Publications by authors named "Jijian Zheng"

37 Publications

Yohimbine Directly Induces Cardiotoxicity on Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Cardiovasc Toxicol 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.

Yohimbine is a highly selective and potent α-adrenoceptor antagonist, which is usually treated as an adjunction for impotence, as well for weight loss and natural bodybuilding aids. However, it was recently reported that Yohimbine causes myocardial injury and controversial results were reported in the setting of cardiac diseases. Here, we used human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model system to explore electrophysiologic characterization after exposure to Yohimbine. HiPSC-CMs were differentiated by employment of inhibitory Wnt compounds. For analysis of electrophysiological properties, conventional whole-cell patch-clamp recording was used. Specifically, spontaneous action potentials, pacemaker currents (I), sodium (Na) channel (I), and calcium (Ca) channel currents (I) were assessed in hiPSC-CMs after exposure to Yohimbine. HiPSC-CMs expressed sarcomeric-α-actinin and MLC2V proteins, as well as exhibited ventricular-like spontaneous action potential waveform. Yohimbine inhibited frequency of hiPSC-CMs spontaneous action potentials and significantly prolonged action potential duration in a dose-dependent manner. In addition, rest potential, threshold potential, amplitude, and maximal diastolic potential were decreased, whereas APD/APD was prolonged. Yohimbine inhibited the amplitude of I in low doses (IC = 14.2 μM, n = 5) and inhibited I in high doses (IC = 139.7 μM, n = 5). Whereas Yohimbine did not affect the activation curves, treatment resulted in left shifts in inactivation curves of both Na and Ca channels. Here, we show that Yohimbine induces direct cardiotoxic effects on spontaneous action potentials of I and I in hiPSC-CMs. Importantly, these effects were not mediated by α-adrenoceptor signaling. Our results strongly suggest that Yohimbine directly and negatively affects electrophysiological properties of human cardiomyocytes. These findings are highly relevant for potential application of Yohimbine in patients with atrioventricular conduction disorder.
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http://dx.doi.org/10.1007/s12012-021-09709-3DOI Listing
November 2021

Effects of age on sugammadex reversal of neuromuscular blockade induced by rocuronium in Chinese children: a prospective pilot trial.

BMC Anesthesiol 2021 10 19;21(1):248. Epub 2021 Oct 19.

Department of Anesthesiology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Background: Sugammadex reverses neuromuscular blockade induced by steroidal relaxants. We compared the recovery for neuromuscular blockade reversal with sugammadex in children aged 1-12 years.

Methods: From August 2019 to August 2020, patients who received 2.0 mg·kg sugammadex for neuromuscular blockade reversal after surgery were recruited. The primary outcome was the time for the train-of-four ratio (TOFR) to recover to 0.9; secondary outcomes included the incidence of the TOFR < 0.9, extubation time, length of stay at the post-anesthesia care unit, and adverse events. Hemodynamic parameters before and 5 min after sugammadex administration and vital signs in the recovery room were also recorded.

Results: Eighty-six children were recruited (1 to < 3 years, n = 23; 3 to < 5 years, n = 33; 5 to ≤12 years, n = 30). Intergroup differences in the recovery of the TOFR to 0.9 were not statistically significant (F = 0.691, p = 0.504). Recurrence of the TOFR < 0.9 was not observed in any group. Five minutes after sugammadex administration, the heart rates of patients aged 3 to < 5 and 5 to ≤12 years were significantly lower than those at baseline (p < 0.05). Extubation time was similar in patients aged 1 to ≤12 years. Length of stay and end-tidal capnography at the post-anesthesia care unit as well as adverse events did not differ significantly.

Conclusion: A moderate (TOF count two) rocuronium-induced neuromuscular blockade can be effectively and similarly reversed with sugammadex 2 mg·kg in Chinese children aged 1-12 years.

Trial Registration: Chinese Clinical Trial Registry: ChiCTR1900023715 (June 8, 2019).
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http://dx.doi.org/10.1186/s12871-021-01465-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524895PMC
October 2021

Age-Related Changes in Cerebral Hemodynamics in Children Undergoing Congenital Cardiac Surgery: A Prospective Observational Study.

J Cardiothorac Vasc Anesth 2021 Sep 4. Epub 2021 Sep 4.

Department of Anesthesiology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Objective: To explore age-related cerebral hemodynamic characteristics before and after pediatric cardiac surgery.

Design: Prospective observational study.

Setting: Single-center study based at a tertiary care center in Shanghai, China.

Patients: Fifty-three children with congenital heart disease (CHD) aged zero-to-six years undergoing cardiac surgery with cardiopulmonary bypass were enrolled, and 44 children finally were analyzed.

Intervention: Cerebral hemodynamics were measured by transcranial color-coded duplex sonography in the right temporal window before and after surgery. The resistance index (RI), pulsatility index (PI), and cerebral blood flow velocity (CBFV), including time average maximum flow velocity (V), mean blood flow velocity (V), and the peak systolic flow velocity (V), of the right middle cerebral artery (MCA) and regional cerebral oxygen saturation (rScO) of the right frontal lobe were measured and analyzed. Heart rate and mean arterial pressure were also recorded during ultrasound.

Measurements And Main Results: RI and PI decreased exponentially with age before and after cardiac surgery. While PI remained unchanged after cardiac surgery, RI was significantly reduced. Furthermore, RI reduction after cardiac surgery was more significant in children >18 months compared to those ≤18 months. CBFV of the right MCA also showed exponential increase with age, but rScO linearly increased. Cardiac surgery significantly changed the cerebral hemodynamics, but it did not affect rScO in children regardless of age.

Conclusions: Age-related cerebral hemodynamic changes exist in children with CHD. Cardiopulmonary bypass surgery led to greater cerebrovascular dilation in children aged ≤18 months than those >18 months.
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http://dx.doi.org/10.1053/j.jvca.2021.08.099DOI Listing
September 2021

Paediatric preoperative sedation practices in tertiary maternity and children's hospitals in China: a questionnaire survey.

BMC Pediatr 2021 08 9;21(1):336. Epub 2021 Aug 9.

Department of Anaesthesiology, Shanghai Children's Medical Center, National Children's Medical Center, 1678 Dongfang Road, Shanghai, China.

Background: Preoperative anxiety is a common problem in the paediatric population, and several studies have reported that it is related to adverse events such as emergence delirium and postoperative psychological and behavioural changes. In recent years, increasing attention has been paid to paediatric preoperative anxiety in China. A variety of strategies, including sedatives, parental presence, and audio-visual interventions, have been used to relieve paediatric preoperative anxiety, but there is no well-recognised procedure for paediatric preoperative sedation. Therefore, this study aimed to investigate current paediatric preoperative sedation practices in tertiary children's hospitals in China.

