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Purpose To prospectively explore the incidence and risk factors of moderate to severe pain after primary and secondary orbital implantation following evisceration or enucleation surgery. Methods One hundred eighteen patients under general anesthesia for orbital implantation were enrolled in this study. In 91 patients, primary orbital implantation followed evisceration, and in 27 patients, the implantation was secondary after previous evisceration or enucleation surgery. Medical interventions for all participants were followed by standardized surgical, anesthetic, and analgesic protocols. Postoperative pain (POP) intensity was quantified by an 11-point numerical rating scale within 72 hours after the surgery, numerical rating scale ≥4 was considered moderate to severe POP. Multivariate logistic regression was utilized to identify the risk factors related to the development of POP. Results Thirty-five patients (29.7%) displayed moderate to severe POP, particularly within 6 to 24 hours after surgery, which peaked at 24 hours. Of these patients, 26 patients who were unable to tolerate the pain received additional doses of analgesics during in-hospital stay. Logistic regression model revealed that preoperative anxiety (odds ratios = 4.890; p = 0.002), congenital microphthalmia (odds ratios = 14.602; p = 0.038), and surgical time longer than 60 minutes (odds ratios = 5.586; p = 0.001) were significantly associated with moderate to severe POP after orbital implantation. Conclusions Orbital implantation after evisceration or enucleation surgery is likely to cause moderate to severe pain intensity in the early postoperative period. Preoperative anxiety, prolonged surgical time, and congenital microphthalmia were the risk factors.

Background Acute glaucoma, characterized by a sudden elevation in intraocular pressure (IOP) and retinal ganglion cells (RGCs) death, is a major cause of irreversible blindness worldwide that lacks approved effective therapies, validated treatment targets and clear molecular mechanisms. We sought to explore the potential molecular mechanisms underlying the causal link between high IOP and glaucomatous RGCs death. Methods A murine retinal ischemia/ reperfusion (RIR) model and an in vitro oxygen and glucose deprivation/reoxygenation (OGDR) model were used to investigate the pathogenic mechanisms of acute glaucoma. Results Our findings reveal a novel mechanism of microglia-induced pyroptosis-mediated RGCs death associated with glaucomatous vision loss. Genetic deletion of gasdermin D (GSDMD), the effector of pyroptosis, markedly ameliorated the RGCs death and retinal tissue damage in acute glaucoma. Moreover, GSDMD cleavage of microglial cells was dependent on caspase-8 (CASP8)-hypoxia-inducible factor-1α (HIF-1α) signaling. Mechanistically, the newly identified nucleotide-binding leucine-rich repeat-containing receptor (NLR) family pyrin domain-containing 12 (NLRP12) collaborated with NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) downstream of the CASP8-HIF-1α axis, to elicit pyroptotic processes and interleukin-1β (IL-1β) maturation through caspase-1 activation, facilitating pyroptosis and neuroinflammation in acute glaucoma. Interestingly, processing of IL-1β in turn magnified the CASP8-HIF-1α-NLRP12/NLRP3/NLRC4-pyroptosis circuit to accelerate inflammatory cascades. Conclusions These data not only indicate that the collaborative effects of NLRP12, NLRP3 and NLRC4 on pyroptosis are responsible for RGCs death, but also shed novel mechanistic insights into microglial pyroptosis, paving novel therapeutic avenues for the treatment of glaucoma-induced irreversible vision loss through simultaneously targeting of pyroptosis.

Background and Aims: Postoperative nausea and vomiting (PONV), one of the common complications following strabismus surgery, would delay the ambulatory discharge time. The aim of this retrospective study was to determine the risk factors of PONV in patients undergoing ambulatory strabismus surgery under general anaesthesia, with the treatments of dexamethasone and 5-HT3 antagonist combination. Methods: We reviewed 721 consecutive patients (12–60 years old) undergoing ambulatory strabismus surgery under general anaesthesia at an academic eye centre between December 2016 and January 2019. Patients received prophylactic treatment of dexamethasone and 5-HT3 antagonist combination during anaesthesia induction, and PONV was evaluated during the early recovery period before discharge. Results: The dexamethasone and 5-HT3 antagonist combination effectively reduced the incidence of PONV (3.05%, 22/721), and the patients who experienced PONV had statistically prolonged phase II recovery time as compared those who did not (P = 0.006). The sum of the extraocular muscles manipulated and the use of nalbuphine (vs flurbiprofen axetil) were the independent risk factors for PONV (P < 0.05). Conclusion: The sum of the extraocular muscles manipulated and the use of nalbuphine are potentially modifiable risk factors for PONV after strabismus surgery with the treatments of dexamethasone and 5-HT3 antagonist combination.

Purpose To verify the feasibility of the clinical-based discharge (CBD) criteria and identify the reasons of long postanesthesia care unit length of stay (PACU-LOS) for ophthalmic ambulatory surgical patients under general anesthesia. Design A prospectively observational study conducted at a tertiary eye center in China. Methods Medical records were collected from patients admitted for strabismus ambulatory surgery under general anesthesia from September 2018 to March 2019. The patients were discharged home once met the CBD criteria based on a combination of the modified Aldrete's scoring system and Chung's Post-Anesthetic Discharge Scoring System. Postoperative complications were recorded in the PACU and within 24 hours after discharge. Multivariate logistic regression was applied to identify the factors relating to late discharges. Findings All patients (N = 400) were safely and successfully same-day discharged home as none of the patients informed severe emergency events or unanticipated readmission. Nine displayed discharge delays mainly because of mild postoperative nausea and vomiting (PONV) although met the discharge criteria. About 85.5% of patients were discharged within a PACU-LOS of 150 minutes, 379 (94.8%) were within 180 minutes, and the cutoff time in PACU-LOS was 150 minutes. Multivariable analysis indicated that sevoflurane anesthesia and the presence of PONV were related to late discharges (PACU-LOS of greater than 150 minutes, all P Conclusions The CBD criteria can efficiently and safely guide the ophthalmic ambulatory surgical patients to discharge home on the same-surgery day, whereas sevoflurane anesthesia and the presence of PONV are associated with a relatively long PACU-LOS.

