Contributions of the NICHD neonatal research network's generic database to documenting and advancing the outcomes of extremely preterm infants

The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) maintains a database of extremely preterm infants known as the Generic Database (GDB). Begun in 1987, this database now includes more than 91,000 infants, most of whom are extremely preterm (<29 weeks gestation). The GDB has been the backbone of the NRN, providing high quality, prospectively collected data to study the changing epidemiology of extreme prematurity and its outcomes over time. In addition, GDB data have been used to generate hypotheses for prospective studies and to develop new clinical trials by providing information about the numbers and characteristics of available subjects and the expected event rates for conditions and complications to be studied. Since its inception, the GDB has been the basis of more than 200 publications in peer-reviewed journals, many of which have had a significant impact on the field of neonatology.     

Methodological advances in the design of peptide-based vaccines

The tremendous advances in genomics, recombinant DNA technology, bioengineering and nanotechnology, in conjunction with the development of high-end computations, have been instrumental in the process of rational design of peptide-based vaccines. The use of peptide vaccines was limited owing to their inherent instability when systemically administered; however, advanced formulation techniques have been developed for their systemic delivery, thereby overcoming their degradation, clearance, cellular uptake and off-target effects. With the rise of sophisticated immunological predictors and experimental techniques, several methodological advances have occurred in this field. This review examines contemporary methods to identify and optimize epitopes, engineer their immunogenic properties and develop their safe and efficient delivery into the host.     

HIV/AIDS患者结核潜伏感染的影响因素研究

背景 结核病是导致人免疫缺陷病毒/获得性免疫缺陷综合征（HIV/AIDS）患者死亡的首要原因，而HIV感染也是导致结核潜伏感染（LTBI）发展为结核病的主要危险因素。因此，对HIV/AIDS患者进行LTBI筛查和治疗是预防该类人群结核病的发生从而减少其死亡的重要举措。 目的 对宁夏回族自治区银川市市区内HIV/AIDS患者进行LTBI筛查，并分析其影响因素，识别高危人群，为HIV/AIDS患者结核病的预防性治疗提供科学依据。 方法 选取2021年3—8月于宁夏回族自治区银川市市区内定点管理单位治疗的546例HIV/AIDS患者为研究对象。通过现场问卷调查及查阅患者管理档案的方式收集HIV/AIDS患者的一般资料，其中一般人口学特征包括性别、年龄、民族、学历、婚姻状况、家庭人均年收入、职业类型、体质指数（BMI）、吸烟情况、饮酒情况等；临床资料包括慢性病患病情况、与结核病患者密切接触情况、HIV/AIDS确诊时长、抗病毒治疗时长、合并其他感染情况、近期CD4+ T淋巴细胞计数（CD4）等。通过结核菌素皮肤试验（TST）对研究对象进行LTBI筛查，根据TST结果将546例HIV/AIDS患者分为非LTBI组（TST阴性413例）和LTBI组（TST阳性133例）。比较两组患者的一般资料，采用多因素Logistic回归分析探讨HIV/AIDS患者发生LTBI的影响因素，并利用R软件建立限制性立方样条模型拟合CD4与LTBI风险之间的量效关系。 结果 银川市市区内HIV/AIDS患者的TST阳性率为24.4%。已婚〔OR=0.544，95%CI（0.321，0.922），P<0.05〕是HIV/AIDS患者发生LTBI的保护因素；吸烟〔OR=1.919，95%CI（1.213，3.037），P<0.05〕、与结核病患者有过密切接触〔OR=11.100，95%CI（2.889，42.648），P<0.05〕是HIV/AIDS患者发生LTBI的危险因素。限制性立方样条模型拟合结果显示，HIV/AIDS患者的CD4与LTBI风险呈近似"n"形的非线性关系（非线性检验χ2=29.080，P<0.001）。 结论 应重点关注HIV/AIDS患者中未婚、吸烟、与结核病患者有过密切接触人群LTBI的发生情况，并及时进行预防性治疗；对于CD4较低的患者，建议采用多种方法进行LTBI筛查。     

