Total Survival Research Articles

Effect of stocking density and feeding regime on larval growth, survival, and larval development of Japanese flounder, Paralichthys olivaceus, using live feeds

This research examined the effect of initial stocking density and feeding regime on larval growth and survival of Japanese flounder, Paralichthys olivaceus. Larval rearing trials were conducted in nine 50‐L tanks with different initial stocking densities combined with different feed rations (20 larvae/L with standard feed ration [LD], 80 larvae/L with standard feed ration [HD], and 80 larvae/L with four times the standard feed ration [HD+]). Larvae were stocked on 0 days posthatch (DPH) following hatching of the fertilized embryos. Larval total length (TL), survival rates, and final densities were observed on larval settlement (32 DPH) to evaluate larval rearing performance. At 32 DPH, there were no significant differences (p > .05) in TL or survival rates between the LD (46.5 ± 17.0%) and HD+ (40.3 ± 9.4%). The TL and survival rate of HD (23.1 ± 3.5%) were significantly lower than that of LD and HD+ (p < .05). However, the larval density of HD was significantly higher than that of LD (p < .05). HD+ achieved the best larvae production (32.27 ± 7.51 larvae/L), supported by sufficient food source, high water exchange, and proper water quality management (routine siphoning, surface skimming). The larval‐rearing protocols and larval development from hatching to metamorphosis is described in detail, with corresponding photographs taken during the experiment.

'Love at first sight': The effect of personality and colouration patterns in the reproductive success of zebrafish (Danio rerio).

Individual differences in animal personality and external appearance such as colouration patterns have both been extensively studied separately. A significant body of research has explored many of pertinent ecological and biological aspects that can be affected by them and their impact upon fitness. Currently little is known about how both factors interact and their effect on reproductive success. In this study, we evaluated two major parameters contributing to the fitness of the species: reproduction and offspring survival. We selected two different phenotypes of the zebrafish (Danio rerio) selected by their colouration patterns: phenotype 1) named Wild type, UAB line (WT-UAB) with a homogeneous colouration pattern (clear and defined lateral stripes) and phenotype 2) Wild type indefinite (WT-I) had a heterogeneous colouration pattern and different degrees of lateral stripe definition. All animals were also screened for personality. We then compared their reproductive success (spawning rate) and offspring survival at different stages, from egg to larvae, and for 2 successive generations (parental generation was G0; First and second generations were G1 and G2 respectively). Our results show that personality traits were the main source of variability between the fitness components measured: both personalities had similar total numbers of eggs spawned but proactive animals, for both colour phenotypes, had higher reproductive success. This was reflected in a higher percentage of spawning viability at 1day post fertilization (dpf), higher total survival and growth rates at larval stages. Proactive phenotypes from WT-UAB population had a higher overall fitness in comparison to the other phenotypes studied. Our findings imply that fitness of this species when kept under similar husbandry conditions is significantly influenced by parental personality and not by their external appearance. Under these conditions the reproductive success is enhanced. The implications of this study are important for zebrafish breeding and husbandry in captivity and are relevant toward understanding the underlying drivers of trait selection in natural environments.

The mid-term follow-up study of capecitabine combined with oxaliplatin in the treatment of 26 patients with advanced gastric cancer

Objective To investigate the effect of XELOX chemotherapy protocols on the prognosis of patients with advanced gastric cancer. Methods From May 2014 to May 2016, a total of 52 patients with advanced gastric cancer in the Western Branch of the Second Hospital of Shanxi Medical University were selected and divided into control group and study group according to the random number table, with 26 cases in each group.The control group was treated with the FOLFOX chemotherapy protocols, and the study group was treated with the XELOX chemotherapy protocols.All the patients were treated for 3 cycles.After treatment, the clinical efficacy and serum gastrin-17 (GAS-17) levels before and after treatment of the two groups were statistically analyzed.At the end of the treatment and following up until now, the survival rate of the two groups was statistically analyzed. Results The effective rate of the study group (76.92%) was significantly higher than that of the control group (50.00%)(χ2=4.064, P<0.05). After treatment, the serum level of GAS-17 of the two groups decreased compared with before treatment, and which of the study group was lower than that of the control group (t=7.399, P<0.05). The median progression free survival (9.3 months) and median total survival (12.6 months) in the study group were longer than those in the control group(all P<0.05). Conclusion XELOX chemotherapy in the treatment of advanced gastric cancer can effectively reduce the level of serum GAS-17, improve the therapeutic effect and prolong the duration of life of the patients. Key words: Stomach neoplasms; Antineoplastic combined chemotherapy protocols; Capecitabine; Oxaliplatin; Gastrins; Follow-up studies

