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Cerebral hypoxia often brings irreversible damage to the central nervous system, which seriously endangers human health. It is of great significance to further explore the mechanism of hypoxia-associated brain injury. As a programmed cell death, ferroptosis mainly manifests as cell death caused by excessive accumulation of iron-dependent lipid peroxides. It is associated with abnormal glutathione metabolism, lipid peroxidation and iron metabolism, and is involved in the occurrence and development of various diseases. Studies have found that ferroptosis plays an important role in hypoxia-associated brain injury. This review summarizes the mechanism of ferroptosis, and describes its research progress in cerebral ischemia reperfusion injury, neonatal hypoxic-ischemic brain damage, obstructive sleep apnea-induced brain injury and high-altitude hypoxic brain injury.
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Humanos , Recém-Nascido , Ferroptose , Apoptose , Hipóxia-Isquemia Encefálica , Lesões Encefálicas , Ferro , Traumatismo por ReperfusãoRESUMO
In order to clarify the influence of acute hypobaric hypoxia on the bile acids of the rat small intestine, we used ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to identify bile acids in the contents of the small intestine from untreated and acute hypobaric hypoxia-treated rats. Thirty-nine bile acids were detected; PCA and OPLS-DA analysis revealed marked differences in the composition of bile acids between the untreated and the acute hypobaric hypoxia groups. Bile acids were screened with VIP > 1, |log2FC| ≥ 1, P < 0.05, and a total of 7 bile acids with significant differences in content between the two groups were obtained, including 5 conjugated bile acids, 2 unconjugated bile acids; in addition, the content of conjugated bile acids has risen in the treated group. This study demonstrated the influence of high-altitude hypoxic environment on bile acid composition and metabolism in rats. All the animal experiments in this study were approved by the 940th Hospital Ethics Committee (approval No: 2020KYLL012).
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Objective To evaluate the efficacy of low frequency pulsed electromagnetic field (LFPEMF) on peritumoral edema in patients with glioma, providing a theoretical basis for clinical treatment of peritumoral edema. Methods This study included 32 patients with recurrent cerebral glioma with peritumoral edema after the operation of glioma in department of glioma, Beijing Shijitan Hospital, Capital Medical University from March 2017 to December 2018.The period of LFPEMF treatment was 10-14 days.The clinical symptoms related to brain edema were recorded before and after treatment.The National Institutes of Health Stroke Scale (National Institute of health stroke scale, NIHSS), Karnofsky quality of life score (KPS), brain edema and tumor range in cranial MRI, T lymphocyte subgroup CD4+/CD8+, superoxide dismutase (SOD) were recorded.The SPSS21.0 statistical analysis software was used to carry out analysis by using self controlled study.P < 0.05 was statistically significant. Results After the treatment of LFPEMF, the results showed that LFPEMF was effective in 25 patients, invalid in 7 patients, and the total effective percentage was 78.13%.The area of brain edema was significantly improved after using LFPEMF(P < 0.05).There was no significant improvement in the area of brain tumor after using LFPEMF therapy (P>0.05).KPS and NIHSS scores improved significantly after using LFPEMF (P < 0.05). Conclusion In the patients with peritumoral edema of glioma, the application of LFPEMF in the patients′ Yongquan point and Lao Gong point can reduce peritumoral edema, and improve clinical symptoms.
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Objective To evaluate the efficacy of low frequency pulsed electromagnetic field (LFPEMF) on peritumoral edema in patients with glioma, providing a theoretical basis for clinical treatment of peritumoral edema. Methods This study included 32 patients with recurrent cerebral glioma with peritumoral edema after the operation of glioma in department of glioma, Beijing Shijitan Hospital, Capital Medical University from March 2017 to December 2018.The period of LFPEMF treatment was 10-14 days.The clinical symptoms related to brain edema were recorded before and after treatment.The National Institutes of Health Stroke Scale (National Institute of health stroke scale, NIHSS), Karnofsky quality of life score (KPS), brain edema and tumor range in cranial MRI, T lymphocyte subgroup CD4+/CD8+, superoxide dismutase (SOD) were recorded.The SPSS21.0 statistical analysis software was used to carry out analysis by using self controlled study.P < 0.05 was statistically significant. Results After the treatment of LFPEMF, the results showed that LFPEMF was effective in 25 patients, invalid in 7 patients, and the total effective percentage was 78.13%.The area of brain edema was significantly improved after using LFPEMF(P < 0.05).There was no significant improvement in the area of brain tumor after using LFPEMF therapy (P>0.05).KPS and NIHSS scores improved significantly after using LFPEMF (P < 0.05). Conclusion In the patients with peritumoral edema of glioma, the application of LFPEMF in the patients′ Yongquan point and Lao Gong point can reduce peritumoral edema, and improve clinical symptoms.
