[Attach importance to the moderate diagnosis and treatment of multiple pulmonary nodules].

With the popularization of chest computed tomography examination in physical examination, the detection rate of multiple pulmonary nodules has significantly increased. However, there are no unified guidelines or consensus for the diagnosis and treatment of multiple pulmonary nodules, and the clinical diagnosis and treatment of such patients are often inadequate or excessive. Therefore, it is of great clinical significance to attach importance to the moderate diagnosis and treatment of multiple pulmonary nodules and formulate unified clinical practice standards for the prevention of lung cancer and the diagnosis and treatment of multiple pulmonary nodules.

[Lamotrigine induced hypersensitivity syndrome in children: a case report].

Drug induced hypersensitivity syndrome (DIHS) is often manifested as severe systemic drug trans-reactions characterized by acute and extensive skin lesions (mostly measles-like rash), fever, enlargement of lymph nodes, multiple organ involvement (hepatitis, nephritis, and pneumonia), eosinophilia and mononucleosis,within 2-6 weeks of the application of sensitizing drugs. In the early stage of the lesion, macular papules or erythema multiforme were common, and in severe cases, exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis were also common. Most of them developed after taking allergic drugs for 2-6 weeks (average: 3 weeks). Symptoms persisted after discontinuation of allergic drugs. It takes more than one month to alleviate, which may endanger life in severe cases. Documents report that the most common drugs causing DIHS are phenytoin sodium, carbamazepine and phenobarbital aromatic drugs. However, it was reported that phenobarbital sodium was the most common anticonvulsant among allergenic drugs in children, followed by antipyretics, analgesics and antibiotics, which may be related to the spectrum of childhood diseases and the particularity of the drug. Lamotrigine has been reported to cause DIHS in adults in China, but less in children. In order to improve the understanding of clinical diagnosis and treatment of DIHS in children, reduce misdiagnosis, missed diagnosis, and untimely treatment, and prevent the aggravation of the disease, we studied the case of a 4-year-old 7-month-old girl who presented with systemic erythematous papules, fever, hepatosplenomegaly, marked increase of white blood cells, marked decrease of anemia and platelets, abnormal liver function and coagulation routine after taking lamotrigine for one month due to epilepsy seizures. Now, according to the DIHS diagnostic criteria established by Registration of Severe Cutaneous Adverse Reactions Drug Review Group in 2007, plasma exchange was immediately given to replace the toxic metabolites in hemorrhagic plasma, and methylprednisolone was given intravenously for three days. At the same time, after symptomatic supportive treatments, such as loratadine and albumin, the condition gradually improved without recurrence. Through a case report of Drug reaction with eosinophilia and systemic symptoms in a child caused by lamotrigine, we can strengthen our understanding and improve the level of diagnosis and treatment of drug hypersensitivity syndrome in children. Lamotrigine can cause DIHS in children, which is very dangerous. Early diagnosis and early withdrawal of allergenic drugs, plasma exchange and glucocorticoid therapy are the key to treatment.

Protease sensitivity and redistribution of CD71 and glycophorin A on K562 cells.

Transmembrane proteins are delivered to plasma membrane from the endoplasmic reticulum and Golgi complex by vesicular transport along with the cytoskeletal network. Disruption of this process likely affects transmembrane protein expression. K562 cells were digested with Streptomyces griseus protease for different periods of time, and then re-cultured with different cytoskeletal and glycosylation inhibitors. Cell viability and surface expression of transferrin receptor (CD71) and glycophorin A (GPA) were analyzed before and after re-culture by flow cytometry. We found that digestion with protease almost completely removed extracellular CD71 and GPA but their expression recovered to the initial levels after re-culture for 8 h and 24 h, respectively. The microtubule depolymerizer colchicine promoted cell surface recovery of CD71 but inhibited that of GPA; the microtubule stabilizer paclitaxel inhibited cell surface recovery of CD71 but promoted that of GPA; the microfilament depolymerizer cytochalasin D had no effect on cell surface recovery of CD71 and GPA; the microfilament stabilizer phalloidin inhibited cell surface recovery of GPA. The glycosylation inhibitor tunicamycin inhibited the recovery of both CD71 and GPA, and BADGP inhibited the recovery of GPA. These studies show differential sensitivities of surface proteins on K562 cells to proteases, and suggest molecular mechanisms of transmembrane protein transport and cycling.

Long-term exposure of K562 cells to benzene metabolites inhibited erythroid differentiation and elevated methylation in erythroid specific genes.

Benzene is a common occupational hazard and a widespread environmental pollutant. Previous studies have revealed that 72 h exposure to benzene metabolites inhibited hemin-induced erythroid differentiation of K562 cells accompanied with elevated methylation in erythroid specific genes. However, little is known about the effects of long-term and low-dose benzene metabolite exposure. In this study, to elucidate the effects of long-term benzene metabolite exposure on erythroid differentiation, K562 cells were treated with low-concentration phenol, hydroquinone and 1,2,4-benzenetriol for at least 3 weeks. After exposure of K562 cells to benzene metabolites, hemin-induced hemoglobin synthesis declined in a concentration- and time-dependent manner, and the hemin-induced expressions of α-, ß- and γ-globin genes and heme synthesis enzyme porphobilinogen deaminase were significantly suppressed. Furthermore, when K562 cells were continuously cultured without benzene metabolites for another 20 days after exposure to benzene metabolites for 4 weeks, the decreased erythroid differentiation capabilities still remained stable in hydroquinone- and 1,2,4-benzenetriol-exposed cells, but showed a slow increase in phenol-exposed K562 cells. In addition, methyltransferase inhibitor 5-aza-2'-deoxycytidine significantly blocked benzene metabolites inhibiting hemoglobin synthesis and expression of erythroid genes. Quantitative MassARRAY methylation analysis also confirmed that the exposure to benzene metabolites increased DNA methylation levels at several CpG sites in several erythroid-specific genes and their far-upstream regulatory elements. These results demonstrated that long-term and low-dose exposure to benzene metabolites inhibited the hemin-induced erythroid differentiation of K562 cells, in which DNA methylation played a role through the suppression of erythroid specific genes.