The predictive value of right ventricular-pulmonary arterial coupling in patients with pulmonary arterial hypertension / 中国实用内科杂志

OBJECTIVE: To compare the predictive value of Ees/Ea in patients with pulmonary arterial hypertension based on right cardiac catheterization and cardiac magnetic resonance examination. METHODS: A total of 50 pulmonary arterial hypertension patients confirmed by right heart catheterization were retrospectively reviewed and followed up 2 years. The relationship between the baseline clinical data and survival prognosis of patients with pulmonary arterial hypertension were analyzed. The predictive value of baseline Ees/Ea for prognosis in patients with pulmonary arterial hypertension were compared. RESULTS: The Ees/Ea calculated by volume method was significantly correlated with the prognosis of patients with pulmonary arterial hypertension(OR =0.082, 95%CI 0.009-0.814, P=0.032). The two-year survival rate of group Ees/Ea>0.67 was significantly higher than that of Ees/Ea≤0.67(86.7% vs. 50%, P=0.003). Conclution Ees/Ea calculated by volume method is an independent influence factor of the survival prognosis of patients with pulmonary arterial hypertension. When Ees/Ea≤0.67, the patients with pulmonary arterial hypertension is more likely to deteriorate.

Efficacy analysis of unrelated cord blood transplantation in the treatment of refractory and relapsed adult acute leukemia / 中华血液学杂志

Objective: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of refractory and relapsed acute leukemia (AL) patients. Methods: The clinical data of 22 refractory and relapsed AL patients who were treated with UCBT as salvage therapy from November 2009 to May 2017 were retrospectively analyzed. All patients received a myeloablative conditioning regimen for prevention of graft-versus-host disease (GVHD) with cyclosporine A (CSA)/short course of mycophenolate mofetil (MMF). Results: ①Of 22 patients, 9 cases were male and 13 female. The median age was 23 (15-44) years and median weight of 52.5 (43-82) kg. All patients were transplanted with a median umbilical cord blood nucleated cells of 3.07 (1.71-5.30)×107/kg (by weight), the median CD34+ cells was 1.60 (0.63-3.04)×105/kg (by weight). ②The myeloid cumulative implantation rate was 95.5% (95%CI 45.2-99.7%) after transplantation of 42 d, with the median implantation time of 19 (13-27) d. The platelet cumulative implantation rate after transplantation of 120 d was 81.8% (95%CI 54.2-93.6%), the median implantation time of 42 (20-164) d. ③The incidence of Ⅱ-Ⅳ, Ⅲ-Ⅳ aGVHD and the 2 year cumulative incidence of cGVHD were 36.4%, 13.6% and 40.3% respectively. ④ The transplant related mortality (TRM) after transplantation of 180d was 22.7%, 2 year cumulative rate of relapse was 18.7% (95%CI 3.6-42.5%), 2 year disease-free survival rate (DFS) and overall survival rate (OS) were 53.7% and 58.1%, respectively. Conclusion: The preliminary results show that the use of UCBT is safe and effective for refractory and relapsed AL patients who fail to respond to conventional chemotherapy.

Efficacy of endothelin receptor antagonist bosentan on the long-term prognosis in patients after Fontan operation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the long-term effect of bosentan on outcome in patients after Fontan operation.</p><p><b>METHODS</b>Patients after Fontan surgery were randomly divided into bosentan group (B, n = 16) and control group (C, n = 23). Bosentan was applied within 7 days after Fontan surgery as follows: at the first month, 7.8125 mg Bid for patients with body weight ≤ 10 kg; 15.625 mg Bid for patients with body weight between 10-20 kg; 31.25 mg Bid for patients with body weight 20-30 kg and 62.5 mg Bid for patients with body weight > 30 kg. At the second month, the bosentan dose was doubled and Bosentan therapy was continued for more than 1 year. Group C didn't take drugs affecting pulmonary artery pressure. All patients were followed up for 2 years and incidence of mortality, protein losing enteropathy, pulmonary arteriovenous fistulae, 6-minute walk test, heart function were compared between the two groups.</p><p><b>RESULTS</b>After 2 years, mortality tended to be lower in group B compared to group C [6.25% (1/16) vs. 21.8% (5/23), P > 0.05]. Incidence of pulmonary arteriovenous fistulae and protein losing enteropathy were significantly lower in group B than in group C (6.25% vs. 34.78%, P = 0.01;6.25% vs. 39.13%, P = 0.02, respectively) . The results of 6-minute walk test[ (485 ± 44) m vs. (302 ± 183) m] and heart function in group B (3 NYHA III/IV patients in group B vs. 14 NYHA III/IV patients in group C, all P < 0.05) were all better than group C. The concentrations of vasoactive factors such as brain natriuretic peptide (BNP, 279.07 ± 128.17 vs. 457.67 ± 221.30), endothelin (ET, 3.30 ± 0.61 vs. 4.98 ± 1.24) and thromboxane (TXA2, 97.2 ± 24.0 vs. 163.22 ± 24.4) were also significantly lower in group B than in group C (all P < 0.05). Prostacyclin (PGI2) level and incidence of arrhythmias were similar between the two groups. There was no thrombotic event in both groups during follow up.</p><p><b>CONCLUSION</b>Bosentan trerapy in patients post Fontan operation could reduce the incidence of pulmonary arteriovenous fistulae and protein losing enteropathy and improve heart function.</p>

