Gentiopicroside ameliorates the lipopolysaccharide-induced inflammatory response and hypertrophy in chondrocytes.

PURPOSE: This study aimed to evaluate the protective effects of gentiopicroside against lipopolysaccharide-induced chondrocyte inflammation. METHODS: SW 1353 chondrosarcoma cells were stimulated with LPS (5 µg/ml) for 24 h and treated with different concentrations of gentiopicroside (GPS) for 24 h. The toxic effects of GPS on chondrocytes were determined using a CCK-8 assay and EdU staining. Western blotting, qPCR, and immunofluorescence analysis were used to examine the protective effect of GPS against the inflammatory response in chondrocytes induced by lipopolysaccharide (LPS). One-way ANOVA was used to compare the differences between the groups (significance level of 0.05). RESULTS: The CCK-8 results showed that 10, 20 and 40 µM GPS had no significant toxic effects on chondrocytes; GPS effectively reduced the production of IL-1ß and PGE2, reversed LPS-induced extracellular matrix degradation in cartilage by inhibiting the Stat3/Runx2 signaling pathway, and suppressed the hypertrophic transformation of SW 1353 chondrosarcoma cells. CONCLUSION: Our study demonstrated that GPS significantly inhibited the LPS-induced inflammatory response and hypertrophic cellular degeneration in SW 1353 chondrosarcoma cells and is a valuable traditional Chinese medicine for the treatment of knee osteoarthritis.

Design and preparation of novel antioxidant and antibacterial films containing procyanidins and phycocyanin for food packaging.

The purpose of this study was to design a novel antioxidant and antibacterial film for food packaging using food-grade raw materials. The films were designed and fabricated based on carboxymethyl chitosan and pectin incorporated with procyanidins (PCs) and phycocyanin (Phy) by the tape casting method. The effects of different proportions of PCs and Phy on the properties and functions of the prepared films were studied. The results showed that the thickness of films could range from 55 to 70 µm, with dense network structure and uniform distribution of elements. Compared with C-Film group, the film loaded with PCs and Phy had lower water solubility and swelling rate, and higher tensile strength and elongation at break. FITR and XRD spectra revealed the molecular interaction mechanism among carboxymethyl chitosan, pectin, PCs and Phy, which could effectively endow the films with ultraviolet barrier properties. Moreover, the addition of PCs and Phy could effectively improve the antioxidant capacity and antibacterial effect of films, for example, the free radical scavenging abilities of most films were above 80% when the concentration of PCs was 40 µg mL-1. In view of these functional properties, the prepared film containing PCs and Phy have been successfully used in food packaging, which was proved by the preservation experiment of grapes. This study can provide theoretical and technical guidance for the preparation of biodegradable antibacterial films, and their application in the food packaging field.

Pineal cysts may promote pubertal development in girls with central precocious puberty: a single-center study from China.

Introduction: Pineal cysts have long been considered a benign intracranial variation. However, in our clinical practice, it has been observed that some children with central precocious puberty (CPP) who have pineal cysts experience rapid progression in adolescent development. In recent years, there has been a significant increase in the prevalence of CPP in girls, leading to more diagnoses of CPP among children with pineal cysts. Despite this, there is no consensus regarding whether pineal cysts contribute to CPP as one of its organic factors. This study aimed to analyze the clinical characteristics of pineal cysts in children with CPP and explore the potential effects of pineal cysts on puberty development. Methods: This single-center study retrospectively analyzed clinical data from girls aged 3 to 10 years who underwent head/pituitary magnetic resonance imaging at the Children's Hospital Affiliated to Zhengzhou University between 2019 and 2022. The study categorized the detection rates of pineal cysts based on systematic disease classification and compared the rates of cyst detection between girls diagnosed with CPP and those without CPP. Subsequently, CPP-diagnosed girls with pineal cysts were examined. Among CPP-diagnosed girls meeting the study's criteria, those with pineal cysts formed the 'cyst group,' while those without cysts were matched in a 1:1 ratio based on age and body mass index to form the 'non-cyst group.' Comparative analyses were conducted to assess the clinical characteristics between these two groups. CPP-diagnosed girls with cysts were further subdivided into three groups according to cyst size (≤5 mm, 5.1-9.9 mm, and ≥10 mm) to investigate potential differences in clinical characteristics among these subgroups. The study involved an analysis of clinical data from girls diagnosed with CPP and included imaging follow-ups to explore the progression of pineal cysts over time. Results: Among the 23,245 girls who underwent head/pituitary magnetic resonance imaging scans, the detection rate of pineal cysts was 3.6% (837/23,245), with most cases being associated with endocrine diseases. The detection rate of pineal cysts in CPP patients was 6.4% (262/4099), which was significantly higher than the 3.0% (575/19,146) in patients without CPP. In comparison to the non-cyst group, the cyst group exhibited statistically significant increases in estradiol levels, peak luteinizing hormone (LH) levels, peak LH/follicle-stimulating hormone (FSH) ratios, uterine body length, and cervix length (P < 0.001). As cyst size increased, there were significant rises in LH peak, peak LH/FSH ratio, uterine body length, and cervical length (P < 0.01). Estradiol levels and left ovarian volume also showed an increasing trend (P < 0.05). Among girls who underwent follow-up imaging, 26.3% (5/19) exhibited an increase in cyst size. Conclusion: Pineal cysts are relatively common in children with CPP. They may affect the pubertal development process, with larger cysts correlating to faster pubertal development. Therefore, the authors hypothesize that pineal cysts may trigger CPP in some cases, especially when the cysts are larger than 5 mm in size, as indicated by our data.

