Résumé
Objective:To evaluate the role of ryanodine receptor 2 (RyR2) in postoperative cognitive dysfunction (POCD) in aged rats.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), POCD group (group P) and dantrolene group (group D). A rat POCD model was prepared by closed reduction and internal fixation of left tibial fractures with sevoflurane anesthesia in P and D groups. RyR inhibitor dantrolene 2 mg/kg was injected via a tail vein at 30 min before surgery in group D. Morris water maze tests were conducted on day 1 before surgery and day 7 after surgery to evaluate the cognitive function. An open field test was conducted to detect the spontaneous motor function starting from day 7 after surgery. The rats were sacrificed after the end of Morris water maze tests and hippocampal tissues were taken for determination of the expression of RyR2 and cleaved caspase-3 (by Western blot), apoptosis rate and cytoplasmic calcium ion concentrations (by flow cytometry) and for microscopic examination of the pathological changes in hippocampal CA1 area (using HE staining). Results:There was no significant difference in the speed, distance and duration of stay in the center in the open field test among the three groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged after surgery, the number of crossing the original platform was reduced, the expression of RyR2 and cleaved caspase-3 was up-regulated, and the neuronal apoptosis rate and cytoplasmic calcium ion concentration were increased ( P<0.05), and the pathological changes were found in the hippocampal CA1 area in group P. Compared with group P, the escape latency was significantly shortened after surgery, the number of crossing the original platform was increased, the expression of RyR2 and cleaved caspase-3 was down-regulated, and the neuronal apoptosis rate and cytoplasmic calcium ion concentration were decreased ( P<0.05), and the pathological changes were significantly reduced in the hippocampal CA1 area in group D. Conclusions:RyR2 activation is involved in the process of POCD in aged rats, which may be associated with increased calcium overload-induced hippocampal neuronal apoptosis.
Résumé
Purpose To analyze the morphological charac-teristics of papillary thyroid carcinoma(PTC)patients with NTRK gene fusion in order to provide more important morpholog-ic evidences for molecular detection.Methods A retrospective collection of 790 cases PTC was conducted.Then the patients with NTRK gene fusion were selected.The histopathological fea-tures of PTC patients with NTRK gene fusion were compared with those of classical PTC.Results Nine cases(1.1%)of NTRK fusion positive PTC were detected,including 2 cases of NTRK1 and 7 cases of NTRK3 gene fusion.The main his-topathological features were follicular subtypes,with tumors ex-hibiting multinodular infiltration or"jumping"infiltration.The cytoplasm was associated with hyaline change.The cell morphol-ogy was slight irregularity.Conclusion The incidence of NTRK fusion is low in PTC and it tends to occur in the young group.Follicular subtype is the main characteristic histopatholo-gy,with mild tumor cells.But the ability of the invasion and metastasis is strong.Therefore,NGS detection should be per-formed for early intervention and prolonging the survival of PTC patients.
Résumé
Objective:To prepare and preliminary verify dezocine polylactic acid-glycolic acid block copolymer (PLGA) microspheres.Methods:Preparation of dezocine PLGA microspheres Dezocine 120 mg, PLGA 0.1 g and the solubilizing additive poloxamer 0.1 g were dispersed in tetrahydrofuran solvent to form an organic phase solution. Sodium chloride and polyethylene glycol were dissolved in water for injection to form an inner aqueous phase solution and an outer aqueous phase solution. After the organic phase solution 20 ml was mixed with the inner aqueous phase solution 20 ml to form a water/oil colostrum, the water/oil colostrum was added to the outer aqueous phase solution to form a water/oil/water multiple emulsion, which was fully mixed with lyophilized powder protective agent and freeze-dried to prepare dezocine PLGA microspheres. Verification Eighteen clean-grade healthy male Sprague-Dawley rats, aged 10-12 weeks, weighing 220-260 g, were divided into 3 groups ( n=6 each) by a random number table method: control group (group C), dezocine ordinary preparation group (group D 1) and dezocine PLGA microspheres group (group D 2). Normal saline, dezocine injectio (dose 1 mg) and dezocine PLGA microsphere injectio (dose 0.2 μg) 0.2 ml were intramuscularly injected in C, D 1 and D 2 groups, respectively. The concentrations of dezocine in plasma were measured at 30 min and 1, 2, 3, 4, 5, 6, 7 and 8 h after administration, and thermal paw withdrawal latency was measured at T 1-T 3, T 5 and T 9. Tissues from the injection site were obtained on day 7 after intramuscular injection, and the inflammatory response was observed after HE staining. Results:Compared with group C, the thermal paw withdrawal latency was significantly prolonged at T 1-T 3 in group D 1 and at T 1-T 3, T 5 and T 9 in group D 2 ( P<0.05). Compared with group D 1, the thermal paw withdrawal latency was significantly prolonged at T 5 and T 9, and the plasma concentrations of dezocine were increased at T 6-T 9 in group D 2 ( P<0.05). Compared with the values at T 2, the plasma concentrations of dezocine were significantly decreased at T 4-T 9 in group D 1 ( P<0.05), and no significant change was found in the plasma concentrations of dezocine at T 3-T 9 in group D 2 ( P>0.05). On 7 days after injection, no inflammation was found in the local tissues in C, D 1 and D 2 groups, and no significant difference was found among the three groups. Conclusions:The sustained-release formulation of dezocine PLGA microspheres is successfully prepared, and it can maintain stable blood concentrations, effectively prolongs the action time of the drug and has significant sustained-release effect in rats.
