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.

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.

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.

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.

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.

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.

"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.

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.

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.

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.

BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced rat DIC model.

This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on disseminated intravascular coagulation (DIC) model rats and to further explore the underlying mechanism. A rat model of lipopolysaccharide (LPS)-induced DIC was successfully established, as indicated by impaired plasma hemostatic parameters and damaged organ functions in rats. Importantly, pre-treatment with rat allogeneic BMSCs before LPS injection significantly alleviated systemic intravascular coagulation, reduced plasma levels of organ dysfunction indicators and pro-inflammatory cytokines, suppressed fibrin microthrombi formation, ameliorated liver, heart, and renal injuries, and increased 24-hour survival rates in LPS-induced DIC rats. The protection of BMSCs against DIC was in a moderately dose-dependent manner. Further investigation revealed that BMSCs co-cultured with peripheral blood mononuclear cells (PBMCs) significantly inhibited the LPS-stimulated PBMCs proliferation and the release of pro-inflammatory cytokines from PBMCs. Of note, upregulation of immunosuppressive factors including indoleamine 2,3-dioxygenase and interleukin-10, which was induced by interferon-γ, contributed to BMSCs-mediated inhibition of LPS-stimulated PBMCs proliferation. These effects do not depend on the direct cell-cell contact. In conclusion, BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced DIC model rats. The protection of BMSCs may be attributed to their anti-inflammatory and immunomodulatory properties, which render BMSCs a promising source for stem cell-based therapeutic approaches in inflammation-related DIC.

Oxygenation impairment after total arch replacement with a stented elephant trunk for type-A dissection.

OBJECTIVE: To study the risk factors of oxygenation impairment in patients with type-A acute aortic dissection who underwent total arch replacement with a stented elephant trunk. METHODS: In this study, 169 consecutive patients were enrolled who were diagnosed with type-A acute aortic dissection and underwent a total arch replacement procedure at the Qilu Hospital of Shandong University between January 2015 and February 2017. Postoperative oxygenation impairment was defined as arterial oxygen partial pressure/inspired oxygen fraction ≤ 200 with positive end expiratory pressure ≥ 5 cm H2O that occurred within 72 hours of surgery. Perioperative clinical characteristics of all patients were collected and univariable analyses were performed. Risk factors associated with oxygenation impairment identified by univariable analyses were included in the multivariable regression analysis. RESULTS: The incidence of postoperative oxygenation impairment was 48.5%. Postoperative oxygenation impairment was associated with prolonged mechanical ventilation time, intensive care unit stay, and hospital stay. Multivariable regression analysis demonstrated that body mass index (odds ratio [OR], 1.204; 95% confidence interval [CI], 1.065-1.361; P = .003), preoperative oxygenation impairment (OR, 9.768; 95% CI, 4.159-22.941; P < .001), preoperative homocysteine (OR, 1.080; 95% CI, 1.006-1.158; P = .032), circulatory arrest time (OR, 1.123; 95% CI, 1.044-1.207; P = .002), and plasma transfusion (OR, 1.002; 95% CI, 1.001-1.003; P = .002) were significantly associated with postoperative oxygenation impairment. CONCLUSIONS: Postoperative oxygenation impairment is a common complication of surgery for type-A acute aortic dissection. Body mass index, preoperative oxygenation impairment, preoperative homocysteine, circulatory arrest time, and plasma transfusion were independent risk factors for oxygenation impairment after a total arch replacement procedure.

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.

Functional characterization of a novel jasmonate ZIM-domain interactor (NINJA) from upland cotton (Gossypium hirsutum).

The jasmonic acid (JA) signalling pathway plays roles in plant development and defence against biotic and abiotic stresses. We isolated a cotton NINJA (novel interactor of JA ZIM-domain) gene, designated GhNINJA, which contains a 1305 bp open read frame. The GhNINJA gene encodes a 434 amino acid peptide. According to quantitative real-time PCR analysis, GhNINJA is preferentially expressed in roots, and its expression level is greatly induced by Verticillium dahliae infection. Through a virus-induced gene silencing technique, we developed GhNINJA-silenced cotton plants, which had significantly decreased expression of the target gene with an average expression of 6% of the control. The regenerating lateral root growth of silenced plants was largely inhibited compared to the control. Analysis by microscopy demonstrated that the cell length of the root differentiation zone in GhNINJA-silenced plants is significantly shorter than those of the control. Moreover, the silenced plants exhibited higher tolerance to V. dahliae infection compared to the control, which was linked to the increased expression of the defence marker genes PDF1.2 and PR4. Together, these data indicated that knockdown of GhNINJA represses the root growth and enhances the tolerance to V. dahliae. Therefore, GhNINJA gene can be used as a candidate gene to breed the new cultivars for improving cotton yield and disease resistance.

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.

Controlled Hybrid-Assembly of HPV16/18 L1 Bi VLPs in Vitro.

