Assessment of causal associations between obesity and peripheral artery disease: a bidirectional Mendelian randomization study.

Background: Several observational studies have documented a potential link between obesity and peripheral artery disease (PAD), although conflicting findings exist. The causal relationship between obesity and PAD continues to be a subject of ongoing debate in the medical community. Objectives: In this study, we employed a bidirectional Mendelian randomization (MR) analysis to explore the potential causal relationship between obesity and the risk of PAD. Methods: To investigate these causal relationships, we conducted bidirectional MR analysis using publicly available genome-wide association study (GWAS) data. Effect estimates were calculated using the random-effects inverse variance-weighted (IVW) method. Results: We identified eight independent single nucleotide polymorphisms (SNPs) associated with obesity in 218,735 samples involving 16,380,465 SNPs, all of which met the genome-wide significance threshold (p < 5 × 10-8). The IVW analysis indicates a significant positive association between genetic obesity and multiple datasets with PAD as the outcome: Queue-1 (GWAS ID: finn-b-I9_PAD) (OR = 1.138, 95% CI: 1.027-1.261, p = 0.013), Queue-2 (GWAS ID: bbj-a-144) (OR = 1.190, 95% CI: 1.019-1.390, p = 0.028), Queue-3 (GWAS ID: ebi-a-GCST90018670) (OR = 1.174, 95% CI: 1.014-1.360, p = 0.032), and Queue-4 (GWAS ID: ebi-a-GCST90018890) (OR = 1.194, 95% CI: 1.099-1.296, p < 0.001). However, we did not observe a significant genetic-level association between obesity and PAD for Queue-5 (GWAS ID: ukb-d-I9_PAD) (OR = 1.001, 95% CI: 1.000-1.002, p = 0.071). Furthermore, we conducted a reverse causal MR analysis to explore the potential reverse causal relationship between obesity and PAD. This comprehensive analysis did not provide evidence of a reverse causal association between these two factors. Conclusions: In summary, our study offers genetic evidence suggesting a possible causal link between obesity and PAD. While we did not find evidence supporting the "obesity paradox", prudent weight management remains crucial, as lower weight does not necessarily guarantee better outcomes. As with any study, caution is required in interpreting the findings. Further research is essential to assess the clinical relevance of weight in preventing PAD, which could inform the development of more precise intervention strategies.

Air Transportation Impact on a Late Preterm Neonate.

BACKGROUND: Neonatal air transportation is a crucial means of moving critically ill or sick neonates to specialized neonatal intensive care units or medical centers for consultation, regardless of distance or geographical limits. Proper preparation and consideration of air transport can help alleviate medical emergencies and ensure safe delivery. However, crewmembers and neonates may face stress during transportation. To date, there are few studies on neonatal air transportation in Taiwan.CASE REPORT: We present the case of a late preterm neonate born with neonatal respiratory distress syndrome and polycythemia, who was also diagnosed with patent ductus arteriosus and mild pulmonary arterial hypertension on echocardiography. Due to disease progression, the neonate underwent endotracheal intubation and was subsequently transported to a medical center in Taiwan via a rotary-wing aircraft at 3 d of age. During takeoff and landing, a temporary oxygen desaturation event occurred. The physiological changes in these patients have seldom been discussed. This case emphasizes the important considerations of neonatal transport in Taiwan.DISCUSSION: The air transport process could be influenced by both the patient's medical condition and environmental factors. In preterm infants with cardiopulmonary conditions, thorough assessment is necessary for ensuring safe transportation.Li S-P, Hsu P-C, Huang C-Y, Wu P-W, Fang H-H. Air transportation impact on a late preterm neonate. Aerosp Med Hum Perform. 2024; 95(4):219-222.

The correlation between clinical features and ultrastructure of testis of non-mosaic Klinefelter's syndrome patients with hypogonadism and androgen deficiency: A case report.

