Advances in applications of artificial intelligence algorithms for cancer-related miRNA research. / äººå·¥æ™ºèƒ½ç®—æ³•åœ¨ç™Œç—‡ç›¸å ³å¾®RNAç ”ç©¶ä¸­çš„åº”ç”¨è¿›å±•.

MiRNAs are a class of small non-coding RNAs, which regulate gene expression post-transcriptionally by partial complementary base pairing. Aberrant miRNA expressions have been reported in tumor tissues and peripheral blood of cancer patients. In recent years, artificial intelligence algorithms such as machine learning and deep learning have been widely used in bioinformatic research. Compared to traditional bioinformatic tools, miRNA target prediction tools based on artificial intelligence algorithms have higher accuracy, and can successfully predict subcellular localization and redistribution of miRNAs to deepen our understanding. Additionally, the construction of clinical models based on artificial intelligence algorithms could significantly improve the mining efficiency of miRNA used as biomarkers. In this article, we summarize recent development of bioinformatic miRNA tools based on artificial intelligence algorithms, focusing on the potential of machine learning and deep learning in cancer-related miRNA research.

Development and characterization of anti-HPV16 monoclonal antibodies for assembly of an HPV16 detection kit.

Quality control is very important during the development of 3-valent (16/18/58), 9-valent (6/11/16/18/31/33/45/52/58), and 15-valent human papillomavirus (HPV) vaccines (6/11/16/18/31/33/35/39/45/52/56/58/59/68). All 3-valent, 9-valent, and 15-valent HPV vaccines contain the HPV16 antigen; therefore, a detection method that can specifically identify HPV16 in vaccines is urgently required. This study aimed to develop and characterize monoclonal antibodies to assemble a highly specific HPV16 detection kit. The HPV16 L1 pentameric protein developed as an immunogen was used to prepare monoclonal antibodies. From the pool of prepared monoclonal antibodies, we selected 4G12 and 5A6 to screen and evaluate their subtypes, specificity, neutralizing activity, serum competition, binding affinity, and gene sequencing. After these characterizations, an enzyme-linked immunosorbent assay kit for these monoclonal antibodies was developed, and excellent quality was demonstrated in the assessment of linearity, repeatability, and specificity. The developed detection kit has great potential for wide use in clinical testing and quality control in vaccine production processes.

Development of HPV58 type-specific antibodies and detection kit.

Currently, human papillomavirus (HPV) vaccines are in short supply, so the development of HPV vaccines has a broad market prospect. The 3-, 9-, and 15-valent HPV vaccines developed by ourselves all contain HPV58-derived antigen components. It is important to detect HPV 58 during vaccine production. Here, we introduced a development process of HPV58 type-specific antibodies and a detection kit. Briefly, HPV58 L1-Virus Like Particles (VLPs) were used as antigens to immunize mice, followed by extraction of the ascites to prepare hybridoma cells. After culturing, the supernatants containing secreted antibodies were harvested, purified, and screened to obtain monoclonal antibodies (mAbs). In the pool of attained monoclonal antibodies, we selected 2F7 and 2G7 to evaluate their subtypes, specificity, neutralizing activity, serum competition, binding affinity and gene sequencing. Finally, an enzyme-linked immunosorbent assay (ELISA) detection kit was assembled with 2F7 and 2G7 mAbs which possessed high specificity to HPV58 L1-VLPs. The detection kit developed by 2F7 and 2G7 could be adopted to specifically detect HPV58 L1 protein with good linearity and detection range, which could be widely used in clinical testing and quality control in the production of HPV vaccines.Abbreviations: BSA: Bovine serum albumin; CDRs: Complementarity-determining regions; CV: Coefficient of variation; DTT: Dithiothreitol; ELISA: Enzyme-linked immunosorbent assay; HAT: Hypoxanthine-aminopterin-thymidine; HPV: Human Papillomavirus; IC50: 50% inhibition rate; IC90: 90% inhibition rate; mAbs: Monoclonal antibodies; VLP: Virus-like particle.

Synthetic Studies toward Leucosceptroid Family of Natural Products.

Leucosceptroids are sesterterpenoids with potent antifeedant and antifungal activities. In this paper, efforts on two synthetic strategies toward stereoselective total synthesis of the leucosceptroid family of natural products are reported. Intramolecular addition cyclization strategy could lead to a stereochemically mismatched core structure, while intermolecular addition/ring-closing metathesis cyclization strategy successfully furnished an advanced common intermediate bearing eight contiguous stereogenic centers, including three tetra-substituted ones, which fully matches all the stereochemistry on the tricyclic framework in leucosceptroid H. Late-stage transformation of this intermediate to leucosceptroid H encountered difficulty in oxidizing the secondary hydroxyl group to a carbonyl group in the target. Instead of the desired oxidation, an interesting tricyclic spiral product originating from a C-C bond cleavage was observed.

