The association between blood glucose levels and lipids in the general adult population: results from NHANES (2005-2016).

OBJECTIVE: Although abnormal lipid metabolism is one of the major risk factors for diabetes, the correlation between lipids and glucose is rarely discussed in the general population. The differences in lipid-glucose correlations across gender and ethnicity have been even more rarely studied. We examined the association between fasting blood glucose (FBG) and lipids, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (ApoB), using 6,093 participants aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES). METHODS: Analyses were performed using multiple logistic regression and generalised additive models. RESULTS: When other confounders were considered, we found that fasting glucose was positively correlated with triglycerides and negatively correlated with HDL-C, whereas total cholesterol, LDL-C cholesterol, and fasting glucose were related to each other in a U-curve fashion, with inflection points of 5.17 mmol/L and 2.3 mmol/L, respectively.This relationship persisted in subgroups of different sexes and races. A positive correlation was found between fasting glucose and ApoB, but subgroup analyses revealed that this relationship was not correlated across gender and race. CONCLUSION: In the general population, fasting blood glucose levels were positively correlated with TG, negatively correlated with HDL-C, and U-shaped with total cholesterol and LDL-C. The likelihood of developing diabetes was 40% higher when LDL-C was greater than 2.3 mmol/L than in patients with LDL-C less than 2.3 mmol/L.

Long-term outcome of robotic-guided closed reduction internal fixation for Delbet II femoral neck fractures in children.

OBJECTIVE: To retrospectively analyze and assess the long-term effectiveness of robotic navigation and traditional closed reduction internal fixation in the treatment of Delbet type II femoral neck fracture in children. METHODS: A total of fifty-five patients diagnosed with pediatric Delbet type II femoral neck fracture, who were admitted to Foshan Hospital of Traditional Chinese Medicine between January 2018 and June 2022, were included in this study. Among them, 22 cases of nailing under robotic navigation were set as the observation group, and 33 cases of nailing under fluoroscopy of the C-arm machine were set as the control group. All patients had their femoral neck fractures closed and repositioned first. After confirming the satisfactory fracture repositioning under the fluoroscopic view of the C-arm machine, internal fixation was performed by inserting hollow compression screws in the corresponding surgical way.A comparative analysis was conducted between the two groups to assess the disparity in the amount of X-ray exposure during surgery, the number of guide pins inserted, and the duration of the surgical procedure. The quality of comparative fracture reduction was assessed according to the Haidukewych criteria on the first postoperative hip X-ray, and the parallelism and distribution of the comparative screws were measured. The incidence of hip function and postoperative complications according to the Ratliff criteria were evaluated between each of the subgroups at the final follow-up. RESULTS: Comparison of general information, operation duration, and quality of fracture reduction between the two groups failed to reveal statistically significant results (P > 0.05). The observation group had a lower number of X-ray exposures and guide pin placements compared to the control group, and this difference was statistically significant (P < 0.05).At the last follow-up, the observation group exhibited superior screw parallelism and distribution, as well as hip joint function, compared to the control group, and this difference was statistically significant (P < 0.05). The incidence of complications in the observation group was lower than that in the control group; however, the difference was not statistically significant (P > 0.05). CONCLUSION: Closed reduction and internal fixation under orthopedic robot navigation can achieve better long-term efficacy in treating Delbet type II femoral neck fracture in children.

Effect of the combined use of ivabradine and metoprolol in patients with acute myocardial infarction early after percutaneous coronary intervention: A randomized controlled study.

Objective: To investigate the effect and safety of the combined use of ivabradine and metoprolol in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Methods: Eighty patients with AMI were randomly divided into the ivabradine group and the control group. The ivabradine group was treated with ivabradine combined with metoprolol after PCI, while the control group was treated with metoprolol only. Both groups were treated continuously for 1 year. Echocardiography-derived parameters, heart rate, cardiopulmonary exercise testing (CPET) data, major adverse cardiac events (MACE) and myocardial markers were analyzed. The primary endpoint was the left ventricular ejection fraction (LVEF). The safety outcomes were blood pressure, liver and kidney function. Results: The LVEF was significantly higher in the ivabradine group than in the control group at 1 week, 3 months and 1 year after PCI. The heart rate of the ivabradine group was significantly lower than that of the control group at 1 week and 1month after PCI. The VO2max, metabolic equivalents, anaerobic threshold heart rate, peak heart rate, and heart rate recovery at 8 min of the ivabradine group were significantly higher than those of the control group at 1 year after PCI. Kaplan-Meier analysis demonstrated the one-year total incidence of MACE in the ivabradine group was significantly lower than that in the control group. The B-type natriuretic peptide of the ivabradine group was significantly lower than that of the control group on Day 2 and Day 3 after PCI. The high-sensitivity cardiac troponin I level of the ivabradine group was significantly lower than that of the control group on Day 5 after PCI. Conclusion: Early use of ivabradine in patients with AMI after PCI can achieve effective heart rate control, reduce myocardial injury, improve cardiac function and exercise tolerance, and may reduce the incidence of major adverse cardiac events. (Clinical research registration number: ChiCTR2000032731).

