To evaluate the efficacy and safety of interferon-alpha-2b (IFN-α-2b) in polycythemia vera patients(PV patient) with or without post-polycythemic myelofibrosis (post-PV MF), 30 patients with mutated JAK2V617F were enrolled in this study, from which 29 patients were evaluable. The percentage of mutated JAK2V617F allele (V617F%) was evaluated by real-time polymerase chain reaction (RT-PCR) before and after treatment with IFN-α-2b. The correlation of V617F allele burden with the major clinical outcomes was studied. Adverse effects appeared in patients was observed. The results showed that the median follow-up was 24 (12 - 42) months for 29 evaluable patients. Complete hematologic response was achieved in 10%, 48%, 72% and 78% of patients after treatment for 6, 12, 24 and 36 months respectively. The detection of V617F allele burden revealed that the molecular remission of patients (V617F%) was achieved in 41%, 76%, 89% and 89% after treatment for 6, 12, 24 and 36 months respectively. Molecular complete remission (JAK2V617F undetectable) was achieved in 4 patients, lasted from 6 to 12 months after IFN-α-2b discontinuation. The decrease of V617F% in patients with post-PV MF was significantly higher than that in patients without post-PV MF (53 ± 18% vs 32 ± 22%, respectively; p = 0.031) after treatment for 12 months. PV patients had a good tolerance to IFN-α-2b. It is concluded that IFN-α-2b can decrease the mutated V617F allele burden. Patients with PV, especially with post-PV MF, can achieve molecular remission after treatment with IFN-α-2b.
Adult ; Alleles ; Female ; Humans ; Interferon-alpha ; therapeutic use ; Janus Kinase 2 ; genetics ; Male ; Middle Aged ; Mutation ; Polycythemia Vera ; drug therapy ; genetics ; pathology ; Primary Myelofibrosis ; drug therapy ; genetics ; pathology ; Recombinant Proteins ; therapeutic use

The aim of this study was to investigate the effects of interferon (IFN)-γ on biological characteristics and immunomodulatory property of human umbilical cord-derived mesenchymal stem cells (hUC-MSC). hUC-MSC were treated with IFN-γ 10 ng/ml (IFN-γ group) or without IFN-γ (control group). The phenotype of hUC-MSC was detected by flow cytometry. The proliferation status was detected by CCK-8 method, and its differentiation ability was assessed by oil red O and von Kossa staining. The production of PGE-2 was measured by ELISA, and the mRNA expression levels of COX-2, IDO-1 and IDO-2 in hUC-MSC were detected by real-time quantitative PCR. Furthermore, the proliferation of human peripheral blood mononuclear cells (hPBMNC) was evaluated after co-culture with hUC-MSC, IFN-γ pretreatment or not. The results showed that after IFN-γ stimulation, the expression of SSEA-4 on hUC-MSC decreased significantly [(8.15 ± 2.94) vs (16.42 ± 8.5), P < 0.05], and the expression of CD54 increased [(96.64 ± 3.29) vs (84.12 ± 10.73), P = 0.051]. The immunomodulatory property of hUC-MSC on the proliferation of hPBMNC was enhanced (P < 0.05). All the above mentioned effects were IFN-γ concentration-dependent. When hUC-MSC were stimulated by IFN-γ for 24 h, the production of PGE-2 secreted by hUC-MSC decreased significantly (P < 0.01). The mRNA expression level of COX-2 also decreased though the difference did not reach to statistically significant level. Compared with control group, IDO-1 expression level in IFN-γ group increased significantly (P < 0.01), and the mRNA expression level of IDO-2 remained unchanged. It is concluded that IFN-γ can influence the phenotype of hUC-MSC and enhance the immunomodulatory property of hUC-MSC.
Cells, Cultured ; Cyclooxygenase 2 ; metabolism ; Flow Cytometry ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; metabolism ; Interferon-gamma ; pharmacology ; Mesenchymal Stromal Cells ; cytology ; drug effects ; immunology ; Umbilical Cord ; cytology

OBJECTIVETo describe the prevalence of anemia and yearly trends (1993-2003) among women who came to the hospitals or maternal and child health units for premarital examinations in 6 counties of Jiangsu and Zhejiang provinces.

METHODSData were obtained from the records of the premarital examinations in perinatal health care surveillance system that had been established since 1992 in these areas. We reviewed hemoglobin levels of those women who were enrolled in the perinatal health care surveillance system from 1993 to 2003. Anemia was defined according to the WHO (2001) criterion. We calculated the prevalence of anemia and analyzed the yearly trends based on the data of hemoglobin concentration.

RESULTSIn the period of 1993-2003, there were 82 995 anemia cases identified among 193,434 women with an overall anemia rate as 42.9%. The rates of anemia were high (65.5%) in 1993 but low (25.8%) in 2003. 99.7% of the anemic women whose hemoglobin concentration were between 80-119.9 g/L. Time trend analysis indicated a significant decline on anemia rate while monthly analysis showed that the prevalence rates were high (48.2%) in September and low in March (39.5%). The results also showed that the prevalence rates of anemia were relatively higher in farmers and workers in rural enterprises, and lower in Han ethnicity than minorities. The higher prevalence rates of anemia were presented among the women with less education, lower body mass index, or at older age.

