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Asthma is a chronic inflammatory airway disease,and airway inflammation,airway hyper-respon-siveness and airway remodeling are the major pathological alterations in asthma.Numerous studies have demon-strated sphingosine metabolism disorders exist in asthma patients,and sphingosine-1-phosphate(S1P)is the end product of sphingolipid metabolism,which has become the focus of research as an important mediator of immune and inflammatory diseases,and is closely related to the development of asthma.In this paper,we summarize the role of S1P in the pathological changes of asthma from the relationship between S1P and asthma as well as its application in the clinical diagnosis,treatment and efficacy assessment of asthma,with a view to exploring more directions in the diagnosis and treatment of asthma.
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Objective:To explore the mechanism by which miRNA-4469 (miR-4469) regulates the proliferation and invasion of renal cancer cells in vitro.Methods:The survival differences of patients with different expression levels of miR-4469 were analyzed based on the OncomiR database. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) method was used to detect the expression of miR-4469 in renal cancer cell lines ACHN, OS-RC-2, SK-RC-20, 769-P, A498 and normal renal tubular epithelial cell line HK-2, and the renal cancer cells with the lowest expression level of miR-4469 were divided into miR-4469 group and control group, and were transfected with miR-4469 mimic and negative control sequence, respectively. The CCK-8 assay was used to detect the cell proliferation ability (expressed as absorbance value) in the two groups, and Transwell assay was used to analyze the number of invasive cells in the two groups. TargetScan Release 8.0 software was used to predict the binding site between miR-4469 and protein disulfide isomerase A4 (PDIA4) mRNA, and dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-4469 and PDIA4 mRNA. qRT-PCR method was used to detect the expression of PDIA4 mRNA in cells of each group, and Western blotting method was used to detect the expression levels of PDIA4 protein and PI3K-AKT-m-TOR pathway proteins in cells of each group.Results:Analysis of relevant data from the OncomiR database showed that compared with patients with low miR-4469 expression, the overall survival of renal cancer patients with high miR-4469 expression was better ( P < 0.001). The relative expression of miR-4469 in each renal cancer cell line was lower than that in HK-2 cells (all P < 0.05), and the expression of miR-4469 in 769-P cells was the lowest, which were selected to perform the subsequent experiments. The proliferation ability of 769-P cells in the miR-4469 group was lower than that in the control group ( P < 0.01). The number of 769-P cell invasions in the miR-4469 group were less than that in the control group [(19±3) cells vs. (64±7) cells, t = 5.44, P = 0.002]. Compared with the co-transfection of wild-type PDIA4 and miR-4469 negative sequence group, the relative luciferase activity of cells in the co-transfection of wild-type PDIA4 and miR-4469 mimic sequence group was lower (0.42±0.07 vs. 1.01±0.08, t = 5.74, P = 0.001); there was no statistical difference in cell luciferase activity between the co-transfected mutant PDIA4 and miR-4469 negative sequence group and the co-transfected mutant PDIA4 and miR-4469 mimic sequence group (0.99±0.11 vs. 1.02±0.11, t = 0.19, P = 0.001). The relative expression levels of PDIA4 mRNA in 769-P cells in the miR-4469 group were lower than that in the control group (0.98±0.23 vs. 7.19±2.23, t = 2.77, P = 0.032). Compared with the control group, the expression of PDIA4 protein and PI3K-AKT-m-TOR pathway-related p-PI3K, p-AKT, p-mTOR, and p-SGK1 proteins in 769-P cells in the miR-4469 group were all lower (all P < 0.05). Conclusions:miR-4469 may be related to the survival of renal cancer patients, and its expression is down-regulated in various renal cancer cell lines. miR-4469 may inhibit the proliferation and invasion of renal cancer 769-P cells by regulating the PI3K-AKT-m-TOR pathway through PDIA4.
