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OBJECTIVE To evaluate the cost-effectiveness of trastuzumab biosimilars (Hanquyou) versus original drug (Hesaiting) in the treatment of recurrent/metastatic human epidermal growth factor receptor-2 (HER-2) positive breast cancer. METHODS A partitional survival model was constructed based on the NCT03084237 trial data. The simulation period was 3 weeks, and the simulation time was 10 years. Using costs and quality-adjusted life year (QALY) as the output indicator, the cost- utility analysis method was used to evaluate the cost-effectiveness of the two schemes mentioned above. Univariate and probabilistic sensitivity analyses were performed to verify the robustness of the basic analysis. RESULTS The costs of the trastuzumab biosimilars group and original drug group were 111 516.72 yuan and 111 122.30 yuan respectively, with health utility values of 1.52 QALYs and 1.36 QALYs, and ICER of 2 465.12 yuan/QALY, which were less than 3 times China’s per capita gross domestic product (GDP) in 2023 as the threshold for willingness-to-pay (WTP) (268 200 yuan/QALY). Univariate sensitivity analysis showed that the cost of the trastuzumab biosimilars and original drug had a great impact on the ICER. The probabilistic sensitivity analysis showed that the probability of trastuzumab biosimilars being cost-effective was 100% at WTP threshold of 14 902 yuan/QALY. CONCLUSIONS When WTP threshold is 3 times China’s GDP in 2023 (268 200 yuan/QALY), compared with original drug, trastuzumab biosimilars have good cost-effectiveness in the treatment of recurrent/metastatic HER-2 positive breast cancer.
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OBJECTIVE To provide theoretical basis for the rational use of drugs in medical institutions, assist in improving the quality of pharmaceutical services, and thus meet clinical drug demands. METHODS Adopting consensus meetings, Liaoning Pharmaceutical Association,Jilin Pharmaceutical Association and Heilongjiang Pharmaceutical Association collaborated with clinical and pharmaceutical experts in the region to compile the expert consensus on off-label drug use in the three Northeastern provinces of China after many votes and discussions by collecting and collating the information related to off-label drug use in medical institutions from the three northeastern provinces of China,and referring to and citing off-label drug use stated in some expert consensus and medication catalog. RESULTS Finally, a total of 198 pieces of off-label drug use information for 70 drugs were included in the two sections of solid tumors and hematological diseases in Consensus of Experts on Drug Use beyond the Instructions in the Three Provinces of Northeast China. CONCLUSIONS Consensus of Experts on Off-label Drug Use in the Three Northeastern Provinces of Northeast China (solid tumors and hematology)offers a theoretical foundation for rational drug use in the treatment of solid tumors and hematological diseases within medical institutions,and has a positive significance in improving the effectiveness and safety of drug treatment.
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OBJECTIVE@#To investigate the effects of novel bioactive glasses (BG) including PSC with high phosphorus component and FBG with fluorine-doped element on promoting remineralization of artificial dentin caries.@*METHODS@#(1) BGs were used in this study as follows: PSC (10.8%P2O5-54.2%SiO2-35.0%CaO, mol.%) were synthesized using phytic acid as the phosphorus precursor through sol-gel method. FBG (6.1%P2O5-37.0%SiO2-53.9%CaO-3.0%CaF2, mol.%) and 45S5(6.0%P2O5-45.0%SiO2-24.5%CaO-24.5%Na2O, mol.%) were synthesized by traditional melt method. (2) The above BGs were soaked in simulated body fluid (SBF) for 24 hours. Then X-ray diffraction (XRD) was used to analyze the formation of hydroxyapatite (HA) crystals. (3) Prepared 1 mm thick dentin slices were soaked in 17% ethylene diamine tetraacetic acid (EDTA) for 1 week to demineralize the dentin. Then the dentin slices treated by BG were soaked in SBF for 1 week. Field emission scanning electron micro-scopy (FE-SEM) was used to observe the surface morphology of the dentin slices. (4) Four cavities were prepared to 1 mm depth in each 2 mm thick dentin slice, then were treated with lactic acid for 2 weeks to form the artificial dentin caries. Wax, mineral trioxide aggregate (MTA), PSC and FBG were used to fill four cavities as blank control group, MTA group, PSC group and FBG group respectively. Then the spe-cimens were soaked in SBF for 4 weeks. The changes of depth and density of demineralized dentin were analyzed using Micro-CT before filling and after 2 and 4 weeks filling.