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2.
Neurotoxicology ; 90: 256-264, 2022 05.
Article in English | MEDLINE | ID: mdl-35472370

ABSTRACT

Prolonged sevoflurane exposure leads to neurotoxicity. Autophagy plays an important role in promoting cell survival in different conditions. However, the role and mechanism of autophagy in sevoflurane-induced neurotoxicity were not fully elucidated. We attempted to indicate whether sevoflurane could activate the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)-mediated autophagy to attenuate anesthetics-induced neuronal injury in this study. Sevoflurane treatment significantly decreased the cell viability and induced apoptosis of SH-SY5Y cells. The expression level of Bcl-2 decreased, while that of Bax remarkably increased. Meanwhile, autophagy was activated by sevoflurane exposure as evidenced by increased expression levels of autophagy-related proteins (LC3-II and Atg5), decreased expression level of autophagic substrate P62, and increased autophagosomes and autolysosomes. Further autophagosomes and fewer autolysosomes were observed in the presence of Bafilomycin A1, an autolysosomes degradation inhibitor, suggesting that sevoflurane induced autophagic flux rather than inhibiting degradation of autophagy. Activation of autophagy by rapamycin partly reversed the sevoflurane-decreased cell viability. In contrast, inhibition of autophagy by 3-Methyladenine (3-MA) or Atg5-targeted small interfering RNA (siRNA) aggravated the sevoflurane-induced neurotoxicity. Further examination revealed that sevoflurane-induced autophagy was mediated by the AMPK/mTOR signaling pathway, with increased p-AMPK expression and decreased p-mTOR expression. Collectively, these results indicated that sevoflurane activates autophagy by regulating the AMPK/mTOR signaling pathway, which is protective against sevoflurane-induced damage in SH-SY5Y cells. Our results may assist clinicians to develop further promising therapeutic strategies for the neurotoxicity induced by inhaled anesthetics.


Subject(s)
AMP-Activated Protein Kinases , Neuroblastoma , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Apoptosis , Autophagy , Cell Line, Tumor , Humans , Neuroblastoma/metabolism , Sevoflurane/pharmacology , Signal Transduction , Sirolimus/pharmacology , TOR Serine-Threonine Kinases
3.
BMC Anesthesiol ; 21(1): 268, 2021 11 04.
Article in English | MEDLINE | ID: mdl-34736416

ABSTRACT

BACKGROUND: The anatomical dimensions of the lumbar dural sac determine the sensory block level of spinal anesthesia; however, whether they show the same predictive value during continuous epidural anesthesia (CEA) remains undetermined. We designed the present study to verify the efficacy of the anatomical dimensions of the lumbar dural sac in predicting the sensory block level during labor analgesia. METHODS: A total of 122 parturients with singleton pregnancies requesting labor analgesia were included in this study. The lumbar dural sac diameter (DSD), lumbar dural sac length (DSL), lumbar dural sac surface area (DSA), and lumbar dural sac volume (DSV) were measured with an ultrasound color Doppler diagnostic apparatus. CEA was performed at the L2-L3 interspace. After epidural cannulation, an electronic infusion pump containing 0.08% ropivacaine and sufentanil 0.4 µg/ml was connected. The sensory block level was determined with alcohol-soaked cotton, a cotton swab, and a pinprick. The analgesic efficacy of CEA was determined with a visual analog scale (VAS). The parturients were divided into two groups, "ideal analgesia" and "nonideal analgesia," and the groups were compared by t test. Pearson's correlation was performed to evaluate the association between the anatomical dimensions of the lumbar dural sac and sensory block level. Multiple linear regression analysis was used to create a model for predicting the sensory block level. RESULTS: In the ideal analgesia group, the height, DSL, DSA, DSV and DSD were significantly smaller, and the body mass index (BMI) was significantly larger (P < 0.05). In addition, the DSL demonstrated the strongest correlation with the peak level of pain block (r = - 0.816, P < 0.0001; Fig. 2A), temperature block (r = - 0.874, P < 0.0001; Fig. 3A) and tactile block (r = - 0.727, P < 0.0001; Fig. 4A). Finally, the multiple linear regression analysis revealed that DSL and BMI contributed to predicting the peak sensory block level. CONCLUSION: In conclusion, our study shows that the sensory block level of CEA is higher when the DSL, DSA, DSV and DSD of puerperae are lower. DSL and BMI can be treated as predictors of the peak sensory block level in CEA during labor analgesia.