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Objective:To investigate the effect of ultrasound-guided stellate ganglion block (SGB) on cerebral oxygen metabolism and serum S100B protein during carotid endarterectomy (CEA).Methods:Patients aged 40-75 years old, classified as Grade Ⅱ-Ⅲ by the American Society of Anesthesiologists (ASA), and underwent elective CEA under general anesthesia at the Affiliated Suzhou Hospital of Nanjing Medical University from June 2021 to April 2023 were prospectively enrolled. They were randomly divided into an SGB group and a control group. Before anesthesia induction, the SGB group underwent ipsilateral SGB under the ultrasound guidance, while the control group did not undergo SGB. The right subclavian vein catheterization was performed under the ultrasound guidance during the general anesthesia. The mean arterial pressure (MAP) and heart rate (HR) were recorded before induction of general anesthesia (T0), during tracheal intubation (T1), before vascular occlusion (T2), after vascular opening (T3), and at the end of surgery (T4), as well as the pressure of the jugular vein bulb at each time point from T1 to T4. Arterial blood and jugular venous bulb blood were collected at various time points for blood gas analysis. Jugular venous bulb oxygen saturation (SjvO 2), arteriovenous oxygen content difference (AVDO 2), cerebral oxygen extraction rate (COER), lactate production rate (LPR) and lactate oxygen index (LOI) were calculated. The serum S100B concentration in the jugular vein bulb blood at various time points was detected with enzyme-linked immunosorbent assay. The incidence of postoperative hoarseness, hematoma, dizziness, diaphragmatic nerve block, nausea, and vomiting were recorded. Results:A total of 82 patients conducted CEA were included, with 41 patients in the SGB group and 41 in the control group. During anesthesia induction and surgery in the SGB group, HR was significantly lower than that in the control group, and the MAP and HR during tracheal intubation and at the beginning of surgery were also more stable than those in the control group (all P<0.05). In the SGB group, the changes in SjvO 2, AVDO 2, and COER were relatively smaller from T1 to T3, while SjvO 2 increased, and AVDO 2 and CEOR decreased at T4. In contrast, the control group showed a decrease in SjvO 2, AVDO 2, and COER at T3 and a slight increase at T4. At all time points, SjvO 2 in the SGB group was significantly higher than that in the control group ( P<0.05). AVDO 2 and COER in both groups gradually decreased over time, and the control group was significantly higher than the SGB group at all time points (all P<0.05). LPR and LOI increased at T1 to T4 in both groups, reaching their highest value at T3 and decreasing at T4. There was statistically significant difference at T4 and at T2 in the control group (all P<0.05). The LPR and LOI of the control group were significantly higher than those of the SGB group at all time points (all P<0.05). In addition, the serum S100B levels in both groups increased first and then decreased, but the T2-T4 levels in the SGB group were significantly lower than those in the control group at all time points (all P<0.05). The incidence of perioperative adverse events in the SGB group was significantly lower than that in the control group ( P<0.05). Conclusion:Performing ipsilateral SGB before CEA surgery can effectively inhibit stress response, maintain intraoperative hemodynamic stability, improve brain tissue oxygen supply, and have a certain neuroprotective effect.
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Objective:The relative expression of lncRNA NPIPA9 in prostate cancer tissues was analyzed, and the relative expression of miR-210-3p and its effect on the growth and migration of prostate cancer cells were detected by overexpressing lncRNA NPIPA9.Methods:The relative expression of lncRNA NPIPA9 in prostate cancer tissues was analyzed by Oncomine database. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the relative expression of lncRNA NPIPA9 in prostate cancer cell lines DU-145, PC-3, C4-2B, 22Rv1, LNCaP and normal prostate epithelial cell RWPE-1. Prostate cancer PC-3 cells were cultured in vitro and divided into control group (transfected with control vector 100 nmol/L) and NPIPA9 group (transfected with lncRNA NPIPA9 vector 100 nmol/L). The proliferation activity of PC-3 cells was detected by CCK-8 method. The migration ability of PC-3 cells was detected by Transwell method. Potential target of lncRNA NPIPA9 were predicted using bioinformatics techniques. The dual-luciferase reporter gene assay determined the target binding relationship between lncRNA NPIPA9 and miR-210-3p. The effect of lncRNA NPIPA9 on the relative expression of miR-210-3p in prostate cancer cells was detected by RT-qPCR. The effect of lncRNA NPIPA9 on the expression of nuclear factor kappa-B (NF-κB) pathway proteins in prostate cancer cells was detected by Western blotting. Measurement data were expressed as mean±standard deviation ( ± s), and t-test was used for comparison between two groups, one-way analysis of variance was used for comparison between multiple groups. Results:The expression of lncRNA NPIPA9 in prostate cancer tissue was lower than that in adjacent tissue, the difference was statistically significant ( P<0.01). The relative expression of lncRNA NPIPA9 in prostate cancer cell lines was lower than that in RWPE-1 cells, the difference was statistically significant ( P<0.01), and the relative expression of lncRNA NPIPA9 in prostate cancer PC-3 cells was the lowest, the difference was statistically significant ( P<0.01). Compared with the control group, lncRNA NPIPA9 had an inhibitory effect on the viability of prostate cancer PC-3 cells, the difference was statistically significant ( P<0.05). The migration numbers of PC-3 cells in the control group and NPIPA9 group were 101.70±8.63 and 45.97±8.83, respectively, and lncRNA NPIPA9 had an inhibitory effect on PC-3 cell migration, the difference was statistically significant ( P<0.01). lncRNA NPIPA9 can directly target miR-210-3p, the difference was statistically significant ( P<0.01). The relative expression of miR-210-3p in PC-3 cells in control group and NPIPA9 group were 5.32 ± 0.79 and 1.11 ± 0.56, respectively, and lncRNA NPIPA9 could directly down-regulate the expression of miR-210-3p in PC-3 cells, the difference was statistically significant ( P<0.01). Compared with the control group, lncRNA NPIPA9 can reduce the expression of NF-κB pathway proteins c-Myc, MMP-9, VEGF, p65, p50 in PC-3 cells. Conclusion:The expression of lncRNA NPIPA9 is down-regulated in prostate cancer tissues, and it reduces the proliferation and migration ability of prostate cancer PC-3 cells by targeting and negatively regulating miR-210-3p.
