Lung cancer with bilateral internal jugular vein thrombosis.

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Impact of angiotensin receptor-neprilysin inhibition (ARNI) in improving ejection fraction and left and right ventricular remodeling in heart failure.

Angiotensin receptor neprilysin inhibitors (ARNI), a new therapeutic class of agents acting on the renin angiotensin aldosterone system (RAAS) and neutral endopeptidase system has been developed in treatment of ventricular remodeling and has attracted considerable attention. The first in class is LCZ696, which is a molecule that combines Valsartan (ARB) and Sacubitril (neprilysin inhibitor) within a single substance. Sacubitril-Valsartan is the first angiotensin receptor enkephalin inhibitors (ARNI), which can block angiotensin II type 1 receptor (AT1R) while inhibiting enkephalin (NEP) and effectively reverse ventricular remodeling in heart failure patients. It has been recommended by the European and American authoritative guidelines on heart failure as Class I for the treatment of chronic heart failure particularly as intensive care medicine. Sacubitril-Valsartan demonstrated significant effects in improving left ventricular performance and remodeling in patients with heart failure with reduced ejection fraction. Sacubitril acts on increased levels of circulating natriuretic peptides by preventing their enzymatic breakdown and Valsartan, which acts to lessen the effects of the RAAS. However, not more research has been done on its effects on the right ventricle remodeling. This review aimed to assess the impact of angiotensin receptor neprilysin inhibitors on left and right ventricular remodeling in heart failure patients.

An Analysis Regarding the Article: Insight Into the Optimal Timing of Percutaneous Coronary Intervention and Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) is an emerging minimally invasive treatment modality that has been shown to reduce mortality significantly compared to medical therapy alone and is superior or noninferior to conventional surgical aortic valve replacement (SAVR) in patients with severe and symptomatic aortic stenosis (AS) deemed to have an intermediate or higher operative risk. AS patients at intermediate surgical risk, although complications of each procedure were different; with vascular complications and paravalvular leak (PVL) being more common in the TAVI group, whereas several other complications were more frequently found in the SAVR group, including new-onset atrial fibrillation, acute kidney injury and life-threatening bleeding. The risk factors associated with TAVR include larger annulus size (based on MSCT), pre-TAVI transvalvular Vmax, and aortic valve calcification; aortic valve calcification was found to be an independent predictor of PVL.

Lyophilized apoptotic vesicle-encapsulated adhesive hydrogel sponge as a rapid hemostat for traumatic hemorrhage in coagulopathy.

Rapid hemostasis of uncontrolled bleeding following traumatic injuries, especially accompanied by coagulopathies, remains a significant clinical challenge. Extracellular vesicles (EVs) show therapeutic effects for fast clotting. However, low yield, specific storage conditions, and lack of proper carriers have hindered EVs' clinical application. Herein, we establish an optimized procedure method to generate lyophilized mesenchymal stem cell-derived apoptotic vesicles (apoVs) with adhesive hydrogel sponge to show superior procoagulant activity for traumatic hemorrhage. Mechanistically, apoVs' procoagulant ability stems from their high tissue factor (TF) and phosphatidylserine (PS) expression independent of hemocytes and circulating procoagulant microparticles (cMPs). Their stable hemostatic capability was maintained after 2-month room temperature storage. Subsequently, we mixed apoVs with both phenylboronic acid grafted oxidized hyaluronic acid (PBA-HA) and poly(vinyl alcohol) (PVA) simultaneously, followed by lyophilization to construct a novel apoV-encapsulated hydrogel sponge (apoV-HS). Compared to commercial hemostats, apoV-HS exhibits rapid procoagulant ability in liver-laceration and femoral artery hemorrhage in rat and rabbit models of coagulopathies. The combination of high productivity, physiological stability, injectability, plasticity, excellent adhesivity, biocompatibility, and rapid coagulant property indicates that apoV-HS is a promising therapeutic approach for heavy hemorrhage in civilian and military populations.

Recurrent right atrial thrombosis in Ebstein's anomaly.

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Right atrial thrombosis and lymphoblastic leukemia.

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Human-Machine Interaction Methods for Minimally Invasive Surgical Robotic Arms.

