Progress of research on the pharmacological effects and mechanisms of emodin / 中国药科大学学报

@#As an active hydroxyanthraquinone ingredient, emodin is abundant in Chinese medicine herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum.Modern pharmacological studies have shown that emodin has a variety of pharmacological activities including anti-tumor, anti-inflammatory and immunoregulatory, antibacterial and anti-viral effects, myocardial protection, neuroprotection, renal protection, bone protection, antifibrosis and so on, which indicate its high medicinal value and broad application prospects.This article aims to summarize the progress in the pharmacological activity and mechanism of action of emodin published in domestic and international journals over the last 5 years and highlight the potential targets and molecular signaling pathways linked with emodin, so as to provide some clues and references for further development and clinical application of emodin.

Study on the Effects of Deoxyschizandrin on the Proliferation ，Migration and Invasion of Human Nasopharyngeal Carcinoma Cell HONE- 1 via Met/PI 3K/Akt Signaling Pathway / 中国药房

OBJECTIVE：To study the effects and potential mechani sm of deoxyschizandrin on the proliferation ，migration and invasion of nasopharyngeal carcinoma cell HONE- 1. METHODS ：HONE-1 cell was set as cell model ，while CCK- 8 test，wound healing assay and Transwell chamber test were used to detect the proliferation ，migration and invasion ability changes of HONE- 1 cells after treatment with different concentrations [ 0（blank control ），10，20，40 μmol/L] of deoxyschizandrin. Computer molecular docking was performed to analyze the binding ability between deoxyschizandrin and Met protein. Western blotting assay was used to detect the relative protein expressions of p-Met ，p-PI3K，p-Akt，Bcl-2 and N-cadherin in cells. RESULTS ：Compared with blank control ，the proliferation ，migration and invasion ability of cells after treated with 10，20，40 μmol/L deoxyschizandrin were all decreased significantly （P＜0.05）. Results of molecular docking revealed that deoxyschizandrin could stably bind with the activity pocket of Met protein. Results of Western blotting assay demonstrated that compared with blank control ，10，20，40 μmol/L deoxyschizandrin all decreased the relative protein expressions of p-Met ，p-PI3K，p-Akt，Bcl-2 and N-cadherin in cells significantly（P＜0.05）. CONCLUSIONS ：Deoxyschizandrin can inhibit the proliferation ，migration and invasion of HONE- 1 cell via inhibiting the activation of Met/PI 3K/Akt signaling pathway.

Clinical study on rheumatoid arthritis combined with femur head necrosis / 中国医师进修杂志

Objective To investigate the clinical features of rheumatoid arthritis combined with femur head necrosis. Methods The clinical data of 22 patients with rheumatoid arthritis combined with femur head necrosi were retrospectively analyzed. Results Among the 22 patients with rheumatoid arthritis combined with femur head necrosi, male was in 5 cases, female was in 17 cases, age was 28-69 (56.3 ± 1.9) years, and the disease duration of rheumatoid arthritis was 4-30 (14.1 ± 1.2) years. All patients had ≥ 2 grade femur head necrosis, with bilateral femur head necrosis in 9 cases, right femur head necrosis in 9 cases and left femur head necrosis in 4 cases. Only 2 cases did not take glucocorticosteroid, and the other 20 cases used glucocorticosteroid in the long-term. The treatment was no standardized. The multiple fracture was found in 4 cases by X-ray examination (the patients had no history of trauma); 4 cases examined bone density, and the results showed they all were osteoporosis. Conclusions Rheumatoid arthritis combined with femur head necrosis is not uncommon. The majority of patients receive long-term glucocorticosteroid treatment. Treatment is not standardized, and some patients are combined with osteoporosis.

Gene mutations from 511 myelodysplastic syndromes patients performed by targeted gene sequencing / 中华血液学杂志

