电容法在线活细胞量传感器在黑曲霉带渣发酵生产柠檬酸中的应用

以黑曲霉带渣发酵生产柠檬酸的培养过程为对象,探讨了用电容法在线活细胞量传感器测量复合培养基中可结团丝状菌的活细胞量的可能性。通过实验确定了仪器的最佳分析条件:低通滤波值为60,测定频率为双频(580,10 085 kHz)。实验结果表明,电容法活细胞量传感器的电容值与活细胞量之间有着较好的线性对应关系,其线性相关系数为0.994。在发酵培养液采用带渣发酵的情况下,考察了在线活细胞电容值与常规的离线测定菌浓方法,如细胞干重、波长600nm处吸光度OD600和菌体离心体积之间的关系结果表明,在0～20 h,各离线参数与电容值之间的线性相关系数最好的仅为0.91。同时利用在线活细胞传感器的电容值能较好地估计出比生长速率,比通过在线间接参数OUR、CER估计更准确。因此,电容传感器为黑曲酶带渣发酵提供了一个可靠的工具。

在线活细胞定量检测模型的建立及其在辅酶Q10中的应用

在类球红细菌发酵生产辅酶Q10的过程中,其菌体生长代谢情况及产物合成与有活力的细胞量密切相关。活细胞传感仪通过利用细胞的介电特性,能够检测发酵液中的活细胞量,且检测结果不受死细胞、气泡的影响。在辅酶Q10的发酵过程中,运用活细胞传感仪采用全频扫描模式对检测到的电容值进行校正,校正后的电容值与CFU具有良好的线性关系,R^(2)=0.995,可以准确预测发酵液中菌体生长状态和活细胞量。基于电导率和校正后的电容值对辅酶Q10发酵过程中补料策略进行优化,辅酶Q10产量最终达到3420 mg/L。

基于活细胞量测量的利福霉素发酵过程氮源优化策略

在发酵生产利福霉素SV的过程中,其菌丝体的生长代谢情况及产物发酵合成都与有活力的菌丝量密切相关。介绍了在线活细胞传感仪测定活细胞量的方法,它利用细胞的介电特性,能够排除发酵液中固含物的干扰,测得的电容值与活细胞浓度呈线性相关,可以作为工艺优化过程中的关键参数。通过电容变化反映的前期生长出现的二次生长现象,进行了通过使用迟效氮源豆饼粉代替了原培养基中价格昂贵的速效氮源蛋白胨,成功消除了发酵前期由于氮源利用转换造成的生长停滞期,利用豆饼粉情况下培养前期的OUR和CER达到了14.8和15.3 mmol/L/h,明显高于利用速效氮源蛋白胨A组的8.6和11.3 mmol/L/h,保证了持续较高的比生长速率,对于促进菌体的氧消耗速率的增加和维持有着重要的作用,明显有利于利福霉素的合成与速率的维持,氮源替代组的发酵效价达到了5969±19 U/ml,与对照组(5030±17U/ml)相比显著提升发酵单位18.7%以上。

Impact of comorbid anxiety and depression on quality of life and cellular immunity changes in patients with digestive tract cancers

