Background
Central neck dissection and total thyroidectomy are standard treatments for patients with papillary thyroid carcinoma (PTC) with clinically involved central nodes. However, prophylactic ...central neck dissection (pCND) in patients with clinically uninvolved cN0 has been beneficial in some studies but ineffective in others. We conducted a meta-analysis to evaluate the efficacy and safety of pCND in patients with central neck lymph nodes cN0 PTC.
Methods
The PubMed, EMBASE, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry were electronically searched for studies published until September 2017. The meta-analysis was conducted to calculate the pooled effect size by using random-effects model. Treatment efficacies were measured by determining locoregional recurrence (LRR). Secondary outcomes included transient recurrent laryngeal nerve (RLN) injury, permanent RLN injury, transient hypocalcemia, and permanent hypocalcemia.
Results
Twenty-three retrospective and prospective cohort studies involving 18,376 patients were reviewed. Patients who underwent pCND had significantly lower LRR (odds ratio OR 0.65; 95% confidence interval CI 0.48–0.88) but significantly higher incidence rates of transient RLN injury (OR 2.03; 95% CI 1.32–3.13), transient hypocalcemia (OR 2.23; 95% CI 1.84–2.70), and permanent hypocalcemia (OR 2.22; 95% CI 1.58–3.13) than that of no pCND group.
Conclusion
Compared with no pCND, pCND significantly reduces LRR but is accompanied by numerous adverse effects. The clinical decision should be made after the shared decision-making process of clinicians and patients.
Background
Respiratory syncytial virus (RSV) infection is epidemiologically linked to asthma. During RSV infection, IL‐33 is elevated and promotes immune cell activation, leading to the development ...of asthma. However, which immune cells are responsible for triggering airway hyperreactivity (AHR), inflammation and eosinophilia remained to be clarified. We aimed to elucidate the individual roles of IL‐33‐activated innate immune cells, including ILC2s and ST2+ myeloid cells, in RSV infection‐triggered pathophysiology.
Methods
The role of IL‐33/ILC2 axis in RSV‐induced AHR inflammation and eosinophilia were evaluated in the IL‐33‐deficient and YetCre‐13 Rosa‐DTA mice. Myeloid‐specific, IL‐33‐deficient or ST2‐deficient mice were employed to examine the role of IL‐33 and ST2 signaling in myeloid cells.
Results
We found that IL‐33‐activated ILC2s were crucial for the development of AHR and airway inflammation, during RSV infection. ILC2‐derived IL‐13 was sufficient for RSV‐driven AHR, since reconstitution of wild‐type ILC2 rescued RSV‐driven AHR in IL‐13‐deficient mice. Meanwhile, myeloid cell‐derived IL‐33 was required for airway inflammation, ST2+ myeloid cells contributed to exacerbation of airway inflammation, suggesting the importance of IL‐33 signaling in these cells. Local and peripheral eosinophilia is linked to both ILC2 and myeloid IL‐33 signaling.
Conclusions
This study highlights the importance of IL‐33‐activated ILC2s in mediating RSV‐triggered AHR and eosinophilia. In addition, IL‐33 signaling in myeloid cells is crucial for airway inflammation.
Respiratory syncytial virus induces ILC2 to produce IL‐5 and IL‐13 through IL‐33, which is crucial for the development of airway hyperreactivity and airway inflammation. Myeloid cell‐derived IL‐33 and suppression of tumorigenicity 2‐positive myeloid cells contribute to cytokine production and cellular inflammation in airway. Both ILC2 and myeloid cell IL‐33 signaling contribute to local and peripheral eosinophilia.
The rating result reflects not only the performance of the candidate but some extent of the examiner’s preference. Examiner bias could be objective, which means it can’t be changed by the examiner ...like gender, age, race, educational level, or professional experience. No study about examiner bias was performed in the dental education realm, especially in the orthodontic field. Therefore, this study aimed to figure out possible influencing factors in examiners from examples of the Taiwan Board of Orthodontist examination.
The examiner groups comprised 29 males and 21 females selected from the certificated Taiwan Board of Orthodontists. Every examiner would receive a series of lectures about rating standards before the exam. The score data were collected from 2009 to 2019.
As for the univariate regression model of the Taiwan Board of Orthodontist examination, the experienced examiner with a certification of more than 15 years tends to rate more leniently, but female examiners tend to rate harsher. The scores would increase with the examiner’s age in both the univariate regression model of self-prepared and assigned cases.
As for the multivariate model of self-prepared exams, the elder and the examiner who work in private practice clinics tend to rate more leniently. As for the multivariate model of the assigned case exam, the score would be only affected by age. However, further studies are necessary to determine the direct relation among these factors.
