OBJECTIVES: To investigate the antioxidative mechanism of snake venom-derived protein C activator (PCA) in mitigating vascular endothelial cell injury. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in DMEM containing 1.0 g/L D-glucose and exposed to hypoxia (1% O₂) for 6 h followed by reoxygenation for 2 h to establish a cell model of oxygen-glucose deprivation/reoxygenation (OGD/R). The cell model was treated with 2 μg/mL PCA alone or in combination with 2-ME2 (a HIF-1α inhibitor) or DMOG (a HIF-1α stabilizer), and intracellular production of reactive oxygen species (ROS) and protein expression levels of HIF-1α, BNIP3, and Beclin-1 were detected using DCFH-DA fluorescence probe, flow cytometry, and Western blotting. The OGD/R cell model was transfected with a BNIP3-specific siRNA or a scrambled control sequence prior to PCA treatment, and the changes in protein expressions of HIF-1α, BNIP3 and Beclin-1 and intracellular ROS production were examined. RESULTS: In the OGD/R cell model, PCA treatment significantly upregulated HIF-1α, BNIP3 and Beclin-1 expressions and reduced ROS production. The effects of PCA were obviously attenuated by co-treatment with 2-ME2 but augmented by treatment with DMOG (a HIF-1α stabilizer). In the cell model with BNIP3 knockdown, PCA treatment increased BNIP3 expression and decreased ROS production without causing significant changes in HIF-1α expression. Compared with HUVECs with PCA treatment only, the cells with BNIP3 knockdown prior to PCA treatment showed significantly lower Beclin-1 expression and higher ROS levels. CONCLUSIONS Snake venom PCA alleviates OGD/R-induced endothelial cell injury by upregulating HIF-1α/BNIP3 signaling to suppress ROS generation, suggesting its potential as a therapeutic agent against oxidative stress in vascular pathologies.
Humans ; Reactive Oxygen Species/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Human Umbilical Vein Endothelial Cells/drug effects* ; Membrane Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Up-Regulation ; Cell Hypoxia ; Cells, Cultured ; Snake Venoms/chemistry* ; Beclin-1

Objective To analyze the effects of intravenous tirofiban following endovascular treatment on the prognosis of patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization.Methods This retrospective study included consecutive patients with acute anterior circulation ischemic stroke who underwent endovascular treatment but did not achieve successful recanalization.These patients were retrospectively enrolled from the Department of Neurology at Nanjing Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,the Second Affiliated Hospital of Soochow University,Wuhan No.1 Hospital,and Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College)between January 2015 and April 2023.Baseline and clinical data were collected including age,sex,medical history(hypertension,diabetes,atrial fibrillation,hyperlipidemia),personal history(smoking and drinking),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification(large artery atherosclerosis,cardioembolism,or other types),Alberta stroke program early CT score(ASPECTS)on admission,intravenous thrombolysis,onset-to-puncture time(OTP),collateral circulation status(poor collaterals:American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]score 0-2;good collateral:ASTIN/SIR score 3-4),procedure duration(from femoral or radial artery puncture to device removal),occlusion site,number of passes for thrombus retrieval,and post-procedural modified thrombolysis in cerebral infarction(mTICI)grade.Patients were divided into a tirofiban group and a non-tirofiban group based on whether they received post-procedural intravenous tirofiban.The primary outcome is a favorable functional outcome at 90-day since onset(modified Rankin scale[mRS]score ≤ 3).Safety outcomes included mortality at 90-day since onset(mRS score 6),any intracranial hemorrhage within 24 h post-procedure,and symptomatic intracranial hemorrhage within 24 h post-procedure.1∶1 propensity score matchings using the nearest neighbor method was performed based on variables with P＜0.05 in the comparison between the tirofiban and non-tirofiban groups.Differences in primary and safety outcomes between the matched groups were compared.Univariate and multivariate Logistic regression analyses were conducted with favorable outcomes at 90 days as the dependent variable to evaluate the effect of intravenous tirofiban administration after endovascular therapy on 90-day prognosis in patients without successful recanalization.Results A total of 356 patients without successful recanalization after endovascular treatment were included,comprising 195 males and 161 females,with a median age of 70(61,78)years(32-92 years).Among them,76 and 280patients were assigned to the tirofiban and non-tirofiban groups,respectively.At 90 days,114 patients had favorable outcomes,while 242 had unfavorable outcomes.(1)Before the 1∶1 propensity score matching,significant differences were observed between the tirofiban and non-tirofiban groups in terms of admission NIHSS score,ASPECTS,good collateral circulation,intravenous thrombolysis,and mTICI grade(all P＜0.05).After 1∶1 propensity score matching,66 matched pairs(132 patients)were obtained.No significant differences in the baseline and clinical characteristics were found between the two groups after matching(all P＞0.05).(2)After 1∶1 matching,a significant difference was observed in the rate of favorable outcomes at 90 days between the two groups(48.5％[32/66]vs.30.3％[20/66],P=0.033)after propensity score matching,while no significant differences were found in 90-day mortality,intracranial hemorrhage within 24h,or symptomatic intracranial hemorrhage within 24h(all P＞0.05).(3)Univariate analysis after 1∶1 matching indicated that age,atrial fibrillation,smoking history,admission NIHSS score,M2 segment middle cerebral artery occlusion,good collateral circulation,number of passes for thrombus retrieval,and tirofiban treatment were factors influencing favorable outcomes at 90 days.Multivariate Logistic regression analysis showed that younger age(aOR,0.942,95％CI 0.906-0.978,P=0.002),lower admission NIHSS score(aOR,0.855,95％CI 0.777-0.941,P=0.001),good collateral circulation(aOR,5.534,95％CI 2.141-14.301,P＜0.01),tirofiban treatment(aOR,2.774,95％CI 1.092-7.046,P=0.032),and M2 segment MCA occlusion(reference:internal carotid artery occlusion;aOR,4.874,95％CI 1.428-16.632,P=0.011)were independent predictors of favorable outcomes at 90 days.Conclusions Intravenous tirofiban administration after endovascular therapy may improve 90-day neurological outcomes in patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization without increasing the risk of hemorrhage.Further large-scale randomized controlled trials are warranted to validate these findings.

