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Objective To detect the binding ability of the molecular probe of neuropilin-1( NRP-1) to mouse ectopic glioma by magnetic resonance imaging ( MRI) . Methods Glioma model mice were pre-pared by glioma tissue transplantation.Thirty tumor bearing mice were randomly selected for tissue anatomy(n=12) and other 18 mice were randomly divided into 3 groups:the control group ( group A) ,the probe con-trol group (group B) and the probe group (group C),which were given 20 μl saline,20 μl USPIO-PEG, 20μl USPIO-PEG-tLyP-1 through the tail vein of the mice respectively.And at 0h,6h,12h,24h after admin-istration,T2WI and T2MAPPING sequences were detected by MRI. Then the tumor bearing mice were killed immediately and the glioma tissue was used to detect the iron content by Prussian blue staining to detect the binding ability of the glioma tissue with the new molecular probe. The biological toxicity of the new molecular probe was detected by pathological staining. Results The expression of NRP-1 in glioma tissues was signifi-cantly higher than that in the liver,kidney and brain(P<0.05).The 24h relaxation time ((14.19±0.87)ms) of the glioma tissue in the C group was significantly lower than that in the B group ((25.94±0.77)ms) (P<0.05) ,and the blue staining particles in the C group were more than those in the B group(P<0.05) . Conclu-sion In the animal experiment,the molecular probe with NRP-1 as the target has obvious targeting effect and good biocompatibility,which provides a clinical basis of glioma for further clinical diagnosis.
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Objectives@#To explore the association between the polymorphism of persistent obesity and genetic variations in the LEP (human leptin gene, LEP) and LEPR (leptin receptor gene, LEPR) genes and different molecular subtypes of breast cancer.@*Methods@#All 703 female patients of breast cancer diagnosed by histopathology in the Sichuan Cancer Hospital or the West China Hospital, excluding patients with metastatic breast cancer or mental disease, were selected as cases from April 2014 to May 2015. At the same time, 805 healthy women received physical examination in medical examination center of Sichuan People Hospital or Shuangliu maternal and child health care hospital, excluding those with therioma, breast disease, and mental disease, were enrolled in control group. A uniform questionnaire was used to collect general information including demographic characteristic, reproductive history height, weight, and so on. And the obesity status in recent 10 years was judged. Time of Flight Mass Spectrometer was used to determine the genotypes of LEP rs7799039, LEPR rs1137100 and LEPR rs1137101, while the multinomial logistic regression analysis was conducted to estimate the effect of risk factors related to breast cancer in different molecular subtypes; and then, the association between polymorphism of persistent obesity, the LEP, LEPR genes and breast cancer of different molecular subtypes was analyzed by binary logistic regression models.@*Results@#The average age of controls was (48.98±8.83) years old, while the age of cases of TNBC, Luminal A, Luminal B, and HER-2+ were (51.43±11.33), (49.94±10.10), (49.73±9.38), (50.50±9.04) years old, respectively. The frequency of genotype LEP rs7799039, LEPR rs1137100 and LEPR rs1137101 in control group was separately 74.8%(1 157/1 546), 83.6%(1 339/1 602) and 88.4%(1 416/1 602); while 77.6% (1 074/1 384), 82.4% (1 155/1 402) and 87.9% (1 232/1 402) respectively in case group. Compared with non-persistent obesity subjects, the persistent obesity ones showed an increased risk in TNBC (OR=3.58, 95%CI: 1.90-6.72), Luminal A (OR=2.65, 95%CI: 1.35-5.21) and Luminal B (OR=1.90, 95%CI: 1.26-2.89) breast cancer. LEP rs7799039-AA was relevant with the upward risk of Luminal B independently (OR=1.30, 95%CI: 1.00-1.69). Besides, persistent obesity was found to have a combined effect on Luminal B (β=3.34, 95% CI: 1.00-11.12) with LEPR rs1137101-GG.@*Conclusion@#Persistent obesity could increase the potential risk of TNBC, Luminal A and Luminal B breast cancer. Women who were suffered from persistent obesity with a genotype of LEPR rs1137101-GG were more susceptible to Luminal B breast cancer.
