Intermittent ethanol exposure in adolescent rats: dose-dependent impairments in trace conditioning

BACKGROUND: Recent studies have revealed that the adolescent brain may be especially vulnerable to ethanol-induced toxicity. Corticolimbic regions are more severely damaged following ethanol exposure during adolescence than during adulthood. The consequences of adolescent ethanol exposure on cognition however, have only recently begun to be explored. METHODS: Male and female rats were administered 0, 1.5, 2.5 or 4.5 g/kg ethanol (20% v/v) by acute intragastric gavage during adolescence (postnatal days [PD] 28, 30, 32 and 34). On PD 40, half of the subjects in each dose group were given 5 pairings of a 10-sec flashing light (CS; conditioned stimulus) immediately followed by mild footshock (US; unconditioned stimulus), a procedure known as delay conditioning. The other half were also given 5 CS-US pairings, but the US was presented 10 sec after CS offset, a procedure known as trace conditioning. All subjects were tested for CS-elicited freezing 24 h later. RESULTS: There was no effect of adolescent ethanol exposure on delay conditioned responding, with all subjects demonstrating comparable levels of CS-elicited freezing. In contrast, the amount of freezing in the trace conditioned subjects was negatively correlated with prior ethanol dose. Specifically, exposure to 2.5 or 4.5 g/kg during adolescence resulted in a deficit in trace conditioned responding. CONCLUSIONS: These data indicate that intermittent exposure to ethanol during adolescence results in impairment in hippocampal-dependent trace conditioning that persists beyond the period of ethanol exposure. Delay conditioning was unaffected by prior ethanol treatment, indicating that there was no difficulty in detecting the CS or US, or in the ability to engage in freezing behavior. These results suggest that the adolescent brain may be particularly vulnerable to the effects of repeated exposure to ethanol that can have consequences for nonspatial, hippocampal-dependent cognitive abilities.     

Adolescent but not adult rats exhibit ethanol-mediated appetitive second-order conditioning

Background: Adolescent rats are less sensitive to the sedative effects of ethanol than older animals. They also seem to perceive the reinforcing properties of ethanol. However, unlike neonates or infants, ethanol‐mediated appetitive behavior is yet to be clearly shown in adolescents. Appetitive ethanol reinforcement was assessed in adolescent (postnatal day 33, P33) and adult rats (P71) through second‐order conditioning (SOC). Methods: On P32 or P70, animals were intragastrically administered ethanol (0.5 or 2.0 g/kg) paired with intra‐oral pulses of sucrose (CS₁, first‐order conditioning phase). CS₁ delivery took place either 5–20 (early pairing) or 30–45 minutes (late pairing) following ethanol administration. The time interval between CS₁ exposure and ethanol administration was 240 minutes in unpaired controls. On P33 or P71, animals were presented the CS₁ (second‐order conditioning phase) in a distinctive chamber (CS₂, second‐order conditioning). Then they were tested for CS₂ preference. Results: Early and late paired adolescents, but not adults, had greater preference for the CS₂ than controls, a result indicative of ontogenetic variation in ethanol‐mediated reinforcement. During the CS₁‐CS₂ associative phase, paired adolescents given 2.0 g/kg ethanol wall‐climbed more than controls. Blood and brain ethanol levels associated with the 0.5 and 2.0 g/kg doses at the onset of each conditioning phase did not differ substantially across age, with mean blood ethanol concentration of 38 and 112 mg%. Conclusions: These data indicate age‐related differences between adolescent and adult rats in terms of sensitivity to ethanol’s motivational effects. Adolescents exhibited high sensitivity for ethanol’s appetitive effects. These animals also showed ethanol‐mediated behavioral activation during the SOC phase. The SOC preparation provides a valuable conditioning model for assessing ethanol’s motivational effects across ontogeny.     

