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The chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine is the key core skeleton of potent Bruton's tyrosine kinase (BTK) inhibitor Zanubrutinib, and the catalyst-controlled asymmetric hydrogenation of planar multinuclear pyrimidine heteroarenes with multiple N atoms could provide an efficient route toward its synthesis. Owing to the strong aromaticity and poisoning effect toward chiral transition metal catalyst, asymmetric hydrogenation of pyrazolo[1,5-a]pyrimidines with multiple nitrogen atoms is still a challenge for synthesizing the chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrimidine. Herein, an efficient iridium-catalyzed asymmetric hydrogenation of pyrazolo[1,5-a]pyrimidines has been developed using substrate activation strategy, with up to 99% ee. The decagram scale synthesis further demonstrated the potential and promise of this procedure in the synthesis of Zanubrutinib. In addition, a mechanistic study indicated that the hydrogenation starts with 1,2-hydrogenation.
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Objective To construct a quantitative evaluation system for professional competency of healthcare-associated infection(HAI)management professionals,and provide scientific basis for the training of professionals through scientific evaluation.Methods Literature and experience summary were adopted to construct evaluation key points.Evaluation key points were selected through expert consultation method,and the weight coefficient of evaluation key points was calculated.The hierarchical evaluation content options for each evaluation key point were designed and assigned score values by expert group.The product of the score of each evaluation key point and its weight was the score for this point,and the total score of the evaluated person was calculated based on the total score of all evaluation points.Results The evaluation system included 25 evaluation key points in 9 dimensions,in-cluding"basic conditions""recognition competency in HAI""monitoring competency in HAI""prevention and con-trol technology application competency in HAI""emergency response competency""organization and coordination competency""quality improvement competency""education and training competency"and"professional scientific re-search competency in HAI prevention and control".Each evaluation key point contained three hierarchical quantita-tive score contents.The internal consistency reliability of the expert's questionnaire consultation Cronbach's a coef-ficient was 0.873,the total scale-level content validity index(S-CVI)was 0.868,and the item-level content validity index(I-CVI)ranged 0.71-1.Conclusion The quantitative evaluation system constructed in this study meets the requirements for reliability and validity.It is scientifically feasible for evaluating the professional competency of HAI management professionals.It can effectively identify weakness in their competency,determine training directions and priorities,and provide a scientific basis for talent development and team building for HAI management profe-ssionals in medical institutions,and promotes high-quality development within hospitals.
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The prognosis of various cardiovascular diseases eventually leads to heart failure (HF). An energy metabolism disorder of cardiomyocytes is important in explaining the molecular basis of HF; this will aid global research regarding treatment options for HF from the perspective of myocardial metabolism. There are many drugs to improve myocardial metabolism for the treatment of HF, including angiotensin receptor blocker-neprilysin inhibitor (ARNi) and sodium glucose cotransporter 2 (SGLT-2) inhibitors. Although Western medicine has made considerable progress in HF therapy, the morbidity and mortality of the disease remain high. Therefore, HF has attracted attention from researchers worldwide. In recent years, the application of traditional Chinese medicine (TCM) in HF treatment has been gradually accepted, and many studies have investigated the mechanism whereby TCM improves myocardial metabolism; the TCMs studied include Danshen yin, Fufang Danshen dripping pill, and Shenmai injection. This enables the clinical application of TCM in the treatment of HF by improving myocardial metabolism. We systematically reviewed the efficacy of TCM for improving myocardial metabolism during HF as well as the pharmacological effects of active TCM ingredients on the cardiovascular system and the potential mechanisms underlying their ability to improve myocardial metabolism. The results indicate that TCM may serve as a complementary and alternative approach for the prevention of HF. However, further rigorously designed randomized controlled trials are warranted to assess the effect of TCM on long-term hard endpoints in patients with cardiovascular disease.