Objective To analyze the effects of intravenous tirofiban following endovascular treatment on the prognosis of patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization.Methods This retrospective study included consecutive patients with acute anterior circulation ischemic stroke who underwent endovascular treatment but did not achieve successful recanalization.These patients were retrospectively enrolled from the Department of Neurology at Nanjing Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,the Second Affiliated Hospital of Soochow University,Wuhan No.1 Hospital,and Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College)between January 2015 and April 2023.Baseline and clinical data were collected including age,sex,medical history(hypertension,diabetes,atrial fibrillation,hyperlipidemia),personal history(smoking and drinking),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification(large artery atherosclerosis,cardioembolism,or other types),Alberta stroke program early CT score(ASPECTS)on admission,intravenous thrombolysis,onset-to-puncture time(OTP),collateral circulation status(poor collaterals:American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]score 0-2;good collateral:ASTIN/SIR score 3-4),procedure duration(from femoral or radial artery puncture to device removal),occlusion site,number of passes for thrombus retrieval,and post-procedural modified thrombolysis in cerebral infarction(mTICI)grade.Patients were divided into a tirofiban group and a non-tirofiban group based on whether they received post-procedural intravenous tirofiban.The primary outcome is a favorable functional outcome at 90-day since onset(modified Rankin scale[mRS]score ≤ 3).Safety outcomes included mortality at 90-day since onset(mRS score 6),any intracranial hemorrhage within 24 h post-procedure,and symptomatic intracranial hemorrhage within 24 h post-procedure.1∶1 propensity score matchings using the nearest neighbor method was performed based on variables with P＜0.05 in the comparison between the tirofiban and non-tirofiban groups.Differences in primary and safety outcomes between the matched groups were compared.Univariate and multivariate Logistic regression analyses were conducted with favorable outcomes at 90 days as the dependent variable to evaluate the effect of intravenous tirofiban administration after endovascular therapy on 90-day prognosis in patients without successful recanalization.Results A total of 356 patients without successful recanalization after endovascular treatment were included,comprising 195 males and 161 females,with a median age of 70(61,78)years(32-92 years).Among them,76 and 280patients were assigned to the tirofiban and non-tirofiban groups,respectively.At 90 days,114 patients had favorable outcomes,while 242 had unfavorable outcomes.(1)Before the 1∶1 propensity score matching,significant differences were observed between the tirofiban and non-tirofiban groups in terms of admission NIHSS score,ASPECTS,good collateral circulation,intravenous thrombolysis,and mTICI grade(all P＜0.05).After 1∶1 propensity score matching,66 matched pairs(132 patients)were obtained.No significant differences in the baseline and clinical characteristics were found between the two groups after matching(all P＞0.05).(2)After 1∶1 matching,a significant difference was observed in the rate of favorable outcomes at 90 days between the two groups(48.5％[32/66]vs.30.3％[20/66],P=0.033)after propensity score matching,while no significant differences were found in 90-day mortality,intracranial hemorrhage within 24h,or symptomatic intracranial hemorrhage within 24h(all P＞0.05).(3)Univariate analysis after 1∶1 matching indicated that age,atrial fibrillation,smoking history,admission NIHSS score,M2 segment middle cerebral artery occlusion,good collateral circulation,number of passes for thrombus retrieval,and tirofiban treatment were factors influencing favorable outcomes at 90 days.Multivariate Logistic regression analysis showed that younger age(aOR,0.942,95％CI 0.906-0.978,P=0.002),lower admission NIHSS score(aOR,0.855,95％CI 0.777-0.941,P=0.001),good collateral circulation(aOR,5.534,95％CI 2.141-14.301,P＜0.01),tirofiban treatment(aOR,2.774,95％CI 1.092-7.046,P=0.032),and M2 segment MCA occlusion(reference:internal carotid artery occlusion;aOR,4.874,95％CI 1.428-16.632,P=0.011)were independent predictors of favorable outcomes at 90 days.Conclusions Intravenous tirofiban administration after endovascular therapy may improve 90-day neurological outcomes in patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization without increasing the risk of hemorrhage.Further large-scale randomized controlled trials are warranted to validate these findings.