AIM:A study was performed to investigate the impact of comorbid anxiety and depression (CAD) on quality of life (QOL) and cellular immunity changes in patients with digestive tract cancers. METHODS: One hundred and fifty-six cases of both sexes with cancers of the digestive tract admitted between March 2001 and February 2004 in the Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University were randomly enrolled in the study. Depressive and anxiety disorder diagnoses were assessed by using the Structured Clinical Interview for DSM-IV. All adult patients were evaluated with the Hamilton depressive scale (HAMD, the 24-item version), the Hamilton anxiety scale (HAMA, a modified 14-item version), quality of life questionnaire-core 30 (QLQ-C30), social support rating scale (SSRS), simple coping style questionnaire (SCSQ), and other questionnaires, respectively. In terms of HAMD ≥ 20 and HAMA ≥ 14, the patients were categorized, including CAD (n = 31) in group A, anxiety disorder (n = 23) in group B, depressive disorder (n = 37) in group C, and non-disorder (n = 65) in group D. Immunological parameters such as T-lymphocyte subsets and natural killer (NK) cell activities in peripheral blood were determined and compared among the four groups. RESULTS: The incidence of CAD was 21.15% in patients with digestive tract cancers. The average scores of social support was 43.67±7.05 for 156 cases, active coping 20.34±7.33, and passive coping 9.55±5.51. Compared with group D, subjective support was enhanced slightly in group A, but social support, objective support, and utilization of support reduced, especially utilization of support with significance (6.16 vs7.80, P<0.05); total scores of active coping decreased, while passive coping reversed; granulocytes proliferated, monocytes declined, and lymphocytes declined significantly (32.87 vs 34.00, P<0.05); moreover, the percentage of CD3, CD4, CD8 and CD56 in T lymphocyte subsets was in lower level, respectively, and CD56 showed a significant decline in group A (26.02 vs 32.20, P<0.05), however, CD4/CD8 ratio increased. Physical function, role function, fatigue, sleeplessness and constipation had significant changes among different groups by one-way ANOVA, and group A was in poor QOL. It revealed that global health-related quality of life (QL) were positively correlated with active coping and CD56; CAD was negatively correlated with QL, active coping and CD56. Furthermore, the step-wise regression analysis suggested that utilization of support, CD56, active coping, fatigue, sleeplessness and depression were significant factors contributing to QOL. CONCLUSION: CAD, which can impair QOL and cellular immunity, occurs with a higher incidence in patients with digestive tract cancers. Hence, it is essential to improve mental health for them with specifically tailored interventions.

Comparison of laparoscopic vs open liver lobectomy(segmentectomy) for hepatocellular carcinoma

AIM:To investigate the effects of laparoscopic hepatectomy for the treatment of hepatocellular carcinoma(HCC) .METHODS:From 2006 to January 2011,laparoscopic hepatectomies were performed on 30 cases of HCC at Northern Jiangsu People's Hospital. During this sametime period,30 patients elected to undergo conventional open hepatectomy over laparoscopic hepatectomy at the time of informed consent. The degree of invasiveness and outcomes of laparoscopic hepatectomy compared to open hepatectomy for HCC were evaluated.RESULTS:Both groups presented with similar bloodloss amounts,operating times and complications. Patients in the laparoscopic hepatectomy group started walking and eating significantly earlier than those inthe open hepatectomy group,and these more rapid recoveries allowed for shorter hospitalizations. There were no significant differences between procedures insurvival rate.CONCLUSION:Laparoscopic hepatectomy is beneficial for patient quality of life if the indications are appropriately based on preoperative liver function and the location and size of the HCC.

Survival,recovery and microcystin release of Microcystis aeruginosa in cold or dark condition

Microcystis often dominates phytoplankton in eutrophic lakes and must survive a long period of cold or dark conditions. However, the survival strategies of Microcystis to withstand cold or dark stress are less well known. In this study, we conducted experiments on the responses of two toxic Microcystis aeruginosa strains （FACHB-905 and FACHB-915） and their microcystin release in conditions of low temperature （15℃ or 4℃, with illumination） or darkness, and subsequent recovery in standard conditions （25℃ with illumination）. On exposure to 15℃, a small decrease in cell viability was observed, but the cell number increased gradually, suggesting that M. aeruginosa FACHB-905 and FACHB-915 cells seem in general tolerant in 15℃. Interestingly, our results show that a higher carotenoid content and microcystin release potentially enhance the fitness of surviving cells at 15℃. M. aeruginosa cells exposed to lower temperature light stress （4℃） did not completely lose viability and retained the ability to reinitiate growth. In darkness, the maximum quantum yield （Fv/Fm） and the maximum electron transport rate （ETRmax） values and cell viability of M. aeruginosa cells gradually decreased with time. During the recovery period, the photosynthetic efficiency of M. aeruginosa reverted to the normal level. Additionally, M. aeruginosa FACHB-905 and FACHB-915 exposed to low temperature had increased caspase-3-1ike activity and DNA fragmentation, which suggests the occurrence of a type of cell death in M. aeruginosa cells under cold stress similar to programmed cell death. Overall, our findings could confer certain advantages on the Microcystis for surviving cold or dark conditions encountered in the annual cycle, and help explain its repeated occurrence in water blooms in large and shallow lakes.

