山东沿海农村地区的新生儿听力筛查

目的探讨如何在农村地区开展新生儿听力筛查。方法调查2004年1-12月在山东省莱州市人民医院出生的3922例新生儿，2004年莱州市年鉴显示：农业人口约占79％。采用瞬态诱发耳声发射快速筛查程序对出生后2～7d的新生儿进行听力筛查。未通过者在生后的4～6周进行复筛，复筛仍未通过者随访并做诊断性检查。结果3612例接受筛查占该院总出生人数的92．1％（3612／3922）；其中6％贫困儿享受免费筛查。初筛通过2527例，占总筛查人数的69．96％；未通过1085例（30．4％）。未接受筛查310例（7．9％）。应复筛1085例，实际按时复筛633例（58．34％），未能复筛452例（41．66％）。其中高危新生儿163例，按时筛查114例（69．94％），放弃筛查49例（30．06％）。复筛未通过者共14例，11例接受了诊断性听性脑干反应检查，2例双耳中度听力损伤，2例双耳重度听力损伤，4例单耳轻度听力损伤，3例正常。结论在农村地区开展新生儿听力筛查是可行的，也是必要的，建议应该尽快地建立和完善农村地区新生儿听力筛查模式，让更多的贫困婴儿享受免费筛查，真正做到人人享有健康。     

Acquired immune hemolytic anemia associated with IgA erythrocyte coating: investigation of hemolytic mechanisms

We have investigated the hemolytic mechanisms in a patient with acquired immune hemolytic anemia whose red cells appeared to be coated with IgA alone. The clinical course was similar to that of patients with hemolytic anemia mediated by warm-reacting IgG antibody. Splenic sequestration of red cells was demonstrated, and marked reduction of hemolysis occurred after corticosteroid therapy. Antibody was eluted from the patient's red cells and used to sensitize normal red cells in vitro. These sensitized red cells were not lysed by fresh autologous serum, nor did they fix detectable amounts of C3. However, red cells sensitized by eluted antibody were lysed by normal human peripheral blood monocytes in a system designed to demonstrate antibody-dependent cell-mediated cytotoxicity. Monocyte-mediated hemolysis of sensitized red cells was inhibited by the addition of low concentrations of normal serum IgA to the system, but not by IgG. The ability of the eluate to induce monocyte-mediated hemolysis was abolished by its adsorption on Sepharose-bound anti-IgA, but not by preincubation with Sepharose-bound anti-IgG. In addition, normal human monocytes were demonstrated to ingest eluate-sensitized red cells. These data demonstrate an in vitro interaction of IgA-sensitized red cells with leukocytes and suggest a possible mechanism for the patient's hemolysis.     

万古霉素与利奈唑胺治疗脓毒症对C反应蛋白和降钙素原的影响

目的 探讨万古霉素与利奈唑胺治疗脓毒症对C反应蛋白和降钙素原的影响。方法 选择2016年1月~2020年12月我院收治的268例脓毒症患者为研究对象,均采用万古霉素或利奈唑胺治疗,运用倾向性评分匹配法矫正组间混杂因素,通过重复测量方差分析法对用药前、用药3 d时的CRP和PCT水平变化情况。结果 268例患者中,120例行万古霉素治疗,148例行利奈唑胺治疗;在利奈唑胺组中,用药3 d时的CRP和PCT水平均低于用药前（P<0.05）;而在万古霉素组中,用药前后的CRP和PCT水平比较无差异（P>0.05）;同时,经倾向性评分匹配对混杂因素进行矫正后,两组患者的治疗有效率和生存率比较差异无统计学意义（P>0.05）。结论 临床上在治疗脓毒症患者时,使用利奈唑胺治疗后,能够使CRP和PCT水平降低,起效时间短,但是万古霉素和利奈唑胺在治疗结局方面无明显差异。     

Gender Differences in the Clinical Characteristics and Atrioventricular Nodal Conduction Properties in Patients With Atrioventricular Nodal Reentrant Tachycardia

Gender Differences in Patients With AVNRT. Introduction: The detailed electrophysiological characteristics of the gender differences associated with atrioventricular nodal reentrant tachycardia (AVNRT) have not been clarified. This study investigated the gender‐related electrophysiological differences in a large series of patients undergoing radiofrequency catheter ablation. Methods and Results: A total of 2,088 consecutive AVNRT patients (men/women 869/1,219) who underwent catheter ablation were enrolled in this study. We evaluated the gender differences in their electrophysiological characteristics. Women had a significantly younger age of onset, higher incidence of multiple jumps, shorter AH interval, atrial effective refractory period (ERP), anterograde fast pathway ERP, anterograde slow pathway ERP, and retrograde slow pathway ERP, and longer ventricular ERP than men. The incidence of baseline ventriculoatrial dissociation was lower in women than in men. Women needed less isoproterenol/atropine to induce AVNRT. No gender differences in the radiation exposure time, procedure time, complication rate, acute success rate, or second procedure rate were noted. Both typical and atypical AVNRT were more predominant in women. In the patients with atypical AVNRT, there was no significant gender difference in incidence of baseline ventriculoatrial dissociation; however, the retrograde slow pathway ERP was significantly shorter in women than in men. Women of premenopausal age (≤50 years old) had a significantly higher incidence of anterograde multiple jumps and a retrograde jump phenomenon, and a shorter anterograde slow pathway ERP and retrograde slow pathway ERP than those of women over 50 years old. Conclusion: Gender differences in the anterograde and retrograde AV nodal electrophysiology were noted in the patients with AVNRT. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1114‐1119)     

