Effects of budesonide on proliferation and apoptosis of airway smooth muscle cells in asthmatic rats / 解剖学报

Objective To investigate the effect of budesonide ( BUD) inhalation on the proliferation and apoptosis of airway smooth muscle cells ( ASMCs) in asthmatic rats and its molecular biological mechanism. Methods Totally 40 SD rats were randomly divided into control group, asthma model group, low (0. 25 mg/kg) and high (2 mg/kg) BUD group. The rat asthma model was induced by ovalbumin (VOA) combined with aluminium hydroxide Gel sensitization stimulation. After sensitization, the intervention group inhaled different doses of BUD before stimulation. The related parameters of lung tissue and airway were measured and calculated by medical image analysis system, immunofluorescence was used to detect the expression of type I collagen ( Col I ) and Col III in rat airway smooth muscle ( ASM ), and the protein expressions of Bcl-2, Bax, Caspase-3, phosphorylated ERK 1 and 2(p-ERK 1 / 2), p-p38 MAPK were detected by Western blotting. The proliferation activity of ASMCs was detected by MTT method, and the apoptosis rate of ASMCs was detected by flow cytometry. Results Compared with the control group, airway remodeling occurred in the asthmatic model group, and the airway wall thickness ( WAt/Pbm ), inner wall thickness ( WAi/Pbm ) and smooth muscle thickness ( WAm/Pbm ) increased, compared with the model group, the airway remodeling was inhibited in BUD intervention group, and the tracheal WAt/Pbm, WAi/Pbm and WAm/Pbm decreased in bud treatment group. BUD could decrease the proliferation activity of ASMCs, increase the apoptosis rate of ASMCs, inhibit the expression of Col I and Col III, deregulate the expression of Bcl-2, upregulate the expression of Bax and Caspase-3 ( all P<0. 05), and inhibit the activity of ERK 1/2 and p38 MAPK signal pathway. Conclusion BUD can inhibit the proliferation and the promote apoptosis of ASMCs in asthmatic rats, which may be related to the inhibition of ERK 1/2 and p38 MAPK signal pathways.

Effects of recombinant fusion protein interleukin-18 on expression of immune-inflammatory factors in mice infected with Staphylococcus aureus / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe the effects of recombinant fusion protein interleukin (IL)-18 on the expression of immune-inflammatory factors in the mice infected with Staphylococcus aureus (SA), and to investigate the mechanism of action of IL-18 in defense of SA infection in vivo.</p><p><b>METHODS</b>A total of 40 specific pathogen-free female BLAB/c mice were randomly divided into four groups: control, SA infection, immunized, and intervention. A mouse model of SA infection was established by nasal inoculation with SA liquid. The immunized group and the intervention group were intranasally given IL-18 before SA modeling, and then the SA infection group and the intervention group received the nasal inoculation with SA liquid; the control group was treated with phosphate buffered saline instead. The levels of IL-4, interferon (IFN)-γ, tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), IgM in the serum and bronchoalveolar lavage fluid (BALF) of mice were measured by enzyme-linked immunosorbent assay. The expression of macrophage inflammatory protein (MIP)-1α mRNA and MIP-2β mRNA in the lung tissue of mice were determined by real-time fluorescent quantitative PCR.</p><p><b>RESULTS</b>Compared with the control group, the SA infection group and the immunized group had significantly higher levels of IL-4, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue (P<0.05); the SA infection group had a significantly lower level of IFN-γ and a significantly higher level of TNF in the serum and BALF (P<0.05); the immunized group had a significantly higher level of IFN-γ in the serum and BALF (P<0.05). Compared with the SA infection group, the intervention group had significantly higher levels of IL-4, IFN-γ, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA in the lung tissue. In contrast, the intervention group showed a significantly lower level of TNF in the serum and BALF and expression of MIP-2β mRNA in the lung tissue (P<0.05). All the above indicators in the intervention group were significantly higher than those in the control group (P<0.05), except the serum level of IFN-γ.</p><p><b>CONCLUSIONS</b>In the mice infected with SA, the recombinant fusion protein IL-18 by mucosal immunity can affect inflammatory factors in the serum and BALF and the expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue to promote the anti-infective immune response and enhance the ability to clear pathogens.</p>

