Low-Dose Azacitidine with DNMT1 Level Monitoring to Treat Post-Transplantation Acute Myelogenous Leukemia or Myelodysplastic Syndrome Relapse

Patients with early relapse of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after hematopoietic cell transplantation (HCT) have a poor prognosis, and no standard treatment. Twenty-nine patients with early disease recurrence post-transplantation were treated with azacitidine (AZA; median dose, 40 mg/m²/day for 5 to 7 days). At a median follow-up of 6.3 months (range, 1.3 to 41.1 months), 7 patients (27%) had a response to AZA, defined as complete remission, hematologic improvement, or improved donor chimerism. Response occurred after a median of 3 cycles, and the median duration of response was 70 days (range, 26 to 464 days). Median survival was 6.8 months (95% confidence interval, 3.8 to 11.1 months). Survival was similar in the patients receiving an AZA dose ≤40 mg/m² and those receiving an AZA dose >40 mg/m². Six patients receiving donor lymphocyte infusion with AZA had a response or stable disease without worsening graft-versus-host-disease. We retrospectively used a flow cytometry assay to explore DNA-methyltransferase-1 in blood mononuclear cells as a potential pharmacodynamic marker to assess intracellular drug targeting in 8 patients. No correlation with AZA dose or response was observed. Low-dose AZA appears to have comparable efficacy to higher-dose AZA post-HCT. A significant proportion of this poor-risk population responded to low-dose AZA, suggesting a dose-independent, noncytotoxic mechanism for antileukemic activity.     

Management of Critically Ill Patients with Severe Acute Respiratory Syndrome (SARS)

Severe acute respiratory syndrome (SARS) is frequently complicated with acute respiratory failure. In this article, we aim to focus on the management of the subgroup of SARS patients who are critically ill. Most SARS patients would require high flow oxygen supplementation, 20-30% required intensive care unit (ICU) or high dependency care, and 13-26% developed acute respiratory distress syndrome (ARDS). In some of these patients, the clinical course can progress relentlessly to septic shock and/or multiple organ dysfunction syndrome (MODS). The management of critically ill SARS patients requires timely institution of pharmacotherapy where applicable and supportive treatment (oxygen therapy, noninvasive and invasive ventilation). Superimposed bacterial and other opportunistic infections are common, especially in those treated with mechanical ventilation. Subcutaneous emphysema, pneumothoraces and pneumomediastinum may arise spontaneously or as a result of positive ventilatory assistance. Older age is a consistently a poor prognostic factor. Appropriate use of personal protection equipment and adherence to infection control measures is mandatory for effective infection control. Much of the knowledge about the clinical aspects of SARS is based on retrospective observational data and randomized-controlled trials are required for confirmation. Physicians and scientists all over the world should collaborate to study this condition which may potentially threaten human existence.     

SARS病人外周血T淋巴细胞的动态变化及其在发病进程和发病机理中的意义

目的 :通过研究严重急性呼吸综合征 (SevereAcuteRespiratorySyndrome,SARS)患者外周血免疫细胞的动态变化 ,探讨外周血免疫细胞在SARS发病进程中的意义 ,初步探讨SARS的发病机理 ,并为SARS的诊断和治疗提供有力的实验室依据。方法 :回顾性动态观察我院收治的已治愈SARS病例和SARS死亡病例外周血CD4 + 和CD8+ T淋巴细胞 ,评估外周血免疫细胞在SARS发病进程及预后中的作用。实验方法为流式细胞术检测和分析免疫细胞表面特异性荧光抗体标记 ,T细胞表面标志组合为CD3 CD8 CD4 5 CD4。结果 :所有治愈的SARS病人的CD4 + 和CD8+ T淋巴细胞都有不同程度的可逆性下降 ,而所有的死亡病例有不可逆性显著下降 ,直至死亡。T细胞下降程度和维持的时间与病情密切相关。普通型SARS病例最低CD4 + T淋巴细胞数为 30 5± 15 0cells μl(P <0 .0 0 1)、重型为 139± 6 9cells μl(P <0 .0 0 1) ,普通型SARS病例最低CD8+ T淋巴细胞数为 2 2 3± 89cells μl(P <0 .0 0 1)、重型为 171± 92cells μl(P <0 .0 0 1)。所有普通型病例和大部分重型病例T淋巴细胞恢复正常 ,个别重型病例低于正常或接近正常 ,恢复后普通型平均为 991± 2 86cells μl,重型平均为 5 4 5± 2 2 5cells μl。恢复时间有所不同 ,普通型平均为 17± 5天     

Beneficial Effect of Eucommia Polysaccharides on Systemic Lupus Erythematosus-like Syndrome Induced by Campylobacter jejuni in BALB/c Mice

The stem bark of Eucommia ulmoides Oliv. is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia in traditional Chinese medicine. This study was to determine whether the crude polysaccharides (EUPs) isolated from the stem bark of E. ulmoides had beneficial effects on lupus-like syndrome in mice. BALB/c mice were immunized with CJ-S₁₃₁ in Freund’s complete adjuvant on day 0, and then boosted on day 14. EUPs 15 or 30 mg kg⁻¹·day⁻¹, or prednisone 5 mg kg⁻¹·day⁻¹ was given to BALB/c mice intragastrically from day 0 to 34. Treatment with EUPs 15 or 30 mg kg⁻¹·day⁻¹ for 35 days protected kidney from glomerular injury with reduced immunoglobulin deposition and lowered proteinuria. The increased production of serum autoantibodies and total immunoglobulin G (IgG) was also inhibited. These findings suggested that Eucommia polysaccharides had a beneficial effect on systemic lupus erythematosus-like syndrome induced by CJ-S₁₃₁ in BALB/c mice.     

