Résumé
The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
Résumé
Objective:To develop and evaluate a rapid and sensitive point-of-care chemiluminescent assay(POC-CLIA)for β-human chorionic gonadotropin(β-HCG).Methods:POC-CLIA was constructed based on alkaline phosphatase(Alp)-AMPPD lumi-nescence system and magnetic particles(Mps)carrier.Performance of POC-CLIA,including sensitivity,precision,accuracy,linear dilution,specificity,stability,hook effect and clinical application were evaluated.Results:Detection limit of β-HCG was 0.71 mU/ml,linear detection range was 0.710~1.092×104 mU/ml,and was no hook effect up to 1.7×105 mU/ml.Intra and inter batch coefficients of variation were less than 10%,and could be stored stably at 37℃ for 10 days.Accuracy deviation was within±10%,so results were reliable.There was no cross-reactivity between interfering substances and anti-β-HCG antibdies.For detecting β-HCG in 100 clinical serum samples,results were highly correlated with those that were tested by clinical standard methods(R2=0.997 0).Turnaround time for single sample was less than 15 min and throughput could reach 200 T/h.Conclusion:This method is adequate that can be widely used in grassroots communities to help large-scale screening of pregnancy and related diseases.
Résumé
Objective:To explore the clinical value of recurrent laryngeal nerve dissection in the surgical treatment for congenital pyriform sinus fistula(CPSF). Methods:The clinical data of 42 patients with CPSF were retrospectively analyzed. All patients were diagnosed and treated in the First Affiliated Hospital of Guangdong Pharmaceutical University. Results:During the operation, all patients' recurrent laryngeal nerves were dissected successfully, and fistulas were resected completely,no patients had complication of recurrent laryngeal nerve's damage.There were no recurrence cases during the 13 to 48 months of follow-up. Conclusion:The trend of congenital pyriform sinus fistula is closely related to recurrent laryngeal nerve, it's important to dissect the recurrent laryngeal nerve during the operation for congenital pyriform sinus fistula.
Sujets)
Humains , Cou , Nerf laryngé récurrent/chirurgie , Études rétrospectives , Sinus piriforme/chirurgie , Fistule/chirurgieRésumé
Objective:To investigate the effects of ceftriaxone(CTX) on nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4) pathway and ferroptosis in early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Forty-eight clean grade male SD rats were randomly divided into sham operation group (Sham group), SAH group, SAH+ CTX group and SAH+ CTX+ Nrf2 inhibitor group (SAH+ CTX+ ML385 group) according to the random number table with 12 rats in each group.Seven days before modeling, rats in SAH+ CTX+ ML385 group were injected intraperitoneally with ML385 (30 mg · kg -1) once a day for consecutive 7 days.And 5 days before modeling, rats in SAH+ CTX group and SAH+ CTX+ ML385 group were treated with CTX(200 mg · kg -1) by intraperitoneal injection once a day for five consecutive days.Rats in Sham group and SAH group were intraperitoneally injected with the same amount of 0.9% sodium chloride solution.After 24 hours of modeling, the neurological function score and brain tissue water content of rats in each group were measured.HE staining was used to observe the morphology of neurons in CA1 and CA3 regions of hippocampus.Prussian blue staining was used to observe the iron deposition in cerebral cortex.Spectrophotometer was used to determine the iron content, malonic dialdehyde(MDA) content, glutathione(GSH) content and GPX4 activity in cerebral cortex.Western blot was used to detect the expression levels of Nrf2 and GPX4 proteins in cerebral cortex.SPSS 23.0 was used for statistical analysis.One-way ANOVA was used to compare the mean of multiple groups of samples, and Dunnett- t test was used for further pairwise comparison between groups. Results:There was a statistically significant difference in the neurological function scores of rats in the four groups 24 hours after SAH ( F=48.40, P<0.001). The neurological function score of rats in the SAH group 24 hours after SAH was significantly lower than those in Sham group and SAH+ CTX group (both P<0.05). The brain water content of rats in the four groups 24 h after SAH was statistically significant ( F=49.61, P<0.001). The brain water content of rats in the SAH group 24 h after SAH was significantly higher than that in Sham group and SAH+ CTX group(both P<0.05). There was statistically significant differences in the number of neuronal necrosis in CA1 and