The relationship between total cholesterol and survival rate in patients with myocardial infarction

The relationship between total cholesterol and survival rate in patients with myocardial infarction

Clinical characteristics and prognosis of 34 cases of acute myeloid leukemia with FLT3 internal tandem duplication and MLL gene rearrangement

目的探讨同时伴FLT3-ITD突变及MLL基因异常的急性髓系白血病（AML）患者的临床特征及转归。方法回顾性分析34例同时伴FLT3-ITD突变及MLL基因异常的AML患者的临床资料，比较化疗、化疗加靶向药物治疗及allo-HSCT的疗效及影响因素。结果34例同时伴FLT3-ITD突变及MLL基因异常的AML患者占同期住院AML患者的2.02%。入院时WBC>30×109/L的患者占63.6%，其中WBC>50×109/L者占39.4%。FAB亚型中以M5比例最高，占35.3%，染色体核型异常者达63.6%，其中复杂异常占12.1%。34例患者中仅有FLT3-ITD及MLL基因异常（双基因异常）者11例（32.4%），具FLT3及MLL以外的1种及1种以上的基因异常（多基因异常）者23例（67.6%）。34例患者2个疗程完全缓解（CR）率为29.4%，7例（20.6%）化疗≥3个疗程后CR，CR患者的早期复发率为52.9%。WBC>50×109/L以及多基因异常的患者2个疗程CR率较低（7.7%、5.4%），其中具有3种以上基因异常的患者无一例CR。34例患者2年总生存（OS）率为28.8%（95%CI 13.5%~46.0%），2年无病生存（DFS）率为27.1%（95% CI 12.5%~44.0%）。18例仅使用化疗或化疗加靶向药物治疗的患者，17例在2年内死亡，1例放弃治疗后失访。接受allo-HSCT治疗的患者3年OS率为43.4%（95%CI 13.7%~70.4%），3年DFS率为42.7%（95% CI 13.4%~69.7%）。结论同时伴FLT3-ITD突变及MLL基因异常的AML患者FAB分型以M5多见，常伴高白细胞血症、细胞遗传学异常及多基因异常。患者化疗缓解率低，早期复发率高，长期生存率低。高白细胞血症、多基因异常可能是此类患者疗效差的重要原因，allo-HSCT可改善患者的转归。

Decrease in total lesion glycolysis and survival after yttrium-90-radioembolization in poorly differentiated hepatocellular carcinoma with portal vein tumour thrombosis

This study aims to evaluate the prognostic role of the decrease in total lesion glycolysis (TLG) assessed by fluorine-18-fluorodeoxyglucose (F-FDG) PET-computed tomography (CT) 1 month after yttrium-90-radioembolization (Y-RE) in patients affected by hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT). Twenty-one patients with histologically proven poorly differentiated HCC and evidence of PVTT at the enhanced multislice CT underwent Y-RE. All patients underwent an F-FDG PET-CT scan at baseline and 1 month after the loco-regional therapy. The variation in TLG (ΔTLG) between the two studies was calculated. Patients were divided in two groups (group 1: 1 month ΔTLG >50%, group 2: ΔTLG <50%). Statistical analysis was carried out to assess the prognostic role of TLG in overall survival (OS). On the 21 patients enrolled, all presented a decrease in TLG after the administration of Y-microspheres. The OS was 11.5±1.2 months. Nine out of 21 (42.9%) patients showed ΔTLG more than 50% with a mean OS of 16.8±1.3 months, whereas the remaining 12 (57.1%) patients had ΔTLG less than 50% with a mean OS of 7.5±0.5 months. Statistical analysis showed ΔTLG to be a significant (P<0.001) predictor of survival. None of the other examined variables including age, Child-Pugh classification, previously performed therapies, the presence of extrahepatic metastases, α-fetoprotein and bilirubin levels had a significant prognostic impact on patients' outcome. Decrease in TLG measured by F-FDG PET-CT is correlated with a trend towards a longer median survival in patients affected by HCC and PVTT who have undergone Y-RE.