Evidence for depletion of CASP5 Ala90Thr heterozygous genotype in aged subjects

Our previous studies, which included genotyping of multiple coding apoptotic gene polymorphisms, unexpectedly demonstrated a depletion of heterozygous CASP5 Ala90Thr (rs507879, c.268 G > A) genotypes in elderly subjects. Present investigation was aimed to validate this trend. An analysis of 510 subjects aged 75–103 years revealed 205 (40%) CASP5 Ala90Thr heterozygotes as compared to 254 (50%) expected from the minor allele frequency 0.470 (p = 0.000014). This deviation was not observed in 549 middle-aged (18–50 years) controls (270 (49%) heterozygotes observed vs. 274 (50%) expected; minor allele frequency 0.475; p = 0.743). Unfavorable significance of CASP5 heterozygous genotype may be explained by the role of the caspase-5 in inflammation-related processes. Almost all prior gene-longevity association studies focused on discrimination between “good” and “bad” gene variants. Here we present a distinct situation, where the combination of alternative alleles (i.e., heterozygosity) appears to be unfavorable as compared to the homozygous carriership of either gene variant.     

内毒素耐受THP-1细胞中糖皮质激素受体-α在炎症反应中的作用

目的:应用脂多糖(Lipopolysaccharide,LPS)刺激人单核细胞白血病细胞系THP-1细胞,模拟体外脓毒症模型,了解单核细胞系统在产生内毒素耐受时,糖皮质激素受体-α(Glucocorticoid receptor-α,GR-α)在转录水平上的表达。方法:用无血清培养基培养人THP-1细胞,将细胞随机分为4组(A、B、C、D),分别用不同浓度LPS刺激THP-1细胞24 h后,再改变LPS浓度刺激上述各组细胞24 h,分别提取RNA和蛋白质,以逆转录聚合酶链反应(RT-PCR)检测GR-α的mRNA表达,用西部印迹法(Western Blotting)检测NF-κB蛋白质表达,以酶联免疫吸附试验(ELISA)检测培养液中肿瘤坏死因子-α(TNF-α),白细胞介素1β(IL-1β),白细胞介素10(IL-10)水平。结果:A、B、C、D组GR-αmRNA与-βactin比值,NF-κB蛋白与GAPDH比值差异有统计学意义(P<0.01),在受到LPS刺激时,GR-αmRNA与NF-κB蛋白的表达负相关(r=0.816,P<0.01)。结论:内毒素耐受的THP-1细胞GR-α表达上调,这可能在THP-1细胞的内毒素耐受时炎症反应的发生起到重要作用。     

Founder mutations in early-onset, familial and bilateral breast cancer patients from Russia

Previous studies indicate that founder mutations may play a noticeable role in breast cancer (BC) predisposition in Russia. Here we performed a systematic analysis of eight recurrent mutations in 302 BC cases (St.-Petersburg, Russia), which were selected due to the presence of clinical indicators of hereditary disease (bilaterality and/or early onset (≤40 years) and/or family history). BC-associated alleles were revealed in 46 (15.2%) women. BRCA1 5382insC mutation was detected in 29 (9.6%) patients, CHEK2 1100delC in 9 (3.0%), BRCA1 4153delA in 3 (1.0%), CHEK2 IVS2+1G>A in 2 (0.7%), and BRCA1 185delAG, BRCA2 6174delT and NBS1 657del5 in 1 (0.3%) patient each. No cases with BRCA1 300T>G (C61G) mutation was identified. The obtained data suggest that a significant fraction of hereditary BC cases in Russia can be diagnosed using only a limited number of simple PCR tests.     

Nonrandom distribution of oncogene amplifications in bilateral breast carcinomas: Possible role of host factors and survival bias

Amplification of HER2, C-MYC and CCND1 oncogenes is a hallmark of breast cancer (BC); however, its involvement in the bilateral form of this disease has not been investigated yet. In this study, 50 bilateral BC (biBC) pairs (100 tumors) and 72 control unilateral BC were examined using real-time PCR analysis of microdissected archival tissues. In biBC, the frequency of >3-fold oncogene amplification was 6/100 (6%) for HER2, 6/100 (6%) for C-MYC and 7/100 (7%) for CCND1. Altogether, 18/100 (18%) biBC tumors had increased gene dosage of at least one oncogene. Tumors forming synchronous biBC pairs had amplification in 11/46 cases (24%). In 3 of 8 patients with amplification-positive carcinomas, the amplification was detected in both neoplasms: 2 biBC had concordant activation of the same oncogene (HER2 and CCND1, respectively), and in the remaining case distinct oncogenes were affected (HER2 and C-MYC). In contrast, amplifications in metachronous biBC were strongly discordant: none of 27 first carcinomas carried this abnormality, while the frequency of amplification in second tumors (7/27; 26%) was similar to the one observed in unilateral BC (20/72; 28%). The trend toward concordance of oncogene amplification status in synchronous but not in metachronous biBC pairs can be explained by the nearly identical natural history of the disease in simultaneously arising tumors. The skewed pattern of amplifications in metachronous biBC might be attributed to their association with adverse BC prognosis; it appears that only patients with amplification-negative first BC have sufficient chances to survive until the development of the contralateral carcinoma.