Publications
383 results found
Wu X, Gao Y, Shi C, et al., 2023, Complement C1q drives microglia-dependent synaptic loss and cognitive impairments in a mouse model of lipopolysaccharide-induced neuroinflammation., Neuropharmacology, Vol: 237
Activated microglia and subsequent release of pro-inflammatory cytokines result in neuroinflammatory status which further damage neurological function including cognitive impairments in various neurological conditions. However, the underlying molecular mechanisms during these pathological processing remain unknown. In the current study, mice received intraperitoneal administrations of LPS (0.5 mg/kg, daily, Escherichia coli O55:B5) for seven consecutive days and their different cohorts were used for behavioral assessment with open field, Y maze, and novel object recognition test or for electrophysiology recordings of mEPSC, LFP or LTP in in vivo or ex vivo preparation. The hippocampus from some cohorts were harvested for immunostaining or Western blotting of c1q, Iba-1, CD68, PSD95 and dendritic spine density or for transcriptome and proteomics analysis. Repeated LPS injections induced an up-regulation of complement system protein c1q and distinct microglial phenotype with an enrichment of the complement-phagosome pathway. Microglial synaptic engulfment and profound synaptic loss were found. These pathological changes were accompanied with the significantly decreased excitatory synaptic transmission, disturbed theta oscillations, impaired hippocampal long-term potentiation, and cognitive impairments. Notably, neutralization of c1q signaling robustly prevented these changes. Collectively, our data provide evidence that activated microglia and complement cascade c1q signaling in the hippocampus may account for synaptic loss and cognitive impairments in a mouse model of neuroinflammation induced by repeated LPS injections. Our work implicates that complement system may be a therapeutic target for developing therapies to prevent or treat cognitive disorders related to neuroinflammation or other disease conditions including neurodegenerative disease per se.
Zhang Y, Su Y, Wang Z, et al., 2023, TAK1 Reduces Surgery-induced Overactivation of RIPK1 to Relieve Neuroinflammation and Cognitive Dysfunction in Aged Rats., Neurochem Res, Vol: 48, Pages: 3073-3083
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.
Zhu J, Chen C, Wu J, et al., 2023, Effects of propofol and sevoflurane on social and anxiety-related behaviours in sleep-deprived rats., Br J Anaesth, Vol: 131, Pages: 531-541
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Zhai Q, Zhang Y, Ye M, et al., 2023, Reducing complement activation during sleep deprivation yields cognitive improvement by dexmedetomidine., Br J Anaesth, Vol: 131, Pages: 542-555
BACKGROUND: 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. METHODS: 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. RESULTS: 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 α2A 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. CONCLUSIONS: 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.
Duan W, Zhou C-M, Yang J-J, et al., 2023, A long duration of intraoperative hypotension is associated with postoperative delirium occurrence following thoracic and orthopedic surgery in elderly., J Clin Anesth, Vol: 88
BACKGROUND: Postoperative delirium (POD) is a common surgical complication associated with increased morbidity and mortality in elderly. Although the underlying mechanisms remain elusive, perioperative risk factors were reported to be closely related to its development. This study was designed to investigate the association between the duration of intraoperative hypotension and POD incidence following thoracic and orthopedic surgery in elderly. METHOD: The perioperative data from 605 elderly undergoing thoracic and orthopedic surgery from January 2021 to July 2022 were analyzed. The primary exposure was a cumulative duration of mean arterial pressure (MAP) ≤ 65 mmHg. The primary end-point was the POD incidence assessed with confusion assessment method (CAM) or CAM-ICU for three days after surgery. Restricted cubic spline (RCS) was conducted to examine the continuous relationship between the duration of intraoperative hypotension and POD incidence adjusted with patients' demographics and surgery related factors. Then the duration of intraoperative hypotension was categorized into three groups: no hypotension, short (< 5 mins) or long duration (≥ 5 mins) of hypotension for further analysis. RESULT: The incidence of POD was 14.7% (89 cases out of 605) within three days after surgery. The duration of hypotension presented a non-linear and "inverted L-shaped" effect on POD development. Compared to no hypotension, long duration (adjusted OR 3.93; 95% CI: 2.07-7.45; P < 0.001) rather than short duration of MAP ≤65 mmHg (adjusted OR 1.18; 95% CI: 0.56-2.50; P = 0.671) was closely related to the POD incidence. CONCLUSION: Intraoperative hypotension (MAP ≤65 mmHg) for ≥5 mins was associated with an increased incidence of POD after thoracic and orthopedic surgery in elderly.