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OBJECTIVES@#To systematically evaluate the value of the platelet-to-lymphocyte ratio (PLR) in predicting coronary artery lesions (CAL) in Chinese children with Kawasaki Disease (KD).@*METHODS@#A comprehensive search was conducted in databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, China Biomedical Literature Database, and China Science and Technology Journal Database from inception to December 2022. The quality of the included literature was assessed using the Newcastle-Ottawa Scale, and a Meta analysis was performed using Stata 15.1.@*RESULTS@#A total of ten published reports, involving 3 664 Chinese children with KD, were included in this Meta analysis, of whom 1 328 developed CAL. The Meta analysis revealed a sensitivity of 0.78 (95%CI: 0.71-0.83), specificity of 0.71 (95%CI: 0.61-0.80), overall diagnostic odds ratio of 8.69 (95%CI: 5.02-15.06), and an area under the curve of the summary receiver operating characteristic of 0.82 (95%CI: 0.78-0.85) for PLR in predicting CAL in the children with KD. The sensitivity, specificity, and area under the curve of summary receiver operating characteristic were lower for PLR alone compared to PLR in combination with other indicators. Sensitivity analysis demonstrated the stability of the Meta analysis results with no significant changes upon excluding individual studies. However, a significant publication bias was observed (P<0.001).@*CONCLUSIONS@#PLR demonstrates certain predictive value for CAL in Chinese children with KD.
الموضوعات
Child , Humans , Mucocutaneous Lymph Node Syndrome/pathology , Coronary Vessels/pathology , Lymphocytes , Biomarkers , China , Coronary Artery Disease/pathologyالملخص
Damp-heat syndrome is one of the common syndromes of various clinical diseases.Current studies have shown that intestinal flora is closely related to damp-heat syndrome,but the specific molecular biological mechanism related to intestinal flora and damp-heat syndrome is not yet clear.In this paper,the molecular biological mechanism of damp-heat syndrome is discussed from the perspective of intestinal flora related signaling pathways,so as to provide ideas for the essence of damp-heat syndrome and clinical diagnosis and treatment.
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AIM: To analyze the effects of aromatase inhibitors(AIs)on the ocular surface microenvironment of the users.METHODS: A cross-sectional observational study was conducted. The study included postmenopausal women who received AIs treatment at galactophore department of our hospital from November 2022 to May 2023. Participants were divided into two groups based on the mechanism of AIs: the steroidal group and the non-steroidal group. The control group consisted of age-matched women who underwent occupational health examinations. All participants completed the ocular surface disease index(OSDI)questionnaire and underwent detailed ophthalmic examinations, including best-corrected visual acuity, intraocular pressure, axial length, corneal curvature, radius of curvature of curved lacrimal river surface, tear osmolarity, tear film break-up time, corneal fluorescein staining score, Schirmer Ⅰ test, and meibomian gland infrared score.RESULTS: There were no statistically significant differences in age, best-corrected visual acuity, intraocular pressure, axial length, and corneal curvature between control group and steroidal and non-steroidal group(P>0.05). The duration of drug treatment between the steroidal group and the non-steroidal group also showed no statistically significant difference(P>0.05). However, statistically significant differences were observed between the control group and the steroidal and non-steroidal group in OSDI scores, radius of curvature of curved lacrimal river surface, tear osmolarity, tear film break-up time, corneal fluorescein staining score, Schirmer Ⅰ test, and meibomian gland infrared score(P<0.05). The Schirmer Ⅰ test also showed statistically significant differences between the steroidal group and the non-steroidal group(P<0.05), while other data showed no statistically significant differences(P>0.05).CONCLUSION: Postmenopausal patients receiving AIs treatment experienced significant changes in the ocular microenvironment, with both decreased tear secretion and excessive tear evaporation contributing to the occurrence of dry eye. Notably, patients receiving non-steroidal AIs treatment showed a more significant reduction in main lacrimal gland secretion.