Methods: All tertiary maternity and children's hospitals registered with the National Health Commission of the People's Republic of China were invited to participate in an electronic survey, which included information on the preoperative sedation caseload, sites where preoperative sedation was performed, preoperative sedation methods used in different age groups, choice of sedatives, contraindications for premedication, staff structure for sedative administration and monitoring, and patient-monitoring practices.

Results: All 81 hospitals participating in our study completed the survey, and 38 hospitals (46.9 %) provided their preoperative sedation protocols. Twenty-four hospitals performed fewer than 5,000 preoperative sedation cases annually, and 9 hospitals performed more than 10,000 cases annually. Preoperative sedation was performed in preoperative preparation areas, preoperative holding areas, and operation rooms in 47.4 %, 26.3 %, and 13.2 % of hospitals, respectively. Sedatives were the most used interventions for paediatric preoperative sedation in all age groups, and the most widely used sedatives were propofol (intravenous) and dexmedetomidine (intranasal). The most common contraindications were American Society of Anesthesiologists class ≥ 3, emergency operation, and airway infection within 2 weeks. Sedatives were administered mainly by anaesthesiologists (63.2 %), and children were monitored mainly by anaesthesiologists (44.7 %) and nurses (39.5 %) after administration. Pulse oximetry was the most widely used monitoring device.

Conclusions: Fewer than half of the tertiary maternity and children's hospitals in China provide paediatric preoperative sedation service, and the service practices vary widely. Further improvements are required to ensure the quality of paediatric preoperative sedation services and establish standard operating procedures.
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http://dx.doi.org/10.1186/s12887-021-02802-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351349PMC
August 2021

A randomized controlled trial of ultrasound-assisted technique versus conventional puncture method for saphenous venous cannulations in children with congenital heart disease.

BMC Anesthesiol 2021 04 27;21(1):131. Epub 2021 Apr 27.

Department of Anesthesiology, Shanghai Children's Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, Pudong, Shanghai, 200127, China.

Background: The study investigated the success rate of the great saphenous venous catheter placement performed by ultrasound-assisted technique compared with the conventional puncture method in infants and toddlers with congenital heart disease and aimed to assess the efficiency and feasibility of this method within the context of pediatric peripheral venous access.

Methods: We selected infants and toddlers who underwent congenital cardiac surgery in our medical center from June 1, 2020, to September 7, 2020, by convenience sampling. Children were stratified by the presence of the manifesting cardiac types (cyanotic or acyanotic heart disease). They were assigned to the conventional puncture method group or the ultrasound-assisted group through randomly blocked randomization. The primary outcome was the success rate of the first attempt. The second outcomes included the time to cannulation at the first attempt, the redirections of the first attempt, overall puncture time, and overall redirections of efforts. Besides, a binary logistic regression model was implemented to identify the possible variables related to the success rate of the first attempt.

Results: A total of 144 children in our medical center were recruited in the study. The success rate of the first attempt in the ultrasound-assisted group was higher than that of the conventional puncture method group in the stratification of cyanotic children (66.7% vs. 33.3%, P = 0.035). Among children of acyanotic kind, the difference in the success rate of the first attempt between the two groups was not significant (57.6% vs. 42.4%, P = 0.194). Overall puncture time (45.5 s vs. 94 s, P = 0.00) and the time to cannulation at the first attempt (41.0 s vs. 60 s, P = 0.00) in the ultrasound-assisted group was less than the conventional puncture method group. The ultrasound-assisted group also required fewer redirections of the first attempt (three attempts vs. seven attempts, P = 0.002) and fewer total redirections of efforts (two attempts vs. three attempts, P = 0.027) than the conventional puncture method group. The result of binary Logistic regression showed that the success rate of the first attempt was related to age (OR:1.141; 95% CI = 1.010-1.290, P = 0.034), the redirections of the first attempt (OR:0.698; 95% CI = 0.528-0.923, P = 0.012) and the saphenous venous width (OR:1.181; 95% CI = 1.023-1.364, P = 0.023).

Conclusions: The ultrasound-assisted technique improves the saphenous venous cannulation sufficiently in children with difficult peripheral veins. The younger age is associated with a higher likelihood of peripheral venous difficulty. The ultrasound-assisted methods can effectively screen peripheral veins, e.g., selecting thicker diameter peripheral veins, making puncture less uncomfortable, and improving success rates. This method can be used as one of the effective and practical ways of peripheral venipuncture in children, especially in difficult situations. It should be widely applied as one of the alternative ultrasound techniques in the operating room.

Trial Registration: ChiCTR.org.cn ( ChiCTR-2,000,033,368 ). Prospectively registered May 29, 2020.
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http://dx.doi.org/10.1186/s12871-021-01349-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077689PMC
April 2021

Dexmedetomidine exhibits antiarrhythmic effects on human-induced pluripotent stem cell-derived cardiomyocytes through a Na/Ca channel-mediated mechanism.

Ann Transl Med 2021 Mar;9(5):399

Department of Pediatric Cardiothoracic Surgery, Shanghai Children's Medical Center; School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Ventricular-like human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exhibit the electrophysiological characteristics of spontaneous beating. Previous studies demonstrated that dexmedetomidine (DMED), a highly selective and widely used α-adrenoceptor agonist for sedation, analgesia, and stress management, may induce antiarrhythmic effects, especially ventricular tachycardia. However, the underlying mechanisms of the DMED-mediated antiarrhythmic effects remain to be fully elucidated.

Methods: A conventional patch-clamp recording method was used to investigate the direct effects of DMED on spontaneous action potentials, pacemaker currents ( ), potassium (K) channel currents ( and ), sodium (Na) channel currents ( ), and calcium (Ca) channel currents ( ) in ventricular-like hiPSC-CMs.

Results: DMED dose-dependently altered the frequency of ventricular-like spontaneous action potentials with a half-maximal inhibitory concentration (IC) of 27.9 µM (n=6) and significantly prolonged the action potential duration at 90% repolarization (APD). DMED also inhibited the amplitudes of the and without affecting the activation and inactivation curves of these channels. DMED decreased the time constant of the Na and Ca channel activation at potential -40 to -20 mv, and -20 mv. DMED increased the time constant of inactivation of the Na and Ca channels. However, DMED did not affect the , , , and their current-voltage relationship. The ability of DMED to decrease the spontaneous action potential frequency and the Na and Ca channel amplitudes, were not blocked by yohimbine, idazoxan, or phentolamine.

Conclusions: DMED could inhibit the frequency of spontaneous action potentials and decrease the and of hiPSC-CMs via mechanisms that were independent of the α-adrenoceptor, the imidazoline receptor, and the α-adrenoceptor. These inhibitory effects on hiPSC-CMs may contribute to the antiarrhythmic effects of DMED.
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http://dx.doi.org/10.21037/atm-20-5898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033317PMC
March 2021

Lateral Habenula Glutamatergic Neurons Modulate Isoflurane Anesthesia in Mice.

Front Mol Neurosci 2021 4;14:628996. Epub 2021 Mar 4.

Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep-wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep-wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings , we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.
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http://dx.doi.org/10.3389/fnmol.2021.628996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969819PMC
March 2021

Integrin-dependent microgliosis mediates ketamine-induced neuronal apoptosis during postnatal rat retinal development.

Exp Neurol 2021 06 26;340:113659. Epub 2021 Feb 26.

Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China; Center for Brain Science, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. Electronic address:

Purpose: Remodeling of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) plays a pivotal role for microglia in developing retina. We tested whether integrin-dependent microgliosis mediates ketamine-induced neuronal apoptosis in the developing rat retina.

Methods: We performed immunofluorescence assays to investigate the role of integrin receptors expressed in the microglia in ketamine-induced neuronal apoptosis. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to investigate the protein and mRNA levels of cytokines (TNF-α, IL-1β) and/or chemokines (CCL2, CXCL6, CXCL10, and CXCL12). Experiments were performed using whole-mount retinas dissected from P7 Sprague-Dawley rats.

Results: Integrin receptors expressed in microglia were upregulated in ketamine-induced neuronal apoptosis in the early developing rat retina. Downregulating integrin receptors with RGD peptide ameliorated ketamine-induced microgliosis through: 1) ameliorating the change in microglia morphology from immature ramified microglia to an amoeboid state; 2) decreasing the number of microglia and intensity of activated microglia in the retinal ganglion cell layer (GCL); and 3) decreasing cytokine (TNF-α and IL-1β) and chemokine (CCL2, CXCL10) levels in the retinal tissue. Inhibition of activated microglia with minocycline or the blockade of cytokines (TNF-α and IL-1β) with a receptor antagonist (RA) attenuated neuronal apoptosis after exposure to ketamine.

Conclusions: The upregulation of integrin β1 receptors in the microglia acts as a signaling molecule, triggering microgliosis to aggravate ketamine-induced neuronal apoptosis via the release of TNF-α and IL-1β in the early developing rat retina.
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http://dx.doi.org/10.1016/j.expneurol.2021.113659DOI Listing
June 2021

Effectiveness of postural lung recruitment on postoperative atelectasis assessed by lung ultrasound in children undergoing lateral thoracotomy cardiac surgery with cardiopulmonary bypass.

Pediatr Pulmonol 2021 06 23;56(6):1724-1732. Epub 2021 Feb 23.

Department of Anesthesiology, School of Medicine, Shanghai Children's Medical Centre, Shanghai Jiao Tong University, Shanghai, China.

Objectives: To assess the effects of postural lung recruitment maneuvers on the postoperative atelectasis assessed by lung ultrasound (LUS) compared with supine position recruitment maneuvers in children undergoing right lateral thoracotomy cardiac surgery with cardiopulmonary bypass.

Methods: In this randomized and controlled trial, 84 patients aged 3 years or younger, scheduled for right lateral thoracotomy cardiac surgery with cardiopulmonary bypass (CPB) were randomly allocated to postural lung recruitment group or control group. The first LUS exam was performed immediately upon completion of the cardiac surgery (T1), and a repeat ultrasound exam started 1 min after lung recruitment maneuvers (T2). The primary outcome was the incidence of significant atelectasis at T2.

Results: The incidence of significant atelectasis at T2 in the postural lung recruitment maneuver group was lower compared with that in the control group (30.2% vs. 58.1%; odds ratio: 0.31; 95% confidence interval: 0.13-0.76; p = .009). The LUS scores for consolidations and B-lines of the left lung were higher than those of the right lung in both groups at T1. More significant reduction of the left LUS scores and sizes of atelectatic areas were found in the postural lung recruitment group than those in the control group.

Conclusions: Postoperative postural recruitment maneuver was more effective to improve reaeration of lung than supine position recruitment maneuver in children undergoing right lateral thoracotomy cardiac surgery with CPB.
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http://dx.doi.org/10.1002/ppul.25315DOI Listing
June 2021

Laminin degradation by matrix metalloproteinase 9 promotes ketamine-induced neuronal apoptosis in the early developing rat retina.

CNS Neurosci Ther 2020 Jun 20. Epub 2020 Jun 20.

Department of Anesthesiology, Shanghai Children's Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Aims: During early development, laminin degradation contributes to the death of neurons. This study aims to investigate the role and regulation of laminin in ketamine-induced apoptosis.

Methods: We performed terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and immunohistochemical assays to investigate the roles of the non-integrin laminin receptor, matrix metalloproteinase 9 (MMP9) in ketamine-induced neuronal apoptosis. In situ zymography, Western blot, and immunofluorescence were used to explore the relationships between laminin, MMP9 activity, and Zn . Experiments were performed using whole-mount retinas dissected from Sprague Dawley rats.

Results: The TUNEL and immunohistochemical assays indicated that ketamine-induced neuronal apoptosis in early developing rat retina. Blockade of non-integrin laminin receptor promoted ketamine-induced apoptosis, while non-integrin laminin receptor activation attenuated ketamine-induced apoptosis. Ketamine-induced laminin degradation, possibly by enhancing the activity of MMP9. MMP9 inhibition reduced ketamine-induced apoptosis by reducing laminin degradation. Downregulation of Zn attenuated the increased MMP9 activity, laminin degradation caused by ketamine and significantly reduced ketamine-induced neuronal apoptosis.

Conclusion: Laminin degradation by MMP9 promoted ketamine-induced neuronal apoptosis in early developing rat retina. The non-integrin laminin receptor may be a pathway involved in ketamine-induced apoptosis. Zn downregulation may play a protective role against ketamine-induced neuronal apoptosis through inhibiting MMP9 activity.
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http://dx.doi.org/10.1111/cns.13428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539835PMC
June 2020

Anesthesia timing for children undergoing therapeutic cardiac catheterization after upper respiratory infection: a prospective observational study.

Minerva Anestesiol 2020 08 6;86(8):835-843. Epub 2020 Apr 6.

Department of Anesthesiology, Shanghai Children's Medical Center, School of Medicine and National Children's Medical Center, Shanghai Jiao Tong University, Shanghai, China -

Background: We aimed to analyze anesthesia timing and perioperative respiratory adverse event (PRAE) risk factors in children undergoing therapeutic cardiac catheterization after upper respiratory tract infection (URI).

Methods: We prospectively included children for elective therapeutic cardiac catheterization. Parents or legal guardians were asked to complete a questionnaire on the child's demographics, tobacco exposure, and URI symptoms. PRAEs (laryngospasm, bronchospasm, coughing, airway secretion, airway obstruction, and oxygen desaturation) as well as details of anesthesia management were recorded.

