Long-Term Prognosis of Patients Undergoing Percutaneous Coronary Intervention: The Impact of Serum Creatinine Levels on All-Cause Mortality.

BACKGROUND The correlation between serum creatinine levels and the long-term prognosis of patients undergoing percutaneous coronary intervention (PCI) has not yet been systematically investigated. This study aimed to evaluate the association between long-term prognosis and serum creatinine levels in patients after PCI. MATERIAL AND METHODS This was an observational cohort study of 2533 patients who received PCI and completed serum creatinine and other tests in China. The study's primary prognostic indicators were the frequency of clinical adverse events, all-cause death, cardiac death, acute myocardial infarction, and stroke. All-cause death referred to death from all causes during the follow-up period, whereas cardiac death was death due to cardiac injury resulting in severe cardiac dysfunction or failure. Clinical events included death, ischemia, and stroke. Yao et al completed the entire study and uploaded the data to the DATADRYAD website. We used only this data for secondary analysis. RESULTS The study involved 2533 participants, with a mean age of 59.9±11.1 years and a median follow-up of 29.8 months. The analysis, controlling for confounding factors, revealed a positive correlation between serum creatinine and all-cause death (OR: 2.178, 95% CI: 1.317-3.603, P<0.05), which was confirmed by the results of sensitivity analysis (P for trend <0.05). However, no direct linear correlation was found between serum creatinine and acute myocardial infarction, cardiac death, or stroke. CONCLUSIONS There was a linear correlation between serum creatinine and all-cause death in the long-term prognosis of patients after PCI, independent of acute myocardial infarction, cardiac death, and stroke.

Application of double plate fixation combined with Masquelet technique for large segmental bone defects of distal tibia: a retrospective study and literature review.

BACKGROUND: There is no effective consensus on the choice of internal fixation method for the Masquelet technique in the treatment of large segmental bone defects of the distal tibia. Thus, the study aimed to investigate the outcomes of the Masquelet technique combined with double plate fixation in the treatment of large segmental bone defects. METHODS: This was a retrospective study involving 21 patients with large segmental bone defects of the distal tibia who were treated between June 2017 and June 2020. The length of bone defect ranged from 6.0 cm to 11 cm (mean, 8.19 cm). In the first stage of treatment, following complete debridement, a cement spacer was placed to induce membrane formation. In the second stage, double plate fixation and autologous cancellous bone grafting were employed for bone reconstruction. Each patient's full weight-bearing time, bone healing time, and Iowa ankle score were recorded, and the occurrence of any complications was noted. RESULTS: All patients were followed up for 16 to 26 months (mean, 19.48 months). The group mean full weight-bearing time and bone healing time after bone grafting were 2.41 (± 0.37) months and 6.29 (± 0.66) months, respectively. During the treatment, one patient had a wound infection on the medial side of the leg, so the medial plate was removed. The wound completely healed after debridement without any recurrence. After extraction of iliac bone for grafting, one patient had a severe iliac bone defect, which was managed by filling the gap with a cement spacer. Most patients reported mild pain in the left bone extraction area after surgery. The postoperative Iowa ankle score range was 84-94 (P < 0.05). In this cohort, 15 cases were rated as "excellent", and 6 cases as "good" on the Iowa ankle scoring system. CONCLUSION: The Masquelet technique combined with double plate fixation is a safe and effective method for the treatment of large segmental bone defects of the distal tibia.

Efficacy and safety of self-made covered coronary stent in the treatment of coronary artery perforation.

OBJECTIVE: To observe the efficacy and safety of self-made covered coronary stent in the treatment of coronary artery perforation. METHODS: Covered coronary stent was prepared by wrapping 3 M film on the surface of coronary stents. The beagle dogs were divided into control group and experimental group. A drug-eluting stent (DES) was implanted in the control group. The covered stent was applied to block the coronary branches of beagle dogs. The CaIMR value after stent placement was calculated by FlashAngio software. The effect of blocking the coronary branches on blood flow was observed by coronary angiography (CAG). The condition of the implanted stent was observed by optical coherence tomography (OCT), and the histopathologic examination of the coronary vessel implanted stent was performed by HE staining. RESULTS: The best number of layers was 2. Compared with the control group, the CaIMR of the experimental group increased (p < 0.05). A lot of in-stent thrombosis were found in the experimental group and obvious blood flow obstruction during follow-up. HE staining showed that stents implanted in the two groups adhered well to the wall of the blood vessel, but in-stent thrombosis and intimal hyperplasia were founded in the experimental group, while the in-stent restenosis was not founded. CONCLUSION: The self-made coronary covered stent can effectively block the leakage caused by coronary perforation, but the stent endothelialization is poor, which easily causes stent thrombosis and restenosis, so it is not recommended as a routine remedy.