@*RESULTS@#(1) PSC and FBG promoted mineral formation on the surfaces of the demineralized dentin. And the speed was faster and crystallinity was higher in PSC group than the FBG and 45S5 groups. (2) The increased mineral density of artificial dentin caries in PSC group were (185.98 ± 55.66) mg/cm3 and (213.64 ± 36.01) mg/cm3 2 and 4 weeks after filling respectively, which were significantly higher than the control group [(20.38 ± 7.55) mg/cm3, P=0.006; (36.46 ± 10.79) mg/cm3, P=0.001]. At meanwhile, PSC group was also higher than MTA group [(57.29 ± 10.09) mg/cm3; (111.02 ± 22.06) mg/cm3], and it had statistical difference (P=0.015; P=0.006). The depth of remineralized dentin in PSC group were (40.0 ± 16.9) μm and (54.5 ± 17.8) μm 2 and 4 weeks respectively, which were also statistically different from the control group (P =0.010;P=0.001). There were no statistical differences between the control group and MTA group. The above effects of FBG group were between PSC and MTA.@*CONCLUSION@#PSC has advantages in the speed, quality and depth of mineral deposition in the demineralized layer of artificial dentin caries. It would be expected to be an ideal material to promote the remineralization of dentin caries.
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Dentina , Dióxido de Silício/farmacologia , Suscetibilidade à Cárie Dentária , Minerais/farmacologia , Fósforo/farmacologia , Remineralização Dentária/métodosRESUMO
Objectives: To investigate the clinical characteristics and prognoses of patients with anaplastic thyroid carcinoma(ATC), and to explore the value of multi-modality treatment in improving overall survival(OS) of ATC patients. Methods: Medical records including clinicopathological data of patients diagnosed with ATC at Cancer Hospital, Chinese Academy of Medical Sciences between 2001 and 2020 were retrospectively analyzed. The cohort were divided into surgery-only and multi-modality subgroups, and the latter included patients treated with surgery plus radiotherapy and/or medical therapy(including chemotherapy, target therapy and immunotherapy). Univariate survival analysis was conducted through Kaplan-Meier method, and multivariate survival analysis was performed using Cox proportional hazard model. Results: A total of 47 patients were included in the study, including 24 males and 23 females, with a median age of 63 years. After a median follow-up duration of 3.37 months, 42 patients died due to tumor recurrence or progression. The median OS of the cohort was 4.33 months. Univariate survival analysis demonstrated that symptoms of recurrent laryngeal nerve(RLN) involvement, distant metastasis, leukocyte elevation, and treatment modality were significantly associated with OS (P values all<0.05). Multivariate analysis showed that symptoms of RLN involvement(HR=2.49, 95%CI: 1.16-5.32, P=0.019), distant metastasis(HR=2.33, 95%CI: 1.06-5.16, P=0.036), and leukocyte elevation(HR=2.50, 95%CI: 1.16-5.40, P=0.020) were all independent risk factors for OS, while multi-modality therapy significantly prolonged OS compared with surgery alone(HR=0.22, 95%CI: 0.10-0.47, P<0.001). Conclusions: Among ATC patients, absence of symptoms of RLN invasion, normal leukocyte level and absence of distant metastasis at initial diagnosis are all independent protective factors for OS and multi-modality treatment can help to improve the prognosis.
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Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma Anaplásico da Tireoide/terapia , Recidiva Local de Neoplasia , Prognóstico , Neoplasias da Glândula Tireoide/terapiaRESUMO
OBJECTIVE@#To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism.@*METHODS@#The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT.@*RESULTS@#Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G1 phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1, and CDKN1A, while decrease the mRNA level of MYC. It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells.@*CONCLUSION@#TPA induces NB4 cell cycle arrest in G1 phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.
