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Objective To investigate the efficacy of Jingangteng Capsules combined with Guizhi Fuling Capsules(GFC)for the treatment of patients with chronic pelvic inflammation of damp-heat and stasis obstruction type and to observe their effects on serum granulocyte-macrophage colony-stimulating factor(GM-CSF)and matrix metalloproteinase 2(MMP-2)levels.Methods Ninety patients with chronic pelvic inflammation of damp-heat and stasis obstruction type were randomly divided into the combined group and the GFC group,with 45 patients in each group.Patients in the GFC group were treated with Guizhi Fuling Capsules,while patients in the combined group were given Jingangteng Capsules together with GFC.The treatment period lasted for 2 weeks and then one-month follow-up was conducted.The changes of traditional Chinese medicine(TCM)scores,serum GM-CSF and MMP-2 levels in the two groups were observed before and after treatment.And the clinical efficacy,time for the relief of symptoms,recurrence of disease and occurrence of adverse reactions in the two groups were compared.Results(1)After 2 weeks of treatment,the total effective rate of the combined group was 93.33%(42/45),and that of the GFC group was 66.67%(30/45).The intergroup comparison showed that the therapeutic effect of the combined group was significantly superior to that of the GFC group when comparing the two groups(P<0.01).(2)After treatment,the scores of TCM symptoms of lower abdominal pain,lumbosacral pain,leukorrhagia,profuse menstruation,dysmenorrhea,and fatigue in both groups were significantly lower than those before treatment(P<0.05),and the reduction of TCM syndrome scores in the combined group was significantly superior to that in the GFC group(P<0.05).(3)The time for leucorrhea recovering normal and the time for the relief of lower abdominal distension and abdominal pain in the combined group were significantly shorter than those in the GFC group after treatment(P<0.01).(4)After treatment,the serum serological indicators of GM-CSF and MMP-2 levels in the two groups were significantly decreased compared with those before treatment(P<0.05),and the reduction of serum GM-CSF and MMP-2 levels in the combined group was significantly superior to that in the GFC group(P<0.05 or P<0.01).(5)The recurrence rate and the incidence rate of adverse reactions in the combined group were 11.11%(5/45)and 13.33%(6/45),respectively,and were significantly lower than those in the GFC group[all being 35.56%(16/45)],the differences being all statistically significant(P<0.05 or P<0.01).Conclusion Jingangteng Capsules combined with Guizhi Fuling Capsules can significantly enhance the clinical efficacy of the patients with chronic pelvic inflammatory of damp-heat and stasis obstruction type,effectively shorten the time for the relief of symptoms,and decrease the serum GM-CSF and MMP-2 levels.
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Objective To study the feasibility on automatic contouring of pelvic intestinal tube based on deep learning for radiotherapy images.Methods A total of 100 patients with diagnosis of rectal cancer,received radiotherapy in Zhongshan Hospital,Fudan University from 2019 to 2021,were randomly selected.Sixty cases were randomly enrolled to train the models,and the other 40 cases were applied to test.Based on the original small intestine model in automatic segmentation software AccuContour,60,40 and 20(2 groups)cases in the model cases were used to train the models Rec60,Rec40,Rec20A and Rec20B with manual contouring as ground truth.Other 40 cases for test were applied to evaluate the Dice similarity coefficient(DSC),95%Hausdorff distance(HD95)and average symmetric surface distance(ASSD)between the manual contouring and original model along with model Rec60.The DSC of the 5 groups of auto-segmentations were compared as well.The paired t tests were performed for each pair of the original model and 4 trained models.Results The small bowel contoured by trained models were more similar to the manual contouring.They could distinguish the boundary of the intestinal tube better and distinguish the small bowel from the colon.The average DSC,HD95 and ASSD of Rec60 were 0.16 higher(P<0.001),12.4 lower(P<0.001)and 5.14 lower(P<0.001)than the original model respectively.According to the paired t tests,there were no statistical differences in DSC between the 4 training models and the original model.No statistical difference was observed between Rec60 and Rec40,while they were both significantly different from the two Rec20 models.There was no statistical difference between Rec20B and Rec20B.Conclusion For radiotherapy images,model training can effectively improve the accuracy of intestinal tube delineation.Forty cases were enough for training an optimal model of automatic segmentation for pelvic intestinal tube in AccuContour software.
