KCHIP1基因一种新剪切型的发现

为寻求KCHIP1基因与乳腺癌之间的关系,对收集到的12例乳腺癌组织、12例正常乳腺组织样本进行KCHIP1基因cDNA扩增、突变检测。经测序证实,在这些乳腺癌组织样本中没有发现KCHIP1基因的突变,但发现了KCHIP1基因一种新的剪接型,这个新剪接型是在原来KCHIP1基因外显子1和外显子2之间多了一个162bp的插入片段(AY780424)。

GM-CSF和其诱导的破骨细胞对成骨细胞的影响

目的探讨GM-CSF和其诱导的破骨细胞对成骨细胞生长的影响。方法采用分组对照、细胞计数等方法进行研究。结果GM-CSF和其诱导的破骨细胞可以促进成骨细胞生长。结论GM-CSF和其诱导的破骨细胞促进成骨细胞增殖、分化,可能是通过破骨细胞内GM-CSF介导的信号通路而发挥作用。

Total pancreatectomy with islet cell transplantation vs intrathecal narcotic pump infusion for pain control in chronic pancreatitis

AIM: To evaluate pain control in chronic pancreatitis patients who underwent total pancreatectomy with islet cell transplantation or intrathecal narcotic pump infusion.METHODS: We recognized 13 patients who underwent intrathecal narcotic pump(ITNP) infusion and 57 patients who underwent total pancreatectomy with autologous islet cell transplantation(TP + ICT) for chronic pancreatitis(CP) pain control between 1998 and 2008 at Indiana University Hospital. All patients had already failed multiple other modalities for pain control and the decision to proceed with either intervention was made at the discretion of the patients and their treating physicians. All patients were evaluated retrospectively using a questionnaire inquiring about their pain control(using a 0-10 pain scale), daily narcotic dose usage, and hospital admission days for pain control before each intervention and during their last follow-up. RESULTS: All 13 ITNP patients and 30 available TP + ICT patients were evaluated. The mean age was approximately 40 years in both groups. The median duration of pain before intervention was 6 years and 7 years in the ITNP and TP + ICT groups, respectively. The median pain score dropped from 8 to 2.5(on a scale of 0-10) in both groups on their last follow up. The median daily dose of narcotics also decreased from 393 mg equivalent of morphine sulfate to 8 mg in the ITNP group and from 300 mg to 40 mg in the TP + ICT group. No patient had diabetes mellitus(DM) before either procedure whereas 85% of those who underwent pancreatectomy were insulin dependent on their last evaluation despite ICT. CONCLUSION: ITNP and TP + ICT are comparable for pain control in patients with CP however with high incidence of DM among those who underwent TP + ICT. Prospective comparative studies and longer follow up are needed to better define treatment outcomes.

Gene editing for corneal disease management

Gene editing has recently emerged as a promising technology to engineer genetic modifications precisely in the genome to achieve long-term relief from corneal disorders.Recent advances in the molecular biology leading to the development of clustered regularly interspaced short palindromic repeats(CRISPRs) and CRISPR-associated systems,zinc finger nucleases and transcription activator like effector nucleases have ushered in a new era for high throughput in vitro and in vivo genome engineering.Genome editing can be successfully used to decipher complex molecular mechanisms underlying disease pathophysiology,develop innovative next generation gene therapy,stem cell-based regenerative therapy,and personalized medicine for corneal and other ocular diseases.In this review we describe latest developments in the field of genome editing,current challenges,and future prospects for the development of personalized genebased medicine for corneal diseases.The gene editing approach is expected to revolutionize current diagnostic and treatment practices for curing blindness.

Stroke and Left Ventricular Assist Device (LVAD)

Treatment of ischemic stroke for a patient on left ventricular assist device (LVAD) by neurointerventional means is rare and many anesthesia providers are unfamiliar with both LVAD and neurointerventional protocols. Examples of this include: 1) filling for continuous-flow LVAD depend on preload and the flow is inversely related to afterload;as mean arterial pressure (MAP) increases above 80 to90 mmHg, flow decreases;2) there may be no palpable pulse in patients with continuous flow LVADs;3) pulse oximetry may not work when pump flow is high and native myocardial function is minimal;4) increasing MAP above80 mmHg potentially will maintain ischemic brain tissue—the penumbra—until flow is restored. This latter example creates a paradoxical management goal: increasing the mean arterial pressure (MAP) above80 mmHg while maintaining ischemic brain tissue, may decrease flow to the LVAD. Finally, there is controversy regarding which type of anesthesia is most efficacious for neuro interventional procedures. We describe three patients on LVAD suffering ischemic stroke requiring anesthesia for embolectomy and angioplasty during neruointeventioal radiology procedures.

