Clinical Study on the Management of Aortic Dissection Involving the Aortic Arch through Endovascular Isolation and In Situ Fenestration with Covered Stent.

Objective: This study aimed to investigate the clinical effectiveness of the SilverFlow branch stent through endovascular isolation and in situ fenestration (ISF) for the treatment of aortic dissection (AD) involving the aortic arch. Methods: A total of 21 patients with AD involving the aortic arch, admitted to our hospital between September 2021 and January 2023, were selected for this prospective study. All patients underwent treatment with an endoluminal isolated ISF-covered stent, with the branch stent being the SilverFlow, developed by Shenzhen Xianjian Company. We assessed the success rate of the ISF procedure stent-related complications and compared the volumes of the true and false cavities before and after treatment. Follow-up evaluations were conducted 1, 3, and 6 months post-operation, focusing on neurological complications, mortality, and the need for secondary interventional treatment. Results: Among the 21 AD patients with aortic arch involvement, 20 (95.23%) underwent non-emergency surgery, while 1 (4.76%) required emergency surgery due to cardiac ischemia and signs of dissection rupture. All surgeries were successfully completed. After treatment, the average volume of the true lumen significantly decreased compared to pre-treatment levels, while the volume of the false lumen significantly increased (P < .05). The success rate was 100%, with only one case (4.76%) experiencing type I internal leakage. There were no cases of stent displacement, distortion, or fenestration vessel occlusion. One patient (4.76%) succumbed to acute pericardial tamponade, resulting in a mortality rate of 4.76%. Another patient (4.76%) suffered from upper limb ischemia, significantly improving with antithrombotic drug treatment. No occurrences of stroke, visceral ischemia, or other complications were reported, and no secondary interventional treatments were required. Conclusions: The application of the SilverFlow branch stent for endovascular isolation of ISF in AD cases involving the aortic arch demonstrates a high success rate, low complication and mortality rates, and significant clinical feasibility and value.

Pharmacokinetic Properties of Humanized IgG1 and IgG4 Antibodies in Preclinical Species: Translational Evaluation.

Assessment of the factors that regulate antibody exposure-response relationships in the relevant animal models is critical for the design of successful translational strategies from discovery to the clinic. Depending on the specific clinical indication, preclinical development paradigms may require that the efficacy or dosing-related attributes for the existing antibody be assessed in various species when cross-reactivity of the lead antibody to the intended species is justified. Additionally, with the success of monoclonal antibodies for management of various human conditions, a parallel interest in therapeutic use of these novel modalities in various veterinary species has followed. The protective role of neonatal Fc receptor (FcRn) in regulation of IgG homeostasis and clearance is now well recognized and the "nonspecific clearance" of antibodies through bone marrow-derived phagocytic and vascular endothelial cells (via lysosomal processes) is modulated by interactions with FcRn receptors. In this study, we have attempted to examine the PK properties of human IgG antibodies in dog and monkey. These studies establish a translational framework for evaluation of IgG antibody PK properties across species.

Integrative Pharmacology: Advancing Development of Effective Immunotherapies.

With the recent advances in cancer immunotherapy, it is now evident that the antigen-specific activation of the patients' immune responses can be utilized for achieving significant therapeutic benefits. Novel molecules have been developed and promising advances have been achieved in cancer therapy. The recent success of cancer immunotherapy clearly reflects the novelty of the approach and importance of this class of therapeutics. Due to the nature of immunotherapy, i.e., harnessing the patient's immune system, it becomes critical to evaluate the important variables that can guide preclinical development, translational strategies, patient selection, and effective clinical dosing paradigms following single and combination therapies. To further boost the durability and efficacy profiles of IO (immuno-oncology) drugs following single agent therapy, novel combination therapies are being sought. Combination strategies have become critical for enhancing the anti-tumor immunity in broader cancer indications. Comprehensive methods are being developed to quantify the synergistic combination effect profiles at various development phases. Further evaluation of the signaling and pathway components can potentially establish a unique "signature" characteristic for specific combination therapies following modulation of various immunomodulatory pathways. In this article, critical topics related to preclinical, translational, and clinical development of IO agents are discussed.

Baicalein protects against cardiac hypertrophy through blocking MEK-ERK1/2 signaling.

Baicalein, a flavonoid present in the root of Scutellaria baicalensis, is well known for its antibacterial, antiviral, anti-inflammatory, antithrombotic, and antioxidant effects. Here we show that baicalein also attenuates cardiac hypertrophy. Aortic banding (AB) was performed to induce cardiac hypertrophy secondary to pressure overload in mice. Mouse chow containing 0.05% baicalein (dose: 100 mg/kg/day baicalein) was begun 1 week prior to surgery and continued for 8 weeks after surgery. Our data demonstrated that baicalein prevented cardiac hypertrophy and fibrosis induced by AB, as assessed by echocardiographic and hemodynamic parameters and by pathological and molecular analysis. The inhibitory action of baicalein on cardiac hypertrophy was mediated by effects on mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinases (ERK1/2) signaling and GATA-4 activation. In vitro studies performed in rat cardiac H9c2 cells confirmed that baicalein attenuated cardiomyocyte hypertrophy induced by angiotensin II, which was associated with inhibiting MEK-ERK1/2 signaling. In conclusion, our results suggest that baicalein has protective potential for targeting cardiac hypertrophy and fibrosis through suppression of MEK-ERK1/2 signaling. Baicalein warrants further research as a potential antihypertrophic agent that might be clinically useful to treat cardiac hypertrophy and heart failure.

[Chen Shigong's contributions to the history of TCM surgery].

Chen Shigong is a famous surgery doctor in our country. He has been researching surgery from youth and finished the book Wai Ke Zheng Zong (Surgery Authority) based on forty years' treatment experience. Chen dedicated in innovation and emphasized combining the ins and outs in curing surgery ailment. Chen changes the behindhand status that surgeon only pay attention to skill and don't research the medical knowledge, and plays an important roll in the development of surgery.