经颈前超声波对颈椎间盘变性的诊断价值

目的为了探讨超声波下颈椎间盘变性的图像特点。方法选择经手术证实的63例颈椎间盘变性的超声图像进行回顾性分析。结果利用超声波对椎间盘水分含量变化的敏感性，能够直接反映颈椎盘变性的程度，与手术的诊断符合率达94．4％（85／90）。结论超声波能清晰显示颈椎间盘的外形及内部回声，对临床诊断工作具有指导意义。     

Antimicrobial and antileishmanial activities of hypocrellins A and B

Hypocrellins A and B were evaluated for in vitro antimicrobial and antileishmanial activities. Hypocrellin A exhibited promising activity against Candida albicans and moderate activity against Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, and Mycobacterium intracellulare. Hypocrellin B showed weak antimicrobial activities. Hypocrellin A exhibited potent antileishmanial activity, while hypocrellin B was only moderately active. These results of promising antifungal and antileishmanial activity of hypocrellin A may be useful for further structure-activity relationship and in vivo studies.     

Stroke service: How can we improve and measure outcomes? Consensus summary from a global stroke forum

The success of acute stroke treatment is first and foremost time‐dependent, and the need for improvement in acute stroke management is demonstrated by the fact that only a minority of patients gain access to treatment – in particular, intravenous recombinant tissue plasminogen activator (IV tPA) – within the necessary time window. Standards of acute stroke care vary widely both regionally and nationally; consequently, various healthcare organizations have undertaken initiatives to measure and improve quality of care. To date, most quality measures have been process‐based, focusing primarily on metrics of patient care in the acute hospital‐based setting (e.g., time to recombinant tPA administration). Therefore, there remains a need for metrics designed to assess how improvements in process translate into patient outcomes. A global forum was convened to share best practice and provide consensus recommendations on core metrics for measuring improvements in access to care and patient outcomes. Recommendations for core metrics of patient outcomes include hospital‐based outcomes (e.g., neurological status at 24 h, ambulatory status at discharge) and post‐discharge outcomes (e.g., modified Rankin Scale score at 30 and/or 90 days). Recommendations for best practice relating to aspects of people, process, and technology involved in the stroke treatment pathway that may help provide improvements in these core outcome measures are also outlined.     

Should Stage T2 Esophageal Squamous Cell Carcinoma Be Subclassified?

Background

In patients with esophageal squamous cell carcinoma (ESCC), pathologic examination allows T2 tumors to be further subclassified according to whether the circular or longitudinal muscle layers are invaded. Therefore, we aimed to investigate whether subclassifying the T2 stages can aid in determining the prognosis for patients with ESCC.

Methods

The clinical and pathologic characteristics of 85 ESCC patients with T2 tumors who underwent thoracoscopic esophagectomy between 2008 and 2013 were retrospectively analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. The Kaplan–Meier method was used to compare survival differences with respect to each prognostic factor.

Results

Thirty-nine patients had tumors invading the circular muscle layer and were designated as having T2a disease. The remaining 46 patients had T2b disease, with tumors invading the longitudinal muscle layer. The overall 1-, 3-, and 5-year survival rates were 96.1, 53.8, and 36.4 %, respectively, with a median survival of 39.0 months. Univariate analysis indicated that sex, smoking history, grade, location, and tumor length did not significantly influence on survival. Only T stage (P = 0.017) and N stage (P = 0.003) were associated with survival. The results of multivariate Cox proportional hazard regression analysis showed that T stage (P = 0.045) and N stage (P = 0.003) were independent prognostic factors.

Conclusions

N stage and subclassified T stage are independent prognostic factors in patients with T2 tumors. Therefore, we concluded that T2 tumors can be subclassified further into T2a and T2b stages, and patients with different T2 stages may have different prognoses.     