Purpose: To evaluate retinal and choroidal microvascular features of VKH patients in acute and convalescent phases after treatment using OCTA. Methods: A prospective, observational study was conducted in patients with initial VKH at the acute stage (n = 15) and healthy participants (n = 15) served as controls. After 3-month systemic corticosteroid treatment, patients’ vascular parameters were recorded by OCTA before and after treatment and compared with results observed in healthy participants. Results: Our findings first uncovered that there are two types of abnormalities in the choriocapillary layer of patients with VKH in the acute stage: one is characterized as multiple dark spots of choriocapillary flow void and the other involves highly reflective areas surrounded by light spots with an increased flow area. During the convalescent stage, all eyes showed multifocal dark spots in the choriocapillary layer, leading to a reduced choroidal flow area. Conclusions: OCTA provides a better display of the microvascular appearance of the choroid to noninvasively evaluate choriocapillaris abnormalities in VKH disease.

Background Emergence delirium is a common complication in children, especially in preschool children undergoing ophthalmic surgery. The aim of the study was to investigate the effects of visual preconditioning (application of an eyepatch over the eye to be operated for ≥3 h the day before surgery) on emergence delirium after ophthalmic surgery under sevoflurane anaesthesia. Methods One hundred and seventy-nine children undergoing unilateral cataract surgery, aged 3–7 yr, were involved in this prospective, blinded, randomised study. Subjects were randomised to receive visual preconditioning (Group P, n=89) or to receive programmed explanation the day before surgery (Group C, n=90). The primary outcome was incidence of emergence delirium evaluated by the paediatric anaesthesia emergence delirium (PAED) scale. The secondary outcomes included emergence time and post-anaesthesia care unit (PACU) stay time. Results Children in Group P had a significantly lower incidence of emergence delirium than those in Group C [16.9% vs 44.4%, odds ratio (OR) 4.0, 95% confidence interval (CI) 2.0 to 8.0]. The maximal PAED score was lower in Group P than in Group C [4 (0–20) vs 9 (0–20), median difference –3.0, 95% CI –5.0 to –1.0]. Visual preconditioning prolonged emergence time (P Conclusion Visual disturbance contributes to emergence delirium in preschool children undergoing ophthalmic surgery with sevoflurane, and prophylactic eyepatch treatment can reduce emergence delirium. Clinical trials registration NCT02590744.

Objectives Mucosal atomization device (MAD) was designed to increase the bioavailability of intranasal medications by facilitating absorption, the present study aimed to evaluate and compare the sedation effects of intranasal dexmedetomidine delivered as drops versus sprays on pediatric responses to intravenous cannulation. Methods One hundred and six pediatric patients (aged from 2 to 5 years) scheduled for elective ophthalmic surgery were intranasally received a dose of 2 μg/kg in 20 μl/kg of dexmedetomidine for sedation to reduce response to venous cannulation. The patients were randomized into syringe group and MAD group in which dexmedetomidine was delivered as drops or sprays via syringe or MAD respectively. The primary outcome was the response to peripheral vein cannulation assessed by the FLACC scores (faces, legs, activity, cry and consolability) 30 min after intranasal administration of dexmedetomidine. The secondary outcomes included acceptance for intranasal medication, sedation onset time, and needle insertion times and any adverse event at the preoperative holding area. Results The FLACC scores in MAD group were significantly decreased than that treated by drops (P = 0.021). The acceptance for intranasal administration between both groups was comparable (P > 0.05), the onset time and the incidences in two and more times of needle insertion did not differ significantly between syringe and MAD groups (all P > 0.05). None of patients were required to clinically intervene in heart rates reduction and none suffered respiratory depression after administrations of dexmedetomidine in either group. Conclusion Intranasal dexmedetomidine by sprays offers better sedation effects to reduce responses to venous cannulation than drops.

Purpose We evaluated the clinical utility of a novel anterior segment optical coherence tomography (AS-OCT) device, CASIA2, to evaluate parameters indicative of anterior chamber (AC) inflammation severity in uveitis, including AC cell number, flare, and keratic precipitates (KPs). Design Prospective evaluation of a diagnostic device. Methods Uveitis eyes were classified into active and inactive groups. The number of hyperreflective dots representing AC cells and optical density ratio (aqueous-to-air relative intensity [ARI] index) for flare qualification were calculated from AS-OCT images. In addition, a program was designed to quantify the posterior corneal surface smoothness (PCSS) of each image for KPs evaluation. The maximum, minimum, and average PCSS values were calculated from 128 images per eye and compared among active uveitis, inactive uveitis, and control eyes. Correlations between Standardization of Uveitis Nomenclature grade and both hyperreflective dot number and ARI index were evaluated. Receiver operating characteristic (ROC) curves were constructed to test the values of these indicators for uveitis diagnosis. Results AC hyperreflective dot count, ARI index, and maximum and average PCSS values were all significantly higher in the active uveitis group than in the inactive and control groups. Hyperreflective dot count and ARI index were associated with Standardization of Uveitis Nomenclature cell and flare grade. According to ROC curve analysis, maximum PCSS was the best indicator for the diagnosis of uveitis involving the anterior segment, meanwhile the hyperreflective dot number was the best to identify active AC inflammation from the inactive. Conclusions Quantification of AC cell number, flare, and KPs using the CASIA2 device is a promising strategy for the objective assessment of AC inflammation.

Purpose Dry eye disease (DED) is a common and multifactor-induced autoimmune ocular surface disease. Environmental factors, such as desiccating stress (DS) and hyperosmolarity, affect the corneal epithelium to induce ocular surface inflammation in DED. We aimed to explore the potential mechanisms by which innate immunity and pyroptosis are initiated in the mucosal epithelium in response to environmental stress. Methods Experimental dry eye was established in C57BL/6 J mice and genetic mice on the background of C57BL/6 J mice by subcutaneous injection of scopolamine and exposure to a desiccating environment. SDHCEC cell line was subjected to hyperosmolarity stress (450 mOsM). The phenol red thread tear test and corneal epithelial defects evaluation were used as assessments of severity of DED. RNA-sequencing, quantitative real-time PCR, western blotting and immunofluorescence staining were performed in this study. Results Loss-of-function studies indicated that genetic deletion of GSDMD alleviates DS-induced corneal epithelium defects, and GSDMD is needed for IL-33 processing. We further found that NLRP12 collaborates with NLRC4 inflammasome to initiate GSDMD-dependent pyroptosis, which requires TLR4-induced caspase-8 (CASP8) activation in the mucosal corneal epithelium in response to DS. Conclusions These findings provide compelling evidence that GSDMD-dependent pyroptosis plays a pivotal role in DED. A novel mechanism involving NLRP12 and NLRC4 inflammasomes-induced GSDMD-dependent pyroptosis, accompanied by IL-33 processing is responsible for ocular surface epithelial defects in response to environmental stress. GSDMD is required for IL-33 processing and the subsequent amplification of inflammatory cascades. These findings reveal novel therapeutic targets for treating DED.