Objective:To provide references on evaluating autonomic nervous stability training effect of military flying personnel by studying the evaluation index of heart rate variability (HRV).Methods:The ECG signals of 98 military flying personnel before and after three-stage autonomic nervous stability training were collected, and the ratio of 0.1Hz power (R) of HRV was calculated. The R value before and after personal training was marked as R 1 and R 2 respectively, and the D value was used to represent the difference value between R 2 and R 1. The feasibility of using R 2 and D to evaluate the training effect was analyzed to formulate evaluation standards. In order to more intuitively display an individual′s autonomic nervous stability training level, the Z value was used to convert the original score of R 2 and D, and the evaluation criteria were formulated. Results:The R value after autonomic nervous stability training (R 2=0.473±0.248) was significantly higher than that before (R 1=0.197±0.092, P<0.01), and the individuals with lower R value before training have more obvious growth trend of R value after training. Conclusions:"0.1Hz index" is suitable to be the evaluation index of autonomic nervous stability training effect. The evaluation of autonomic nervous stability training effect of flying personnel should comprehensively consider the grade evaluation results of R 2 and D.

Objective:To provide references on evaluating autonomic nervous stability training effect of military flying personnel by studying the evaluation index of heart rate variability (HRV).Methods:The ECG signals of 98 military flying personnel before and after three-stage autonomic nervous stability training were collected, and the ratio of 0.1Hz power (R) of HRV was calculated. The R value before and after personal training was marked as R 1 and R 2 respectively, and the D value was used to represent the difference value between R 2 and R 1. The feasibility of using R 2 and D to evaluate the training effect was analyzed to formulate evaluation standards. In order to more intuitively display an individual′s autonomic nervous stability training level, the Z value was used to convert the original score of R 2 and D, and the evaluation criteria were formulated. Results:The R value after autonomic nervous stability training (R 2=0.473±0.248) was significantly higher than that before (R 1=0.197±0.092, P<0.01), and the individuals with lower R value before training have more obvious growth trend of R value after training. Conclusions:"0.1Hz index" is suitable to be the evaluation index of autonomic nervous stability training effect. The evaluation of autonomic nervous stability training effect of flying personnel should comprehensively consider the grade evaluation results of R 2 and D.