Results: Of 332 children, 201 had a history of URI in the preceding eight weeks. The occurrence rate of PRAEs in children with URI≤two weeks reached the highest proportion, which was higher than that in children without URI (66.3% vs. 46.6%, P=0.007). The overall incidence of PRAEs in children with URI in 3-8 weeks was significantly lower than that in children with URI in the recent ≤two weeks (49.0% vs. 66.3%, P=0.007), and similar to that in the control group (49.0% vs. 46.6%). Multivariate analysis showed association between PRAEs and type of congenital heart disease (CHD) (P<0.001), anesthesia timing (P=0.007), and age (P=0.021). Delayed schedule (two weeks after URI) minimized the risk of PRAEs to the level comparable to that observed in children without URI (OR, 1.11; 95% CI: 0.64-1.91; P=0.707).

Conclusions: If treatment is not urgent, a pediatric patient at a high risk of PRAEs will be benefit from the postponement of an interventional operation by at least two weeks after URI.
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http://dx.doi.org/10.23736/S0375-9393.20.14293-7DOI Listing
August 2020

Lung ultrasound evaluation of incremental PEEP recruitment maneuver in children undergoing cardiac surgery.

Pediatr Pulmonol 2020 05 9;55(5):1273-1281. Epub 2020 Mar 9.

Department of Anesthesiology and Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Aim: To explore the effect of incremental positive end-expiratory pressure recruitment maneuver (iPEEPRM) in children with congenital heart diseases (CHDs) using lung ultrasound.

Methods: Thirty-six children aged 3 months to 5 years scheduled for cardiac surgery participated. iPEEPRM was performed with PEEP stepwise increase (0-5-10-15 cmH O) and decrease at the same rate before and after surgery. Atelectatic areas, ultrasound scores, arterial oxygen pressure (PaO ), and respiratory system dynamic compliance per kilogram body weight (CDyn/kg) were analyzed before and after iPEEPRM. The primary outcome is the incidence of atelectasis. Secondary outcomes are oxygenation, ventilation, CDyn/kg, and atelectasis area.

Results: iPEEPRM was successfully applied in 92% (33/36) children before surgery and 71% (24/34) children after surgery. The incidence of atelectasis was significantly reduced by iPEEPRM from 76% to 15% before surgery and from 92% to 38% after surgery, respectively (P < .001). Before surgery, iPEEPRM significantly reduced atelectatic areas and ultrasound scores: 32.5 (0-128.1) mm vs 0 (0-0) mm and 8 (3-12) vs 2 (0-4). PaO and CDyn/kg were significantly increased after iPEEPRM: 243 (129-275) mm Hg vs 278 (207-323) mm Hg and 0.6 (0.4-0.7) mL/cmH O/kg vs 0.8 (0.6-1.0) mL/cmH O/kg. After surgery, iPEEPRM significantly reduced atelectatic areas and ultrasound scores: 45.7 (13.1-115.8) mm vs 0 (0-34.7) mm , and 9 (6-12) vs 3 (0-5). PaO and CDyn/kg were also significantly increased after iPEEPRM.

Conclusions: iPEEPRM effectively reduced atelectasis, improved lung aeration, oxygenation, and CDyn/kg in children undergoing cardiac surgery.
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http://dx.doi.org/10.1002/ppul.24720DOI Listing
May 2020

Moderate and deep sedation for non-invasive paediatric procedures in tertiary maternity and children's hospitals in China: a questionnaire survey from China.

BMC Health Serv Res 2020 Jan 8;20(1):28. Epub 2020 Jan 8.

Department of Anaesthesiology, Shanghai Children's Medical Center, Affiliated with Shanghai Jiao Tong University School of Medicine, National Children's Medical Center, 1678 Dong Fang Road, Shanghai, 200127, China.

Background: Moderate and deep sedation are well-established techniques in many developed countries, and several guidelines have been published. However, they have received attention in China only in recent years. The aim of this study is to investigate current paediatric sedation practices in tertiary children's hospitals and tertiary maternity and children hospitals in China.

Methods: All tertiary children's hospitals and tertiary maternity and children hospitals registered with the National Health Commission of the People's Republic of China were invited to participate in an electronic survey, which included information on the sedation caseload, facility availability, staff structure, clinical skill requirements for sedation providers, fasting guidelines, patient-monitoring practices, and choice of sedatives.

Results: Fifty-eight of the 63 hospitals that completed the survey (92.1%) provided moderate and deep sedation. Dedicated sedation rooms and post-sedation recovery rooms were found in 14 (24.1%) and 19 (32.8%) hospitals, respectively. Sedation for non-invasive procedures was primarily performed by anaesthesiologists (69.0%); however, 75.9% of the sedation providers had not received paediatric basic or advanced life-support training. Children were asked to fast from clear liquids for at least 2 h in 44.8% of hospitals and up to 6 h in 5.2% of hospitals; they were asked to fast from solid food/milk for at least 4 h in 27.6% of hospitals and more than 8 h in 1.7% of hospitals. The most commonly used sedative in all groups was chloral hydrate. For rescue, propofol was the most widely used sedative, particularly for children older than 4 years.

Conclusions: Moderate and deep sedation practices vary widely in tertiary children's hospitals and tertiary maternity and children hospitals in China. Optimised practices should be established to improve the quality of moderate and deep sedation.
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http://dx.doi.org/10.1186/s12913-019-4885-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951005PMC
January 2020

Prediction of Hemodynamic Reactivity by Electroencephalographically Derived Pain Threshold Index in Children Undergoing General Anesthesia: A Prospective Observational Study.

J Pain Res 2019 3;12:3245-3255. Epub 2019 Dec 3.

Department of Anesthesiology, Shanghai Children's Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, Pudong, Shanghai, People's Republic of China.

Purpose: The pain threshold index (PTI) is a novel measure of nociception based on integrated electroencephalogram parameters during general anesthesia. The wavelet index (WLI) reflects the depth of sedation. This study aims to evaluate the ability of the PTI and WLI to predict hemodynamic reactivity after tracheal intubation and skin incision in pediatric patients.

Patients And Methods: Pediatric patients (n=134) undergoing elective general surgery or urinary surgery were analyzed. Measurements at predefined time-points during tracheal intubation and skin incision included the PTI, WLI, heart rate (HR), and mean blood pressure (MBP). Receiver-operating characteristic (ROC) curves were computed to evaluate the predictive performance of the PTI and WLI in measuring hemodynamic reactivity (an increase of more than 20% in either MBP or HR) during general anesthesia.

Results: Of the 134 patients evaluated, positive reactivity of HR and MBP was observed in 95 (70.9%) and 61 (45.5%) patients induced by intubation, respectively, and 19 (14.2%) and 24 (17.9%) patients induced by skin incision, respectively. Using either HR or MBP reactivity induced by intubation as a dichotomous variable, the areas under the curves (AUCs) [95% CI] of PTI and WLI were 0.81[0.73-0.87] and 0.58[0.49-0.67] with the best cutoff values of 62 and 49. The AUCs [95% CI] of PTI and WLI were 0.82[0.75-0.88] and 0.61[0.52-0.69] after skin incision. The best cutoff values of PTI and WLI were 60 and 46, respectively.

