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Cancer is a growing global burden; there were an estimated 18 million new cancer diagnoses worldwide in 2020. Excisional surgery remains one of the main treatments for solid organ tumours in cancer patients and is potentially curative. Cancer- and surgery-induced inflammatory processes can facilitate residual tumour cell survival, growth, and subsequent recurrence. However, it has been hypothesised that anaesthetic and analgesic techniques during surgery might influence the risk of cancer recurrence. This narrative review aims to provide an updated summary of recent observational studies and new randomised controlled clinical trials on whether certain specific anaesthetic and analgesic techniques or perioperative interventions during tumour resection surgery of curative intent materially affect long-term oncologic outcomes. [ABSTRACT FROM AUTHOR]

The article discusses the condition of postoperative cognitive decline (POCD), its timing and duration of symptoms. POCD is clinically defined as an impairment of cognitive functions including memory, learning and concentration and manifested days or weeks after surgery. It cites the need for neuropsychological testing to detect POCD and the early identification of high-risk patients so their treatment can be optimized to modulate the processes that mediate cognitive change.

Abstract: Xenon, an NMDA receptor antagonist and dexmedetomidine (Dex), an α2-adrenoceptor agonist, both exhibit neuroprotective effects. We investigated the nature of their interaction. In vitro: a primary co-culture of neuronal and glial cells derived from neonatal mice was exposed to oxygen and glucose deprivation (OGD) and the resulting neuronal injury was assessed by the release of lactate dehydrogenase (LDH). In vivo: Postnatal rats aged 7 days underwent right common carotid artery ligation followed by 90min of hypoxia. The area of infarction was assessed at four days post-injury by morphological criteria. Long-term neurological function was evaluated at 30 days post-injury by testing co-ordination on rotarod. Both xenon and Dex concentration-dependently reduced LDH release with IC50 values of 42% atm (95% CI: 35–52) and 0.10μM (95% CI: 0.08–0.16), respectively. Isobolographic analysis showed that combined effect of xenon and Dex in vitro was additive. In vivo, a combination of xenon and Dex, at doses that are individually not neuroprotective, produced significant neuroprotective effect as measured by reduction in area of infarction. The long-term neurological function data corroborated these morphological data. Our study demonstrates that the combination of xenon and Dex offers neuroprotection additively in vitro and synergistically in vivo. [Copyright &y& Elsevier]

Which of the three α2-adrenoceptor subtypes of α2A, α2B, or α2C mediates the neuroprotective effect of dexmedetomidine was examined in cell culture as well as in an in vivo model of neonatal asphyxia. Dexmedetomidine dose-dependently attenuated neuronal injury (IC50=83±1 nM) in neuronal-glial co-cultures derived from wild-type mice; contrastingly, dexmedetomidine did not exert neuroprotection in injured cells from transgenic mice (D79N) expressing dysfunctional α2A-adrenoceptors. An α2A-adrenoceptor subtype-preferring antagonist 2-[(4,5-Dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole maleate (BRL44408) completely reversed dexmedetomidine-induced neuroprotection, while other subtype-preferring antagonists 2-[2-(4-(2-Methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione dihydrochloride (ARC239) (α2B) and rauwolscine (α2C) had no significant effect on the neuroprotective effect of dexmedetomidine in neuronal-glial co-cultures. Dexmedetomidine also protected against exogenous glutamate induced cell death in pure cortical neuron cultures assessed by flow cytometry and reduced both apoptotic and necrotic types of cell death. Likewise this neuroprotective effect was antagonised by BRL44408 but not ARC239 or rauwolscine. Dexmedetomidine exhibited dose-dependent protection against brain matter loss in vivo (IC50=40.3±6.1 μg/kg) and improved the neurologic functional deficit induced by the hypoxic-ischemic insult. Protection by dexmedetomidine against hypoxic-ischemic-induced brain matter loss was reversed by the α2A-adrenoceptor subtype-preferring antagonist BRL44408; neither ARC239 nor rauwolscine reversed the neuroprotective effect of dexmedetomidine in vivo. Our data suggest that the neuroprotective effect of dexmedetomidine is mediated by activation of the α2A adrenergic receptor subtype. [Copyright &y& Elsevier]

Investigates the radiological features of SARS. Suggestion that air-space disease is typical in SARS and may be indistinguishable from pneumonia of other causes; Progression of ground glass opacities on chest radiographs to focal, multifocal or diffuse consolidation; Unilateral movement; Utility of high resolution computed tomography and CT scans; Suggestion that some residual opacities found may not be reversible.

Cognitive function is an important ability of the brain, but cognitive dysfunction can easily develop once the brain is injured in various neuropathological conditions or diseases. Photobiomodulation therapy is a type of noninvasive physical therapy that is gradually emerging in the field of neuroscience. Transcranial photobiomodulation has been commonly used to regulate neural activity in the superficial cortex. To stimulate deeper brain activity, advanced photobiomodulation techniques in conjunction with photosensitive nanoparticles have been developed. This review addresses the mechanisms of photobiomodulation on neurons and neural networks and discusses the advantages, disadvantages and potential applications of photobiomodulation alone or in combination with photosensitive nanoparticles. Photobiomodulation and its associated strategies may provide new breakthrough treatments for cognitive improvement. [ABSTRACT FROM AUTHOR]

Memory impairment is one of the main characteristics of postoperative cognitive dysfunction. It remains elusive how postoperative pathological changes of the brain link to the memory impairment. The clinical setting of perioperation was mimicked via partial hepatectomy under sevoflurane anaesthesia together with preoperative restraint stress (Hep‐Sev‐stress) in mice. Memory changes were assessed with fear conditioning. The medial prefrontal cortex (mPFC)‐dorsal hippocampus connectivity was evaluated with injecting neurotracer 28 days before surgery. Astrocytic activation was limited via injecting AAV‐GFAP‐hM4Di‐eGFP into the mPFC. Astrocytic and microglial phagocytosis of synapses were visualised with co‐labelling hippocampal neuronal axon terminals with PSD‐95 and S100β or Iba1. Neuroinflammation and oxidative stress status were also detected. Hep‐Sev‐stress impaired the memory consolidation (mean [standard error], 49.91 [2.55]% vs. 35.40 [3.97]% in the contextual memory, p = 0.007; 40.72 [2.78]% vs. 27.77 [2.22]% in cued memory, p = 0.002) and the cued memory retrieval (39.00 [3.08]% vs. 24.11 [2.06]%, p = 0.001) in mice when compared with these in the naïve controls. Hep‐Sev‐stress damaged the connectivity from the dorsal hippocampus to mPFC but not from the mPFC to the dorsal hippocampus and increased the astrocytic but not microglial phagocytosis of hippocampal neuronal axon terminals in the mPFC. The intervention also induced neuroinflammation and oxidative stress in the dorsal hippocampus and the mPFC in a regional‐dependent manner. Limiting astrocyte activation in the mPFC alleviated memory consolidation impairment induced by Hep‐Sev‐stress. Postoperative memory consolidation was impaired due to astrocytic phagocytosis‐induced connectivity injury from the dorsal hippocampus to the medial prefrontal cortex. [ABSTRACT FROM AUTHOR]

