Anlotinib plus camrelizumab achieved long-term survival in a patient with metastatic esophageal neuroendocrine carcinoma.

BACKGROUND: Esophageal neuroendocrine carcinoma (NEC) is a rare cancer with an extremely poor prognosis. The average overall survival of patients with metastatic disease is only 1 year. The efficacy of anti-angiogenic agents combined with immune checkpoint inhibitors remains unknown. CASE PRESENTATION: A 64-year-old man, initially diagnosed with esophageal NEC, underwent neoadjuvant chemotherapy and esophagectomy. Although the patient remained disease-free for 11 months, eventually the tumor progressed and did not respond to three lines of combined therapy (etoposide plus carboplatin with local radiotherapy, albumin-bound paclitaxel plus durvalumab, and irinotecan plus nedaplatin). The patient then received anlotinib plus camrelizumab, and a dramatic regression was observed (confirmed by positron emission tomography-computed tomography). The patient has been disease-free for over 29 months and has survived for over 4 years since diagnosis. CONCLUSION: Combined therapy with anti-angiogenic agents and immune checkpoint inhibitors may be a promising strategy for esophageal NEC, although more evidence is warranted to validate its efficacy.

The influence of 10-year Nuss bar placement on bar removal: a case report.

BACKGROUND: The Nuss bar is commonly used for minimally invasive correction of pectus excavatum and is usually removed within 2-3 years. Here, we report a case of 10-year bar placement after the Nuss procedure accompanied by unique complications of thoracic malformation that have not been described before. The asymmetric pectus carinatum caused by bar displacement and significant rib periosteal hyperplasia is described for the first time. CASE PRESENTATION: A 23-year-old man was admitted to our hospital due to the main complaint of obvious chest discomfort when lifting heavy weights. The bar removal was seriously delayed due to his loss to follow-up. Chest asymmetry and distant heart sounds were found during a physical examination. A chest CT scan demonstrated that the right end of the lower bar originally fixed outside the ribs had shifted into the thoracic cavity, and the left costal cartilage was obviously protruding. Additionally, the displaced bars were separated from the sternum and tightly attached to the pericardium, resulting in abnormalities of the anterior mediastinum. These secondary thoracic deformities made the patient extremely prone to massive hemorrhage or multiple rib fractures when sliding the bars out. However, serious consequences were avoided due to reasonable adjustments to the usual bar removal procedures. CONCLUSION: This case demonstrates a specific type of bar displacement caused by prolonged placement of the bars and highlights the importance of rigorous follow-up of patients after the Nuss procedure.

Glycemic control and neonatal outcomes in women with gestational diabetes mellitus treated using glyburide, metformin, or insulin: a pairwise and network meta-analysis.

AIMS: We aimed to assess the comparative efficiency and safety of the use of glyburide, metformin, and insulin in gestational diabetes mellitus (GDM). METHODS: We searched for randomized controlled trials that compared glyburide, metformin, and insulin in GDM. Data regarding glycemic control and neonatal safety were collected and analyzed in pairwise and network meta-analyses. RESULTS: A total of 4533 individuals from 23 trials were included. Compared with glyburide, metformin reduced 2-h postprandial blood glucose (2HPG) to a greater extent (standard mean difference (SMD) 0.18; 95% credible interval (CI) 0.01, 0.34). There were significantly lower prevalence of neonatal hypoglycemia (risk difference (RD) - 0.07; 95%CI - 0.11, - 0.02) and preeclampsia (RD - 0.03; 95%CI - 0.06, 0) in the metformin group than in the insulin group. The metformin group had significantly lower birth weight (SMD - 0.17; 95%CI - 0.25, - 0.08) and maternal weight gain (SMD - 0.61; 95%CI - 0.86,- 0.35) compared with the insulin group. Network meta-analysis suggested that metformin had the highest probability of successfully controlling glycemia and preventing neonatal complications. CONCLUSIONS: The present meta-analysis suggests that metformin may be as effective as insulin for glycemic control and is the most promising drug for the prevention of neonatal and maternal complications.

Prognostic impact of micropapillary component in patients with node-negative subcentimeter lung adenocarcinoma: A Chinese cohort study.