Xia M, Ma W, Zuo M, et al., 2023, Expert consensus on difficult airway assessment., Hepatobiliary Surg Nutr, Vol: 12, Pages: 545-566, ISSN: 2304-3881
BACKGROUND: Identifying a potentially difficult airway is crucial both in anaesthesia in the operating room (OR) and non-operation room sites. There are no guidelines or expert consensus focused on the assessment of the difficult airway before, so this expert consensus is developed to provide guidance for airway assessment, making this process more standardized and accurate to reduce airway-related complications and improve safety. METHODS: Seven members from the Airway Management Group of the Chinese Society of Anaesthesiology (CSA) met to discuss the first draft and then this was sent to 15 international experts for review, comment, and approval. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) is used to determine the level of evidence and grade the strength of recommendations. The recommendations were revised through a three-round Delphi survey from experts. RESULTS: This expert consensus provides a comprehensive approach to airway assessment based on the medical history, physical examination, comprehensive scores, imaging, and new developments including transnasal endoscopy, virtual laryngoscopy, and 3D printing. In addition, this consensus also reviews some new technologies currently under development such as prediction from facial images and voice information with the aim of proposing new research directions for the assessment of difficult airway. CONCLUSIONS: This consensus applies to anesthesiologists, critical care, and emergency physicians refining the preoperative airway assessment and preparing an appropriate intubation strategy for patients with a potentially difficult airway.
Cao S-J, Zhang Y, Zhang Y-X, et al., 2023, Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial., Br J Anaesth, Vol: 131, Pages: 253-265
BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).
Cao S-J, Zhang Y, Zhang Y-X, et al., 2023, Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial., Br J Anaesth, Vol: 131, Pages: 266-275
BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.
West R, Soo CP, Murphy J, et al., 2023, A protocol for a pilot study to assess the feasibility of a randomised clinical trial of perioperative intravenous lidocaine on colorectal cancer outcome after surgery (FLICOR trial)., BJA Open, Vol: 6
BACKGROUND: Cancer recurrence after curative cancer surgery significantly impacts patients and healthcare services. Before surgery, a small number of clinically undetectable circulating tumour cells are often present. The surgical stress response promotes the distribution and proliferation of circulating tumour cells leading to cancer recurrence and metastasis. Preclinical evidence suggests that lidocaine may exert 'anti-cancer' effects and alleviate pro-metastatic environments. The Feasibility Study of Lidocaine Infusion During Bowel Cancer Surgery for Cancer Outcome (FLICOR) will assess the feasibility of conducting a clinical trial on perioperative intravenous lidocaine infusion for postoperative colorectal cancer outcomes. METHODS: The study is a double-blinded, randomised, controlled pilot study for a full trial comparing intravenous lidocaine administration at 1.5 mg kg-1 bolus followed by 1.5 mg kg-1 h-1 infusion for 24 h with placebo in patients undergoing minimally invasive (laparoscopy or robotic) colorectal cancer surgery. The feasibility of data collection instruments will be measured, including those for future economic evaluation and clinical and patient-reported outcomes. For the exploratory outcomes, blood samples will be collected before and after surgery on days 0, 1, and 3. Recruitment is planned for two NHS Trusts over 6 months with a 12-month follow-up. Patients and clinicians will be asked for their feedback on the study process. DISSEMINATION PLAN: Study data will be disseminated to trial participants, the public, and academic communities. The work will be presented at national and international conferences to stimulate interest and enthusiasm for centres to participate in the future definitive trial. This research will also be published in peer-reviewed open-access journals. CLINICAL TRIAL REGISTRATION: ISRCTN29594895 (ISRCTN), NCT05250791 (ClinicalTrials.gov). PROTOCOL VERSION NUMBER AND DATE: 3.0, February 8, 2023.
