Subxiphoid and subcostal thoracoscopic surgical approach for thymectomy.

BACKGROUND: The continuous evolvement of minimally invasive thymectomy over the last decades has potential advantages over trans-sternal thymectomy with similar oncologic outcomes of thymoma and complete remission for myasthenia gravis patients. A variety of different minimally invasive approaches have been described previously. The aim of this article is to present our subxiphoid and subcostal approaches in thymectomy for patients with myasthenia gravis and thymomas and to investigate the early surgical outcomes of these patients. METHODS: A retrospective analysis was performed of 95 patients who underwent thymectomy via a subxiphoid and subcostal approach for MG and/or thymoma at our department during the period of 2015 to 2017. The clinical characteristics and early surgical outcomes of these patients were reviewed and analyzed. RESULTS: Complete thymectomy and extended thymectomy was accomplished through the subxiphoid and subcostal approach in 93 of the 95 (97.9%) patients. Two patients (3.2%) required conversion to sternotomy for the invasion of a thymoma. The mean operative time was 109 min (range 70-170 min), with the mean estimated blood loss of 47 ml (range 20-350 ml). Postoperative complications included two cases of myasthenic crisis: one case of pleural effusion and one case of wound infection. In a mean follow-up of 31 months no patients showed recurrence of the tumor. In 41 MG patients followed up for 31 months, the improvement rate was 87.8% and the rate of complete remission was 29.3%. CONCLUSION: Subxiphoid and subcostal thoracoscopic thymectomy may be a safe and feasible approach for treating MG and anterior mediastinal tumors.

NCBP1 promotes the development of lung adenocarcinoma through up-regulation of CUL4B.

Lung cancer is the most frequent cancer type and is the leading cause of tumour-associated deaths worldwide. Nuclear cap-binding protein 1 (NCBP1) is necessary for capped RNA processing and intracellular localization. It has been reported that silencing of NCBP1 resulted in cell growth reduction in HeLa cells. Nevertheless, its clinical significance and underlying molecular mechanisms in non-small-cell lung cancer remain unclear. In this study, we found that NCBP1 was significantly overexpressed in lung cancer tissues and several lung cancer cell lines. Through knockdown and overexpression experiments, we showed that NCBP1 promoted lung cancer cell growth, wound healing ability, migration and epithelial-mesenchymal transition. Mechanistically, we found that cullin 4B (CUL4B) was a downstream target gene of NCBP1 in NSCLC. NCBP1 up-regulated CUL4B expression via interaction with nuclear cap-binding protein 3 (NCBP3). CUL4B silencing significantly reversed NCBP1-induced tumorigenesis in vitro. Based on these findings, we propose a model involving the NCBP1-NCBP3-CUL4B oncoprotein axis, providing novel insight into how CUL4B is activated and contributes to LUAD progression.

Surgical treatment of posterior mediastinal neurogenic tumors.

BACKGROUND: Posterior mediastinal neurogenic tumors are among the most frequent mediastinal masses in adults. These tumors may be dumbbell shaped, extending into the spinal canal, exclusively paraspinal or apical tumors extending in the cervical region. In this report, we present our experience in the surgical resection of these tumors and discuss the surgical strategies for such tumors. METHODS: A retrospective analysis was performed of 121 patients who underwent surgery for posterior mediastinal neurogenic tumors at our department during the period 2009 to 2016. Seventy-four tumors were excised via video-assisted thoracic surgery (VATS). Other approaches included thoracotomy, supraclavicular incision, supraclavicular incision plus thoracotomy/VATS, and a posterior approach with laminectomy combined with thoracotomy/VATS. RESULTS: Tumors were resected completely in 119 cases and partially in two. The majority of the tumors were benign nerve sheath tumors. No recurrence developed during postoperative median follow-up period of 31 months. CONCLUSION: Most posterior neurogenic tumors can be resected via VATS. Thoracotomy is the appropriate surgical approach for large tumors. A supraclavicular approach is recommended for tumors extending in the cervical region, and this can be combined with VATS or thoracotomy in case of larger masses. A posterior approach could be used for patients with dumbbell tumors.

Function and regulation of LAG3 on CD4+CD25- T cells in non-small cell lung cancer.

