Mild hypothermia alleviates excessive autophagy and mitophagy in a rat model of asphyxial cardiac arrest

Mild hypothermia is an effective therapeutic strategy to improve poor neurological outcomes in patients following cardiac arrest (CA). However, the underlying mechanism remains unclear. The aim of the study was to evaluate the effect of mild hypothermia on intracellular autophagy and mitophagy in hippocampal neurons in a rat model of CA. CA was induced in Sprague–Dawley (SD) rats by asphyxia for 5 min. After successful resuscitation, the surviving rats were randomly divided into two groups, the normothermia (NT) group and the hypothermia (HT) group. Mild hypothermia (32 °C) was induced following CA for 4 h, and animals were rewarmed at a rate of 0.5 °C/h. Neurologic deficit scores (NDS) were used to determine the status of neurological function. Cytoplasmic and mitochondrial protein from the hippocampus was extracted, and the expression of LC3B-II/I and Parkin were measured as markers of intracellular autophagy and mitophagy, respectively. Of the 60 rats that underwent CA, 44 were successfully resuscitated (73 %), and 33 survived until the end of the experiment (55 %). Mild hypothermia maintained eumorphism of nuclear and mitochondrial structures and significantly improved NDS (p < 0.05). Expression of LC3B-II/I and Parkin in hippocampal nerve cells were significantly increased (p < 0.05) in the NT group relative to the control. Meanwhile, mild hypothermia reduced the level of LC3B-II/I and Parkin (p < 0.05) relative to the NT group. Mild hypothermia protected mitochondria and improved neurological function following CA and resuscitation after ischemia/reperfusion (I/R) injury, likely by reducing excessive autophagy and mitophagy in neurons.     

Lumbar trabecular bone mineral density distribution in patients with and without vertebral fractures: a case–control study

Purpose

The proportion of load transmitted through the lumbar neural arch increases with aging, spinal degeneration, and lordosis, effectively shielding the lumbar vertebral bodies from load. This stress shielding may contribute to bone loss in the vertebral body, leading to increased fracture risk. To test his hypothesis, we performed a study to determine if vertebral body fractures were associated with a higher neural arch/vertebral body volumetric bone mineral density (vBMD) ratio.

Methods

Trabecular vBMD was calculated by quantitative CT in the L3 vertebral body and neural arch (pars interarticularis) of 36 women with vertebral compression fractures and 39 controls. Neural arch/vertebral body vBMD ratio was calculated, and its relationship to fracture status was determined using linear regression models adjusted for age and body mass index.

Results

Vertebral body trabecular vBMD was lower in fracture cases as compared to controls (mean ± SD, 49.0 ± 36.0 vs. 87.5 ± 36.8 mg/cm³, respectively; P < 0.001), whereas trabecular vBMD of the neural arch was similar (96.1 ± 57.6 in cases vs. 118.2 ± 57.4 mg/cm³ in controls; P = 0.182). The neural arch/vertebral body vBMD ratio was significantly greater in the fracture group than in controls (2.31 ± 1.07 vs. 1.44 ± 0.57, respectively; P < 0.001).

Conclusion

These results support the hypothesis that stress shielding is a contributor to vertebral body bone loss and may increase fracture risk. Although further studies are needed, there may be a role for interventions that can shift vertebral loading in the spine to help prevent fracture.     

基于多中心真实世界研究再评价舒泌通胶囊治疗湿热瘀滞证慢性前列腺炎的临床疗效

目的:再评价舒泌通胶囊治疗湿热瘀滞证型慢性前列腺炎(CP)的临床疗效。方法:纳入1872例CP患者,在其常规治疗的基础上服用舒泌通胶囊治疗,每次4粒,每日3次,4周为1个疗程,观察治疗2个疗程。观察治疗前后NIH-CPSI评分(包括疼痛症状评分、排尿症状评分及生活质量评分),治疗前后症状分级量化积分情况,并观察不良反应。结果:治疗后总有效率为95.5%,治疗后NIH-CPSI总分及疼痛症状、排尿症状、生活质量评分较治疗前均显著减少(P<0.05);治疗后中医证候总有效率达98.9%,单项证候总有效率在79.5%~97.6%之间。结论:舒泌通胶囊可显著改善CP患者的临床症状,值得临床进一步研究及应用。     

