The Effects of Hypoxia-Preconditioned Dental Stem Cell-Derived Secretome on Tissue Regeneration.

Mesenchymal stroma cells derived from oral tissues are known as dental stem cells (DSCs). Owing to their unique therapeutic niche and clinical accessibility, DSCs serve as a promising treatment option for bone defects and oral tissue regeneration. DSCs exist in a hypoxic microenvironment in vivo, which is far lower than the current 20% oxygen concentration used in in vitro culture. It has been widely reported that the application of an oxygen concentration less than 5% in the culture of DSCs is beneficial for preserving stemness and promoting proliferation, migration, and paracrine activity. The paracrine function of DSCs involves the secretome, which includes conditioned media (CM) and soluble bioactive molecules, as well as extracellular vesicles extracted from CM. Hypoxia can play a role in immunomodulation and angiogenesis by altering the protein or nucleic acid components in the secretory group, which enhances the therapeutic potential of DSCs. This review summarizes the biological characteristics of DSCs, the influence of hypoxia on DSCs, the impact of hypoxia on the secretory group of DSCs, and the latest progress on the use of DSCs secretory group in tissue regeneration based on hypoxia pretreatment. We highlighted the multifunctional biological effect of hypoxia culture on tissue regeneration and provided a summary of the current mechanism of hypoxia in the pretreatment of DSCs.

Effect of Helicobacter Pylori Infection on Glucose Metabolism, Lipid Metabolism and Inflammatory Cytokines in Nonalcoholic Fatty Liver Disease Patients.

Objective: To probe into the influence of Helicobacter pylori (Hp) infection on glucose metabolism, lipid metabolism, and inflammatory cytokines in patients with nonalcoholic fatty liver disease (MASLD). Methods: A total of 140 MASLD patients admitted to our Hospital between June 2020 and May 2021 were selected as the research objects. Based on the presence or absence of Hp infection, they were divided into the study group (73 cases with infection) and control group (67 cases without infection). Glucose metabolism indicators [fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), fasting insulin (FINS), glycated hemoglobin (HbAlc)], lipid metabolism indicators [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], and inflammatory indicators [interleukin-37 (IL-37), interleukin-18 (IL-18)] were measured and compared between the two groups. Results: In terms of glucose metabolism indicators, the study group exhibited higher levels of FBG (5.84±0.49 vs 5.40±0.51, t=2.535, P=0.012), 2hPG (7.26±1.30 vs 6.50±1.53, t=3.321, P<0.001), and FINS (11.13±4.13 vs 9.12±3.72, t=3.224, P<0.001), and Insulin resistance index (HOMA-IR) (2.97±0.35 VS 2.13±0.54, t=3.761, P<0.001) and a lower level of HbAlc (5.25±0.56 vs 6.12±0.57, t=5.473, P<0.001) compared to the control group. Regarding lipid metabolism indicators, the study group exhibited higher levels of TC (5.64±1.49 vs 5.01±1.32, t=3.332, P<0.001), TG (1.89±0.34 vs 1.32±0.43, t=3.411, P<0.001), and LDL-C (3.31±0.43 vs 2.12±0.29, t=4.142, P<0.001), and a lower level of HDL-C (1.45±0.21 vs 1.78±0.42, t=4.347, P<0.001) compared to the control group. As for the inflammatory indicators, the study group exhibited higher levels of IL-37 (45.56±6.02 vs 34.02±3.28, t=9.332, P<0.001) and IL-18 (73.57±5.82 vs 60.34±4.84, t=10.141, P<0.001) compared to the control group. Conclusion: It is crucial to place appropriate emphasis on the impact of Hp infection on the glucose metabolism, lipid metabolism, and inflammatory response in MASLD patients, warranting careful consideration during the treatment of these patients.

Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in choroidal neovascularization model.

