The super elongation complex (SEC) mediates phase transition of SPT5 during transcriptional pause release.

Release of promoter-proximally paused RNA Pol II into elongation is a tightly regulated and rate-limiting step in metazoan gene transcription. However, the biophysical mechanism underlying pause release remains unclear. Here, we demonstrate that the pausing and elongation regulator SPT5 undergoes phase transition during transcriptional pause release. SPT5 per se is prone to form clusters. The disordered domain in SPT5 is required for pause release and gene activation. During early elongation, the super elongation complex (SEC) induces SPT5 transition into elongation droplets. Depletion of SEC increases SPT5 pausing clusters. Furthermore, disease-associated SEC mutations impair phase properties of elongation droplets and transcription. Our study suggests that SEC-mediated SPT5 phase transition might be essential for pause release and early elongation and that aberrant phase properties could contribute to transcription abnormality in diseases.

27-Hydroxycholesterol inhibits trophoblast fusion during placenta development by activating PI3K/AKT/mTOR signaling pathway.

Trophoblast cell syncytialization is essential for placental and fetal development. Abnormal trophoblast cell fusion leads to pregnancy pathologies, such as preeclampsia (PE), intrauterine growth restriction (IUGR), and miscarriage. 27-hydroxycholesterol (27-OHC) is the most abundant oxysterol in human peripheral blood synthesized by sterol 27-hydroxylase (CYP27A1) and is considered a critical mediator between hypercholesterolemia and a variety of related disorders. Gestational hypercholesterolemia was associated with spontaneous preterm delivery and low birth weight (LBW) in term infants, yet the mechanism is unclear. In this study, two trophoblast cell models and CD-1 mice were used to evaluate the effects of 27-OHC on trophoblast fusion during placenta development. Two different kinds of trophoblast cells received a dosage of 2.5, 5, or 10 uM 27-OHC. Three groups of pregnant mice were randomly assigned: control, full treatment (E0.5-E17.5), or late treatment (E13.5-E17.5). All mice received daily intraperitoneal injections of saline (control group) and 27-OHC (treatment group; 5.5 mg/kg). In vitro experiments, we found that 27-OHC inhibited trophoblast cell fusion in primary human trophoblasts (PHT) and forskolin (FSK)-induced BeWo cells. 27-OHC up-regulated the expression of the PI3K/AKT/mTOR signaling pathway-related proteins. Moreover, the PI3K inhibitor LY294002 rescued the inhibitory effect of 27-OHC. Inhibition of trophoblast cell fusion by 27-OHC was also observed in CD-1 mice. Furthermore, fetal weight and placental efficiency decreased and fetal blood vessel development was inhibited in pregnant mice treated with 27-OHC. This study was the first to prove that 27-OHC inhibits trophoblast cell fusion by Activating PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism by which dyslipidemia during pregnancy results in adverse pregnancy outcomes.

Study of association of leptin with leukocyte telomere length in a Chinese rural population.

BACKGROUND: Previous studies have demonstrated the relationship between adipocyte factors, insulin resistance, and other indicators with telomere length. However, these studies did not consider the influence of changes in different indicators on telomere length over time. Therefore, the aim of this study is to elucidate the impact of changes in adipocyte factors, HOMA-IR, and other indicators on the dynamic variation of telomere length. METHODS: The data were from a cohort study conducted in Ningxia, China. A total of 1624 subjects were analyzed. Adipokines and relative leukocyte telomere length (RLTL) were measured, and changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment for ß-Cell Function (HOMA-ß), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. Generalized linear models evaluated associations between changes in adipokines and RLTL changes. Furthermore, univariate analyses examined the effects of changes in adipokines and insulin resistance indicators on ΔRLTL. RESULTS: The research findings indicate that females generally have shorter telomeres compared to males. In comparison to the low-level group of Δleptin (LEP), the high-level group of ΔLEP shows a negative correlation with ΔRLTL (B=-1.32, 95% CI (-2.38, -0.27)). Even after multivariable adjustments, this relationship persists (B=-1.31, 95% CI (-2.24, -0.23)). Further analysis reveals that after adjusting for ΔHOMA-IR, ΔHOMA-ß, and ΔQUICKI, the high-level group of ΔLEP still exhibits a significant negative correlation with ΔRLTL (B=-1.37, 95% CI (-2.43, -0.31)). However, the interaction effects between ΔHOMA-IR, ΔHOMA-ß, ΔQUICKI, and ΔLEP do not affect ΔRLTL. CONCLUSIONS: Elevated levels of leptin were significantly correlated with shortened telomere length. This suggests that increased leptin levels may impact overall individual health by affecting telomere length, underscoring the importance of measures to reduce leptin levels to mitigate the onset and progression of related diseases.