LAG3 is a surface molecule found on a subset of immune cells. The precise function of LAG3 appears to be context-dependent. In this study, we investigated the effect of LAG3 on CD4+CD25- T cells from non-small cell lung cancer (NSCLC) patients. We found that in the peripheral blood mononuclear cells of NSCLC patients, LAG3 was significantly increased in CD4+ T cells directly ex vivo and primarily in the CD4+CD25- fraction, which was regulated by prolonged TCR stimulation and the presence of IL-27. TCR stimulation also increased CD25 expression, but not Foxp3 expression, in LAG3-expressing CD4+CD25- cells Compared to LAG3-nonexpressing CD4+CD25- cells, LAG3-expressing CD4+CD25- cells presented significantly higher levels of PD1 and TIM3, two inhibitory receptors best described in exhausted CD8+ T effector cells. LAG3-expressing CD4+CD25- cells also presented impaired proliferation compared with LAG3-nonexpressing CD4+CD25- cells but could be partially rescued by inhibiting both PD1 and TIM3. Interestingly, CD8+ T cells co-incubated with LAG3-expressing CD4+CD25- cells at equal cell numbers demonstrated significantly lower proliferation than CD8+ T cells incubated alone. Co-culture with CD8+ T cell and LAG3-expressing CD4+CD25- T cell also upregulated soluble IL-10 level in the supernatant, of which the concentration was positively correlated with the number of LAG3-expressing CD4+CD25- T cells. In addition, we found that LAG3-expressing CD4+CD25- T cells infiltrated the resected tumors and were present at higher frequencies of in metastases than in primary tumors. Taken together, these data suggest that LAG3-expressing CD4+CD25- T cells represent another regulatory immune cell type with potential to interfere with anti-tumor immunity.

Ablation of Lgr4 enhances energy adaptation in skeletal muscle via activation of Ampk/Sirt1/Pgc1α pathway.

Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is a newfound obese-associated gene. Previous study reveals that heterozygous mutation of Lgr4 correlates with decreased body weight in human. In our recent study, we demonstrate that Lgr4 ablation promotes browning of white adipose tissue and improves whole-body metabolic status. However little is known about its role in other metabolic tissues. Herein, we show that Lgr4 homozygous mutant (Lgr4(m/m)) mice show increased respiratory exchange ratio (RER, closer to 1.0) than wild-type mice at 12:00 AM (food-intake time for mice) while decreased RER (closer to 0.75) at 12:00 PM (fasting for mice), indicating a glucose-prone versus fatty acid-prone metabolic pattern, respectively. Furthermore, Lgr4 ablation increases lipid oxidation-related gene expression while suppresses glucose transporter type 4 (Glut4) levels in skeletal muscle under fasting condition. These data suggest that Lgr4 ablation enhances the flexibility of skeletal muscle to switch energy provider from glucose to fatty acid in response to glucose depletion. We further reveal the activation of Ampk/Sirt1/Pgc1α pathway during this adaptive fuel shift due to Lgr4 ablation. This study suggests that Lgr4 might serve as an adaptive regulator between glucose and lipid metabolism in skeletal muscle and reveals a potentially new regulator for a well-established adaptive network.

Regulatory role of the miR-142-3p/CDC25C axis in modulating autophagy in non-small cell lung cancer.

Background: With its diverse genetic foundation and heterogeneous nature, non-small cell lung cancer (NSCLC) needs a better comprehension of prognostic evaluation and efficient treatment targeting. Methods: Bioinformatics analysis was performed of The Cancer Genome Atlas (TCGA)-NSCLC and GSE68571 dataset. Overlapping differentially expressed genes (DEGs) were used for functional enrichment analysis and constructing the protein-protein interaction (PPI) network. In addition, key prognostic genes were identified through prognostic risk models, and their expression levels were verified. The phenotypic effects of cell division cycle 25C (CDC25C) regulation on NSCLC cell lines were assessed by in vitro experiments using various techniques such as flow cytometry, Transwell, and colony formation. Protein levels related to autophagy and apoptosis were assessed, specifically examining the impact of autophagy inhibition [3-methyladenine (3-MA)] and the miR-142-3p/CDC25C axis on this regulatory system. Results: CDC25C was identified as a key prognostic marker in NSCLC, showing high expression in tumor samples. In vitro experiments showed that CDC25C knockdown markedly reduced the capacity of cells to proliferate, migrate, invade, trigger apoptosis, and initiate cell cycle arrest. CDC25C and miR-142-3p displayed a reciprocal regulatory relationship. CDC25C reversed the inhibitory impacts of miR-142-3p on NSCLC cell cycle proliferation and progression. The synergy of miR-142-3p inhibition, CDC25C silencing, and 3-MA treatment was shown to regulate NSCLC cell processes including proliferation, apoptosis, and autophagy. Conclusions: MiR-142-3p emerged as a key player in governing autophagy and apoptosis by directly targeting CDC25C expression. This emphasizes the pivotal role of the miR-142-3p/CDC25C axis as a critical regulatory pathway in NSCLC.