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Abstract@#Through in-depth investigation into Japanese nutrition health educators post content, configuration, training mode, advanced education practice and the difficulties, the paper explores the effective ways of integrating nutrition health education into the school health education teacher and curriculum system as well as health promotion, so as to guide teachers and students to establish a correct concept of health, enhance health literacy and develop a healthy lifestyle. Additionally, the paper aims at providing suggestions for the construction of nutrition and health school as well as the future development of nutrition health education in China.
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Liposome nanomedicine is a new drug preparation with nano scale, which is encapsulated by lipid bilayer vesicle structure. As a drug delivery carrier, liposome has many advantages such as good biocompatibility, biodegradation in vivo and strong targeting. The application of liposome nano drug delivery system can improve the pharmacokinetic behavior and efficacy of some drugs in vivo to a certain extent, and reduce toxic and side effects. After liposome nanomedicine enter into the body, free drugs will be released, so there will be loaded drugs and free drugs in the body. Loaded drugs are drug repositories, free drugs are related to their efficacy and adverse reactions. Therefore, the pharmacokinetics study of liposomes should focus on both loaded drugs and free drugs. Quantitative analysis of free drugs, liposome particles and their materials is a big challenge. The bioanalysis and pharmacokinetics of liposome nanomedicines will be introduced and discussed in this review. We hope this review will provide a reference for the development of liposome nanomedicine.
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Pro-inflammatory macrophages play key regulatory role in the occurrence and development of rheumatoid arthritis (RA). In this study, we constructed a celastrol (Cel)-loaded polyamide-amine dendrimer (PAMAM) drug delivery system, which could target folate receptor and mitochondria. It could target inflammatory macrophages and realize chemo-photothermal synergistic therapy. Using PAMAM as the nano-carrier, folate receptor-targeting group folic acid (FA) and mitochondria-targeting group IR808 (also known as the photothermal agent) were conjugated with PAMAM through amide reaction, and then complexed with anti-inflammatory drug Cel to prepare the FA-PAMAM-IR808/Cel nanocomplex. In vitro characterization results showed that the drug loading efficiency of the nanocomplex was 50.90%, particle size was between 130 and 160 nm, average potential was between 1.0 and 3.5 mV, the drug release showed pH sensitivity, temperature reached to 42.5 ℃ after near-infrared (NIR) light irradiation for 10 min. In vitro cellular uptake experiments showed that the nanocomplex had obvious folate receptor-targeting and mitochondria-targeting ability. Following irradiation with NIR light, the cytotoxicity and cellular apoptosis enhanced. The secretion of pro-inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and nitric oxide (NO) decreased in a concentration-dependent manner. This study provided insights for the development of novel anti-RA nanomedicines.
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Objective: To systematically evaluate the acceptance of pre-exposure prophylaxis (PrEP)among men who have sex with men (MSM) in China, so as to provide reference for the promotion of preventive drug use before human immunodeficiency virus exposure in China. Methods: By searching the databases of China national knowledge infrastructure, VIP database, Wanfan knowledge service platform, PubMed, Web of Science, Embase and The Cochrane Library with key words of "men who have sex with men" "pre-exposure prophylaxis" "PrEP" and "MSM". The literature on the willingness of Chinese MSM population to accept PrEP was systematically collected, and the data of the literature meeting the inclusion criteria were extracted for Meta analysis. Results: A total of 12 articles were selected in this study, including 6 articles in English and 6 in Chinese. The score of bias risk assessment of eligible articles was 14-18, which was more than 70% of the total score. The total number of samples was 11 269. The overall acceptance rate of PrEP was 0.77(95%CI:0.71-0.82). In subgroup analysis, the acceptance rates of different nationalities, marriage, household registration, age, education background, income, sexual orientation, sexual behavior and awareness of PrEP were statistically significant. Conclusion: In general, the acceptance rate of PrEP in MSM population is higher, but the awareness rate is low. There are differences in the acceptance rate among different groups.
