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1.
Crit Care Med ; 52(6): e268-e278, 2024 06 01.
Article in English | MEDLINE | ID: mdl-38441040

ABSTRACT

OBJECTIVE: Comparing the effects of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) on outcomes in patients with in-hospital cardiac arrest (IHCA) in China. The benefits of ECPR over CCPR in patients with IHCA remain controversial. DESIGN: This article analyzed data from the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA) study, which consecutively enrolled patients with IHCA from July 1, 2019, to December 31, 2020. Patients who received ECPR were selected as the case group and matched with patients who received CCPR as the control group by propensity score at a ratio of 1:4. A parallel questionnaire survey of participating hospitals was conducted, to collect data on ECPR cases from January 1, 2021 to November 30, 2021. The primary outcome was survival to discharge or 30-day survival. SETTING: We included 39 hospitals across 31 provinces in China. PATIENTS: Patients receiving cardiopulmonary resuscitation and without contraindications to ECPR were selected from the BASIC-IHCA database. Patients older than 75 years, not witnessed, or with cardiopulmonary resuscitation duration less than 10 min were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 4853 patients met the inclusion criteria before matching, with 34 undergoing ECPR (median age, 56.5 yr; 67.65% male) and 4819 underwent CCPR (median age, 59 yr; 64.52% male). There were 132 patients receiving CCPR and 33 patients receiving ECPR who were eventually matched. The ECPR group had significantly higher survival rates at discharge or 30-day survival (21.21% vs. 7.58%, p = 0.048). The ECPR group had significantly lower mortality rates (hazard ratio 0.57; 95% CI, 0.38-0.91) than the CCPR group at discharge or 30 days. Besides the BASIC-IHCA study, the volume of ECPR implementations and the survival rate of patients with ECPR (29.4% vs. 10.4%. p = 0.004) in participating hospitals significantly improved. CONCLUSIONS: ECPR may be beneficial compared with CCPR for patient survival after IHCA and should be considered for eligible patients with IHCA.


Subject(s)
Cardiopulmonary Resuscitation , Extracorporeal Membrane Oxygenation , Heart Arrest , Propensity Score , Humans , Male , Middle Aged , Female , Cardiopulmonary Resuscitation/methods , Heart Arrest/therapy , Heart Arrest/mortality , Extracorporeal Membrane Oxygenation/methods , Extracorporeal Membrane Oxygenation/mortality , China/epidemiology , Aged , Cohort Studies , Adult , Hospital Mortality
3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(4): 398-403, 2023 Apr.
Article in Chinese | MEDLINE | ID: mdl-37308196

ABSTRACT

OBJECTIVE: To investigate the protective effect and potential mechanism of tubastatin A (TubA), a specific inhibitor of histone deacetylase 6 (HDAC6), on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in swine. METHODS: Twenty-five healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 10) and TubA intervention group (n = 9) using a random number table. The porcine model of CPR was reproduced by 9-minute cardiac arrest induced by electrical stimulation via right ventricle followed by 6-minute CPR. The animals in the Sham group only underwent the regular operation including endotracheal intubation, catheterization, and anesthetic monitoring. At 5 minutes after successful resuscitation, a dose of 4.5 mg/kg of TubA was infused via the femoral vein within 1 hour in the TubA intervention group. The same volume of normal saline was infused in the Sham and CPR model groups. Venous samples were collected before modeling and 1, 2, 4, 24 hours after resuscitation, and the levels of serum creatinine (SCr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO) in serum were determined by enzyme-linked immunoadsordent assay (ELISA). At 24 hours after resuscitation, the upper pole of left kidney and terminal ileum were harvested to detect cell apoptosis by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and the expression levels of receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) were detected by Western blotting. RESULTS: After resuscitation, renal dysfunction and intestinal mucous injury were observed in the CPR model and TubA intervention groups when compared with the Sham group, which was indicated by significantly increased levels of SCr, BUN, I-FABP and DAO in serum. However, the serum levels of SCr and DAO starting 1 hour after resuscitation, the serum levels of BUN starting 2 hours after resuscitation, and the serum levels of I-FABP starting 4 hours after resuscitation were significantly decreased in the TubA intervention group when compared with the CPR model group [1-hour SCr (µmol/L): 87±6 vs. 122±7, 1-hour DAO (kU/L): 8.1±1.2 vs. 10.3±0.8, 2-hour BUN (mmol/L): 12.3±1.2 vs. 14.7±1.3, 4-hour I-FABP (ng/L): 661±39 vs. 751±38, all P < 0.05]. The detection of tissue samples indicated that cell apoptosis and necroptosis in the kidney and intestine at 24 hours after resuscitation were significantly greater in the CPR model and TubA intervention groups when compared with the Sham group, which were indicated by significantly increased apoptotic index and markedly elevated expression levels of RIP3 and MLKL. Nevertheless, compared with the CPR model group, renal and intestinal apoptotic indexes at 24 hours after resuscitation in the TubA intervention group were significantly decreased [renal apoptosis index: (21.4±4.6)% vs. (55.2±9.5)%, intestinal apoptosis index: (21.3±4.5)% vs. (50.9±7.0)%, both P < 0.05], and the expression levels of RIP3 and MLKL were significantly reduced [renal tissue: RIP3 protein (RIP3/GAPDH) was 1.11±0.07 vs. 1.39±0.17, MLKL protein (MLKL/GAPDH) was 1.20±0.14 vs. 1.51±0.26; intestinal tissue: RIP3 protein (RIP3/GAPDH) was 1.24±0.18 vs. 1.69±0.28, MLKL protein (MLKL/GAPDH) was 1.38±0.15 vs. 1.80±0.26, all P < 0.05]. CONCLUSIONS: TubA has the protective effect on alleviating post-resuscitation renal dysfunction and intestinal mucous injury, and its mechanism may be related to inhibition of cell apoptosis and necroptosis.


