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1.
Journal of Experimental Hematology ; (6): 553-561, 2023.
Artículo en Chino | WPRIM | ID: wpr-982094

RESUMEN

OBJECTIVE@#To explore the similarities and variations of biological phenotype and cytotoxicity of human umbilical cord blood natural killer cells (hUC- NK) after human umbilical cord blood-derived mononuclear cells (hUC-MNC) activated and expanded by two in vitro high-efficient strategies.@*METHODS@#Umbilical cord blood mononuclear cells (MNC) from healthy donor were enriched by Ficoll-based density gradient centrifugation. Then, the phenotype, subpopulations, cell viability and cytotoxicity of NK cells derived from Miltenyi medium (denoted as M-NK) and X-VIVO 15 (denoted as X-NK) were compared using a "3IL" strategy.@*RESULTS@#After a 14-day's culture, the contents of CD3-CD56+ NK cells were elevated from 4.25%±0.04% (d 0) to 71%±0.18% (M-NK) and 75.2%±1.1% (X-NK) respectively. Compared with X-NK group, the proportion of CD3+CD4+ T cells and CD3+CD56+ NKT cells in M-NK group decreased significantly. The percentages of CD16+, NKG2D+, NKp44+, CD25+ NK cells in X-NK group was higher than those in the M-NK group, while the total number of expanded NK cells in X-NK group was half of that in M-NK group. There were no significant differences between X-NK and M-NK groups in cell proliferation and cell cycle, except for the lower percentage of Annexin V+ apoptotic cells in M-NK group. Compared with X-NK group, the proportion of CD107a+ NK cells in M-NK group were higher under the same effector-target ratio (E∶T) (P<0.05).@*CONCLUSION@#The two strategies were adequate for high-efficient generation of NK cells with high level of activation in vitro, however, there are differences in biological phenotypes and tumor cytotoxicity.


Asunto(s)
Humanos , Sangre Fetal , Células Asesinas Naturales , Linfocitos T , Leucocitos Mononucleares/metabolismo , Proliferación Celular , Antígeno CD56/metabolismo
2.
Chinese Journal of Hematology ; (12): 295-301, 2023.
Artículo en Chino | WPRIM | ID: wpr-984618

RESUMEN

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.


Asunto(s)
Humanos , Masculino , Adolescente , Adulto , Femenino , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidor de la Tirosina Quinasa , Resultado del Tratamiento , Estudios Retrospectivos , Dasatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Trombocitopenia
3.
Journal of Traditional Chinese Medicine ; (12): 2188-2191, 2023.
Artículo en Chino | WPRIM | ID: wpr-997284

RESUMEN

Bronchiectasis is characterized by a “vicious cycle” involving compromised host defense, mpaired clearance of airway mucus, bacterial colonization, infections, and inflammation, leading to frequent acute exacerbations and diminished quality of life. Based on the hypothesis of “vicious circle”, this paper explores the treatment of bronchiectasis by traditional Chinese medicine (TCM) from three aspects. Firstly, dissipating excessive “phlegm” secretion and enhancing airway clearance form the foundation of the treatment, aiming to improve the condition of mucus hypersecretion. Secondly, invigorating spleen for strengthening vital energy can improve the function of immune system and reduce recurrent infections and acute attacks. Lastly, clearing heat and purging the lung can alleviate infection and inflammatory damage. By employing these methods, TCM can disrupt the progression of the “vicious circle”, delaying disease advancement, minimizing acute exacerbations, and improving the quality of life for patients.

