Key Process Parameters Study for the Fill Finish of Vaccines Containing Aluminum Hydroxide Adjuvant.

Vaccine manufacturing is one of the most challenging and complex processes in pharmaceutical industry, and the process control strategy is critical for the safety, effectiveness, and consistency of a vaccine. The efficacy of aluminum salt adjuvant on vaccines strongly depends on its physicochemical properties, such as size, structure, surface charge, etc. However, stresses during the vaccine manufacturing may affect the stability of adjuvant. In this study, the impacts of cold/thermal stress, autoclaving, pumping, mixing, and filling shear stress on the physicochemical properties of aluminum hydroxide (AH) adjuvant were evaluated as part of the manufacturing process development. The results showed that the autoclaving process would slightly influence the structure and properties of the investigated AH adjuvant, but thermal incubation at 2-8 °C, 25 °C and 40 °C for 4 weeks did not. However, -20 °C freezing AH adjuvant led to the adjuvant agglomeration and rapid sedimentation. For the high shear stress study with mixing at 500 rpm in a 1-L mixing bag and pumping at 220 rpm for up to 24 h, the average particle dimension of the bulk AH adjuvant decreased, along with decreasing protein adsorption ratio. The studies indicate that various stresses during manufacturing process could affect the structure and physicochemical properties of AH adjuvant, which calls for more attention on the control of adjuvant process parameters during manufacturing.

A Novel Deep Learning Model for Medical Image Segmentation with Convolutional Neural Network and Transformer.

Accurate segmentation of medical images is essential for clinical decision-making, and deep learning techniques have shown remarkable results in this area. However, existing segmentation models that combine transformer and convolutional neural networks often use skip connections in U-shaped networks, which may limit their ability to capture contextual information in medical images. To address this limitation, we propose a coordinated mobile and residual transformer UNet (MRC-TransUNet) that combines the strengths of transformer and UNet architectures. Our approach uses a lightweight MR-ViT to address the semantic gap and a reciprocal attention module to compensate for the potential loss of details. To better explore long-range contextual information, we use skip connections only in the first layer and add MR-ViT and RPA modules in the subsequent downsampling layers. In our study, we evaluated the effectiveness of our proposed method on three different medical image segmentation datasets, namely, breast, brain, and lung. Our proposed method outperformed state-of-the-art methods in terms of various evaluation metrics, including the Dice coefficient and Hausdorff distance. These results demonstrate that our proposed method can significantly improve the accuracy of medical image segmentation and has the potential for clinical applications. Illustration of the proposed MRC-TransUNet. For the input medical images, we first subject them to an intrinsic downsampling operation and then replace the original jump connection structure using MR-ViT. The output feature representations at different scales are fused by the RPA module. Finally, an upsampling operation is performed to fuse the features to restore them to the same resolution as the input image.

Influence of cutting velocity on surface roughness during the ultra-precision cutting of titanium alloys based on a comparison between simulation and experiment.

The Ti-6Al-4V titanium alloy is a kind of light alloy material with high specific strength, corrosion resistance and heat resistance. Because of its excellent performance, it has become an important material in aerospace industry. However, this kind of alloy has very poor machinability, and rapid tool wear is a very serious problem in titanium alloy processing. At present, it is difficult to guarantee the ultra-precision machining quality of titanium alloy materials, which limits its application in high-tech fields. In order to solve this problem, the influence of cutting speed on ultra-precision cutting process of titanium alloy was analyzed comprehensively. and it was found that better surface quality could be obtained at lower cutting speed. In order to study the influence of cutting speed in ultra-precision cutting of titanium alloys, cutting experiments have been carried out. Additionally, a finite element model was established to analyze the ultra-precision cutting process. Also, the constitutive model, damage model, friction model, and heat transfer in the modeling process were discussed. The chip morphology, cutting temperature, cutting force, and surface morphology under different cutting velocities are analyzed by simulation. Then, the simulation results were compared with the experimental results. The findings show that cutting speed has great influence on the ultra-precision turning of the Ti-6Al-4V alloy and the surface roughness obtained by ultra-precision cutting of titanium alloy can be lower than 20 nm at a lower cutting speed.

