Cancer is still one of the major diseases threatening human life and health. At present, how to achieve precise diagnosis and treatment of tumors is the biggest challenge in cancer treatment. Prodrugs use the tumor specificity of targeting molecules to deliver anticancer drugs to tumor sites, which can effectively improve drug bioavailability, therapeutic efficacy and safety, and are currently a hot spot in the research and development of anticancer drugs. The targeting molecules of prodrugs mainly include nucleic acid aptamers, polymers, antibodies, polypeptides, etc. Among them, polypeptides have the advantages of good biocompatibility, controllable degradation performance, high in vivo responsiveness, and simple and easy preparation methods, and are widely used. It is used to construct peptide-drug conjugates (PDC) prodrugs to achieve targeted therapy of tumors. In recent years, with the development of phage peptide library technology and peptide standard solid-phase synthesis technology, more and more targeted peptides have been discovered and effectively synthesized and modified, providing strong support for the development of PDC. This review briefly introduces the types and functions of functional peptides and linkers in PDC, and discusses the application of PDC in chemotherapy, immunotherapy and photodynamic therapy in tumor targeted diagnosis and treatment, and finally summarizes the difficulties faced by PDC drug development.

OBJECTIVE:To explore the relevant factors that led to the adverse drug reaction(ADR)of netilmicin.METHODS:ADR cases resulted from netilmicin reported in12kinds of Chinese periodicals from1998to2003were analyzed statistically.RESULTS:The ADR of netilmicin involved multiple organs and systems,the clinical manifestation were compli-cated and diversified,which manifested mainly on the renal toxicity,toxicity of nervous system and allergic reaction.CON-CLUSION:Clinician and pharmacists should be alert to the ADR of netilmicin and keep using drugs rationally.

OBJECTIVE: To provide reference for the prevention of authority dissimilation of drug registration.METHODS: The economic model concerning drug registration was constructed with principal-agent theory.RESULTS: The occurrence of authority dissimilation of drug registration could be cut down by reducing public monitoring costs,improving the rate of prosecution and increasing the costs for dealing with moral risks.CONCLUSION: The authority dissimilation could be effectively prevented by balancing authority for drug registration,improving transparency of drug registration and supervisory system.

Animals ; Heme Oxygenase-1 ; biosynthesis ; Kidney ; drug effects ; metabolism ; Male ; Mercuric Chloride ; toxicity ; Oxidative Stress ; drug effects ; Random Allocation ; Rats ; Rats, Wistar

Objective To investigate the expression of nerve growth factor(NGF) and slouble Fas(sFas) in children with viral myocarditis(VM),and the relationship with immunity,with the aim to provide evidence and basis for the diagnosis and treatment of VM.Methods The serum levels of NGF and sFas were detected by two-site enzyme-linked immunosorbent assy(ELISA) in 43 children with VM,and 20 normal heathy children as controls.Results The serum levels of both NGF and sFas in children with the acute stage(course in less than month and 1-2 months)and the procrastinate and chronic stages of VM were significantly higher than those of healthy children(P0.05).Conclusion The increased serum expression levels of NGF and sFas are related to the process of viral myocarditis,which confirms the relationship between the onset of VM and immune factors.