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Objective:To investigate the effect of salidroside on the proliferation and invasion of prostate cancer PC-3M cells and the possible molecular mechanism.Methods:PC-3M cells were treated with different concentrations (0, 50, 100, 150, 200 nmol/L) of salidroside for 48 h, and MTS assay was used to detect the effect of salidroside on the proliferation of PC-3M cells. The PC-3M cells treated with the most obvious inhibitory effect concentration of salidroside were selected as the salidroside group, and the PC-3M cells treated with 0.9% NaCl were selected as the control group. Transwell assay was used to detect the effect of salidroside on PC-3M cell invasion. The expression difference of LINC01207 between prostate cancer tissues and adjacent tissues was analyzed by using GEPIA database. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC01207 and miR-1182 in PC-3M cells after salidroside treatment. Western blot was used to detect the expressions of proliferation and invasion related proteins in PC-3M cells after salidroside treatment.Results:After treated with 0, 50, 100, 150, and 200 nmol/L salidroside, the absorbance values of prostate cancer PC-3M cells were 0.98±0.17, 0.72±0.08, 0.47±0.10, 0.12±0.03, and 0.42±0.05, respectively, and the difference was statistically significant ( F = 42.02, P < 0.05); and 150 nmol/L salidroside had the most significant inhibitory effect. The salidroside group (150 nmol/L salidroside) was performed to do the subsequent experiment. The invasion number of PC-3M cells in the control group and the salidroside group were (80±11) and (36±13), respectively ( t = 5.15, P < 0.05). GEPIA database online analysis showed that the expression of LINC01207 in prostate cancer tissues was higher than that in paracancerous tissues ( P < 0.01). qRT-PCR results showed that the relative expression level of LINC01207 in PC-3M cells of the control group and the salidroside group was (6.2±1.1) and (1.2±0.7), respectively; and the expression of LINC01207 in PC-3M cells of the salidroside group was lower than that of the control group ( t = 7.88, P < 0.01). The relative expression level of miRNA-1182 was (1.00±0.20) and (7.02±0.35), respectively; the expression of miRNA-1182 in PC-3M cells of the salidroside group was higher than that of the control group ( t = 30.07, P < 0.01). Western blot results showed that after PC-3M cells were treated with salidroside, the expressions of cell proliferation proteins CDK2 and cyclin E decreased; the expressions of cell invasion proteins CD147, matrix metalloproteinases (MMP)-2, MMP-9 decreased. Conclusions:Salidroside inhibits prostate cancer PC-3M cell proliferation and invasion by downregulating LINC01207 expression and activating miRNA-1182 expression.
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Objective:To investigate the safety of tirofiban in patients with anterior circulation acute large vessel occlusion cerebral infarction during bridging endovascular treatment (EVT) after intravenous thrombolysis (IVT).Methods:Two hundred and three patients received bridging EVT after IVT in Department of Intervention, First Affiliated Hospital of Soochow University from January 2017 to January 2022 were chosen. Patients were divided into tirofiban group ( n=80) and non-tirofiban group ( n=123) according to whether or not tirofiban was used during EVT, and then patients from tirofiban group were subdivided into stent implantation group ( n=52) and non-stent implantation group ( n=28) according to whether or not emergency stent implantation was performed. The clinical data, safety indexes (intracranial hemorrhage [ICH] rate 24 h, 2-3 d, and 90 d after EVT, new ICH incidence 3-90 d after EVT, fatal ICH rate, and mortality 90 d after EVT), and prognoses 90 d after EVT were compared. Results:(1) Compared with the non-tirofiban group, the tirofiban group had significantly higher proportions of males, and patients with tandem occlusion, balloon dilation or stent implantation, and statistically lower proportion of patients with atrial fibrillation, significantly longer surgical time, and significantly different distribution of stroke types ( P<0.05). No significant differences were noted in ICH incidences 24 h after EVT, 2-3 d after EVT and 90 d after EVT, fatal ICH incidence, mortality incidence 90 d after EVT, or good prognosis rate 90 d after surgery between tirofiban group and non-tirofiban group ( P>0.05). (2) Patients in the stent implantation group had significantly higher percentages of tandem occlusion and balloon dilation compared with those in the non-stent implantation group ( P<0.05). No significant difference was noted in good prognosis rate 90 d after EVT or new ICH incidence 3-90 d after EVT between the stent implantation group and the non-stent implantation group ( P>0.05). Compared with the non-stent implantation group, the stent implantation group had statistically higher ICH incidences 24 h after EVT, 2-3 d after EVT, and 90 d after EVT, significantly higher fatal ICH incidence and mortality 90 d after EVT ( P<0.05). Conclusion:Tirofiban is safe in patients with anterior circulation acute large vessel occlusion cerebral infarction during EVT after IVT; however, if emergency stent implantation is performed, it will lead to increased intracranial hemorrhage and mortality.