Four-corners traction combined with continuous everting suture technique as a modification in bicaval anastomosis for orthotopic heart transplantation.

BACKGROUND: Although standard bicaval techniques has become popular in orthotopic heart transplantation, distortion, bleeding, thrombosis and arrhythmia were still causes for concern. This study was designed to compare the standard bicaval techniques and modified bicaval techniques in our institution. MATERIALS AND METHODS: A total of 70 recipients underwent orthotopic heart transplantation at our center from June 2015 to April 2019 (standard group = 24 cases, modified group = 46 cases). The average follow-up period was 46.4 ± 17.4 months. Atrioventricular cavity diameter was measured by ultrasonography and left atrial morphology was evaluated by CT-angiography and three-dimensional reconstruction. RESULTS: Recipients in both groups were similar with pre-operative characteristics. Total ischemic, cardiopulmonary bypass and cross-clamp times were similar. The modified bicaval techniques group has a significantly fewer blood transfusion, lower post-transplant tricuspid regurgitation grade and the incidence of post-operative atrial arrhythmia than standard bicaval techniques group. CT-angiography and three-dimensional reconstruction illustrated ideal and physiologic left atrial morphological structure. Short-term survival differed significantly and the cumulative proportion of survival was significantly higher in the modified bicaval techniques group than that in the standard bicaval techniques group. CONCLUSIONS: This study showed that modified bicaval techniques offers a better early outcome than standard bicaval techniques. The significant reduction of intraoperative blood transfusion and post-transplant tricuspid regurgitation grade in the modified bicaval techniques group may has a major impact on the short-term survival.

Effect of parameters on surface roughness during the ultra-precision polishing of titanium alloy.

Titanium alloys have great potential in ultra-precision situations due to the excellent properties, such as high corrosion resistance, high specific-strength and high biocompatibility. However, the application of titanium alloys in ultra-precision field is limited by the poor machinability. There are difficulties in obtaining the optical surface. In this study, the possibility for obtaining optically graded surfaces of titanium alloys by ultra-precision polishing was investigated. Before the ultra-precision polishing, ultra-precision turning with a single point diamond tool was used to get all sample surfaces. But, titanium alloy is difficult to obtain good surface quality by ultra-precision diamond turning. The samples results confirmed that most of the surface roughness values are higher than 30 nm. In order to explore the polishing process, a large number of ultra-precision polishing experiments were conducted. In addition, the effects of different ultra-precision polishing parameters on the surface profiles of titanium alloy Ti6Al4V were investigated in depth. The results show that the average values of surface roughness of titanium alloy parts with ultra-precision turning can be further reduced by 70% or so by ultra-precision polishing. Using a reasonable combination of high spindle speed and large cutting depth, the value of surface roughness can even be lower than 2 nm.

Effect of novel bicaval anastomosis technique for transplantation with and without prior cardiac surgery history.

BACKGROUND: To evaluate the graft outcomes after orthotopic heart transplantation (HTx) with a novel bicaval anastomosis technique between recipients with and without a history of prior cardiac surgery. METHODS: Of 70 patients who underwent HTx with a novel four-corners traction bicaval anastomosis technique from August 2017 to November 2019, 60 recipients underwent the HTx procedure as their first cardiac surgery (group A), while 10 recipients underwent HTx after prior cardiac surgery (group B). Patients in the two groups were compared in terms of their preoperative baseline variables such as etiological categories, history of blood transfusion and panel reactive antibody (PRA), intraoperative operation time and blood infusion volume, postoperative treatment time, and complications such as acute rejection and 30-day mortality as well as survival rates. RESULTS: Preoperative variables were comparable in group A and group B except for the history of blood transfusion (0% vs. 90.0%, P<0.001, respectively); the level of PRA was 7.5%±5.8% and 9.5%±10.9% for group A and B, respectively (P=0.583), but the time of the operation was nearly 1 hour longer for group B than group A (all P<0.05). No cases of left atrial thrombosis and donor heart distortion were observed in either group. Reoperation (1.7% vs. 10.0%, P=0.267), infection (0% vs. 10.0%, P=0.142), other postoperative complications as well as the 30-day mortality (1.7% vs. 10.0%, P=0.267), and postoperative survival rates (91.5% vs. 90.0%, P=0.805) were comparable between the two groups (all P>0.05). CONCLUSIONS: Four-corner traction bicaval anastomosis combined with a continuous everting suture technique may result in approximately comparable prognoses for heart recipients with a history of cardiac surgery when compared with those without a history of cardiac surgery and this technique may reduce the incidence of left atrial thrombosis and distortion. Further follow-up of the long-term outcomes will be required to validate these results.