Objective To investigate the relationship between the maturity and function of dendritic cells (DC) and hepatitis B virus covalently closed circular DNA (HBV cccDNA) load in the peripheral blood mononuclear cells (PBMC)/monocyte-derived DC in patients with chronic hepatitis B (CHB). Methods The peripheral blood samples were collected from 29 patients with CHB and 10healthy controls. PBMC were isolated freshly and induced with granulocyte/macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). A large amount of DC were harvested after seven days of culture. The expressions of CD209, CD80, CD86, human leucocyte antigen (HLA)-DR and CD1a of DC were analyzed by flow cytometry. The HBV cccDNA load in PBMC and DC were measured by real-time polymerase chain reaction (PCR). The interleukin-12 (IL-12) level in the culture supernatant of DC was determined by enzyme linked immunosorbent assay (ELISA). The effects on T lymphocyte proliferation induced by DC were tested by mixed lymphocyte reaction (MLR). The data was compared by t test and analysis of variance. Results HBV cccDNA could be detected in PBMC from 16 patients, but not in DC from all 29 patients. HBV cccDNA load was all negatively correlated with the expressions of CD209 (r= -0. 793, P＜0.01), CD80 (r= -0. 581,P＜0.05), CD86 (r=-0. 698, P＜0.01), HLA-DR (r=-0. 817, P＜0.01), CD1a (r=-0. 734, P＜0.01), IL-12 level (r=-0. 632, P＜0.05) and allogenic T lymphocyte proliferation induced by DC (r=-0. 617, P＜0.05). The expressions of CD209, CD80, CD86, CD1a and HLA-DR on DC,IL-12 level in culture supernatant of DC and the allogenic T lymphocyte proliferation induced by DC in patients with positive PBMC HBV cccDNA were all significantly lower compared to those in healthy controls, and the changes of the parameters mentioned above were greater in PBMC HBV cccDNA positive patients than those in PBMC HBV cccDNA negative patients (P ＜ 0. 05 or P ＜ 0. 01).Conclusions The function and maturity of DC are impaired in CHB patients. HBV cccDNA can be detected in PBMC from CHB patients. Moreover, the higher PBMC HBV cccDNA is, the worse DC function and maturity are, which could be one of the important mechanisms of HBV persistent infection.

Actins ; metabolism ; Angiomyolipoma ; metabolism ; pathology ; surgery ; Epiglottis ; Factor VIII ; metabolism ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged

In the middle of 1990 s, it was discovered that sirolimus had inhibitory effect on the proliferation of T lymphocytes , therefore, it is used for the treatment of anti-tumor cells.At present, the dosage forms of sirolimus are capsules , oral liquid and tab-lets.However, because of good fat-soluble and poor water-soluble property, its bioavailability is low with many side reactions .In order to provide reference for the further studies of sirolimus , the literatures in recent years were searched in Pubmed , Springer, CJFD,VIP Chinese periodical database and Wanfang data , and the research progress in the new dosage forms of sirolimus was summarized .

Objective To compare the sonographic and pathologic features of calcified and non-calcified ductal carcinoma in situ DCIS Methods A total of 83 lesions in 82 consecutive patients with pathologically confirmed pure DCIS were recruited One patient had bilateral lesions All lesions were divided into calcified DCIS and non-calcified DCIS according to the presence of calcifications on mammography Their sonographic features and pathologic reports for all patients with DCIS were retrospectively reviewed Statistical comparisons were performed using the chi-square test Results 1 Calcified DCIS showed positive ultrasound US findings in 80% 44 55 of cases The most common US finding was nonmass lesions 43 6% 24 55 Nine cases had pure ductal dilatations 16 4% 9 55 Non-calcified DCIS showed positive US findings in 96 4% 27 28 of cases The most common US finding was mass 89 2% 25 28 Two cases had pure ductal dilatations 7 1 % 2 28 No significant difference was found in the shape margin orientation posterior feature of a mass between the calcified and non-calcified groups P >0 05 Significant difference was observed in the size boundary echogenicity on ultrasound of the two groups P <0 05 2 At histopathology the pathological scores high nuclear grade positive ER status positive PR status positive Ki67 status and the presence of Her-2 neu oncogene were more common in the calcified group than in the non-calcified group Conclusions Calcified and non-calcified pure DCIS have different pathologic and sonographic features Calcified DCIS has more aggressive histological features than non-calcified DCIS.

Objective To study formulation and characteristics of self-microemulsifying drug delivery system for breviscapine(BRV-SMEDDS).Methods The optimum formulations of BRV-SMEDDS were screened by solubility tests,formula compatibility,and pseudo-ternary phase diagrams.And the physicochemical characters,dissolution in vitro and in situ rat's intestine absorption of BRV-SMEDDS were also observed.Results The optimum formulation of SMEDDS was composed of Maisine 35-1-Cremophor RH40-PEG400-TEA=25∶40∶35∶7.The particle diameter was 88.6 nm.The percent of accumulated dissolution of BRV in SMEDDS in vitro was up to 97.8% at 1h,which was 8.0 times as much as that of BRV powder,and 5.1 times as BRV tablets.In the tests of in situ rat's intestine absorption,the permeability coefficient of BRV-SMEDDS was increased by 3.4 times as much as BRV powder,and 3.3 times as BRV tablets.Conclusion The dissolution and absorption of BRV is improved by formulation of SMEDDS.It could provide reference for the new dosage form of BRV.