目的:初步探讨成人原发免疫性血小板减少症(ITP)与中医体质的关系.方法:采用《中医体质量表》记录60例成人原发ITP患者的一般资料和体质类型,分析不同性别、不同病程患者中医体质类型的分布情况,并进行统计学分析.结果:60例成人原发ITP患者,统计体质频次98例次,气虚质所占的比例最大,为22例次(22.45％),其后分别为阴虚质＞痰湿质＞阳虚质/平和质＞血瘀质＞特禀质＞湿热质＞气郁质;不同性别体质类型的比较,无显著差异;平和质在不同病程中的构成比不同,差异具有统计学意义(P＜0.05).结论:从气虚、阴虚角度调理ITP具有一定优势.

Objective:To investigate the relationship between mitogen-activated protein kinase (MAPK) signaling pathway related signal molecules and the apoptosis of acute promyelocytic leukemia NB4 cells induced by puerariae radix flavones (PRF) and its significance.Methods:The cells were divided into control group [0.025% dimethyl sulfoxide (DMSO) to replace PRF] and 10, 30, 50 μg/ml PRF groups. The proliferation inhibition rate of NB4 cells exposed with PRF for 24, 48 and 72 hours was determined by methyl thiazolyl tetrazolium (MTT) method, and the nuclear morphology was determined by confocal laser scanning microscope after 48 hours. NB4 cells were divided into control group (adding 0.025% DMSO) and 10, 30 and 50 μg/ml PRF with or without 10 μmol/L c-Jun N-terminal kinase (JNK) inhibitor (SP600125) group, and the cells were treated for 48 hours and the changes in the expressions of MAPK pathway related proteins JNK, tumor necrosis factor α (TNF-α), extracellular signal-regulated kinase (ERK) and p38 MAPK were tested by Western blot.Results:10, 30 and 50 μg/ml PRF inhibited the proliferation of NB4 cells in 24, 48 and 72 hours, which was in time- and dose-dependent manners (all P < 0.05). The half-maximal inhibitory concentration (IC 50) at 24, 48 and 72 hours were (40.03±2.23) μg/ml, (22.92±1.72) μg/ml and (17.99±1.48) μg/ml, respectively. The confocal laser scanning microscope showed that NB4 cells displayed distinct apoptotic characteristics after PRF treatment. After co-cultivating NB4 cells with 10 μmol/L SP600125 and different concentrations of PRF for 48 hours, the expression of JNK1 in NB4 cells was suppressed ( P < 0.05), and the expressions of JNK2/3 and p38 MAPK decreased, but the differences were not statistically significant (both P > 0.05). The expressions of ERK1 and ERK2 gradually increased in the single-drug group, while the expression in the combined drug group decreased. The expression of TNF-α in the 50 μg/ml PRF+SP600125 group was down-regulated compared with the 50 μg/ml PRF single-drug group, while the expressions in the 10 and 30 μg/ml PRF+SP600125 groups were up-regulated compared with the 10 and 30 μg/ml PRF single-drug groups. Conclusion:10-50 μg/ml PRF may activate the MAPK signaling pathway through TNF-α. JNK, ERK1/2 and p38 MAPK interact with each other to activate pro-apoptotic related proteins and induce NB4 cells apoptosis.

To describe the health-related quality of life (HRQoL) and fatigue burden among adult patients with immune thrombocytopenia (ITP) in China and determine whether they vary with disease phase. This is a cross-sectional, multi-centre observational study of adult ITP patients and the general population. Participants completed the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). We compared HRQoL and fatigue between ITP patients and the general population, overall and by disease phase (newly diagnosed, persistent, and chronic), using propensity score matching. 203 Patients and 269 members of the general population were recruited. Thirty-six ITP patients (17.7%) were newly diagnosed, 46 (22.7%) were persistent, and 121 (59.6%) were chronic. Compared with the general population, ITP patients had impaired HRQoL and greater fatigue burden. The persistent ITP group showed the largest number of SF-36 scales exceeding the minimally important difference: physical functioning [− 10.5; 95% confidence interval (CI) − 24.5 to 3.5; P < 0.001], role physical (− 16.7; 95% CI − 36.4 to 3.0; P < 0.001), social functioning (− 15.6; 95% CI − 34.5 to 3.3; P < 0.001), and role emotional (− 12.1; 95% CI − 26.0 to 1.8; P < 0.001). Chronic ITP patients had the worst FACIT-F scores (36.89 ± 5.21). Higher fatigue severity was associated with lower physical and mental HRQoL. The HRQoL and fatigue burden of Chinese adult patients with ITP vary by disease phase. Persistent ITP patients were the most vulnerable subgroup in terms of HRQoL, while chronic ITP patients bear the heaviest fatigue burden.