4.
Journal of Integrative Medicine ; (12): 464-473, 2023.
Artículo en Inglés | WPRIM | ID: wpr-1010956

RESUMEN

OBJECTIVE@#Acute liver failure (ALF) is characterized by severe liver dysfunction, rapid progression and high mortality and is difficult to treat. Studies have found that sulforaphane (SFN), a nuclear factor E2-related factor 2 (NRF2) agonist, has anti-inflammatory, antioxidant and anticancer effects, and has certain protective effects on neurodegenerative diseases, cancer and liver fibrosis. This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action.@*METHODS@#Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo. NRF2 agonist SFN and histone deacetylase 6 (HDAC6) inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, lactate dehydrogenase (LDH), Fe2+, glutathione (GSH) and malondialdehyde (MDA) were detected. The expression of HDAC6, NRF2, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting and immunofluorescence.@*RESULTS@#Our results show that NRF2 was activated by SFN. LDH, Fe2+, MDA and ACSL4 were downregulated, while GSH, GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo, indicating the inhibitory effect of SFN on ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.@*CONCLUSION@#SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6. Please cite this article as: Zhang YQ, Shi CX, Zhang DM, Zhang LY, Wang LW, Gong ZJ. Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity. J Integr Med. 2023; 21(5): 464-473.


Asunto(s)
Humanos , Ferroptosis , Factor 2 Relacionado con NF-E2/genética , Fallo Hepático Agudo/tratamiento farmacológico , Isotiocianatos/farmacología , Glutatión , Histona Desacetilasa 6
5.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 222-230, 2022.
Artículo en Chino | WPRIM | ID: wpr-940406

RESUMEN

This study aims to summarize the clinical research evidence on oral Chinese patent medicines for the treatment of influenza with the method of scoping review, and thus clarify the status quo and problems. Specifically, the target medicines were selected from related drug catalogues and diagnosis and treatment protocols, and the basic information of the medicines on the specifications was collected. Articles on these medicines were retrieved from Chinese and English databases for statistical analysis and visualization. Finally, 36 medicines and 87 articles were included. The main efficacy of the medicines is clearing heat and removing toxin, and the main components of the medicines are Lonicerae Japonicae Flos, Forsythiae Fructus, and Isatidis Radix. A total of 12 medicines can be used for the treatment of mumps and acute bronchitis in addition to influenza. Only 6 medicines have contraindications and adverse reactions labeled on the specifications. Papers on oral Chinese patent medicines in the treatment of influenza show an increasing trend, and the authors are from 25 provinces and cities in China. Among them, papers on Lianhuaqingwen preparations take up the largest proportion. The studies were mostly randomized controlled trials, non-randomized controlled trials, and retrospective research. A total of 13 studies were supported by national funding, and only 9 studies included more than 200 cases. The most frequently used method was the comparison of the intervention effect of Chinese patent medicines with western medicine, and the treatment course was generally 3-14 days. A total of 7 outcome indicators were used in the studies and the frequency was in the order of ① composite effective rate,② antipyretic effect, ③ symptom improvement, ④ safety indicator, ⑤ virological examination, ⑥ serum inflammatory factor, and ⑦ traditional Chinese medicine (TCM) syndrome score. The conclusions in the clinical studies show difference from the information in drug catalogues. The drug specifications are generally not standard. The available clinical studies have the limitations of small quantity, low in quality, and no demonstration of TCM advantages. In the future, it is necessary to optimize the specifications of Chinese patent medicines, enhance clinical research, further standardize the design of clinical research, and highlight the characteristics of Chinese patent medicines, thereby providing evidence to support the comprehensive clinical evaluation of oral Chinese patent medicines for influenza.

6.
Journal of Forensic Medicine ; (6): 719-725, 2022.
Artículo en Inglés | WPRIM | ID: wpr-984163

RESUMEN

OBJECTIVES@#To establish a system for simultaneous detection of miR-888 and miR-891a by droplet digital PCR (ddPCR), and to evaluate its application value in semen identification.@*METHODS@#The hydrolysis probes with different fluorescence modified reporter groups were designed to realize the detection of miR-888 and miR-891a by duplex ddPCR. A total of 75 samples of 5 body fluids (including peripheral blood, menstrual blood, semen, saliva and vaginal secretion) were detected. The difference analysis was conducted by Mann-Whitney U test. The semen differentiation ability of miR-888 and miR-891a was evaluated by ROC curve analysis and the optimal cut-off value was obtained.@*RESULTS@#There was no significant difference between the dual-plex assay and the single assay in this system. The detection sensitivity was up to 0.1 ng total RNA, and the intra- and inter-batch coefficients of variation were less than 15%. The expression levels of miR-888 and miR-891a detected by duplex ddPCR in semen were both higher than those in other body fluids. ROC curve analysis showed that the AUC of miR-888 was 0.976, the optimal cut-off value was 2.250 copies/μL, and the discrimination accuracy was 97.33%; the AUC of miR-891a was 1.000, the optimal cut-off value was 1.100 copies/μL, and the discrimination accuracy was 100%.@*CONCLUSIONS@#In this study, a method for detection of miR-888 and miR-891a by duplex ddPCR was successfully established. The system has good stability and repeatability and can be used for semen identification. Both miR-888 and miR-891a have high ability to identify semen, and the discrimination accuracy of miR-891a is higher.


