BACKGROUND:The immunological rejection between host and graft is the leading cause of organ
transplantation failure. The traditional immunosuppressive agents have been unable to meet the needs of clinical treatment. Antibody-drug conjugate, as a type of new drugs, may be hope for the treatment of immune rejection. OBJECTIVE:To comprehensively analyze the composition of antibody-drug conjugates, mechanism of action, clinical research progress as wel as the development trend.
METHODS:A computer-based online retrieval was performed to search papers in CNKI and PubMed database using the key words of ADCs, immunosuppressive agents, immunotoxins, organ transplantation, graft rejection in Chinese and English. Recently published or published in the prestigious journals were selected in the same field. After excluding objective-independent papers and repeated studies, 42 papers were included for further analysis. RESULTS AND CONCLUSION:Antibody-drug conjugates, as highly effective and lowly toxic immunosuppressant, have achieved a breakthrough in treatment of targeting tumor, while the role of it in anti-immune rejection is stil at the exploratory stage. For islet transplantation, novel antibody-drug conjugates are required to block CD8+T effector by CD103/E-Cadherin pathway, and wil probably serve as a potential drug intervention for al ograft rejection.

Objective To study the effect of myocardial ischemic preconditioning on activity of ATPase and creatine kinase(CK) in high blood fat rat. Methods High blood fat rat mode was established from SD rats.The rats were randomly divided into three groups: ischemic preconditioning(IPC), ischemic/reperfusion(I/R) and control group.The activity of CK in coronary outflow,the activity of malonyldialdehyde(MDA),superoxide dismutase(SOD),glutathione perodxidase(GSH-Px) and ATPase in myocardium were dectected. Results CK and MDA were significantly less in IPC group than those in I/R group.In IPC group,the activity of SOD,GSH-Px,Na~(+)-K~(+)-ATPase,Ca~(2+)-ATPase and Ca~(2+)-Mg~(2+)-ATPase were much higher than those in I/R group. Conclusion Myocardial ischemic preconditioning can protect high blood fat rat from ischemic/reperfusion injury.

Objective To evaluate the predictive values of ABCD,ABCD2 ,SPI-Ⅱ and ESSEN score models for the patients with high-risk transient ischemic attack (TIA)to develop to cerebral infarction in short and long term. Methods The ABCD, ABCD2 , SPI-Ⅱ and ESSEN scores of 235 cases of TIA patients were retrospectively analyzed.The incidence of cerebral infarction was followed up for 7 d and 1 year, and the receiver operating characteristic curve (ROC)was drawn to calculate the area under curve (AUC)to assess the accuracy of the score models,and compared with the original model and the relative risk (RR)value was calculated.Results The 7 d-incidence and 1 year-incidence of cerebral infarction in the 235 TIA patients were 9.36 % and 20.43%.The AUC of ABCD,ABCD2 ,SPI-Ⅱ and ESSEN models for 7 d were 0.70,0.74,0.67,and 0.62.The AUC of 1 year were 0.62,0.62,0.64,and 0.65.Compared with the orginal models,the RRs for 7 d of ABCD score model of the TIA patients in low,middle,and high risk groups were 0.09,0.92,and 0.72;the RRs of ABCD2 score model were 0.49,0.59,and 0.65;the RRs of SPI-Ⅱ score model were 0.58,0.87,and 0.55;the RRs of ESSEN score model were 0.11,0.18,and 0.55.Conclusion ABCD,ABCD2 ,SPI-Ⅱ and ESSEN score models can be used to assess the risk of cerebral infarction after TIA in Chinese population.The ABCD2 score model is of great value for short-term risk prediction,and the ESSEN score model is more value for long-term risk prediction.

OBJECTIVETo explore HEPACAM mutations in a Chinese family with megalencephalic leukoencephaloptathy with subcortical cysts (MLC).

METHODGenomic DNA samples were extracted from peripheral blood of the proband and her parents. All exons and exon-intron boundaries of HEPACAM and MLC1 were amplified in the MLC family by polymerase chain reaction (PCR) followed by direct DNA sequencing.

RESULTTwo heterozygous mutations of HEPACAM located in exon 2, c.203A > T(p.K68M) and c.395C > A(p.T132N), were identified in the proband. The proband's mother had the heterozygous mutations c.203A > T(p.K68M), and her father had the heterozygous mutation-c.395C > A(p.T132N). There was no variation found in MLC1 gene.