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Female , Humans , Male , China/epidemiology , HIV Infections/prevention & control , Health Knowledge, Attitudes, Practice , Homosexuality, Male , Patient Acceptance of Health Care , Pre-Exposure Prophylaxis , Sexual Behavior , Sexual and Gender MinoritiesABSTRACT
To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg~(-1)·d~(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-β-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.
Subject(s)
Animals , Mice , Bile Acids and Salts , Chromatography, Liquid , Drugs, Chinese Herbal , Ileum , Liver , Sleep Initiation and Maintenance Disorders/drug therapy , Tandem Mass SpectrometryABSTRACT
β3-adrenergic agonists induce adaptive thermogenesis and promote beiging of white fat. However, it remains unclear which metabolites mediate the stimulatory effects of β3-adrenergic agonists on thermogenesis of brown and beige fat. In this study, adipose tissue was isolated from 8-week-old C57/BL6J male mice by intraperitoneal administration of β3-adrenergic agonist CL316,243 for RNA-Seq, which revealed that histidine decarboxylase, a key enzyme in histamine synthesis, was strongly induced in adipose by CL316,243. Therefore, we speculated that histamine might be involved in the process of thermogenesis in adipose tissue. We determined the physiological role and mechanism by which histamine promotes fat thermogenesis by intravenous administering histamine to C57BL/6J mice fed a normal or a high-fat diet. The results showed that intravenous injection of histamine into C57BL/6J mice fed a normal diet stimulated the expression of thermogenic genes, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and uncoupling protein 1 (UCP1), in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT). H&E staining also suggested that histamine treatment decreased the size of lipid droplets in adipocytes. Moreover, histamine treatment also enhanced thermogenesis of fat in high-fat diet induced obese mice, and improved glucose intolerance and fatty liver phenotype. Finally, we demonstrated that the effects of histamine on the thermogenic program were cell autonomous. Our data suggest that histamine may mediate the effects of β3-adrenergic agonists on thermogenesis of fat.
Subject(s)
Animals , Male , Mice , Adipose Tissue, Beige , Adipose Tissue, Brown , Histamine , Mice, Inbred C57BL , Thermogenesis , Uncoupling Protein 1/geneticsABSTRACT
OBJECTIVE@#To reveal the effect and mechanism of Jiaotai Pill (, JTP) on insomniac rats.@*METHODS@#The insomniac model was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). In behavioral experiments, rats were divided into control, insomniac model, JTP [3.3 g/(kg•d)], and diazepam [4 mg/(kg•d)] groups. The treatment effect of JTP was evaluated by weight measurement (increasement of body weight), open field test (number of crossings) and forced swimming test (immobility time). A high performance liquid chromatography-electrochemical detection (HPLC-ECD) method was built to determine the concentration of monoamine transmitters in hypothalamus and peripheral organs from normal, model, JTP, citalopram [30 mg/(kg•d)], maprotiline [40 mg/(kg•d)] and bupropion [40 mg/(kg•d)] groups. Expressions of serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET) were analyzed by quantitative polymerase chain reaction (qPCR) and Western blot in normal, model and JTP groups. A high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) method was established to determine the pharmacokinetics, urine cumulative excretion of metformin in vivo, and tissue slice uptake in vitro, which were applied to assess the activity of organic cation transporters (OCTs) in hypothalamus and peripheral organs.@*RESULTS@#Compared with the insomniac model group, the body weight and spontaneous locomotor were increased, and the immobility time was decreased after treatment with JTP (P<0.01). Both serotonin and dopamine contents in hypothalamus and peripheral organs were increased (P<0.01). The norepinephrine content was increased in peripheral organs and decreased in hypothalamus (P<0.05 or P<0.01). At the same time, SERT, DAT, OCT1, OCT2, and OCT3 were down-regulated in hypothalamus and peripheral organs (P<0.05). NET was down-regulated in peripheral organs and up-regulated in hypothalamus (P<0.05 or P<0.01). Moreover, the activity of OCTs in hypothalamus and peripheral organs was inhibited (P<0.05).@*CONCLUSION@#JTP alleviates insomnia through regulation of monoaminergic system and OCTs in hypothalamus and peripheral organs.
