Spatial distribution and influencing factors analysis of national key rural tourism villages in the Yangtze River Delta region based on geographically weighted regression.

National key rural tourism villages (NKRTVs) can lead to the high-quality development of rural tourism, and their spatial distribution is influenced by a variety of factors. However, existing studies have neglected the fact that influencing factors can have different directions and effects in different geographic spaces. This study investigates 156 NKRTVs in the Yangtze River Delta region of China as the research object and employs ArcGIS spatial analysis technology to examine their spatial distribution characteristics. Additionally, two new indicators of land and culture are introduced to enhance the index system of influencing factors. A geographically weighted regression model is utilized to identify the spatial heterogeneity of various factors that affect the spatial distribution of NKRTVs. The results of this study indicate the following: (1) The spatial distribution of NKRTVs in the Yangtze River Delta region is characterized by "small clustering and large dispersion." The spatial distribution exhibits strong spatial correlation, with Shanghai serving as the primary spatial clustering core and Huangshan city forming a secondary spatial clustering subcore. The distribution of NKRTVs is relatively scattered in other areas, with obvious differences in the spatial distribution of cold and hot spots. (2) The results of the geographically weighted regression model show that with the change in spatial location, the influence effect of each influencing factor on the spatial distribution of NKRTVs has obvious spatial differences. Based on the spatial heterogeneity of the influencing factors, this study proposes targeted suggestions for the development of rural tourism in different regions.

Prognostic biomarkers for sepsis mortality based on the literature and LC-MS-based metabolomics of sepsis patients.

OBJECTIVES: The management of sepsis, a potentially lethal overreaction to infection, is limited by the lack of prognostic tools to guide its treatment. Our aim is to identify a novel metabolic biomarker panel for predicting sepsis mortality based on a literature review and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. METHODS: In the literature, we found metabolomics biomarkers reported to predict sepsis mortality. We determined the classifications, reported frequency, and KEGG pathway enrichment of these markers. Using serum samples from 20 sepsis survivors and 20 non-survivors within 28 days after admission to the intensive care unit (ICU), we performed LC-MS-based metabolomics. Based on the literature review and metabolomics, a prognostic biomarker panel for sepsis was identified and its area under the curve (AUC) values was assessed. RESULTS: Kynurenate, caffeine, and lysoPC 22:4 were selected as a prognostic biomarker panel for sepsis. The panel had an area under the curve (AUC) of 0.885 (95% CI, 0.694-1) evaluated by linear support vector machine (SVM) and 0.849 (0.699-1) by random forest (RF), which was higher than that of the Sequential Organ Failure Assessment (SOFA). A combination of kynurenate, caffeine, and lysoPC 22:4 and SOFA provided the best discriminating performance, with AUCs of 0.961 (0.878-1) for SVM and 0.916 (0.774-1) for RF. CONCLUSIONS: The prognostic biomarker panel consisting of kynurenate, caffeine, and lysoPC 22:4 may aid in the identification of sepsis patients at a high risk of death, leading to personalized therapy in clinical practice that will improve sepsis survival.

MicroRNA-989 targets 5-hydroxytryptamine receptor1 to regulate ovarian development and eggs production in Culex pipiens pallens.

BACKGROUND: Female mosquitoes need a blood meal after mating for their eggs to develop, and this behavior leads to the spread of pathogens. Therefore, understanding the molecular regulation of reproduction in female mosquitoes is essential to control mosquito vector populations. In this study, we reported that microRNA-989 (miR-989), which targets 5-HTR1 (encoding secreted 5-hydroxytryptamine receptor1), is essential for mosquito reproduction. METHODS: The spatiotemporal expression profile of miR-989 was detected using quantitative real-time reverse transcription PCR (RT-qPCR). miR-989 antagomirs and antagomir-negative control (NC) were designed and synthesized to knock down the expression of endogenous miR-989 in female mosquitoes. RNA sequencing was used to analyze the ovarian response to miR-989 deletion. The targets of miR-989 were predicted and confirmed using RNAhybrid and dual-luciferase assays. RESULTS: miR-989 is exclusively expressed in female mosquito ovaries and responds to blood feeding. Injection of the miR-989 antagomir resulted in smaller ovaries and reduced egg production. 5-HTR1 was demonstrated as a target of miR-989. The deletion of miR-989 contributed to the upregulation of 5-HTR1 expression. Knockdown of 5-HTR1 rescued the adverse egg production caused by miR-989 silencing. Thus, miR-989 might play an essential role in female reproduction by targeting 5-HTR1. CONCLUSIONS: We found that miR-989 targets 5-HTR1 and participates in the regulation of reproduction in female mosquitoes. These findings expand our understanding of reproduction-related miRNAs and promote new control strategies for mosquitoes.

