江苏省13家医院新生儿严重高胆红素血症现状调查

目的 了解江苏省新生儿严重高胆红素血症的发生情况及诊治、随访等管理情况,为新生儿严重高胆红素血症的预防及规范化管理提供依据。方法 以2018年1~12月江苏省13家医院收治的严重高胆红素血症新生儿为研究对象,回顾性分析患儿的临床资料及随访资料。结果 江苏省13家医院2018年严重高胆红素血症新生儿病例共上报740例,占新生儿科收治病例总数的2.70%（740/27 386）,其中重度高胆红素血症620例（83.8%）,极重度高胆红素血症106例（14.3%）,危险性高胆红血症14例（1.9%）;诊断为急性胆红素脑病共4例（0.5%）。484例（65.4%）新生儿于分娩机构出院后因严重高胆红素血症返回医院住院治疗,中位入院日龄为7 d,其中214例（44.2%）再入院前进行过门诊黄疸随访,第1次门诊中位随访日龄为6 d。住院期间行头颅MRI检查211例（28.5%）,其中85例（40.3%）提示双侧基底节、苍白球T1WI信号偏高;行脑干听觉诱发电位检查238例（32.2%）,其中14例（5.9%）仅一侧通过,7例（2.9%）双侧均未通过。急性胆红素脑病或危险性高胆红素血症患儿（共17例）进行了随访,除1例失访外,均无异常神经系统症状。结论 新生儿严重高胆红素血症在新生儿科住院病人中的占比较高;新生儿从分娩机构出院后黄疸监测及管理需要加强;对并发了严重高胆红素血症的患儿,住院期间相关检查需更完善,出院后均需全面系统地随访。     

Enhancement of the immunogenicity of DNA replicon vaccine of Clostridium botulinum neurotoxin serotype A by GM-CSF gene adjuvant

Granulocyte-macrophage clony-stimulating factor (GM-CSF) is an attractive adjuvant for a DNA vaccine on account of its ability to recruit antigen-presenting cells to the site of antigen synthesis as well as stimulate the maturation of dendritic cells.This study evaluated the utility of GM-CSF as a plasmid DNA replicon vaccine adjuvants for botulinum neurotoxin serotype A (BoNT/A) in mouse model. In balb/c mice that received the plasmid DNA replicon vaccines derived from Semliki Forest virus (SFV) carrying the Hc gene of BoNT/A (AHc), both antibody and lymphoproliferative response specific to AHc were induced, the immunogenicity was enhanced by co-delivery or coexpress of the GM-CSF gene. In particular, when AHc and GM-CSF were coexpressed within the SFV based DNA vaccine, the anti-AHc antibody titers and survival rates of immunized mice after challenged with BoNT/A were significantly increased, and further enhanced by coimmunization with aluminum phosphate adjuvant.     

妊娠期高血压疾病患者载脂蛋白C3基因单核苷酸多态性

目的:探讨载脂蛋白C3(apolipoprotein C3)第四外显子3’非编码区第3 175位(C→G)SstⅠ单核苷酸多态性(single nucleotide polymorphism,SNP)与妊娠期高血压疾病患者发病的关系。方法:采用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)技术,检测84例妊娠期高血压疾病患者(妊娠期高血压疾病组,其中妊娠期高血压28例、子痫前期-轻度13例、子痫前期-重度32例、子痫11例)和81例正常晚期妊娠妇女(正常孕妇组)的载脂蛋白C3第3 175位SstⅠ基因型。结果:①妊娠期高血压疾病组孕妇载脂蛋白C3基因第3 175位基因型频率CC、GC、GG分别为48.81%、36.90%、14.29%,正常孕妇组分别为54.32%、35.80%、9.87%,两组孕妇载脂蛋白C3第3 175位基因型频率比较,差异无统计学意义(P>0.05)。妊娠期高血压疾病组孕妇载脂蛋白C3基因第3 175位等位基因频率C、G分别为67.26%、32.74%,正常孕妇组孕妇分别为72.22%、27.78%,两组孕妇载脂蛋白C3基因第3 175位等位基因频率比较,差异无统计学意义(P>0.05)。②妊娠期高血压疾病组由轻到重的妊娠期高血压亚组、子痫前期-轻度亚组、子痫前期-重度亚组、子痫亚组孕妇载脂蛋白C3第3 175位等位基因频率比较,差异无统计学意义(P>0.05)。③比较妊娠期高血压疾病组载脂蛋白C3基因第3 175位CC、GC、GG 3种基因型孕妇血压升高程度及尿蛋白阳性率,差异无统计学意义(P值均>0.05)。结论:载脂蛋白C3基因第3 175位SNP与妊娠期高血压疾病发病无相关性,与妊娠期高血压疾病严重程度、血压升高程度和蛋白尿阳性率无相关性。     