Background: Klinefelter Syndrome (KS) is a sex chromosomal syndrome usually with an extra X chromosome (47, XXY) in males, which has various phenotype (mosaicism 47, XXY/46, XY, or more chromosomes 48, XXXY, 49, XXXXY) and clinical features, including eunuchoid body proportions, abnormally long legs and arm span, gynecomastia, ynecomastia, absent or decreased facial and pubic hair, small hyalinized testes, small penis, below-normal verbal intelligence quotient, and learning difficulties. At present, there are no studies on the correlation between the clinical characteristics of patients with KS and the ultrastructural changes of intracellular organelles in testicular tissue in China. Case presentation: Here we report the ultrastructure manifestation of the testis tissues in a KS patient with hypogonadism and androgen deficiency, to find a relationship between ultrastructural changes of organelles and spermatogenic dysfunction, clinical features, timing of surgery and metabolic abnormalities. It has been shown that the spermatocytes are absent and the ultrastructure of Sertoli cells and Leydig cells is obviously abnormal, which may lead to spermatogenic dysfunction, androgen deficiency, impaired glucose tolerance (IGT), and abdominal fat accumulation. Conclusions: Based on the European Academy of Andrology (EAA) Gudilines on Klinefelter Syndrome, this study conducted a retrospective study on the diagnosis and treatment of one adult patient with KS, aiming to provide a standardized diagnosis and treatment for patients with KS. This study is also highly concerned with the correlation between the ultrastructural changes of target organs and clinical symptoms.

Genome-Wide Identification of WRKY Gene Family and Functional Characterization of CcWRKY25 in Capsicum chinense.

Pepper is renowned worldwide for its distinctive spicy flavor. While the gene expression characteristics of the capsaicinoid biosynthesis pathway have been extensively studied, there are already a few reports regarding transcriptional regulation in capsaicin biosynthesis. In this study, 73 WRKYs were identified in the genome of Capsicum chinense, and their physicochemical traits, DNA, and protein sequence characteristics were found to be complex. Combining RNA-seq and qRT-PCR data, the WRKY transcription factor CA06g13580, which was associated with the accumulation tendency of capsaicinoid, was screened and named CcWRKY25. CcWRKY25 was highly expressed in the placenta of spicy peppers. The heterologous expression of CcWRKY25 in Arabidopsis promoted the expression of genes PAL, 4CL1, 4CL2, 4CL3, CCR, and CCoAOMT and led to the accumulation of lignin and flavonoids. Furthermore, the expression of the capsaicinoid biosynthesis pathway genes (CBGs) pAMT, AT3, and KAS was significantly reduced in CcWRKY25-silenced pepper plants, resulting in a decrease in the amount of capsaicin. However, there was no noticeable difference in lignin accumulation. The findings suggested that CcWRKY25 could be involved in regulating capsaicinoid synthesis by promoting the expression of genes upstream of the phenylpropanoid pathway and inhibiting CBGs' expression. Moreover, the results highlighted the role of CcWRKY25 in controlling the pungency of pepper and suggested that the competitive relationship between lignin and capsaicin could also regulate the spiciness of the pepper.

Bioflocculation characteristics of bound extracellular polymers substances from Pseudomonas sp. XD-3 and behavior of polysaccharides.

This study aimed to investigate the bioflocculation characteristics of bound extracellular polymers substances (B-EPS), which were extracted from Pseudomonas sp. XD-3. The flocculation efficiency of B-EPS achieved about 80%- 95% with an initial pH of 4-7, kaolin concentrations of 3-7 g L-1, temperature of 25-100 â„ƒ and B-EPS dosage of 9-105 mg L-1. The bioflocculation process of B-EPS conformed to pseudo-second-order kinetic mode, suggesting that the bioflocculation belonged to chemical adsorption process. Enzymatic hydrolysis experiments demonstrated that both polysaccharides and proteins were active components for bioflocculation. The polysaccharides were irregular aggregates with rough and porous surfaces and contained hydroxyl and carboxyl groups, which helped to promote bridging effect. Ribose, glucose and galactose were the main monosaccharides of polysaccharides. The molecular weight of the polysaccharides was relatively small, but the relatively loose configuration exposed more ion bridging sites, thus promoting the bioflocculation. Optimizing the ingredients of culture medium and culture time for B-EPS were effective strategies to increase the yield of flocculation active components. When the conditions were 10% of 2 g L-1 KH2PO4 + 5 g L-1 K2HPO4, 0.05% of Tween-80, citrate as carbon source and 32-48 h of culture time, both proteins and polysaccharides in B-EPS were significantly improved. This study gives an in-deep understanding on the flocculation characteristics of a novel bioflocculant from Pseudomonas sp. XD-3, which is conducive to the widespread application of bioflocculation.

Analysis of Volatile Aroma Components and Regulatory Genes in Different Kinds and Development Stages of Pepper Fruits Based on Non-Targeted Metabolome Combined with Transcriptome.

