higher in the BSHX-treated rats than in the models ([28.14 +/- 7.43]% vs [18.28 +/- 4.07]%, P < 0.01), but lower than in the control animals ([33.57 +/- 6.85]%, P < 0.05). Compared with the control group, the BPH models and BSHX-treated rats both exhibited markedly decreased apoptosis of epithelial cells in the proximal prostatic duct ([39.42 +/- 9.20]% vs [3.86 +/- 1.34]%, P < 0.01, and [31.14 +/- 5.64]%, P < 0.01) and distal prostatic duct ([17.60 +/- 4.86]% vs [3.07 +/- 1.14]%, P < 0.01, and [12.37 +/- 2.25]%, P < 0.05). The apoptosis rate of epithelial cells in the prostatic ductal system was significantly higher in the BSHX-treated rats than in the BPH models (P < 0.01).

CONCLUSIONBy upregulating the expression of TGF-beta, BSHX can suppress the reduction of smooth muscle cells in the proximal prostatic duct, promote the apoptosis of prostatic epithelial cells, and thus effectively inhibit benign prostatic hyperplasia.

Actins ; metabolism ; Animals ; Apoptosis ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Epithelial Cells ; drug effects ; pathology ; Male ; Prostatic Hyperplasia ; drug therapy ; metabolism ; pathology ; Rats ; Rats, Wistar ; Transforming Growth Factor beta1 ; metabolism

The aim of the present study is to investigate the effects of Panax notoginseng saponins (PNS) on pneumocyte apoptosis and apoptosis-related protein, as well as c-Jun N-terminal kinase (JNK) in lung ischemia/reperfusion (I/R) injury. Thirty Wistar rats were randomly divided into control group, I/R group and PNS group. The unilateral lung I/R model was replicated by obstruction of left lung hilus for 30 min and reperfusion for 120 min in vivo. The rats in PNS group were given intraperitoneal injection of PNS at 60 min before ischemia and 10 min before reperfusion. Some lung tissues sampled at the end of the experiment were assayed for wet/dry weight ratio (W/T). The expressions of phosphorylated JNK (p-JNK) and JNK protein were detected by Western blot. The expressions of Bcl-2, Bax and Caspase-3 protein were detected by immunocytochemistry techniques. The pneumocyte apoptotic index (AI) was detected by terminal deoxynuleotidy1 transferase mediated dUTP nick end labeling (TUNEL). The morphological and ultrastructure changes were observed under light microscope and electron microscope, and the injured alveolus rate (IAR) was counted as well. The results showed that compared to control group, I/R group showed increased expressions of p-JNK, Bcl-2, Bax and Caspase-3 protein (all P < 0.01), decreased ratio of Bcl-2/Bax (P < 0.05), and increased values of AI, W/T and IAR (all P < 0.01). Moreover, light microscope and electron microscope showed serious morphological and ultrastructure injury in I/R group. Compared to I/R group, PNS group showed markedly decreased expressions of p-JNK, Bax and Caspase-3 protein (all P < 0.01), increased expression of Bcl-2 protein and ratio of Bcl-2/Bax (both P < 0.01), and lower values of AI, W/T and IAR (all P < 0.01). Meanwhile, light morphological and ultrastructure injury was found to be alleviated in PNS group. These results suggest that PNS can protect lung tissue from I/R injury, and the mechanism may correlate with suppressing JNK signal pathway, up-regulating the ratio of Bcl-2/Bax which results in inhibition of Caspase-3 dependent apoptosis.
Alveolar Epithelial Cells ; drug effects ; Animals ; Apoptosis ; drug effects ; Female ; Ischemia ; physiopathology ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Lung ; blood supply ; metabolism ; pathology ; Male ; Panax notoginseng ; chemistry ; Rats ; Rats, Wistar ; Reperfusion Injury ; prevention & control ; Saponins ; isolation & purification ; pharmacology ; Signal Transduction ; drug effects

OBJECTIVETo investigate the protective effects and mechanism of SP600125-specificity inhibitor of c-Jun N-terminal kinase (JNK)on lung ischemia /reperfusion injury in rats.

METHODSThe unilateral lung ischemia/reperfusion model was replicated in vivo. Rats were randomly divided into three groups (n = 10): control group, ischemia/reperfusion group ( I/R group) and ischemia/reperfusion + SP600125 group (SP600125 group). The lung tissues sampled at the end of each experiment were assayed for wet/dry weight ratio (W/D),the injured alveoli rate (IAR), the expression of phosphorylation JNK (p-JNK) and JNK protein were detected by Western blot, the expression of Bcl-2, Bax, Caspase3 protein were detected by immunocytochemistry techniques, the pneumocyte apoptosis index (AI) was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end abeling(TUNEL), the ultrastructure changes were observed under electron microscope.

RESULTSCompared to I/R group, the expression of p-JNK, Bcl-2, Bax and caspase-3 protein were markedly decreased (all P < 0.01), the expression of Bcl-2 protein and the ratio of Bcl-2/Bax were markedly increased in SP600125 group(all P < 0.01). The value of AI, W/D, IAR showed significantly lower than those in I/R group (all P <0.01). Meanwhile, light morphological and ultrastructure injury were found in SP600125 group.

CONCLUSIONSP600125 can suppress JNK signal pathway, up-regulate the ratio of Bcl-2/Bax to inhibit Caspase-3 dependent apoptosis, so that it protects lung tissue from ischemia/reperfusion injury.

Animals ; Anthracenes ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Lung ; blood supply ; metabolism ; pathology ; MAP Kinase Signaling System ; Phosphorylation ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; pathology ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo investigate the distribution of tetracycline-arginine-glycine-aspartate-tyrosine (T-RGDY) in mice and its effect on bone.

METHODS125-labeled T-RGDY was studied for its distribution in mice and for its effects on bone by histomorphometry in ovariectomized rats.

RESULTSThe 125I-labeled T-RGDY was more concentrated in the osteoporotic bone than in the normal bone. Compared with ovariectomy group, the morphologic index such as trabecular bone volume/total tissue volume (TBV/TTV), TBV/sponge bone volume (SBV), and mean trabecular plate thickness (MTPT) in T-RGDY group significantly increased (P < 0.05). As compared with sham operation group, MTPT significantly increased in T-RGDY group (P < 0.05), while TBV/SBV and mean trabecular plate density significantly decreased (P < 0.05), and TBV/TYV and mean trabecular plate spacing were almost the same as those in sham operation group (P > 0.05).

CONCLUSIONT-RGDY may concentrate in bone tissue to a certain degree, which is closely related with the status of bone remodeling. T-RGDY may inhibit the bone loss caused by ovariectomy.

Animals ; Bone Density ; drug effects ; Bone Remodeling ; drug effects ; Female ; Mice ; Oligopeptides ; pharmacokinetics ; pharmacology ; Osteoporosis ; metabolism ; prevention & control ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Tetracycline ; pharmacokinetics ; pharmacology ; Tissue Distribution ; Tyrosine ; pharmacokinetics ; pharmacology