Postoperative neurocognitive disorders (pNCD) are a common neurological complication, especially in elderly following anesthesia and surgery. Yet, the underlying mechanisms of pNCD remain elusive. This study aimed to investigate the molecular mechanisms that compromise synaptic metaplasticity in pNCD development with a focus on the involvement of Nogo‐66 receptor 1 (NgR1) in the pathogenesis of pNCD in aged mice. Aged mice subjected to anesthesia and laparotomy surgery exhibited anxiety‐like behavior and contextual fear memory impairment. Moreover, the procedure significantly increased NogoA and NgR1 expressions, particularly in the hippocampal CA1 and CA3 regions. This increase led to the depolymerization of F‐actin, attributed to the activation of the RhoA‐GTPase, resulting in a reduction of dendritic spines and changes in their morphology. Additionally, these changes hindered the efficient postsynaptic delivery of the subunit GluA1 and GluA2 of AMPA receptors (AMPARs), consequently diminishing excitatory neurotransmission in the hippocampus. Importantly, administering the competitive NgR1 antagonist peptide NEP1‐40 (Nogo‐A extracellular peptide residues 1–40 amino acids of Nogo‐66) and Fasudil (a Rho‐kinase inhibitor) effectively mitigated synaptic impairments and reversed neurocognitive deficits in aged mice following anesthesia and surgery. Our work indicates that high hippocampal Nogo66‐NgR1 signaling disrupts postsynaptic AMPA receptor surface delivery due to F‐actin depolymerization in the pathophysiology of pNCD. [ABSTRACT FROM AUTHOR]

Background: Postoperative neurocognitive disorders (PNDs) frequently occur following orthopedic surgery and are closely associated with adverse prognosis. PNDs are an emerging concept that includes both postoperative cognitive dysfunction (POCD) and postoperative delirium (POD). The prevention of combined use of peripheral nerve block (PNB) and general anesthesia (GA) on POCD and/or POD incidence following orthopedic surgery remains unknown. We aimed to investigate the effect of this combined anesthesia method on POCD/POD incidence after orthopedic surgery, compared with GA. Methods: The databases of PubMed, Web of Science, Embase via Ovid, and the Cochrane Central Register of Controlled Trials were searched for all available randomized controlled trials (RCTs). The incidence of POD/POCD was the primary outcome. Continuous and dichotomous outcomes are represented as standardized mean differences [SMD, 95% confidence interval (CI)] and risk ratios [RR, 95%CI], respectively. Results: Meta-analysis of twelve RCTs with a total of 1488 patients revealed that compared with GA, PNB plus GA decreased the incidence of POCD (RR: 0.58, 95%CI: 0.35 to 0.95, P = 0.03, I2 = 0%), while the incidence of POD had no significant difference (RR: 0.87, 95%CI: 0.54 to 1.40, P = 0.57, I2 = 67%). Compared with GA alone, a significant decrease of intraoperative and postoperative opioid consumption (SMD: -1.54, 95%CI: -2.26 to -0.82, P < 0.0001, I2 = 89%; SMD: -7.00, 95%CI: -9.89 to -4.11, P < 0.00001, I2 = 99%) and postoperative nausea and vomiting incidence (RR: 0.16, 95%CI: 0.06 to 0.44, P = 0.0004, I2 = 0%) was found with PNB plus GA. Conclusions: The combined use of PNB and GA decreases the incidence of POCD but not POD following orthopedic surgery. Trial registration: The protocol of this study was registered with PROSPERO (Registration Number: CRD42022366454). [ABSTRACT FROM AUTHOR]

Inappropriate perioperative fluid load can lead to postoperative complications and death. This retrospective study was designed to investigate the association between intraoperative fluid load and outcomes in neonates undergoing non-cardiac surgery. From April 2020 to September 2022, 940 neonates who underwent non-cardiac surgery were retrospectively enrolled and their perioperative data were harvested for further analysis. According to recorded intraoperative fluid volumes defined as ml.kg−1 h−1, patients were mandatorily divided into quintile with fluid load as restrictive (quintile 1, Q1), moderately restrictive (Q2), moderate (Q3), moderately liberal (Q4), and liberal (Q5). The primary outcomes were defined as prolonged length of hospital stay (LOS) (postoperative LOS ≥ 14 days), complications beyond prolonged LOS, and 30-day mortality. Secondary outcomes included postoperative complications within 14 days of hospital stay. The intraoperative fluid load was in Q1 of 6.5 (5.3–7.3) (median and IQR); Q2: 9.2 (8.7–9.9); Q3: 12.2 (11.4–13.2); Q4: 16.5 (15.4–18.0); and Q5: 26.5 (22.3–32.2) ml.kg−1 h−1. The odd of prolonged LOS was positively correlated with an increase fluid volume (Q5 quintile: OR 2.602 [95% CI 1.444–4.690], P = 0.001), as well as complications beyond prolonged LOS (Q5: OR 3.322 [95% CI 1.656–6.275], P = 0.001). The overall 30-day mortality rate was increased with high intraoperative fluid load but did not reach to a statistical significance after adjusted with confounders. Furthermore, the highest quintile of fluid load (26.5 ml.kg−1 h−1, IQR [22.3–32.2]) (Q5 quintile) was significantly associated with longer postoperative mechanical ventilation time compared with Q1 (Q5: OR 2.212 [95% CI 1.101–4.445], P = 0.026). Conclusion: Restrictive intraoperative fluid load had overall better outcomes, whilst high fluid load was significantly associated with prolonged LOS and complications after non-cardiac surgery in neonates. Trial registration: Chictr.org.cn Identifier: ChiCTR2200066823 (December 19, 2022). What is Known: • Inappropriate perioperative fluid load can lead to postoperative complications and even death. What is New: • High perioperative fluid load was significantly associated with an increased length of stay after non-cardiac surgery in neonates, whilst low fluid load was consistently related to better postoperative outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Removal of the primary tumor is the best treatment for solid tumor disease. However, perioperative factors such as surgical stress, pain, or anemia disrupt the innate and adaptive antitumor immune response and compromise the postoperative benefits of oncological surgery. Alternative strategies could be implemented during the perioperative period to improve immunosurveillance and reduce the incidence of recurrence. Here, we provide a comprehensive list of immunosuppressive factors occurring during the perioperative period and discuss pharmacological and non-pharmacological methods supporting the immune system, with the aim of assisting clinicians in their practice. Surgical excision of the primary tumor represents the most frequent and curative procedure for solid malignancies. Compelling evidence suggests that, despite its beneficial effects, surgery may impair immunosurveillance by triggering an immunosuppressive inflammatory stress response and favor recurrence by stimulating minimal residual disease. In addition, many factors interfere with the immune effectors before and after cancer procedures, such as malnutrition, anemia, or subsequent transfusion. Thus, the perioperative period plays a key role in determining oncological outcomes and represents a short phase to circumvent anesthetic and surgical deleterious factors by supporting the immune system through the use of synergistic pharmacological and non-pharmacological approaches. In line with this, accumulating studies indicate that anesthetic agents could drive both protumor or antitumor signaling pathways during or after cancer surgery. While preclinical investigations focusing on anesthetics' impact on the behavior of cancer cells are quite convincing, limited clinical trials studying the consequences on survival and recurrences remain inconclusive. Herein, we highlight the main factors occurring during the perioperative period of cancer surgery and their potential impact on immunomodulation and cancer progression. We also discuss patient management prior to and during surgery, taking into consideration the latest advances in the literature. [ABSTRACT FROM AUTHOR]