Minimally invasive surgery has a smaller incision area than traditional open surgery, which can greatly reduce damage to the human body and improve the utilization of medical devices. However, minimally invasive surgery also has disadvantages such as limited flexibility and operational characteristics. The interactive minimally invasive surgical robot system not only improves the stability, safety, and accuracy of minimally invasive surgery but also introduces force feedback in controlling the surgical robot, which is a new development direction in the field of minimally invasive surgery. This paper reviews the development status of interactive minimally invasive surgical robotic systems and key technologies to achieve human-robot interaction and finally provides an outlook and summary of its development. Fuzzy theory and reinforcement learning are introduced into the parameter adjustment process of the variable guide control model, and a human-robot interaction method for minimally invasive surgical robot posture adjustment is proposed.

Metabolic engineering of yeasts for green and sustainable production of bioactive ginsenosides F2 and 3ß,20S-Di-O-Glc-DM.

Both natural ginsenoside F2 and unnatural ginsenoside 3ß,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity. Traditional approaches for producing them rely on direct extraction from Panax ginseng, enzymatic catalysis or chemical synthesis, all of which result in low yield and high cost. Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products. Hence we engineered the complete biosynthetic pathways of F2 and 3ß,20S-Di-O-Glc-DM in Saccharomyces cerevisiae via the CRISPR/Cas9 system. The titers of F2 and 3ß,20S-Di-O-Glc-DM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level, respectively, by multistep metabolic engineering strategies. Additionally, pharmacological evaluation showed that both F2 and 3ß,20S-Di-O-Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3ß,20S-Di-O-Glc-DM was even better. Furthermore, the titer of 3ß,20S-Di-O-Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor. To our knowledge, this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3ß,20S-Di-O-Glc-DM, and achieving their de novo biosynthesis by the engineered yeasts. Our work presents an alternative approach to produce F2 and 3ß,20S-Di-O-Glc-DM from renewable biomass, which lays a foundation for drug research and development.

Selective Capture, Separation, and Photothermal Inactivation of Methicillin-Resistant Staphylococcus aureus (MRSA) Using Functional Magnetic Nanoparticles.

Antibiotic-free antimicrobial strategies are urgently needed to address the rapid evolution of antimicrobial resistance and transmission of multidrug-resistance bacterial infections. Herein, we fabricated polydopamine-coated porous magnetic nanoparticles (pMNPs@PDA) for effective separation and photothermal killing of methicillin-resistant Staphylococcus aureus (MRSA). Taking advantage of the excellent bacteria-affinitive property of polydopamine, the nanoparticles were anchored on the surface of bacteria, permitting rapid and efficient MRSA capture and separation with over 99% removal via the application of a magnetic field in 30 min. It was found, for the first time, that polydopamine-coated magnetic nanoparticles displayed a selective capture of Gram-positive bacteria when compared with Gram-negative bacteria. The selectivity was attributed to the preferable binding capability of pMNPs@PDA to peptidoglycan (PGN) of Gram-positive bacteria, compared to the lipopolysaccharide (LPS) of Gram-negative bacteria. With the magnetic separation and photothermal properties, pMNPs@PDA exhibited efficient killing of the captured MRSA under the irradiation of near-infrared (NIR) light. Cell cytotoxicity testing demonstrated good biocompatibility of the nanoparticles. These antibiotic-free nanoparticles capable of fast capture, separation, and inactivation of MRSA may be potentially used for water disinfection, blood purification, and treatment of bacterial infections.

Interpenetrating Polymer Network Hydrogels Formed Using Antibiotics as a Dynamic Crosslinker for Treatment of Infected Wounds.

Antibacterial hydrogels, particularly antibiotic-loaded hydrogels, are promising wound dressing materials for treatment of bacteria-infected wound. However, it is challenging to achieve sustained release of antibiotics from hydrogels through physical encapsulation of the antibiotics. Herein, an interpenetrating polymer network P(AA-co-HEMA)Gen hydrogel is reported with double crosslinking formed by free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) and acrylic acid (AA), while using the antibiotic gentamicin (Gen) as the dynamic physical crosslinker. Gentamicin is incorporated into the hydrogel networks via electrostatic interaction between the carboxyl groups of poly(acrylic acid) and the amino groups of gentamicin, which leads to pH-responsive drug release and a significant increase in mechanical strength (i.e., elastic modulus, viscous modulus, and compressive modulus). More importantly, the hydrogels with optimal compositions demonstrate long-lasting antibacterial activity against both Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) over 28 d. The in vivo studies that are conducted in an S. aureus-infected full-thickness skin wound model demonstrate that the double crosslinking hydrogels loaded with gentamicin eliminate bacteria in the wounds more effectively and significantly accelerate wound healing as compared to 3M dressing and the control without any treatment. Taken together, this antibiotic-loaded interpenetrating polymer network hydrogel is potentially a promising wound dressing material for the treatment of bacteria-infected wound.

