A rare case of monozygotic triplets with Duchenne muscular dystrophy

Twins with Duchenne muscular dystrophy (DMD) have been widely studied. We report the first rare case of monozygotic triplets with DMD who shared consistent phenotypes, including delayed motor and language milestones, muscle wasting and weakness, joint contracture, and lumbar lordosis. Muscle magnetic resonance imaging and biopsy revealed the similar muscle injury characteristics and dystrophin absence. Short tandem repeat analysis confirmed monozygosity. A de novo mutation (exon 49–52 deletion) was found in the triplets but not in their mother. Treatment included prednisone, idebenone, and rehabilitation management. At the 2-year follow-up, motor function had deteriorated, and muscle fatty infiltration was more extensive and severe. Our case offers a unique opportunity for genetic and therapeutic research. Furthermore, it highlights the critical role of genetic factors in DMD phenotypes and provides a potential choice for treatment observations.     

妊娠期高血压患者血清微小RNA-210、-204-5p、-376c与其血液流变学指标的相关性及其诊断价值研究

目的探讨妊娠期高血压患者血清微小RNA(miRNA)-210、-204-5p、-376c与其血液流变学指标的相关性，以及其诊断价值。 方法采用简单随机抽样方法，随机抽取2016年10月至2018年10月，于河北省黄骅市人民医院收治的妊娠期高血压患者80例为研究对象，并纳入研究组(n＝80)。采用相同抽样方法，随机抽取同期于本院接受定期产前检查的80例中孕期正常妊娠妇女为对照，纳入对照组(n＝80)。采用实时荧光定量PCR，检测2组受试者血清miRNA-210、-204-5p及-376c的相对表达量。采用全自动血细胞分析仪，检测2组受试者的血液流变学指标。2组受试者血清miRNA-210、-204-5p、-376c相对表达量及血液流变学指标比较，采用成组t检验。采用受试者工作曲线下面积(ROC-AUC)，分析血清miRNA-210、-204-5p及-376c的相对表达量，对妊娠期高血压的诊断价值。采用Pearson相关系数分析妊娠期高血压患者血清miRNA-210、-204-5p及-376c的相对表达量与其血液流变学指标的相关性。本研究获得河北省黄骅市人民医院伦理委员会批准(批准文号：18101523)，并且受试者均签署临床研究知情同意书。2组受试者的年龄、入组时孕龄、孕前人体质量指数、孕次、产次等一般临床资料分别比较，差异均无统计学意义(P>0.05)。 结果①研究组患者血清miRNA-210、-204-5p的相对表达量分别为(1.56±0.35)与(1.78±0.40)，均显著高于对照组的(0.59±0.11)与(0.72±0.15)，研究组患者血清miRNA-376c的相对表达量为(0.33±0.09)，却显著低于对照组的(1.24±0.32)，2组上述指标分别比较，差异均有统计学意义(t＝23.648、22.193、24.485，均为P<0.001)。②血清miRNA-210、-204-5p及-376c的相对表达量诊断妊娠期高血压的ROC-AUC分别为0.824(95%CI：0.738～0.902，P<0.001)，0.871(95%CI：0.810～0.943，P<0.001)，0.833(95%CI：0.746～0.908，P<0.001)。根据约登指数最大原则，血清miRNA-210、-204-5p及-376c的相对表达量，对于诊断妊娠期高血压的最佳临界值分别为0.696、1.512及0.712，此时其诊断妊娠期高血压的敏感度分别为83.3%、93.1%及85.0%，特异度分别为85.0%、75.0%及85.0%。③研究组患者的全血低切黏度(WRV)、低切还原黏度(LSRV)、血浆黏度(PV)分别为(7.9±1.5) mPa·s、(17.6±3.6) mPa·s、(1.6±0.3) mPa·s，分别显著高于对照组的(7.2±1.3) mPa·s、(15.6±3.4) mPa·s、(1.2±0.2) mPa·s，2组上述指标比较，差异均有统计学意义(t＝3.154、P＝0.002，t＝3.613、P<0.001，t＝9.923、P<0.001)。④妊娠期高血压患者血清miRNA-210相对表达量与其WRV、LSRV、PV，均呈正相关关系(r＝0.343、P＝0.002，r＝0.415、P<0.001，r＝0.287，P＝0.001)；血清miRNA-204-5p相对表达量与PV亦呈正相关关系(r＝0.326、P＝0.003)；miRNA-376c相对表达量与WRV、LSRV，均呈正相关关系(r＝0.317、P＝0.004，r＝0.351、P＝0.001)。 结论妊娠期高血压患者血清miRNA-210、-204-5p、-376c相对表达量与其血液流变学指标存在相关性，并且有望成为诊断妊娠期高血压的潜在生物标志物。     