Adverse effects of knocking down chitin synthase A on female reproduction in Culex pipiens pallens (Diptera: Culicidae).

BACKGROUND: Current mosquito-borne disease vector control strategies, largely based on chemical insecticides, are seriously threatened by increasing resistance worldwide. There is also growing concerned about the adverse effects of insecticides on nontarget organisms and the environment, therefore effective and ecologically friendly alternative approaches are urgently needed. Targeting critical steps of reproduction is considered a potential way to control mosquito populations. Herein, we focused on the roles of chitin synthase A (encoded by chsa) in the reproduction of female mosquitoes. RESULTS: The injection of small interfering RNA targeting Cpchsa in female Culex pipiens pallens (Diptera: Culicidae) had antireproductive effects, including decreased follicle numbers, egg-laying, and hatching rate. Scanning electron microscopy observations showed that Cpchsa silencing caused a defective egg envelope, including absence of the vitelline membrane and cracked chorion layers, which resulted in abnormal permeability. Widely distributed nurse cell apoptosis and follicular epithelial cell autophagy were observed in Cpchsa-silenced ovaries during the vitellogenesis phase. Consistent with the detective egg envelope formation during oogenesis, the exochorionic eggshell structures were also affected in eggs deposited by Cpchsa-silenced mosquitoes. CONCLUSION: This study provided fundamental evidence for the role of chitin synthase A in the female reproductive process of mosquitoes and might result in a novel alternative strategy for mosquito control. © 2023 Society of Chemical Industry.

Identification and functional analysis of ABC transporter genes related to deltamethrin resistance in Culex pipiens pallens.

BACKGROUND: Pathogens that reproduce or develop in mosquitoes can transmit several diseases, endanger human health, and overwhelm health systems. Synthetic pyrethroids are the most widely used insecticides against adult mosquitoes, but their widespread use has led to resistance. The adenosine triphosphate (ATP)-binding cassette (ABC) transporters are involved in the resistance monitoring of insects, but their role and underlying mechanisms in insecticide resistance have not been fully elucidated. In the present study, we identified ABC transporter genes in Culex pipiens and investigated their role in the development of insecticide resistance. RESULTS: We identified 63 ABC transporter genes in Cx. pipiens and classified them as per the ABC transporter subfamilies. We also performed phylogenetic analysis. The knockdown rate of the mosquitoes orally fed with the ABC transporter inhibitor verapamil increased after deltamethrin treatment compared with that of the control group. Several genes from the ABCB, ABCC, and ABCG subfamilies were highly expressed in resistant mosquitoes. Immunofluorescence analysis revealed that ABCG6032427 was expressed in the head, chest, abdomen, wings, and legs, and the expression was the highest in the legs. Subsequently, knockdown of ABCG6032427 using RNA interference (RNAi) increased the sensitivity of the mosquitoes to deltamethrin, and scanning and transmission electron microscopy revealed that ABCG6032427 knockdown reduced cuticle thickness and the cuticle became loose and irregular. CONCLUSIONS: ABCG6032427 may modulate cuticle thickness and structure, thus play an important role in the development of deltamethrin resistance in mosquitoes. Thus, it could be a potential target for deltamethrin resistance management in Cx. pipiens. © 2023 Society of Chemical Industry.

Toxic Effects of Perilla frutescens (L.) Britt. Essential Oil and Its Main Component on Culex pipiens pallens (Diptera: Culicidae).