Asunto(s)
Femenino , Humanos , Masculino , Líquidos Corporales/química , MicroARNs/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Saliva/química , Semen/química
7.
Journal of Experimental Hematology ; (6): 607-612, 2022.
Artículo en Chino | WPRIM | ID: wpr-928761

RESUMEN

OBJECTIVE@#To investigate the regulatory effect and mechanism of DNA methyltransferase 3A (DNMT3a) in hydroquinone-induced hematopoietic stem cell toxicity.@*METHODS@#Cells (HSPC-1) were divided into 4 groups, that is A: normal HSPC-1; B: HQ-intervented HSPC-1; C: group B + pcDNA3 empty vector; D: group B + pcDNA3- DNMT3a. RT-qPCR and Western blot were used to detect the expression levels of DNMT3a and PARP-1 mRNA and protein, respectively. Cell morphology was observe; Cell viability and apoptosis rate of HSPC-1 were detected by MTT and flow cytometry, respectively.@*RESULTS@#Compared with group A, the expression levels of DNMT3a mRNA and protein in HSPC-1 of group B were decreased, while PARP-1 mRNA and protein were increased (P<0.05); there was no significant difference in the above indexes between group C and group B; compared with group B, the expression levels of DNMT3a mRNA and protein showed increased, while PARP-1 mRNA and protein were decreased significantly in cells of group D transfected with DNMT3a (P<0.05). Cells in each group were transfected with DNMT3a and cultured for 24 h, HSPC-1 in group A showed high density growth and mononuclear fusion growth, while the number of HSPC-1 in group B and C decreased and grew slowly. Compared with group B and C, the cell growth rate of group D was accelerated. The MTT analysis showed that cell viability of HSPC-1 in group B were lower than that of group A at 24 h, 48 h and 72 h (P<0.05); after transfected with DNMT3a, the cell viability of HSPC-1 in group D were higher than that of group B at 24 h, 48 h and 72 h (P<0.05). The apoptosis rate of cells in group B was significantly higher than that of group A (P<0.001), while the apoptosis rate in group D was lower than that of group B (P<0.001).@*CONCLUSION@#DNMT3a may be involved in the damage of hematopoietic stem cells induced by hydroquinone, which may be related to the regulation of PARP-1 activity by hydroquinone-inhibited DNMT3a.


Asunto(s)
Humanos , Apoptosis , Proliferación Celular , ADN Metiltransferasa 3A , Células Madre Hematopoyéticas/efectos de los fármacos , Hidroquinonas/toxicidad , Poli(ADP-Ribosa) Polimerasa-1 , ARN Mensajero/metabolismo
8.
Journal of Experimental Hematology ; (6): 36-42, 2022.
Artículo en Chino | WPRIM | ID: wpr-928667

RESUMEN

OBJECTIVE@#To investigate regulatory T cells (Tregs) relative content in peripheral blood and bone marrow of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with or without decitabine (DAC), analyze the immunomodulatory of Tregs in pathogenesis and remission of MDS and AML, as well as effect of DAC on Tregs.@*METHODS@#From October 2018 to February 2019, 15 patients with MDS and 49 patients with AML (newly diagnosed, treated with DAC or other chemotherapy regimens) were enrolled in this study, and 14 cases with iron deficiency or megaloblastic anemia while without malignant tumor and autoimmune disease as controls. The Tregs relative contents in bone marrow and peripheral blood were analyzed by flow cytometry, meanwhile clinical data of the objects were collected.@*RESULTS@#In peripheral blood and bone marrow of the patients with MDS and AML, the Tregs relative contents at newly diagnosed were higher than those of the control group (P=0.05, P=0.043). The Tregs relative content of AML patients in DAC regimen treatment group was significantly lower than that in the newly diagnosed group and non-DAC chemotherapy group (P<0.05). In DAC regimen treatment group, the Tregs relative contents was significantly lower in remission group than in non-remission group (P<0.05). There was no difference between DAC regimen treatment group and control group in Tregs relative content.@*CONCLUSION@#DAC may increase the body's anti-tumor immunity by consuming Tregs content, enhance the body's immune function to identify and kill tumor cells, thereby promote the patients' reliefs.


