Haematological acclimation and re-acclimation to hypoxia in the mouse

Haematological responses throughout 4 w of initial acclimation (IA) and three paradigms of re-acclimation (RA) to hypoxia (FI_O2=0.12${\text{FI}}_{{\text{O}}_2}=0.12$) were examined in female mice. We hypothesised that (i) haematological responses would be increased during re-exposure, resulting in greater O₂-carrying capacity in RA compared to IA; and (ii) further improvements would occur when abbreviating the de-acclimation period to 1 w (RA_↓DA) or extending the IA period to 8 w (RA_↑IA). The serum [EPO] response was blunted in all RA groups compared to IA but the resulting reticulocyte response was similar in all experimental groups. The [Hb] response was the same in RA and RA_↓DA as in IA but was blunted in RA_↑IA due to a reduction in mean corpuscular Hb. The sensitivity of EPO-producing cells appears blunted but the sensitivity of erythroid precursors to EPO is enhanced by recent hypoxic exposure. Erythropoietic regulation is altered during RA in a manner that is dependent on the paradigm of initial exposure.     

Altered aquaporins in the brains of mice submitted to intermittent hypoxia model of sleep apnea

Rostral fluid displacement has been proposed as a pathophysiologic mechanism of both central and obstructive sleep apnea. Aquaporins are membrane proteins that regulate water transport across the cell membrane and are involved in brain edema formation and resolution. The present study investigated the effect of intermittent hypoxia (IH), a model of sleep apnea, on brain aquaporins.     

间歇低氧对大鼠颏舌肌运动皮质区经颅磁刺激反应的影响

目的 应用经颅磁刺激技术探讨间歇低氧对颏舌肌运动皮质区的影响.方法 选取Sprague-Dawley雄性大鼠80只按照随机数字表法分为正常对照组(10只)和间歇低氧组(各低氧组10只),应用经颅磁刺激刺激两组大鼠颏舌肌运动皮质区并记录刺激后的反应,测量并比较反应潜伏期和幅度,多组间数据比较采用单因素方差分析.结果 大鼠大脑皮质前外侧区是颏舌肌运动皮质区最佳经颅磁刺激位点.与对照组(5.20 ±0.64)ms,(1.21±0.53) mV]相比,间歇低氧大鼠颏舌肌运动皮质区的经颅磁刺激反应潜伏期在低氧第1天[( 4.90±0.54) ms]和第14天[(4.64±1.71)ms]显著缩短,差异有统计学意义(F=3.294,P＜0.01);反应幅度在低氧第1天[(2.28±0.57)mV]和第7天[ (1.89 ±0.20)mV]显著增高(F=1.905,P＜0.05).结论 间歇低氧可以引起大鼠颏舌肌运动皮质区的反应性增加.     

间歇性肝门阻断是原发性肝癌术后早期肝内复发的一项危险因素

目的 探讨间歇性肝门阻断对原发性肝癌术后肝内转移的影响.方法 回顾性分析335例原发性肝癌患者临床资料.所有患者均行肝叶切除术,以阻断入肝血流的方法分为两组:(1)间歇性肝门阻断组:97例,Pringle方法间歇性阻断肝门,每个循环阻断15 min,开放5 min.可重复2～3个循环.(2)其他阻断方法(对照)组:238例,包括预处理阻断法、单纯Pringle法、选择性入肝血流阻断法等.术后每4周,定期复查肝脏功能各项指标及甲胎蛋白,肝脏彩色多普勒超声和(或)CT、MRI,平均随访26.5个月.结果 围手术期死亡6例(1.8％).间歇性肝门阻断组1、2年复发率分别为31.6％(30/95)和48.4％(46/95),明显高于对照组的21.4％(50/234)和38.0％(89/234)(P＜0.05).间歇性肝门阻断组1、2年的生存率分别为70.5％(67/95)和53.7％(51/95),与对照组的68.8％(161/234)和55.6％(130/234)比较,无统计学差异(P＞0.05).为排除其他肝内复发相关因素的影响,我们调整了观察病例标准:肿瘤≥5 cm;术后4周AFP降至正常;术中B超阴性.间歇性肝门阻断组与对照组纳入病例分别为79例和155例.结果两组1、2年复发率分别为29.1％比18.7和46.8％比35.5％,间歇性肝门阻断组仍明显高于对照组(P＜0.05),但1、2年生存率无明显差别.结论 间歇性肝门阻断是导致原发性肝癌术后早期肝内复发的一项危险因素,临床应慎用.     

