Impact of thirteen-valent pneumococcal conjugate vaccine on nasopharyngeal carriage in healthy children under 24 months in Okinawa,Japan

In November 2013, a 13-valent pneumococcal conjugate vaccine (PCV13) for all infants aged younger than 5 years was incorporated into the Japan national immunization program. An annual survey of nasopharyngeal carriage rates was performed on healthy infants aged 2–24 months from Okinawa, Japan to evaluate the effect of PCV13 on pneumococcal colonization. Of 756 evaluable infants, 203 pneumococcal strains were detected in 193 infants. The overall nasopharyngeal carriage rate was 25.5%, which was not different from our previously reported isolation rate before the introduction of PCV13. The main serotypes of the Streptococcus pneumoniae strains are 15A (18.2%), non-typeable (14.8%), and 15B (11.8%). The carriage rates of pneumococcal strains with 7-valent pneumococcal conjugate vaccine serotypes and PCV13 serotypes were 3.0% and 9.9%, respectively. These values were significantly lower than we reported before the introduction of PCV13. However, the carriage rates of non-PCV13 serotypes have increased. Multivariate logistic regression analysis suggested that siblings and day care attendance are risk factors for pneumococcal carriage.     

参芪排毒汤对宫颈癌组织人乳头瘤病毒E6/E7、P53和PRb基因蛋白表达的影响

目的:研究参芪排毒汤对宫颈癌组织人乳头瘤病毒(HPV)E6/E7 mRNA、肿瘤抑制基因(P53)、视网膜母细胞瘤蛋白(PRb)表达水平的影响与意义。方法:选取112例宫颈癌患者进入研究,按随机数字表划分成对照组与治疗组,两组均给予新辅助化疗联合腹腔镜宫颈癌根治术治疗,治疗组在新辅助化疗的同时给予参芪排毒汤口服; 术前评估两组临床疗效,统计不良反应发生情况,术中取癌旁健康组织与病灶病理组织样本检测HPV E6和E7 mRNA表达水平并计算E6/E7比值,检测样本中P53、PRb表达水平; 随访至少3年,比较两组患者的3年无病情进展生存时间(PFS)、总生存时间(OS),分析新辅助化疗后病理组织中HPV E6/E7、P53、PRb表达水平对PFS、OS的预测价值。结果:治疗组缓解率为83.93%,对照组为62.50%,治疗组缓解率高于对照组(P<0.05); 治疗组不良反应发生率为12.50%,对照组为17.86%,差异比较无统计学意义(P>0.05); 化疗后两组患者癌旁组织中HPV E6/E7比值比较,差异无统计学意义(P>0.05),病理组中HPV E6/E7表达高于治疗组(均P<0.05),两组癌旁与病理组织中P53、PRb比较,差异有统计学意义(均P>0.05); 化疗后宫颈癌组织中HPV E6/E7、P53、PRb表达水平对于患者无病情进展生存时间PFS、OS均具有较高预测价值(AUC>0.9,P<0.05); 治疗组患者PFS、OS均长于对照组(均P<0.05)。结论:在腹腔镜宫颈癌根治术前新辅助化疗中联合应用参芪排毒汤,能够提高术前疗效,抑制宫颈癌组织中HPV E6/E7表达、提升P53、PRb表达水平,从而起到延长患者无病情进展生存时间与总生存时间,改善预后的作用。     

PLA2R、 THSD7A与IgG亚型在特发性膜性肾病中的诊断价值

目的探讨特发性膜性肾病(idiopathic membranous nephropathy,IMN)患者血清抗磷脂酶A2受体(phospholipase A2 receptor,PLA2R)抗体水平、肾小球PLA2R、1型血小板反应蛋白7A域(thrombospondin type I domain containing 7A,THSD7A)、免疫球蛋白G(immunoglobulin G,IgG)亚型的表达及其在IMN中的诊断价值。方法选取2016年1月至2019年6月在雅安市人民医院肾内科经肾活检并确诊的IMN患者72例,以同期72例非IMN肾小球疾病患者为对照。采用酶联免疫吸附法检测血清抗PLA2R抗体滴度,免疫荧光法检测肾小球PLA2R、THSD7A及IgG亚型表达。采用受试者工作特征(ROC)曲线分析血清抗PLA2R抗体、肾小球PLA2R、THSD7A、IgG4诊断IMN的价值。结果血清抗PLA2R抗体、肾小球PLA2R、IgG4、THSD7A诊断IMN的灵敏度分别为61.11%、80.56%、97.22%、8.33%,特异度分别为97.22%、100.00%、97.22%、100.00%。血清抗PLA2R抗体和肾小球PLA2R任一指标阳性即诊断IMN的敏感性为83.33%;肾小球PLA2R、THSD7A和IgG4中任一指标阳性即诊断IMN的敏感性为97.22%。结论血清抗PLA2R抗体、肾小球PLA2R、THSD7A及IgG4亚型对于IMN诊断具有较高的临床价值。血清抗PLA2R抗体及肾小球PLA2R抗原的联合检测,肾小球PLA2R、THSD7A与IgG4的联合检测可以增加IMN诊断的敏感性。     