孕期抗病毒治疗结合标准阻断措施对乙型肝炎高病毒载量孕妇所生婴儿母婴传播阻断的影响

目的分析乙型肝炎(乙肝)病毒(Hepatitis B virus,HBV)高载量孕妇孕期HBV脱氧核糖核酸(HBV desoxyribonucleic acid,HBV-DNA)水平和HBVe抗原(HBV e antigen,HBeAg)阳性率以及孕期抗病毒治疗结合标准阻断措施对其所生婴儿母婴传播阻断失败率的影响。方法通过医院信息系统收集HBV-DNA高载量(≥2×10^6IU/mL)孕妇血清学检测结果、抗病毒药物使用等信息,描述HBV-DNA载量和HBeAg阳性率;对HBV-DNA高载量孕妇所生婴儿进行乙肝疫苗(Hepatitis B vaccine,HepB)和乙肝免疫球蛋白(Hepatitis B immunoglobulin,HBIG)联合免疫,在完成第3剂HepB后7月龄-2岁对乙肝表面抗原和HBV-DNA进行随访检测,分析母婴传播阻断失败率。结果共纳入1822名HBV-DNA高载量孕妇,接受、未接受抗病毒治疗分别占75.19%、24.81%。孕妇妊娠期、分娩前HBV-DNA≥1.0×10^8IU/mL比例分别为68.10%(933/1370)、0.15%(2/1370)(χ^2=2692.27,P<0.0001)。接受抗病毒治疗组妊娠期、分娩前HBeAg阳性率分别为96.53%(1001/1037)、96.16%(1251/1301)(χ^2=0.23,P=0.635),未接受抗病毒治疗组妊娠期、分娩前HBeAg阳性率分别为97.70%(298/305)、96.98%(417/430)(χ^2=0.36,P=0.550)。两组HepB和HBIG联合免疫后母婴传播阻断失败率分别为0.42%(3/714)、6.67%(14/210)(χ^2=31.69,P<0.0001)。结论孕妇HBV-DNA高载量以≥1.0×10^8IU/mL为主,孕期抗病毒治疗可显著降低孕妇HBV-DNA载量,结合HepB和HBIG联合免疫可显著降低其所生婴儿HBV母婴传播阻断失败率。     

Synaptopodin Is Dispensable for Normal Podocyte Homeostasis but Is Protective in the Context of Acute Podocyte Injury

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肺癌合并慢性阻塞性肺疾病外科治疗的肺功能评价

目的评价慢性阻塞性肺疾病(COPD)患者合并肺癌行肺叶切除的手术风险和手术对肺功能的影响.方法回顾分析1998年1月至2005年1月我院收治的中度COPD合并周围型非小细胞肺癌32例患者的临床资料.其中,男29例,女3例;平均年龄(65.0±5.4)岁.病理分型:鳞癌2l例,腺癌11例;病理分期:Ⅰ期2例,Ⅱ期5例,Ⅲa期24例,Ⅲb期l例.所有患者均接受肺叶切除术.结果术前患者肺功能第1秒用力呼吸容积(FEV1)和动脉氧分压平均值分别为(64±9)%和(85±12)mmHg,术后分别为(62±10)%和(87±11)mmHg,虽然FEV1略有下降,但均无显著性差异(P＞0.05).本组无围手术期死亡者.结论中度COPD患者仍有一定的肺功能储备,可耐受肺叶切除手术.     