The activation of hepatic stellate cells (HSCs) is a significant phenomenon during the pathogenesis of liver disorders, including liver cirrhosis and fibrosis. Here, we identified that the extract ...from a gorgonian coral
sp. (Pin) induced apoptosis of HSC-T6 cells. Pin inhibited the viability of HSC-T6 cells and increased their subG1 population, DNA fragmentation, caspase-3 activation, and reactive oxygen species (ROS) production in a concentration-dependent manner. The Pin-induced ROS generation and apoptotic effects were significantly reversed by a thiol antioxidant,
-acetylcysteine (NAC). Additionally, Pin induced ERK/JNK phosphorylation and pharmacological inhibition of ERK/JNK rescued the Pin-induced cell death. Pin-activated ERK/JNK were significantly reduced after the administration of NAC; however, the inhibition of ERK/JNK failed to change the Pin-induced ROS production. Similarly, pinnigorgiol A, a pure compound isolated from Pin, elicited ROS production and apoptosis in HSC-T6 cells. The pinnigorgiol A-induced apoptosis was retrained by NAC. Together, it appears that Pin leads to apoptosis in HSC-T6 cells through ROS-mediated ERK/JNK signaling and caspase-3 activation. Pinnigorgiol A serves as a bioactive compound of Pin and may exhibit therapeutic potential by clearance of HSCs.
The major cause of heart failure is myocardium death consequent to detrimental cardiac remodeling and fibrosis following myocardial infarction. The cardiac protective cytokine interleukin (IL)-33, ...which signals by ST2 receptor binding, is associated with group 2 innate lymphoid cell (ILC2) activation and regulates tissue homeostasis and repair following tissue injury in various tissues. However, the distribution and role of IL-33-responsive ILC2s in cardiac fibrosis remain unclear. In this study, we elucidated the roles of IL-33-responsive cardiac-resident ILC2s and IL-33-mediated immunomodulatory functions in cardiac fibrosis.
We examined the distribution of cardiac ILC2s by using flow cytometry. The roles of IL-33-mediated ILC2 expansion in cardiac fibrosis was evaluated in the mouse model of catecholamine-induced cardiac fibrosis. ILC-deficient
mice were implemented to determine the contribution of endogenous ILC in the progression of cardiac fibrosis. Histopathological assessments, speckle tracking echocardiography, and transcriptome profile analysis were performed to determine the effects of IL-33-mediated cardiac protective functions.
We identified the resident cardiac ILC2s, which share similar cell surface marker and transcriptional factor expression characteristics as peripheral blood and lung tissue ILC2s. IL-33 treatment induced ILC2 expansion via ST2.
, ILC-deficient
mice developed exacerbated cardiac fibrosis following catecholamine-induced stress cardiac injury. IL-33 treatment expanded cardiac ILC2s and revealed protective effects against cardiac tissue damage with reduced cardiomyocyte death, immune cell infiltration, tissue fibrosis, and improved myocardial function. Transcriptome analysis revealed that IL-33 attenuated extracellular matrix synthesis- and fibroblast activation-associated gene expressions.
-knockout or epidermal growth factor receptor (EGFR) inhibition abolished IL-33-mediated cardiac protective function, confirming IL-13 and EGFR signaling as crucial for IL-33-mediated cardioprotective responses. Moreover, ILC2-produced BMP-7 served as a novel anti-fibrotic factor to inhibit TGF-β1-induced cardiac fibroblast activation.
Our findings indicate the presence of IL-33-responsive ILC2s in cardiac tissue and that IL-33-mediated ILC2 expansion affords optimal cardioprotective function via ILC2-derived factors. IL-33-mediated immunomodulation is thus a promising strategy to promote tissue repair and alleviate cardiac fibrosis following acute cardiac injury.
Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in innate and adaptive immune responses. IL-33 triggers pleiotropic immune functions in multiple types of immune cells, ...which express the IL-33 receptor, ST2. Recent studies have revealed the potential applications of IL-33 for treating acute kidney injury in preclinical animal models. However, IL-33 and IL-33-responding immune cells are reported to exhibit both detrimental and beneficial roles. The IL-33-mediated immunomodulatory functions have been investigated using loss-of-function approaches, such as IL33-deficient mice, IL-33 antagonists, or administration of exogenous IL-33 recombinant protein. This review will discuss the key findings on IL-33-mediated activation of kidney resident group 2 innate lymphoid cells (ILC2s) and summarize the current understanding of the differential functions of endogenous IL-33 and exogenous IL-33 and their potential implications in treating acute kidney injury.