Conclusion: The PTI can predict hemodynamic reactivity with the best cutoff values of 62 and 60 after tracheal intubation and skin incision in pediatric patients during general anesthesia. The WLI failed in predicting hemodynamic changes.
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http://dx.doi.org/10.2147/JPR.S231596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899069PMC
December 2019

Intranasal dexmedetomidine premedication in children with recent upper respiratory tract infection undergoing interventional cardiac catheterisation: A randomised controlled trial.

Eur J Anaesthesiol 2020 Feb;37(2):85-90

From the Department of Anaesthesiology (SZ, RZ, MC, KZ, MZ, JZ) and Paediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Centre, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (MZ, JZ).

Background: Recent upper respiratory tract infection (URI) is a risk factor for the occurrence of peri-operative respiratory adverse events (PRAE). This risk may be higher in children with congenital heart disease (CHD), particularly in those undergoing interventional cardiac catheterisation. It is therefore essential to adapt the anaesthetic strategy in these children to prevent from the occurrence of PRAE.

Objective: To determine whether intranasal dexmedetomidine (DEX) premedication can reduce the incidence of PRAE in children with recent URI undergoing interventional cardiac catheterisation.

Design: Randomised controlled trial.

Setting: Single-centre study based at a tertiary care centre in Shanghai, China.

Patients: A total of 134 children with CHD aged 0 to 16 years with recent URI undergoing interventional cardiac catheterisation.

Interventions: Children were randomised to receive either intranasal DEX 1.5 μg kg (DEX group) or intranasal saline (Placebo group) 30 to 45 min before anaesthesia induction.

Main Outcome Measures: The incidence of PRAE.

Results: Intranasal DEX significantly reduced the incidence of PRAE (P = 0.001), particularly oxygen desaturation (P = 0.012). Most PRAE were observed during the emergence phase. The incidence of PRAE was comparable among the three types of left-right shunt CHD children in both groups. In children aged less than 3 years, the incidence of PRAE was significantly lower in the DEX group (P = 0.003). In contrast, the incidence of PRAE was comparable between the two groups in children aged at least 3 years. No differences in the incidence of emergence agitation, fever and vomiting between the two groups were noted.

Conclusion: Administration of intranasal DEX 1.5 μg kg 30 to 45 min before induction led to a reduction in the incidence of PRAE in children aged less than 3 years with recent URI undergoing interventional cardiac catheterisation.

Trial Registration: chictr.org.cn identifier: ChiCTR-RRC-17012519.
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http://dx.doi.org/10.1097/EJA.0000000000001097DOI Listing
February 2020

A new technique to facilitate lung lavage for pulmonary alveolar proteinosis in a 3-month-old infant: Bronchial-blocker-out-of-endotracheal-tube technique.

J Clin Anesth 2020 Feb 3;59:82-83. Epub 2019 Jul 3.

Department of Anesthesiology, Shanghai Children's Medical Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1016/j.jclinane.2019.06.018DOI Listing
February 2020

Newborn infant parasympathetic evaluation (NIPE) as a predictor of hemodynamic response in children younger than 2 years under general anesthesia: an observational pilot study.

BMC Anesthesiol 2019 06 11;19(1):98. Epub 2019 Jun 11.

Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine & National Children's Medical Center (Shanghai), 1678 Dongfang Road, Shanghai, 200127, China.

Background: It is still unknown whether newborn infant parasympathetic evaluation (NIPE), based on heart rate variability (HRV) as a reflection of parasympathetic nerve tone, can predict the hemodynamic response to a nociception stimulus in children less than 2 years old.

Methods: Fifty-five children undergoing elective surgery were analyzed in this prospective observational study. Noninvasive mean blood pressure (MBP), heart rate (HR) and NIPE values were recorded just before and 1 min after general anesthesia with endotracheal intubation as well as skin incision. The predictive performance of NIPE was evaluated by receiver-operating characteristic (ROC) curve analysis. A significant hemodynamic response was defined by a > 20% increase in HR and/or MBP.

Results: Endotracheal intubation and skin incision caused HR increases of 22.2% (95% confidence interval [CI] 17.5-26.9%) and 3.8% (2.1-5.5%), MBP increases of 18.2% (12.0-24.4%) and 10.6% (7.7-13.4%), and conversely, NIPE decreases of 9.9% (5.3-14.4%) and 5.6% (2.1-9.1%), respectively (all P < 0.01 vs. pre-event value). Positive hemodynamic responses were observed in 32 patients (62.7%) during tracheal intubation and 13 patients (23.6%) during skin incision. The area under the ROC curve values for the ability of NIPE to predict positive hemodynamic responses at endotracheal intubation and skin incision were 0.65 (0.50-0.78) and 0.58 (0.44-0.71), respectively.

Conclusions: NIPE reflected nociceptive events as well as anesthestic induction in children less than 2 years undergoing general anaesthetia. Nevertheless, NIPE may not serve as a sensitive and specific predictor to changes in hemodynamics.

Trial Registration: This study was registered on May 3, 2018 in the Chinese Clinical Trail Registry; the registration number is ( ChiCTR1800015973 ).
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http://dx.doi.org/10.1186/s12871-019-0774-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560820PMC
June 2019

Modified Lung Ultrasound Examinations in Assessment and Monitoring of Positive End-Expiratory Pressure-Induced Lung Reaeration in Young Children With Congenital Heart Disease Under General Anesthesia.

Pediatr Crit Care Med 2019 05;20(5):442-449

Department of Anesthesiology & Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objectives: Lung ultrasound can reliably diagnose pulmonary atelectasis. The object of this study is to determine the most efficient region to assess changes in atelectasis in children with congenital heart disease under general anesthesia.

Design: Randomized controlled trial.

Setting: Operating room at university-affiliated children's hospital.

Patients: Children between 3 months and 3 years old, scheduled for elective congenital heart disease surgery under general anesthesia.

Interventions: Forty children with congenital heart disease were randomly allocated to either a 5 cm H2O positive end-expiratory pressure group or a standard therapy control group.

Measurements And Main Results: Preoperative lung ultrasound was performed twice in each patient-after 1 and 15 minutes of mechanical ventilation. Atelectatic areas and B-lines were compared between two examinations. Different ultrasound regions were evaluated using Bland-Altman plots. The occurrence rate of atelectasis was much higher in inferoposterior lung regions (Scans 4-6) than in anterior and lateral regions (Scans 1-3). The median (interquartile range) lung ultrasound scores were lower in the positive end-expiratory pressure group than in the control group after treatment: 8 (3.3-9.8) versus 13 (8.3-17.5; p < 0.001). The atelectatic area was significantly decreased after treatment in the positive end-expiratory pressure group: 128 mm (34.5.5-213.3 mm) versus 49.5 mm (5.3-75.5 mm; p < 0.001). Bland-Altman plots revealed concordance between measurements in Scans 1-6 and those in Scans 4-6. In the posterior axillary line regions, changes in atelectatic area were significantly larger in the positive end-expiratory pressure group than in the control group (p = 0.03, 0.007, and 0.018).

