Objectives To determine the predictive effect of the transvaginal ultrasonographic cervical measurement in induction of labor among the nulliparous. Methods This prospective observational study recruited women with singleton gestation scheduled for induction of labor at ≥37 weeks. All the pregnancy women were nulliparous. Transvaginal ultrasonographic cervical measurement was performed and Bishop score was detemined, each by operators masked to the other measurement. Data were collected on parity, gestational age, mode of delivery, induction agent, induction onset of labor interval, Bishop score and cervical measurement. Results A total 121 women were included. A stepwise regression model identified cervical length was the best linear predictor of induction to onset of labor interval. ( r=0.67, P

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

The emerging nano-black phosphorus materials have created a new platform for biomedical research. Nano-black phosphorus has the following advantages: black phosphorus can produce singlet oxygen under near-infrared light irradiation, so it can be used as a photosensitizer for photodynamic therapy;black phosphorus has extensive light absorption in the long wavelength region, and this near-infrared photothermal property can be used in photothermal therapy. The high specific surface area and unique fold structure of the black phosphorus nanosheet make it have very high drug loading.This paper mainly reviews the applications of black phosphorus in biological imaging, photothermal therapy, photodynamic therapy, and as a drug carrier in recent years. Based on the photoelectric properties of black phosphorus nanomaterials combined with intelligent drug delivery platform, the synergistic effects of light/heat/chemistry, light/chemistry/gene, and light/chemistry/immunity can be produced, which has a broad application prospect.

OBJECTIVETo explore the mechanism of Alpha-fetoprotein (AFP) effects on hepatocellular carcinoma cells (HCC) resistances apoptosis induced by tumor necrosis factor-related apoptosis inducing-ligand (TRAIL).

METHODSThe expressed alteration of TRAIL receptor-2 (DR5) after the human hepatoma cells line Bel 7402 (AFP-producing) and HLE cells (non-AFP producing) were treated with all trans retinoic acid (ATRA) were determined by Western blot; Interaction of AFP with RAR-beta was analyzed by co-immunoprecipitation (Co-IP); Laser confocal microscopy was used to observe co-localization of AFP and RAR-beta; Short small RNA interfering (RNAi) was applied to knock down the expression of AFP in Bel 7402 cells; The full AFP gene cDNA was inserted into pcDNA3.1 vector and constructed the expressed vector of AFP (named pcDNA3.1-afp); The growth of hepatoma cells was analyzed by MTT.

RESULTSBel 7402 and HLE cells expressed DR5, lowed dosage of ATRA (40mumol/L) had no influence on the expression of DR5 in Bel 7402 cells, but ATRA (160mumol/L) could inhibit the expression of AFP and promote the expression of DR5 significantly; Co-IP indicated that AFP had a property for interacting with RAR-beta; The results also demonstrated AFP co-localization with RAR-beta in cytoplasm of Bel 7202 cells; The expression of DR5 was enhanced while the expression of AFP was knocked down by RNAi. pcDNA3.1-afp vector was transfected into HLE cells, the growth of HLE cells were stimulated and TRAIL cytotoxicity of HLE cells were reduced. But when the expression of AFP was knocked down the sensitivity of Bel 7402 cells to TRAIL was enhanced.

CONCLUSIONSThese data provided that AFP had a capability to interact with RAR-beta and suppressed the expression of DR5. AFP could play pivotal role on hepatoma cells resistance-induced apoptosis by TRAIL.

Apoptosis ; Cell Line, Tumor ; metabolism ; Humans ; Receptors, Retinoic Acid ; metabolism ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Tretinoin ; pharmacology ; alpha-Fetoproteins ; metabolism

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.
Antibodies, Monoclonal ; pharmacokinetics ; Cytotoxins ; pharmacokinetics ; Humans ; Immunoconjugates ; pharmacokinetics ; Neoplasms ; drug therapy

OBJECTIVETo investigate the effect of sphingosine kinase 1 (SphK1) on the proliferation, apoptosis, migration and invasion of colon cancer TH-29 cells and to explore its molecular mechanisms.

METHODSPhorbol 12-myristate 13-acetate (PMA) was used to induce the activity of SphK1 and N, N-dimethylsphingosine (DMS) was used to suppress the activity of SphK1. Cell prolieration and apoptosis were detected by MTT assay and flow cytometry, respectively. The migration and invasion capabilities of the cells were assessed in Transwell chambers. The activity of SphK1 was assayed by autoradiography. Western blot was used to evaluate the protein expression of SphK1, p38, phosphorylated p38 (p-p38) and SAPK/JNK.