Objective@#To study the characteristics of gene mutations in Chinese myelodysplastic syndromes (MDS) patients.@*Methods@#A total of 511 Chinese patients with MDS performed 112-gene targeted sequencing were retrospectively analyzed.@*Results@#Eighty-three distinct mutant genes were found in 511 patients with MDS. Amongst these, the most frequent mutations was associated with epigenetics (50%) , followed by spliceosome (37%) , signal transduction (34%) , transcription factors (24%) and cell cycle/apoptosis (17%) . 439 subjects (86%) had at least one gene mutation. The mean number of mutations in refractory anemia with unilineage dysplasia (RCUD) was 1.25, refractory anemia with multilineage dysplasia (RCMD) was 1.73, refractory anemia with ring sideroblasts (RARS) was 2.79, refractory anemia with excess blasts-1 (RAEB-1) was 2.22, RAEB-2 was 2.34, MDS with isolated 5q- was 2.67, MDS, unclassified (MDS-U) was 2.00. U2AF1 mutant subjects were more likely to have isolated+8[Q<0.001, OR=4.42 (95% CI 2.23-8.68) ]and less likely to have complex karyotypes[Q=0.005, OR=0.22 (95% CI 0.04-0.72) ]. According to the number of gene mutations, all subjects were categorized into three groups, namely group with 0-1 mutation, with 2 mutations and with three or more mutations. There was a significant difference in overall survival (OS) among three groups (P=0.041) .@*Conclusion@#About 90% patients with MDS have at least one gene mutation. Genes associated with epigenetics and spliceosome are most common mutated genes in MDS. The increased numbers of gene mutations accompany with disease evolution and associate with poor prognosis.

Policy implementation of targeted admission medical education program in rural areas / 中国卫生政策研究

This study aims to investigate the current situation of the enrollment , training model and career planning of medical students in the targeted admission program .After analyzing the implementation process of this targeted admission policy in medical education , we raised some feasible strategies to increase the attraction and reten-tion of health professionals in rural China .The study covered 4 medical universities in central and western China .A cohort of 308 medical graduates from this targeted admission program were recruited in June 2015 .A baseline survey , including questionnaire survey , in-depth interviews and the focus group discussions , were conducted right before their graduation .The first follow-up online survey was done 6 months after their graduation .he findings of this investiga-tion show that 72.9%of the investigated students in the program used to live in rural areas before 15 years old.The average annual household income was 28,200 Yuan.The top three reasons of choosing this program were guaranteed job after graduation , low performance in the college entrance examination , and wavier of tuition fee .There were sig-nificant differences of implementation of this policy between different provinces , especially the contract-signing and job deployment .Income and working environment were the main influencing factors of the medical graduates 'job-see-king intention .Based on the findings of this study , it can be concluded that the targeted admission program is rather successful in attracting medical graduates for rural health services .However , extra efforts are needed to improve the implementation of the policy and to retain the medical graduates in rural area .

The assessment of symptomatic burden among Ph/BCR- ABL negative myeloproliferative neoplasm patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the value of myeloproliferative neoplasms Symptom Assessment Form total symptom score (MPN-SAF-TSS)in assessing constitutional symptoms among Ph/BCR- ABL negative myeloproliferative neoplasm (MPN)patients.</p><p><b>METHODS</b>A cohort of 628 MPN patients were evaluated by MPN- SAF- TSS.</p><p><b>RESULTS</b>Fatigue was the most common symptom (76.0%, 76.2%vs 89.9%)and the highest average severity of all the symptoms (3.46±2.97, 3.47±2.99vs 4.74±3.04 scores)among polycythemia vera (PV), essential thrombocythemia (ET)and primary myelofibrosis (PMF)patients. Using the MPN- SAF- TSS analysis, PMF patients showed highest burden of symptoms (28.9 ± 19.1), followed by PV patients (19.2 ± 16.8), and finally ET patients (17.1 ± 15.3). Instinct differences were observed between PMF and PV patients (χ(2)=6.371,P=0.021), PMF and ET patients (χ(2)= 14.020,P<0.001). No significant difference was found between PV and ET patients (χ(2)=2.281,P=0.191).</p><p><b>CONCLUSION</b>MPN- SAF- TSS was effective in evaluating the symptomatic burden among Ph/BCRABL negative MPN patients and could be used for serial assessment in this clinical setting.</p>

