The effect of enhanced recovery after minimally invasive esophagectomy: a randomized controlled trial.

BACKGROUND: The purpose of this randomized controlled trial was to determine if enhanced recovery after surgery (ERAS) would improve outcomes for three-stage minimally invasive esophagectomy (MIE). METHODS: Patients with esophageal cancer undergoing MIE between March 2016 and August 2018 were consecutively enrolled, and were randomly divided into 2 groups: ERAS+group that received a guideline-based ERAS protocol, and ERAS- group that received standard care. The primary endpoint was morbidity after MIE. The secondary endpoints were the length of stay (LOS) and time to ambulation after the surgery. The perioperative results including the Surgical Apgar Score (SAS) and Visualized Analgesia Score (VAS) were also collected and compared. RESULTS: A total of 60 patients in the ERAS+ group and 58 patients in the ERAS- group were included. Postoperatively, lower morbidity and pulmonary complication rate were recorded in the ERAS+ group (33.3% vs. 51.7%; p = 0.04, 16.7% vs. 32.8%; p = 0.04), while the incidence of anastomotic leakage remained comparable (11.7% vs. 15.5%; p = 0.54). There was an earlier ambulation (3 [2-3] days vs. 3 [3-4] days, p = 0.001), but comparable LOS (10 [9-11.25] days vs. 10 [9-13] days; p = 0.165) recorded in ERAS+ group. The ERAS protocol led to close scores in both SAS (7.80 ± 1.03 vs. 8.07 ± 0.89, p = 0.21) and VAS (1.74 ± 0.85 vs. 1.78 ± 1.06, p = 0.84). CONCLUSIONS: Implementation of an ERAS protocol for patients undergoing MIE resulted in earlier ambulation and lower pulmonary complications, without a change in anastomotic leakage or length of hospital stay. Further studies on minimizing leakage should be addressed in ERAS for MIE.

The effect of perineural dexamethasone on rebound pain after ropivacaine single-injection nerve block: a randomized controlled trial.

BACKGROUND: Rebound pain after a single-shot nerve block challenges the real benefit of this technique. We aimed to investigate whether perineural dexamethasone addition decreased the incidence of rebound pain after a single-shot nerve block. METHODS: We randomly allocated 132 patients scheduled for open reduction internal fixation of an upper extremity closed fracture under single-shot peripheral nerve block and sedation into two groups. Patients in the dexamethasone group received nerve block with 0.375% ropivacaine and 8 mg dexamethasone, while those in the control group received ropivacaine only. Sixty-three patients in the dexamethasone group and 60 patients in the control group were analyzed for the incidence of rebound pain 48 h after block administration, which was the primary outcome. The secondary outcomes included the highest self-reported numeric rating scale (NRS) pain score, and NRS at 8, 12, 24, and 48 h after the block, sufentanil consumption, sleep quality on the night of surgery, patient satisfaction with the pain therapy, blood glucose at 6 h after the block, pain and paresthesia at 30 days after surgery. RESULTS: The incidence of rebound pain was significantly lower in the dexamethasone group (7 [11.1%] of 63 patients) than in the control group (28 [48.8%] of 60 patients [RR = 0.238, 95% CI (0.113-0.504), p = 0.001]. Dexamethasone decreased opioid consumption in 24 h after surgery (p < 0.001) and improved the sleep quality score on the night of surgery (p = 0.01) and satisfaction with pain therapy (p = 0.001). Multivariate logistic regression analysis showed that only group allocation was associated with the occurrence of rebound pain [OR = 0.062, 95% CI (0.015-0.256)]. Patients in the dexamethasone group reported later onset pain (19.7 ± 6.6 h vs 14.7 ± 4.8 h since block administration, mean ± SD, p < 0.001) and lower peak NRS scores [5 (3, 6) vs 8 (5, 9), median (IQR), p < 0.001] than those in the control group. CONCLUSIONS: The perineural administration of 8 mg dexamethasone reduces rebound pain after a single-shot nerve block in patients receiving ORIF for an upper limb fracture. TRIAL REGISTRATION: This study was retrospectively registered in the Chinese Clinical Trial Registry ( ChiCTR-IPR-17011365 ) on May 11th, 2017.

Intubation and Ventilation amid the COVID-19 Outbreak: Wuhan's Experience.