The PB2 and M genes are critical for the superiority of genotype S H9N2 virus to genotype H in optimizing viral fitness of H5Nx and H7N9 avian influenza viruses in mice

Genotype S H9N2 avian influenza virus, which has been predominant in China since 2010, contributed its entire internal gene cassette to the genesis of novel reassortant influenza viruses, including H5Nx, H7N9 and H10N8 viruses that pose great threat to poultry and humans. A key feature of the genotype S H9N2 virus is the substitution of G1‐like M and PB2 genes for the earlier F/98‐like M and PB2 of genotype H virus. However, how this gene substitution has influenced viral adaptability of emerging influenza viruses in mammals remains unclear. We report here that reassortant H5Nx and H7N9 viruses with the genotype S internal gene cassette displayed enhanced replication and virulence over those with genotype H internal gene cassette in cell cultures as well as in the mouse models. We showed that the G1‐like PB2 gene was associated with increased polymerase activity and improved nuclear accumulation compared with the F/98‐like counterpart, while the G1‐like M gene facilitated effective translocation of RNP to cytoplasm. Our findings suggest that the genotype S H9N2 internal gene cassette, which possesses G1‐like M and PB2 genes, is superior to that of genotype H, in optimizing viral fitness, and thus have implications for assessing the potential risk of these gene introductions to generate emerging influenza viruses.     

Pathogenicity of porcine reproductive and respiratory syndrome virus (ORF5 RFLP 1‐7‐4 viruses) in China

Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus that causes reproductive failure in sows and respiratory problems in piglets. PRRSV infection leads to substantial pig mortality and causing huge economic losses so that disease outbreaks caused by the new PRRSV strain from other regions have caused great concern in China. In this study, we analysed the pathogenicity of the novel ORF5 RFLP 1‐7‐4‐like PRRSV strain, named PRRSV‐ZDXYL‐China‐2018‐1 in pigs. The viral challenge test showed that PRRSV‐ZDXYL‐China‐2018‐1 infection can cause persistent fever, moderate dyspnoea, serum viraemia and interstitial pneumonia in piglets. The levels of viral loads in serum and PRRSV‐specific antigen were also detected in lung tissues were used one‐step Taq‐Man RT‐qPCR and Immunohistochemistry, respectively. At 28dpi, the level of specific antibodies was increased among infected piglets. Importantly, the new virus appeared be a moderately virulent isolate with pathogenicity compared to HP‐PRRSV strain LQ (JXA1‐like strain). Histological examination revealed severe monocyte haemorrhage and interstitial pneumonia associated with monocyte infiltration in the lung tissue of pigs infected with PRRSV‐ZDXYL‐China‐2018‐1 and LQ‐JXA1 strains. Immunohistochemistry (IHC) results showed positive brown‐red epithelial cells and macrophages in pig lungs. Therefore, it is critical to establish an effective strategy to control the spread of PRRSV in China.     

AR-V7表达与去势抵抗性前列腺癌阿比特龙治疗敏感性的相关性研究

目的:探讨去势抵抗性前列腺癌(CRPC)患者中雄激素受体剪切变异体7(AR-V7)的表达与阿比特龙治疗敏感性的相关性。方法:采用前瞻性队列研究对2016年1月至2019年1月北京大学肿瘤医院收治的年龄≥18岁,存在1≥处全身转移,拟使用阿比特龙治疗的新发CRPC患者行外周血循环肿瘤细胞(CTCs)AR-V7检测,根据检测结果将患者分为AR-V7阳性组和AR-V7阴性组,对两组患者PSA下降时间、PSA无进展生存(PFS)、临床状态PFS、影像学PFS以及总生存进行统计分析。结果:共入组77例患者,其中AR-V7阴性组49例,AR-V7阳性组28例。AR-V7阴性组PSA下降时间[(72.04±66.92)d与(190.11±102.44)d,P=0.000]、PSA无应答率[6.12%(3/49)与21.4%(6/28),P=0.040]明显小于AR-V7阳性组,而PSA PFS[(489.17±269.39)d与(130.56±120)d,P=0.010]、临床状态PFS[(551.91±322.05)d与(261.44±200.85)d,P=0.018]、影像学PFS[(523.7±223.28)d与(247.56±202.80)d,P=0.003]明显长于AR-V7阳性组。AR-V7阳性组和AR-V7阴性组的肿瘤特异性生存时间分别为(1246.89±375.65)d和(1001.42±248.94)d(P=0.159),总生存率分别为89.8%(44/49)和89.3%(25/28)(P=0.176),差异均无统计学意义。结论:CRPC患者中,AR-V7表达与阿比特龙治疗敏感性及患者预后密切相关,阳性表达患者阿比特龙治疗效果及预后较差。     