Sustainable control of mosquitoes, vectors of many pathogens and parasites, is a critical challenge. Chemical insecticides are gradually losing their effectiveness because of development of resistance, and plant metabolites are increasingly being recognized as potential alternatives to chemical insecticides. This study aimed to analyze the main components of Perilla frutescens essential oil (PE-EO), investigate the specific activity of PE-EO as a botanical insecticide and mosquito repellent, and explore whether its main constituents are potential candidates for further research. The larvicidal activity assay showed that LC50 of PE-EO and 2-hexanoylfuran was 45 and 25 mg/L, respectively. In the ovicidal activity assay, both 120 mg/L PE-EO and 80 mg/L 2-hexanoylfuran could achieve 98% egg mortality. Moreover, PE-EO and 2-hexanoylfuran showed repellency and oviposition deterrence effects. Notably, 10% PE-EO maintained a high rate of protection for 360 min. Although PE-EO and its main component had certain toxic effects on zebrafish, no significant harmful effects were detected in human embryonic kidney cells. Therefore, perilla essential oil is an effective agent for mosquito control at several life stages and that its main component, 2-hexanoylfuran, is a potential candidate for developing novel plant biopesticides.

Overexpression of KCNJ2 enhances maturation of human-induced pluripotent stem cell-derived cardiomyocytes.

BACKGROUND: Although human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are a promising cell resource for cardiovascular research, these cells exhibit an immature phenotype that hampers their potential applications. The inwardly rectifying potassium channel Kir2.1, encoded by the KCNJ2 gene, has been thought as an important target for promoting electrical maturation of iPSC-CMs. However, a comprehensive characterization of morphological and functional changes in iPSC-CMs overexpressing KCNJ2 (KCNJ2 OE) is still lacking. METHODS: iPSC-CMs were generated using a 2D in vitro monolayer differentiation protocol. Human KCNJ2 construct with green fluorescent protein (GFP) tag was created and overexpressed in iPSC-CMs via lentiviral transduction. The mixture of iPSC-CMs and mesenchymal cells was cocultured with decellularized natural heart matrix for generation of 3D human engineered heart tissues (EHTs). RESULTS: We showed that mRNA expression level of KCNJ2 in iPSC-CMs was dramatically lower than that in human left ventricular tissues. KCNJ2 OE iPSC-CMs yielded significantly increased protein expression of Kir2.1 and current density of Kir2.1-encoded IK1. The larger IK1 linked to a quiescent phenotype that required pacing to elicit action potentials in KCNJ2 OE iPSC-CMs, which can be reversed by IK1 blocker BaCl2. KCNJ2 OE also led to significantly hyperpolarized maximal diastolic potential (MDP), shortened action potential duration (APD) and increased maximal upstroke velocity. The enhanced electrophysiological maturation in KCNJ2 OE iPSC-CMs was accompanied by improvements in Ca2+ signaling, mitochondrial energy metabolism and transcriptomic profile. Notably, KCNJ2 OE iPSC-CMs exhibited enlarged cell size and more elongated and stretched shape, indicating a morphological phenotype toward structural maturation. Drug testing using hERG blocker E-4031 revealed that a more stable MDP in KCNJ2 OE iPSC-CMs allowed for obtaining significant drug response of APD prolongation in a concentration-dependent manner. Moreover, KCNJ2 OE iPSC-CMs formed more mature human EHTs with better tissue structure and cell junction. CONCLUSIONS: Overexpression of KCNJ2 can robustly enhance maturation of iPSC-CMs in electrophysiology, Ca2+ signaling, metabolism, transcriptomic profile, cardiomyocyte structure and tissue engineering, thus providing more accurate cellular model for elucidating cellular and molecular mechanisms of cardiovascular diseases, screening drug-induced cardiotoxicity, and developing personalized and precision cardiovascular medicine.

A novel bidirectional side exiting pledgetted suture for valve replacement surgery.

The pledgetted mattress suture is one of the most widely used suture techniques for valve replacement surgery. However, the traditional pledgetted suture has several defects including intertwining of the sutures and the pledget flipping over. Here we present a novel side exiting pledgetted suture that can overcome these defects. It offers cardiac surgeons a new alternative for valve replacement surgeries.

Association Between Plasma Lipoprotein Levels and Aortic Valve Calcification Among Patients with Aortic Valve Replacement Surgery: A Retrospective Study.