Subject(s)
Abdominal Injuries , Cardiopulmonary Resuscitation , Kidney Diseases , Male , Animals , Swine , Apoptosis
5.
Front Med (Lausanne) ; 9: 1057000, 2022.
Article in English | MEDLINE | ID: mdl-36619612

ABSTRACT

Aim: The primary mission of cardiopulmonary resuscitation (CPR) is to provide adequate blood flow and oxygen delivery for restoring spontaneous circulation from cardiac arrest (CA) events. Previously, studies demonstrated that chest compression synchronized ventilation (CCSV) improved systemic oxygen supply during CPR, and aortic balloon occlusion (ABO) augments the efficacy of external CPR by increasing blood perfusion to vital organs. However, both them failed to make a significant improvement in return of spontaneous circulation (ROSC). In this study, we investigated the effects of combined CCSV and ABO on the outcomes of CPR in swine. Methods: Thirty-one male domestic swine were subjected to 8 min of electrically induced and untreated CA followed by 8 min of CPR. CPR was performed by continuous chest compressions and mechanical ventilation. At the beginning of CPR, the animals were randomized to receive intermittent positive pressure ventilation (IPPV, n = 10), CCSV (n = 7), IPPV + ABO (n = 7), or CCSV + ABO (n = 7). During CPR, gas exchange and systemic hemodynamics were measured, and ROSC was recorded. After resuscitation, the function and injury biomarkers of vital organs including heart, brain, kidney, and intestine were evaluated. Results: During CPR, PaO2 was significantly higher accompanied by significantly greater regional cerebral oxygen saturation in the CCSV and CCSV + ABO groups than the IPPV group. Coronary perfusion pressure, end-tidal carbon dioxide, and carotid blood flow were significantly increased in the IPPV + ABO and CCSV + ABO groups compared with the IPPV group. ROSC was achieved in five of ten (IPPV), five of seven (CCSV), six of seven (IPPV + ABO), and seven of seven (CCSV + ABO) swine, with the rate of resuscitation success being significantly higher in the CCSV + ABO group than the IPPV group (P = 0.044). After resuscitation, significantly improved myocardial and neurological function, and markedly less cardiac, cerebral, renal, and intestinal injuries were observed in the CCSV + ABO group compared with the IPPV group. Conclusion: The combination of CCSV and ABO improved both ventilatory and hemodynamic efficacy during CPR, promoted ROSC, and alleviated post-resuscitation multiple organ injury in swine.

6.
Biosci Biotechnol Biochem ; 85(5): 1183-1193, 2021 Apr 24.
Article in English | MEDLINE | ID: mdl-33704405

ABSTRACT

Obesity is one of the most critical risk factors for diabetes mellitus and plays a significant role in diabetic nephropathy (DN). The present investigation aimed to evaluate the possible mechanism of action of vitexin on obesity-induced DN in a high-fat diet (HFD)-fed experimental C57BL/6 mice model. Obesity was induced in male C57BL/6 mice by chronic administration of HFD, and mice were concomitantly treated with vitexin (15, 30, and 60 mg/kg, p.o.). HFD-induced increased renal oxido-nitrosative stress and proinflammatory cytokine levels were significantly inhibited by vitexin. The Western blot analysis suggested that alteration in renal NF-κB, IκBα, nephrin, AMPK, and ACC phosphorylation levels was effectively restored by vitexin treatment. Histological aberration induced in renal tissue after chronic administration of HFD was also reduced by vitexin. In conclusion, vitexin suppressed the progression of obesity-induced DN via modulation of NF-κB/IkBα and AMPK/ACC pathways in an experimental model of HFD-induced DN in C57BL/6J mice.