Background: Whilst concerns have been raised about the detrimental effects of general anaesthetics on the brain's development and function in the young, reports have indicated that thyroid hormones are able to promote neurogenesis in the developing brain. This present study aimed to investigate the effects of triiodothyronine (T3) on the neonatal rat brain, following sevoflurane exposure.Methods: Postnatal day 7 (P7) ratpups were treated with Triiodothyronine (T3) (1 µg/100 g body weight, i.p. injection, once/day for 3 days) after 2% sevoflurane exposure for 6 h. They were sacrificed at either P7 (immediately), P15 or P30 and their brains were harvested to assess cell death, proliferation in the hippocampus, N-methyl-D-aspartate (NMDA) receptor subunit A and B, and a post-synaptic protein (PSD-95 in the hippocampus,). Neuro-behavioral changes in other cohorts between P27 and P30 were evaluated with Morris water maze and open field tests.Results: Sevoflurane exposure caused cell death and suppressed the proliferation of astrocytes and neurons, as well as the dendritic growth of neurons in the hippocampus which were all reversed by the administration of T3. Moreover, cognitive function, including learning, memory, and adaptability to a new environment, were impaired by sevoflurane exposure, which was also negated by T3 treatment. Furthermore, sevoflurane decreased the expression of NMDA receptor subunits NR2A and NR2B, as well as PSD-95 in the hippocampus at P15 and those effects of sevoflurane were abolished by T3 administration.Conclusions: A potential therapeutic role of T3 in protecting general anesthetic induced neuronal injury in the developing brain is likely to occur through enhancing expression of PSD-95 and the NMDA NR2A and NR2B expression. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is an important cellular messenger molecule in the cardiovascular, nervous and immune systems. Real-time monitoring of NO activity in specific organelles of live cells is important to understand its biological function. In this work, a nucleus targetable ratiometric NO probe, Hoe–Rh-NO, is developed by linking Hoechst to rhodamine spirolactam. The Hoechst part conducts nucleus targeting and the rhodamine spirolactam senses NO. The two fluorophores constitute a NO switchable FRET system for ratiometric imaging. This newly developed probe Hoe–Rh-NO displays good nucleus targeting ability, high sensitivity and selectivity towards NO, low cytotoxicity and most importantly detects NO through ratiometric fluorescence imaging. By using Hoe–Rh-NO, we confirmed the presence of NO in the nucleus and detected endogenous NO during inflammation in cells and zebrafishes. [ABSTRACT FROM AUTHOR]

Delirium is the most common neurological complication after cardiac surgery with adverse impacts on surgical outcomes. Advanced age is an independent risk factor for delirium occurrence but its underlying mechanisms are not fully understood. Although increased A1 astrocytes and abnormal hippocampal networks are involved in neurodegenerative diseases, whether A1 astrocytes and hippocampal network changes are involved in the delirium‐like behavior of aged mice remains unknown. In the present study, a mice model of myocardial ischemia–reperfusion mimicking cardiac surgery and various assessments were used to investigate the different susceptibility of the occurrence of delirium‐like behavior between young and aged mice and the underlying mechanisms. The results showed that surgery significantly increased hippocampal A1 astrocyte activation in aged compared to young mice. The high neuroinflammatory state induced by surgery resulted in glutamate accumulation in the extrasynaptic space, which subsequently decreased the excitability of pyramidal neurons and increased the PV interneurons inhibition through enhancing N‐methyl‐D‐aspartate receptors' tonic currents in the hippocampus. These further induced the abnormal activities of the hippocampal neural networks and consequently contributed to delirium‐like behavior in aged mice. Notably, the intraperitoneal administration of exendin‐4, a glucagon‐like peptide‐1 receptor agonist, downregulated A1 astrocyte activation and alleviated delirium‐like behavior in aged mice, while IL‐1α, TNF‐α, and C1q in combination administered intracerebroventricularly upregulated A1 astrocyte activation and induced delirium‐like behavior in young mice. Therefore, our study suggested that cardiac surgery increased A1 astrocyte activation which subsequently impaired the hippocampal neural networks and triggered delirium development. [ABSTRACT FROM AUTHOR]

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence‐based Medicine Center of Lanzhou University, was established to develop evidence‐based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta‐analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi‐based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment. [ABSTRACT FROM AUTHOR]

Postoperative delirium is a relatively common and serious complication. It increases hospital stay by 2-3 days and is associated with a 30-day mortality of 7-10%. It is most prevalent in older patients, those with existing neurocognitive disorders, and those undergoing complex or emergency procedures. Preclinical and clinical research in recent years has uncovered more about the pathophysiology of postoperative delirium and may yield more potential therapeutic options. Using the enhanced recovery pathway framework of risk stratification, risk reduction, and rescue treatment, we have reviewed the current clinical evidence on the validity of delirium prediction scores for the surgical population, the effectiveness of perioperative delirium risk reduction interventions, and management options for established delirium. Effective perioperative interventions include depth of anaesthesia monitoring, intraoperative dexmedetomidine infusion, and multimodal analgesia. Choice of general anaesthetic agent may not be associated with significant difference in delirium risk. Several other factors, such as preoperative fasting, temperature control, and blood pressure management have some association with the risk of postoperative delirium; these will require further studies. Because of the limited treatment options available for established delirium, we propose that risk assessment and perioperative risk reduction may be the most effective approaches in managing postoperative delirium. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The effects of MCA and MPP on aluminum flame were investigated experimentally. • Flame propagation behaviors and flame temperatures were studied systematically. • Detailed suppression mechanisms by the MCA and MPP were proposed. • MPP was a better option as a suppressant for aluminum flame suppression system. Abstract The suppression effect of melamine cyanurate (MCA) and melamine polyphosphate (MPP) on the flame propagation of aluminum dust were studied experimentally. The results indicated that the concentration of MPP required to supress the aluminum dust explosion was lower than MCA. As the concentration of suppressant increased, the acceleration and the maximum flame speed extremely decreased, and the flame morphology became isolated spot flames. The MPP addition exerted a stronger suppression effect on the temperature of aluminum flame compared to MCA addition. Meanwhile, the mechanism of flame suppression was further investigated. Decomposition of MCA and MPP particles could absorb the heat released from the flame front. Scanning electron microscopy demonstrated that the gas phase reaction of aluminum particles was suppressed by MCA and MPP, resulting in a larger particle size of the explosion products. XRD results indicated that MCA and MPP did not react with aluminum. Gaseous products of suppressant decomposition altered flame chemistry by radically recombining O atom and reducing AlO, which resulted in less amount of heat release, lower flame speed and lower flame temperature. [ABSTRACT FROM AUTHOR]