Effect of different types of cerebral perfusion for acute type A aortic dissection undergoing aortic arch procedure, unilateral versus bilateral.

BACKGROUND: Antegrade cerebral perfusion (ACP), including unilateral and bilateral, is most commonly used for cerebral protection in aortic surgery. There is still no consensus on the superiority of the two methods. Our research aimed to investigate the clinical effects of u-ACP and b-ACP. METHODS: 321 of 356 patients with type A aortic dissection were studied retrospectively. 124 patients (38.6%) received u-ACP, and 197 patients (61.4%) received b-ACP. We compared the incidence of postoperative neurological complications and other collected data between two groups. Besides, we also analyzed perioperative variables to find the potential associated factors for neurological dysfunction (ND). RESULTS: For u-ACP group, 54 patients (43.5%) had postoperative neurological complications, including 22 patients (17.7%) with permanent neurologic dysfunction (PND) and 32 patients (25.8%) with temporary neurologic dysfunction (TND). For b-ACP group, 47 patients (23.8%) experienced postoperative neurological complications, including 16 patients (8.1%) of PND and 31 patients (15.7%) of TND. The incidence of PND and TND were significantly different between two groups along with shorter CPB time (p = 0.016), higher nasopharyngeal temperature (p≦0.000), shorter ventilation time (p = 0.018), and lower incidence of hypoxia (p = 0.022). Furthermore, multivariate stepwise logistic regression analysis confirmed that preoperative neurological dysfunction (OR = 1.20, p = 0.028), CPB duration (OR = 3.21, p = 0.002), and type of cerebral perfusion (OR = 1.48, p = 0.017) were strongly associated with postoperative ND. CONCLUSIONS: In our study, it was observed that b-ACP procedure exhibited shorter CPB time, milder hypothermia, shorter ventilation time, lower incidence of postoperative hypoxia, and neurological dysfunction compared to u-ACP. Meanwhile, the incidence of ND was independently associated with three factors: preoperative neurological dysfunction, CPB time, and type of cerebral perfusion.

Bone Marrow-Derived Mesenchymal Stem Cells-Mediated Protection Against Organ Dysfunction in Disseminated Intravascular Coagulation Is Associated With Peripheral Immune Responses.

Disseminated intravascular coagulation (DIC) is a fatal thrombohemorrhagic disorder. Bone marrow-derived mesenchymal stem cells (BMSCs) are multipotent stem cells that have tremendous therapeutic effect. Our aim was to explore whether the immune mechanisms were associated with BMSCs-afforded protection against DIC. We generated a rat model of DIC by lipopolysaccharide (LPS, 3 mg/kg) injection via the tail vein. In the treatment group, rats were pre-treated with 1 × l03 , 1 × l04 , 1 × l05 , and 1 × l06 allogeneic BMSCs before LPS injection. Blood sample was withdrawn from the abdominal aorta at 0 (before), 4, and 8 h after LPS injection and used for biochemical analyses. After experiments, the mice were sacrificed and their organs were harvested and observed by H&E and PTAH staining. Continuous infusion of LPS into the rats gradually impaired the hemostatic parameters and damaged organ functions. However, pre-treatment with BMSCs dose-dependently improved the hemostatic parameters. Meanwhile, the treatment significantly suppressed the fibrin microthrombi formation and alleviated liver, heart, lung, and renal injuries. Flow cytometry analysis demonstrated that BMSCs pre-treatment inhibited LPS-induced upregulation of CD3+ CD8+ T cells and CD3+ /CD161a+ NKT cells in the peripheral blood. BMSCs pre-treatment reversed the upregualtion of the B-cell population and the percentage of CD43+ /CD172a+ monocytes in the DIC models. Finally, BMSCs pre-treatment decreased the levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) and increased the levels of interleukin-10 (IL-10) in LPS-induced DIC models. Pre-treatment with BMSCs can reduce coagulation and alleviate organ dysfunction via peripheral immune responses in LPS-induced DIC rat model. J. Cell. Biochem. 118: 3184-3192, 2017. © 2017 Wiley Periodicals, Inc.

