Metformin reduces the relapse rate of tuberculosis patients with diabetes mellitus: experiences from 3-year follow-up

The role of metformin (MET) on treatment effect of diabetic tuberculosis (TB) patients has not been studied in China. Thus, we conducted a retrospective study to investigate whether MET exhibited more efficacy in combination with anti-TB regimens for diabetic TB patients. All patients recruited came from five tuberculosis control and prevention institutes from July 2009 to July 2016 and completed 3 years of follow-up. We used chi-square test or Fisher’s exact test to evaluate the demographic characteristics and the frequency of clinical outcome between MET and non-MET group. A total of 58 TB patients with diabetes mellitus (DM), of these 27.6% (16/58) patients in the MET group and 72.4% (42/58) patients in the non-MET group, there was no significant difference in blood glucose level between MET and non-MET group (P?=?0.494), in addition, there was a higher proportion of treatment success (93.8 vs. 71.4%) and culture conversions by the end of 2 months (87.5 vs. 71.4%) among MET group; the relapse rates of patients in MET and non-MET group were 6.3% (1/16) and 35.7% (15/42) through a 3-year follow-up (P?=?0.045). Our data revealed that the use of MET as a combination drug with existing regimen improved the success rate of anti-TB treatment and reduced the relapse rate in TB patients with DM.     

Fiberoptic Bronchoscopy-Assisted Endotracheal Intubation in a Patient With a Large Tracheal Tumor

In the event of a high degree of airway obstruction, endotracheal intubation can be impossible and even dangerous, because it can cause complete airway obstruction, especially in patients with high tracheal lesions. However, a smaller endotracheal tube under the guidance of a bronchoscope can be insinuated past obstructive tumor in most noncircumferential cases. Here we report a case of successful fiberoptic bronchoscopy-assisted endotracheal intubation in a patient undergoing surgical resection of a large, high tracheal tumor causing severe tracheal stenosis. A 42-year-old Chinese man presented with dyspnea, intermittent irritable cough, and sleep deprivation for one and a half years. X-rays and computed tomography scan of the chest revealed an irregular pedunculated soft tissue mass within the tracheal lumen. The mass occupied over 90% of the lumen and caused severe tracheal stenosis. Endotracheal intubation was done to perform tracheal tumor resection under general anesthesia. After several failed conventional endotracheal intubation attempts, fiberoptic bronchoscopy-assisted intubation was successful. The patient received mechanical ventilation and then underwent tumor resection and a permanent tracheostomy. This case provides evidence of the usefulness of the fiberoptic bronchoscopy-assisted intubation technique in management of an anticipated difficult airway and suggests that tracheal intubation can be performed directly in patients with a tracheal tumor who can sleep in the supine position, even if they have occasional sleep deprivation and severe tracheal obstruction as revealed by imaging techniques.Key words: Tracheal tumors, Fiberoptic bronchoscopy, Difficulty intubation, Difficult airwayPrimary tumors of the trachea, mostly malignant, are rare, accounting for fewer than 0.1% of all tumors.¹ Surgical resection is the major option that has the potential to cure all patients with benign and low-grade tumors and most patients with malignant tracheal tumors.¹ Since surgical procedure often requires the airway to be shared by the anesthetist and the surgeon, patients who undergo tracheal tumor resection often present with a considerable degree of airway obstruction, which makes anesthetic management during surgical resection challenging.² In the event of a high degree of airway obstruction, endotracheal intubation can be impossible and even dangerous because it can cause complete airway obstruction, especially in patients with high tracheal lesions.³ However, tumors are not circumferential in most cases, and a small endotracheal tube can be insinuated past a highly obstructive tumor under the guidance of bronchoscopy.³ Here we report a case of successful fiberoptic bronchoscopy-assisted endotracheal intubation in a patient undergoing surgical resection of a large, high tracheal tumor causing severe tracheal stenosis.     

FGF23 Is Endogenously Phosphorylated in Bone Cells

Levels of serum phosphate are controlled by the peptide hormone FGF23, secreted from bone osteocytes. Elevated levels of circulating FGF23 are a key factor in several hypophosphatemic disorders and play a role in chronic kidney disease. Posttranslational processing of FGF23 includes multi‐site O‐glycosylation, which reduces intracellular cleavage by proprotein convertases. The FGF23 protein also contains four serine phosphorylation consensus sequences (S‐X‐D/E); in this work, we asked whether FGF23 is a substrate for secretory phosphorylation. Both HEK cells as well as IDG‐SW3 cells, an osteocyte model, incorporated radiolabeled orthophosphate into intact FGF23, as well as into the 14‐kDa carboxy‐terminal—but not the 17‐kDa N‐terminal—fragment. Sequential serine‐to‐alanine site‐directed mutagenesis of four kinase consensus sites showed that labeling occurred on three serines within the carboxy‐terminal fragment, Ser180 (adjacent to the cleavage site), Ser207, and Ser212. Liquid chromatography‐coupled mass spectroscopy indicated the presence of phosphate at Ser212 in recombinant R&D mouse FGF23^R179Q, confirming labeling results. A phosphopeptide‐specific antibody was raised against phospho‐Ser212 and exhibited immunoreactivity in osteocytes present in mouse long bone, providing further evidence that FGF23 is naturally phosphorylated in bone. Bone SIBLING proteins are serine‐phosphorylated by the ubiquitous Golgi secretory kinase FAM20C. Cotransfection of HEK and MC3T3 cells with FGF23 and active, but not inactive, FAM20C kinase increased the storage and release of FGF23 in radiolabeling experiments, indicating potential effects of phosphorylation on FGF23 stability. Collectively, these data point to an important role for phosphorylation of FGF23 in bone. © 2014 American Society for Bone and Mineral Research.     

