Misdiagnosis of a twin pregnancy with double-corner uterine rupture following salpingectomy and protrusion of the amniotic sac as an adnexal cyst: a case report.

BACKGROUND: Salpingectomy-associated uterine rupture during intrauterine pregnancy is rare in the clinic. We report a case of pregnancy with bilateral rupture of the uterine horns after bilateral salpingectomy. CASE PRESENTATION: A 30-year-old woman of Han ethnicity presented with right epigastric pain at 28 weeks and 6 days of gestation. Examination by colour Doppler ultrasound showed the following: "Twin live births with normal foetal umbilical artery blood flow indexes and a 183 mm × 112 mm anechoic zone in the right front of the uterus". Initially, we made an incorrect judgement wherein we considered the amniotic sac that was protruding into the abdominal cavity to be an adnexal cyst. Fortunately, the diagnosis of uterine rupture was confirmed before the protruded amniotic sac broke. The mother did not bleed much, and the twin foetuses survived in our case. CONCLUSION: A previous history of salpingectomy via laparoscopy could be a risk factor for uterine rupture in pregnant women. Attention should be paid to rare complications of pregnancy. To avoid adverse events, we should pay special attention to women with a history of laparoscopic salpingectomy who complain about abdominal discomfort and offer them a relevant ultrasound examination.

Reduced and mutant lysozyme refolding with lipid vesicles. Model study of disulfide impact on equilibria and dynamics.

The recovery of secondary structure in disordered, disulfide-reduced hen egg white lysozyme (HEWL) upon interaction with lipid vesicles was studied using circular dichroism (CD), fluorescence and infrared (IR) spectroscopic techniques. Lipid vesicles having negative head groups, such as DMPG, interact with reduced HEWL to induce formation of more helical structure than in native HEWL, but no stable tertiary structure was evident. Changes in tertiary structure, as evidenced by local environment of the tryptophan residues, were monitored by fluorescence. Spectra for oxidized HEWL, reduced HEWL and mutants with no or just one disulfide bond developed variable degrees of increased helicity when added to negatively charged lipid vesicles, mostly depending on packing of tails. When mixed with zwitterionic lipid vesicles, reduced HEWL developed ß-sheet structure with no change in helicity, indicating an altered interaction mechanism. Stopped flow CD and fluorescence dynamics, were fit to multi-exponential forms, consistent with refolding to metastable intermediates of increasing helicity for HEWL interacting with lipid vesicles. Formation of an intermediate after rapid interaction of the lipid vesicles and the protein is supported by the correlation of faster steps in CD and fluorescence kinetics, and largely appears driven by electrostatic interaction. In subsequent slower steps, the partially refolded intermediate further alters structure, gaining helicity and modifying tryptophan packing, as driven by hydrophobic interactions.

Interaction of reduced lysozyme with surfactants: disulfide effects on reformed structure in micelles.

The reformation of secondary structure for unfolded, disulfide reduced hen egg white lysozyme (HEWL) upon interaction with surfactants was studied using CD, fluorescence and IR (infrared) techniques. Equilibrium CD studies showed that reduced HEWL when mixed with negatively charged surfactants, such as SDS (sodium dodecyl sulfate), gradually regains average helical structure to a level equivalent to that obtained for the oxidized form also in SDS, but both forms lose tertiary structure in such environments. This non-native structure recovery process begins with monomer surfactant interaction but at higher concentrations is in part dependent on micelle formation, with the helical fraction reaching its maximum value with each surfactant only above the CMC. Fluorescence changes were more complex, evidencing an intermediate state at lower surfactant concentration. With positively charged surfactants the degree of helicity recovered was less, and the intermediate state in fluorescence was not seen. Stopped flow dynamics studies showed the CD kinetics fit to two exponentials as did the fluorescence. The faster steps in CD and fluorescence detected kinetics appear to be correlated which suggests formation of an intermediate on rapid interaction of the micelle and protein. The second step then reflected attainment of a stable surfactant solvated state which attains maximum helicity and moves the Trps to a more hydrophobic environment, which may occur in independent steps, as the slower kinetics are not well correlated.

Acute effects of outdoor air pollution on emergency department visits due to five clinical subtypes of coronary heart diseases in shanghai, china.