The COVID-19 outbreak has led to 80,409 diagnosed cases and 3,012 deaths in mainland China based on the data released on March 4, 2020. Approximately 3.2% of patients with COVID-19 required intubation and invasive ventilation at some point in the disease course. Providing best practices regarding intubation and ventilation for an overwhelming number of patients with COVID-19 amid an enhanced risk of cross-infection is a daunting undertaking. The authors presented the experience of caring for the critically ill patients with COVID-19 in Wuhan. It is extremely important to follow strict self-protection precautions. Timely, but not premature, intubation is crucial to counter a progressively enlarging oxygen debt despite high-flow oxygen therapy and bilevel positive airway pressure ventilation. Thorough preparation, satisfactory preoxygenation, modified rapid sequence induction, and rapid intubation using a video laryngoscope are widely used intubation strategies in Wuhan. Lung-protective ventilation, prone position ventilation, and adequate sedation and analgesia are essential components of ventilation management.

Emergency tracheal intubation in 202 patients with COVID-19 in Wuhan, China: lessons learnt and international expert recommendations.

Tracheal intubation in coronavirus disease 2019 (COVID-19) patients creates a risk to physiologically compromised patients and to attending healthcare providers. Clinical information on airway management and expert recommendations in these patients are urgently needed. By analysing a two-centre retrospective observational case series from Wuhan, China, a panel of international airway management experts discussed the results and formulated consensus recommendations for the management of tracheal intubation in COVID-19 patients. Of 202 COVID-19 patients undergoing emergency tracheal intubation, most were males (n=136; 67.3%) and aged 65 yr or more (n=128; 63.4%). Most patients (n=152; 75.2%) were hypoxaemic (Sao2 <90%) before intubation. Personal protective equipment was worn by all intubating healthcare workers. Rapid sequence induction (RSI) or modified RSI was used with an intubation success rate of 89.1% on the first attempt and 100% overall. Hypoxaemia (Sao2 <90%) was common during intubation (n=148; 73.3%). Hypotension (arterial pressure <90/60 mm Hg) occurred in 36 (17.8%) patients during and 45 (22.3%) after intubation with cardiac arrest in four (2.0%). Pneumothorax occurred in 12 (5.9%) patients and death within 24 h in 21 (10.4%). Up to 14 days post-procedure, there was no evidence of cross infection in the anaesthesiologists who intubated the COVID-19 patients. Based on clinical information and expert recommendation, we propose detailed planning, strategy, and methods for tracheal intubation in COVID-19 patients.

Expert Recommendations for Tracheal Intubation in Critically ill Patients with Noval Coronavirus Disease 2019.

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), is a highly contagious disease. It firstly appeared in Wuhan, Hubei province of China in December 2019. During the next two months, it moved rapidly throughout China and spread to multiple countries through infected persons travelling by air. Most of the infected patients have mild symptoms including fever, fatigue and cough. But in severe cases, patients can progress rapidly and develop to the acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulopathy. The new coronavirus was reported to spread via droplets, contact and natural aerosols from human-to-human. Therefore, high-risk aerosol-producing procedures such as endotracheal intubation may put the anesthesiologists at high risk of nosocomial infections. In fact, SARS-CoV-2 infection of anesthesiologists after endotracheal intubation for confirmed COVID-19 patients have been reported in hospitals in Wuhan. The expert panel of airway management in Chinese Society of Anaesthesiology has deliberated and drafted this recommendation, by which we hope to guide the performance of endotracheal intubation by frontline anesthesiologists and critical care physicians. During the airway management, enhanced droplet/airborne PPE should be applied to the health care providers. A good airway assessment before airway intervention is of vital importance. For patients with normal airway, awake intubation should be avoided and modified rapid sequence induction is strongly recommended. Sufficient muscle relaxant should be assured before intubation. For patients with difficult airway, good preparation of airway devices and detailed intubation plans should be made.

Propofol Regulates Neural Stem Cell Proliferation and Differentiation via Calmodulin-Dependent Protein Kinase II/AMPK/ATF5 Signaling Axis.