外阴细胞性血管纤维瘤1例

Cellular angiofibroma is a benign growth initially described in 1997, with few reports to date. A 31-year-oldwoman presented with a 3-year history of a small left labial mass, which had recently increased in size to 5 cm, and was clinically thought to be a lipoma. A simple excisionwas performed. Histologically, the mass was consistent with a cellular angiofibroma. Ten months later, the growth has not recurred. Cellular angiofibroma is a rare, benign mesenchymal lesion typically occurring on the vulva, and should be considered in the differential diagnosis of a painless, soft, vulvar mass.

Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis

While emerging data suggest nucleotide oligomerization domain receptor 1(NOD1),a cytoplasmic pattern recognition receptor,may play an important and complementary role in the immune response to bacterial infection,its role in cancer metastasis is entirely unknown.Hence,we sought to determine the effects of NOD1 on metastasis.NOD1 expression in paired human primary colon cancer,human and murine colon cancer cells were determined using immunohistochemistry and immunoblotting(WB).Clinical significance of NOD1 was assessed using TCGA survival data.A series of in vitro and in vivo functional assays,including adhesion,migration,and metastasis,was conducted to assess the effect of NOD1.C12-iE-DAP,a highly selective NOD1 ligand derived from gram-negative bacteria,was used to activate NOD1.ML130,a specific NOD1 inhibitor,was used to block C12-iE-DAP stimulation.Stable knockdown(KD)of NOD1 in human colon cancer cells(HT29)was constructed with shRNA lentiviral transduction and the functional assays were thus repeated.Lastly,the predominant signaling pathway of NOD1-activation was identified using WB and functional assays in the presence of specific kinase inhibitors.Our data demonstrate that NOD1 is highly expressed in human colorectal cancer(CRC)and human and murine CRC cell lines.Clinically,we demonstrate that this increased NOD1 expression negatively impacts survival in patients with CRC.Subsequently,we identify NOD1 activation by C12-iE-DAP augments CRC cell adhesion,migration and metastasis.These effects are predominantly mediated via the p38 mitogen activated protein kinase(MAPK)pathway.This is the first study implicating NOD1 in cancer metastasis,and thus identifying this receptor as a putative therapeutic target.

Clinical Factors Associated with Hepatocellular Iron Deposition in End-stage Liver Disease

Background and Aims: Hepatocellular iron accumulation in patients with chronic liver disease has been linked to adverse outcomes. The objective of this study was to identify clinical factors associated with hemosiderosis. Methods: A total of 103 consecutive liver transplant recipients were identified, in whom liver biopsy had been performed prior to transplantation. Laboratory and clinical data at biopsy and transplant were abstracted from the medical records and hepatocyte iron was graded in the biopsy and explant. The association of change in iron score from biopsy to transplant, with the time interval between these two events, was examined using linear mixed model analysis for repeated measures. Results: Most subjects had advanced fibrosis (F3-F4) at liver biopsy, which was performed on average about 2.5 years before transplant. Over 80% of patients had no or 1+ hepatocyte iron at biopsy;iron increased between biopsy and transplant in about 40%. The only demographic or clinical feature that correlated with increased iron was the presence of a transjugular intrahepatic portosystemic shunt. Increased iron at transplant was associated with higher serum iron and transferrin saturation at biopsy, and with lower hemoglobin level, greater mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, higher ferritin and model for end-stage liver disease score at transplant.Conclusions: The development of hemosiderosis in end-stage liver disease is associated with lower hemoglobin levels and alterations in red blood cell indices that are suggestive of hemolysis. These observations suggest that extravascular hemolysis may play a role in the development of secondary iron overload.