Search

Qi-Ge Qi,1,* Ya Tuo,2,* Li-Xue Liu,2,* Cong-Xiang Yu,2,* Ai-Ning Wu2 1Department of Clinical Laboratory and Pathology, The 969th Hospital of P.L.A., Hohhot, Inner Mongolia, 010051, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia University, Hohhot, Inner Mongolia, 010050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ai-Ning WuDepartment of Obstetrics and Gynecology, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia University, No. 1 Of Tongdao North Road, Hui District, Hohhot, Inner Mongolia, 010050, People’s Republic of ChinaTel +86 0471-6636630Email wuaining_vu@163.comObjective: The present study aimed to evaluate and analyze the results of karyotyping by amniocentesis and next generation sequencing (NGS)-based noninvasive prenatal DNA testing (NIPT) for the prenatal diagnosis of fetal chromosomal disorders.Methods: A total of 2267 high-risk pregnant females with the indications for prenatal diagnosis who met the enrollment criteria between January 2015 and May 2019 at the Affiliated Hospital of Inner Mongolia Medical University were included and underwent NGS-based NIPT in the present study. Amniocentesis, chromosome karyotyping by cell culture, and follow-up of the pregnancy outcomes were also conducted in the NIPT-positive pregnant females to assess the consistency between NIPT and results of karyotyping by amniocentesis.Results: Among the 2267 cases, 29 cases were positive for NIPT, including 10 cases with a high risk of trisomy 21, 2 cases with a high risk of trisomy 18, 2 cases with a high risk of chromosome 13, and 20 cases with sex chromosome abnormalities. All the above NIPT-positive cases underwent amniocentesis, and 20 cases were eventually diagnosed. The sensitivity and specificity of NIPT for the diagnosis of trisomy 21, trisomy 13, and trisomy 18 were 100%, 99.96%, 100%, and 99.96%, 100%, 100%, respectively, and the positive predictive values were 91.67%, 66.67%, and 100%, respectively.Conclusion: NGS of the fetal free DNA from the peripheral blood of pregnant females was an important complement to the prenatal diagnosis of chromosomal disorders represented by fetal chromosome aneuploidy with high sensitivity and specificity. In combination with the traditional karyotyping by amniocentesis, it could improve the diagnostic efficacy for fetal chromosomal disorders.Keywords: next generation sequencing, karyotyping by amniocentesis, prenatal diagnosis, prenatal screening, fetal free DNA

The determination of cause of death is one of the most important tasks in forensic practice. However, asphyxia is a difficult cause of death to determine, especially when the deceased has an underlying disease that can lead to a sudden unexpected death, such as coronary atherosclerotic heart disease (CAHD, which is the leading cause of sudden cardiac death, SCD), because its determination is currently still based on an exclusion strategy. In this study, gas chromatography coupled with high-resolution mass spectrometry (GC-HRMS)-based untargeted metabolomics was employed to obtain the pulmonary metabolic profiles of rats who died from asphyxia and SCD. First, fourteen metabolites were identified to investigate the mechanism of death from asphyxia, and we proposed some explanations that may account for these metabolic alterations, including the perturbation of amino acid metabolism, lipid metabolism, and energy metabolism (TCA cycle). Second, we discovered eight potential biomarkers to differentiate between asphyxia and SCD as the cause of death. The excellent classification performances of the eight individual biomarkers and their combination in fresh lung tissue were observed. Third, we also explored the relative change in the concentration of the eight metabolites and their classification performance in decomposed tissue (at 24 h postmortem). Lactic acid, pantothenic acid, and the combination of the eight biomarkers can be recognized as perfect classifiers to discriminate asphyxia from SCD even when decomposition has occurred. Our results showed that GC-HRMS-based untargeted metabolomics can be used as a promising tool to explore the metabolic alterations of the death process and to determine the cause of death.