• The suppressed flame configurations, propagation velocities and temperatures in 100 nm PMMA dust explosions were investigated. • The critical suppression proportion of ABC powder on 100 nm PMMA dust explosions was determined. • Detailed suppression mechanism was revealed. The suppression effects of ABC powder on 100 nm polymethyl methacrylate (PMMA) dust explosions with different mass densities were experimentally studied. Results showed that the suppressed flames were dim and the flame propagation was slowed down with the addition of ABC powder. When the proportion of suppressant increased, the average propagation velocity was decreased. After adding 30% ABC powder to 650 g/m3 PMMA dust cloud, the maximum suppression ratio for velocity was 93%. After adding 10% ABC powder, the temperatures of PMMA dust cloud with the mass densities of 250 g/m3, 450 g/m3 and 650 g/m3 were decreased to 19.8%, 27.4% and 33.1%, respectively. Meanwhile, the critical suppression proportion of PMMA dust explosion with three mass densities were 25%, 35% and 35%. Thermal analysis results showed that the addition of suppressant could increase the thermal stability of PMMA. The suppression mechanisms were comprised of physical suppression and chemical suppression which reflected on the consumption of H and OH radicals. The chemical kinetic models indicated that PO 2 and HOPO played a catalytic role in the combination of H and OH. [ABSTRACT FROM AUTHOR]

Background: Postoperative cognitive dysfunction (POCD) is a common clinical complication in elderly patients, but its underlying mechanism remains unclear. Receptor-interacting protein kinase 1 (RIPK1), a key molecule mediating necroptosis and regulated by transforming growth factor β-activated kinase 1 (TAK1), was reported to be associated with cognitive impairment in several neurodegenerative diseases. This study was conducted to investigate the possible role of TAK1/RIPK1 signalling in POCD development following surgery in rats. Methods: Young (2-month-old) and old (24-month-old) Sprague–Dawley rats were subjected to splenectomy under isoflurane anaesthesia. The young rats were treated with the TAK1 inhibitor takinib or the RIPK1 inhibitor necrostatin-1 (Nec-1) before surgery, and old rats received adeno-associated virus (AAV)-TAK1 before surgery. The open field test and contextual fear conditioning test were conducted on postoperative day 3. The changes in TNF-α, pro-IL-1β, AP-1, NF-κB p65, pRIPK1, pTAK1 and TAK1 expression and astrocyte and microglia activation in the hippocampus were assessed. Results: Old rats had low TAK1 expression and were more susceptible to surgery-induced POCD and neuroinflammation than young rats. TAK1 inhibition exacerbated surgery-induced pRIPK1 expression, neuroinflammation and cognitive dysfunction in young rats, and this effect was reversed by a RIPK1 inhibitor. Conversely, genetic TAK1 overexpression attenuated surgery-induced pRIPK1 expression, neuroinflammation and cognitive dysfunction in old rats. Conclusion: Ageing-related decreases in TAK1 expression may contribute to surgery-induced RIPK1 overactivation, resulting in neuroinflammation and cognitive impairment in old rats. [ABSTRACT FROM AUTHOR]

Objectives : Patients with obstruction jaundice are at a high risk of hypotension and need high volume of fluids and a high dose of catecholamine to maintain organ perfusion during operation procedure. All these likely contribute to high perioperative morbidity and mortality. The aim of the study is to evaluate the effects of methylene blue on the hemodynamics in patients undergoing surgeries associated with obstructive jaundice. Design: A prospective, randomized, and controlled clinical study. Setting: The enrolled patients randomly received 2 mg/kg of methylene blue in saline or saline (50 ml) before anesthesia induction. The primary outcome was the frequency and dose of noradrenaline administration to maintain mean arterial blood pressure over 65 mmHg or > 80% of baseline, and systemic vascular resistance (SVR) over 800 dyne/s/cm5 during operation. The secondary outcomes were liver and kidney functions, and ICU stay. Patients: Seventy patients were enrolled in the study and randomly assigned to receive either methylene blue or control (n = 35/group). Results: Fewer patients received noradrenaline in the methylene blue group when compared with the control group (13/35 vs 23/35, P = 0.017), and the noradrenaline dose administrated during operation was reduced in the methylene blue group when compared with the control group (0.32 ± 0.57 mg vs 1.787 ± 3.51 mg, P = 0.018). The blood level of creatinine, glutamic oxalacetic transaminase, and glutamic–pyruvic transaminase after the operation was reduced in the methylene blue group when compared with the control group. Conclusions: Prophylactic administration of methylene blue before operation associated with obstructive jaundice improves hemodynamic stability and short-term prognosis. Question: Methylene blue use prevented refractory hypotension during cardiac surgery, sepsis, or anaphylactic shock. It is still unknown that methylene blue on the vascular hypo-tone associated with obstructive jaundice. Findings: Prophylactic administration with methylene blue improved peri-operative hemodynamic stability, and hepatic and kidney function on the patients with obstructive jaundice. Meanings: Methylene blue is a promising and recommended drug for the patients undergoing the surgeries of relief obstructive jaundice during peri-operation management. [ABSTRACT FROM AUTHOR]

Sleep loss and its associated conditions (e.g. cognitive deficits) represent a large societal burden, but the underlying mechanisms of these cognitive deficits remain unknown. This study assessed the effect of dexmedetomidine (DEX) on cognitive decline induced by sleep loss. C57BL/6 mice were subjected to chronic sleep restriction (CSR) for 20 h (5 pm–1 pm the next day) daily for 7 days, and cognitive tests were subsequently carried out. The neuromolecular and cellular changes that occurred in the presence and absence of DEX (100 μg kg−1, i.v., at 1 pm and 3 pm every day) were also investigated. CSR mice displayed a decline in learning and memory by 12% (P <0.05) in the Y-maze and by 18% (P <0.01) in the novel object recognition test; these changes were associated with increases in microglial activation, CD68+ microglial phagosome counts, astrocyte-derived complement C3 secretion, and microglial C3a receptor expression (all P <0.05). Synapse elimination, as indicated by a 66% decrease in synaptophysin expression (P =0.0004) and a 45% decrease in postsynaptic density protein-95 expression (P =0.0003), was associated with the occurrence of cognitive deficits. DEX activated astrocytic α 2A adrenoceptors and inhibited astrocytic complement C3 release to attenuate synapse elimination through microglial phagocytosis. DEX restored synaptic connections and reversed cognitive deficits induced by CSR. The results demonstrate that complement pathway activation associated with synapse elimination contributes to sleep loss-related cognitive deficits and that dexmedetomidine protects against sleep deprivation-induced complement activation. Dexmedetomidine holds potential for preventing cognitive deficits associated with sleep loss, which warrants further study. [ABSTRACT FROM AUTHOR]