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Cardiovascular Diseases , Drugs, Chinese Herbal , Heart Failure , Salvia miltiorrhiza , Angiotensin Receptor Antagonists/therapeutic use , Cardiovascular Diseases/drug therapy , Drugs, Chinese Herbal/adverse effects , Heart Failure/chemically induced , Heart Failure/drug therapy , Humans , Medicine, Chinese Traditional/methodsABSTRACT
Aim To investigate the role of long noncoding RNA Kcnqlotl in mice with diabetic cardiomyopathy (DCM) and its mechanism. Methods C57BL/6 mice were divided into control group and diabetic group (DM). DM model was established by intraperitoneal injection of streptozocin. The DCM model was established by feeding for eight weeks. Kcnqlotl - shRNA lentivirus was injected to inhibit Kcnqlotl. The expression levels of Kcnqlotl in the left ventricle of mice in each group were detected by qRT-PCR. The function and structure of the left ventricular were evaluated using echocardiography, HE and Masson staining. The expression levels of collagen I, collagen M and TGF-β1/Smads signaling pathway were detected by Western blot. The expression levels of NLRP3, caspase-1, IL-1β and GSDMD-N in the left ventricular tissue of mice were detected by immunohistochemistry, qRT-PCR and Western blot. Results qRT-PCR showed that the expression of Kcnqlotl in the left ventricular tissues of diabetic mice significantly increased compared with the control group, and was significantly inhibited by Kcnqlotl-shRNA. The systolic and diastolic functions of diabetic hearts significantly decreased, and cardiomyocyte hypertrophy and myocardial fibrosis appeared as well. The cardiac function and structure of the diabetic mice were significantly improved, collagen expression levels were down-regulated and the TGF-β1/Smads pathways were inhibited after silencing Kcnqlotl. The expression levels of the pyroptosis related factors were down-regulated in the DM + Kcnqlotl-shRNA group. Conclusions The expression levels of IncRNA Kcnqlotl increase in the STZ-induced diabetic mice. Silencing Kcnqlotl can alleviate the pyroptosis and inhibit the TGF-β1/Smads pathway, thus ameliorating myocardial fibrosis.
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Objective@#To analyze the phenomenon of alcohol drinking among school-aged children in Beijing, and to provide a reference for making measures for possible preventive interventions.@*Methods@#Data were from the Beijing Students’ Nutrition and Health Surveillance among 3 776 school-aged children in Beijing in 2015. Prevalence, frequency and pattern of drinking, daily consumption of alcoholic drinks, as well as influencing factors were described.@*Results@#Drinking was found in 11.2% of school-aged children, the drinking differences of students of different genders, grades, areas were of statistical significance(χ2=8.49, 126.91, 18.36, P<0.01), and the average age of the 423 drinking students was (10.5±1.6)years old. 290 children reported alcohol drinking once or twice in the past 1 week, accounting for 68.6% of the drinking children. 93 children reported drinking for three to six times, accounting for 22.0%, 40 students reported drinking for more than 7 times. Blending wine(58.2%) ranked as the most preferred, followed by beer(33.3%).Drinking was more likely reported among school-aged children who were boys, in higher grade, living in suburbs of Beijing, while children whose parents were more likely to drink in the past month, or from family with lower income and lower education level were also more likely to drink(P<0.05).@*Conclusion@#Drinking among school-aged children in Beijing in the past 1 is common, but their drinking amount per day was relatively low. Drinking was influenced by age, gender, living place, family and other factors. It is recommended that non-alcoholic intervention should be carried out as soon as possible for them.