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The intestinal flora is a diverse microbial community living in the digestive tract of humans and animals. This microbial community can modify drugs in unpredictable ways, leading to changes in the pharmacokinetics of drugs in vivo and affecting their clinical efficacy. Here we review drug metabolism mediated by intestinal flora from three aspects: prodrug activation, drug inactivation, and toxicity. The effect of the stable hypoxic environment on the composition and quantity of intestinal flora and the effect on drug metabolism are discussed. Understanding the influence of intestinal flora on drug metabolism is not only conducive to individualized medication, but also conducive to rational drug design, allowing us to predict and understand individual drug response and regulate the intestinal microbiome to improve drug efficacy, thus promoting personalized medicine.
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BACKGROUND@#Conventional treatment has limited efficacy in relapsed/refractory B-cell lymphoma. Since chimeric antigen receptor T-cell (CAR-T) technology has shown high safety and results in high remission rates, we investigated its efficacy and safety in B-cell lymphoma treatment and analyzed potential affecting factors to provide evidence for therapeutic strategies and applications.@*METHODS@#We searched databases including PubMed, Embase, and Cochrane up to July 2019. Meta-analysis 1 was conducted to study the efficacy of CAR-T cell for treating B-cell lymphoma, measuring the response rate and complete remission rate as outcomes. Sub-group analysis was performed for age, pathological type, target antigen, co-stimulatory molecule, and conditioning chemotherapy. Meta-analysis 2 was undertaken on the safety of the treatment with the incidence rate of toxicity (cytokine-releasing syndrome [CRS], neurotoxicity) as an outcome.@*RESULTS@#Seventeen studies were included in the systematic review and meta-analysis. It was found that CAR-T cells had good therapeutic effects in the following cases: B-cell lymphoma (patients ≥65 years old); diffuse large B-cell lymphoma pathological type; patients with treatment target antigen other than CD19; patients treated with co-stimulatory molecules other than CD28, including 4-1BB+CD28 or 4-1BB; and patients treated with cyclophosphamide/fludarabine pre-treatment protocol conditioning chemotherapy. Although the CRS and neurotoxicity incidences were high, most were reversible with minimal risk of death.@*CONCLUSION@#CAR-T cell treatment is safe for clinical application; however, toxicity effects should be monitored.
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Objective To investigate the reasons of natural extinction of Oncomelania hupensis snails by comparing the difference of the water chemical properties between the snail-breeding marshland and non-snail marshland in Eastern Dongting Lake areas. Methods Three adjoining marshlands in Eastern Dongting Lake areas were selected, one was a snail-breeding marshland, the second was a non-snail marshland, and the third was a boundary zone between them. During the periods of water-rising season, wet season and water-falling season, the water samples from the bottom of 0.5 m were collected by the systematic random sampling method (200 m × 200 m grid method). In addition, the water samples below the surface of 0.5 m were also collected in the wet season. The physicochemical indexes of the sampling water were detected. Results According to the Surface Water Environmental Quality Standard (GB 3838–2002), the water quality indicators which were less than the detection limit were Cr, Cd, Zn, Hg, Cu, S－ and CN－ during the three sampling seasons. The pollutants which were slightly higher than Grade III but lower than Grade IV (Hg ≤ 1 μg/L, TP ≤ 0.1 mg/L) were Hg and TP. The pollutants below the Grade III included As and F－. The temperature and pH values were within the Grade III. The oxygen consumption indicators covering DO, COD and BOD in the water-rising season and wet season were within the Grade III, while the value of BOD was beyond the scope of Grade III but was between Grade Ⅳ (≤ 6 mg/L) and Grade V (≤ 10 mg/L) in the water-falling season. The differences of the water pollution indexes between the snail-breeding marshland and non-snail marshland were statistically significant, and these indexes included F－, As and pH in the water-rising season (P < 0.05); pH, BOD and Fat the surface layer in the wet season (P < 0.05); F－ at the bottom in the wet season (P < 0.05); TP and F－ in the water-falling season. Moreover, the above-mentioned indexes in the non-snail marshland of Qianliang Lake were higher than those in the snail-breeding marshland of Junshan Park. Thus, F－ was the only index which had statistical differences in every sampling season, and the concentration of F－ at the non-snail marshland was also higher than that at the snail-breeding marshland. In the water-rising season, the pH value at the non-snail marshland exceeded the suitable range for the growth of snails (6.8 to 7.8). Conclusion In the Eastern Dongting Lake area, the high concentration of F－ and pH of water may be responsible for the natural extinction of O. hupensis snails.