Esophagus and regenerative medicine

In addition to squamous cell carcinoma,the incidence of Barrett's esophagus with high-grade dysplasia and esophageal adenocarcinoma is rapidly increasing worldwide.Unfortunately,the current standard of care for esophageal pathology involves resection of the affected tissue,sometimes involving radical esophagectomy.Without exception,these procedures are associated with a high morbidity,compromised quality of life,and unacceptable mortality rates.Regenerative medicine approaches to functional tissue replacement include the use of biological and synthetic scaffolds to promote tissue remodeling and growth.In the case of esophageal repair,extracellular matrix(ECM) scaffolds have proven to be effective for the reconstruction of small patch defects,anastomosis reinforcement,and the prevention of stricture formation after endomucosal resection(EMR).More so,esophageal cancer patients treated with ECM scaffolds have shown complete restoration of a normal,functional,and disease-free epithelium after EMR.These studies provide evidence that a regenerative medicine approach may enable aggressive resection of neoplastic tissue without the need for radical esophagectomy and its associated complications.

Shenfu injection plus vinorelbine for elderly patients with non-small cell lung cancer in promoting the quality of life: a randomized controlled clinical trial

Objective： The present study aimed to investigate the efficacy of Shenfu injection plus vinorelbine on the promotion of the quality of life （QOL） in elderly non-small cell lung cancer （NSCLC） patients. Methods： A randomized single blind trial method was used. Forty-six patients with stage IIIB-IV of HSCLC were randomly divided into experimental group and control group. In the experimental group, the patients were treated with 50 mL Shenfu injection from day 1 to 14, plus vinorelbine （NVB） 25 mg/m^2 on day 1 and 8. In the control group, the patients were only treated with NVB 25 mg/m^2 on day 1 and 8. After two cycle＇s of treatment, QOL, efficacy and toxicity were observed. Results： The QOL was enhanced in both experimental group and control group. However, the difference of KPS after treatment in the experimental group was markedly higher than in the control group （14 ± 10 vs. 8 ± 10, t = 2.116, P = 0.04）, improvement rate of QOL was better than in the control group （76.2% vs. 45.0%, χ^2 = 4.188, P = 0.041）, treatment related toxicity in the experimental group was also markedly lower than in the control group （χ^2 = 3.866, P = 0.049）, but the difference of efficacy between the two groups was not significant （14.3% vs. 15.0%, χ^2 = 0.161, P = 0.688）. Conclusion： Shenfu injection plus vinorelbine can enhance QOL in elderly NSCLC patients.

Competition between TRAF2 and TRAF6 Regulates NF-κB Activation in Human B Lymphocytes

Objective To investigate the role of TNF receptor-associated factor 2 (TRAF-2) and TRAF6 in CD40-induced nuclear factor-κB (NF-κB) signaling pathway and whether CD40 signaling requires TRAF2. Methods Human B cell lines were transfected with plasmids expressing wild type TRAF2 or dominant negative TRAF2,TRAF2-shRNA,or TRAF6-shRNA. The activation of NF-κB was detected by Western blot,kinase assay,transfactor enzyme-linked immunosorbent assay (ELISA),and fluorescence resonance energy transfer (FRET). Analysis of the role of TRAF-2 and TRAF-6 in CD40-mediated NF-κB activity was examined following stimulation with recombinant CD154. Results TRAF2 induced activity of IκB-kinases (IKKα,IKKi/ε),phosphorylation of IκBα,as well as nuclear translocation and phosphorylation of p65/RelA. In contrast,TRAF6 strongly induced NF-κB activation and nuclear translocation of p65 as well as p50 and c-Rel. Engagement of CD154-induced nuclear translocation of p65 was inhibited by a TRAF6-shRNA,but conversely was enhanced by a TRAF2-shRNA. Examination of direct interactions between CD40 and TRAFs by FRET documented that both TRAF2 and TRAF6 directly interacted with CD40. However,the two TRAFs competed for CD40 binding. Conclusions These results indicate that TRAF2 can signal in human B cells,but it is not essential for CD40-mediated NF-κB activation. Moreover,TRAF2 can compete with TRAF6 for CD40 binding,and thereby limit the capacity of CD40 engagement to induce NF-κB activation.