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With the increasing understanding of inflammatory pathogenesis of acne inversa, as well as with the development and application of biological agents in the treatment of autoimmune inflammatory diseases, some biological agents have shown good efficacy and potential for the treatment of acne inversa in clinical research and practice. This review mainly summarizes the research progress in biotherapy of acne inversa in recent years.
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@#Abstract: Objective To analyze and compare the effects of different clinical characteristics on the negative conversion time of nucleic acid detection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection, and to provide a scientific basis for the isolation and treatment of coronavirus disease 2019 (COVID-19). Methods The epidemiological and clinical data of 228 mild SARS-CoV-2 Omicron variant infected patients diagnosed in Shanghai were retrospectively collected from April 27, 2022 to June 8, 2022 in Wujiaochang designated Hospital, Yangpu District, Shanghai. The negative conversion time of nucleic acid detection was used as the outcome variable, and the patients were divided into A (≤18 days) and B (>18 days). Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of the negative conversion time of nucleic acid detection. Results The mean nucleic acid conversion time of 228 patients was (18.7±12.1) d, with the median time of 18 (2-46) d. Among them, 120 patients in group A had an average nucleic acid conversion time of (13.2±2.0) d, and 108 cases in group B had an average nucleic acid conversion time of (20.8±1.3) d. Univariate analysis showed that there were no statistically significant differences in the effects of hypertension, coronary heart disease, diabetes, hypokalemia, malignant tumors, neuropsychiatric diseases, chronic digestive diseases on the negative nucleic acid conversion time (P>0.05); however, there were significant differences in the effects of combined cerebrovascular disease, leukopenia, chronic respiratory system diseases and vaccination on the negative nucleic acid conversion time (P<0.05). Further multivariate logistic regression analysis revealed that the combination of chronic respiratory diseases and non-vaccination were significant risk factors for prolongation of negative nucleic acid conversion time (P<0.05). Conclusions The results of this study show that gender, age and whether hypertension, coronary heart disease, diabetes mellitus, hypokalemia, malignant tumor, neuropsychiatric disease and chronic digestive disease have no significant effect on the nucleic acid conversion time, whereas chronic respiratory disease and no vaccination are significantly correlated with the prolongation of nucleic acid conversion time in SARS-CoV-2 Omicron-infected patients.
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Objective To reveal the incidence,mortality,and risk factors of bleeding-related perioperative cardiac arrest(POCA). Methods We carried out a single-center retrospective case-control study which enrolled all the POCA cases reported from January 2010 to September 2020 in the patient safety incident reporting system of Peking Union Medical College Hospital.For the screening of risk factors,the patients were respectively assigned into the POCA group and the control group at a ratio of 1∶3 according to the same sex,age,American Society of Anesthesiologists(ASA)physical status,and type of surgery in the same month.Potential risk factors for POCA were first selected by univariate analysis.The significant risk factors were then checked based on the clinical experience and further included in the multivariate Logistic regression model. Results Totally 16 bleeding-related POCA cases were collected from the patient safety incident reporting system among the study period,with an overall incidence of 0.36/10 000.The blood loss volume of POCA group and control group was(7 037.50±5 477.70)ml and(375.63±675.14)ml,respectively(P<0.001),and 14(87.5%)patients suffering from bleeding-related POCA died within three days after anesthesia.According to the univariate analysis,patients' body mass index[(21.79±3.57)kg/m2 vs.(24.26±3.91)kg/m2,P=0.043],hemoglobin level[(113.44±31.08)g/L vs.(131.75±19.70)g/L,P=0.039],and alanine aminotransferase level[(17.31±7.73)U/L vs.(26.91±24.73)U/L,P=0.022]were significantly lower in the POCA group than in the control group.Further Logistic regression analysis showed that smaller body mass index and lower preoperative hemoglobin level were independently associated with the occurrence of bleeding-related POCA. Conclusions Bleeding-related POCA rarely occurred but had high mortality.Adequate precautions should be taken for the patients who are to receive surgeries with high risk of intraoperative massive bleeding.Elevating preoperative hemoglobin level might decrease the incidence of bleeding-related POCA.