CA3 regions of hippocampus in the four groups 24 hours after SAH ( F=17.44, 246.50, both P<0.001). The numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH group were significantly higher than those in Sham group and SAH+ CTX group, and the numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH+ CTX+ ML385 group were significantly higher than those in SAH+ CTX group (all P<0.05). Twenty-four hours after SAH, the amount of iron deposited in the cerebral cortex of rats in the four groups was statistically significant ( F=2 363.0, P<0.001). The iron deposition in the cerebral cortex of rats in the SAH group was significantly higher than those in Sham group and SAH+ CTX group (both P<0.05). There were significant differences in iron content, MDA content, GSH content and GPX4 activity in the cerebral cortex of the four groups 24 h after SAH( F=2 380.0, 1 322.0, 789.1, 815.5, all P<0.001). The content of iron and MDA in the cerebral cortex of rats in SAH group were significantly higher than those in Sham group, while the content of GSH and the activity of GPX4 were significantly lower than those in Sham group (all P<0.05). The content of iron and MDA in the cerebral cortex of rats in SAH+ CTX group were lower than those in SAH group, and the content of GSH and the activity of GPX4 were higher than those in SAH group (all P<0.05). At 24 h after SAH, the expression levels of Nrf2 and GPX4 protein in the cerebral cortex of the four groups were statistically significant ( F=888.7, 1 556.0, both P<0.001). The protein expression levels of Nrf2 (0.382±0.014) and GPX4 (0.329±0.019) in the cerebral cortex in SAH group were lower than those in Sham group ((0.746±0.009), (0.953±0.009)) (both P<0.05). The expression levels of Nrf2 (0.631±0.006) and GPX4 (0.833±0.008) protein in the cerebral cortex in the SAH+ CTX group were significantly higher than those in the SAH group (both P<0.05). The expression levels of Nrf2 (0.427±0.009) and GPX4 (0.525±0.011) protein in the cerebral cortex in SAH+ CTX+ ML385 group were significantly lower than those in SAH+ CTX group (both P<0.05). Conclusion:Ceftriaxone may inhibit ferroptosis during EBI in SAH rats by regulating Nrf2/GPX4 signal axis.
Résumé
Objective@#To investigate the relationship between urinary monohydroxylated metabolites of hydroxyl polycyclic aromatic hydrocarbons (OH-PAHs) and lung function, as well as the role of oxidative stress in these associations, so as to provide a scientific basis for air pollution control and policy formulation.@*Methods@#A panel study was carried out among 45 young healthy adults. Four follow up surveys and health examinations were conducted from November 2017 to October 2018 to measure lung function parameters [forced vital capacity (FVC), second forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), FEV1/FVC, and forced expiratory flow between 25% and 75% vital capacity (FEF 25%~75% )], markers of exposure to 7OHPAHs [∑ 7OH PAHs], and markers of oxidative stress[8 hydroxy 2 deoxyguanosine (8 OHdG) and 8 isoprostaglandin F 2α (8 iso PGF 2α )]. The relationship between urinary PAH metabolites and lung function was quantified by linear mixed effects models. Mediation analysis was performed to assess the role of oxidative stress in the relationship between OH PAHs and lung function.@*Results@#The median values of FVC, FEV1, FEVI/FVC, PEF, and FEF 25%-75% were 4.37 L, 3.58 L, 83.00%, 4.38 L/s, and 3.32 L/s, respectively. The results showed that each 1 unit increase in log transformed value of 2 Hydroxyfluorene (2 OHFlu) was associated with a 5.05% decrease ( β %=-5.05%,95% CI =-8.85%--1.09%) in FVC, 4.15% decrease ( β %=-4.15%,95% CI =-7.94%- -0.22% ) in FEV1 and 5.87% decrease ( β %=-5.87%,95% CI =-11.35%--0.05%) in FEF 25%-75% , respectively. Each 1 unit increase in log transformed values of 2 OHFlu and 9 Phenanthrol (9 OHPhe) was associated with a 7.03% decrease ( β %=-7.03%,95% CI =-12.60%--1.11%) and a 7.08% decrease ( β%=-7.08%,95% CI =-13.50%--0.17%) in PEF, respectively. Additionally, urinary ∑ 7OH PAHs had a positive correlation with the levels of urinary 8 OHdG and 8 iso PGF 2α ( r =0.64, 0.69, P <0.01). Meanwhile, the levels of 8 OHdG mediated 17.06% and 15.71% of the association between 2 OHFlu with FVC and FEV1.@*Conclusion@#The finding reveales a negative relationship between urinary OH PAHs and lung function among young healthy adults. The 8 OHdG plays a mediated role in the correlation of 2 OHFlu with FVC and FEV1. Active relevant policies are needed to control air pollution and maintain the healthy living conditions of young people.
