Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer’s disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65–88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2–4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (−51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 µM) in MCI subjects were associated with no conversion to dementia during the ensuing 2–4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI.

Human granulocyte colony-stimulating-factor (G-CSF) is widely used for treatment of neutropenia and to mobilize stem/progenitor cells for bone marrow transplantation. In studies of thousands of healthy donor subjects treated with G-CSF to mobilize stem/progenitor cells, the side-effect profile has been reported to be mild and reversible. In pre-clinical studies, G-CSF was reported to improve spatial learning performance and to markedly reduce amyloid deposition in hippocampus and entorhinal cortex in a murine model of Alzheimer's disease (AD). The present study investigated the effects of a five day schedule of G-CSF administration on tolerability, safety, and cognition in eight patients with mild to moderate stage AD. A double-blind placebo control, cross-over design was implemented. Treatment with G-CSF did not result in serious adverse events. The most common and expected side effects were transient increases in white blood cell count, myalgias and diffuse aching that improved with non-steroidal anti-inflammatory medications. Of a battery of cognitive tests administered using the CANTAB computerized system, only the mean paired associate learning (PAL total trials adjusted) was significantly improved at the final visit of the study compared to baseline values (p < 0.05). There were no significant differences in amyloid-β1-42 levels in cerebrospinal fluid measured two weeks after G-CSF and two weeks after placebo treatments. In conclusion, administration of G-CSF in a dosage regimen commonly used for bone marrow donors was well tolerated and safe, and provided a signal of positive change in a hippocampal-dependent task of cognitive performance.

Objective CT-Urography combined with 3D printing technology, digital design, construction of individualized PCNL puncture guides, and preliminary analyze their efficacy, safety puncture positioning for PCNL. Methods Twenty-two patients with renal calculi were randomly selected at the affiliated Hospital of Xuzhou Medical University during 2017–2018. We randomly divided the patients into two groups: in 10 experimental groups, we used our 3D printing personalized percutaneous puncture guide access plate for PCNL, and in the control group, 12 patients with standard USG guide PCNL. The accuracy of puncture position, puncture time, and intraoperative blood loss was compared. Results In the experimental group, 10 patients with 3D printing personalized percutaneous puncture guide access plate. The puncture needle was accessed through the guide plate and verified by the color Doppler. The single puncture, needle position, and depth success rate were 100.00% (10/10). The angles were consistent with the preoperative design. In the control group, 12 patients via USG guided PCNL success rate was 75.00% (9/12). The puncture time and amount of hemorrhage was (7.78 ± 0.94) min and (49.31 ± 6.43) mL, and (9.04 ± 1.09) min and (60.08 ± 12.18) mL, respectively. The above data of the two groups were statistically significant (P < 0.05). Conclusion 3D printing personalized percutaneous nephrolithotomy guide plate for PCNL can improve PCNL renal puncture channel positioning accuracy, shorten puncture time, reduce intraoperative blood loss, bleeding-related complications and provide a new method for PCNL renal puncture positioning, which is worthy of further clinical exploration.

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