Sleep disorders can profoundly affect neurological function. We investigated changes in social and anxiety-related brain functional connectivity induced by sleep deprivation, and the potential therapeutic effects of the general anaesthetics propofol and sevoflurane in rats. Twelve-week-old male Sprague–Dawley rats were subjected to sleep deprivation for 20 h per day (from 14:00 to 10:00 the next day) for 4 consecutive weeks. They were free from sleep deprivation for the remaining 4 h during which they received propofol (40 mg kg–1 i.p.) or sevoflurane (2% for 2 h) per day or no treatment. These cohorts were instrumented for EEG/EMG recordings on days 2, 14, and 28. Different cohorts were used for open field and three-chambered social behavioural tests, functional MRI, nuclear magnetic resonance spectroscopy, and positron emission tomography imaging 48 h after 4 weeks of sleep deprivation. Propofol protected against sleep deprivation-induced anxiety behaviours with more time (44.7 [8.9] s vs 24.2 [4.1] s for the sleep-deprivation controls; P<0.001) spent in the central area of the open field test and improved social preference index by 30% (all P<0.01). Compared with the sleep-deprived rats, propofol treatment enhanced overall functional connectivity by 74% (P<0.05) and overall glucose metabolism by 30% (P<0.01), and improved glutamate kinetics by 20% (P<0.05). In contrast, these effects were not found after sevoflurane treatment. Unlike sevoflurane, propofol reduced sleep deprivation-induced social and anxiety-related behaviours. Propofol might be superior to sevoflurane for patients with sleep disorders who receive anaesthesia, which should be studied in clinical studies. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic power of using vertebral hydroxyapatite concentration measurements in unenhanced and contrast-enhanced spectral CT for detecting and predicting the risk of osteoporosis-associated fractures. Methods: L1 of 210 patients (105 men, 105 women; mean age, 64 years, range, 19–103 years) who had undergone spectral CT examinations from January 1, 2018, to March 1, 2019, were retrospectively analyzed. Patient data for 3 years after spectral CT were retrieved from electronic medical record information systems to obtain the incidence of osteoporotic fractures. Baseline vertebral cancellous hydroxyapatite concentration from unenhanced and contrast-enhanced late-arterial-phase images was measured. The receiver operating characteristic curves were used to evaluate the diagnostic power for detecting and predicting the 3-year risk of osteoporosis-associated fractures using hydroxyapatite concentrations in both phases. Results: The hydroxyapatite concentrations in both phases had good diagnostic power to detect fractures at baseline. The sensitivity and specificity for predicting one or more osteoporosis-associated fractures within 3 years after spectral CT were 76.80% and 93.10%, respectively, using the cutoff of 74.79 mg/cm3 in vertebral hydroxyapatite concentration in the unenhanced CT phase, and 82.87% and 82.76%, respectively, using the cutoff of 84.65 mg/cm3 in the late-arterial phase. Furthermore, there was no significant difference in the diagnosis between unenhanced and enhanced CT-derived hydroxyapatite concentrations (p = 0.360). Conclusions: Both unenhanced and enhanced spectral CT-derived hydroxyapatite concentrations can accurately detect and predict future risk of osteoporosis-associated fractures. The hydroxyapatite concentration assessed in the late-arterial phase may have a similar diagnostic efficacy to that in the unenhanced phase. Key Points: • A cutoff of 74.79 mg/cm3 of vertebral hydroxyapatite concentration in the unenhanced CT scans had 76.80% sensitivity and 93.10% specificity to predict one or more osteoporosis-associated fractures within 3 years after spectral CT examinations. • A cutoff of 84.65 mg/cm3 of vertebral hydroxyapatite concentration in the late-arterial-enhanced CT scans had 82.87% sensitivity and 82.76% specificity to predict one or more osteoporosis-associated fractures within 3 years after spectral CT examinations. • The hydroxyapatite concentration assessed in the late-arterial phase may have a similar diagnostic efficacy to that in the unenhanced phase. [ABSTRACT FROM AUTHOR]

The development of acute kidney injury after surgery is associated with significant mortality and morbidity and with worse short and long-term outcomes. Patients who develop acute kidney injury are at an increased risk of developing long-term renal dysfunction, which leads to lower quality of life and greater financial burden on the healthcare system. Although there are various systems to classify the severity of acute kidney injury, most systems only measure components that deteriorate after significant renal damage, such as urine output and serum creatinine. Surgical trauma and stress trigger acute kidney injury development, in addition to multiple co-morbidities, cardiovascular disease, and postoperative factors. The pathophysiology of acute kidney injury is complex, and this is reflected in the heterogenous population that is affected. Treatment is largely supportive and focuses on ensuring adequate renal perfusion, correcting electrolyte abnormalities and avoiding further renal injury. Current research focuses on novel biomarkers that detect decreased renal function earlier and that the deteriorating renal function can be treated before long-lasting damage occurs. This review discusses the epidemiology, aetiology, risk factors, and short and long-term surgical outcomes of acute kidney injury. Treatment, prevention, and recent developments in future research are also discussed. [ABSTRACT FROM AUTHOR]

Abstract: Rationale and objectives: To assess the use of chest digital radiograph (DR) assisted with a real-time interactive pulmonary nodule analysis system in large population lung cancer screening. Materials and methods: 346 DR/CR patient studies with corresponding CT images were selected from 12,500 patients screened for lung cancer from year 2007 to 2009. Two expert chest radiologists established CT-confirmed Gold Standard of nodules on DR/CR images with consensus. These cases were read by eight other chest radiologists (participating radiologists) first without using a real-time interactive pulmonary nodule analysis system and then re-read using the system. Performances of participating radiologists and the computer system were analyzed. Results: The computer system achieved similar performance on DR and CR images, with a detection rate of 76% and an average FPs of 2.0 per image. Before and after using the computer-aided detection system, the nodule detection sensitivities of the participating radiologists were 62.3% and 77.3% respectively, and the A z values increased from 0.794 to 0.831. Statistical analysis demonstrated statically significant improvement for the participating radiologists after using the computer analysis system with a P-value 0.05. Conclusion: The computer system could help radiologists identify more lesions, especially small ones that are more likely to be overlooked on chest DR/CR images, and could help reduce inter-observer diagnostic variations, while its FPs were easy to recognize and dismiss. It is suggested that DR/CR assisted by the real-time interactive pulmonary nodule analysis system may be an effective means to screen large populations for lung cancer. [Copyright &y& Elsevier]