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Objective::To extract crude polysaccharides from Dictamnus dasycarpus (DDP) for separation and purification, and study its anti-psoriasis effect. Method::After interception of DDP with a molecular weight of less than 10 kDa (DDP-UF) using membrane separation technology, four components (DDP-UF-1, DDP-UF-2, DDP-UF-3, DDP-UF-4) were isolated and purified by DEAE-52 cellulose column. Then, the physical and chemical properties and structural characteristics of DDP-UF-1-4 samples were determined by infrared spectroscopy, high performance gel permeability chromatography (HPGPC), high performance liquid chromatography (HPLC) and scanning electron microscope (SEM). Imiquimod cream was selected to induce mouse models of psoriasis, diethylstilbestrol was used to induce vaginal epithelial cell proliferation in female mice, interleulein-17(IL-17) and IL-23 contents of serum in each mouse group were detected by enzyme-linked immunosorbent assay (ELISA), and skin tissues of the mouse back and vaginal epithelial cells had mitotic index changes by hematoxylin-eosin staining (HE). Result::DDP-UF-1-4 all exhibited the characteristic absorption peaks of polysaccharide, and the molecular weights of DDP-UF-1-4 were 10 948, 40 148, 32 222 and 19 943 Da, respectively. The monosaccharide compositions and mole ratios of DDP-UF-1-4 were mannose-glucose-galactose(32.45∶11.35∶8.69), mannose-rhamnose-glucuronic acid-glucose-xylose(25.68∶23.44∶21.62∶18.86∶3.68), mannose-rhamnose-glucuronic acid-galacturonic acid-xylose-galactose(18.68∶4.61∶3.89∶1.65∶5.36∶6.21), glucuronic acid-galacturonic acid-glucose-xylose-galactose(11.63∶15.26∶5.32∶2.08∶3.46), respectively. SEM showed that the morphological structures of DDP-UF-1-4 were flaky or spongy. The drug groups of DDP-UF-1 and DDP-UF-3 improved the skin condition of the psoriasis mice back, inhibited mitosis of female vaginal epithelial cells and significantly reduced the contents of IL-17 and IL-23 in serum (P<0.05, P<0.01). Conclusion::Both DDP-UF-1 and DDP-UF-3 have good anti-psoriasis effects, which may be related to the inhibition of IL-23/IL-17 signaling pathway.
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Objective To establish the risk prediction scoring model of central line-associated bloodstream infection (CLABSI) in elderly patients, provide basis for screening high-risk population, and effectively prevent and control bloodstream infection (BSI) in elderly patients.Methods According to the inclusion and exclusion criteria, data of elderly patients who underwent central catheterization during hospitalization from January 1, 2015 to December 31, 2017 were collected, patients were randomly divided into modeling group and verification group according to the ratio of 7∶3 (random seed was 20180708), risk factors of data of modeling group were distinguished, logistic regression model was constructed. The corresponding score of each risk factor was assigned according to β value, infection risk scoring model was established, prediction accuracy of model was evaluated by receiver operating characteristic (ROC) curve; according to the established infection risk scoring model, cases in validation group were scored, prediction accuracy of model was evaluated by ROC curve. Decision curve was constructed using R software.Results Logistic regression analysis showed that the number of operation≥3 times, length of stay in intensive care unit (ICU) ≥2 days, duration of indwelling central venous catheterization≥7 days, and use of antimicrobial agents were independent risk factors for CLABSI in elderly patients; the corresponding points in risk prediction scoring model were 3, 4, 4, and 9 respectively, and the score of 13-17 points were high-risk population of CLABSI; the area of ROC curve (AUC) was 0.74 in the modeling group; ROC curve was plotted based on the risk score of patients in validation group, AUC was 0.70. The decision curve showed that the net benefit of the risk scoring model was higher in the high risk thershold of 0.01-0.05.Conclusion The established risk prediction scoring model has good discriminant validity and application value, and can be used in the identification of susceptible high risk population of CLABSI in elderly patients, so as to achieve early prevention and control.