ABSTRACT Objectives: The great majority of adult patients with immune thrombocytopenia (ITP) who fail to respond to first-line medication or who relapse following response require additional treatment. Although broad guidelines currently exist for second-line and subsequent therapies, none to date have been prescriptive. The purpose of this systematic review and network meta-analysis was to establish a clinically relevant ranking of the efficacy and safety of medications for adults (≥18 years old) with previously treated ITP. Methods: Relevant publications from Medline, Embase, and the Cochrane database were searched from their inceptions through July 31, 2018. The primary outcome was the overall response (OR, defined as a platelet count ≥50 × 109/L at the end of treatment without rescue therapy), while the secondary endpoints included early response (ER; i.e. a platelet count ≥50 × 109/L at week 2 after initiation of treatment) and therapy-related severe adverse events (AEs). Results: Thirteen randomized controlled trials (1,202 patients) were included in this study. According to pooled results, romiplostim appears to be the most suitable treatment in terms of OR, followed by avatrombopag, eltrombopag, fostamatinib, and rituximab. Avatrombopag produced more satisfactory outcomes than romiplostim, eltrombopag, and rituximab in terms of ER; severe AEs profiles were similar across all treatment arms. Conclusion: Romiplostim appears to be the best option for patients who fail to respond to prior treatment or relapse thereafter, while avatrombopag and eltrombopag are reasonable alternatives. Rituximab monotherapy is not recommended, as it produces the lowest OR and ER rates.

OBJECTIVE:To investigate the effects of oridonin (ORI) on the proliferation and apoptosis of human multiple myeloma cell line H929 and its possible mechanism.METHODS:H929 cells were exposed to ORI 0、4、8、12、16、20、24、28、32 μmol/L for 12, 24 and 36 hours respectively. The prolifcration inhibitory effect of ORI on H929 cells was determined by MTT assay and then the working concentrations of ORI were determined. The morphological changes and apoptosis of H929 cells were observed by TUNEL (TdT-mediated dUTP Nick-End Labeling) and fluorescence microscopy. The apoptosis rate of H929 cells was detected by flow cytometry with Annexin V-FITC/PI staining. The protein expressions of pro-caspase-3, BCL-2，p-PI3K, p-Akt, BAX, Cleaved PARP and p-JNK, p-ERK and p-p38 in H929 cells were detected by Western blot.RESULTS:Compared with the control group, the proliferation of H929 cells treated with the ORI of 8-16 μmol/L was significantly inhibited and the apoptosis of H929 cells was obviously increased in dose- and time-dependent manners. As for morphological changes, the characteristics of apoptotic cells were presented in H929 cells treated with ORI for 24 hours. The protein levels of pro-caspase-3, BCL-2，p-PI3K, p-Akt were down-regulated with increasing of ORI concentration（r=0.9861, r=0.9725, r=0.9413, r=0.9373）, while the BAX, Cleaved PARP and p-JNK, p-ERK and p-p38 were up-regulated（r=0.9178, r=0.8877, r=0.882, r=0.9645, r=0.8623）.CONCLUSION:The ORI possesses anti-myeloma effects, can inhibit the proliferation and induce the apoptosis of H929 cell line in vitro. Its potential mechanism may be related with up-regulating the MAPK and down-regulating the PI3K/Akt signal pathways.

Background: Acute promyelocytic leukaemia (APL) is a special subtype of acute myeloid leukaemia. The aim of this study was to investigate the anti-tumour effects of puerariae radix flavones (PRF), the total flavonoids from Chinese herb puerariae radix (PR), on the human APL cell line NB4 and to explore the potential mechanisms. Methods: NB4 cells were exposed to various concentrations (0, 10, 30, 50 μg/ml) of PRF. Cell viability was measured by MTT assay. The cell cycle, the extent of cell apoptosis and the mitochondrial transmembrane potential were analysed with flow cytometry (FCM). The expression of apoptosis-related proteins was assayed by western blot. Results: We found that PRF inhibited cell viability of NB4 cells in a timeand dose-dependent manner. The cell cycle was arrested in the G0/G1 phase. FCM assays showed that PRF induced apoptosis and decreased mitochondrial membrane potential in a dose-dependent manner. NB4 cells treated with PRF expressed higher levels of cleaved caspase-3, caspase-9 and poly ADP-ribose polymerase (PARP) with an increased Bax/Bcl-2 ratio and Bcl-xL expression. Western blot analysis showed that expression of JNK was significantly lower while the expression of p-JNK was greater. Further analysis showed activation of the JNK pathway of NB4 cells by PRF. Conclusions: Our data, taken together, indicate that PRF exerted a potent anti-tumour effect on NB4 cells by inducing apoptosis, the mechanism of which might be accompanied with the JNK pathway and the mitochondrial pathway activation.

Autophagy plays an important role in plasma cell ontogeny and in the pathophysiology of multiple myeloma. Autophagy is usually considered a pro-survival mechanism, and cooperates with the ubiquitin proteasome system in maintaining the homeostasis of myeloma cells by degrading excessive and misfolded proteins for energy recycling. Therefore, the inhibition of autophagy could effectively induce death in myeloma cells, and could synergize with proteasome inhibitors. However, the excessive activation of autophagy could also lead to the extreme degradation of the organelles that induce autophagic cell death. Hence, the activation of autophagic cell death might also represent a promising approach for treating myeloma. Recent studies have demonstrated that autophagy also mediates drug resistance in myeloma cells and the complications of myeloma, while the inhibition of autophagy may reverse the response to drugs. In this study, we have mainly reviewed recent research on autophagy in relationship to the therapeutic effect, the reversal of drug resistance, and the mediation of complications.