Incidence and Risk Factors of Delirium in Patients After Type-A Aortic Dissection Surgery.

OBJECTIVE: To study the incidence and related risk factors for postoperative delirium after type-A aortic dissection in patients who underwent Sun's procedure (total arch replacement using a tetrafurcate graft with stented elephant trunk implantation). DESIGN: A retrospective study. SETTING: A cardiac surgical intensive care unit. PARTICIPANTS: The study comprised 100 patients admitted to the intensive care unit for type-A aortic dissection. INTERVENTIONS: All patients underwent Sun's procedure with uniform preoperative and anesthetic treatment. MEASUREMENTS AND MAIN RESULTS: Delirium was evaluated using the Confusion Assessment Method for the intensive care unit. Baseline demographics and preoperative, intraoperative, and postoperative data were recorded and analyzed retrospectively via univariate analysis and multivariate logistic regression. The incidence of postoperative delirium was 34%, according to Confusion Assessment Method for the intensive care unit criteria. Univariate analysis revealed that 17 variables differed significantly among patients with and without delirium. Additional multivariate stepwise logistic regression analysis confirmed that cerebrovascular disease history, surgery duration, cardiopulmonary bypass duration, intubation time, and hypoxia were strongly associated with postoperative delirium. CONCLUSIONS: Delirium is a common postoperative complication of aortic dissection. Cerebrovascular disease history, surgery and cardiopulmonary bypass duration, postoperative hypoxia, and intubation time are independently associated with the development of delirium. Early diagnosis of delirium and modifying these factors properly may be helpful to improve patients' prognosis.

Perioperative levosimendan therapy is associated with a lower incidence of acute kidney injury after cardiac surgery: a meta-analysis.

OBJECTIVE: Levosimendan is a calcium sensitizer that enhances myocardial contractility without increasing myocardial oxygen use. Limited data are available on its renal-protective effect, and no statistically significant effects have been found. A meta-analysis was conducted for randomized studies to show whether perioperative levosimendan use could reduce acute kidney injury (AKI) in patients undergoing cardiac surgery. DATA SOURCES: BioMed Central, PubMed EMBASE, and the Cochrane Central Register of Controlled Trials were searched for pertinent studies. STUDY SELECTION: Randomized trials that compared levosimendan versus placebo or any other control in cardiac surgery with data on AKI were included. Exclusion criteria were duplicate publications, nonadult studies, oral administration of levosimendan, and studies with no data on AKI. DATA EXTRACTION: Study endpoints, study design, population, clinical setting, levosimendan dosage, and treatment duration were extracted. DATA SYNTHESIS: Data from 529 patients in 5 randomized trials were analyzed. The analysis showed that levosimendan decreased postoperative incidence of AKI in the levosimendan group. CONCLUSIONS: This analysis suggests that levosimendan might reduce renal injury in adult patients undergoing cardiac surgery. More prospective randomized studies are needed to further demonstrate the benefits of levosimendan on renal protection in cardiac surgery.

Ethyl pyruvate ameliorates monocrotaline-induced pulmonary arterial hypertension in rats.

BACKGROUND: Ethyl pyruvate (EP) is an anti-inflammatory and anti-oxidant agent associated with many diseases. In this study, we evaluated whether EP could attenuate monocrotaline-induced pulmonary arterial hypertension (PAH). METHODS: A PAH model was established by subcutaneously injecting a single dose of monocrotaline (60 mg/kg). And then a daily intraperitoneal injection of EP (50 mg/kg) was administered on day 1 to day 28 (preventive EP treatment) or day 15 to day 28 (therapeutic EP treatment). Hemodynamic changes were measured by catheterization, and the right ventricle hypertrophy index, the medial wall thickness, and the medial wall areas were also calculated. Enzyme-linked immunosorbent assay and immunohistochemical analysis were used to determine the serum levels and expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and endothelin-1 (ET-1) in the lung tissue. RESULTS: Both preventive and therapeutic EP treatment significantly ameliorated hemodynamic changes and vascular remodeling indicators (all P < 0.05). The serum levels and expression of TNF-α, IL-6, and ET-1 in the lung tissue were also significantly decreased (all P < 0.05). CONCLUSIONS: EP ameliorates monocrotaline-induced PAH and reverses pulmonary vascular remolding in rats by inhibiting the release of TNF-α and IL-6 and reducing the expression of ET-1.

Degradation Mechanism Study for Secondary Degradants in Rosuvastatin Calcium and Determination of Degradant Acetaldehyde Using Static Headspace Gas Chromatography Coupled with Matrix Precipitation.