CONCLUSIONThe proband was heterozygous compound MLC patient carrying on one allele with the c.203A > T(p.K68M) mutation inherited from her mother, and the other allele with the c.395C > A(p.T132N) mutation inherited from her father. The parents both are heterozygous carriers with normal phenotype. The disease-causing gene for this family was resulted in HEPACAM mutation other than MLC1 mutation.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Cysts ; genetics ; pathology ; DNA Mutational Analysis ; Exons ; Female ; Genotype ; Hereditary Central Nervous System Demyelinating Diseases ; genetics ; pathology ; Heterozygote ; Humans ; Membrane Proteins ; genetics ; Mutation ; Pedigree ; Phenotype ; Proteins ; genetics

OBJECTIVETo assess the clinical usefulness, accuracy, and safety of tele-manipulation for frameless stereotactic surgery using the CAS-R-5 robot system.

METHODSWe prospectively evaluated 32 patients underwent tele-manipulation of frameless stereotactic operations from Sep. 2005 to Sep. 2006. Tele-manipulations were performed via a digital data network by a neurosurgeon in Beijing while the patients were located in Yan'an. The distance is 1300 kilometers away. The accuracy of location and improvement of symptom were observed after operation. The period of follow-up was from 3 to 14 months (the average was 12 months).

RESULTSThe surgical operations in 32 cases were successful. Remote fiducial registration was performed with a mean accuracy of 1. 50 mm and the standard difference were 0.32 mm between the planned and actual target. There were no complications.

CONCLUSIONSDiagnosis and treatment for intracranial disease by tele-manipulation frameless stereotactic surgeries are reliable and safe.

Adolescent ; Adult ; Aged ; Brain ; pathology ; surgery ; Brain Diseases ; surgery ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Reproducibility of Results ; Retrospective Studies ; Robotics ; methods ; Stereotaxic Techniques ; Surgery, Computer-Assisted ; Treatment Outcome

OBJECTIVESTo block the synthesis of ryanodine receptor 2 (RyR2) in myocardial cells by RNA interference and to investigate its biological impact on ischemia-reperfusion (I/R) in rat myocardial cells.

METHODSRat myocardial cells were isolated and cultured for an I/R model in vitro. RNA interference technique was used to block the synthesis of RyR2 in myocardial cells. Changes of LDH level, apoptosis, RyR2 mRNA expression and cytosolic Ca(2+) concentration were analyzed accordingly.

RESULTSMyocardial cells after I/R manipolation were severely injuried (LDH leakage, 125 IU/L vs 12 IU/L, P < 0.05), apoptosis (60.1% vs 5.5%, P < 0.05), significant cytosolic Ca(2+) overload (21.2 vs 7.6, P < 0.05) and remarkable mitochondrial membrane potential loss (37.2 vs 85.1, P < 0.05). However, no visible change of RyR2 was observed (20.1 vs 22.7, P > 0.05). Pre-treatment with RyR2 specified siRNA demonstrated suppressed expression of RyR2 (6.8 vs 20.1, P < 0.05), increased mitochondrial membrane potential (55.8 vs 37.2, P < 0.05), attenuated cytosolic Ca(2+) overload (8.6 vs 21.2) and cellular apoptosis (31.2% vs 60.1%, P < 0.05).

CONCLUSIONRyR2 gene silencing enables to protect myocardial cells from I/R injury in vitro.

Animals ; Apoptosis ; drug effects ; genetics ; Cells, Cultured ; Gene Silencing ; immunology ; physiology ; Membrane Potential, Mitochondrial ; drug effects ; immunology ; Myocardial Reperfusion Injury ; immunology ; pathology ; Myocytes, Cardiac ; drug effects ; pathology ; Oxygen ; metabolism ; RNA Interference ; RNA, Small Interfering ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; immunology ; pathology ; Ryanodine Receptor Calcium Release Channel ; drug effects ; genetics

The paper dilates upon purpose and meaning of the building of multipath remote consultation platform based on medical alliance,introduces its building scheme,which includes implementation method,technology roadmap and technology feasibility analysis,compares the domestic and overseas situations in the area and discusses its future.