瞬时脉冲足底静脉泵在髋膝关节置换术后预防深静脉血栓形成的应用研究

目的 探讨瞬时脉冲足底静脉泵预防全髋/膝关节置换术后深静脉血栓形成（DVT）的效果,为临床医护人员选择最优的机械预防方式提供参考依据。方法 选取2019年11月至2020年8月在我院关节外科拟行全髋/膝关节置换术的病人210例,随机分为观察组（105例）和对照组（105例）;术后,观察组和对照组分别使用瞬时脉冲足底静脉泵和间歇性充气加压装置预防DVT。观察比较两组病人术后DVT的发生率、术后D-二聚体、C-反应蛋白、白细胞介素-6和患肢肿胀情况,住院时间和使用机械设备预防DVT的舒适度。结果 术后2周,观察组DVT总发生率为6.67%,对照组为9.52%,两组比较,差异无统计学意义（P＞0.05）;观察组病人机械设备使用的舒适度高于对照组,差异有统计学意义（P＜0.05）。结论 瞬时脉冲足底静脉泵可有效预防全髋/膝关节置换术后DVT,且舒适度高于间歇充气加压装置,预防DVT的时间成本低,值得临床推广。     

两种牵引方式治疗腰椎间盘突出症的疗效评价

目的　观察间歇牵引和持续牵引治疗腰椎间盘突出症的疗效。方法　将 180例腰椎间盘突出症患者随机分为间歇牵引和持续牵引组 ,在温热和中频电治疗的同时分别给以间歇牵引和持续牵引 ,然后测定治疗前、后的下背痛评价表得分 ,并对其评测验结果进行比较分析。结果　治疗前 ,A组积分 10 .8±4.45 ,B组积分 11.2± 4.17;治疗 10次后 ,A组积分 2 0 .7± 5 .5 3 ,B组积分 18.8± 4.16;治疗 2 0次后 ,A组积分 2 7.1± 5 .75 ,B组积分 2 1.3± 5 .3 3。结论　两种治疗方法均有显著疗效 ,间歇牵引的疗效引优于持续牵引     

Clean intermittent catheterization rates after initial and subsequent treatments with onabotulinumtoxinA for non-neurogenic overactive bladder in real-world clinical settings

Objective: Previous randomized controlled trials have reported a 6.1–6.9% incidence of clean intermittent catheterization (CIC) following treatment with onabotulinumtoxinA in non-neurogenic overactive bladder (OAB) patients who were inadequately managed by ≥1 anticholinergic. A multi-center retrospective chart review assessed the real-world rate of voiding dysfunction requiring catheterization.

Methods: Patients received onabotulinumtoxinA 100?U (approved dose) administered by experienced injectors between January 2013 and June 2015. Patients using CIC or an indwelling catheter for ≥24?hours for voiding dysfunction prior to onabotulinumtoxinA injections were excluded. The primary outcome was post-treatment CIC (lasting >24?hours; per individual physician’s clinical judgment considering patient’s voiding symptoms, post-void residual [PVR] urine volumes and patient bother). Potential baseline predictors of CIC (history of pelvic prolapse, cystocele, diabetes, PVR urine volume and age) were assessed using multivariable logistic regression.

Results: Overall, 299 patients received their first treatment with onabotulinumtoxinA 100?U. Mean age was 66.4 years; 98.3% were female. The incidence of CIC was 2.7% in the total study population after the first treatment with onabotulinumtoxinA. The de novo CIC rate in treatments 2 and 3 combined was similarly low (3.2%). None of the evaluated baseline characteristics were significant predictors of CIC initiation due to the low CIC incidence.

Conclusions: This real-world study of non-neurogenic OAB patients treated with onabotulinumtoxinA suggests that the CIC rate is lower than the rates reported in previous studies. There were no significant correlations between baseline predictors and CIC initiation, although statistical significance may not have been reached because of the low incidence of CIC.     

间歇呼吸暂停联合低水平PEEP通气策略在输尿管软镜手术中的应用

目的 探讨间歇呼吸暂停联合低水平呼气末正压(PEEP)通气策略对输尿管软镜手术患者的影响。方法 选择接受输尿管软镜钬激光碎石术的患者73例,男59例,女14例,年龄25~60岁,BMI 18~28 kg/m²,ASA Ⅰ或Ⅱ级,随机分为三组：呼吸暂停联合低水平PEEP组（P组,n=25）、呼吸暂停组（A组,n=28）和对照组(C组,n=20)。P组术中采用呼吸暂停联合低水平PEEP (5 cmH₂O)通气模式,A组术中采用传统呼吸暂停通气模式,C组术中采用常规通气模式。P组和A组于麻醉诱导前（T0）、插管后10 min（T1）、第1次呼吸暂停前（T2）、最后1次呼吸暂停结束后即刻（T3）和拔管后30 min（T4）时,C组于T0—T1、术者第1次要求呼吸暂停前（T2）、碎石结束后即刻（T3）、T4时记录基本生命体征并抽取桡动脉及颈内静脉血进行血气分析,术后24 h（T5）时抽取颈内静脉血。记录T0—T4时PaCO₂、pH、氧合指数（OI）、脑氧饱和度（rSO₂）、脑氧摄取率（CERO₂）、动脉和颈内静脉血氧分压差（Pa-jvO2）、动脉和颈内静脉血氧饱和度差（Sa-jvO2）;T0、T4—T5时血清肺Clara细胞分泌蛋白(CC16)、静脉血清S100β蛋白含量、静脉血清肌钙蛋白（cTnT和cTnI）、肌红蛋白（Mb）和肌酸激酶同工酶（CK-MB）。记录激光碎石时间和术者满意程度评分。结果 与C组比较,T3时A组PaCO₂明显升高、pH、OI明显降低（P<0.05）。与A组比较,T3时P组PaCO₂明显降低、pH、OI明显升高（P<0.05）。三组不同时点rSO₂、CERO₂、Pa-jvO2、Sa-jvO2、CC16、S100β蛋白、cTnT、cTnI、Mb、CK-MB差异均无统计学意义。与C组比较,P组和A组激光碎石时间明显缩短（P<0.05）,术者满意程度评分明显升高（P<0.05）。结论 间歇呼吸暂停联合低水平PEEP(5 cmH₂O)通气策略可安全地用于输尿管软镜手术,既保留了传统呼吸暂停通气策略的优势,同时减少了其带来的不利影响,是一种更优化的通气策略。     