Optimizing irrigation and nitrogen addition to balance grassland biomass production with greenhouse gas emissions: A mesocosm study.

Achieving a balance between greenhouse gas mitigation and biomass production in grasslands necessitates optimizing irrigation frequency and nitrogen addition, which significantly influence grassland productivity and soil nitrous oxide emissions, and consequently impact the ecosystem carbon dioxide exchange. This study aimed to elucidate these influences using a controlled mesocosm experiment where bermudagrass (Cynodon dactylon L.) was cultivated under varied irrigation frequencies (daily and every 6 days) with (100 kg ha-1) or without nitrogen addition; measurements of net ecosystem carbon dioxide exchange, ecosystem respiration, soil respiration, and nitrous oxide emissions across two cutting events were performed as well. The findings revealed a critical interaction between water-filled pore space, regulated by irrigation, and nitrogen availability, with the latter exerting a more substantial influence on aboveground biomass growth and ecosystem carbon dioxide exchange than water availability. Moreover, the total dry matter was significantly higher with nitrogen addition compared to without nitrogen addition, irrespective of the irrigation frequency. In contrast, soil nitrous oxide emissions were observed to be significantly higher with increased irrigation frequency and nitrogen addition. The effects of nitrogen addition on soil respiration components appeared to depend on water availability, with autotrophic respiration seeing a significant rise with nitrogen addition under limited irrigation (5.4 ± 0.6 µmol m-2 s-1). Interestingly, the lower irrigation frequency did not result in water stress, suggesting resilience in bermudagrass. These findings highlight the importance of considering interactions between irrigation and nitrogen addition to optimize water and nitrogen input in grasslands for a synergistic balance between grassland biomass production and greenhouse gas emission mitigation.

A retrospective cohort study of clinical characteristics and outcomes of type 2 diabetic patients with kidney disease.

Background: Type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD) poses a serious health threat and becomes a new challenge. T2DM patients with CKD fall into three categories, diabetic nephropathy (DN), non-diabetic kidney disease (NDKD), and diabetic nephropathy plus non-diabetic kidney disease (DN + NDKD), according to kidney biopsy. The purpose of our study was to compare the clinical characteristics and kidney outcomes of DN, NDKD, and DN + NDKD patients. Methods: Data on clinical characteristics, pathological findings, and prognosis were collected from June 2016 to July 2022 in patients with previously diagnosed T2DM and confirmed DN and or NDKD by kidney biopsy at Tongji Hospital in Wuhan, China. The endpoint was defined as kidney transplantation, dialysis, or a twofold increase in serum creatinine. Results: In our 6-year retrospective cohort research, a total of 268 diabetic patients were admitted and categorized into three groups by kidney biopsy. The 268 patients were assigned to DN (n = 74), NDKD (n = 109), and DN + NDKD (n = 85) groups. The most frequent NDKD was membranous nephropathy (MN) (n = 45,41.28%). Hypertensive nephropathy was the most common subtype in the DN+NDKD group (n = 34,40%). A total of 34 patients (12.7%) reached the endpoint. The difference between the Kaplan-Meier survival curves of the DN, NDKD, and DN + NDKD groups was significant (p < 0.05). Multifactorial analysis showed that increased SBP [HR (95% CI): 1.018(1.002-1.035), p = 0.025], lower Hb [HR(95% CI): 0.979(0.961-0.997), p = 0.023], higher glycosylated hemoglobin [HR(95% CI): 1.338(1.080-1.658), p = 0.008] and reduced serum ALB [HR(95% CI): 0.952(0.910-0.996), p = 0.032] were risk factors for outcomes in the T2DM patients with CKD. Conclusions: This research based on a Chinese cohort demonstrated that the risk of endpoint events differed among DN, NDKD, and DN+NDKD patients. In T2DM patients with CKD, DN patients displayed worse kidney prognosis than those with NDKD or DN + NDKD. Increased SBP, higher glycosylated hemoglobin, lower Hb, and decreased serum ALB may be correlated with adverse kidney outcomes in T2DM patients.