Choroidal neovascularization (CNV) is a hallmark of neovascular age-related macular degeneration (nAMD) and a major contributor to vision loss in nAMD cases. However, the identification of specific cell types associated with nAMD remains challenging. Herein, we performed single-cell sequencing to comprehensively explore the cellular diversity and understand the foundational components of the retinal pigment epithelium (RPE)/choroid complex. We unveiled 10 distinct cell types within the RPE/choroid complex. Notably, we observed significant heterogeneity within endothelial cells (ECs), fibroblasts, and macrophages, underscoring the intricate nature of the cellular composition in the RPE/choroid complex. Within the EC category, four distinct clusters were identified and EC cluster 0 was tightly associated with choroidal neovascularization. We identified five clusters of fibroblasts actively involved in the pathogenesis of nAMD, influencing fibrotic responses, angiogenic effects, and photoreceptor function. Additionally, three clusters of macrophages were identified, suggesting their potential roles in regulating the progression of nAMD through immunomodulation and inflammation regulation. Through CellChat analysis, we constructed a complex cell-cell communication network, revealing the role of EC clusters in interacting with fibroblasts and macrophages in the context of nAMD. These interactions were found to govern angiogenic effects, fibrotic responses, and inflammatory processes. In summary, this study reveals noteworthy cellular heterogeneity in the RPE/choroid complex and provides valuable insights into the pathogenesis of CNV. These findings will open up potential avenues for deep understanding and targeted therapeutic interventions in nAMD.

SAA1 regulated by S1P/S1PR1 promotes the progression of ESCC via ß-catenin activation.

Serum amyloid A1 (SAA1), an inflammation-related molecule, is associated with the malignant progression of many tumors. This study aimed to investigate the role of SAA1 in the progression of esophageal squamous cell carcinoma (ESCC) and its molecular mechanisms. The expression of SAA1 in ESCC tissues and cell lines was analyzed using bioinformatics analysis, western blotting, and reverse transcription-quantitative PCR (RT‒qPCR). SAA1-overexpressing or SAA1-knockdown ESCC cells were used to assess the effects of SAA1 on the proliferation, migration, apoptosis of cancer cells and the growth of xenograft tumors in nude mice. Western blotting, immunofluorescence and RT‒qPCR were used to investigate the relationship between SAA1 and ß-catenin and SAA1 and sphingosine 1-phosphate (S1P)/sphingosine 1-phosphate receptor 1 (S1PR1). SAA1 was highly expressed in ESCC tissues and cell lines. Overexpression of SAA1 significantly promoted the proliferation, migration and the growth of tumors in nude mice. Knockdown of SAA1 had the opposite effects and promoted the apoptosis of ESCC cells. Moreover, SAA1 overexpression promoted the phosphorylation of ß-catenin at Ser675 and increased the expression levels of the ß-catenin target genes MYC and MMP9. Knockdown of SAA1 had the opposite effects. S1P/S1PR1 upregulated SAA1 expression and ß-catenin phosphorylation at Ser675 in ESCC cells. In conclusion, SAA1 promotes the progression of ESCC by increasing ß-catenin phosphorylation at Ser675, and the S1P/S1PR1 pathway plays an important role in its upstream regulation.

Effect of combining evolocumab with statin on carotid intraplaque neovascularization in patients with premature coronary artery disease (EPOCH).

BACKGROUND AND AIMS: We aimed to explore the effect of PCSK9 inhibitor based on the background of statin on carotid intraplaque neovascularization (IPN) assessed by serial contrast-enhanced ultrasound (CEUS) analysis in Chinese patients with premature coronary artery disease (PCAD). METHODS: 41 patients were included to receive treatments with biweekly evolocumab (n = 22) or placebo (n = 19) in addition to statin therapy for 52 weeks. All patients were newly diagnosed with PCAD and treatments were initiated at baseline of the observations. Baseline and 52-week CEUS were acquired to measure the max plaque height (MPH) and IPN. The primary outcome was the 52-week IPN changes, the secondary endpoints included the 52-week MPH changes and major adverse cardiovascular events. RESULTS: The mean ± SD age of the participants was 46.76 ± 8.56 years, and 61% (25/41) of patients were on statins before the start of the study. There was no statistically significant difference in the history of statins treatment and the initiated lipid-lowering therapy of atorvastatin and rosuvastatin between groups (p > 0.05). At 52 weeks, the evolocumab group showed a lower LDL level (0.84 ± 0.45 mmol/L vs. 1.58 ± 0.51 mmol/L, p < 0.001) and a greater decrease in percent reduction of LDL-C level (-65% vs. -32%) and a higher percent of achieving lipid-lowering target (95% vs. 53%, p < 0.05) compared with the placebo group. At 52 weeks, IPN (evolocumab group: 0.50 ± 0.60 vs. 1.50 ± 0.80, p < 0.001; placebo group: 0.79 ± 0.54 vs. 1.26 ± 0.65, p < 0.05) and MPH (evolocumab group: 2.01 ± 0.44 mm vs. 2.57 ± 0.90 mm, p < 0.05, placebo group: 2.21 ± 0.58 mm vs. 2.92 ± 0.86 mm, p < 0.05) reduced significantly in both groups from baseline to 52-week follow-up. IPN and MPH were decreased by both treatments. Still, there was no significant difference in delta (52 weeks - baseline) MPH by an ANOVA analysis between the two groups [evolocumab group: -0.56 mm (2.01 mm-2.57 mm); placebo group: -0.71 mm (2.21 mm-2.92 mm), p > 0.05]. In the evolocumab group, the change in the mean reduction of IPN from baseline [-1.00 (0.50-1.50) vs. -0.47 (0.79-1.26), p < 0.05] and the incidence of patients with carotid IPN decrease were significantly greater reduction (90% vs. 58%, p < 0.05). CONCLUSIONS: If compared to placebo, the PCSK9 inhibitor evolocumab combined with statins resulted in a greater decrease in LDL-C and plaque neovascularization in Chinese patients with PCAD.

