二甲双胍与美沙拉嗪在小鼠结肠炎中的疗效比较

目的 探讨二甲双胍与美沙拉嗪在治疗小鼠结肠炎中的疗效差异性。方法 选取6 ~ 8周龄的C57BL/6雄性小鼠32只,随机分为Control组、硫酸葡聚糖（DSS）组、DSS+美沙拉嗪组、DSS+二甲双胍组,每组8只。Control组小鼠自由饮用高压灭菌双蒸水,并每日予0.2 ml 磷酸盐缓冲液（PBS）灌胃。采用3%DSS诱导C57BL/6雄性小鼠结肠炎模型。DSS组小鼠自由饮用3%DSS溶液,每日予0.2 ml PBS灌胃,DSS+美沙拉嗪组、DSS+二甲双胍组自由饮用3%DSS溶液,予100 mg/（kg·d） 的美沙拉嗪或100 mg/（kg·d） 二甲双胍灌胃。评估各组小鼠体质量变化、结肠长度、疾病活动指数、组织病理学改变及肠道炎症因子表达情况。结果 与DSS组相比,DSS+二甲双胍与DSS+美沙拉嗪组均可降低小鼠结肠炎所致的体质量丢失、疾病活动度评分、组织病理学评分及肠道炎症因子表达水平（P均< 0.05）,但DSS+二甲双胍组与DSS+美沙拉嗪组上述指标比较差异均无统计学意义（P均> 0.05）。结论 二甲双胍可以减轻DSS诱导的小鼠结肠炎,其疗效不亚于美沙拉嗪。     

Effects of APOE ɛ4 on brain amyloid,lacunar infarcts,and white matter lesions: a study among patients with subcortical vascular cognitive impairment

The relationship between the apolipoprotein E ?4 allele (APOE4) and factors associated with vascular cognitive impairment (VCI) is unclear. We aimed to examine the effects of APOE4 on brain amyloid beta using Pittsburg compound B (PiB) and subcortical cerebrovascular disease, as assessed by lacunes and white matter hyperintensities (WMH) in subcortical VCI (SVCI) patients. We recruited 230 subjects with normal cognition, 111 subjects with cognitive impairment due to clinically defined Alzheimer’s disease (ADCI), and 134 subjects with clinically defined SVCI. A PiB retention ratio greater than 1.5 was considered to be PiB positive. Logistic regression analysis was performed to investigate whether APOE4 increased the risk for each cognitive impairment group. Multiple linear regression analysis was performed to investigate whether APOE4 was associated with brain amyloid beta, lacunes, and WMH. APOE4 did not increase the risk of PiB(−) SVCI (odds ratio [OR], 1.50; 95% confidence interval [CI], 0.79–2.84), whereas APOE4 increased the risk of PiB(+) SVCI (OR, 4.52; 95% CI, 1.70–11.97) and PiB(+) ADCI (odds ratio, 4.84; 95% CI, 2.54–7.91). In SVCI patients, APOE4 was positively associated with PiB retention ratio, whereas APOE4 was not associated with the number of lacunes or with WMH volume. Our results suggest that amyloid beta burden can occur in patients with and without subcortical cerebrovascular disease, and that it is associated with APOE4. However APOE4 might be independent of subcortical cerebrovascular disease.     

B Cell Production of Tumor Necrosis Factor in Response to Pneumocystis murina Infection in Mice

Pneumocystis species are opportunistic fungal pathogens that induce tumor necrosis factor (TNF) production by alveolar macrophages. Here we report that B cells from the draining lymph nodes as well as lung CD4⁺ T cells are important producers of TNF upon Pneumocystis murina infection. To determine the importance of B cell-derived TNF in the primary response to P. murina, we generated bone marrow chimeras whose B cells were unable to produce TNF. The lung P. murina burden at 10 days postinfection in TNF knockout (TNFKO) chimeras was significantly higher than that in wild-type (WT) chimeras, which corresponded to reduced numbers of activated CD4⁺ T cells in the lungs at this early time point. Furthermore, CD4⁺ T cells isolated from P. murina-infected TNFKO chimeras were unable to stimulate clearance of P. murina upon adoptive transfer to recombinase-deficient (RAG1KO) hosts. Together, these data indicate that B cell-derived TNF plays an important function in promoting CD4⁺ T cell expansion and production of TNF and facilitating protection against P. murina infection.     