Long-term Outcomes of Temporal Hollowing Augmentation by Targeted Volume Restoration of Fat Compartments in Chinese Adults.

Previous anatomical and clinical studies have suggested that targeted restoration of the volume and distribution of fat compartments using appropriate cannula entry sites and injection planes is an excellent fat-grafting technique for facial contouring and hand rejuvenation. To perform subjective and objective evaluations of the safe and effective profile of the targeted fat-grafting technique for temporal hollowing augmentation. In a retrospective cohort study, a total of 96 consecutive patients with temporal hollowing were treated at the Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai, China, with the targeted fat-grafting technique from January 1, 2009, to January 1, 2017. The safety and efficacy profile of this technique was evaluated by the following methods: (1) a quantitative measurement of fat-graft survival and temporal augmentation rates by using 3-dimensional laser scanning, (2) a subjective assessment using a satisfaction survey and the Hollowness Severity Rating Scale (grades range from 0-3, with higher grades representing more hollowness), and (3) the complication rate. Of the 96 study patients, 94 (97.9%) were women and the mean (SD) age was 34.4 (7.4) years. Of the 142 autologous fat-grafting procedures performed, the mean (SD) total follow-up time was 16.3 (3.2) months, with a mean (SD) of 1.5 (0.7) procedures performed. The mean (SD) baseline volume requirement per temple for each patient was 12.8 (4.8) mL, and the total volume of the fat graft per temple was 17.8 (7.5) mL. Quantitative analysis revealed that the mean (SD) total augmentation volume per temple was 11.7 (3.0) mL, the total survival rate of the fat grafts was 65.7% (12.6%), and total augmentation rate of hollowness was 91.4% (23.4%). Subjective analysis revealed that all patients showed an improved appearance after fat grafting, and 142 temples (74.0%) exhibited clinical improvement by more than 2 grades. In all, 88 patients (91.7%) were satisfied with the outcomes, with a low complication rate reported. The targeted fat-grafting technique allows the transplant of fat tissue into 4 separate fat compartments in a double-plane manner through a unique cannula entry site that avoids severe neurovascular injury. The long-term results demonstrate that this technique is an effective, reproducible, and safe approach for temporal hollowing augmentation. 4.

Challenges in using CellTracker Green on foraminifers that host algal endosymbionts.

The uses of fluorescent microscopy and fluorescent probes, such as the metabolically activated probe CellTracker™ Green CMFDA (CTG), have become common in studies of living Foraminifera. This metabolic requirement, as well as the relatively quick production of the fluorescent reaction products, makes CTG a prime candidate for determining mortality in bioassay and other laboratory experiments. Previous work with the foraminifer Amphistegina gibbosa, which hosts diatom endosymbionts, has shown that the species is capable of surviving both acute chemical exposure and extended periods of total darkness by entering a low-activity dormant state. This paper explores the use of CTG and fluorescent microscopy to determine mortality in such experiments, as well as to explore the physiology of dormant foraminifers. The application of CTG was found to be complicated by the autofluorescence of the diatom symbionts, which masks the signal of the CTG, as well as by interactions between CTG and propylene glycol, a chemical of interest known to cause dormancy. These complications necessitated adapting methods from earlier studies using CTG. Here we present observations on CTG fluorescence and autofluorescence in A. gibbosa following both chemical exposure and periods of total darkness. While CTG can indicate vital activity in dormant foraminifers, complications include underestimates of total survival and recovery, and falsely indicating dead individuals as live due to rapid microbial colonization. Nonetheless, the brightness of the CTG signal in dormant individuals exposed to propylene glycol supports previously published results of survival patterns in A. gibbosa. Observations of CTG fluorescence in individuals kept for extended periods in aphotic conditions indicate uptake of CTG may begin within 30 min of exposure to light, suggesting darkness-induced dormancy and subsequent recovery can occur on short time scales. These results suggest that CTG accurately reflects changes associated with dormancy, and can be useful in laboratory experiments utilizing symbiont-bearing foraminifers.

Clinical characteristics of long-term survival with noninvasive ventilation and factors affecting the transition to invasive ventilation in amyotrophic lateral sclerosis.