Puerarin attenuates remifentanil­induced postoperative hyperalgesia via targeting PAX6 to regulate the transcription of TRPV1.

Remifentanil­induced hyperalgesia (RIH) is characterized by the emergence of stimulation­induced pain, including phenomena such as allodynia and thermal hyperalgesia following remifentanil infusion. As a sequence­specific DNA binding transcription factor, PAX6 positively and negatively regulates transcription and is expressed in multiple cell types in the developing and adult central nervous system. It was hypothesized that puerarin could relieve RIH via targeting PAX6 to regulate transcription of transient receptor potential cation channel subfamily V Member 1 (TRPV1). A total of 32 rats were randomly divided into five groups, namely control group, RI group, RI + 10 mg/kg puerarin group (RI + puerarin10), RI + 20 mg/kg puerarin group (RI + puerarin20), and RI + 40 mg/kg puerarin group (RI + puerarin40). Mechanical and thermal hyperalgesia were tested at ­24, 2, 6, 24 and 48 h after remifentanil infusion. Following the sacrifice of rats after the last behavioral test, western blot was used to detect the expression levels of TRPV1 in the tissues; Immunofluorescence staining and western blotting were used to detect the expression of PAX6 in the spinal cord. PharmMapper and JASPAR were used to predict the binding sites of puerarin/PAX6/TRPV1. Chromatin immunoprecipitation­PCR and dual luciferase reporter assay were used to verify the targeting relationship between PAX6 and TRPV1. Immunofluorescence was used to detect the expression levels of TRPV1 and p­NR2B. The results revealed that puerarin (10, 20, 40 mg/kg) dose­dependently reduced thermal and mechanical hyperalgesia from 2 to 48 h after remifentanil infusion. Remifentanil infusion remarkably stimulated the expression of phosphorylated (p­)NR2B. Nevertheless, the increased amount of p­NR2B by RIH was dose­dependently suppressed by puerarin in rats. In conclusion, puerarin was revealed to attenuate postoperative RIH via targeting PAX6 to regulate the transcription of TRPV1.

Modulation of gut microbiota by crude mulberry polysaccharide attenuates knee osteoarthritis progression in rats.

Mulberry (Morus alba L.), a kind of common fruits widely cultivated worldwide, has been proven various biological activities. However, its potential role in the progression of knee osteoarthritis (KOA) remains unclear. This study aims to investigate the potential protective effects of crude polysaccharide extracted from mulberry fruit, referred to as a complex blend of polysaccharides and other unidentified extracted impurities, on KOA progression. The KOA rats were established by injection of 1 mg sodium monoiodoacetate into knee, and administrated with crude mulberry polysaccharide (Mup) by gastric gavage for 4 weeks. Furthermore, intestinal bacteria clearance assay (IBCA) and fecal microbiota transplantation were conducted for the evaluation of the effect of gut microbiota (GM) on KOA. Our findings demonstrated that Mup, particularly at a dosage of 200 mg/kg, effectively improved abnormal gait patterns, reduced the level of inflammation, mitigated subchondral bone loss, restored compromised joint surfaces, alleviated cartilage destruction, and positively modulated the dysregulated profile of GM in KOA rats. Moreover, IBCA compromised the protective effects of Mup, while transplantation of fecal bacteria from Mup-treated rats facilitated KOA recovery. Collectively, our study suggested that Mup had the potential to ameliorate the progression of KOA, potentially through its modulation of GM profile.