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Objective@#To explore the effects of X-ray repair cross complementing gene 1 (XRCC1) polymorphism and low dose ionizing radiation exposure on radiology professionals’ peripheral blood lymphocyte micronucleus.@*Methods@#A matched case-control study was designed. From 2013 to 2015, 1 102 radiology professionals with micronucleus test rusults, and 45 cases with present micronucleus were enroled into case group. 180 diagnostic radiology technicians detecting no micronucleus were chosen as control group, cases and controls were 1∶4 mached on gender, age ≤40 or >40 years old. According to the detection of micronucleus levels (0‰, 1‰, 2‰) , the objects of our study were divided into the reference group, the low detection group and the medium detection group. The form of radiation workers’ occupational health examination was used to collect the general baseline of the research objects, history of smoking, drinking, poisonous and harmful material exposure, past medical history, accumulated illuminated dose and lymphocyte micronucleus rates (‰) , etc. Using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) technology for genotyping; Compared the baseline data and radiation exposure level between the differentmicrokernel detection groups; Adopted multivariate logistic regression to analysis the combination effect of XRCC1 Arg399Gln gene polymorphism and accumulated illuminated dosefor micronucleus rate.@*Results@#The accumulated illuminated dose in the reference group, the low detection group and the medium detection group were (23.44±15.23) , (21.76±2.56) , (24.22±18.61) mSv, respectively. There was no statistically significant difference among the groups (P>0.05) . Under the dominant inheritance mode, after adjusted age, smoking and drinking factors, the results suggested that XRCC1 Arg399Gln micronucleus medium detection group compared with the reference group, Arg399Gln-GG as reference, Arg399Gln-GA+AA decreased the occurrence of micronucleus (OR=0.175, 95%CI: 0.036-0.848) . Arg194Trp and Arg280His did not affect the incidence of micronucleus (P>0.05) . Did not find the combination effect of XRCC1 Arg399Gln gene polymorphism and accumulated illuminated dose for micronucleus rate (P>0.05) .@*Conclusion@#XRCC1 Arg399Gln gene polymorphism can affect the incidence of micronucleus, and carrying the XRCC1 Arg399Gln-GA+AA genotype is a protective factor of micronucleus’s occurrence, but low dose ionizing radiation may not affect the occurrence of micronucleus independently.
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Objective To study the clinical effect of personalized intervention on elderly patients with colostomy after Miles operation for rectal carcinoma. Methods 114 cases elderly patients with colonic stoma after Miles operation for rectal cancer from June 2014 to January 2016 were divided into control group and observation group by random number method, 57 cases in each. The control group were treated with routine intervention, while patients in observation group was treated with personalized intervention. the self-care ability score before intervention, the incidence of complications, intervention satisfaction and life quality score were compared between the two groups at the same time. Results The total complication rate in the observation group was significantly lower than that in control group ( 5.25% vs 22.80%) (χ2 = 8.36, P = 0.000); the intervention satisfaction of the observation group was significantly higher than that in control group (91.23% vs 75.44%) (χ2 = 6.60, P = 0.010). After intervention, the self-care ability score and life quality score of observation group were significantly higher than that in control group (P < 0.01). Conclusion The personalized intervention can reduce the complications, significantly improve the patients' life quality score and self-care ability, and effectively alleviate the negative situation, improve the patients intervention satisfaction, with a higher development value, it is worth of clinical promoting.
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Objective To evaluate the effectiveness of melformin sustained release tablets in treatment of patients with abnormal glucose tolerance. Methods 78 cases with abnormal glucose tolerances were selected and divided into two groups. Patients in treatment group took melformin sustained release tablets, while patients in control group took normal therapy. The impaired glucose tolerance (IGT) and body mass index (BMI) were observed and compared. Results The blood glucose level of OGTT 2 h in treatment group was (7.61±1.04)mmol/L, while it was only (9.96±1.08) mmol/L in control group. The BMI of treatment group was 23.71±3.41, while it was 29.53±3.72 in control group. The glycosylated hemoglobin was (5.79±0.41)%, while it was (6.23±0.52)%in control group. The fasting blood glucose in treatment group was (5.34±0.39)mmol/L and in control group was (8.16±0.48)mmol/L. The differences of those indicators between two groups were signiifcant. Conclusion Melformin gains excellent clinical effects in treating patients with abnormal glucose tolerance. It can adjust blood glucose, improve glucose tolerance, and decrease blood glucose level of OGTT 2 h and BMI effectively.
