OBJECTIVE: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations. RESULTS: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery. CONCLUSION Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Humans ; Child ; Female ; Fibrinogen/genetics* ; Pedigree ; Afibrinogenemia/genetics* ; Mutation ; Blood Transfusion

OBJECTIVE: To explore the characteristics of ADC value changes in DWI of newly diagnosed symptomatic MM patients and its correlation with R-ISS stage. METHODS: The data of 148 newly diagnosed symptomatic MM patients treated by whole-body DWI scan at The First Affiliated Hospital of Soochow University from June 2016 to June 2019 were selected and retrospectively analyzed and 30 cases of age-matched healthy people were selected as controls. The differences of ADC values between the patients in normal control group, DWI^- group and DWI⁺ group were compared, and the relationship between ADC values and R-ISS stage in MM patients was compared. RESULTS: The plasma cell percentage of the patients in DWI⁺ group was higher than those in DWI^- group. ADC values of vertebra, sternum, rib, pectoral girdle, pelvic girdle of the patients in DWI⁺ group were significantly higher than those in DWI^- group and normal control group. The ADC values of each part of the patients in DWI^- group were higher than those in normal control group. ADC values of sternum, rib and pectoral girdle in the patients at R-ISS stage III were higher than those at R-ISS stage I and II, while, there was no statistical difference between R-ISS stage I and II groups. And there was no significant difference in ADC values of other bone parts such as vertebra and pelvic girdle in patients at R-ISS stage Ⅰ-Ⅲ. CONCLUSION DWI⁺ in MM patients is related to higher tumor invasion. The ADC values of the DWI⁺ group are higher than those of the DWI^- group; the bone ADC values of the DWI^- patients are still higher than the normal ones. And there is a certain relationship between ADC value and R-ISS stage.
Bone Diseases ; Diffusion Magnetic Resonance Imaging ; Humans ; Multiple Myeloma/diagnostic imaging* ; Retrospective Studies ; Whole Body Imaging

OBJECTIVE: The clinical symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) can be effectively improved by traditional Chinese medicine (TCM) treatment, based on the usage of specific therapies for different TCM syndromes. However, in the stage of diagnosis, the standard criteria for the classification of TCM syndrome were still deficient. Through serum metabolic profiling, this study aimed to explore potential biomarkers in IBS-D patients with different TCM syndromes, which can assist in diagnosis of the disease. METHODS: Serum samples were collected from healthy controls (30 cases), IBS-D patients with Liver-Stagnation and Spleen-Deficiency syndrome (LSSD, 30 cases), Yang Deficiency of Spleen and Kidney syndrome (YDSK, 11 cases) and Damp Abundance due to Spleen-Deficiency syndrome (DASD, 22 cases). Serum metabolic profiling was conducted by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential biomarkers were screened by orthogonal partial least square-discriminate analysis, while metabolic pathways undergoing alterations were identified by pathway enrichment analysis in MetaboAnalyst 4.0. RESULTS: Overall, 34 potential biomarkers were identified in LSSD group, 36 in YDSK group and 31 in DASD group. And the 13 metabolites shared by three groups were determined as the potential biomarkers of IBS-D. Glycerophospholipid metabolism was disturbed significantly in IBS-D patients, which may play a role in IBS-D through inflammation. What's more, three TCM syndromes have the specific potential biomarkers in glycerophospholipid metabolism. CONCLUSION The serum metabolomics revealed that different TCM syndrome types in IBS-D may have different metabolic patterns during disease progression and glycerophospholipid metabolism was one of the pathways, whose metabolism was disturbed differently among three TCM syndromes in IBS-D. Therefore, the specific potential biomarkers in glycerophospholipid metabolism of three TCM syndromes in IBS-D can serve as the objective indicators, which can facilitate the TCM-syndrome objective classification of IBS-D.

The mammalian target of rapamycin (mTOR)-sterol regulatory element-binding proteins (SREBPs) signaling promotes lipogenesis. However, mTOR inhibitors also displayed a significant side effect of hyperlipidemia. Thus, it is essential to develop mTOR-specific inhibitors to inhibit lipogenesis. Here, we screened the endogenous inhibitors of mTOR, and identified that FKBP38 as a vital regulator of lipid metabolism. FKBP38 decreased the lipid content