Résumé
Renal replacement therapy and perioperative management have difficulties in hemophilia patients with end-stage renal disease. The paper summarized the diagnosis and treatment experience of six hemophilia patients complicated with end-stage renal disease from January 1, 2000 to March 31, 2023 in Peking Union Medical College Hospital. Among 6 patients treated with peritoneal dialysis, 3 were treated with hemodialysis or continuous venous-venous hemodialysis. Altogether 11 dialysis access procedures were conducted successfully, and no serious bleeding or thrombotic events. In further conjunction with literature review, the paper summarized the key points of dialysis access appliance relevant to such patients, to provide reference for renal replacement treatment paths.
Résumé
Objective:To evaluate the relationship between Karyopherin β2 (Kapβ2)-mediated nuclear translocation of nuclear inhomogeneous ribonucleoprotein A2/B1 (hnRNPA2/B1) and sevoflurane-induced brain neurotoxicity in a cellular experiment.Methods:The mouse hippocampal neuronal cell line HT22 cells were inoculated in confocal culture dishes and 6-well culture plates at a density of 2×10 5 cells/well and 1×10 6 cells/well and divided into 4 groups( n=12 each) by a random number table method: control group (GFP-C group) carrying green fluorescent protein (GFP) with empty adenovirus transfection, sevoflurane group (GFP-Sev group) carrying GFP with empty adenovirus transfection, control group (GFP-Sev group) transfected with Kapβ2 gene-overexpressing adenovirus, and sevoflurane group (Kapβ2-Sev group) transfected with Kapβ2 gene-overexpressing adenovirus. After 48 h of conventional incubation, empty adenovirus-carrying GFP (GFP-C and GFP-Sev groups) and Kapβ2 gene-overexpressing adenovirus (Kapβ2-C and Kapβ2-Sev groups) were transfected. After 48 h of transfection, the cells were conventionally incubated continuously in GFP-C and Kapβ2-C groups, and the cells were incubated for 3 h with 3% sevoflurane and then were conventionally incubated for 48 h in GFP-Sev and Kapβ2-Sev groups. The expression of Kapβ2, synaptophysin (SYP), postsynaptic density protein 95 (PSD95) and hnRNPA2/B1 nucleoplasmic ratio were measured in cells by Western blot. Immunofluorescence assay was used for hnRNPA2/B1 subcellular localization. Results:Compared with GFP-C group, the expression of SYP and PSD95 was significantly down-regulated, hnRNPA2/B1 nucleoplasmic ratio was decreased, and cytoplasmic hnRNPA2/B1 expression was up-regulated in GFP-Sev group, and Kapβ2 expression was significantly up-regulated in Kapβ2-C group ( P<0.05). Compared with Kapβ2-C group, the expression of SYP and PSD95 was significantly down-regulated, hnRNPA2/B1 nucleoplasmic ratio was decreased, and cytoplasmic hnRNPA2/B1 expression was up-regulated in Kapβ2-Sev group ( P<0.05). Compared with GFP-Sev group, the expression of Kapβ2, SYP and PSD95 was significantly up-regulated, hnRNPA2/B1 nucleoplasmic ratio was increased, and cytoplasmic hnRNPA2/B1 expression was down-regulated in Kapβ2-Sev group ( P<0.05). Conclusions:Kapβ2-mediated hnRNPA2/B1 nuclear translocation may be the endogenous protective mechanism against sevoflurane-induced brain neurotoxicity.