During the development of headspace gas chromatography (HSGC) method for assessing residual solvents in rosuvastatin calcium (RSV) drug substance, acetaldehyde (AA) was detected in obtained chromatograms, with a calculated concentration of up to 226 ppm. After a series of experiments, it was established that acetaldehyde originates from matrix interference due to direct degradation of Imp-C, which is accompanied by the formation of impurity at relative retention time (RRT) 2.18, without the involvement of impurity at RRT 2.31. The thermal instability of Imp-C also results in the formation of impurity at RRT 2.31 through dehydration and decarboxylation. In addition, cyclization reaction of degradant at RRT 2.18 further resulted in the generation of impurity at RRT 2.22. The structure of these three degradants, were confirmed by liquid chromatography-mass spectrometry (LC-MS), 1D and 2D nuclear magnetic resonance (NMR) measurement. In order to minimize the said matrix interference, a simple precipitation procedure was proposed as a pretreatment to mitigate the impact of Imp-C. Subsequently, an HSGC method was developed for the simultaneous determination of the degradant AA and the other five residual solvents used in RSV synthetic process. The final method was validated concerning precision, limit of detection (LOD) and limit of quantitation (LOQ), linearity, and accuracy.

Obesity is associated with higher long-term mortality after aortic valve replacement with small prosthesis.

OBJECTIVE: Although many studies have evaluated the impacts of obesity on various medical treatments, it is not known whether obesity is related to late mortality with implantation of small aortic prosthesis. This study evaluated the effect of obesity on late survival of patients after aortic valve replacement (AVR) with implantation of small aortic prosthesis (size ≤ 21 mm). METHODS: From January 1998 to December 2008, 536 patients in our institution who underwent primary AVR (307 patients with smaller prostheses) survived the 30 days after surgery. Patients were categorised as normal weight if body mass index (BMI) was ≤ 25 kg/m(2), as overweight if BMI 25-30 kg/m(2), and as obese if BMI ≥ 30 kg/m(2). Data were collected at the third-month (M), sixth-M, first-year (Y), third-Y, fifth-Y, and eighth-Y after operation. RESULTS: By multivariable analysis, obesity was a significant independent factor of late mortality (hazard ratio [HR]: 1.59; p=0.006). The obese and overweight groups of patients exhibited lower survival (p<0.001) and a higher proportion in NYHA class III/IV (p<0.01) compared with the normal group. Lower EOAI and higher left ventricular mass index were found in the obese and overweight groups, but we saw no significant variance in LVEF among the three groups. CONCLUSIONS: Obesity was associated with increased late mortality of patients after AVR with implantation of small aortic prosthesis. Being obese or and overweight may also affect the NYHA classification, even in the longer term.

Development and validation of a stability-indicating RP-HPLC method for the determination of fifteen impurities in rivaroxaban.

A simple and stability-indicating reverse phase high-performance liquid chromatographic (RP-HPLC) method for the determination of rivaroxaban (RIX) and its related substances was developed. Fifteen impurities of RIX, including three unreported isomers, were identified, synthesized, purified, and confirmed using MS, 1H NMR, 13C NMR, and HSQC spectral methods. This new method offered baseline separation for all monitored impurities, and was fast and reliable when compared to the European Pharmacopoeia method. Optimum separation for RIX and its related impurities was achieved on an octyldecyl silica column (YMC Core C18, 4.6 ×100 mm, 2.7 µm) by using a gradient HPLC method in 38 min. The final method was validated with respect to precision, LOD and LOQ, linearity, accuracy, and robustness. This developed method was suitable for routine quality control and drug analysis of RIX active substance.

Immunogenicity and protective effects of recombinant bivalent COVID-19 vaccine in mice and rhesus macaques.

Coronavirus disease (COVID-19) is still spreading rapidly worldwide, and a safe, effective, and cheap vaccine is still required to combat the COVID-19 pandemic. Here, we report a recombinant bivalent COVID-19 vaccine containing the RBD proteins of the prototype strain and beta variant. Immunization studies in mice demonstrated that this bivalent vaccine had far greater immunogenicity than the ZF2001, a marketed monovalent recombinant protein COVID-19 vaccine, and exhibited good immunization effects against the original COVID-19 strain and various variants. Rhesus macaque challenge experiments showed that this bivalent vaccine drastically decreased the lung viral load and reduced lung lesions in SARS-CoV-2 (the causative virus of COVID-19)-infected rhesus macaques. In summary, this bivalent vaccine showed immunogenicity and protective efficacy that was far superior to the monovalent recombinant protein vaccine against the prototype strain and provided an important basis for developing broad-spectrum COVID-19 vaccines.