From Lab Formulation Development to CTM Manufacturing of KO-947 Injectable Drug Products: a Case Study and Lessons Learned.

Formulation development of KO-947-K mesylate injectable drug products was described. Solution formulations were initially attempted, and key parameters such as drug concentration, buffer, pH, complexing agent, and tonicity modifying agent were carefully evaluated in the lab setting, mainly focusing on solubility and chemical stability. A lead solution formulation was advanced to a scaleup campaign. An unexpected stability issue was encountered, and the root cause was attributed to the heterogeneous liquid freezing process of the formulated solution at -20°C, which had not been captured in the lab setting. A lyophilized product was then designed to overcome the issue and supplied to the phase I clinical trial.

Exosomes from dendritic cells with Mettl3 gene knockdown prevent immune rejection in a mouse cardiac allograft model.

We have previously demonstrated that Mettl3-silencing dendritic cells (DCs) exhibited immature properties and prolonged allograft survival in a murine heart transplantation model. Exosomes derived from donor DCs (Dex) are involved in the immune rejection of organ transplantation, and blocking Dex transfer may suppress immune rejection. Herein, this study aimed to investigate whether Mettl3 knockdown inhibits the secretion and activity of donor Dex, thereby inhibiting donor Dex-mediated immune rejection. The imDex, mDex, shCtrl-mDex, and shMettl3-mDex were obtained from the culture supernatant of DCs (immature DCs, mature DCs, shCtrl-infected mature DCs, shMettl3-infected mature DCs) derived from donor BALB/c mouse bone marrow and then co-cultured with splenic T cell lymphocyte suspension from recipient C57BL/6 mice in vitro or injected into recipient C57BL/6 mice before the cardiac transplantation. Donor shMettl3-mDex expressed lower concentration of exosomes and lower expression of Mettl3, Dex markers (ICAM-1, MHC-I, MHC-II), as well as lower ability to activate T cell immune response than shCtrl-mDex. Administration of donor shMettl3-mDex attenuated immune rejection after mouse heart transplantation and prolonged the allograft survival. In summary, Mettl3 knockdown inhibits the immune rejection of Dex in a mouse cardiac allograft model.

Odorranalectin modified PEG-PLGA/PEG-PBLG curcumin-loaded nanoparticle for intranasal administration.

Curcumin (Cur) is a promising drug for neurological diseases. Nevertheless, the application of Cur has been limited due to its difficulty in penetrating blood-brain barrier (BBB). Intranasal drug delivery, a noninvasive alternative delivery of Cur, can effectively help Cur cross BBB and inert into central nervous system directly. Odorranalectin (OL) which is the smallest lectin can prolong the residence time of Cur in the nasal mucosa and promote cellular uptake. In this work, a nasal delivery system incorporating OL modified Cur-loaded nanoparticles (Cur-OL-NPs) was developed and expected to bypass BBB and promote the absorption of Cur. We conjugated OL to polyethylene glycol-poly (lactic-co-glycolic acid) (PEG-PLGA), and combined polyethylene glycol-poly (γ-benzyl-L-glutamate) (PEG-PBLG) and OL-PEG-PLGA to prepare nanoparticles to improve the stability, bioavailability and targeting of Cur. Compared with unmodified NPs, increased efficiency of Cur-OL-NPs cellular uptake by Calu-3 cells had been obtained with no severe toxicity. Furthermore, in vivo pharmacokinetic studies also showed that Cur-OL-NPs had higher relative bioavailability. Thus, it is concluded that the results indicated that OL-NPs as carriers of Cur had a promising future in nasal drug delivery system.

