الملخص
Objective:To evaluate the effect of electroacupuncture on the heme oxygenase-1 (HO-1)/PTEN-induced putative kinase 1 (PINK1)/Parkin signaling pathway during acute kidney injury in endotoxemic rats.Methods:Twenty-four SPF healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 180-220 g, were divided into 4 groups ( n=6 each) by a random number table method: control group(group C), endotoxemia group(group E), acupoint electroacupuncture+ endotoxemia group(group EE), and non-acupoint electroacupuncture+ endotoxemia group(group NE). The endotoxemia model was developed by intraperitoneal injection of lipopolysaccharide 10 mg/kg. The equal volume of normal salinewas injected in group C. LPS 10 mg/kg was intraperitoneally injected in group E. In group EE, 30-min electroacupuncture was performed at bilateral Zusanli and Shenshu acupoints using disperse-dense waves with a frequency of 2/15 Hz to induce slight muscle tremor once a day starting from 5 days before developing the model, and the needle was retained until 6 h after injection. Electroacupuncture was performed at the points 0.5 cm lateral to the acupoints of Zusanli and Shenshu in group NE. The rats were anesthetized at 6 h after lipopolysaccharide injection, and blood samples from the femoral vein were obtained for determination of the serum creatinine (Cr) and urea nitrogen (BUN) concentrations(with a biochemical analyzer) and concentrations of neutrophil gelatinase-associated lipid transport protein (NGAL), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and kidney injury molecule-1(KIM-1) in serum (by enzyme-linked immunosorbent assay). Then the rats were sacrificed and kidney tissues were taken for determination of histological score of kidneys (HSK, using HE staining) and expression of HO-1, PINK1, Parkin, mitochondrial fusion protein 2(Mfn2), optic atrophy protein 1(OPA1) and mitochondrial dynamic-related protein 1 (Drp1) (by Western blot). Results:Compared with group C, serum concentrations of Cr, BUN, KIM-1, NGAL, IL-6 and TNF-α and HSK score of renal tissues were significantly increased, the expression of HO-1, PINK1, Parkin and Drp1 was up-regulated, and the expression of Mfn2 and OPA1 was down-regulated in E, EE and NE groups ( P<0.05). Compared with group E, serum concentrations of Cr, BUN, KIM-1, NGAL, IL-6 and TNF-α and HSK score of renal tissues were significantly decreased, and the expression of HO-1, PINK1, Parkin, Mfn2 and OPA1 was up-regulated, and Drp1 expression was down-regulated in group EE( P<0.05), and no significant change was found in the parameters mentioned above in group NE ( P>0.05). Conclusions:The mechanism by which electroacupuncture alleviates acute kidney injury is associated with activation of HO-1/PINK1/Parkin signaling pathway in endotoxemic rats.
الملخص
Objective:To evaluate the effect of ozone preconditioning on splenic natural killer (NK) cells in septic mice.Methods:Twenty-four SPF-grade male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) according to the random number table method: control group (group C), lipopolysaccharide (LPS)group, ozone+ LPS group (O 3+ LPS) and air+ LPS group (Air+ LPS). The sepsis was induced by intraperitoneal injection of LPS 10 mg/kg. Ozone preconditioning was started at 5 days before developing the model: ozone 1 mg/kg was intraperitoneally injected once a day for 5 consecutive days, the equal volume of air was injected in Air+ LPS group. The survival was observed within 72 h after LPS injection, and sepsis score and ear temperature (once every 2 h, an average was calculated) were recorded. The posterior orbital venous blood samples were taken at 6 and 24 h after LPS injection for determination of serum interferon-γ (IFN-γ) and interleukin-10 (IL-10) concentrations using enzyme-linked immunosorbent assay. The spleen was then taken, and a single cell suspension of the spleen was prepared for measurement of the percentage of NK cells in the spleen by flow cytometry. Results:Compared with C group, the ear temperature, sepsis score and 72-h survival rate were significantly decreased, serum IFN-γ and IL-10 concentrations were increased at each time point after LPS injection, and the percentage of splenic NK cells was increased at 6 h after LPS injection and decreased at 24 h after LPS injection in LPS, Air+ LPS and O 3+ LPS groups ( P<0.05). Compared with LPS group, the ear temperature, sepsis score and 72-h survival rate were significantly increased, serum IFN-γ concentrations were decreased at each time point after LPS injection, serum IL-10 concentrations were increased at each time point after LPS injection, and the percentage of splenic NK cells was decreased at 6 h after LPS injection and increased at 24 h after LPS injection in O 3+ LPS group ( P<0.05), and no significant change was found in the parameters mentioned above in Air+ LPS group ( P>0.05). Conclusions:The mechanism by which ozone preconditioning reduces sepsis may be related to reduction of inflammatory responses and regulation of splenic NK cell levels in septic mice.