Objective:To observe the hemodynamic change and inhibitory effect on stress response of oxycodone during induction, maintenance and resuscitation period of general anesthesia in patients undergoing gastric cancer surgery.Methods:60 patients with general anesthesia undergoing elective gastric cancer from March 2018-March 2019 in No.904 Hospital were selected. According to the random number table method, they were randomly divided into two groups ( n=30): Oxycodone group (group O) and Fentanyl group (group F). The anesthesia was induced by intravenous oxycodone 0.3 mg/kg (group O) or fentanyl 3 μg/kg (group F), propofol 2 mg/kg and cisatracurium 0.25 mg/kg. Oxycodone (group O) or fentanyl (group F) with sevoflurane were used for maintenance of general anesthesia. The mean arterial pressure (MAP) and heart rate (HR) were recorded before anesthesia induction (T 0), immediately intubation (T 1), 1 min (T 2) and 5 min (T 3) after intubation, immediately skin incision (T 4), surgery for 1 h (T 5), the end of operation (T 6) and 1 min (T 7) and 5 min (T 8) after extubation. The concentration of glucose (Glu), cortisol (Cor), epinephrine (E) and norepinephrine (NE) were detected in time T 0,T 2, T 4,T 5 and T 7. The time of extubation and the visual analogue scale (VAS) scores after extubation and 30 min after entering postanesthesia care unit (PACU) were recorded. The incidence of cough during induction, dysphoria during extubation and the adverse effects such as nausea, vomit and respiratory depression during PACU were also observed. Results:There were no significant difference between two groups in MAP and HR at the time point from T 0 to T 8 ( P>0.05); there were no significant difference about concentrations of Glu, Cor, E and NE at the time point of T 0,T 2,T 4,T 5 and T 7 ( P>0.05). Extubation time and VAS scores of 30 min after entering PACU in group O were significantly lower than those of group F ( P<0.05). Meanwhile, the incidences of cough during induction, dysphoria during extubation and respiratory depression in group O were significantly lower than in group F ( P<0.05). There was no significant difference in the incidence of nausea and vomiting ( P>0.05). Conclusions:Oxycodone can be safely and effectively used for induction and maintenance of general anesthesia in gastric cancer surgery, inhibit intraoperative stress response, and improve the quality of recovery period.

Objective:To explore the influence of hypophosphatemia on weaning from mechanical ventilation.Methods:An observational study was conducted. The medical records of 30 mechanical ventilated patients with hypophosphatemia admitted to intensive care unit of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to August 2020 were analyzed; another 60 mechanical ventilated patients with normophosphatemia around the same time were enrolled as controls by 1∶2 case-control matching based on gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score. And then the duration of invasive mechanical ventilation, times of spontaneous breathing trial (SBT), the diaphragmatic ultrasonography movement indexes, and outcome of weaning and prognosis during hospitalization were compared between the two groups. Receiver operator characteristic curve (ROC curve) was plotted to calculate the areas under ROC curve (AUC) and cut-off values of serum phosphorus for successful weaning and hospital survival. The correlations between the diaphragmatic ultrasonography movement indexes and serum phosphorus were analyzed by Pearson partial correlation analysis.Results:Compared with normophosphatemic group, the duration of invasive mechanical ventilation in hypophosphatemia group was significantly longer [days: 13.0 (7.0, 22.0) vs. 10.0 (5.5, 14.0), P < 0.05], and SBT attempts were more often [times: 3 (0, 5) vs. 1 (1, 2), P < 0.01], while the rate of successful weaning was lower (53.3% vs. 91.7%, P < 0.01), and the hospital mortality was higher (20.0% vs. 1.7%, P < 0.01). ROC curve analysis showed that serum phosphorus could predict successful weaning of mechanical ventilated patients, the AUC was 0.795, and the optimum cut-off value of serum phosphorus was 0.85 mmol/L with sensitivity of 73.2% and specificity of 84.2%. Serum phosphorus could predict hospital survival of mechanical ventilated patients, the AUC was 0.782, and the optimum cut-off value of serum phosphorus was 0.48 mmol/L with sensitivity of 81.9% and specificity of 85.7%. Compared with normophosphatemic group, diaphragm thickness at the end of inspiration (DTei), diaphragm thickness at the end of expiration (DTee), diaphragm thickening fraction (DTF), diaphragm excursion (DE) in hypophosphatemia group were all significantly decreased [DTei (cm): 0.19±0.07 vs. 0.27±0.08, DTee (cm): 0.14±0.05 vs. 0.19±0.06, DTF: (33.55±16.17)% vs. (45.04±18.66)%, DE (cm): 1.17±0.49 vs. 2.28±0.69, all P < 0.01]. Pearson partial correlation analysis showed that linear correlations were found between serum phosphorus and DTei, DTee, DTF, DE ( r values were 0.442, 0.351, 0.293, 0.628 respectively, all P < 0.01). Conclusions:Serum phosphorus may have correlation with the diaphragmatic ultrasonography movement indexes. Hypophosphatemia may impair the contractile properties of diaphragm, induce more SBT attempts and longer duration of invasive mechanical ventilation, and affect outcome of weaning and prognosis.