Extinction,generalization, and return of fear: A critical review of renewal research in humans

The main behavioral signature of fear extinction is its fragility. This is exemplified by the renewal effect, where a change in the background context produces recovery of fear to a conditioned-and-extinguished stimulus. Renewal is the backbone of a widely accepted theory of extinction in animal research, as well as an important experimental model to screen novel treatment techniques. This has led to an explosion of fear renewal research in humans. However, the mere observation of return of fear in a renewal procedure is not sufficient to validate this particular theory of extinction in the tested sample/procedure. Here, we systematically outline a set of experimental tests that aid in evaluating alternative extinction/renewal mechanisms. We examine published renewal studies in human fear conditioning and conclude that the prevailing theory of extinction is often taken for granted, but critical tests are lacking. Including these tests in future research will not only reveal the fear extinction mechanism in humans, but also inspire further developments in extinction treatment research.     

宫颈癌初始治疗后腹主动脉旁淋巴结转移调强放疗的临床观察

目的 对比单纯调强放疗(IMRT)与IMRT同步TP方案化疗治疗宫颈癌初始治疗后腹主动脉旁淋巴结(PALN)转移的疗效和不良反应.方法 选取2008年10月至2013年8月宫颈癌初始治疗后出现PALN转移的56例患者,PALN转移病灶给予放疗剂量GTV 55～60 Gy,CTV45 ～ 50 Gy,共25 ～ 30次,5～6周,接受同步放化疗(CRT组)者36例,单纯放疗(RT组)者20例.CRT组的同步化疗方案为TP方案,第1天紫杉醇135 mg/m2,顺铂60 mg/m2 2 d,21 d重复.单纯PALN转移(iPALN)患者33例,合并其他部位复发转移(niPALN)患者23例.结果 中位随访时间22.7个月(2.7 ～74.4个月).98.2％(55/56)的患者完成了放疗,CRT组中,38.9％的患者完成化疗2～3个周期,61.1％的患者完成化疗1个周期.CRT和RT组的有效率(CR +PR)分别为91.7％(33/36)和85％ (17/20)(x2=0.516,P＞0.05).两组患者的中位总生存(OS)时间为38和23个月,3年OS率分别为57.5％和32.7％ (x2 =4.059,P＜0.05),中位无进展生存时间(PFS)为68.3和16个月,3年PFS率分别为50.4％和29.2％(x2=4.184,P＜0.05).单纯PALN转移(iPALN)(33例)患者与合并其他部位复发转移(niPALN)患者(23例)的中位OS分别为71.2和21.4个月,3年OS率分别为53％和39.5％(x2=4.265,P＜ 0.05).CRT和RT组出现3或4级白细胞低下的患者分别为10例(27.8％)和6例(30％),3级消化道反应各有1例,差异均无统计学意义(x2=0.693、0.847,P＞ 0.05).结论 IMRT同步TP化疗对PALN转移的患者近期效果和远期生存均优于单纯放疗的患者,且不良反应可耐受.     

Total costs and clinical outcome of hematopoietic stem cell transplantation in adults with leukemia: comparison between reduced‐intensity and myeloablative conditioning

The total cost of hematopoietic stem cell transplantation (HSCT) as well as the financial impact of HSCT on the house holds of patients have been elusive. Between 2005 and 2012, we analyzed 191 HSCT in adult patients with leukemia with reduced‐intensity conditioning (RIC) regimen (n = 79) and with myeloablative conditioning (MAC) regimen (n = 112). The direct medical costs were calculated from healthcare claims obtained from the Seoul National University Hospital, and the direct non‐medical and the indirect costs were calculated from national statistics. The mean direct medical cost was $55 039, direct non‐medical cost was $6394, and indirect cost was $7503 from transplantation to one yr after transplantation in the RIC group and $72 916, $6993, and $9057 in the MAC group, respectively, based on the exchange rate of Korean won 1060 = US$1. The total costs for one yr were $68 938 and $88 967, constituting for 273% and 357% of the per capita income, respectively. The total costs, direct medical costs, and indirect costs showed statistically significant differences (p = 0.006, p = 0.007, and p = 0.017). No significant differences were found for leukemia‐free survival and overall survival. RIC‐HSCT provides lower costs within the first year of transplantation with comparable long‐term clinical outcomes.     

