Clinical characteristics and correlation analysis of IVIG resistance in children with kawasaki disease complicated with hip synovitis: case-control study

ObjectiveTo investigate the clinical characteristics and risk factors of Kawasaki disease (KD) complicated with hip synovitis.MethodsChildren with KD admitted from January 1, 2011, to December 31, 2020, in the KD database of Yuying Children's Hospital Affiliated with Wenzhou Medical University were retrospectively included. We selected KD children with hip synovitis as the case group and KD children without hip synovitis as the control group to analyze the possible risk factors of hip synovitis in KD children.ResultsAmong 2,871 KD children admitted to our center in recent years, 28 had hip synovitis. In this study 140 KD children were enrolled, including 28 KD children with hip synovitis and 112 children with general KD (within one month of admission). The onset age of KD patients with hip synovitis was 30.92 (23.23–49.99) months, and there were 17 cases of bilateral hip involvement. The course of synovitis (limited movement, joint pain, lameness, unwillingness to stand, etc.) ranged from 1 to 19 days, with an average of (8.8 ± 4.6) days. We treated all KD children with IVIG (Intravenous immunoglobulin) plus aspirin, among which five patients in the case group developed coronary artery damage, six acquired IVIG resistance, and synovial inflammation disappeared within two weeks. Age, weight, length of stay, and incidence of IVIG resistance significantly differed between the two groups (P = 0.001, 0.005, <0.001, and 0.035, respectively). Logistic regression analysis showed that KD combined with hip synovitis was an independent risk factor for developing propyl pellet resistance, with an OR value of 4.625 (95% CI: 1.095, 19.526).ConclusionKD combined with hip synovitis mainly involves bilateral hip joints, and joint pain and limited movement are the main clinical features. The symptoms are mild and self-limiting. KD combined with hip synovitis is a risk factor for IVIG resistance. Hip synovitis is a good predictor of IVIG resistance

Interaction between microbiota and immunity and its implication in colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the world. Besides genetic causes, colonic inflammation is one of the major risk factors for CRC development, which is synergistically regulated by multiple components, including innate and adaptive immune cells, cytokine signaling, and microbiota. The complex interaction between CRC and the gut microbiome has emerged as an important area of current CRC research. Metagenomic profiling has identified a number of prominent CRC-associated bacteria that are enriched in CRC patients, linking the microbiota composition to colitis and cancer development. Some microbiota species have been reported to promote colitis and CRC development in preclinical models, while a few others are identified as immune modulators to induce potent protective immunity against colitis and CRC. Mechanistically, microbiota regulates the activation of different immune cell populations, inflammation, and CRC via crosstalk between innate and adaptive immune signaling pathways, including nuclear factor kappa B (NF-κB), type I interferon, and inflammasome. In this review, we provide an overview of the potential interactions between gut microbiota and host immunity and how their crosstalk could synergistically regulate inflammation and CRC, thus highlighting the potential roles and mechanisms of gut microbiota in the development of microbiota-based therapies to prevent or alleviate colitis and CRC

Antifungal Activity of Coumarin Against Candida albicans Is Related to Apoptosis

Coumarin (1,2-benzopyrone), an aromatic oxygen-containing heterocyclic compound, has various biological functions. Previous studies have demonstrated that coumarin and its derivatives exhibit antifungal activity against Candida albicans. In this study, we investigated the exact mechanism by which coumarin works against this fungus using Annexin V-FITC/PI double staining, TUNEL assay, and DAPI staining, and found that it induced a series of apoptotic features, including phosphatidylserine (PS) externalization, DNA fragmentation, and nuclear condensation. Moreover, it also induced cytochrome c release from the mitochondria to the cytoplasm and metacaspase activation. Further study revealed that intracellular reactive oxygen species (ROS) levels were increased and mitochondrial functions, such as mitochondrial membrane potential and mitochondrial morphology, were altered after treatment with coumarin. Cytosolic and mitochondrial Ca2+ levels were also found to be elevated. However, pretreatment with ruthenium red (RR), a known mitochondrial Ca2+ channel inhibitor, attenuated coumarin-mediated DNA fragmentation and metacaspase activity, indicating that the coumarin-induced C. albicans apoptosis is associated with mitochondrial Ca2+ influx. Finally, coumarin was found to be low-toxic and effective in prolonging the survival of C. albicans-infected mice. This study highlights the antifungal activity and mechanism of coumarin against C. albicans and provides a potential treatment strategy for C. albicans infection