Effect of moderate-intensity statin on carotid intraplaque neovascularization of coronary artery disease: a retrospective cohort study.

Background: Statin treatment can reduce atherosclerotic plaque as detected via invasive intracoronary methods. However, few studies have evaluated the effect of moderate-intensity statin therapy on carotid intraplaque neovascularization (IPN) using semiquantitative indices. This study thus aimed to assess the effect of statin on the carotid IPN of coronary artery disease with contrast-enhanced ultrasound (CEUS). Methods: In this noncontrol, retrospective, cohort study, 35 inpatients who underwent coronary angiography, serial CEUS, and laboratory evaluations were consecutively enrolled from June 2020 to December 2022 at the Department of Cardiology, Chinese PLA General Hospital. All patients were administered moderate-intensity statin during serial CEUS, and continuous and categorical assessment of IPN and maximum plaque height (MPH) of carotid plaque was performed. Patients with a target low-density lipoprotein cholesterol (LDL-C) <1.8 mmol/L at 12-month follow-up were compared with those who did not reach the LDL-C 1.8 mmol/L target. Results: From baseline to 12-month follow-up, there were significant differences in the LDL-C levels between patients (2.71±1.29 vs. 1.35±0.83 mmol/L), those with 12-month follow-up LDL-C <1.8 mmol/L (2.58±1.24 vs. 1.08±0.52 mmol/L), and those with 12-month follow-up LDL-C ≥1.8 mmol/L (3.24±1.44 vs. 2.56±0.85 mmol/L) all P values <0.05, with decreases of 41%, 49%, and 11% from baseline, respectively. The mean MPH (12 months to baseline) decreased from 2.47±0.63 to 2.22±0.60 mm (P<0.05), and the IPN also decreased from 1.15±0.62 to 0.58±0.56, representing a reduction of 0.57±0.59 from baseline (P<0.001). In the LDL-C <1.8 mmol/L patients, there were significant differences between baseline and 12 months in MPH (2.37±0.56 vs. 2.03±0.52 mm; P<0.05) and IPN (1.32±0.77 vs. 0.54±0.63; P<0.05) compared with those with a follow-up LDL-C ≥1.8 mmol/L. Patients with a follow-up LDL-C <1.8 mmol/L, compared with those with a follow-up LDL-C ≥1.8 mmol/L, showed a significantly greater reduction in MPH (-0.34±0.46 vs. -0.13±0.39; P<0.05) and IPN (-0.79±0.63 vs. -0.57±0.79; P<0.05). Additionally, patients with carotid IPN regression showed a higher percent change in LDL-C compared with those without carotid IPN regression (-53.31±23.20 vs. -29.55±19.47; P<0.05). Conclusions: Controlling the LDL-C to <1.8 mmol/L under moderate-intensity statin can stabilize and reduce carotid IPN as detected by the semiquantitative noninvasive CEUS.

Diagnostic value of contrast-enhanced ultrasound in the activity of idiopathic retroperitoneal fibrosis: a retrospective study.

OBJECTIVES: To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) in the disease activity of idiopathic retroperitoneal fibrosis (IRPF). METHODS: This retrospective study included 148 CEUS examinations from 63 patients with IRPF treated in our hospital from April 2016 to September 2021. They were divided into two groups: IRPF active group (69 examinations) and inactive group (79 examinations). Uni- and multivariable analyses were used to identify independent risk factors for IRPF activity. Receiver operating characteristic (ROC) curves were drawn to establish different diagnostic models to evaluate the diagnostic value of IRPF activity. The z test was used to compare the differences of the area under the curves (AUCs). The value of CEUS in evaluating the variation of disease activity over time was also investigated between repeat patient studies. RESULTS: Univariate and multivariate logistic regression analyses revealed the thickness [odds ratio (OR) = 14.125, 95% confidence interval (CI) = 3.017-66.123] was the most significant independent risk factor for IRPF activity (P < 0.01). The best diagnostic model was model 3, which was established by CEUS score combined with thickness. The AUC was 0.944 (95%CI = 0.912-0.977), and the sensitivity and specificity were 89.86% and 86.08%, respectively. The diagnostic performance was not significantly improved after combining clinical symptom (back pain) and laboratory indicators [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)]. Compared with before treatment, the CEUS score and thickness were significantly decreased after treatment (x2 = 14.580, P < 0.001 and z = 4.708, P < 0.001, respectively). CONCLUSION: CEUS has good diagnostic value for IRPF disease activity. Key points • Thickness and contrast-enhanced ultrasound score were significantly higher in the active group than those in inactive group (P < 0.001). • With thickness of 4 mm and contrast-enhanced ultrasound 2 score as optimal cut-off values, the sensitivity and specificity were 89.86%, 81.01% and 52.17%, 100.00%, respectively. • During follow-up, when the disease progressed, the change of CEUS score was earlier than the change of thickness.