BACKGROUND: Propofol can cause degeneration of developing brain cells and subsequent long-term learning or memory impairment. However, at the early stage of embryonic development, the molecular mechanism of propofol-induced inhibition in neural stem cells (NSCs) neurogenesis is still unclear. The aim of this study was to determine the role of propofol in NSCs neurogenesis and, more importantly, to explore the underlying mechanism. METHODS: First, a single intraperitoneal injection of propofol was performed in pregnant mice, and 6 hours after administration of propofol, the hippocampus RNA and the protein of the embryos' brains was extracted to analyze the expression of neuron-specific markers. Second, the primary NSCs were isolated from the hippocampus of mouse embryonic brain and then treated with propofol for cell viability, immunostaining, and transwell assays; more importantly, we performed RNA sequencing (RNA-seq) and q-reverse transcription polymerase chain reaction assays to identify genes regulated by propofol; the Western blot, small interfering RNA (SiRNA), and luciferase reporter assays were used to study the effects of propofol on calmodulin-dependent protein kinase (CaMk) II/5' adenosine monophosphate-activated protein kinase (AMPK)/activating transcription factor 5 (ATF5) signaling pathway. RESULTS: Our results indicated that propofol treatment could inhibit the proliferation, migration, and differentiation of NSCs. The results of RNA-seq assays showed that propofol treatment resulted in downregulation of a group of Ca-dependent genes. The following mechanism studies showed that propofol regulates the proliferation, differentiation, and migration of NSCs through the CaMkII/phosphorylation of serine at amino acid position 485 (pS485)/AMPK/ATF5 signaling pathway. CONCLUSIONS: The results from study demonstrated that propofol inhibits the proliferation, differentiation, and migration of NSCs, and these effects are partially mediated by CaMkII/pS485/AMPK/ATF5 signaling pathway.

Effects of resveratrol pretreatment on endoplasmic reticulum stress and cognitive function after surgery in aged mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) seriously reduces quality of life and is associated with increased morbidity and mortality. The causes and neuropathogenesis of POCD remain largely unknown. Resveratrol, a sirtuin 1 (Sirt1) activator, is a polyphenol compound found in red wine that has protective functions in neuropathology paradigms. Endoplasmic reticulum stress (ERS) is a primary cellular response that activates the unfolded protein response (UPR). ERS and UPR mediate molecular and biochemical mechanisms related to neurodegeneration; however, the roles of ERS and Sirt1 in POCD remain unclear. The properties of resveratrol might be useful in the setting of POCD. METHODS: In the present study, we investigated learning and memory function and ERS pathways in aged mice after surgery under local anesthesia, and we evaluated the effects of resveratrol pretreatment. RESULTS: We found that resveratrol attenuated postoperative learning and memory impairment in aged mice postoperatively but did not alter locomotor activity. Resveratrol significantly decreased postoperative expression of ERS pathway UPR-related proteins and inflammatory mediators including nuclear factor-κB (NF-κB) in the hippocampus. This was accompanied by higher Sirt1 protein expression levels. Pretreatment with resveratrol did not affect the number of hippocampal neurons in aged mice after surgery. CONCLUSION: Overall, resveratrol pretreatment attenuated short-term learning and memory impairment and the ERS pathway UPR in aged mice after surgery under local anesthesia.

Pink1 attenuates propofol-induced apoptosis and oxidative stress in developing neurons.

BACKGROUND: The underlying mechanisms of propofol-induced neurotoxicity in developing neurons are still not completely understood. We examined the role of PTEN-induced kinase 1 (Pink1), an antioxidant protein, in propofol-induced apoptosis in developing neurons. MATERIALS AND METHODS: Primary hippocampal neurons isolated from neonatal Sprague-Dawley rats were exposed to propofol 20 µM for 2, 4, 6 and 12 h. Subsequently, neurons underwent overexpression and knockdown of Pink1, followed by propofol exposure (20 µM, 6 h). Neuron apoptosis was detected by terminal transferase deoxyuridine triphosphate-biotin nick-end labeling (TUNEL). Reactive oxygen species (ROS) production in neurons was detected by using a 2,7-dichlorodihydro-fluorescein diacetate probe and target protein or mRNA levels were analyzed by Western blotting or real-time polymerase chain reaction. RESULTS: Propofol treatment time-dependently increased the number of TUNEL-positive neurons and the expression levels of cleaved caspase-3 and B-cell lymphoma 2 (BcL-2) associated X protein, but decreased expression levels of BcL-2. Furthermore, propofol treatment time-dependently reduced the expression levels of Pink1 mRNA and protein. ROS production and the markers of oxidative stress, 2,4-dinitrophenol and 4-hydroxynonenal, were increased by propofol treatment. However, these propofol-induced changes were significantly restored by Pink1 overexpression. CONCLUSIONS: Pink1 plays an important role in neuronal apoptosis induced by propofol. Our results may provide some new insights in propofol-induced neurotoxicity in developing neurons.