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Objective To investigate the reasons of natural extinction of Oncomelania hupensis snails by comparing the difference of the water chemical properties between the snail-breeding marshland and non-snail marshland in Eastern Dongting Lake areas. Methods Three adjoining marshlands in Eastern Dongting Lake areas were selected, one was a snail-breeding marshland, the second was a non-snail marshland, and the third was a boundary zone between them. During the periods of water-rising season, wet season and water-falling season, the water samples from the bottom of 0.5 m were collected by the systematic random sampling method (200 m × 200 m grid method). In addition, the water samples below the surface of 0.5 m were also collected in the wet season. The physicochemical indexes of the sampling water were detected. Results According to the Surface Water Environmental Quality Standard (GB 3838–2002), the water quality indicators which were less than the detection limit were Cr, Cd, Zn, Hg, Cu, S－ and CN－ during the three sampling seasons. The pollutants which were slightly higher than Grade III but lower than Grade IV (Hg ≤ 1 μg/L, TP ≤ 0.1 mg/L) were Hg and TP. The pollutants below the Grade III included As and F－. The temperature and pH values were within the Grade III. The oxygen consumption indicators covering DO, COD and BOD in the water-rising season and wet season were within the Grade III, while the value of BOD was beyond the scope of Grade III but was between Grade Ⅳ (≤ 6 mg/L) and Grade V (≤ 10 mg/L) in the water-falling season. The differences of the water pollution indexes between the snail-breeding marshland and non-snail marshland were statistically significant, and these indexes included F－, As and pH in the water-rising season (P < 0.05); pH, BOD and Fat the surface layer in the wet season (P < 0.05); F－ at the bottom in the wet season (P < 0.05); TP and F－ in the water-falling season. Moreover, the above-mentioned indexes in the non-snail marshland of Qianliang Lake were higher than those in the snail-breeding marshland of Junshan Park. Thus, F－ was the only index which had statistical differences in every sampling season, and the concentration of F－ at the non-snail marshland was also higher than that at the snail-breeding marshland. In the water-rising season, the pH value at the non-snail marshland exceeded the suitable range for the growth of snails (6.8 to 7.8). Conclusion In the Eastern Dongting Lake area, the high concentration of F－ and pH of water may be responsible for the natural extinction of O. hupensis snails.
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OBJECTIVE@#To investigate whether Ershen Pill (ESP, ) could alleviate the symptom of Pi (Spleen)-Shen (Kidney) yang deficiency (PSYD)-induced diarrhea in rat model and explore its anti-diarrhea mechanism.@*METHODS@#Seventy-five Sprague-Dawley rats were divided into 5 groups by a random number table, including control, positive, model, low-dose (LD) and high-dose (HD) ESP groups, 15 rats in each group. All the rats, except those in the control group, were developed PSYD induced-diarrhea based on its pathology and etiology. The rats in positive, LD and HD ESP groups were treated with Shenling Baizhu Pill (), LD (1.05 g/kg) or HD (3.50 g/kg) ESP petroleum ether extract once a day for 2 weeks, respectively. Body weight change and diarrhea index were measured. The histology scores of the kidney were evaluated via hematoxylin and eosin (HE) staining. Aquaporin-3 (AQP3) expression in the colon was analyzed by immunofluorescence, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot, respectively.@*RESULTS@#Compared with the model group, oral administration of LD and HD ESP prevented body weight loss and inhibited diarrhea after 2-week treatment (P<0.05). Kidney deterioration was impeded, and the histology score in LD and HD ESP groups were 8.2 and 10.5, respectively, which were both higher than those in the model group (P<0.05). In addition, ESP treatment alleviated rat colitis, and HD ESP significantly improved the AQP3 positive staining intensity in the colon tissue compared with the model group. The result from Western blot revealed that AQP3 protein synthesis in colon tissue of LD and HD ESP groups increased by 2.1- and 5.9-fold compared with the model group (P<0.05). qRT-PCR result showed that AQP3 gene expression in the HD ESP group was also up-regulated by 2.5-fold normalized to the model group (P<0.05).@*CONCLUSION@#ESP extract effectively alleviates the symptoms of PSYD and relieves PSYD-induced diarrhea by improving AQP3 synthesis in the colon.