Clinical Value ofF-FDG PET/CT for Patients with B Cell Lymphoma-Associated Hemophagocytic Syndrome / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical value ofF-FDG PET/CT for patients with B cell lymphoma-associated hemophagocytic syndrome.</p><p><b>METHODS</b>The clinical characteristics, laboratory parameters andF-FDG PET/CT data of 23 newly diagnosed patients sufferred from B cell lymphoma-associated hemophagocytic syndrome were retrospectively analyzed. The correlation between PET and laboratory parameters were determined using Spearman correlation test. The prognostic factors were analyzed by the Kaplan-Meier method.</p><p><b>RESULTS</b>23 patients were all examined byF-FDG PET/CT before chemotherapy, theF-FDG uptake of spleen positively correlated with neutrophil count and hemoglobin content (r=0.588, P=0.035;r=0.699, P=0.008), respectively, and theF-FDG uptake of bone marrow positively correlated with neutrophil count only (r=0.691, P=0.009). Among all the clinical or laboratorial parameters andF-FDG PET/CT, only PET parameter was poor factor affecting prognosis of patients with B cell lymphoma-associated hemophagocytic syndrome. Out of 6 patients received PET/CT scans after 6 cycles of treatment, the 5 patients with negative PET/CT survived, and one patient with positive result died.</p><p><b>CONCLUSION</b>BaselineF-FDG PET/CT may provide prognostic information for the management of patients with B cell lymphoma-associated hemophagocytic syndrome, and the data ofF-FDG PET/CT before chemotherapy may predict the pregnosis of the patients with negative results, and the negative PET/CT results after chemotherapy betokens a better prognosis of patients.</p>

Clinicopathological study of sporadic Burkitt lymphoma in children / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Non-Hodgkin lymphoma is the fourth most common malignant tumors in children, Burkitt lymphoma (BL) accounts for 30-50% of all pediatric lymphomas. The aim of this study was to investigate the clinicopathologic features, immunophenotype, Epstein-Barr virus (EBV) infection and c-myc gene rearrangement of sporadic BL in children.</p><p><b>METHODS</b>Ninety-two cases of pediatric BL were retrospectively analyzed for clinical features, immunohistochemistry, EBV-encoded RNA (EBER) status by in situ hybridization and c-myc gene rearrangement by fluorescence in situ hybridization.</p><p><b>RESULTS</b>In the 92 cases, male is predominant in sex distribution (M: F = 3.38:1). The average age at diagnosis was 4.97 years. Polypoid BL showed a lower clinical stage (P = 0.002), and advanced clinical stage and low serum albumin level at diagnosis were associated with poor outcome (P = 0.024 and 0.053, respectively). The positive expression of CDl0, B-cell lymphoma-6, MUMl and EBER were 95.7% (88 cases), 92.4% (85 cases), 22.8% (21 cases), 41.3% (38 cases), respectively. The expression of MUM1 were not associated with EBV infection status (P = 1.000). c-myc gene rearrangement was detected in 94.6% (87/92). Clinical treatment information for 54 cases was collected, 21 patients died of tumor after surgery alone, 33 patients received surgery and chemotherapy, and of which six patients died shortly afterwords (MUM1 positive expression in 3 cases, P = 0.076).</p><p><b>CONCLUSIONS</b>The anatomical location, growth pattern and serum albumin level of BL were associated with biological behavior. MUM1 may be a potential adverse prognostic marker, and not associated with EBV infection status.</p>