Minocycline attenuates post-operative cognitive impairment in aged mice by inhibiting microglia activation.

Although it is known that isoflurane exposure or surgery leads to post-operative cognitive dysfunction in aged rodents, there are few clinical interventions and treatments available to prevent this disorder. Minocycline (MINO) produces neuroprotection from several neurodegenerative diseases and various experimental animal models. Therefore, we set out to investigate the effects of MINO pre-treatment on isoflurane or surgery induced cognitive impairment in aged mice by assessing the hippocampal-dependent spatial memory performance using the Morris water maze task. Hippocampal tissues were isolated from mice and evaluated by Western blot analysis, immunofluorescence procedures and protein array system. Our results elucidate that MINO down-regulated the isoflurane-induced and surgery-induced enhancement in the protein levels of pro-inflammatory cytokine tumour necrosis factor alpha, interleukin (IL)-1ß, interferon-γ and microglia marker Iba-1, and up-regulated protein levels of the anti-inflammatory cytokine IL-4 and IL-10. These findings suggest that pre-treatment with MINO attenuated isoflurane or surgery induced cognitive impairment by inhibiting the overactivation of microglia in aged mice.

Genomic distribution of 5-Hydroxymethylcytosine in mouse kidney and its relationship with gene expression.

Ten-Eleven Translocation (TET) proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytonsie (5hmC). Our recent work found a decline in global 5hmC level in mouse kidney insulted by ischemia reperfusion (IR). However, the genomic distribution of 5hmC in mouse kidney and its relationship with gene expression remain elusive. Here, we profiled the DNA hydroxymethylome of mouse kidney by hMeDIP-seq and revealed that 5hmC is enriched in genic regions but depleted from intergenic regions. Correlation analyses showed that 5hmC enrichment in gene body is positively associated with gene expression level in mouse kidney. Moreover, IR injury-associated genes (both up- and down-regulated genes during renal IR injury) in mouse kidney exhibit significantly higher 5hmC enrichment in their gene body regions when compared to those un-changed genes. Collectively, our study not only provides the first DNA hydroxymethylome of kidney tissues but also suggests that DNA hyper-hydroxymethylation in gene body may be a novel epigenetic marker of IR injury-associated genes.

Intraoperative infusion of branched-chain amino acids in patients undergoing gastrointestinal tumor surgery.

BACKGROUND: The purpose of this study is to investigate the effects of intraoperative infusion of branched-chain amino acids (BCAA) in patients undergoing gastrointestinal tumor surgery. METHODS: Sixty-one patients with gastrointestinal tumors undergoing gastrointestinal surgery were enrolled and randomly assigned to receive an intraoperative infusion of 3-compound BCAA solution (N = 20), amino acids (AA) solution (N = 21), or normal saline (NS) (N = 20). Nasopharyngeal temperature, blood glucose (BG), plasma insulin, and blood free fatty acids (FFA) concentrations were measured at 30 min before and 10 min after induction (T 0,T 1), 30 min and 2 h after skin incision (T 2,T 3), and 1 h after tracheal extubation (T 4). Intensity of shivering and pain was accessed at 1 h after extubation. RESULTS: The temperature in the BCAA and AA group was significantly higher than that in the NS group at T 4 (P = 0.014 and 0.033). The incidence of shivering in the BCAA and AA group was significantly lower than in the NS group (P = 0.027 and 0.012). BG increased in AA group at T 3 and T 4 (P = 0.001 and 0.045). The plasma insulin concentration increased in the BCAA and AA group from T 1 to T 3. The plasma FFA concentrations in the BCAA group were lower than in the AA and NS group from T 2 to T 4. CONCLUSIONS: Intraoperative BCAA and AA infusion alleviated postoperative hypothermia and shivering. BCAA infusion also inhibited fat mobilization, without adversely affecting blood glucose. TRIAL REGISTRATION: ChiCTR-TRC-14004668.