Neonatal necrotizing enterocolitis (NEC) is a leading cause of intestine inflammatory disease, and macrophage is significantly activated during NEC development. Posttranslational modifications (PTMs) of proteins, particularly ubiquitination, play critical roles in immune response. This study aimed to investigate the effects of ubiquitin-modified proteins on macrophage activation and NEC, and discover novel NEC-related inflammatory proteins. Proteomic and ubiquitin proteomic analyses of intestinal macrophages in NEC/healthy mouse pups were carried out. In vitro macrophage inflammation model and in vivo NEC mouse model, as well as clinical human samples were used for further verification the inhibitor of nuclear factor-κB kinase α (IKKα) ubiquitination on NEC development through Western blot, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry. We report here that IKKα was a new ubiquitin-modified protein during NEC through ubiquitin proteomics, and RING finger protein 31 (RNF31) acted as an E3 ligase to be involved in IKKα degradation. Inhibition of IKKα ubiquitination and degradation with siRNF31 or proteasome inhibitor decreased nuclear factor-κB (NF-κB) activation, thereby decreasing the expression of pro-inflammatory factors and M1 macrophage polarization, resulting in reliving the severity of NEC. Our study suggests the activation of RNF31-IKKα-NF-κB axis triggering NEC development and suppressing RNF31-mediated IKKα degradation may be therapeutic strategies to be developed for NEC treatment. [ABSTRACT FROM AUTHOR]

Circular ribonucleic acids (circRNAs) are a class of long non-coding RNA that were once regarded as non-functional transcription byproducts. However, recent studies suggested that circRNAs may exhibit important regulatory roles in many critical biological pathways and disease pathologies. These studies have identified significantly differential expression profiles of circRNAs upon changes in physiological and pathological conditions of eukaryotic cells. Importantly, a substantial number of studies have suggested that circRNAs may play critical roles in organ injuries. This review aims to provide a summary of recent studies on circRNAs in organ injuries with respect to (1) changes in circRNAs expression patterns, (2) main mechanism axi(e)s, (3) therapeutic implications and (4) future study prospective. With the increasing attention to this research area and the advancement in high-throughput nucleic acid sequencing techniques, our knowledge of circRNAs may bring fruitful outcomes from basic and clinical research. [ABSTRACT FROM AUTHOR]

Background: There is a need to assess the long-term outcomes of survivors of critical illness from COVID-19.Methods: Ninety-two survivors of critical illness from COVID-19 from four hospitals in Hubei Province, China participated in this prospective cohort study. Multiple characteristics, including lung function (lung volumes, diffusing capacity for carbon monoxide, chest computed tomography scores, and walking capacity); immune status (SARS-CoV-2-neutralising antibody and all subtypes of immunoglobulin (Ig) G against SARS-CoV-2, immune cells in response to ex vivo antigen peptide stimuli, and lymphocyte count and its subtypes); liver, coagulation, and kidney functions; quality of life; cognitive function; and mental status, were assessed after 3, 6, and 12 months of follow-up.Results: Amongst the 92 enrolled survivors, 72 (78%) patients required mechanical ventilation. At 12 months, the predicted percentage diffusing capacity of lung for carbon monoxide was 82% (inter-quartile range [IQR]: 76-97%) with a residual volume of 77 (64-88)%. Other lung function parameters and the 6-min walk test improved gradually over time and were almost back to normal by 12 months. The titres of IgG and neutralising antibody to COVID-19 remained high at 12 months compared with those of controls who were not infected with COVID-19, although IgG titres decreased significantly from 34.0 (IQR: 23.8-74.3) to 15.0 (5.8-24.3) AU ml-1 (P<0.001), whereas neutralising antibodies decreased from 29.99 (IQR: 19.43-53.93) AU ml-1 at 6 months to 19.75 (13.1-29.8) AU ml-1 (P<0.001) at 12 months. In general, liver, kidney, physical, and mental functions also improved over time.Conclusions: Survivors of critical illness from COVID-19 show some persistent long-term impairments in lung function. However, a majority of these tests were normal by 12 months. These patients still had detectable levels of neutralising antibodies against SARS-CoV-2 and all types of IgG at 12 months, but the levels had declined over this time period.Clinical Trial Registration: None. [ABSTRACT FROM AUTHOR]

Abstract: Xenon and other inhalational agents induce cell and organ protection through different and only partially elucidated molecular mechanisms. Anesthesia induced or pharmacologic preconditioning is a recognized mechanism of cell protection. In this study we explored the gene transcription of activity-dependent neuroprotective protein (ADNP) in neonatal rat brain as consequence to xenon exposure, comparing the noble gas to nitrogen. Seven-day-old Sprague Dawley rats were exposed for 120min to 75% xenon and 25% oxygen or control condition consisting of 75% nitrogen and 25% oxygen (Air). ADNP was found to be differentially expressed by SSH, validated by Relative Real-Time PCR (RT-PCR) and confirmed by western blot and immunohistochemistry. The differential expression of ADNP in the rat neonatal brain may account for the preconditioning and neuroprotective effects exerted by gas xenon. [Copyright &y& Elsevier]

Background: Dexmedetomidine (DEX) has a pharmacological profile that should allow rapid recovery and prevent undesirable outcomes such as pulmonary complications. Methods: This large retrospective study compared the beneficial effects of perioperative infusion of DEX with propofol on the postoperative outcome after coronary artery bypass graft surgery. We reviewed patients' medical notes at Luoyang Central Hospital from 1st January 2012 to 31st December 2019. All continuous variables, if normally distributed, were presented as mean ± SD; Otherwise, the non-normally distributed data and categorical data were presented as median (25-75 IQR) or number (percentage). The Mann-Whitney U test and Chi-square test were used to evaluate the difference of variables between the DEX and propofol groups. Multivariate logistic regression analysis was performed on the main related and differential factors in the perioperative period. Results: A total of 1388 patients were included in the study; of those, 557 patients received propofol infusion, and 831 patients received dexmedetomidine. DEX significantly reduced postoperative pulmonary complications compared with propofol, 7.82% vs 13.29%; P < 0.01, respectively. When compared with propofol, DEX significantly shortened the duration of mechanical lung ventilation, 18 (13,25) hours vs 21 (16,37) hours; P < 0.001, the length of stay in the intensive care unit, 51 (42,90) vs 59 (46,94.5) hours; P = 0.001 and hospital stay, 20 (17,24) vs 22 (17,28) days; P < 0.001, respectively. The incidences of postoperative wound dehiscence and infection were significantly reduced with DEX compared with propofol groups, 2.53% vs 6.64%; P < 0.001, respectively. Interestingly, patients receiving DEX had significantly shorter surgical time compared to propofol; 275 (240,310) vs 280 (250,320) minutes respectively (P = 0.005) and less estimated blood loss (P = 0.001). Conclusion: Perioperative infusion of dexmedetomidine improved the desirable outcomes in patients who had coronary artery bypass graft surgery compared with propofol. [ABSTRACT FROM AUTHOR]