Dendritic cells with METTL3 gene knockdown exhibit immature properties and prolong allograft survival.

Maturation of dendritic cells (DCs) initiates adaptive immune responses and thereby provokes allograft rejection. Here, this study aimed to explore the effect of Methyltransferase-like protein 3 (METTL3) silencing on DC function and the role of METTL3-silencing donor DCs in the immune response after mouse heart transplantation. Bone marrow-derived DCs from donor BALB/c mice were infected with lentiviruses expressing METTL3-specific short hairpin RNA (LV-METTL3 shRNA) to silence METTL3. Then METTL3-silencing DCs were treated with lipopolysaccharide (LPS) for another 48 h to induce DC maturation. Recipient C57BL/6 mice were injected with phosphate-buffered saline (PBS), immature DCs, and METTL3 shRNA-DCs prior to the cardiac transplantation involving the transfer of hearts from donor BALB/c mice to recipient C57BL/6 mice. In vitro we demonstrated that METTL3-silencing DCs had lower expression of MHCII, costimulatory molecules (CD80, CD86), and DC-related cytokines (IFN-γ, IL-12) as well as lower ability to activate T-cell proliferation, which were consistent with the characteristics of tolerogenic DCs. In vivo we found that METTL3-silencing donor DCs induced immune tolerance after mouse heart transplantation and prolonged the allograft survival, which might be associated with Th1/Th2 immune deviation. In summary, METTL3-silencing DCs exhibit immature properties and prolong allograft survival.

Epidemiologic and clinical characteristics of heart transplant recipients during the 2019 coronavirus outbreak in Wuhan, China: A descriptive survey report.

BACKGROUND: The epidemiologic and clinical characteristics of heart transplant (HTx) recipients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We studied the characteristics of HTx recipients from December 20, 2019, to February 25, 2020, in an effort to understand their risk and outcomes. METHODS: All accessible HTx recipients were included in this single-center retrospective study. We collected information on the recipients using a web-based questionnaire as well as the hospital database. RESULTS: We followed 87 HTx recipients (72.4% were men, and the average age was 51 years). A total of 79 recipients resided in Hubei, and 57 recipients had a Wuhan-related history of travel or contact. Most took precautionary measures while in contact with suspicious crowds, and 96.6% of the families and communities undertook prevention and quarantine procedures. Four upper airway infections were reported, and 3 of them tested negative for SARS-CoV-2 (the fourth recovered and was not tested). All cases were mild and successfully recovered after proper treatment. Laboratory results of 47 HTx cases within the last 2 months were extracted. Of these, 21.3% of recipients had pre-existing lymphopenia, and 87.2% of recipients had a therapeutic concentration of tacrolimus (5-12 ng/ml). Liver and kidney insufficiency was seen in 5 and 6 recipients, respectively. CONCLUSION: HTx recipients who practiced appropriate prevention measures had a low rate of infection with SARS-CoV-2 and transition to the associated disease COVID-19. These early data will require confirmation as the pandemic establishes around the world.

Obesity is a risk factor for preoperative hypoxemia in Stanford A acute aortic dissection.