Relationship between Resting Heart Rate and Coronary Syndrome / 中国康复理论与实践

@#Objective To investigate the relationship between resting heart rate (RHR) and coronary heart disease (CHD) and to explore the value of RHR in predicting the occurrence of acute coronary syndrome. Methods 445 patients with CHD were divided into stable angina group and acute coronary syndrome group. RHR, risk factors for coronary heart disease and their correlation were analyzed. Results RHR was higher in the acute coronary syndrome group than in the stable angina group (P<0.01). Logistic regression analysis showed that RHR (OR =1.052, 95% CI: 1.009~1.097, P=0.017), systolic blood pressure (OR=1.027, 95% CI: 1.003~1.053, P=0.031) and hyperglycemia (OR=2.743, 95% CI: 1.207~6.233, P=0.016) were independent risk factors for acute coronary syndrome. Conclusion RHR is an independent risk factor for incidence of acute coronary syndrome.

Monte Carlo simulation in risk analysis of battle casualty forecasting in urban aggressive military action / 第二军医大学学报

Objective: To improve the present method for casualty forecasting using the risk analysis theory. Methods: Empirical data were extracted from 11 urban aggressive combats during and after WW II, and the distribution of daily casualty was determined. Based on quantitative judgment model, several factors such as the number of soldiers, terrain, weather, general situation, suddenness, and combat efficacy were configured; Monte Carlo simulation was applied for simulation,and a forecasting model was setup with Microsoft Excel and Crystal Ball 2000 software for risk analysis of the simulation outcome. Results: The distribution of daily casualty during urban aggressive military action could be represented by normal distribution. With the values of the aforementioned factors, the result of 1000 tests showed that the mean daily casualty rate was 0. 42%, with the standard deviation being 0. 21%. Conclusion: Monte Carlo simulation is an effective means to improve the present casualty forecasting method.

Comparative study on inorganic composition and crystallographic properties of cortical and cancellous bone / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To comparatively investigate the inorganic composition and crystallographic properties of cortical and cancellous bone via thermal treatment under 700 °C.</p><p><b>METHODS</b>Thermogravimetric measurement, infrared spectrometer, X-ray diffraction, chemical analysis and X-ray photo-electron spectrometer were used to test the physical and chemical properties of cortical and cancellous bone at room temperature 250 °C, 450 °C, and 650 °C, respectively.</p><p><b>RESULTS</b>The process of heat treatment induced an extension in the a-lattice parameter and changes of the c-lattice parameter, and an increase in the crystallinity reflecting lattice rearrangement after release of lattice carbonate and possible lattice water. The mineral content in cortical and cancellous bone was 73.2wt% and 71.5wt%, respectively. For cortical bone, the weight loss was 6.7% at the temperature from 60 °C to 250 °C, 17.4% from 250 °C to 450 °C, and 2.7% from 450 °C to 700 °C. While the weight loss for the cancellous bone was 5.8%, 19.9%, and 2.8 % at each temperature range, the Ca/P ratio of cortical bone was 1.69 which is higher than the 1.67 of stoichiometric HA due to the B-type CO₃²⁻ substitution in apatite lattice. The Ca/P ratio of cancellous bone was lower than 1.67, suggesting the presence of more calcium deficient apatite.</p><p><b>CONCLUSION</b>The collagen fibers of cortical bone were arrayed more orderly than those of cancellous bone, while their mineralized fibers ollkded similar. The minerals in both cortical and cancellous bone are composed of poorly crystallized nano-size apatite crystals with lattice carbonate and possible lattice water. The process of heat treatment induces a change of the lattice parameter, resulting in lattice rearrangement after the release of lattice carbonate and lattice water and causing an increase in crystal size and crystallinity. This finding is helpful for future biomaterial design, preparation and application.</p>