Cancer Stem Cells and Immunosuppressive Microenvironment in Glioma

Glioma is one of the most common malignant tumors of the central nervous system and is characterized by extensive infiltrative growth, neovascularization, and resistance to various combined therapies. In addition to heterogenous populations of tumor cells, the glioma stem cells (GSCs) and other nontumor cells present in the glioma microenvironment serve as critical regulators of tumor progression and recurrence. In this review, we discuss the role of several resident or peripheral factors with distinct tumor-promoting features and their dynamic interactions in the development of glioma. Localized antitumor factors could be silenced or even converted to suppressive phenotypes, due to stemness-related cell reprogramming and immunosuppressive mediators in glioma-derived microenvironment. Furthermore, we summarize the latest knowledge on GSCs and key microenvironment components, and discuss the emerging immunotherapeutic strategies to cure this disease

miR-27b Suppresses Endothelial Cell Proliferation and Migration by Targeting Smad7 in Kawasaki Disease

Background/Aims: Increasing evidence indicates that microRNAs (miRNAs) play important roles in Kawasaki disease (KD). Our previous study demonstrated that hsa-miR-27b-3p (miR-27b) was up-regulated in KD serum. However, the specific role of miR-27b in KD remains unclear. We aimed to investigate that miR-27b could be a biomarker and therapeutic target for KD treatment. As well, the specific mechanism of miR-27b effecting endothelial cell functions was studied. Methods: The expression of miR-27b and Smad7 was measured by qRT-PCR. Gain-of-function strategy was used to observe the effect of miR-27b on human umbilical vein endothelial cells (HUVECs) proliferation and migration. Bioinformatics analyses were applied to predict miR-27b targets and then we verified Smad7 by a luciferase reporter assay. Western blot was performed to detect the protein expression of Smad7, PCNA, MMP9, MMP12 and TGF-β-related genes. Results: We confirmed that miR-27b was shown to be dramatically up-regulated in KD serum and KD serum-treated HUVECs and that elevated expression of miR-27b suppressed the proliferation and migration of HUVECs. Furthermore, our results verified that miR-27b mediated cell functions by affecting the TGF-β via targeting Smad7 in HUVECs. Conclusion: These results suggested that up-regulated miR-27b had a protective role in HUVECs proliferation and migration via targeting Smad7 and affecting TGF-β pathway. Therefore, miR-27b represented a potential biomarker for KD and may serve as a promising therapeutic target for KD treatment

Melatonin Ameliorates Coxsackievirus B3-Induced Myocarditis by Regulating Apoptosis and Autophagy

Current therapeutics options for viral myocarditis are unsatisfactory. Melatonin (MLT), a hormone secreted by the pineal gland and other organs, has protective effects on ischemic heart injury. However, the potential therapeutic effect of MLT on viral myocarditis is unknown. In this study, we investigated the protective effect of MLT on viral myocarditis in a mouse model of myocarditis infected with coxsackievirus B3 (CVB3) and explored the probable mechanisms. Mice with CVB3-induced myocarditis displayed inflammatory cell infiltration and interstitial edema. MLT treatment significantly ameliorated the myocardial injuries. In addition, the rate of autophagy changed, although apoptosis was inhibited in mouse hearts following treatment with MLT. These results suggest that MLT has a strong therapeutic effect on acute viral myocarditis, which is associated with changes in autophagy and apoptosis in the heart. Thus, MLT could be a promising novel therapeutic approach against viral myocarditis

Management of granulomatous lobular mastitis: an international multidisciplinary consensus (2021 edition)

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.Improving the Ability of Diagnosis and Treatment of Difficult Disease

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Search for hidden-charm tetraquark with strangeness in e+e−→K+Ds∗−D∗0+c.c.e^{+}e^{-}\rightarrow K^+ D_{s}^{*-} D^{*0}+c.c.