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.

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.

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.

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.

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.

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.

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.

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.].

Effects of renal denervation therapy on cardiac function and malignant arrhythmia in patients with reduced left ventricular ejection fraction and narrow QRS complexes treated with implantable cardioverter defibrillator.

Objective : The purpose of this study was to explore the effects of renal denervation (RDN) on cardiac function and malignant arrhythmia in patients with reduced left ventricular ejection fraction (HFrEF) and narrow QRS treated with an implantable cardioverter defibrillator (ICD). Methods: A total of 20 eligible HFrEF patients [left ventricular ejection fraction (LVEF) <40%] and narrow QRS complexes (QRS duration <120 ms) were randomized into either the ICD plus RDN group or the ICD only group during 17 April 2014 to 22 November 2016. Clinical data, including clinical characteristics, blood biochemistry, B-type natriuretic peptide, echocardiographic indexes, 6-min walk distance (6MWD), New York Heart Association (NYHA) classification, and count of ICD discharge events before and after the operation were analyzed. Patients were followed up for up to 3 years post ICD or ICD plus RDN. Results: Baseline clinical data were comparable between the two groups. Higher LVEF (%) (mixed model repeated measure, p = 0.0306) (39.50% ± 9.63% vs. 31.20% ± 4.52% at 1 year; 41.57% ± 9.62% vs. 31.40% ± 8.14% at 3 years), systolic blood pressure (p = 0.0356), and longer 6MWD (p < 0.0001) as well as reduction of NYHA classification (p < 0.0001) were evidenced in the ICD plus RDN group compared to ICD only group during follow-up. Patients in the ICD plus RDN group experienced fewer ICD discharge events (2 vs. 40) and decreased diuretic use; rehospitalization rate (30% vs. 100%, p = 0.0031) and cardiogenic mortality rate (0% vs. 50%, p = 0.0325) were also significantly lower in the ICD plus RDN group than in the ICD only group during follow-up. Conclusion: ICD implantation plus RDN could significantly improve cardiac function and cardiac outcome as well as increase exercise capacity compared to ICD only for HFrEF patients with narrow QRS complexes.

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.

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.

Simplified regimen for the management of hypertension with telemedicine and blood pressure self-monitoring (SIMPLE): study protocol for a randomised controlled trial.

INTRODUCTION: Telemedicine and blood pressure (BP) self-monitoring conduces to management of hypertension. Recent hypertension guidelines highly recommended single pill combination (SPC) for the initial treatment of essential hypertension. Based on this fact, an SPC-based telemedicine titration regimen with BP self-monitoring could be a better way in managing hypertension. This trial aims to elucidate whether telemedicine combined with BP self-monitoring is superior to self-monitoring alone during hypertension management. METHODS AND ANALYSIS: This study will be a multicentred, open-labelled, randomised controlled trial. A minimum sample of 358 hypertensive patients with uncontrolled BP from four centres will be included. The intervention group will include BP self-monitoring and tele-monitoring plus a free SPC-based telemedicine titration therapy for 6 months, they will be recommended to take BP measurements at least once every 7 days, in the meantime, researchers will call to give a consultation on lifestyle or titration advice once a fortnight. The control group will be required to self-monitor BP at the same time interval as intervention group, without any therapy change. Primary outcome of the trial will be the difference in systolic blood pressure at 6-month follow-up between intervention and control group, adjusted for baseline variables. Secondary outcomes such as BP control rate, major adverse cardiovascular events, medication adherence, quality of life will be investigated. ETHICS AND DISSEMINATION: Ethics approval was granted by Ethical Committee of Shanghai Tenth People's Hospital (SHSY-IEC-4.1/20-194/01). The results will be disseminated in peer-reviewed literature, and to policy-makers and healthcare partners. TRIAL REGISTRATION NUMBER: ChiCTR2000037217.

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.