Résumé
Objective:To identify the risk factors for postoperative cognitive dysfunction (POCD) and develop the prediction model in elderly patients undergoing lumbar surgery under general anesthesia.Methods:The elderly patients undergoing elective lumbar surgery under general anesthesia in our hospital from July 2021 to July 2022 were enrolled. Cognitive function was assessed at 7 days after surgery using Mini-Mental State Examination and Montreal Cognitive Assessment. When the decrease in both scales≥ 1 standard deviation, the patients were considered as having POCD. The patients were divided into POCD group and non-POCD group according to whether POCD developed. The propensity score matching was used to balance the confounding bias between two groups. The multivariate logistic regression analysis was used to identify the risk factors for POCD. The prediction model was constructed, and a nomogram was drawn for visualization of the model. The receiver operating characteristic curve, calibration plot and decision curve analysis (DCA) were drawn to evaluate the differentiation, consistency and clinical validity of the model, respectively.Results:A total of 159 patients were enrolled in this study, and the incidence of POCD was 31.4%. There were statistically significant differences in the ratio of intraoperative blood transfusion, cumulative time of hypotension, total infusion volume and operation time between two groups ( n=32 each) after propensity score matching ( P<0.05). The results of multivariate logistic regression showed that age, educational levels, diabetes mellitus, previous two or more operations under general anesthesia, APTT and cumulative time of hypotension were independent risk factors for POCD in elderly patients undergoing lumbar surgery under general anesthesia ( P<0.05). A model was developed based on the risk factors mentioned above: LogitP=-15.878+ 0.263 × Age (years) - 0.122 × Educational Level (years)+ 1.601 × Diabetes Mellitus+ 1.468 × History of General Anesthesia for 2 or more times+ 0.608 × Cumulative Time of Hypotension(min) - 0.140 × APTT (s). The area under the receiver operating characteristic curve was 0.930 (95% CI 0.887-0.973), the sensitivity was 0.920, specificity was 0.798 and Youden index was 0.718. After visualizing the model via nomogram, the model was verified by Hosmer-Lemeshow test, P=0.403, C index was 0.930, and corrected C index was 0.914. Conclusions:Age, educational levels, diabetes mellitus, previous multiple operations under general anesthesia, APTT and cumulative time of hypotension are independent risk factors for POCD in elderly patients undergoing lumbar surgery under general anesthesia, and the established risk prediction model can effectively predict the occurrence of POCD in elderly patients undergoing lumbar surgery under general anesthesia.
Résumé
Objective:To evaluate the role of Homer1a/metabotropic glutamate receptor 5 (mGluR5) signaling pathway in sleep deprivation-induced cognitive dysfunction in aged rats.Methods:One hundred and four SPF healthy male Sprague-Dawley rats, aged 22-24 months, weighing 320-360 g, were divided into 4 groups ( n=26 each) using a random number table method: normal control group (group Control), sleep deprivation+ vehicle group (group SD+ Vehicle), sleep deprivation+ mGluR5 forward allosteric agent CDPPB group (group SD+ CDPPB), and sleep deprivation+ mGluR5 antagonist MPEP group (group SD+ MPEP). A 48-h sleep deprivation model was developed by sleep-deprived rod method. At the beginning of developing the model and 24 h after developing the model, CDPPB 10 mg/kg, MPEP 10 mg/kg and the equal volume of 1% Tween 80 were intraperitoneally injected in group SD+ CDPPB, group SD+ MPEP and group SD+ Vehicle, respectively.Morris water maze and novel object recognition tests were conducted to evaluate cognitive function after development of the model. The expression of Homer1a and mGluR5 in the hippocampus was detected by Western blot, the dendritic spine density in the hippocampal CA1 region was detected by Golgi staining, and the field excitatory postsynaptic potential (fEPSP) slope in the hippocampal CA1 region was detected by isolated electrophysiology. Results:Compared with Control group, the number of crossing the original platform, time of staying at the target quadrant, and novel object recognition index at 1 and 24 h after training were significantly decreased, the expression of Homer1a in the hippocampus was up-regulated, the expression of mGluR5 in the hippocampus was down-regulated, and the density of dendritic spine and fEPSP slope in the hippocampal CA1 region were decreased in group SD+ Vehicle ( P<0.05). Compared with group SD+ Vehicle, the number of crossing the original platform, time of staying at target quadrant, and novel object recognition index at 1 and 24 h after training were significantly increased, the expression of mGluR5 in hippocampus was up-regulated, and the density of dendritic spines and fEPSP slope in the hippocampal CA1 region were increased in group SD+ MPEP( P<0.05), and no statistically significant change was found in the parameters mentioned above in group SD+ CDPPB ( P>0.05). Conclusions:Sleep deprivation impairs the synaptic plasticity of hippocampal neurons by regulating Homer1a/mGluR5 signaling pathway, and thus mediating the process of cognitive dysfunction in aged rats.