Subject(s)
Anti-Obesity Agents/pharmacology , Apigenin/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , Hypoglycemic Agents/pharmacology , Obesity/drug therapy , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/genetics , Acetyl-CoA Carboxylase/metabolism , Animals , Anti-Obesity Agents/isolation & purification , Apigenin/isolation & purification , Diabetes Mellitus, Experimental/etiology , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/etiology , Diabetic Nephropathies/genetics , Diabetic Nephropathies/pathology , Diet, High-Fat/adverse effects , Gene Expression Regulation , Hypoglycemic Agents/isolation & purification , I-kappa B Kinase/genetics , I-kappa B Kinase/metabolism , Male , Malondialdehyde/antagonists & inhibitors , Malondialdehyde/metabolism , Mice , Mice, Inbred C57BL , NF-kappa B/genetics , NF-kappa B/metabolism , Obesity/etiology , Obesity/genetics , Obesity/pathology , Plant Extracts/chemistry , Signal Transduction , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Trigonella/chemistry , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
7.
Medicine (Baltimore) ; 100(9): e24886, 2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33655948

ABSTRACT

BACKGROUND: Assessing the effectiveness and safety of acupuncture for chronic constipation in patients with diabetes mellitus is the main purpose of this systematic review protocol. METHODS: The following electronic databases will be searched from their respective inception dates to December 1st 2020: PubMed, the Cochrane Library, Embase, World Science Net, the Allied and Complementary Medicine Database, the Web of Science, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database and the Wanfang Database. All published randomized controlled trials in English or Chinese related to acupuncture for constipation in patient with diabetes mellitus will be included. The Bristol stool scale, spontaneous complete bowel movements, and observing symptoms (yes/no) including defecation feeling, defecation weakness, feeling of incomplete evacuation, bloating, and flatulence were considered as primary measures. The treatment efficiency consideration according to Bristol stool scale was considered as secondary measure. Two reviewers will conduct the study selection, data extraction and assessment independently. The assessment of risk of bias and data synthesis will be conducted with Review Manager Software (RevMan) V.5.2. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide an evidence to judge whether.Acupuncture is an effective intervention for chronic constipation in patients with diabetes mellitus. ETHICS AND DISSEMINATION: Formal ethical approval is not necessary as the data cannot be individualized. The results of this protocol will be disseminated in a peer-reviewed journal or presented at relevant conferences. PROSPERO REGISTRATION NUMBER: INPLASY202110079.


Subject(s)
Acupuncture Therapy/methods , Constipation/therapy , Diabetes Mellitus , Quality of Life , Chronic Disease , Humans
8.
Toxicol Appl Pharmacol ; 404: 115179, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32745479

ABSTRACT

Epithelial-mesenchymal transition (EMT), the transition of epithelial cells into mesenchymal cells, plays important roles in the metastasis of solid tumors. 8-Oxo-epiberberine (OPB) is a natural alkaloid extracted from the roots of Coptis chinensis Franch. In this study, The effect and the underlying mechanism of OPB on EMT in a TGF-ß1-induced model and the inhibitory effect of OPB on lung metastasis were investigated. TGF-ß1-stimulated lung cancer cells were co-treated with OPB, the morphological changes were examined. The protein expression of EMT biomarkers E-cadherin and N-cadherin was determined by Western blotting and immunofluorescence. The transcription activity of smad2/3 promoter was analyzed by a luciferase reporter assay. The effect of OPB on cell migration, invasion, and adhesion was detected by wound-healing, adhesion, and transwell assays. The in vivo anti-metastatic effect of OPB was evaluated using a 4 T1 cell xenograft mouse model. Results showed that OPB significantly reversed TGF-ß1-triggered morphological changes, expression of EMT biomarkers, and migration, adhesion, and invasion. Furthermore, OPB suppressed TGF-ß1-induced Smad2/3 activation, Smad3 phosphorylation and nuclear translocation, and interaction of Smad3 with Smad4. Besides, OPB dramatically decreased the metastatic nodules in the lung without affecting the growth of primary tumors. In conclusion, OPB inhibited TGF-ß1-induced EMT possibly by interfering with Smad3. OPB might have therapeutic potentials for the treatment of metastatic cancers.