The therapeutic effect of Picroside II in renal ischemia-reperfusion induced acute kidney injury: An experimental study.

The microcirculation hemodynamics change and inflammatory response are the two main pathophysiological mechanisms of renal ischemia-reperfusion injury (IRI) induced acute kidney injury (AKI). The treatment of microcirculation hemodynamics and inflammatory response can effectively alleviate renal injury and correct renal function. Picroside II (P II) has a wide range of pharmacological effects. Still, there are few studies on protecting IRI-AKI, and whether P II can improve renal microcirculation perfusion is still being determined. This study aims to explore the protective effect of P II on IRI-AKI and evaluate its ability to enhance renal microcirculation perfusion. In this study, a bilateral renal IRI-AKI model in mice was established, and the changes in renal microcirculation and inflammatory response were quantitatively evaluated before and after P II intervention by contrast-enhanced ultrasound (CEUS). At the same time, serum and tissue markers were measured to assess the changes in renal function. The results showed that after P II intervention, the levels of serum creatinine (Scr), blood urea nitrogen (BUN), serum cystatin C (Cys-C), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and superoxide dismutase (SOD), as well as the time-to-peak (TTP), peak intensity (PI) and area under the curve (AUC), and the normalized intensity difference (NID) were all alleviated. In conclusion, P II can improve renal microcirculation perfusion changes caused by IRI-AKI, reduce inflammatory reactions during AKI, and enhance renal antioxidant stress capacity. P II may be a new and promising drug for treating IRI-AKI.

Extraction, purification, structural characteristics and biological properties of the polysaccharides from Armillaria mellea (Vahl) P. Kumm.: A review.

Armillaria mellea (Vahl) P. Kumm. is a well-known homoeopathic plant with medicinal and culinary uses. Modern phytochemical researchers have successfully extracted and purified over 40 types of A. mellea polysaccharides (AMPs) from the fruiting bodies, hyphae and fermentation broth of A. mellea, and some of them have been analyzed and identified by their chemical structures. The impressive biological activity of these polysaccharides has been recognized by scientists worldwide. Many studies show that AMPs have remarkable antioxidant, anti-diabetic, anti-tumor, anti-inflammatory, immunoregulatory, hypolipidemic, thrombectomy, anti-aging, pulmonary protective, hepatic protective, anti-Alzheimer's properties, etc. However, the current understanding of the relationships between their chemical structure and biological activity, toxicological effects and pharmacokinetics remains limited. This article provides a systematic review of the research conducted over the past decades on the extraction and purification methods, structural characteristics, biological activity and mechanism of action of AMPs. The aim is to provide a research base that will benefit the future application of AMPs as therapeutic drugs and functional foods, and also provide insights for the further development of AMPs.

Effects of Monascus purpureus on ripe Pu-erh tea in different fermentation methods and identification of characteristic volatile compounds.

The present study aimed to explore the key volatile compounds (VCs) that lead to the formation of characteristic flavors in ripe Pu-erh tea (RIPT) fermented by Monascus purpureus (M. purpureus). Headspace solid-phase microextraction coupled with gas chromatography/mass spectrometry (HS-SPME-GC-MS), orthogonal partial least square-discriminant analysis (OPLS-DA) were employed for a comprehensive analysis of the VCs present in RIPT fermented via different methods and were further identified by odor activity value (OAV). The VCs 1,2-dimethoxybenzene, 1,2,3-trimethoxybenzene, (E)-linalool oxide (pyranoid), methyl salicylate, linalool, ß-ionone, ß-damascenone were the key characteristic VCs of RIPT fermented by M. purpureus. OAV and Gas chromatography-olfactometry (GC-O) further indicated that ß-damascenone was the highest contribution VCs to the characteristic flavor of RIPT fermented by M. purpureus. This study reveals the specificities and contributions of VCs present in RIPT under different fermentation methods, thus providing new insights into the influence of microorganisms on RIPT flavor.

Efficacy and safety of sedation with dexmedetomidine in adults undergoing gastrointestinal endoscopic procedures: systematic review and meta-analysis of randomized controlled trials.