A new immune signature for survival prediction and immune checkpoint molecules in non-small cell lung cancer.

Background: Immune checkpoint blockade (ICB) therapy has brought remarkable clinical benefits to patients with advanced non-small cell lung carcinoma (NSCLC). However, the prognosis remains largely variable. Methods: The profiles of immune-related genes for patients with NSCLC were extracted from TCGA database, ImmPort dataset, and IMGT/GENE-DB database. Coexpression modules were constructed using WGCNA and 4 modules were identified. The hub genes of the module with the highest correlations with tumor samples were identified. Then integrative bioinformatics analyses were performed to unveil the hub genes participating in tumor progression and cancer-associated immunology of NSCLC. Cox regression and Lasso regression analyses were conducted to screen prognostic signature and to develop a risk model. Results: Functional analysis showed that immune-related hub genes were involved in the migration, activation, response, and cytokine-cytokine receptor interaction of immune cells. Most of the hub genes had a high frequency of gene amplifications. MASP1 and SEMA5A presented the highest mutation rate. The ratio of M2 macrophages and naïve B cells revealed a strong negative association while the ratio of CD8 T cells and activated CD4 memory T cells showed a strong positive association. Resting mast cells predicted superior overall survival. Interactions including protein-protein, lncRNA and transcription factor interactions were analyzed and 9 genes were selected by LASSO regression analysis to construct and verify a prognostic signature. Unsupervised hub genes clustering resulted in 2 distinct NSCLC subgroups. The TIDE score and the drug sensitivity of gemcitabine, cisplatin, docetaxel, erlotinib and paclitaxel were significantly different between the 2 immune-related hub gene subgroups. Conclusions: These findings suggested that our immune-related genes can provide clinical guidance for the diagnosis and prognosis of different immunophenotypes and facilitate the management of immunotherapy in NSCLC.

Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-κB pathway.

Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration of SVS for 1month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-α, IL6, IL10, IL1ß, KC, MIP-1α, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-κB) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-κB pathway.

Thoracoscopic Anatomic Left Lower Lobe S6b Subsegmentectomy.

Although thoracoscopic lung segmentectomy has made significant achievements, there is little known about how to perform subsegmentectomy, which can also acquire a safe margin for curability but with more pulmonary volume reserved. This report presents the surgical procedure for subsegmental anatomic resection of left lower lobe subsegment 6b guided by the simulation of bronchovascular branching through the use of 3-dimensional computed tomographic bronchography and angiography.

GREM2 is associated with human central obesity and inhibits visceral preadipocyte browning.

BACKGROUND: Some circulating proteins are linked to central adiposity. Gremlin 2 (GREM2) functions as a secreted factor involved in osteogenesis and adipogenesis. Here, we investigated the association of blood GREM2 levels and central adiposity, and the biological roles of GREM2 in the browning program of visceral preadipocytes. METHODS: Three independent cohorts were applied to detect circulating GREM2 levels. Recombinant Grem2 protein, Grem2 overexpression and knockout mouse models, and preadipocyte-specific Bmpr2 knockout mice were used to assess the roles of Grem2 in the browning program. FINDINGS: We detected the presence of GREM2 protein in human serum using an ELISA approach. We revealed elevated GREM2 levels in severely obese subjects and validated this finding in a large-scale community population involving 10,327 subjects. Notably, serum GREM2 was positively associated with visceral fat volume, as quantified by 3D reconstruction methods. In mice, Grem2 was highly expressed in visceral fat and liver tissues, while surgical removal of visceral fat lowered circulating Grem2 levels. Visceral fat secreted more Grem2 in obese mice. Grem2-overexpressed mice exhibited a reduced browning ability of visceral fat, whereas Grem2 ablation enhanced the browning capacity and reduced visceral fat content. Mechanistically, Grem2 attenuated the browning program of visceral preadipocytes partially by antagonizing BMP4/7-SMAD1/5/8 signaling pathway. Further, genetic deletion of Bmpr2 in Pdgfrα+ preadipocytes abolished the antagonistic effect of Grem2. INTERPRETATION: These findings indicate that GREM2 might function as a circulating protein factor associated with human visceral adiposity, and Grem2 inhibits the browning capacity of visceral preadipocytes partially by BMP4/7-BMPR2 signaling pathway. FUNDING: The complete list of funders can be found in the Acknowledgement section.