Asunto(s)
Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Médula Ósea , Decitabina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Linfocitos T Reguladores , Resultado del Tratamiento
9.
Chinese Journal of Hematology ; (12): 54-62, 2022.
Artículo en Chino | WPRIM | ID: wpr-929530

RESUMEN

Objective: To explore the impacts of socio-demographic and clinical co-variates on treatment responses and outcomes in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitor (TKI) and identified the predictive models for them. Methods: Data of newly diagnosed adult patients with CML-CP receiving first-line TKI and having complete socio-demographic data and clinical information were reviewed. Cox model was used to identify the independent variables associated with complete cytogenetic response (CCyR) , major molecular response (MMR) , molecular response 4 (MR(4)) and molecular response 4.5 (MR(4.5)) , as well as failure-free survival (FFS) , progression-free survival (PFS) , overall survival (OS) and CML-related OS. Results: A total of 1414 CML-CP patients treated with first-line imatinib (n=1176) , nilotinib (n=170) or dasatinib (n=68) were reviewed. Median age was 40 (18-83) years and 873 patients (61.7% ) were males. Result of the multivariate analysis showed that lower educational level (P<0.001-0.070) and EUTOS long-term survival intermediate or high-risk (P<0.001-0.009) were significantly associated with lower cumulative incidences of CCyR, MMR, MR(4) and MR(4.5), as well as the inferior FFS, PFS, OS and CML-related OS. In addition, those who were males, from rural households, had white blood cells (WBC) ≥120×10(9)/L, hemoglobin (HGB) <115 g/L and treated with first-line imatinib had significantly lower cumulative incidences of cytogenetic and/or molecular responses. Being single, divorced or widowed, having, rural household registration, WBC≥120×10(9)/L, HGB<15 g/L, and comorbidity (ies) was significantly associated with inferior FFS, PFS, OS, and/or CML-related OS. Thereafter, the patients were classified into several subgroups using the socio-demographic characteristics and clinical variables by cytogenetic and molecular responses, treatment failure and disease progression, as well as overall survival and CML-related OS, respectively. There were significant differences in treatment responses and outcomes among the subgroups (P<0.001) . Conclusion: Except for clinical co-variates, socio-demographic co-variates significantly correlated with TKI treatment responses and outcomes in CML-CP patients. Models established by the combination of independent socio-demographic and clinical co-variates could effectively predict the responses and outcome.


Asunto(s)
Adulto , Humanos , Masculino , Antineoplásicos/uso terapéutico , Dasatinib/uso terapéutico , Demografía , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
10.
Chinese Acupuncture & Moxibustion ; (12): 1276-1280, 2021.
Artículo en Chino | WPRIM | ID: wpr-921045

RESUMEN

Taking the clinical trial of acupuncture in treatment of postprandial distress syndrome as an example, this paper proposes that the acupuncture clinical trial protocol should be optimized in view of acupuncture prescription, acupuncture frequency and outcomes. Besides, the data quality of acupuncture clinical trial should be improved in consideration of data sharing and electronic data capture so as to provide a reference for the majority of researchers to optimize and implement acupuncture clinical trial.