Conclusions: Lung ultrasound in inferoposterior lung regions may be more likely to reflect changes in atelectasis and save examination time; 5 cm H2O positive end-expiratory pressure may be useful in lung reaeration and can reduce, but not eliminate, atelectasis in children with congenital heart disease.
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http://dx.doi.org/10.1097/PCC.0000000000001865DOI Listing
May 2019

Feasibility of lung ultrasound to assess pulmonary overflow in congenital heart disease children.

Pediatr Pulmonol 2018 11 24;53(11):1525-1532. Epub 2018 Sep 24.

Department of Anesthesiology and Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Pulmonary overflow (PO) is one of the most common complications in congenital heart disease (CHD) children with an incidence of 48-60% approximately. This study explored the feasibility of using lung ultrasound (LUS) to assess pulmonary overcirculation in CHD children and compare the diagnostic performance of LUS and chest radiography (CXR) for the detection of pulmonary overcirculation.

Method: The upper anterior area, lower anterior area, upper lateral area, and lower posterior area, in each hemithorax were scanned in 59 children in the supine position. A-lines, B-lines in each scanned region were recorded, and the worst LUS abnormality in the video clip was considered to characterize the examined region. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of LUS and CXR were compared using computed tomography (CT) as a standard criterion.

Results: PO was diagnosed in 53% (31/59), 63% (37/59), and 51% (30/59) children with CT, CXR, and LUS, respectively. The sensitivity, specificity, and diagnostic accuracy of PO were 96%, 94%, and 95% for LUS and 74%, 50%, and 63% for CXR. The percentage of mild, moderate, and severe PO diagnosed via LUS were 31% (18/59), 19% (11/59), and 2% (1/59), respectively. Furthermore, the PO incidence diagnosed by LUS in CHD children less than 1 year old were significantly higher than those beyond 1 year old.

Conclusion: LUS is a noninvasive and useful tool for the detection and assessment of PO in CHD children at the operating room, and is better than CXR in sensitivity and specificity, comparable to CT.
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http://dx.doi.org/10.1002/ppul.24169DOI Listing
November 2018

Nicotinic Acetylcholine Receptors are Associated with Ketamine-induced Neuronal Apoptosis in the Developing Rat Retina.

Neuroscience 2018 04 8;376:1-12. Epub 2018 Feb 8.

Department of Anesthesiology & Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Early synchronized spontaneous network activity is a hallmark of the brain growth spurt period, during which general anesthetics cause widespread neuronal apoptosis and subsequent cognitive dysfunction. However, the relationship of such activity to anesthetic-induced neuronal apoptosis remains to be determined. In this study, we utilized patch-clamp electrophysiological recording, immunohistochemistry, and TUNEL assays to investigate the potential roles of spontaneous network activity in ketamine-induced neuronal apoptosis during early development. All experiments were performed using acutely dissected whole-mount Sprague-Dawley rat retinas (0-14 postnatal days [P0-P14]). Ketamine reversibly blocked spontaneous network activity in the rat retina from P0 to P9 and irreversibly blocked such activity from P10 to P12. The peak of physiological and ketamine-induced neuronal apoptosis mainly occurred from P7 to P9. Blockade of nicotinic acetylcholine receptors (nAChRs) also induced reversible inhibition of spontaneous network activity from P0 to P7 and extensive neuronal apoptosis in the P7 rat retina, while activation of nAChRs or increases in endogenous ACh levels attenuated ketamine-induced apoptotic responses. Furthermore, blockade of α7-nAChR and ß2-nAChR subtypes induced neuronal apoptosis in the developing retina, while activation of the α7-nAChR subtype attenuated ketamine-induced apoptotic responses. These results demonstrate that ketamine may inhibit early synchronized spontaneous network activity by blocking nAChRs, and that such inhibition may contribute to ketamine-induced neuronal apoptosis in the developing rat retina.
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http://dx.doi.org/10.1016/j.neuroscience.2018.01.057DOI Listing
April 2018

Differential Roles of the Right and Left Toe Perfusion Index in Predicting the Incidence of Postspinal Hypotension During Cesarean Delivery.

Anesth Analg 2017 11;125(5):1560-1566

From the *Department of Anesthesiology, the International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; and †Department of Anesthesiology & Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Aortocaval compression by the gravid uterus, low baseline vasomotor tone, and spinal anesthesia-related sympathetic blockade contribute to spinal anesthesia-induced hypotension during cesarean delivery. The finger perfusion index (PI) can predict spinal hypotension by reflecting baseline vasomotor tone, but cannot directly reflect aortocaval compression by the gravid uterus. This study aimed to examine whether baseline toe PIs predict the incidence of maternal hypotension and reflect aortocaval compression by the gravid uterus during cesarean delivery under spinal anesthesia.

Methods: One hundred parturients undergoing elective cesarean delivery were enrolled. The relationship between baseline toe PI and the incidence of hypotension after induction of spinal anesthesia was quantified using area under the receiver operator curves, and results compared for the right and left toe PIs.

Results: The area under the receiver operator curves for left and right toe baseline PIs were 0.81 (95% confidence interval, 0.71-0.88) and 0.76 (95% confidence interval, 0.66-0.84), respectively. After induction of spinal anesthesia, the toe PIs did not change in parturients with hypotension, but increased significantly among those who did not develop hypotension.

Conclusions: Our study demonstrated that baseline toe PIs were inversely associated with the incidence of postspinal hypotension during cesarean delivery. Continuous monitoring of toe PIs during induction of spinal anesthesia might help to predict the development of postspinal hypotension and reflect the aortocaval compression by the gravid uterus.
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http://dx.doi.org/10.1213/ANE.0000000000002393DOI Listing
November 2017

The expression profile of developmental stage-dependent circular RNA in the immature rat retina.

Mol Vis 2017 20;23:457-469. Epub 2017 Jul 20.

Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: Physiologic neuronal apoptosis, which facilitates the developmental maturation of the nervous system, is regulated by neuronal activity and gene expression. Circular RNA (circRNA), a class of non-coding RNA, regulates RNA and protein expression. As the relationship between circRNA and apoptosis is unknown, we explored changes in expression patterns of circRNA during physiologic neuronal apoptosis.

Methods: High-throughput sequencing was used to explore changes in the expression of circRNA in the postnatal developing rat retina. Neuronal apoptosis was determined with immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in the rat retinal ganglion cell layer.

Results: In total, 2,654, 7,201, and 5,628 circRNA species were detected in the postnatal day (P)3, P7, and P12 rat retina, respectively. Of these circRNA species, 1,371 changed statistically significantly between P3 and P7 and 1,112 changed statistically significantly between P7 and P12. Normal developmental apoptosis, measured with the ratio of apoptotic (caspase-3- or TUNEL-positive) cells to normal cells, showed an increase from P3 to P7 and then a reduction from P7 to P12. In addition, 15 circRNAs whose host genes were associated with apoptosis were differentially expressed during the early development period.