This study aimed to test the hypothesis that premedication with a single dose of intranasal dexmedetomidine (DEX) could not only reduce preoperative anxiety but also minimize the emergence agitation in children undergoing cataract surgery with sevoflurane anesthesia.Single-blinded, randomized, placebo-controlled clinical comparison study.Academic medical center.Ninety American Society of Anesthesiologists physical status 1 and 2 children scheduled for cataract surgery.Patients were randomized into 3 groups: group D1, group D2, and saline group (group C), in which the children received 1 or 2 μg/kg of intranasal DEX or saline, respectively, and each group comprises 30 patients.The mask induction score and the incidences of postoperative emergence agitation evaluated by the Pediatric Anesthesia Emergence Delirium scale were assessed. The emergence time, postanesthesia care unit (PACU) stay time, and any adverse events were recorded.The mask induction scores were significantly higher in the saline group than those in the D1 and D2 groups (P.001). The incidences of emergence agitation in the D1 and D2 groups were significantly lower than that in the saline group (7/30 in group D1 and 3/30 in group D2 vs 24/30 in group C, P.001). The emergence time and PACU stay time were comparable among the 3 groups (P.05). The emergence time and PACU stay time did not differ significantly in DEX-treated groups as compared with the saline group; there were no differences between 1- and 2-μg/kg groups. None of the patients exhibited significant clinical complications.Intranasal DEX (1 or 2 μg/kg) dose independently improves the incidences of mask acceptance and prevents the incidences of postoperative emergency agitation mainly from sevoflurane without delaying the emergency time or inducing severe adverse events.

Purpose It is a challenge to rescue ophthalmology examinations performed in children in the sedation room after initial chloral hydrate failure. Intranasal dexmedetomidine can be used in rescue sedation in children undergoing computed tomography. The present study aimed to assess the efficacy and tolerability of intranasal dexmedetomidine use in children undergoing ophthalmic examination after chloral hydrate failure. Methods Sixty uncooperative pediatric patients with cataract (aged 5–36 months; weight, 7–15 kg) presented for follow-up ophthalmic examination. Patients who experienced chloral hydrate failure were randomized to 1 of 2 groups to receive intranasal dexmedetomidine 1 or 2 μg/kg for rescue sedation. Each group contained 30 patients. The primary outcome was the rate of a successful ophthalmic examination. Secondary outcomes included sedation onset time, recovery time, duration of examination, discharge time, and adverse events, including percentage of heart rate reduction, respiratory depression, vomiting, and postsedative agitation. Findings A successful ophthalmic examination was achieved in 93.3% (28/30) of patients in the 2-μg/kg dose group and in 66.7% (20/30) of patients in the 1-μg/kg dose group ( P = 0.021). The onset time, recovery time, and discharge time did not significantly differ between the 2 groups. None of the patients required clinical intervention due to heart rate reduction, and none of the patients in either group experienced vomiting, respiratory depression, or agitation after the administration of dexmedetomidine. Implications In children undergoing ophthalmic examination, intranasal dexmedetomidine can be administered in the sedation room for rescue sedation after chloral hydrate failure, with the 2-μg/kg dose being more efficacious than the 1-μg/kg dose, as measured by success rate. ClinicalTrials.gov identifier: NCT02077712.

Both oxidative stress and mast cell (MC) degranulation participate in the process of small intestinal ischemia reperfusion (IIR) injury, and oxidative stress induces MC degranulation. Propofol, an anesthetic with antioxidant property, can attenuate IIR injury. We postulated that propofol can protect against IIR injury by inhibiting oxidative stress subsequent from NADPH oxidase mediated MC activation. Cultured RBL-2H3 cells were pretreated with antioxidant N-acetylcysteine (NAC) or propofol and subjected to hydrogen peroxide (H2O2) stimulation without or with MC degranulator compound 48/80 (CP). H2O2 significantly increased cells degranulation, which was abolished by NAC or propofol. MC degranulation by CP further aggravated H2O2 induced cell degranulation of small intestinal epithelial cell, IEC-6 cells, stimulated by tryptase. Rats subjected to IIR showed significant increases in cellular injury and elevations of NADPH oxidase subunits p47(phox) and gp91(phox) protein expression, increases of the specific lipid peroxidation product 15-F2t-Isoprostane and interleukin-6, and reductions in superoxide dismutase activity with concomitant enhancements in tryptase and β-hexosaminidase. MC degranulation by CP further aggravated IIR injury. And all these changes were attenuated by NAC or propofol pretreatment, which also abrogated CP-mediated exacerbation of IIR injury. It is concluded that pretreatment of propofol confers protection against IIR injury by suppressing NADPH oxidase mediated MC activation.

Study objective Procedural sedation for non-painful pediatric examinations outside the operating room remains a challenge, this study was designed to compare the safety and effectiveness of sedation provided by dexmedetomidine versus other sedatives including chloral hydrate, midazolam, and pentobarbital for pediatric patients to complete diagnostic examinations. Design Systematic review and meta-analysis of RCTs. Setting Pediatric procedural sedation. Interventions Comparison of sedation by dexmedetomidine and chloral hydrate, or pentobarbital, or midazolam for pediatric non-painful sedation. Patients The PubMed, Embase, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched and limited the studies to those published in English through July 30, 2018. Measurements Prospective randomized clinical trials (RCTs) comparing dexmedetomidine to chloral hydrate, pentobarbital, and midazolam for pediatric procedural examinations outside the operating room were included in the meta-analysis. Search terms included dexmedetomidine, precede, adrenergic alpha-2 receptor agonists, adrenergic alpha 2 agonists, adrenergic alpha-agonists, adrenergic alpha 2 receptor agonists, chloral hydrate, pentobarbital, midazolam, AND sedation. Main results A total of 1486 studies were screened and nine RCTs were identified; 1076 patients were analyzed. Sedation with dexmedetomidine provided statistically higher incidences in completing examinations with fewer episodes of desaturation than the other sedatives did (OR 2.90, 95% CI: 1.39–6.07, P = 0.005, I2 = 77%; OR 0.29, 95% CI: 0.15–0.57, P = 0.0004, I2 = 0%, respectively). Conclusions The meta-analysis shows that sedation by dexmedetomidine has lower incidence of respiratory depression and provides higher success rates in completing examinations than other traditional sedatives without compromising safety, indicating a prospective clinical use for procedural sedation.