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Objective To observe the expression of forkhead or winged helix transcription 3 (Foxp3) in colon cancer tissue and paracancerous tissue,and detect the level of serum interleukin (IL)-17 in colon cancer patients and healthy human,to explore the changes of regulatory T cell (Treg cell) and Th17 cell in the process of occurrence and development of colon cancer.Methods The expression of Foxp3 in 56 patients with colon cancer and paracancerous tissue and 15 cases with normal colon tissue was measured by immunohistochemical SP method and the level of serum IL-17 was determined by enzyme-linked immunosorbent method.Results The level of serum IL-17 in colon cancer tissue was higher than that in normal colon tissue [(9.1 ± 2.3) ng/L vs.(6.2 ± 1.5) ng/L],and there was significant difference (P =0.007).Foxp3 positive cell number in colon cancer tissue was more than that in normal colon tissue and paracancerous tissue (24.1 ± 6.4 vs.2.7 ± 1.1 and 8.7 ± 2.3),paracancerous tissue was more than normal colon tissue,and there was significant difference (P ＜ 0.01).The level of serum IL-17 in colon cancer tissue with TNM Ⅲ was higher than that in TNM Ⅰ-Ⅱ [(8.5 ± 2.1) ng/L vs.(5.4 ± 0.9) ng/L],Foxp3 was more than that in TNM Ⅰ-Ⅱ (25.8 ± 6.2 vs.18.2 ± 4.4),and there was significant difference (P＜ 0.01).There was no significant difference in the level of serum IL-17 between middle-high differentiated adenocarcinoma and low differentiated adenocarcinoma [(9.4 ± 1.1) ng/L vs.(8.9 ± 1.8) ng/L] (P ＞ 0.05).Foxp3 in middlehigh differentiated adenocarcinoma was more than that in low differentiated adenocarcinoma (26.8 ± 5.5 vs.17.2 ± 3.2),and there was significant difference (P ＜ 0.01).Conclusions Detection of IL-17 and Foxp3 can provide a new way of targeting therapy for colon cancer.IL-17 levels and Foxp3 expression are closely related to the immune status of local tumor tissues,the joint detection is benefitial to the further understanding of the patients with tumor immune state,provide basic information for tumor immunotherapy.
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Objective To construct green fluorescent protein (GFP)-labeled pSELECT-GFP zeohBMP2 eukaryotic expression vector. Methods The encoding fragment of hBMP2 gene was obtained from a recombinant plasmid pcDNA3.1/CT-hBMP2 by using polymerase chain reaction (PCR). hBMP2 gene was inserted into pTA2-T-easy and pSELECT-GFPzeo-MCS eukaryotic expression vector, and then transferred into competence DHSα cells. After screening, pSELEC-GFPzeo-hBMP2 was obtained and identified by sequence analysis. The recombinant vector pSELECT-GFP zeo-rhBMP2 was transfected into CHO cells. The successful trasfection was verified by fluorescence microscope in 48-72 hours. The RT-PCR and immunofluorescence was used to confirm the hBMP2 expression. Western Blotting was used to detect the secretion of hBMP2.Results A 1216 bp fragment was obtained by PCR, the same as expectant fragment. The recombined pSE-LECT-GFPzeo-hBMP2 eukaryotic expression vector was identified by restriction mapping and sequence analysis. The results were identical with that of reported hBMP2 sequence (Genebank NM-001200). The successful transfection was verified by fluorescence microscope in 48-72 hours. The stable expression in eukaryotic cells was confirmed by immunofluorescence and RT-PCR which showed an obvious band between 1000-2000 bp. Western Blotting identified the immunogenicity of recombinant human BMP2 with the molecular weight of about 17×103. Conclusion The pSELECT-GFPzeo-hBMP2 eukaryotic expression vector was constructed successfully.