Background: The sedative role of dexmedetomidine (DEX) in gastrointestinal endoscopic procedures is unclear. We performed this systematic review and meta-analysis to assess the efficacy and safety of sedation with DEX during gastrointestinal endoscopic procedures with a view to providing evidence-based references for clinical decision-making. Methods: The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) that compared DEX with different sedatives comparators (such as propofol, midazolam, and ketamine) for sedation in a variety of adult gastrointestinal endoscopic procedures from inception to 1 July 2022. Standardized mean difference (SMD) and weighted mean difference (WMD) with 95% confidence interval (CI) or pooled risk ratios (RR) with 95% CI were used for continuous outcomes or dichotomous outcomes, respectively, and a random-effect model was selected regardless of the significance of the heterogeneity. Results: Forty studies with 2,955 patients were assessed, of which 1,333 patients were in the DEX group and 1,622 patients were in the control (without DEX) group. The results suggested that the primary outcomes of sedation level of DEX are comparable to other sedatives, with similar RSS score and patient satisfaction level, and better in some clinical outcomes, with a reduced risk of body movements or gagging (RR: 0.60; 95% CI: 0.37 to 0.97; p = 0.04; I2 = 68%), and a reduced additional requirement for other sedatives, and increased endoscopist satisfaction level (SMD: 0.41; 95% CI: 0.05 to 0.77; p = 0.03; I2 = 86%). In terms of secondary outcomes of adverse events, DEX may benefit patients in some clinical outcomes, with a reduced risk of hypoxia (RR:0.34; 95% CI: 0.20 to 0.55; p < 0.0001; I2 = 52%) and cough (RR: 0.25; 95% CI: 0.12 to 0.54; p = 0.0004; I2 = 0%), no significant difference in the risk of hypotension, while an increased risk of bradycardia (RR: 3.08; 95% CI: 2.12 to 4.48; p < 0.00001; I2 = 6%). Conclusion: This meta-analysis indicates that DEX is a safe and effective sedative agent for gastrointestinal endoscopy because of its benefits for patients in some clinical outcomes. Remarkably, DEX is comparable to midazolam and propofol in terms of sedation level. In conclusion, DEX provides an additional option in sedation for gastrointestinal endoscopic procedures. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced.

Inter-observer variation in two-dimensional and three-dimensional ultrasound measurement of papillary thyroid microcarcinoma.

BACKGROUNDS: The reliable ultrasound (US) measurements of papillary thyroid microcarcinoma (PTMC) are very important during active surveillance. This prospective study was design to investigate the inter-observer reliability and agreement of two- dimensional ultrasound(2DUS) and three-dimensional ultrasound(3DUS) in the measurement of maximum diameter and volume for PTMC. METHODS: This prospective study included 51 consecutive patients with solitary PTMC confirmed by biopsy. Two independent observers performed measurements of each tumor using a standardized measurement protocol. The maximum diameter was the largest one of the three diameters measured on the largest transverse and longitudinal 2DUS images. 2DUS volume was calculated using ellipsoid formula method. The virtual organ computer aided analysis(VOCAL) was used to determine 3DUS volume. The inter-observer reliability was assessed using intraclass correlation coefficient(ICC) with 95% confidence intervals(CIs). Bland-Altman analysis was used to evaluate agreement, and expressed as a bias with 95% limits of agreement(LOA). RESULTS: The maximum diameter was 0.78 ± 0.14 cm. Volume measured by 3DUS was significantly smaller than that by 2DUS(0.163 ± 0.074 cm3 vs. 0.175 ± 0.078 cm3, P = 0.005). The ICCs of inter-observer reliability of maximum diameter, 2DUS volume and 3DUS volume was 0.922(0.864-0.955), 0.928(0.874-0.959), and 0.974(0.955-0.985), respectively. The ICCs of 2DUS and 3DUS volume was 0.955(0.909-0.976). The inter-observer agreement of maximum diameter, 2DUS volume and 3DUS volume was 1.096(0.7322 to 1.459), 1.008(0.5802-1.435), and 1.011(0.7576-1.265), respectively. The inter-observer agreement of 2DUS and 3DUS volume was 1.096(0.7322 to 1.459). CONCLUSION: Maximum diameter had the lowest degree of observer variation among all the measurements. Volume measured by 3DUS had lower variability and higher repeatability than that by 2DUS, which might be helpful to provide more reliable estimates of tumor size for PTMC.

