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Background. Persistent peripheral CD4+T cell differentiation towards T helper (Th)2 rather than Th1 has been proved to be related to immunosuppression and poor prognosis in sepsis. However, it is unclear whether these circulating Th1 and Th2 subtype accumulations differed in septic populations of distinct infection sites and presented different associations with outcomes among patients with pulmonary versus nonpulmonary sepsis. Methods. From a secondary analysis of a prospective observational study, seventy-four previously immunocompetent patients with community-acquired severe sepsis within 24 hours upon onset were enrolled. Whole blood was collected on the admission day (D0), 3rd day (D3), and 7th day (D7). The patients were classified as pulmonary (n=52) and nonpulmonary sepsis (n=22). Circulating Th1 and Th2 populations were evaluated by flow cytometry, and clinical data related to disease severity and inflammatory response were collected. The associations of circulating Th1 and Th2 subset accumulations with distinct infection sites or outcomes within subgroups were explored. Results. Patients with pulmonary sepsis held similar disease severity and 28-day mortality with those of nonpulmonary sepsis. Of note is the finding that circulating Th2 levels on D7 (P=0.04) as well as Th2/Th1 on D3 (P=0.01) and D7 (P=0.04) were higher in the pulmonary sepsis compared with nonpulmonary sepsis while Th1 levels were lower on D0, D3, and D7 (P=0.01, P<0.05, HR>1), rather than nonpulmonary sepsis. Conclusions. Circulating Th2 accumulation was more apparent among pulmonary sepsis while nonpulmonary sepsis was characterized with the hyperactive circulating Th1 subset among previously immunocompetent patients. This finding suggested that circulating Th1 and Th2 subset accumulations vary in septic subgroups with different infection sites.

An important feature characteristic of the data streams in many of today's big data applications is the intrinsic uncertainty, which could happen for both item occurrence and attribute value. While this has already posed great challenges for fundamental data mining tasks such as classification, things are made even more complicated by the fact that completely-labeled examples are usually unavailable in such settings, leaving researchers the only option to learn classifiers on partially-labeled examples on uncertain data streams. Furthermore, there will be concept drift on evolving data streams. To address these challenges, this paper therefore focuses on the study of learning from positive and unlabeled examples (PU) on uncertain data streams. To the best of our knowledge, this paper is the first work to address the uncertainty issue in both item occurrence (occurrence level) and attribute value (attribute level) for the problem of PU learning over streaming data. Firstly, we propose an algorithm to classify positive and unlabeled examples with both uncertainties (PUU). The algorithm extracts reliable positive and negative examples by clustering-based method, and then trains the classifier with Weighted Extreme Learning Machine (Weighted ELM). Secondly, we propose an algorithm of PU learning over uncertain data streams (PUUS). It adopts ensemble model and trains base classification by PUU. In order to detect concept drift, PUUS uses cluster set similarities between the current data block and history data block. We propose different update strategies for different concept drift to adapt to evolving uncertain data streams. Experimental results show that PUUS can effectively classify uncertain data streams with just positive and unlabeled data, while achieving in the meantime good performance in detecting and handling concept drifts.

Chronic pain is the most prominent and disabling symptom in the patients with osteoarthritis (OA), and the underlying mechanism largely remains unclear. Interleukin-6 (IL-6), a proinflammatory cytokine, is critically involved in the development and maintenance of central sensitization in several rodent models of chronic pain. The present study aims to elucidate the IL-6 mediated neurological adaptation in dorsal horn in the rat with monosodium iodoacetate (MIA) - induced OA. Significant upregulation of IL-6 expression was detected in the dorsal horn in the modeled rats. Blockade of IL-6 function by tocilizumab markedly suppressed the activation of astrocytes and microglia in the ipsilateral dorsal horn, reduced c-Fos immunoreactivity in dorsal horn neurons, and attenuated the upregulation of glutamate receptor subunits GluR1 and NR2B in dorsal horn in the rats with MIA-induced OA. It was further reported that administration of tocilizumab significantly improved the performance in weight-bearing test and mitigated the mechanical allodynia in the modeled rats. These data illustrated spinal IL-6 mediated mechanism underlying the chronic pain, and proposed the potential therapeutic effect of tocilizumab on the chronic pain in the setting of OA.