This paper systematically reviews the latest and relevant literatures and policy documents on the in-tegrated health services in Canada in recent years. Therefore, it summarizes the practice and mode of integrated serv-ice delivery in Ontario, Alberta and Quebec wherein the integration among health organization, health service team, and a series of health services are included. The contributing factors and impeding factors ( the barriers) of organiza-tional integration and specific integration strategy were summarized. Finally, according to the actual practical situa-tion, it is proposed that China should adhere to the government-led approach in promoting the integration of health services, and give a full play to the positive role of the market mechanism. Through strengthening the network man-agement and group service of primary health services, emphasis will be put on health services of population groups and specific diseases. Therefore, integration will be regarded as a strategic priority, increasing incentives and boos-ting promotion of nursing personnel on the process of Integrated Service Delivery, building the health information sys-tem that is conducive to integration in order to continuously advance Hierarchical Diagnosis and bridge the fragmented service system. This will help in providing residents with personalized, convenient, comprehensive, and continuous health services.

OBJECTIVETo explore the effects of BTZ plus HHT on proliferation and apoptosis of K562 cells, and to clarify the relationship between the mechanism inderlying the effect of BTZ plus HHT on K562 cells and BCL-2, BAX, MCL-1 proteins.

METHODSThe K562 cells were divided into 4 groups by different treatment: BTZ(20 nmol/L), HHT(40 ng/ml), BTZ(20 nmol/L)+HHT(40 ng/ml) and control. The proliferation inhibition rates of K562 cells in each group were detected by using MTT, and the early apoptosis rates of K562 cells in each group were assayed by using flow cytometry with Annexin V-FITC/PI staining. The proteins level of BCL-2, BAX and MCL-1 in each group were examined by using Western blot.

RESULTSThe inhibition rate of K562 cell proliferation in combined group was higher than that in BTZ, HHT alone group(P<0.01). The early apoptosis rate of K562 cells in combined group was increased significantly in comparison with BTZ and HHT alone group(P<0.05). The BCL-2 protein level of K562 cells in combined group was significantly lower than that in BTZ and HHT alone group(P<0.05). BAX protein level of K562 cells in combined group was higher than that in BTZ and HHT alone group(P<0.05). The Orders of the MCL-1 protein level of K562 cells in 4 groups were BTZ>Control>BTZ plus HHT>HHT(P<0.05 ).

CONCLUSIONThe combination of BTZ and HHT exerts the synergistic effect of anti-proliferative activity and induces apoptosis against K562 cells in vitro. The combination can induce apoptosis of K562 cells via suppression of BCL-2 protein and up-regulation of BAX protein. HHT can increase the sensitivity of K562 cells to BTZ by down-regulating the expression of MCL-1 protein.

Apoptosis ; Bortezomib ; pharmacology ; Cell Proliferation ; Harringtonines ; pharmacology ; Homoharringtonine ; Humans ; K562 Cells

OBJECTIVETo investigate the antitumor effect of lycorine on renal cell carcinoma ACHN cells and explore the possible mechanism.

METHODSWe used flow cytometry to examine the effect of lycorine on ACHN cell cycle and apoptosis. The cell proliferation, migration and invasion were assessed with MTS assay, wound healing assay, and Transwell assay, respectively. Colony forming assay was performed, and the mRNA and protein levels of Bax, Bcl-2, survivin, caspase-3, cyclin D1 and CDK4 were measured with qRT-PCR and Western blotting.

RESULTSLycorine obviously inhibited the proliferation of ACHN cells with an IC(50) of 24.34 µmol/L. Lycorine also induced apoptosis of ACHN cells, caused cell cycle arrest at G(0)/G(1) phase, and suppressed the colony forming ability of the cells in a dose-dependent manner. The migration and invasion of ACHN cells were significantly inhibited by 5 µmol/L lycorine. Lycorine up-regulated the mRNA levels of CDK4, Bax, caspase-3 while down-regulated the levels of survivin, Bcl-2 and Cyclin D1; the protein levels of CDK4 and Bax were increased and cyclin D1, Bcl-2 and surviving expressions were decreased, but caspase-3 expression showed no significant changes following the treatment.

CONCLUSIONLycorine has obvious antitumor effect against ACHN cells, suggesting its value as a new therapeutic agent for renal cell carcinoma.

Amaryllidaceae Alkaloids ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Carcinoma, Renal Cell ; pathology ; Caspase 3 ; metabolism ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Phenanthridines ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo find and identify HLA-A*0201 restricted cytotoxic T lymphocyte (CTL) epitopes from epidermal growth factor pathway substrate number 8 (Eps8) for specific immunotherapy based on Eps8-derived epitopes in clinic.

METHODSOnline biological softwares involved C-proteasomal cleavage, MHC class I binding affinity and TAP transport efficiency were used for prediction of HLA-A*0201 restricted epitopes from Eps8. Then, T2-binding assays and peptide/MHC complex stability tests were used to further verify the predicted epitopes. Specific secretion of IFN-γ from human CTL was assayed using the IFN-γ ELISPOT kit, and cytolytic activity was measured by a 4-h lactate dehydrogenase (LDH) release assay. Finally, the functional effects in vivo were measured in HLA-A*0201/Kb transgenic (Tg) mice.

RESULTSFour natural epitopes were designed through online biological softwares. Of the four epitopes selected, p360-368 was found to have the high binding affinity to HLA-A*0201, while p101-109 and p276-284 showed moderate affinities. DC50 of peptide/MHC complexes of the natural epitopes mentioned were all longer than 8 h. In functional assays with human PBMNC in vitro and in HLA-A*0201/Kb transgenic mice in vivo, CTLs primed by each epitope (p101-109, p276-284 and p360-368) secreted IFN-γ and were toxic to cancer cells from a variety of tissue types in an HLA-A*0201-restricted and Eps8-specific manner.

CONCLUSIONNatural epitopes (p101-109, p276-284 and p360-368) may be the HLA-A*0201 restricted epitope derived from Eps8.

Adaptor Proteins, Signal Transducing ; immunology ; Animals ; Epitopes, T-Lymphocyte ; metabolism ; HLA-A2 Antigen ; metabolism ; Humans ; Mice ; Mice, Transgenic ; T-Lymphocytes, Cytotoxic

OBJECTIVETo investigate the potential value of combined examinations of peripheral blood smear, bone marrow smear, bone marrow biopsy, chromosome banding analysis and flow cytometry (FCM) in the diagnoisis of myelodysplastic syndromes.

METHODSA total of 105 MDS patients who were admitted in our hospital from May 2013 to May 2015 and were diagnosed as MDS according to the criteria formulated by WHO were enrolled in this study. The accordance rate of diagnosis by the double test (peripheral blood smear plus bone marrow smear), triple test (above mentioned 2 tests plus bone marrow biopsy), quadruple test (above 3 tests plus chromosome banding analysis), and quintuple test (above 4 plus FCM) was amalyzed and compared.

RESULTSAmong the 105 MDS patients, the diagnosis accordance rate was 70.48% for double tests, while 83.81%, 84.76% and 93.33% for triple, quadruple and quintuplet tests, respectively which were significantly higher than that for double tests (peripheral blood smear plus bone marrow smear) (P < 0.05).

CONCLUSIONThe combined examination of the 5 methods can improve the accuracy of MDS diagnosis.

Biopsy ; Bone Marrow Examination ; Chromosome Banding ; Flow Cytometry ; Humans ; Myelodysplastic Syndromes ; diagnosis

OBJECTIVETo analyze the influential factors related to mobilization and collection of stem cells so as to improve the collection efficiency of autologous peripheral stem cell transplantation in lymphoma patients.

METHODSThe peripheral blood stem cell collection data of 151 cases of lymphoma in our hospital was analyzed retrospectively. The relationship between the harvested CD34(+) stem cells and some factors, such as age, sex, height, weight, histological type, staging, mobilization programs, collecting days, blood transfusion, time and duration of chemotherapy, was analyzed.

RESULTSThe single factor analysis showed that sex, height, weight, histological type, staging, mobilization program, collecting days, blood transfusion were not significantly associated with CD34(+) stem cells collection, respectively. Age (r = -0.248, P = 0.002), duration of sick and cycles of chemotherapy were significantly associated with CD34(+) cell collection. At the age older than 50 years, the collected CD34(+) cell number decreased significantly; and at the age older than 60 years, the CD34(+) cell number was greatly reduced; CD34(+) cells non-significantly correlated with peripheral blood WBC (r = 0.053, P = 0.527), but significantly with the percentage of mononuclear cells (r = 0.260, P = 0.002) and the absolute value of mononuclear cells (r = 0.338, P = 0.00003) .

CONCLUSIONThe patients less than 60 years old, fewer chemotherapy cycles, shorter duration time or PB mononuclear cells between (2-6) × 10(9)/L may contribute to the better mobilization and collection of peripheral blood stem cells.

Age Factors ; Antigens, CD34 ; metabolism ; Blood Transfusion ; Cell Count ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cells ; cytology ; Humans ; Lymphoma ; therapy ; Peripheral Blood Stem Cell Transplantation ; Retrospective Studies ; Transplantation, Autologous