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Humanos , Leucemia Promielocítica Aguda , Caspase 3/metabolismo , Caspase 9/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína X Associada a bcl-2/metabolismo , Linhagem Celular Tumoral , Divisão Celular , Apoptose , RNA Mensageiro , Proliferação de CélulasRESUMO
This study aimed to explore the application value of new biological specimen oral fluid in SARS-CoV-2 nucleic acid and antibody detection. Oral fluid and paired respiratory and blood specimens from 7 confirmed cases of two COVID-19 cluster epidemic were collected in Beijing from October to November 2021. SARS-CoV-2 virus and IgG antibody were detected by real time PCR kits and serum antibody detection reagents, and SARS-CoV-2 IgG antibody in oral fluids was detected by a new established method of magnetic particle chemiluminescence. The results showed that the nucleic acid amplification test of SARS-CoV-2 on nasopharyngeal swabs, throat swabs and oral fluid specimens from 3 confirmed cases of COVID-19 was positive, among which the Ct value for ORF1a/b and N gene of oral fluid samples in 2 cases was close to that of throat swab, and the Ct value of oral fluid sample for 1 case was higher than that of throat swab. The complete genome sequence of one oral fluid specimen was obtained, which belonged to the VOC/Delta variant strain. The SARS-CoV-2 IgG antibodies of the paired oral fluid and serum were all positive, and the S/CO values of oral fluid were all lower than those of serum. The series of oral fluid results showed that SARS-CoV-2 IgG antibody level increased from 11 to 32 days after the onset of the disease.
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Humanos , COVID-19/diagnóstico , Ácidos Nucleicos , SARS-CoV-2 , Sensibilidade e EspecificidadeRESUMO
The incidence of thyroid cancer continues to increase, among which differentiated thyroid cancer occupies the main position. Development of molecular biology has facilitated early diagnosis and precise treatment of thyroid carcinoma, and hopefully provided potential options for certain subtypes with poor prognosis, such as radioactive iodine-refractory differentiated thyroid carcinoma. This review summarizes the gene variants of high frequency and the mechanism of such gene variants, application of molecular biological detection in clinical diagnosis, as well as the correlation of specific gene variants with clinicopathological characteristics and prognosis for differentiated thyroid carcinoma.
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Objective: To assess the level and trend of varicella-zoster virus (VZV) antibody among healthy population in Beijing in 2017, after the five-year implementation of the two doses varicella vaccination strategy in 2012, and to provide evidence for scientific evaluation of immunization strategy. Methods: A total of 2 144 subjects in ten age groups from 8 districts of Beijing city were recruited in this study using cross-sectional survey based on multi-stage cluster random sampling method. Serum samples were collected and VZV antibody was detected by ELISA. The influencing factors of antibody concentration and positive rate were analyzed and compared with the study in 2012. The antibody concentration and antibody positive rate were analyzed by nonparametric test and χ² test respectively. Results: The ratio of subjects with registered residence in Beijing city to other provinces was 1∶1. The ratio of male to female was 1∶1.08. The median concentration of VZV antibody was 341.4 (78.6, 1 497.8) mIU/ml, and the total antibody positive rate was 71.1% (1 524/2 144). There were significant differences in antibody positive rate (χ²=736.39, P<0.01) and antibody concentration (χ²=740.34, P<0.01) among different age groups. The antibody positive rate generally increased with age (χ²trend=7.32, Ptrend<0.01). Among 862 children under 14 years old, the antibody positive rate of two doses vaccination 72.8% (182/250) was significantly higher than that of one dose vaccination 51.9% (154/297) (χ²=25.14, P<0.01). There was significant difference between 1-4 years old group (χ²=11.71, P<0.01) and 10-14 years old group (χ²=5.95, P=0.02), but not in 5-9 years old group (χ²=3.00, P=0.07). Compared with the study in 2012, the antibody positive rate increased in 5-9 years old group (χ²=14.35, P<0.01) and decreased in 1-4 years old group (χ²=11.51, P=0.01) in 2017. Conclusion: The recommended varicella booster vaccination has significantly improved the VZV antibody level of children in Beijing city. In the future, it is necessary to explore a more optimized two doses varicella vaccination schedule for children in combination with epidemiological evidence.
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Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Anticorpos Antivirais , Varicela/prevenção & controle , Vacina contra Varicela , Estudos Transversais , Herpesvirus Humano 3 , VacinaçãoRESUMO
Vital pulp therapy(VPT)is an important pathway to preserve and maintain pulp tissue in a healthy state. VPT has been improved recently as the new progress achieved in pathobiology, bioactive materials and clinical research. The present review summarizes the clinical outcomes and prognostic factors of VPT, including direct pulp capping, partial pulpotomy and full pulpotomy in mature permanent teeth with carious pulp exposure, and briefly introduces the new progress in this field.