RESULTSPMA and DMS were able to induce and suppress the activity and protein expression of SphK1 in a time-dependent manner, respectively. PMA enhanced and DMS suppressed the cell viability in a time- and dose-dependent manner. Being treated with 100 nmol/L PMA or 50 µmol/L DMS for 0, 6, 12, 24 h, the cell apoptosis rates of PMA group were (9.35 ± 0.84)%, (7.61 ± 0.48)%, (5.53 ± 0.76)% and (0.56 ± 0.33)%, contrastly, that of DMS group were (9.18 ± 0.94)%, (12.06 ± 1.41)%, (19.80 ± 2.36)% and (31.85 ± 3.60)%, respectively. Compared with the control group, the cell migration and invasion capabilities of the PMA group were significantly enhanced, and that of the DMS group were significantly suppressed. The migration cell number of control, PMA and DMS groups were 68.75 ± 6.15, 109.33 ± 11.63 and 10.83 ± 2.48, the invasion cell number of control, PMA and DMS groups were 55.42 ± 4.50, 90.58 ± 7.06 and 9.58 ± 2.39, respectively. With the elevating activity and expression of SphK1, the protein expressions of p38, p-p38 and SAPK/JNK were strikingly suppressed. On the contrary, after treating with DMS the protein expressions of p38, p-p38 and SAPK/JNK were enhanced.

CONCLUSIONSSphK1 potently enhances the prolieration, migration and invasion of colon cancer HT-29 cells, meanwhile suppresses the cell apoptosis. The suppressing of the p38 and SAPK/JNK signalling pathways may be one of its molecular mechanisms.

Apoptosis ; drug effects ; Carcinogens ; administration & dosage ; pharmacology ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Enzyme Inhibitors ; administration & dosage ; pharmacology ; HT29 Cells ; Humans ; MAP Kinase Kinase 4 ; metabolism ; Neoplasm Invasiveness ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor) ; metabolism ; physiology ; Sphingosine ; administration & dosage ; analogs & derivatives ; pharmacology ; Tetradecanoylphorbol Acetate ; administration & dosage ; analogs & derivatives ; pharmacology ; Time Factors ; p38 Mitogen-Activated Protein Kinases ; metabolism

Based on the technology of platelet proteomics, the key regulatory proteins and pathogenesis of coronary heart disease with phlegm and blood stasis syndrome were explored and analyzed. Based on the previous laboratory research, the model of coronary heart disease in mini-swine with phlegm-stasis cementation syndrome was duplicated. The model was judged by the changes in blood lipid and myocardial tissue characteristics. Furthermore, the platelet proteins were studied by quantitative proteomics, and the differentially expressed proteins were screened. The critical regulatory proteins and biological pathways of coronary heart disease with phlegm-stasis cementation syndrome were analyzed by bioinformatics. After ten weeks of modeling, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL-C), triglyceride (TG), creatine kinase (CK) and creatine kinase-MB (CK-MB) in the model group were significantly increased, reflecting the pathological changes such as increased blood lipid, abnormal coagulation function and myocardial ischemia in the model group. In addition, compared with the sham group, there were 26 up-regulated proteins and 8 down-regulated proteins in the platelets of the model group. Combined with bioinformatics analysis, it was found that differential proteins mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction. Among them, lactate dehydrogenase B (LDHB), alcohol dehydrogenase 5 (ADH5), neuroblastoma ratsarcoma viral oncogene homolog (NRAS) and Kirsten ratsarcoma viral oncogene homolog (KRAS) play a central role when interacting with other proteins and simultaneously participate in multiple action pathways. The results showed that LDHB, ADH5, NRAS, and KRAS may be the marker proteins in CHD with phlegm-stasis cementation syndrome by regulating glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction and other biological processes.

OBJECTIVESTo study the pathologic feature of sudden cardiac death in Yunnan province and to investigate the role of myocarditis.

METHODSDuring the period from 1991 to 2006, there were 29 cases of sudden cardiac death with autopsy performed. Fourteen of these cases were diagnosed to have myocarditis based on Dallas criteria and World Heart Federation's consensus. The clinical and pathologic findings were reviewed. The cardiac conduction system was examined in details by serial sectioning in 3 cases.