Résumé
Objective:To explore the effects of enriched environment combined with melatonin on learning and memory function and DNA oxidative damage in senescence accelerated mouse prone 8 (SAMP8) mice.Methods:Twenty-four 6-month-old SPF healthy male SAMP8 mice were randomly divided into model group, enriched environment group, melatonin group and enriched environment+ melatonin group, with 6 mice in each group. Six homologous SAMR1 mice of the same age were used as the control group. The mice in the enriched environment group and the enriched environment+ melatonin group were fed in the enriched environment. At the same time, the mice in the melatonin group and the enriched environment+ melatonin group were subcutaneously injected with melatonin (8 mg /(kg·d)) once a day for 28 d. The mice in the model group, the control group and the enriched environment group were subcutaneously injected with an equal volume of 0.9% sodium chloride solution once a day for 28 days. Aging score was used to evaluate the aging of mice. Morris water maze and Y maze tests were used to evaluate the learning and memory ability of mice. The cell morphology of hippocampus in mice was observed by hematoxylin-eosin staining, and the level of Aβ 1-42 protein in hippocampus of mice was detected by immunohistochemical staining. The levels of γ-H2A histone family member X(γ-H2AX) and 8-hydroxy-2 deoxyguanosine(8-OHdG) proteins in hippocampus of mice were detected by Western blot and Enzyme-linked immunosorbent assay. SPSS 25.0 statistical software was used to process the data. One-way analysis of variance was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1)There was a statistical difference in aging scores among the 5 groups of mice after intervention ( F=126.4, P<0.01). After intervention, the aging scores of mice in the enriched environment group, melatonin group, and enriched environment+ melatonin group were lower than that in the model group (all P<0.05), and the score of the enriched environment+ melatonin group was significantly lower than that in the enriched environment group ( P<0.05). (2)The time and group interaction, group main effect and time main effect of the escape latency among the 5 groups of mice were statistically significant ( F=11.2, 799.9, 121.8, all P<0.01). From day 2 to day 4, the escape latencies of mice in the enriched environment group, melatonin group and enriched environment+ melatonin group were significantly lower than that in the model group (all P<0.05). There was a statistically significant difference in the target quadrant residence time and cross-platform times among the 5 groups ( F=70.38, 48.83, both P<0.01). The target quadrant residence time and cross-platform times of mice in the enriched environment group, melatonin group, and enriched environment+ melatonin group were significantly higher than that in the model group (all P<0.05). (3) There were significant differences in the total number of alternations and correct rates among the 5 groups ( F=291.328, 113.482, both P<0.01). The total numbers of alternations and correct rates in melatonin group ((29.46±3.75)times, (53.16±3.47)%) and the enriched environment+ melatonin group((32.57±3.52)times, (58.60±4.13)%)were significantly higher than those in the model group ((18.62±3.96)times, (43.61±3.92) %)(all P<0.05). (4)The results of hematoxylin-eosin staining and immunohistochemistry staining showed that compared with the model group, the cell structure and morphology of the hippocampus of mice in enriched environment group, melatonin group, and enriched environment+ melatonin group were significantly improved, and the expression of Aβ 1-42 was significantly reduced (all P<0.05). (5) There were statistically significant differences in the levels of γ-H2AX and 8-OHdG proteins in the hippocampus of the 5 groups of mice ( F=78.09, 117.20, both P<0.01). The levels of γ-H2AX and 8-OHdG of mice in the enriched environment+ melatonin group ((1.37±0.26), (4.79±0.35)pg/μg) were significantly lower than those in the enriched environment group ((2.83±0.25), (7.23±0.41)pg/μg) and the melatonin group ((2.43±0.22), (6.69±0.28)pg/μg) (all P<0.05). Conclusion:Both enriched environment and melatonin can significantly improve the learning and memory function of SAMP8 mice, and the combined treatment effect is more significant.The mechanism may be related to the reduction of DNA oxidative damage in hippocampus.