Finite element analysis and clinical application of 3D-printed Ti alloy implant for the reconstruction of mandibular defects.

BACKGROUND: The reconstruction of segmental defect of the mandible has always been a challenge. The customized reconstruction plate without a bone graft is also considered a transitional means of rehabilitation and reconstruction in some cases. METHODS: This study evaluated the biomechanical behaviors of customized plates with different structural designs comparing with commercial plates using the finite element method in reconstrution of the lateral mandible defect. RESULTS: Simulations revealed the stress state in the plate bodies, bone tissues and screws were associated with the width, height, thickness of the plates as well as the distribution of screws. In all of the groups, the system of 16 mm-high, 2.8 mm-thick customized reconstruction plate with 10 screws was considered to be the most ideal design because of the most harmonious biomechanical state. What's more, the stress shielding effects were not obvious in this experiment. Based on the above findings, we conducted a clinical case analysis to verify the mechanical properties of customized reconstruction and obtained a satisfactory operation result. CONCLUSIONS: The results show that by adjusting the contour parameters of the reconstruction plates, an ideal and reliable customized plate can be manufactured. And the customized 3D-printed Ti alloy implant will be a new way to achieve mandibular reconstruction in patients unable to perform autologous bone graft surgery. TRIAL REGISTRATION: The present trial has been registered with ChiCTR, the registration number is ChiCTR 2,000,038,973 on 11/10/2020.

Backfilling Patients in Phase I Dose-Escalation Trials Using Bayesian Optimal Interval Design (BOIN).

In recent years, there has been increased interest in incorporation of backfilling into dose-escalation clinical trials, which involves concurrently assigning patients to doses that have been previously cleared for safety by the dose-escalation design. Backfilling generates additional information on safety, tolerability, and preliminary activity on a range of doses below the maximum tolerated dose (MTD), which is relevant for selection of the recommended phase II dose and dose optimization. However, in practice, backfilling may not be rigorously defined in trial protocols and implemented consistently. Furthermore, backfilling designs require careful planning to minimize the probability of treating additional patients with potentially inactive agents (and/or subtherapeutic doses). In this paper, we propose a simple and principled approach to incorporate backfilling into the Bayesian optimal interval design (BOIN). The design integrates data from the dose-escalation and backfilling components of the design and ensures that the additional patients are treated at doses where some activity has been seen. Simulation studies demonstrated that the proposed backfilling BOIN design (BF-BOIN) generates additional data for future dose optimization, maintains the accuracy of the MTD identification, and improves patient safety without prolonging the trial duration.

Breaking the Barrier: Strategies for Mitigating Shuttle Effect in Lithium-Sulfur Batteries Using Advanced Separators.

Lithium-sulfur (Li-S) batteries are considered one of the most promising energy storage systems due to their high theoretical capacity, high theoretical capacity density, and low cost. However, challenges such as poor conductivity of sulfur (S) elements in active materials, the "shuttle effect" caused by lithium polysulfide, and the growth of lithium dendrites impede the commercial development of Li-S batteries. As a crucial component of the battery, the separator plays a vital role in mitigating the shuttle effect caused by polysulfide. Traditional polypropylene, polyethylene, and polyimide separators are constrained by their inherent limitations, rendering them unsuitable for direct application in lithium-sulfur batteries. Therefore, there is an urgent need for the development of novel separators. This review summarizes the applications of different separator preparation methods and separator modification methods in lithium-sulfur batteries and analyzes their electrochemical performance.