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BACKGROUND@#Previous studies have shown that endogenous T cells play an important role in the prolonged survival time of high-grade glioma (HGG) patients. Our objectives were to investigate the features of T-cell receptor (TCR) repertoires in HGG patients and to elucidate any potential therapeutic value.@*METHODS@#During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing Tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). Then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in TCR beta chain (TRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data.@*RESULTS@#The Shannon diversity index (SHDI) of TRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). The SHDI of TRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ± 0.31 vs. 6.21 ± 0.33, t = -5.49, P = 0.002) and blood cells (6.02 ± 0.66 vs. 7.44 ± 0.32, t = -2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of TRBV9 and TRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of TRBV4 and TRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic TCR sequence.@*CONCLUSIONS@#HGG patients have less species diversity of TCR repertoires compared with that of healthy individuals. TRBV9 regions in TCRs may be protective factors for long-term survival of GBM patients.
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Glioma , Genética , Metabolismo , Mortalidade , Terapêutica , Imunoterapia , Reação em Cadeia da Polimerase , Receptores de Antígenos de Linfócitos T , Química , Genética , Fatores de TempoRESUMO
Objective:To study the effect of weight relief raise on acromiohumeral distance in patients with thoracolumbar spinal cord injury. Methods:The acromiohumeral distance of 20 patients with thoracolumbar spinal cord injury was measured by ultrasonic diagnostic system, respectively in the resting position and the supporting decompression position. Results:The acromiohumeral distance was significantly larger in the resting position than in the supporting decompression position (t = 6.933, P < 0.001). Conclusion:Support could reduce the subacromial space in patients with spinal cord injury and become a potential factor for subacromial tissue injury.
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Background@#Previous studies have shown that endogenous T cells play an important role in the prolonged survival time of highgrade glioma (HGG) patients. Our objectives were to investigate the features of T-cell receptor (TCR) repertoires in HGG patients and to elucidate any potential therapeutic value.@*Methods@#During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing Tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). Then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in TCR beta chain (TRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data.@*Results@#The Shannon diversity index (SHDI) of TRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). The SHDI of TRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ± 0.31 vs. 6.21 ± 0.33, t = -5.49, P = 0.002) and blood cells (6.02 ± 0.66 vs. 7.44 ± 0.32, t = -2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of TRBV9 and TRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of TRBV4 and TRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic TCR sequence.@*Conclusions@#HGG patients have less species diversity of TCR repertoires compared with that of healthy individuals. TRBV9 regions in TCRs may be protective factors for long-term survival of GBM patients.
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Objective Based on the main morphological traits and chemical constituents of 42 Glycyrrhiza uralensis germplasm in China, the genetic diversity of them was analyzed comprehensively. Methods Twelve morphological traits and five kinds of chemical components of G. uralensis germplasm transplanted in the same place were collected. The genetic diversity index and coefficient of variation were calculated, using cluster analysis and principal component analysis for statistical analysis. Results Among the five chemical constituents, the highest genetic diversity index of liquiritin content was 2.05; The maximum coefficient of variation of isoliquiritin content was 99.50%; The content of liquiritin was moderately correlated with the content of isoliquiritin. Among 12 morphological traits, the highest genetic diversity index of plant height was 2.08, and the maximum coefficient of variation of actual fruit sequence was 37.09%. The variation of fruit type and plant type was greater than that of leaf type. Cluster analysis divided 42 germplasms into three types, and the second group had better germplasm quality. The principal component analysis reduced 17 indicators to six factors, with a cumulative contribution rate of 72.96%. Factor 6 was a factor that represents glycyrrhizic acid, liquiritin, and isoliquiritin. Conclusion The genetic diversity of the main morphological traits and chemical constituents of 42 G. uralensis germplasms is rich, and six excellent germplasms are V08, V10, V17, V34, V36, and V38.