We evaluated post-noninvasive ventilation survival and factors for the transition to tracheostomy in amyotrophic lateral sclerosis (ALS). We analyzed 197 patients using a prospectively collected database with 114 patients since 2000. Among 114 patients, 59 patients underwent noninvasive ventilation (NIV), which prolonged the total median survival time to 43 months compared with 32 months without treatment. The best post-NIV survival was associated with a lack of bulbar symptoms, higher measured pulmonary function, and a slower rate of progression at diagnosis. The transition rate from NIV to tracheostomy gradually decreased over the years. Patients using NIV for more than 6 months were more likely to refuse tracheostomy and to be women. This study confirmed a positive survival effect with NIV, which was less effective in patients with bulbar dysfunction. Additional studies are required to determine the best timing for using NIV with ALS in patients with bulbar dysfunction. Muscle Nerve 58:770-776 2018.

Clinical effect of selective bronchial artery infusion chemotherapy for central squamous cell carcinoma of the lung

Objective To investigate the clinical effect of selective bronchial artery infusion chemotherapy for central squamous cell carcinoma of the lung. Methods 93 cases of central lung squamous cell carcinoma patients who were treated in our hospital from February 2015 to February 2017 were enrolled in the study. They were divided into the observation group (n=45) and the control group (n=48) according to the patients' final treatment. The observation group was treated with bronchial artery perfusion chemotherapy, and the control group was treated with systemic venous chemotherapy. The short-term effect and the improvement of lung function in the two groups were observed, and the prognosis of the patients was followed up. Results The short-term effect of the observation group was better than that of the control group (P<0.05), and the total effective rate of the observation group was 95.56%; The forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) of the observation group were (75.39±6.88)% and (78.19±7.79)%, respectively, which were significantly higher than those in the control group (P<0.05). The reoperation ratio of the observation group was 44.44% after chemotherapy, which was significantly higher than that of the control group, with statistically significant difference (P<0.05). The median total survival time of the observation group was 17 months, which was significantly higher than that of the control group, with statistically significant difference (P<0.05). The incidence of adverse reaction in the observation group was 6.67%, which was significantly lower than that in the control group, with statistically significant difference (P<0.05). Conclusions Selective bronchial artery infusion chemotherapy for central lung cancer is effective and worthy of clinical application. Key words: Carcinoma, squamous cell/DT; Lung neoplasms/DT; Bronchial arteries/SU; Chemotherapy, cancer, regional perfusion

Economic evaluation of postoperative hypofractionated radiation therapy in patients with breast cancer

Breast cancer remains the most common malignant neoplasm in women. According to the current standards, radiation therapy is one of the most important components of the multi-disciplinary treatment. The efficacy of the postoperative radiotherapy in both the traditional fractionation regimen and in the hypofractionation mode is not questioned. Contrary to the conventional fractionation, hypofractionation implies an increase in the daily dose and a reduction in the total treatment time. This approach helps reduce the treatment costs in patients with breast cancer while maintaining a high treatment efficacy and quality of life.The aim of the study was to analyze the economic efficiency of the dose hypofractionation as compared to the traditional mode of dose fractionation during postoperative radiation therapy in patients with breast cancer.Materials and methods. The study included 220 patients with breast cancer who received a combined treatment. Of these, 120 patients (study group) received hypofractionated radiotherapy (40.5 Gy in 15 fractions) whereas 100 patients of the control group were treated by the conventional therapy of 50 Gy in 25 fractions. Patients of the both groups were comparable by stages of the disease, systemic treatment, age and molecular type of tumor. The cost of treatment was calculated from the price list of this research center.Results. The present economic analysis showed that the method of hypofractionation was more (30% on average) cost-efficient than the conventional regimen while both modalities produced similar rates of total and relapse-free survival. We were then able to identify the main items in the list of medical services that contributed to the estimated difference in the treatment costs. Reducing the number of examinations and the treatment duration help reduce the expenditure of this medical organization.Сonclusion. Hypofractionation of postoperative radiotherapy in patients with breast cancer allows one to reduce the treatment costs as compared to the conventional fractionation regimen. The funds saved by optimizing the costs of postoperative radiation can be directed to the development of additional means of cancer treatment.