Changes in proprioception at different time points following anterior cruciate ligament injury or reconstruction.

PURPOSE: To investigate the changes in 30° and 60° position sense in patients with anterior cruciate ligament (ACL) injury at different time points after injury and reconstruction. METHODS: Patients were divided into six groups according to time after ACL injury and reconstruction: group A (ACL injury 1.5-6 months), group B (ACL injury 6-12 months), group C (ACL injury > 12 months), group D (postoperative ACL reconstruction 1-6 months), group E (postoperative ACL reconstruction > 6 months), and group F consisting of 14 healthy adults (control group). The ability of the affected leg to reproduce the same joint position during knee flexion was tested using active joint position sense assays to assess proprioception in both the lower extremities of the patient or between groups. RESULTS: Proprioception decreased rapidly during the early stages of ACL injury. Significant difference in the affected side at 30° compared to the healthy side (Group A: 4.70 (4.78, 9.00) vs 4.15 (3.35, 6.13), P = 0.03; Group B: 2.90 (0.48, 4.56) vs 8.30 (4.18, 10.43), P = 0.001; Group E: 6.25 (2.55, 11.60) vs 9.60 (3.90, 12.73), P = 0.009). However, no significant differences were detected for a double lower limb contrast of 60° (Group A: 5.1 (1.00, 8.00) vs 3.00 (0.75, 3.55), P = 0.044). Finally, the affected side of patients in groups C, D and E had significant differences in position perception at 30° compared with healthy subjects (P < 0.01), and the affected side of patients in groups C and E had significant differences in position sense at 60° compared with healthy subjects (P < 0.01). CONCLUSION: ACL injury had a greater impact on the patient's 30° position sense, with only a small impact for 60°. Further, the early and middle proprioception recovery stages after ACL injury were the best before surgery. Finally, proprioception recovery training should be performed soon after injury.

In vivo self-assembled small RNA targets H19 lncRNA for the treatment of colorectal cancer.

The majority of molecularly targeted therapies in clinical use target disease-related proteins, but only a small fraction (∼1.5%) of human genome is protein-coding region. Considering that ∼70% of human genome is transcribed to noncoding RNAs, targeting noncoding RNAs rather than protein-coding RNAs can significantly expand the proportion of human genome that can be manipulated. H19 long noncoding RNA (lncRNA) is aberrantly expressed in a variety of cancer types and actively contributes to multiple steps of tumorigenesis. Therefore, we selected H19 as a representative target and designed synthetic anti-H19 construct for the self-assembly and delivery of anti-H19 small RNA (sRNA) to prevent colorectal cancer development and metastasis based on the natural ability of the host liver to package sRNA-encapsulating small extracellular vesicles (sEVs) and the endogenous circulating sEVs to transfer sRNA. As anticipated, the synthetic anti-H19 construct successfully generated anti-H19 sRNA-encapsulating sEVs and exhibited high silencing efficiency on H19 lncRNA in an ex vivo model. In orthotopic and lung metastasis mouse models of colorectal cancer, the anti-H19 construct exhibited significantly superior therapeutic efficacy over 5-fluorouracil (5-Fu) in preventing primary tumor growth and lung metastasis. Particularly, the anti-H19 sRNA-encapsulating sEVs were generated in a nontoxic, nonimmunogenic and biocompatible manner. In summary, this study demonstrates that the in vivo self-assembled anti-H19 sRNA can serve as a new therapeutic agent for colorectal cancer.

Advances in highly active one-carbon metabolism in cancer diagnosis, treatment and drug resistance: A systematic review.

Study background objectives: Cancer poses a significant health concern as it is incurable. Every year, research on how to treat and eradicate this chronic condition is done. This systematic review will unmask the recent developments concerning highly active 1C metabolism with regard to cancer diagnosis, treatment, and drug resistance. The significance of this study is rolling out evidence-based evidence on the importance of one-carbon metabolism in cancer diagnosis and treatment. Methods: Eight randomized controlled trials (RCTs) were reviewed from five electronic databases - EMBASE, Scopus Review, Google Scholar, Web of Science, and PubMed. Outcomes from the eight studies were analyzed to paint a picture of the topic in question. While the Preferred Reporting Items for Systematic Reviews and Meta-Analysis' (PRISMA) protocol guided the initial literature search, The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach informed quality assessments of the eligible studies. Conclusion: Since its emergence in the 1980s, 1C metabolism has been investigated and broadened to capture essential aspects of cancer treatment, diagnosis, and drug resistance. The review found that metabolites like folic acid could be used to detect different types of cancer. The metabolic pathways could induce tumorigenesis and DNA methylation, hence drug resistance. Systematic review registration: https://inplasy.com/projects/, identifier INPLASY2022110099.

