Effectiveness of novel,lower cost molecular human papillomavirus‐based tests for cervical cancer screening in rural china

This study examined the efficacy of the OncoE6? Cervical Test, careHPV? and visual inspection with acetic acid (VIA) in identifying women at risk for cervical cancer and their capability to detect incident cervical precancer and cancer at 1‐year follow‐up. In a population of 7,543 women living in rural China, women provided a self‐collected and two clinician‐collected specimens and underwent VIA. All screen positive women for any of the tests, a ～10% random sample of test‐negative women that underwent colposcopy at baseline, and an additional ～10% random sample of test‐negative women who did not undergo colposcopy at baseline (n = 3,290) were recruited. 2,904 women were rescreened 1 year later using the same tests, colposcopic referral criteria, and procedures. Sensitivities of baseline tests to detect 1‐year cumulative cervical intraepithelial neoplasia Grade 3 or cancer (CIN3+) were 96.5% and 81.6% for careHPV? on clinician‐collected and self‐collected specimens, respectively, and 54.4% for OncoE6? test. The OncoE6? test was very specific (99.1%) and had the greatest positive predictive value (PPV; 47.7%) for CIN3+. Baseline and 1‐year follow‐up cervical specimens testing HPV DNA positive was sensitive (88.0%) but poorly predictive (5.5–6.0%) of incident CIN2+, whereas testing repeat HPV16, 18 and 45 E6 positive identified only 24.0% of incident CIN2+ but had a predictive value of 33.3%. This study highlights the different utility of HPV DNA and E6 tests, the former as a screening and the latter as a diagnostic test, for detection of cervical precancer and cancer.     

健康教育和呼吸功能训练在心胸外科患者围术期综合应用的研究

目的探讨规范的呼吸系统健康教育和呼吸功能训练对心胸外科手术病人康复的影响。方法选择2006年6～11月开胸手术患者50例为对照组,2006年12月～2007年9月开胸手术患者为实验组,对照组按临床常规护理进行指导,实验组进行规范的呼吸系统健康教育和深慢呼吸、缩唇呼吸、咳嗽训练、吹气球训练等呼吸功能训练,观察比较两组患者术后并发症、胸管留置时间、住院天数,并进行统计学分折。结果实验组明显优于对照组,P<0.05。结论规范的呼吸系统健康教育和呼吸功能训练可减少开胸手术病人术后并发症、缩短胸管留置和患者住院时间,促进病人早日康复。     

HPLC法测定百咳静颗粒中8个成分的含量

目的:建立HPLC法同时测定百咳静颗粒中盐酸麻黄碱、盐酸伪麻黄碱、苦杏仁苷、甘草苷、橙皮苷、黄芩苷、黄芩素、汉黄芩素8个成分的含量。方法:采用Diamonsil C18色谱柱(250 mm×4.6 mm,5μm),以乙醇-0.1%磷酸水溶液为流动相,梯度洗脱,流速为1.0 mL·min-1,柱温45℃,检测波长为215 nm(麻黄碱、伪麻黄碱、苦杏仁苷)、280 nm(甘草苷、橙皮苷、黄芩苷、黄芩素、汉黄芩素),进样量10μL。结果:盐酸麻黄碱、盐酸伪麻黄碱、苦杏仁苷、甘草苷、橙皮苷、黄芩苷、黄芩素、汉黄芩素8个成分的含量测定结果分别为0.312～1.018、0.321～1.175、0.315～0.723、0.876～1.735、0.982～2.604、0.824～9.999、1.635～2.888、0.812～1.661 mg·g-1;8个成分均可实现较好的分离,在拟定的浓度范围内,各成分均有良好的线性关系(r≥0.999);平均回收率97.4%～99.7%,RSD为0.65%～1.5%。结论:本方法简便准确,重复性好,可用于百咳静颗粒的质量控制与评价。     

Analysis of lumbar vertebrae fractures among inpatients in a primary hospital: A 10-year epidemiological study