Subject(s)
Analgesia, Epidural/methods , Analgesia, Obstetrical/methods , Dura Mater/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Adolescent , Adult , Analgesics, Opioid/administration & dosage , Anesthetics, Local/administration & dosage , Body Mass Index , Female , Humans , Labor, Obstetric , Middle Aged , Pregnancy , Ropivacaine/administration & dosage , Sufentanil/administration & dosage , Ultrasonography, Doppler, Color , Young Adult
4.
J Gastroenterol Hepatol ; 36(2): 474-481, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32677707

ABSTRACT

BACKGROUND AND AIM: Remimazolam tosilate (RT) is a new short-acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy. METHODS: This positive-controlled, non-inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety. RESULTS: The success rate of sedation in the RT group was non-inferior to that in the propofol group (97.34% vs 100.00%; difference in rate -2.66%, 95% CI -4.96 to -0.36, meeting criteria for non-inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment-related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001). CONCLUSION: This trial established non-inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.


Subject(s)
Benzodiazepines/administration & dosage , Conscious Sedation/methods , Endoscopy, Gastrointestinal , Adult , Aged , Anesthesia Recovery Period , Benzodiazepines/adverse effects , Feasibility Studies , Female , Humans , Hypertension/chemically induced , Hypertension/epidemiology , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/adverse effects , Incidence , Male , Middle Aged , Propofol/administration & dosage , Propofol/adverse effects , Respiratory Insufficiency/chemically induced , Respiratory Insufficiency/epidemiology , Safety
5.
Am J Transl Res ; 12(8): 4594-4603, 2020.
Article in English | MEDLINE | ID: mdl-32913533

ABSTRACT

This study aimed to evaluate the efficacy and safety of remimazolam tosylate versus propofol in patients undergoing colonoscopy. In this multicentered, blinded, randomized, active-controlled, non-inferior phase III trial, 384 eligible patients who were about to undergo colonoscopy were randomized as a ratio of 1:1 into remimazolam and propofol group. Procedure success was assessed and defined as the completion of colonoscopy without administration of rescue sedative agent or more than 5 top-ups of trial drug in any 15 minute-period after initial administration of trial drug. Sedation quality was evaluated by Modified Observer's Assessment of Alertness/Sedation score. Treatment-emergent adverse events were recorded. Procedure success rate was 96.91% (188/194) in remimazolam group and 100% (190/190) in propofol group, and the difference in rate was -3.09% with 95% confidence interval (CI) of -5.53%~-0.66%. Since the lower limit of 95% CI was greater than the non-inferiority margin of -8.00%, the efficacy of remimazolam tosylate was non-inferior to propofol. Besides, induction time of sedation was increased (P<0.001), while hypotension and respiratory depression was decreased in remimazolam group compared to propofol group; however, time to fully alert (P>0.05) or time to discharge (P>0.05) were unchanged. For safety assessment, total treatment-emergent adverse events were decreased in remimazolam group compared to propofol group (P<0.001); specifically, administration site pain (P<0.001), increased bilirubin (P=0.019), decreased respiratory rate (P<0.001) and decreased SpO2 (P<0.001) were less frequent in remimazolam group compared with propofol group. In conclusion, remimazolam tosylate is non-inferior in sedation efficacy while safer than propofol in patients undergoing colonoscopy.

6.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(9): 1301-1306, 2020 Sep 30.
Article in Chinese | MEDLINE | ID: mdl-32990226