Assessment of the effects of myopic and hyperopic anisometropia on choroidal vascular structure in children using SS-OCTA.

OBJECTIVE: To compare large- and medium-sized choroidal vascularity and the choriocapillaris (CC) flow area in children with different refractive errors using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Forty-two anisometropic children were enrolled and divided into hyperopic anisometropia (HA) and myopic anisometropia (MA) groups. SS-OCTA was performed to analyse choroidal vascularity. Mean choroidal thickness (CT), choroidal vascularity volume (CVV), choroidal vascularity index (CVI) and CC flow area were compared between the two eyes. The inter-ocular differences between the two groups were also determined. RESULTS: Mean CT and CVV were highest in eyes with shorter axial lengths in both refractive groups, and the difference between the two eyes was positively correlated with the difference in axial length at the foveal region. Significant differences in the CVI in the MA group were only found in the parafoveal region. Inter-ocular differences in the CC were significantly reduced in eyes with longer axial lengths in the foveal and parafoveal regions of the HA and MA groups, respectively. Comparing inter-ocular differences, CC was significantly greater in the parafoveal region of the MA group than the HA group. CONCLUSIONS: All layers of choroidal vasculature were thinner in eyes with longer axial lengths in all groups. The inter-ocular CC difference was greater in the MA than in the HA group, with similar differences in axial length. This suggests that both medium-to-large choroidal vascular and choroidal capillaries may play a role in myopia development.

Nuclear Binding Protein 2/Nesfatin-1 Affects Trophoblast Cell Fusion during Placental Development via the EGFR-PLCG1-CAMK4 Pathway.

Previous studies have shown that nuclear binding protein 2 (NUCB2) is expressed in the human placenta and increases with an increase in the syncytialization of trophoblast cells. This study aimed to investigate the role of NUCB2 in the differentiation and fusion of trophectoderm cells. In this study, the expression levels of NUCB2 and E-cadherin in the placentas of rats at different gestation stages were investigated. The results showed that there was an opposite trend between the expression of placental NUCB2 and E-cadherin in rat placentas in different trimesters. When primary human trophoblast (PHT) and BeWo cells were treated with high concentrations of Nesfatin-1, the trophoblast cell syncytialization was significantly inhibited. The effects of NUCB2 knockdown in BeWo cells and Forskolin-induced syncytialization were investigated. These cells showed a significantly decreased cell fusion rate. The mechanism underlying NUCB2-regulated trophoblast cell syncytialization was explored using RNA-Seq and the results indicated that the epidermal growth factor receptor (EGFR)-phospholipase C gamma 1 (PLCG1)-calmodulin-dependent protein kinase IV (CAMK4) pathway might be involved. The results suggested that the placental expression of NUCB2 plays an important role in the fusion of trophoblasts during differentiation via the EGFR-PLCG1-CAMK4 pathway.

Choroid vascular changes in hyperopic anisometropia amblyopia using SS-OCTA.

PURPOSE: To observe and understand the structural changes in choroidal vessels in eyes with hyperopic anisometropic amblyopia using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: A total of 44 patients were enrolled in this study: 22 children with hyperopic anisometropic amblyopia and 22 age-matched controls. SS-OCTA was used to scan the 6*6 mm macular area of their eyes. The average choroidal thickness (CT) and choroidal capillary flow area (CC) in a 3 mm diameter area centered on the macular area were obtained. The choroidal vascularity volume (CVV) was automatically extracted and 3D reconstructed by inbuild software, and the three-dimensional choroidal vascularity index (3D-CVI) was calculated. The effect of amblyopia on the choroidal vessel structure was assessed using generalized linear estimating equations (GEEs) corrected for axial length, sex, age, and best-corrected visual acuity. RESULTS: The CC was greater in amblyopic eyes than in fellow eyes (P = 0.014) but was not significantly different from that in control eyes (P = 0.963). After correcting for sex, age, axial length, and visual acuity using GEEs, the mean CT in the amblyopic eyes was greater than that in the fellow eyes (P = 0.030) but was not significantly different from that in the control eyes (P = 0.160). The 3D-CVI in amblyopic eyes was higher than that in control eyes (P = 0.038) but was not significantly different from that in fellow eyes (P = 0.407). The three-dimensional choroidal vascularity volume (3D-CVV) was higher in amblyopic eyes than in fellow eyes (P = 0.046) and control eyes (P = 0.023). CONCLUSIONS: We found that eyes with hyperopic anisometropic amblyopia demonstrated higher CT, CC and 3D-CVV values than the contralateral eyes after correction, while the 3D-CVI was unchanged. Compared with control eyes, amblyopic eyes had higher 3D-CVV and 3D-CVI values but similar CT and CC values. Amblyopic eyes may have different choroidal vascular structures from fellow and control eyes.