Background Quadratus lumborum block (QLB) can reduce pain and opioid consumption after cesarean delivery. This systematic review investigated the effectiveness of QLB in reducing postoperative opioid use and its effect on pain scores compared with other analgesic methods after cesarean delivery. Methods Six medical databases were searched from their inception to August 2019. Trials were eligible if parturients underwent cesarean delivery under spinal anesthesia (not epidural or general anesthesia). The primary outcome was postoperative opioid consumption during the first 24 and 48 h. Secondary outcomes included pain scores, patient satisfaction, and side effects. The risk of bias was assessed using the Cochrane tool. Where possible, meta-analytic techniques were used to synthesize data, presented as mean difference with 95% confidence interval (CI). Results Twelve studies involving 904 patients were identified and analyzed. Opioid (intravenous morphine) consumption was significantly reduced with QLB when compared with placebo or no block during the first 24 h by 14.1 mg, (95% CI −20.8 to −7.5 mg) and 48 h by 20.8 mg, (95% CI −33.1 to −8.5 mg). Additionally, QLB significantly reduced 12-h pain scores at rest and during movement. However, this difference disappeared at 24 and 48 h. There was insufficient evidence regarding postoperative opioid use or pain scores with the use of QLB compared to intrathecal morphine. Conclusions The review findings show the superior analgesic effect of QLB when compared with systemic opioids in reducing postoperative opioid consumption, when intrathecal morphine is not administered.

Background Low differentiation rates of mesenchymal stem cells (MSCs) limit their therapeutic effects on patients in clinical studies. Our previous study demonstrated that overexpressing p130 or E2F4 affected the multipotential differentiation of MSCs, and the underlying mechanism was attributed to the regulation of the G1 phase. Improving the efficiency of MSC differentiation into epithelial cells is considered to be a new method. Therefore, this study was conducted to evaluate the effects of overexpressing p130 or E2F4 in MSCs on improving re-epithelization in lipopolysaccharide (LPS)-induced ARDS animals. Methods Mouse MSCs (mMSCs) stably transfected with p130 and E2F4 were transplanted intratracheally into LPS-induced ARDS mice. After 7 and 14 days, the mice were sacrificed, and the histopathology of the lungs was assessed by haematoxylin-eosin staining and lung injury scoring. Homing and differentiation of mMSCs were analysed by labelling and tracking mMSCs with NIR815 dye and immunofluorescent staining. Surfactant proteins A and C and occludin in the lungs were assessed by western blot. Permeability was evaluated by analysing the protein concentration of BALF using ELISA. Alveolar fluid clearance was assessed by absorbance measurements of BALF. Lung fibrosis was assessed by Masson’s trichrome staining and Ashcroft scoring. Results The engraftment of mMSCs overexpressing p130 or E2F4 led to attenuated histopathological impairment of the lung tissue, and the lung injury scores of the LPS+mBM-MSC-p130 and LPS+mBM-MSC-E2F4 groups were also decreased (p p p p p Conclusion Overexpressing p130 or E2F4 in mMSCs could further improve the injured structure and function of epithelial cells in the lungs of ARDS mice as a result of improved differentiation of mMSCs into epithelial cells.

Background 5-HT3 receptor antagonists are effective antiemetics for perioperative use. However, their effects on myometrial contractility remain unknown. We examined whether three different 5-HT3 receptor antagonists could affect the contraction of human myometrium. Methods Samples of human myometrium were taken from parturients undergoing elective cesarean delivery. Effects of ondansetron, granisetron and tropisetron (over a range of 1–10 4 ng/mL) on spontaneous contraction (ratios of amplitude, interval, and duration of the contraction) were examined and compared to saline controls (n=6 for each agent). Results None of the three 5-HT3 receptor antagonists significantly affected myometrial contraction. Conclusion 5-HT3 receptor antagonists do not affect the contraction of myometrial strips isolated from term pregnant women.

Cannabinoid receptor type-2 (CB2, CB2 receptor or CB2-R) mediates analgesia via two mechanisms. CB2 receptors contained in peripheral immune tissue mediate analgesia by altering cytokine profiles, and thus have little adverse effects on central nervous systems (CNSs). CB2 is also expressed in the neurons and glial cells of the CNS. This neuronal expression may also contribute to pain attenuation. The CB2 receptor has been proposed as a potential target in treating chronic pain of several etiologies.

Complex regional pain syndrome type 1 (CRPS-I) remains one of the most clinically challenging neuropathic pain syndromes and its mechanism has not been fully characterized. Cannabinoid receptor 2 (CB2) has emerged as a promising target for treating different neuropathic pain syndromes. In neuropathic pain models, activated microglia expressing CB2 receptors are seen in the spinal cord. Chemokine fractalkine receptor (CX3CR1) plays a substantial role in microglial activation and neuroinflammation. We hypothesized that a CB2 agonist could modulate neuroinflammation and neuropathic pain in an ischemia model of CRPS by regulating CB2 and CX3CR1 signaling. We used chronic post-ischemia pain (CPIP) as a model of CRPS-I. Rats in the CPIP group exhibited significant hyperemia and edema of the ischemic hindpaw and spontaneous pain behaviors (hindpaw shaking and licking). Intraperitoneal administration of MDA7 (a selective CB2 agonist) attenuated mechanical allodynia induced by CPIP. MDA7 treatment was found to interfere with early events in the CRPS-I neuroinflammatory response by suppressing peripheral edema, spinal microglial activation and expression of CX3CR1 and CB2 receptors on the microglia in the spinal cord. MDA7 also mitigated the loss of intraepidermal nerve fibers induced by CPIP. Neuroprotective effects of MDA7 were blocked by a CB2 antagonist, AM630. Our findings suggest that MDA7, a novel CB2 agonist, may offer an innovative therapeutic approach for treating neuropathic symptoms and neuroinflammatory responses induced by CRPS-I in the setting of ischemia and reperfusion injury.