To investigate the protective effects of recombinant human tumor necrosis factor receptor II: IgG Fc fusion protein (rhu TNFR: Fc) against the lipopolysaccharide (LPS) induced intestinal damage of rats and its underlying mechanism. SD rats were randomly divided into four groups: control group, rhuTNFR: Fc group, LPS group and rhu TNFR: Fc + LPS group. Mean arterial pressure (MAP) was continuously monitored and the mortality rates were assessed. The levels of TNF-alpha and its bioactivity in the serum were assessed by ELISA and flow cytometry respectively. Pathologic changes of intestinal tissue were observed by HE staining. The rats of control and rhu TNFR: Fc group all survived with stable MAP, and the low level and bioactivity of TNF-alpha in the serum were maintained. While 83% of the rats in LPS group died by 6 h with the levels and bioactivity of TNF-alpha increasing significantly. In rhu TNFR: Fc + LPS group, the mortality rate of rats dropped to 33%. The TNF-alpha level increased compared with control group but its bioactivity decreased significantly compared with LPS group. The MPO activity and content of MDA decreased significantly. The status of pathological manifestation in the intestine was also ameliorated. These data suggest that rhu TNFR: Fc could protect rats from the acute intestine injury induced by LPS through ablating the rise in serum TNF-alpha level and bioactivity as well as anti-oxidation.
Animals ; Disease Models, Animal ; Etanercept ; Female ; Humans ; Immunoglobulin G ; pharmacology ; Intestines ; drug effects ; metabolism ; pathology ; Lipopolysaccharides ; adverse effects ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Tumor Necrosis Factor ; Receptors, Tumor Necrosis Factor, Type II ; pharmacology ; Recombinant Fusion Proteins ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

Objective To investigate the role of nasal mucosa fibrosis on radiation induced nasal mucosa injury. Methods Seventy two male rats were randomly divided into two groups, control group and irradiation injured group (radiation dose were 40 Gy);the rats were killed 1 week, 2 weeks, 4 weeks, 8 weeks, 3 months and 6 months after the finish of radiation. The middle turbinates of the animals were removed. The pathological change of the nasal mucosa were observed with scanning electron microscope, transmission electron microscope, hematoxylin and eosin (HE), alcian blue-periodic acid-Sehif (AB-PAS), and Masson Trichrome (MT). The Hyp content in nasal mucosa was measured with chemo-chromatometry. Results After radiation, the pathological characteristics in early stage (within 4 weeks) was acute inflammatory reaction. The repair of nasal mucosa started 4 weeks after radiation, lasted to 6 months. The deposition of collagen in nasal mucosa could be found 1 week after irradiation and increased gradually. Conclusion Irradiation could induce a serials of pathological changes on nasal mucosa. The nasal mucosa fibrosis may be one of the reasons of persistent irradiation induced nasal mucosa injury.

Objective:To investigate the association of single nucleotide polymorphism at the estrogen receptor 1(ESR1) gene rs1801132 with the risk of brick-tea type skeletal fluorosis.Methods:The typical brick-tea type fluorosis areas in Qinghai, Xinjiang, and Inner Mongolia were selected as the survey sites for a cross-sectional study. An epidemiological questionnaire was conducted by the staffs on the sites for participants older than 16 years, and physical examination and X-ray diagnosis were performed. Brick tea, blood, and urine samples were collected at the same time. The diagnosis of skeletal fluorosis through X-ray was based on the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS/T 192-2008); The determination of tea's fluoride and urinary fluoride was performed by fluoride ion-selective electrode method; gene sequencing analysis of rs1801132 locus of ESR1 gene was done by Sequenom MassARRAY flight mass spectrometry system.Results:A total of 994 patients were included in this study. The total prevalence of skeletal fluorosis was 23.9% (238/994). The prevalence of skeletal fluorosis in Tibetans(39.9%, 123/308) was higher than those of Mongolian and Han nationality [22.2% (58/261), 13.4% (57/425), χ 2=20.435, 67.811, P < 0.05]. Based on binary logistic analysis, the daily tea fluoride intake ≤ 3.5 mg, urinary fluoride content ≤1.6 mg/L, and age ≤45 years were used as the reference groups, and then, when the daily tea fluoride intake > 7.0 mg ( OR=2.865, 95% CI: 1.923-4.268), urinary fluoride content > 1.6-3.2 mg/L ( OR=2.368, 95% CI: 1.686-3.326) and > 3.2 mg/L ( OR=3.559, 95% CI: 2.401-5.276), the age > 45-65 years old ( OR=2.361, 95% CI: 1.603-3.477) and > 65 years old ( OR=4.556, 95% CI: 2.845-7.296), the risk of fluorosis was higher than that of the reference group, respectively. When the daily tea fluoride intake was > 3.5-7.0 mg and the level of urinary fluoride was > 1.6-3.2 mg/L, G allele had a protective effect on skeletal fluorosis in Mongolian population (adjusted OR=0.207, 95% CI: 0.044-0.974); when the daily tea fluoride intake was > 3.5-7.0 mg, gender was male group, G allele had a protective effect on skeletal fluorosis in Han population (adjusted OR=0.315, 95% CI: 0.112-0.887). Conclusion:The single nucleotide polymorphism of the rs1801132 locus at the ESR1 gene may be associated with the risk of susceptibility to brick-tea type skeletal fluorosis in Mongolian and Han nationality.