Subject(s)
Berberine/analogs & derivatives , Epithelial-Mesenchymal Transition/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Berberine/chemistry , Berberine/pharmacology , Cell Adhesion , Cell Line, Tumor , Cell Movement , Female , Humans , Lung Neoplasms/drug therapy , Mice , Mice, Inbred BALB C , Neoplasms, Experimental , Smad3 Protein/genetics , Transforming Growth Factor beta1/genetics
9.
J Craniofac Surg ; 31(5): 1266-1269, 2020.
Article in English | MEDLINE | ID: mdl-32282479

ABSTRACT

OBJECTIVE: This study aimed to investigate the clinical outcomes of endoscopic transnasal optic canal decompression (ETOCD) for patients with indirect traumatic optic neuropathy (TON) and identify the relevant prognostic factors. METHODS: Seventy-two indirect TON patients who underwent ETOCD surgery from August 2017 to May 2019 were analyzed retrospectively. The paired t-test was used to compare the visual acuity (VA) before and after ETOCD, and multiple linear regression analysis was used to distinguish the potential prognostic factors. RESULTS: Among the patients analyzed, postoperative VA (-2.87 ±â€Š0.19) was significantly higher than the preoperative VA (-3.92 ±â€Š0.13) (P < 0.05). Multiple linear regression analysis models showed that poor initial VA and longer time to surgery were independent risk factors for VA prognosis (P < 0.05), but surgical time alone was significantly associated with the improvement degree of visual acuity (IDVA) (P < 0.05). Optic canal fracture, orbital fracture, and hemorrhage within the ethmoid and/or sphenoid sinus were not significantly correlated with IDVA and VA prognosis (P > 0.05). CONCLUSIONS: ETOCD surgery could salvage VA impairment in patients with indirect TON. A better initial VA indicates better final VA outcomes after surgery. Additionally, shorter time to surgery implies better VA prognosis and higher IDVA.


Subject(s)
Optic Nerve Injuries/surgery , Adolescent , Adult , Aged , Decompression, Surgical , Endoscopy , Female , Humans , Male , Middle Aged , Operative Time , Postoperative Period , Prognosis , Regression Analysis , Retrospective Studies , Risk Factors , Sphenoid Bone/surgery , Visual Acuity , Young Adult
10.
Pak J Med Sci ; 36(2): 296-298, 2020.
Article in English | MEDLINE | ID: mdl-32063979

ABSTRACT

Gastric perforation is a rare complication of cardiopulmonary resuscitation (CPR), mostly resulting from incorrect airway management. If left unrecognized, it is associated with high mortality and morbidity. We present a case of gastric perforation after improper CPR. A 56-year-old drunken male was sent to the emergency department due to coma after fall onto the ground. He was thought to have cardiac arrest at scene and was saved with CPR maneuver by his friends who has never been trained before. He was taken to the hospital by emergency medical service personnel and presented with abdominal distention and extensive pneumoperitoneum. Emergency laparotomy was performed which revealed gastric perforation at the lesser curvature of the stomach. The laceration was repaired without any difficulty and the patient was discharged home without any neurological deficit. The aim of this report is to remind the public and emergency physicians that gastric perforation should be suspected in patients with distended abdomen and pneumoperitoneum after CPR. Because the most common risk factor for CPR-related gastric perforation is the bystander-provided resuscitation, it is encouraged for the public to take formal CPR training.

11.
J Int Med Res ; 48(4): 300060519894440, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31884870

ABSTRACT

OBJECTIVE: We evaluated the quality of 2-minute continuous chest compressions (CCCs) performed by emergency staff in 30-second intervals to determine the effect of a feedback system on maintaining the quality of CCCs. METHODS: Two hundred three physicians and nurses were randomised into two groups. Each participant performed 2-minute CCCs both with and without feedback. Group A performed CCCs under the guidance of a feedback device followed by performance without feedback, and Group B performed these tasks in reverse order. The primary outcome was the proportion of optimal compressions; i.e., compressions at both the correct rate (100-120 beats/minute) and correct depth (5-6 cm). RESULTS: During 2-minute CCCs, the proportion of optimal compressions was poor in personnel without feedback. The proportion of optimal compressions was unchanged and low from 2.4% (interquartile range, 0.0%-32.8%) in the first 30 seconds to 3.3% (0.0%-47.7%) in the last 30 seconds of the 2-minute period. Use of the feedback device significantly improved and maintained the quality of compressions from the first 30 seconds (53.3%; 29.2%-70.4%) to the last 30 seconds (82.8%; 50.8%-96.2%). CONCLUSION: Use of the feedback device was helpful for maintaining the quality of CCCs.