Aroma is a crucial attribute affecting the quality of pepper and its processed products, which has significant commercial value. However, little is known about the composition of volatile aroma compounds (VACs) in pepper fruits and their potential molecular regulatory mechanisms. In this study, HS-SPME-GC-MS combined with transcriptome sequencing is used to analyze the composition and formation mechanism of VACs in different kinds and development stages of pepper fruits. The results showed that 149 VACs, such as esters, alcohols, aldehydes, and terpenoids, were identified from 4 varieties and 3 development stages, and there were significant quantitative differences among different samples. Volatile esters were the most important aroma components in pepper fruits. PCA analysis showed that pepper fruits of different developmental stages had significantly different marker aroma compounds, which may be an important provider of pepper's characteristic aroma. Transcriptome analysis showed that many differential genes (DEGs) were enriched in the metabolic pathways related to the synthesis of VACs, such as fatty acids, amino acids, MVA, and MEP in pepper fruits. In addition, we identified a large number of differential transcription factors (TFs) that may regulate the synthesis of VACs. Combined analysis of differential aroma metabolites and DEGs identified two co-expression network modules highly correlated with the relative content of VACs in pepper fruit. This study confirmed the basic information on the changes of VACs in the fruits of several Chinese spicy peppers at different stages of development, screened out the characteristic aroma components of different varieties, and revealed the molecular mechanism of aroma formation, providing a valuable reference for the quality breeding of pepper.

Bioinspired PROTAC-induced macrophage fate determination alleviates atherosclerosis.

Atherosclerosis is a major cause of death and disability in cardiovascular disease. Atherosclerosis associated with lipid accumulation and chronic inflammation leads to plaques formation in arterial walls and luminal stenosis in carotid arteries. Current approaches such as surgery or treatment with statins encounter big challenges in curing atherosclerosis plaque. The infiltration of proinflammatory M1 macrophages plays an essential role in the occurrence and development of atherosclerosis plaque. A recent study shows that TRIM24, an E3 ubiquitin ligase of a Trim family protein, acts as a valve to inhibit the polarization of anti-inflammatory M2 macrophages, and elimination of TRIM24 opens an avenue to achieve the M2 polarization. Proteolysis-targeting chimera (PROTAC) technology has emerged as a novel tool for the selective degradation of targeting proteins. But the low bioavailability and cell specificity of PROTAC reagents hinder their applications in treating atherosclerosis plaque. In this study we constructed a type of bioinspired PROTAC by coating the PROTAC degrader (dTRIM24)-loaded PLGA nanoparticles with M2 macrophage membrane (MELT) for atherosclerosis treatment. MELT was characterized by morphology, size, and stability. MELT displayed enhanced specificity to M1 macrophages as well as acidic-responsive release of dTRIM24. After intravenous administration, MELT showed significantly improved accumulation in atherosclerotic plaque of high fat and high cholesterol diet-fed atherosclerotic (ApoE-/-) mice through binding to M1 macrophages and inducing effective and precise TRIM24 degradation, thus resulting in the polarization of M2 macrophages, which led to great reduction of plaque formation. These results suggest that MELT can be considered a potential therapeutic agent for targeting atherosclerotic plaque and alleviating atherosclerosis progression, providing an effective strategy for targeted atherosclerosis therapy.

MYB24 Negatively Regulates the Biosynthesis of Lignin and Capsaicin by Affecting the Expression of Key Genes in the Phenylpropanoid Metabolism Pathway in Capsicum chinense.

The wide application of pepper is mostly related to the content of capsaicin, and phenylpropanoid metabolism and its branch pathways may play an important role in the biosynthesis of capsaicin. The expression level of MYB24, a transcription factor screened from the transcriptome data of the pepper fruit development stage, was closely related to the spicy taste. In this experiment, CcMYB24 was cloned from Hainan Huangdenglong pepper, a hot aromatic pepper variety popular in the world for processing, and its function was confirmed by tissue expression characteristics, heterologous transformation in Arabidopsis thaliana, and VIGS technology. The results showed that the relative expression level of CcMYB24 was stable in the early stage of pepper fruit development, and increased significantly from 30 to 50 days after flowering. Heterologous expression led to a significant increase in the expression of CcMYB24 and decrease in lignin content in transgenic Arabidopsis thaliana plants. CcMYB24 silencing led to a significant increase in the expression of phenylpropanoid metabolism pathway genes PAL, 4CL, and pAMT; lignin branch CCR1 and CAD; and capsaicin pathway CS, AT3, and COMT genes in the placenta of pepper, with capsaicin content increased by more than 31.72% and lignin content increased by 20.78%. However, the expression of PAL, pAMT, AT3, COMT, etc., in the corresponding pericarps did not change significantly. Although CS, CCR1, and CAD increased significantly, the relative expression amount was smaller than that in placental tissue, and the lignin content did not change significantly. As indicated above, CcMYB24 may negatively regulate the formation of capsaicin and lignin by regulating the expression of genes from phenylpropanoid metabolism and its branch pathways.

