Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; pathology ; DNA Mutational Analysis ; DNA, Neoplasm ; genetics ; isolation & purification ; Genes, erbB-1 ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Mutation ; Paraffin Embedding ; methods ; Polymerase Chain Reaction ; methods ; Real-Time Polymerase Chain Reaction ; methods ; Receptor, Epidermal Growth Factor ; genetics

Objective To understand the mechanism of how cardiomyocytes exit from the cell cycle,we examined the expression of polo-like kinase 1(plk1) in the postnatal developmental process of cardiac myocytes. Methods Mitotic Index(MI) of cardiomyocytes was examined in the neonatal,2-week-old,4-week-old,and adult rat hearts(five cases per groups) by double immunofluorescence stained with H3P and ?-sarcomeric actin antibodies.plk1 mRNA and protein expression during the postnatal developmental process of cardiac myocytes were detected by RT-PCR and Western blot analysis in rat hearts. Results The MI of cardiomyocytes in 0-day-old hearts(0.905?0.087%) was approximately 2.4 times over that in 2-week-old hearts(0.372?0.094%)(P

The therapeutic effects and mechanisms of traditional Chinese kidney-tonifying drugs in treating osteoporosis have become the focus under study. Pharmacological studies have shown that traditional Chinese kidney-tonifying drugs are promoters for the proliferation of osteoblasts, inhibitors for the activity of osteoclasts, regulators for the estrogen level and its receptor, plays important roles in promoting osteogenesis and suppressing adipogenesis of marrow mesenchymal stem cells (MSCs), modulating the function of OPG/RANK/RANKL system and the metabolism of calcium and phosphorus, as well as antioxidation. The anti-osteoporotic active ingredients and pharmacological action mechanism of traditional Chinese kidney-tonifying drugs are summarized from the perspective of molecular and cell biology in this paper, so as to provide references for the study of their mechanism of anti-osteoporosis and for the development of traditional Chinese kidney-tonifying and bone-strengthening drugs.
Animals ; Bone and Bones ; drug effects ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Kidney ; drug effects ; physiopathology ; Osteoporosis ; drug therapy ; physiopathology

Objective To screen thyroid function among planned pregnant women in Chongqing, to guide prenatal and postnatal care. Methods Proportional multi-stage stratified cluster random sampling method was adopted to enroll 11 953 planned pregnant women for questionnaire, physical examination, and serum samples collection. Results The median TSH was 2. 04 mIU/ L, P25 = 1. 36 mIU/ L,P75 = 2. 99 mIU/ L. TSH levels being normal, higher, and lower than the reference were 91. 47% , 6. 20% , and 2. 33% , respectively. In Northeast Chongqing, the proportions of median TSH level and TSH level above the upper limit were higher than those in other regions(P<0. 05). With improved education, proportions of TSH above the upper limit and below the lower limit declined(P<0. 05). With the increase in body mass index, the proportion of those whose TSH was above the upper limit showed elevated trend(P<0. 05). In women with history of adverse pregnancy outcomes, their median TSH was higher than that in the control group, and those, whose TSH level exceeded the upper limit, yield higher results than those in the control group(P<0. 05). In women with higher fasting blood glucose The median TSH level was lower than that in normal blood glucose group( P<0. 05), with the fasting plasma glucose concentration and TSH negatively correlated(P<0. 05). Conclusion The abnormal rate of TSH level in planned pregnant women was 8. 53% in Chongqing. The abnormal rate varies by different regions, education levels, body mass indexes, and blood glucose levels. Previous history of adverse pregnancy outcomes was related to elevated TSH levels. It is necessary to take pre-pregnancy thyroid function screening investigation.