A novel distractor-assisted reduction combined with the sinus tarsi approach for joint depression-type calcaneal fractures.

PURPOSE: A novel percutaneous distractor with the advantage of axial and direct distraction was designed for the minimally invasive treatment of calcaneal fractures. The purpose of this study was to investigate the clinical results and complications of a novel distractor combined with sinus tarsi approach (STA) in treatment of the joint depression-type of calcaneal fractures. METHODS: Fifty-four patients with the depression-type of calcaneal fractures (30 Sanders type II, 22 Sanders type III, 2 Sanders type IV) who were subjected to the novel distractor combined with STA were retrospectively assessed. Calcaneal height, width, and length; Bohler's angle; and the Gissane angle were evaluated pre-operatively and post-operatively. Clinical outcomes were assessed using the American Orthopedic Foot and Ankle Society (AOFAS) and visual analog scale (VAS) pain scores from the last follow-up. Complications were also recorded. RESULTS: Fifty-two patients achieved an average follow-up of 24.3 months (range 18 to 34 months), and two patients were lost to follow-up six months post-operatively. There was significant difference between pre-operative and post-operative calcaneal height, width, and length; Bohler's angle; and Gissane angle (p < 0.01), but no significant difference was detected between the post-operative and normal side Bohler's angle (p > 0.05). The AOFAS ankle and hind foot score was 88.4 ± 6.6, and the VAS score was 1.9 ± 0.7 at the last follow-up. Nine (17.3%) patients developed complications: One experienced skin necrosis and two had screws loosening; three patients developed early degenerative changes of the subtalar joint; two had no symptoms; one had light pain around the subtalar joint without medical treatment; complex regional pain syndrome (CRPS) developed in one patient after seven months post-operatively; and two developed transient ankle stiffness. CONCLUSION: The novel distractor combined with the STA effectively reconstructs the facet depression-type of calcaneal fractures (sanders type II and III) with minimal complications.

Effects and mechanism of renal denervation on ventricular arrhythmia after acute myocardial infarction in rats.

BACKGROUND: Renal denervation (RDN) can reduce ventricular arrhythmia after acute myocardial infarction (AMI), but the mechanism is not clear. The purpose of this study is to study its mechanism. METHODS: Thirty-two Sprague-Dawley rats were divided into four groups: control group, AMI group, RDN-1d + AMI group, RDN-2w + AMI group. The AMI model was established 1 day after RDN in the RDN-1d + AMI group and 2 weeks after RDN in the RDN-2w + AMI group. At the same time, 8 normal rats were subjected to AMI modelling (the AMI group). The control group consisted of 8 rats without RDN intervention or AMI modelling. RESULTS: The study confirmed that RDN can reduce the occurrence of ventricular tachycardia in AMI rats, reduce renal sympathetic nerve discharge, and inhibit the activity of local sympathetic nerves and cell growth factor (NGF) protein expression in the heart after AMI. In addition, RDN decreased the expression of norepinephrine (NE) and glutamate in the hypothalamus,and NE in cerebrospinal fluid, and increased the expression level of γ aminobutyric acid (GABA) in the hypothalamus after AMI. CONCLUSION: RDN can effectively reduce the occurrence of ventricular arrhythmia after AMI, and its main mechanism may be via the inhibition of central sympathetic nerve discharge.

The impacts of China's crops trade on virtual water flow and water use sustainability of the "Belt and Road".