Novamin infusion: a new method to cure postoperative shivering with hypothermia.

BACKGROUND: Postoperative shivering is a frequent complication of surgery in developing countries and there is no satisfying method to treat it, let alone to cure it. We studied whether intravenous amino acid (AA) infusion can cure postoperative shivering in the postanesthesia care unit. METHODS: Sixty postanesthesia care unit patients with shivering grade 2 or higher and tympanic temperature <36°C received randomly either infusion of Novamin 18 AAs (2 mL/kg/h), pethidine (0.5 mg/kg), or tramadol (1 mg/kg). Tympanic temperature, shivering grade, and thermal comfort were assessed every 5 min for 60 min. Blood glucose and lactic acid concentrations were measured before and after treatment. Postoperative nausea and vomiting were also recorded. RESULTS: Shivering stopped within 5 min in the pethidine and tramadol groups versus 90% stopped within 15 min in AA group. There were five cases of reshivering in the tramadol group versus none in the AA or pethidine groups. Tympanic temperature increased slowly in all patients but increased significantly faster in the AA group. Thermal comfort improved significantly faster in the AA group versus the other two groups, thermal comfort was significantly higher in the tramadol versus the pethidine group ≥35 min. Blood glucose concentration in AA group increased to 135.18 ± 9.18 mg/dL. There were some cases of nausea and vomiting in pethidine and tramadol groups but none in the AA group. CONCLUSION: Novamin infusion can stop postoperative shivering and alleviates hypothermia and improves thermal comfort more effectively than tramadol and pethidine with less nausea and vomiting and causes a clinically acceptable blood glucose increase with no reshivering episodes.

Moderate-dose glucocorticoids as salvage therapy for severe pneumonia in renal transplant recipients: a single-center feasibility study.

This study aimed to assess the effectiveness and safety of moderate-dose glucocorticoids (GCs) with mechanical ventilation as salvage therapy for renal transplant recipients with severe pneumonia, which was non-responsive to conventional treatment. A retrospective study was conducted involving renal transplant recipients diagnosed with severe pneumonia and did not respond to conventional treatment. All immunosuppressants were then completely withdrawn, and the patients were initially administered with methylprednisolone at doses of 2.0-2.5 mg/kg/day once every 12 h. This dosage was continued until oxygenation improved, and the treatment was gradually tapered (by 20 mg every 2-3 days) to the previous maintenance dosage. Ten patients were recruited from year 2008 to 2012. Two patients who underwent emergency endotracheal intubation were intubated on days 3 and 8, respectively, another one died from recurrent pneumothorax. The mean PaO2/FiO2 of the nine survivors was significantly increased by the increasing treatment duration; whereas the lung injury scores (LIS) and the sequential organ failure assessment (SOFA) score were both significantly decreased. The use of moderate-dose GCs may play a role as salvage therapy for renal transplant recipients with severe pneumonia. However, further study with larger trials to is needed.

Sevoflurane/propofol coadministration provides better recovery than sevoflurane in combined general/epidural anesthesia: a randomized clinical trial.

PURPOSE: A classic general anesthesia is performed by induction with an intravenous hypnotic (such as propofol) and maintenance with a volatile anesthetic (such as sevoflurane). The aim of the present study was to compare the effects of a propofol/sevoflurane maintenance regimen with that of a sevoflurane regimen on recovery profiles. METHODS: One hundred and sixty patients, who were ASA 1 or 2, 45-65 years of age, and scheduled for elective gastrointestinal surgery under combined general/epidural anesthesia, were allocated randomly to receive the sevoflurane maintenance regimen (group S, n = 80) or sevoflurane/propofol regimen (group SP, n = 80). After induction, anesthesia was maintained with sevoflurane in group S and sevoflurane with propofol (1.2 µg/ml target plasma concentration) in group SP. Bispectral index (BIS) values were maintained within 40-60 during the maintenance. Time to extubation, incidence of serious coughing and agitation, and other recovery characteristics were evaluated during emergence. RESULTS: The time to awakening and extubation in group SP were 7.2 ± 2 min and 8.0 ± 1.8 min, respectively, which were shorter than those results in group S (12.3 ± 1.5 and 12.8 ± 1.6 min, respectively) (P < 0.05). The incidence of serious coughing and agitation in SP (30% and 25%) was lower than that of group S (68% and 53%) (P < 0.05). BIS value, pain score, requirements of analgesics and antiemetics in the PACU, and length of stay in the PACU were similar in the two groups. CONCLUSIONS: Compared to sevoflurane maintenance, coadministration of propofol and sevoflurane provides faster awakening and extubation with a low incidence of emergence coughing and agitation.