Objective To explore the role of dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) in the tubulointerstitial lesions of immune-mediated nephrotoxic nephritis (NTN) and the intervention regulation by anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb). Methods WKY rats were randomly divided into control,NTN and PsL-EGFmAb-treated groups. The mrs in NTN group were injected with 1 ml nephrotoxic rabbit serum per kilogram of rat body weight; the ones in PsL-EGFmAb-treated group were injected with 2 mg PsL-EGFmAb per kilogram of rat body weight simultaneously and 2 h later after nephrotoxic rabbit serum injection; and those in control group were injected with equal volume of 0.9% saline. Renal function and pathology were observed at day 4, 7 and 14 after the induction of NTN. Distribution of DC-SIGN + dendritic cells (DCs) in renal tissues was measured by immunofluorescence. Real-time PCR was performed to examine the expression of P-selectin,RANTES, TNF-α, IL-10, IFN-γ and IL-4. Expression of MHC Ⅱ , CD80 and DC-SIGN on dendritic cells was analyzed by flow cytometry. Transendothelial migration was used to detect the ability of DCs migration. DCs ability to activate T cells was determined by mixed lymphocyte reaction (MLR). ELISA was used to detect the concentration of IFN-γ and IL-4 in the supernatant of MLR. Results At day 4, immature DC-SIGN+ DCs infiltrated the rat renal tubulointerstium of NTN group, matured at day 14, and enhanced the ability to migrate and activate T cells. The distribution of DC-SIGN + DCs was significantly related to the form of crescent, tubulointerstial lesions and renal function. In addition, expression of chemokine RANTES and proinflammatory cytokine TNF-α continuously augmented since day 4, while anti-inflammatory eytokine IL-10 decreased after markedly increased at day 4. At day 14, IFN-γ/IL-4 mRNA increased, which was obviously related to DCs maturation. The intervention of PsL-EGFmAb supressed the expression of DC-SIGN and CD80 on DCs, depressed DCs maturation, migration and ability to activate T cells,down-regulated proinflammatory cytokines and up-regulated anti-inflammatory cytokines in kidney,and thus regulated Th1/Th2 bias. At the same time, kidneys showed the decrease of crescents,improvement of tnbulointerstium damage and renal function. Conclusions DC-SIGN may mediate DCs tubulointerstitial infiltration. It may be also a potent regulator of local immune reaction imbalance and pathology of tubulointerstium. PsL-EGFmAb may depress DCs migration and downregulate DCs maturation and function through DC-SIGN, and thus having a role in prevention and treatment.

OBJECTIVETo explore the efficacy of tumor-ablative individualized allogeneic hematopoietic stem cell transplantation for the treatment of patients with high risk/refractory leukemia.

METHODSFivety-seven patients with high risk/refractory leukemia were enrolled. Tumor-ablative individualized conditioning regimens included HDAra-C + Bu/Cy, Ara-C + Bu/Fludarabine, G-CSF primed HDAra-C + Bu/Cy, and FLAG followed by reduced-intensified BuCy. Overall survival (OS), disease free survival (DFS), graft versus host disease, infection and relapse post grafting were analyzed.

RESULTSFifty-six patients attained durable engraftment. The median follow-up duration was 17.5 (2 - 34) months. The 18 months probabilities of OS and DFS were (74.7 ± 6.1)% and (62.4 ± 6.7)%, respectively. In addition, the 18 months probabilities of OS and DFS in patients who attained complete remission (CR) before transplantation were (74.2 ± 7.1)% and (58.8 ± 8.1)%, respectively, while in those not attained CR were (77.0 ± 11.8)% and (72.7 ± 11.7)%, respectively. Twenty nine patients developed acute GVHD (aGVHD) (grade I in 18, grade II in 4, grade III in 2 and grade IV in 5). The probabilities of aGVHD was (50.9 ± 6.6)% by Kaplan-Meier curve analysis. The probabilities of grades 2-4 and grades 3-4 aGVHD were (19.3 ± 5.2)% and (12.3 ± 4.3)% respectively. Extensive chronic GVHD (cGVHD) was observed in 36 patients. The probabilities of cGVHD was (64.3 ± 6.4)% by Kaplan-Meier curve analysis. Cytomegaloviremia (CMV) was observed in 39 (68.42%) patients, hemorrhagic cystitis in 13 (22.8%) patients, fungous infection in 16 (28.07%) patients and bacterial infection in 38 (66.67%) patients. Relapse occurred in 14 patients (hematologic relapse in 11 and extramedullary relapse in 3), probabilities of relapse being (24.6 ± 5.7)%. The 17.5-month probability of relapse in patients who attained CR before transplantation was (28.1 ± 7.7)%, while in those not attained CR was (15.6 ± 10.2)%. Fifteen patients died (6 from hematological relapse, 5 from infection of bacterial and fungous, 4 from cGVHD) after 100 days.