BACKGROUND: Air pollution can be a contributing cause to the development and exacerbation of coronary heart disease (CHD), but there is little knowledge about the acute effects of air pollution on different clinical subtypes of CHD. METHODS: We conducted a time-series study to investigate the association of air pollution (particulate matter with an aerodynamic diameter < 10 µm [PM10], sulfur dioxide [SO2], and nitrogen dioxide [NO2]) on emergency department (ED) visits due to five different subtypes of CHD in Shanghai, China, from 2010 to 2012. We applied an over-dispersed Poisson generalized addictive model to analyze the associations after controlling for the seasonality, day of the week, and weather conditions. RESULTS: We identified a total of 47 523 ED visits for CHD. A 10-µg/m(3) increase in the present-day concentrations of PM10, SO2, and NO2 was associated with respective increases of 1.10% (95% confidence interval [CI] 0.33%-1.87%), 0.90% (95% CI -0.14%-1.93%), and 1.44% (95% CI 0.63%-2.26%) for total ED visits for CHD. These associations varied greatly by clinical type, with strong effects on sudden cardiac death, moderate effects on acute myocardial infarction and angina, weak effects on ischemic cardiomyopathy, and no effect on occult CHD. The associations were stronger among people aged 65 years or more than in younger individuals and in the cool season versus the warm one. CONCLUSIONS: Outdoor air pollution may have different effects of air pollution on 5 subtypes of CHD. Our results might be useful for the primary prevention of various subtypes of CHD exacerbated by air pollution.

Nrf2 deficiency exacerbated pulmonary pyroptosis in maternal hypoxia-induced intrauterine growth restriction offspring mice.

Maternal prenatal hypoxia is an important contributor to intrauterine growth restriction (IUGR), which impedes fetal lung maturation and leads to the development of chronic lung diseases. Although evidence suggests the involvement of pyroptosis in IUGR, the molecular mechanism of pyroptosis is still unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been found to potentially interact with gasdermin D (GSDMD), the key protein responsible for pyroptosis, indicating its crucial role in inhibiting pyroptosis. Therefore, we hypothesized that Nrf2 deficiency is a key molecular responsible for lung pyroptosis in maternal hypoxia-induced IUGR offspring mice. Pregnant WT and Nrf2-/- mice were exposed to hypoxia (10.5% O2) to mimic IUGR model. We assessed body weight, lung histopathology, pulmonary angiogenesis, oxidative stress levels, as well as mRNA and protein expressions related to inflammation in the 2-week-old offspring. Additionally, we conducted a dual-luciferase reporter assay to confirm the targeting relationship between Nrf2 and GSDMD. Our findings revealed that offspring with maternal hypoxia-induced IUGR exhibited reduced birth weight, catch-up growth delay, and pulmonary dysplasia. Furthermore, we observed impaired nuclear translocation of Nrf2 and increased GSDMD-mediated pyroptosis in these offspring with IUGR. Moreover, the dual-luciferase reporter assay demonstrated that Nrf2 could directly inhibit GSDMD transcription; deficiency of Nrf2 exacerbated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR. Collectively, our findings suggest that Nrf2 deficiency induces GSDMD-mediated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR; thus highlighting the potential therapeutic approach of targeting Nrf2 for treating prenatal hypoxia-induced pulmonary dysplasia in offspring.

Silencing RPL8 inhibits the progression of hepatocellular carcinoma by down-regulating the mTORC1 signalling pathway.

This study aimed to explore the role of ribosomal protein L8 (RPL8) in controlling hepatocellular carcinoma (LIHC) development. We measured RPL8 expression, apoptosis, cell viability, proliferation, migration, invasion, glucose uptake, lactate production, and the ATP/ADP ratio of LIHC cells to investigate the effect of RPL8 on LIHC. Bioinformatic analysis was employed to analyse RPL8 expression and its potential mechanism in LIHC. RPL8 was upregulated in LIHC tissues and cells. RPL8 silencing accelerated apoptosis and suppressed viability, growth, and movement of LIHC cells. Additionally, RPL8 silencing inhibited glycolysis in LIHC cells. Bioinformatic analysis revealed that RPL8 is regulated by the upstream transcription factor upstream stimulating factor 1 (USF1) and activates the mTORC1 signalling pathway. USF1 overexpression eliminated the inhibitory effect of RPL8 silencing in LIHC cells. RPL8 overexpression increased cell growth, movement, and glycolysis in LIHC. However, inhibition of the mTORC1 signalling pathway eliminated the effect of RPL8 overexpression on LIHC cells. In conclusion, RPL8 may affect LIHC progression by regulating the mTORC1 signalling pathway.

Highly acidic pH facilitates enamel protein self-assembly, apatite crystal growth and enamel protein interactions in the early enamel matrix.