Effects of L-carnitine Administration on Sperm and Sex Hormone Levels in a Male Wistar Rat Reproductive System Injury Model in a High-Altitude Hypobaric Hypoxic Environment.

The plateau environment impacts male reproductive function, causing decreased sperm quality and testosterone levels. L-carnitine can improve the semen microenvironment. However, the role of L-carnitine in a high-altitude environment remains unclear. In our study, we investigated the effects of L-carnitine administration in a male Wistar rat reproductive system injury model in the context of a simulated high-altitude environment. Rats were randomly divided into a normal control group (group A1, A2-low dose and A3-high dose) and high-altitude model groups (group B, C-low dose and D-high dose) with 20 rats in each group. With the exception of the normal control group exposed to normoxic conditions, the other groups were maintained in a hypobaric oxygen chamber that simulated an altitude of 6000 m for 28 days. In the experimental period, the low-dose groups (A2 and C) were administered 50 mg/kg L-carnitine via intraperitoneal injection once a day, and the high-dose groups (A3 and D) were given 100 mg/kg. After the feeding period, blood samples were collected to assess blood gas, serum hormone levels and oxidative stress. Sperm from the epididymis were collected to analyse various sperm parameters. After obtaining the testicular tissue, the morphological and pathological changes were observed under a light microscope and transmission electron microscopy (TEM). The impact of the simulated high-altitude environment on the rat testis tissue is obvious. Specifically, a decreased testicular organ index and altered indices of arterial blood gas and serum sex hormone levels caused testicular tissue morphological damage, reduced sperm quality, increased sperm deformity rate and altered malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) concentrations. The results demonstrate that L-carnitine can be administered as a preventive intervention to reduce the reproductive damage caused by high-altitude hypobaric and hypoxic environments and improve semen quality in a rat model.

A Teleoperated Robotic System-Assisted Percutaneous Transiliac-Transsacral Screw Fixation Technique.

Transiliac-transsacral screw fixation is challenging in clinical practice as the screws need to break through six layers of cortical bone. Transiliac-transsacral screws provide a longer lever arm to withstand the perpendicular vertical shear forces. However, the screw channel is so long that a minor discrepancy can lead to iatrogenic neurovascular injuries. The development of medical robots has improved the precision of surgery. The present protocol describes how to use a new teleoperated robotic system to execute transiliac-transacral screw fixation. The Robot was operated remotely to position the entry point and adjust the orientation of the sleeve. The screw positions were evaluated using postoperative computed tomography (CT). All the screws were safely implanted, as confirmed using intraoperative fluoroscopy. Postoperative CT confirmed that all the screws were in the cancellous bone. This system combines the doctor's initiative with the Robot's stability. The remote control of this procedure is possible. Robot-assisted surgery has a higher position-retention capacity compared with conventional methods. In contrast to active robotic systems, surgeons have full control over the operation. The robot system is fully compatible with operating room systems and does not require additional equipment.

Injectable temperature-sensitive hydrogel system incorporating deferoxamine-loaded microspheres promotes H-type blood vessel-related bone repair of a critical size femoral defect.