The mode of progressive disease affects the prognosis of patients with metastatic breast cancer

BackgroundAccording to the Response Evaluation Criteria in Solid Tumors (RECIST), progressive disease (PD) is diagnosed under two conditions: an increase in size of pre-existing lesions (IS) and the appearance of new lesions (NL). We retrospectively investigated the difference in the prognosis between IS and NL.MethodsPatients receiving drug therapies for metastatic breast cancer between 2004 and 2015 at our institution were reviewed. The survival time after NL and IS was compared and the frequency of NL with each drug calculated.ResultsFor the 107 eligible patients, the survival time after NL at second-line chemotherapy was significantly worse than after IS (median survival time 4.3 months vs. 20.3 months, p = 0.0048). Maintenance therapy with bevacizumab or trastuzumab had a high frequency of NL (88.9%), and third-line eribulin had a low frequency of NL (16.7%). A multivariate analysis showed that NL at second-line chemotherapy was not an independent risk factor (hazard ratio 1.02, 95%; confidence interval 0.54–1.93, p = 0.95) for the total survival time.ConclusionsPatients with IS had a better survival after PD than those with NL. We may be able to avoid changing drug therapy for patients without NL and allow them to continue drug therapy for longer.

Effects of sowing time and seeding rates on the field germinability and survival of winter wheat

The aim and tasks of the study. The study purpose was to determine the integrated effect of sowing time, seeding rates, and weather conditions during the growing season on the field germinability and survival of bread winter wheat plants, variety Astet.Material and methods. The study was carried out in the eight-field fallow-grain-tilled crop rotation in the experimental field of the Chair of Plant Production of the KhNAU nd. a. VV Dokuchaev. The experiment was laid out by the conventional split plot method. The first order plots were the following sowing time variants: (1) – September 5–7; (2) – September 15–17; (3) – September 25–27. The second order plots were seeding rates of 4.0, 4.5, 5.0 and 5.5 mln seeds/ha. The cultivation technology, except for the issues under investigation, was conventional for the study region. The experiment was conducted in four replicas; the total number of the second order plots was 48. The area of the elementary registration plot was 45 m2.Results and discussion. Of the studied agrotechnical factors, the sowing time had the greatest effect on the variability of the field germinability of winter wheat seeds. The shares of seeding rates were negligible: 0.5% after bare fallow steam and 2.7% after buckwheat. The effect of anthropogenic factors was more pronounced on the total survival of plants. This was observed on winter wheat crops sown after buckwheat. Thus, the shares of the seeding rates and sowing time in the total variability of the survival of winter wheat sown after bare fallow were 6.0% and 2.5%, respectively, and after buckwheat – 21.4% and 6.0%, respectively. There was no significant effect of interaction between any of the agrotechnical factors under study. A tendency of the interaction effect was only noticed.Conclusions. We proved the influence of the seeding rate and sowing time on the variability of the total survival of bread winter wheat plants during the vegetation period. The best field germinability of seeds and the plant survival in most of the study years were achieved with sowing time (2) (September 15–17).To plant survival to a greater extent depended on the seeding rate, with the share in the change in this index of 21.4% after bare fallow and 6.0% after buckwheat.The increase in the seeding rate from 4.0 mln seeds/ha to 5.0 mln seeds/ha did not significantly reduced the plant survival after the both predecessors, which gives grounds to consider the seed rate variations within this range as possible without significant reduction in the plant survival, that is, without significant aggravation of competition between them.

Effects of acetamiprid on life cycle development of predatory mite Amblyseius cucumeris (Acari: Phytoseiidae) after contact exposure

Amblyseius cucumeris (Oudemans) is a beneficial non-target arthropod (NTA) and a key predator of pest mites in integrated pest management (IPM) programs across china. The toxic effects of insecticides have been extensively reported on predatory mites, but few studies devoted to the toxicity of compounds to A. cucumeris. In this study, the effects of a single application of acetamiprid against the A. cucumeris were investigated in a 48-h acute and a 30-d chronic test. In both tests the insecticide acetamiprid was applied once. In the acute test, the “open glass plate method” was used, with a 48-h LC50 value of 223.6 (149.8–336.9) mg a. i. L−1 for adult female. The LC50 was 1.49-fold the Maximum field recommended concentration. In the chronic test, exposure concentrations (1.12, 2.24, 4.47, 8.94, and 22.4 mg a. i. L−1) were designed based on a preliminary 48-h LC50 value for adult female. Above treatment levels of 2.24–4.47 mg a. i. L−1 reduce the total development time, survival rates and food consumption of A. cucumeris in different development stages. In addition, at acetamiprid concentrations higher than 2.24 mg a. i. L−1 serious effect on the capacity of oviposition of female adults were observed. However, even the highest treatment level of 22.4 mg a. i. L−1 did not affect egg hatching rates of exposed eggs. Acetamiprid had significant adverse effects on different development life stages of A. cucumeris. The results provide informative data for implementing biological and chemical control strategies in integrated pest management of spider mites.