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OBJECTIVE@#To investigate the characteristic changes of the plasma cytokine profile in Chinese patients with idiopathic multicentric Castleman diseases (iMCD).@*METHODS@#The plasma samples from 22 patients with confirmed diagnosis of iMCD were collected before treatments; Specimens from 17 patients with newly diagnosed multiple myeloma, 10 non Hodgkin's lymphoma, and 15 healthy donors were used as control. Seventeen kinds of cytokines were measured by cytokine beads array (CBA) and ELISA respectively.@*RESULTS@#Six cytokines were measured by ELISA. The concentrations of IL-2, IL-6, IL-21 and VEGF were significantly higher in the plasma of iMCD patients than those of the healthy donors (P<0.01) and the level of IL-21 was highest in the iMCD group. There was no significant difference in the levels of IL-1β and IL-4 between the iMCD and healthy donor groups. Thirteen cytokines were measured by CBA assay, besides IL-6 level was confirmed to be higher in iMCD group than that in healthy controls (P<0.01), IL-12-p70 and IL-33 levels were also higher in iMCD group than those in control group (P<0.05), no significant difference of the rest cytokines was found between iMCD and the control group.@*CONCLUSION@#IL-6 and VEGF has shown to involved in the pathogenesis of iMCD, the results of preliminary study imply the role of IL-2 、IL-21、IL-12-p70 and IL-33 in this rare lymphoproliferative disease. Further studies are needed to elucidate the mechanism of these cytokines, which may shed some light on the identification of novel therapeutic targets against iMCD.
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Humans , Castleman Disease , Cytokines , Interleukin-12 , Interleukin-1beta , PlasmaABSTRACT
OBJECTIVE@#To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma.@*METHODS@#The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively.@*RESULTS@#The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43∶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31∶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 349 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods.@*CONCLUSION@#Bone lymphoma is usually concealed onset,an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.
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Female , Humans , Male , Middle Aged , Bone Neoplasms , Hematopoietic Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse , Positron Emission Tomography Computed Tomography , Prognosis , Retrospective StudiesABSTRACT
Buplewrum falcatum is a traditional Chinese medicine,which is mainly used for the treatment of cold and liver protection. B. falcatum is dominantly cultivated in Japan as well as planted in China,Korea and other countries and regions. In order to determine the appropriate sequencing strategy,the genome survey before large-scale genome sequencing is needed. This survey can provide information about the size and complexity of the whole genome of the target species. In the present study,the next generation sequencing technology( Illumina Hiseq 2000) was used to analyze the genome size and complexity of B. falcatum. In addition,SSR loci were analyzed from the sequenced data. Primer 3 was used to design specific primers and 33 pairs of primers were randomly selected for PCR with template DNA of B. falcatum,and the PCR system and optimal annealing temperature were screened. A total of 288. 64 G genome sequence data was obtained,and the estimated genome size of B. falcatum was 2 119. 58 Mb. The measured genome data depth was138×; the rate of heterozygosity was 1. 84%; and the ratio of repeat sequence was 83. 89%. It is speculated that the genome of B. falcatum is complex. The preliminary assembly was performed with K-mer = 41,and the contig N50 was 224 bp,the total length 896. 97 Mb,the scaffold N50 313 bp,and the total length was 922. 67 Mb. A total of 91 377 SSR sequences were detected in the sequenced genome data which were distributed in 70 809 unigenes.The main type is dinucleotide repeats,with 49 680 sequences,accounting for70. 16%. Among the 33 pairs of primers randomly synthesized according to the obtained SSR sequences,21 pairs were successfully amplifying the target sequences. The results will be helpful for later large scale genome sequencing and SSR molecular markers development for germplasm identification and trait mapping.
Subject(s)
Bupleurum/genetics , Genome, Plant , Microsatellite Repeats , Plants, Medicinal/genetics , Polymorphism, GeneticABSTRACT
Objective To optimize extraction process of walnut quinone from Juglans green peel. Methods On the basis of single factor tests, taking material-liquid ratio, extracting temperature and ethanol concentration as independent variables, yield of walnut quinone in response to as a value, according to Box-Behnken experiment design principle, extraction process of walnut quinone from Juglans green peel was optimized by response surface analysis. Results The optimum extraction process of walnut quinone was: 14.30 times the amount of 89.81% ethanol;30.28 ℃ constant temperature. The extracting amount of walnut quinone was 2.034 mg/g, which was close to the experimental results of 1.957 mg/g. Conclusion The optimized extraction process is reasonable and feasible, which can provide reference for the extraction of walnut quinone from Juglans green peel.