Résumé
Objective:To explore the effects and possible mechanisms of melatonin combined with enriched environment on the learning and memory ability of senescence-accelerated mouse prone 8(SAMP8).Methods:Forty-eight SAMP8 male mice aged 4 months were randomly divided into model group, enriched environment group, melatonin group and melatonin combined with enriched environment group (combined intervention group) by random number table method, with 12 mice in each group. Mice in the melatonin group and combined intervention group were subcutaneously injected with melatonin at a dose of 8 mg·kg -1·d -1, and the mice in the model group and the enriched environment group were given the same amount of normal saline instead.The mice in model group and melatonin group were raised in a standard environment, and the mice in enriched environment group and combined intervention group were raised in an enriched environment.The intervention lasted 28 days. The aging degree of mice was scored before and 28 days after the intervention. Morris water maze test was used to detect the learning and memory ability of mice. Nissl staining and TUNEL staining were used to observe the Nissl staining positive cells and apoptotic cells in the CA1 area of hippocampus.ELISA was used to detect the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the hippocampus of mice. Western blot was used to detect the levels of amyloid β-protein (Aβ) 1-42, microtubule-associated protein tau (tau) phosphorylated at threonine (Thr) 205 (Tau pT205), Toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB) p65 protein in the hippocampus of mice. qRT-PCR was used to detect the levels of TLR4, NF-κB p65 mRNA in the hippocampus of mice. SPSS 22. 0 statistical software was used for repeated measure ANOVA, one-way ANOVA and LSD test. Results:(1) Aging score: after intervention, the aging scores of mice in the four groups were significantly different ( F=120.601, P<0.01). The aging scores of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group (all P<0.05), while the aging score of mice in the combined intervention group was significantly lower than those in the enriched environment group and melatonin group (both P<0.05). (2) The results of the location navigation experiment showed that the time × group interaction effect of the escape latencies of mice in the four groups were significant ( F=30.524, P<0.001). From the 2nd to 4th day, the escape latencies of mice in the enriched environment group, melatonin group and combined intervention group were all lower than that in the model group (all P<0.05). The results of the space exploration experiment showed that the residence time in the target quadrant and the number of platform crossings of mice in the four groups were significantly different ( F=291.328, 113.482, both P<0.01). The residence time in the target quadrant ((29.45±1.70)s, (32.44±1.55)s, (37.48±0.84) s) and the number of platform crossings ((6.44±0.61) times, (7.16±0.70) times, (12.60±1.23) times) of mice in the enriched environment group, melatonin group and combined intervention group were higher than those in the model group ((15.07±1.28) s, (4.10±0.61) times), while the residence time in the target quadrant and the number of platform crossings of mice in the enriched environment group and the melatonin group were significantly lower than those in the combined intervention group (all P<0.05). (3) Nissl and TUNEL staining showed that the number of Nissl positive neurons in the hippocampal CA1 region of mice in the four groups were significantly different ( F=809.264, P<0.01), and the number of apoptotic cells in the hippocampal CA1 region were also significantly different ( F=1 060.583, P<0.01). The number of Nissl stained positive neurons in the hippocampal CA1 region of mice in the combined intervention group was more than those in the model group, enriched environment group, and melatonin group (all P<0.05), and the number of apoptotic cells were less than those in the model group, enriched environment group, and melatonin group (all P<0.05). (4) The results of ELISA assay showed that there were significantly different in the levels of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the four groups ( F=152.887, 63.506, 432.026, all P<0.01). The contents of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group(all P<0.05). Among them, the contents of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). (5) Western blot analysis showed that there were significantly different in the protein expression levels of Aβ1~42, tau pT205, TLR4, NF-κB p65 in the hippocampus of mice in the four groups ( F=122.349, 98.934, 201.635, 116.553, all P<0.01). The protein expression levels of Aβ1-42, tau pT205, TLR4, and NF-κB p65 in the hippocampus of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group.Among them, the protein expression levels of Aβ1-42, tau pT205, TLR4, NF-κB p65 in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). (6) qRT-PCR showed that the mRNA expression levels of TLR4 and NF-κB p65 in the hippocampus of mice in the four groups were significantly different ( F=42.913, 102.446, both P<0.01). The mRNA expression levels of TLR4 ((0.63±0.05), (0.55±0.04), (0.42±0.03)) and NF-κB p65 ((0.98±0.06), (0.82±0.04), (0.72±0.04)) in the hippocampus of mice in the enriched environment group, melatonin group and combined intervention group were lower than those in the model group ((0.74±0.07), (1.20±0.05)) (all P<0.05). Among them, the mRNA expression levels of TLR4 and NF-κB p65 in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). Conclusion:Melatonin combined with enriched environment can improve the learning and memory ability and neuroinflammatory response of SAMP8 mice, and its mechanism may be related with the down-regulation of TLR4/NF-κB p65 signaling pathway.
Résumé
Objective:To evaluate the value of preoperative aspartate aminotransferaseto platelet ratio index (APRI) and fibrosis index 4 (Fib4) in predicting posthepatectomy liver failure (PHLF) of primary hepatocellular carcinoma.Methods:The data of 587 patients with hepatocellular carcinoma admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2014 to January 2020 were retrospectively collected and analyzed, including 412 males and 175 females, aged (56.8±11.2) years. Univariate and multivariate logistic regression were used to analyze the influencing factors of PHLF. The ability of Child-Pugh score, model for end-stage liver diseas (MELD) score, APRI and Fib4 to predict PHLF was evaluated through the receiver operating characteristic (ROC) curve of subjects.Results:Among 587 patients, 186 (31.7%) had liver failure after hepatectomy. In multivariate logistic regression analysis, APRI ( OR=2.660, 95% CI: 1.314-5.384, P=0.007) and Fib4 ( OR=1.322, 95% CI: 1.157-1.511, P<0.001) were risk factors for PHLF in patients with hepatocellular carcinoma. The higher the number, the greater the risk of PHLF. The predicted area under the ROC curve of PHLF in patients with hepatocellular carcinoma was Fib4(0.719)>APRI(0.686)>MELD score(0.618)>Child-Pugh score(0.565). Conclusion:APRI and Fib4 were risk factors of PHLF in patients with hepatocellular carcinoma. They predict the occurrence of PHLF better than Child-Pugh score and MELD score.
