Ventral Hippocampal CA1 Pyramidal Neurons Encode Nociceptive Information.

As a main structure of the limbic system, the hippocampus plays a critical role in pain perception and chronicity. The ventral hippocampal CA1 (vCA1) is closely associated with negative emotions such as anxiety, stress, and fear, yet how vCA1 neurons encode nociceptive information remains unclear. Using in vivo electrophysiological recording, we characterized vCA1 pyramidal neuron subpopulations that exhibited inhibitory or excitatory responses to plantar stimuli and were implicated in encoding stimuli modalities in naïve rats. Functional heterogeneity of the vCA1 pyramidal neurons was further identified in neuropathic pain conditions: the proportion and magnitude of the inhibitory response neurons paralleled mechanical allodynia and contributed to the confounded encoding of innocuous and noxious stimuli, whereas the excitatory response neurons were still instrumental in the discrimination of stimulus properties. Increased theta power and theta-spike coupling in vCA1 correlated with nociceptive behaviors. Optogenetic inhibition of vCA1 pyramidal neurons induced mechanical allodynia in naïve rats, whereas chemogenetic reversal of the overall suppressed vCA1 activity had analgesic effects in rats with neuropathic pain. These results provide direct evidence for the representations of nociceptive information in vCA1.

[Clinical study on the treatment of acute paraquat poisoning with sequential whole gastric and bowel irrigation].

OBJECTIVE: To explore the clinical efficacy of early application of sequential gastrointestinal lavage in patients with acute paraquat poisoning by analyzing the clinical data of 97 patients. METHODS: A total of 97 eligible patients with acute paraquat poisoning were divided into conventional treatment group (n = 48) and sequential treatment group (n = 49). The conventional treatment group received routine gastric lavage with water. Then 30 g of montmorillonite powder, 30 g of activated charcoal, and mannitol were given to remove intestinal toxins once a day for five days. The sequential treatment group received 60 g of montmorillonite powder for oral administration, followed by small-volume low-pressure manual gastric lavage with 2.5%bicarbonate liquid. Then 30 g of activated charcoal, 30 g of montmorillonite powder, and polyethylene glycol electrolyte lavage solution were given one after another for gastrointestinal lavage once a day for five days. Both groups received large doses of corticosteroids, blood perfusion, and anti-oxidation treatment. The levels of serum potassium, serum amylase (AMY) alanine aminotransferase (ALT), total bilirubin (TBIL), blood urea nitrogen (BUN), creatinine (Cr), lactate (Lac), and PaO2of patients were determined at 1, 3, 5, 7, and 10 days. Laxative time, mortality, and survival time of dead cases were evaluated in the two groups. RESULTS: The incidence rates of hypokalemia (<3.5 mmol/L) and AMY (>110 U/L) were significantly lower in the sequential treatment group than in the conventional treatment group (P < 0.05). There were no significant differences in the incidence of ALT (>80 U/L), TBIL (>34.2 µmol/L), BUN (>7.2 mmol/L), and Cr (>177 µmol/L) between the two groups (P>0.05). However, the highest levels of ALT, TBIL, BUN, Cr, and Lac were significantly lower in the sequential treatment group than in the conventional treatment group (P < 0.05). Moreover, the sequential treatment group had significantly lower incidence of PaO2(<60 mmHg), shorter average laxative time, lower mortality, and longer survival time of dead cases than the conventional treatment group (P < 0.05). CONCLUSION: The early application of sequential gastrointestinal lavage can shorten laxative time, alleviate organ damage in the liver, kidney, lung, and pancreas, reduce mortality, and prolong the survival time of dead cases in patients with acute paraquat poisoning.

Anti-inflammatory effects of propofol on lipopolysaccharides-treated rat hepatic Kupffer cells.

This study is set to explore the role of commonly used intravenous anesthetic propofol on the inflammatory response of rat liver Kupffer cells (KCs) induced by lipopolysaccharides (LPS). The isolated KCs were cultured at the density of 1 × 10(5)/ml, divided into five groups randomly after 48 h culture: group C, control group; group L, KCs were treated with 1 µg/ml LPS for 24 h; groups P1, P2, P3, KCs were pretreated with propofol at low (25 µM), medium (50 µM), high (100 µM) concentration for 2 h, respectively, and then were stimulated with 1 µg/ml LPS for 24 h. The expressions of tumor necrosis factor-α (TNF-α) mRNA and interleukin-1ß (IL-1ß) mRNA of every group were measured by RT-PCR. Nuclear NF-ΚB p65 was determined by Western blot. The concentrations of IL-1ß and TNF-α in supernatant were measured by ELISA. Compared with the group C, TNF-α mRNA and IL-1ß mRNA in group L were significantly up-regulated and NF-ΚB p65 was significantly up-regulated after LPS treatment (P < 0.05). Meanwhile, TNF-α and IL-1ß were also significantly increased (P < 0.05). With propofol the mRNA expressions of aforementioned inflammatory mediators were significantly down-regulated and NF-ΚB p65 was significantly inhibited in group P2 and P3 (P < 0.05), compared with group L. However, low propofol concentration did not exhibit any effect (group P1, P > 0.05). Propofol at medium and high concentration can counteract the LPS-induced inflammatory response in KCs by regulating NF-ΚB p65 protein expression.

The epidemiology, antifungal use and risk factors of death in elderly patients with candidemia: a multicentre retrospective study.

BACKGROUND: The elderly patients affected by candidemia are growing in proportion to inpatients, but available data are limited. We aimed to determine the epidemiology, antifungal management and clinical risk factors of death in the elderly population with candidemia in China. METHODS: This retrospective study included 63 elderly (≥65 years) and 84 younger patients (16-60 years) at 4 tertiary hospitals. Multivariable logistic regression model was used to identify independent risk factors of death in elderly patients. RESULTS: The distribution of Candida species did not differ between elderly and younger patients (p >0.05). Resistance to fluconazole and voriconazole for non-Candida albicans species in elderly patients was approximately double that in younger patients. Host-related risk factors (e.g., underlying solid tumour, diabetes mellitus and chronic renal failure) and hospital-related factors (e.g., prior stay in an intensive care unit, mechanical ventilation, central vascular and urethral catheters placement) were identified more common in elderly patients. Elderly patients less often received triazoles and were less likely to receive antifungal therapies mostly because elderly or their guardians quit antifungal therapies. APACHE II scores and 30-day mortality were higher for elderly than younger patients (31.7% vs. 16.7%, p =0.032). For elderly patients, antifungal therapy administered before microbiological documentation was the only protective factor for death, whereas absence of antifungal therapies, receipt of mechanical ventilation and APACHE II score ≥20 were independent predictors of death. CONCLUSIONS: Elderly patients with candidemia had poor prognoses characterized by certain host and hospital-related risk factors and special pathogen resistance features. More awareness of the burden of this disease is required, and the absence of antifungal therapies should be avoided to improve the prognoses of elderly patients with this severe infection.