Asunto(s)
Humanos , Terapia por Acupuntura , Ensayos Clínicos como Asunto , Dispepsia/terapia , Investigadores , Gastropatías/terapia , Resultado del Tratamiento
11.
Chinese Acupuncture & Moxibustion ; (12): 583-587, 2021.
Artículo en Chino | WPRIM | ID: wpr-877663

RESUMEN

OBJECTIVE@#To evaluate the clinical effect of acupuncture for the improvements in various dyspeptic symptoms of postprandial distress syndrome.@*METHODS@#The secondary analysis on the data of a multi-center randomized controlled trial (RCT) was conducted. 278 patients with postprandial distress syndrome were randomized into an acupuncture group (138 cases) and a sham-acupuncture group (140 cases). In the acupuncture group, acupuncture was applied to Baihui (GV 20), Danzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), Zusanli (ST 36), etc. In the sham-acupuncture group, 6 sites, neither located on meridians nor belonged to meridian acupoints, were selected and punctured shallowly. The duration of treatment was 20 min each time, 3 times a week, for 4 weeks totally in the two groups. The follow-up visit lasted for 12 weeks. The scores of dyspeptic symptoms were compared between the two groups before treatment, during treatment (in week 1, 2, 3 and 4) and during follow-up (in week 8, 12 and 16) separately.@*RESULTS@#Besides the scores of early satiety and vomiting in the sham-acupuncture group in week 1, the scores of the other dyspepsia symptoms during treatment and follow-up were all reduced in the two groups as compared with those before treatment (@*CONCLUSION@#Acupuncture remarkably relieves postprandial fullness, early satiety, upper abdominal bloating and belching in patients with postprandial distress syndrome.


Asunto(s)
Humanos , Puntos de Acupuntura , Terapia por Acupuntura , Dispepsia/terapia , Meridianos , Resultado del Tratamiento
12.
Chinese Acupuncture & Moxibustion ; (12): 325-329, 2021.
Artículo en Chino | WPRIM | ID: wpr-877614

RESUMEN

Pilot study is essential prerequisite for large-scale research. Acupuncture is a complex intervention measure. The factors of its clinical effect and effect mechanism are complicated. Hence, the resource waste is easily induced in research if the large-scale clinical research is rashly carried out before scientific verification. Currently, there is still a lack of high-quality evidence of clinical research, which affects the promotion and application of the curative effect of acupuncture. The pilot study of acupuncture can evaluate the feasibility and the process coordination of trial, optimize program and process and provide the basis of sample size calculation prior to launching a full-scale trial. Thereby, the methodological quality of acupuncture research and the reliability of trial results can be improved. In the paper, the arguments focus on the definition, design and report of pilot study so as to provide the approaches and references for the design and implementation of pilot study of clinical research of acupuncture.


Asunto(s)
Terapia por Acupuntura , Proyectos Piloto , Reproducibilidad de los Resultados , Proyectos de Investigación , Resultado del Tratamiento
13.
Chinese Acupuncture & Moxibustion ; (12): 27-30, 2021.
Artículo en Chino | WPRIM | ID: wpr-877544

RESUMEN

OBJECTIVE@#To verify the clinical effect of acupuncture on knee osteoarthritis (KOA).@*METHODS@#Forty-two patients with KOA were randomly divided into an acupuncture group (21 cases, 1 case dropped off) and a sham acupuncture group (21 cases, 1 case dropped off). The patients in the acupuncture group were treated with routine acupuncture at 5-6 local acupoints [Dubi (ST 35), Neixiyan (EX-LE 4), Heding (EX-LE 2), Yinlingquan (SP 9), Xuehai (SP 10), Zusanli (ST 36), etc.] and 3-4 distal acupoints [Fengshi (GB 31), Waiqiu (GB 36), Xuanzhong (GB 39), Zulinqi (GB 41), etc.]. The patients in the sham acupuncture group were treated with shallow needling technique at non-acupoint. The needles were retained for 30 min in both groups. All the treatment was given three times a week for 8 weeks. Knee injury and osteoarthritis outcome score (KOOS) were recorded before and after treatment and 18-week follow-up.@*RESULTS@#Compared before treatment, the scores of 5 dimensions of KOOS [pain, symptoms (except pain), daily activities, sports and entertainment, and quality of life] were increased after treatment and during follow-up in the two groups (@*CONCLUSION@#Acupuncture can reduce the pain symptoms and improve daily activities in patients with KOA.