Since the "Belt and Road" initiative was put forward, the trade of crops between China and the countries have increased markedly. Agriculture is the most water-consuming sector, the trade of crops could influence national water availability via virtual water embodied in the products. In order to gain an in-depth understanding of the water use of crops traded in countries along the "Belt and Road", from the perspective of import and export of China's crops, based on the characteristics and driving factors of virtual water trade, we proposed the Water Use Potential Index (WUPI) to assess sustainability of countries and their crops, and constructed a more comprehensive virtual water trade research framework. Results showed that the import and export of virtual water in 64 countries was dominated by green virtual water content from 2001 to 2017, and China was in a virtual water trade surplus. The Association of South-East Asian Nations was China's leading importer and exporter. The level of agricultural available water resources, the proportion of the agricultural population, the scale of agricultural production and the virtual water intensity could promote the growth of virtual water trade in crops between China and countries along the "Belt and Road", while economic model and the population structure played a restraining role. In terms of water use potential, China and Kazakhstan had great sustainable water use potential for crops, and the trade structure of other countries still needed to be further optimized. Understanding the virtual water trade in crops can provide a reference for the rational planning of crop cultivation and water resource conservation.

TEMPO-Enabled Electrochemical Enantioselective Oxidative Coupling of Secondary Acyclic Amines with Ketones.

An electrochemical asymmetric coupling of secondary acyclic amines with ketones via a Shono-type oxidation has been described, affording the corresponding amino acid derivatives with good to excellent diastereoselectivity and enantioselectivity. The addition of an N-oxyl radical as a redox mediator could selectively oxidize the substrate rather than the product, although their oxidation potential difference is subtle (about 13 mV). This electrochemical transformation proceeds in the absence of stoichiometric additives, including metals, oxidants, and electrolytes, which gives it good functional group compatibility. Mechanistic studies suggest that proton-mediated racemization of the product is prevented by the reduction of protons at the cathode.

The Clinical Application of Medial Sural Vessels as Recipient Vessels in Repairing Traumatic Tissue Defects in the Lower Limbs.

BACKGROUND: The use of medial sural vessels (MSVs) as recipient vessels to repair wounds in the lower limbs has been previously reported. However, there is controversy regarding the methods used to expose MSVs and the repairable area of the wound. METHODS: Eight fresh cadavers were used to determine the shape, outer diameter, and length of the MSVs arising from the popliteal vessels. Lower extremity wounds were repaired in 7 patients using free latissimus dorsi flaps with the MSVs as recipient vessels. The flap area ranged from 18 × 11 cm to 24 × 17 cm, and the postoperative follow-up time ranged from 7 to 60 months. RESULTS: The outer diameter of the medial sural artery from the starting point of the popliteal artery was 2.48 ± 0.24 mm. After descending 29.98 ± 4.62 mm, the vessels entered the muscle; the outer diameter of the blood vessel upon entry was 2.24 ± 0.17 mm. Notably, the outer diameter of the vessel was 1.88 ± 0.09 mm only 2 cm after entering the muscle. Seven cases were treated clinically. In 6 cases, we used an approach between the medial head of the gastrocnemius muscle and the tibia to expose and anastomose the MSVs. In 1 case, the vascular diameter was mismatched. After surgery, the flap survived completely in 6 cases. The remaining case experienced epidermal necrosis in the distal part of the flap, which resolved spontaneously. There were no obvious complications. CONCLUSIONS: An approach between the medial head of the gastrocnemius muscle and the tibia can easily expose and anastomose the MSVs in a lateral position. Latissimus dorsi flaps were useful in repairing limb wounds as far as the talocrural region with the MSVs as the recipient vessels.

A new rapamycin-abluminally coated chitosan/heparin stent system accelerates early re-endothelialisation and improves anti-coagulant properties in porcine coronary artery models.

PURPOSE: Drug-eluting stents (DES) in percutaneous coronary intervention are more effective in preventing in-stent restenosis compared with bare metal stents (BMS); however, DES may cause late stent thrombosis, which has limited its use. In this study, the functional properties of a newly developed DES (RAP/CS/HEP), in which rapamycin was abluminally-loaded onto a chitosan/heparin coating stent (CS/HEP), were investigated in large animal artery injury models. METHODS: The effectiveness of BMS, RAP (the traditional version of rapamycin DES), CS/HEP and RAP/CS/HEP stents in preventing coagulation and promoting re-endothelialisation was examined and compared in the porcine coronary artery models with arteriovenous shunt, high load thrombus and coronary balloon injury at day 7 and 28, respectively, after stent implantation. The re-endothelialisation on these stents was further evaluated in terms of endothelial gene expression using quantitative RT-PCR. RESULTS: In the porcine coronary artery injury models, both RAP and RAP/CS/HEP stents were potent in reducing neointimal thickness, thus enlarging lumen area efficiently in the stented artery region compared with BMS and CS/HEP. RAP/CS/HEP stents facilitated re-endothelialisation and inhibited thrombosis more efficiently than BMS and RAP. Consistent with this, the expression of endothelial genes, such as CD31, CD34, eNOS and VEGF, was significantly elevated with RAP/CS/HEP stents compared with RAP and BMS stents. CONCLUSION: Abluminal coating of rapamycin onto the endothelialisation-accelerated CS/HEP stent and may prove to be an efficient treatment for tackling the late stent thrombosis associated with the traditionally circumferential RAP stent. This new RAP/CS/HEP stent system exhibits considerably improved therapeutic activity.

