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.     

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。     

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.     

In vivo near infrared fluorescence imaging and dynamic quantification of pancreatic metastatic tumors using folic acid conjugated biodegradable mesoporous silica nanoparticles

Cancer metastasis is one of the biggest challenges in cancer treatments since it increases the likelihood that a patient will die from the disease. Therefore, the availability of techniques for the early detection and quantification of tumors is very important. We have prepared cyanine 7.5 NHS ester (Cy_7.5) and folic acid (FA) conjugated biodegradable mesoporous silica nanoparticles (bMSN@Cy_7.5-FA NPs) (~100 nm) for visualizing tumors in vivo. The fluorescence spectra revealed that the emission peak of bMSN@Cy_7.5-FA NPs had a red-shift of 1 nm. Confocal immunofluorescent images showed that bMSN@Cy_7.5-FA NPs had an excellent targeting ability for visualizing cancer cells. In vivo fluorescence imaging has been conducted using an orthotopic model for pancreatic cancer within 48 h, and the fluorescence intensity reached a maximum at a post injection time-point of 12 h, which demonstrated that the use of bMSN@Cy_7.5-FA NPs provides an excellent imaging platform for tumor precision therapy in mice.     

Neuroprotective effect of gold nanoparticles composites in Parkinson's disease model

Parkinson’s disease (PD) is second most common neurodegenerative disorder worldwide. Although drugs and surgery can relieve the symptoms of PD, these therapies are incapable of fundamentally treating the disease. For PD patients, over-expression of α-synuclein (SNCA) leads to the death of dopaminergic neurons. This process can be prevented by suppressing SNCA over-expression through RNA interference. Here, we successfully synthesized gold nanoparticles (GNP) composites (CTS@GNP-pDNA-NGF) via the combination of electrostatic adsorption and photochemical immobilization, which could load plasmid DNA (pDNA) and target specific cell types. GNP was transfected into cells via endocytosis to inhibiting the apoptosis of PC12 cells and dopaminergic neurons. Simultaneously, GNP composites are also used in PD models in vivo, and it can successfully cross the blood-brain barrier by contents of GNP in the mice brain. In general, all the works demonstrated that GNP composites have good therapeutic effects for PD models in vitro and in vivo.