Résumé
5-Aminolevulinic acid (5-ALA) has been approved for clinical photodynamic therapy (PDT) due to its negligible photosensitive toxicity. However, the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells. Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair, a liposomal nanomedicine (MFLs@5-ALA/DFO) with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA, which was prepared by co-encapsulating 5-ALA and DFO (deferoxamine, a special iron chelator) into the membrane fusion liposomes (MFLs). MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery. MFLs@5-ALA/DFO could efficiently reduce iron ion, thus blocking the biotransformation of photosensitive protoporphyrin IX (PpIX) to heme, realizing significant accumulation of photosensitivity. Meanwhile, the activity of DNA repair enzyme was also inhibited with the reduction of iron ion, resulting in the aggravated DNA damage in tumor cells. Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.
Résumé
Objective To understand the public mental health status and related influencing factors during the epidemic of coronavirus disease 2019(COVID-19). Methods A structured questionnaire was used to conduct a questionnaire survey of the research subjects through an online platform. The public mental health status was assessed using the Symptom Checklist (SCL-90). Logistic regression analysis was used to analyze related influencing factors. Results The survey included 1 078 eligible questionnaires, of which 252 (23.38%) were positive on the SCL-90 scale. For each SCL-90 factor, the highest positive rate was anxiety (41.28%), followed by horror (35.16%), and depression (33.21%). Multivariate logistic regression analysis showed that from Hubei (OR=1.64, P=0.014), male (OR=1.37, P=0.036), medical related occupations or professions (OR=1.57, P=0.008), and high concern over the epidemic (OR=2.19, P=0.013) and known people with suspected or confirmed cases (OR=2.75, P<0.001) were risk factors influencing public mental health. Conclusion The mental health problems of the population during the epidemic of COVID-19 were serious, especially in Hubei. Male groups, medical workers, and people with relatives and friends who have a case need to pay attention to their own mental health. The government should increase the publicity of mental health knowledge to effectively prevent the occurrence and development of mental illness in these people.
Résumé
Due to its deep anatomic location and complex blood supply characteristics, hepatocellular carcinoma originating from the caudate lobe has become the difficulty in surgical resection, and radiofrequency ablation (RFA) is gradually applied to the treatment of hepatocellular carcinoma originating from the caudate lobe with the help of its advantages of precision and minimal invasiveness. This article briefly describes the anatomic characteristics of the caudate lobe, introduces the advances in radiofrequency approach for the caudate lobe, intraoperative guidance, and selection of RFA needle in detail, and summarizes the surgical safety and effectiveness of RFA associated with the caudate lobe through an analysis of the latest articles in recent ten years. It is concluded that RFA is a promising alternative for the treatment of hepatocellular carcinoma originating from the caudate lobe with the advantages of minimal invasiveness, good repeatability, and few complications, and it can also achieve the goal of complete ablation.
Résumé
Objective: To investigate the therapeutic effect of ceftriaxone in the rats with subarachnoid hemorrhage (SAH), and to clarify its mechanism. Methods: A total of 48 adult male SD rats were randomly divided into sham operation group, SAH group, 3-methyl adenine (3-MA) group and ceftriaxone (CEF) group; there were 12 rats in each group. The SAH models were established by intravascular puncture; the rats were administered intraperitoneally; the dose of 3-MA was 15 mg · kg-1, and the dose of CEF was 500 mg · kg-1. The rats were sacrificed 24 h after model establishment, and the pathology of brain tissue of the rats was observed by HE staining. The apoptosis of neurons was detected by TUNEL staining. The number of autophagy-related proteins Beclin-1 and LC3-II and the apoptosis factor Caspase-3 protein in hippocampus tissue of the rats in various groups were detected by immunohistochemistry and Western blotting methods. Results: Compared with SAH group, the neurological score of the rats in CEF group was significantly increased (P<0. 01). The HE staining results showed the nerve cells in the hippocampus area of the rats in SAH group were swollen with loose cytoplasm and had obvious nuclear condensation, fragmentation and dissolution; compared with SAH group, the neural degeneration of the rats in CEF group was improved, and more normal nerve tissue morphology appeared; while the nerve cell damage in 3-MA group was more serious, the dead nerve cells were in full filed, and the cell layers were disordered. The quantitative analysis results showed that the number of necrotic nerve cells in CEF group was significantly lower than that in SAH, and the number of necrotic nerve cells in 3-MA group was significantly higher than that in SAH group (P< 0. 05). The immunohistochemical staining results showed that the number of Beclin-1 and LC3-II posivive cells in hippocampus tissue of the rats in CEF group was significantly higher than that in SAH group (P<0. 05); the number of Beclin-1 and LC3-II positive cells in 3-MA group was significantly lower than that in SAH group (P< 0. 05). The TUNEL staining resluts showed that the number of apoptotic nerve cells in CEF group was significantly lower than that in SAH group (P<0. 05), and the number of apoptotic nerve cells in 3-MA group was higher than that in SAH group (P<0. 05). The Western blotting results showed that the expression level of Caspase-3 protein in hippocampus tissue of the rats in CEF group was significantly lower than that in SAH group (P<0. 05), while the expression level of Caspase-3 protein in 3-MA group was significantly higher than that in SAH group (P< 0. 05). Conclusion: CEF has the protective effect on the nerve injury of the rats with SAH, and its mechanism may be related to up-regulation of autophagy and reduction of apoptosis of the neurons.