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Salvia miltiorrhiza is one of the commonly used bulk medicinal materials, which has significant effect on cardiovascular disease, and are heavy demanded in Asia, Europe, North America, Russia and Africa. Consequently, increasing the yield and quality of S. miltiorrhiza has become a major concern worldwide. With the current wild resources of S. miltiorrhiza gradually decreasing, cultivated products occupy most of the markets. However, the cultivation area is widely distributed and the cultivation techniques is different, which lead to the quality and yield of S. miltiorrhiza in consistent. This paper combined visiting survey with document analysis to carry out the cultivation situation of S. miltiorrhiza in main cultivation areas of Shandong, Henan, Sichuan, Shanxi and Hebei provinces. There exist big differences of the ecological environment, mode of cultivation, fertilization, pest control, harvesting processing among the producing areas. We should carry on the ecological suitability zoning analysis and suitable cultivation of each area study to form a pattern of high quality and high yield for the sustainable development of S. miltiorrhiza cultivation.
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Agricultura , Métodos , Europa (Continente) , Plantas Medicinais , Salvia miltiorrhizaRESUMO
Drug metabolism is significantly affected under hypoxia environment with changes of pharmacokinetics, expression and function of drug-metabolizing enzymes and transporters. Studies have shown that hypoxia increases the release of a series of inflammatory cytokines which can modulate drug metabolism. Besides, both hypoxia inducible factor 1α (HIF-1α) and microRNA-mediated pathways play a role in regulating drug metabolism. This article reviewed the impact and single-factor modulating mechanisms of drug metabolism under hypoxia, and put forward the speculation and prospects of multi-factor modulating mechanisms.
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Humanos , Hipóxia Celular , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Fisiologia , Proteínas de Membrana Transportadoras , Fisiologia , MicroRNAs , Fisiologia , Preparações Farmacêuticas , MetabolismoRESUMO
Objective · To analyze the multidetector CT (MDCT) manifestations of mesenteric venous thrombosis (MVT) and further explore the diagnostic value of MDCT in acute and chronic MVT. Methods · MDCT findings of 47 MVT patients clinically confirmed in Shanghai Sixth People's Hospital, Shanghai Jiao Tong University and Second People's Hospital in Kashgar from January 2012 to October 2018 were retrospectively analyzed. The mean CT value of thrombus on CT axial images of acute and chronic MVT was measured and calculated. According to CT values and CT manifestations, differences between the two groups were statistically analyzed. Results · Among 47 patients with MVT, there were 46 (97.87％) with filling defect of mesenteric vein and its branches, 34 (72.34％) with dilatation of blood vessels at the thrombosis site, 30 (63.82％) with intestinal wall thickening, 9 (19.15％) with enhanced delamination of intestinal wall, 11 (23.40％) with intestinal dilatation, 21 (44.68％) with ascites, and 25 (53.19％) with mesenteric edema. The mean CT value of MVT thrombus in acute group [ (42.88±17.77) HU] was higher than that in chronic group [ (31.80±6.18) HU] (P＜0.05). The proportion of MVT with vasodilation and target sign in acute group was higher than that in chronic group (P＜0.05). There was no difference in the ratio of other signs between the two groups. Conclusion · The MDCT findings of MVT patients are characteristic. CT value of thrombus, vasodilation and target sign are valuable in evaluating acute and chronic MVT.
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In this study, the change of intestinal microflora in rat fecal samples after amoxicillin administration was observed. In vitro incubation experiments combined with LC-MS/MS assay were used to test the role of intestinal flora in the metabolism of nifedipine. The effect of changes of intestinal flora was determined after amoxicillin administration on the metabolism of nifedipine. We found that the number and types of intestinal flora decreased after taking amoxicillin. After incubation for 12 h, the results showed that the remaining amounts of nifedipine in the N1 group (nifedipine) and N2 group (amoxicillin + nifedipine) were 0.057 6 and 0.064 8 μmol·L-1, respectively, while the remaining amounts of nifedipine after 24 h of incubation were 0.039 6 and 0.050 4 μmol·L-1, respectively. These results show that the intestinal flora is involved in the metabolism of nifedipine. After administration of amoxicillin, the metabolism of nifedipine was slowed down, the AUC0-t was increased by 39.10%, tmax was advanced by 0.45 h, and the CL was reduced 34.71%. The data suggest that the combination may enhance the therapeutic effect of nifedipine. Therefore, drug-drug interactions mediated by gut microbiota cannot be ignored when combined with antibiotics and nifedipine, one of the important factors affecting drug efficacy.