Résumé
This paper summarized the clinical experience of XU Fengqin in the treatment of hypertension in the elderly. It is believed that the basic pathogenesis of hypertension in the elderly is liver and kidney depletion， and the key is ascendant hyperactivity of liver yang and spleen failing to transport. Therefore， the theory of “combination of disease and symptoms” is put forward that the four common clinical symptoms of hypertension in the elderly， including morning hypertension， non-dipper hypertension with abnormal circadian rhythm， postprandial hypotension and orthostatic hypotension， should be differentiated and treated with prescription in accordance with the characteristics of the corresponding pathogenesis. Specifically， the pathogenesis of morning hypertension is mainly liver-kidney yin deficiency and ascendant hyperactivity of liver yang， for which the treatment method of enriching liver and boosting kidney， calming the liver and subduing yang is suggested， and Qingxuan Jiangya Decoction （清眩降压汤） in modifications can be used. For non-dipper hypertension with abnormal circadian rhythm， the pathogenesis is mainly phlegm-dampness obstruction and clear yang failing to ascend， and treatment method should be dissolving phlegm and dispelling dampness， calming the liver and extinguishing wind， with Banxia Baizhu Tianma Decoction and Modified Honglong Xiahai Decoction （半夏白术天麻汤合加味红龙夏海汤） in its modifications. Regarding postprandial hypotension and orthostatic hypotension， the pathogenesis is mainly spleen-stomach depletion and clear yang failing to ascend， and thus the method of supplementing the center and boosting qi， raising yang and lifting the sunken is advised with Buzhong Yiqi Decoction （补中益气汤） or Yiqi Congming Decoction （益气聪明汤） in the modifications.
Résumé
Objective:To explore the effects of acute sleep fragmentation (SF) on cognitive function and the relationship between hippocampal Homer1a and synaptic plasticity in aged rats.Methods:One hundred and eight SPF grade male SD rats aged 22 to 24 months were divided into three groups according to random number table: control group (Control group), non-sleep fragmentation group (NSF group) and sleep fragmentation group (SF group), with 36 rats in each group.A sleep fragmentation model was established by sleep deprivation rod method.Morris water maze and novel object recognition tests were used to evaluate the learning and memory function of rats.Homer1a expression in hippocampus was detected by Western blot, and its distribution in CA1 area of hippocampus was observed by immunohistochemical staining.Golgi staining was used to observe the density of dendritic spines in CA1 area of hippocampus, and in vitro electrophysiological patch clamp test was used to detect the slope of field excitatory postsynaptic potential(fEPSP) from CA3 to CA1 in hippocampus.SPSS 22.0 and GraphPad Prism 9.3 softwares were used for data statistical analysis and mapping.One-way ANOVA was used for comparison among groups, and Tukey-Kramer test was used for further pairwise comparison. Results:(1)In the behavioral tests, there were statistical differences in the times of crossing the original platform, the target quadrant residence time and the new object recognition index at 1 h and 24 h among the three groups( F=13.63, 11.34, 21.26, 16.22, all P<0.01). The times of crossing the original platform in SF group((2.00±1.27) times) was lower than that of Control group ((5.67±2.16) times) and NSF group ((6.50±2.35) times) (both P<0.05). The target quadrant residence time in SF group ((9.02±4.84) s) was shorter than that in Control group ((24.73±7.37) s) and NSF group ((27.81±8.37)s) (both P<0.05). The new object recognition index at 1 h and 24 h in SF group were lower than those in Control group and NSF group (all P<0.05). (2) In Western blot assay, the expression of Homer1a protein in hippocampus of SF group(0.91±0.13) was higher than that of Control group(0.70±0.05) and NSF group(0.74±0.04)(both P<0.05). (3) In immunohistochemical staining, the optical density value of the Homer1a protein in CA1 area of hippocampus in the SF group was higher than that in the Control group and NSF group(both P<0.05). (4) In Golgi staining, the density of dendritic spines in CA1 area of hippocampus in SF group was lower than that in Control group and NSF group (both P<0.05). (5) In vitro electrophysiological test showed that the slope of fEPSP in CA3-CA1 area of hippocampus in SF group were lower than that in Control group and NSF group (both P<0.05). Conclusion:Acute SF intervention in aged rats can cause cognitive impairment, which may be associated with the inhibition of hippocampal synaptic plasticity induced by hippocampal Homer1a overexpression.