急性冠脉综合征（Acute Coronary Syndrome）

一、基本概念(The basal concept):指主要是由于冠状动脉严重粥样硬化导致持续性狭窄或间断性冠脉痉挛引起心肌缺血性损伤,在此病理基础上甚至进一步引起冠脉内血栓形成严重者引起急性心肌梗塞(AMI)或心源性猝死所致的临床综合征。 二、主要内容:(一)不稳定型心绞痛(Unstable Angina);(二)急性心肌梗塞(Acuts Myocardial Infarction)包括有Q波     

Two Cases of Refractory Thrombocytopenia in Systemic Lupus Erythematosus that Responded to Intravenous Low-Dose Cyclophosphamide

Treatment of thrombocytopenia in systemic lupus erythematosus (SLE) is considered in cases of current bleeding, severe bruising, or a platelet count below 50,000/µL. Corticosteroid is the first choice of medication for inducing remission, and immunosuppressive agents can be added when thrombocytopenia is refractory to corticosteroid or recurs despite it. We presented two SLE patients with thrombocytopenia who successfully induced remission after intravenous administration of low-dose cyclophosphamide (CYC) (500 mg fixed dose, biweekly for 3 months), followed by azathioprine (AZA) or mycophenolate mofetil (MMF). Both patients developed severe thrombocytopenia in SLE that did not respond to pulsed methylprednisolone therapy, and started the intravenous low-dose CYC therapy. In case 1, the platelet count increased to 50,000/µL after the first CYC infusion, and remission was maintained with low dose prednisolone and AZA. The case 2 achieved remission after three cycles of CYC, and the remission continued with low dose prednisolone and MMF.     

Severe Acute Respiratory Syndrome (SARS): loud clang of the Leper's bell

Severe acute respiratory syndrome (SARS) or the "Chinese Chernobyl" emerged against an alarming background of rising infectious disease in poor rural China and to a backdrop of interregional and global polarization of population well-being and vulnerability. SARS has added its own dissonant note to "health disturbance", caused fear and panic and disrupted international commerce. Its emergence should be perceived as a disturbing alarm that underscores the need to strengthen public health and facilitate construction of a human security "umbrella" in the event of future disasters. Although SARS has produced a relatively insignificant level of damage when compared to other threats, its long-term effects on health should not be underestimated, based on its unexpected appearance and still unknown properties. This essay presents a qualitative flowchart that follows SARS from its origin in China to the accumulation of global damage. Two future scenarios were formulated, covering a worse-case outcome and containment outcome, which currently appears to be the case. In the event of the worst-case scenario it is doubtful whether any health service in Europe could cope. In either case, the development of a European Union Center for Disease Control is mandatory.     

低温对大鼠内毒素性ARDS的有利影响

目的 观察32．5—33％低温对大鼠内毒素性急性呼吸窘迫综合征（ARDS）的有利影响。方法 采用大鼠腹腔注射内毒素（LPS），16h后再行气管内滴注LPS的方法建立ARDS模型。34只雄性SD大鼠被随机分为4组：生理盐水常温组（NN）、生理盐水低温组（NH）、ARDS低温组（AH）、ARDS常温组（AN）。观察气管内滴注前（基础值）、达到ARDS时、ARDS后1、2、3各时间点动脉血氧分压／吸入氧浓度（PaO2／FiO2）、平均动脉压（MAP）、中心静脉压（CVP）和二氧化碳分压（PaCO2）的变化。ARDS后3h处死动物，开胸取右肺上叶作肺形态学观察，取左肺计算湿重／干重（W／D）比值，并采用溴甲酚绿法测定支气管肺泡灌洗液（BALF）中白蛋白的含量。结果 AN、AH组滴注LPS后PaO2／FiO2比值逐渐下降，在ARDS时、ARDS后1、2、3h较基础值和NN组相应时间点相比降低非常明显（P〈0．01）。AN组PaCO2在ARDS时、ARDS后1、2、3h较基础值升高非常显著（P〈0．01）。AH组PaCO2在ARDS时、ARDS后1、2h与基础值和NN组相比升高显著（P〈0．05）；在ARDS后3h与基础值及NN组相比无显著差异（P〉0．05），但与AN组相比明显降低（P〈0．05）。AH组BALF中白蛋白含量、左肺W／D较AN组降低明显（P〈0．05）；且与NN组相比无统计学差异（P〉0．05）。肺组织病理显示AH组肺泡壁充血增厚，肺间质和肺泡腔内炎性细胞浸润均较AN组减轻。结论 低温对大鼠内毒素性ARDS有一定的有利影响。     