RESULTSFourteen cases suffered with myocarditis, which accounted for 48% of all cases of sudden cardiac death studied. The age of the deceased ranged from 8 to 68 years (mean = 30 years), with male-to-female ratio equaled to 9:5. Lymphocytic myocarditis and neutrophil myocarditis were the two major types, affecting 11 and 3 cases, respectively. The inflammatory infiltrates were often patchy rather than diffuse. The inflammatory foci were detected only in 8% to 42% (average = 20%) of the paraffin sections of the heart tissue. These lesions were usually located in the lateral wall of left ventricle and occasionally in interventricular septum and right ventricular wall. Myocardial injury was mild in most cases while patchy myocytolysis or coagulation necrosis was observed only in a few cases. Most of the lesions were relatively new and histologic evidence of myocardial repairing sometimes coexisted. Pericarditis and subacute endocarditis were also identified in 4 and 1 cases, respectively. Atrioventricular node was involved by myocarditis in 1 of the 3 cases examined for cardiac conduction system. Two cases showed gross evidence of cardiac dilatation (either left ventricle or biventricular). Respiratory tract and pulmonary infection was present in 5 cases.

CONCLUSIONSMyocarditis represents one of the major pathologic changes of sudden cardiac death occurring in Yunnan province. The inflammation is usually focal. Further studies are required for delineation of possible etiologies which may include virus, bacteria or exogenous toxin.

Adolescent ; Adult ; Aged ; Atrioventricular Node ; pathology ; Child ; China ; epidemiology ; Death, Sudden, Cardiac ; epidemiology ; pathology ; Dilatation, Pathologic ; pathology ; Endocarditis ; pathology ; Female ; Humans ; Inflammation ; pathology ; Lymphocytes ; pathology ; Male ; Middle Aged ; Myocarditis ; diagnosis ; epidemiology ; mortality ; pathology ; Myocardium ; pathology ; Pericarditis ; pathology

Objective To investigate the efficacy of transplantation of mesenchymal stem cells(MSC) with gelatin micrespheres containing vascular endothelial growth factor in ischemie regions in infracted swine hearts. Methods Twelve Chinese mini swines with infarction were randomized to receive autogenetic MSC injection to the peri-infarction area of left ventricular wall (MSC group, n=6) or MSC transplantation with gelatin hydrogel microspheres incorporating vascular endothelial growth factor (VEGF-MSC group, n=6). Three weeks later, left ventricular function was assessed by magnetic resonance imaging (MRI). The contrast of the MSC hypointense lesion was determined using the difference in signal intensity between the hypointenso and normal myocardium divided by signal intensity of the normal region. Myocardial capillary density, the number of DAPI positive MSC and the apoptotic MSC were also determined. Results The diameter of the microspheres averaged (104.0±22.6) μm. At 24 hours after transplantation, MSC were identified by MRI as large intramyocardial signal voids at injection sites which persisted up to 3 weeks. There was no significant difference in the contrast of the lesions and in the size of the lesions at 24 hours between two groups. At 3 weeks after injection, the size of the lesions and the contrast of the lesion were decreased (P<0.05) in both groups. The capillary density of the injection site was significantly more in the MSC-VEGF microsphere group than that in MSC group [ (15.2±5.4)/HPF vs. (10.2±5.0)/HPF, t=2.43, P<0.05], and there were more dense DAPI labeled MSC per high power fields in injection sites of MSC-VEGF mieresphere group than that in MSC group [(354±83)/HPF vs. (278±97)/HPF, t=3.14, P<0.05]. Moreover, the apoptosis rate of MSCs of MSCs-VEGF mieresphere group was less than that of MSCgroup [(6.4±4.1)% vs. (11.9±4.8)%, t=2.97, P<0.05]. Conclusions MSC transplantation with gelatin hydrogel microspheres incorporating VEGF enhanced the efficacy of MSC in this swine model of myocardial infarction. MRI tracking of MSC is feasible and represents a preferred method for studying the engraftment of MSCs in infracted tissue.

OBJECTIVETo study the relationship of Chinese familial Parkinson disease with alpha-synuclein gene.

METHODSPolymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and polymerase chain reaction-heteroduplex analysis(PCR-HA) were employed to detect the abnormal mobilization in the familial Parkinson disease and sporadic Parkinson disease patients, then it was verified by gene sequencing.

RESULTSNo mutation was found in alpha-synuclein gene exons 3 and 4 by PCR-SSCP together with PCR-HA. An inserted c and an inserted t were found in intron 4, position 23 and position 67 respectively.

CONCLUSION(1) Exons 3 and 4 of alpha-synuclein gene are not the mutational hot spots of Chinese familial Parkinson disease. (2) Two polymorphisms were found in intron 4 of alpha-synuclein gene. They are 23 ins c and 67 ins t.

Adult ; Aged ; Exons ; Female ; Heteroduplex Analysis ; Humans ; Male ; Middle Aged ; Mutation ; Nerve Tissue Proteins ; genetics ; Parkinson Disease ; genetics ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Synucleins ; alpha-Synuclein