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BACKGROUND: Bone morphogenetic protein-2(BMP-2) production of targeted cells is promoted by transfection of adenoviral vectors containing gene, but there are some immune responses. Transfection with plasmid as vector holds promise.OBJECTIVE: To explore the feasibility to construct human bone morphogenetic protein-2 eukaryotic expression vector labeled with green fluorescent protein (GFP).DESIGN: Single sample observation.SETTING: Tianjin Hospital.MATERIALS: The experiment was performed at the Key Laboratory of Hormone and Development, Ministry of Health, Tianjin Medical University from March 2006 to March 2007. pcDNA3.1/CT-hBMP2 plasmid containing full-length hBMP2 gene fragment was provided by Dr. Li; bicistronic eukaryotic expression vector pSELECT-GFPzeo-MCS and Zeo was provided by Invivogen; pTA2(R)-T Easy by Dingguo, China; restriction enzymes BamHI and NheI, T4 DNA ligase by Jingmei Biotech; PCR upstream and downstream primer synthesis and sequencing by Augct, Beijing.METHODS: With pcDNA3.1/CT-hBMP2 as template, hBMP2 target fragment was subcloned by PCR binding with designed specific primers. The fragment was bound with pTA2-T-easy and pSELECT-GFPzeo-MCS, separately, and transfected into DH5 α cells. pSELECT-GFPzeo-hBMP2 containing GFP was obtained after screening.MAIN OUTCOME MEASURES: hBMP2 sequence was identified by PCR; whether hBMP2 was cloned into pTA2-hBMP2 and pSELECT-GFPzeo-MCS was identified by digestion and sequencing.RESULTS: A target fragment of 1 216 bp was obtained by PCR amplification, and cloned into pTA2-T-easy and pSELECT-GFPZeo-MCS. The screening and sequencing results showed that the target fragment was 100% matched with BMP2cDNA sequence (NM-001200) from GenBank.CONCLUSION: hBMP2 eukaryotic expression vector labeled with green fluorescent protein is successfully constructed.
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2% hydroxypropyl methyl cellulose (HPMC, medical grade, Taian Ruitai Cellulose Co., Ltd.) was added into calcium phosphate cement (Orthopedics Institute of General Hospital of Chinese PLA) and the mixture was put into distilled water to observe whether the surface was corrupt. Some calcium phosphate cement was immersed in water at different time and the residual cement was weighed 24 hours later. The results showed that there was no surface corruption in calcium phosphate cement with 2% HPMC after shake; the residual weight measured 24 hours later showed that 2% HPMC could shorten calcium phosphate cement cohesion time from 4 minutes to 1 minutes. The experiment indicates that 2% HPMC can significantly increase the waterproof performance of calcium phosphate cement, increase the work time and is adaptable in clinical application.
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OBJECTIVE:To study the efficacy of Urokinase vs.Low Molecular Weight Heparin in the treatment of acute pulmonary thromboembolism.METHODS:A total of 35 patients with acute pulmonary thromboembolism who had no past history of heart and lung diseases were enrolled and randomly assigned to two groups following ultrasonography and pulmonary ventilation/perfusion scanning:15 were given thrombolysis therapy with urokinase,and 20 given anticoagulation therapy with low molecular weight heparin.Symptoms,arterial blood gas analysis,electrocardiogram,echocardiogram were compared in two groups before and after treatment.RESULTS:The patients receiving thrombolysis therapy had better improvement in symptoms,arterial blood gas index,echocardiogram and the pulmonary ventilation/perfusion scanning than in those receiving anticoagulation therapy(P
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0.1), but which were inhibited significantly in the left ventricular cardiac myocytes of the subjects with heart failure(P≤0.05). Both carvedilol and metoprolol exhibited no effect on eNOS activity in all the investigated cardiac myocytes. CONCLUSIONS: Nebivolol does no effect on eNOS activity of left ventricular cadiocytes in subjects or rats without hear failure but it can inhibit eNOS activity of cadiocytes in subjects or rats with heart failure so as to exert its beneficial clinical effect.