Subject(s)
Cardiopulmonary Resuscitation , Computer Simulation , Feedback , Humans , Pressure , Thorax
12.
J Biochem Mol Toxicol ; 33(11): e22400, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31593355

ABSTRACT

Inflammatory bowel disease (IBD) is a continual ailment condition which engrosses the entire alimentary canal. The IBD can be primarily distinguished into two forms, ulcerative colitis, and Crohn's disease. The major symptoms of IBD include pustules or abscesses, severe abdominal pain, diarrhea, fistula, and stenosis, which may directly affect the patient's quality of life. A variety of mediators can stimulate the circumstances of IBD, some examples include infections by microbes such as bacteria, perturbation of the immune system and the surrounding environment of the intestines. Severe colitis was stimulated in the experimental animals through administering 4% dextran sulfate sodium (DSS) which is mixed in water ad libitum for 6 days. Eriocitrin (30 mg/kg) was then administered to the experimental animals followed by the induction of severe colitis to evaluate the therapeutic prospective of eriocitrin against the colon inflammation stimulated by DSS. In this study, eriocitrin (30 mg/kg) demonstrated significant (P < .05) attenuation activity against the DSS-stimulated severe colitis in experimental animals. Eriocitrin counteracted all of the clinical deleterious effects induced by DSS, such as body-weight loss, colon shortening, histopathological injury, accretion of infiltrated inflammatory cells at the inflamed region and the secretion of inflammatory cytokines. The results clearly showed that eriocitrin effectively attenuated DSS-induced acute colitis in experimental animals.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Colitis/chemically induced , Colitis/drug therapy , Dextran Sulfate/pharmacology , Flavanones/therapeutic use , Plant Extracts/therapeutic use , Animals , Anti-Inflammatory Agents/administration & dosage , Citrus/chemistry , Colon/drug effects , Colon/pathology , Cyclooxygenase 2/analysis , Cytokines/metabolism , Disease Models, Animal , Flavanones/administration & dosage , Inflammation/metabolism , Male , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/analysis , Peroxidase/metabolism , Plant Extracts/administration & dosage , Severity of Illness Index , Weight Loss/drug effects
13.
Dose Response ; 17(3): 1559325819862449, 2019.
Article in English | MEDLINE | ID: mdl-31360147

ABSTRACT

Neonatal-streptozotocin (n-STZ)-induced diabetes mimics most of the clinicopathological symptoms of type 2 diabetes mellitus (T2DM) peripheral neuropathy. Berberine, a plant alkaloid, is reported to have antidiabetic, antioxidant, anti-inflammatory, and neuroprotective potential. The aim of the present study was to investigate the potential of berberine against n-STZ-induced painful diabetic peripheral polyneuropathy by assessing various biochemical, electrophysiological, morphological, and ultrastructural studies. Type 2 diabetes mellitus was produced neonatal at the age of 2 days (10-12 g) by STZ (90 mg/kg intraperitoneal). After confirmation of neuropathy at 6 weeks, rats were treated with berberine (10, 20, and 40 mg/kg). Administration of n-STZ resulted in T2DM-induced neuropathic pain reflected by a significant alterations (P < .05) in hyperalgesia, allodynia, and motor as well as sensory nerve conduction velocities whereas berberine (20 and 40 mg/kg) treatment significantly attenuated (P < .05) these alterations. Berberine treatment significantly inhibited (P < .05) STZ-induced alterations in aldose reductase, glycated hemoglobin, serum insulin, hepatic cholesterol, and triglyceride levels. The elevated oxido-nitrosative stress and decreased Na-K-ATPase and pulse Ox levels were significantly attenuated (P < .05) by berberine. It also significantly downregulated (P < .05) neural tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6 messenger RNA (mRNA), and protein expressions both. Streptozotocin-induced downregulated mRNA expressions of brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), and peroxisome proliferator-activated receptors-γ (PPAR-γ) in sciatic nerve were significantly upregulated (P < .05) by berberine. Western blot analysis revealed that STZ-induced alterations in adenosine monophosphate protein kinase (AMPK; Thr-172) and protein phosphatase 2C-α protein expressions in dorsal root ganglia were inhibited by berberine. It also attenuated histological and ultrastructural alterations induced in sciatic nerve by STZ. In conclusion, berberine exerts its neuroprotective effect against n-STZ-induced diabetic peripheral neuropathy via modulation of pro-inflammatory cytokines (TNF α, IL-1ß, and IL-6), oxido-nitrosative stress, BDNF, IGF-1, PPAR-γ, and AMPK expression to ameliorate impaired allodynia, hyperalgesia, and nerve conduction velocity during T2DM.