Pharmaceutical properties of calycosin, the major bioactive isoflavonoid in the dry root extract of Radix astragali.

CONTEXT: Radix astragali (Fabaceae astragalus propinquus Schischkin) is a Chinese medicinal herb traditionally used for the treatment of several diseases. Calycosin is the major bioactive chemical in the dry root extract of this medical plant. OBJECTIVE: This work presents a brief overview of recent reports on the potential effects of calycosin on several diseases and the possible mechanisms of action of this chemical. MATERIALS AND METHODS: This review gathers information from the scientific literature (before 1 June 2013) that was compiled from various databases, such as Science Direct, PubMed, Google Scholar, and Scopus. RESULTS: The potential pharmaceutical properties of calycosin in the treatment of tumors, inflammation, stroke, and cardiovascular diseases have gained increasing attention in the recent years. The literature survey showed that calycosin exhibits promising effects for the treatment of several diseases and that these effects may be due to its isoflavonoid and phytoestrogenic properties. The effects of calycosin most likely result from its interaction with the ER receptors on the cell membrane and the modulation of the MAPK signaling pathway. CONCLUSION: Calycosin exhibits great potential as a therapeutic drug and may be a successful example of the standardization and modernization of traditional Chinese herbal medicine.

[Effect of catheter-based renal sympathetic denervation in pigs with rapid pacing induced heart failure].

OBJECTIVE: This study investigated the effect of catheter-based renal sympathetic denervation (RDN) in pigs with rapid pacing induced heart failure. METHODS: Heart failure was induced by rapid right ventricular pacing in 12 pigs and pigs were randomly divided into RDN group (n = 6): pacing+RDN at 7 days post pacing; control group (n = 6): pacing only. Echocardiography examination (LVEF, LVEDD and LVESD) was performed before pacing and at 1 and 2 weeks post pacing. Serum biochemical markers including renin, aldosterone and creatinine were also measured at baseline, 1 and 2 weeks after pacing. Repeated renal artery angiography was performed at 1 week after RDN. All pigs were sacrificed to examine the heart and renal pathology and renal artery sympathetic nerve staining at 2 weeks post pacing. RESULTS: LVEF decreased 1 week after rapid pacing from (60.5 ± 6.0)% to (35.3 ± 9.8)%. LVEF was significantly higher [(42.8 ± 5.9) % vs. (33.4 ± 9.7)%, P = 0.001 8] while LVESD was significantly lower [(28.4 ± 3.7) mm vs. (33.0 ± 2.0) mm, P = 0.001 6] in the RDN group than in the control group at 2 weeks post pacing. At 2 weeks after pacing, plasma concentrations of renin and aldosterone were significantly lower in RDN group compared to the control group (all P < 0.05) . Kidney function and blood pressure were comparable between the two groups at 2 weeks post pacing. There were no signs of renal damages such as renal artery stenosis, dissection and thrombus in all pigs after 2 weeks pacing. Sympathetic neurons of adventitia were injured in RND group. CONCLUSION: RDN could significantly improve cardiac function and attenuate left ventricular remodeling via inhibiting renin-angiotensin-aldosterone system in this pacing induced pig heart failure model.

Mutation of TRPML1 Channel and Pathogenesis of Neurodegeneration in Haimeria.