Special Application of ms/ms Method on Determination of Regiochemistry of Sugammadex Series Compounds: Synthesis, Isolation and Structural Characterization for Two Potential Oxidative Impurities in Sugammadex Sodium Finished Pharmaceutical Product.

Two oxidative degradation impurities of sugammadex sodium have been successfully synthesized under stress conditions and isolated by preparative high performance liquid chromatography, which would be extremely difficult to prepare stochiometrically by conventional methods due to their structural complexity. Characteristic fragmentation pattern observed by mass spectrometry for sugammadex series compounds helped distinguish the two regioisomeric di-sulfoxide impurities. Confirmed by nuclear magnetic resonance analysis, Impurity I was identified as ortho-disulfoxide sugammadex and Impurity II as meta-disulfoxide sugammadex. It is the first time detailed structures of these two impurities are reported. Additionally, HPLC analysis also indicated the observance of these two impurities in long-term stored sugammadex sodium finished pharmaceutical product but absence in three pilot batches of sugammadex sodium drug substance which met ICH requirements. The compounded analysis technique has proven to be successful and reliable, and we hope that it could be well applied to structure identification for other sugammadex impurities and will be beneficial for other researchers focusing on this field.

"Ghost peaks" of olmesartan medoxomil: Two solution degradation products of olmesartan medoxomil via oxidation mediated by metal ions.

Two unknown solution degradants were found during the dissolution testing in 0.1-M HCl for olmesartan medoxomil (OLM) tablets. The structure of the degradants was identified and characterized by liquid chromatography-ultraviolet (LC-UV), liquid chromatography with tandem mass spectrometry (LC-MS/MS), and nuclear magnetic resonance (NMR) and demonstrated to be cyclization of tetrazole and benzene in the olmesartan (OL) and OLM structures. A series of studies including stress studies, simulation studies, and mechanism-based studies were performed to reveal the potential mechanisms that lead to the formation of the unknown degradants. The study results demonstrated that the degradation was catalyzed with radicals that originated from the metal ions leached from the inner surface of high-performance liquid chromatography (HPLC) glass vials with dissolved oxygen under acidic condition. Prerinsing the glass vials with acidic solution dissolved with EDTA can effectively avoid the generation of such oxidative impurities. The present work provides new insights into the understanding of degradation pathways of OLM, which might support the development of OLM tablets.

[Pretreatment of isolated vein with rapamycin nanoparticles inhibits vein graft stenosis in rabbits].

OBJECTIVE: To explore the effects of pretreatment of carbopol-encapsulated rapamycin-loaded nanoparticles (RPM-NP) on vein graft stenosis in a rabbit vein graft model. METHODS: A segment of common carotid artery was replaced with a segment of external jugular vein in 40 rabbits. They were separated into four treatment groups, i.e. Group A: vein grafts were pretreated with intraluminal RPM-NP perfusion; Group B: peripheral venous veins were injected with RPM-NP; Group C: vein grafts received an equivalent perfusion of empty vehicle; Group D: vein grafts received no treatment. At Day 28 post-operation, the grafts and normal veins were harvested for histological examinations to analyze the indicators of intimal thickness, internal diameter, intimal/media thickness ratio and collagen volume index. RESULTS: At Day 28 post-operation, the intimal/media thickness ratios were 0.26 ± 0.02, 0.73 ± 0.05, 0.71 ± 0.04, 0.69 ± 0.03 and 0.24 ± 0.01 in Groups A, B, C and D and the normal vein; the collagen volume index 0.24 ± 0.03, 0.56 ± 0.06, 0.53 ± 0.07, 0.49 ± 0.08 and 0.21 ± 0.01 respectively. Compared with the normal veins, the pathological indicators of vein graft intimal thickness, internal diameter, intimal/media thickness ratio and collagen volume index had significant differences in Groups B, C and D (all P < 0.05). But there were no significant differences among 3 groups (all P > 0.05). Compared with the normal vein, the parameters of vein graft intimal thickness, internal diameter, intimal/media thickness ratio and collagen volume index had no significant difference in Group A (all P > 0.05). But as compared with other groups, these indicators had statistical significant difference in Group A (all P < 0.05). CONCLUSION: The local pretreatment of isolated vein with rapamycin nanoparticles may inhibit neointimal hyperplasia and prevent effectively vein graft stenosis.