ObjectiveOur previous retrospective study demonstrated that perioperative dexmedetomidine (Dex) administration was associated with low systemic inflammatory response syndrome (SIRS) incidence. The present study was designed to investigate whether perioperative administration of Dex decreases the incidence of postpercutaneous nephrolithotomy lithotripsy (PCNL) SIRS in patients who undergo PCNL.DesignA randomised controlled trial was designed.ParticipantsA total of 190 patients were randomly assigned to receive Dex (DEX group, n=95) or saline control (CON group, n=95) and completed the study. In the DEX group, Dex was loaded (1 µg/kg) before anaesthesia induction and was infused (0.5 µg/kg/h) during surgery.OutcomesThe incidences of postoperative SIRS were recorded. Serum interleukin-6 (IL-6) and tumour necrosis factor α(TNF-α) were measured.ResultsThe incidence rates of SIRS were significantly lower in the DEX group than in the CON group (35.8% vs 50.5%, p=0.04). No patients developed sepsis in either group. These results might be attributed to inhibition of inflammatory responses and the resulting lower serum levels of IL-6 and TNF-α, caused by Dex administration. However, compared with the CON group, the lower incidence rate of SIRS in the DEX group did not result in better outcomes, such as shorter postoperative hospitalisation stays and lower costs.ConclusionThe present study showed that Dex administration during PCNL might be beneficial for decreasing the incidence of SIRS through inhibiting the release of inflammatory mediators, but not clinical consequences such as postoperative hospitalisation duration and costs. Further effects of Dex administration on SIRS in patients who are scheduled for PCNL should be explored in future studies.Trial registration numberChiCTR-ICR-15006167.

The optimal size selection of laryngeal mask airway (LMA) based on body weight is not always applicable. This study was prospectively conducted to evaluate the efficacy of cricoid-mental distance-based method versus weight-based method in optimal size selection of LMA in adults. Seventy-four patients (aged from 18 to 65) undergoing ophthalmic surgery were randomly assigned into cricoid-mental (CM) distance-based group or weight-based group to select appropriate size of LMA. The primary outcome was oropharyngeal leak pressure (OLP). Secondary outcomes included overall insertion success rate, number of insertion attempts, time to successful insertion, ease of insertion, score of fiber-optic view, peak inspiratory pressure during mechanical ventilation and postoperative pharyngolaryngeal morbidity. The OLP was significantly higher in CM distance-based group than that in weight-based group (19.38 ± 3.52 vs. 17.50 ± 3.18, P = 0.022). The successful placement at the first attempt in CM distance-based group was dramatically increased as compared with weight-based group (89.2% vs. 62.2%, P = 0.005). The overall success rate of LMA insertion in CM distance-based group was slightly increased in comparison with the weight-based group (100% vs. 91.9%, P = 0.240). There were no significant differences in score of fiber-optic view and postoperative pharyngolaryngeal morbidity between both groups (all P > 0.05). CM distance-based criteria is an alternative choice for optimizing size selection of classic LMA in adults.

Fang Tan,1,2,* Xiaoliang Gan,3,* Yingqing Deng,1 Xiaoyun Li,1 Na Guo,1 Ziqing Hei,1 Qianqian Zhu,1 Zhuang-Gui Chen,4 Shaoli Zhou1 1Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Anesthesiology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Department of Anesthesiology, Zhongshan Ophthalmic Center of Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally tothis work Purpose: Dexmedetomidine (DEX) has been reported to attenuate inflammation in rats. Thepresent retrospective cohort study aimed to investigate whether intraoperative administration with DEX could reduce the incidence of postoperative systemic inflammatory response syndrome (SIRS) in patients following percutaneous nephrolithotomy (PCNL). Patients and methods: A total of 251 patients were included in the analysis. Among these patients, 175 received intravenous DEX infusion during the intraoperative period and 76 did not. The primary outcome measures were the incidences of postoperative SIRS and fever. Secondary outcomes included patient-controlled analgesia (tramadol) requirements, length of postoperative hospitalization stay, serum creatinine (Scr) and serum blood urea nitrogen (BUN) concentration, and adverse events (bradycardia, hypotension, renal artery thrombosis). Results: Administration of DEX not only significantly attenuated the incidence of SIRS and fever (P=0.029, P=0.042, respectively), but also reduced analgesia requirements (P=0.028). The length of postoperative hospitalization stay, Scr and BUN concentration, and adverse events did not differ significantly between the two groups. Further univariate and multivariate logistic regression analysis indicated that intraoperative DEX administration was a protective factor against SIRS after PCNL (OR 0.476 [95% CI: 0.257–0.835]; P=0.019). Conclusion: Intraoperative administration of DEX might be associated with reductions in the incidences of SIRS and fever after PCNL. Keywords: PCNL, SIRS, risk factor, dexmedetomidine

SummaryBackground and aim Pediatric ophthalmic examinations can be conducted under sedation either by chloral hydrate or by dexmedetomidine. The objective was to compare the success rates and quality of ophthalmic examination of children sedated by intranasal dexmedetomidine vs oral chloral hydrate. Methods One hundred and forty-one children aged from 3 to 36 months (5–15 kg) scheduled to ophthalmic examinations were randomly sedated by either intranasal dexmedetomidine (2 μg·kg−1, n = 71) or oral chloral hydrate (80 mg·kg−1, n = 70). The primary endpoint was successful sedation to complete the examinations including slit-lamp photography, tonometry, anterior segment analysis, and refractive error inspection. The secondary endpoints included quality of eye position, intraocular pressure, onset time, duration of examination, recovery time, discharge time, any side effects during examination, and within 48 h after discharge. Results Sixty-one children were sedated by dexmedetomidine with a success rate of 85.9%, which is significantly higher than that by chloral hydrate (64.3%) [OR 3.39, 95% CI: 1.48–7.76, P = 0.003]. Furthermore, children in the dexmedetomidine group displayed better eye position in anterior segment analysis than in chloral hydrate group median difference. All children displayed stable hemodynamics and none suffered hypoxemia in both groups. Oral chloral hydrate induced higher percentages of vomiting and altered bowel habit after discharge than dexmedetomidine. Conclusions Intranasal dexmedetomidine provides more successful sedation and better quality of ophthalmic examinations than oral chloral hydrate for small children.