Obese individuals are apt to develop Stanford A acute aortic dissection (AAD) complicated with acute lung injury (ALI), but the mechanism is still not well defined. We aim to investigate whether oxidative stress and inflammatory are involved in the aortic dissection lung injury caused by obesity.Seventy-nine patients were categorized into AAD with obesity group (n = 17) and AAD without obesity group (n = 62) according to body mass index (BMI). Inflammatory reactions including interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), IL-6, C-reactive protein (CRP) and white blood cell (WBC) count, and oxidative stress including malondialdehyde (MDA), superoxide dismutase were determined using enzyme-linked immunosorbent assays and chemiluminescence. All the patients received ascending aorta replacement combined with total arch replacement and stented elephant trunk. The postoperative complications were recorded.The incidence of preoperative hypoxemia (94.1% vs 35.5%, P < .01) and postoperative ALI (88.2% vs 40.3%, P < .01) in obese patients was significantly higher than that in non-obese patients. Besides, the ICU stay (119.2 ±â€Š59.2 vs 87.8 ±â€Š31.2 h, P < .01) and hospitalization duration (18.8 ±â€Š8.5 vs 14.3 ±â€Š8.1d, P = .048) were increased in the obese patients with AAD. The expression of IL-1ß, TNF-α, IL-6, CRP, and WBC was remarkably increased (P < .01) in obese group compared with non-obese group.Oxidative stress and inflammatory response may be involved in the process of ALI of aortic dissection caused by obesity, which provides new ideas for the treatment of ALI of the aortic dissection.

Avß3 Single-Stranded DNA Aptamer Attenuates Vascular Smooth Muscle Cell Proliferation and Migration via Ras-PI3K/MAPK Pathway.

OBJECTIVES: To observe the effect of avß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is currently the preferred method for the treatment of coronary heart disease. However, vascular restenosis still occurs after PTCA treatment, severely affecting the clinical efficacy of PTCA. Integrin avß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. METHODS: In this experiment, we used systematic evolution of ligands by exponential enrichment (SELEX) to screen out avß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. ß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. ß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. ß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. RESULTS: In the present study, we found that avß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. P < 0.05). Avß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. P < 0.05). AvP < 0.05). Av. CONCLUSIONS: The findings suggest that avß3 ssDNA inhibited the proliferation and migration of VSMCs by suppressing the activation of Ras-PI3K/MAPK signaling.ß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism.

Avß3 single-stranded DNA aptamer attenuates vascular restenosis via Ras-PI3K/MAPK pathway in rats after percutaneous transluminal coronary angioplasty.

Our aim was to investigate the effect of avß3 single-stranded DNA aptamer (avß3 ssDNA) on vascular restenosis in rats after percutaneous transluminal coronary angioplasty (PTCA) via the Ras-PI3K/MAPK pathway. Sixty Sprague-Dawley rats were randomly divided into six groups: sham-operated, PTCA, PTCA+cilengitide (18 mg/kg, n = 8), and avß3 ssDNA treatment at 50, 100, and 200 µg/kg. Hematoxylin-eosin staining was performed to evaluate the successful establishment of the PTCA model and to assess the degree of intimal hyperplasia. Immunofluorescence and in situ hybridization were carried out to observe the level of avß3. Immunohistochemistry was used to detect the expression of E-cadherin, N-cadherin, α-smooth muscle actin (α-SMA), angiotensin 1 (ANG1), and ANG2. The expression of osteopontin (OPN), focal adhesion kinase (FAK), Ras, mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), signal transducer and activator of transcription 1 (STAT1), and GTPase was observed by the western blot and quantitative reverse transcription polymerase chain reaction. Compared with rats subjected to PTCA only, those treated with avß3 ssDNA showed significantly decreased vascular occlusion rate (P < .05). The protein expression of avß3, OPN, p-FAK, ANG2, and E-cadherin was significantly increased by avß3 ssDNA (P < .05), while the levels of ANG1, α-SMA, N-cadherin Ras, MAPK, PI3K, STAT1, and GTPase were significantly decreased (P < .05). Avß3 ssDNA reduced the proliferation, migration, epithelial-mesenchymal transition, and vascular remodeling of vascular smooth muscle cells, and the mechanism may be related to the Ras-PI3K/MAPK pathway.

Morbidity and Mortality of Nosocomial Infection after Cardiovascular Surgery: A Report of 1606 Cases.