Neurodegenerative diseases, a group of debilitating disorders, have garnered increasing attention due to their escalating prevalence, particularly among aging populations. Alzheimer's disease (AD) reigns as a prominent exemplar within this category, distinguished by its relentless progression of cognitive impairment and the accumulation of aberrant protein aggregates within the intricate landscape of the brain. While the intricate pathogenesis of neurodegenerative diseases has been the subject of extensive investigation, recent scientific inquiry has unveiled a novel player in this complex scenario-transient receptor potential mucolipin 1 (TRPML1) channels. This comprehensive review embarks on an exploration of the intricate interplay between TRPML1 channels and neurodegenerative diseases, with an explicit spotlight on Alzheimer's disease. It immerses itself in the intricate molecular mechanisms governing TRPML1 channel functionality and elucidates their profound implications for the well-being of neurons. Furthermore, the review ventures into the realm of therapeutic potential, pondering the possibilities and challenges associated with targeting TRPML1 channels as a promising avenue for the amelioration of neurodegenerative disorders. As we traverse this multifaceted terrain of neurodegeneration and the enigmatic role of TRPML1 channels, we embark on a journey that not only broadens our understanding of the intricate machinery governing neuronal health but also holds promise for the development of innovative therapeutic interventions in the relentless battle against neurodegenerative diseases.

Study of platelet-rich plasma application for skin and plastic surgery in recent 20 years: A bibliometric analysis.

BACKGROUND: In recent years, platelet-rich plasma (PRP) has been used in plastic surgery, dermatology, and other treatment procedures worldwide. Since the number of scientific writings has been significantly increasing, it is challenging to generate a manual compilation and systematic review of PRP's therapeutic applications in dermatology and plastic surgeries. This study aimed to make a bibliometric analysis of the literature in the field and evaluate research hotspots and frontiers in this field in the past 20 years. METHODS: Using the Academic Search Premier and ScienceDirect defined search terms, we searched the Web of Science Core Collection (WoSCC) and Scopus databases. All data were analyzed using CiteSpace 5.8.R3 and VOSviewer, including countries, institutions, authors, keywords, cited authors, cited journals, cited references, discovered research hotspots, and frontiers. RESULTS: A total of 1931 studies were retrieved. The number of publications on PRP application in dermatology and plastic surgeries showed a yearly increase. The United States was the most significant contributor to this field, while Italy's contribution was noteworthy. The journal with the highest number of relevant articles in dermatology and plastic surgery included the Journal of Cosmetic Dermatology. However, the Wound Repair and Regeneration and International Journal of Molecular Sciences were the leading journals that should be paid attention to in the future. Author Anitua E from the Tor Vergata University of Rome published the most publications in this field. In the keyword co-occurrence analysis, all keywords were divided into six clusters, and the most common one in recent years was "PRP for facial beauty." Facial rejuvenation, scar, and alopecia were the main hotspots and research trends in this field. CONCLUSIONS: Based on the current global trends, the use of PRP in cosmetics and skin care is receiving increasing attention from researchers and clinicians. Recently, an increasing number of articles on PRP's application in skin tissue repair have been published in the United States and Italy. The number of studies on hair loss, facial rejuvenation, and scar management is increasing, suggesting that these subjects may become research hotspots for PRP in dermatology and cosmetic surgeries in recent years.

Ginsenoside Re attenuates myocardial ischemia/reperfusion induced ferroptosis via miR-144-3p/SLC7A11.

BACKGROUND: Ginsenoside Re is an active component in ginseng that confers protection against myocardial ischemia/reperfusion (I/R) injury. Ferroptosis is a type of regulated cell death found in various diseases. PURPOSE: Our study aims to investigate the role of ferroptosis and the protective mechanism of Ginsenoside Re in myocardial ischemia/reperfusion. METHODS: In the present study, we treated rats for five days with Ginsenoside Re, then established the myocardial ischemia/reperfusion injury rat model to detect molecular implications in myocardial ischemia/reperfusion regulation and to determine the underlying mechanism. RESULTS: This study identifies the mechanism behind ginsenoside Re's effect on myocardial ischemia/reperfusion injury and its regulation of ferroptosis through miR-144-3p. Ginsenoside Re significantly reduced cardiac damage caused by ferroptosis during myocardial ischemia/reperfusion injury and glutathione decline. To determine how Ginsenoside Re regulated ferroptosis, we isolated exosomes from VEGFR2+ endothelial progenitor cells after ischemia/reperfusion injury and performed miRNA profiling to screen the miRNAs aberrantly expressed in the process of myocardial ischemia/reperfusion injury and ginsenoside Re treatment. We identified that miR-144-3p was upregulated in myocardial ischemia/reperfusion injury by luciferase report and qRT-PCR. We further confirmed that the solute carrier family 7 member 11 (SLC7A11) was the target gene of miR-144-3p by database analysis and western blot. In comparison with ferropstatin-1, a ferroptosis inhibitor, in vivo studies confirmed that ferropstatin-1 also diminished myocardial ischemia/reperfusion injury induced cardiac function damage. CONCLUSION: We demonstrated that ginsenoside Re attenuates myocardial ischemia/reperfusion induced ferroptosis via miR-144-3p/SLC7A11.