非典型布鲁杆菌脊柱炎的诊断与治疗

目的：探讨非典型布鲁杆菌脊柱炎的诊断与治疗,以进一步提高临床医师对该病的认识水平及诊治能力。方法回顾分析19例布鲁杆菌脊柱炎患者,病变节段位于腰椎17例、颈椎2例。14例有羊、牛接触史。19例均行 X 线检查,16例行 CT 检查,11例行 MRI 检查,所有患者标准血清试管凝集试验（SAT）滴度均＞1∶160,虎红平板凝集试验（RBP）均为阳性。均采用规范抗菌治疗,3例患者行手术治疗。结果患者均获随访,时间3～12个月,经规范抗菌治疗后治愈18例,治愈率18／19。3例手术患者术后恢复良好。末次随访时,ESR （10．5±5．1）mm／1h,CRP （4．3±2．5）mg／L,VAS 评分（0．9±0．7）分、JOA 评分（25．0±1．8）分,JOA下腰痛评分治疗改善率78．9％;ESR、VAS 及 JOA 评分与治疗前比较差异均有统计学意义（P ＜0．05）,而 CRP与治疗前比较差异无统计学意义（P ＝0．442）。结论布鲁杆菌脊柱炎易被误诊误治,对可疑患者宜早期行血清学检验,一经确诊应规范、联合、长期、足量抗菌治疗,必要时采用手术治疗,可取得良好效果。     

电针结合健脾调神法针刺治疗腹泻型肠易激综合征的临床观察

目的：比较电针结合健脾调神法与单纯电针治疗腹泻型肠易激综合征的效果,寻找治疗肠易激综合征更有效的方法。方法将60例腹泻型肠易激综合征患者运用自然数随机排列表法分为治疗组和对照组,每组各30例。治疗组30例采用电针结合健脾调神法治疗,对照组30例采用单纯电针针刺治疗,并在治疗前后根据IBS生活质量量表进行评价。结果两组患者治疗后各量表计分均较治疗前有明显改善（ P＜0.05）。治疗组总有效率为93.3％,对照组总有效率为73.3％,差异有统计学意义（ P＜0.05）。结论电针结合健脾调神法针刺治疗腹泻型肠易激综合征较单纯电针治疗更有效。     

华蟾素片联合SOX方案治疗晚期胃癌的临床研究

目的探讨华蟾素片联合SOX方案(奥沙利铂+替吉奥)治疗晚期胃癌的临床疗效。方法选取2015年1月—2017年12月涟水县人民医院收治的60例晚期胃癌患者作为研究对象,根据不同的治疗方式将患者分为对照组和治疗组,每组各30例。对照组患者采用SOX方案治疗:静滴注射用奥沙利铂130 mg/(m~2·d),用10%葡萄糖注射液500 mL稀释后静滴3 h,21 d给药1次;同时餐后用温水送服替吉奥胶囊,80 mg/(m~2·d),2次/d,连续14 d,停药7 d。治疗组在对照组基础上口服华蟾素片,3片/次,3次/d。21 d为1个周期,两组患者均进行2个周期的治疗。观察两组患者的临床疗效,同时比较两组治疗前后的血清肿瘤指标水平、疼痛评分(VAS)和生活质量综合评定问卷评分。结果治疗后,治疗组的总有效率(RR)和肿瘤控制率(DCR)分别为63.3%、83.3%,均明显高于对照组的36.7%、60.0%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者的癌胚抗原(CEA)和糖类抗原19-9(CA19-9)水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05),且治疗后治疗组血清肿瘤指标均明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者VAS评分均明显降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组的VAS评分明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者的社会功能、心理功能、功能和物质生活评分均明显提高,同组治疗前后比较差异具有统计学意义(P0.05),且治疗后治疗组生活质量水平显著高于对照组,两组比较差异具有统计学意义(P0.05)。结论华蟾素片联合SOX化疗方案治疗晚期胃癌具有较好的临床疗效,在不增加化疗副反应的情况下,可有效缓解患者的癌性疼痛状况并可改善患者的预后,值得临床推广应用。