Effects of disulfide bonds formed during isolation process on the structure of the postsynaptic density

The biochemical, morphological and structural properties of rat postsynaptic densities (PSDs) isolated under conditions where disulfide bond formation was allowed or curtailed were studied here. Biochemical analyses revealed that the isolated PSDs were composed by a similar set of proteins regardless of the differences in their isolation processes. The PSDs isolated under the conditions where disulfide bond formation was curtailed were more easily dissociated by treatments with urea, guanidine hydrochloride and deoxycholate than the PSDs isolated under conditions where disulfide bond formation was allowed. Consistently, the structure of the PSDs isolated under the former condition appeared to be more fragmented than those isolated under the latter condition, as revealed by electron microscopy. The results indicate that the disulfide bonds formed during the isolation process significantly tighten the PSD structure and further suggest that the PSD in vivo is a protein aggregate whose constituent proteins be held together primarily by non-covalent interactions.     

Ultra-low-dose naloxone enhances the antinociceptive effect of morphine in PTX-treated rats: Regulation on global histone methylation

ObjectiveEpigenetic reprogramming may have a possible role in neuropathic pain development; the present study examined the global patterns of lysine histone modification. In this serial study we analyzed the levels of histone 3 lysine 4 monomethylation, histone 3 lysine 4 dimethylation, and histone 3 lysine 9 trimethylation in pertussis toxin (PTX)-induced thermal hyperalgesic rat spinal cords.MethodsMale Wistar rats implanted with an intrathecal catheter received a single intrathecal PTX (1 μg in 5 μl saline) injection. Four days later, they were randomly assigned to receive either a single injection of saline, or ultra-low-dose naloxone (15 ng in 5 μl saline), followed by morphine (10 μg in 5 μl saline) injection 30 minutes later.ResultsThe results showed that PTX injection induced thermal hyperalgesia and significant increase of global histone methylation in the spinal cords. Intrathecal morphine alone did not affect the thermal hyperalgesia and global histone methylation. In contrast, intrathecal administration of ultra-low-dose naloxone plus morphine significantly attenuated the PTX-induced thermal hyperalgesia and down-regulated the global histone methylation.ConclusionThe results suggest that ultra-low-dose naloxone might be clinical valuable for neuropathic pain management via regulating global histone modification.     

Rectal wall sparing by dosimetric effect of rectal balloon used during intensity-modulated radiation therapy (IMRT) for prostate cancer.