Résumé
ObjectiveTo explore the effect of transcranial direct current stimulation (tDCS) combined with acupuncture on central and upper limb function in stroke patients at flaccid stage based on central-peripheral-central theory. MethodsFrom September, 2018 to December, 2021, 120 patients with upper limb dysfunction after stroke in Guangdong Work Injury Rehabilitation Hospital were selected and randomly divided into control group 1 (n = 40), control group 2 (n = 40) and experimental group (n = 40). All the groups received conventional rehabilitation treatment. In addition, the control group 1 received acupuncture treatment, the control group 2 received anodal tDCS, and the experimental group received combined treatment of both, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI) before and after treatment. Electroencephalograph (EEG) was used to detect brain symmetry index (BSI), and electromyography (EMG) was used to detect root mean square values (RMS) of triceps brachii, biceps brachii, extensor wrist and flexor wrist of the affected upper limbs. ResultsTwo cases in the control group 1, one in the control group 2 and one in the experimental group dropped off, respectively. After treatment, the scores of FMA-UE and MBI significantly increased in all the groups (t > 11.757, P < 0.001), and they were higer in the experimental group than in the control groups (P < 0.001); the BSI decreased in the control group 2 and the experimental group (t > 2.324, P < 0.05), and it was less in the experimental group than in the control group 2 (P < 0.05); the RMS of biceps increased in all the groups (t > 2.953, P < 0.01), and was higer in the experimental group than in the control groups (P < 0.05); the RMS of flexor wrist and triceps increased in the control group 1 and the experimental group (t > 2.230, P < 0.05), and were higher in the experimental group than in the control group 1 (P < 0.05); the RMS of wrist extensor muscle increased only in the experimental group (t = 3.350, P < 0.01). ConclusiontDCS combined with acupuncture based on central-peripheral-central theory could effectively improve the upper limb function of stroke patients at flaccid stage, with advantages in improving hemispheric asymmetry and enhancing the activation level of affected muscles.
Résumé
Objective:To evaluate the effect of propofol on the sensitivity of glioma cells to temozolomide and the role of long noncoding RNAs (lncRNAs)-growth arrest-specific transcript 5 (GAS5) in it.Methods:Human glioma cell line U251 were cultured in vitro and seeded in 6-, 24- or 96-well plates at a density of 1×10 5 cells/ml, and were divided into 5 groups ( n=30 each) using a random number table method: control group (group C), temozolomide group (group T), propofol + temozolomide group (group PT), negative-siRNA + propofol + temozolomide group (group NPT) and GAS5-siRNA + propofol + temozolomide group (group GPT). The U251 cells in group C were cultured in the common culture medium.In group T, temozolomide 400 μmol/L was added to the culture medium.In group PT, the cells were cultured with propofol 8 μg/ml first and then with temozolomide 400 μmol/L.In group NPT and group GPT, U251 cells were transfected with negative-siRNA and GAS5-siRNA, respectively, and then cultured in the same way as previously described in group PT.The expression of lncRNA-GAS5 in U251 cells was detected by quantitative real-time polymerase chain reaction, the cell survival rate was measured by CCK-8 assay, the apoptosis rate was determined by flow cytometry, cell invasion was determined by Transwell invasion assay, and the expression of c-Myc, glutathione S-transferase mu 3 (GSTM3) and P21 was detected by Western blot. Results:Compared with group C, the cell survival rate was significantly decreased, the apoptosis rate was increased, the number of invasive cells was decreased, the expression of c-Myc and GSTM3 was down-regulated, and the expression of P21 and lncRNA-GAS5 was up-regulated in the other four groups ( P<0.05). Compared with group T, the cell survival rate was significantly decreased, the apoptosis rate was increased, the number of invasive cells was decreased, the expression of c-Myc and GSTM3 was down-regulated, and the expression of P21 and lncRNA-GAS5 was up-regulated in group PT and group NPT ( P<0.05). Compared with group PT, the cell survival rate was significantly increased, the apoptosis rate was decreased, the number of invasive cells was increased, the expression of c-Myc and GSTM3 was up-regulated, and the expression of P21 and lncRNA-GAS5 was down-regulated in group GPT ( P<0.05), and no significant change was found in the parameters mentioned above in group NPT ( P>0.05). Conclusions:Propofol can enhance the sensitivity of glioma cells to temozolomide, and the expression of lncRNA-GAS5 is involved in the process.