质量常数方法应用于麸炒苍术饮片等级评价研究

目的 将质量常数中药饮片等级划分方法应用于麸炒苍术饮片的等级评价中,以期建立合理的麸炒苍术饮片等级标准。方法 收集来自主要中药材交易市场及其道地产区、主产区的不同厂家、不同规格、不同批号、不同产地的22批麸炒苍术饮片样品,对其外观形态参数、指标成分含量进行测定,通过计算其质量常数（A）及百分质量常数（A%）对22批麸炒苍术饮片样品进行等级划分。结果 所收集的22批麸炒苍术饮片样品的A为0.92~3.37;若将麸炒苍术样品分为3个等级,一等品为A%≥80%（A≥2.70）的麸炒苍术饮片,共有1批;二等品为50%≤A%<80%的麸炒苍术饮片（1.69≤A<2.70）,共有11批;其余10批为三等品,即A%<50 %（A<1.69）的饮片。结论 质量常数方法用于划分麸炒苍术饮片等级是可行的,能更为全面、客观地反映不同等级麸炒苍术饮片的质量。     

Is melatonin ready to be used in preterm infants as a neuroprotectant?

The prevention of neurological disabilities following preterm birth remains a major public health challenge and efforts are still needed to test the neuroprotective properties of candidate molecules. Melatonin serves as a neuroprotectant in adult models of cerebral ischemia through its potent antioxidant and anti‐inflammatory effects. An increasing number of preclinical studies have consistently demonstrated that melatonin protects the damaged developing brain by preventing abnormal myelination and an inflammatory glial reaction, a major cause of white matter injury. The main questions asked in this review are whether preclinical data on the neuroprotective properties of melatonin are sufficient to translate this concept into the clinical setting, and whether melatonin can reduce white matter damage in preterm infants. This review provides support for our view that melatonin is now ready to be tested in human preterm neonates, and discusses ongoing and planned clinical trials.     

Regional brain metabolism in a murine systemic lupus erythematosus model

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb+ mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood–brain barrier (BBB) breach. In DNRAb+ mice, metabolism declined at the site of BBB breach in the first 2 weeks and increased over the next 2 weeks. In contrast, DNRAb− mice exhibited metabolic increases in these regions over the 4 weeks after the insult. Memory impairment was present in DNRAb+ animals with hippocampal BBB breach and altered fear conditioning in DNRAb+ mice with amygdala BBB breach. In DNRAb+ mice, we observed an inverse relationship between neuron number and regional metabolism, while a positive correlation was observed in DNRAb− mice. These findings suggest that local metabolic alterations in this model take place through different mechanisms with distinct time courses, with important implications for the interpretation of imaging data in SLE subjects.     

Transgenic expression of decoy receptor 3 protects islets from spontaneous and chemical-induced autoimmune destruction in nonobese diabetic mice

Decoy receptor 3 (DCR3) halts both Fas ligand- and LIGHT-induced cell deaths, which are required for pancreatic beta cell damage in autoimmune diabetes. To directly investigate the therapeutic potential of DCR3 in preventing this disease, we generated transgenic nonobese diabetic mice, which overexpressed DCR3 in beta cells. Transgenic DCR3 protected mice from autoimmune and cyclophosphamide-induced diabetes in a dose-dependent manner and significantly reduced the severity of insulitis. Local expression of the transgene did not alter the diabetogenic properties of systemic lymphocytes or the development of T helper 1 or T regulatory cells. The transgenic islets had a higher transplantation success rate and survived for longer than wild-type islets. We have demonstrated for the first time that the immune-evasion function of DCR3 inhibits autoimmunity and that genetic manipulation of grafts may improve the success and survival of islet transplants.     

