HIV treatment outcomes among people who acquired HIV via injecting drug use in the Asia‐Pacific region: a longitudinal cohort study

INTRODUCTIONData on HIV treatment outcomes in people who inject drugs (PWID) in the Asia‐Pacific are sparse despite the high burden of drug use. We assessed immunological and virological responses, AIDS‐defining events and mortality among PWID receiving antiretroviral therapy (ART).METHODSWe investigated HIV treatment outcomes among people who acquired HIV via injecting drug use in the TREAT Asia HIV Observational Database (TAHOD) between January 2003 and March 2019. Trends in CD4 count and viral suppression (VS, HIV viral load <1000 copies/mL) were assessed. Factors associated with mean CD4 changes were analysed using repeated measures linear regression, and combined AIDS event and mortality were analysed using survival analysis.RESULTSOf 622 PWID from 12 countries in the Asia‐Pacific, 93% were male and the median age at ART initiation was 31 years (IQR, 28 to 34). The median pre‐ART CD4 count was 71 cells/µL. CD4 counts increased over time, with a mean difference of 401 (95% CI, 372 to 457) cells/µL at year‐10 (n = 78). Higher follow‐up HIV viral load and pre‐ART CD4 counts were associated with smaller increases in CD4 counts. Among 361 PWID with ≥1 viral load after six months on ART, proportions with VS were 82%, 88% and 93% at 2‐, 5‐ and 10‐years following ART initiation. There were 52 new AIDS‐defining events and 50 deaths during 3347 person‐years of follow‐up (PYS) (incidence 3.05/100 PYS, 95% CI, 2.51 to 3.70). Previous AIDS or TB diagnosis, lower current CD4 count and adherence <95% were associated with combined new AIDS‐defining event and death.CONCLUSIONSDespite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings.     

Do antiarrhythmic drugs work? some reflections on the implications of the cardiac arrhythmia suppression trial

Despite major advances in our understanding of the mechanisms of cardiac arrhythmias and how antiarrhythmic drugs appear to work, there remains much doubt whether these agents reduce arrhythmic mortality except in certain subsets of patients. The results of the Cardiac Arrhythmia Suppression Trial (CAST) have indicated that certain antiarrhythmic drugs not only "fail to work" but may substantially increase mortality. The effects of Class Ic agents in CAST and the meta-analysis of randomized antiarrhythmic trials in the survivors of acute infarction suggest that drugs that act primarily by delaying conduction are particularly deleterious in the survivors of acute infarction. Whether these data have a wide applicability in terms of all ventricular arrhythmias is unclear, but beta-blockers remain the only class of agents that in control trials have been shown to reduce sudden death. The effect appears to be related to beta-blockade and not to suppression of premature ventricular contractions (PVCs). Beta blockers appear to act by preventing ventricular fibrillation. It is reasonable to assume that PVC suppression per se is unlikely to produce a reduction in sudden death. Uncontrolled data with amiodarone suggests that it has the potential to prolong survival by controlling arrhythmias. The effects of amiodarone and beta blockers, both significantly attenuating adrenergic stimulation, provide pharmacologic probes to define the crucial determinants of efficacy of a compound for mortality reduction in high risk survivors of myocardial infarction. The focus must now shift from antiectopic and antiarrhythmic agents that delay conduction to those that exert antifibrillatory actions by sympathetic antagonism and those that exhibit the added property of lengthening myocardial refractoriness.     

SETDB1: A perspective into immune cell function and cancer immunotherapy

Oncogene SET Domain Bifurcated 1 (SETDB1)/ESET, an H3K9 methyltransferase, was originally discovered over two decades ago; however, its function in the immune response was not first reported until 2011. SETDB1 immune functions include B cell maturation, T cell activity regulation, and immune escape in cancer cells. In B lymphocytes, SETDB1 mediates the transition from pro-B to pre-B cells and represses endogenous retroviruses (ERV) to encourage B cell lineage differentiation and maturation. SETDB1 alters T cell function by methylating IL-2 and IL-17 promoters and mediating T cell lineage commitment and development. In addition, SETDB1 plays a critical role in ERV silencing within a variety of immune cells, which can indirectly weaken the immune response. Although SETDB1 is critical for normal immune cell function, overexpression in cancer cells negatively impacts immune cell fights against cancer through decreased tumour immunogenicity. Within cancer cells, SETDB1 overexpression represses production and infiltration of antitumour immune cells, mediates immune escape through TE and ERV silencing, represses the type I interferon pathway, and interferes in immune checkpoint blockade (ICB) outcomes by regulation of PD-L1 expression and IFN signalling. In this review, we further discuss the immunological mechanisms of SETDB1 in normal and cancerous cells and its implications in cancer immunotherapy.     