14.
FEBS Open Bio ; 9(7): 1249-1258, 2019 07.
Article in English | MEDLINE | ID: mdl-31077568

ABSTRACT

Diabetic nephropathy (DN) is a complication of diabetes mellitus (DM) that frequently results in renal disease, and is characterized by a variety of symptoms, including albuminuria. It has been shown that apoptosis of glomerular mesangial cells (MCs) can aggravate albuminuria and contribute to the development of diabetic glomerulosclerosis. Hence, determination of the mechanisms leading to MC apoptosis may help us gain insights into the pathogenesis of DN. As our understanding of the role of high glucose (HG) in MC apoptosis remains elusive, we explored the interplay between X-box binding protein 1 (XBP1) and MC apoptosis in this study. XBP1 was observed to be downregulated both in vivo and in vitro. Treatment of XBP1-overexpressing cells with HG resulted in a decrease of reactive oxygen species (ROS) and a suppression of cell apoptosis, concomitant with decreases in cleaved caspase-3 and Bax. Subsequent analyses demonstrated that XBP1 overexpression inhibited the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and enhanced the activation of AKT in MCs exposed to HG. In addition, XBP1-induced injuries in MC were reversed by overexpression of PTEN, and XBP1 inhibited apoptosis, which was mediated by the activated PTEN/AKT signaling pathway. Thus, our data indicate that XBP1 can activate the PTEN/AKT signaling pathway, thereby alleviating oxidative stress caused by HG or MC apoptosis. These findings suggest that XBP1 may have potential in the development of treatment methods for DN.


Subject(s)
Apoptosis/physiology , Diabetic Nephropathies/metabolism , X-Box Binding Protein 1/metabolism , Animals , Apoptosis/drug effects , Cell Line , Diabetes Mellitus, Experimental/genetics , Disease Models, Animal , Glucose/metabolism , Male , Mesangial Cells/metabolism , Mice , Mice, Inbred C57BL , Oxidative Stress/drug effects , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Reactive Oxygen Species/metabolism , Signal Transduction/physiology , X-Box Binding Protein 1/physiology
15.
Shock ; 52(4): 456-467, 2019 10.
Article in English | MEDLINE | ID: mdl-30335673

ABSTRACT

Rapid induction of hypothermia early after resuscitation can be an effective strategy against post-cardiac arrest syndrome (PCAS). Preliminary data suggested that continuous renal replacement therapy (CRRT) might be an efficient method to rapidly induce hypothermia. In this study, we investigated the efficacy of cooling induced by CRRT and its effects on the outcomes of PCAS in a porcine model.Thirty-two male domestic pigs weighing 36 ±â€Š2 kg were randomized into 4 groups: sham control (n = 5), normothermia (n = 9), surface cooling (SC, n = 9), and CRRT (n = 9). Sham animals underwent the surgical preparation only. The animal model was established by 8 min of untreated ventricular fibrillation and then 5 min of cardiopulmonary resuscitation. At 5 min after resuscitation, the animals were cooled by either the combination of an earlier 8-h CRRT and later 16-h SC or the whole 24-h SC in the 2 hypothermic groups. For the other 2 groups, a normal temperature of 38.0 ±â€Š0.5°C was maintained throughout the experiment.Blood temperature was decreased to 33°C within 28 min in animals treated with CRRT, which was significantly faster than that in the SC group requiring 185 min to achieve target temperature. Post-resuscitation myocardial dysfunction, brain injury, and systemic inflammation were significantly improved in the 2 hypothermic groups compared to the normothermia group. However, the improvement was significantly greater in the CRRT group than in the SC group.In conclusion, fast hypothermia was successfully induced by CRRT and significantly alleviated the severity of PCAS in a porcine model.


Subject(s)
Hypothermia, Induced , Post-Cardiac Arrest Syndrome , Renal Replacement Therapy , Animals , Disease Models, Animal , Post-Cardiac Arrest Syndrome/physiopathology , Post-Cardiac Arrest Syndrome/therapy , Swine
16.
Shock ; 52(3): e12-e21, 2019 09.
Article in English | MEDLINE | ID: mdl-30052583