Nosocomial infection (NI) is one of the most significant complications arising after open heart surgery, and leads to increased mortality, hospitalization time and health resource allocation. This study investigated the morbidity, mortality, and independent risk factors associated with NI following open heart surgery. We retrospectively surveyed the records of 1606 consecutive cardiovascular surgical patients to identify those that developed NI. The NI selection criteria were based on the Centers for Disease Control and Prevention (CDC) guidelines. The term NI encompasses surgical site infection (SSI), central venous catheter-related infection (CVCRI), urinary tract infection (UTI), respiratory tract infection and pneumonia (RTIP), as well as other types of infections. Of 1606 cardiovascular surgery patients, 125 developed NI (7.8%, 125/1606). The rates of NI following surgery for congenital malformation, valve replacement, and coronary artery bypass graft were 2.6% (15/587), 5.5% (26/473) and 13.6% (32/236), respectively. The NI rate following surgical repair of aortic aneurysm or dissection was 16.8% (52/310). Increased risk of NI was detected for patients with a prior preoperative stay ≥3 days (OR=2.11, 95% CI=1.39-3.20), diabetes (OR=2.00, 95%=CI 1.26-3.20), length of surgery ≥6 h (OR=2.26, 95% CI=1.47-3.47), or postoperative cerebrovascular accident (OR=4.08, 95% CI=1.79-9.29). Greater attention should be paid toward compliance with ventilator and catheter regulations in order to decrease NI morbidity and mortality following cardiovascular procedures.

Assessing Serum Levels of ADAMTS1 and ADAMTS4 as New Biomarkers for Patients with Type A Acute Aortic Dissection.

BACKGROUND Type A AAD, a serious cardiovascular emergency requiring urgent surgery, is the most common and serious AAD. The aim of this study was to investigate the diagnostic value of ADAMTS1 and ADAMTS4 in patients with type A acute aortic dissection (AAD). MATERIAL AND METHODS Immunohistochemistry and qRT-PCR were used to evaluate the protein and mRNA expression levels of ADAMTS1 and ADAMTS4 in 14 type A acute aortic dissection (AAD) tissues and 10 control aortic tissues. Serum ADAMTS1 and ADAMTS4 expression levels in 74 patients with type A AAD, 36 patients with hypertension (HPT), and 34 healthy donors were examined by ELISA. The diagnostic value of serum ADAMTS1 and ADAMTS4 were determined by receiver operator characteristic curve (ROC). Furthermore, the dynamic change of serum ADAMTS1, ADAMTS4, D-dimer, and CRP were detected before and after surgery at different time-points in 14 patients with type A AAD. RESULTS ADAMTS1 and ADAMTS4 protein and mRNA expression levels were found to be significantly higher in 14 type A AAD tissues (p<0.0001) compared with 10 control tissues. Serum ADAMTS1 and ADAMTS4 levels were significant higher in patients with type A AAD than those in the HPT and HD group (p<0.0001 for both). The AUC value, sensitivity, and specificity of ADAMTS1 were 0.9710 (95% CI: 0.9429 to 0.9991), 87.84%, and 97.06%, respectively, and those of ADAMTS4 were 0.9893 (95% CI: 0.9765 to 1.002), 94.59%, and 97.06%, respectively. In addition, serum ADAMTS4 level was gradually decreased with the time extension after surgery, similar to D-dimer change. CONCLUSIONS These data suggest that measurement of serum ADAMTS1 and ADAMTS4 levels could be potential diagnostic biomarkers for type A AAD, and ADAMTS4 might be a risk factor associated with type A AAD.

Blocking the ERK1/2 signal pathway can inhibit S100A12 induced human aortic smooth muscle cells damage.