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This study is to provide the basis of establishing a quality evaluation system, based on the differences in appearance and internal components of Astragali Radix from different sources. The diameter of 18 batches of Astragali Radix, the content of alcohol(water) extract and 7 kinds of flavonoids were determined. The peak area ratio of flavonoid aglycon to aglycone was calculated. PCA and CA were carried out by synthesizing various indexes. The results of PCA and CA showed that Astragali Radix was obviously clustered into three types. Alcohol extract, formononetin/formosan glycosides,(pilose isoflavones+astragalus flavonoid A)/pilose isoflavone glucoside are the most significant differences in the variable importance projection index(VIP) of Astragali Radix. Combining the diameter, alcohol(water) extract, flavonoid aglycon to aglycone peak area ratio can provide an analysis method for the establishment of the grade evaluation system of Astragali Radix.
Subject(s)
Astragalus Plant , Drugs, Chinese Herbal , Glucosides , Glycosides , Plant RootsABSTRACT
To investigate the changes of bile acid(BA) levels in mice with sleep deprivation and the regulatory effect of Jiaotai Pills(JTP) on bile acid metabolism, this study established an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 23 BAs in mice. A total of 24 ICR mice were randomized into normal group, model group, and JTP group. Mice in the model group and JTP group were deprived of sleep at 20 h·d~(-1) by sleep deprivation apparatus for 8 consecutive days. Mice in the JTP group were given(ig, qd) JTP 3.3 g·kg~(-1) and those in the normal group and model group received(ig) the same volume of purified water. UPLC conditions are as follows: Waters ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm), gradient elution with the mobile phase of 0.1% formic acid in water-methanol. MS conditions are as below: negative-ion electrospray ionization, multiple reaction monitoring(MRM). Thereby, the content of 23 BAs in serum, liver, and ileum was determined and methodological investigation of the method was performed. The results showed that 23 BAs could be accurately determined within 15 min and the correlation coefficients were all higher than 0.99. The precision, accuracy, specificity, reproducibility, matrix effect, and recovery of BAs all met the requirement. The levels of BAs were significantly increased in the serum, liver, and ileum of sleep-deprived mice, but JTP can significantly reduce the levels. The UPLC-MS/MS method is simple, rapid, and accurate, which can be used for the determination of 23 BAs in biological samples, and JTP can adjust the elevated BA levels of sleep-deprived mice.