We report a search for a heavier partner of the recently observed $Z_{cs}(3985)^{-}$ state, denoted as $Z_{cs}^{\prime -}$, in the process $e^{+} e^{-}\rightarrow K^{+}D_{s}^{*-}D^{* 0}+c.c.$, based on $e^+e^-$ collision data collected at the center-of-mass energies of $\sqrt{s}=4.661$, 4.682 and 4.699 GeV with the BESIII detector. The $Z_{cs}^{\prime -}$ is of interest as it is expected to be a candidate for a hidden-charm and open-strange tetraquark. A partial-reconstruction technique is used to isolate $K^+$ recoil-mass spectra, which are probed for a potential contribution from $Z_{cs}^{\prime -}\to D_{s}^{*-}D^{* 0}$ ($c.c.$). We find an excess of $Z_{cs}^{\prime -}\rightarrow D_{s}^{*-}D^{*0}$ ($c.c.$) candidates with a significance of $2.9\sigma$, after considering systematic uncertainties, at a mass of $(4123.5 \pm 0.7_{\mathrm{stat.}} \pm 1.1_{\mathrm{syst.}}) \mathrm{MeV}/c^{2}$. As the data set is limited in size, the upper limits are evaluated at the 90% confidence level on the product of the Born cross section and the branching fraction of $Z_{cs}^{\prime-}\rightarrow D_{s}^{*-}D^{* 0}$, $\sigma^{\rm Born}\cdot\mathcal{B}$ at the three energy points, under different assumptions of the $Z_{cs}^{\prime -}$ mass from 4.120 to 4.140 MeV and of the width from 10 to 50 MeV. Under various mass and width assumptions, the upper limits of $\sigma^{\rm Born}\cdot\mathcal{B}$ are found to lie in the range of $2\sim6$, $3\sim7$ and $3\sim6$ pb at $\sqrt{s}=4.661$, 4.682 and 4.699 GeV, respectively. The larger data samples that will be collected in the coming years will allow a clearer picture to emerge concerning the existence and nature of the $Z_{cs}^{\prime -}$ state.Comment: 17 pages, 7 figure

Precise Measurements of Decay Parameters and CPCP Asymmetry with Entangled Λ−Λˉ\Lambda-\bar{\Lambda} Pairs

Based on 10 billion $J/\psi$ events collected at the BESIII experiment, a search for $CP$ violation in $\Lambda$ decay is performed in the difference between $CP$-odd decay parameters $\alpha_{-}$ for $\Lambda \rightarrow p\pi^-$ and $\alpha_{+}$ for $\bar\Lambda \rightarrow \bar{p}\pi^+$ by using the process $e^+e^- \to J/\psi \rightarrow \Lambda \bar\Lambda$. With a five-dimensional fit to the full angular distributions of the daughter baryon, the most precise values for the decay parameters are determined to be $\alpha_{-} = 0.7519 \pm 0.0036 \pm 0.0024$ and $\alpha_{+} = -0.7559 \pm 0.0036 \pm 0.0030$, respectively. The $\Lambda$ and $\bar{\Lambda}$ averaged value of the decay parameter is extracted to be $\alpha_{\rm{avg}} = 0.7542 \pm 0.0010 \pm 0.0024$ with unprecedented accuracy. The $CP$ asymmetry $A_{CP}=(\alpha_{-}+\alpha_{+})/(\alpha_{-}-\alpha_{+})$ is determined to be $-0.0025 \pm 0.0046 \pm 0.0012$, which is one of the most precise measurements in the baryon sector. The reported results for the decay parameter will play an important role in the studies of the polarizations and $CP$ violations for the strange, charmed and beauty baryons