Increased levels of S100A12 and activated matrix metalloproteinase 2/9 (MMP-2/9) produced by human aortic smooth muscle cells (HASMCs) have recently implicated in the development of thoracic aortic disease. In the present study, we investigated the effect of S100A12 on HASMCs and identified the intracellular signal pathways involved by Western blot. The results were shown that up-expression of S100A12 in HASMCs induced cell apoptosis and inhibited cell proliferation. Additionally, S100A12 significantly increased the expression of MMP-2, MMP-9, and VCAM-1 in HASMCs at translational levels. Furthermore, our results also showed that S100A12 induced HASMCs damage by increased related proteins expression was mediated by the activation of ERK1/2 signal pathway, whereas p38 MAPK had no effect on those processes. Blocked the activation of ERK1/2 could decrease S100A12 induced the apoptosis and inhibited cell proliferation of HASMCs. In conclusion, these results indicated that S100A12 could increase the expression of MMP-2, MMP-9, and vascular cell adhesion molecule 1 (VCAM-1) in HASMCs via activation of ERK1/2 signal pathway, which leads to injury of HASMCs. Therefore, antagonists of ERK1/2 may be useful for treating thoracic aortic dissection.

Simplified total aortic arch replacement with an in situ stent graft fenestration technique for acute type A aortic dissection.

OBJECTIVE: Total arch replacement combined with stented elephant trunk implantation in the descending aorta has successfully improved the outcomes of acute type A aortic dissection (AAAD). However, the optimal surgical strategy for the left subclavian artery (LSA) during the procedure remains a challenge. This study aimed to present our new technique of in situ stent graft fenestration to simplify the surgical procedure for suitable cases of AAAD. METHODS: From August 2008 to December 2015, a total of 106 patients underwent simplified total aortic arch replacement with an in situ stent graft fenestration technique. The mean age of the patients was 50.71 ± 11.54 years (range, 24-78 years). Both perioperative variables and postoperative follow-up outcome of the procedure were assessed. RESULTS: The in-hospital mortality rate was 7.5%. The mean cardiopulmonary bypass time was 162.73 ± 68.49 minutes, cross-clamp time was 93.13 ± 22.29 minutes, and circulatory arrest time was 23.28 ± 5.56 minutes. Transient neurologic dysfunction was observed in five patients. No permanent neurologic dysfunction was observed, and no stroke or left arm ischemia occurred. During the follow-up period (mean, 43.4 ± 21.53 months), the survival rates of patients were 90.6%, 85.5%, and 78.8% at 1 year, 2 years, and 7 years, respectively. No stroke or left limb ischemia was observed. The LSA perfusion was well preserved in all surviving patients, and there was no endoleak or dissection around the LSA. All patients were free from reoperation. CONCLUSIONS: The in situ graft fenestration technique could simplify the procedure of LSA reconstruction during total arch replacement, provide a good surgical view for anastomosis and hemostasis, shorten the operation time, and yield satisfactory early and midterm results. It is a safe and effective alternative approach for suitable patients with AAAD. However, the long-term results of this technique need further evaluation.

Effects of S100A12 reduction on H2O2-induced injury of human vascular smooth muscle cells (HVSMCs).

Thoracic aortic dissection is a catastrophic acute aortic disease with a high postoperative mortality. Although TAD results from various risk factors, the final common pathway for its development is tunica media dysfunction with vascular inflammation. The aim of the present study was to investigate the protective effects of S100A12 reduction on hydrogen peroxide (H2O2)-induced human vascular smooth muscle cells (HVSMCs) injury and evaluate the relevance of S100A12 and aortic disease. In this study, HVSMCs were exposed to the H2O2 in the presence or absence of S100A12, then cell viability was detected by MTT assay, cell apoptosis was performed with the flow cytometry kit, IL-6 and TNFα production evaluated by ELISA and apoptotic proteins were investigated by western blot. The results showed that H2O2 inhibited cell proliferation, induced cell apoptosis, IL-6 and TNFα release, the increase of caspase-3 protein and the decrease of Bcl-2, while transfection with S10012A shRNA significantly repaired the situation above. Our findings suggested that reduction of S100A12 protects HVSMCs against H2O2-induced injury, and may be useful as a treatment for aortic disease.