Subject(s)
Animals , Mice , Bile Acids and Salts , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drugs, Chinese Herbal , Mice, Inbred ICR , Reproducibility of Results , Sleep , Tandem Mass SpectrometryABSTRACT
To explore the pathogenesis of heart and kidney imbalance insomnia and the regulatory effect of Jiaotai Pills, in order to study the changes of central and peripheral neurotransmitters in rat. Insomnia rats with heart and kidney imbalance were induced through intraperitoneal injection with p-chlorophenylalanine(PCPA, 400 mg·kg~(-1)·d~(-1)), and the model rats were intragastrically administrated with Jiaotai Pills(3.3 g·kg~(-1)·d~(-1)) for 7 days. Nine neurotransmitters were determined by UPLC-MS/MS and principal component analysis(PCA) method in serum, urine, brain, heart, liver, kidney and adrenal gland of rats. The results showed that the ratio of 5-HT and 5-HIAA in platelet of insomnia rats was significantly lower than that in the normal group, and Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, the changed neurotransmitters in blood of insomnia rats were 5-HIAA, E, NE, DA, Glu and ACH, and except ACH, the changes of 7 kinds of neurotransmitters in urine were more significant, Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, all of the 8 neurotransmitters in insomnia rats except HVA were changed. Jiaotai Pills could regulate the neurotransmitters in each tissue of insomnia rats, especially in brain, liver and adrenal gland. In conclusion, insomnia is caused by not only a change of neurotransmitters in brain, but also a series of changes in peripheral tissues. It indicates that insomnia is a systematic imbalance of neurotransmitters. Jiaotai Pills not only regulates the central nervous system, but also has a certain protective effect on other organs, reflecting the multi-target and systematic effect of Jiaotai Pills in the treatment of insomnia.
Subject(s)
Animals , Rats , Chromatography, Liquid , Drugs, Chinese Herbal , Neurotransmitter Agents , Sleep Initiation and Maintenance Disorders , Tandem Mass SpectrometryABSTRACT
ObjectiveThe role of human tumor-related calcium signal transductor 2 (TACSTD2) in promoting tumorigenesis has been noticed recently. We predicted the molecular structure and biological function of TACSTD2 by bioinformatic methods, in order to provide reference for further study of TACSTD2.MethodsThe homo sapiens TACSTD2 mRNA and protein amino acid sequences were obtained from the National Center for Biotechnology Information (NCBI) database. The bioinformatic methods were used to analyze the open reading frame(ORF) of TACSTD2, physicochemical properties, signal peptide and protein localization, subcellular localization, and prediction of transmembrane structure and secondary structure, tertiary structure, potential protein modification sites, domains, protein modification sites proteins, protein interacting with TACSTD2, biological functions of TACSTD2, and expression of TACSTD2 in human normal tissues and certain tumor types.ResultsAccording to the mRNA sequence of TACSTD2, there are 12 ORFs, and the longest is ORF1, with a total of 972bp, encoding 323 amino acids. The hydrophilic amino acid of TACSTD2 is more than that of hydrophobic amino acid, indicating that TACSTD2 belongs to hydrophilic protein. TACSTD2 is a highly conserved alkaline secreted protein with a transmembrane region both inside and outside the cytoplasm. The presence of nuclear localization signal(NLS) in the amino acid sequence of TACSTD2 suggests that TACSTD2 can locate in cell nucleus. TACSTD2 mainly distribute in cytoplasmic membrane, extracellular, nucleus and cytoplasm. The secondary structure prediction results showed that the main structure of TACSTD2 was random coil, followed by a α helix. TACSTD2 has 15 serine modification sites, 17 threonine modification sites, and 8 tyrosine modification sites. The TACSTD2 has protein interactions with Claudin(CLDN) protein family; and participating in signaling pathway such as cell surface receptor, cell proliferation, negative regulation of epithelial cell migration, and so on. Comparing with normal human tissues, its mRNA expression is up-regulated in most tumor types such as cervical cancer, lung cancer, thyroid cancer, uterine cancer, liver cancer, colorectal cancer.ConclusionAccording to the analysis of the structure and function of TACSTD2, TACSTD2 is highly-expression in multiple malignancies. It can participate in the process of proliferation, migration and adhesion of malignant tumor cells through cell surface receptor signaling pathways. This study provide reference for the further research about the function of TACSTD2.
