Tumor immune checkpoint therapy is a clinical treatment strategy developed based on the new principle of the inhibition of negative immune regulation. In this article, the tumor immune checkpoint therapy and the drug delivery strategies were reviewed, mainly including immunity and tumor therapy, tumor immune checkpoint therapy and its mechanism of action, clinical application of tumor immune checkpoint therapy and therapeutic drugs, immune resistance of programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PDL1) treatment and countermeasures, drug delivery strategies for tumor immune checkpoint therapeutic agents, etc. As a revolutionary new immunotherapy strategy, tumor immune checkpoint therapy has shown obvious superior therapeutic efficacy in a variety types of tumor. However, tumor immune checkpoint therapy is also faced with a big challenge, namely, immunotherapy resistance. With the discovery of new mechanism, the continuous development of new therapeutic drugs and delivery strategies, tumor immune checkpoint therapy is expected to further improve the clinical efficacy of tumor.

Objective To evaluate the two-stage repair in hypospadias cripples.Methods 35 patients with hypospadias cripples underwent two-stage repair.At the first stage,a full-thickness graft of skin or buccal mucosa was used for urethral plate reconstruction after the release of chordee.The second stage was performed 6 months after completion of the first stage.Tubularization of the replaced urethral plate was the preferred technique.Results There was no urethra stricture or “preplaced urethral plate ” atrophy.Fistula developed in 2 of 35 cases.Conclusion The twostaged technique was a useful strategy to deal with the myriad abnormalities encountered in crippled hypospadias.This technique could not only create a neourethra successfully,but also give the penis a near-normal shape and appearance.

OBJECTIVETo explore the correlation between Beijing genotype (Beijing family) strains of Mycobacterium tuberculosis (MTB) and drug resistance.

METHODSA computer retrieval of Medline, Embase, SCI, EBSCO, CNKI, Weipu and Wanfang databases from 1990 to 2010 was conducted. A total of 525 articles exploring the relationship of Beijing genotype of MTB and drug resistance were found through literature search. Following the inclusion and exclusion criteria, a Meta-subgroup analysis was conducted in Beijing genotype of MTB and drug resistance.

RESULTSA total of 38 articles were selected, including 22 articles on isoniazid resistance, 24 articles on rifampin resistance, 19 articles on ethambutol resistance, 18 articles on ethambutol resistance, 26 articles on multi-drug resistance (MDR). Meta-subgroup analysis showed that in China, there was an association between Beijing genotype and resistance to rifampin, ethambutol and MDR: rifampin (OR = 1.62, 95%CI: 1.13 - 2.31), ethambutol (OR = 1.67, 95%CI: 1.16 - 2.40), MDR (OR = 1.79, 95%CI: 1.20 - 2.68); in Russia, there was an association between Beijing genotype and resistance to isoniazid, rifampin, ethambutol and MDR: isoniazid (OR = 4.82, 95%CI: 3.19 - 7.29), rifampin (OR = 4.84, 95%CI: 3.84 - 6.10), ethambutol (OR = 3.32, 95%CI: 2.51 - 4.40), MDR (OR = 5.42, 95%CI: 3.36 - 8.74); in Vietnam, there was an association between Beijing genotype and resistance to isoniazid, rifampin, ethambutol and MDR: isoniazid (OR = 2.12, 95%CI: 1.55 - 2.91), rifampin (OR = 4.71, 95%CI: 3.01 - 7.36), ethambutol (OR = 3.78, 95%CI: 1.63 - 8.77), MDR (OR = 4.21, 95%CI: 1.58 - 11.18); in other countries, there was an association between Beijing genotype and resistance to isoniazid, rifampin, ethambutol and MDR: isoniazid (OR = 1.69, 95%CI: 1.19 - 2.42), rifampin (OR = 2.48, 95%CI: 1.92 - 3.19), ethambutol (OR = 3.04, 95%CI: 2.13 - 4.33), MDR (OR = 2.36, 95%CI: 1.52 - 3.68).

CONCLUSIONBeijing genotype of MTB was positively associated with three kinds of first-line anti-tuberculosis drugs (isoniazid, rifampin, ethambutol) and MDR, and the relationship intensity was different in different countries.