ABSTRACT

OBJECTIVE: To establish a micellar electrokinetic capillary chromatography-based method for identification and quantitative detection of interleukin-12 (IL-12) and analysis of its unfolding process. METHODS: An uncoated fused-silica capillary (inner diameter 50 µm) with a total length of 48.5 cm (40 cm to the detector) was used for the experiment. The factors influencing the separation efficiency of IL-12 were analyzed, and a standard curve of IL-12 concentration was established. The mixture of IL-12 and anti-IL-12 antibody was incubated in a water bath at 38 ℃ for 40 min, and capillary electrophoresis was then performed under the same conditions. The results were compared with those of IL-12 and anti-IL-12 antibody to identify IL-12. IL-12 and dithiothreitol (DTT) were incubated at 60 ℃ in water bath for different lengths of times, and the unfolding process of IL-12 was analyzed based on electrophoresis results of IL-12 in different states. RESULTS: A micellar capillary electrophoresis on-line sweep method was established with 80 mmol/L borate (pH=9.3) containing 30 mmol/L sodium dodecyl sulfate (SDS) as the buffer solution. This system showed a good linear relationship between the peak area and the mass concentration of IL-12 with a linear correlation coefficient of 0.9991 within the linear range of 2 to 120 ng/L. As the incubation time of IL-12 and DTT prolonged, the disulfide bond of IL-12 gradually opened and resulted in distinct changes in the protein peak. CONCLUSIONS: This capillary electrophoresis-based method is simple and sensitive for IL-2 analysis and allows rapid detection of changes in IL-12 content in the setting of tumors and analysis of the possible causes.


Subject(s)
Chromatography, Micellar Electrokinetic Capillary , Electrophoresis, Capillary , Interleukin-12 , Micelles , Protein Unfolding
7.
J Int Med Res ; 48(5): 300060520925325, 2020 May.
Article in English | MEDLINE | ID: mdl-32459108

ABSTRACT

OBJECTIVE: We investigated the "BURP" maneuver's effect on the association between difficult laryngoscopy and difficult intubation, and predictors of a difficult airway. METHODS: Adult patients who underwent general anesthesia and tracheal intubation from September 2016 to May 2018 were included. The "BURP" maneuver was performed when glottic exposure was classified as Cormack-Lehane grade 3 or 4, suggesting difficult laryngoscopy. The thyromental distance, modified Mallampati score, and interincisor distance were assessed before anesthesia. RESULTS: Among this study's 2028 patients, the "BURP" maneuver decreased difficult laryngoscopies from 428 (21.1%) to 124 (6.1%) cases and increased the difficult intubation to difficult laryngoscopy ratio from 53/428 (12.4%) to 52/124 (41.9%). For laryngoscopies classified as difficult without the "BURP" maneuver, the area under the curve (AUC) of the thyromental distance, modified Mallampati score, and interincisor distance was 0.60, 0.57, and 0.66, respectively. In difficult laryngoscopies using the "BURP" maneuver, the AUC of the thyromental distance, modified Mallampati score, and interincisor distance was 0.71, 0.67, and 0.76, respectively. CONCLUSIONS: The "BURP" maneuver improves the laryngoscopic view and assists in difficult laryngoscopies. Compared with difficult laryngoscopies without the "BURP" maneuver, those with the "BURP" maneuver are more closely associated with difficult intubations and are more predictable. Trial registration: www.chictr.org.cn identifier: ChiCTR-ROC- 16009050.


Subject(s)
Anesthesia, General/methods , Glottis/diagnostic imaging , Intubation, Intratracheal/methods , Laryngoscopy/methods , Adult , Aged , Aged, 80 and over , Anesthesia, General/instrumentation , Female , Humans , Intubation, Intratracheal/instrumentation , Laryngoscopy/instrumentation , Male , Middle Aged , Prospective Studies , Treatment Outcome , Young Adult
8.
FASEB J ; 34(5): 6038-6054, 2020 05.
Article in English | MEDLINE | ID: mdl-32202355

ABSTRACT

Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF-1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF-1α pathway were determined by measuring expression of VEGF, EGF, HIF-1α, and HSP-90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF-1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α-SMA in skin tissues, and reduced TNF-α, IL-1ß, and IL-6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF-1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF-1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF-1α pathway.


Subject(s)
Blood Preservation/methods , Blood Transfusion, Autologous/methods , Diabetes Mellitus, Experimental/therapy , Disease Models, Animal , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Neovascularization, Physiologic , Wound Healing , Animals , Cell Movement , Cell Proliferation , Diabetes Mellitus, Experimental/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Male , Mice
9.
Curr Mol Med ; 20(3): 240-246, 2020.
Article in English | MEDLINE | ID: mdl-31702490