Huang J, Gao X, Wang M, et al., 2023, Prophylactic Administration with Methylene Blue Improves Hemodynamic Stabilization During Obstructive Jaundice-Related Diseases' Operation: a Blinded Randomized Controlled Trial., J Gastrointest Surg
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 shoc
Chang E, Wang Y, Zhu R, et al., 2023, General anesthetic action profile on the human prefrontal cortex cells through comprehensive single-cell RNA-seq analysis, iScience, Vol: 26, Pages: 1-19, ISSN: 2589-0042
The cellular and molecular actions of general anesthetics to induce anesthesia state and also cellular signaling changes for subsequent potential "long term" effects remain largely elusive. General anesthetics were reported to act on voltage-gated ion channels and ligand-gated ion channels. Here we used single-cell RNA-sequencing complemented with whole-cell patch clamp and calcium transient techniques to examine the gene transcriptome and ion channels profiling of sevoflurane and propofol, both commonly used clinically, on the human fetal prefrontal cortex (PFC) mixed cell cultures. Both propofol and sevoflurane at clinically relevant dose/concentration promoted "microgliosis" but only sevoflurane decreased microglia transcriptional similarity. Propofol and sevoflurane each extensively but transiently (<2 h) altered transcriptome profiling across microglia, excitatory neurons, interneurons, astrocytes and oligodendrocyte progenitor cells. Utilizing scRNA-seq as a robust and high-through put tool, our work may provide a comprehensive blueprint for future mechanistic studies of general anesthetics in clinically relevant settings.
Mok V, Nixon J, Hu J, et al., 2023, The impact of perioperative acute kidney injury/failure on short and long surgical outcomes, Anesthesiology and Perioperative Science, Vol: 1
<jats:title>Abstract</jats:title><jats:p>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.</jats:p> <jats:p><jats:bold>Graphical Abstract</jats:bold></jats:p>
Saito J, Zao H, Wu L, et al., 2023, "Anti-cancer" effect of ketamine in comparison with MK801 on neuroglioma and lung cancer cells., Eur J Pharmacol, Vol: 945
Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, is commonly used to induce anaesthesia during cancer surgery and relieve neuropathic and cancer pain. This study was conducted to assess whether ketamine has any inhibiting effects on neuroglioma (H4) and lung cancer cells (A549) in vitro. The cultured H4 and A549 cells were treated with ketamine and MK801 (0.1, 1, 10, 100, or 1000 μM) for 24 h. The expressions of glutamate receptors on both types of cancer cells were assessed with qRT-PCR. In addition, cell proliferation and migration were assessed with cell counting Kit-8 and wound healing assays. Cyclin D1, matrix metalloproteinase 9 (MMP9), phosphorylation of extracellular signal-regulated kinase (pERK), and cleaved-caspase-3 expression together with reactive oxygen species (ROS) were also assessed with Western blot, immunostaining, and/or flowcytometry. NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors were expressed on both H4 and A549 cells. Ketamine inhibited cancer cell proliferation and migration in a dose-dependent manner by suppressing the cell cycle and inducing apoptosis. Ketamine decreased cyclin D1, pERK, and MMP9 expression. In addition, ketamine increased ROS and cleaved caspase-3 expression and induced apoptosis. The anti-cancer effect of ketamine was more pronounced in A549 cells when compared with H4 cells. MK801 showed similar effects to those of ketamine. Ketamine suppressed cell proliferation and migration in both neuroglioma and lung cancer cells, likely through the antagonization of NMDA receptors.
Li X, Chang E, Cui J, et al., 2023, Bv8 mediates myeloid cell migration and enhances malignancy of colorectal cancer, Frontiers in Immunology, Vol: 14, Pages: 1-13, ISSN: 1664-3224
Colorectal cancer (CRC) is the third most predominant malignancy in the world. Although the importance of immune system in cancer development has been well established, the underlying mechanisms remain to be investigated further. Here we studied a novel protein prokineticin 2 (Prok2, also known as Bv8) as a key pro-tumoral factor in CRC progression in in vitro and ex vivo settings. Human colorectal tumor tissues, myeloid cell lines (U937 cells and HL60 cells) and colorectal cancer cell line (Caco-2 cells) were used for various studies. Myeloid cell infiltration (especially neutrophils) and Bv8 accumulation were detected in human colorectal tumor tissue with immunostaining. The chemotactic effects of Bv8 on myeloid cells were presented in the transwell assay and chemotaxis assy. Cultured CRC cells treated with myeloid cells or Bv8 produced reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF). Furthermore, ROS and VEGF acted as pro-angiogenesis buffer in myeloid cell-infiltrated CRC microenvironment. Moreover, myeloid cells or Bv8 enhanced energy consumption of glycolysis ATP and mitochondria ATP of CRC cells. Interestingly, myeloid cells increased CRC cell viability, but CRC cells decreased the viability of myeloid cells. ERK signalling pathway in CRC cells was activated in the presence of Bv8 or co-cultured myeloid cells. In conclusion, our data indicated the vital roles of Bv8 in myeloid cell infiltration and CRC development, suggesting that Bv8 may be a potential therapeutic target for colorectal cancer-related immunotherapy.