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BACKGROUND: Triiodothyronine (T3) is an important regulation factor at the critical period of brain development. It maybe control the successive differentiation during the development of central nervous system (CNS).OBJECTIVE: To monitor the differentiation of neural stem cells (NSCs) induced by T3 and the thyroid hormone receptor (TR) mRNA expression changes.DESIGN: Open experiment.SETTING: Department of Pathology, Tianjin Medical College of Chinese People's Armed Police Force; Institute of Endocrinology of Tianjin Medical University.MATERIALS: This study was carried out in the Tianjin Medical University between January 2003 and March 2005.Ten-to-twelve-week-old aborted fetuses were obtained from the General Hospital of Tianjin Medical University with the approval of the local ethical committee. Informed consents were obtained from the mothers and their relatives.METHODS: ①Under the aseptic condition, the bilateral cortex of human fetal brain was removed and dissociated by brief mechanical trituration in D-Hanks. Then, 20 μg/L bFGF and 30 nmol/L T3 were used to induce the proliferation of NSCs and inoculated to poly-L-lysine-coated 24-well plate and 25 mL culture flask for routine culture at 1 ×109 L-1. The culture medium was DMEM/F12 serum-free complemented with N2. Half of the culture medium was changed every 48 hours.Seven days later, bFGF was discarded, only T3 was used for induction and differentiation. ② At 1, 2 and 3 weeks of culture, cells were collected, and RT-PCR was semiquantitatively used to detect TR mRNA expression changes at different stages of differentiation of NSCs. Isoforms were identified by immuocytochemistry.MAIN OUTCOME MEASURES: ①Cellular morphology observation and isoforms identification before and after differentiation of NSCs induced by T3. ② TR mRNA expression changes during the differentiation of NSCs.RESULTS: ①The hNSCs were round and had a smooth surface and gradually gathered to neurospheres. The proliferative hNSCs were nestin-positive and incorporated BrdU. When NSCs were induced by T3 for one week, most of the cells took on monopole or double poles, and had long and thin processes. The differentiated cells were neurofilament protein (NFP)-positive, galactocerebroside (GC)-positive or glial fibrillary acidic protein (GFAP)-positive. When NSCs were induced by T3 for three weeks, most of the cells were big, with unclear cell membrane, round nucleus, many thick processes which had many branches. The spider-like cells were scattered, and 80% of the cells were myelin basic protein-positive. ② TRα1 mRNA expression level was the highest before inducing NSCs. With the induction of T3, the expression level was decreased gradually, and was the lowest at 2 weeks, and then was rebounded gradually, but the final level was still lower than that of NSC (F =32.49, P =0.008). The tendency of TRα2 mRNA expression alteration was identical with that of TRα1 mRNA. TRβ1 mRNA expression level was the lowest in NSC, was increased gradually with the induction of T3 and attained the highest level at 2 weeks of induction of T3. Furthermore, the expression level of TRβ1 mRNA was also higher than that of TRα1 at the same time (t =15.64,P =0.001), and it reached the lowest level at 3 weeks of the induction. TRα3 expression level was firstly decreased after the differentiation induced by T3, and was close to the expression level of NSC at 2 weeks of induction (F =51.94, P =0.378), then was decreased to lower lever.CONCLUSION: T3 can induce NSC to differentiate into neurons, oligodendrocyte and astrocytes. TR mRNAs are expressed in different time intervals during the differentiation of NSCs.
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BACKGROUND: Clinical observation demonstrates that accelerated fracture healing or lower limb heterotopic ossifications always occur in patients with paraplegia. It indicates that peripheral nervous system may play an important role in fracture healing process.OBJECTIVE: To observe bone histomorphometery parameter, callus formation and biochemical change during the process of fracture healing of unilateral lower limb denervated tibia.DESIGN: Self-control animal experiment.SETTING: Tianjin Hospital.MATERIALS: Totally 36 six-month-old healthy male Wistar rats, with mean body mass of 210 g, were used in this experiment.METHODS: This experiment was carried out at Animal Experimental Center of Tianjin Hospital from March 2001 to March 2004. Denervated tibia fracture model and innervated tibia fracture model were made in the same rat. Animals were executed under anaesthetic status at week 2 and week 4 after fracture. Bilateral tibias were chosen to take radiografts.Biomachamical strength was measured and non-decalcification sections were prepared to perform bone histomorphometery observation.MAIN OUTCOME MEASURES: ① Comparison of wet weight of bilateral tibias and callus of rats between two groups after fracture. ②X-ray plain film scoring. ③ Biomechanical testing of tibial samples. ④ Histomorphological observation of fracture healing RESULTS: ① Wet weight of bilateral tibia and callus of rats in denervated group was much higher than that in innervated group at weeks 2 and 4 after fracture [(0.94±0.15) vs (0.76±0.14) g, (1.06±0.26)vs (0.81±0.10) g,P ＜ 0.05]. ②In X-ray plain film scoring, callus formation was significantly increased in denervated group (P ＜ 0.01). ③In biomechanical testing of three-point bending of tibial sample, callus intensity was significantly lower at weeks 2 and 4 after fracture in denervated group than in innervated group[ (9.88±8.49)vs ( 16.62±13.38 ) N, ( 12.77±7.55 )vs (20.19±10.60) N,P ＜ 0.05]. ④Bone histomorphometery showed that compared with innervated group, mineralized bone trabecula width of denervated group was significantly reduced (P ＜ 0.05), osteoid width was increased , osteoclast index and bone absorption area were significantly increased (P ＜ 0.05), and there were no significant difference of fibroblast index and bone formation area between two groups; Compared with innervated group, mineralized deposition rate in the denervated group was significantly reduced (P ＜ 0.05), the mature time of osteoid was elongated (P ＜ 0.05).CONCLUSION: Peripheral nervous system may play an important role during early and middle period of fracture healing. Intact innervation is essential for normal fracture healing.