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Humanos , Compostos de Cálcio , Cárie Dentária/terapia , Capeamento da Polpa Dentária , Dentição Permanente , Pulpotomia , Silicatos , Resultado do TratamentoRESUMO
Essential oils(EOs) from Chinese medicinals, which can be used as adjuvants and exert certain therapeutic effect, are directly used in Chinese medicine formulas. Conventional research strategy for EOs from Chinese medicinals is to compare the efficacy of the prescriptions before and after the addition of EOs, and the penetration-enhancing mechanisms of EOs remain unclear. In modern research on EOs from Chinese medicinals, the method for studying chemical penetration enhancers is often used, which fails to reflect the overall efficacy of EOs. This study clarified the property regularity of EOs from Chinese medicinals as transdermal penetration enhancers, and thereby proposed a research model which integrated the medicinal and adjuvant properties of EOs from Chinese medicinals via "component-delivery-effect" characterization route. The core concept is that constituents of EOs from Chinese medicinals and their delivery process play a key role in their external application. This research model is expected to serve as a reference for further research on EOs from Chinese medicinals for transdermal application.
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Adjuvantes Farmacêuticos , Administração Cutânea , China , Medicamentos de Ervas Chinesas/farmacologia , Óleos Voláteis/farmacologiaRESUMO
Objective:To investigate the incidence of asthma and the characteristics of acute attacks in children aged 3-14 in different administrative areas of Wuxi, and to analyze the correlation of asthma with the outdoor environmental factors.Methods:A total of 10 175 children aged 3-14 were randomly selected from 5 different administrative regions in Wuxi City, Jiangsu Province for childhood asthma epidemiological survey from January to December in 2017.Results:The complete questionnaires were collected from 8 318 children with a response rate of 81.70%.There were 6 734 valid questionnaires.Asthma occurred to 259 children, and the prevalence rate was 3.84%.The prevalence of asthma in male and female children was 4.89% (163 cases) and 2.82% (96 cases), respectively.The ratio of male patients to female patients was 1.70∶1.00, and the difference was significant ( χ2=19.72, P<0.01). Children were most prone to suffer from asthma attacks at the turn of seasons (87/259 cases, 33.59%). The frequency of asthma was the lowest from June to August (9/259 cases, 3.47%). Among 244 cases attacked by acute asthma, the prevailing time period of acute attacks was irregular in 88 patients (36.07%), bedtime in 64 cases (26.23%). In different regions of the city, the lowest prevalence rate of asthma was found in Binhu District (50/1 830 cases, 2.73%), the highest prevalence rate of asthma was found in Xinwu District (71/1 502 cases, 4.72%), the difference between the highest and lowest prevalence rates of asthma was significant ( χ2=13.19, P<0.05). In terms of the air quality in different admi-nistrative regions of Wuxi, the nitrogen dioxide (NO 2) concentration, the carbon monoxide (CO) concentration, PM 10 and PM 2.5 in Binhu District were lower than other 4 regions.In different seasons in Wuxi city, the sulfur dioxide(SO 2) concentration, the NO 2 concentration, the CO concentration, PM 10 and PM 2.5 from June to August were significantly lower than those in other months.The prevalence of asthma in children in different administrative districts of Wuxi was weakly positively correlated with the SO 2 concentration, the NO 2 concentration and PM 10 ( r=0.10, P<0.01; r=0.22, P<0.01; r=0.06, P<0.01, respectively). The prevalence of asthma was weakly negatively associated with the ozone(O 3) concentration ( r=-0.06, P<0.01). Acute asthma attacks were weakly positively correlated with the SO 2 concentration ( r=0.22, P<0.01), the NO 2 concentration ( r=0.28, P<0.01), the CO concentration ( r=0.23, P<0.01), PM 10 ( r=0.18, P<0.01) and PM 2.5 ( r=0.18, P<0.01), and weakly negatively correlated with the O 3 concentration ( r=-0.40, P<0.01). Conclusions:The prevalence of asthma in Wuxi is higher in boys than in girls, and the frequency of asthma attacks is related to the season.The SO 2, NO 2, CO, PM 10, PM 2.5 and O 3 concentration affect the prevalence and acute attacks of asthma.