The Association of Blood Urea Nitrogen to Creatinine Ratio and the Prognosis of Critically Ill Patients with Cerebral Infarction: A Cohort Study.

Background: To evaluate the association between blood urea nitrogen (BUN) to creatinine (Cr) (BUN/Cr) ratio and the in-hospital mortality of critically ill patients with cerebral infarction in intensive care unit (ICU). Methods: In this cohort study, the data of 3059 participants with cerebral infarction were collected from the Medical Information Mart for Intensive Care (MIMIC)-III and the MIMIC-IV database. After propensity score matching (PSM) on age and gender, 2085 people were involved in and divided into the alive group (n = 1390) and the dead group (n = 695) based on the results of follow-up. Multivariate logistic analyses were applied to identify the confounders and the association between BUN/Cr and mortality of cerebral infarction. Results: The median follow-up time was 10.5 days. Among 2778 participants, 695 were dead at the end of follow-up. Univariate analysis revealed that BUN/Cr [risk ratio (RR) = 1.01, 95% confidence interval (CI): 1.01-1.02] might be associated with the in-hospital mortality of cerebral infarction patients. After adjusting for respiratory failure, malignant cancer, anticoagulation, liver disease, white blood cell (WBC), red cell distribution width (RDW), glucose, bicarbonate, and temperature, BUN/Cr had week correlation with the increased risk of in-hospital mortality of cerebral infarction patients (RR = 1.01, 95% CI: 1.01-1.02). Conclusion: This study evaluated the association between BUN/Cr and the in-hospital mortality of cerebral infarction patients in ICU and found that BUN/Cr had weak correlation with the increased risk of in-hospital mortality of patients with cerebral infarction in ICU especially in males and those with respiratory failure, malignant cancer, and without liver disease, as well as those receiving anticoagulation.

The Long Noncoding Transcript HNSCAT1 Activates KRT80 and Triggers Therapeutic Efficacy in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous carcinoma (HNSC) is the most prevalent malignancy of the head and neck regions. Long noncoding RNAs (lncRNAs) are vital in tumorigenesis regulation. However, the role of lncRNAs in HNSC requires further exploration. Herein, through bioinformatic assays using The Cancer Genome Atlas (TCGA) datasets, rapid amplification of cDNA ends (RACE) assays, and RNA-FISH, we revealed that a novel cytoplasmic transcript, HNSC-associated transcript 1 (HNSCAT1, previously recognized as linc01269), was downregulated in tumor samples and advanced tumor stages and was also associated with favorable outcomes in HNSC. Overexpression of HNSCAT1 triggered treatment efficacy in HNSCs both in vivo and in vitro. More importantly, through high-throughput transcriptome analysis (RNA-seq, in NODE database, OEZ007550), we identified KRT80, a tumor suppressor in HNSC, as the target of HNSCAT1. KRT80 expression was modulated by lncRNA HNSCAT1 and presented a positive correlation in tumor samples (R = 0.52, p < 0.001). Intriguingly, we identified that miR-1245 simultaneously interacts with KRT80 and HNSCAT1, which bridges the regulatory function between KRT80 and HNSCAT1. Conclusively, our study demonstrated that lncRNA HNSCAT1 functions as a necessary tumor inhibitor in HNSC, which provides a novel mechanism of lncRNA function and provides alternative targets for the diagnosis and treatment of HNSC.

Identification and functional analysis of a three-miRNA ceRNA network in hypertrophic scars.