Objective: Calcific aortic valve disease (CAVD) is a prevalent type of valvular heart disease, its association with dyslipidemia remains controversial. Methods: Of 449 CAVD patients who underwent aortic valve replacement, 228 formed the aortic valve calcification (AVC) group, and 221 were the non-calcification group. We retrospectively reviewed the preoperative and one-year postoperative plasma lipoprotein levels of both and performed a logistic regression to evaluate the factors associated with AVC. Results: Preoperatively, AVC patients had significantly higher coronary heart disease (43.0% vs 24.9%, p<0.001), peripheral vascular disease (41.7% vs 26.2%, p<0.001), and heart failure rates (63.6% vs 47.1%, p<0.001), and a higher level of total cholesterol (4.1±0.9 vs 3.9±0.8 mmol/L, p=0.032) and very low-density cholesterol (0.6 (0.4-0.7) vs 0.5 (0.3-0.7) mmol/L, p=0.054). Echocardiography revealed a significant difference of aortic stenosis in both AVC and non-AVC groups (p<0.05), and also identified aortic regurgitation (AR) with a significant difference between these two groups (p=0.003). The peak transaortic jet velocity, peak transaortic gradient, and mean transaortic gradient were significantly higher in the calcification group (all p<0.001), but the aortic valve area (0.7 (0.5-1.0) vs 4 (0.9-4.5) cm2; p<0.001) was smaller. Age (OR=1.023), total cholesterol (OR=1.272), and mean transaortic gradient (OR=1.182) were AVC risk factors. A larger aortic valve area (OR=0.010) were protective factors. The one-year mortality and perivalvular leakage rates were significantly higher in the calcification group. Conclusion: Total cholesterol was significantly higher in AVC patients and may be an AVC risk factor along with age and mean transaortic gradient. AVC patients had a relatively poorer outcome within one year.

Minimally Invasive Isolated Tricuspid Valve Repair After Left-Sided Valve Surgery: A Single-Center Experience.

Background: Tricuspid regurgitation after left-sided valve surgery was associated with terrible outcomes and high perioperative mortality for surgical treatment. In current years, minimally invasive isolated tricuspid valve repair is increasingly performed in our institution to address tricuspid regurgitation. Methods: Thirty-seven consecutive patients with previous left-sided valve surgery underwent minimally invasive isolated tricuspid valve repair in our institution between November 2017 and December 2020. Twenty-nine patients(78.4%) were women and the mean age of patients was 58.4 ± 8.5 years. Follow-up was 100% complete with a mean follow-up time of 17.2 ± 9.5 months. Results: Both the in-hospital and 30-day mortalities were 2.7%. The overall NYHA class had improved significantly during the follow-up (p < 0.001). The grade of TR had decreased before discharge (p < 0.001) and during the follow-up (p < 0.001) compared with the preoperative level although severe TR was recurrent in one patient. Conclusions: Minimally invasive isolated tricuspid valve repair has acceptable early and midterm outcomes, may be the preferred surgical option to address tricuspid regurgitation after previous left-sided valve surgery when it is feasible.

Case Report: Using Medtronic AP360 mechanical prosthesis in mitral valve replacement for patients with mitral insufficiency after primum atrial septal defect repair to reduce left ventricular outflow tract obstruction risk.

Background: Atrial septal defect is one of the most common congenital heart diseases in adults. Primum atrial septal defect (PASD) accounts for 4%-5% of congenital heart defects. Patients with PASD frequently suffer mitral insufficiency (MI), and thus, mitral valvuloplasty (MVP) or mitral valve replacement (MVR) is often required at the time of PASD repair. Unfortunately, recurrent unrepairable severe mitral regurgitation can develop in many patients undergoing PASD repair plus MVP in either short- or long-term after the repair surgery, requiring a re-do MVR. In those patients, the risk of left ventricular outflow tract obstruction (LVOTO) has increased. Case presentation: We present five such cases, ranging in age from 24 to 47 years, who had a PASD repair plus MVP or MVR for 14-40 years while suffering moderate to severe mitral regurgitation. Using Medtronic AP360 mechanical mitral prostheses, only one patient experienced mild LVOTO. Conclusions: The use of Medtronic AP360 mechanical mitral prostheses to perform MVR in patients with MI who had a history of PASD repair can potentially reduce the risk of LVOTO. Long-term follow-up is required to further confirm this clinical benefit associated with AP360 implantation in patients with PASD.