Résumé
Heterogeneous nuclear rib nucleoproteins belong to a class of RNA-binding proteins and possess highly conserved structures. Among them, the heterogeneous nuclear rib nucleoprotein A2/B1 (heterogeneous nuclear rib nucleoprotein A2, hnRNPA2/B1) is involved in many processes such as transcription and translation. In recent years, in the field of neurodegenerative diseases, it has been found that hnRNPA2/B1 promotes the accumulation of fibrin in the cytoplasm and participates in the formation of stress granules in neurons, which involves a variety of processes related to cognitive function, and is closely related to neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer′s disease and so on. This article reviews the related research, summarizes the important role and mechanism of hnRNPA2/B1 in neurodegenerative diseases, and provides help for the diagnosis and treatment of neurodegenerative diseases in the future.
Résumé
Objective:To calculate the conversion coefficient from dose area product (DAP) to organ absorbed dose by Monte Carlo method in order to conveniently estimate doses to patient organ during coronary intervention procedure.Methods:The Geant4 Monte Carlo simulation kit was used to calculate the organ absorbed dose conversion coefficients by simulating exposure scene.Results:The conversion coefficients used in coronary angiography (CAG) for lung, bone marrow, liver and heart were (0.283±0.068), (0.169±0.049), (0.110±0.077) and (0.080±0.032) mGy/(Gy·cm 2) for male, and (0.376±0.121), (0.192±0.056), (0.153±0.105), and (0.102±0.033) mGy/(Gy·cm 2) for female, respectively. These were similar to those in the case of percutaneous coronary intervention (PCI). The DAPs for different interventional procedures were statistically significant ( t=-6.012, P<0.05). The DAPs for difference gender groups had no statistically significant ( P>0.05). Conclusions:Conversion coefficient for organ absorbed dose has little correlation with CAG and PCI in the same sex group. Dose conversion coefficients for female group are greater than those for male group in the same procedure. Conversion coefficients from DAP to organ absorbed dose calculated with Monte Carlo method can provide convenience for rapidly estimating the organ absorbed dose to clinical patients.
Résumé
A set of new operational quantities for external radiation protection was proposed in ICRU Report 95. The new operational quantities were designed to overcome the conceptual and technical shortcomings of the existing operational quantities, and to achieve a better estimation of the protection quantities. This paper introduces the development of operational quantities, and the changes in their definitions, calculation phantoms and the application scopes, so as to fully understand the significance of the changes in the new operational quantities, which can be used as a reference for the relevant professionals.
Résumé
Objective:To investigate the relationship between autophagy and nuclear factor E2 related factor 2(Nrf2) signaling pathway during high glucose-induced damage to Schwann cells.Methods:RSC96 were cells cultured in vitro and seeded in 96-well plates (1×10 4 cells/ml, 200 μl/well) or in 6-well plates (1×10 6 cells/ml, 2 ml/well) for 48 h. The cells were divided into 3 groups ( n=25 each) using a random number table method: control group (group C), high glucose group (group H) and high glucose+ autophagy agonist rapamycin group ( group H+ RAP). The cells were cultured in the common culture medium in group C. In group H, 50 mmol/L of glucose was added to the culture medium.In group H+ RAP, 50 mmol/L of glucose and 5 μmol/L rapamycin were added to the culture medium.At 48 h of incubation, the growth of cells was observed with inverted phase contrast microscope, the cell viability was measured using MTT method, apoptosis rate was determined by flow cytometry, malondialdehyde (MDA) content was determined by thiobarbituric acid method, superoxide dismutase (SOD) activity was detected using xanthine oxidase method, and the expression of Nrf2, P62 and microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) was determined by Western blot. Results:Compared with group C, the cell viability and SOD activity were significantly decreased, apoptotic rate and MDA content were increased, and expression of Nrf2, P62 and LC3Ⅱ was up-regulated in group H and group H+ RAP ( P<0.05). Compared with group H, the cell viability and SOD activity were significantly increased, apoptosis rate and MDA content were decreased, the expression of Nrf2 and LCII was up-regulated and P62 expression was down-regulated in group H+ RAP ( P<0.05). Conclusion:Enhanced autophagy can activate Nrf2 signaling pathway, which is the endogenous protective mechanism of Schwann cell injury induced by high glucose.