Résumé
Objective@#To investigate the detection of thyroid nodules and related risk factors in nuclear power workers, and to provide scientific evidence for thyroid protection of nuclear power workers.@*Methods@#In December 2018, select 295 workers of a nuclear power production enterprise and 238 administrative staff of it, and select 250 staff members of a thermal power generation enterprise 70 kilometers away from the nuclear power station to conduct thyroid ultrasound examination and questionnaire survey for single factor. Analysis and further multivariate logistic regression analysis were used to study the risk factors of thyroid nodules in the population.@*Results@#Women and smoking history were independent risk factors for the increased incidence of thyroid nodules in the study population; three shifts work pattern was an independent risk factor for the increased prevalence of thyroid nodules in nuclear power workers (P<0.05) , and other factors such as the history of nuclear exposure had no significant correlation with thyroid nodules (P>0.05) .@*Conclusion@#Nuclear exposure has little effect on the prevalence of thyroid nodules in nuclear power workers.
Résumé
Objective Toinvestigatetheconsistencyofultrasoundand MSCTindiagnosing microvascularinvasion (MVI)in hepatocellularcarcinoma,andtocomparethediagnosticefficiencyofbothtwomethods.Methods TheultrasoundandMSCTdataof 82patientswithhepatocellularcarcinomawerecollected.Accordingtothepostoperativepathologicalresults,theconsistencyanddiagnostic efficiencyofultrasoundandMSCTindiagnosingMVIinhepatocellularcarcinomawerecompared.Results Accordingtothepostoperative pathologicalfindingsof82patients,30caseswerepositiveofMVI,while52caseswerenegative.ThepreoperativeMSCTandultrasound examinations had a strong consistency (Cohen’s Kappa=0.829 ,P<0.001 ).The sensitivity ,specificity and accuracy of preoperative ultrasoundinpredictingtheMVIinhepatocellularcarcinomawere76.67% (23/30),67.31% (35/52)and70.73% (58/82),respectively. Thesensitivity,specificityandaccuracyofpreoperativeMSCTinpredictinghepatocellularcarcinomaMVIwere83.33% (25/30),73.08%(38/52)and75.61% (63/82),respectively.Conclusion Preoperativeultrasoundand MSCThavegoodconsistencyandhighdiagnostic efficiencyindiagnosing MVIinhepatocellularcarcinoma.
Résumé
Objective To investigate the interaction between traditional Chinese medicine syndromes of patients with chronic heart failure (CHF) and the primary pathogenesis of CHF, so as to grasp the distribution regularity of TCM syndrome caused by different primary diseases and provide reference for better intervention of CHF. Methods A total of 580 patients with CHF were included in the clinical cross-sectional study. The baseline data of the patients, the primary disease and the four diagnosis information of TCM were collected. The syndromes of TCM were judged and the logistic regression method was used to analyze the correlation of CHF and the distribution of syndromes. Results Analysis of TCM Syndromes of CHF showed that the main syndromes were Qi deficiency syndrome, blood stasis syndrome, water retention syndrome, yin deficiency syndrome, phlegm syndrome, and yang deficiency syndrome. Further analysis showed that the above causes of CHF were related to the distribution of TCM syndromes. When coronary heart disease is the primary disease, blood stasis syndrome, yang deficiency syndrome, and yin deficiency syndrome are related to the occurrence of CHF (χ2 values are 0.480, 4.445, 0.192, P<0.05). When hypertension is the primary disease, blood stasis syndrome and phlegm syndrome are related to the occurrence of CHF (χ2 values are 12.344, 10.990, P<0.05); dilated cardiomyopathy is the primary disease, blood stasis syndrome and yang deficiency syndrome and chronic heart failure It is related (χ2=5.222, 3.456, P<0.05). Conclusions The distribution patterns of TCM Syndromes of CHF caused by different primary diseases were different, which was related to the pathogenesis of CHF. It is of great significance for better application of traditional Chinese medicine CHF syndrome differentiation during treatment, so as to form optimal treatment to reduce re-admitted into hospitalization rate and mortality in patients with CHF.