Conclusions: These results associate circRNAs with neuronal apoptosis, providing potential mechanisms and treatment targets for physiologic and drug-induced apoptosis in the developing nervous system.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524268PMC
April 2018

Dopamine attenuates ethanol-induced neuroapoptosis in the developing rat retina via the cAMP/PKA pathway.

Mol Med Rep 2017 Aug 20;16(2):1982-1990. Epub 2017 Jun 20.

Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China.

Apoptosis has been identified as the primary cause of fetal alcohol spectrum disorder (FASD), and the development of methods to prevent and treat FASD have been based on the mechanisms of alcohol-induced apoptosis. The present study aimed to explore the effects of dopamine on alcohol‑induced neuronal apoptosis using whole‑mount cultures of rat retinas (postnatal day 7). Retinas were initially incubated with ethanol (100, 200 or 500 mM), and in subsequent analyses retinas were co‑incubated with ethanol (200 mM) and dopamine (10 µM). In addition, several antagonists and inhibitors were used, including a D1 dopamine receptor (D1R) antagonist (SCH23390; 10 µM), a D2R antagonist (raclopride; 40 µM), an adenosine A2A receptor (AA2AR) antagonist (SCH58261; 100 nM), an adenylyl cyclase (AC) inhibitor (SQ22536; 100 µM) and a PKA inhibitor (H‑89; 1 µM). The results demonstrated that exposure increased neuroapoptosis in the retinal ganglion cell layer (GCL) in a dose‑dependent manner. Dopamine treatment significantly attenuated ethanol‑induced neuronal apoptosis. D1R, D2R and AA2AR antagonists partially inhibited the protective effects of dopamine against ethanol‑induced apoptosis; similar results were observed with AC and PKA inhibitor treatments. In summary, the present study demonstrated that dopamine treatment may be able to attenuate alcohol‑induced neuroapoptosis in the developing rat retina by activating D1R, D2R and AA2AR, and by upregulating cyclic AMP/protein kinase A signaling.
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http://dx.doi.org/10.3892/mmr.2017.6823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561998PMC
August 2017

A comparison of classic laryngeal mask airway insertion between lightwand- and standard index finger-guided techniques.

J Clin Anesth 2016 Sep 18;33:309-14. Epub 2016 May 18.

Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China. Electronic address:

Study Objective: To compare the efficacy of lightwand-guided classic laryngeal mask airway (cLMA) real-time insertion technique with the standard recommended index finger-guided insertion technique.

Design: Prospective, randomized controlled study.

Setting: University-affiliated hospital.

Patients: Three hundred patients undergoing minor gynecological or orthopedic surgeries under general anesthesia using the cLMA as an airway management tool.

Interventions: Patients were randomly divided into either lightwand-guided group or standard group.

Measurements: Fiberoptic bronchoscopy was used to determine the cLMA position after a cLMA was inserted. The first attempt and total success rates of the cLMA insertion, insertion time, distances from the end of cLMA pilot tube to the upper central incisors, views of fiberoptic bronchoscopy, blood staining, tidal volume, airway pressure, end-tidal CO2, SpO2, noninvasive hemodynamic parameters, and others were compared.

Main Results: The cLMA was all successfully inserted within 3 attempts except for 2 patients in the standard group. The success rates of lightwand-guided insertion technique at first attempt were significantly higher than standard insertion technique; the ideal view rates assessed by fiberoptic bronchoscopy in lightwand-guided group patients were also significantly higher than in standard group patients, but the insertion time of first successful attempt was similar; the blood staining rates on the cLMA in lightwand-guided group patients were significantly less than in standard group patients. The depths of cLMA insertion in standard group patients were significantly deeper than those in lightwand-guided group patients. There was no significant difference in end-tidal CO2, SpO2, airway pressure, and hemodynamic variables.

Conclusion: Lightwand-guided cLMA insertion technique can provide a more objective indicator for correct cLMA positioning, higher first attempt success rates, better glottic views, and less damage to oropharyngeal or esophagus tissues than standard index finger-guided cLMA insertion technique.
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http://dx.doi.org/10.1016/j.jclinane.2016.04.032DOI Listing
September 2016

Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

Mol Neurobiol 2017 07 13;54(5):3407-3417. Epub 2016 May 13.

Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University, 1678 Dongfang Road, Shanghai, 200127, China.

Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.
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http://dx.doi.org/10.1007/s12035-016-9914-2DOI Listing
July 2017

The regulation of sGC on the rat model of neuropathic pain is mediated by 5-HT1ARs and NO/cGMP pathway.

Am J Transl Res 2016 15;8(2):1027-36. Epub 2016 Feb 15.

Department of Anesthesiology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University Shanghai 20080, China.

Inadequate management of neuropathic pain results in poor clinical outcomes and reduces quality of life for the patient all over the world, but intricate interplay between wide variety of the pathophysiological mechanisms involved in the development and progression of neuropathic pain makes it difficult to design effective therapeutic strategies. The present study aims to elucidate the interaction of 5-HT1A receptors (5-HT1ARs), soluble guanylate cyclase (sGC) and NO/cGMP signaling pathway in the development of neuropathic pain. The results showed that after sciatic nerve crush procedure, the protein level of sGC in the spinal cord was greatly increased. The mechanical threshold in rats was significantly enhanced by the sGC inhibitor ODQ and neuronal NO synthase (nNOS) inhibitor SMTC, indicating the role of sGC and nNOS in the process of neuropathic pain. The treatment of NO donors (SNP and SIN-1) and cGMP-selective phosphodiesterase inhibitor (Zaprinast) all significantly decreased the mechanical threshold in rats, but the 5-HT1ARs inhibitor WAY100635 significantly increased the mechanical threshold in rats, demonstrating the role of NO/cGMP pathway and 5-HT1ARs in the development of neuropathic pain. Finally, the protein levels of sGC was greatly increased by SNP and Zaprinast but decreased by WAY100635 and SMTC, showing the regulation of NO/cGMP pathway and 5-HT1ARs on the protein expression of sGC. Taken together, it is suggested that sGC in the spinal cord regulates the neuropathic pain, which is mediated by 5-HT1ARs and NO/cGMP pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846945PMC
May 2016

Paroxetine alleviates rat limb post-ischemia induced allodynia through GRK2 upregulation in superior cervical ganglia.

Int J Clin Exp Med 2015 15;8(2):2065-76. Epub 2015 Feb 15.

Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital 650 Xin Songjiang Road, Shanghai 201620, China.

