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Background: The kidney-brain crosstalk has been involved in Alzheimer’s disease (AD) with the mechanism remaining unclear. The anti-aging factor Klotho was reported to attenuate both kidney injury and AD pathologies. Objective: To investigate whether plasma Klotho participated in kidney-brain crosstalk in AD. Methods: We enrolled 33 PiB-PET-positive AD patients and 33 amyloid-β (Aβ)-negative age- and sex-matched cognitively normal (CN) controls from the Chongqing Ageing & Dementia Study (CADS). The levels of plasma Klotho, Aβ, and tau in the cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. Results: We found higher plasma Klotho and lower estimated glomerular filtration rate (eGFR) levels in AD patients compared with CN. The eGFR was positively associated with Aβ42, Aβ40 levels in CSF and negatively associated with CSF T-tau levels. Plasma Klotho levels were both negatively correlated with CSF Aβ42 and eGFR. Mediation analysis showed that plasma Klotho mediated 24.96% of the association between eGFR and CSF Aβ42. Conclusion: Renal function impacts brain Aβ metabolism via the kidney-brain crosstalk, in which the plasma Klotho may be involved as a mediator. Targeting Klotho to regulate the kidney-brain crosstalk provides potential therapeutic approaches for AD.

Cerebrospinal fluid (CSF) biomarkers are essential for the accurate diagnosis of Alzheimer’s disease (AD), yet their measurement levels vary widely across centers and regions, leaving no uniform cutoff values to date. Diagnostic cutoff values of CSF biomarkers for AD are lacking for the Chinese population. As a member of the Alzheimer’s Association Quality Control program for CSF biomarkers, we aimed to establish diagnostic models based on CSF biomarkers and risk factors for AD in a Chinese cohort. A total of 64 AD dementia patients and 105 age- and sex-matched cognitively normal (CN) controls from the Chongqing Ageing & Dementia Study cohort were included. CSF Aβ42, P-tau181, and T-tau levels were measured by ELISA. Combined biomarker models and integrative models with demographic characteristics were established by logistic regression. The cutoff values to distinguish AD from CN were 933 pg/mL for Aβ42, 48.7 pg/mL for P-tau181 and 313 pg/mL for T-tau. The AN model, including Aβ42 and T-tau, had a higher diagnostic accuracy of 89.9%. Integrating age and APOE ε4 status to AN model (the ANA’E model) increased the diagnostic accuracy to 90.5% and improved the model performance. This study established cutoff values of CSF biomarkers and optimal combined models for AD diagnosis in a Chinese cohort.

Fibroblast growth factor-inducible-14 (Fn14), a receptor for tumor necrosis-like weak inducer of apoptosis, is expressed in the neurons of dorsal root ganglion (DRG). Its mRNA is increased in the injured DRG following peripheral nerve injury. Whether this increase contributes to neuropathic pain is unknown. We reported here that peripheral nerve injury caused by spinal nerve ligation (SNL) increased the expression of Fn14 at both protein and mRNA levels in the injured DRG. Blocking this increase attenuated the development of SNL-induced mechanical, thermal, and cold pain hypersensitivities. Conversely, mimicking this increase produced the increases in the levels of phosphorylated extracellular signal-regulated kinase ½ and glial fibrillary acidic protein in ipsilateral dorsal horn and the enhanced responses to mechanical, thermal, and cold stimuli in the absence of SNL. Mechanistically, the increased Fn14 activated the NF-κB pathway through promoting the translocation of p65 into the nucleus of the injured DRG neurons. Our findings suggest that Fn14 may be a potential target for the therapeutic treatment of peripheral neuropathic pain.