CONCLUSIONFor those premarital women in 6 counties of Jiangsu and Zhejiang provinces, the overall anemic rate presented a significant downward trend between 1993 and 2003 while the prevalence of anemia remained high, especially for the women with less education, lower body mass index or older ages.

Adolescent ; Adult ; Anemia ; epidemiology ; China ; epidemiology ; Female ; Humans ; Middle Aged ; Premarital Examinations ; Young Adult

BACKGROUNDDecreases in the bioavailability of rifampicin (RFP) can lead to the development of drug resistance and treatment failure. Therefore, we investigated the relative bioavailability of RFP from one four-drug fixed-dose combination (FDC; formulation A) and three two-drug FDCs (formulations B, C, and D) used in China, compared with RFP in free combinations of these drugs (reference), in healthy volunteers.

METHODSEighteen and twenty healthy Chinese male volunteers participated in two open-label, randomized two-period crossover (formulations A and C) or one three-period crossover (formulations B and D) study, respectively. The washout period between treatments was 7 days. Bioequivalence was assessed based on 90% confidence intervals, according to two one-sided t-tests. All analyses were done with DAS 3.1.5 (Mathematical Pharmacology Professional Committee of China, Shanghai, China).

RESULTSMean pharmacokinetic parameter values of RFP obtained for formulations A, B, C, and D products were 11.42 ± 3.41 μg/ml, 7.86 ± 5.78 μg/ml, 13.05 ± 6.80 μg/ml, and 16.18 ± 3.87 μg/ml, respectively, for peak plasma concentration (C max ), 91.43 ± 30.82 μg·h-1·ml-1 , 55.49 ± 37.58 μg·h-1·ml-1 , 96.50 ± 47.24 μg·h-1·ml-1 , 101.47 ± 33.07 μg·h-1·ml-1 , respectively, for area under the concentration-time curve (AUC 0-24 h ).

CONCLUSIONSAlthough the concentrations of RFP for formulations A, C, and D were within the reported acceptable therapeutic range, only formulation A was bioequivalent to the reference product. The three two-drug FDCs (formulations B, C and D) displayed inferior RFP bioavailability compared with the reference (Chinese Clinical Trials registration number: ChiCTR-TTRCC-12002451).

Adult ; Asian Continental Ancestry Group ; Biological Availability ; Drug Combinations ; Humans ; Male ; Rifampin ; administration & dosage ; pharmacokinetics ; therapeutic use ; Tuberculosis ; drug therapy ; Young Adult

Acute coronary syndrome (ACS),with increasing mortality year by year,has become a major public health problem in China.Exercise rehabilitation as an important part of the out-of-hospital rehabilitation for the patients with heart diseases can further reduce the mortality of patients on the basis of drug treatment.The available studies have proved that high-intensity interval training (HIIT) is more effective and efficient than moderate-intensity continuous training (MICT) such as walking and jogging on chronic cardiovascular diseases such as heart failure,stable coronary heart disease,and hypertension and has high security.According to the latest research,HIIT can reduce the platelet response,mitigate myocardial ischemia-reperfusion injury,and increase the exercise compliance of ACS patients more significantly than MICT.Moreover,it does not increase the risk of thrombotic adverse events or malignant arrhythmia.Therefore,HIIT is expected to become an important part of exercise prescription in out-of-hospital cardiac rehabilitation strategy for the patients with ACS.
Humans ; Cardiac Rehabilitation ; High-Intensity Interval Training ; Acute Coronary Syndrome ; Heart Failure ; Blood Platelets

OBJECTIVE: To investigate the effects of IRF1 on the homeostasis and differentiation of K562 cells. METHODS: Three different vectors were constructed to screen the best strategy for IRF1 overexpression. The effect of IRF1 on cell proliferation and apoptosis was explored by cell count and apoptotic surface marker detection. Likely, the effect of IRF1 on cell differentiation was analyzed by differentiational surface marker assay. Finally, the regulation mechanism at mRNA level was analyzed by RT-qPCR. RESULTS: The single open reading frame constructed by P2A-T2A element showed the highest expression intensity, and it was the best approach to realize IRF1 enhancement. Cell counts showed that IRF1 had no significant effect on the proliferation of K562. Annexin V and 7-AAD labeling exhibited strong anti-apoptotic function of IRF1 against AraC induction. Flow cytometry revealed that IRF1 overexpression could also further increase the proportion of CD71CD235a cells. RT-qPCR confirmed its upregulation effect on CD235a and TAL1. CONCLUSION IRF1 enhancement alters the homeostasis characteristics of K562 cells, increases the anti-apoptotic ability and raises the potential to downstream differentiation, suggesting that IRF1 may play an important regulatory role in the hematopoietic development, including erythropoiesis.