Transcatheter closure for decompression sickness with a patent foramen ovale: A case report.

A patent foramen ovale is one of the predisposing factors of neurotic decompression sickness. Transcatheter closure of a patent foramen ovale is effective in the secondary prevention of decompression sickness associated with intracardiac shunt. The size of the umbrella should not be limited to the diagnosis of a patent foramen ovale or an atrial septal defect but should be determined by the supporting force of the soft margin of the atrial septum. The surgical method of patent foramen ovale closure is the same as that of the closure of an atrial septal defect, but the closure umbrella of a patent foramen ovale is different from that of the closure umbrella of an atrial septal defect. The size of the umbrella of the right atrium is larger than that of the left atrium, and it is better to close the atrial septum.

[Synthetic biology of plants-derived medicinal natural products].

Medicinal natural products derived from plants are usually of low content and difficult to extract and isolate. Moreover, these compounds are structurally complex, making it difficult to obtain them by environmental unfriendly chemical synthesis. Biosynthesis of medicinal natural products through synthetic biology is a novel, environment-friendly and sustainable approach. Taking terpenoids (ginsenosides, paclitaxel, artemisinin, tanshinones), alkaloids (vincristine and morphine), and flavonoids (breviscapine) as examples, this review summarizes the advances of the biosynthetic pathways and synthetic biology strategies of plant-derived medicinal natural products. Moreover, we introduce the key technologies and methods of synthetic biology used in the research of medicinal natural products, and provide future prospects in this area.

Applications and developments of gene therapy drug delivery systems for genetic diseases.

Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity. Currently, gene therapy drugs such as siRNA, shRNA, antisense oligonucleotide, CRISPR/Cas9 system, plasmid DNA and miRNA have shown great potential in biomedical applications. To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues, cells and organelles, the development of excellent drug delivery vehicles is of utmost importance. Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression. With the development of nanotechnology, novel nanocarriers are gradually replacing viral vectors, emerging superior performance. This review mainly illuminates the current widely used gene therapy drugs, summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs, and sums up the application of gene therapy to treat genetic diseases. Additionally, the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.

High-level soluble expression of human Cu,Zn superoxide dismutase with high activity in Escherichia coli.

As the most important member of antioxidant defense system, human Cu,Zn superoxide dismutase (hCu,Zn-SOD) protects cells against the free radicals produced by aerobic metabolism. hCu,Zn-SOD has been widely used in food, cosmetic and medicine industry due to its health benefits and therapeutic potentials. However, a more extensive application of hCu,Zn-SOD is limited by the challenge of expensive and low production of high-activity hCu,Zn-SOD in large scale. In this study, the codon-optimized hCu,Zn-SOD gene was synthesized, cloned into pET-28a( +) and transformed into Escherichia coli BL21(DE3). After induction with IPTG or lactose, hCu,Zn-SOD was highly expressed as soluble form in LB medium with 800 µM Cu2+ and 20 µM Zn2+ at 25 °C. The recombinant hCu,Zn-SOD was efficiently purified by nickel affinity chromatography. Through optimization of fed-batch fermentation conditions, 342 mg purified hCu,Zn-SOD was obtained from 1 L cultures fermented in a 3-L bioreactor. Furthermore, the recombinant hCu,Zn-SOD retained the enzymatic specific activity of 46,541 U/mg. This study has opened up an effective avenue for industrial production of hCu,Zn-SOD through microbial fermentation in the future.

Catheter-Based Renal Denervation Attenuates Kidney Interstitial Fibrosis in a Canine Model of High-Fat Diet-Induced Hypertension.