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ObjectiveThe role of human tumor-related calcium signal transductor 2 (TACSTD2) in promoting tumorigenesis has been noticed recently. We predicted the molecular structure and biological function of TACSTD2 by bioinformatic methods, in order to provide reference for further study of TACSTD2.MethodsThe homo sapiens TACSTD2 mRNA and protein amino acid sequences were obtained from the National Center for Biotechnology Information (NCBI) database. The bioinformatic methods were used to analyze the open reading frame(ORF) of TACSTD2, physicochemical properties, signal peptide and protein localization, subcellular localization, and prediction of transmembrane structure and secondary structure, tertiary structure, potential protein modification sites, domains, protein modification sites proteins, protein interacting with TACSTD2, biological functions of TACSTD2, and expression of TACSTD2 in human normal tissues and certain tumor types.ResultsAccording to the mRNA sequence of TACSTD2, there are 12 ORFs, and the longest is ORF1, with a total of 972bp, encoding 323 amino acids. The hydrophilic amino acid of TACSTD2 is more than that of hydrophobic amino acid, indicating that TACSTD2 belongs to hydrophilic protein. TACSTD2 is a highly conserved alkaline secreted protein with a transmembrane region both inside and outside the cytoplasm. The presence of nuclear localization signal(NLS) in the amino acid sequence of TACSTD2 suggests that TACSTD2 can locate in cell nucleus. TACSTD2 mainly distribute in cytoplasmic membrane, extracellular, nucleus and cytoplasm. The secondary structure prediction results showed that the main structure of TACSTD2 was random coil, followed by a α helix. TACSTD2 has 15 serine modification sites, 17 threonine modification sites, and 8 tyrosine modification sites. The TACSTD2 has protein interactions with Claudin(CLDN) protein family; and participating in signaling pathway such as cell surface receptor, cell proliferation, negative regulation of epithelial cell migration, and so on. Comparing with normal human tissues, its mRNA expression is up-regulated in most tumor types such as cervical cancer, lung cancer, thyroid cancer, uterine cancer, liver cancer, colorectal cancer.ConclusionAccording to the analysis of the structure and function of TACSTD2, TACSTD2 is highly-expression in multiple malignancies. It can participate in the process of proliferation, migration and adhesion of malignant tumor cells through cell surface receptor signaling pathways. This study provide reference for the further research about the function of TACSTD2.
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Objective::To investigate in vivo and in vitro metabolites of coptisine and their metabolic pathways. Method::SD rats were given coptisine by single gavage (dose of 25 mg·kg-1). Urine and feces from 0 h to 48 h, bile from 0 h to 24 h, and plasma and brain tissue samples at 0.25, 1, 2 h after administration were collected.In vitro metabolism was incubated with rat liver microsomes and intestinal flora.The metabolites were analyzed and identified by the high-resolution HPLC-MS/MS technique.The liquid chromatography separation was carried out on ZORBAX SB-C18 column (4.6 mm×150 mm, 5 μm) with acetonitrile-0.1% formic acid solution as the mobile phase for gradient elution, the flow rate was 1.0 mL·min-1, and column temperature was 25 ℃.The mass spectra were obtained in positive and negative ion mode with electrospray ionization (ESI), the scanning range was m/z 50-1 200.The relative molecular weight was determined according to the quasi-molecular ion peaks.The structures of metabolites were elucidated by comparing the data with literature data, including main ion peaks, UV spectrum and HPLC retention time information. Result::A total of 17 metabolites were identified in each sample, including 11 phase Ⅰ metabolites and 6 phase Ⅱ metabolites.The pathways to these metabolites were hydroxylation, demethylation, dehydrogenation, sulfation and glucuronide conjugation. Conclusion::Coptisine can produce metabolic reaction of phase Ⅰ and phase Ⅱ in rat, and metabolites are predominantly present in urine, and the main metabolic site is liver.Coptisine is poorly absorbed and rarely metabolized in gastrointestinal tract, so it is mostly excreted through feces by prototype.This experiment can provide material basis for the pharmacodynamics and pharmacology of coptisine.