Proliferative glomerulonephritis with monoclonal IgG Lambda deposits caused by plasmablastic lymphoma: a case report.

INTRODUCTION: As a very rare form of B-cell lymphoma, plasmablastic lymphoma (PBL) typically occurs in patients with underlying immunosuppression, including human immunodeficiency virus (HIV), organ transplantation, and autoimmune diseases. For HIV-positive patients, PBL normally originates in the gastrointestinal tract, especially from the oral cavity in most cases. It is extremely rare to find abdominal cavity involvement in PBL, and there has been no previously reported instance of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) attributed to monoclonal IgG (MIgG) lambda secreted by PBL. CASE PRESENTATION: We report the case of an HIV-negative female with nephrotic syndrome, renal insufficiency, and multiple swollen lymph nodes. Ascitic fluid cytology revealed a high level of plasmablast-like lymphocytes with the restriction of lambda light chains. Besides, the renal biopsy revealed PGNMID, which could presumably be secondary to MIgG-lambda-secreting by PBL. MIgG-lambda-restricted expression was discovered earlier in the kidney tissue than in the blood. CONCLUSION: The diagnostic landscape for PBL is notoriously intricate, necessitating a multifaceted and nuanced approach to mitigate the risks of erroneous identification.

[Effect of moxibustion of acupoints for both lung and intestine disorders on lung inflammation and intestinal short-chain fatty acids in asthmatic model rats].

OBJECTIVE: To explore the mechanism of moxibustion in the treatment of asthmatic inflammation from the point of short-chain fatty acids (SCFAs) in rats with asthma. METHODS: A total of 48 SD rats (half male and half female) were randomly divided into 4 groups： normal, model, lung treatment and joint-treatment of lung and intestine (joint-treatment), with 12 rats in each group. The asthma model was made by subcutaneous (bilateral back and inguinal regions) and intraperitoneal injection of mixture solution of ovalbumin and aluminium hydroxide gel (on day 1 and 8) and followed by inhalation of atomized 1% ovalbumin (20 min from day 15, once daily for one week). Moxibustion was applied to bilateral "Feishu" (BL13) for rats of the lung treatment group or bilateral "Feishu" (BL13) and "Tianshu" (ST25) for rats of the joint treatment group. One hour after the intervention, the rats in the later three groups were separately given atomized 1% ovalbumin solution inhalation for 20 min. The treatment was conducted for 30 min, once daily for 14 consecutive days. At the end of the intervention, the percentage of inflammatory cells in blood was detected by biochemical method and histopathological changes of the lung were observed after H.E. staining. The inflammatory cells in the bronchoalveolar lavage fluid (BALF) were counted after Wright-Giemsa staining. The mRNA expressions of interleukin (IL)-4, IL-5, IL-13, IL-17, IL-33, leukotriene (LT), thymic stromal lymphopoietin (TSLP) and prostaglandin D2 (PGD2) were detected by real-time PCR, and the contents of SCFAs in rats' feces were detected by gas chromatography-mass spectrometry. RESULTS: Relevant to the normal group, the model group had an obvious increase in the percentages of neutrophils, lymphocytes and eosinophils in the blood, the percentages of neutrophils and eosinophils in the BALF, and in the expression levels of PGD2, TSLP, LT, IL-4, IL-5, IL-13, IL-17 and IL-33 mRNAs in the lung tissues (P<0.01, P<0.05), and a marked decrease in the contents of acetic acid, propionic acid, isobutyric acid, butyric acid and valeric acid in feces (P<0.05, P<0.01). After the treatment, the percentages of neutrophils and lymphocytes in the peripheral blood, eosinophils in the BALF, and the expression levels of PGD2, TSLP, LT, IL-4, IL-17, IL-33 mRNAs in the lung tissues in both the lung treatment and joint treatment groups, as well as neutrophils of BALF, and expression of IL-5 and IL-13 mRNAs in the joint treatment group were significantly down-regulated (P<0.01, P<0.05), while the contents of acetic acid, propionic acid and valerate in the lung treatment group, and acetic acid, propionic acid, isobutyric acid, butyric acid and valeric acid in the joint treatment group were all strikingly increased (P<0.05, P<0.01). The effect of the joint treatment was superior to that of lung treatment in down-regulating the expressions of LT and IL-5 mRNAs (P<0.05, P<0.01) and up-requlating the content of propionic acid (P<0.05). Results of H.E. staining showed thickened alveolar wall, infiltration of a large number of inflammatory cells and interstitial fibrous tissue hyperplasia around the bronchus and scattered arrangement of cells of the lung tissue in the model group, which was relatively milder in both lung treatment and joint treatment groups, particularly the later. CONCLUSION: Joint treatment of asthma from the lung and intestine can better regulate the contents of intestinal SCFAs and alleviate the inflammatory response of asthmatic model rats, thus, intestinal SCFAs may be involved in the process of moxibustion in improving inflammatory response.