Fissistigma oldhamii is widely used in traditional Chinese medicine to treat rheumatoid arthritis. Activation of neutrophils is a key feature of inflammatory diseases. Herein, the anti-inflammatory ...functions of isopedicin, a flavanone derived from
F. oldhamii, and its underlying mechanisms were investigated in human neutrophils. Isopedicin potently and concentration-dependently inhibited superoxide anion (O
2
−
) production in formyl-
l-methionyl-
l-leucyl-
l-phenylalanine (FMLP)-activated human neutrophils with an IC
50 value of 0.34
±
0.03 μM. Furthermore, isopedicin displayed no superoxide-scavenging ability, and it failed to alter subcellular NADPH oxidase activity. The inhibitory effect of isopedicin on O
2
−
production was reversed by protein kinase A (PKA) inhibitors. Moreover, isopedicin increased cAMP formation and PKA activity in FMLP-activated human neutrophils, which occurred through the inhibition of phosphodiesterase (PDE) activity but not an increase in adenylate cyclase function. In addition, isopedicin reduced FMLP-induced phosphorylation of extracellular regulated kinase and c-Jun N-terminal kinase, which was reversed by the PKA inhibitor. In contrast, isopedicin failed to alter FMLP-induced phosphorylation of p38 mitogen-activated protein kinase and calcium mobilization. In summary, these results demonstrate that inhibition of O
2
−
production in human neutrophils by isopedicin is associated with an elevation of cellular cAMP and activation of PKA through its inhibition of cAMP-specific PDE.
In this paper, we demonstrate the potential of liquid crystals (LCs) on the applications of small, simple, and tunable optical guided channels. Experimental results show that three operation modes of ...beam coupling can be achieved, depending on the feature of the electrically controllable refractive index, the incident position, and the specific design of electrodes. The dependence of the beam polarization on self-focusing and coupling effect are also discussed. The electrically controllable self-focusing and beam coupling are highly potential on integrated photonic circuits.
The monolayered intrarenal urothelium covers the renal papilla and ureteropelvic junction (UPJ). In response to increased renal pressure during obstruction or ischemic injuries, intrarenal urothelial ...cells begin to proliferate and form a multilayered urothelium. Little is known regarding the mechanism and pathophysiological role of urothelium hyperplasia during renal obstruction. In this study, we investigated the expression of interleukin (IL)-33, an IL-1 family cytokine, in kidneys with unilateral ureteral obstruction (UUO)-induced obstructive injury. IL-33 levels in hydronephrotic urine and serum were upregulated 2 days after UUO. The number of ST2-expressing immune cells was increased in the UUO kidney. We found that IL-33 was upregulated in vimentin-positive cells in the cortical and medullar layers and the UPJ stroma. Moreover, IL-33 expression was predominantly induced in multilayered keratin 5-positive urothelial cells in the UPJ. IL-33 was not detected in terminally differentiated superficial umbrella cells expressing uroplakin 3a. In vivo, we confirmed that deficiency of IL33 or its receptor ST2 attenuated UUO-induced hyperplasia of the UPJ urothelium. Deficiency of IL33 attenuated the expression of UUO-induced type 2 inflammatory cytokines and upregulated uroplakins and urothelial differentiation signaling in UPJ tissues. Our results collectively suggest that the IL-33/ST2 axis mediates the activation of innate immune responses and contributes to urothelial hyperplasia by regulating urothelial differentiation in obstructive kidney injury.
Indigo naturalis is used by traditional Chinese medicine to treat various inflammatory diseases.
Topical indigo naturalis ointment showed efficacy in treating psoriasis in our previous clinical ...studies. In this study, we investigated the anti-inflammatory effects of the extract of indigo naturalis (QD) and its main components indirubin, indigo, and tryptanthrin in human neutrophils.
Superoxide anion (O
2
−) generation and elastase release were measured by spectrophotometry. Some important signals including mitogen-activated protein kinase (MAPK), cAMP, and calcium were studied by Western blot analysis, an enzyme immunoassay, and spectrofluorometry.
QD significantly inhibited O
2
− generation and elastase release in formyl-
l-methionyl-
l-leucyl-
l-phenylalanine (FMLP)-activated human neutrophils in a concentration-dependent fashion, while neither indirubin, indigo, nor tryptanthrin produced a comparable result. QD attenuated the FMLP-induced phosphorylation of extracellular regulated kinase, p38 MAPK, and
c-
Jun N-terminal kinase. Furthermore, QD inhibited calcium mobilization caused by FMLP. However, QD did not affect cellular cAMP levels. On the other hand, neither indirubin, indigo, nor tryptanthrin produced similar changes in human neutrophils.
Taken collectively, these findings indicate that QD, but not indirubin, indigo, or tryptanthrin, inhibited O
2
− generation and elastase release in FMLP-induced human neutrophils, which was at least partially mediated by the inhibition of MAPK activation and regulation of calcium mobilization.
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