Insufficient vascularization is a major challenge in the repair of critical-sized bone defects. Deferoxamine (DFO) has been reported to play a potential role in promoting the formation of H-type blood vessels, a specialized vascular subtype with coupled angiogenesis and osteogenesis. However, whether DFO promotes the expression of H-type vessels in critical femoral defects with complete periosteal damage remains unknown. Moreover, stable drug loading systems need to be designed owing to the short half-life and high-dose toxic effects of DFO. In this study, we developed an injectable DFO-gelatin microspheres (GMs) hydrogel complex as a stable drug loading system for the treatment of critical femoral defects in rats. Our results showed that sustained release of DFO in critical femoral defects stimulated the generation of functional H-type vessels. The DFO-GMs hydrogel complex effectively promoted proliferation, formation, and migration of human umbilical vein endothelial cells in vitro. In vivo, the application of the DFO-GMs hydrogel complex expanded the distribution range and prolonged the expression time of H-type vessels in the defect area and was positively correlated with the number of osterix+ cells and new bone tissue. Topical application of the HIF-1α inhibitor PX-478 partially blocked the stimulation of H-type vessels by DFO, whereas the osteogenic potential of the latter was also weakened. Our results extended the local application of DFO and provided a theoretical basis for targeting H-type vessels to treat large femoral defects. STATEMENT OF SIGNIFICANCE: Abundant functional blood vessels are essential for bone repair. The H-type blood vessel is a functional subtype with angiogenesis and osteogenesis coupling potential. A drug loading system with long-term controlled release was first used to investigate the formation of H-type blood vessels in critical femoral defects and promotion of bone repair. Our results showed that the application of DFO-GMs hydrogel complex expanded the distribution range and expression time of H-type vessels, and was positively correlated with the number of osteoblasts and volume of new bone tissue. These results expanded the local application approach of DFO and provide a theoretical basis for targeting H-type vessels to treat large femoral defects.

Insight into the effect of low temperature treatment on trichome density and related differentially expressed genes in Chinese cabbage.

Trichome is important for help plant resist adversity and external damage. However, it often affects the appearance and taste of vegetables. In the present study, the trichome density of leaves from two Chinese cabbage cultivars with and without trichomes treated at low temperature are analyzed by biological microscope, and the differentially expressed genes related to trichomes formation were screened through transcriptome sequencing. The results showed that the number of leaves trichomes was reduced by 34.7% at low temperature compared with room temperature. A total of 661 differentially expression genes effecting trichomes formation were identified at the CT vs C, LCT vs LC, CT vs LCT. Several differentially expression genes from every comparison group were enriched in plant hormone signal transduction and amino acid biosynthesis pathway. Combined with the central genes obtained by WGCNA analysis, five candidate genes Bra029778, Bra026393, Bra030270, Bra037264 and Bra009655 were screened. qRT-PCR analysis verified that the gene expression differences were in line with the trend of transcriptome data. This study not only found possible new key genes and laid a foundation for revealing the molecular mechanism regulating the formation of trichome in Chinese cabbage, but also provided a new way to study plant surface trichomes.

High-grade endometrial stromal sarcoma in cesarean section scar isthmocele - case report.

OBJECTIVE: Cesarean section scar defect isthmocele, the pouchlike defect in the anterior uterine wall of the prior cesarean site. No previous report of malignant neoplasm in the isthmocele have been published. We reported a case of High-grade endometrial stromal sarcoma in isthmocele. CASE REPORT: A 45-year-old patient with gravida 4, parity 2, two previous cesarean section presents of recurrent heavy vaginal bleeding. Curettage and hormone therapy were unsuccessful. She underwent hysteroscopic isthmoplasty. The pathology revealed high-grade sarcoma. Patient was referred to a tertiary medical center and she underwent total hysterectomy with bilateral salpingo-oophorectomy, aortic & pelvic LNs dissection. The final diagnosis was High-grade endometrial stromal sarcoma (HG-ESS) stage IA (pT1a N0) involving isthmocele. CONCLUSION: The presence of this rare tumor in the isthmocele is very interested. We stress the necessity for a high degree of suspicion to diagnose the malignancy in perimenopausal women with isthmocele and persisted abnormal uterine bleeding.

Interactions of circRNAs with methylation: An important aspect of circRNA biogenesis and function (Review).

Circular RNA (circRNA) molecules are noncoding RNAs with unique circular covalently closed structures that contribute to gene expression regulation, protein translation and act as microRNA sponges. circRNAs also have important roles in human disease, particularly tumorigenesis and antitumor processes. Methylation is an epigenetic modification that regulates the expression and roles of DNA and coding RNA and their interactions, as well as of noncoding RNA molecules. Previous studies have focused on the effects of methylation modification on circRNA expression, transport, stability, translation and degradation of circRNAs, as well as how circRNA methylation occurs and the influence of circRNAs on methylation modification processes. circRNA and methylation can also regulate disease pathogenesis via these interactions. In the present study, we define the relationship between circRNAs and methylation, as well as the functions and mechanisms of their interactions during disease progression.

