B超引导下胸椎旁神经阻滞治疗急性带状疱疹肋间神经痛的研究

目的:探讨B超引导下胸椎旁神经阻滞在治疗急性带状疱疹肋间神经痛中的临床疗效。方法:80例胸背部急性带状疱疹伴肋间神经痛患者随机分为两组,每组各40例。A组(对照组)予常规抗病毒及按需口服镇痛药物治疗,B组(试验组)同时接受在B超引导下选择性胸椎旁神经阻滞治疗。观察治疗后7、14及30天两组患者疼痛视觉模拟评分(VAS)、辅助镇痛药用量、不良反应及后遗神经痛(PHN)发生率。结果:治疗后各观察时间点两组VAS评分均较治疗前降低(P0.009),组间比较差异显著,B组明显低于A组(P0.05)。辅助镇痛药物用量、PHN发生率B组亦显著低于A组(P0.05)。两组均无明显不良反应发生。结论:B超引导下胸椎旁神经阻滞联合抗毒治疗急性带状疱疹肋间神经痛安全有效,明显优于单纯药物治疗,并可减少后遗神经痛的发生率,值得临床推广应用。     

Cells infected with herpes simplex virus 1 export to uninfected cells exosomes containing STING,viral mRNAs,and microRNAs

STING (stimulator of IFN genes) activates the IFN-dependent innate immune response to infection on sensing the presence of DNA in cytosol. The quantity of STING accumulating in cultured cells varies; it is relatively high in some cell lines [e.g., HEp-2, human embryonic lung fibroblasts (HEL), and HeLa] and low in others (e.g., Vero cells). In a preceding publication we reported that STING was stable in four cell lines infected with herpes simplex virus 1 and that it was actively stabilized in at least two cell lines derived from human cancers. In this report we show that STING is exported from HEp-2 cells to Vero cells along with virions, viral mRNAs, microRNAs, and the exosome marker protein CD9. The virions and exosomes copurified. The quantity of STING and CD9 exported from one cell line to another was inoculum-size–dependent and reflected the levels of STING and CD9 accumulating in the cells in which the virus inoculum was made. The export of STING, an innate immune sensor, and of viral mRNAs whose major role may be in silencing viral genes in latently infected neurons, suggests that the virus has evolved mechanisms that curtail rather than foster the spread of infection under certain conditions.The stimulator of IFN genes (STING) is a sensor of cytoplasmic DNA and activates immune responses to intracellular pathogens (1–3). Knockout of STING exacerbates the pathogenicity of herpes simplex virus (HSV-1) and of other pathogens in mice (2, 3). Two observations reported earlier add to the role of STING in HSV-1 infected cells. Specifically, (i) STING was readily detectable and stable in four different cell lines infected with wild-type virus (4). The stability of STING in cells infected with an HSV-1 mutant lacking the gene encoding ICP0 (infected cell protein no. 0), a key viral regulatory protein, varied. STING was stable in ΔICP0 mutant virus infected cells derived from normal tissues but was rapidly degraded in infected cells derived from human cancers (4). Implicit in this observation is that ICP0 is required to stabilize STING, although STING could also be stabilized in the absence of ICP0 by a cellular function. (ii) Depletion of STING increased wild-type virus yield 10-fold in cells derived from normal tissues but decreased the yield by the same amount in cells derived from human cancer (4). Thus, at least in cells derived from normal tissues, HSV-1 expresses ICP0 that enables the stabilization of STING even though STING is inimical to virus growth. The results of these studies suggest that HSV-1 recruits STING for a specific function, even though the persistence of STING is not beneficial to virus growth, at least in cells derived from normal tissues (4).Here we report that STING, along with viral RNAs contained in structures that coprecipitate with exosome marker proteins, is exported from the cells in which virus is produced to uninfected cells. The quantities introduced into uninfected cells are dose-dependent and reflect the amounts produced in donor cells.Cells continuously secrete a large number of microvesicles, macromolecular complexes, and small molecules into the extracellular space (5, 6). Of the secreted microvesicles, exosomes are 30–120 nm in diameter, containing nucleic acid and proteins, and are perceived to be carriers of this cargo between diverse locations. They are distinguished in their genesis by being budded into endosomes to form multivesicular bodies (MVBs) in the cytoplasm. The exosomes are released to extracellular fluids by fusion of these multivesicular bodies with the cell surface, resulting in secretion (7–10).Several pathogens use the exosomes to manipulate their microenvironment (11, 12). Viruses, especially small retroviruses such as HIV, use the exosome pathway for egress and immune evasion (13–15). The hepatitis C virus uses exosomes for invasion and spread (16–18). EBV-infected cells release exosomes containing the latent membrane protein 1 to induce T-cell anergy (19–23). In the case of human cytomegalovirus the exosomes carrying viral antigens exacerbate the transplant rejection process (24). It is likely that viruses that establish long-term, latent, or chronic infections modulate exosomes to enhance their persistence (11).Here we report that the exosomes secreted by HSV-1–infected cells deliver to uninfected cells the innate immune sensor STING along with viral RNAs. We speculate that in the long run the strategy serves the virus to fulfill its mission: to spread effectively from person to person.     