Molecular genetic features of sporadic Burkitt's lymphoma in children / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the molecular genetic features and diagnostic aspects of sporadic Burkitt's lymphoma (BL) in children.</p><p><b>METHODS</b>Tissue microarray was constructed to include 64 cases of pediatric BL and 6 cases of pediatric diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry and fluorescence in-situ hybridization for c-myc, bcl-2, bcl-6, IgH, myc/IgH and bcl-2/IgH gene were performed. Cases of pediatric Burkitt's lymphomas were subclassified into three groups based on their cellular orgins: the germinal center (GC) group, the late-germinal center (late-GC) group and the post-germinal center (post-GC) group.</p><p><b>RESULTS</b>Among 64 Burkitt's lymphomas studied, expression of CD20, CD10, bcl-6, bcl-2 and MUM1 by immunohistochemistry were 100% (64 cases), 98.4% (63 cases), 96.9% (62 cases), 0 (0 cases) and 23.4% (15 cases), respectively. Various gene rearrangements were found involving the c-myc 93.1% (54/58 cases) and IgH 82.8% (48/58 cases). Detailed rearrangements are as follows: 46 cases (85.2%) myc/IgH gene translocation along with c-myc and IgH gene rearrangement; 4 cases (7.4%) c-myc gene rearrangement without IgH and myc/IgH abnormality; 4 cases (7.4%) without c-myc, IgH or myc/IgH gene rearrangement. No case showed bcl-2 gene abnormality (100%). Fifty nine cases showed normal bcl-6 gene status. One case had bcl-6 gene rearrangement and amplification with the pathologic and immunophenotypic characteristics of BL, leading to a revised pathological diagnosis of B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma (DLBCL/BL). Two cases showed c-myc gene rearrangement. Two cases showed bcl-6 gene amplification and 6 DLBCL cases had a normal status of bcl-2/IgH.</p><p><b>CONCLUSIONS</b>A majority of pediatric sporadic BL arise from the germinal center B cells, most of which have c-myc gene rearrangement. It is useful to distinguish BL and DLBCL by multiple genes detection.</p>

Clinicopathologic and immunohistochemical study of intra-abdominal non-Hodgkin B-cell lymphoma occurring in children / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunohistochemical findings, EBV and c-myc gene status of intra-abdominal non-Hodgkin B-cell lymphoma occurring in children.</p><p><b>METHODS</b>Seventy-four cases of pediatric intra-abdominal non-Hodgkin B-cell lymphoma were retrieved from the archival file. The cases were classified according to the 2008 WHO classification. Tissue microarray including tumor tissues from all the 74 cases was produced. Immunohistochemical study (SP method) for CD20, CD3, CD79a, CD10, bcl-6, MUM1, bcl-2, CD43, CD38 and Ki-67 was performed. In-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) and fluorescence in-situ hybridization for c-myc gene were also carried out.</p><p><b>RESULTS</b>Amongst the 74 cases studied, 65 of them (87.8%) were Burkitt lymphoma (BL), 4 cases (5.4%) were diffuse large B-cell lymphoma (DLBCL) and the remaining 5 cases (6.8%) showed features in-between DLBCL and BL (DLBCL/BL). The patients often presented with abdominal pain, abdominal masses, ileus and intussusception. The ileocecal bowel wall and mesenteric lymph nodes were commonly involved. The lymphoma cells were of high histologic grade and suggested an aggressive clinical behavior. The staining for CD20 and CD79a were positive in all of the cases, while CD3 was negative. The positive rates of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER in BL were 96.9% (63 cases), 95.4% (62 cases), 0 (0 case), 23.1% (15 cases), 70.8% (46 cases), 96.9% (63 cases) and 41.5% (27 cases), respectively. Fifty-four cases carried translocation of c-myc gene. As for DLBCL, the positive cases of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER were 3 cases, 2 cases, 3 cases, 2 cases, 2 cases, 2 cases and 0 case, respectively. One of these cases showed c-myc gene translocation. Amongst the 4 cases of DLBCL, 2 of them belonged to germinal center B-cell-like subtype, while the remaining 2 cases were of non-germinal center B-cell-like subtype. The expression rates of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER in DLBCL/BL were 5/5, 4/5, 0, 3/5, 5/5, 3/5 and 0, respectively. Three of the cases were positive for c-myc gene translocation.</p><p><b>CONCLUSIONS</b>The majority of pediatric intra-abdominal non-Hodgkin B-cell lymphoma belonged to BL. They have characteristic clinical presentation and sites of predilection and are often associated with an aggressive clinical behavior. Thorough morphologic assessment, immunohistochemistry and in-situ hybridization play an important role in subtyping this group of lymphoid malignancy.</p>