الملخص
Objective:To investigate the safety and efficacy of remimazolam combined with afentanyl for fiberoptic bronchoscopy.Methods:Sixty patients admitted to Chifeng Hospital for fiberbronchoscopy from January to April 2022 were selected and divided into two groups by random number table method: remimazolam group (group R) and propofol group (group P), 30cases in each group. After intravenous injection of alfentanil for anesthesia induction, group R was sedated by intravenous injection of remidazolam besylate, and group P was sedated by intravenous injection of propofol emulsion. When sufficient sedation was achieved, fiberoptic bronchoscopy was performed. The patients were scored with the Mini-Mental State Examination (MMSE) before examination and before leaving the room. The recovery rate of sedation and the recovery rate of drugs during operation were compared. Blood pressure, heart rate (HR), bispectral index (BIS), SpO 2 value and Modified Observer′s Assessment of Alertness/Sedation (MOAA/S) score were compared before induction (T 0), at the beginning of examination (T 1), immediately when fiber bronchoscope reached juga (T 2), at the end of surgery (T 3), immediately, when patients regained consciousness (T 4). Drug onset and recovery time (time out of hospital) as well as the incidence of intraoperative and postoperative adverse reactions were recorded in both groups. Results:There was no statistically significant difference in general condition, MMSE score and examination time between the two groups (all P>0.05). There was no statistically significant difference between the two groups in the success rate of sedation and the number of sedative remedy times (all P>0.05). The number of additional drugs in group R was significantly higher than that in group P ( P<0.05). The systolic blood pressure, diastolic blood pressure and BIS values of patients in group P at T 1 and T 2 were significantly lower than those in group R (all P<0.05). After administration, the MOAA/S score of the two groups began to decrease, and the decrease of the P group was significantly greater than that of the R group, and the MOAA/S value of the patients was the lowest at the 3rd and 4th minutes after administration, respectively. The time from the beginning of administration to the MOAA/S score ≤3 in group P was significantly shorter than that in group R (all P<0.05). The incidence of pain and respiratory depression after injection in group P was significantly higher than that in group R ( P<0.05). Conclusions:The application of afentanil combined with remimazolam in the patients undergoing fiberoptic bronchoscopy has good sedative effect and high anesthesia quality, and has no obvious effect on cognitive function and few adverse reactions, so it is safe and effective.