Anemia and digestive diseases: An update for the clinician

Anemia and iron deficiency are so common in digestive diseases that often are underestimated and undertreated. Our goal is to review from classif ication to treatment of the diverse types of anemias in different digestive diseases to update our knowledge on diagnosis and treatment. With the goal of improving the prognosis and quality of life of digestive diseases patients, we will review current transfusion, intravenous iron, and erythropoietin roles in the treatment of anemia.

Effect of hypoxia on the blood of large yellow croaker (Pseudosciaena crocea)

Large areas of hypoxic water have recently been reported in the East China Sea. It is hypothesized that hypoxia may be partially responsible for the decline of some fish stocks. We evaluated the effect of hypoxia on large yellow croaker (Pseudosciaena crocea). The fish were exposed to three concentrations of dissolved oxygen (DO; 1.5 mg/L and 2.0 mg/L, and 6.5 mg/L control). We collected blood after 6, 12, 24, 48, and 96 h exposure. There was a significant increase in red blood count, hematocrit, hemoglobin concentration, and mean corpuscular hemoglobin in the group exposed to 1.5 mg/L DO after 6 h or 12 h, and a delayed increase (only elevated after 48 h and 96 h) in these indices in the group exposed to 2.0 mg/L DO. Plasma glucose concentrations increased significantly in both hypoxic groups after 24 h. Furthermore, plasma lactate and lactate dehydrogenase activity increased significantly after the first 6 h exposure in both hypoxic groups. Our results suggest that large yellow croakers could not maintain the aerobic pathway and instead use anaerobic metabolism for survival when DO levels fall below 2.0 mg/L. We conclude that the occurrence of hypoxia (<2 mg/L DO) in the East China Sea could cause metabolic stress for large yellow croakers and may be partially responsible for the population decline of this species.

电容法在线测定发酵过程中毕赤酵母浓度的研究

活细胞量是与细胞生长、代谢、生产力相关的重要生理参数。在线活细胞测定仪能够利用电容的原理检测发酵液中的活细胞量。本文详细介绍了国产在线活细胞测定仪的检测原理,并说明了其在毕赤酵母发酵过程中的应用情况。结果表明,我们设计的在线活细胞测定仪能够直接、实时、在线获得发酵过程中可靠的活细胞量,且有效避免采样操作的干扰。这一技术符合过程分析技术(PAT)的要求,并可以与其他参数相结合进行分析,作为发酵过程开发、控制和优化的有利工具。

Cytotoxicity of mitochondrial-targeting silica-coated manganese oxide nanoparticles

The mitochondrion is a promising target for diagnosis and therapy. Mitochondrial-targeting silica-coated manganese oxide nanoparticles(Mn O@Si O2-PPh3+ NPs) were successfully synthesized to explore the mitochondrial cytotoxicity of nanoparticles. The mitochondrial targeting property was confirmed by a laser scanning confocal microscopy experiment. Even after incubation for only 4 h, the cytotoxicity of Mn O@Si O2-PPh3+ NPs against cancer cells was obvious; the ATP content was significantly decreased to 40%; and the mitochondrial membrane potential was depleted. All of these results indicated the collapse of mitochondrial function and the start of a cell apoptosis pathway. Our findings suggest that mitochondrial-mediated apoptosis could be strengthened by targeting to the subcellular compartment.