环孢菌素A外用实验研究

目的 从定性、定时二方面探讨环孢菌素Ａ透皮能力。方法 通过对豚鼠的活体、体外透皮实验及抑制实验测定ＣＹＡ透皮能力。结果 （１）环孢菌素Ａ在活体透皮实验中,在促渗剂相同的条件下,随ＣＹＡ浓度增加透皮量增加。（２）环孢菌素Ａ在活体秀皮实验中,在相同的ＣＹＡ浓度条件下加入促渗剂氮酮透皮量多于加入丙二醇透皮量。（３）环孢菌素Ａ在离体透皮实验中,在促渗剂相同的条件下随ＣＹＡ浓度增加透过量增加。（４）环孢菌素     

Comparison between nafarelin acetate andd-Trp6-LHRH for temporary pituitary suppression in in vitro fertilization (IVF) patients: A prospective crossover study

Purpose Nafarelin acetate is a new gonadotropin releasing (GnRH) agonist analogue with unique potency, intranasal administration, and convenient storage. Hence, nafarelin was considered as an alternative for temporary pituitary suppression in patients undergoing ovulation induction in IVF. A crossover treatment in a prospective study was performed including 40 women with bilateral obstructed tubes and normal ovarian function, treated in 80 ovulation induction cycles using the long protocol. Twenty patients used nafarelin acetate 600 g/daily in their first cycle and received d-Trp6-LHRH, 0.5 mg/daily, in their following cycle. The other 20 women used decapeptyl in their first cycle and received nafarelin in the second.Results Estradiol suppression was achieved by both d-Trp6-LHRH and nafarelin at equal time intervals. The average total number of ampoules (P=0.0005) and the length of administration of hMG required for ovarian stimulation (P=0.0002) and the time interval between GnRHa initiation to oocyte retrieval (P=0.04) was significantly lower in nafarelin cycles. The number and the distribution between large and small follicles as well as the average number of oocytes retrieved did not differ between the two GnRH analogues.Conclusion Our results demonstrate that nafarelin acetate is comparable to d-Trp6-LHRH for temporary pituitary suppression used for controlled ovarian stimulation in IVF patients. However, using nafarelin ovarian stimulation was achieved with fewer ampoules of hMG, administered for a shorter period of time, thus with a lesser cost.     

MR脂肪抑制技术开发与临床应用

目的：通过ＭＲ脂肪抑制技术开发的结果,鉴别Ｔ_１加权像高信号病变。方法：利用荷兰ＰＨＩＬＩＰＳ０．５Ｔ磁共振机对３例对照组和６例病变组进行常规ＭＲ扫描和脂肪抑制（ＳＴＩＲ）扫描。结果：３例对照组的岩尖脂肪、枕项皮下脂肪。肾周脂肪常规扫描,Ｔ１Ｗ和Ｔ２Ｗ均为相似的高信号,脂肪抑制扫描无信号。病变组６例,即头部３例,颈椎及胸椎各１例,颈髓１例,常规扫描Ｔ_１Ｗ及Ｔ_２Ｗ均为高信号,脂肪抑制扫描则无信号。结论：Ｔ_１Ｗ为高信号时进行脂肪抑制扫描,脂肪受到抑制后出现特异性的无信号,可用来鉴别Ｔ_１Ｗ高信号病变。     

小鼠骨髓巨噬细胞培养液的造血抑制活性研究

观察了小鼠骨髓型正常巨噬细胞株经６Ｇｙ＾６０Ｃｏ照射后细胞培养上对ＣＦＵ－Ｅ和ＣＦＵ－Ｇ同期怕影响,结果未照射和照射后Ａｎａ－１细胞培养３上清对ＣＦＵ－Ｅ和ＣＦＵ－ＧＭ的形成均垢抑制活性,但照射后抑制活性更强,上清经灭活后抑制活性减弱,结论;小鼠骨髓巨噬 培养上清对ＣＦＵ－＝Ｅ和ＣＦＵ－ＧＭ均的抑制活性,这种抑制活性可能是抑制因子和细胞毒共同作用的结果。     

免疫状态对Fv—4基因抗Friend MuLV作用的影响

通过检测免疫抑制的Ｆ１小鼠和杂合子Ｆ２裸鼠对Ｆｒｉｅｎｄ小鼠白血病病毒（Ｆｒ．ＭｕＬＶ）感染的敏感性,探讨免疫状态对Ｆｖ－４基因（特别是对Ｆｖ－４基因杂合子）抗ＦｒｉｅｎｄＭｕＬＶ作用的影响,经腹腔接种Ｆｒ．ＭｕＬＶ病毒液攻击小鼠或Ｆ２裸鼠后,检查其计中Ｆｒ．ＭｕＬＶ的增主其发病情况,结果表明,免疫抑制的Ｆ１小鼠和杂合子Ｆ１裸鼠都可被Ｆｒ．ＭｕＬＶ脾脏中有病毒增殖,并用约２／３的杂合子Ｆ２裸鼠与Ｂ     

Effects of chlordiazepoxide,morphine and amphetamine on responding suppressed by different levels of electric shock in the pigeon are rate dependent

In general, chlordiazepoxide (CDP) and amphetamine reduce high rates of responding and increase low rates (rate-dependent effect). However, unlike CDP, amphetamine does not typically increase low rates resulting from suppression of responding by noxious stimuli. In the present experiment, key pecking by pigeons was reinforced under a random ratio schedule of food presentation. This responding was then suppressed by stimuli correlated with electric shocks of varying intensity (2 or 4 mA) or reduced by the omission of the food (extinction). Treatment with CDP (0.3–10.0 mg/kg) and morphine (0.3–10.0 mg/kg) increased the rate of suppressed responding: lower rates being increased to a proportionately greater extent than high rates.d-Amphetamine (0.1–1.0 mg/kg) further reduced the rate of suppressed responding: the lower rates being reduced proportionately more than the higher rates. Thus the effects of all three drugs depended upon the control rates of responding, but the effects of amphetamine were the inverse of those of CDP and morphine. The effects of amphetamine on low, suppressed or punished response rates are therefore not an exception to the generality of rate-dependency, but a different aspect of the same principle — inverse rate-dependency.