ABSTRACT

OBJECTIVE: This study aims to investigate the effect of morphine with naloxone on intestinal peristalsis and the number of interstitial cells of Cajal (ICC) in colon tissues of rabbits. METHODS: Thirty rabbits were randomly divided into five groups (n=6, each group): saline control group (NS group), low concentration of morphine group (L group), medium concentration of morphine group (M group), high concentration of morphine group (H group), medium concentration of morphine and naloxone mixed with antagonist group (NM group). Rabbits in these five groups were administered with an epidural puncture tube and dorsal epidural analgesia pump, and were continuously infused for seven days. Fecal characteristics were observed, and the ink propulsion rate was calculated. The expression level of ICC C-kit protein in colon tissues was tested by western blot. RESULTS: The stool characteristics in the L, M and H groups were more severe than those in the NS and NM groups. Furthermore, the intestinal propulsion rate in the L, M and H groups was lower than that in the NS and NM groups. The C-kit mRNA and protein expression in the colon of rabbits were significantly lower in the L, M and H groups, when compared to the NS and NM groups. CONCLUSION: Naloxone blocked the mRNA and protein expression of C-kit, and improved intestinal motor function.


Subject(s)
Colon/cytology , Gastrointestinal Transit/drug effects , Interstitial Cells of Cajal/cytology , Morphine/pharmacology , Animals , Feces , Gene Expression Regulation/drug effects , Interstitial Cells of Cajal/drug effects , Male , Proto-Oncogene Proteins c-kit/genetics , Proto-Oncogene Proteins c-kit/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rabbits
10.
Mol Ther Nucleic Acids ; 17: 504-515, 2019 Sep 06.
Article in English | MEDLINE | ID: mdl-31344658

ABSTRACT

Impaired wound healing is a debilitating complication of diabetes. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recognized to be differentially expressed in various diseases. However, its underlying mechanism in diabetes has not been fully understood. Notably, we aim to examine the expression of MALAT1 in diabetic mice and its role in wound healing involving the hypoxia-inducible factor-1α (HIF-1α) signaling pathway with a modified autologous blood preservative solution reported. A mouse model of diabetes was established. MALAT1 was identified to promote the activation of the HIF-1α signaling pathway and to be enriched in autologous blood through modified preservation, which might facilitate the improvement of physiological function of blood cells. Through gain- or loss-of-function approaches, viability of fibroblasts cultured in high glucose, wound healing of mice, and collagen expression in wound areas were enhanced by MALAT1 and HIF-1α. Taken together, the present study demonstrated that the physiological status of mouse blood was effectively improved by modified autologous blood preservation, which exhibited upregulated MALAT1, thereby accelerating the fibroblast activation and wound healing in diabetic mice via the activation of the HIF-1α signaling pathway. The upregulation of MALAT1 activating the HIF-1α signaling pathway provides a novel insight into drug targets against diabetes.

11.
Minerva Anestesiol ; 85(5): 478-486, 2019 05.
Article in English | MEDLINE | ID: mdl-30035456

ABSTRACT

BACKGROUND: Compared with men, women often have a shorter interincisor distance and a shorter thyromental distance but are less likely to have difficult airway. The hypothesis is that the prediction criteria of difficult airway differ between men and women. The aim of this study was to investigate differences in the prediction criteria of anatomic predictors for difficult airways in men and women. METHODS: We enrolled adult patients who underwent general anesthesia and tracheal intubation. The interincisor distance, thyromental distance, modified Mallampati test results, upper lip bite test results, and tongue thickness of each patient were evaluated prior to the initiation of anesthesia. The primary outcome was difficult tracheal intubation. Receiver operating characteristic (ROC) curve analysis and Youden's index were used to determine the criteria for predictors in men and women. RESULTS: In total, 1059 men and 1195 women were examined. Compared with women, men had a higher incidence of difficult tracheal intubation (P<0.001). The cut-off values for predicting difficult tracheal intubation of the interincisor distance, thyromental distance, modified Mallampati test results, upper lip bite test results, and tongue thickness determined by Youden's index were ≤38 mm, ≤70 mm, >3, >2, and >62 mm, respectively, for men, and ≤33 mm, ≤65 mm, >2, >1, and >60 mm, respectively, for women. CONCLUSIONS: The optimal cut-off values of predictors of difficult airway differ between males and females.