Background Dexmedetomidine (DEX) has been administered to patients during neurosurgery. Some studies have found that DEX could reduce perioperative opioid consumption and postoperative pain intensity. However, no firm conclusions have been reached. The purpose of this meta-analysis was to assess the efficacy of DEX for managing pain in neurosurgical patients. Materials and methods A comprehensive literature review was conducted to identify randomized controlled trials (RCTs) focusing on the effects of DEX on perioperative opioid consumption and postoperative pain intensity in patients undergoing neurosurgery. PubMed, the Web of science, the Cochrane Library, and Scopus were searched. The resulting data were combined to calculate the pooled mean differences (MDs), standard MDs or odds ratios (ORs), and 95% confidence intervals (CIs), as appropriate. Heterogeneity and potential publication bias were assessed. Furthermore, a trial sequential analysis was performed to improve the precision of our findings. Results A total of 11 published RCTs involving 674 patients undergoing neurosurgery (335 patients, 339 controls) were included in this meta-analysis. There were significant differences in postanesthesia care unit (PACU) visual analog scale scores between the groups (MD=-1.54, 95% CI, -2.33 to 0.75, I=87%, P=0.0001). In addition, there were significant differences in PACU opioid requirements between the treatment and control groups (standard MD=-0.88, 95% CI, -1.74 to 0.02, I=91%, P=0.05). Furthermore, intraoperative opioid consumption was significantly reduced in the treatment group (MD=-127.75, 95% CI, -208.62 to 46.89, I=98%, P=0.002). Conclusions DEX could reduce perioperative and PACU opioid consumption as well as postoperative pain intensity.

Rebuilding of infarcted myocardium by mesenchymal stem cells (MSCs) has not been successful because of poor cell survival due in part to insufficient blood supply after myocardial infarction (MI). We hypothesize that targeted delivery of vascular endothelial growth factor (VEGF) to MI can help regenerate vasculature in support of MSC therapy in a rat model of MI. VEGF-encapsulated immunoliposomes targeting overexpressed P-selectin in MI tissue were infused by tail vein immediately after MI. One week later, MSCs were injected intramyocardially. The cardiac function loss was moderated slightly by targeted delivery of VEGF or MSC treatment. Targeted VEGF+MSC combination treatment showed highest attenuation in cardiac function loss. The combination treatment also increased blood vessel density (80%) and decreased collagen content in post-MI tissue (33%). Engraftment of MSCs in the combination treatment group was significantly increased and the engrafted cells contributed to the restoration of blood vessels. From the Clinical Editor VEGF immunoliposomes targeting myocardial infarction tissue resulted in significantly higher attenuation of cardiac function loss when used in combination with mesenchymal stem cells. MSCs were previously found to have poor ability to restore cardiac tissue, likely as a result of poor blood supply in the affected areas. This new method counterbalances that weakness by the known effects of VEGF, as demonstrated in a rat model.

Aim of the study Mast cell (MC) degranulation contributes to the protection mediated by ischemic preconditioning (IPC); however, the precise mechanisms underlying this protection remain largely unknown. Mast cell carboxypeptidase A (MC-CPA) is released solely from MCs and plays a critical role in degrading toxins and endothelin 1 (ET-1). The present study sought to explore whether MC-CPA is involved in the process of IPC in a rodent model of small intestinal ischemia reperfusion (IIR) injury. Materials and methods IIR injuries were induced in Sprague–Dawley rats by clamping the superior mesenteric artery for 60 min followed by reperfusion for 2 h. One cycle of 10 min intestinal ischemia and 10 min of reperfusion was used in the IPC group, and the MC stabilizer cromolyn sodium and MC potato carboxypeptidase inhibitor were administered before the start of IPC. At the end of experiment, intestine tissue was obtained for assays of the MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents and myeloperoxidase activities. Intestinal histologic injury scores and MC degranulation were assessed. Apoptosis indices and cleaved caspase- 3 protein expressions were quantified. Results IIR resulted in severe injury, as evidenced by significant increases in injury scores and MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents that were accompanied with concomitant elevations in cleaved caspase 3 expression, apoptosis indices, and myeloperoxidase activities. IPC induced a significant increase in MC-CPA3, induced MC degranulation, and attenuated IIR injury by downregulating IIR-induced biochemical changes, whereas cromolyn sodium and potato carboxypeptidase inhibitor abolished the IPC-mediated changes. Conclusions These data suggest that IPC protected against IIR injury via the MC degranulation-mediated release of MC-CPA.

Mast cell (MC) degranulation has been implicated in small intestinal ischemia reperfusion (IIR) injury, therein, inhibiting overproduction of histamine released from activated MC may provide promising strategies against IIR-mediated liver injuries. The aim of the present study was to explore whether anti-histamine treatment contribute to attenuating IIR-mediated liver injury. Adult SD rats were randomized into sham-operated group (S group), sole IIR group (IIR group), and IIR treated with Ketotifen, a histamine antagonist (IIR+K group), Cromolyn Sodium, a MC stabilizer (IIR+C group), and Compound 48/80, a MC degranulator (IIR+CP group), respectively. IIR was induced by superior mesenteric artery occlusion for 75 min followed by 4 h of reperfusion. The agents were intravenously administrated 5 min before reperfusion to induce different levels of histamine. Subsequently, serum concentrations of ALT, AST and histamine; levels of LDH,TNF-α, IL-8 and MDA as well as SOD activities in the liver were assessed. Histopathologic changes were also evaluated. IIR resulted in severe liver injury as demonstrated by significant increases in injury scores, with concomitant significant increases in serum ALT, AST and histamine levels, as well as LDH, TNF-α, IL-8, and MDA levels in the liver, accompanied by reduction in SOD activities (all P ＜ 0.05, IIR vs. S). Treatments by Ketotifen and Cromolyn Sodium similarly markedly alleviated IIR-mediated liver injury as confirmed by significant reduction of the above biomedical changes whereas Compound 48/80 further aggravated IIR-mediated liver injury by dramatically enhancing the above biomedical changes. Data of our study suggest that anti-histamine treatments may provide promising benefits in alleviating liver injury triggered by IIR.