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Objective To observe the variations of thyroid hormone receptors(RTs) mRNA experession during the human brain devlopment. Methods We investigated the ontogeny of TR isoforms in the first and second trimester human fetal different brain areas by semi-quantitative reverse transcriptase-polymerase chain reaction analysis. When we amplified the TR? 2 by PCR, the other sequence was amplified at the same time, it is about 100pb less than the RT? 2, so we cloned it into pGEM-T easy vector to determine its sequence. Results In the first and second trimester human fatal brain, RTs mRNAs were detected in cerebrum, cerebellum, brain, stem, hippocampus, spinal cord, thalamus. TRs mRNAs were relatively higher in cerebrum, cerebellum, hippocampus. In the first trimester human fatal brain, the TR? isoforms mRNAs were higher than TR? 1, In the second trimester human fatal brain, the TR? 2 and TR? 1 were higher than TR? 1. An additional truncated species was detected with the TR? 2 primer set. We submitted its sequencing results to Genbank, comparing it with TR? 2 by BLAST software, the results showed that it is identical to TR? 2 with the exception that it is missing 42 amino acids at 371-412 of TR? 2 sequence, so it is the human TR? 3. At the same time we acquired the Genbank accession number AF522368. Conclusion The spatial and temporal expressions of TR isoforms mRNAs exist in CNS development. We firstly assure the different sequence between human TR?2 and TR?3.
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Objective The aim of the study was to assess the human neural stem cells (NSCs) induced by mitogens in vitro and investigate effects of TH(T 3) on differentiation. Methods The cerebral hemispheres of human fetal at 10-12 weeks of gestation were minced and mechanically dissociated. Cells were seeded at a concentration of 10 5 per ml into defined medium that consisted of DMEM/F12 Epidermal growth factor (EGF,20??g/L) and basic fibroblast growth factor (bFGF,20??g/L) were added respectively as mitogens for 7 days. In some cases, triiodothyronine (T 3, 30??g/L) was added through the culture period. Upon differentiation, the cell cultures were exposured to a substrate and treated with or without T 3 after removing the mitogens. To detect the phenotypes of differentiated cells, immunochemistry staining was performed with the antibody to NF 200, GFAP, MBP and Gal C. To recognize the different stages of oligodendrocytes development, the antibodies O4 and A2B5 were used. The proportion of each neural cell type was determined by counting positive cells in standardized fields at 40? magnifications. Results NSCs induced by EGF and/or bFGF grew in culture as free floating spheres(neurospheres) and were immunoreactive for the intermediate filament nestin. After removing EGF and bFGF, the cells cease mitosis and can be induced to differentiate into neurons, astrocytes, and oligodendrocytes regardless of whether T 3 was presented. T 3 favored an neuroglia cell fate especially when combining EGF with T 3 and differentiated cells appeared more early when added of T 3.MBP positive cell is over 80%. The O4 and A2B5 positive cells can be observed at early stage of differentiation only after process grew from neurospheres after adhesion to certain substrate, which indicated that the neuronal network could promote the maturity of oligodendrocyte.Discussion The timing of NSCs differentiation depends on both intracellular mechanisms and extracellular signals. TH is such a signal to activate the effector component of a “clock” mechanism that induces oligodendrocyte differentiation after a limited number of cell divisions.[