Comparison of the morphological characteristics of the choroidal sublayer between idiopathic macular holes and epiretinal membranes with automatic analysis.

PURPOSE: To compare the choroidal sublayer morphologic features between idiopathic macular hole (IMH) and idiopathic epiretinal membrane (iERM) on spectral-domain optical coherent tomography (SD-OCT) using an automatic segmentation model. METHODS: Thirty-three patients with idiopathic IMHs and 44 with iERMs who underwent vitrectomies were involved. The enhanced depth imaging mode of SD-OCT was used to obtain the B-scan image after single line scanning of the macular fovea. The choroidal sublayer automatic analysis model divides the choroidal into the choroidal large vessel layer, the middle vessel layer and the small vessel layer (LVCL, MVCL and SVCL, respectively) and calculates the choroidal thickness (overall, LVCL, MVCL and SVCL) and vascular index (overall, LVCL, MVCL and SVCL). The morphological characteristics of the choroidal sublayer in the ERM eyes and the IMH eyes were compared. RESULTS: The mean choroidal thickness in the macular centre of the IMH eyes was significantly thinner than that of the ERM eyes (206.35 ± 81.72 vs. 273.33 ± 82.31 µm; P < 0.001). The analysis of the choroidal sublayer showed that the MVCL and SVCL macular centres and 0.5-1.5 mm of the nasal and temporal macula were significantly thinner in the IMH eyes than in the ERM eyes (P < 0.05), and there was a difference in the macular centre of the LVCL between the two groups (P < 0.05). In contrast, the choroidal vascular index of the macular centre in the IMH eyes was significantly higher than that in iERM eyes (0.2480 ± 0.0536 vs. 0.2120 ± 0.0616; P < 0.05). There was no significant difference in the CVI of other parts of the macula, the LVCL or MVCL between the two groups. CONCLUSION: The choroidal thickness of the IMH eyes was significantly thinner than that of the iERM eyes, which was mainly observed in 3 mm of the macular centre and the MVCL and SVCL layers of the choroid. The choroidal vascular index of the IMH eyes was higher than that of the iERM eyes. These findings suggest that the choroid may be involved in the pathogenesis of IMH and iERM.

Positive correlation between hypertensive retinopathy and albuminuria in hypertensive adults.

PURPOSE: We investigated the association between albuminuria and hypertensive retinopathy (HR) in hypertensive adults. METHODS: This was a cross-sectional subgroup analysis of data from the China Stroke Primary Prevention Trial. We enrolled 2,964 hypertensive adults in this study. Keith-Wagener-Barker stages was used to assess HR. The urinary albumin to creatinine ratio (UACR) was calculated to evaluate albuminuria. RESULTS: HR was found in 76.6% (n = 2, 271) of the participants, albuminuria was found in 11.1% (n = 330). The UACR levels were significantly higher in subjects with HR than in those without HR (grade 1, ß = 1.42, 95% confidence intervals [CI]: -0.12, 2.95, p = 0.070; grade 2, ß = 2.62, 95% CI: 0.56, 4.67, p = 0.013; grade 3, ß = 5.17, 95% CI: 1.13, 9.20, p = 0.012). In the subgroup analyses, the association between HR and UACR was stronger in current smokers (p for interaction = 0.014). The correlation between HR grades 1 and 2 and UACR was stronger in subjects with higher triglyceride levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglycerides levels (< 1.7 mmol/L, p for interaction = 0.023). The odds of albuminuria were significantly higher in subjects with HR than in those without HR (grade 1, odds ratio [OR] = 1.57, 95% CI: 1.08, 2.29, p = 0.019; grade 2, OR = 2.02, 95% CI: 1.28, 3.18, p = 0.002; grade 3, OR = 2.12, 95% CI: 0.99, 4.55, p = 0.053). In the subgroup analyses, the association between HR grades 1 and 2 and albuminuria was stronger in subjects with higher triglycerides levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglyceride levels (< 1.7 mmol/L, p for interaction = 0.014). CONCLUSION: HR was positively correlated with albuminuria in hypertensive Chinese adults. This correlation was more remarkable when the population was stratified by triglycerides levels and smoking status. HR can be used as an indicator of early renal injury.

Bisphenol A interferes with lncRNA Fhadlos2 and RUNX3 association in adolescent mouse ovary.