Background Dexmedetomidine (DEX) improves postoperative pain scores and prolongs the duration of blockage when combined with local anesthetics (LAs) for neuraxial and brachial plexus block; however, there is little information about the effectiveness of DEX as an adjuvant to LAs in paravertebral block (PVB). Therefore, a systematic review and meta-analysis were performed to evaluate the safety and efficacy of DEX combined with LAs in PVB. Method An electronic database search from inception date to February 2018 was performed. Randomized controlled trials (RCTs) comparing DEX as an adjuvant to LAs with LAs alone for PVB in adult patients were included. Postoperative pain scores, duration of analgesia, cumulative perioperative analgesic consumption, and adverse events were analyzed. Result We identified 7 trials enrolling 350 patients and found that DEX reduced pain scores at rest by standardized mean differences (SMD) −0.86 cm (95% confidence interval [CI] [−1.55, −0.17], P = .01) and SMD −0.93 cm (95% CI [−1.41, −0.26], P =.008) at postoperative 12 hours and 24 hours, respectively. DEX reduced pain scores while dynamic by SMD −1.63 cm (95% CI [−2.92, −0.34], P =.01) and SMD −1.78 cm (95% CI [−2.66, −0.90], P =.007) for postoperative 12 hours and 24 hours, respectively. DEX extended the duration of analgesia by weighted mean differences (WMD) 201.53 minutes (95% CI [33.45, 369.61], P =.02); and reduced cumulative postoperative analgesic consumption by WMD −7.71 mg (95% CI [−10.64, −4.78], P

Compared with the lung isolation using double-lumen endobronchial tube intubation, the artificial capnothorax using single-lumen endotracheal tube intubation has shown to be a safe, more convenient, and cost-effective procedure for thoracoscopic esophagectomy. However, the impact of capnothorax on coagulation is not well defined. Herein, we evaluate the impact of a capnothorax on coagulation and fibrinolysis in patients who undergoing thoracoscopic esophagectomy.Between March 2014 and August 2014, 24 patients underwent thoracoscopic esophagectomies for esophageal cancer with the procedure of artificial capnothorax (group P); we also performed 24 thoracoscopic esophagectomy cases without using capnothorax (group N). The demographics and arterial blood gas, as well as the parameters of coagulation and fibrinolysis, of the two groups were analyzed.The pH value of group P after CO2 insufflation was significantly lower than in group N (P 0.05), and the partial pressure of carbon dioxide (PaCO2) was significantly increased compared with group N (P 0.05). The R and K values after CO2 insufflation were significantly longer than before anesthesia (P 0.05), and both α angle and MA value after CO2 insufflation were significantly lower than those before anesthesia (P 0.05). No significant differences in R value, K value, α angle, or MA value were observed between pre-anesthesia and termination of capnothorax. No significant difference in LY30 data was found between different groups (P 0.05).Artificial capnothorax in patients receiving endoscopic resection of esophageal carcinoma had a significant impact on coagulation. These patients showed significant impairments in coagulation not observed in patients without artificial capnothorax.

We aim to assess efficacy and safety of remifentanil or sulfentanyl combined with propofol during painless gastroscopic examination in patients. In this study, 270 patients were randomly divided into 3 groups: propofol was given only in group P; propofol and remifentanil in group PR; propofol and sulfentanyl in group PS during the gastroscopic examination. Efficiency of group P was significantly higher than that of group PR and PS (P0.01) [corrected]. Efficiency of group PR was lower than that of group PS (P0.05). Incidence of chest wall rigidity and oxygen desaturation in group PR were higher than group P and PS (P0.05), whereas there was no difference between groups P and PS (P0.05). Propofol combined with remifentanil could provide satisfying anesthesia and more respiratory depression, whereas sulfentanyl at equivalent dose combined with propofol could also provide with satisfying anesthesia and less respiratory depression. Combined sufentanyl with propofol would be an effective anesthesia technique in the daytime procedure.

Excitatory amino acid transporters (EAATs) appear to participate in the pathogenesis of neuropathic pain. The present study was performed to evaluate the effects of the tricyclic antidepressant amitriptyline on the expressions of EAATs in neuropathic pain rats. Using spared nerve injured (SNI) male Sprague Dawley rats, we found that SNI induced an initial EAATs upregulation on postoperative day 1 within the ipsilateral spinal cord dorsal horn, followed by a downregulation on postoperative days 3 and 5. Intraperitoneal administration of amitriptyline reversed the downregulation of EAATs in SNI rats on postoperative days 3-5 and attenuated the mechanical allodynia. We further demonstrated that administration of amitriptyline alone induced an upregulation of EAATs in sham-operated rat but do not produce an antinociceptive effect. These results indicate that amitriptyline could increase the expression of EAATs which may be one of its mechanisms in the treatment of neuropathic pain.