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<p><b>OBJECTIVE</b>To analyze the incidence of bone marrow involvement in patients with different pathological types of lymphoma.</p><p><b>METHODS</b>The results of bone marrow tests including bone marrow aspiration(BMA), flow cytometry detection, bone marrow biopsy(BMB) and F-FDG PET/CT, were analyzed retrospectively in 702 cases of newly diagnosed lymphoma with bone marrow assessment in our hospital from October 2000 to September 2016. If one of the above-mentioned 4 tests showed positive, the lymphoma patient was judged as bone marrow involved.</p><p><b>RESULTS</b>The incidence of bone marrow involvement (BMI ) in the patients with NHL was much higher than that in patients with HL [32.6 %(201/616) vs 15%(13/86)](P<0.05). For patients with NHL, the incidence of bone marrow involvement in B-cell lymphoma was higher than that in T-cell lymphoma (37.0% vs 22.6%)(P<0.05). According to different pathological types, the incidences of BMI in the patient with mantle cell lymphoma, hepatosplenic T-cell lymphoma, diffuse large B-cell lymphoma (DLBCL) and follical lymphoma (FL) were 88% (25/22), 100% (5/5), 21.8% (56/257), and 38.5% (15/39) , respectively.</p><p><b>CONCLUSION</b>The incidence of bone marrow involvement varies in different pathological types of lymphoma.Bone marrow assessment has significant importance for stading of newly diagnosed lymphoma patients.</p>
Subject(s)
Humans , Biopsy , Bone Marrow , Fluorodeoxyglucose F18 , Incidence , Lymphoma , Positron Emission Tomography Computed Tomography , Retrospective StudiesABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of CD160 on the surface of human natural killer (NK) cells and its possible relationship with hematological malignancies.</p><p><b>METHODS</b>CD160 expression on human leukemia cell line NK92 cells was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The proliferation characteristics and cell surface markers of this cell line were determined. Cytotoxicity of NK92 against 2 human myeloid leukemia cell lines, K562 and THP-1 was analyzed ex vivo. CD160 blocking antibody CL1-R2 was employed to clarify its role in NK cell mediated cytolysis. Then, the expression of CD160 on NK cells in peripheral blood from various patients with hematological malignancies were measured by flow cytometry.</p><p><b>RESULTS</b>The mRNA and protein levels of CD160 expressions on NK92 cells were confirmed by RT-PCR and Western blot, respectively. The flow cytometry results demonstrated that the strong positive expression of CD160 could be detected on the NK92 cell surface. NK92 could effectively kill K562 and THP-1 cells, while the cytolysis effect was abrogated in the presence of CD160 blocking antibody CL1-R2. The high levels of HVEM were expressed on both target cells, but the HLA class I molecules were absent on K562. The expression of CD160 on CD3CD56 NK cells in peripheral blood from patients with acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients was significant lower than that in the normal controls (P<0.05).</p><p><b>CONCLUSION</b>The cytolysis function of human NK cells is mediated partially by CD160 molecule. The decrease of CD160 expression on NK cells from patients with various hematological malignancies implies that down-regulation of CD160 expression may be a novel mechanism of tumor immune escape.</p>
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Objective: To study the mutation of ENG, ACVRL1, and SMAD4 genes in one of a family of hereditary hemorrhagic telangiectasia (HHT) and explore its molecular pathogenesis. Methods: A family spectrum of a patient with a clinical diagnosis of HHT was surveyed. Peripheral blood samples from proband and their eldest were collected, and ENG, ACVRL1 and SMAD4 gene analysis was performed by chip capture high-throughput sequencing. The mutation detected was verified by Sanger. Results: 9 of the 71 family members were diagnosed with HHT with the main manifestation of recurrent nasal bleeding. Genetic analysis showed that the proband and the eldest son of ENG gene exon 9 frameshift mutation: c.1502-1503insGG (p.Gly501GlyfsX18) , and mutations in ACVRL1 and SMAD4 genes were not detected. Conclusion: The frameshift mutation c.1502-1503insGG (p.Gly501GlyfsX18) of the ENG gene is the genetic basis for the pathogenesis of this HHT family.