TNF-alpha induces leukemic clonal evolution ex vivo in Fanconi anemia group C murine stem cells

The molecular pathogenesis of the myeloid leukemias that frequently occur in patients with Fanconi anemia (FA) is not well defined. Hematopoietic stem cells bearing inactivating mutations of FA complementation group C (FANCC) are genetically unstable and hypersensitive to apoptotic cytokine cues including IFN-gamma and TNF-alpha, but neoplastic stem cell clones that arise frequently in vivo are resistant to these cytokines. Reasoning that the combination of genetic instability and cytokine hypersensitivity might create an environment supporting the emergence of leukemic stem cells, we tested the leukemia-promoting effects of TNF-alpha in murine stem cells. TNF-alpha exposure initially profoundly inhibited the growth of Fancc-/- stem cells. However, longer-term exposure of these cells promoted the outgrowth of cytogenetically abnormal clones that, upon transplantation into congenic WT mice, led to acute myelogenous leukemia. TNF-alpha induced ROS-dependent genetic instability in Fancc-/- but not in WT cells. The leukemic clones were TNF-alpha resistant but retained their characteristic hypersensitivity to mitomycin C and exhibited high levels of chromosomal instability. Expression of FANCC cDNA in Fancc-/- stem cells protected them from TNF-alpha-induced clonal evolution. We conclude that TNF-alpha exposure creates an environment in which somatically mutated preleukemic stem cell clones are selected and from which unaltered TNF-alpha-hypersensitive Fancc-/- stem cells are purged.     

不同药物用于治疗重酒石酸长春瑞滨外渗后疗效的实验观察

[目的]探讨重酒石酸长春瑞滨(盖诺)外渗后理想的处理方法。[方法]制作盖诺外渗的动物坏死模型,分别采用临床上常用的3种处理方法进行动物实验,并进行肉眼及组织学观察。[结果]1∶5000呋喃西林加季德胜蛇药外涂对盖诺外渗的局部组织坏死疗效最佳,复方利多卡因次之,50%硫酸镁湿敷疗效甚微,对照组无效。[结论]1∶5000呋喃西林加季德胜蛇药外涂治疗盖诺外渗是一种行之有效的处理方法。     

High miR-196a and low miR-367 cooperatively correlate with unfavorable prognosis of high-grade glioma

Identification of microRNAs (miRNAs) could be beneficial for the diagnosis and prognosis of glioma. Therefore, we attempted to identify and develop specific miRNAs as prognostic and predictive markers for glioma patients. We compared the expression profiles of 365 miRNAs between 4 glioblastomas (GBMs, WHO grade IV) and 4 anaplastic astrocytomas (AAs, WHO grade III) using miRNA qPCR Array. MiR-196a (P = 0.004, fold change = 289.86) and miR-367 (P = 0.044, fold change = 0.03) were identified as the most up-regulated and down-regulated miRNAs in GBMs compared with AAs, respectively. We subsequently examined miR-196a and miR-367 expression levels in an independent series of 63 gliomas including 50 GBMs and 13 AAs, as well as 10 non-neoplastic brain tissues, and statistically analyzed the associations between miRNA expression and clinicopathological characteristics and survivals of these glioma patients. MiR-196a and miR-367 showed significant increased and decreased expression in high-grade gliomas relative to non-neoplastic brains, as well as in GBMs versus AAs, respectively. Additionally, high-miR-196a and low-miR-367 expression, alone or in combination, statistically correlated with aggressive clinicopathological features of gliomas. Furthermore, overall survivals of glioma patients with high-miR-196a, low-miR-367 and high-miR-196a/low-miR-367 expression tended to be shorter than the corresponding control groups (all P ≤ 0.001). Moreover, multivariate analysis indicated high-miR-196a/low-miR-367 as an independent prognostic indicator for glioma patients (P = 0.005, risk ratio = 1.8). Our results suggested that both high-miR-196a and low-miR-367 expression may be associated with aggressive progression and unfavorable clinical outcome in glioma patients. And combination of high-miR-196a and low-miR-367 expression may be a novel biomarker in identifying a poor prognosis group of high-grade glioma.     

Changes of mesenchymal stromal cells mobilization and bone turnover in an experimental bone fracture model in ovariectomized mice

Objective: The aim of this study was to characterize the mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) mobilization, and bone turnover in osteoporotic fracture healing in ovariectomized mice. Methods: In total, 112 female C57/BL mice were divided into two groups. The first group was sham-operated (SO), and the other group was ovariectomized (OVX). After three weeks, the right femora of the mice were fractured under anesthesia and internally fixed with steel pin. Peripheral blood and bone marrow were was collected for flow cytometry analysis, at 0 hours (h), 12 h, 24 h, 72 h and 168 h after fracture. MSCs and EPCs levels were assessed using cell surface antigens in different combinations (CD44+ CD34-CD45-, and CD34+ KDR+CD45-) by flow cytometry. At 0, 14, 28 and 42 days after fracture, sera were assayed for circulating levels of procollagen type I-N-terminal propeptide (P1NP) and C-terminal telopeptide of type I-collagen (CTX) by ELISA. Femurs were harvested at 2 weeks and 6 weeks after fracture for X-ray radiography, micro-computed tomography (micro-CT) and histology. Results: Our results showed that bone marrow and peripheral blood MSCs numbers of the OVX mice were significantly lower than the SO mice, at 12 h, 24 h and 72 h after fracture. In addition, circulating P1NP and CTX levels of the OVX mice were significantly higher than the SO mice, at 2 and 4 weeks. Conclusion: Results of the present study revealed disorders of bone marrow MSCs mobilization and bone turnover may partially account for the delay of osteoporotic fracture healing.