Résumé
Objective To investigate the effects of fasudil hydrochloride on learning and memory, and the autophagy in hippocampal CA1 neurons in subarachnoid hemorrhage (SAH) rats. Methods Fifty-four male Sprague-Dawley rats were randomly divided into sham group (n=18), SAH group (n=18) and drug group (n=18). Subarachnoid hemorrhage model was established with internal carotid artery punc-ture. The drug group was injected fasudil hydrochloride 10 mg/kg intraperitoneally after modeling per 24 hours, while the sham group and SAH group were injected the same volume of saline. They were tested with shuttle box test 6, 24 and 72 hours after intervention, then the hippocampal CA1 area was stained with HE and immunohistochemistry to observe the morphology of cells and the expression of Beclin-1 and microtubule-associated protein 1 light chain 3 II (LC3-II). Results Compared with the sham group, the frequence of avoidance de-creased in SAH group at each time point (P<0.05), while the avoidance reaction time increased (P<0.05);the survival of neurons in hippo-campal CA1 area decreased (P<0.05), and the expression of Beclin-1 and LC3-II increased (P<0.05). Compared with SAH group, the fre-quence of avoidance increased in the drug group at each time point (P<0.05), while the avoidance reaction time decreased (P<0.05);the sur-vival of neurons in hippocampal CA1 area increased (P<0.05) and the expression of Beclin-1 and LC3-II increased further (P<0.05). Con-clusion Fasudil hydrochloride can improve learning and memory ability and protect neurons from damage, which may associate with the ex-cess of autophagy activation in hippocampal CA1 areas in SAH rats.
Résumé
Objective To explore the regulation of PI3K-mTOR signaling pathways on autophagy of hippocampus nerve cells after subarachnoid hemorrhage (SAH)in rats.Methods We randomly divided 72 male Sprague-Dawley rats into sham group,SAH model group and LY294002 group with 24 rats in each group.We established SAH model with the secondary injection of blood method while the sham group was not injected with blood.PI3K signaling pathways specific inhibitor LY294002 was injected with 500μmol per rat 30 minutes before modeling.After 6,24,72 and 144 h morphologic changes of hippocampus CA1 neural cells were observed by microscopy;the expression levels of PI3K,mTOR,Beclin-1 and LC3-Ⅱ were detected by immunohistochemical method.Results The density of survival neurons in the SAH group was significantly lower than that in the control group (P<0.05),PI3K-mTOR signaling pathways were activated obviously,and the expressions of Beclin 1 and LC3-Ⅱ were significantly higher than those in the control group (P<0.05 ).The number of survival neurons significantly decreased in the LY294002 group compared with the SAH group at each time point (P<0.05),PI3K-mTOR signaling pathways were suppressed.The expressions of Beclin-1 and LC3-Ⅱ were significantly lower than those in the SAH group (P<0.05).Conclusion PI3K-mTOR signaling pathways protect neurons by activating the autophagy of neurons after SAH.