MiR-329 regulates the sensitivity of 5-FU in chemotherapy of colorectal cancer by targeting E2F1.

Colorectal cancer (CRC) is a common digestive system malignancy with high morbidity and mortality. Accumulating studies have shown that miRNAs play a critical role in the progression of CRC. Here, we explored the effect of miR-329 and its target gene on the sensitivity of 5-fluorouracil (5-FU) in the chemotherapy of CRC. RT-qPCR was utilized to determine the expression of miR-329 in cancer tissues, adjacent tissues and cells. CCK-8 and Transwell assays were introduced to detect the role of miR-329 overexpression in cell viability and invasion. Luciferase reporter assay was performed to verify that E2F1 was a direct target of miR-329. Protein expression of E2F1 was accessed by western blot analysis. The expression level of miR-329 was decreased in CRC tissues and tumor tissues at stage III+IV with lymph node metastasis, and the patients' total survival time was positively associated with the expression of miR-329. Overexpression of miR-329 significantly attenuated the viability and invasiveness of tumor cells. The viability of drug-resistant cells was markedly higher than that of non-resistant cells under the same dose of 5-FU treatment. The expression of miR-329 in tumor cells was negatively associated with drug sensitivity. Luciferase reporter assay showed that E2F1 was the direct target of miR-329. Besides, the expression of E2F1 protein in drug-resistant cells was remarkably higher than that in the non-resistant cells, while the overexpression of miR-329 significantly decreased the expression of E2F1 protein. E2F1 overexpression increased cell viability, but overexpression of both E2F1 and miR-329 in turn decreased cell viability. miR-329 expression is reduced in CRC, and overexpression of miR-329 promotes the sensitivity of 5-FU in the chemotherapy of CRC by degrading the target gene E2F1.

The Impact of Age-Matching on Graft Function and Graft Survival After Living Donor Kidney Transplantation

Introduction The number of patients on the waiting list for kidney transplants is increasing. To overcome the shortage of organs, the influence of age matching in deceased donor kidney transplantation(DDKT) has been studied, but there is no enough data for living donor kidney transplantation (LDKT). We analyzed the impact of age-matching on graft function and graft survival after LDKT. Method The data of 2621 recipients who underwent LDKT were reviewed. Patients were divided into four groups according to the cutoff values of donor age 45 years and recipient age 25 years; CtrlD-CtrlR, CtrlD-RiskR, RiskD-CtrlR, and RiskD-RiskR. The renal function, the total graft survival and the death censored graft survival were compared among the groups. Result At 1, 3, 5, 15, and 20 years after transplant, the estimated glomerular filtration rate(eGFR) of recipients from control donor was significantly higher than that of recipients from risk donor regardless of recipient age group (Control recipients, P<0.001; Risk recipients, P=0.005). When we compare the total graft survival rate for 20 years, CtrlD-CtrlR showed the highest survival rate and RiskD-RiskR showed the worst survival rate (P<0.001). When we compare death censored graft survival, the result was amplified (P<0.001). In multivariate analysis, pretransplant dialysis, acute rejection within 1year and age group were the independent risk factor for death censored graft survival.Conclusion The younger living donors provide the best outcomes for recipients regardless of the age. This should be considered at the time of donor evaluation, especially when several donors are available. For elderly recipients, the next best alternative option is receiving old living kidneys rather than dialysis or DDKT.