Follicular cytotoxic CD8 T cells present high cytokine expression, and are more susceptible to Breg-mediated suppression in non-small cell lung cancer.

Tumor-infiltrating CD8 T cells are instrumental to antitumor immunity. In this study, we found that a subset of CXCR5-expressing CD8 T cells, termed follicular cytotoxic T (Tfc) cells, potently infiltrated the untreated tumors from non-small cell lung cancer (NSCLC) patients. On average, Tfc cells represented 14% of total tumor-infiltrating CD8 T cells and 6.6% of total tumor-infiltrating lymphocytes. Upon antigenic stimulation, Tfc cells presented significantly higher degranulation and stronger release of proinflammatory cytokines, including IFNg, IL2, and TNF, and the pleiotropic cytokine IL10 than non-Tfc cells. However, the expression of granzyme B and perforin was significantly lower in Tfc cells than in non-Tfc CD8 T cells. B regulatory (Breg) cells could significantly suppress proinflammatory cytokine production in both Tfc cells and non-Tfc CD8 T cells, but in Tfc cells, a lower concentration was required. Moreover, Breg cells could significantly elevate IL10 expression by Tfc cells but could not affect IL-10 expression by non-Tfc CD8 T cells. The neutralization of IL10 significantly reduced the extent of Breg-mediated regulation. Together, this study demonstrated that Tfc cells represented a significant proportion of tumor-infiltrating CD8 T cells in lung carcinoma. These Tfc cells were different from non-Tfc CD8 T cells in terms of cytokine expression and granzyme and perforin release and were more susceptible to Breg-mediated suppression in an IL-10-dependent manner.

CTNNB1/ß-catenin dysfunction contributes to adiposity by regulating the cross-talk of mature adipocytes and preadipocytes.

Overnutrition results in adiposity and chronic inflammation with expansion of white adipose tissue (WAT). However, genetic factors controlling fat mass and adiposity remain largely undetermined. We applied whole-exome sequencing in young obese subjects and identified rare gain-of-function mutations in CTNNB1/ß-catenin associated with increased obesity risk. Specific ablation of ß-catenin in mature adipocytes attenuated high-fat diet-induced obesity and reduced sWAT mass expansion with less proliferated Pdgfrα+ preadipocytes and less mature adipocytes. Mechanistically, ß-catenin regulated the transcription of serum amyloid A3 (Saa3), an adipocyte-derived chemokine, through ß-catenin-TCF (T-Cell-Specific Transcription Factor) complex in mature adipocytes, and Saa3 activated macrophages to secrete several factors, including Pdgf-aa, which further promoted the proliferation of preadipocytes, suggesting that ß-catenin/Saa3/macrophages may mediate mature adipocyte-preadipocyte cross-talk and fat expansion in sWAT. The identification of ß-catenin as a key regulator in fat expansion and human adiposity provides the basis for developing drugs targeting Wnt/ß-catenin pathway to combat obesity.

Expression of adiponectin receptors in mouse adrenal glands and the adrenocortical Y-1 cell line: adiponectin regulates steroidogenesis.

Obesity is frequently associated with malfunctions of the hypothalamus-pituitary-adrenal (HPA) axis and hyperaldosteronism, but the mechanism underlying this association remains unclear. Since the adrenal glands are embedded in adipose tissue, direct cross-talk between adipose tissue and the adrenal gland has been proposed. A previous study found that adiponectin receptor mRNA was expressed in human adrenal glands and aldosterone-producing adenoma (APA). However, the expression of adiponectin receptors in adrenal glands has not been confirmed at the protein level or in other species. Furthermore, it is unclear whether adiponectin receptors expressed in adrenal cells are functional. We found, for the first time, that adiponectin receptor (AdipoR1 and AdipoR2) mRNA and protein were expressed in mouse adrenal and adrenocortical Y-1 cells. However, adiponectin itself was not expressed in mouse adrenal or Y-1 cells. Furthermore, adiponectin acutely reduced basal levels of corticosterone and aldosterone secretion. ACTH-induced steroid secretion was also inhibited by adiponectin, and this was accompanied by a parallel change in the expression of the key genes involved in steroidogenesis. These findings indicate that adiponectin may take part in the modulation of steroidogenesis. Thus, adiponectin is likely to have physiological and/or pathophysiological significance as an endocrine regulator of adrenocortical function.