Background:To analyze the epidemiological characteristics and changing trends of lumbar fractures in Xingtai Orthopedic Hospital in the past 10 years, and to improve the prevention and treatment of lumbar fractures.Methods:Using the hospital information system, data on patients with lumbar fractures in our hospital from 2009 to 2018 were collected regarding their age, gender, fracture time, injury mechanism, and the type of fracture. The epidemiological characteristics and trends of lumbar fractures for the period were summarized and analyzed.Results:The age of male patients with a high incidence of lumbar fractures was 61 to 70 years, followed by 51 to 60 years. The age of female patients with the highest incidence rate was 61 to 70 years, followed by 51 to 60 years (19.22%). Lumbar fractures in group A were predominantly of men. The majority of lumbar fractures in group B were of women. In group A, the incidence rate was higher in young men (21–50 years) than in women and higher in women >51 years. Most of the affected individuals were women. In group B, there were more middle-aged and young men (21–50 years) than women; however, there were more women than men aged ≥51 years. Car accident injury was the main cause of fractures, but in group B women, low-energy injuries were the main cause of fractures. The periods of high incidence in groups A and B were 4 to 6 years and 7 to 9 years, respectively. The number of injuries in group A was the highest and burst fracture was the main fracture type. In group B, the number of fall injuries was the highest, followed by car accident injuries, and compression fracture was the main fracture type.Conclusion:The number of lumbar fractures in women caused by low-energy injuries showed an increasing trend. The type of compression fracture increased, which might be related to osteoporosis caused by the decrease in the estrogen level after menopause.     

中国女性卵巢癌流行现状和趋势及预测分析

目的：　对1990至2019年中国女性卵巢癌流行趋势及危险因素进行分析,为我国卵巢癌的预防提供更科学的依据。方法：　从全球疾病负担2019数据库获取中国及其他地区卵巢癌发病、死亡及伤残调整寿命年指标的估计数和标准化率,比较评估中国卵巢癌的流行负担及危险因素变化。用GLOBOCAN库对2020至2040年中国卵巢癌发病及死亡人数进行预测。结果：　1990至2019年,中国大陆和中国台湾省卵巢癌的年龄标准化发病率分别由2.56/10万和4.72/10万增至4.54/10万和8.68/10万,年龄标准化死亡率由1.76/10万和2.63/10万增至2.77/10万和3.84/10万,增幅超过全球、日本及新加坡。其中,50~54岁年龄组女性发病人数最多,发病率的峰值出现在70~74岁。2019年卵巢癌死亡的三大危险因素分别是高空腹血糖、高体质指数和职业性石棉暴露。30年间,中国卵巢癌的年龄标准化伤残调整寿命年率（disability-adjusted life year,DALY）随社会人口学指数（socio-demographic index,SDI）增加而增加。此外,据GLOBOCAN数据库预测,中国卵巢癌疾病负担会持续加重,预计到2040年,发病人数较2020年增加17.9%,死亡人数增加33.0%。结论：　中国女性卵巢癌疾病负担仍然较重,且在不断上升,需要针对不同年龄段及风险人群采取相应的有效预防措施,加强对高风险人群的监测,以进一步降低疾病负担。     

Preparation and Properties of Different Polyether-Type Defoamers for Concrete

In this study, a series of polyether-type defoamers for concrete which consist of the same alkyl chain (hydrophobic part) but different polyether chains (hydrophilic part) was prepared, and the structure–property relationship of the defoamers was investigated for the first time. Using oleyl alcohol (OA) as the starting agent (alkyl chain), the polyether defoamers with different polyether chains were prepared by changing the amount and sequence of ethylene oxide (EO) and propylene oxide (PO) units. The properties of different defoamers were tested in aqueous solutions, and fresh and hardened mortars; the structure–property relationship of the defoamers was thus studied. The results indicated that the defoaming capacity of the polyether defoamers decreased with an increased EO amount, and the defoamers linked with both EO and PO units (PO before EO) had a stronger defoaming capacity than those linked with EO only. This study is beneficial for the development and applications of novel synthetic polyether-type defoamers for concrete.     

Novel Slow-Release Defoamers for Concrete Using Porous Nanoparticles as Carriers

Excess large and unstable air bubbles can reduce the compressive strength of hardened concrete, and traditional defoamers always fail because of adsorption and encapsulation on cement with the progress of cement hydration in later stages. It is necessary to develop a novel defoamer that shows a sustained defoaming ability in fresh concrete. A novel slow-release defoamer for concrete using porous nanoparticles as carriers is reported for the first time. The porous nanoparticles/polyether defoamer composite (SiO₂-Def) was prepared via sol-gel method. SiO₂-Def is a spherical composite nanoparticle with a size range of 160–200 nm and a uniform pore size distribution. SiO₂-Def shows a high load rate of about 16.4% and an excellent release under an alkali and salt environment. It has a weak initial defoaming ability but shows a sustained defoaming ability with time, so that it can avoid the failures of defoamers and eliminate harmful bubbles entrained during the processes of pumping and transportation. Moreover, SiO₂-Def produced a higher compressive strength of the hardened cement mortars.     