Multidisciplinary intensive care in extensive necrotizing fasciitis.

This is a case report of extensive necrotizing fasciitis (NF). A 65-year-old man presented with high fever, pain, swelling, and redness of the perineum, scrotum, and right lower limb. Based on the clinical symptoms and an imaging examination, a diagnosis of NF was made. The patient underwent an extensive exploration followed by daily bedside debridement. A diversion colostomy and six additional debridement procedures on the right thigh and perineum were subsequently performed. Although the patient had an eventful course, he recovered well under a multidisciplinary treatment regimen. The treatment and hospital course of the patient are described.

Effect of admission time on mortality in an intensive care unit in Mainland China: a propensity score matching analysis.

INTRODUCTION: The relationship between admission time and intensive care unit (ICU) mortality is inconclusive and influenced by various factors. This study aims to estimate the effect of admission time on ICU outcomes in a tertiary teaching hospital in China by propensity score matching (PSM) and stratified analysis. METHODS: A total of 2,891 consecutive patients were enrolled in this study from 1 January 2009 to 29 December 2011. Multivariate logistic regression and survival analysis were performed in this retrospective study. PSM and stratified analysis were applied for confounding factors, such as Acute Physiology and Chronic Health Evaluation II (APACHE II) score and admission types. RESULTS: Compared with office hour subgroup (n = 2,716), nighttime (NT, n = 175) subgroup had higher APACHE II scores (14 vs. 8, P < 0.001), prolonged length of stay in the ICU (42 vs. 24 h, P = 0.011), and higher percentages of medical (8.6% vs. 3.3%, P < 0.001) and emergency (59.4% vs. 12.2%, P < 0.001) patients. Moreover, NT admissions were related to higher ICU mortality [odds ratio (OR), 1.725 (95% CI 1.118-2.744), P = 0.01] and elevated mortality risk at 28 days [14.3% vs. 3.2%; OR, 1.920 (95% CI 1.171-3.150), P = 0.01]. PSM showed that admission time remained related to ICU outcome (P = 0.045) and mortality risk at 28 days [OR, 2.187 (95% CI 1.119-4.271), P = 0.022]. However, no mortality difference was found between weekend and workday admissions (P = 0.849), even if weekend admissions were more related to higher APACHE II scores compared with workday admissions. CONCLUSIONS: NT admission was associated with poor ICU outcomes. This finding may be related to shortage of onsite intensivists and qualified residents during NT. The current staffing model and training system should be improved in the future.

Combination of caspofungin and low-dose trimethoprim/sulfamethoxazole for the treatment of severe Pneumocystis jirovecii pneumonia in renal transplant recipients.

Pneumocystis jirovecii pneumonia (PJP) is a severe and life-threatening complication in immunocompromised patients. Trimethoprim/sulfamethoxazole (TMP-SMZ) is well known for its effectiveness as prophylaxis of PJP. However, the use of TMP-SMZ is associated with various adverse effects that may not be tolerated by critically ill patients. Caspofungin is recommended for invasive fungal infections, but the treatment of PJP after solid organ transplantation (SOT) is an off-label use of this drug. In this study, three cases of severe PJP in renal transplant recipients treated with a combination of caspofungin and low-dose TMP-SMZ were presented. Initial findings indicated that the combined treatment may be beneficial for the treatment of PJP and decrease the incidence of TMP-SMZ-related adverse effects.

Effects of different loading doses of dexmedetomidine on bispectral index under stepwise propofol target-controlled infusion.