الملخص
Objective:To investigate whether idebenone can improve behavioral disorders in mice with Parkinson disease (PD) by increasing PHB2 mediated mitophagy.Methods:In the first small experiment, thirty mice were randomly divided into normal control group, model group and treatment group according to the random number table method, with 10 animals in each group.The aim of this study was to observe the effect of idebenone on the behavior of Parkinson disease model mice. In the second experiment, 20 mice were randomly divided into blank control group, MPTP group, shRNA-PHB2 group and shRNA-PHB2+ MPTP group, with 5 mice in each group. The changes of tyrosine dehydrogenase (TH) in brain tissue were detected by immunofluorescence assay. In the third experiment, 30 mice were randomly divided into blank control group, shRNA-PHB2 group, MPTP+ idebenone group, shRNA-PHB2+ MPTP group, shRNA-PHB2+ idebenone group and shRNA-PHB2+ MPTP+ idebenone group, with 5 animals in each group. The aim of this study was to investigate the effect of idebenone on mitochondrial autophagy in mouse brain.C57BL-6 mice were intraperitoneally injected with MPTP to establish the animal model of chronic PD. Then 200 mg / kg idebenone was given by gavage for 21 days. And the expression of PHB2 in brain was inhibited by microinjection of adeno-associated virus 9 (AAV9) shRNA inhibin 2(PHB2) into lateral ventricle. The behavioral changes of the PD mice were detected by Morris water maze, and the changes of tyrosine dehydrogenase (TH) induced by inhibiting PHB2 were detected by immunohistochemistry. The protein expression of LC3 and PHB2 in substantia nigra of midbrain was detected by Western blot.The data were analyzed by GraphPad 7.0 and SPSS 22.0.Results:(1) In the water maze test data of the first small experiment, the repeated measurement ANOVA showed that the group-time interaction effects of latency of mice from 1 to 7 days were significant ( Ftime×group=20.51, P<0.05). Simple effect analysis showed that on the 5th, 6th and 7th day, the incubation period of the treatment group was significantly shortened (all P<0.05). Univariate analysis of variance showed that on the 7th day of the test, the differences between the control group and the model group, the model group and the treatment group, the control group and the treatment group were all statistically significant( t=-49.95, -21.81, 28.14; all P<0.01). In the third small experiment, repeated measurement analysis of variance showed that the interaction between time and group was significant ( Ftime×group=42.11, P<0.01). Simple effect analysis showed that compared with MPTP+ idebenone group, the latency of shRNA-PHB2+ MPTP+ idebenone group was significantly prolonged (all P<0.05). There were no significant difference between shRNA-PHB2+ MPTP+ idebenone group and shRNA-PHB2+ MPTP group except the 4th day ( P<0.05). On the 7th day, compared with MPTP+ idebenone group, the residence time of shRNA-PHB2+ MPTP+ idebenone group was significantly increased ( t=-34.36, P<0.001), but there was no significant difference between shRNA-PHB2+ MPTP group and shRNA-PHB2+ MPTP+ idebenone group ( t=2.94, P>0.05). (2)The results of immunofluorescence experiment showed that the relative expression of TH in the control group, model group, shRNA-PHB2 group and shRNA-PHB2+ MPTP group were (41.03±3.01), (24.20±4.18), (38.39±3.31) and (13.12±2.65), respectively. Compared with the control group, the expression of TH in the midbrain of the MPTP group was significantly down-regulated, the difference was statistically significant( t=7.98, P<0.01). Compared with the MPTP group, the expression of TH in shRNA-PHB2 group was down regulated ( t=-6.73, P<0.05). (3) Western blot results showed that the relative expression of LC3 in midbrain tissue of control group, shRNA-PHB2 group, MPTP+ idebenone group, shRNA-PHB2+ MPTP group, shRNA-PHB2+ idebenone group and shRNA-PHB2+ MPTP+ idebenone group were (0.86±0.07), (0.77±0.08), (0.42±0.05), (0.21±0.05), (0.66±0.09) and (0.27±0.07). The relative expression of PHB2 were (1.13±0.14), (0.56±0.11), (1.08±0.14), (0.27±0.07), (0.68±0.14) and (0.24±0.10). Compared with MPTP+ idebenone group, the relative expression of LC3 and PHB2 in shRNA-PHB2+ MPTP+ idebenone group was significantly decreased ( F=1.96, P<0.01). Conclusion:Idebenone can increase the level of mitophagy in PD mice through PHB2, thus improving the behavioral disorder.