Population Pharmacokinetics and Dosing Simulations of Ceftazidime in Chinese Neonates

An accurate dosage determination is required in neonates when antibiotics are used. The adult data cannot be simply extrapolated to the pediatric population due to significant individual differences. We aimed to identify factors impacting ceftazidime exposure in neonates and to provide drug dosing guidance to clinicians. Forty-three neonates aged less than 60 days with proven or suspected infections were enrolled in this study. After intravenous administration, blood samples were collected, and plasma ceftazidime concentration was determined using a HPLC method. Pharmacokinetic data were fitted using a nonlinear mixed-effects model approach. One-compartmental model could nicely characterize the ceftazidime in vivo behavior. The covariate test found that the postmenstrual age (day) was strongly associated with systemic drug clearance (L/h), and the effect of body weight (kg) was identified as the covariate on distribution volume (L). Compared with the base model, the addition of covariates improved the goodness-of-fit of the final model. Model validation (bootstrap, visual predictive check, and prediction-corrected visual predictive check) suggested a robust and reliable pharmacokinetic model was developed. Personalized dosage regimens were provided based on model simulations. The intravenous dose should be adjusted according to postmenstrual age, body weight, and minimum inhibitory concentration.     

Sustained Release of Minocycline From Minocycline-Calcium-Dextran Sulfate Complex Microparticles for Periodontitis Treatment

It is important to address the periodontitis-associated bacteria in the residual subgingival plaque after scaling and root planing to successfully treat periodontitis. In this study, we explored the possibility of exploiting the ion pairing/complexation of minocycline, Ca²⁺, and sulfate/sulfonate-bearing biopolymers to develop an intrapocket delivery system of minocycline as an adjunct to scaling and root planing. Minocycline-calcium-dextran sulfate complex microparticles were synthesized from minocycline, CaCl₂, and dextran sulfate. They were characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. An in vitro release study was conducted to evaluate the release kinetics of minocycline from these microparticles. Agar disk diffusion assays and biofilm-grown bacteria assays were used to assess antibacterial capability. High loading efficiency (96.98% ± 0.12%) and high loading content (44.69% ± 0.03%) for minocycline were observed for these complex microparticles. Mino-Ca-DS microparticles achieved sustained release of minocycline for at least 9 days at pH 7.4 and 18 days at pH 6.4 in phosphate-buffered saline, respectively. They also demonstrated potent antimicrobial effects against Streptococcus mutans and Aggregatibacter actinomycetemcomitans in agar disk diffusion and biofilm assays. These results suggested that the ion pairing/complexation of minocycline, Ca²⁺, and sulfonate/sulfate-bearing biopolymers can be exploited to develop complex microparticles as local delivery systems for periodontitis treatment.     

A visible fluorescent nanovaccine based on functional genipin crosslinked ovalbumin protein nanoparticles

Accurate and efficient antigen delivery is crucial for inducing a strong and long-term immune response. A visible protein nanovaccine made from antigen could provide a novel and promising technology for secure and efficient delivery of the antigen with imaging visualization. In this study, a functional nanovaccine based on genipin crosslinked ovalbumin (OVA) fluorescent nanoparticles with chitosan (CS-OVA-NPs) was developed. The nanovaccine can carry abundant antigens by self-crosslinking without additional carriers. The fluorescence imaging technique was applied to monitor and reveal the process of antigen delivery in vivo based on the fluorescence of genipin with a non-invasive and real-time manner. This functional OVA nanovaccine can enhance the uptake of OVA in Dendritic Cells (DCs) and further promote DCs to maturate in vitro. In vivo study further indicated CS-OVA-NPs could trigger antigen-specific immune responses, which demonstrated that this fluorescent nanovaccine provided a novel design approach for accurate and efficient vaccine delivery.