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Objective:To investigate the differential expression of long non-coding RNA (lncRNA) in placental tissues of women with preeclampsia (PE) and the effect of MIR210HG on the biological function of HTR8/SVneo cells.Methods:A total of 39 cases of PE women (PE group) and 39 cases of normal pregnant women (CTL group) admitted to the Affiliated Hospital of Qingdao University from July 2018 to July 2019 were collected. (1) Transcriptome sequencing (RNA-seq) was used to analyze the differentially expressed lncRNAs in the placental tissues of the two groups. (2) The expression level of MIR210HG, one of the differentially expressed lncRNAs, in the placental tissues of the two groups was detected by real-time quantitative PCR. And the correlations between the expression level of MIR210HG and systolic blood pressure, diastolic blood pressure and neonatal birth weight were analyzed. (3) The constructed small interfering RNA and negative control (NC) RNA were transfected into the HTR8/SVneo cells. The cells were divided into MIR210HG knockdown (KD) group and NC group. The effects of living cell counting (CCK-8) and transwell assay on the proliferation and migration of HTR8/SVneo cells were detected. (4) RNA interacting with MIR210HG was predicted using the Encyclopedia of RNA Interactomes (ENCORI) database. Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Gene and Genomes (KEGG) and BioCarta pathway enrichment analysis were performed.Results:(1) A total of 26 significantly differentially expressed lncRNAs were found by RNA-seq, among which 21 lncRNAs were up-regulated and 5 lncRNAs were down-regulated. (2) The relative expression level of MIR210HG in the PE group was significantly higher than that in the CTL group (9.30±1.90 and 1.10±0.20, respectively; t=4.425, P<0.01). The relative expression level of MIR210HG had positive linear correlation with systolic blood pressure ( r2=0.234, P<0.05) and diastolic blood pressure ( r2=0.190, P<0.05), but had a negative linear correlation with newborn birth weight ( r2=0.157, P<0.05). (3) Compared with the NC group, the proliferation and migration ability of HTR8/SVneo cells in the KD group were increased (all P<0.05). (4) A total of 38 RNAs that might interact with MIR210HG were predicted by ENCORI database. GO functional annotation analysis showed that MIR210HG might be involved in the functions of 27 pathways, including the regulation of production of molecular mediator of immune response, etc; KEGG pathway analysis showed that MIR210HG might be involved in the function of 8 pathways including allograft rejection, etc; Biocarta pathway analysis showed that MIR210HG may be involved in the functions of 8 pathways, including the eukaryotic initiation factor (eIF) pathway, etc. Conclusion:The expression of MIR210HG is up-regulated in the placental tissue of PE women, and MIR210HG might be a regulator of the biological behavior of trophoblast cells.
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OBJECTIVE:To establish the method for simultaneous determination of 5-fluorouracil(5-FU)and its metabolites 5-fluoro-5,6-dihydrouracil (5-FUH2) in human plasma ,and apply it in the clinic. METHODS :After plasma samples were processed twice by ethyl acetate ,UPLC-MS/MS method was adopted using 5-bromouracil (5-Bru) as internal standard. The determination was performed on Acquity UPLC HSS T 3 column with mobile phase consisted of methanol-water (30 ∶ 70,V/V)at the flow rate of 0.3 mL/min. The column temperature was 20 ℃,and sample size was 5 μL. An electrospray ion source was used to carry out negative ion scanning with multiple reaction monitoring. The capillary voltage was 1.5 kV;the taper hole voltage was 20 V;the desolvent temperature was 450 ℃;the desolvent air flow was 850 L/h;the cone hole gas velocity was 50 L/h. The ion transitions for quantitative analysis were m/z 129.00→41.90(5-FU),m/z 130.87→82.92(5-FUH2),m/z 189.00→42.10(5-Bru), respectively. From Aug. to Oct. 2020,10 patients with advanced colorectal cancer were treated with continuous intravenous drip of 5-FU for 46 hours were collected from Harbin Medicinal University Cancer Hospital. Steady-state plasma concentration of 5-FU and plasma concentration of 5-FUH2 were determined at 18-30 h of continuous intravenous drip. The area under the curve (AUC)for 5-FU and concentration ratio of 5-FUH2/5-FU were calculated. RESULTS :The linear range of 5-FU and 5-FUH2 were 20 to 1 000 μg/mL(R 2>0.990). The quantification limits were 20 ng/mL. RSDs of precision test were all lower than 20%,and relative error ranged ±10%. The extraction recovery and matrix effects didn ’t affect the determination of substance to be measured. Among 10 patients with advanced colorectal cancer ,the steady-state concentration of 5-FU were 180.04-622.83 ng/mL,and AUC of 5-FU ranged from 8.28 to 28.65 mg·h/L. The concentration of 5-FUH2 ranged 336.48-948.43 ng/mL,and concentration ratio of 5-FUH2/ 5-FU ranged 0.93-4.21. AUC of 5-FU in 10 patients had about 3-4 fold individual differences. CONCLUSIONS :The established method has good precision and accuracy ,high sensitivity ,and simple operation. It can be used for plasma monitoring of 5-FU in patients with advanced colorectal cancer.