Subject(s)
Airway Management/methods , Intubation, Intratracheal/methods , Adolescent , Adult , Aged , Aged, 80 and over , Anesthesia, Inhalation , Asian People , Decision Support Systems, Clinical , Female , Humans , Incidence , Intraoperative Complications/epidemiology , Laryngoscopy , Lip/anatomy & histology , Male , Middle Aged , Predictive Value of Tests , ROC Curve , Respiratory System/anatomy & histology , Sensitivity and Specificity , Sex Characteristics , Tongue/anatomy & histology , Tooth/anatomy & histology , Treatment Outcome , Young Adult
12.
Oral Dis ; 25(2): 535-542, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30506619

ABSTRACT

OBJECTIVE: Genome-wide association studies (GWAS) found NTN1, NOG and the region between CREBBP and ADCY9 were risks to non-syndromic cleft lip with or without cleft palate (NSCL/P). However, the association of single nucleotide polymorphisms (SNPs) in these genes with NSCL/P in Western China is unknown. SUBJECTS AND METHODS: We selected seven SNPs in NTN1, NOG and between CREBBP and ADCY9, and then performed transmission disequilibrium test (TDT), parent-of-origin effect and sliding window haplotype analysis to test the associations among 302 NSCL/P case-parent trios from Western Han Chinese. RESULTS: We found allele G at rs4791774 in NTN1 was significantly overtransmitted among non-syndromic cleft lip only (NSCLO) (p = 0.0067, OR = 1.79, 95% CI: 1.17-2.74); rs4791774 and rs9915089 tightly linked with each other among NSCL/P (D' = 0.87, r2  = 0.67) and haplotypes carrying the risk allele G at rs4791774 were always found to be overtransmitted from parents to cases. Motif analysis indicated that allele G at rs4791774 could greatly alter the affinity of Myc_disc7, so allele G at rs4791774 in NTN1 might modulate C-MYC transcription to participate in the aetiology of NSCLO. CONCLUSIONS: Our study suggested allele G at rs4791774 in NTN1 gene is risk of NSCLO, which could greatly increase the risk to have a baby with cleft.


Subject(s)
Asian People/genetics , Cleft Lip/genetics , Netrin-1/genetics , Alleles , China , Female , Haplotypes , Humans , Male , Pedigree , Polymorphism, Single Nucleotide , Risk Factors
13.
Cell Commun Signal ; 16(1): 84, 2018 11 20.
Article in English | MEDLINE | ID: mdl-30458806

ABSTRACT

BACKGROUND: Impaired wound healing frequently occurs in diabetes mellitus (DM) and is implicated in impaired angiogenesis. Long non-coding RNA (lncRNA) H19 has been reported as being reduced in DM and played a critical role in inducing angiogenesis. Thus, we hypothesized that H19 may affect impaired wound healing in streptozotocin (STZ)-induced diabetic mice transfused with autologous blood preserved in standard preservative fluid or modified preservative fluid. METHODS: Fibroblasts in injured skin were isolated and cultured in vitro. After location of H19 in fibroblasts using fluorescence in situ hybridization (FISH), RNA-pull down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), Co immunoprecipitation (COIP) and dual luciferase reporter gene assay were used to verify the binding of H19 to HIF-1α. RESULTS: The modified preservative fluid preserved autologous blood increased the H19 expression in fibroblasts, and maintained better oxygen-carrying and oxygen release capacities as well as coagulation function. Furthermore, H19 promoted HIF-1α histone H3K4me3 methylation and increased HIF-1α expression by recruiting EZH2. H19 promoted fibroblast activation by activating HIF-1α signaling pathway in fibroblasts and enhanced wound healing in diabetic mice. CONCLUSIONS: Taken together, H19 accelerated fibroblast activation by recruiting EZH2-mediated histone methylation and modulating the HIF-1α signaling pathway, whereby augmenting the process of modified preservative fluid preserved autologous blood enhancing the postoperative wound healing in diabetic mice.