BACKGROUND/AIMS: Catheter-based renal denervation (RDN) has emerged as an innovative interventional approach for reducing blood pressure (BP), suppressing ventricular substrate remodeling, and attenuating heart failure, which suggests that it might reduce kidney fibrosis in a canine model of high-fat diet-induced hypertension. This study thus sought to assess whether RDN could reduce kidney fibrosis and halt the progression of renal impairment in a canine model of high-fat diet-induced hypertension. METHODS: Thirty-two beagles were randomized into either the normal control group (normal diet, n = 10) or the hypertension group (high-fat diet, n = 22). After successful establishment of the model, the hypertension model group was randomized to either the RDN group (n = 9) or the sham-surgery group (n = 8). Renal artery angiography, BP, heart rate (HR), and blood and urine biochemistry results were assessed at 1, 3, and 6 months after surgery. Canines were sacrificed at 6 months after surgery. The extent of kidney interstitial fibrosis, transforming growth factor-beta 1, alpha-smooth muscle actin, connective tissue growth factor, and E-cadherin protein were measured. RESULTS: The group fed a high-fat diet had significantly (p ˂ 0.05) increased body weight, BP, and HR and higher levels of urine albumin, serum noradrenaline (NE), and angiotensin II (AngII) than the control group. The sham-surgery group and RDN group also had higher levels than the control group (p ˂ 0.05). Compared with the sham-surgery group, the RDN group had lower BP, urine albumin, serum NE, and AngII and less fibrotic tissue (all p ˂ 0.05). CONCLUSION: RDN reduced BP, slowed progression of albuminuria, and suppressed renal remodeling in a canine model of high-fat diet-induced hypertension.

PHACTR1 regulates oxidative stress and inflammation to coronary artery endothelial cells via interaction with NF-κB/p65.

BACKGROUND AND AIMS: Genome-wide association studies have showed that genetic variants in phosphatase and actin regulator 1 (PHACTR1) are associated with coronary artery disease and myocardial infarction. However, the underlying mechanism of PHACTR1 in atherosclerosis remains unknown. METHODS: Immunoblots were performed to evaluate the expression of PHACTR1 and phosphorylation of NF-κB signaling. Reactive oxygen species (ROS) labeled with DCFH-DA were assessed by flow cytometry. Fluorescence microscope was used to detect the translocation of p65 in human coronary artery endothelial cells (HACECs). Co-immunoprecipitation was performed to determine the interaction of PHACTR1 with MRTF-A. RESULTS: The mRNA and protein levels of PHACTR1 were markedly increased in carotid plaquescompared with normal carotid arteries. Immunofluorescence staining indicated that PHACTR1 was constitutively expressed in endothelial cells in carotid plaques. Knockdown of PHACTR1 reduced excessive ICAM-1, VCAM-1 and VE-cadherin expression induced by oxidized low density lipoprotein (ox-LDL) in HCAECs. Additionally, silencing PHACTR1 alleviated p47phox phosphorylation and intracellular oxidative stress reflected by the reduction of ROS. Molecular experiments revealed that knockdown of PHACTR1 attenuated NF-κB activity without affecting IκBα and IKKα/ß phosphorylation. In contrast, nuclear translation of p65 was blocked by depletion of PHACTR1. Furthermore, co-immunoprecipitation showed that PHACTR1 interacted with MRTF-A and p65 in HCAECs. Knockdown of MRTF-A suppressed the interaction of PHACTR1 with p65, subsequently blocking the nuclear translocation of p65. CONCLUSIONS: Our finding suggest that silencing PHACTR1 alleviates the nuclear accumulation of p65 and NF-κB via interaction with MRTF-A, ensuing attenuating oxidative stress and inflammation in HCAECs.

Bowel symptoms and self-care strategies of survivors in the process of restoration after low anterior resection of rectal cancer.

BACKGROUND: The purpose of this research is to identify the bowel symptoms and self-care strategies for rectal cancer survivors during the recovery process following low anterior resection surgery. METHODS: A total of 100 participants were investigated under the structured interview guide based on the dimensions of "symptom management theory". RESULTS: 92% of participants reported changes in bowel habits, the most common being the frequent bowel movements and narrower stools, which we named it finger-shaped consistency stools. The 6 most frequently reported bowel symptoms were excessive flatus (93%), clustering (86%), urgency (77%), straining (62%), bowel frequency (57%) and anal pendant expansion (53%). Periodic bowel movements occurred in 19% participants. For a group of 79 participants at 6 to 24 months post-operation, 86.1% reported a significant improvement of bowel symptoms. Among 68 participants of this subgroup with significant improvements, 70.5% participants reported the length of time it took was at least 6 months. Self-care strategies adopted by participants included diet, bowel medications, practice management and exercise. CONCLUSIONS: It is necessary to educate patients on the symptoms experienced following low anterior resection surgery. Through the process of trial and error, participants have acquired self-care strategies. Healthcare professionals should learn knowledge of such strategies and help them build effective interventions.