Long-lasting neuroplastic changes induced by transient decrease in G protein-coupled receptor kinase 2 (GRK2) in nociceptors enhances and prolongs inflammatory hyperalgesia. Here, we investigated the effects of paroxetine (a selective serotonin reuptake inhibitor and GRK2 inhibitor) on GRK2 expression in superior cervical ganglion (SCG) in a rat model of complex regional pain syndrome type I (CRPS-I). After ischemia-reperfusion (I/R) injury, the ipsilateral 50% paw withdrawal thresholds (PWTs) to mechanical stimuli and the expression levels of GRK2 protein and mRNA in the ipsilateral SCGs all decreased significantly; the ipsilateral cold allodynia scores increased significantly. No significant differences were found in the contralateral side except GRK2 mRNA reduced significantly at day 2-day 9 after I/R injury, but still higher than those in ipsilateral SCGs. After paroxetine administration, the ipsilateral 50% PWTs at day 2, 7, 14, and 21 were significantly higher than those in control group; The GRK2 protein and mRNA levels in ipsilateral SCGs were also significantly up-regulated after day1; The ipsilateral cold allodynia scores were significantly reduced after day7. No significant differences were found in the contralateral 50% PWTs, cold allodynia scores, and GRK2 protein level except GRK2 mRNA levels increased significantly at day1-day7 after paroxetine administration. Therefore, a transient decrease of GRK2 expression in SCG neurons might be involved in the development and maintenance of allodynia in CRPS-I and paroxetine might alleviate this allodynia through GRK2 protein upregulation in SCGs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402784PMC
May 2015

Bilirubin modulates acetylcholine receptors in rat superior cervical ganglionic neurons in a bidirectional manner.

Sci Rep 2014 Dec 15;4:7475. Epub 2014 Dec 15.

Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.

Autonomic dysfunction as a partial contributing factor to cardiovascular instability in jaundiced patients is often associated with increased serum bilirubin levels. Whether increased serum bilirubin levels could directly inhibit sympathetic ganglion transmission by blocking neuronal nicotinic acetylcholine receptors (nAChRs) remains to be elucidated. Conventional patch-clamp recordings were used to study the effect of bilirubin on nAChRs currents from enzymatically dissociated rat superior cervical ganglia (SCG) neurons. The results showed that low concnetrations (0.5 and 2 μM) of bilirubin enhanced the peak ACh-evoked currents, while high concentrations (3 to 5.5 µM) of bilirubin suppressed the currents with an IC50 of 4 ± 0.5 μM. In addition, bilirubin decreased the extent of desensitization of nAChRs in a concentration-dependent manner. This inhibitory effect of bilirubin on nAChRs channel currents was non-competitive and voltage independent. Bilirubin partly improved the inhibitory effect of forskolin on ACh-induced currents without affecting the action of H-89. These data suggest that the dual effects of enhancement and suppression of bilirubin on nAChR function may be ascribed to the action mechanism of positive allosteric modulation and direct blockade. Thus, suppression of sympathetic ganglionic transmission through postganglionic nAChRs inhibition may partially contribute to the adverse cardiovascular effects in jaundiced patients.
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http://dx.doi.org/10.1038/srep07475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265787PMC
December 2014

Dexmedetomidine alleviates rat post-ischemia induced allodynia through GRK2 upregulation in superior cervical ganglia.

Auton Neurosci 2015 Jan 1;187:76-83. Epub 2014 Nov 1.

Department of Anesthesiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University affiliated Shanghai First People's Hospital, Shanghai 201620, China. Electronic address:

A transient decrease in G protein-coupled receptor kinase 2 (GRK2) in nociceptors can produce long-lasting neuroplastic changes in nociceptor function, eventually enhancing and prolonging inflammatory hyperalgesia. Here, we investigated the effects of selective α2-adrenoceptor agonist dexmedetomidine (DMED) on GRK2 expression in superior cervical ganglion (SCG) in a rat model of complex regional pain syndrome type I (CRPS-I). The ipsilateral 50% paw withdrawal thresholds (PWTs) to mechanical stimuli decreased significantly starting from 24 h after ischemia-reperfusion (I/R) injury, and lasted for over 3 weeks; the ipsilateral cold allodynia scores, GRK2 protein and mRNA levels in SCGs all increased significantly. No significant differences were found in the contralateral side except GRK2 mRNA reduced significantly after 48 h I/R injury, but still higher than those in the ipsilateral side. Following daily injection of 10 μg/kg of DMED for a maximum of 7 days, the ipsilateral PWTs on days 1, 2, 7, 14, and 21 after DMED administration were significantly higher than those in control group; the GRK2 protein and mRNA expressions in the ipsilateral SCGs were also significantly upregulated; the ipsilateral cold allodynia scores were significantly reduced. No significant differences were found in the contralateral 50%PWTs, cold allodynia scores, and GRK2 protein level except GRK2 mRNA levels increased significantly on days 1 to 7 after DMED administration. Therefore, a transient decrease of GRK2 expression in SCG neurons might be involved in the development and maintenance of allodynia in CRPS-I and DMED might alleviate this allodynia through GRK2 upregulation in SCG neurons.
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http://dx.doi.org/10.1016/j.autneu.2014.10.024DOI Listing
January 2015

Pharmacological interventions for acceleration of the onset time of rocuronium: a meta-analysis.

PLoS One 2014 2;9(12):e114231. Epub 2014 Dec 2.

Department of Anesthesiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Rocuronium is an acceptable alternative when succinylcholine is contraindicated for facilitating the endotracheal intubation. However, the onset time of rocuronium for good intubation condition is still slower than that condition of succinylcholine. This study systematically investigated the most efficacious pharmacological interventions for accelerating the onset time of rocuronium.

Methods: Medline, Embase, Cochrane Library databases, www.clinicaltrials.gov, and hand searching from the reference lists of identified papers were searched for randomized controlled trials comparing drug interventions with placebo or another drug to shorten the onset time of rocuronium. Statistical analyses were performed using RevMan5.2 and ADDIS 1.16.5 softwares. Mean differences (MDs) with their 95% confidence intervals (95% CIs) were used to analyze the effects of drug interventions on the onset time of rocuronium.

Results: 43 randomized controlled trials with 2,465 patients were analyzed. The average onset time of rocuronium was 102.4±24.9 s. Priming with rocuronium [Mean difference (MD) -21.0 s, 95% confidence interval (95% CI) (-27.6 to -14.3 s)], pretreatment with ephedrine [-22.3 s (-29.1 to -15.5 s)], pretreatment with magnesium sulphate [-28.2 s (-50.9 to -5.6 s)] were all effective in reducing the onset time of rocuronium. Statistical testing of indirect comparisons showed that rocuronium priming, pretreatment with ephedrine, and pretreatment with magnesium sulphate had the similar efficacy.

Conclusion: Rocuronium priming, pretreatment with ephedrine, and pretreatment with magnesium sulphate were all effective in accelerating the onset time of rocuronium, and furthermore their efficacies were similar. Considering the convenience and efficacy, priming with rocuronium is recommended for accelerating the onset time of rocuronium. However, more strict clinical trials are still needed to reach a more solid conclusion due to the large heterogeneities exist among different studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114231PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252114PMC
January 2016
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