Effects of renal denervation on cardiac function after percutaneous coronary intervention in patients with acute myocardial infarction.

Objective: To observe the effect of renal artery denervation (RDN) on cardiac function in patients with acute myocardial infarction after percutaneous coronary intervention (AMI-PCI). Methods: This is a single-centre, prospective randomized controlled study. A total of 108 AMI-PCI patients were randomly assigned to the RDN group or the control group at 1:1 ratio. All patients received standardized drug therapy after PCI, and patients in the RDN group underwent additional RDN at 4 weeks after the PCI. The follow-up period was 6 months after RDN. Echocardiography-derived parameters, cardiopulmonary exercise testing (CPET) data, Holter electrocardiogram, heart rate variability (HRV) at baseline and at the 6 months-follow up were analyzed. Results: Baseline indexes were similar between the two groups (all P > 0.05). After 6 months of follow-up, the echocardiography-derived left ventricular ejection fraction was significantly higher in the RDN group than those in the control group. Cardiopulmonary exercise test indicators VO2Max, metabolic equivalents were significantly higher in the RDN group than in the control group. HRV analysis showed that standard deviation of the normal-to-normal R-R intervals, levels of square root of the mean squared difference of successive RR intervals were significantly higher in the RDN group than those in the control group. Conclusions: RDN intervention after PCI in AMI patients is associated with improved cardiac function, improved exercise tolerance in AMI patients post PCI. The underlying mechanism of RDN induced beneficial effects may be related to the inhibition of sympathetic nerve activity and restoration of the sympathetic-vagal balance in these patients.

Therapeutic Effect and Mechanism of Cinnamyl Alcohol on Myocardial Ischemia-Reperfusion Injury.

Objective: To investigate the effect of CA on autophagy and its molecular mechanism after myocardial ischemia/reperfusion injury (MI/RI). Methods: The MI/RI model was established by the ligation of the left anterior descending coronary artery with ischemia and reperfusion. In vitro cell models were established using hypoxia/reoxygenation. Western blot was used to determine the expression levels of beclin-1, P62, and LC3 II. The expression levels of IL-1ß, IL-6, TNFα, and apoptosis-related genes Bax, Cyt-c, and Bcl-2 were detected by qRT-PCR. Cell activity was detected by CCK-8. Apoptosis was detected by TUNEL staining. Results: Beclin-1, P62, and LC3 II protein expression and LC3 II/LC3 I level were significantly increased after myocardial ischemia-reperfusion injury. Compared with model group, CA downregulated beclin-1, P62, and LC3 II protein expression and LC3 II/LC3 I level in the myocardium. The results of cell-level experiments showed that CA inhibited the autophagy response of the cardiomyocytes induced by hypoxia-reperfusion injury. Mechanism studies showed that CA targeted the inhibition of ATG12. Knocking down ATG12 reduces the production of inflammatory cytokines induced by H/R. The knockdown of ATG12 also reduced apoptosis and injury of the myocardial cells. Conclusion: Myocardial ischemia-reperfusion can enhance autophagy response and promote apoptosis. CA plays a protective role in myocardium by targeting ATG12, thereby inhibiting autophagy and improving myocardial cell apoptosis.

Muscone Inhibits the Excessive Inflammatory Response in Myocardial Infarction by Targeting TREM-1.