CONCLUSIONTumor-ablative individualized allogeneic hematopoietic stem cell transplantation is a promising and safe choice for treatment of high risk/refractory leukemia, even with high leukemia burden.

Cytarabine ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; Transplantation Conditioning

OBJECTIVE: To determine whether the introducer curving technique is useful in decreasing the degree of tilting of transfemoral Tulip filters. MATERIALS AND METHODS: The study sample group consisted of 108 patients with deep vein thrombosis who were enrolled and planned to undergo thrombolysis, and who accepted transfemoral Tulip filter insertion procedure. The patients were randomly divided into Group C and Group T. The introducer curving technique was Adopted in Group T. The post-implantation filter tilting angle (ACF) was measured in an anteroposterior projection. The retrieval hook adhering to the vascular wall was measured via tangential cavogram during retrieval. RESULTS: The overall average ACF was 5.8 +/- 4.14 degrees. In Group C, the average ACF was 7.1 +/- 4.52 degrees. In Group T, the average ACF was 4.4 +/- 3.20 degrees. The groups displayed a statistically significant difference (t = 3.573, p = 0.001) in ACF. Additionally, the difference of ACF between the left and right approaches turned out to be statistically significant (7.1 +/- 4.59 vs. 5.1 +/- 3.82, t = 2.301, p = 0.023). The proportion of severe tilt (ACF > or = 10degrees) in Group T was significantly lower than that in Group C (9.3% vs. 24.1%, chi2 = 4.267, p = 0.039). Between the groups, the difference in the rate of the retrieval hook adhering to the vascular wall was also statistically significant (2.9% vs. 24.2%, chi2 = 5.030, p = 0.025). CONCLUSION: The introducer curving technique appears to minimize the incidence and extent of transfemoral Tulip filter tilting.
Blood Vessel Prosthesis Implantation/instrumentation/*methods ; Chi-Square Distribution ; Device Removal ; Double-Blind Method ; Female ; Femoral Vein ; Humans ; Male ; Middle Aged ; Prosthesis Design ; Pulmonary Embolism/*prevention & control ; Statistics, Nonparametric ; Thrombolytic Therapy ; Treatment Outcome ; *Vena Cava Filters ; Venous Thrombosis/*complications

PURPOSETo evaluate midazolam sequential with dexmedetomidine for agitated patients undergoing weaning to implement light sedation in ICU.

METHODSThis randomized, prospective study was conducted in Tianjin Third Central Hospital, China. Using a sealed-envelope method, the patients were randomly divided into 2 groups (40 patients per group). Each patient of group A received an initial loading dose of midazolam at 0.3-3mg/kg·h 24 h before extubation, followed by an infusion of dexmedetomidine at a rate of 0.2-1 μg/kg·h until extubation. Each patient of group B received midazolam at a dose of 0.3-3 mg/kg·h until extubation. The dose of sedation was regulated according to RASS sedative scores maintaining in the range of -2-1. All patients were continuously monitored for 60 min after extubation. During the course, heart rate (HR), mean artery pressure (MAP), extubation time, adverse reactions, ICU stay, and hospital stay were observed and recorded continuously at the following time points: 24 h before extubation (T1), 12 h before extubation (T2), extubation (T3), 30 min after extubation (T4), 60 min after extubation (T5).

RESULTSBoth groups reached the goal of sedation needed for ICU patients. Dexmedetomidine was associated with a significant increase in extubation quality compared with midazolam, reflected in the prevalence of delirium after extubation (20% (8/40) vs 45% (18/40)), respectively (p= 0.017). There were no clinically significant decreases in HR and MAP after infusing dexmedetomidine or midazolam. In the group A, HR was not significantly increased after extubation; however, in the group B, HR was significantly increased compared with the preextubation values (p < 0.05). HR was significantly higher in the group B compared with the group A at 30 and 60 min after extubation (both, p <0.05). Compared with preextubation values, MAP was significantly increased at extubation in the group B (p < 0.05) and MAP was significantly higher at T3, T4, T5 in the group B than group A (p < 0.05). There was a significant difference in extubation time ((3.0 ± 1.5) d vs (4.3 ± 2.2) d, p < 0.05), ICU stay ((5.4 ± 2.1) d vs (8.0 ± 1.4) d, p < 0.05), hospital stay ((10.1 ± 3.0) d vs (15.3 ± 2.6) d, p <0.05) between group A and B.