Résumé
Cholangiocarcinoma is a malignant tumor originating from the bile duct epithelium, with the increasing incidence year by year. Its early symptoms are atypical and the diagnosis rate is low. Most of the patients are already in advanced stage when they are diagnosed, losing the best surgery period. Currently, the conservative treatments for unresectable extrahepatic cholangiocarcinoma include stent placement, radiofrequency ablation, radiotherapy and chemotherapy, targeted and immunotherapy and other systemic treatments. But due to the high malignancy of biliary tract tumors, the tendency to develop drug resistance and the limited population benefited from the emerging treatment modalities, we urgently need to explore new treatment strategies to break this bottleneck. As a new treatment for cholangiocarcinoma, photodynamic therapy has attracted much attention for its clinical application and therapeutic effects. In this paper, we summarize the principles of photodynamic therapy, the combination of photodynamic and other therapeutic modalities, especially the combination of photodynamic with emerging immune and targeted therapies, and describe the current hotspot directions of photodynamic therapy research at home and abroad to provide reference for clinical treatment and research.
Résumé
As the populations are aging, concerns about cognitive decline are becoming a common topic in medical consultations. The occurrence of postoperative cognitive change involves many factors such as their own situation and perioperative period. Alzheimer′s disease (AD) is the main concern about postoperative cognitive change. For years it was widely believed that cognitive dysfunction caused by anesthesia, some studies suggest that anesthetics may cause mitochondrial damage, while most studies suggest that mitochondrial dysfunction may affect AD. But it is rarely noticed, that cells can maintain the stability following mitochondrial stress by a series of integrated stress responses (ISR) and alleviate mitochondrial stress in progeny. We reviewed the research progress of mitochondrial stress in AD.
Résumé
Objective:To be aware of the needs of the young students for nuclear and radiation science popularization, and to provide scientific basis for accurate science popularization.Methods:A simple random sampling method was used to select 1 primary school, 5 middle schools and 2 universities in the Beijing-Tianjin-Hebei region in December 2020. Questionnaires were distributed through teachers. In addition, convenience sampling method was used to distribute questionnaires in friend circle and other areas to expand the survey scope, with a total of 1 345 respondents. SPSS was used to conduct statistical analysis on the basic information of the respondents, the understanding and concern of nuclear and radiation science popularization and the demand for nuclear and radiation science popularization.Results:A total of 1 120 valid questionnaires were collected, of which 52.4% mainly remained at the conceptual level for the cognition of radiation, 52.2% occasionally paid attention to nuclear and radiation science popularization, 65.3% and 41.3% paid attention to life reference and hobbies, respectively. Radiation protection and its sources and effects received high concern, accounting for 72.6% and 68.3% respectively. Illustration and short video were popular science forms of young students, making up 45.7% and 44.3%, respectively. The students of different genders differed in radiation cognition, degree of concern, purpose of concern and content demand for radiation protection science popularization, and the differences are statistically significant( χ2=10.017, 26.859, 56.237, 17.305, P<0.05). Conclusions:Nuclear and radiation science popularization should consistent with the law of public demand, accurately locate the demand characteristics of young students, and consider the characteristics of different genders, concerns over radiation protection, treatment and damage knowledge from the point of life and fun, so as to improve the public′s attention, enhance the national nuclear science culture, and create a good nuclear safety culture atmosphere.