Subject(s)
Blood Transfusion, Autologous , Diabetes Mellitus, Experimental/therapy , Gene Expression Regulation , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , RNA, Long Noncoding/genetics , Signal Transduction/genetics , Wound Healing/genetics , Animals , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Enhancer of Zeste Homolog 2 Protein/metabolism , Epigenesis, Genetic , Fibroblasts/metabolism , Histones/metabolism , Male , Methylation , Mice
14.
J Surg Res ; 225: 82-89, 2018 05.
Article in English | MEDLINE | ID: mdl-29605039

ABSTRACT

BACKGROUND: Our previous study demonstrated that ventilators increase diaphragmatic lipid accumulation in rabbits, but their cellular mechanism is poorly understood. Mammalian target of rapamycin (mTOR) plays an important role in atherosclerosis in rat vascular smooth muscle cells. The present study investigated the role of mTOR pathway activation in the diaphragmatic muscle of ventilated rats and hypoxia-induced C2C12 cells. MATERIALS AND METHODS: Male Sprague-Dawly rats were randomized into a control group (n = 8), controlled mechanical ventilation (CMV) group (n = 8), and CMV + Rapa group (n = 8). We evaluated the diaphragmatic contractility, lipid accumulation, and protein expression of the mTOR pathways. To explore the mechanism underlying ventilator-induced lipid accumulation, we observed protein expression of the mTOR and low-density lipoprotein receptor (LDLr) pathways in C2C12 cells under hypoxic and mTOR pathway inhibitor treatments. RESULTS: Compared with the control group, there was a significant decrease in the peak twitch and peak tetanic forces in the CMV group (384.24 ± 70.39 versus 496.33 ± 78.64 g/cm2, P < 0.05, and 869.24 ± 76.67 versus 1090.72 ± 118.91 g/cm2, P < 0.05, respectively). There was a significant increase in peak twitch and peak tetanic forces in the CMV + Rapa group compared with that in the CMV group (501.81 ± 23.15 versus 384.24 ± 70.39 g/cm2, P < 0.05, and 992.91 ± 88.99 versus 869.24 ± 76.67 g/cm2, P < 0.05, respectively). In the CMV group, there were significant increases in lipid accumulation (0.086 ± 0.009 versus 0.005 ± 0.002, P < 0.05) and expression of mTOR in diaphragmatic fibers compared with those in the control group (P < 0.05). Rapamycin prevented lipid accumulation in rats of the CMV + Rapa group compared with that in the CMV group rats (0.024 ± 0.004 versus 0.086 ± 0.009, P < 0.05). Compared with the CMV group, there was a significant decrease in the phosphorylated protein expression levels of mTOR in rats of the CMV + Rapa group (P < 0.05). Hypoxic conditions activated the mTOR and LDLr pathways in C2C12 cells, which were correlated with an increase in expression of the mTOR and LDLr pathways compared with the control group (P < 0.05). In C2C12 cells treated with hypoxia + rapamycin, activation of the mTOR and LDLr pathways was blocked compared with C2C12 cells treated with hypoxia (P < 0.05). CONCLUSIONS: These data suggest that CMV and hypoxia-induced activation of the mTOR pathway, resulting in lipid accumulation, and impaired the diaphragmatic contractile function. Therefore, pharmacologic agents that inhibit the mTOR pathway could potentially be useful for mitigating the diaphragmatic contractile dysfunction induced by mechanical ventilation.


Subject(s)
Diaphragm/drug effects , Lipid Metabolism/drug effects , Muscular Dystrophies/prevention & control , Respiration, Artificial/adverse effects , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/metabolism , Animals , Cell Hypoxia/physiology , Diaphragm/metabolism , Diaphragm/physiopathology , Disease Models, Animal , Electromyography , Humans , Male , Mice , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscular Dystrophies/diagnosis , Muscular Dystrophies/etiology , Muscular Dystrophies/physiopathology , Phosphorylation/drug effects , Rats , Rats, Sprague-Dawley , Receptors, LDL/metabolism , Signal Transduction/drug effects , Sirolimus/therapeutic use , TOR Serine-Threonine Kinases/antagonists & inhibitors , Treatment Outcome
15.
Sci Rep ; 8(1): 1055, 2018 01 18.
Article in English | MEDLINE | ID: mdl-29348559

ABSTRACT

Sepsis and sepsis-associated intestinal barrier dysfunction are common in intensive care units, with high mortality. The aim of this study is to investigate whether Polo-like kinase 1 (PLK1) ameliorates sepsis-induced intestinal barrier dysfunction in the intestinal epithelium. The mouse intestinal barrier was disrupted after Lipopolysaccharide (LPS) injection due to intestinal epithelial cell apoptosis and proliferation inhibition, accompanied by decreased PLK1. In HT-29 intestinal epithelial cells, LPS stimulation induced cell apoptosis and inhibited cell proliferation. Overexpression of PLK1 partly rescued the apoptosis and proliferation inhibition in HT29 cells caused by LPS. Finally, LPS stimulation promoted the reduction of PLK1, resulting in apoptosis and proliferation inhibition in intestinal epithelial cells, disrupting the intestinal epithelial barrier. These findings indicate that PLK1 might be a potential therapeutic target for the treatment of sepsis-induced intestinal barrier dysfunction.