Protective effects of melatonin against spinal cord injury induced oxidative damage in rat kidney: A morphological and biochemical study

Spinal cord injury (SCI) induced oxidative stress affects multiple organ systems including the kidney. We studied the possible protective effects of melatonin on SCI-induced oxidative damage in renal tissues of rats. Wistar albino rats (n = 24) were exposed to SCI and divided into vehicle- or melatonin-treated SCI groups. Melatonin was administred intraperitoneally at a dose of 10 mg/kg for seven days. Renal tissues were investigated by light and electron microscopy. Furthermore, tissue malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and superoxide dismutase (SOD) activities were also determined. In the vehicle-treated SCI group, the renal histology was disturbed compared to controls, whereas the melatonin-treated SCI group showed significantly reduced degeneration of renal tissue as seen by both light and electron microscopy. MDA levels, MPO and SOD activities were increased and GSH levels were decreased in the vehicle-treated SCI group compared to controls. On the other hand, decreased MDA levels and MPO activities and increased GSH levels were observed in the melatonin-treated SCI group compared to vehicle-treated SCI group. These results showed that experimentally induced SCI caused oxidative stress in the rat kidney, whereas melatonin treatment reduced oxidative stress, suggesting that it may be used as a complementary therapy of renal problems occurring following SCI.     

Preparation and phase transition behaviors of temperature-responsive 3-butoxy-2-hydroxypropyl hydroxyethyl celluloses

2-Hydroxy-3-butoxypropyl hydroxyethyl celluloses (HBPEC), which are thermoresponsive polymers, are prepared by grafting butyl glycidyl ether onto hydroxyethyl cellulose. The effects of several factors on the cloud point (Tc) of the HBPEC are also investigated. The Tc of HBPEC can be tuned to a ranging from 17.0 to 43.0 °C by changing the molar substitution of hydrophobic groups. Increasing the concentration of HBPEC leads to a faster phase transition as well as a corresponding linear decrease in the Tc. A series of salts with common anions or cations are used to investigate the effects of specific anions or cations on the Tc of HBPEC aqueous solutions. It is discovered that the Tc of HBPEC is largely influenced by the variation of cation identity and concentration. Plotting Tc as a function of cation activity shows that the Tc can be classified by charge density.     

Multimodal MRI assessment for first episode psychosis: A major change in the thalamus and an efficient stratification of a subgroup

Multi‐institutional brain imaging studies have emerged to resolve conflicting results among individual studies. However, adjusting multiple variables at the technical and cohort levels is challenging. Therefore, it is important to explore approaches that provide meaningful results from relatively small samples at institutional levels. We studied 87 first episode psychosis (FEP) patients and 62 healthy subjects by combining supervised integrated factor analysis (SIFA) with a novel pipeline for automated structure‐based analysis, an efficient and comprehensive method for dimensional data reduction that our group recently established. We integrated multiple MRI features (volume, DTI indices, resting state fMRI—rsfMRI) in the whole brain of each participant in an unbiased manner. The automated structure‐based analysis showed widespread DTI abnormalities in FEP and rs‐fMRI differences between FEP and healthy subjects mostly centered in thalamus. The combination of multiple modalities with SIFA was more efficient than the use of single modalities to stratify a subgroup of FEP (individuals with schizophrenia or schizoaffective disorder) that had more robust deficits from the overall FEP group. The information from multiple MRI modalities and analytical methods highlighted the thalamus as significantly abnormal in FEP. This study serves as a proof‐of‐concept for the potential of this methodology to reveal disease underpins and to stratify populations into more homogeneous sub‐groups.     

Texture Analysis of Three-Dimensional MRI Images May Differentiate Borderline and Malignant Epithelial Ovarian Tumors

ObjectiveTo explore the value of magnetic resonance imaging (MRI)-based whole tumor texture analysis in differentiating borderline epithelial ovarian tumors (BEOTs) from FIGO stage I/II malignant epithelial ovarian tumors (MEOTs).Materials and MethodsA total of 88 patients with histopathologically confirmed ovarian epithelial tumors after surgical resection, including 30 BEOT and 58 MEOT patients, were divided into a training group (n = 62) and a test group (n = 26). The clinical and conventional MRI features were retrospectively reviewed. The texture features of tumors, based on T2-weighted imaging, diffusion-weighted imaging, and contrast-enhanced T1-weighted imaging, were extracted using MaZda software and the three top weighted texture features were selected by using the Random Forest algorithm. A non-texture logistic regression model in the training group was built to include those clinical and conventional MRI variables with p value < 0.10. Subsequently, a combined model integrating non-texture information and texture features was built for the training group. The model, evaluated using patients in the training group, was then applied to patients in the test group. Finally, receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of the models.ResultsThe combined model showed superior performance in categorizing BEOTs and MEOTs (sensitivity, 92.5%; specificity, 86.4%; accuracy, 90.3%; area under the ROC curve [AUC], 0.962) than the non-texture model (sensitivity, 78.3%; specificity, 84.6%; accuracy, 82.3%; AUC, 0.818). The AUCs were statistically different (p value = 0.038). In the test group, the AUCs, sensitivity, specificity, and accuracy were 0.840, 73.3%, 90.1%, and 80.8% when the non-texture model was used and 0.896, 75.0%, 94.0%, and 88.5% when the combined model was used.ConclusionMRI-based texture features combined with clinical and conventional MRI features may assist in differentitating between BEOT and FIGO stage I/II MEOT patients.