Subject(s)
Humans , Endoglin , Exons , Genetic Testing , Mutation , Telangiectasia, Hereditary HemorrhagicABSTRACT
<p><b>OBJECTIVE</b>To study the expression of stromal cell derived factor-1α (SDF-1α) receptor CXCR7 in acute monocytic leukemia (AML-M5), and its effects on proliferation, apoptosis, invasion of acute monocytic leukemia cell line THP-1.</p><p><b>METHODS</b>CXCR7 protein and mRNA expression levels in THP-1 cells and peripheral blood mononuclear cells (PBMNC) from the newly diagnosed AML-M5 patients and normal individuals were detected by flow cytometry, Western blot and RT-PCR respectively. CCK8, Annexin V/PI double staining and Transwell assay were used to observe the effects of CXCR7 on the proliferation, apoptosis, and invasion of THP-1 cells in vitro.</p><p><b>RESULTS</b>The expression of CXCR7 on immature cell surface of the newly diagnosed AML-M5 patients was significantly higher than that in the control group (P<0.05). CXCR7 was also highly expressed on THP-1 cells surface. The CXCR7 protein and mRNA levels in THP-1 cells and PBMNC of AML-M5 patients were significantly higher than those in the control group (P<0.05). The THP-1 cell proliferation activity was higher in SDF-1α-treated group, but this activity could be inhibited by CXCR7 antibody (P<0.01). CXCR7 antibody did not affect THP-1 cell apoptosis (P>0.05). CXCR7 antibody could inhibit SDF-1α -induced THP-1 cell invasiveness (P<0.01).</p><p><b>CONCLUSION</b>CXCR7 highly expresses in AML-M5 patients and THP-1 cells, and involves in cell proliferation and invasion. The blocking CXCR7 expression can reduce the risk of AML-M5 cell infiltration.</p>
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<p><b>OBJECTIVE</b>To explore the prognostic value of interimF-FDG PET/CT (i-PET/CT) scan for the patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>A total of 70 cases of initially diagnosed of DLBCL by 158F-FDG PET/CT scans in our hospital were retrospectively analyzed. The 5-point scale, the Lugano classification and maximum standardized uptake value induction (ΔSUVmax) criteria were used respectively to assess i-PET/CT scans. Receiver-operating characteristics (ROC) analysis was used to determine an optimal cutoff for ΔSUVmax. Progression-free survival (PFS) and overall survival (OS) times were estimated as prognostic indicators using the Kaplan-Meier method and Cox regression.</p><p><b>RESULTS</b>Optimal cutoff to predict progression or death was 62% for ΔSUVmax. The positive predictive value (PPV) for 2-year PFS and OS of i-PET/CT diagnosed by 5-point scale was low, and could be improved by using the Lugano classification with decreased sensitivity or ΔSUVmax criteria. Kaplan-Meier survival curve analysis showed that the Lugano classification and ΔSUVmax were good predictors for PFS and OS, respectively, while the 5-point scale could only predict OS. Cox regression univariate analysis showed that the International Prognostic Index (IPI) score was better to predict PFS than 5-point scale, but worse than the three assessments in predicting OS. COX regression multivariate analysis showed that ΔSUVmax<62% was an independent risk factor of prognosis, while the Lugano classification was only the OS independent prognostic predictor.</p><p><b>CONCLUSION</b>Assessing i-PET/CT by 5-point scale is a limited value for predicting PFS and OS in DLBCL patients. The Lugano classification is recommended to discriminate the patients with poorer outcomes. The ΔSUVmax criteria for i-PET/CT of DLBCL patients is an independent prognostic predictor for PFS and OS, better than the IPI score.</p>