Antitubercular Agents ; pharmacology ; China ; DNA, Bacterial ; Drug Resistance, Multiple, Bacterial ; Genotype ; Humans ; Mycobacterium tuberculosis ; drug effects ; genetics ; isolation & purification ; Russia ; Tuberculosis, Multidrug-Resistant ; genetics ; microbiology ; Vietnam

Objective To investigate the value of partial hepatectomy and vascular resection in the treatment of hilar cholangiocarcinoma. Methods Seventy four patients with hilar cholangiocarcinoma who underwent hepatectomy of Chinese People' s Liberation Army from January 2008 through December 2011 were analyzed retrospectively.Results Of the 74 patients,33 underwent radical resection and 19 palliative resection,22 received internal or external drainage.In the radical resection group,the median survival time was 27 months,and the overall survival rate at 1,2 and 3 years were 79％,64％ and 49％.In the palliative resection group,the median survival time was 14 months and the overall survival rate at 1,2 and 3 years were 56％,25％,and 19％.In the drainage group,the median survival time was 9 months and the overall survival rate at 1,2 and 3 years were 23％,15％,0.Conclusions Hepatectomy combined with hilar vascular resection helps increase survival rate of patients in radical excision of hilar cholangiocarcinoma and Surgical resection is the most elective method for treatment of hepatic hilar cholangiocarcinoma,and the radical resection might improve the prognosis of the patients with hilar cholangiocarcinoma.

OBJECTIVETo screen and identify the peptides that specifically bind to CD13 on monocytes.

METHODSThe phages capable of specific binding to CD13 were screened in the phage-displayed 12-peptide library. The affinity of the selected phages with CD13 was verified with enzyme-linked immunosorbent assay (ELISA). The sequences of the peptides bound to the phages were deduced according to the phage DNA sequences, and the functional peptides aligned using the BLASTP on the Website NCBI were synthesized. To analyze the biological function of the screened peptides, the location of the peptides bound to THP-1 cells was detected using immunofluorescence assay. The blocking effect of WM15 on the peptide binding to THP-1 cells was assessed by immunofluorescence assay.

RESULTSThe phages that specifically bound to CD13 were effectively enriched to approach saturation after 4 rounds of panning. The recovery rate in the fourth round was 30 times that in the first round. Twenty selected phages were verified by ELISA, and the signals of 10 phages were higher than the control. The sequences of the peptides P9 and P7 showed 83% and 100% identity with those of human cytomegalovirus (HCMV) UL38 and UL105, respectively. The peptides bound to the cell membrane of THP-1 cells as shown by immunofluorescence assay. The binding of the peptides P9 and P7 to THP-1 cells was blocked by CD13-specific monoclonal antibody WM15 at different levels.

CONCLUSIONTwo peptides (P7 and P9) that can specifically bind to CD13 have been screened successfully, and these two peptides show specific binding to CD13 on the membrane of THP-1 cells.

Amino Acid Sequence ; Binding, Competitive ; CD13 Antigens ; analysis ; metabolism ; Cell Line ; Humans ; Molecular Sequence Data ; Peptide Library ; Peptides ; metabolism ; Protein Binding

To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of epirubicin hydrochloride (EPI) in rat plasma, daunorubicin hydrochloride was used as internal standard. The plasma samples were deproteinated with methanol, and separation was performed on a reversed-phase CAPCELL PAK C18 column (3.0 mm x 50 mm, 3 microm). The mobile phase contained methanol-0.1% formic acid (80:20). Detection was carried out by multiple reaction monitoring on a HP1200-6410 QQQ LC/MS system. Different preparations of EPI solution, EPI-LIP (EPI-liposome) and EPI-LTSL (EPI-thermosensitive liposome) was administered in rats by i.v with the same dosage (12 mg kg(-1)). The pharmacokinetic model and parameters were fitted and calculated by the DAS ver2.0 software. The calibration curve was linear in the range of 0.01-50 microg mL(-1). The limit of quantification was 0.01 microg mL(-1). RSDs of intra- and interbatch precisions were all less than 11.9%. The average extract recovery was 89.3% and 92.1%, respectively. The pharmacokinetics of EPI in rats with all preparations were fitted to three compartments, which all fast distributed and slowly eliminated. The t1/2 alpha, t1/2 beta, t1/2 gamma, AUC(0-infinity), and MRT(0-infinity) of EPI-LTSL group were 7.5, 1.3, 12.6, 12.9, 3.7 times those of EPI solution group; and 1.6, 1.4, 12.3, 2.9, 2.6 times those of EPI-LIP group. Moreover, the CL of the latter two groups was about 13.4 times of the former EPI-LTSL group. EPI-LTSL can significantly improve AUC and prolong the circulation time of EPI in rat plasma.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; Drug Carriers ; Epirubicin ; administration & dosage ; blood ; pharmacokinetics ; Liposomes ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Tandem Mass Spectrometry

OBJECTIVETo investigate the prognostic factors and the principles of treatment of primary esophageal small cell carcinoma (SCEC) retrospectively.

METHODSThe data of 126 patients with histologically confirmed SCEC treated in our department between May 1985 and June 2005 were retrospectively analyzed. 85 patients were in limited disease stage (LD) and 41 patients as extensive disease stage (ED) according to the Veterans Administration Lung Study Group staging system. Among the 84 patients treated with esophagectomy, 8 cases were in stage I, 16 in stage IIa, 10 in stage IIb, 40 in stage III, 4 in stage IVa and 6 in stage IVb, according to the TNM system (6(th) edition, AJCC). Cox's hazard regression model was used to identify the prognostic factors, and Chi-square test to detect the difference of frequencies among different groups. Kaplan-Meier and log-rank methods were used to estimate and compare the survival rates.