Rampes S, Ma D, 2023, The potential impact of COVID-19 disease caused multi-organ injuries on patients' surgical outcomes, Anesthesiology and Perioperative Science, Vol: 1
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>To provide an expert commentary on the impact of prior COVID-19 infection on patient’s surgical outcomes and postoperative recovery. To highlight the need for greater focus on peri-operative care of patients who have recovered from COVID-19.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>A narrative review of the literature was conducted by searching Pubmed and EMBASE for relevant articles using keywords such as “COVID-19”, “Coronavirus”, “surgery” and “peri-operative infection”.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Post-COVID-19 condition also known as long COVID has an estimated incidence of between 3.0 to 11.7%. COVID-19 has been shown to cause a series of short and long-term sequelae including cardiopulmonary complications, renal impairment, chronic fatigue and muscular deconditioning. Peri-operative infection with COVID-19 is associated with increased peri-operative mortality. Elective surgery patients who developed COVID-19 were 26 times more likely to die whilst in hospital compared to controls without COVID-19 infection, and for emergency surgery patients with COVID-19 infection were six times more likely to die. A large international prospective cohort study identified that patients who had surgery delayed over 7 weeks from the date of COVID-19 infection had no increased 30-day postoperative mortality, except those with ongoing symptoms.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>COVID-19 infection and its complications have be
Zhu Y, Zhou M, Jia X, et al., 2023, Inflammation Disrupts the Brain Network of Executive Function after Cardiac Surgery, ANNALS OF SURGERY, Vol: 277, Pages: E689-E698, ISSN: 0003-4932
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Pan W-T, Liu P-M, Ma D, et al., 2023, Advances in photobiomodulation for cognitive improvement by near-infrared derived multiple strategies., J Transl Med, Vol: 21
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.
Ye R, Lin Q, Xiao W, et al., 2023, miR-150-5p in neutrophil-derived extracellular vesicles associated with sepsis-induced cardiomyopathy in septic patients, CELL DEATH DISCOVERY, Vol: 9
Li P, Wang Y, Li H, et al., 2023, Prediction of postoperative infection in elderly using deep learning-based analysis: an observational cohort study, AGING CLINICAL AND EXPERIMENTAL RESEARCH, ISSN: 1594-0667
Chen Q, Liu X, Liu Z, et al., 2023, Tackling regulated cell death yields enhanced protection in lung grafts., Theranostics, Vol: 13, Pages: 4376-4390
Background: Effective preservation strategies to ameliorate lung graft ischaemia injury are needed to rescue 'extended criteria' or 'marginal' lung grafts, and to improve recipient outcomes after transplantation. Methods: Lung grafts from male Lewis rats were extracted after 40 min of cardiocirculatory death, and healthy human lung tissues were collected from patients undergoing a lobectomy. Lung samples were then preserved in a 4°C preservation solution supplemented with 0.1 nM Dexmedetomidine (Dex, α2-adrenoceptor agonist) for 16 h. In vitro, human lung epithelial A549 cells were preserved in the 4°C preservation solution with 0.1 nM Dex for 24 h, then re-cultured in the cell culture medium at 37°C to mimic the clinical scenario of cold ischaemia and warm reperfusion. Lung tissues and cells were then analysed with various techniques including western blot, immunostaining and electron microscope, to determine injuries and the protection of Dex. Results: Prolonged warm ischaemia after cardiocirculatory death initiated Rip kinase-mediated necroptosis, which was exacerbated by cold storage insult and enhanced lung graft injury. Dex supplementation significantly reduced necroptosis through upregulating Nrf2 activation and reducing oxidative stress, thereby significantly improving lung graft morphology. Dex treatment also attenuated endoplasmic reticulum stress, stabilised lysosomes and promoted cell membrane resealing function, consequently reducing cell death and inflammatory activation after hypothermic hypoxia-reoxygenation in A549 cells. Conclusions: Inhibition of regulated cell death through Dex supplementation to the graft preservation solution improves allograft quality which may aid to expand the donor lung pool and enhance lung transplant outcomes per se.