الموضوعات
Humans , Case-Control Studies , Heart Arrest/etiology , Hemoglobins , Retrospective Studies , Risk Factorsالملخص
Objective:To explore the expression level of miR-769-3p in bladder cancer tissues, and observe the effect of silencing miR-769-3p on the migration ability and cell cycle of J82 cells by down-regulating the expression level of miR-769-3p in bladder cancer J82 cells.Methods:The OncomiR database was used to analyze the expression differences of miR-769-3p in bladder cancer tissues and adjacent tissues. J82 cells were transfected with Lipofectamine 2000 transfection reagent and divided into si-miR-769-3p group (transfected with miR-769-3p small molecule interference fragments) and control group (transfected with meaningless sequences). quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of miR-769-3p after transfection. The cell scratch test and flow cytometry were used to compare the migration ability and cell cycle differences between the two groups of J82 cells. The bioinformatics software MicroRNAdb was used to predict the target gene of miR-769-3p. The dual-luciferase reporter gene assay was used to verify the complementary binding of miR-769-3p to the target gene. qRT-PCR and Western blotting were used to detect the expression levels of miR-769-3p target gene. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between two groups. Results:The expression of miR-769-3p was significantly increased in bladder cancer tissues compared with adjacent tissues, the difference was statistically significant ( P<0.01). The relative expression of miR-769-3p in the si-miR-769-3p group (1.02 ± 0.16) was significantly lower than that of the control group (4.50 ± 0.60), the difference was statistically significant ( P<0.01). The cell migration rate of the si-miR-769-3p group [(26.67±3.98)%] was significantly lower than that of the control group [(61.86±4.70)%], the difference was statistically significant ( P<0.01). The proportion of cells in the G 0-G 1 phase in the si-miR-769-3p group [(57.66±5.74)%] was significantly higher than that in the control group [(31.26±3.24)%], the difference was statistically significant ( P<0.01). Dual-luciferase reporter gene assay confirmed that endothelin 3 ( EDN3) was the target gene of miR-769-3p. The relative expression of EDN3 mRNA in J82 cells in control group and si-miR-769-3p group was 1.99 ± 0.66 and 6.98 ± 0.76, compared with the control group, the EDN3 mRNA relative expression level of the si-miR-769-3p group was significantly higher than that of the control group, the difference was statistically significant ( P<0.01). Conclusion:Low expression of miR-769-3p can inhibit the migration of bladder cancer J82 cells and block the J82 cell cycle by promoting the expression of EDN3 gene.
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Objective:To investigate the effect of vancomycin (Vm)-loaded microbubbles (MBs) combined with ultrasound targeted microbubble destruction (UTMD) technique on the morphological structure, thickness and bacterial viability of methicillin-resistant Staphylococcus aureus (MRSA) biofilms.Methods:Vm-MBs were prepared by thin film hydration. Sterile coverslips in a diameter of 13 mm were placed in 24-well plates to construct in vitro biofilm models using MRSA as the test strain, and the biofilm morphology was observed by naked eye and light microscopy after crystal violet staining. LIVE/DEAD, SYTO59 and DIL were used to stain biofilms and MBs, respectively. After staining, the biofilm morphology and position of the biofilm in relation to MBs were observed using laser confocal scanning microscopy. The biofilms were divided into control group, Vm group, Vm-MBs group, UTMD group and Vm-MBs+UTMD group according to the random number table method, with 9 samples in each group. After biofilms of each group were treated accordingly for 24 hours, the morphological and structural changes of biofilms in each group were observed using laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining; the difference in biofilm density in each group was measured with the aid of an enzyme marker following crystal violet staining; the difference in biofilm thickness and bacterial viability in each group were observed by laser confocal scanning microscopy. Results:The prepared Vm-MBs met the experimental requirements. The constructed biofilm model observed by naked eye, light microscopy and laser confocal scanning microscopy showed that the biofilm structure was dense with a relatively uniform thickness of (13.8±0.2)nm, a small amount of dead bacteria inside the membrane and the percentage of live bacteria of (94.9±0.3)%. Laser confocal scanning microscopy showed that MBs could penetrate into deeper layers of biofilms. After the respective treatment was given to each group for 24 hours, Laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining showed that the biofilm morphological structure was most significantly disrupted in Vm-MBs+UTMD group compared to control, Vm, Vm-MBs and UTMD groups. In Vm-MBs+UTMD group, a large number of dead bacteria was observed, with only a few scattered planktonic bacteria and irregular changes in cell membrane morphology. Crystal