The inhibitory effect of muscone on the hyperinflammatory response after myocardial ischemia reperfusion injury (MIRI) was investigated, and the target and signal pathways of muscone were explored. The levels of inflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor alpha were detected through qRT-PCR and ELISA. The expression levels of p38 and NF-κB signaling pathway-related proteins were detected through Western blot. TREM-1 siRNA was transfected into macrophages in vitro. The rat model of myocardial ischemia was established and used in studying the inhibitory effect of muscone on the inflammatory response and its protective effect muscone on myocardial apoptosis. The expression of TREM-1 was upregulated during myocardial ischemia. Knocking down TREM-1 decreased the increase in inflammatory cytokines in the supernatant of macrophages induced by rmHMGB1 (1 µg/mL) and rmHSP60 (1 mol/mL). In addition, knocking down TREM-1 decreased p38 and NF-κB signaling activation. Muscone can protect myocardial cells by inhibiting the expression of TREM-1 and the inflammatory response after myocardial infarction. Further study showed that muscone inhibited the production of DAM-triggered (damage-associated molecular pattern trigger) inflammatory cytokines. In addition, muscone inhibited the activation of p38 and NF-κB signals under DAM-induced conditions. Muscone and TREM-1 gene knockout reduced cell apoptosis and provided protection against MIRI by inhibiting p38 and NF-κB signaling activation. Mechanism studies showed that muscone inhibited the production and release of inflammatory cytokines by inhibiting TREM-1, and thereby reducing the inflammatory response and providing protection against MIRI.

Chitosan/Gelatin Composite Nonwoven Fabric Scaffold Seeding Minimal Function Unit of Skin for Functional Skin Regeneration.

The construction of intact functional skin is a challenging field in tissue engineering. Traditional skin tissue engineering, using "seed cells" as a bioactive source for scaffolding materials maybe not efficient enough. Here a new strategy is shown for constructing functional tissue-engineered skin with Minimal Functional Unit of Skin (MFUS) as the source of bioactivity. Chitosan/gelatin non-woven fabric is used as the scaffold. MFUS is derived from autologous skin with full-thickness skin microstructure and complete functional skin unit harvesting. A mathematical model is used to calculate the MFUS Minimal Harvest Diameter and Angle (MHDA). Chitosan/gelatin non-woven fabric (CS+GEL) is porous and absorbable, with an elastic modulus meeting the requirement of skin engineering. It supports layered and 3D growth of MFUS. The degradation rate of chitosan, including filament diameter and density is evaluated in vivo. MFUS-engineered skin could reduce the density of local nerve fibers in the early stage, potentially reducing pain during wound healing, as well as could limit excessive fibroblast cell migration in the later stage, potentially reducing scar formation. This study proposes a new strategy for the clinical treatment of large full-thickness skin defects by constructing intact functional at minimal cost.

Evaluation of Herb-Drug Interaction Between Danshen and Rivaroxaban in Rat and Human Liver Microsomes.

The combination of Salvia miltiorrhiza (Danshen) and rivaroxaban is a promising treatment option in clinical practice in China, but the herb-drug interaction between Danshen and rivaroxaban remains unclear. Therefore, this study aims to reveal the interaction between Danshen and rivaroxaban. We not only investigated the inhibitory properties of Danshen tablet on rivaroxaban metabolism in rat and human liver microsomes but also evaluated the inhibitory effects of Danshen tablet and its eight active components (dihydrotanshinone I, tanshinone I, tanshinone IIA, cryptotanshinone, danshensu, salvianolic acid A, salvianolic acid B, and salvianolic acid C) on cytochrome P450 (CYP) enzymes. The results showed that Danshen tablet potently inhibited the metabolism of rivaroxaban in rat and human liver microsomes. In the CYP inhibition study, we found that dihydrotanshinone I, the active component of Danshen tablet, potently inhibited the activities of rat CYP3A and CYP2J, with IC50 values at 13.85 and 6.39 µM, respectively. In further inhibition kinetic study, we found that Danshen tablet is a mixed inhibitor in rivaroxaban metabolism in rat and human liver microsomes, with the K i value at 0.72 and 0.25 mg/ml, respectively. In conclusion, there is a potential interaction between Danshen tablet and rivaroxaban. Danshen tablet inhibits the metabolism of rivaroxaban, which may be because its lipid-soluble components such as dihydrotanshinone I strongly inhibit the activities of CYP enzymes, especially CYP3A and CYP2J. Therefore, when Danshen tablet and rivaroxaban are used simultaneously in the clinic, it is necessary to strengthen the drug monitoring of rivaroxaban and adjust the dosage.

Corrigendum: Evaluation of herb-drug interaction between Danshen and rivaroxaban in rat and human liver microsomes.

[This corrects the article DOI: 10.3389/fphar.2022.950525.].