Liu X, Wang Y, Wu J, et al., 2023, Emergence delirium and postoperative delirium associated with high plasma NfL and GFAP: an observational study., Front Med (Lausanne), Vol: 10, ISSN: 2296-858X
BACKGROUND: Neuroinflammation and neuronal injury have been reported to be associated with the development of postoperative delirium in both preclinical and clinical settings. This study aimed to investigate the potential correlation between biomarkers of neurofilament light chain and glial fibrillary acidic protein and emergence and postoperative delirium in elderly patients undergoing surgery. METHODS: Patients who developed emergence delirium (n = 30) and postoperative delirium (n = 32), along with their matched controls, were enrolled after obtaining ethics approval and written informed consent. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit or Confusion Assessment Method scale, and blood samples were collected before and after surgery for plasma neurofilament light chain and glial fibrillary acidic protein measurements using a single-molecule array. RESULTS: The study found that in patients with emergence delirium, the increase in plasma neurofilament light chain protein levels during surgery was significantly higher than in non-delirium patients (P = 0.002). Additionally, in patients with postoperative delirium, both the increase in plasma neurofilament light chain protein levels (P < 0.001) and the increase in plasma glial fibrillary acidic protein levels during surgery (P = 0.008) were significantly higher than in non-delirium patients. Multivariate logistic regression analysis showed that the increase in plasma neurofilament light chain protein was associated with emergence delirium (adjusted OR = 1.872, P = 0.005), and the increase in plasma glial fibrillary acidic protein was associated with postoperative delirium (adjusted OR = 1.419, P = 0.016). Moreover, the American Society of Anesthesiologists Physical Status Classification and surgical duration were also found to be associated with delirium in elderly patients. CONCLUSION: Our findings suggest that emergence delirium is linked to elevated levels of neurofi
Lai D, Zhu K, Li S, et al., 2023, SARS-CoV-2 N Protein Triggers Acute Lung Injury via Modulating Macrophage Activation and Infiltration in in vitro and in vivo., J Inflamm Res, Vol: 16, Pages: 1867-1877, ISSN: 1178-7031
BACKGROUND: SARS-CoV-2-induced acute lung injury but its nucleocapsid (N) and/or Spike (S) protein involvements in the disease pathology remain elusive. METHODS: In vitro, the cultured THP-1 macrophages were stimulated with alive SARS-CoV-2 virus at different loading dose, N protein or S protein with/without TICAM2-siRNA, TIRAP-siRNA or MyD88-siRNA. The TICAM2, TIRAP and MyD88 expression in the THP-1 cells after N protein stimulation were determined. In vivo, naïve mice or mice with depletion macrophages were injected with N protein or dead SARS-CoV-2. The macrophages in the lung were analyzed with flow cytometry, and lung sections were stained with H&E or immunohistochemistry. Culture supernatants and serum were harvested for cytokines measurements with cytometric bead array. RESULTS: Alive SARS-CoV-2 virus or N protein but not S protein induced high cytokine releases from macrophages in a time or virus loading dependent manner. MyD88 and TIRAP but not TICAM2 were highly involved in macrophage activation triggered by N protein whilst both inhibited with siRNA decreased inflammatory responses. Moreover, N protein and dead SARS-CoV-2 caused systemic inflammation, macrophage accumulation and acute lung injury in mice. Macrophage depletion in mice decreased cytokines in response to N protein. CONCLUSION: SARS-CoV-2 and its N protein but not S protein induced acute lung injury and systemic inflammation, which was closely related to macrophage activation, infiltration and release cytokines.