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Ultra performance liquid chromatography-tandem mass spectrometry( UPLC-MS/MS) was used to establish the simultaneous determination method of eight neurotransmitters in brain,liver,kidney,adrenal gland,serum and urine,including serotonin,5-hydroxyindole acetic acid,epinephrine,norepinephrine,dopamine,glutamic acid,γ-aminobutyric acid,and acetylcholine,and then investigate the distribution characteristics of neurotransmitters in rat tissues,blood and urine. Waters ACQUITY UPLC BEH C_(18) column( 2. 1 mm×100 mm,1. 7 μm) was used,with 0. 3% formic acid solution-acetonitrile as the mobile phase for gradient elution.Multiple reaction monitoring( MRM) scanning method under positive mode by atmospheric pressure electrospray ion source( ESI) was also performed to establish the detection method of neurotransmitters for methodological research. The plasma,urine and tissues of normal rats were pre-treated including homogenization,centrifuging,and protein removal,then the 2 μL supernatant was injected for analysis. The results showed that eight kinds of neurotransmitters could be accurately determined within 7 min,with linear correlation coefficients all greater than 0. 99. This method showed high accuracy and good precision,with specificity,stability,extraction recovery and matrix effects all complying with the biological sample analysis requirements. The most abundant transmitters in the brain,liver,kidney,kidney gland,blood and urine were γ-aminobutyric acid,glutamic acid,glutamic acid,adrenaline,glutamic acid and dopamine.The method is sensitive,rapid,precise,accurate and specific,and can be used for simultaneous quantitative analysis of eight neurotransmitters in biological samples. The investigation of the distribution ratio of transmitters in rats is of important significance to disease prevention and treatment.
Subject(s)
Animals , Rats , Chromatography, High Pressure Liquid , Chromatography, Liquid , Neurotransmitter Agents/urine , Reproducibility of Results , Sensitivity and Specificity , Tandem Mass SpectrometryABSTRACT
Background@#Low handgrip strength (HS) and declining gait speed (GS) are increasingly obvious with aging, requiring effective, and safe medication for treatment. Trimetazidine (TMZ) modified release tablets, a common anti-angina drug, has potential benefits for alleviating the condition, but this has not yet been fully studied and therefore is the aim of this study.@*Methods@#This is a prospective randomized controlled study. Fifty-eight eligible patients will be randomly assigned to one of two study groups: TMZ group or control group. For the TMZ group, a dose of 35 mg of oral TMZ will be administered with a meal twice a day for 3 months, in addition to any conventional treatments for angina. Only conventional treatments for angina will be administrated in the control group. The primary outcome will be the 6-min walking distance and the secondary outcomes will be: muscle strength (HS and pinch strength), GS, muscle endurance (five times sit-to-stand test), balance maintenance (tandem standing test), and the frequency of angina per week. Additionally, body mass index, circumferences (biceps, waist, hip, and calf), albumin levels, and the score on a five-question scale for sarcopenia will be obtained during the study.@*Discussion@#This study aims to evaluate the usefulness of TMZ in a population with poor muscle function. The results may provide an effective and safe medical treatment to people with low muscle strength or physical performance.@*Trial registration@#Chinese Clinical Trial Registry, ChiCTR1800015000; www.chictr.org.cn/showproj.aspx?proj=25445.