Three-dimensional (3D) printing,a key technique of rapid prototyping (RP),is developing rapidly all over the world.As 3D printing has a significant advantage of personalized manufacturing,it has exerted a profound effect on medicine.The high demand for personalized manufacturing in the field of orthosis provides an excellent opportunity for widespread use of 3D printing technique.This review briefly introduces the principles and characteristics of different forming methods of 3D printing,the types and characteristics of 3D printing materials widely used at present,and classification and clinical application of orthoses.We also summarize the domestic and international research on and manufacture oforthoses using 3D printing techniques,and discuss current problems and future development of 3D printing techniques in orthosis.

OBJECTIVE: To explore the change of the amplitude of P wave, T wave and ST segment of 12 lead electrocardiogram (ECG) in children with breath holding spell.
 METHODS: A total of 29 children (24 males and 5 females) with breath holding spell in Second Xiangya Hospital, Central South University were enrolled for this study from October, 2009 to September, 2015. Their ages ranged from 3 months to 6 years, with an average of 1.82±1.27 years old. The control group consisted of 30 age-matched and gender-matched healthy children. All subjects were underwent electrocardiography by the SR-1000A comprehensive automatic electrocardiograph analyzer, and the changes of the ECG parameters were compared between the two groups.
 RESULTS: Compared with the control group, the amplitude of P-wave of V5 lead was decreased [(44.10±23.98) vs (58.30±21.19) μV, P<0.05], the amplitude of T-wave of V6 lead was increased [(423.80±122.6) vs (350.00±105.73) μV, P<0.05], the amplitude of ST segment of II lead was increased [(84.80±39.97) vs (57.30±38.77) μV, P<0.05], the amplitude of ST segment of aVR lead was increased [(-77.60±37.41) vs (-51.00±33.46) μV, P<0.05], the amplitude of ST segment of aVL lead was increased [(35.20±28.24) vs (17.70±33.90) μV, P<0.05], the amplitude of ST segment of V5 lead was increased [(111.00±59.36) vs (69.00±36.33) μV, P<0.05], the amplitude of ST segment of V6 lead was increased [(79.30±45.51) vs (51.30±33.19) μV, P<0.05]. 
 CONCLUSION The children with breath holding spell have autonomic nerve dysfunction. The amplitude of ST segment changes is sensitive.
Breath Holding ; Brugada Syndrome ; Cardiac Conduction System Disease ; Electrocardiography ; Female ; Heart Conduction System ; Humans ; Infant ; Male

In the HPLC analysis of bendamustine hydrochloride, two related substances(IMP01 and IMP02)were detected. These two related substances were identified by LC-MS/MS and their structural confirmation was unambiguously carried out by synthesis followed by characterization using Q-TOF/MS and NMR. Based on the spectral data, related substances IMP01 and IMP02 were characterized as 4-(1-methyl-5-morpholino-1H-benzo［d］imidazol-2-yl)butyric acid hydrochloride and 4-{1-methyl-5-［(2-chloroethyl)(2-hydroxyethyl)amino］-1H-benzo［d］imidazol-2-yl)} butyric acid hydrochloride, respectively. Bendamustine hydrochloride and its related substances were separated under the established LC-MS condition. HPLC is a useful method for the determination of the related substances in bendamustine hydrochloride. Results obtained are valuable for its manufacturing process and quality control.