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OBJECTIVES@#To develop a method for the simultaneous and rapid detection of five mushroom toxins (α-amanitin, phallacidin, muscimol, muscarine and psilocin) in blood by ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS).@*METHODS@#The blood samples were precipitated with acetonitrile-water solution(Vacetonitril∶Vwater=3∶1) and PAX powder, then separated on ACQUITY Premier C18 column, eluted gradient. Five kinds of mushroom toxins were monitored by FullMS-ddMS2/positive ion scanning mode, and qualitative and quantitative analysis was conducted according to the accurate mass numbers of primary and secondary fragment ions.@*RESULTS@#All the five mushroom toxins had good linearity in their linear range, with a determination coefficient (R2)≥0.99. The detection limit was 0.2-20 ng/mL. The ration limit was 0.5-50 ng/mL. The recoveries of low, medium and high additive levels were 89.6%-101.4%, the relative standard deviation was 1.7%-6.7%, the accuracy was 90.4%-101.3%, the intra-day precision was 0.6%-9.0%, the daytime precision was 1.7%-6.3%, and the matrix effect was 42.2%-129.8%.@*CONCLUSIONS@#The method is simple, rapid, high recovery rate, and could be used for rapid and accurate qualitative screening and quantitative analysis of various mushroom toxins in biological samples at the same time, so as to provide basis for the identification of mushroom poisoning events.
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Humanos , Agaricales , Cromatografia Líquida de Alta Pressão , Intoxicação Alimentar por Cogumelos/diagnóstico , Espectrometria de Massas em Tandem/métodosRESUMO
Objective To study the changes of metabolites in serum and tissues (kidney, liver and heart) of mice died of acute tetracaine poisoning by metabolomics, to search for potential biomarkers and related metabolic pathways, and to provide new ideas for the identification of cause of death and research on toxicological mechanism of acute tetracaine poisoning. Methods Forty ICR mice were randomly divided into control group and acute tetracaine poisoning death group. The model of death from acute poisoning was established by intraperitoneal injection of tetracaine, and the metabolic profile of serum and tissues of mice was obtained by ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry (UPLC-Orbitrap HRMS). Multivariate statistical principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were used, combined with t-test and fold change to identify the differential metabolites associated with death from acute tetracaine poisoning. Results Compared with the control group, the metabolic profiles of serum and tissues in the mice from acute tetracaine poisoning death group were significantly different. Eleven differential metabolites were identified in serum, including xanthine, spermine, 3-hydroxybutylamine, etc.; twenty-five differential metabolites were identified in liver, including adenylate, adenosine, citric acid, etc.; twelve differential metabolites were identified in heart, including hypoxanthine, guanine, guanosine, etc; four differential metabolites were identified in kidney, including taurochenodeoxycholic acid, 11, 12-epoxyeicosatrienoic acid, dimethylethanolamine and indole. Acute tetracaine poisoning mainly affected purine metabolism, tricarboxylic acid cycle, as well as metabolism of alanine, aspartic acid and glutamic acid. Conclusion The differential metabolites in serum and tissues of mice died of acute tetracaine poisoning are expected to be candidate biomarkers for this cause of death. The results can provide research basis for the mechanism and identification of acute tetracaine poisoning.