Background and Aim. Interleukin-6 (IL-6) modulates neurons–glia crosstalk and subsequently triggers hyperalgesia. This study is aimed at investigating whether the interaction between protein kinase C epsilon (PKCε) and signal transducer and activator of transcription 3 (STAT3) mediated IL-6-induced hyperalgesia and neurocyte activation. Methods. A rat hyperalgesia model was induced using an intraplantar injection of Freund's complete adjuvant (FCA) or an intrathecal injection of IL-6. Mechanical allodynia was evaluated using von Frey filament tests after intrathecal injections of T-5224 (c-Fos/AP-1 inhibitor), minocycline (Mino, a specific microglia inhibitor), L-2-aminoadipic acid (LAA, an astroglial toxin), PKCε inhibitor peptide, APTSTAT3-9R (STAT3 inhibitor), or anti-IL-6 antibody. The c-Fos, GFAP, Iba-1, PKCε, STAT3, pSTAT3Tyr705 and pSTAT3Ser727, and IL-6 expression at the spinal cord level was assessed by Western blot analysis. The interactive effects of PKCε and STAT3 were determined using immunofluorescence staining and immunoprecipitation in vivo and in vitro. Interleukin-6 promoter activity was examined using luciferase assays. Results. T-5224, Mino, and LAA attenuated FCA- or IL-6-mediated inflammatory pain, with a decrease in c-Fos, GFAP, Iba-1, PKCε, and IL-6 expression. PKCε inhibitor peptide and APTSTAT3-9R reversed FCA-induced nociceptive behavior, while decreasing pSTAT3Ser727, IL-6, c-Fos, GFAP, and Iba-1 expression and PKCε and STAT3 coexpression. Interleukin-6 promoter activity increased in the presence of PKCε and STAT3. The interaction with PKCε increased on phosphorylating STAT3 at Ser727 but not at Tyr705. Conclusion. STAT3 phosphorylation at Ser 727 and the interaction with PKCε contribute to hyperalgesia via the IL-6-mediated signaling pathway, thus regulating neuron–glia crosstalk during inflammatory pain. [ABSTRACT FROM AUTHOR]

Chemotherapy-related cognitive impairment (CRCI) is highly prevalent in patients with cancer and is associated with poor outcomes and quality of life. To date, the management of CRCI remains a clinical challenge. Herein, we aim to determine the preventive effects of probiotics on CRCI development and underlying mechanisms. We conducted a randomised, double-blind and placebo-controlled trial (ChiCTR-INQ-17014181) of 159 patients with breast cancer and further investigated the underlying mechanism in a pre-clinical setting. From 2018 to 2019, patients with breast cancer (Stage I-III) who needed adjuvant chemotherapy were screened, enrolled and randomly assigned to receive either probiotics or placebo (three capsules, twice/day) during chemotherapy. Their cognition, anxiety and depression were assessed with well-established assays; their plasma biomarkers, metabolites and faecal microbiota compositions were measured. In addition, the systemic effects of the metabolites found in the clinical trial on long-term potentiation, synapse injury, oxidative stress and glial activation were assessed in rats. Probiotics supplement significantly decreased the incidence of CRCI, improved the allover cognitive functions, changed the gut microbial composition and modulated nine plasma metabolite changes. Among these metabolites, p-Mentha-1,8-dien-7-ol, Linoelaidyl carnitine and 1-aminocyclopropane-1-carboxylic acid were negatively correlated with the occurrence of CRCI. Furthermore, probiotics supplement increased plasma p-Mentha-1,8-dien-7-ol in rats. Administration of exogenous p-Mentha-1,8-dien-7-ol significantly alleviated chemotherapy-induced long-term potentiation impairment, synapse injury, oxidative stress and glial activation in the hippocampus of rats. Our data indicated that probiotics supplement prevents the occurrence of CRCI in patients with breast cancer via modulating plasma metabolites, including p-Mentha-1,8-dien-7-ol. Chinese Clinical Trial Registry (ChiCTR-INQ-17014181) [ http://www.chictr.org.cn/showproj.aspx?proj=24294 ]. • Probiotics prevented chemotherapy-related cognitive impairment in patients. • Probiotics supplement mitigated chemotherapy-induced metabolic abnormalities. • p-Mentha-1,8-dien-7-ol(i.p.) alleviated CRCI-related brain impairment in rats. [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic encephalopathy (HIE) is a major cause of newborn brain injury. Apoptosis and necroptosis are two forms of cell death which may occur in HIE but reported data are yet limited. This study investigates the expression of receptor interacting protein kinase (RIPK) 1 and 3, and caspase3, the key modulators of necroptosis and apoptosis, respectively, in a model of HIE to determine whether both forms of cell death occur in the corresponding brain regions. Postneonatal day 7 Sprague-Dawley rats were subjected to right carotid artery ligation followed by hypoxia or subjected to skin incision under surgical anesthesia without ligation and hypoxia. Neuroglioma (H4) cell was cultured and subjected to 24 h hypoxic insults. Necrostatin-1, a RIPK1 inhibitor, was administered in both in vivo and in vitro settings before insult. After hypoxic-ischemic insults, both RIPK1 and RIPK3 expression were significantly increased in the region of hippocampal dentate gyrus in the injurious hemisphere. However, cleaved caspase3 was significantly increased in the hippocampal cornu ammonis 1 region in the injurious hemisphere. After hypoxic insults, RIPK1 and RIPK3 expression was also found in H4 cells. In addition, it was identified that the increased RIPK1 and RIPK3 can be inhibited by necrostatin-1 in both in vivo and in vitro. These data indicated that apoptosis and necroptosis occur in different brain regions of hippocampus in a model of HIE which may suggest that strategies to prevent each form of neuronal death is valuable to be developed. [ABSTRACT FROM AUTHOR]