Stabilizing mast cells (MCs) can either inhibit or augment inflammation; however, how improved therapeutic benefits against small intestinal ischemia-reperfusion injury (IIRI) can be achieved by stabilizing MCs remains to be elucidated. The present study was designed to evaluate different treatments with cromolyn sodium (CS, an MC stabilizer), which was administrated either prior to ischemia or after reperfusion. Kunming mice were randomized into a sham-operated group (SH), a sole IIR group (M), in which mice were subjected to 30 min superior mesenteric artery occlusion followed by 3 day or 3 h reperfusion, or IIR, treated with CS 15 min prior to ischemia or 15 min after reperfusion in the PreCr and PostCr groups. The survival rate and Chiu's scores were evaluated. The levels of ET-1, histamine, TNF-α and IL-6, and expression of MC protease 7 (MCP7), MC counts and myeloperoxidase (MPO) activity were quantified. IIR resulted in severe injury as demonstrated by significant increases in mortality and injury score. IIR also led to substantial elevations in the levels of ET-1, histamine, TNF-α and IL-6, expression of MCP7, MC counts and MPO activities (P0.05, M vs. SH groups). All biochemical changes were markedly reduced in the PostCr group (P0.05, PostCr vs. M groups), whereas pretreatment of IIR mice with CS prior to ischemia exhibited no changes of ET-1 levels, injury score and inflammation (P0.05, PreCr vs. M groups). In conclusion, administration of CS after reperfusion, but not prior to ischemia, attenuates IIRI by downregulating ET-1 and suppressing sustained MC activation.

Findings of previous studies have revealed that intestinal mucosal mast cells (IMMCs) are involved in small intestinal ischemia‑reperfusion injury (IIRI). However, time-course changes of mast cell counts and mast cell function in this process remain unclear. The present study aimed to observe the number of IMMCs and to investigate the correlation between their activation and small intestine injury at various time points during the period of small intestinal ischemia reperfusion (IIR). Healthy male Kunming mice were randomly divided into five groups, and were subjected to occlusion of the superior mesenteric artery (SMA) for 30 min and followed by reperfusion for 1, 3, 6 and 12 h. By contrast, the SMA was isolated but not clamped in the baseline group. Chiu's scores were assessed by light microscopy, tryptase protein and MCP7 protein expression in the intestine were quantified, and mast cell counts and levels of histamine and TNF-α in the intestine were measured. The results showed that IIR induced severe intestine injury within 12 h as demonstrated by Chiu's scores that was greatly increased as compared to the baseline group, accompanied by increased mast cell counts, histamine and TNF-α levels. However, the Chiu's scores were reduced in the IIR 12 h group compared with the IIR 1 h, IIR 3 h and IIR 6 h groups, with concomitant decreased mast cell counts, histamine and TNF-α levels. The tryptase and MCP7 protein expression was markedly increased in the IIR 1 h and IIR 3 h groups as compared with the baseline group, whereas this expression was gradually decreased at 6 and 12 h after reperfusion. The results of the present study suggest that IIR results in severe mucosal destruction within 6 h after reperfusion, associated with mast cell activation and substantial increases in the mast cell counts.

Children are quite different from adults in terms of anatomy, physiology, pharmacology, etc. Thus, anesthesia in children should take into full consideration the unique characteristics of pediatric patients. Pediatric surgical patients cannot be viewed as merely miniature of adults; the anesthesia methods, doses, and devices used for adults may not be appropriate for children. Several factors must be taken into account when choosing the anesthetic agents and techniques for pediatric patients, including the anatomical, physiological, and psychological characteristics, the pharmacokinetic and pharmacodynamic profiles, the approach of lens surgery, and the estimated duration of surgery. For pediatric patients, extra caution must be exercised to maintain a stable internal environment during anesthesia, ensure safe and effective anesthesia and surgery, and facilitate recovery after surgery.

Mast cell activation plays a key role in the process of small intestinal ischemia-reperfusion (IIR) injury; however, the precise role of tryptase released from mast cell on IIR injury remains poorly understood. The aim of this study was to determine the protective role against IIR injury by using tryptase inhibitor protamine after ischemia and to explore the underlying mechanism.Adult Sprague-Dawley rats were randomized into sham-operated group (S), sole IIR group (IIR) in which rats were subjected to 75-minute superior mesenteric artery occlusion followed by 4-hour reperfusion, or IIR being respectively treated with mast cell stabilizer cromolyn sodium (CS group), with the mast cell degranulator compound 48/80 (CP group), or with protamine (P group). The previously mentioned agents were, respectively, administered intravenously 5 minutes before reperfusion. The intestine tissue was obtained for histologic assessment and assays for protein expressions of tryptase and mast cell protease 7 and protease-activated receptor 2 (PAR-2). The intestine mast cell number and levels of tumor necrosis factor κ and interleukin 8 were quantified.IIR resulted in intestinal injury evidenced as significant increases in Chiu's scores, accompanied with concomitant increases of mast cell counts and intestinal tryptase and mast cell protease 7 protein expressions. IIR also increased intestinal PAR-2 expressions, tumor necrosis factor κ, and interleukin 8 levels. Cromolyn sodium and protamine significantly reduced the responses to IIR injury while compound 48/80 further aggravated the previously mentioned biochemical changes.Tryptase releasing from mast cell activation participates in IIR injury through PAR-2, and inhibiting tryptase after ischemia provides promising benefits in limiting IIR injury.