Based on the helix4-exchanged HPV16 L1 and HPV18 L1, HPV16 L1 Bi and HPV18 L1 Bi, we have successfully realized the controlled hybrid-assembly of HPV16/18 L1 Bi VLPs (bihybrid-VLPs) in vitro. The bihybrid-VLPs were further confirmed by fluorescence resonance energy transfer (FRET) and complex-immunoprecipitation (Co-IP) assays. The ratio of 16 L1 Bi and 18 L1 Bi in bihybrid-VLPs was verified to be 3:5 based on a modified magnetic Co-IP procedure, when mixing 1 equiv pentamer in assembly buffer solution, but it changed with conditions. In addition, the bihybrid-VLPs showed identical thermal stability as that of normal VLPs, suggesting high potential in practical applications. The present study is significant because it modified one of the vital steps of virus life cycle at the stage of virus assembly, supplying a new approach not only to deepen structural insights but also a possibility to prepare stable, low-cost, bivalent antivirus vaccine. Furthermore, the controlled hybrid-assembly of bihybrid-VLPs in vitro provides suggestions for the design of effective multivalent hybrid-VLPs, being a potential to develop broad-spectrum vaccines for the prevention of infection with multiple types of HPV.

A single-center experience of hemofiltration treatment for acute aortic dissection (Stanford type A) complicated with postoperative acute renal failure.

OBJECTIVE: To investigate the effect of continuous venovenous hemofiltration (CVVH) for aortic dissection patients with acute renal failure after surgery in retrospective manner. METHODS: A total of thirty-seven aortic dissection patients with postoperative acute renal failure accepted CVVH therapy. The effect of CVVH was evaluated by analyzing clinical condition changes and laboratory examination results. RESULTS: After treatment of CVVH, renal function and clinical symptoms were significantly improved in thirty patients. Eight of the thirty patients got completely renal function recovery within two weeks after CVVH therapy; and twenty-two of the thirty patients got completely renal function recovery within four weeks after CVVH therapy. Nevertheless, seven patients got no benefit from CVVH therapy with poor prognosis. CONCLUSION: CVVH is an effective treatment to most aortic dissection patients with postoperative acute renal failure. The effect of CVVH was correlated with original renal function, early CVVH therapy, and continuous intensive care.

Combined hypoxia inducible factor-1α and homogeneous endothelial progenitor cell therapy attenuates shunt flow-induced pulmonary arterial hypertension in rabbits.

BACKGROUND: Hyperkinetic pulmonary arterial hypertension (PAH) is a common complication in congenital heart disease, and affects operations, indications, and prognoses for patients. Gene-based stem cell transplantation is an alternative treatment that can attenuate PAH. METHODS: Hyperkinetic PAH rabbit models were successfully established, using common carotid artery and jugular vein anastomosis. Endothelial progenitor cells (EPCs) were isolated from the bone marrow, cultured, and transfected with human hypoxia inducible factor-1 alpha (hHIF-1α), using lentiviruses. Two weeks after the transfected EPCs were transplanted into the rabbits, catheterization was applied to collect hemodynamic data. The hypertrophy of the right ventricle and pulmonary vascular remodeling were evaluated by measuring the right ventricle hypertrophy index, the medial wall thickness, and the medial wall area. Western blot and immunohistochemistry analyses were used to detect the expression of hHIF-1α in the pulmonary small arteries. RESULTS: Two weeks after transplantation, systolic pulmonary arterial pressure and mean pulmonary arterial pressure were both attenuated. The hypertrophy of the right ventricle, and pulmonary vascular remodeling were reversed. Expression of hHIF-1α in the hHIF-1α-transfected EPCs that had been transplanted was high, and the number of pulmonary small arteries had increased. In addition, combined HIF-1α and homogeneous EPC therapy was more effective at attenuating PAH and increasing the density of pulmonary small arteries, compared with EPC transplantation alone. CONCLUSIONS: Both the therapy with HIF-1α-transfected EPCs, and EPC transplantation, attenuated shunt flow-induced PAH, by means of an angiogenic effect. The former therapeutic method was more effective.

Establishment and comparison of two reliable hyperkinetic pulmonary hypertension models in rabbits.

OBJECTIVES: We sought to explore and create a reliable, convenient, and economic hyperkinetic pulmonary artery hypertension (PAH) model and confirm the exact time of establishing a reversible or irreversible model to serve as a platform for future studies. METHODS: We used a common carotid artery and jugular vein shunt with an anastomosis and cuff to create a hyperkinetic PAH model in rabbits. At 1, 2, 3, 6, and 12 months postoperatively, the systolic pressure, mean pulmonary arterial pressure, and mean arterial pressure were measured by catheterization and the right ventricle hypertrophy index was calculated. Pathologic changes in the small pulmonary arteries were observed with hematoxylin and eosin staining, and the Heath-Edwards classification system was used to evaluate PAH. RESULTS: The anastomosis and cuff graft groups both increased in systolic pressure, mean pulmonary arterial pressure (P<.05), and right ventricle hypertrophy index (P<.05). However, the anastomosis method resulted in a lower mortality rate, greater patency, and overall success rate compared with the cuff graft method (P<.05). Furthermore, from the observed pathologic changes and the Heath-Edwards classification system, a reversible and an irreversible PAH model was established at 3 and 6 months postoperatively, respectively. CONCLUSIONS: The common carotid artery and jugular vein anastomosis method is a stable hyperkinetic PAH model in rabbits. Reversible and irreversible PAH models were established at 3 and 6 months postoperatively, respectively.