Stereoselective Construction of the Highly Congested Tricyclic Core Structure in Leucosceptroid H.

Leucosceptroids are sesterterpenoids with potent antifeedant and antifungal activities. An efficient stereoselective construction of the highly congested [5,6,5] tricyclic framework of leucosceptroid H is presented. This framework bearing eight contiguous stereogenic centers, including three tetrasubstituted ones, could serve as a common intermediate for the collective total synthesis of the leucosceptroid family of natural products.

[Study of adventitial inflammation and inflammatory factors in pathogenesis of allograft arteriosclerosis in rats].

OBJECTIVE: To study the roles of serum inflammatory factors IL-6 and TNF-alpha and allograft adventitial inflammation in the pathogenesis of allograft arteriosclerosis in rats. METHODS: Thirty-six allogeneic allograft rats and 16 syngeneic allograft rats were randomly divided into 4 groups (9 rats in each experimental group and 4 in each control group): A, harvested at Week 1 post-operation; B, harvested at Week 2 post-operation; C, harvested at Week 3 post-operation; D, harvested at Week 4 post-operation. Blood samples were collected before transplantation and after harvest. The method of ELISA was used for testing serum inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor-alpha(TNF-alpha), HE staining for pathologic changes of aortic allograft and immunohistochemical method for expression of alpha-actin, cyclin dependent kinase-1 (CDK(1)) and proliferating cell nuclear antigen (PCNA). Compare the inflammatory factors and other observations between groups and preoperative. RESULTS: At Week 1 post-operation, a large amount of inflammatory cell infiltration in adventitia was observed; at Week 2 post-operation, slight collagen fibers hyperplasia with inflammatory infiltration; at Week 4 post-operation, obvious adventitia thickening with a large number of smooth muscle cells, collagen fibers and inflammatory cells, smooth muscle cells migration from adventitia to intima. Expressions of alpha-actin, CDK(1) and PCNA kept increasing with time in adventitia (P < 0.05). There was a significant increase in serum TNF-alpha level in Groups A, B, C and D, as compared with pre-operative basal level (P < 0.01). There was no difference between controls and pre-operative basal level. IL-6 level slightly declined in the middle stage, but finally increased in experimental group B (P < 0.05) while it significantly increased in Groups A, C, D (P < 0.01). In the control groups A, B, C, it was higher than pre-operative level (P < 0.05). In experimental groups A, C, D, it had a significant increase as compared with controls (P < 0.01). CONCLUSIONS: In abdominal aortic allograft models, obvious angiosclerosis was found in adventitia and intima in accordance with the severity of adventitial inflammation. Thus the inflammatory factors and inflammatory cell infiltration in adventitia are both involved in the pathogenesis of early allograft arteriosclerosis.

[Comparative study on the immunogenicity of human homologous cardiac valve and great artery homograft cryopreserved with liquid nitrogen].

OBJECTIVE: To study the differences on the immunogenicity of the leaflets, arterial wall and myocardium of conduit valved homograft (CVH) cryopreserved with liquid nitrogen. METHODS: Mono-cell suspension of leaflets cells and arterial cells of CVH were respectively co-cultured with human lymphatic cells whose blood groups were the same with that of CVH donors. Expressive levels of CD25 and HLA-DR of these lymphatic cells were detected by flow cytometry in the different cultural duration and compared with that of lymph cells alone cultured (comparative group). RESULTS: The immunogenicity of CVH artery walls was more severe than that of CVH leaflets, and expressive level of whose CD25 and HLA-DR was higher. The immunogenicity of CVH myocardium was not studied because the myocardial cell suspension were not be acquired in this study. CONCLUSION: It is proved that in vitro experimental study that the immunogenicity of arterial walls of cryopreserved CVH is more severe than that of leaflets.

Susceptibility for NSAIDs-induced apoptosis correlates to p53 gene status in gastric cancer cells.

The anti-tumor effect of non-steroidal anti-inflammatory drugs (NSAIDs) remains unclear. Here, we found that the susceptibility for NSAIDs-induced apoptosis might correlate with the status of the p53 gene in gastric cancer cells. Apoptosis in gastric cancer cells expressing wild-type p53 is induced through up-regulation of bax and down-regulation of bcl-2 and that regulation of the bax-bcl-2 heterodimer may be a major target of NSAIDs. As to gastric cancer cells expressing mutant-type p53, other key factors may exist in the NSAIDs' growth inhibition action.