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Animais , Camundongos , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Metaboloma , Metabolômica , Camundongos Endogâmicos ICR , TetracaínaRESUMO
OBJECTIVE@#To investigate the effects of phytic acid derived bioactive P2O5-SiO2-CaO gel-glasses (PSC) on the proliferation, differentiation and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro.@*METHODS@#HUVECs were cultured in PSC extracts, which were prepared with endothelial cell medium (ECM) at a gradient concentration of 0.01, 0.1, 1 and 2 g/L. Cells cultured in ECM were used as the control. The effect of PSC on HUVECs proliferation was assessed on the 1st, 3rd, 5th, 7th and 10th days with (4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide assay (MTT), and the optimum PSC concentration for HUVECs proliferation was used in the following experiments. The subsequent experiments were divided into two groups. The experimental group used PSC extracts to culture HUVECs (PSC group) and the control group used ECM to culture HUVECs (ECM group). Gene expression of angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), was detected on the 2nd, 4th and 7th days by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). The morphology and number of tubules formation were observed at the 4th and 10th hours. Image J software was used for counting and quantitative analysis.@*RESULTS@#The results of MTT assay showed that 0.1 g/L PSC group had the most significant effect on promoting HUVECs proliferation. The optical density values of 0.1 g/L PSC group on the 5th and 7th days were significantly higher than those of the other PSC groups and the control group (P < 0.05). The result of real-time RT-PCR showed that 0.1 g/L PSC extract up-regulated the mRNA expression of VEGF and bFGF significantly (P < 0.05). On the 4th day, the gene expressions of VEGF and bFGF in PSC group were 1.59 and 1.45 times higher than those in ECM group respectively, and on the 7th day, the gene levels of VEGF and bFGF in PSC group were 1.98 and 1.37 times higher than those in ECM group respectively. The tubule formation assay showed that the maturity and density of the tubules in 0.1 g/L PSC group was much better than that in the ECM group at the 10th hour. The quantitative analysis by Image J indicated that the tubules number in PSC group (29.63±2.29) was higher than in the ECM group (20.13±2.36), with statistical significance (P < 0.05).@*CONCLUSION@#PSC showed significant promoting effects on HUVECs' proliferation, differentiation and angiogenesis in vitro.
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Humanos , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana , Dióxido de Silício , Fator A de Crescimento do Endotélio VascularRESUMO
To investigate the surgical effect of hip arthroscopic labrum reconstruction. A retrospective study was performed on the clinical data of 12 patients who underwent hip arthroscopic labrum reconstruction in our department from September 2017 to February 2021 and were followed up for 5-46 months, with an average of 21.5 months. All the patients had a hip joint space of more than 2 mm, and Tonnis grade less than level Ⅱ. These 12 patients underwent arthroscopic debridement of hyperplastic synovium, femoral head and neck and/or acetabular osteoplasty, and labrum reconstruction using autograft iliotibial band or gracilis tendon. After the surgery, we conducted follow-up and data collection, recorded the satisfaction of the patients and occurrence of complications, as well as the cartilage lesion of hip joint observed under the arthroscopy. We compared the alpha angle of Dunn X-ray film, center-edge angle (CE angle) of AP X-ray film, modified Harris hip score (mHHS score), hip outcome score (HOS), international hip outcome tool 12 score (iHOT12 Score), and visual analogue scale (VAS scale) before and after the arthroscopic operation, to assess clinical symptom relief and joint function recovery. The 12 patients were followed up for 5-46 (21.5±12.8) months. The VAS scale were (5.3±2.5) and (2.5±1.4) before and after the surgery, showing significant decrease (P=0.018). The mHHS score were (60.6±22.2) and (83.1±5.8) before and after the surgery, showing significant increase (P=0.003). The patient satisfaction was high (7.8±2.0) (range: 0-10). None of the 12 patients had serious complications, revision surgery, or total hip replacement at the end of the last follow-up. Autologous tendon transplantation for reconstruction of acetabular labrum under arthroscopy can improve the clinical symptoms and joint function of patients with femoroacetabular impingement (FAI), which is a safe and effective treatment.