Résumé
Objective:To investigate the relationship between the mechanism of exogenous hydrogen sulfide (H 2S)-induced reduction of apoptosis in neurons during focal cerebral ischemia-reperfusion (I/R) and PINK1/Parkin pathway-mediated mitochondrial autophagy in rats. Methods:Two hundred and sixteen healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 250-270 g, were divided into 4 groups ( n=54 each) using a random number table method: control group (group C), I/R group, H 2S group and H 2S plus 3-methyladenine (3-MA) group (H 2S+ 3-MA group). Focal cerebral ischemia was induced by middle cerebral artery occlusion in anesthetized rats.In group H 2S+ 3-MA, 3-MA 10 mg/kg was intraperitoneally injected at 15 min before the onset of reperfusion, while the equal volume of normal saline was given instead in the other groups.In H 2S and H 2S+ 3-MA groups, 0.25% NaSH (a donor of exogenous H 2S) 10 mg/kg was intraperitoneally injected at the onset of reperfusion, while the equal volume of normal saline was given instead in the other groups.At 1, 3 and 7 days of reperfusion, neural function was scored, and corner test (the percentage of left turn was calculated) was performed.Brains were removed and brain tissues were obtained for determination of the cerebral infarct size, Bax, Bcl-2 and caspase-3 positive cells, cell apoptosis, and expression of mitophagy-related protein microtubule-associated protein 1 light chain 3 (LC3), PINK1 and Parkin (by Western blot). The percentage of cerebral infarct size, rate of Bax, Bcl-2 and caspase-3 positive cells and apoptosis rate were calculated.The ratio of LC3-Ⅱexpression to LC3-Ⅰexpression (LC3-Ⅱ/LC3-Ⅰ) was also calculated. Results:Compared with group C, the neural function score was significantly decreased, the percentage of left turn, percentage of cerebral infarct size, rate of Bax, Bcl-2 and caspase-3 positive cells, apoptosis rate of neurons, and LC3-Ⅱ/LC3-Ⅰ were increased, and the expression of PINK1 and Parkin was up-regulated at each time point of reperfusion in group I/R ( P<0.05). Compared with group I/R, the neural function score and rate of Bcl-2 positive cells were significantly increased, the percentage of left turn, percentage of cerebral infarct size, rate of Bax and caspase-3 positive cells, and apoptosis rate of neurons were decreased, the expression of PINK1 and Parkin was up-regulated, and LC3-Ⅱ/LC3-Ⅰ were increased at each time point of reperfusion in group H 2S ( P<0.05), and no significant change was found in the parameters mentioned above in group H 2S+ 3-MA ( P>0.05). Compared with group H 2S, the neural function score and rate of Bcl-2 positive cells were significantly decreased, the percentage of left turn, percentage of cerebral infarct size, rate of Bax and caspase-3 positive cells, and apoptosis rate of neurons were increased, the expression of PINK1 and Parkin was down-regulated, and LC3-Ⅱ/LC3-Ⅰ was decreased at each time point of reperfusion in H 2S+ 3-MA group ( P<0.05). Conclusion:The mechanism by which exogenous H 2S inhibits apoptosis in neurons during focal cerebral I/R is related to enhancing mitochondrial autophagy mediated by the PINK1/Parkin pathway in rats.
Résumé
Objective:To evaluate the relationship between dexmedetomidine-induced reduction of sevoflurane-induced neurotoxicity and cation-chloride cotransporters Na + -K + -2Cl --1 (NKCC1) /K + -2Cl --2 (KCC2) in neonatal rats. Methods:Eighty healthy male Sprague-Dawley rats at postnatal day 7 were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S), dexmedetomidine group (group D), and sevoflurane and dexmedetomidine group (group SD). Rats were exposed to 2.5% sevoflurane for 6 h to establish the model of sevoflurane anesthesia in group S. Dexmedetomidine 1.0 μg/kg was intraperitoneally injected, and then sevoflurane anesthesia was performed in group SD.The expression of cleaved caspase-3, NKCC1 and KCC2 was detected by Western blot at 24 h after the end of anesthesia.At 35 days after the end of anesthesia, the cognitive function was assessed using the Y maze test, and the neurons in the hippocampal CA1 area were counted using the Nissan staining method. Results:Compared with group C, the percentage of time spent in novel arm and the number of neurons in hippocampal CA1 area were significantly decreased, the expression of cleaved caspase-3 and NKCC1 was up-regulated, the expression of KCC2 was down-regulated, and the ratio of NKCC1/KCC2 was increased in S and SD groups ( P<0.05), and no change was found in the above indicators in group D ( P>0.05). Compared with group S, the percentage of time spent in novel arm and the number of neurons in hippocampal CA1 area were significantly increased, the expression of cleaved caspase-3 and NKCC1 was down-regulated, the expression of KCC2 was up-regulated, and the ratio of NKCC1/KCC2 was decreased in group SD ( P<0.05). Conclusion:The mechanism of dexmedetomidine attenuating sevoflurane-induced neurotoxicity may be related to maintaining the relatively stable expression of NKCC1/KCC2 in neonatal rats.