Subject(s)
Cell Cycle Proteins/genetics , Cell Membrane Permeability/genetics , Intestinal Diseases/etiology , Intestinal Diseases/metabolism , Intestinal Mucosa/metabolism , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/genetics , Sepsis/complications , Animals , Apoptosis/genetics , Biomarkers , Cell Cycle Proteins/metabolism , Cell Line , Cell Proliferation , Disease Models, Animal , Gene Expression Regulation , Humans , Intestinal Diseases/pathology , Intestinal Mucosa/pathology , Lipopolysaccharides/adverse effects , Lipopolysaccharides/immunology , Male , Mice , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Polo-Like Kinase 1
17.
J Clin Monit Comput ; 32(5): 915-920, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29234929

ABSTRACT

Using the thyromental distance (TMD) measured based on the ultrasonographic location of the thyroid cartilage prominence as the criterion, we investigated the accuracy of TMD measurement by surface landmark identification of the thyroid cartilage prominence. Twenty-nine anesthetist resident volunteers were recruited, including 10 first-year residents, 9 second-year residents and 10 third-year residents. Each volunteer measured the other 28 volunteers' TMD. Then, the thyroid cartilage prominence of each volunteer was identified by ultrasonography of the junction of the vocal cord and thyroid cartilage, and the TMD was measured precisely. The error of the TMD measurement was determined by the minimal detectable difference (MDD) compared to the ultrasound measurement. A difference of greater than 5.4 mm between the TMD measured by volunteers and that based on ultrasound localization was defined as a measurement error. The measurement error rate of females' TMD was significantly higher than that of males' (50 vs 10%, P < 0.001). The error rates of anesthetist residents of first-year, second-year and third-year were 34, 27, and 31%, respectively, and were not significantly different. The error of TMD measurement by surface landmark identification is often, especially for women. More clinic experience don't improve it.


Subject(s)
Thyroid Cartilage/diagnostic imaging , Adult , Airway Management , Female , Healthy Volunteers , Humans , Intubation, Intratracheal , Male , Mandible/diagnostic imaging , Predictive Value of Tests , Ultrasonography , Young Adult
18.
Medicine (Baltimore) ; 96(41): e8275, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29019899

ABSTRACT

BACKGROUND: The purpose of this study was to investigate effect of cerebral oxygen saturation (SCTO2) on postoperative nausea and vomiting (PONV) in female patients who underwent laparoscopic surgery. METHODS: This study included 90 female patients who underwent laparoscopic surgery (60 cases of gynecological operations and 30 cases of gallbladder operations). All patients were allocated into 3 groups of 30 patients each: group A (gynecological laparoscopic surgery), group B (gynecological laparoscopic surgery with mannitol treatment) and group C (laparoscopic cholecystectomy surgery). Perioperative SCTO2, mean blood flow velocity of vertebral artery (VM), vascular resistance index of vertebral artery (RI), and PONV (within 48 hours after surgery) were investigated. RESULTS: No differences in age, body weight, operation time, and hemoglobin levels were observed among the patients (P > .05). The SCTO2 values for groups B and C were lower than those for group A in both brain hemispheres at T4 and T5 (P < .05). The VM was higher in group B than in groups A and C at T3 (P < .05), but differences in VM were not observed between groups B and C at T4 or T5. However, the VM of group A was still lower than the other groups (P < .05), and no difference in VM was observed among the 3 groups at T6 (P > .05). The RI was higher in group C than in groups A and B at T4 (P < .05). The incidence of PONV within 48 hours after surgery was significantly higher in group A than in the other 2 groups (P < .05). CONCLUSION: Strategies that maintain normal SCTO2 may reduce the incidence of PONV in female patients who underwent laparoscopy surgery by reducing perioperative intracranial pressure.