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Humanos , Acetábulo/cirurgia , Artroscopia , Impacto Femoroacetabular/cirurgia , Seguimentos , Articulação do Quadril/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE@#To summarize the extraintestinal manifestations and intestinal complications in children with Crohn's disease (CD).@*METHODS@#The clinical data of 54 children who were diagnosed with CD in Peking Union Medical College Hospital from January 2008 to December 2018 were collected for retrospective analysis of extraintestinal manifestations and intestinal complications. According to the location of the lesion, the children were divided into ileocolonic group (30 cases), colonic group (6 cases), and ileal group (18 cases).@*RESULTS@#In the 54 children, the mean age at diagnosis was 14.5±2.7 years, and the median duration from disease onset to definite diagnosis was 20 months (range: 1-36 months). Twenty-four patients (44%) had extraintestinal manifestations, with the two most common manifestations being growth retardation (11 cases, 20%) and oral mucosal ulcer (10 cases, 19%), followed by arthritis (2 cases, 4%), erythema nodosum (2 cases, 4%), and cholecystitis (2 cases, 4%). There were no significant differences in the incidence of extraintestinal manifestations among the three groups (P=0.792). The most common intestinal complications were anal fistula/perianal abscess (13 cases, 24%), followed by intestinal fistula (5 cases, 9%) and intestinal obstruction (4 cases, 7%). There was a significant difference in the incidence of intestinal complications among the three groups (P=0.0406). No intestinal complications were reported in the colonic group.@*CONCLUSIONS@#Extraintestinal manifestations and intestinal complications are common in children with CD. Perianal examinations should be performed in children with suspected CD. Intestinal complications are less common in children with colonic CD, which may be associated with relatively mild disease condition.
Assuntos
Adolescente , Criança , Humanos , Doença de Crohn , Incidência , Intestinos , Estudos RetrospectivosRESUMO
Objective:To investigate any effect of different environments on the levels of adrenocorticotropic hormone (ACTH), cortisol and testosterone using SAMP8 senescence-accelerated mice.Methods:Thirty SAMP8 mice were randomly divided into an enriched environment (EE) group, an impoverished environment (IE) group and a standard environment (SE) group, each of 10. The serum levels of ACTH, cortisol and testosterone were measured in all of the mice after they had lived in their respective environments for 8 weeks.Results:The average ACTH concentrations of the IE, EE and SE groups were (60.54±16.22), (48.98±15.30) and (28.49±8.24)pg/ml respectively. The average cortisol concentrations were (5.37±0.81), (4.09±0.92) and (3.19±0.88)ng/ml. The average testosterone concentrations being (2.35±0.90), (7.07±1.57) and (3.16±1.10)ng/ml. The average ACTH and cortisol levels were significantly different between the SE and IE groups. The average ACTH and testosterone levels differed significantly between the SE and EE groups and between the EE and IE groups.Conclusions:An impoverished environment can increase the secretion of ACTH and cortisol and activate the hypothalamic-pituitary-adrenal axis, at least in SAMP8 mice. An enriched environment can promote the secretion of ACTH and testosterone, but not that of cortisol.
RESUMO
Objective:To analyze the general situation and traditional Chinese medicine (TCM) syndrome characteristics in patients with coronavirus disease-2019(COVID-19) in Anhui province, and to provide a basis for clinical diagnosis and treatment. Method:The 144 cases of COVID-19 patients in Anhui province were collected from designated hospitals by means of multi-center cross-sectional epidemiological survey. The TCM syndrome information collection table of patients with novel coronavirus pneumonia was created to collect the general data, etiology and pathogenesis, pulse and signs, syndrome type and frequency statistics of the patients, and then summarize and analyze the main symptoms and syndrome distribution characteristics of patients with novel coronavirus pneumonia. Result:The mean age of 144 patients with COVID-19 infection was (43.54±15.91) years old, and the number of males was larger than the number of females (9/7). The age distribution and gender difference of the patients were statistically significant (P<0.05). 36.11%(52/144) of the patients had a history of travel/residence in Wuhan/Hubei province, and 63.89% (92/144) of the patients had a history of close contact with the confirmed patients. The main clinical manifestations included fever, cough, diarrhea, fatigue and poor tolerance. Light red tongue and red tongue were dominant in tongue quality, with mainly greasy coating, slippery pulse, rapid pulse and soft pulse were the main types of pulse. The main types of syndrome differentiation were the common type (76.38%, 110/144), most of which were demonstrated as dampness obstructing the lung and spleen (56.25%, 81/144). There was no significant difference in gender composition and age distribution between two groups. Conclusion:The pathogenesis of COVID-19 patients in Anhui province is closely related to the lung and spleen, and the dampness caused by pathogen of the epidemic virus is the main pathological factor of disease, which is in line with characteristics of dampness epidemic in TCM, also can see concurrently "heat, poison, stasis" for a characteristic.