Mast cell has been demonstrated to be involved in the small intestinal ischemia-reperfusion (IIR) injury, however, the precise role of tryptase released from mast cell on acute lung injury(ALI) induced by IIR remains to be elucidated, our study aimed to observe the roles of tryptase on ALI triggered by IIR and its underlying mechanism. Adult SD rats were randomized into sham-operated group, sole IIR group in which rats were subjected to 75 min superior mesenteric artery occlusion followed by 4 h reperfusion, or IIR being respectively treated with cromolyn sodium, protamine, and compound 48/80. The above agents were, respectively, administrated intravenously 5 min before reperfusion. At the end of experiment, lung tissue was obtained for assays for protein expressions of tryptase and mast cell protease 7 (MCP7) and protease-activated receptor 2 (PAR-2). Pulmonary mast cell number and levels of IL-8 were quantified. Lung histologic injury scores and lung water content were measured. IIR resulted in lung injury evidenced as significant increases in lung histological scores and lung water contents, accompanied with concomitant increases of expressions of tryptase and MCP7, and elevations in PAR-2 expressions and IL-8 levels in lungs. Stabilizing mast cell with cromolyn sodium and inhibiting tryptase with protamine significantly reduced IIR-mediated ALI and the above biochemical changes while activating mast cell with compound 48/80 further aggravated IIR-mediated ALI and the increases of above parameters. Tryptase released from mast cells mediates ALI induced by intestinal ischemia-reperfusion by activating PAR-2 to produce IL-8.

Propofol bolus injection has been reported to influence cardiovascular functions. However, the detailed mechanism underlying this action has not been elucidated. This study was designed to investigate the effects of propofol i.v. bolus on the left ventricular function, the myocardial β-adrenoceptor (β-AR) binding-site density (Bmax) and Kd (apparent dissociation constant) in a 30-minute period. One hundred and four male Wistar rats were randomly divided into four groups: group C (control group), group I (intralipid group), group P1 (5mg/kg propofol) and group P2 (10 mg/kg propofol). The results showed a significant downregulation of HR, LVSP, +dp/dt(subscript max) and -dp/dt(subscript max) in both groups P1 and P2 (especially after bolus injection in 7 min) than those of group C (P＜0.05), whereas no significant difference was found between the P1 and P2 groups (P＞0.05). Likely, Bmax was remarkably upregulated in both groups P1 and P2 (P＜0.05, vs. groups C and I), and there was no significant difference between these two groups (P＞0.05). Of note, the Kd value in group P2 (10 mg/kg propofol) was found dramatically increased in 30 min than that in the low-dose propofol-treated group (group P1) as well as in groups C and I (P＜0.05). In conclusion, these results indicate that intravenous injection of propofol bolus can inhibit the cardiac function partially via upregulation of Bmax and downregulation of the β-AR affinity at higher-dose injection of propofol bolus.

Both oxidative stress and mast cell (MC) degranulation participate in the process of small intestinal ischemia reperfusion (IIR) injury, and oxidative stress induces MC degranulation. Propofol, an anesthetic with antioxidant property, can attenuate IIR injury. We postulated that propofol can protect against IIR injury by inhibiting oxidative stress subsequent from NADPH oxidase mediated MC activation. Cultured RBL-2H3 cells were pretreated with antioxidant N-acetylcysteine (NAC) or propofol and subjected to hydrogen peroxide (H2O2) stimulation without or with MC degranulator compound 48/80 (CP). H2O2significantly increased cells degranulation, which was abolished by NAC or propofol. MC degranulation by CP further aggravated H2O2induced cell degranulation of small intestinal epithelial cell, IEC-6 cells, stimulated by tryptase. Rats subjected to IIR showed significant increases in cellular injury and elevations of NADPH oxidase subunits p47phoxand gp91phoxprotein expression, increases of the specific lipid peroxidation product 15-F2t-Isoprostane and interleukin-6, and reductions in superoxide dismutase activity with concomitant enhancements in tryptase andβ-hexosaminidase. MC degranulation by CP further aggravated IIR injury. And all these changes were attenuated by NAC or propofol pretreatment, which also abrogated CP-mediated exacerbation of IIR injury. It is concluded that pretreatment of propofol confers protection against IIR injury by suppressing NADPH oxidase mediated MC activation.

Background The mechanism of mucosal damage induced by ischemia-reperfusion (IR) after hemorrhagic shock is complex; mast cells (MC) degranulation is associated with the mucosal damage. Astragalus membranaceus can protect intestinal mucosa against intestinal oxidative damage after hemorrhagic shock, and some antioxidant agents could prevent MC against degranulation. This study aimed to observe the effects of astragalus membranaceus injection on the activity of intestinal mucosal mast cells (IMMC) after hemorrhage shock-reperfusion in rats Methods Thirty-two Wistar rats were randomly divided into the normal group, model group, low dosage group, (treated with Astragalus membranacaus injection, 10 g crude medication/kg) and high dosage group (treated with Astragalus membranacaus injection, 20 g crude medication/kg). The rat model of hemorrhagic shock-reperfusion was induced by hemorrhage for 60 minutes followed by 90 minutes of reperfusion. The animals were administrated with 3 ml of the test drug solution before reperfusion. At the end of study, intestinal pathology, ultrastructure of IMMC, and expression of tryptase were assayed. The levels of malondisldehyde (MDA), TNF-α, histamine, and superoxide dismutase (SOD) activity in intestine were detected, and the number of IMMC was counted. Results The Chiu’s score of the rats in the model group was higher than in other groups (P0.01). The Chiu’s score in the high dosage group was higher than that in the low dosage group (P0.05). Hemorrhage-reperfusion induced IMMC degranulation: Astragalus membranaceus injection attenuated this degranulation. Expression of tryptase and the number of IMMC in the model group increased compared with the other groups (P0.01) and was significantly reduced by the treatments of Astragalus membranaceus injection at both doses. There was no significant difference between the two treatment groups (P0.05). MDA content and concentration of TNF-α in the model group were higher than that in the other three groups (P0.05), and the concentration of TNF-α in the low dosage group was higher than that in the high dosage group (P0.05). SOD activity and the concentration of histamine in the model group were lower than the other three groups (P0.05). There was a negative correlation betweenthe Chiu’s score and the concentration of histamine and a positive correlation between the Chiu’s score and the concentration of TNF-α and between the SOD activity and the concentration of histamine in the four groups (P0.05). Conclusion Astragalus membranaceus injection may reduce the damage to small intestine mucosa by inhibiting the activated IMMC after hemorrhagic shock.