Long-term outcomes of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To estimate the long-term outcomes and the prognostic factors of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia (AML).</p><p><b>METHODS</b>The CR rate, overall survival (OS) rate, relapse free survival (RFS) rate were retrospectively assayed in 143 de novo AML patients who received the HAD/HAI induction chemotherapy. The outcomes were compared among prognostic groups according to world health organization (WHO) classification, genetic prognosis and initial white blood cell (WBC) count. The role of consolidation chemotherapy consisting of middle-dosage Ara-C (MD-Ara-C) on long term survival was evaluated.</p><p><b>RESULTS</b>Of 143 patients, 112 (78.3%) achieved CR after the first course of HAD/HAI induction treatment, and early death occurred in only one case. Notably, the CR rate of patients with an initial WBC count ≥100×10(9)/L was not significantly different from those with an initial WBC count<100× 10(9)/L (70.4% vs 80.2%, P=0.266). The CR rate for the patients with favorable, intermediate and unfavorable integrated genetics risk factors was 93.7%, 71.4% and 61.3%, respectively, the difference between groups was statistically significant (P=0.001). Patients with FLT3-ITD mutation obtained similar CR rate (70.6%) to that of patients with FLT3 wild type (79.3%, P=0.528).The estimated 5-year OS rate and 5-year RFS rate for all patients was 40.0% and 37.0%, respectively, with a median follow-up of 24 (range 1-104) months. The median survival time was 30 [95%CI (12, 48)] months. 5-year OS and 5-year RFS of the 96 patients who achieved CR after first course chemotherapy without undergoing allo-HSCT in complete remission was 47.0% and 38.0%, respectively. 5-year OS was significantly higher in MD-Ara-C consolidation group than in no MD-Ara-C consolidation group among CR patients without allo-HSCT (58.0%, 19.0%, respectively, P=0.004). In patients who obtained CR after first course and received MD-Ara-C consolidation without allo-HSCT, the 5-year OS of patients with hyperleukocytosis was not significantly lower than that of patients without hyperleukocytosis (55.5%, 58.8%, respectively,P=0.419). FLT3-ITD mutation patients showed similar 5-year OS to that of wild type FLT3 patients (51.4%, 60.2%, respectively, P=0.482). And furthermore, 5-year OS of favorable, intermediate and unfavorable integrated genetics groups were 59.1%, 62.5%, 51.9%, respectively (P=0.332) in this subgroup.</p><p><b>CONCLUSION</b>HAD/HAI induction chemotherapy with sequential consolidation of MD-Ara-C could obtain satisfactory CR rate and long-term survival rate in de novo AML, especially for patients with hyperleukocytosis or FLT3-ITD mutation. It yet remains to be verified by large sample, prospective studies.</p>

Clinical and laboratory characteristics in patients of myelodysplastic syndrome with PNH clones / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical, laboratory characteristics and PIG-A gene mutations in patients of myelodysplastic syndromes (MDS) with PNH clones.</p><p><b>METHODS</b>218 MDS patients diagnosed from August 2013 to August 2015 were analyzed. The PIG-A gene mutations were tested in 13 cases of MDS with PNH clones, 17 cases of AA-PNH and 14 cases of PNH selected contemporaneously by PCR and direct sequencing.</p><p><b>RESULTS</b>13 (5.96%) MDS patients were detected with PNH clones (13/218 cases). 9 patients were treated with cyclosporin A (CsA). Patients showed hematological improvement (HI). There were significant differences between MDS-PNH and PNH patients in terms of granulocyte clone size, red cell clone size and LDH levels [19.2% (1.0%-97.7%) vs 60.2% (3.1%-98.0%), P=0.007; 4.3% (0-67.2%) vs 27.9% (2.5%-83.6%), P=0.026; 246 (89-2014) U/L vs 1137 (195-2239) U/L, P=0.049], while the differences were not statistically significant in patients between MDS-PNH and AA-PNH patients [19.2% (1.0%-97.7%) vs 23.2% (1.5%-96.0%), P=0.843; 4.3% (0-67.2%) vs 14.4% (1.1%-62.8%), P=0.079; 246 (89-2014) U/L vs 406 (192-1148) U/L, P=0.107]. PIG-A gene mutations were detected in 7 MDS-PNH patients, of them, six were missense mutations, one were frameshift mutation and four cases with the same mutation of c.356G>A (R119Q). The PIG-A gene mutations were also detected in 9/11 AA-PNH patients and 11/14 PNH patients, both of them had the mutation of c.356G>A (R119Q). The PIG-A gene mutations of MDS-PNH, AA-PNH, PNH patients were all small mutations, the majority of those (59%) were missense mutation and mainly located in exon 2.</p><p><b>CONCLUSION</b>MDS patients with PNH clones had better response to CsA, smaller PNH clone size. The PIG-A gene mutations of MDS-PNH patients mainly located in exon 2, which could be a mutational hotspot of these patients.</p>