Different expression of mimecan as a marker for differential diagnosis between NSCLC and SCLC.

Mimecan mRNA was present in a limited number of mouse and human tissues, however, abundant mimecan mRNA was observed in the lung tissue. Therefore, we hypothesize that mimecan could serve as a biomarker for differentiating various histological types of lung cancers. In humans, the mimecan mRNA was found most abundant in ovary and less abundant in lung by using Northern blot analysis. Moreover, the mimecan was expressed strongly in the epithelial cells of the bronchial wall and weaker in the epithelial cells of the alveolar sacs by in situ hybridization and immunohistochemical analysis. Furthermore, the mimecan immunoreactivity was found in 103 (97.2%) of 106 non-small cell lung cancers (NSCLCs). Nevertheless, a large majority of small cell lung cancers (SCLCs) (50/56, 89.3%) showed negative immunoreactivity to mimecan polyclonal antibody. A significant difference of mimecan immunoreactivity was found between NSCLC and SCLC (P<0.00001). This is the first study showing that mimecan could serve as an excellent pathological biomarker to distinguish NSCLCs from SCLCs.

Surgical treatment of thoracic dumbbell tumors.

BACKGROUND: Thoracic dumbbell tumors are uncommon neoplasms arising from neurogenic elements of the posterior mediastinum. Surgical removal of these tumors with mediastinal, neuroforaminal and intraspinal components can often be challenging. The purpose of this study is to present our experience of single-stage removal of dumbbell tumors of the posterior mediastinum and to discuss the surgical strategies for such tumors. METHOD: A retrospective analysis was performed on 20 patients who underwent surgery for thoracic dumbbell tumors at our department during the period 2008 to 2016. Patient demographics, clinical features, operative reports, and pre- and postoperative images were reviewed. RESULT: Complete resection was achieved in all patients, with no postoperative mortality. Surgical excision was performed by laminectomy plus Video-assisted thoracoscopic surgery (VATS) in 10 patients and laminectomy plus thoracotomy in 4 patients. Two patients underwent VATS alone. Supraclavicular and transthoracic approach was performed in 2 patients. Another 2 patients were treated with supraclavicular approach alone. The mean operative time was 244 min (range 55-370 min), with mean estimated blood loss (EBL) of 360 ml (range 50-790 ml). Postoperative complications included one case of Horner's syndrome and one case of cerebrospinal fluid (CSF) leakage. At a mean follow-up of 29 months no patients showed recurrence of the tumor. CONCLUSION: Thoracic dumbbell tumors should be evaluated for intraspinal and neuroforaminal involvement. Single-stage posterior laminectomy plus VATS/thoracotomy, VATS/thoracotomy, and supraclavicular alone or combined with transthoracic approach all could be the preferred method for removing these dumbbell tumors with satisfactory outcomes.

Uterus globulin associated protein 1 (UGRP1) is a potential marker of progression of Graves' disease into hypothyroidism.

Approximately 20% of Graves' disease (GD) patients may result eventually in hypothyroidism in their natural course. Uterus globulin-associated protein 1 (UGRP1) was associated with GD in our previous study. Here we investigated the role of UGRP1 in the development of autoimmune thyroid disease (AITD). The results showed that UGRP1 was expressed in the thyrocytes of most Hashimoto's thyroiditis (HT) patients and a proportion of GD patients (293 HT and 198 GD). The pathologic features of UGRP1-positive thyrocytes resembled "Hürthle cells", and were surrounded by infiltrated leukocytes. The positivity rate of TPOAb in UGRP1-positive GD patients was much higher than that in -negative GD patients. Moreover, UGRP1 was co-expressed with Fas and HLA-DR in the thyrocytes of AITD patients. We also found IL-1ß but not Th1 or Th2 cytokines was able to upregulate the expression of UGRP1. Our findings indicated that UGRP1 may be a novel marker in thyrocytes to predict GD patients who develop hypothyroidism.

SRC1 Deficiency in Hypothalamic Arcuate Nucleus Increases Appetite and Body Weight.