Multipotential differentiation and potential applications of adipose-derived stem cells / 生物工程学报

Adipose tissue contains a population of multipotent cells called adipose-derived stem cells (ADSCs). With the similar properties of marrow-derived mesenchymal stem cells, ADSCs have the ability to differentiate differentiate towards adipogenic, osteogenic, chondrogenic, myogenic, endothelial, hematopoietic, hepatic, islet, and neurogenic cell lineages. As adipose tissue in harvested in large amounts with minimal morbidity, it can be widely used in tissue engineering, organ repair and gene therapy. This paper focused on the plasticity of ADSCs and reviewed the new advances of this field. Finally, the problems and prospect for application was also discussed.

The targeting study of human serum albumin gene / 生物工程学报

To generate transgenic porcine which expresses human serum albumin (HSA), the HSA gene targeting vector was constructed with HSA cDNA as the gene of interestand partial porcine serum albumin (PSA) gene as homologous arms which respectively were 7.2 kb 5' regulation sequence and 2.8 kb genomic sequence from the first intron to the fourth intron. The resistant gene neo was inserted into intron 1 and tk was ligated to the 3' end of the construct. Linearized targeting construct DNA was introduced into the fibroblast cells obtained from porcine fetus by electroporation. The positive-negative selection was performed and survival clones were screened by PCR and Southern blot. Three colonies with correct homologous recombination were obtained. Our results set a good basis for the establishment of transgenic porcine by gene target and nuclear transfer methods.

CT perfusion study of acute local cerebral infarction in rhesus monkeys / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the value of CT perfusion in early diagnosis and management of superacute local cerebral infarction in rhesus monkeys.</p><p><b>METHOD</b>Acute local cerebral infarction was induced in the rhesus monkeys during digital subtraction angiography (DSA) by introduction of pale thrombus prepared from autologous blood into the M1 branch of the middle cerebral artery (MCA). Plain CT scan and CT perfusion scanning were performed at different time points before and after DSA operation, and the results were analyzed in conjunction with the pathologic changes.</p><p><b>RESULTS</b>Ischemic lesions were displayed on CT perfusion images, which showed local hypoperfusion, reduced cerebral blood flow and volume, and mean transit time delay in the compromised area. Local hypointense infarct area was identified in plain CT scan 24 h after the DSA operation, and the results were in good agreement with pathological examination during autopsy.</p><p><b>CONCLUSION</b>CT perfusion imaging of the brain can accurately capture the cerebral perfusion deficits in acute ischemic stroke before morphologic changes take place, and therefore provides good means for thrombolytic treatment evaluation of stroke.</p>

Advance of Ser/Thr Kinase Pololike Kinase 1 (Plk1) Research / 中国生物工程杂志

Pololike kinase 1(Plk1)contain an Nterminal Ser/Thr kinase catalytic domain and a Cterminal region that contains two poloboxes.As a key regulator of multiple steps during cell cycle across eukaryotic species,many proteins interact with Plk1.Plk1 is highly expressed in malignant cells and serves as a negative prognostic marker in specific human cancer types.Plk1 is a potential target for cancer therapy.Some novel smallmolecule inhibitors of pololike kinase 1 provide novel opportunities for cancerdrug discovery,such as BI 2536,ON01910.

Cure effects of Jiangu Fufang on osteoporotic model induced by ovariectomy / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the cure effects of Jiangu Fufang on osteoporotic model induced by ovariectomy.</p><p><b>METHOD</b>Rats were ovariectomized and administered drugs for 3 monthes. Bone mineral density and biomechanics properties, histomorphometric analysis and biochemical index such as calcium, phosphorus, alkaline phosphatase were detected.</p><p><b>RESULT</b>Jiangu Fufang could significantly increase bone density and biomechanics properties. The level of calcium, phosphorus and alkaline phosphatase were restored by Jiangu Fufang. Jiangu Fufang could significantly increase area of bone trabecula, thickness of cortical bone and bone trabecula.</p><p><b>CONCLUSION</b>Jiangu Fufang could cure osteoporosis through increasing bone mineral density, improving bone biomechanics properties, and effecting bone metabolism.</p>

The synthesis and function analysis of omega-3 fatty acid desaturase gene from Caenorhabditis briggssae / 生物工程学报

Omega-3 polyunsaturated fatty acids (PUFAs) have been broadly investigated and shown to exert many preventive and therapeutic actions besides their important role in maintenances human health and normal development. In mammals, the level of omega-3 PUFAs is relatively too low compared with omega-6 PUFAs, which metabolically and functionally distinct from omega-3 PUFAs and often have important opposing physiological functions. Either the inefficiency of omega-3 PUFAs or the excess of omega-6 PUFAs will cause many healthy problems. So methods have been sought to increase the amount of omega-3 PUFAs and to improve the omega-6/omega-3 ratio in body. In this study, the sFat-1 gene, which putatively encodes a omega-3 fatty acid desaturase, was chemically synthesized according to the sequence from Caenorhabditis briggssae (with codon usage modified), and constructed into a mammal expression vector pcDNA3. 1-sFat1-EGFP. This vector was introduced into CHO cells by lipid-mediated transfection, and it's expression quickly and effectively elevated the cellular omega-3 PUFAs (from 18-carbon to 22-carbon) contents and dramatically improved the ratio of omega-6/omega-3 PUFAs. Cellular lipids extracts from stably selected cells were analyzed with GC-MS and the results showed that amount of total omega-6 PUFAs dropped from 48.97% (in GFP cells)to 35.29% (in sFat-1 cells), whereas the amount of total omega-3 PUFAs increased from 7.86% to 24.02%, respectively. The omega-6/omega-3 ratio also dropped from 6.23 to 1.47. These data demonstrates the Caenorhabditis briggssae omega-3 Fatty Acid Desaturase gene, sFat-1, was synthesized successfully and can produce omega-3 PUFAs by using the corresponding omega-6 PUFAs as substrates, which shows its potential for use in the production of omega-3 PUFAs in transgenic animals.

The construction and characterization of human pro-urokinase mutant / 生物工程学报

It is very easy for the pro-UK to lose it's biological activity because of the digestion of pro-UK by the thrombin or the inhibition of pro-UK by the PAI-I. So three pro-UK mutant (pro-UK) genes were constructed in this experiment with the PCR point-mutant method. The thrombin cleavage site Arg156 in pro-UK was mutated into His156, and named as pro-UKM1; PAI binding sites Arg178, Arg179, Arg181 were mutated into Lys178, Lys179, His181, named as pro-UKM2; The mutant containing His156, Lys178, Lys179, His181 as pro-UKM3. Three mutants were expressed in CHO cells respectively and analyzed with SDS-PAGE fibrin plate assay and western blot. The results showed that the three mutants and the native pro-UK have the same single electrophoresis band indicating most of the pro-UK was single chain. In vitro plasma clot lysis assays indicated that the pro-UKM1 have the ability to resistant against thrombin digestion; pro-UK2 could resist against PAI inhibition; while pro-UK3 improved resistances against both thrombin and PAI. It looks very promising that the pro-UK3 can be a new medicine of dissolving thrombus.

The ht-PAm cDNA knock-in the goat beta-casein gene locus / 生物工程学报

The production of recombinant protein is one of the major successes of biotechnology, animal cells are required to synthesize proteins with the appropriate post-translational modifications. Transgenic animal mammary gland bioreactor are being used for this purpose. Gene targeting is a more powerful method to produce mammary gland bioreactor, and nuclear transfer from cultured somatic cells provides an wonderful means of cell-mediated transgensis. Here we describe efficient and reproducible gene targeting in goat fetal fibroblasts to place the human tissue plasminogen activator mutant (ht-PAm) cDNA at the beta-casein locus, and would produce the transgenic goat by nuclear transfer. To construct the gene targeting vector pGBC4tPA, the milk goat beta-casein genomic DNA sequence for homologous arms had been cloned firstly. The left arm was 6.3 kb fragment including goat beta-casein gene 5' flanking sequence, and the right arm was 2.4 kb fragement including beta-casein gene from exon 8 to exon 9. The ht-PAm cDNA was subcloned in the goat beta-casein gene exon 2, and the endogenous start condon was replaced by that of ht-PAm. The bacterial neomycin (neo) gene as positive selection marker gene, was placed in the beta-casein gene intron 7, the thymidine kinase (tk) as the negative selection marker gene, was just outside the right arm. The validity of the positive-negative selection vector (PNS), was tested, and targeting homologous recombination (HR) were elevated to 5-fold with the negative selection marker using the drug GANC. The DNA fragment in which two LoxP sequence was delected effectively using Cre recombinase in vitro. Goat fetal fibroblasts were thawed and cultured to subconfluence before transfection, about 10(7) fibroblasts were electoporated at 240V, 600 microF in 0.8 mL PBS buffer containing linear pGBC4tPA. transfected cells were cultured in collagen-coated 96-wellplate for 24h without selection, then added the drug G418 (600 microg/mL) and GANC (2 micromol/L). After 12 days of selection, well separated G418r/GANCr clones were isolated and expanded in 24-wellplate. 244 clones were selected, and only 90 clones could grow and be tested by PCR screening for targeting. The primary result demonstrated that 31 targeting cell clones with homologous recombination events were obtained, and 2 cell clones was verified by DNA sequence analysis on the homologous recombination region.

Experimental studies on male reproductive toxicity of bisphenol A in vitro and vivo / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the effects of Bisphenol A in adult rats and its possible mechanisms.</p><p><b>METHODS</b>BPA (in corn oil) was administered orally to 9-week-old male Sprague-Dawley rats for 14 days (0, 1 and 5 g/kg bw), and incubated primary Sertoli cells from pubertal SD rats with 0, 10(-7), 10(-6), 10(-5), 10(-4) mol/L BPA.</p><p><b>RESULTS</b>After oral administration, a significant decrease in right testis weight was observed in 5 g/kg dose group, but not in the 1 g/kg bw dose group. Germ cells were detached from basement membrane of seminiferous tubules and Sertoli cells in BPA-treated groups. Administration of BPA at 1 g/kg bw and 5 g/kg bw produced both nucleus pycnosis and vacuolized nucleus in germ cells and Sertoli cells. A marked loss in vimentin staining in Sertoli cells from testis of BPA-treated rats was detected. No change in levels of serum estradiol and testosterone was observed after two-week exposure to BPA. In Sertoli cell primary culture, BPA destroyed the cytoskeleton and cell-cell junctions, and elongated Sertoli cells.</p><p><b>CONCLUSION</b>These results suggest that BPA may injure reproductive function of male rats by destroying the cytoskeleton and changing the form of Sertoli cells.</p>

Production of mammary gland bioreactor by gene targeting of somatic cells / 生物工程学报

Producing mammary gland bioreactor showed great advantage over many years, but the level of transgenic expression was low in transgenic animals and the diversity was more great because of the position effect of transgene and the artificial recombination of the gene elements. Gene targeting based on the principle of gene homologous recombination had been studied and applied, because the transgene could be integrated precisely in the chromosome. This review summary the current status of producing mammary gland bioreactor by the technology of gene targeting and nuclear transfer using the somatic cell lines. These aspects were discussed, including the characteristic and difficulties of gene targeting, the strategies to improve the efficiency of gene targeting, the different features of between the strategy of promoter-trap and the Cre-LoxP system, etc; for the others, how to select the cell lines with the different strategies of gene targeting, how to raise the times of cell lines that was cultured after the gene targeting. Somatic cell nuclear transfer offers new and exciting opportunities in the areas of the gene targeting. However, the field as a whole is still difficult and complex. In this paper, we described recent advances and novel approaches, which resulted in progress during the last year. Key problems hindering further progress are addressed, for example, how to increase the efficiency of nuclear transfer. With the technology of gene targeting and nuclear transfer, it should provide a general way to produce specific genetic changes in several mammalian species. We are clearly at the dawn of a new era in mammalian genetic technology.

EFFECT OF INDUCERS ON LEUKEMIA CELL / 第二军医大学学报

The effect of inducers on leukemia cell line K562 was studied in liquid culture system in vitro. Our experimental results showed that hemin induced cells only to produce hemoglobin without suppressing the growth of cells; Butyric sodium inhibited only the growth of cells without induction of hemoglobin; Cytosine arabinoside and harring-tonine could induce the hemoglobin of cells in their toxicant quantification.The results suggest that hemin and butyric sodium may have not be a therapeutic effect on leukemia patient; The effect of induced differentiation and cell toxicity of cytosine arabin- oside and harringtonine may be closely interconnected. Clinically, there is still the possibility of cell toxicity in treatment of leukemia patients with small dosage of those drugs, and the effect of those drugs may be the combination of cell toxicity, induced differentiation and cell sensitivity.