CONCLUSIONMidazolam sequential with dexmedetomidine can reach the goal of sedation for ICU agitated patients, meanwhile it can maintain the respiratory and circulation parameters and reduce adverse reactions.

Adult ; Aged ; Critical Care ; methods ; Delirium ; drug therapy ; etiology ; Dexmedetomidine ; administration & dosage ; Female ; Humans ; Hypnotics and Sedatives ; administration & dosage ; Intensive Care Units ; Length of Stay ; Male ; Midazolam ; administration & dosage ; Middle Aged ; Prognosis ; Prospective Studies ; Respiration, Artificial ; adverse effects ; methods ; Risk Assessment ; Statistics, Nonparametric ; Treatment Outcome ; Ventilator Weaning ; adverse effects ; psychology

OBJECTIVETo study the effects of glial cell derived neurotrophic factor (GDNF) on regeneration of facial nerve defects by autogenous facial vein conduit.

METHODSThirty-six rabbits were used in this study and 10 mm-length facial nerve defects were made on both sides of all animals. The nerve gaps were bridged using autogenous posterior facial vein graft of the same side. The animals received injection of either saline (group A, n=16) or GDNF (group B, n=16) into the veins. Nerve function was evaluated by evoking nerve action potential immediately after operation and 4, 8 and 16 weeks after operation. Regenerated nerve samples were harvested at 4, 8, and 16 weeks after operation and processed for histology and transmitting electron microscopic examination (TEM).

RESULTSAction potential did not exist immediately after operation but it was evoked at 4, 8, and 16 weeks in both groups. At 4 and 8 weeks after operation, the amplitude and width of action potential were significantly higher in group B than group A (P < 0.01), except wave width at 4 weeks, which showed no significant differences, while the latency period was significantly shorter in group B than that in group A (P < 0.01). At 16 weeks, action potential was similar between two groups, except wave amptitude, which was higher in group B than group A (P < 0.01). Morphologic and TEM examinations showed more matured myelinated nerve fibers and active Schwann's cells in group B when compared group A during the whole regeneration process.

CONCLUSIONGDNF can promote nerve regeneraat early stage during reconstruction of facial nerve defects by autogenous facial vein conduit and combination of GDNF and autogenous vein graft provides a valuable method for clinical reconstruction of facial nerve defects.

Animals ; Facial Nerve ; Nerve Growth Factors ; Nerve Regeneration ; Neuroglia ; Rabbits ; Regeneration

The pharmaceutical ethynylestradiol (EE) is a potent endocrine modulator. Application enlargement of ethynylestradiol in clinics and abuse in livestock farming and fishing make it important to explore ethynylestradiol toxicological action on vertebrate embryonic development and to establish an in vivo method for EE toxicity detection efficiently and conveniently. In the present study, using a model animal zebrafish and 17alpha-ethynylestradiol as a representative compound, we have investigated EE2 teratogenicity, target tissues and target genes on zebrafish embryo. The results show that median teratogenesis concentration (TC50) of EE2 is 0.8 microg x mL(-1), and median lethal dose (LD50) is 3.3 microg x mL(-1). Targets of EE2 action were implicated in brain, eyes, heart, muscle, skeleton, pigment and viscera. Embryonic cardiac arrhythmia caused by EE2 is probably resulted from heart abnormal structure. The embryonic stage sensitive to EE2 mainly started at cleavage and last up to the organogenesis with time-accumulating effect. RT-PCR results indicate that EE2 treatment disturbed gene expression pattern at the early period of zebrafish embryonic development by suppressing transcription of gene boz that promotes brain development, upregulating genes for trunk and tail, such as ntl, spt, shh, and perturbing Nodal signal expression of TGFbeta superfamily, for example, cyc, sqt and oep. Using zebrafish, an efficient in vivo method for quick evaluation of EE toxicity on embryonic development has been developed.
Abnormalities, Drug-Induced ; etiology ; Animals ; Arrhythmias, Cardiac ; chemically induced ; embryology ; Dose-Response Relationship, Drug ; Embryo, Nonmammalian ; abnormalities ; drug effects ; Embryonic Development ; drug effects ; Ethinyl Estradiol ; administration & dosage ; toxicity ; Gene Expression Regulation, Developmental ; Teratogens ; toxicity ; Zebrafish ; abnormalities ; embryology