Background Guidelines recommend invasive mediastinal staging for patients with non-small cell lung cancer and a “central” tumor. However, there is no consensus definition for central location. As such, the decision to perform invasive staging largely remains on an empirical foundation. Research Question Should patients with peripheral T1 lung tumors undergo invasive mediastinal staging? Study Design and Methods All participants with a screen-detected cancer with a solid component between 8 and 30 mm were identified from the National Lung Screening Trial. After translation of CT data, cancer location was identified and the X, Y, Z coordinates were determined as well as distance from the main carina. A multivariable logistic regression model was constructed to evaluate for predictors associated with lymph node metastasis. Results Three hundred thirty-two participants were identified, of which 69 had lymph node involvement (20.8%). Of those with lymph node metastasis, 39.1% were N2. There was no difference in rate of lymph node metastasis based on tumor size (OR, 1.03; P = .248). There was also no statistical difference in rate of lymph node metastasis based on location, either by distance from the carina (OR, 0.99; P = .156) or tumor coordinates (X: P = .180; Y: P = .311; Z: P = .292). When adjusted for age, sex, histology, and smoking history, there was no change in the magnitude of the risk, and tests of significance were not altered. Interpretation Our data indicate a high rate of N2 metastasis among T1 tumors and no significant relationship between tumor diameter or location. This suggests that patients with small, peripheral lung cancers may benefit from invasive mediastinal staging.

To investigate correlation between abnormal replicative senescence of endometrial gland epithelial cells (EGECs) in shedding and non-shedding endometria and endometriosis cyst during menstruation. Musashi-1 expression, β-catenin expression, and EGECs ultrastructure in shedding and non-shedding endometrium when menstruation were observed through real-time PCR and transmission electron microscopy technologies. (1) Musashi-1 and β-catenin exhibited a high expression in shedding and non-shedding endometria in experimental group, showing a positive correlation between each other; and were significantly higher than that in control group. However; there was no correlation between these two in control group. (2) Transmission electron microscopy results: In experimental group, organelles in EGECs in shedding endometrium obtained were abundant on the first day of menstruation, nuclei were irregular, double nucleoli could be observed, and chromatin was rich. Furthermore, morphology of EGECs in non-shedding endometrium was irregular, organelles were abundant, basement membrane was irregular with abnormal curvature, and a large amount of collagenic fibers were found in intercellular spaces. On the fifth day of menstruation, the cilia and microvilli on secretory cells in endometrium increased and prolongated, and organelles became extremely rich. EGECs have potentials of division, proliferation, invasion and migration; and is associated with formation of endometriosis cysts.摘要 本研究目的是探究月经期间脱落和未脱落子宫内膜腺上皮细胞（endometrial gland epithelial cells, EGECs）的异常复制衰老与子宫内膜异位囊肿的相关性。通过实时PCR和透射电子显微镜技术观察月经期间脱落和未脱落子宫内膜中Musashi-1和β-catenin的表达以及EGECs的超微结构。（1）Musashi-1和β-catenin在实验组脱落和未脱落子宫内膜中存在高表达, 两者呈正相关, 并且显著高于对照组。然而, 在对照组中这两者之间无相关性。（2）透射电镜结果：实验组在月经第一天获得的脱落子宫内膜中EGECs所含的细胞器丰富, 细胞核不规则, 可见双核仁, 染色质丰富。此外, 在未脱落的子宫内膜中EGECs形态不规则, 细胞器丰富, 基底膜不规则, 曲率异常, 细胞间隙存在大量胶原纤维。在月经第5天, 子宫内膜分泌细胞上的纤毛和微绒毛增多并延长, 细胞器变得极为丰富。EGECs具有分裂、增殖、侵袭和迁移的潜力, 并且与子宫内膜异位囊肿的形成有关。.

Post-mortem interval (PMI) estimation is one of the most challenging tasks in forensic practice. Therefore, for PMI estimation, attenuated total reflection Fourier transform infrared (ATR-FTIR) spe...

Bacterial surface layers (S-layers) are cell envelope structures ubiquitously found in gram-negative and gram-positive bacteria, including Lactobacillus. S-layers play a role in the determination and maintenance of cell shape as virulence factors, mediate cell adhesion, and regulate immature dendritic and T cells. In this study, we sought to understand the involvement of MAPK serine/threonine kinases in alterations in Endometrial epithelial cells (ESC) growth induced by Lactobacillus crispatus (L. crispatus) slpA, an S-layer protein. We applied various concentrations of L. crispatus to cultured ESCs and observed growth and changes in the phosphorylation status of ERK1/2, JNK, and p38. Similar experiments were conducted using L. crispatus lacking and overexpressing slpA. We found that ESC growth was altered by slpA primarily via ERK1/2. Our findings suggest that L. crispatus slpA promotes ESC growth mainly through an ERK1/2-dependent pathway.