Subject(s)
Brain , Cholecystectomy, Laparoscopic/adverse effects , Gynecologic Surgical Procedures/adverse effects , Laparoscopy/adverse effects , Oxygen Consumption/physiology , Postoperative Nausea and Vomiting , Vertebral Artery/physiopathology , Adult , Blood Flow Velocity , Brain/blood supply , Brain/metabolism , Diuretics, Osmotic/therapeutic use , Female , Gynecologic Surgical Procedures/methods , Humans , Laparoscopy/methods , Mannitol/therapeutic use , Middle Aged , Perioperative Care/methods , Postoperative Nausea and Vomiting/diagnosis , Postoperative Nausea and Vomiting/metabolism , Postoperative Nausea and Vomiting/physiopathology , Postoperative Nausea and Vomiting/prevention & control , Statistics as Topic , Vascular Resistance
19.
Sci Rep ; 7(1): 13927, 2017 10 24.
Article in English | MEDLINE | ID: mdl-29066717

ABSTRACT

Inadvertent intraoperative hypothermia (core temperature <36 °C) is a frequent but preventable complication of general anesthesia. Accurate risk assessment of individual patients may help physicians identify patients at risk for hypothermia and apply preventive approaches, which include active intraoperative warming. This study aimed to develop and validate a risk-prediction model for intraoperative hypothermia. Two independent observational studies in China, the Beijing Regional Survey and the China National Survey, were conducted in 2013 and 2014, respectively, to determine the incidence of hypothermia and its underlying risk factors. In this study, using data from these two studies, we first derived a risk calculation equation, estimating the predictive risk of hypothermia using National Survey data (3132 patients), then validated the equation using the Beijing Regional Survey data (830 patients). Measures of accuracy, discrimination and calibration were calculated in the validation data set. Through validation, this model, named Predictors Score, had sound overall accuracy (Brier Score = 0.211), good discrimination (C-Statistic = 0.759) and excellent calibration (Hosmer-Lemeshow, P = 0.5611). We conclude that the Predictors Score is a valid predictor of the risk of operative hypothermia and can be used in deciding whether intraoperative warming is a cost-effective measure in preventing the hypothermia.


Subject(s)
Anesthesia, General/adverse effects , Hypothermia/etiology , Intraoperative Complications/etiology , Risk Assessment/methods , Aged , Decision Making , Female , Humans , Male , Middle Aged , Regression Analysis , Retrospective Studies , Risk Factors
20.
Oncotarget ; 8(32): 52923-52934, 2017 Aug 08.
Article in English | MEDLINE | ID: mdl-28881783

ABSTRACT

OBJECTIVE: To explore the effects of inhibition of PI3K/Akt/mTOR signal pathway on chronic neuropathic pain (CNP) and spinal microglia in a rat model of chronic constriction injury (CCI). METHODS: Male SD rats were assigned into control, sham, CCI, wortmannin, dimethyl sulfoxide (DMSO) and wortmannin-positive control groups. Paw withdrawal mechanical threshold (PWMT) and thermal withdrawal latency (TWL) were recorded. qRT-PCR and Western blotting were used to detect PI3K, Akt and mTOR expressions and their phosphorylation. OX-4 expression was detected by immunohistochemistry and glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) expressions by immunofluorescence. RESULTS: PWMT and TWL decreased in the CCI group than in the sham group on the 7th and 14th day after operation. Compared with the control and sham groups, the CCI group showed increased PI3K, Akt and mTOR mRNA expressions and elevated PI3K, p-Akt, p-mTOR and P70S6K protein expressions. More OX-42-positive cells and higher integrated optical density (IOD) of GFAP and NGF were found in the CCI group than the sham group at the 14th day after operation. Compared with the DMSO group, the wortmannin group had higher PWMT and TWL, decreased PI3K, Akt and mTOR mRNA expressions and reduced PI3K, p-Akt, p-mTOR and P70S6K protein expressions. Less OX-42-positive cells and lower IOD of GFAP and NGF were found in the wortmannin group than the DMSO group 14th day after operation. CONCLUSION: Inhibition of PI3K/Akt/mTOR signal pathway may alleviate CNP and reduce microglia and GFAP and NGF expressions in marrow in a rat model of CCI.

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