中西药综合治疗肛周复发性生殖器疱疹54例临床观察

为观察中药祛毒内服方口服、祛毒外用方熏洗坐浴,结合西药伐昔洛韦口服、重组人干扰素a-2b乳膏外用治疗肛周复发性生殖器疱疹的疗效,将90例肛周复发性生殖器疱疹患者随机分为两组。治疗组54例采用中药祛毒内服方口服、中药祛毒外用方熏洗坐浴,结合西药伐昔洛韦口服、重组人干扰素a-2b乳膏外用;对照组36例采用口服伐昔洛韦,外用重组人干扰素a-2b乳膏。结果显示,治疗组治愈38例,显效4例,有效4例,无效8例,总有效率85．2％;对照组治愈18例,显效6例,有效2例,无效10例,总有效率72．2％。两组总有效率比较有显著性差异（P〈0．05）,治疗组复发率低于对照组（P〈0．05）。结果表明,中西药综合治疗肛周复发性生殖器疱疹的疗效明显优于单纯西药治疗。     

超声引导下椎旁神经阻滞治疗带状疱疹相关疼痛的Meta分析

文题释义： 椎旁神经阻滞：是通过将局麻药物注射到椎旁间隙内而实现,阻滞包括椎旁脊神经和其分支以及交感干,具有简单、易行、有效及低廉等特点。 带状疱疹相关疼痛：是由于潜伏在感觉神经节的水痘带状疱疹病毒被重新激活引起的近期或远期疼痛。主要包括带状疱疹急性期疼痛(即带状疱疹痛)和带状疱疹后神经痛。疼痛常表现为典型的病理性神经痛特点,主要特征是自发痛、痛觉过敏、感觉异常等,呈电击样、烧灼样、针刺样等疼痛。 背景：目前临床研究显示超声引导下椎旁神经阻滞治疗胸腰段带状疱疹相关疼痛有显著效果,并在临床上得到了广泛使用。 目的：系统评价超声引导下椎旁神经阻滞治疗胸腰段带状疱疹相关疼痛的有效性及安全性,为临床治疗提供参考依据。 方法：检索PubMed、The Cochrane Library、EMBASE、CNKI、WanFang Data、VIP以及CBM等数据库,检索时限为建库至2019-01-01。根据制定的纳入和排除标准,收集有关超声引导下椎旁神经阻滞治疗及药物治疗胸腰段带状疱疹急性期疼痛或带状疱疹后神经痛的随机对照试验,以超声引导下胸椎旁神经阻滞组作为实验组,药物治疗组或传统椎旁神经阻滞组作为对照组。依据Cochrane Handbook 5.1.0偏倚风险评估工具评价纳入文献质量。通过Revman 5.3软件对文献数据进行Meta分析。 结果与结论：①最终纳入11项随机对照试验研究文献,共916例受试者;②Meta分析结果显示：与对照组相比,超声引导下椎旁神经阻滞组的镇痛效果更好,在1-4周内临床镇痛效果最佳,采用随机效应模型下分析,1周：MD=-0.91,95%CI(-1.22,-0.61),P < 0.000 01;2周：MD=-1.11,95%CI(-1.52,-0.70),P < 0.000 01;3周：MD= -1.26,95%CI(-1.79,-0.74),P < 0.000 01;4周：MD= -0.90,95%CI(-1.57,-0.24),P=0.007;同时睡眠质量及治疗有效率均有提高[固定效应模型下分析,OR=3.63,95%CI(2.38,5.53),P < 0.000 01],统计结果差异有显著性意义,并且具有未增加整个治疗过程的不良反应等优点;③结果说明,超声引导下椎旁神经阻滞治疗胸腰段带状疱疹相关疼痛是安全和有效的。 ORCID: 0000-0001-7945-6411(宋旭东) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