Contrast-enhanced ultrasound in evaluating the severity of acute kidney injury: An animal experimental study.

PURPOSE: Early assessment of the severity of acute kidney injury (AKI) is critical to the prognosis of patients. Renal microcirculation hemodynamic changes and inflammatory response are the essential links of AKI induced by ischemia-reperfusion injury (IRI). This study aims to explore the value of contrast-enhanced ultrasound (CEUS) based on vascular cell adhesion molecule-1 (VCAM-1) targeted microbubbles (TM) in evaluating the renal microcirculation hemodynamics and inflammatory response of different severity of AKI. METHODS: Eighteen male C57BL/6J mice were randomly divided into three groups (n = 6): sham operation (sham) group, mild IRI-AKI (m-AKI) group, and severe IRI-AKI (s-AKI) group. CEUS based on VCAM-1 TM was used to evaluate renal microcirculation perfusion and inflammatory response. Pearson's correlation was used to analyze the correlation between ultrasonic variables and pro-inflammatory factors. RESULTS: Compared with the sham group, AUC in m-AKI and s-AKI groups was significantly decreased, and s-AKI group was lower than m-AKI group (P < 0.05). NID of m-AKI and s-AKI groups was significantly higher than that of the sham group, and s-AKI group was higher than that of m-AKI group (P < 0.05). There was a linear positive correlation between NID and VCAM-1 protein expression (r = 0.7384, P < 0.05). NID and AUC were correlated with TNF-α and IL-6 levels (P < 0.05). Compared with early AKI biomarkers, CEUS based on VCAM-1 TM has higher sensitivity in evaluating the severity of AKI. CONCLUSIONS: CEUS based on VCAM-1 TM can evaluate renal microcirculation perfusion and inflammatory response in mild and severe AKI, which may provide helpful information for assessing the severity of AKI.

Corrigendum: Induction of RIPK3/MLKL-mediated necroptosis by Erigeron breviscapus injection exhibits potent antitumor effect.

[This corrects the article DOI: 10.3389/fphar.2023.1219362.].

Induction of RIPK3/MLKL-mediated necroptosis by Erigeron breviscapus injection exhibits potent antitumor effect.

Colorectal cancer (CRC) is the second leading cause of tumor-related deaths worldwide. Resistance of tumor cells to drug-induced apoptosis highlights the need for safe and effective antitumor alternatives. Erigeron breviscapus (Dengzhanxixin in China) injection (EBI), extracted from the natural herb Erigeron breviscapus (Vant.) Hand.-Mazz (EHM), has been widely used in clinical practice for cardiovascular diseases. Recent studies have suggested that EBI's main active ingredients exhibit potential antitumor effects. This study aims to explore the anti-CRC effect of EBI and elucidate the underlying mechanism. The anti-CRC effect of EBI was evaluated in vitro using CCK-8, flow cytometry, and transwell analysis, and in vivo through a xenograft mice model. RNA sequencing was utilized to compare the differentially expressed genes, and the proposed mechanism was verified through in vitro and in vivo experiments. Our study demonstrates that EBI significantly inhibits the proliferation of three human CRC cell lines and effectively suppresses the migration and invasion of SW620 cells. Moreover, in the SW620 xenograft mice model, EBI markedly retards tumor growth and lung metastasis. RNA-seq analysis revealed that EBI might exert antitumor effects by inducing necroptosis of tumor cells. Additionally, EBI activates the RIPK3/MLKL signaling pathway, a classical pathway of necroptosis and greatly promotes the generation of intracellular ROS. Furthermore, the antitumor effect of EBI on SW620 is significantly alleviated after the pretreatment of GW806742X, the MLKL inhibitor. Our findings suggest that EBI is a safe and effective inducer of necroptosis for CRC treatment. Notably, necroptosis is a non-apoptotic programmed cell death pathway that can effectively circumvent resistance to apoptosis, which provides a novel approach for overcoming tumor drug resistance.