violet staining showed that the biofilm density was significantly lower in Vm-MBs+UTMD group compared to control group ( P<0.05), while the differences between Vm, Vm-MBs and UTMD groups were not statistically significant (all P>0.05). Laser confocal microscopy showed that the biofilm thickness was thinner in Vm-MBs, UTMD and Vm-MBs+UTMD groups compared to control group (all P<0.05), with no significant difference between Vm group and control group ( P>0.05) and that the biofilm thickness was thinner in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), with no significant differences between the other groups (all P>0.05). Bacterial activity in Vm, Vm-MBs, UTMD and Vm-MBs+UTMD groups was significantly lower than that in control group (all P<0.01), with lower in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), but without significant difference between the other groups (all P>0.05). Conclusion:Vm-MBs combined with UTMD technology can effectively destroy the biofilm morphological structure to reduce biofilm thickness. Meanwhile, Vm-MBs combined with UTMD technology can release antibiotics and significantly decrease bacterial viability to improve antibiotic bactericidal efficacy.
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AIM: To investigate the role of sorafenib in promoting ferroptosis in HCC, and whether cell death can be induced by activating mitochondrial oxidative stress and consequent mitochondrial dysfunction. METHODS: Hepatocellular carcinoma cell lines Huh7 and HCC-LM3 were treated with different concentrations of sorafenib, the cell viability was determined by CCK-8 assay; mitochondrial membrane potential (MMP) was measured by Tetramethylrhodamine (TMRM) staining; The mitochondrial oxygen consumption rate was monitored by the Seahorse XF24 Analyzer; mitochondrial superoxide indicator (Mitosox) was used to determine the level of reactive oxygen species (ROS) in mitochondria; the formation of total ROS was determined by dichlorofluorescein diacetate (DCF-DA) staning. Finally, The recovery of oxidative damage and cell death induced by sorafenib was observed after pretreated by glutathione (GSH). RESULTS: With the increasing concentration of sorafenib, the survival of the Huh7 and HCC-LM3 was significantly decreased. Sorafenib also inhibited the oxygen consumption rate and decreased oxidative phosphorylation, which results in the depolarization of MMP, ROS accumulation and eventually ferroptosis of HCC cells. However, the occurrence of oxidative stress induced by sorafenib in HCC cells can be effectively reversed by the pretreatment of GSH. CONCLUSION: The ferroptosis can be induced by sorafenib through inducing mitochondrial dysfunction and ROS accumulation in HCC cells. However, the GSH can restore oxidative damage. Therefore, induction of the GSH deficiency in HCC may be a potential therapeutic option to enhance the efficacy of sorafenib.
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@#The blood-retinal barrier is an important structural basis for maintaining the homeostasis of the retinal environment, but there is still a lack of further research on its complete structure and function. The <i>in vitro</i> blood-retinal barrier model has the characteristics of controllable, efficient, fast and stable, and has become an effective tool to study the specific structure and function of the barrier. This paper mainly reviews the structure, function and <i>in vitro</i> model of blood-retinal barrier, which is helpful to promote the study of physiology, biochemistry, pathopharmacology and clinic of blood-retinal barrier. It also provides a common and key experimental basis for the study of fundus vascular diseases such as diabetic retinopathy.
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@#Inflammation of the oral mucosa induced by radiotherapy and/or chemotherapy may cause pain, difficulty speaking and swallowing, an increased risk of local and systemic infections, and even interrupt cancer treatment, which can seriously affect a patient′s quality of life. The pathogenesis of oral mucositis is complicated. There is still a lack of prevention and treatment modalities for oral mucositis in the clinic. Animal models play a vital role in exploring the pathogenesis of oral mucositis and developing better prevention and treatment methods. This article reviews the current research progress on the establishment and assessment of animal models of oral mucositis. The literature review results showed that animal models of oral mucositis have been established, such as mouse, rat, and gold hamster models. In the replication of animal models, radiotherapy-induced oral mucositis is generally induced by local single-dose or fractionated irradiation using X-ray equipment, either alone or in combination with the chemotherapy drugs 5-fluorouracil or cisplatin; cesium can also be used used as a radioactive source for local irradiation. Oral mucositis induced by the chemotherapy drug 5-fluorouracil alone is generally mild, so 5-fluorouracil was combined with mechanical trauma or acetic acid. The main methods for assessing oral mucositis are gross observation as well as histopathological observation.