The use of an air-filled rectal balloon has been shown to decrease prostate motion during prostate radiotherapy. However, the perturbation of radiation dose near the air-tissue interfaces has raised clinical concerns of underdosing the prostate gland. The aim of this study was to investigate the dosimetric effects of an air-filled rectal balloon on the rectal wall/mucosa and prostate gland. Clinical rectal toxicity and dose-volume histogram (DVH) were also assessed to evaluate for any correlation. A film phantom was constructed to simulate the 4-cm diameter air cavity created by a rectal balloon. Kodak XV2 films were utilized to measure and compare dose distribution with and without air cavity. To study the effect in a typical clinical situation, the phantom was computed tomography (CT) scanned on a Siemens DR CT scanner for intensity-modulated radiation therapy (IMRT) treatment planning. A target object was drawn on the phantom CT images to simulate the treatment of prostate cancer. Because patients were treated in prone position, the air cavity was situated superiorly to the target. The treatment used a serial tomotherapy technique with the Multivane Intensity Modulating Collimator (MIMiC) in arc treatment mode. Rectal toxicity was assessed in 116 patients treated with IMRT to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). They were treated in the prone position, immobilized using a Vac-Loktrade mark bag and carrier-box system. Rectal balloon inflated with 100 cc of air was used for prostate gland immobilization during daily treatment. Rectal toxicity was assessed using modifications of the Radiation Therapy Oncology Group (RTOG) and late effects Normal Tissue Task Force (LENT) scales systems. DVH of the rectum was also evaluated. From film dosimetry, there was a dose reduction at the distal air-tissue interface as much as 60% compared with the same geometry without the air cavity for 15-MV photon beam and 2x2-cm field size. The dose beyond the interface recovered quickly and the dose reductions due to air cavity were 50%, 28%, 11%, and 1% at 2, 5, 10, and 15 mm, respectively, from the distal air-tissue interface. Evaluating the dose profiles of the more clinically relevant situation revealed the dose at air-tissue interface was approximately 15% lower in comparison to that without an air cavity. The dose built up rapidly so that at 1 and 2 mm, there was only an 8% and 5% differential, respectively. The dosimetric coverage at the depth of the posterior prostate wall was essentially equal with or without the air cavity. The median follow-up was 31.3 months. Rectal toxicity profile was very favorable: 81% (94/116) patients had no rectal complaint while 10.3% (12/116), 6.9% (8/116), and 1.7% (2/116) had grade 1, 2, and 3 toxicity, respectively. There was no grade 4 rectal toxicity. DVH analysis revealed that none of the patients had more than 25% of the rectum receiving 70 Gy or greater. Rectal balloon has rendered anterior rectal wall sparing by its dosimetric effects. In addition, it has reduced rectal volume, especially posterior and lateral rectal wall receiving high-dose radiation by rectal wall distension. Both factors may have contributed to decreased rectal toxicity achieved by IMRT despite dose escalation and higher than conventional fraction size. The findings have clinical significance for future very high-dose escalation trials whereby radiation proctitis is a major limiting factor.     

Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

PURPOSE: To explore long-term immune responses after combined radio-gene-hormonal therapy. METHODS AND MATERIALS: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). RESULTS: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR+CD8+ T cells were increased at all timepoints up to 8 months. The mean percentages of DR+CD4+ T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. CONCLUSIONS: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer.     

Evaluation of a recombinant Hc of Clostridium botulinum neurotoxin serotype F as an effective subunit vaccine

A new gene encoding the Hc domain of Clostridium botulinum neurotoxin serotype F (FHc) was designed and completely synthesized with oligonucleotides. A soluble recombinant Hc of C. botulinum neurotoxin serotype F was highly expressed in Escherichia coli with this synthetic FHc gene. Subsequently, the purified FHc was used to vaccinate mice and evaluate their survival against challenge with active botulinum neurotoxin serotype F (BoNT/F). After the administration of FHc protein mixed with Freund adjuvant via the subcutaneous route, a strong protective immune response was elicited in the vaccinated mice. Mice that were given two or three vaccinations with a dosage of 1 or 10 μg of FHc were completely protected against an intraperitoneal administration of 20,000 50% lethal doses (LD₅₀) of BoNT/F. The BoNT/F neutralization assay showed that the sera from these vaccinated mice contained high titers of protective antibodies. Furthermore, mice were vaccinated once, twice, or three times at four different dosages of FHc using Alhydrogel (Sigma) adjuvant via the intramuscular route and subsequently challenged with 20,000 LD₅₀ of neurotoxin serotype F. A dose response was observed in both the antibody titer and the protective efficacy with increasing dosage of FHc and number of vaccinations. Mice that received one injection of 5 μg or two injections of ≥0.04 μg of FHc were completely protected. These findings suggest that the recombinant FHc expressed in E. coli is efficacious in protecting mice against challenge with BoNT/F and that the recombinant FHc subunit vaccine may be useful in humans.