Objective. To estimate the additive interaction of body mass index (BMI) and family history of hypertension (FHH) on hypertension and explore whether the interaction could be influenced by behavioural risk factors. Methods. The cross-sectional data on 5791 participants were from the China National Health Survey in Gansu province in 2016. We assessed the additive interaction by calculating the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (SI). Results. ORs for hypertension were highest in Han (13.52, 95% CI: 9.45 to 19.34) and Yugur (13.85, 95% CI: 8.48 to 22.63) with the combination of obesity and FHH. The interaction of BMI and FHH was significant in Han people, with the RERI, AP, and SI and their 95% CIs being 2.48 (1.13 to 3.82), 0.33 (0.19 to 0.47), and 1.61 (1.26 to 2.07) for overweight and FHH and 6.32 (1.91 to 10.73), 0.47 (0.27 to 0.67), and 2.02 (1.33 to 3.07) for obesity and FHH, respectively. The interaction of BMI and FHH was not significant in Yugur people. Adjustment for behavioural risk factors had little influence on the interactions, and risks of hypertension remained increased. Conclusions. BMI and FHH were associated with hypertension, and the interaction of BMI and FHH on hypertension was significant in Han but not in Yugur people. Behavioural risk factors had little influence on the associations and interactions. The exacerbation of hypertension risks by overweight or obesity in hypertension families deserves attention in weight control and community care.

Despite the progress that has been made during the past several decades in forensic pathology, post-mortem diagnosis of hyperthermia remains difficult. The current study aimed to investigate the spectral changes in rat liver under hyperthermic conditions compared with the control groups of fatal asphyxiation, brainstem injury, and massive haemorrhage, using Fourier transform infrared (FTIR) microspectroscopy. Forty Sprague–Dawley rats were randomly divided into four groups: hyperthermia; asphyxiation; brainstem injury; and massive haemorrhage. The absorbance of ten major absorption bands (1238, 1307, 1396, 1454, 1540, 2850, 2919, 2958, 3070 and 3290 cm−1) was significant higher in the hyperthermia group compared with the groups of asphyxiation, brainstem injury and massive haemorrhage. The band absorbance ratios of A2958/A2850 and A1650/A1540 were significantly lower, whereas the A1454/A1238, A1396/A1238 and A1307/A1238 ratios were significantly higher in the hyperthermia group compared with the other thr...

Many studies have proven the usefulness of biofluid-based infrared spectroscopy in the clinical domain for diagnosis and monitoring the progression of diseases. Here we present a state-of-the-art study in the forensic field that employed Fourier transform infrared microspectroscopy for postmortem diagnosis of sudden cardiac death (SCD) by in situ biochemical investigation of alveolar edema fluid in lung tissue sections. The results of amide-related spectral absorbance analysis demonstrated that the pulmonary edema fluid of the SCD group was richer in protein components than that of the neurologic catastrophe (NC) and lethal multiple injuries (LMI) groups. The complementary results of unsupervised principle component analysis (PCA) and genetic algorithm-guided partial least-squares discriminant analysis (GA-PLS-DA) further indicated different global spectral band patterns of pulmonary edema fluids between these three groups. Ultimately, a random forest (RF) classification model for postmortem diagnosis of SCD was built and achieved good sensitivity and specificity scores of 97.3% and 95.5%, respectively. Classification predictions of unknown pulmonary edema fluid collected from 16 cases were also performed by the model, resulting in 100% correct discrimination. This pilot study demonstrates that FTIR microspectroscopy in combination with chemometrics has the potential to be an effective aid for postmortem diagnosis of SCD.

Estimation of the postmortem interval (PMI) is a complicated task in forensic medicine, especially during homicide and unwitnessed death investigations. Many biological, chemical, and physical indicators can be used to determine the postmortem interval, but most are not accurate. Here, we present a novel matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method that can be used for the estimation of PMI using molecular images and multivariate analyses. In this study, we demonstrate that both rat and human liver tissues of various PMIs (0, 2, 4, and 6days) can be discriminated using MALDI imaging and principal component analysis (PCA). Using genetic algorithm (GA), supervised neural network (SNN), and quick classifier (QC) methods, we built 6 classification models, which showed high recognition capability and good cross-validation. The histological changes in all the samples at different time points were also consistent with the changes seen in MALDI imaging. Our work suggests that MALDI-TOF MS, along with multivariate analysis, can be used to determine intermediate PMIs.