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BACKGROUND@#Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis (SAP), and controlling such inflammation is vital for managing this often fatal disease. Dexmedetomidine has been reported to possess protective properties in inflammatory diseases. Therefore, this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate, and if so, to determine the potential mechanism.@*METHODS@#SAP was induced with sodium taurocholate. Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration. α-bungarotoxin, a selective alpha-7 nicotinic acetylcholine receptor (α7nAchR) antagonist, was injected intra-peritoneally 30 min before dexmedetomidine administration. The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine. Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition & Analysis System. Six hours after onset, serum pro-inflammatory cytokine (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer, respectively. Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria.@*RESULTS@#Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α, IL-6, and amylase, strongly alleviating pathological pancreatic injury in the rat model of SAP (TNF-α: 174.2 ± 30.2 vs. 256.1±42.4 pg/ml; IL-6: 293.3 ± 46.8 vs. 421.7 ± 48.3 pg/ml; amylase: 2102.3 ± 165.3 vs. 3186.4 ± 245.2 U/L). However, the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration of α-bungarotoxin. Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model (discharge frequency: 456.8 ± 50.3 vs. 332.4 ± 25.1 Hz; discharge amplitude: 33.4 ± 5.3 vs. 20.5 ± 2.9 μV).@*CONCLUSIONS@#Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus- and α7nAChR-dependent mechanisms.
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Objective: To evaluate the feasibility of color coding of DSA (CC-DSA) in assessment of hemodynamic changes before and after carotid artery stenting (CAS). Methods: Data of 16 patients with severe stenosis at the beginning of internal carotid artery who underwent CAS were analyzed retrospectively. DSA images before and after CAS were processed with CC-DSA software to get the corresponding color coded images. The points of interest (POI) were set up in common carotid artery, C1 segment of internal carotid artery, M1 segment of middle cerebral artery and transverse sinus, respectively, and the time to peak (TTP) as well as the relative time to peak (rTTP) of each POI were collected. Meanwhile, the peak systolic velocity (PSV) and end-diastolic velocity (EDV) of the anterior and posterior carotid artery stenosis segments and the distal end of the internal carotid artery C1 segment (normal lumen) were collected. Results: TTP and rTTP of C1 segment of internal carotid artery and M1 segment of middle cerebral artery after CAS were lower than those before CAS (all P0.05). Compared with those before CAS, PSV and EDV in carotid artery stenosis segment decreased, and PSV in the distal segment C1 of internal carotid artery increased after CAS (all P<0.05). The change value of TTP in C1 segment of internal carotid artery before and after CAS was positively correlated with the change values of PSV (rs=0.500, P=0.049) and EDV (rs=0.522, P=0.038) at the distal end. Conclusion: CC-DSA can quantitatively evaluate the hemodynamic changes before and after CAS in patients with internal carotid artery stenosis.
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<b>Objective::Evaluate the effects of Danhong injection for perioperative percutaneous coronary intervention (PCI) on cardiac function and thrombolysis in myocardial infarction (TIMI) in patients with acute myocardial infarction (AMI). <b>Method::Computer retrieving CNKI, Wanfang database, VIP database, PubMed, CBM, Web of Science, The Cochrane Library, gathering Danhong injection in percutaneous coronary intervention perioperative application in the treatment of acute myocardial infarction clinic trials. The Cochrane risk evaluation is adopted to improve the quality of literature evaluation, with Revman 5.3 software for Meta-analysis. <b>Result::Participants included in 12 clinic trials contains a total of 1 131 patients, including 569 patients in Danhong treatment and 562 patients in control group. The results showed that compared with conventional treatment, Danhong injection treated patients had LVEF increased obviously [mean difference (MD)=6.62, 95% confidence interval (CI) (4.91, 8.34), <italic>P</italic><0.000 01], the number of TIMI class 3 patients significantly increased[relative risk (RR)=0.22, 95%CI(0.12, 0.41), <italic>P</italic><0.000 01], and BNP levels significantly decreased [MD=151.86, 95%CI (-247.00, -56.72), <italic>P</italic>=0.002]. <b>Conclusion::Danhong injection can improve the function of acute myocardial infarction after percutaneous coronary intervention.