Tooth enamel develops within a pH sensitive amelogenin-rich protein matrix. The purpose of the present study is to shed light on the intimate relationship between enamel matrix pH, enamel protein self-assembly, and enamel crystal growth during early amelogenesis. Universal indicator dye staining revealed highly acidic pH values (pH 3-4) at the exocytosis site of secretory ameloblasts. When increasing the pH of an amelogenin solution from pH 5 to pH 7, there was a gradual increase in subunit compartment size from 2 nm diameter subunits at pH 5 to a stretched configuration at pH6 and to 20 nm subunits at pH 7. HSQC NMR spectra revealed that the formation of the insoluble amelogenin self-assembly structure at pH6 was critically mediated by at least seven of the 11 histidine residues of the amelogenin coil domain (AA 46-117). Comparing calcium crystal growth on polystyrene plates, crystal length was more than 20-fold elevated at pH 4 when compared to crystals grown at pH 6 or pH 7. To illustrate the effect of pH on enamel protein self-assembly at the site of initial enamel formation, molar teeth were immersed in phosphate buffer at pH4 and pH7, resulting in the formation of intricate berry tree-like assemblies surrounding initial enamel crystal assemblies at pH4 that were not evident at pH7 nor in citrate buffer. Amelogenin and ameloblastin enamel proteins interacted at the secretory ameloblast pole and in the initial enamel layer, and co-immunoprecipitation studies revealed that this amelogenin/ameloblastin interaction preferentially takes place at pH 4-pH 4.5. Together, these studies highlight the highly acidic pH of the very early enamel matrix as an essential contributing factor for enamel protein structure and self-assembly, apatite crystal growth, and enamel protein interactions.

Factors predicting successful vaginal birth after caesarean section: protocol for evidence-based consensus recommendations using a Delphi survey.

INTRODUCTION: With the wide adoption of the two-child policy in China since 2016, a large percentage of women with a history of caesarean delivery plan to have a second child. Accordingly, the rate of vaginal birth after caesarean (VBAC) delivery is increasing. Women attempting repeat VBAC may experience multiple morbidities, which is also one of the leading causes of maternal and perinatal mortality. However, it remains to be addressed how we evaluate factors for successful VBAC. This study aims to use a novel approach to identify a set of potential predictive factors for successful VBAC, especially for Chinese women, to be included in prediction models which can be most applicable to pregnant women in China. We plan to assess all potential predictive factors collected through a comprehensive literature review. Then the certainty of the evidence for the identified potential predictive factors will be assessed using the Grading of Recommendations Assessment, Development and Evaluation process. Finally, a two-round international Delphi survey will be conducted to determine the level of consensus. METHODS AND ANALYSIS: This study will apply a methodology through an evidence-based approach. A long list of potential predictive factors for successful VBAC will be extracted and identified through the following stages: First, an up-to-date systematic review of the published literature will be conducted to extract identified potential predictive factors for successful VBAC. Second, an online Delphi survey will be performed to achieve expert consensus on which factors should be included in future prediction models. The online questionnaires will be developed in the field of patient, maternal and fetal-related factors. A two-round international Delphi survey will be distributed to the expert panel in the field of perinatal medicine using Google Forms. Experts will be asked to score each factor using the 9-point Likert rating scale to establish potential predictive factors for the successful VBAC. The expert panel will determine on whether to include, potentially include or exclude predictive factors, based on a systematic review of clinical evidence and the Delphi method. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board of the Jiaxing Maternity and Children Healthcare Hospital (approval number: 2019-79). The results of this study will be submitted to international peer-reviewed journals or conferences in perinatal medicine or obstetrics.

MicroRNA-650 targets ING4 to promote gastric cancer tumorigenicity.

MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of target mRNAs. Altered expression of specific miRNAs in human gastric cancer progression has been reported; however, the role of miR-650 in gastric cancer is poorly understood. In this study, we show that miR-650 is involved in lymphatic and distant metastasis in human gastric cancer, and we find that ectopic expression of miR-650 promotes tumorigenesis and proliferation of gastric cancer cells. A luciferase reporter assay demonstrates that Inhibitor of Growth 4 (ING4) is a direct target of miR-650. Collectively, our study demonstrates that over-expression of miR-650 in gastric cancer may promote proliferation and growth of cancer cells, at least partially through directly targeting ING4. These findings help clarify the molecular mechanisms involved in gastric carcinogenesis and indicate that miR-650 modulation may be a bona fide miRNA-based treatment of gastric cancer.

Integrative Temporo-Spatial, Mineralogic, Spectroscopic, and Proteomic Analysis of Postnatal Enamel Development in Teeth with Limited Growth.