OBJECTIVE: To improve the performance of glomerular filtration rate (GFR) estimating equation in Chinese type 2 diabetic patients by modification of the CKD-EPI equation. DESIGN AND PATIENTS: A total of 1196 subjects were enrolled. Measured GFR was calibrated to the dual plasma sample 99mTc-DTPA-GFR. GFRs estimated by the re-expressed 4-variable MDRD equation, the CKD-EPI equation and the Asian modified CKD-EPI equation were compared in 351 diabetic/non-diabetic pairs. And a new modified CKD-EPI equation was reconstructed in a total of 589 type 2 diabetic patients. RESULTS: In terms of both precision and accuracy, GFR estimating equations all achieved better results in the non-diabetic cohort comparing with those in the type 2 diabetic cohort (30% accuracy, P≤0.01 for all comparisons). In the validation data set, the new modified equation showed less bias (median difference, 2.3 ml/min/1.73 m2 for the new modified equation vs. ranged from -3.8 to -7.9 ml/min/1.73 m2 for the other 3 equations [P

The study aimed to investigate whether sevoflurane preconditioning can protect against small intestinal ischemia reperfusion (IIR) injury and to explore whether mast cell (MC) is involved in the protections provided by sevoflurane preconditioning. Sprague-Dawley rats exposed to sevoflurane or treated with MC stabilizer cromolyn sodium (CS) were subjected to 75-minute superior mesenteric artery occlusion followed by 2-hour reperfusion in the presence or absence of MC degranulator compound 48/80 (CP). Small intestinal ischemia reperfusion resulted in severe intestinal injury as demonstrated by significant elevations in intestinal injury scores and p47phoxand gp91phox, ICAM-1 protein expressions and malondialdehyde and IL-6 contents, and MPO activities as well as significant reductions in SOD activities, accompanied with concomitant increases in mast cell degranulation evidenced by significant increases in MC counts, tryptase expression, andβ-hexosaminidase concentrations, and those alterations were further upregulated in the presence of CP. Sevoflurane preconditioning dramatically attenuated the previous IIR-induced alterations except MC counts, tryptase, andβ-hexosaminidase which were significantly reduced by CS treatment. Furthermore, CP exacerbated IIR injury was abrogated by CS but not by sevoflurane preconditioning. The data collectively indicate that sevoflurane preconditioning confers protections against IIR injury, and MC is not involved in the protective process.

Liver abnormalities are seen in a small proportion of patients following anaesthesia with sevoflurane.To investigate whether the cytotoxicity of sevoflurane against rat liver cells was mediated by gap junction intercellular communications, and the effect of propofol on sevoflurane-induced cytotoxicity.Experimental study.The study was carried out in the central laboratory of The Third Affiliated Hospital, Sun Yat-sen University.BRL-3A rat liver cells.Immortal rat liver cells BRL-3A were grown at low and high density. Colony-forming assays were performed to determine clonogenic growth of these cells. To investigate the effect of oleamide and propofol on gap junction function, we measured fluorescence transmission between cells using parachute dye-coupling assays. Immunoblotting assays were performed to determine connexin32 and connexin43 expression.Our colony formation assays revealed that, in low-density culture, sevoflurane caused no apparent inhibition of clonogenic growth of BRL-3A cells. In high-density culture, 2.2 to 4.4% sevoflurane markedly inhibited clonogenic growth of BRL-3A cells with 67.6 (0.34)% and 61.2 (0.17)% of the cells being viable, respectively (P = 0.003 vs. low-density culture), suggesting cell density dependency of sevoflurane-induced cytotoxicity. Our colony formation assays revealed that propofol markedly attenuated the suppression by sevoflurane of the clonogenic growth of BRL-3A cells (viability: propofol and sevoflurane, 91.5 (0.014)% vs. sevoflurane, 56.6 (0.019)%; P 0.01). Blocking gap junctions with 10 μmol l oleamide significantly attenuated 4.4% sevoflurane-induced suppression with a viability of 83.6 ± 0.138% (oleamide and sevoflurane vs. sevoflurane, P 0.01). Immunoblotting assays further showed that propofol (3.2 μg ml) markedly reduced CX32 levels and significantly inhibited gap junctional intercellular communications as revealed by parachute dye-coupling assays. Values are mean (SD).This study provides the first direct evidence that sevoflurane-induced cytotoxicity, which is mediated through gap junctions, is attenuated by propofol, possibly by its action on Cx32 homomeric or heteromeric complexes.

Both oxidative stress and mast cells are involved in acute lung injuries (ALIs) that are induced by intestinal ischemia-reperfusion (IIR). The aim of this study was to further investigate the interaction between oxidative stress and mast cells during the process of IIR-induced ALI.Thirty adult Sprague-Dawley rats were randomly divided into five groups: sham, IIR, IIR + compound 48/80 (CP), N-acetylcysteine (NAC) + IIR, and NAC + IIR + CP. All rats except those in the sham group were subjected to 75 min of superior mesenteric artery occlusion, followed by 2 h of reperfusion. The rats in the NAC + IIR and NAC + IIR + CP groups were injected intraperitoneally with NAC (0.5 g/kg) for three successive days before undergoing IIR. The rats in the IIR + CP and NAC + IIR + CP groups were treated with CP (0.75 mg/kg), which was administered intravenously 5 min before the reperfusion. At the end of the experiment, lung tissue was obtained for pathologic and biochemical assays.IIR resulted in ALI, which was detected by elevated pathology scores, a higher lung wet-to-dry ratio, and decreased expression of prosurfactant protein C (P 0.05). Concomitant elevations were observed in the expression levels of the nicotinamide adenine dinucleotide phosphate oxidase subunits p47(phox) and gp91(phox) and the levels of hydrogen peroxide and malondialdehyde. However, superoxide dismutase activity in the lung was reduced (P 0.05). The level of interleukin 6, the activity of myeloperoxidase, and the expression of intercellular adhesion molecule 1 were also increased in the lung. IIR led to pulmonary mast cell degranulation and increases in the plasma and pulmonary β-hexosaminidase levels, mast cell counts, and tryptase expression in lung tissue. CP aggravated these conditions, altering the measurements further, whereas NAC attenuated the IIR-induced ALI and all biochemical changes (P 0.05). However, CP abolished some of the protective effects of NAC.Oxidative stress and mast cells interact with each other and promote IIR-induced ALI.