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<p><b>OBJECTIVE</b>To assess the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treating patients with relapsed and refractory lymphoma.</p><p><b>METHODS</b>Thirty-one consecutive patients with relapsed or refractory lymphoma received allo-HSCT. Used conditioning regimens included conditioning based on BEAM regimen(12 cases), conditioning based on modified Bu/Cy regimen(11 cases), conditioning based on Cy/TBI regemen(6 cases) and conditioning of Bu/Cy regimen(1 case). For provention of GVHD, the MMF was used on the basis of classcal protocol consisting of CsA combined with MTX. The infused HSC included the HLA-matched related HSC(11 cases), HLA nonidentical related HSC(13 cases) and HLA-matched unrelated HSC(6 cases). The bone marrow plus peripheral blood HSC were infused in 21 cases, while only peripheral blood HSC were infused in 9 cases. Among the 31 cases of relapse/refractory lymphoma, 18 patients were male and 13 were female, 4 cases were Hodgkin's lymphoma and 27 cases were non-Hodgkin's lymphoma. ALL of the 31 patients were qualified, as they were not in complete remission (CR) or in advanced stage at the time of transplantation.</p><p><b>RESULTS</b>Twenty-seven evaluable patients showed the engraftment of both neutrophil and platelet at a median of 12 days(range 10-20) and 13 days(range 9-34) respectively, 9 cases developed II-IV aGVHD, and cGVHD was observed in 3 patients, 5 patients can not achieve CR at 3 months after transplantation, and 6 patients relapsed after CR, the median follow-up of all the 31 patients after transplantation was 11.5 months (ranged, 0-141 months), and the 2-year OS was 46.1%±9.5% with median survival of 40 (9-141) months in the 15 survivors. The age (P<0.05), disease status before transplantation (P=0.020) and remission after transplantation(P=0.000) were significantly related with survival. Cox's proportional hazards regression model analysis showed that the age (P=0.041) and disease statue (P=0.020) before allo-HSCT were independent predictive factors for survival.</p><p><b>CONCLUSION</b>Allo-HSCT is an optimal treatment strategy for the patients with relapsed and refractory lymphoma who failed to most, if not all, available options.</p>
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<p><b>OBJECTIVE</b>To investigate the effects of valproic acid(VPA) on the expression of intracellular domain of Notch1 (ICN1) and Hes1 in multiple myeloma RPMI 8226 cell line.</p><p><b>METHODS</b>Experiments were divided into 4 group: blank control group and groups of cells treated with VPA of different concentration (2, 4, 8 mmol/L), the cell proliferation was detected by MTT method, RT-PCR was applied to detect the mRNA expression level of ICN1 and Hes1. Western blot was used to detect the protein expression of ICN1 and Hes1.</p><p><b>RESULTS</b>The proliferation of the RPMI 8226 cell was obviously inhibited by different concentration of VPA (2, 4, 8 mmol/L) at the same time. The same concentration of VPA was used to treat RPMI8226 cell for different time (24, 48, 72 h), the cell proliferation was obviously inhibited. Compared with control group, the mRNA and protein expression of ICN1 was significantly depressed at different concentration of VPA(2, 4, 8 mmol/L) for 48 h (P<0.05). Compared with control group, the mRNA and protein expression of Hes1 was depressed at different concentration 2, 4, 8 mmol/L)of VPA for 48 h (P<0.05).</p><p><b>CONCLUSION</b>VPA inhibits the proliferation of the RPMI 8226 cell in a time- and dose- dependent manner; VPA down-regulates the mRNA and protein expression level of ICN1 and Hes1 in RPMI8226 cell; thus VPA might inhibit cell proliferation possibly through the inhibition of Notch signaling pathway in multiple myeloma cells.</p>