Tooth amelogenesis is a complex process beginning with enamel organ cell differentiation and enamel matrix secretion, transitioning through changes in ameloblast polarity, cytoskeletal, and matrix organization, that affects crucial biomineralization events such as mineral nucleation, enamel crystal growth, and enamel prism organization. Here we have harvested the enamel organ including the pliable enamel matrix of postnatal first mandibular mouse molars during the first 8 days of tooth enamel development to conduct a step-wise cross-sectional analysis of the changes in the mineral and protein phase. Mineral phase diffraction pattern analysis using single-crystal, powder sample X-ray diffraction analysis indicated conversion of calcium phosphate precursors to partially fluoride substituted hydroxyapatite from postnatal day 4 (4 dpn) onwards. Attenuated total reflectance spectra (ATR) revealed a substantial elevation in phosphate and carbonate incorporation as well as structural reconfiguration between postnatal days 6 and 8. Nanoscale liquid chromatography coupled with tandem mass spectrometry (nanoLC-MS/MS) demonstrated highest protein counts for ECM/cell surface proteins, stress/heat shock proteins, and alkaline phosphatase on postnatal day 2, high counts for ameloblast cytoskeletal proteins such as tubulin ß5, tropomyosin, ß-actin, and vimentin on postnatal day 4, and elevated levels of cofilin-1, calmodulin, and peptidyl-prolyl cis-trans isomerase on day 6. Western blot analysis of hydrophobic enamel proteins illustrated continuously increasing amelogenin levels from 1 dpn until 8 dpn, while enamelin peaked on days 1 and 2 dpn, and ameloblastin on days 1-5 dpn. In summary, these data document the substantial changes in the enamel matrix protein and mineral phase that take place during postnatal mouse molar amelogenesis from a systems biological perspective, including (i) relatively high levels of matrix protein expression during the early secretory stage on postnatal day 2, (ii) conversion of calcium phosphates to apatite, peak protein folding and stress protein counts, and increased cytoskeletal protein levels such as actin and tubulin on day 4, as well as (iii) secondary structure changes, isomerase activity, highest amelogenin levels, and peak phosphate/carbonate incorporation between postnatal days 6 and 8. Together, this study provides a baseline for a comprehensive understanding of the mineralogic and proteomic events that contribute to the complexity of mammalian tooth enamel development.

Collagen-collagen interactions mediated by plant-derived proanthocyanidins: A spectroscopic and atomic force microscopy study.

UNLABELLED: Collagen cross-linkings are determinant of biological tissue stability and function. Plant-derived proanthocyanidins (PACs) mimic different hierarchical levels of collagen cross-links by non-enzymatic interactions resulting in the enhancement to the biomechanics and biostability of collagen-rich tissues such as dentin. This study investigated the interaction of PACs from Vitis vinifera grape seed extract with type I collagen in solubilized form and in the demineralized dentin matrix (DDM) by fluorescence spectral analysis; collagen-collagen binding forces in presence of cross-linking solutions by atomic force microscopy (AFM); and spectroscopic analysis of the DDM using attenuated total reflectance Fourier transform-infrared spectroscopy (ATR-FTIR). Glutaraldehyde (GA) and carbodiimide hydrochloride (EDC) with known cross-linking mechanisms were selected for comparative analyses. Changes in fluorescence upon interaction of solubilized type I collagen with PACs, EDC and GA reflected pronounced modifications in collagen conformation. PACs also promoted stronger collagen-collagen fibrils interaction than EDC and GA. A new feature was observed using ATR-FTIR spectroscopic analysis in PACs-treated collagen and DDM. The findings suggest covalent interactions between collagen and PACs. The mechanisms of interaction between PACs-collagen hold attractive and promising tissue-tailored biomedical applications and the binding forces that potentially drive such interaction were characterized. STATEMENT OF SIGNIFICANCE: Connective tissues such as skin, bone and dentin are mainly composed of type I collagen, which is cross-linked to promote tissue stability, strength and function. Novel therapies using substances that mimic cross-links have been proposed to promote repair of collagen-based-tissues. In dentistry, naturally occurring proanthocyanidins (PACs) have the potential to enhance dentin mechanical properties and reduce its enzymatic degradation, but their mechanisms of cross-linking are unclear. The present study investigated the specific interactions between PACs-type I collagen in purified and dentin collagen and compared to the well described cross-linking mechanisms promoted by synthetic chemical substances. Findings reveal that covalent-like bonds are induced by plant PACs in type I collagen as well as in complex dental native tissue, promoting strong collagen-collagen interactions.