腹腔镜辅助结肠次全切除经肛门取出标本治疗慢传输型便秘

目的：探讨腹腔镜辅助结肠次全切除、经肛门取出标本治疗慢传输型便秘的临床应用价值。方法回顾性分析2013年2-11月间行腹腔镜辅助结肠次全切除、经肛门取出标本并进行升结肠直肠吻合术的8例慢传输型便秘患者的临床资料。采用Wexner便秘与失禁评分来评估术后便秘情况,采用胃肠生活质量评分来评估术后生活质量。结果全组患者手术完成顺利,无肠瘘、盆腔感染、吻合口狭窄、术后肠梗阻和肛门失禁等并发症发生。手术时间（287．6±21．5） min,术中出血量（109．7±41．1） ml,术后肛门排气时间（2．5±0．9） d。患者术后便秘症状评分为4.7±1.9,较术前的15.1±2.8明显降低（P＜0．05）。术后胃肠生活质量评分为97．3±15．7,较术前的71．5±14．7明显提高（P＜0．05）;术后Wexner便秘与失禁评分为8．8±3．7,较术前20．4±5．7明显降低（P＜0．05）。结论腹腔镜辅助结肠次全切除、经肛门取出标本并进行升结肠直肠吻合术治疗慢传输型便秘,近期疗效满意,生活质量改善明显。     

1H-MRS检测正常中老年人纹状体和黑质代谢功能

目的探讨中老年人纹状体和黑质1 H-MRS各参数值正常参考范围。方法纳入健康中老年志愿者32名,采用单体素PRESS序列对纹状体、多体素PRESS序列对黑质进行1 H-MRS扫描,分析N-乙酰天门冬氨酸(NAA)、胆碱(Cho)和肌酸(Cr)含量及各参数比值。结果左右侧纹状体和黑质NAA/Cr、Cho/Cr、NAA/Cho、NAA/(Cho+Cr)差异均无统计学意义(P均0.05)。综合两侧结果,纹状体NAA/Cr、Cho/Cr、NAA/Cho、NAA/(Cho+Cr)均值及95%CI分别为1.39(1.33~1.45)、0.90(0.86~0.94)、1.58(1.50~1.66)、0.73(0.70~0.76);黑质上述比值均值及95%CI分别为2.36(1.85~2.87)、1.38(1.12~1.65)、1.70(1.59~1.81)、0.93(0.86~1.00);纹状体及黑质中NAA/(Cho+Cr)比值均最稳定。结论正常中老年人黑质和纹状体1 H-MRS各参数中,NAA/(Cho+Cr)比值最稳定,可为研究累及黑质和纹状体区域的疾病提供正常参照。     

Prognostic Value of Diametrically Polarized Tumor-Associated Macrophages in Renal Cell Carcinoma

Background

As the most abundant tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) are significant for fostering tumor progression. CD68⁺ TAMs display diversely polarized programs comprising CD11c⁺ proinflammatory macrophages (M1) and CD206⁺ immunosuppressive macrophages (M2). The aim of this study was to determine the survival impact of diametrically polarized TAMs in clear-cell renal cell carcinoma (ccRCC) and their application to stratification of patients according to their prognostic values.

Methods

The study included 185 consecutive patients with ccRCC who underwent nephrectomy between 1999 and 2001. CD68⁺ total and diametrically polarized (CD11c⁺ M1 and CD206⁺ M2) TAM densities were assessed by immunohistochemistry, and the relationships with clinicopathologic features and prognosis were evaluated.

Results

Low CD11c⁺ TAM density and high CD206⁺ TAM density were associated with reduced cancer-specific survival (P = 0.043 and P = 0.017, respectively), whereas CD68⁺ TAM density only had borderline prognostic significance (P = 0.062). Furthermore, combined analysis of CD11c⁺ and CD206⁺ TAMs (CD11c/CD206 signature) had a better power to predict patients’ outcome (P = 0.010). Together with TNM stage, tumor necrosis, and performance status, CD11c/CD206 signature was an independent prognostic factor (P = 0.010). When applied to the University of California Integrated Staging System intermediate-/high-risk group for localized ccRCC, CD11c/CD206 signature could further distinguish patients with dismal prognosis (P = 0.004).

Conclusions

Intratumoral balance of diametrically polarized TAMs is a novel independent predictor for survival in patients with ccRCC. Tipping the balance toward an antitumoral phenotype might be a promising target of postoperative adjuvant therapy.