Myeloid Mineralocorticoid Receptor Activation Contributes to Progressive Kidney Disease

Clinical and experimental studies have shown that mineralocorticoid receptor (MR) antagonists substantially reduce kidney injury. However, the specific cellular targets and mechanisms by which MR antagonists protect against kidney injury must be identified. We used conditional gene deletion of MR signaling in myeloid cells (MR^flox/flox LysM^Cre mice; MyMRKO) or podocytes (MR^flox/flox Pod^Cre mice; PodMRKO) to establish the role of MR in these cell types in the development of mouse GN. Accelerated anti–glomerular basement membrane GN was examined in groups of mice: MyMRKO, PodMRKO, wild-type (WT) littermates, and WT mice receiving eplerenone (100 mg/kg twice a day; EPL-treated). At day 15 of disease, WT mice had glomerular crescents (37%±5%), severe proteinuria, and a 6-fold increase in serum cystatin-C. MyMRKO, PodMRKO, and EPL-treated mice with GN displayed proteinuria similar to that in these disease controls. However, MyMRKO and EPL-treated groups had a 35% reduction in serum cystatin-C levels and reduced crescent numbers compared with WT mice, whereas PodMRKO mice were not protected. The protection observed in MyMRKO mice appeared to result predominantly from reduced recruitment of macrophages and neutrophils into the inflamed kidney. Suppression of kidney leukocyte accumulation in MyMRKO mice correlated with reductions in gene expression of proinflammatory molecules (TNF-α, inducible nitric oxide synthase, chemokine (C-C motif) ligand 2, matrix metalloproteinase-12), tubular damage, and renal fibrosis and was similar in EPL-treated mice. In conclusion, MR signaling in myeloid cells, but not podocytes, contributes to the progression of renal injury in mouse GN, and myeloid deficiency of MR provides protection similar to eplerenone in this disease.Mineralocorticoid receptor (MR) antagonists are known to inhibit renal and cardiovascular disease (CVD) by direct blockade of MR in tissues and by reducing hypertension.¹ They can also suppress kidney damage in animal models of GN and diabetic nephropathy without affecting BP.^2–6 In addition, MR antagonists provide added protection against proteinuria and loss of renal function when used with standard antihypertensive therapies in patients with diabetic and nondiabetic CKD.^7–9The clinical use of MR antagonists is limited by the development of hyperkalemia due to the importance of the MR in tubular regulation of salt balance.¹⁰ This consequence of MR blockade in the distal tubule is most evident during renal impairment and can require a reduction in the dosage of MR antagonist or withdrawal of the agent as a therapy.^7,8 The specific renal cell types that are targeted by MR antagonists to reduce injury during kidney disease have not been clearly identified. Establishing the identity of these cells is an important step toward developing more selective inhibitors of MR signaling that do not interfere with tubular cell function.Animal studies demonstrate that the protection afforded by MR antagonists in GN and diabetic nephropathy is associated with reductions in renal inflammation, proteinuria, and glomerular injury.^2,3,5,11 These studies also link MR blockade to suppression of leukocyte recruitment and podocyte injury. This suggests that the major pathologic effects of MR signaling may occur in podocytes and inflammatory cells.Recent in vitro studies have suggested that MR signaling can induce apoptosis in podocytes and oxidative stress in macrophages,^12,13 which supports a role for MR signaling in these cell types in kidney disease. In addition, an MR deficiency in myeloid cells protects against cardiovascular injury and ischemic cerebral infarcts by reducing inflammation and fibrosis.^14–16 However, no in vivo studies have identified whether MR signaling in podocytes or macrophages is specifically important to the development of kidney disease.In this study, we created mice with a selective genetic deficiency of MR in myeloid cells or podocytes and used these strains to evaluate the hypothesis that MR signaling in macrophages or podocytes is required for the development of renal injury in a normotensive model of progressive GN.     