Degarelix as an Intermittent Androgen Deprivation Therapy for One or More Treatment Cycles in Patients with Prostate Cancer

Background

Guidelines for prostate cancer treatment suggest that intermittent androgen deprivation (IAD) can be considered for certain patients.

Objective

To evaluate the efficacy and safety of degarelix as IAD for one or more treatment cycle(s) in prostate cancer patients requiring androgen deprivation.

Design, setting, and participants

This open-label uncontrolled multicenter study included patients with prostate-specific antigen (PSA) >4 to 50 ng/ml or PSA doubling time <24 mo. Induction included 7-mo treatment. Off-treatment period started when PSA was ≤4 ng/ml and lasted up to 24 mo based on PSA and testosterone levels. Treatment was reinitiated when PSA was >4 ng/ml.

Intervention

Each induction period included a starting dose of degarelix 240 mg, and thereafter 80 mg once a month for 6 mo, followed by off-treatment periods.

Outcome measurements and statistical analysis

The primary end point was time to PSA >4 ng/ml. Secondary end points were subgroup analysis of the primary end point, time to testosterone >0.5 and >2.2 ng/ml, quality of life (QoL), and sexual function during the first off-treatment period.

Results and limitations

Of 213 patients in the first induction period, 191 entered the first off-treatment period, 35 patients entered the second induction, and 30 entered the second off-treatment period. Only two patients entered the third cycle. Median time to PSA >4 ng/ml and duration of first off-treatment period was 392 d each. Significant differences in time to PSA >4 ng/ml were observed between subgroups stratified by prognostic factors (previous curative treatment, cancer stage, PSA levels, and Gleason scores). Time to testosterone >0.5 and >2.2 ng/ml was 112 and 168 d, respectively. Change in QoL remained nonsignificant, and sexual function gradually improved during the off-treatment period. Adverse events were fewer during the off-treatment period and subsequent treatment cycles.

Conclusions

IAD with degarelix resulted in an improvement in sexual function commensurate with increased testosterone levels while PSA remained suppressed. The treatment for one treatment cycle or more was well tolerated.

Patient summary

Guidelines for prostate cancer treatment suggest that intermittent androgen deprivation (IAD) can be considered for certain patients. IAD with degarelix resulted in improved sexual function commensurate with increased testosterone levels while prostate-specific antigen remained suppressed. The treatment for one treatment cycle or more was well tolerated.

Trial registration

Clinicaltrials.gov identifier NCT00801242.     

Metallothionein as a compensatory component prevents intermittent hypoxia-induced cardiomyopathy in mice

Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (IH) to induce cardiovascular disease, which may be related to oxidative damage. Metallothionein (MT) has been extensively proved to be an endogenous and highly inducible antioxidant protein expressed in the heart. Therefore, we tested the hypotheses that oxidative stress plays a critical role in OSA induced cardiac damage and MT protects the heart from OSA-induced cardiomyopathy. To mimic hypoxia/reoxygenation events that occur in adult OSA patients, mice were exposed to IH for 3 days to 8 weeks. The IH paradigm consisted of alternating cycles of 20.9% O₂/8% O₂ F_IO₂ (30 episodes per hour) with 20 s at the nadir F_IO₂ for 12 h a day during daylight. IH significantly increased the ratio of heart weight to tibia length at 4 weeks with a decrease in cardiac function from 4 to 8 weeks. Cardiac oxidative damage and fibrosis were observed after 4 and 8 weeks of IH exposures. Endogenous MT expression was up-regulated in response to 3-day IH, but significantly decreased at 4 and 8 weeks of IH. In support of MT as a major compensatory component, mice with cardiac overexpression of MT gene and mice with global MT gene deletion were completely resistant, and highly sensitive, respectively, to chronic IH induced cardiac effects. These findings suggest that chronic IH induces cardiomyopathy characterized by oxidative stress-mediated cardiac damage and the antioxidant MT protects the heart from such pathological and functional changes.