Asunto(s)
Humanos , Puntos de Acupuntura , Terapia por Acupuntura , Traumatismos de la Rodilla , Osteoartritis de la Rodilla/terapia , Calidad de Vida , Resultado del Tratamiento
14.
Acta Pharmaceutica Sinica ; (12): 2266-2275, 2021.
Artículo en Chino | WPRIM | ID: wpr-887054

RESUMEN

We previously reported that active Astragalus polysaccharides APS-Ⅱ generate strong immune activity. Here we establish the optimal method for APS-II acid degradation. After preliminary structural studies and separation and preparation of the degradation products, the oligosaccharide active center with the strongest immune activity was identified by in vitro immune cell culture experiments. The optimum acid degradation conditions for APS-II were determined by a single factor experiment and an orthogonal experiment. Astragalus oligosaccharides prepared under the optimal conditions were subjected to structural analysis by hydrophilic interaction chromatography - electrospray ionization source - high resolution time-of-flight mass spectrometry. The products were separated and oligosaccharide fragments with different degrees of polymerization were isolated by preparative purification chromatography. Finally, fragments of the immunologically active centers were identified by in vitro immune cell cultures from multiple perspectives. The results show that the optimal acid hydrolysis conditions for APS-Ⅱ are hydrolysis temperature 80 ℃, trifluoroacetic acid concentration 1.0 mol·L-1, hydrolysis time 1 h. The degradation conditions have good repeatability. The degradation product is a six-carbon aldehyde glycan structure with the main chain 1→4 connected. The immune activity screening experiment for six oligosaccharide fragments showed that larger molecular weight oligosaccharides have stronger immune-promoting effects. It is speculated that the immunologically active center of Astragalus oligosaccharide is located in the sugar chain of DP9-DP19. The animal welfare and the experimental process in this study follow the requirements of the Animal Ethics Committee of Shanxi University. This result suggests a foundation for the structural characterization and structure-activity relationship research of Astragalus oligosaccharides, and may promote the development of Astragalus oligosaccharide drugs.

15.
Acta Pharmaceutica Sinica ; (12): 1936-1944, 2021.
Artículo en Chino | WPRIM | ID: wpr-887009

RESUMEN

italic>Astragalus polysaccharides are the main immunomodulatory substances in Astragali Radix. The structure of polysaccharides is difficult to accurately determine, which limits the in-depth study of the molecular mechanism of Astragalus polysaccharides in vivo. "Polysaccharide receptor theory" believes that there are one or more oligosaccharide fragment "active centers" in immunologically active polysaccharide molecules. Therefore, the degradation of Astragalus polysaccharides into oligosaccharides and the study of the active centers of polysaccharides at the oligosaccharide level provide new ideas in the study of the structure and mechanism of Astragalus polysaccharides. This article adopts endo-α-1,4-glucanase enzymatic hydrolysis, and determines the best degradation conditions through single factor test and orthogonal test to degrade the immunologically active polysaccharide APS-Ⅱ (10 kDa component) into oligomers with different degrees of polymerization. Then through the preparation of polyacrylamide gel chromatography and specific immune and non-specific immune cell tests, the immune activity screening of different oligosaccharide components is carried out. The animal welfare and the experimental process in this study follow the requirements of the Animal Ethics Committee of Shanxi University. The results showed that compared with the immunologically active polysaccharide APS-Ⅱ, different oligosaccharide components have obvious differences in different immunological activities. This paper studies the different immunological activities of Astragalus polysaccharides at the level of oligosaccharides, laying a foundation for further elucidating the structure and function of Astragalus polysaccharides, enriching the theory of polysaccharide receptors, and providing new ideas for the development of Astragalus polysaccharides.