游离带感觉神经肋间动脉穿支皮瓣移植修复手外伤缺损

目的探讨游离带感觉神经肋间动脉穿支皮瓣移植修复手外伤缺损的疗效。方法2010 年 3 月—2015 年 9 月采用游离带感觉神经肋间动脉穿支皮瓣移植修复 19 例手外伤缺损，其中男 16 例，女 3 例；年龄 18～53 岁，平均 35.2 岁。手背 15 例，手掌 4 例。致伤原因：交通事故伤 8 例，热压伤 5 例，绞压伤 4 例，撕脱伤 2 例。均为手部大面积皮肤软组织全层缺损合并指骨、肌腱、血管神经外露，缺损范围为 10.0 cm×7.0 cm～17.0 cm×8.0 cm。其中急诊手术 12 例，择期手术 7 例。皮瓣厚度为 10～25 mm，皮瓣切取范围为 10.0 cm×7.5 cm～17.0 cm×8.0 cm。皮瓣血管蒂与桡动脉鼻烟窝支（12 例）、桡动脉主干（7 例）及其伴行静脉吻合，皮瓣内肋间神经皮支与前臂外侧皮神经缝合。供区创面直接闭合（14 例）或行中厚皮片移植修复（5 例）。结果术后皮瓣及植皮均成活，供受区创面均 Ⅰ 期愈合。19 例患者均获随访，随访时间 10～18 个月，平均 12.7 个月。术后手部受区外观及功能恢复良好，未见皮瓣臃肿；皮瓣两点辨别觉为 7～11 mm，平均 8.8 mm。供区直接闭合者术后仅遗留线性瘢痕，供区感觉功能无明显影响。结论游离带感觉神经肋间动脉穿支皮瓣是修复手外伤缺损的较好方法。     

Taylor 空间外固定架在膝内侧间室骨关节炎下肢力线调整中的临床应用

目的探讨胫骨高位截骨术（high tibial osteotomy，HTO）后采用 Taylor 空间外固定架（Taylor spatial frame，TSF）治疗膝内侧室骨关节炎（medial compartmental osteoarthritis，MCOA）调整下肢力线的安全性和有效性。方法回顾分析 2016 年 10 月—2017 年 4 月采用 HTO 治疗的 30 例 MCOA 患者临床资料，根据固定方法不同分为外固定组（TSF 外固定，16 例）和内固定组（钢板内固定，14 例）。两组患者性别、年龄、侧别、病程、术前下肢力线胫骨股骨机械轴夹角（mechanical femur tibia angle，MFTA）评价等一般资料比较差异均无统计学意义（P>0.05），具有可比性。记录并比较两组患者手术时间、术中出血量；采用 MFTA 评价末次随访时术侧下肢力线恢复情况；术前及术后 2 周、1 个月、3 个月采用美国特种外科医院（HSS）评分评价临床疗效。 结果外固定组手术时间及术中出血量均显著少于内固定组（P<0.05）。两组患者均获随访，随访时间 9～16 个月，平均 12 个月。术后内固定组 2 例截骨延迟愈合，外固定组 1 例延迟愈合，经对症处理后均愈合；两组均无针道感染、截骨处不愈合、骨髓炎等并发症发生。末次随访时采用 MFTA 标准评价下肢力线恢复情况，外固定组均达优，内固定组优 10 例、良 4 例，两组比较差异有统计学意义（Z=–2.258，P=0.024）。两组患者术后各时间点 HSS 评分均较术前显著改善，术后随时间延长 HSS 评分亦逐渐改善，差异均有统计学意义（P<0.05）。除术后 3 个月外固定组 HSS 评分显著高于内固定组（t=2.425，P=0.022）外，其余各时间点两组 HSS 评分比较差异均无统计学意义（P>0.05）。 结论TSF 在 HTO 治疗 MCOA 患者并纠正下肢力线方面拥有独特优势，其手术时间短、出血量少、固定牢固、并发症少，在术后可精确调节下肢力线，是一种安全有效的固定方式。