Background. It was suggested that labor may influence the spread of intrathecal bupivacaine using combined spinal epidural (CSE) technique. However, no previous studies investigated this proposition. We designed this study to investigate the spinal block characteristics of plain bupivacaine between nonlaboring and laboring parturients using CSE technique. Methods. Twenty-five nonlaboring (Group NL) and twenty-five laboring parturients (Group L) undergoing cesarean delivery were enrolled. Following identification of the epidural space at the L3-4 interspace, plain bupivacaine 10 mg was administered intrathecally using CSE technique. The level of sensory block, degree of motor block, and hemodynamic changes were assessed. Results. The baseline systolic blood pressure (SBP) and the maximal decrease of SBP in Group L were significantly higher than those in Group NL ( 𝑃 = 0 . 0 0 2 and 𝑃 = 0 . 0 3 , resp.). The median sensory level tested by cold stimulation was T6 for Group NL and T5 for Group L ( 𝑃 = 0 . 4 6 ). The median sensory level tested by pinprick was T7 for both groups ( 𝑃 = 0 . 3 5 ). The degree of motor block was comparable between the two groups ( 𝑃 = 0 . 8 5 ). Conclusion. We did not detect significant differences in the sensory block levels between laboring and nonlaboring parturients using CSE technique with intrathecal plain bupivacaine.

Background Health care-associated infection (HAI) in children is associated with morbidity and mortality, prolonged hospital stay, and increased health care costs. We report the prevalence of HAIs in children admitted to the pediatric nephrology unit of a large tertiary care pediatric hospital in China between 2000 and 2008. Methods A prospective infection control surveillance program led by physicians identified HAIs in admitted patients and sent monthly summary data to the hospital's Nosocomial Infections Committee. Infections at any body site meeting the Center for Disease Control and Prevention's former National Nosocomial Infection Surveillance System definitions were eligible for inclusion. Over the study period, various infection prevention and control strategies were introduced, including education on hand hygiene, measures to ensure appropriate antimicrobial prophylaxis for patients, and a guideline for antibiotic use. Results Of the 971 patients admitted, 81 had a total of 89 episodes of HAI (9.16%; 89/971); 75 patients (92.6%) had one HAI. The percentage of children acquiring HAI decreased from 12% to 6% over the observation period, representing a statistically significant linear trend. The most common type of HAI was respiratory tract infection (65.16%; n = 58), followed by gastrointestinal tract infection (11.24%; n = 10), skin and soft tissue infection (8.99% (n = 8), bloodstream infection (7.87%; n = 7), and urinary tract infection (6.74%; n = 6). Conclusion The incidence of HAI in a pediatric nephrology ward decreased over an 8-year period, associated with a surveillance program and education directed at hand hygiene and appropriate antibiotic use. Despite a strict visitor policy, respiratory tract infection was the most common HAI seen.

Background Metoclopramide and magnesium sulfate are extensively used agents in obstetrics. In this study, the relaxant properties of metoclopramide and magnesium sulfate on pregnant myometrium, together with the possible reversing influences of oxytocin and cabergoline (a dopamine D 2 receptor agonist), were investigated. Methods Myometrial strips from 24 parturients were randomly allocated to four groups: control (Group CON), magnesium sulfate and oxytocin (Group MSO), metoclopramide and oxytocin (Group MEO), and metoclopramide and cabergoline (Group MEC). Myometrial strips were mounted on a myograph bathed in Krebs buffer. Saline (Group CON) and five incremental doses of magnesium sulfate (Group MSO) or metoclopramide (Groups MEO and MEC) were sequentially microinjected into the bath. Subsequently, oxytocin (Groups CON, MSO and MEO) or cabergoline (Group MEC) was microinjected into the bath. The myometrial contractile characteristics after each drug injection, including contractile force, interval and duration, were analyzed. Results Magnesium sulfate was more potent for prolonging myometrial contractile interval than reducing contractile force. Metoclopramide relaxed myometrial contractions by inhibiting contractile force and prolonging contractile interval in a concentration-dependent manner. Oxytocin reversed both the inhibited contractile force and the prolonged contractile interval caused by a high concentration of magnesium sulfate but accelerated the contractile interval and had no significant effect on the contractile force suppressed by metoclopramide. The relaxant effects of metoclopramide were completely reversed by cabergoline. Conclusions Both magnesium sulfate and metoclopramide relaxed myometrial contractions, and exhibited different responses to subsequent oxytocin treatment. The relaxant mechanism of metoclopramide may be via blockade of dopamine D 2 receptor, which requires further investigation.