Study for Comparison of CD40-mAb and CD40L-Ab Costimulation Blockade after Life-Supporting Orthotopic Cardiac Xenotransplantation of Multi-Transgenic Pig Hearts into Baboons with a Worldwide First Successful Long-Term Survival

Objectives Life-supporting orthotopic cardiac xenotransplantations (OHXTx) in a pig-to-baboon model with GalT-KO/hCD46/hTM transgenic donor pigs were performed with a compatible, non-toxic immunosuppression (IS) based on CD40mAb co-stimulation blockade in group G1 and in a group G2 with a new pasylated, non-thrombogenic CD40L-Ab. Chemical procedure of PASylation prolongs plasma half-life by 170-fold to several days. Primary aims were to realize a constant preclinical long-term survival in a life-supporting cardiac xenotransplantation model and to prevent perioperative cardiac xenograft dysfunction (PCXD) as a kind of cardiac low output. Methods OHXTx according to the technique of Lower and Shumway were performed in 11 baboons with transgenic pig hearts. The new IS consisted of a recombinant mouse-rhesus chimeric CD40 (clone 2C10R4) antibody in G1 (n=7) or a PASylated Fab-CD40L antibody (XL-protein/Wacker-Chemie) in G2 (n=4) combined with ATG, rituximab, MMF (no tacrolimus or cyclosporine!) and steroids. Results Survival in G1 with CD40mAb were 3, 1, 30, 1, 1** and 27 day(s) with 2 cases of PCXD. Using CD40L-Ab in G2 PCXD was observed in 1 case and the recipients survived 1, 18 and 40 days. Ischemic time of the hearts ranged from 112-128 min. Primary cause of death mostly were renal and hepatic failure, one died of a neurological deficit**, another after hematothorax, but no hyperacute or delayed xenograft rejection occurred. After several weeks a pig donor organ (over)growth was found. All long-term surviving baboons were in good general conditions until to the last days. Mean survival in G1 (CD40Ab) was 10.5+/-4.90 days and in G2 (Fab-CD40L) 19.7+/-7.84 days and without PCXD and brain damage** 20+/-6.55 days in G1 and 29+/-7.78 days in G2. In a preliminary modified subgroup (unpublished data und matter of a patent) one baboon with CD40L-Ab survived 50 days and another baboon (B67 with CD40Ab) reached and was successfully terminated at the endpoint of study on day 90 with no signs of rejection of the xenograft. Conclusion Co-stimulation blockade with CD40L antibody tended to prolong survival time after orthotopic cardiac xenotransplantation, but with so far incomplete groups statistically not significant. In total survival in this important life-supporting orthotopic model was significantly prolonged with a less toxic IS and better quality of life. This is an important milestone and progress on the way to a long-term survival of 2 -3 months, which is necessary for first clinical cardiac xenotransplantations. This aim was now first time worldwide reached with our last 90-days surviving baboon B67 in the last subgroup and must be replicated another 5 times before starting a clinical study.

PO-256 The extracorporeal immunopharmacotherapy (EIPHT) and remote results of cervical cancer and ovarian cancer treatment

IntroductionThe aim of this study was to investigate the effect of extracorporeal immunopharmacotherapy on long-term results of treatment of cervical cancer and ovarian cancer.Material and methodsThe study included patients with cervical cancer and ovarian cancer T2–3N0–1M0 stages, w All the patients with ovarian cancer in a combined therapy of adjuvant or neoadjuvant mode comprising combination chemotherapy of cisplatin 75mg/m2+Cyclophosphan 1000mg/m2 for 4 days at 4–6 courses 1 every 3 weeks and surgical treatment within the scope of radical surgery. EIPHT was performed by exfusion of 500–1000 ml of autoblood in ’Gemakon’ or ’Terumo’ sterile containers and its centrifugation at 3000 rpm for 30 min. Then the obtained leukotrombomass and erythrocytic mass were incubated with thymalin in a total dose of 30 mg (for 3 procedures) at 37° C for 60–100 min, with the subsequent return of the conjugate to the circulatory system of patients. In total, patients received 2 sessions of extracorporeal therapy at the beginning of admission to hospital and before discharge from the hospital.Results and discussionsDepending on the type of EIPHT being performed, 4 groups of patients with cervical cancer and OC were isolated. The 1 st group (34 patients) included patients with cervical cancer and OC who did not receive immunotherapy. In 2nd (32 patients) cervical cancer and 42 patients with OC, immunotherapy in the form of subcutaneous injections of thymomimetics (thymalin) in standard doses for 10–14 days was performed. The 3-rd group included 28 patients with cervical cancer and 36 patients with OC, who underwent EIPHT, and group 4 comprised 45 patients with cervical cancer and 47 patients with OC used EIPHT in combination with plasmapharesis. The conducted studies led to the conclusion that the greatest effectiveness in reducing side effects of chemotherapy in the complex treatment of patients with cervical cancer and stage II-III stage II, as well as in improving the subjective state of patients and their quality of life, has an immunotherapy scheme that includes intermittent plasmapheresis with subsequent EIPHT, which reduces the main clinical manifestations of toxicity of chemotherapy, improves the indicators of the subjective state of patients and the quality of their life.ConclusionThe use of EIPHT methods in the complex therapy of oncogynecologic diseases makes it possible to increase the parameters of the five-year total and disease-free survival of patients with cervical cancer and ovarian cancer.