Epigenetic analysis of cell-free DNA by fragmentomic profiling

Cell-free DNA (cfDNA) fragmentation patterns contain important molecular information linked to tissues of origin. We explored the possibility of using fragmentation patterns to predict cytosine-phosphate-guanine (CpG) methylation of cfDNA, obviating the use of bisulfite treatment and associated risks of DNA degradation. This study investigated the cfDNA cleavage profile surrounding a CpG (i.e., within an 11-nucleotide [nt] window) to analyze cfDNA methylation. The cfDNA cleavage proportion across positions within the window appeared nonrandom and exhibited correlation with methylation status. The mean cleavage proportion was ∼twofold higher at the cytosine of methylated CpGs than unmethylated ones in healthy controls. In contrast, the mean cleavage proportion rapidly decreased at the 1-nt position immediately preceding methylated CpGs. Such differential cleavages resulted in a characteristic change in relative presentations of CGN and NCG motifs at 5′ ends, where N represented any nucleotide. CGN/NCG motif ratios were correlated with methylation levels at tissue-specific methylated CpGs (e.g., placenta or liver) (Pearson’s absolute r > 0.86). cfDNA cleavage profiles were thus informative for cfDNA methylation and tissue-of-origin analyses. Using CG-containing end motifs, we achieved an area under a receiver operating characteristic curve (AUC) of 0.98 in differentiating patients with and without hepatocellular carcinoma and enhanced the positive predictive value of nasopharyngeal carcinoma screening (from 19.6 to 26.8%). Furthermore, we elucidated the feasibility of using cfDNA cleavage patterns to deduce CpG methylation at single CpG resolution using a deep learning algorithm and achieved an AUC of 0.93. FRAGmentomics-based Methylation Analysis (FRAGMA) presents many possibilities for noninvasive prenatal, cancer, and organ transplantation assessment.