Effects of carbon disulfide on blood pressure and electrocardiogram for workers exposed to levels below the national maximum allowable concentration / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effects of carbon disulfide exposure within the national maximum allowable concentration(MAC) on blood pressure and electrocardiogram, and associations with selected factors.</p><p><b>METHODS</b>Workers in a chemical fiber factory were divided into two groups based on the type of work: a high exposure group (HEG) of 821 individuals and a low exposure group (LEG) of 259. The CS2 concentration at workplace was controlled under the national MAC. A set of 250 randomly selected people taking routine physical check-ups in the same period and hospital constituted the control group. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured on the arm, and the pulse pressure (PP) and mean arterial blood pressure (MABP) were calculated based on SBP and DBP. The blood pressure data, along with the results of the routine 12-lead electrocardiography taken at rest and records on gender, age, years of work, type of work, and concentrations of triglycerol, cholesterol, and glucose in blood, were compiled for analyses. Risk factors upon CS2 exposure for the increase of blood pressure and occurrence of electrocardiogram abnormalities were identified and rationalized.</p><p><b>RESULTS</b>Significant difference (P < 0.01) in the average values of SBP, DBP, MABP, and the corresponding abnormality incident rates was found between HEG and LEG, and between HEG and the control group. For both HEG and LEG, the incident rate of DBP abnormality (high DBP) is nearly two times as high as that of SBP. Type of work is the largest risk factor in both the high SBP and high DBP subgroups, with odds ratios (OR) of 2.086 and 2.331 respectively, and high CS2 exposure presents more than double the risk than low exposure. On the incident rate of ECG abnormalities, both exposure groups are significantly different (P < 0.01) to the control group. High SBP in LEG and high DBP in HEG were found to be significant risk factors (OR = 3.531 and 1.638 respectively), while blood glucose appears to be a protective factor (OR = 0.747), appealing to further investigation. Meanwhile, factors like years of work and cholesterol were found to be risk factors in the high SBP subgroup with low exposure, and in the high DBP subgroup with high exposure. Within HEG, high DBP is the only blood pressure-related risk factor found for the incident of left ventricular high voltage (OR = 4.140), as is high SBP for LEG (OR = 4.776). High PP is the only risk factor found for repolarization disturbances within LEG (OR = 20.417). While blood sugar is a risk factor for origin disturbances, it is a protection factor for left ventricular high voltage (OR = 0.633).</p><p><b>CONCLUSION</b>The damage of CS2 done to the cardiovascular system is a gradual process. Both early and very low level exposures are detrimental to the human circulatory system. Below the National MAC limit, the toxic effect of CS2 to the cardiovascular system increases with time and level of exposure. The effect of CS2 on DBP is more significant than on SBP, which indicates that CS2 may affect peripheral resistant blood vessels more than the artery. The abnormalities of ECG of workers exposed to CS2 are not only the result of high blood pressure on the heart, but also of the direct toxicity of CS2 on heart and blood vessels.</p>

Clinicopathologic and prognostic study of pediatric immature teratoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and biologic behavior of pediatric immature teratoma.</p><p><b>METHODS</b>The clinical data, pathologic features, immunohistochemical findings (for cyclin D1, P27 and Ki-67) and follow-up information of 39 cases of pediatric immature teratoma were analyzed.</p><p><b>RESULTS</b>Amongst the 39 cases studied, 12 arose in the sacrococcygeal region, 12 in testis, 5 in retroperitoneum, 4 in ovary, 4 in abdomen and 2 in mediastinum. Histologically, 16 cases were of grade 1, 8 cases of grade 2 and 15 cases of grade 3. Seven of the cases contained foci of yolk sac tumor. Immature neuroepithelial features used in histologic grading included the presence of primitive neural tubules, immature rosettes, undifferentiated neuroblastoma cells and primitive neuroectodermal structures. Immunohistochemical study showed that cyclin D1 was positive in 3 cases of grade 1 tumors, 4 cases of grade 2 tumors and 9 cases of grade 3 tumors. The positivity rates for p27 were 8, 3 and 6 cases respectively, while those for Ki-67 were 3, 4 and 13 cases respectively. Follow-up data were available in 30 cases. Three of them, including 2 cases with histologic grade 3 (with or without yolk sac tumor component), recurred after operation.</p><p><b>CONCLUSIONS</b>The expression of cyclin D1 and Ki-67 is a useful adjunct in histologic grading. On the other hand, p27 overexpression shows little correlation with tumor grade. The prognosis of immature teratoma in children is different from that in adults. Sacrococcygeal immature teratoma occurring in patients younger than 1 year old and with low histologic grade do not require postoperative chemotherapy if the tumor is completely excised. Similarly, for testicular immature teratoma occurring in patients below 1 year of age, regardless of tumor grading, need no adjunctive therapy. On the other hand, ovarian immature teratoma with high histologic grade requires postoperative chemotherapy, regardless of age of the patients. The presence of microscopic foci of yolk sac tumor is a useful predictor of recurrence in pediatric immature teratoma.</p>