Zhao J, Le Z, Chu L, et al., 2023, Risk factors and outcomes of intraoperative hypothermia in neonatal and infant patients undergoing general anesthesia and surgery., Front Pediatr, Vol: 11, ISSN: 2296-2360
OBJECTIVE: The incidence of intraoperative hypothermia remains high in pediatric patients during anesthesia and surgery even though core body temperature monitoring and warming systems have been greatly improved in recent years. We analyzed the risk factors and outcomes of intraoperative hypothermia in neonates and infants undergoing general anesthesia and surgery. METHODS: The data on the incidence of intraoperative hypothermia, other clinical characteristics, and outcomes from electronic records of 1,091 patients (501 neonates and 590 infants between 28 days and 1 year old), who received general anesthesia and surgery, were harvested and analyzed. Intraoperative hypothermia was defined as a core temperature below 36°C during surgery. RESULTS: The incidence of intraoperative hypothermia in neonates was 82.83%, which was extremely higher than in infants (38.31%, p < 0.001)-the same as the lowest body temperature (35.05 ± 0.69°C vs. 35.40 ± 0.68°C, p < 0.001) and the hypothermia duration (86.6 ± 44.5 min vs. 75.0 ± 52.4 min, p < 0.001). Intraoperative hypothermia was associated with prolonged PACU, ICU, hospital stay, postoperative bleeding, and transfusion in either age group. Intraoperative hypothermia in infants was also related to prolonged postoperative extubation time and surgical site infection. After univariate and multivariate analyses, the age (OR = 0.902, p < 0.001), weight (OR = 0.480, p = 0.013), prematurity (OR = 2.793, p = 0.036), surgery time of more than 60 min (OR = 3.743, p < 0.001), prewarming (OR = 0.081, p < 0.001), received >20 mL/kg fluid (OR = 2.938, p = 0.004), and emergency surgery (OR = 2.142, p =&
Wong R, Zhang Y, Zhao H, et al., 2022, Circular RNAs in organ injury: recent development, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 20
Zhao T, Shi Z, Ling N, et al., 2022, Sevoflurane Ameliorates Schizophrenia in a Mouse Model and Patients: A Pre-Clinical and Clinical Feasibility Study., Curr Neuropharmacol, Vol: 20, Pages: 2369-2380
BACKGROUND: GABAergic deficits have been considered to be associated with the pathophysiology of schizophrenia, and hence, GABA receptors subtype A (GABAARs) modulators, such as commonly used volatile anesthetic sevoflurane, may have therapeutic values for schizophrenia. The present study investigates the therapeutic effectiveness of low-concentration sevoflurane in MK801-induced schizophrenia-like mice and schizophrenia patients. METHODS: Three weeks after MK801 administration (0.5 mg kg-1, i.p. twice a day for 5 days), mice were exposed to 1% sevoflurane 1hr/day for 5 days. Behavioral tests, immunohistochemical analysis, western blot assay, and electrophysiology assessments were performed 1-week post-exposure. Ten schizophrenia patients received 1% sevoflurane 5 hrs per day for 6 days and were assessed with the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18) at week 1 and week 2. RESULTS: MK801 induced hypolocomotion and social deficits, downregulated expression of NMDARs subunits and postsynaptic density protein 95 (PSD95), reduced parvalbumin - and GAD67-positive neurons, altered amplitude and frequency of mEPSCs and mIPSCs, and increased the excitation/inhibition ratio. All these changes induced by MK-801 were attenuated by sevoflurane administration. Six and eight patients achieved a response defined as a reduction of at least 30% in the PANSS total score at 1st and 2nd week after treatments. The BPRS-18 total score was found to be significantly decreased by 38% at the 2nd week (p < 0.01). CONCLUSION: Low-concentration sevoflurane effectively reversed MK801-induced schizophrenialike disease in mice and alleviated schizophrenia patients' symptoms. Our work suggests sevoflurane to be a valuable therapeutic strategy for treating schizophrenia patients.
Yang Z, Pan X, Wu X, et al., 2022, TREM-1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4/NEMO pathway, FEBS JOURNAL, ISSN: 1742-464X
Hu C, Wang B, Liu Z, et al., 2022, Sevoflurane but not propofol enhances ovarian cancer cell biology through regulating cellular metabolic and signaling mechanisms, CELL BIOLOGY AND TOXICOLOGY, ISSN: 0742-2091
Iwasaki M, Zhao H, Hu C, et al., 2022, The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence, CELL BIOLOGY AND TOXICOLOGY, ISSN: 0742-2091
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Lin JA, Ma D, Wu SY, 2022, Editorial: Impact of anesthetics on cancer behavior and outcome, Frontiers in Pharmacology, Vol: 13
Liu F, Duan M, Fu H, et al., 2022, Orthopedic Surgery Causes Gut Microbiome Dysbiosis and Intestinal Barrier Dysfunction in Prodromal Alzheimer Disease Patients A Prospective Observational Cohort Study, ANNALS OF SURGERY, Vol: 276, Pages: 270-280, ISSN: 0003-4932
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