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Painful diabetic neuropathy is a common complication of diabetes produced by mechanisms that as yet are incompletely defined. The aim of this study was to investigate the roles of nuclear factor-kB (NF-kB) in the regulation of purinergic receptor P2X ligand-gated ion channel 3 (P2X3R) plasticity in dorsal root ganglion (DRG) neurons of rats with painful diabetes. Here, we showed that hindpaw pain hypersensitivity in streptozocininduced diabetic rats was attenuated by treatment with purinergic receptor antagonist suramin or A-317491. The expression and function of P2X3Rs was markedly enhanced in hindpaw-innervated DRG neurons in diabetic rats. The CpG (cytosine guanine dinucleotide) island in the p2x3r gene promoter region was significantly demethylated, and the expression of DNA methyltransferase 3b was remarkably downregulated in DRGs in diabetic rats. The binding ability of p65 (an active form of NF-kB) with the p2x3r gene promoter region and p65 expression were enhanced significantly in diabetes. The inhibition of p65 signaling using the NF-kB inhibitor pyrrolidine dithiocarbamate or recombinant lentiviral vectors designated as lentiviral vector-p65 small interfering RNA remarkably suppressed P2X3R activities and attenuated diabetic pain hypersensitivity. Insulin treatment significantly attenuated pain hypersensitivity and suppressed the expression of p65 and P2X3Rs. Our findings suggest that the p2x3r gene promoter DNA demethylation and enhanced interaction with p65 contributes to P2X3R sensitization and diabetic pain hypersensitivity.

PurposeTherapeutic hypothermia management remains controversial in patients with traumatic brain injury. We conducted a meta-analysis to evaluate the risks and benefits of therapeutic hypothermia management in patients with traumatic brain injury.MethodsWe searched the Web of Science, PubMed, Embase, Cochrane (Central) and Clinical Trials databases from inception to January 17, 2019. Eligible studies were randomised controlled trials that investigated therapeutic hypothermia management versus normothermia management in patients with traumatic brain injury. We collected the individual data of the patients from each included study. Meta-analyses were performed for 6-month mortality, unfavourable functional outcome and pneumonia morbidity. The risk of bias was evaluated using the Cochrane Risk of Bias tool.ResultsTwenty-three trials involving a total of 2796 patients were included. The randomised controlled trials with a high quality show significantly more mortality in the therapeutic hypothermia group [risk ratio (RR) 1.26, 95% confidence interval (CI) 1.04 to 1.53, p = 0.02]. Lower mortality in the therapeutic hypothermia group occurred when therapeutic hypothermia was received within 24 h (RR 0.83, 95% CI 0.71 to 0.96, p = 0.01), when hypothermia was received for treatment (RR 0.66, 95% CI 0.49 to 0.88, p = 0.006) or when hypothermia was combined with post-craniectomy measures (RR 0.69, 95% CI 0.48 to 1.00, p = 0.05). The risk of unfavourable functional outcome following therapeutic hypothermia management appeared to be significantly reduced (RR 0.78, 95% CI 0.67 to 0.91, p = 0.001). The meta-analysis suggested that there was a significant increase in the risk of pneumonia with therapeutic hypothermia management (RR 1.48, 95% CI 1.11 to 1.97, p = 0.007).ConclusionsOur meta-analysis demonstrated that therapeutic hypothermia did not reduce but might increase the mortality rate of patients with traumatic brain injury in some high-quality studies. However, traumatic brain injury patients with elevated intracranial hypertension could benefit from hypothermia in therapeutic management instead of prophylaxis when initiated within 24 h.

Objectives: The aim of this study is to explore the efficacy and safety of flexible ureteroscopy (fURS) with prestenting (PS) for patients and a newly starting department. Method: The data of patients who underwent fURS for calculi with nonprestenting (NPS) after a clinical practice change was compared with PS patients before. Result: In all, 199 patients met the inclusion criteria. There was no significant difference for both groups in basic demography except that the NPS group included more proximal ureteral stone. Subgroup analysis was then used by a different site. There was no significance in sheath success (4/100 vs. 1/99, p = 0.369). Stone free rate (SFR) and success rate between PS and NPS group showed significant difference in total (96.94 vs. 89.58%, p = 0.048, 96.97 vs. 85.00%, p = 0.005 respectively). Better SFR and success rate were found only for the renal stones in subgroup analysis (97.67 vs. 80.49%, p = 0.014, 97.67 vs. 74.42%, p = 0.003 respectively). Operative time was significantly longer based on stenting status (45.969 ± 19.4732 vs. 30.553 ± 8.9645 min, p = 0.01) and there was no difference in subgroup analysis. More complications were found in the NPS group, but no severe complications were encountered. Conclusion: Intentional PS is a feasible try for an amateur fURS surgeon or a newly started department in order to gain a better outcome and lower complications in the whole time. It improves the outcomes when additional small surgery is not the trouble.

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<b><i>Background:</i></b> The relationship between iron accumulation in the central nervous system and cognitive decline in Parkinson’s disease (PD) has not been fully elucidated. This study aimed to explore the value of quantitative susceptibility mapping in assessment of mild cognitive impairment (MCI) in PD. <b><i>Methods:</i></b> Sixteen PD patients with MCI (PD-MCI), sixteen normal cognition PD patients (PD-NC), and 28 healthy controls (HCs) were included. The differences in the magnetic susceptibility and Radiomic indicators among groups and their correlations with Montreal Cognitive Assessment-Basic (MoCA-B) scores and Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) were analyzed. Receiver operating characteristic curves were used to evaluate the diagnostic performance. <b><i>Results:</i></b> Higher iron deposition was observed in the cortical and subcortical structures of the PD patients compared with HCs, including limbic system, orbitofrontal cortex, cuneus, red nucleus, and substantia nigra. Combined magnetic susceptibility and texture index in hippocampus achieved the best diagnostic performance (area under curves: 0.828) in differentiating PD-MCI from PD-NC. The magnetic susceptibilities of the substantia nigra, red nucleus, putamen, globus pallidus, hippocampus, and thalamus were negatively correlated with the MoCA-B scores (all <i>p</i> &#x3c; 0.05), and of the putamen and amygdala were positively correlated with the UPDRS-III scores (both <i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> Higher iron deposition was observed in the cortical and subcortical structures of the PD-MCI and PD-NC groups. The susceptibility values of vulnerable brain subregions shown significant correlation with MoCA-B and UPDRS-III. Together with the texture index, magnetic susceptibility values could provide robust performance in distinguishing PD-MCI patients from PD-NC.