Appetite is tightly controlled by neural and hormonal signals in animals. In general, steroid receptor co-activator 1 (SRC1) enhances steroid hormone signalling in energy balance and serves as a common co-activator of several steroid receptors, such as estrogen and glucocorticoid receptors. However, the key roles of SRC1 in energy balance remain largely unknown. We first confirmed that SRC1 is abundantly expressed in the hypothalamic arcuate nucleus (ARC), which is a critical centre for regulating feeding and energy balance; it is further co-localised with agouti-related protein and proopiomelanocortin neurons in the arcuate nucleus. Interestingly, local SRC1 expression changes with the transition between sufficiency and deficiency of food supply. To identify its direct role in appetite regulation, we repressed SRC1 expression in the hypothalamic ARC using lentivirus shRNA and found that SRC1 deficiency significantly promoted food intake and body weight gain, particularly in mice fed with a high-fat diet. We also found the activation of the AMP-activated protein kinase (AMPK) signalling pathway due to SRC1 deficiency. Thus, our results suggest that SRC1 in the ARC regulates appetite and body weight and that AMPK signalling is involved in this process. We believe that our study results have important implications for recognising the overlapping and integrating effects of several steroid hormones/receptors on accurate appetite regulation in future studies.

Clinical and Physiological Characterization of Elevated Plasma Glucagon-Like Peptide-1 Levels (Hyperglipemia) in a Dipeptidyl Peptidase IV Mutation Carrier.

The clinical application of dipeptidyl peptidase IV inhibitors (DPP4i) increasing active glucagon-like peptide-1 (AGLP-1) levels has been linked to pancreatitis, pancreatic tumors, and cardiovascular events. However, DPP4 mutations in humans or the long-term outcomes of high glucagon-like peptide-1 (GLP-1) level exposure have not been reported. A trio family with a proband showing an extremely high AGLP-1 level [defined here as hyperglipemia (hyper-glucagon-like peptide-1-emia)] were conducted whole-exome sequencing for potential pathogenic genetic defects. One novel DPP4 mutation, p.V486M (c.1456 G>A), was identified in the proband and showed damaged enzymatic activity of DPP4. Ex vivo functional study further showed that the serum from the proband markedly enhanced insulin production of primary rat islet cells. Furthermore, V486M variant and another eight DPP4 variants were identified in our in-home database and seven showed decreased enzymatic activities than wild-type DPP4, consistent with their alterations in their protein expression levels. Of note, the levels of glucose, lipids, and tumor markers (especially for CA15-3 and CA125), increased gradually in the proband during a 4-year follow-up period, although no abnormal physical symptoms or imaging results were observed at present. The other two old carriers in the pedigree both had type 2 diabetes, and one of them also had hyperlipidemia and myocarditis. We first identified hyperglipemia in a female subject harboring a loss-of-function DPP4 mutation with decreased DPP4 activity. Other sporadic DPP4 mutations verified the low-frequent occurrence of genetic inhibition of DPP4 activity, at least in the Chinese population studied. These results may provide new evidence for evaluation of the potential long-term effects of DPP4i and GLP-1 analogs.

C-reactive protein inhibits adiponectin gene expression and secretion in 3T3-L1 adipocytes.

C-reactive protein (CRP) is considered as one of the most sensitive markers of inflammation. The aim of the present study is to investigate the effects of CRP on the production of adiponectin in 3T3-L1 adipocytes. Northern and western blot analysis revealed that CRP treatment inhibited adiponectin mRNA expression and secretion in a dose- and time-dependent manner. Co-incubation of adipocytes with rosiglitazone and CRP decreased induction of adiponectin gene expression by rosiglitazone. However, luciferase reporter assays did not show that CRP affected the activity of approximately 2.1 kb adiponectin gene promoter, which was increased by rosiglitazone alone. Pharmacological inhibition of phosphatidylinositol (PI)-3 kinase by LY294002 partially reversed inhibition of adiponectin gene expression by CRP. These results collectively suggest that CRP suppresses adiponectin gene expression partially through the PI-3 kinase pathway, and that decreased production of adiponectin might represent a mechanism by which CRP regulates insulin sensitivity.

Transcervical resection of tracheal diverticulum.

Tracheal diverticulum is a clinical entity rarely reported in the literature. It can be congenital or acquired in origin, and most cases are asymptomatic, usually being discovered incidentally at CT scan. Therefore, treatment has not been widely reported. We present the case of a 30-year-old man with a 6-month history of repeatedly coughing and tracheobronchitis. CT scanning revealed the lesion. The patient underwent surgical resection of the tracheal diverticulum via a transcervical approach. Symptoms resolved after surgical treatment. Reexamination of the neck, chest, trachea, and lungs of the patient was performed with CT scan postoperative. © 2016 Wiley Periodicals, Inc. Head Neck 39: 187-190, 2017.