16.
Journal of Forensic Medicine ; (6): 293-298, 2020.
Artículo en Inglés | WPRIM | ID: wpr-985115

RESUMEN

Objective To study the expression of the three autophagy-associated proteins, BECN1, LC3 and p62, after the injury of the skeletal muscle of rats and to explore its application in differentiation between antemortem and postmortem injury. Methods The 72 healthy Sprague-Dawley rats were randomly divided into the undamaged control group, the antemortem injury group (0.5 h, 1 h, 2 h, 4 h, 8 h, 16 h and 24 h) and postmortem injury group (0.5 h, 1 h, 2 h and 4 h). A model of the injured right hind limb of rats was constructed. The expressions of the autophagy-associated proteins, BECN1, LC3-2/LC3-1 and p62, in the control group, the antemortem injury group and postmortem injury group were detected by Western blotting method. The data were respectively centralized and standardized and the orthogonal partial least square-discrimination analysis (OPLS-DA) identification model of antemortem and postmortem injury groups was constructed. Results The expression of BECN1, p62 protein and LC3-2/LC3-1 after the injury of the skeletal muscle of the rats showed different degrees of changes, but the differences among the 3 groups had no statistical significance. Antemortem and postmortem injury groups can be distinguished by centralizing and standardizing the expression levels of autophagy protein BECN1 and the ratio of LC3-2/LC3-1. The principal components extracted from OPLS-DA model of antemortem injury and postmortem injury had a relatively good interpretation of the model (Rx2=0.563, Ry2=0.439), but it were less predictive (Q2=0.366). Conclusion The expression of BECN1 and the ratio of LC3-2/LC3-1 in injured local tissue of the rat skeletal muscle can be used for the differentiation of antemortem injury group and postmortem injury group.


Asunto(s)
Animales , Ratas , Autofagia , Músculo Esquelético , Cambios Post Mortem , Proteínas/metabolismo , Ratas Sprague-Dawley
17.
Journal of Experimental Hematology ; (6): 267-274, 2020.
Artículo en Chino | WPRIM | ID: wpr-781453

RESUMEN

OBJECTIVE@#To investigate the effects of human amniotic mesenchymal stem cell(AMSC) on acute graft-versus-host disease (aGVHD) in xenotransplatation.@*METHODS@#NPG mice were injected with human PBMNC via tail vein to establish a xenografted aGVHD model. The mice in the experimental group were divided into PBMNC infusion group and PBMNC+AMSC co-infusion group, the general condition, survival time and manifestations of aGVHD were observed, the body weight and blood routine indicators were detected, the pathological changes of aGVHD target organs (lung, liver, spleen, small intestine) were observed by HE staining, and the levels of human T cells in peripheral blood, tissues and organs of mice was detected by flow cytometry.@*RESULTS@#The manifestations of aGVHD (lassitude hunchback, shrub, weight reduction, etc.) and the pathological damage of the target organs (lung, liver, spleen, intestine) in PBMNC+AMSC co-infusion group were lighter than those in PBMNC infusion group. Moreover, the PBMNC and AMSC co-infusion significantly reduced the implantion proportion of human T lymphocytes (CD3, CD45) in mice and increased the ratio of CD4/CD8.@*CONCLUSION@#Infusion of human-derived AMSC can attenuate the manifestations of aGVHD in mouse xenografts to a certain level, and improve the pathological damage of receptor target organs.

18.
Chinese Journal of Experimental and Clinical Virology ; (6): E006-E006, 2020.
Artículo en Chino | WPRIM | ID: wpr-819275

RESUMEN

Objective To evaluate the clinical experience of extracorporeal membrane oxygenation (ECMO) treatment on two cases of infection with the critical Corona Virus Disease 2019 (COVID-19) complicated by fulminant myocarditis (FM) . Methods This study selects two COVID-19 cases comorbid with fulminant myocarditis and had been treated with ECMO in Shenzhen Third People's Hospital from January 2020 to February 2020. We compare the index of inflammation, immunization, D-dimer and lactic acid before and after ECMO treatment in 24 and 96 hours, cardiopulmonary function before and after ECMO treatment in 24, 48, 72, 96 hours,. We also analyze the complications and clinical outcomes of the two cases during the ECMO treatment. Results Both patients were elderly obese men with chronic cardiopulmonary disease. Comparing the laboratory test results and imaging data of the two patients, the acute lung injury score, oxygenation index, albumin level, hypersensitive C-reactive protein, lactate and lactate dehydrogenase levels in 2 patients after ECMO treatment were improved as compared with those before ECMO treatment. Finally, case 1 died of multiple organ failure and his cardiac function continued to deteriorate, while, case 2 successfully withdrew and his cardiac function gradually improved. Conclusions For critical COVID-19 patients with fulminant myocarditis, ECMO treatment can improve pulmonary function in the short term, provide valuable time for rescuing COVID-19 patients with fulminant myocarditis.