The Role of the Yaa Gene in Lupus Syndrome

The BXSB/MpJ (BXSB) murine strain (H-2^b) spontaneously develops an autoimmune syndrome with features of systemic lupus erythematosus (SLE) that affects males much earlier than females. A mutant gene located on the BXSB Y chromosome, designated Yaa (Y chromosome-linked autoimmune acceleration), is responsible for the acceleration of the disease observed in male BXSB mice. Studies on H-2 congenic and I-E transgenic mice have clearly demonstrated that the MHC class II genes play a crucial role in the development or protection of SLE. However, the MHC effect can be completely masked by the presence of the Yaa gene in mice with certain genetic backgrounds. It is intriguing that the Yaa gene effect is selective on autoimmune responses, varying in different lupus-prone mice. Studies on immune responses against foreign antigens have shown that the Yaa gene potentiates immune responses only against antigens to which mice are genetically (H-2-linked) low-responding, but not high-responding. Thus, the selective immune enhancing activity of the Yaa gene may be related to differences in the capacity of T helper cells specific for given antigens. Moreover, studies on Yaa⁺Yaa^? bone marrow cell chimeric mice have suggested that a specific cognate interaction of T helper cells with Yaa⁺ B cells is responsible for a selective enhancing effect of immune responses to foreign antigens as well as autoantigens. It is significant that unlike the lpr mutation, whose abnormality is associated with the capacity of the Fas antigen to mediate apoptosis, the Yaa gene by itself is unable to induce significant autoimmune responses in mice without apparent SLE background. This suggests that-the molecular defect of the Yaa gene is likely to differ from that of the lpr gene, and that the Yaa gene effect requires the abnormal autosomal genome present in lupus-prone mice. Based on these findings, a possible molecular nature of the Yaa gene abnormality will be discussed.     

Acrolein Scavenger Hydralazine Prevents Streptozotocin‐Induced Painful Diabetic Neuropathy and Spinal Neuroinflammation in Rats

Diabetes‐induced neuropathic pain (DNP) substantially influences people's life qualities. Hyperglycemia‐induced excess free radicals have been considered as the most critical mechanisms underlying DNP. As an unsaturated aldehyde and a reactive product of lipid peroxidation, acrolein plays critical roles in diabetic nephropathy and inflammatory pain. We sought to determine whether acrolein is involved in DNP in this study. Diabetes was induced by a single intraperitoneal (i.p.) injection of 60 mg/kg streptozotocin (STZ). An acrolein scavenger hydralazine (5 mg/kg) was administered through a daily injection for 4 weeks, starting immediately within 30 min after STZ injection. Western blot showed that hydralazine could effectively inhibit STZ‐induced upregulation of acrolein in the spinal dorsal horn on day 7–28 after STZ injection. Behavioral tests showed that STZ injection induced significant mechanical allodynia and thermal hyperalgesia, which could be alleviated by hydralazine. Immunofluorescent histochemistry and Western blot showed that STZ induced significant microglial activation. ELISA data indicated upregulation of inflammatory cytokines IL‐1β and TNF‐α expression in the spinal dorsal horn. Furthermore, hydralazine effectively attenuated microglial activation and expression of inflammatory mediators. Our data indicate that acrolein might be involved in the development of neuroinflammation and behavioral consequences of DNP. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1858–1864, 2017. © 2017 Wiley Periodicals, Inc.     

Longitudinal analysis of Severe Acute Respiratory Syndrome (SARS) coronavirus-specific antibody in SARS patients

The serum antibodies to severe acute respiratory syndrome (SARS) coronavirus of 18 SARS patients were checked at 1 month and every 3 months after disease onset. All of them except one, who missed blood sampling at 1 month, tested positive for the immunoglobulin G (IgG) antibody at 1 month. Fifteen out of 17 tested positive for the IgM antibody at 1 month. The serum IgM antibody of most patients became undetectable within 6 months after the onset of SARS. The IgG antibody of all 17 patients, whose serum was checked 1 year after disease onset, remained positive.     

Longitudinal Analysis of Severe Acute Respiratory Syndrome (SARS) Coronavirus-Specific Antibody in SARS Patients

The serum antibodies to severe acute respiratory syndrome (SARS) coronavirus of 18 SARS patients were checked at 1 month and every 3 months after disease onset. All of them except one, who missed blood sampling at 1 month, tested positive for the immunoglobulin G (IgG) antibody at 1 month. Fifteen out of 17 tested positive for the IgM antibody at 1 month. The serum IgM antibody of most patients became undetectable within 6 months after the onset of SARS. The IgG antibody of all 17 patients, whose serum was checked 1 year after disease onset, remained positive.     

Modulatory Effect of the Euro-Lupus Low-Dose Intravenous Cyclophosphamide Regimen on Circulating Immune Cells in Systemic Lupus Erythematosus

Archivum Immunologiae et Therapiae Experimentalis - A Euro-Lupus regimen of low-dose intravenous cyclophosphamide (CFA) is commonly used to treat severe organ manifestations of systemic lupus...