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BACKGROUND@#Low handgrip strength (HS) and declining gait speed (GS) are increasingly obvious with aging, requiring effective, and safe medication for treatment. Trimetazidine (TMZ) modified release tablets, a common anti-angina drug, has potential benefits for alleviating the condition, but this has not yet been fully studied and therefore is the aim of this study.@*METHODS@#This is a prospective randomized controlled study. Fifty-eight eligible patients will be randomly assigned to one of two study groups: TMZ group or control group. For the TMZ group, a dose of 35 mg of oral TMZ will be administered with a meal twice a day for 3 months, in addition to any conventional treatments for angina. Only conventional treatments for angina will be administrated in the control group. The primary outcome will be the 6-min walking distance and the secondary outcomes will be: muscle strength (HS and pinch strength), GS, muscle endurance (five times sit-to-stand test), balance maintenance (tandem standing test), and the frequency of angina per week. Additionally, body mass index, circumferences (biceps, waist, hip, and calf), albumin levels, and the score on a five-question scale for sarcopenia will be obtained during the study.@*DISCUSSION@#This study aims to evaluate the usefulness of TMZ in a population with poor muscle function. The results may provide an effective and safe medical treatment to people with low muscle strength or physical performance.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry, ChiCTR1800015000; www.chictr.org.cn/showproj.aspx?proj=25445.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Angina, Stable , Drug Therapy , Muscle, Skeletal , Prospective Studies , Treatment Outcome , Trimetazidine , Therapeutic Uses , Vasodilator Agents , Therapeutic UsesABSTRACT
N-methyladenosine (mA), catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14, is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However, the roles and precise mechanisms of mA modification in regulating neuronal development and adult neurogenesis remain unclear. Here, we examined the function of Mettl3, the key component of the complex, in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced mA levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neuronal development and skewed the differentiation of aNSCs more toward glial lineage, but also affected the morphological maturation of newborn neurons in the adult brain. mA immunoprecipitation combined with deep sequencing (MeRIP-seq) revealed that mA was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically, mA was present on the transcripts of histone methyltransferase Ezh2, and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively, our results uncover a crosstalk between RNA and histone modifications and indicate that Mettl3-mediated mA modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.
Subject(s)
Animals , Adenosine , Metabolism , Adult Stem Cells , Cell Biology , Metabolism , Brain , Metabolism , Cell Differentiation , Genetics , Cell Proliferation , Enhancer of Zeste Homolog 2 Protein , Metabolism , Gene Expression Regulation , Methyltransferases , Metabolism , Mice, Inbred C57BL , Neural Stem Cells , Cell Biology , Metabolism , Neurogenesis , Genetics , Neurons , Cell Biology , Metabolism , RNA, Messenger , Genetics , MetabolismABSTRACT
Objective To compare diagnostic value of four fungal scoring methods in invasive Candida infection,provide evidence for early diagnosis and treatment of invasive Candida infection.Methods High-risk patients with invasive Candida infection in the intensive care unit(ICU) in a hospital from 2011 to 2016 were analyzed retrospectively.According to diagnostic criteria,patients were divided into four groups:non-infection group,suspected infection group,clinically diagnosed group,and confirmed group,patients were conducted multi-diseases risk assessment (MDRA) score,invasive fungal infections risk scoring system (IFIRSS) score,Sevilla score,and Candida score,diagnostic value of four scoring methods for invasive Candida infection were evaluated.Results There were 275 high-risk patients,138 in non-infection group,63 in suspected infection group,and 74 in infection group(clinically diagnosed group:n =64;confirmed group:n =10).The age and length of hospital stay in the infection group were all higher than non-infection group (both P<0.05).74 strains of Candida were isolated from 74 infected patients,mainly Candida albicans (n =60,81.1%).Positive rates for MDRA score,Candida score,Sevilla score,and IFIRSSscore were 41.5%(n =114),30.2%(n =83),15.3%(n =42),and 8.4% (n =23) respectively.Of four MDRA scoring methods,MDRA had the higher sensitivity(Se,59%) but lowest specificity(Sp,66%);IFIRSS had higher Sp(91%) but very low Se (9%);Sevilla score had the highest Sp (96%)and higher Se(45%);Candida score had the highest Se(68%) and higher Sp (90%).Conclusion Sevilla score has higher Se and Sp,which can be used in early diagnosis of invasive Candida infection;Candida score has the highest coincidence with clinical diagnostic criteria for invasive Candida infection,both Se and Sp are high,which is of great value for early diagnosis of invasive Candida infection.