19.
Acta Pharmaceutica Sinica ; (12): 2968-2975, 2020.
Artículo en Chino | WPRIM | ID: wpr-862275

RESUMEN

Characterization of the polysaccharides and monosaccharides of Bupleurum chinense was undertaken to identify differences in the Bupleurum chinense's sugar profiles, so as to provide a basis for the identification of different varieties. High performance liquid chromatography (HPLC) was used to generate chromatograms of the total polysaccharides of Bupleurum using an Evaporation Light Detector (ELSD), and a monosaccharide chromatogram was generated using a UV-detector (UV) following polysaccharide derivatization. The data were analyzed using SIMCA software and SPSS software to distinguish different varieties of Bupleurum. The results show that the yield of polysaccharides from Bupleurum falcatum is the highest, while the yield of polysaccharides from Bupleurum chinense is the lowest. The polysaccharide spectrum shows that the molecular weights of the polysaccharides in different Bupleurum differ, and their percentages of the total peak area are also different. The four Bupleurum polysaccharides are composed of mannose, glucuronic acid, rhamnose, galacturonic acid, glucose, galactose, and arabinose, but differ in length. The ratio of glucose to arabinose in Bupleurum chinense, Bupleurum scorzonerifolium, Bupleurum falcatum and Bupleurum marginatum var. stenophyllum is: 3.0-4.0, 5.5-7.0, 12.0-17.0, 9.0-12.0. In this study, a sugar profile technique was developed to provide a new method for the identification of different varieties of Bupleurum.

20.
Chinese Journal of Hematology ; (12): 93-99, 2020.
Artículo en Chino | WPRIM | ID: wpr-1012150

RESUMEN

Objective: To explore the efficacy and prognosis of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia (CML) in the chronic phase (CP) and accelerated phase (AP) . Methods: From January 2008 to November 2018, the data of CML patients who failed first- or second-line tyrosine kinase inhibitor (TKI) -therapy received nilotinib or dasatinib as second-line and third-line therapy were retrospectively reviewed. Results: A total of 226 patients receiving nilotinib or dastinib as second-line (n=183) and third-line (n=43) therapy were included in this study. With a median follow-up of 21 (range, 1-135) months, the cumulative rates of complete hematological response (CHR) , complete cytogenetic response (CCyR) and major molecular response (MMR) were 80.4%, 56.3%and 38.3%, respectively in those receiving TKI as second-line TKI therapy. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 78.7%and 93.1%, respectively. Multivariate analyses showed that Sokal high risk, female gender, the best response achieved <CHR on the first-line TKI-therapy, the interval from diagnosis to switching to second-line TKI ≥18 months, AP or hematologic failure, or non-specific mutation of BCR-ABL kinase domain before second-line TKI therapy, developing severe hematologic toxicity during the second-line TKI therapy were variables associated with poor responses or outcomes on second-line TKI therapy. With a median follow-up of 6 (range, 3-129) months, the cumulative CHR, CCyR and MMR were 95.7%, 29.3%, and 18.6%, respectively in those receiving the third-line TKI therapy. The 2-year PFS and OS rates were 66.8% and 93.8%, respectively. The patients with an interval from diagnosis to starting TKI ≥6 months, achieving no cytogenetic response on the second-line TKI, the interval from diagnosis to starting second-line TKI ≥60 months, and progression to AP before the third-line TKI therapy had lower probabilities of responses and unfavorable outcomes. Conclusions: The efficacy of dasatinib and nilotinib as second- or third-line TKI-therapy were active in the CML patients with TKI-resistance. The best response achieved on previous TKI-therapy, the disease phase before switching TKI, and the severe hematologic toxicity developing on the current TKI-therapy were associated with the responses and outcomes.


Asunto(s)
Femenino , Humanos , Dasatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Pirimidinas/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
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