Evaluation of 5-aminolevulinic acid-mediated photodynamic therapy in postmenopausal women with persistent HPV infection with or without cervical and vaginal low-grade squamous intraepithelial lesions (CIN1/VaIN1)

ObjectiveTo analyze the efficacy and safety of photodynamic therapy (PDT) on postmenopausal women with persistent human papillomavirus (HPV) infection with or without low-grade cervical and vaginal intraepithelial neoplasia (CIN1 and VaIN1).Materials and methodsThe clinicopathological and follow-up data of 86 postmenopausal women with HPV infection (35 cases with chronic cervicitis and 51 cases with CIN1/VaIN1) were collected. All the women in this group met these criteria: menopausal time ≥ 1 year, HPV infection time ≥ 2 years, colposcopy and pathological diagnosis of biopsy ≤ CIN1/VaIN1 before PDT treatment, and 5-aminolaevulinic acid (5-ALA) as photosensitizer treating for 6 times with a week interval. The above patients were followed up 6 months and 12 months after PDT treatment, and the follow-up contents included HPV typing, cytology, colposcopy and pathological examinations. HPV negative conversion rate and lesion remission rate are the evaluation indicators of treatment efficacy. In addition, we also assessed the safety of PDT treatment.ResultsAt 12-month follow-up, the overall HPV clearance rate was 60% (45/75), of which the negative conversion rate of 16/18 HPV was 41.38% (12/29), and non-16/18 HPV was 71.74% (33/46) (p = 0.009). In patients without lesions, the HPV clearance rate was 51.72% (15/29), while in patients with CIN1/VaIN1 (n = 46), the HPV complete remission rate and lesion regression rate were 65.22% (30/46) and 89.13% (41/46), respectively. In addition, the clearance rate of HPV in lesion regression group was significantly higher than that in lesion persistence/progression group (0.00% vs. 73.17%, p = 0.003). The adverse reactions after PDT treatment were mild, mainly manifested as increased vaginal secretions or burning/tingling.ConclusionsPhotodynamic therapy can significantly enhance the elimination rate of persistent HPV infection in postmenopausal women and reduce the progression of CIN1/VaIN1. It could be an effective conservative treatment for persistent HPV infection and CIN1/VaIN1 in postmenopausal women.     

Analytical method for detection and quantification of new emerging drug etaqualone in human blood and urine by gas chromatography tandem mass spectrometry

Analytical procedure for detection and quantification of etaqualone in human blood and urine using GC–MS/MS was established and applied to authentic human samples obtained from volunteers. A liquid–liquid extraction method was employed. Each 1.0 mL of blood or urine was alkalized and extracted with diethyl ether. The solvent layer was evaporated to dryness and reconstituted with methanol then analyzed by GC–MS/MS. linear relationships within the concentration range of 1–100 ng/mL were obtained in calibrators for both blood and urine, demonstrating correlation coefficients values being>0.999. For blood and urine samples, the intra-day assay precision and accuracy values are each less than 3.65%, 7.13%, and 6.02%, 9.12%; those values of the inter-day assay are each less than 1.82%, 6.74%, and 3.99%, 7.41%. The extraction recovery rates for etaqualone ranged from 98.7% to 106%. The lower limit of quantifications was 1.0 ng/mL in both blood and urine. Stabilities of etaqualone in blood and urine were satisfactory under various temperatures within 15 days. 8.51 and 2.06 ng/mL of etaqualone in blood and urine were detected at 4 h later oral ingestion; 6.91 and 3.94 ng/mL of etaqualone were also detected 30 min and 2 h later smoking from blood and urine.     

Ochratoxin A induced differentiation nephrotoxicity in renal tubule and glomeruli via autophagy differential regulation

Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC₅₀ of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation.