Objective To investigate the effects of nitric oxide (NO) inhalation on the expression of TNF-?,IL-8 and CD11b mRNA in lung tissue during acute respiratory distress syndrome (ARDS) induced by intravenous injection of endotoxin in dogs.Methods Twelve pure bred beagle dogs of both sexs weighing 8-12.5 kg were randomly divided into 2 groups: NO group received mechanical ventilation with NO inhalation (n = 6) and control group received only mechanical ventilation ( n = 6) . Sepsis and ARDS were induced by intravenous injection of endotoxin as described in detail in our previous paper. Hemodynamics and pulmonary oxygenation were monitored and shunt fraction was calculated. At the end of experiment the animals were sacrificed and lung tissue was obtained aseptically and stored in the liquid nitrogen at - 180℃ . The total RNA was extracted. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of TNF-?,IL-8 and CD11b mRNA. The total RNA was reversely transcripted to cDNA. Then the cDNA was amplified by PCR. The product of PCR was scanned by gel-image analysis system.?-action was used as internal control. Semi-quantitative method was adopted for measurement of TNF-? ,IL-8 and CD11b mRNA expression. Results The expression of TNF-?, IL-8 and CD11b mRNA in lung tissue was significantly decreased in NO group compared with those in control group.Conclusion NO inhalation reduces expression of TNF-?, IL-8 and CDllb mRNA in lung tissue during ARDS induced by intravenous endotoxin.

The high-fidelity prostate tumor patient-derived xenograft ( PDX) model is the basis for studies of biology and pharmacotherapy of prostate cancer. However, the development and application of prostate tumor has been hampered by a low success rate of transplanted primary tumors in mice as most prostate cancers are highly relevant to hormones. The high-fidelity PDX model of prostate cancer better maintains the histopathology and molecular heterogeneity of the original tumor. Here, we review the improved method of establishing PDX model of prostate cancer, including the testosterone supplementation, the quality of the original tumor tissue as well as the stromal niche, and the application of commonly used therapeutic drugs, and to provide a theoretical basis for clinical studies of prostate tumor. These attempts are very important for development of new agents and research on mechanisms of prostate cancer. It will further promote the individualized treatment of prostate cancer.

The patient-derived orthotopic xenograft (PDOX) model better maintains the genetic characteristics of the primary tumor, and keep stable in histology, transcriptome, polymorphism and copy number variations. It also retains the interaction between the tumor mesenchyma, microvessels and stroma, and the tumor metastatic properties. Therefore, PDOX model can predict disease prognosis more accurately and can be used to screen appropriate individualized treatment strategies, thus, shows perfect prospect in clinical application. However, due to the differences between mouse and human microenvironment, morphological distinctions between orthotopic xenograft tumors and primary tumors still exist, and tumor metastasis can not be ensured by orthotopic xenograft. Thus, in order to construct the individualized PDOX model and to promote its clinical translation, it is necessary to analyze the histomorphology of orthotopic xenografts, to establish database of the transplantation model and share the information of the model. In this review, we will summarize the main features of PDOX models with its advantages and limitations, and looking forward to its application in the future.

A system coupling ethanol fermentation with microalgae culture was developed, in which CO2 produced during ethanol fermentation was used as carbon source for the growth of Tetraselmis subcordiformis, a microalgae accumulating starch intracellularly. The biomass concentration about 2.0 g DCW/L was achieved within the photobioreactor for the batch culture of 7 days, and intracellular starch accumulation was about 45%. Furthermore, ultrasonic pretreatment and enzymatic hydrolysis were applied to the microalgae biomass, and 71.1% of the intracellular starch was converted into glucose that was fermented sequentially to ethanol by Saccharomyces cerevisiae with an ethanol yield of 87.6% of the theoretical value, indicating that the microalgae biomass could be an alternative feedstock for ethanol production to save grain consumption, and in the meantime mitigate the CO2 emission.
Batch Cell Culture Techniques ; Carbon Dioxide ; metabolism ; pharmacology ; Cells, Cultured ; Ethanol ; metabolism ; Fermentation ; Microalgae ; drug effects ; growth & development ; metabolism ; Photobioreactors ; Saccharomyces cerevisiae ; metabolism ; Starch ; metabolism

Objective To investigate the influence of acute hypervolemic hemodilution(HHD)on pharmacokinetics of propofol.Methods Sixteen ASA Ⅰ or Ⅱ patients aged 20-55 yrs undergoing elective surgery under general anesthesia combined with epidural analgesia were randomly allocated into 2 groups(n=8 each);Ⅰ control group and Ⅱ HHD group.The patients were premedicated with intramuscular phenobarbital 0.1 g and scopolamine 0.3 mg.Right internal jugular vein was cannulated for CVP monitoring and blood sampling.Radial artery was cannulated for BP monitoring.All patients in both groups received lactated Ringer's solution(0.7 ml?kg~(-1)? number of hours of fasting before operation)before induction of general anesthesia.In HHD group 4% gelofusine 20 ml?kg~(-1) was infused at the rate of 20 ml?kg~(-1)?h~(-1).Anesthesia was induced with midazolam 0.04 mg?kg~(-1),fentanyl 4 ?g?kg~(-1) and propofol 1.5 mg?kg~(-1).Tracheal intubation was facilitated by succinylcholine 2 mg?kg~(-1).Anesthesia was maintained with isoflurane,fentanyl,vecuronium and epidural analgesia.ECG,BP, SpO_2,P_(ET)CO_2 and CVP were continuously monitored.Blood samples were taken at 1,2,4,6,10,15,30,45, 60,75,90,120,150,180,240,300 and 360 min after propofol was given Ⅳ for determination of plasma concentration of propofol(HPLC).Pharmacokinetic data were analyzed by 3P97 pharmacokinetic software.Results The two groups were comparable with respect to demographic data.Blood propofol concentrations were significantly lower in HHD group than in control group at 1,2,4,6,10 min after propofol injection(P＜0.01), thereafter there was no significant difference in plasma propofol concentration between the two groups(P＞0.05). The pharmacokinetic profile of propofol was well described by a standard three-compartment model.In HHD group V_C was significantly increased,K_(10) and Cl were significantly decreased and T_(1/2?) was significantly prolonged as compared with control group.Conclusion Acute HHD increases V_C,prolongs the T_(1/2?) and decreases K_(10) and Cl, suggesting that the effect of propofol may be potentiated by acute HHD.

OBJECTIVE: To examine the correlation between single nucleotide polymorphism( SNP) in 3' untranslated regions and hearing-related genes and their correlation with susceptibility in noise-induced hearing loss( NIHL) in Chinese Han population. METHODS: A total of 2 507 workers exposed to 72-120 d B( A) of normalized continuous A-weighted sound pressure level equivalent to a 40 h-working-week intensity of continuous noise in three large compressor manufacturing enterprises in Guangzhou were chosen as study subjects by judgment sampling method. A model was set up to define sensitive group( 238 sensitive workers) and resistant group( 238 resistant workers) by testing the workplace noise intensity and worker hearing pure tone threshold test. The genomic DNA from peripheral blood was collected from workers of these two groups. The genetic characteristic analysis was carried out by using the Taq Man probe with chemical fluorescence allelic identification test. RESULTS: The monaural threshold of weighted value( MTWV) of the left ear in sensitive group was higher than that of the right ear( P < 0. 01); the MTWV of left ear and right ear in sensitive group were respectively higher than that of the same ear in resistant group( P < 0. 01). A total of four candidate genes were screened: vesicle associated membrane protein 1( VAMP1),fibroblast growth factor 1( FGF1),potassium inwardly-rectifying channel,subfamily J,member 10( KCNJ10) and myosin IC( MYO1C). The results of SNP loci detection showed that more workers in sensitive group carried FGF1 rs17217562 AC and CC genotype than that of resistant group( P < 0. 05). More workers in sensitive group carried C allele of FGF1 rs17217562 than the resistant group( P < 0. 05). The logistic regression analysis showed that after correcting the confounding factors including age,noise exposure level,length of noise exposure,gender,smoking,drinking,whether or not using headset,organic solvents exposure,heavy metal exposure,high temperature exposure and hand-arm vibration exposure,the people carrying allele of FGF1 rs17217562 had an increased risk of NIHL susceptibility( P < 0. 05). The VAMP1,KCNJ10 and MYO1C gene had no susceptibility correlation with SNP and NIHL.CONCLUSION: Among Chinese Han population,SNP loci located on the FGF1 rs17217562 may be correlated with the susceptibility of NIHL.

Objective: To study the hearing status and analyze the related influencing factors in noise-exposed workers in an automobile manufacture enterprise, and put forward suggestions for prevention of noise-induced hearing loss. Methods: Noise exposure level testing, audiometry testing and questionnaires were performed for noise exposed workers in the automobile manufacture enterprise. To analyze the relationship between different factors and noise-induced hearing loss by cumulative noise exposure(CNE) calculated 8-hour continuous A-weighted equivalent noise level and seniority. Results: The detection rate of hearing loss in noise-exposed workers was 22.8%. The noise exposure intensity of stamping workshop is higher than other workshop, and the hearing loss detection rate of stamping workshop workers is higher than other workshop workers. The detection rate of hearing loss has significant difference in L_{Aeq·8 h}, seniority, CNE, age, high temperature and wearing earplugs (P<0.05). The results of logistic regression analysis showed that CNE, age and high-temperature were risk factors for noise-induced hearing loss (P<0.05 and OR>1) and there was an increasing tendency of hearing loss with increase in length of service and CNE, while using of earplugs was a protective factor (P<0.05 and OR<1). With the increase of CNE, the incidence of hearing loss is the rising trend. Conclusion It is suggested to strengthen the noise control and individual protection and improve the high-temperature working environment, which plays an important role in reducing the occurrence of noise-induced hearing loss.

Objective To evaluate the therapeutic effect of chemotherapeutic drugs on pancreatic carcinoma based on patient-derived xenograft(PDX)models,and to screen an individualized treatment strategy. Methods Fresh human pancreatic carcinoma tissues were subcutaneously transplanted into nude mice to establish PDX models which could be stab-ly passaged. The traceability of PDX models was determined by STR analysis. The PDX models were treated with three dif-ferent clinical chemotherapeutic drugs oxaliplatin, gemcitabine and irinotecan, respectively, and the tumor volumes were measured at different times. The therapeutic effect of those drugs was assessed by TGD mathematical model and plasma CA19-9 test. Results The traceability of patient-derived xenograft samples was up to 99.99%. Compared with the con-trol group,the treatment with irinotecan and gemcitabine inhibited tumor growth significantly(P=0.001), and gemcit-abine had even better result. The minimum toxic effect in the mice was induced by irinotecan treatment,followed by gem-citabine treatment. Conclusions Pancreatic carcinoma PDX models are successfully established and can be stably pas-saged. Gemcitabine shows the most inhibitory effect on tumor growth based on TGD mathematical model assessment, and deserves to be recommended as the preferred drug for individual treatment of pancreatic carcinoma.

Objective:To study the effect of the injected bone marrow mesenchymal stem cells (BMSC) on rats with pulmonary fibrosis induced by paraquat (PQ) during different poisoning periods and explore the potential mechanism.Methods:From October to December 2018, BMSCs of SPF SD rats were isolated and purified by whole-bone marrow adherent culture method and cultured to the Third Generation (P3) . The surface antigens CD29, CD90, CD45 and CD34 of P3 BMSC were detected by Flow cytometry, the formation of alkaline phosphatase (ALP) , calcium nodules and fat droplets were observed by ALP, Alizarin Red staining and oil red O staining. At the same time, 36 SPF male rats were randomly divided into 6 groups: NC Group (Blank Control Group, injected with the same amount of saline) and PQ group (PQ model group, injected with 20% PQ solution 18 mg/kg intraperitoneally) , bMSC-A group, BMSC-B group, BMSC-C group and BMSC-D group were injected with BMSC suspension 1×10 6 cells/mice at 3 h、3 d、7 d and 14 d after PQ poisoning. After 28 days, the rats were killed, the lung organ coefficients were calculated, the hydroxyproline (HYP) content in lung tissue was calculated by alkaline hydrolysis, and the lung injury and fibrosis were observed by HE and Masson staining, serum TGF-1、TNF-α、MMP-9 and TIMP-1 were detected by Elisa. Results:High Purity BMSCs were successfully isolated and obtained. The P3 BMSC generation was positive expression of CD29、CD90、and negative expression of CD34、CD45, and had the potential of osteogenic and adipogenic differentiation. The results of HE staining and Masson staining showed that the alveolar structure in NC group was intact and homogeneous, in PQ group, the alveolar structure was severely damaged and a lot of collagen fibers and fibroblasts were deposited, and the degrees of lung injury in each BMSC intervention group were obviously less than in PQ group, in BMSC-A group and BMSC-B group, the degrees of reduction were obvious. Compared with NC group, the Lung organ coefficient, HYP content in lung tissue and TGF-β1, TIMP-1 levels in serum were significantly higher in PQ group ( P<0.05) , while TNF-α and MMP-9 had no significant difference ( P>0.05) . Compared with PQ group, the lung organ Coefficients, HYP, TGF-1 and TIMP-β1 in BMSC-A and BMSC-B groups were lower than those in PQ group ( P<0.05) . The Lung organ coefficients, TGF-β1 and TIMP-1 in BMSC-C and BMSC-D groups were lower than those in PQ group, there was no significant difference ( P>0.05) . Conclusion:Early BMSC injecting can alleviate pulmonary fibrosis induced by PQ. The mechanism may be that BMSC can reduce pulmonary fibrosis through reducing the level of TGF-β1 and regulating the balance of TIMP-1/MMP-9, threrby reducing inflammatory damage and increasing the degradation of extracellular matrix (ECM) .

Objective:To study the effect of the injected bone marrow mesenchymal stem cells (BMSC) on rats with pulmonary fibrosis induced by paraquat (PQ) during different poisoning periods and explore the potential mechanism.Methods:From October to December 2018, BMSCs of SPF SD rats were isolated and purified by whole-bone marrow adherent culture method and cultured to the Third Generation (P3) . The surface antigens CD29, CD90, CD45 and CD34 of P3 BMSC were detected by Flow cytometry, the formation of alkaline phosphatase (ALP) , calcium nodules and fat droplets were observed by ALP, Alizarin Red staining and oil red O staining. At the same time, 36 SPF male rats were randomly divided into 6 groups: NC Group (Blank Control Group, injected with the same amount of saline) and PQ group (PQ model group, injected with 20% PQ solution 18 mg/kg intraperitoneally) , bMSC-A group, BMSC-B group, BMSC-C group and BMSC-D group were injected with BMSC suspension 1×10 6 cells/mice at 3 h、3 d、7 d and 14 d after PQ poisoning. After 28 days, the rats were killed, the lung organ coefficients were calculated, the hydroxyproline (HYP) content in lung tissue was calculated by alkaline hydrolysis, and the lung injury and fibrosis were observed by HE and Masson staining, serum TGF-1、TNF-α、MMP-9 and TIMP-1 were detected by Elisa. Results:High Purity BMSCs were successfully isolated and obtained. The P3 BMSC generation was positive expression of CD29、CD90、and negative expression of CD34、CD45, and had the potential of osteogenic and adipogenic differentiation. The results of HE staining and Masson staining showed that the alveolar structure in NC group was intact and homogeneous, in PQ group, the alveolar structure was severely damaged and a lot of collagen fibers and fibroblasts were deposited, and the degrees of lung injury in each BMSC intervention group were obviously less than in PQ group, in BMSC-A group and BMSC-B group, the degrees of reduction were obvious. Compared with NC group, the Lung organ coefficient, HYP content in lung tissue and TGF-β1, TIMP-1 levels in serum were significantly higher in PQ group ( P<0.05) , while TNF-α and MMP-9 had no significant difference ( P>0.05) . Compared with PQ group, the lung organ Coefficients, HYP, TGF-1 and TIMP-β1 in BMSC-A and BMSC-B groups were lower than those in PQ group ( P<0.05) . The Lung organ coefficients, TGF-β1 and TIMP-1 in BMSC-C and BMSC-D groups were lower than those in PQ group, there was no significant difference ( P>0.05) . Conclusion:Early BMSC injecting can alleviate pulmonary fibrosis induced by PQ. The mechanism may be that BMSC can reduce pulmonary fibrosis through reducing the level of TGF-β1 and regulating the balance of TIMP-1/MMP-9, threrby reducing inflammatory damage and increasing the degradation of extracellular matrix (ECM) .