الملخص
Objective:To evaluate the effect of electroacupuncture (EA) on pyroptosis in renal tubular epithelial cells of rats with acute kidney injury (AKI) induced by endotoxin.Methods:Twenty-four healthy clean-grade Sprague-Dawley rats of either gender, aged 6-8 weeks, weighing 160-182 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), group AKI, EA plus AKI group (group EA), sham EA at non-acupoint plus AKI group (group SEA). The model of endotoxemia was established by intraperitoneally injecting 10 mg/kg lipopolysaccharide.Bilateral 30 min EA stimulation of Zusanli and Shenyu (according to atlas of animal acupoint) was performed starting from 5 days before establishing the model (once a day) and at 30 min before lipopolysaccharide administration on the day of establishing the model, with disperse-dense waves, frequency of 15 Hz, and the needle was kept until 6 h after injection of LPS in group EA.EA was performed at the points 0.5 cm lateral to the acupoints of Zusanli and Shenyu in group SEA.At 6 h after LPS injection, blood was taken from the heart, and the concentrations of serum blood urea nitrogen (BUN) and creatinine (Cr) were detected by an automatic biochemical analyzer, and the serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay.The rats were then sacrificed, and the left renal cortex was obtained for determination of pyroptosis rate of renal tubular epithelial cells (by TUNEL). The right renal cortex was obtained to detect the expression of caspase-1 and IL-1β by Western blot, and the expression of caspase-1 mRNA and IL-1β mRNA was detected by real-time polymerase chain reaction. Results:Compared with group C, the concentrations of BUN, Cr, NGAL, KIM-1, TNF-α, and IL-6 were significantly increased, the pyroptosis rate of renal tubular epithelial cells was increased, the expression of caspase-1 and IL-1β protein and mRNA in the renal cortex was up-regulated in group AKI ( P<0.05). Compared with group AKI, the concentrations of BUN, Cr, NGAL, KIM-1, TNF-α, and IL-6 were significantly decreased, the pyroptosis rate of renal tubular epithelial cells was decreased, the expression of caspase-1 and IL-1β protein and mRNA in the renal cortex was down-regulated in group SEA ( P>0.05). Conclusion:The mechanism by which EA reduces AKI may be related to inhibiting pyroptosis in renal tubular epithelial cells of rats.
الملخص
Objective:To evaluate the sedative efficacy of remimazolam in outpatients undergoing curettage.Methods:Eighty outpatients, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, aged ≥18 yr, undergoing curettage, were divided into 2 groups according to the random number table method: remimazolam group (group R, n=41) and propofol group (group P, n=39). Anesthesia was induced with alfentanil 10 μg/kg injected intravenously in two groups, and in addition remimazolam 7 mg was intravenously injected in group R, and propofol 1.5 mg/kg was intravenously injected in group P. If the Modified Observer′s Assessment of Alertness/Sedation score ≥3 or the patient could not tolerate the surgical procedure, remimazolam 2.5 mg was given for rescue sedation in group R and propofol 0.5 mg/kg was given for rescue sedation in group P, and alfentanil 1 μg/kg was given as rescue analgesic.The onset time of sedatives, time to eye opening, emergence time and time to discharge were recorded.The success of sedation, intraoperative BIS value, requirement for rescue medications, and occurrence of adverse reactions were recorded. Results:The intraoperative BIS values were maintained at 61-72 and 40-64 in group R and group P, respectively.The success rate of sedation was 95% in group R and 100% in group P, and there was no significant difference between the two groups ( P>0.05). Compared with group P, the rate of rescue sedative agents used and rate of rescue alfentanil given were significantly increased, the onset time of sedative agents was significantly prolonged, the incidence of postoperative nausea and vomiting was increased, and the incidence of respiratory depression and injection pain was decreased in group R ( P<0.05 ). Conclusion:Remimazolam (given according to the instructions) is safer when used for outpatient curettage, but it can only maintain a light sedation status, and the sedative efficacy is inferior to propofol.