Fragmentation patterns of cell-free DNA (cfDNA) molecules contain a wealth of molecular information related to their tissues of origin (1). For instance, compared with the background DNA molecules that are mainly derived from the hematopoietic system (2, 3), size shortening of fetal and tumoral DNA molecules occurs in the plasma DNA of pregnant women and cancer patients, respectively (4–6). In addition, a series of 10-bp periodicities were present in fetal and tumoral DNA molecules below 146 bp, with a relative reduction in the major peak at 166 bp (1). Such characteristic size profiles suggest that the fragmentation of cfDNA may be associated with nucleosome structures (5, 7). Many important characteristics pertaining to cfDNA fragmentation have been unveiled recently, such as nucleosome footprints (8, 9), fragment end motifs (10), preferred ends (7, 11), and jagged ends (12), which are examples of fragmentomic markers (1).cfDNA fragmentomics is an emergent and actively pursued area, with wide-ranging biological and clinical implications. It has been reported that the use of fragmentation patterns of cfDNA could inform the expression status of genes (13, 14). Using mouse models, DNA nucleases (e.g., DNASE1L3) were found to play important roles in the generation of plasma DNA molecules (15, 16). Fragmentomic features, such as cfDNA end motifs and jagged ends, were further demonstrated to be useful for monitoring DNA nuclease activities, providing biomarkers for autoimmune diseases (e.g., systemic lupus erythematosus) (17, 18). In addition, the deficiencies of nuclease activities in a mouse model resulted in altered DNA methylation profiles of plasma DNA molecules (19). However, how cfDNA fragmentation patterns interplay with DNA methylation in human individuals under different pathophysiological conditions, such as pregnancy and oncogenesis, and in healthy patients without nuclease deficiency, is unknown. It is also not known whether fragmentomic features can be used to deduce cfDNA methylation status.A widely employed way to assess DNA methylation is through bisulfite sequencing (20). A key limitation of this approach is the severe degradation of DNA molecules caused by the bisulfite treatment (21), which greatly increases the sampling variation when analyzing rare target molecules (e.g., tumoral cfDNA at early stages of cancer). Many efforts have been made toward overcoming this issue. For example, Vaisvila et al. developed enzymatic methyl sequencing for which DNA molecules were treated using tet methylcytosine dioxygenase 2 and T4 phage β-glucosyltransferase, followed by the apolipoprotein B mRNA editing enzyme catalytic subunit 3A (APOBEC3A) treatment. Cytosine conversion based on enzymatic processes was reported to be much less destructive (22). Recently, researchers developed approaches making use of third-generation sequencing technologies such as single-molecule real-time sequencing (Pacific Biosciences) (23) and nanopore sequencing (24) to analyze cytosine-phosphate-guanine (CpG) methylation patterns in native DNA molecules, theoretically overcoming the above-mentioned limitation. However, compared with second-generation sequencing (also called next-generation sequencing [NGS]) technologies, the throughput of third-generation sequencing technologies is generally lower and the sequencing cost per nucleotide (nt) is much higher, thus restricting its immediate application in clinical settings. Here, we explore the feasibility of enabling the assessment of DNA methylation using fragmentomic characteristics of cfDNA molecules deduced from NGS results without the use of bisulfite or enzymatic treatment. If successful, such an approach could leverage the high throughput of NGS while obviating the use of chemical/enzymatic conversion and could potentially be readily integrated into currently used NGS-based platforms for cfDNA analysis.In this study, we utilize the fragmentation patterns proximal to a CpG site for deducing its methylation status. The fragmentation pattern is depicted by the frequency of cfDNA fragment ends at each position within a certain nt range relative to a CpG of interest, termed a cleavage profile (Fig. 1). Such a cleavage profile varies according to the methylation status of the CpG site of interest, providing the basis for methylation analysis by using fragmentomic features. We further correlated two types of end motifs (CGN and NCG; N represents any nucleotide of A, C, G, or T) resulting from differential cutting in the measurement window related to DNA methylation, attempting to construct a simplified approach for methylation analysis. Modeling CpG methylation using cfDNA fragmentation may facilitate noninvasive prenatal testing, cancer detection, and tissue-of-origin analysis (Fig. 1). Furthermore, we explore the feasibility of using deep learning to deduce the methylation status at single CpG resolution through the cleavage profile (Fig. 1). We refer to this FRAGmentomics-based Methylation Analysis as FRAGMA in this study.Open in a separate windowFig. 1.Schematic for FRAGMA of cfDNA molecules. cfDNA molecules were sequenced by massively parallel sequencing and aligned to the human reference genome. The cleavage proportion within an 11-nt window (the cleavage measurement window) was used to measure the cutting preference of cfDNA molecules. The patterns of cleavage proportion within a window (the cleavage profile) depended on the methylation status of one or more CpG sites associated with that window. For example, a methylated CpG site might confer a higher probability of cfDNA cutting at the cytosine in the CpG context, but an unmethylated site might not. Such methylation-dependent differential fragmentation within a cleavage measurement window resulted in the change in CGN/NCG motif ratio. Thus, the CGN/NCG motif ratio provided a simplified version for reflecting CpG methylation, allowing cfDNA tissue-of-origin analysis of cfDNA and cancer detection. Furthermore, the great number of cleavage profiles derived from cfDNA molecules might provide an opportunity to train a deep learning model for methylation prediction at the single CpG resolution.     

Development and validation of a predictive model for endocervical curettage in patients referred for colposcopy: A multicenter retrospective diagnostic study in China

ObjectiveThis study aimed to develop a nomogram that can predict occult high-grade squamous intraepithelial lesions or worse (HSIL+) and determine the need for endocervical curettage (ECC) in patients referred for colposcopy.MethodsThis retrospective multicenter study included 4,149 patients who were referred to any one of six tertiary hospitals in China for colposcopy between January 2020 and November 2021 because of abnormal screening results. ECC data were extracted from the medical records. Univariate and multivariate logistic regression analyses were performed to identify factors that could predict HSIL+ on ECC. Patients were randomly assigned to a training set or to an internal validation set for performance and comparability testing. The model was externally validated and tested in patients from two additional hospitals. The nomogram was assessed in terms of discrimination and calibration and subjected to decision curve analysis.ResultsHSIL+ was found on ECC in 38.8% (n=388) of cases. Our predictive nomogram included age group, cytology, human papillomavirus (HPV) status, visibility of the cervix and colposcopic impression. The nomogram had good overall discrimination, which was internally validated [area under the receiver-operator characteristic (AUC), 0.839; 95% confidence interval (95% CI), 0.773−0.904]. In terms of external validation, the AUC was 0.843 (95% CI, 0.773−0.912) for the consecutive sample and 0.843 (95% CI, 0.783−0.902) for the comparative sample. Calibration analysis suggested good consistency between predicted and observed probabilities. Decision curve analysis suggested this nomogram would be clinically useful with almost the entire range of threshold probabilities.ConclusionsThis internally and externally validated nomogram can be easily applied and incorporates multiple clinically relevant variables that can be used to identify patients with occult HSIL+ who need ECC.