Four novel suture-sealing techniques to repair varying size paravalvular leaks.

BACKGROUND: Paravalvular leak (PVL) is a well-known complication of aortic valve replacement. Currently, there is no consensus on optimal intraoperative management of patients with mild-to-moderate or moderate PVL. TECHNIQUE: In this paper we present four novel surgical techniques, each combining suturing with sealing technique, to repair aortic PVLs, nullifying the need to replace the prosthesis. CONCLUSION: These techniques will offer cardiac surgeons new alternatives to the repair techniques currently used.

Small Cavity of Left Ventricle Does Not Affect Short-term Outcome in Patients with Rheumatic Mitral Valve Stenosis Undergoing Mitral Valve Replacement.

BACKGROUND: Small cavity left ventricle (SCLV) may affect the clinical outcomes of patients undergoing mitral valve replacement (MVR). This study aims to investigate the incidence of SCLV in patients with rheumatic mitral valve stenosis undergoing MVR and analyze its effect on short-term patient outcomes. METHODS: We retrospectively examined all consecutive patients with isolated or concomitant MVR for rheumatic mitral valve stenosis in our center from 2013 to 2018. SCLV was defined as end-diastolic volume index ≤ 50 ml/m2. After inclusion and exclusion, a total of 1,437 patients were analyzed. The baseline information was collected and compared between SCLV and non-SCLV patients. Multivariate logistic regression analysis was conducted to determine the effect of SCLV on early mortality. RESULTS: A total of 1,437 patients were included in the study. SCLV was detected in 13.57% of the patients. Compared with the non-SCLV group, patients with SCLV were smaller-sized and primarily female. There were no significant differences between SCLV and non-SCLV patients regarding major postoperative complications, nor were there incidence of prosthesis-patient mismatch. Logistic regression analysis showed that SCLV was not a risk factor for short-term mortality (P = 0.998). CONCLUSIONS: Our results demonstrated that SCLV was not associated with poorer early outcomes after MVR surgery in patients with rheumatic mitral valve stenosis.

Mechanics and Microstructure of the Atrioventricular Heart Valve Chordae Tendineae: A Review.

The atrioventricular heart valves (AHVs) are responsible for directing unidirectional blood flow through the heart by properly opening and closing the valve leaflets, which are supported in their function by the chordae tendineae and the papillary muscles. Specifically, the chordae tendineae are critical to distributing forces during systolic closure from the leaflets to the papillary muscles, preventing leaflet prolapse and consequent regurgitation. Current therapies for chordae failure have issues of disease recurrence or suboptimal treatment outcomes. To improve those therapies, researchers have sought to better understand the mechanics and microstructure of the chordae tendineae of the AHVs. The intricate structures of the chordae tendineae have become of increasing interest in recent literature, and there are several key findings that have not been comprehensively summarized in one review. Therefore, in this review paper, we will provide a summary of the current state of biomechanical and microstructural characterizations of the chordae tendineae, and also discuss perspectives for future studies that will aid in a better understanding of the tissue mechanics-microstructure linking of the AHVs' chordae tendineae, and thereby improve the therapeutics for heart valve diseases caused by chordae failures.

An abnormal left ventricular-atrial perforation after radiofrequency catheter ablation: a case report.

BACKGROUND: Cardiac radiofrequency ablation is a popular treatment for arrhythmias. However, it does have some complications, some of which are severe, even fatally. And there were limited reports on cardiac internal perforation after radiofrequency catheter ablation (RFCA) that required a surgical repair. CASE PRESENTATION: A 47-year-old male was admitted to our hospital due to chest congestion for 4 months. He received a radiofrequency catheter ablation (RFCA) 9 months prior to admission. On admission, an echocardiogram showed an abnormal perforation between the left ventricle and the left atrium with moderate mitral valve regurgitation. We therefore performed a mitral valve replacement (MVR) and fixed the abnormal atrial-ventricular breakage via median sternotomy. CONCLUSIONS: Cardiac perforation is a severe complication of cardiac RFCA, operators should be extremely cautious to minimize radiofrequency associated perforations. Such a challenging and complex procedure should be deliberately considered by doctors and patients before implementation.