RESULTSThe median follow-up duration of this series was 13 months. One hundred and eight patients died of the disease during the follow-up, 10 were still alive and 8 were lost to follow-up. The 1-, 3-, and 5-year overall survival rates (OS) were 52.2%, 15.9%, and 12.2%, respectively, with a median survival time (MST) of 12.5 months. The 1-, 2-, and 3-year OS were 62.1%, 30.8%, and 22.4% with a MST of 14.0 months for LD, and 29.3%, 13.6% and 2.7% with a MST of 7.0 months for ED, respectively. There was a statistically significant difference in OS between LD and ED (P = 0.0001). The MST of the patients treated with chemotherapy was 14.5 months, significantly longer than the 5.2 months of the patients without (P = 0.0001). Multivariate analysis showed that stage (HR 1.91, 95% CI 1.26 approximately 2.91, P = 0.002), length of the primary lesion (HR 1.75, 95% CI 1.17 approximately 2.63, P = 0.007), and chemotherapy (HR 0.42, 95% CI 0.28 approximately 0.65, P = 0.000) were independent prognostic factors.

CONCLUSIONEsophageal small cell carcinoma is a systemic disease. The tumor stage (LD or ED), length of the primary lesion and chemotherapy are independent prognostic factors. Therefore, a systemic therapy based on chemotherapy should be recommended.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Small Cell ; pathology ; therapy ; Combined Modality Therapy ; Esophageal Neoplasms ; pathology ; therapy ; Esophagectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, High-Energy ; Retrospective Studies ; Survival Rate

Objective To study the diagnosis and treatment of cytomegalovirus (CMV) infection after liver transplantation. Methods The clinical data of 111 patients who received liver transplantation from November 2000 to December 2007 in our hospital were analyzed retrospectively. The recipients were diagnosed as having CMV infection by the predisposing factors, clinical symptoms and detection of CMV-PP65 and CMV-IgM in peripheral blood specimens in combination with chest X-ray. The treatment of CMV infection was administration of Ganciclovir. Results Five recipients were diagnosed as having CMV infection, with the incidence of 4.5%. Two were diagnosed as having CMV pneumonitis, with the incidence of 1.8% (40% of the recipients having CMV infection). Two were both improved. Three were diagnosed as having CMV active infection. Two of them were cured and one was improved. Conclusion The detection of CMV-PP65 is necessary for early diagnosis and guiding treatment of CMV infection. Ganciclovir can exert significant therapeutic effects on CMV infection.

Multi-central randomized controlled method was used to scientifically verify indications of 33 acupoints and provide definite clinical basis for the indications of single acupoint. Of the 52 studies, 40 studies showed that the therapeutic effect in acupuncture observation groups were better than the control group; 11 studies showed similar therapeutic effect of the two groups, and 1 study showed the acupuncture observation group was worse than the control group. Therefore, results indicate that in a certain observation cycle, acupuncture at single acupoint have different effects on diseases.
Acupuncture Points ; Humans ; Randomized Controlled Trials as Topic

BACKGROUNDOsteopontin (OPN) is one kind of cytokine which can play a number of roles in promoting activation of T lymphocyte, regulating balance between Th1 and Th2, participating in cell-induced immunologic response and stimulating B lymphocyte to express multi-clone antibodies. Some researches have showed that OPN may be involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate possible association of a single nucleotide polymorphism (SNP) at position 9250 in exon 7 of the OPN gene (OPN gene 9250) with SLE in Chinese patients.

METHODSTotally 158 patients (18 males and 140 females) fulfilled the revised criteria for SLE by the American College of Rheumatology in 1982 and 180 healthy volunteer controls (34 males and 146 females), all from the south of China, consented to participate in the study. OPN gene 9250 polymorphism was detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).

RESULTSThe frequency of TT genotype of the OPN gene 9250 was significantly lower (52.5% vs 70%, P < 0.05) and the frequency of TC genotype of the OPN gene 9250 was significantly higher (43.7% vs 29.4%, P < 0.05) in SLE patients than in controls. There were significant differences in OPN gene 9250 allele and phenotype frequencies between the SLE patients and controls (P < 0.05). When the SLE patients and controls were separated into men and women, significant differences of frequencies were noted in TT genotype, TC genotype and allele of the OPN gene 9250 in women (P < 0.05) but not in men (P > 0.05).

CONCLUSIONSOPN gene 9250 polymorphism appears to be associated with susceptibility to SLE in Chinese Han ethnic population.

Adolescent ; Adult ; Aged ; China ; ethnology ; Female ; Humans ; Lupus Erythematosus, Systemic ; genetics ; Lupus Nephritis ; genetics ; Male ; Middle Aged ; Osteopontin ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length