A multicenter prospective trial to asses a new real-time polymerase chain reaction for detection of Treponema pallidum,herpes simplex-1/2 and Haemophilus ducreyi in genital,anal and oropharyngeal ulcers

Treponema pallidum, herpes simplex virus types 1 or 2 (HSV-1/2) and Haemophilus ducreyi are sexually transmitted pathogens that can cause genital, anal and oropharyngeal ulcers. Laboratory evaluation of these pathogens in ulcers requires different types of specimens and tests, increasing the risk of improper specimen handling and time lapse until analysis. We sought to develop a new real-time PCR (TP-HD-HSV1/2 PCR) to facilitate the detection of T. pallidum, HSV-1/2 and H. ducreyi in ulcers. The TP-HD-HSV1/2 PCR was tested (i) in a retrospective study on 193 specimens of various clinical origin and (ii) in a prospective study on 36 patients with genital, anal or oropharyngeal ulcers (ClinicalTrials.gov # NCT01688258). The results of the TP-HD-HSV1/2 PCR were compared with standard diagnostic methods (T. pallidum: serology, dark field microscopy; HSV-1/2: PCR; H. ducreyi: cultivation). Sensitivity and specificity of the TP-HD-HSV1/2 PCR for T. pallidum were both 100%, for HSV-1 100% and 98%, and for HSV-2 100% and 98%, respectively. T. pallidum and HSV-1/2 were detected in 53% and 22% of patients in the prospective study; H. ducreyi was not detected. In the prospective study, 5/19 (26%) specimens were true positive for T. pallidum in the TP-HD-HSV1/2 PCR but non-reactive in the VDRL. The TP-HD-HSV1/2 PCR is sensitive and specific for the detection of T. pallidum and HSV-1/2 in routine clinical practice and it appears superior to serology in early T. pallidum infections.     

Acyclovir-resistant herpes simplex encephalitis in a patient treated with anti-tumor necrosis factor-α monoclonal antibodies

Herpes simplex virus is the most common cause of severe sporadic encephalitis. We report a case of herpes simplex type 1-encephalitis in a 50-year-old woman receiving anti-tumor necrosis factor-α monoclonal antibodies adalimumab. Although she was an acyclovir naïve patient, a mixed viral population (wild-type and acyclovir-resistant bearing a thymidine-kinase mutation) was identified in the cerebrospinal fluid. The virus in cerebrospinal fluid evolved and a second thymidine-kinase mutant virus emerged. Combined foscavir and acyclovir treatment resolved the herpes simplex encephalitis. To our knowledge, this is the first report of acyclovir-resistant herpes simplex encephalitis in a patient treated with adalimumab.     

Auditory neural myelination is associated with early childhood language development in premature infants

Background

Auditory neural myelination (ANM) as evaluated by auditory brainstem evoked response (ABR) during the neonatal period has been used as a surrogate outcome for long-term neurodevelopment. The validity of ANM as a surrogate outcome for long-term neurodevelopment has not been well studied.

Aim

Evaluate the association of ABR I–V interpeak latency (IPL), an index of ANM, at 35 week postmenstrual age (PMA) with language outcome at 3 years of age.

Design

Prospective study.

Subjects

24–33 week gestational age (GA) infants were eligible if they did not meet exclusion criteria: craniofacial malformation, chromosomal disorders, deafness, auditory dys-synchrony, TORCH infection, or non-English speaking parents. Infants with malignancy, head injury, encephalopathy, meningitis, blindness, or who died or relocated were also excluded.

Outcome measures

ABRs were performed at 35 week PMA using 80 dB nHL and I–V IPL (ms) measured. Auditory Comprehension (AC) and Expressive Communication (EC) were evaluated by a speech-language pathologist at 3 years of age using Preschool Language Scale.

Results

Eighty infants were studied. The mean GA and birth weight of infants were 29.2 weeks and 1336 g, respectively. There was association of worse ear I–V IPL and better ear I–V IPL with AC (Coefficient − 5.4, 95% CI: − 9.8 to − 0.9 and Coefficient − 5.5, 95% CI: − 10  to−0.9, respectively) and EC (Coefficient − 5.6, 95% CI: − 9.5  to−1.8 and Coefficient − 6.7, 95% CI: − 10.6  to−2.7, respectively) after controlling for confounders.

Conclusion

The neonatal I–V IPL is a predictor of language development at 3 years of age in preterms.