الملخص
Objective:To investigate the effect of radiological interventional embolization in the treatment of hepatocellular carcinoma with portal vein tumor thrombus, and its effect on the improvement of prognosis.Methods:A total of 100 cases of liver cancer with portal vein tumor thrombus from July 2017 to July 2019 in the People's Hospital of Putuo District of Zhoushan City were selected in the study.The patients were divided into observation group and control group according to the random digital table method, with 50 cases in each group.The control group was treated by hepatic artery chemotherapy alone, and the observation group was treated by transcatheter arterial chemoembolization.The therapeutic effect, liver function changes and quality of life scores were compared between the two groups.Results:In the observation group, 25 cases(50%) with liver tumor shrinking more than 50%, 10 cases(20%) with portal vein tumor thrombus disappearing, those were 16 cases(32%) and 5 cases(10%) in the control group, the differences were statistically significant between the groups(χ 2=6.310, 4.601, all P<0.05). After treatment, the serum albumin, alanine aminotransferase, albumin, platelet count and leukocyte count in the observation group were (23.80±10.60)μmol/L, (68.10±19.83)U/L, (338.60±50.16)g/L, (102.13±20.10)×10 9/L, (4.10±2.10)×10 9/L, respectively, which in the control group were (19.20±7.55)μmol/L, (64.10±11.25)U/L, (32.11±4.83)g/L, (110.45±28.64)×10 9/L, (4.83±2.83)×10 9/L, respectively, the differences between the two groups were statistically significant( t=7.158, 4.301, 82.441, 3.432, 3.645, all P<0.05). The total health score of quality of life in the observation group was (69.20±3.94)points, which was higher than that in the control group[(52.76±2.40)points]( t=25.303, P<0.05). Conclusions:Radiation interventional embolization for liver cancer with portal vein tumor thrombus can rapidly improve liver function and reduce liver cancer or portal vein tumor thrombus lesions.The effect is significant, which is of great significance for improving the quality of life of patients with liver cancer and portal vein tumor thrombosis.It is worthy of promotion.
الملخص
Objective To study the risk factors and outcome of symptomatic BAAS.Methods Eighty symptomatic BAAS patients served as a BAAS group and 80 symptomatic anterior circulation stroke (ACS) patients served as a ACS group in this study.The risk factors for symptomatic BAAS were compared.The symptomatic BAAS patients were further divided into mild-moderate stenosis group (n =43) and severe stenosis group (n=37),progressive stenosis group (n =34) and non-gressive group (n=46),survival group (n=42) and death group (n=38) respectively.The relationship between risk factors and outcome of symptomatic BAAS was analyzed.Results The rate of male patients and the incidence of hypertention were significantly higher in BAAS group than in ACS group (75.0％ vs 57.5％,80.0％ vs 66.3％,P＜0.01).The history of ischemic stroke and smoking was related with the severity of BAAS (P＜0.05).Premonitory symptoms were re lated with the progression of BAAS (P＜0.01).Pulmonary infection and tracheal intubation or tracheotomy were related with the outcome of BAAS (P＜0.01).Conclusion Male gender,hypertension,and history of ischemic stroke and smoking are the independent risk factors for symptomatic BAAS which is less likely to progress in patients with premonitory symptoms.Pulmonary infection and tracheal intubation or tracheotomy are the independent risk factors.
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PURPOSE: The long non-coding RNA H19, a conservatively imprinted gene, acts as a molecular sponge for the let-7 family, which has been identified as a set of tumor suppressors. However, the combined prognostic value of H19 and let-7a signature in breast cancer patients remains unclear. METHODS: In this research we assessed the prognostic value of the combined H19 and let-7a signature in breast cancer patients by retrospectively reviewing that data of 79 patients who underwent neoadjuvant chemotherapy; we also investigated the expression and function of H19 in breast cancer cell lines in vitro. Survival data were calculated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate survival analyses were conducted using the Cox proportional hazards regression method. As determined using X-tile, the optimal cutoff value for the risk score to assess progression-free survival (PFS) based on the combined signature was –0.1. RESULTS: Patients with an overall positive treatment response had higher let-7a and lower H19 levels. In addition, let-7a expression was negatively correlated with H19 expression. Patients with a risk score of >–0.1 had shorter overall survival and PFS. In vitro data showed that chemoresistant cell lines exhibit higher H19 and lower let-7a levels and knockdown H19 restores paclitaxel sensitivity. CONCLUSION: Our results suggest that the combined let-7a and H19 signature is a novel prognostic factor for breast cancer patients treated with neoadjuvant chemotherapy.