ABSTRACT

Aortic balloon occlusion (ABO) facilitates the success of cardiopulmonary resuscitation (CPR) in non-traumatic cardiac arrest, and is also effective in controlling traumatic hemorrhage; however, a prolonged occlusion results in irreversible organ injury and death. In this study, we investigated the effects of ABO on CPR outcomes and its optimal duration for post-resuscitation organ protection in a porcine model of traumatic cardiac arrest (TCA).Twenty-seven male domestic pigs weighing 33 ±â€Š4 kg were utilized. Forty percent of estimated blood volume was removed within 20 min. The animals were then subjected to 5 min of untreated ventricular fibrillation and 5 min of CPR. Coincident with the start of CPR, the animals were randomized to receive either 30-min ABO (n = 7), 60-min ABO (n = 8) or control (n = 12). Meanwhile, fluid resuscitation was initiated by the infusion of normal saline with 1.5 times of hemorrhage volume in 1 h, and finished by the reinfusion of 50% of the shed blood in another 1 h. The resuscitated animals were monitored for 6 h and observed for an additional 18 h.During CPR, coronary perfusion pressure was significantly increased followed by a higher rate of resuscitation success in the 30 and 60-min ABO groups compared with the control group. However, post-resuscitation cardiac, neurologic dysfunction, and injuries were significantly milder accompanied with less renal and intestinal injuries in the 30-min ABO group than in the other two groups.In conclusion, ABO augmented the efficacy of CPR after TCA, and furthermore a 30-min ABO improved post-resuscitation cardiac and neurologic outcomes without exacerbating the injuries of kidney and intestine.


Subject(s)
Balloon Occlusion , Cardiopulmonary Resuscitation , Heart Arrest/therapy , Wounds and Injuries/therapy , Animals , Disease Models, Animal , Swine
17.
Mol Med Rep ; 18(6): 5295-5301, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30272288

ABSTRACT

Osteoarthritis (OA) is the most common type of arthritis, and remains to be social and medical challenge. Thus, identifying novel molecular targets is important for the prevention and treatment of OA. Long noncoding RNAs (lncRNAs) have been reported to modulate various biological and pathological processes. The aim of the present study was to investigate the role of lncRNA­p21 in OA and its underlying mechanism, in order to better understand the development of OA and its treatment. Chondrocytes were isolated from cartilage samples obtained from OA and normal patients. Chondrocytes were transfected with microRNA (miRNA/miR)­451 mimics, miR­451 inhibitor, pcDNA3.1(+)­p21 or small interfering RNA­p21. Flow cytometry was performed to analyze cell apoptosis and reverse transcription­quantitative polymerase chain reaction was conducted to detect the expression of mRNAs and miRNAs. Cell Counting Kit­8 assay was performed to detect cell viability. The results revealed that the level of lncRNA­p21 was significantly upregulated in OA cartilage when compared with the normal cartilage. Silencing of lncRNA­p21 increased cell viability and inhibited the apoptosis rate of chondrocytes in OA, while lncRNA­p21 overexpression decreased cell viability and increased the apoptosis rate of chondrocytes in OA. Overexpression of lncRNA­p21 suppressed the expression of miR­451 while the silencing of lncRNA­p21 reversed this effect. MiR­451 inhibitor effectively inhibited the upregulatory effect of si­p21 on miR­451. The increased cell viability and decreased apoptosis rate induced by lncRNA­p21 silencing was abolished by the miR­451 inhibitor. MiR­451 mimic effectively increased the downregulatory effect of pcDNA3.1­lncRNA­p21 on miR­451. The decreased cell viability and increased apoptosis rate induced by the overexpression of lncRNA­p21 was abolished by the miR­451 mimic. Investigation into the underlying mechanism revealed that lncRNA­p21 interacted with miRNA­451. In addition, lncRNA­p21 negatively regulated the expression of miR­451. Furthermore, lncRNA­p21 promoted the apoptosis of chondrocytes in OA by acting as a sponge for miR­451. Thus, lncRNA­p21 was proposed as a promising target for the treatment of OA.


Subject(s)
Apoptosis/genetics , Chondrocytes/metabolism , Gene Expression Regulation , MicroRNAs/genetics , Osteoarthritis/genetics , RNA Interference , RNA, Long Noncoding/genetics , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Cell Survival/genetics , Cells, Cultured , Humans , Osteoarthritis/metabolism
18.
J Am Heart Assoc ; 7(21): e010283, 2018 11 06.
Article in English | MEDLINE | ID: mdl-30608213

ABSTRACT

Background After cardiopulmonary resuscitation, the protective effects of therapeutic hypothermia induced by conventional cooling are limited. Recently, esophageal cooling ( EC ) has been shown to be an effective, easily performed approach to induce therapeutic hypothermia. In this study we investigated the efficacy of EC and its effects on early markers of postresuscitation cardiac and neurological injury in a porcine model of cardiac arrest. Methods and Results Thirty-two male domestic swine were randomized into 4 groups: sham control, normothermia, surface cooling, and EC . Sham animals underwent the surgical preparation only. Ventricular fibrillation was induced and untreated for 8 minutes while defibrillation was attempted after 5 minutes of cardiopulmonary resuscitation. At 5 minutes after resuscitation, therapeutic hypothermia was induced by either EC or surface cooling to reach a target temperature of 33°C until 24 hours postresuscitation, followed by a rewarming rate of 1°C/h for 5 hours. The temperature was normally maintained in the control and normothermia groups. After resuscitation, a significantly faster decrease in blood temperature was observed in the EC group than in the surface cooling group (2.8±0.7°C/h versus 1.5±0.4°C/h; P<0.05). During the maintenance and rewarming phases the temperature was maintained at an even level between the 2 groups. Postresuscitation cardiac and neurological damage was significantly improved in the 2 hypothermic groups compared with the normothermia group; however, the protective effects were significantly greater in the EC group. Conclusions In a porcine model of cardiac arrest, faster hypothermia successfully induced by EC was significantly better than conventional cooling in improving early markers of postresuscitation cardiac and neurological injury.