Investigating the Effects of Different Sizes of Silicone Rubber Vacuum Extractors during the Course of Delivery on the Fetal Head: A Finite Element Analysis Study.

During certain clinical situations, some parturients require instruments for operative vaginal delivery, and various designs of vacuum extractors may affect the fetal head. To investigate the biomechanical effects of divergent sizes of silicone rubber vacuum extractors, we employed finite element analysis in this study. First, we constructed computer models for different vacuum extractor sizes (diameters: 40 mm, 50 mm, 60 mm, and 70 mm), flat surface, hemispherical ball, and fetal head shape. A hemispherical ball was the main design for the vacuum extractor model, and the material used for the vacuum extractor was silicone rubber. Next, the settings of 1 mm vacuum extractor displacement and vacuum cap pressure of 60 cmHg were applied. The main observation markers of this study were the respective von Mises stresses on the vacuum extractor and skull by the reaction force on the fixed end. The concluded results revealed that vacuum extractors with larger diameters lead to greater reaction force, stress, and strain on fetal heads. Therefore, this study's biomechanical analytic consequences suggest that clinicians avoid selecting larger vacuum extractors during operative instrumental delivery so that fetal heads will experience less external force, deformation, and resultant complications. It could also provide a practical reference for obstetricians for instrumental vaginal delivery with the vacuum extractor made of silicone rubber.

Effect of Yellowing Duration on the Chemical Profile of Yellow Tea and the Associations with Sensory Traits.

The yellowing process is the crucial step to form the characteristic sensory and chemical properties of yellow tea. To investigate the chemical changes and the associations with sensory traits during yellowing, yellow teas with different yellowing times (0-13 h) were prepared for sensory evaluation and chemical analysis. The intensities of umami and green-tea aroma were reduced whereas sweet taste, mellow taste and sweet aroma were increased under long-term yellowing treatment. A total of 230 chemical constituents were determined, among which 25 non-volatiles and 42 volatiles were the key chemical contributors to sensory traits based on orthogonal partial least squares discrimination analysis (OPLS-DA), multiple factor analysis (MFA) and multidimensional alignment (MDA) analysis. The decrease in catechins, flavonol glycosides and caffeine and the increase in certain amino acids contributed to the elevated sweet taste and mellow taste. The sweet, woody and herbal odorants and the fermented and fatty odorants were the key contributors to the characteristic sensory feature of yellow tea with sweet aroma and over-oxidation aroma, including 7 ketones, 5 alcohols, 1 aldehyde, 5 acids, 4 esters, 5 hydrocarbons, 1 phenolic compound and 1 sulfocompound. This study reveals the sensory trait-related chemical changes in the yellowing process of tea, which provides a theoretical basis for the optimization of the yellowing process and quality control of yellow tea.

Targeting HIF-1α/NOTCH1 pathway eliminates CD44+ cancer stem-like cell phenotypes, malignancy, and resistance to therapy in head and neck squamous cell carcinoma.

Poor prognosis of head and neck squamous cell carcinomas (HNSCCs) results from resistance to chemotherapy and radiotherapy. To uncover the drivers of HNSCC resistance, including stemness and hypoxia, in this study, we compared the gene expression between CD44+ and CD44- HNSCC cells and assessed the correlation of CD44 and hypoxia-inducible factor 1α (HIF-1α) expression with mouse features and outcomes of patients with HNSCC. We combined the knockdown or activation of HIF-1α with in vitro and in vivo assays to evaluate effects on stemness and resistance of HNSCC cells. Analysis of clinical data showed that activation of HIF-1α in CD44+ patients with HNSCC was correlated with worse prognosis. Functional assays showed that HIF-1α promoted stemness, resistance, and epithelial-mesenchymal transition in HNSCC CD44+ cells. HIF-1α activated NOTCH1 signaling in HNSCC stem-like cells characterized by CD44 expression. Moreover, inhibition of these signaling proteins using shRNA or Evofosfamide (Evo) development for cancer treatment, reversed chemoresistance in vitro and in vivo. Taken together, our results indicated that targeting HIF-1α attenuated NOTCH1-induced stemness, which regulates responses to chemotherapy or radiotherapy and malignancy in CD44+ HNSCCs. HIF-1α/NOTCH1 signaling may represent a target for HNSCC treatment.

Characteristics of the Dynamic Electrocardiogram in the Elderly with Nonvalvular Atrial Fibrillation Combined with Long R-R Intervals.

