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.

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.

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.

Renal simplicity denervation reduces blood pressure and renal injuries in an obesity-induced hypertension dog model.

This study aimed to investigate the effects of renal sympathetic denervation (RDN) on blood pressure, renal function, and renal tissue pathological changes in obesity-induced hypertensive dogs. Thirty-two beagle dogs (10-12 months) were randomized to the control (n=10) and model groups (n=22). High-fat diet (HFD) was used to establish the obesity-induced hypertensive model. After 3 months of HFD, 20 animals with successfully induced hypertension were randomized to the RDN (n=10) and sham groups (n=10). Renal artery angiography, body weight, blood pressure, heart rate (HR), and blood and urine biochemistry were determined 1, 3 and 6 months after surgery. Models were killed 6 months after surgery. Pathological changes in the renal artery and renal tissue were assessed. The HFD group had significantly (P<.05) increased body weight, HR, and blood pressure, and higher levels of urine albumin, serum noradrenaline, and angiotensin II compared with controls. After RDN, blood pressure was decreased compared with baseline and the sham group (P<.05). In the RDN group, examination of the renal artery and renal tissue showed intact intima of renal artery in the surgical area, renal sympathetic nerve degeneration, necrosis, and dissolution, and widened space between nerve fibres. Hypertension-induced renal pathological changes were mild to moderate in the RDN group, but severe in the sham group. The control group had normal glomerular structure. In conclusion, RDN can effectively lower blood pressure in obesity-induced hypertensive dogs, as well as hypertension-induced renal pathological changes.

[Changes of blood pressure and S-100B, neuron specific enolase protein in hypertensive dogs after renal sympathetic denervation].

OBJECTIVE: To observe the changes of blood pressure and S-100B, neuron specific enolase (NSE) protein in hypertensive dogs with high fat diet after catheter-based renal sympathetic denervation. METHODS: Twelve Beagles were divided into an interventional group (n=6) and a sham-operation group (n=6). After baseline measurements, the Beagles were fed with lard oil for 3 months. After 3 months, the interventional group had renal sympathetic denervation by percutaneous catheter based radiofrequency ablation and the control group had renal angiography. The blood pressure, plasma S-100B, and NSE before the operation and 3 days, 1 week, 2 weeks, 1 month, 2 months and 3 months after the operation were measured. RESULTS: The dogs had significantly higher levels of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MBP) compared to its baselines (P<0.05). The SBP, DBP and MBP in the interventional group were significantly lower than those in the control group 1 month and 3 months after the operation (P<0.05). Three months after the operation, renal angiography in all dogs revealed no sign of renal artery stenosis. Plasma S-100B and NSE expression in the interventional group were higher than those in the control group 3 days, 1 week and 2 weeks after the operation (P<0.05). CONCLUSION: Renal sympathetic denervation can significantly reduce the SBP, DBP and MBP in hypertensive dogs. The plasma S-100B and NSE may be used as indicators for assessment of renal nerve injury after renal sympathetic denervation.

Lung cancer with bilateral internal jugular vein thrombosis.

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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.

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.

A progress of research on the application of fascial plane blocks in surgeries and their future direction: a review article.

Fascial plane blocks (FPBs) are gaining popularity in clinical settings owing to their improved analgesia when combined with either traditional regional anesthesia or general anesthesia during the perioperative phase. The scope of study on FPBs has substantially increased over the past 20 years, yet the exact mechanism, issues linked to the approaches, and direction of future research on FPBs are still up for debate. Given that it can be performed at all levels of the spine and provides analgesia to most areas of the body, the erector spinae plane block, one of the FPBs, has been extensively studied for chronic rational pain, visceral pain, abdominal surgical analgesia, imaging, and anatomical mechanisms. This has led to the contention that the erector spinae plane block is the ultimate Plan A block. Yet even though the future of FPBs is promising, the unstable effect, the probability of local anesthetic poisoning, and the lack of consensus on the definition and assessment of the FPB's success are still the major concerns. In order to precisely administer FPBs to patients who require analgesia in this condition, an algorithm that uses artificial intelligence is required. This algorithm will assist healthcare professionals in practicing precision medicine.

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.

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.

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.

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.