[Display omitted] Intravenous anesthesia with propofol was reported to improve cancer surgical outcomes when compared with inhalational anesthesia. However, the underlying molecular mechanisms largely remain unknown. The anti-tumor effects of propofol and the possible underlying mechanism including altered metabolic and signaling pathways were studied in the current study. The cell viability, proliferation, migration, and invasion of cancer cells were analyzed with CCK-8, Ki-67 staining, wound healing, and Transwell assay, respectively. The protein changes were analyzed with Western blot and immunofluorescent staining. The metabolomics alteration was studied with 1H-NMR spectroscopy. The gene expression regulations were analyzed with PCR gene array and qRT-PCR experiments. In this study, we found that propofol reduced cell viability and inhibited cell proliferation, migration and invasion of lung cancer cells, but not neuroglioma cells. In lung cancer cells, propofol downregulated glucose transporter 1 (GLUT1), mitochondrial pyruvate carrier 1 (MPC1), p-Akt, p-Erk1/2, and hypoxia- inducible factor 1 alpha (HIF-1 α) expressions and upregulated pigment epithelium-derived factor (PEDF) expression. Propofol increased intracellular glutamate and glycine but decreased acetate and formate whilst increased glucose, lactate, glutamine, succinate, pyruvate, arginine, valine, isoleucine, and leucine and glycerol, and decreased acetate, ethanol, isopropanol in the culture media of lung cancer cells. Furthermore, VEGFA, CTBP1, CST7, CTSK, CXCL12, and CXCR4 gene expressions were downregulated, while NR4A3, RB1, NME1, MTSS1, NME4, SYK, APC, and FAT1 were upregulated following the propofol treatment. Consistent with the phenotypical changes, these molecular and metabolic changes were not found in the neuroglioma cells. Our findings indicated anti-tumor effects of propofol on the lung cancer but not brain cancer, through the regulation of tumor metastasis-related genes, multi-cellular signaling and cellular metabolism. [ABSTRACT FROM AUTHOR]

As of 2018 cancer is responsible for almost 9.6 million deaths annually and, with an aging population, the incidence of cancer is expected to continue to rise. Surgery is an important treatment modality for patients with solid organ cancers. It has been postulated that, due to potentially overlapping processes underlying the development of malignancy and the therapeutic pathways of various anesthetic agents, the choice of anesthetic type and method of administration may affect post-operative outcomes in patients with cancer. This is a literature review of the most recent evidence extracted from various databases including PubMed, EMBASE, and the Cochrane, as well as journals and book reference lists. The review highlights the pathophysiological processes underpinning cancer development and the molecular actions of anesthetic agents, pre-clinical and retrospective studies investigating cancer and anesthetics, as well as ongoing clinical trials. Overall, there are conflicting results regarding the impact of regional vs. general anesthesia on cancer recurrence, whilst the majority of data suggest a benefit of the use of intravenous propofol over inhalational volatile anesthetics. The biological changes associated with the surgical inflammatory response offer a unique opportunity to intervene to counteract any potentially cancer-promoting effects. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) was reported to be one of the initiators of chronic kidney disease (CKD) development. Necroinflammation may contribute to the progression from AKI to CKD. Dexmedetomidine (Dex), a highly selective α 2 -adrenoreceptor (AR) agonist, has cytoprotective and "anti-" inflammation effects. This study was designed to investigate the anti-fibrotic properties of Dex in sepsis models. C57BL/6 mice were randomly treated with an i.p. injection of lipopolysaccharides (LPS) (10 mg/kg) alone, LPS with Dex (25 μg/kg), or LPS, Dex and Atipamezole (Atip, an α 2 -adrenoreceptor antagonist) (500 μg/kg) (n=5/group). Human proximal tubular epithelial cells (HK2) were also cultured and then exposed to LPS (1 μg/ml) alone, LPS and Dex (1 μM), transforming growth factor-beta 1 (TGF-β1) (5 ng/ml) alone, TGF-β1 and Dex, with or without Atip (100 μM) in culture media. Epithelial-mesenchymal transition (EMT), cell necrosis, necroptosis and pyroptosis, and c-Jun N-terminal kinase (JNK) phosphorylation were then determined. Dex treatment significantly alleviated LPS-induced AKI, myofibroblast activation, NLRP3 inflammasome activation, and necroptosis in mice. Atip counteracted its protective effects. Dex attenuated LPS or TGF-β1 induced EMT and also prevented necrosis, necroptosis, and pyroptosis in response to LPS stimulation in the HK2 cells. The anti-EMT effects of Dex were associated with JNK phosphorylation. Dex reduced EMT following LPS stimulation whilst simultaneously inhibiting pyroptosis and necroptosis via α 2 -AR activation in the renal tubular cells. The "anti-fibrotic" and cytoprotective properties and its clinical use of Dex need to be further studied. [ABSTRACT FROM AUTHOR]

Background: microRNAs (miRNAs) are single-stranded and noncoding RNA molecules that control post-transcriptional gene regulation. miRNAs can be tumor suppressors or oncogenes through various mechanism including cancer cell biology, cell-to-cell communication, and anti-cancer immunity. Main Body: Anesthetics can affect cell biology through miRNA-mediated regulation of messenger RNA (mRNA). Indeed, sevoflurane was reported to upregulate miR-203 and suppresses breast cancer cell proliferation. Propofol reduces matrix metalloproteinase expression through its impact on miRNAs, leading to anti-cancer microenvironmental changes. Propofol also modifies miRNA expression profile in circulating extracellular vesicles with their subsequent anti-cancer effects via modulating cell-to-cell communication. Conclusion: Inhalational and intravenous anesthetics can alter cancer cell biology through various cellular signaling pathways induced by miRNAs' modification. However, this area of research is insufficient and further study is needed to figure out optimal anesthesia regimens for cancer patients. [ABSTRACT FROM AUTHOR]

Background: Depression is a common and serious complication in new mothers. We investigated the hypothesis that neuraxial labor analgesia is associated with a decreased risk of postpartum depression.Methods: In this multicenter prospective cohort study with propensity score matching, 599 nulliparous women with single term cephalic pregnancy who planned vaginal delivery were enrolled and self-selected neuraxial analgesia or not. The primary outcome was 6-week postpartum depression assessed with the Chinese version Edinburgh Postnatal Depression Scale; a score of ≥10 was set as the threshold of postpartum depression. Logistic regression models were established to assess the association between neuraxial labor analgesia and postpartum depression.Results: Of the 577 parturients who completed the study, 417 (72.3%) received neuraxial analgesia and 160 (27.7%) did not. After propensity score matching, 433 parturients were included in the analysis; of whom, 279 (64.4%) received neuraxial analgesia and 154 (35.6%) did not. The incidence of postpartum depression was lower in parturients with neuraxial analgesia than in those without (14.9% [62/417] vs. 23.8% [38/160], P=0.012 before matching; 13.3% [37/279] vs. 23.4% [36/154], P=0.007 after matching). After adjustment for confounding factors, neuraxial analgesia was associated with decreased odds of postpartum depression (odds ratio [OR] 0.50, 95% CI 0.28-0.88, P=0.015 before matching; OR 0.40, 95% CI 0.21-0.77, P=0.006 after matching).Limitations: As an observational study, unidentified confounders might influence the results.Conclusions: In nulliparae with single term cephalic pregnancy preparing to give vaginal delivery neuraxial analgesia during labor was associated with a decreased risk of 6-week postpartum depression. [ABSTRACT FROM AUTHOR]