BACKGROUND AND PURPOSE: Stepwise propofol target-controlled infusion (TCI) can achieve a less disturbed condition of hemodynamics and respiration. Its combination with dexmedetomidine may have some advantages for patients. We studied the effects of different loading doses of dexmedetomidine on the bispectral index (BIS) under stepwise propofol TCI. METHODS: Forty patients were randomly assigned into groups D(1.0), D(0.5), D(0.25) and D(0), in which dexmedetomidine at 1.0, 0.5, 0.25 or 0 µg•kg(-1) was infused over 10 min followed by 0.5 µg•kg(-1)•h(-1) and stepwise propofol TCI, which was administered with target effect site concentration (Ce) at 0.5 µg•ml(-1), and increased until 2.5 µg•ml(-1) by 1.0 µg•ml(-1) after 5 min reaching target Ce. BIS, heart rate, MAP, pulse oxygen saturation, RR and end-tidal carbon dioxide pressure were recorded before loading dose (T(0)), at 5 min (T(5 min)) and 10 min (T(10 min)) after starting infusion, after 5 min reaching Ce of 0.5, 1.5 and 2.5 µg•ml(-1) (T(p0.5), T(p1.5) and T(p2.5)). RESULTS: BIS values in group D(1.0) were significantly lower compared with those in group D(0) since T(10 min) and those in groups D(0.5) and D(0.25) since T(p0.5). In group D(1.0), heart rate decreased significantly at T(5 min) and T(10 min), heart rate at T(10 min) was significantly lower compared with that in group D(0). MAP remained stable during the loading dose infusion and decreased to some degree after propofol infusion in all groups. Changes in pulse oxygen saturation, RR and end-tidal carbon dioxide pressurewere similar among the groups without respiration depression. CONCLUSION: A loading dose of dexmedetomidine of 1.0 µg•kg(-1), not 0.5 µg•kg(-1) or less, over 10 min followed by 0.5 µg•kg(-1)•h(-1) can definitely decrease the BIS under stepwise propofol TCI with clinically stable blood pressure and without respiration depression, while attention should be paid to decreased heart rate.

Sleep disturbance induces neuroinflammation and impairment of learning and memory.

Hospitalized patients can develop cognitive function decline, the mechanisms of which remain largely to be determined. Sleep disturbance often occurs in hospitalized patients, and neuroinflammation can induce learning and memory impairment. We therefore set out to determine whether sleep disturbance can induce neuroinflammation and impairment of learning and memory in rodents. Five to 6-month-old wild-type C57BL/6J male mice were used in the studies. The mice were placed in rocking cages for 24 h, and two rolling balls were present in each cage. The mice were tested for learning and memory function using the Fear Conditioning Test one and 7 days post-sleep disturbance. Neuroinflammation in the mouse brain tissues was also determined. Of the Fear Conditioning studies at one day and 7 days after sleep disturbance, twenty-four hour sleep disturbance decreased freezing time in the context test, which assesses hippocampus-dependent learning and memory; but not the tone test, which assesses hippocampus-independent learning and memory. Sleep disturbance increased pro-inflammatory cytokine IL-6 levels and induced microglia activation in the mouse hippocampus, but not the cortex. These results suggest that sleep disturbance induces neuroinflammation in the mouse hippocampus, and impairs hippocampus-dependent learning and memory in mice. Pending further studies, these findings suggest that sleep disturbance-induced neuroinflammation and impairment of learning and memory may contribute to the development of cognitive function decline in hospitalized patients.

Reduction of DNA hydroxymethylation in the mouse kidney insulted by ischemia reperfusion.

Ischemia reperfusion (IR) is a frequent pathological injury to the perioperative patients. The molecular mechanism underlying IR injury is still not well characterized. In this study, we investigated the effect of IR injury on DNA hydroxymethylation in mouse kidney. Dot blot and immunochemistry analysis showed that the global level of 5-hydroxymethylcytosine (5hmC) was reduced in mouse kidney insulted by IR; however, the 5-methylcytosine (5mC) level had no significant change. hMeDIP-qPCR validated that IR injury also decreased the 5hmC enrichment at promoter regions of Cxcl10 and Ifngr2 genes. RT-qPCR analysis revealed that the mRNA levels of Cxcl10 and Ifngr2 increased in IR-injured kidney. In addition, mRNA expression of both Tet1 and Tet2 but not Tet3 was dramatically downregulated in IR-injured kidney. Taken together, our data provided the first evidence that IR injury influences DNA hydroxymethylation and Tet gene expression in mouse kidney, which may contribute to the regulation of gene transcription during renal IR injury.