OBJECTIVE: To investigate the characteristics of dynamic electrocardiogram and their clinical implications in elderly patients with nonvalvular atrial fibrillation combined with long R-R intervals. METHODS: Elderly patients diagnosed with nonvalvular atrial fibrillation who were admitted as an inpatient or attended the outpatient department from January 2015 to January 2020 were selected. Patients were divided into two groups based on the presence of a long R-R interval. The characteristics and therapeutic significance of dynamic electrocardiogram between the two groups were compared. RESULTS: A total of 532 patients were included in our analyses. Of these, 399 patients were in the long R-R interval group and 133 in the nonlong R-R interval group. In 399 patients, there were 48,840 long R-R intervals manifested within 24 hours. The average, slowest, and fastest ventricular rates during sleep time were higher than those in nonsleep time, while the number of long R-R intervals in sleep time was significantly smaller than that in nonsleep time (P < 0.05). Clinical parameters including dizziness/syncope, cerebral infarction, ST-segment changes, platelet count, average hematocrit, prothrombin time (PT), left ventricular systolic function, end-diastolic diameter, pulmonary artery pressure, and left ventricular ejection fraction were comparable between the groups (P > 0.05). When compared with the nonlong R-R interval group, the level of C-reactive protein was slightly lower in the long R-R interval group (P < 0.05). In addition, the long R-R interval group had a higher incidence of atrial premature beats but a lower incidence of ventricular premature beats. Furthermore, the probability of long R-R interval combined with paroxysmal atrial tachycardia, transient ventricular arrest, second-degree atrioventricular block, and complete or incomplete right bundle branch block was higher than that of nonlong R-R interval (P < 0.05). In patients with long R-R interval >3 s, the risk of having second-degree atrioventricular block and complete or incomplete right bundle branch block was significantly lower, while the risk of having transient ventricular arrest was higher when compared to patients with long R-R intervals of 2-3 s (P < 0.05P). CONCLUSIONS: Long R-R interval is a common electrocardiographic phenomenon among the elderly with nonvalvular atrial fibrillation. The long R-R interval mostly occurs in nonsleeping time. The average ventricular rate, slowest ventricular rate, and fastest ventricular rate of sleep time are higher than nonsleeping time. Analysis of the characteristics of the dynamic electrocardiogram of these patients may shed light on the mechanisms for long R-R intervals, including the likelihood of concealed conduction and physiological interference in the atrioventricular node, overspeed inhibition, increased vagus nerve tension, or pathological atrioventricular block.

Evans blue staining to detect deep blood vessels in peripheral retina for observing retinal pathology in early-stage diabetic rats.

AIM: To observe and compare the statistical significance of superficial and deep vascular leakage in the pathological changes of the diabetic rats retina after the Evans blue (EB) perfusion, and utilize the modified whole-retina spreading method to make the slides while protecting the periphery of the retina. METHODS: The Sprague-Dawley (SD) rats were randomly divided into 6 groups. Each group named as the normal groups for 4, 8, and 12wk and the diabetic groups for 4, 8, and 12wk. The EB was injected into the cardiovascular system of the rats at the different time points. The retina of each group was obtained for observation. RESULTS: The superficial vascular leakage was found in all 6 groups. The size of leakage area of superficial retinal blood vessels was (0.54±0.23)%, (0.65±0.11)%, and (0.58±0.10)% in normal group. No notable leakage was found in the deep blood vessels [(0.03±0.04)%, (0.03±0.05)%, and (0.03±0.05)%]. The deep retinal vascular leakage was found in the peripheral retina of diabetic rats. The size of leakage area of superficial retinal blood vessels in diabetic group were (0.53±0.22)%, (0.69±0.16)%, and (0.52±0.11)%. The leakage areas of deep blood vessels were (0.54±0.50)%, (1.42±0.16)%, and (1.80±0.07)% at 4, 8, and 12wk, respectively. There was a statistically difference of the leakage area between the 8th week and the 4th week of diabetes group (P=0.003). The statistically significant difference between the diabetes and the control groups was noted at 4wk and 8wk (P<0.001). CONCLUSION: The main retinal pathological changes of early-stage diabetic rats are the vascular leakage of the periphery of deep retina. Diabetic rats modeled after 8wk have semi-quantitative statistical difference compared with the normal rats, thus early intervention treatment research can start at this time point.