Vitamin D and the recurrence of rheumatoid arthritis / 中国医师进修杂志

Objective To identify the correlation between vitamin D prescription and recurrence in rheumatoid arthritis (RA).Methods A randomized controlled trial study was performed in 170 RA patients who were in remission during the past 2 months.According to the level of vitamin D,170 RA patients were divided into normal vitamin D group (84 patients) and deficiency vitamin D group (86 patients).Deficiency vitamin D group were randomly allocated to receive vitamin D treatment(vitamin D treatment group) or without vitamin D treatment (control group).In the 6-month follow-up period,the recurrence status was observed and compared.Results In the 6-month follow-up period,the recurrence rate of RA in normal vitamin D group was 16.7％(14/84),in vitamin D treatment group was 19.0％(8/42) and in control group was 29.5％(13/44),and there was no significant difference (P ＞ 0.05).In vitamin D treatment group,no hypercalcemia and hyperphosphatemia occured.The age,course of disease and remission time in recurrence patients of three groups were no significant difference (P ＞ 0.05).The level of vitamin D in recurrence patients of vitamin D treatment group was higher than that in recurrence patients of control group:(25.5 ± 8.9) ng/L vs.(20.9 ± 8.6)ng/L,and there was significant difference(P＜ 0.05).Conclusion Vitamin D deficiency is not identified to be a risk factor for RA recurrence.Vitamin D does not reduce the recurrence of RA.

Long- term outcome of thalidomide and cyclosporine in patients with IPSS low/intermediate- 1 myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the long- term outcome of cyclosporin A (CsA) combined with thalidomide regime for Chinese patients with IPSS low/intermediate- 1 myelodysplastic syndromes (MDS) without del（5q）and the predictive variables which could impact the response to the therapy.</p><p><b>METHODS</b>Seventy-six MDS patients who were treated with these drugs at a single institute in China were retrospectively analyzed. The polymorphism of cereblon gene, rs1672753, was detected in patients of this cohort by PCR and direct sequencing.</p><p><b>RESULTS</b>A total of 53% of patients showed hematological improvement（HI）to the therapy. Thirty-one patients（31/73, 43%）achieved erythrocyte response（HI-E）; 15 patients（15/50, 30%）achieved neutrophil response（HI-N); 18 patients（18/58, 31%）achieved platelet response（HI-P). Twenty-seven of the 50 patients（46%）who were dependent on red blood cell transfusion achieved HI- E and became independent of transfusion. The median duration of response among the responders was 22 months (range, 1- 131 + months). Bone marrow blasts ≤2% was the only factor associated with longer response duration in univariate analysis （P=0.010）. There was no significant difference between the two groups of celeblon gene rs1672753 polymorphism either on the response rate or the response duration. The median survival of 67 patients without stem cell transplantation was 82 months. In multivariate analyses, factors significantly correlated with survival were IPSS-R（HR=3.461, 95%CI 1.126-10.639, P=0.030), age ≥ 60 y（HR=4.120, 95%CI 1.070-15.867, P=0.040）and HI-N（HR=7.733, 95%CI 1.007-59.396, P=0.049).</p><p><b>CONCLUSION</b>CsA combined with thalidomide regime could improve the anemia symptom in low/int-1 risk MDS patients without del（5q）. The predictive value of cereblon gene polymorphism, rs1672753, could not be verified in this study.</p>

A study of prognostic value of cytogenetics in patients with primary myelofibrosis / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic value of cytogenetics in Chinese with primary myelofibrosis (PMF).</p><p><b>METHODS</b>Four hundred and thirty-nine Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, the Log-rank test, the likelihood ratio test and the COX proportional hazards regression model were used to evaluate the prognostic scoring systems.</p><p><b>RESULTS</b>Four hundred and thirty-nine Chinese patients with PMF were analyzed with a median age of 56 years (range: 8-83), including 298 males and 141 females. The DIPSS-plus system could effectively evaluate prognosis in Chinese patients with PMF. There was significantly higher predictive power for survival for the DIPSS-plus group compared with the DIPSS group (P=0.006, -2 log-likelihood ratios of 989.5 and 1001.9 for the DIPSS-plus and DIPSS systems, respectively). Univariate analysis indicated that the patients with a normal karyotype, a complex karyotype that was not a monosomal karyotype, +8 only or a balanced translocation only had better survival. Following two cytogenetic risk categories were constructed: favorable karyotype including subjects with a normal karyotype, a complex karyotype that was not a monosomal karyotype, +8 only or a balanced translocation only and unfavorable karyotype included all others. The modified DIPSS-Chinese prognostic model was proposed by adopting cytogenetic categories and DIPSS- Chinese risk group. The median survival of patients classified in low risk (163 subjects), intermediate-1 risk (187 subjects), intermediate-2 risk (82 subjects) and high risk (7 subjects) were not reached, 74 (95% CI 42-106), 39 (95% CI 26-52) and 12(95% CI 1-25)months, respectively, and there was a statistically significant difference in overall survival among the four risk groups (P<0.01).</p><p><b>CONCLUSION</b>The DIPSS-plus had significantly higher predictive power than the DIPSS group in Chinese patients with PMF and the modified DIPSS-Chinese system based on the cytogenetic features of Chinese patients was proposed and worked well for prognostic indication.</p>