Evaluation of propolis extract as a disinfectant of Japanese quail (Coturnix coturnix japonica) hatching eggs

This study was carried out to evaluate the effectiveness of an alcoholic propolis extract (15%) as a disinfectant for Japanese quail (Coturnix coturnix japonica) hatching eggs. A total of 600 eggs were randomly divided into four experimental groups: 1) negative control (NC), without disinfection, 2) control (C), fumigated with formaldehyde gas, 3) (A), sprayed with 96% alcohol, and 4) (P), sprayed with 15% alcoholic propolis extract. The eggs were incubated artificially in a BIOS hatching apparatus under standard conditions. On the 14th day, the eggs were candled to determine the number of infertile eggs and dead embryos and samples were collected for microbial analysis. After 17.5 d, fertility, hatchability, embryonic mortality, and eggshell conductance were calculated. Fertile eggs sprayed with propolis were shown to have a lower eggshell conductance constant (egg weight loss) than eggs from groups C and A. Total microbial activity on the eggshells did not differ significantly between groups, but Staphylococcus aureus, Micrococcus spp., Bordetella spp., and Chryseobacterium meningosepticum isolates were significantly affected by the propolis treatment. There were no significant differences between treatments for total hatchability, embryonic mortality, and chick body weight on the 1st, 7th, and 14th days of life. The total chick survivability during the first 2 wk was significantly higher in group P than in the other groups. The results indicate that spraying hatching eggs with 15% propolis as a disinfectant can be recommended as a safe and natural sanitizer in place of formaldehyde, with no negative effect on quail chicks.

Comparison of Tissue-Link combined with Cusa and Pringle in hepatectomy for primary hepatocellular carcinoma

Objective To evaluate the clinical effect of Tissue-Link combined with Cusa and Pringle in hepatectomy for primary hepatocellular carcinoma. Methods From January 2013 to January 2017, the clinical data of ninety-six primary hepatocellular carcinoma patients who had received hepatectomy were collected.45 cases of hepatectomy (control group) were performed by Pringle.The other 51 cases (observation group) were treated with Tissue-Link combined with Cusa.The indexes and survival rates were compared between the two groups during and after operation. Results Compared with the control group, the operation time of the observation group was prolonged ((189.2±45.8) min vs.(151.6±34.7) min, t=-5.101), the intraoperative blood loss ((273.5±141.6) ml vs.(371.3±127.2) ml, t=7.396), total bilirubin at seventh days after the operation ((15.7±8.9) μmol/L vs.(26.5±10.8) μmol/L, t=5.320) and postoperative albumin supplementation((61.0±9.7) g vs.(84.6±9.3) g, t=7.698) of the observation group decreased.The tumor recurrence rate (0 vs.8.9% (4/45)), intrahepatic metastasis rate (7.8% (4/51) vs.20% (9/45)), extrahepatic metastasis rate (3.9% (2/51) vs.17.8% (8/45)) (χ2=.031, 6.315, 6.746) decreased and the differences were statistically significant (P<0.05). The 2 year and 3 year tumor free survival rate (88.2%, 76.5%) of the observation group was higher than those of the control group (64.4%, 44.4%, χ2=5.468, 8.902), and the total survival rate of 3 year after operation (80.4%) in the observation group was significantly, higher than that of the control group (51.1%, χ2=4.896), the difference was statistically significant (P<0.05). Conclusion Tissue-Link combined with Cusa is superior to Tissue-Link combined with Pringle in hepatectomy for primary hepatocellular carolnoma.It has less intraoperative blood loss, less damage to liver function and a lower relapse rate of ineisional margin, and the disease-free survival rate and overall survival rate are improved significantly. Key words: Primary hepatocellular carcinoma; Hepatectomy; Tissue-Link; Cusa