Résumé
Objective Moderate autophagy helps improve the viability of neurocytes.This study aims to investigate the effect of SP600125 on the autophagy and loss of nerve cells in the hippocampus in rats with subarachnoid hemorrhage (SHA).Methods Forty healthy male SD rats were equally randomized into a sham operation, an DMSO group, an SAH model, and an SP600125 group.The SAH model was established by vascular puncture and the rats of the SP600125 group were injected with 10 μL of SP600125 (3 μg/μL) into the lateral cerebral ventricle at 30 minutes before modeling.Sham group and SAH group were injected with equal volume of normal saline, DMSO group was injected with the same amount of DMSO.The animals were sacrificed at 24 hours after modeling for observation of the changes in the morphology and the number of neurons in the hippocampus by HE staining and qualitative and quantitative determination of the expressions of the p-JNK protein and the autophagy markers beclin-1 and LC3-II by immunohistochemistry and Western blot.Results Compared with the sham operation group, the neurons exhibited a disordered arrangement and the cells were polygonal and decreased in number in the hippocampus of the SAH models, while milder neuronal injury and more cells were observed in the rats of the SP600125 group than in the SAH models.The mean optical density values of Beclin-1, LC3-II and p-JNK in the hippocampus were significantly higher in the SAH models (14.66±4.40, 12.62±3.46, and 12.82±3.68) and DMSO (13.85±3.85、11.59±4.52、13.03±3.53), and the SP600125 group (9.86±3.14, 6.78±2.56, and 5.60±2.42) than in the sham operation group (1.56±0.28, 1.60±0.30, and 1.58±0.32) (P<0.05), but markedly lower in the SP600125 than in the SAH model group (P<0.05).The expressions of Beclin-1, LC3-II and p-JNK were remarkably increased in the SAH models (0.474±0.122, 0.668±0.130, and 0.496±0.124) and DMSO (0.432±0.102、0.628±0.113、0.416±0.094) and the SP600125 group (0.264±0.106, 0.332±0.113, and 0.219±0.104) than in the sham operation group (1.56±0.28, 1.60±0.30, and 1.58±0.32) (P<0.05), but significantly decreased in the SP600125 group as compared with the SAH models (P<0.05).Conclusion SP600125 has a protective effect on the neurocytes in the hippocampus of SAH rats, which may be associated with SP600125 moderately activating neuronal autophagy by inhibiting the activity of the JNK signaling pathway.
Résumé
ABSTRACT:Objective To explore role of U0126,the specific inhibitor of ERK signaling pathway,in early brain injury (EBI)and the autophagy of nerve cells in hippocampus area in subarachnoid hemorrhage (SAH). Methods A total of 48 male adult SD rats were randomly divided into control group,SAH group,DMSO+SAH group,and U0126+SAH group,with 12 in each.We established SAH rat model by the puncture of internal carotid artery.The same amount of saline water,DMSO and U0126 solution of 0.5 mL per rat was injected respectively into the rats of different groups 30 min before modeling.The rats were killed at 24 h.To measure brain water content by Wet and dry method after 24 h,the morphological changes of hippocampus CA1 neural cells were observed by microscopy;the expression levels of ERK,Beclin-1 and LC3 were detected by using immunohistochemical method. Results Compared with that in sham group,brain water content increased obviously in SAH model group.The density of surviving neurons in SAH group was significantly lower than that in control group (P<0 .0 5 ).ERK signaling pathway was activated obviously,the expressions of Beclin 1 and LC3-Ⅱ were significantly higher than those in control group (P<0.05).Compared with SAH model group,in U0126 group brain water content increased obviously.Compared with those in SAH group,the density of surviving neurons was significantly lower (P<0.05), ERK signaling pathway was suppressed,the expressions of Beclin-1 and LC3-Ⅱ were significantly lower (P<0.05). Conclusion The U0126,the ERK signaling pathway inhibitor,can inhibit neuron autophagy and increase EBR of SAH.
Résumé
Objective To investigate the relationship of extracellular regulated protein kinases activation and neural cells autophagy in rats after subarachnoid hemorrhage.Methods One hundred twenty male SD rats were randomly divided into sham operated group,SAH group,ERK1/2 inhibitor U0126 group,autophagy inducer rapamycin (Rap) group.The animal models were established by injecting the autologous blood into cisterna magna twice.U0126 (5μ g/μL) and Rap (10nmol/μL) were injected into lateral ventricles in U0126 group and Rap group 30min before SAH.The morphology of hippocampal nerve cells were examined by using light microscopy.The expression levels of phosphorylated ERK 1/2 (p-ERK 1/2),ERK 1/2mRNA and autophagy markers (Beclin-1 and Beclin-1 mRNA、LC3-Ⅱ and LC3mRNA) in the hippocampus were detected by using inmunohistochemistry and real-time fluorescence quantitative PCR.Result Compared with sham group,the rate of dead nerve cells,the mRNA levels of ERK1/2,Beclin-1 and LC3 as well as the levels of the p-ERK1/2,Beclin-1 and LC3-Ⅱ increased in SAH group (P<0.05).Compared with SAH group,the rate of dead nerve cells increased(P<0.05),the ERK1/2 mRNA,Beclin-1 mRNA and LC3 mRN A,and p-ERK1/2,Beclin-landLC3-Ⅱ in U0126 group decreased(P<0.05);the rate of dead nerve cells decreased (P<0.05),the Beclin-1 mRNA and LC3 mRNA,the Beclin-1and LC3-Ⅱ level increased in Rap group(P<0.05),but ERK 1/2 mRNA and p-ERK 1/2 remained unchanged (P>0.05).Conclusion Activation of the ERK1/2 signaling pathway after SAH,can induce nerve cells death by increasing Beclin-1 and LC3-Ⅱ expressions.