BACKGROUND: Hypertrophic scar (HTS) is a fibrotic disorder of skins and may have repercussions on the appearance as well as functions of patients. Recent studies related have shown that competitive endogenous RNA (ceRNA) networks centering around miRNAs may play an influential role in HTS formation. This study aimed to construct and validate a three-miRNA (miR-422a, miR-2116-3p, and miR-3187-3p) ceRNA network, and explore its potential functions. METHODS: Quantitative real­time PCR (qRT­PCR) was used to compare expression levels of miRNAs, lncRNAs, and genes between HTS and normal skin. Target lncRNAs and genes of each miRNA were predicted using starBase as well as TargetScan database to construct a distinct ceRNA network; overlapping target lncRNAs and genes of the three miRNAs were utilized to develop a three-miRNA ceRNA network. For every network, protein-protein interaction (PPI) network analysis was performed to identify its hub genes. For each network and its hub genes, Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to explore their possible functions. RESULTS: MiR-422a, miR-2116-3p, and miR-3187-3p were all downregulated in HTS tissues and fibroblasts. MiR-422a-based ceRNA network consisted of 101 lncRNAs with 133 genes; miR-2116-3p-centered ceRNA network comprised 85 lncRNAs and 978 genes; miR-3187-3p-derived ceRNA network encompassed 84 lncRNAs as well as 1128 genes. The three-miRNA ceRNA network included 2 lncRNAs with 9 genes, where MAPK1, FOSL2, ABI2, KPNA6, CBL, lncRNA-KCNQ1OT1, and lncRNA-EBLN3P were upregulated. According to GO and KEGG analysis, these networks were consistently related to ubiquitination. Three ubiquitination-related genes (CBL, SMURF2, and USP4) were upregulated and negatively correlated with the expression levels of the three miRNAs in HTS tissues. CONCLUSIONS: This study identified a three-miRNA ceRNA network, which might take part in HTS formation and correlate with ubiquitination.

Serum CYR61 as a potential biomarker for the diagnosis of esophagogastric junction tumor.

BACKGROUND: Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. The present study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann-Whitney's U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups. RESULTS: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P<0.0001). The sensitivity, specificity and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P>0.05). CONCLUSION: The present study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.

Effect of Si-Miao-Yong-An decoction on the differentiation of monocytes, macrophages, and regulatory T cells in ApoE-/- mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Miao-Yong-An decoction (SMYAD) is a renowned traditional Chinese medicinal formula. SMYAD was originally recorded in the "Shi Shi Mi Lu", which was edited by medical scientist Chen Shi'duo during the Qing Dynasty. SMYAD has been traditionally used to treat thromboangiitis obliterans. At present, it is mainly used in clinical applications and research of cardiovascular diseases. AIM OF THE STUDY: To explore the effects of SMYAD on the pathological changes of atherosclerosis (AS) and the differentiation of monocytes, macrophages, and regulatory T (Treg) cells in apolipoprotein E knockout (ApoE-/-) mice. MATERIALS AND METHODS: Eight C57BL/6J mice, which were fed with normal diet for 16 weeks, were used as control group. Forty ApoE-/- mice were randomly divided into model group, atorvastatin group, SMYAD low-dose (SMYAD-LD) group, SMYAD medium-dose (SMYAD-MD) group, and SMYAD high-dose (SMYAD-HD) group. ApoE-/- mice were fed with western diet (WD) for 8 weeks, and the drugs were continuously administered for 8 weeks. The levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured by the esterase method. Morphological changes of the aortic sinus in mice were observed by hematoxylin-eosin (HE) staining, the lipid infiltration of the aorta and aortic sinus were observed by oil red O staining, and the spleen index was calculated. The proportion of Ly6Chigh and Ly6Clow monocyte subsets, macrophages, and their M1 phenotype, as well as Treg cells in spleen were measured by flow cytometry. The expressions of cluster of differentiation 36 (CD36), scavenger receptor A1 (SRA1), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), F4/80, and fork head frame protein 3 (FOXP3) in aortic sinus were assessed by immunohistochemical staining. The serum levels of oxidized low density lipoprotein (ox-LDL), interleukin-1ß (IL-1ß), IL-18, transforming growth factor-ß (TGF-ß), and IL-10 were measured by enzyme-linked immunosorbent assays (ELISA). RESULTS: Compared with the model group, the level of serum TC and LDL-C decreased in the SMYAD group, the pathological changes of aortic sinus decreased, and lipid infiltration of aorta and aortic sinus also decreased. These decreases were accompanied by a significant downregulation of CD36, SRA1, and LOX-1. Furthermore, the proportions of Ly6Chigh pro-inflammatory monocyte subsets, macrophages, and their M1 phenotypes in spleen decreased significantly, while the proportion of Treg cells increased. In addition, while the expression of F4/80 decreased, the expression of FOXP3 increased in the aorta sinus. The levels of serum pro-inflammatory factors IL-1ß and IL-18 decreased. CONCLUSIONS: SMYAD can improve the pathological changes associated with AS and can inhibit lipid deposition in ApoE-/- mice induced by WD diet. The likely mechanism is the inhibition of the differentiation and recruitment of monocytes and macrophages, the promotion of the differentiation and recruitment of Treg cells, as well as the reduction of the secretion of pro-inflammatory factors.