BACKGROUND: In this study, we investigated the prognostic significance of a micropapillary (MP) component in patients with subcentimeter lung adenocarcinoma. METHODS: A total of 311 patients with subcentimeter lung adenocarcinoma who underwent surgical resection between January 2009 to December 2012 from seven medical centers were included. Recurrence-free survival (RFS) and overall survival (OS) were analyzed. RESULTS: The five-year RFS was 79.8% in 97 (97/311, 31%) cases of adenocarcinoma with a MP component and 93.5% in the 214 (214/311, 69%) cases without. In multivariate analysis, MP was an independent risk factor for worse RFS (hazard ratio [HR], 3.73; 95% confidence interval [CI]: 1.87-7.42; P < 0.001) and OS (HR, 5.84; 95% CI: 2.20-15.49; P < 0.001). There was no significant difference among wedge resection, segmentectomy and lobectomy on RFS (P = 0.256) and OS (P = 0.103) in patients without MP. Regarding patients with a MP component, lobectomy achieved equivalent prognosis than segmentectomy, and both were better than wedge resection (P = 0.001). CONCLUSIONS: A MP component still suggest a poor prognosis in subcentimeter lung adenocarcinoma. Patients with subcentimeter lung adenocarcinoma with a MP component of 5% or greater treated with wedge resection were at higher risk of recurrence than patients treated with anatomical resection.

miR-210 transferred by lung cancer cell-derived exosomes may act as proangiogenic factor in cancer-associated fibroblasts by modulating JAK2/STAT3 pathway.

It has been generally believed that cancer-associated fibroblasts (CAFs) have the ability to increase the process of tumor angiogenesis. However, the potential mechanisms by which cancer-derived exosomes in lung cancer (LC) remains to be investigated. LC-derived exosomes were administrated to NIH/3T3 cells. A variety of experiments were conducted to investigate the proangiogenic factors of CAFs, including Western blot, RT-PCR, colony formation assay, tube formation assay, Matrigel plug assay et al. In addition, the impact of JAK2/STAT3 signaling pathway were also explored. The role of hsa-miR-210 was identified with microarray profiling and validated in vitro and in vivo assays. The target of miR-210 was screened by RNA pull down, RNA-sequencing and then verified. It was shown that LC-derived exosomes could induce cell reprogramming, thus promoting the fibroblasts transferring into CAFs. In addition, the exosomes with overexpressed miR-210 could increase the level of angiogenesis and vice versa, which suggested the miR-210 secreted by the LC-derived exosomes may initiate the CAF proangiogenic switch. According to our analysis, the miR-210 had the ability of elevating the expression of some proangiogenic factors such as MMP9, FGF2 and vascular endothelial growth factor (VEGF) a (VEGFa) by activating the JAK2/STAT3 signaling pathway, ten-eleven translocation 2 (TET2) was identified as the target of miR-210 in CAFs which has been involved in proangiogenic switch. miR-210 was overexpressed in serum exosomes of untreated non-small cell LC (NSCLC) patients. We concluded that the promotion effect of exosomal miR-210 on proangiogenic switch of CAFs may be explained by the modulation of JAK2/STAT3 signaling pathway and TET2 in recipient fibroblasts.

circGFRA1 Enhances NSCLC Progression by Sponging miR-188-3p.

BACKGROUND: Lung cancer continues to be one of the most dangerous tumors around the world. It is an urgency to explore the molecular mechanism of non-small cell lung cancer (NSCLC) progression for developing novel therapeutic approaches. Circular RNA (circRNA) is a novel type of non-coding RNA with a stable closed loop structure. Abnormally expressed circRNAs have been found in many kinds of cancer including NSCLC. METHODS AND RESULTS: The expression of circGFRA1 and miR-188-3p was detected in NSCLC tissues by RT-qPCR and it was found that circGFRA1 was highly expressed and miR-183-3p was lowly expressed in NSCLC tissues. In NSCLC cell lines, we confirmed that circGFRA1 acted as an miR-188-3p sponge using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) analysis. Overexpression of cirGFRA1 enhanced NSCLC progression while miR-188-3p overexpression inhibited it by CCK8 and colony formation analysis. In vivo tumor xenograft model, circGFRA1 and miR-188-3p synergistically regulated the proliferation of NSCLC tumors. Mechanistic study indicated that circGFRA1 and miR-188-3p regulated the proliferation of NSCLC cells at least through PI3K/AKT signaling pathway. CONCLUSION: Our study elaborated a novel circGFRA-miR-188-3p-PI3K/AKT regulatory pathway, providing a potential diagnostic biomarker and therapeutic target for NSCLC.

Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue.

Brown adipose tissue (BAT) is an exclusive tissue of nonshivering thermogenesis. It is fueled by lipids and glucose and involved in energy and metabolic homeostasis. Intrauterine exposure to hyperglycemia during gestational diabetes mellitus may result in abnormal fetal development and metabolic phenotypes in adulthood. However, whether intrauterine hyperglycemia influences the development of BAT is unknown. In this study, mouse embryos were exposed to the intrauterine hyperglycemia environment by injecting streptozocin into pregnant mice at 1 d post coitum (dpc). The structure of BAT was examined by hematoxylin and eosin staining and immunohistochemical analysis. The glucose uptake in BAT was measured in vivo by [18F]-fluoro-2-deoxyglucose-micro-positron emission tomography. The gene expression in BAT was determined by real-time PCR, and the 5'-C-phosphate-G-3' site-specific methylation was quantitatively analyzed. Intrauterine hyperglycemia exposure resulted in the impaired structure of BAT and decreased glucose uptake function in BAT in adulthood. The expressions of the genes involved in thermogenesis and mitochondrial respiratory chain in BAT, such as Ucp1, Cox5b, and Elovl3, were down-regulated by intrauterine hyperglycemia exposure at 18.5 dpc and at 16 wk of age. Furthermore, higher methylation levels of Ucp1, Cox5b, and Elovl3 were found in offspring of mothers with streptozotocin-induced diabetes. Our results provide the evidence for enduring inhibitory effects of intrauterine hyperglycemia on BAT development in offspring. Intrauterine hyperglycemia is associated with increased DNA methylation of the BAT specific genes in offspring, which support an epigenetic involvement.-Yu, D.-Q., Lv, P.-P., Yan, Y.-S., Xu, G.-X., Sadhukhan, A., Dong, S., Shen, Y., Ren, J., Zhang, X.-Y., Feng, C., Huang, Y.-T., Tian, S., Zhou, Y., Cai, Y.-T., Ming, Z.-H., Ding, G.-L., Zhu, H., Sheng, J.-Z., Jin, M., Huang, H.-F. Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue.

CXXC finger protein 1 is critical for T-cell intrathymic development through regulating H3K4 trimethylation.

T-cell development in the thymus is largely controlled by an epigenetic program, involving in both DNA methylation and histone modifications. Previous studies have identified Cxxc1 as a regulator of both cytosine methylation and histone 3 lysine 4 trimethylation (H3K4me3). However, it is unknown whether Cxxc1 plays a role in thymocyte development. Here we show that T-cell development in the thymus is severely impaired in Cxxc1-deficient mice. Furthermore, we identify genome-wide Cxxc1-binding sites and H3K4me3 modification sites in wild-type and Cxxc1-deficient thymocytes. Our results demonstrate that Cxxc1 directly controls the expression of key genes important for thymocyte survival such as RORγt and for T-cell receptor signalling including Zap70 and CD8, through maintaining the appropriate H3K4me3 on their promoters. Importantly, we show that RORγt, a direct target of Cxxc1, can rescue the survival defects in Cxxc1-deficient thymocytes. Our data strongly support a critical role of Cxxc1 in thymocyte development.

[An improved back-projection algorithm of dynamic electrical impedance tomography].

In this paper, an improved back-projection algorithm of dynamic electrical impedance tomography (EIT) was described. The improved back-projection algorithm modified the computing method of back-projection matrix B. Dynamic reconstruction image was obtained by the improved algorithm, and it was compared to the image obtained by the traditional method of equi-potential back-projection. The results showed that the improved algorithm of equi-potential back-projection could locate the object's position in the field with higher precision, and its speed was very fast. It also could improve the resolution of the reconstructed image in some extent.