Modified band annuloplasty technique for functional tricuspid regurgitation repair in patients with grossly dilated annuli: The three-suture junctional continuous suture band annuloplasty technique.

Functional tricuspid regurgitation (FTR) is the most common of all tricuspid dysfunctions. Ring annuloplasty is an effective treatment strategy for FTR. Currently, the most commonly used suture method for tricuspid ring annuloplasty is the interrupted U-shaped suture method. However, when tricuspid annuli are grossly dilated (septal segments > 60 mm), interrupted sutures are insufficient in avoiding the folding over of the annulus or the tearing of sutures. Therefore, we recommend a new band suture technique; namely, the three-suture junctional continuous suture band annuloplasty technique.

A new technique of managing paravalvular leak using a folding pericardium patch.

Paravalvular leakage (PVL) is one of the most well-recognised complications of prosthetic valve replacement. The size of the leakage is usually about one to two stitches. We would like to introduce a new technique to manage this complication by using a folding pericardium patch, which can surely overcome the disadvantage of second-time valve replacement. By now, we have applied this new technique to at least four cases, all of them worked well. Thus, we present our new technique that can be considered as a good alternative management of intraoperative PVLs, especially in aortic position.

Prosthesis-patient mismatch after mitral valve replacement: a single-centered retrospective analysis in East China.

BACKGROUND: Prosthesis-patient mismatch (PPM) may affect the clinical outcomes of patients undergoing mitral valve replacement (MVR) surgery. We aimed to investigate the incidence of PPM of the mitral position in our center and analyze the possible predictors of PPM as well as its effect on short-term outcomes. METHODS: We retrospectively examined all consecutive patients with isolated or concomitant MVR at our center from 2013 to 2015. PPM was defined as an indexed effective orifice area (iEOA) of ≤1.2 cm2/m2. After inclusion and exclusion, a total of 1067 patients were analyzed. The baseline information were collected and compared between the two groups. Multivariate logistic regression analysis was conducted to determine the preoperative predictors of PPM as well as the effect of PPM on early mortality. RESULTS: A total of 1067 patients were included in the study. PPM was detected in 15.9% of the patients while 12 patients (1.12%) met the criteria for severe PPM. Patients with PPM compared to the non-PPM patients had higher age, larger body surface area and were more likely to be male and obese. Logistic regression analysis showed that higher age, larger BSA, bioprosthesis and smaller left ventricle end-diastolic diameter were predictors of PPM. There were no significant differences between the PPM and non-PPM groups regarding post-operative complications. Logistic regression analysis showed that PPM was not a risk factor of short-term mortality (P = 0.654). Also, there were no significant differences regarding short-/mid-term heart function between the PPM and non PPM groups (P = 0.902). CONCLUSIONS: Our results demonstrated that higher age, bioprosthesis, larger BSA and smaller left ventricle size were associated with mitral PPM. However, PPM was not associated with poorer early outcomes after MVR surgery. In eastern of China, the prevalence of mitral valve stenosis is high; therefore, whether the standard PPM criteria are suitable for patients of this district needs to be further verified.

Case report of refractory pericardial effusion associated with lymphatic fistula due to surgical injury during sternotomy.

RATIONALE: A 35-year old Chinese female was admitted to hospital with refractory pericardial effusions 10 days post mitral valve replacement via median sternotomy. We performed an exploratory resternotomy and found lymphatic leakage on the surface of the diaphragm which was continuously emitting a light yellow fluid. PATIENT CONCERNS: The patient complained of no obvious discomfort except for the concern of massive pericardial effusion drainage. DIAGNOSES: Exploratory resternotomy and biochemical testing lead to a supradiaphragmatic lymphatic fistula being diagnosed as the cause of the refractory pericardial effusion. INTERVENTIONS: The fistula was closed with a continuous suture and no other fistulas were found after a thorough exploration. OUTCOMES: The patient was discharged home on postoperative day 5 and recovery was uneventful. LESSONS: In this case a timely exploratory resternotomy proved effective in seeking the cause of and treating pericardial effusion following cardiac surgery.