Augmentation of Perforator Flap Blood Supply with Vascular Supercharge or Flap Prefabrication: Evaluation in a Rat Model.

BACKGROUND: Vascular supercharge and flap prefabrication are two surgical maneuvers to improve flap blood supply. Although these techniques have been studied intensively, few studies have focused on the differences between supercharge and prefabricated flaps regarding their flap survival areas, vasculatures, and hemodynamics. METHODS: In this study, 21 male Sprague-Dawley rats were divided into three groups as follows: group A, single perforator flap; group B, supercharge flap; and group C, prefabricated flap. Flap survival was measured 1 week after flap elevation. Indocyanine green angiography was applied to visualize flap vascularity and to analyze flap hemodynamics. Von Willebrand factor immunohistochemical staining was applied to assess the number of microvessels in the choke zone of the abdominal wall. RESULTS: The flap survival areas were expanded significantly in the arteriovenous supercharge group and the vascular bundle prefabricated group compared with that in the single-perforator group (81.34 ± 8.12 percent and 75.51 ± 8.08 percent versus 46.27 ± 10.01 percent, respectively; p < 0.05). Hemodynamic analysis suggested that although a significant increase in arterial infusion could be achieved with flap prefabrication, the venous effusion of the prefabricated flap was the worst among the three groups, indicating greater susceptibility to compromised venous return. Active neovascularization was confirmed by an increased number of microvessels in group C. Specifically, the dilatation of choke vessels and the newly formed vessels of the prefabricated pedicle could be appreciated by indocyanine green angiographic mapping. CONCLUSIONS: Both vascular supercharge and flap prefabrication can augment the blood supply of the perforator flap but by means of different mechanisms. Because a supercharge flap is less susceptible to venous compromise, it is suggested to first consider the use of vascular supercharging when feasible.

Conditional survival after surgical resection of primary retroperitoneal tumors: a population-based study.

BACKGROUND: The purpose of this study was to assess conditional survival (CS) after resection of primary retroperitoneal tumors (RPTs). METHODS: The data of 1594 patients with primary RPTs who underwent surgery between 2004 and 2016 were retrieved from the Surveillance Epidemiology and End Results (SEER) database. Multivariate Cox analysis was used to identify prognostic factors affecting overall survival (OS) and cancer-specific survival (CSS). CS was used to calculate the probability of survival for an additional 3 years after the patient had survived x years, according to the formulas: COS3 = OS (x + 3) /OS (x) and CCSS3 = CSS (x + 3)/CSS (x). RESULTS: The 1-, 3-, and 5-year OS rates of all patients were 89.8, 71.8, and 60.8%, while the 1-, 3-, and 5-year CSS rates were 91.9, 77.1, and 67.8%, respectively. Age, sex, FNCLCC grade, size, multifocality, histology, and chemotherapy were independent prognostic factors for OS and CSS. Among patients who survived for 1, 3, and 5 years, the COS3 rates were 72.9, 77.9, and 79.3%, and the CCSS3 rates were 78.1, 82.7, and 85.8%, respectively. Patients with poor clinicopathological characteristics achieved greater improvements in COS3 and CCSS3 rates, and the survival gaps between OS and COS3, as well as CSS and CCSS3 were more obvious. CONCLUSION: Postoperative CS of RPTs was dynamic and increased over time. CS increased more significantly in patients with poor clinicopathological characteristics.

Modulatory mechanisms of NLRP3: Potential roles in inflammasome activation.

The NLRP3 inflammasome regulates innate immune and inflammatory responses by promoting pro-inflammatory cytokines such as IL-18 and IL-1ß. NLRP3 is one of the main factors restricting the activation of the inflammasome, which is closely related to the abundance and localization of NLRP3. A substantial number of studies have focused on specifically targeting NLRP3 to develop inhibitors against NLRP3 inflammasome. Here, we succinctly review the regulation of NLRP3 expression at DNA/chromosome, transcriptional, post-transcriptional, and translation levels. These are critical for the fine regulation of the NLRP3 inflammasome.