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<p><b>OBJECTIVE</b>To investigate the effect of Shouwu Jiangqi Decoction (SJD) on polycystic ovary syndrome (PCOS) with insulin resistance (IR) in rats and to explore the underlining molecular mechanisms.</p><p><b>METHODS</b>A total of 51 female Sprague-Dawley rats were randomly divided into 6 groups: control group (n=7), model group (n=8), SJD high-dose group (n=9), SJD medium-dose group (n=9), SJD low-dose group (n=9) and DMBG group (n=9). Radioimmunoassay was used to measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations and qRT-PCR and western blot were used to examine the expression levels of mRNA and protein respectively of insulin receptor substrate 1 (IRS-1) and phosphatidylinositide 3-kinases (PI3K) p85α in different groups.</p><p><b>RESULTS</b>FSH level significantly decreased in the model group compared with the normal control (P<0.01), and high-dose SJD and DMBG can significantly increase FSH level (P<0.01). LH level showed a mild increase without statistic significance in the model group compared with the control and different dosages of SJD had no significance effect on LH level, while DMBG can significantly decrease LH level (P<0.01). Testosterone level significantly increased in the model group compared with the control group (P<0.01), and high-dose SJD and DMBG can significantly decrease testosterone level (P<0.01). The expression of IRS-1 as well as PI3Kp85α were significantly decreased in the model group compared with the normal control group at both mRNA (P<0.001) and protein (P<0.01) level, and both high-dose SJD and DMBG can enhance IRS-1 and PI3K expression (P<0.05).</p><p><b>CONCLUSIONS</b>SJD has potent therapeutic effects on PCOS with IR in rats. The therapeutic effects of SJD on IR and ovulatory dysfunction are probably achieved through correcting the defective insulin signaling transduction.</p>
Subject(s)
Animals , Female , Blood Glucose , Metabolism , Drugs, Chinese Herbal , Therapeutic Uses , Fasting , Blood , Follicle Stimulating Hormone , Blood , Insulin , Blood , Insulin Receptor Substrate Proteins , Metabolism , Insulin Resistance , Liver , Pathology , Luteinizing Hormone , Blood , Ovary , Pathology , Phosphatidylinositol 3-Kinases , Metabolism , Polycystic Ovary Syndrome , Blood , Drug Therapy , Rats, Sprague-Dawley , Testosterone , BloodABSTRACT
<p><b>OBJECTIVE</b>To investigate the changes in brain injury after the induction chemotherapy in children with acute lymphoblastic leukemia (ALL) by cranial MRI.</p><p><b>METHODS</b>The clinical data and cranial MRI results of 62 children with ALL who were hospitalized from March 2014 to June 2015 were analyzed retrospectively.</p><p><b>RESULTS</b>Before chemotherapy, MRI showed bone marrow infiltration of the skull in 33 patients (53%); the children with WBC<20×10(9)/Lhad a significantly lower incidence rate of bone marrow infiltration of the skull than those with WBC≥20×10(9)/L (16 patients/42% vs 17 patients/71%; P<0.05), and the high-risk group had a significantly higher incidence rate of bone marrow infiltration of the skull than the non-high-risk group (71% vs 44%; P<0.05). Before chemotherapy, there were 4 cases (7%) of brain atrophy, and 2 cases (3%) of abnormal signals in the sensory conduction bundle. MRI reexamination in 28 patients after 3 months of chemotherapy showed 3 new cases (11%) of brain atrophy and 1 aggravated case of brain atrophy.</p><p><b>CONCLUSIONS</b>The children with ALL have bone marrow infiltration of the skull, brain atrophy, and abnormal signals in the sensory conduction bundle before chemotherapy, especially bone marrow infiltration of the skull, and some changes in brain injury disappear after treatment.</p>