Subject(s)
Cardiopulmonary Resuscitation/methods , Esophagus , Heart Arrest/therapy , Hypothermia, Induced/methods , Animals , Biomarkers/blood , Heart Arrest/blood , Heart Arrest/complications , Heart Diseases/blood , Heart Diseases/etiology , Heart Diseases/prevention & control , Male , Nervous System Diseases/blood , Nervous System Diseases/etiology , Nervous System Diseases/prevention & control , Random Allocation , Swine , Time Factors
19.
Nanoscale ; 7(48): 20414-25, 2015 Dec 28.
Article in English | MEDLINE | ID: mdl-26502355

ABSTRACT

We report the synthesis of high quality trimetallic Au/Ag/Pt nanorings (TAAPNs) by using Au/Ag alloy decahedra (AAAD) as templates. The alloying effect and AgCl-directing growth have been investigated in detail during the formation of TAAPN. It was found that the doping of Ag in AAAD changes the surrounding environment of Au atoms and decreases the oxidization reduction potential (ORP) of [AuCl(2)](-)/Au because of the alloying effect, resulting in the dissolved O(2) molecules that serve as an effective etchant for oxidizing Au to Au(I). Ascorbic acid (AA) and chloroplatinic acid (H(2)PtCl(6)) are weak acids which can accelerate the etching by increasing the concentration of H(+). The AgCl selectively absorbs on {100} of the decahedra and induces the preferential deposition of H(2)PtCl(6) here via their complexing interaction. AA reduces Pt(IV) and Ag(I) to atoms which grow on {100} facets. The formed Pt/Ag layer changes the etching direction from along [100] to [111] and generates the TAAPN. Besides, it has been noted that the TAAPNs exhibit good Surface Enhanced Raman Scattering (SERS) performance.

20.
J Surg Res ; 196(2): 358-67, 2015 Jun 15.
Article in English | MEDLINE | ID: mdl-25791824

ABSTRACT

BACKGROUND: Previously reported ideal target mean arterial pressure (MAP) after control of bleeding in traumatic hemorrhagic shock (THS) requires further verification in more clinically related models. The authors explored this issue via gradient volume loading without vasopressor therapy. As certain volume loading can induce secretion of atrial natriuretic peptide (ANP), which has been shown to be protective, the authors also observed its potential role. MATERIALS AND METHODS: Fifty male New Zealand rabbits were submitted to 1.5 h of uncontrolled THS (with another eight rabbits assigned to the sham group). After bleeding control, treated rabbits were randomly (n = 10, respectively) resuscitated with blood and Ringer lactate (1:2) to achieve target MAP of 50, 60, 70, 80, and 90 mm Hg within 1 h. During the following 2 h, they were resuscitated toward baseline MAP. Rabbits were observed until 7 h. RESULTS: After resuscitation, infused fluid was lower and oxidative stress injury was milder in the 70 mm Hg group. Fluid volume loaded during the initial hour after hemostasis was negatively correlated with pH, oxygen saturation, and base excess at the end of resuscitation. It also correlated positively with proinflammatory responses in bronchoalveolar lavage fluid at 7 h and 7-h mortality. Moreover, after volume loading, the 80 mm Hg group showed significantly increased serum ANP level, which correlated with the expression of Akt protein in the jejunum at 7 h. CONCLUSIONS: In rabbits the ideal target MAP during the initial resuscitation of severe THS after hemostasis was 70 mm Hg. ANP may have a critical role in gut protection.


Subject(s)
Atrial Natriuretic Factor/blood , Blood Pressure , Fluid Therapy , Resuscitation/methods , Shock, Hemorrhagic/therapy , Animals , Bronchoalveolar Lavage Fluid/chemistry , Cytokines/analysis , Edema/prevention & control , Hemodynamics , Male , Oxidative Stress , Proto-Oncogene Proteins c-akt/metabolism , Rabbits , Random Allocation , Shock, Hemorrhagic/blood , Water-Electrolyte Balance
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