Biomechanical and anatomical considerations in lumbar spinous process fixation—an in vitro human cadaveric model

Background contextAlthough multiple mechanisms of device attachment to the spinous processes exist, there is a paucity of data regarding lumbar spinous process morphology and peak failure loads.PurposeUsing an in vitro human cadaveric spine model, the primary objective of the present study was to compare the peak load and mechanisms of lumbar spinous process failure with variation in spinous process hole location and pullout direction. A secondary objective was to provide an in-depth characterization of spinous process morphology.Study designBiomechanical and anatomical considerations in lumbar spinous process fixation using an in vitro human cadaveric model.MethodsA total of 12 intact lumbar spines were used in the current investigation. The vertebral segments (L1–L5) were randomly assigned to one of five treatment groups with variation in spinous process hole placement and pullout direction: (1) central hole placement with superior pullout (n=10), (2) central hole placement with inferior pullout (n=10), (3) inferior hole placement with inferior pullout (n=10), (4) superior hole placement with superior pullout (n=10), and (5) intact spinous process with superior pullout (n=14). A 4-mm diameter pin was placed through the hole followed by pullout testing using a material testing system. As well, the bone mineral density (BMD) (g/cm³) was measured for each segment. Data were quantified in terms of anatomical dimensions (mm), peak failure loads (newtons [N]), and fracture mechanisms, with linear regression analysis to identify relationships between anatomical and biomechanical data.ResultsBased on anatomical comparisons, there were significant differences between the anteroposterior and cephalocaudal dimensions of the L5 spinous process versus L1–L4 (p<.05). Statistical analysis of peak load at failure of the four reconstruction treatments and intact condition demonstrated no significant differences between treatments (range, 350–500 N) (p>.05). However, a significant linear correlation was observed between peak failure load and anteroposterior and cephalocaudal dimensions (p<.05). Correlation between BMD and peak spinous processes failure load was approaching statistical significance (p=.08). 30 of 54 specimens failed via direct pullout (plow through), whereas 8 of 54 specimens demonstrated spinous process fracture. The remaining cases failed via plow through followed by fracture of the spinous process (16 of 54; 29%).ConclusionsThe present study demonstrated that variation in spinous process hole placement did not significantly influence failure load. However, there was a strong linear correlation between peak failure load and the anteroposterior and cephalocaudal anatomical dimensions. From a clinical standpoint, the findings of the present study indicate that attachment through the spinous process provides a viable alternative to attachment around the spinous processes. In addition, the anatomical dimensions of the lumbar spinous processes have a greater influence on biomechanical fixation than either hole location or BMD.     

Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia,Glucose Intolerance,and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice

Maternal obesity and gestational diabetes mellitus (GDM) are associated with obesity and diabetes risk in offspring. We tested whether maternal insulin resistance, which frequently coexists with GDM and obesity, could independently contribute to dysregulation of offspring metabolism. Female mice haploinsufficient for insulin receptor substrate-1 (IRS1-het) are hyperinsulinemic and insulin resistant during pregnancy, despite normal plasma glucose and body weight, and thus serve as a model of isolated maternal insulin resistance. Wild-type (WT) offspring of IRS1-het dams insulin resistance-exposed [IR-exposed] were compared with WT offspring of WT dams. Despite no differences in adiposity, male IR-exposed pups were glucose intolerant (P = 0.04) and hyperinsulinemic (1.3-fold increase, P = 0.02) by 1 month of age and developed progressive fasting hyperglycemia. Moreover, male IR-exposed pups challenged with high-fat diet exhibited insulin resistance. Liver lipidomic analysis of 3-week-old IR-exposed males revealed increases in the 16:1n7 fraction of several lipid classes, suggesting increased Scd1 activity. By 6 months of age, IR-exposed males had increased lipid accumulation in liver as well as increased plasma refed fatty acids, consistent with disrupted lipid metabolism. Our results indicate that isolated maternal insulin resistance, even in the absence of hyperglycemia or obesity, can promote metabolic perturbations in male offspring.