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Plateau environment has the characteristic of low ox-ygen and low pressure, which leads to a series of physiological changes and affects the process of drug metabolism in the body. Many factors affect the pharmacokinetic parameters, including gastric emptying, blood rheology, cardiopulmonary function, hepatorenal function, cytochrome P450 enzyme and so on. The present study focuses on drug metabolic enzymes, since drug transporter is the key factor that mediates drugs in their entrance to the body through the cell membrane, producing the curative effect. In order to provide the reference to further research on the effect of plateau hypoxia on pharmacokinetics and guide the rational use of drugs, we review in this paper the classification of the transporter, mediated drug substrates, the influence of hypoxia on expression levels of drug transporter substrates and the regulatory mechanism of drug transporter under the condition of hypoxia.
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BACKGROUND:Due to limited sources,poor hemocompatibility and poor anticoagulation performance,small-diameter tissue-engineered blood vessels cannot be applied in clinical practice.OBJECTIVE:To explore the physicochemical and mechanical properties of sheep carotid arteries after the decellularization in order to find appropriate materials for the preparation of tissue-engineered blood vessels.METHODS:Fresh carotid arteries from sheep were randomly divided into two groups:control group,in which,the sheep carotid arteries were cryopreserved for use after trimming and cleaning;experimental group,in which,after trimming and cleaning,the carotid arteries were decallularized by Triton X-100.sodium deoxycholate and EDTA for 24 hours,rinsed for 72 hours,digested with RNA/DNA enzymes for 24 hours,rinsed for 24 hours and reserved for later use.In both groups,blood samples were subjected to hematoxylin-eosin staining,collagen fiber staining,elastic fiber dyeing,and electron microscopy observation.The physical and chemical properties of the blood vessels are tested by tensile strength,wall tension and thickness.RESULTS AND CONCLUSION:(1) The collagen fibers in both two groups were neat and compact in alignment,with no obvious fracture.(2) Hematoxylin-eosin staining showed that:in the control group,the nuclei were distributed in the inner membrane,middle lamella and outer membrane of the vessels,and the fibers ran regularly;in the experimental group,the fibers ran in order but loosely,and there were no nuclei in the inner membrane,middle lamella and outer membrane of the vessels.(3) Elastic fibers in the control group were regular in alignment and mainly distributed in the middle lamella and outer membrane of the vessels,while in the experimental group,the elastic fibers ran regularly but loosely,and mainly distributed in the middle lamella and outer membrane of the vessels.(4) Under the scanning electron microscope,the originally formed vessels were observed in the experimental group,with no cell residues,and the collagen fibers ran orderly with no fracture and with uniform pore structure.(5) The vessel thickness was lower in the experimental group than the control group (P ＜ 0.01),but the tensile strength showed no difference between the two groups,which was 46.55 kPa in the two groups.To conclude,the decelluarized sheep carotid artery can retain the necessary mechanical properties of the blood vessels after achieving the maximum removal of antigenicity.
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<p><b>Objective</b>A comprehensive review of the network regulation of exosomes and microRNAs (miRNAs) in neurodegenerative diseases was done, centering on the mechanism of the formation of exosomes and miRNAs and the sorting mechanism of exosomal miRNAs, with the aim to provide a theoretical basis in the search of biomarkers and the treatment of neurodegenerative diseases.</p><p><b>Data Sources</b>The comprehensive search used online literature databases including NCBI PubMed, Web of Science, Google Scholar, and Baidu Scholar.</p><p><b>Study Selection</b>The study selection was based on the following keywords: exosomes, miRNAs, central nervous system (CNS), and neurodegenerative diseases. The time limit for literature retrieval was from the year 2000 to 2018, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type.</p><p><b>Results</b>Exosomes are the smallest nanoscale membranous microvesicles secreted by cells and contain important miRNAs, among other rich contents. In the CNS, exosomes can transport amyloid β-protein, α-synuclein, Huntington-associated protein 1, and superoxide dismutase I to other cells. These events relieve the abnormal accumulation of proteins and aggravating neurological diseases. In some neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, miRNAs are pathologically altered as an inexorable course, suggesting that miRNAs may contribute neurodegeneration. Exosomes and miRNAs form a network to regulate the homeostasis of the CNS, both synergistically and individually.</p><p><b>Conclusion</b>The network of exosomes and miRNAs that regulates CNS homeostasis is a promising biomarker for the diagnosis and treatment of neurodegenerative diseases.</p>