Bisphenol A (BPA) has a number of adverse effects on the reproductive development of females. In particular, the mechanism of disruption of ovarian development in adolescent mice is still unclear. Based on transcriptome sequencing results, a differentially expressed lncRNA, Fhad1os2, was detected in the ovaries of BPA-exposed pubertal mice. In our study, the lncRNA Fhad1os2, localized in the ovarian granulosa cell cytoplasm, could regulate the proliferation of mouse ovarian granulosa cells. Mechanistically, the results of RNA pull-down experiments as well as mass spectrometry analysis showed that ERα, an interfering signaling molecule of BPA, could directly bind lncRNA Fhad1os2 and decrease the transcription of lncRNA Fhad1os2 in response to the estrogen-like effect of BPA. BPA exposure also caused abnormal lncRNA Fhad1os2 pulldown protein-related signaling pathways in the ovaries of adolescent mice. Furthermore, lncRNA Fhad1os2 interacted with RUNX3, a transcription factor related to follicle development and hormone synthesis. As a negative regulator, lncRNA Fhad1os2 transactivated the expression of Runx3, which in turn induced RUNX3 to positively regulate aromatase (Cyp19a1) expression in mouse ovarian granulosa cells and promote estrogen synthesis. In conclusion, our study indicates that BPA exposure interferes with ERα-regulated lncRNA Fhad1os2 interactions with RUNX3 in pubertal mice, affecting estrogen synthesis in mouse granulosa cells and contributing to premature ovarian maturation in pubertal mice.

Transcriptome Profiling of Stenotrophomonas sp. Strain WZN-1 Reveals Mechanisms of 2,2',4,4'-Tetrabromodiphenyl Ether (BDE-47) Biotransformation.

The brominated flame retardant 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is extensively used, stable, and difficult to degrade in the environment. The existence of BDE-47 could pose a certain risk to the environment and human health. However, the biotransformation mechanisms of BDE-47 by microorganisms remain unclear. In this study, aerobic degradation of BDE-47 by Stenotrophomonas sp. strain WZN-1 and transcriptome analysis were carried out. BDE-47 degradation by Stenotrophomonas sp. strain WZN-1 was mainly through the biological action of intracellular enzymes via the route of debromination and hydroxylation. The results of the transcriptome sequencing indicated the differentially expressed genes were related to transport, metabolism, and stress response. The key processes involved the microbial transmembrane transportation of BDE-47, energy anabolism, synthesis, and metabolism of functional enzymes, stress response, and other biological processes of gene regulation. In particular, bacterial chemotaxis played a potential role in biodegradation of BDE-47 by Stenotrophomonas sp. strain WZN-1. This study provides the first insights into the biotransformation of Stenotrophomonas sp. strain WZN-1 to BED-47 stress and shows potential for application in remediation of polluted environments.

Association of maternal HDL2-c concentration in the first trimester and the risk of large for gestational age birth.

BACKGROUND: Maternal lipid levels during pregnancy are critical for fetal development. Recent studies revealed that high-density lipoprotein cholesterol (HDL-c) levels during pregnancy were negatively correlated with birthweight. High-density lipoprotein 2 cholesterol (HDL2-c) is one of the major subclasses of HDL-c, and its relationship with birthweight is unclear. Association of HDL2-c concentration in the first trimester and risk of large for gestational age (LGA) was explored. METHODS: This study recruited pregnant women who registered in Fuxing Hospital from October 2018 to January 2020, had regular obstetric examinations during pregnancy, and delivered between June 2019 and September 2020. Finally, 549 participants were recruited for the study. Maternal demographic characteristics and venous blood were collected at the 6th-14th gestational week, and serum total cholesterol (TC), triglyceride (TG), HDL-c, HDL2-c, high-density lipoprotein 3 cholesterol (HDL3-c), and low-density lipoprotein cholesterol (LDL-c) concentrations were detected. Neonatal characteristics were collected at delivery. A logistic regression model was used to explore the relationship between the first trimester HDL2-c concentration and LGA incidence. A nomogram was developed, and the performance was evaluated with a concordance index. RESULTS: Seventy-five mothers delivered LGA infants, and the LGA incidence was 13.66%. LGA mothers had significantly lower serum HDL-c and HDL2-c concentrations than appropriate for gestational age (AGA) mothers. A logistic regression model showed that HDL2-c concentration was negatively correlated with LGA risk (odds ratio (OR) = 0.237, 95% confidence intervals (CI): 0.099-0.567, P = 0.001) when adjusted for age, prepregnancy body mass index (BMI), and parity. A nomogram was generated using all these risk factors. The area under the curve (AUC) was 0.663 (95% CI: 0.593-0.732). CONCLUSIONS: Maternal HDL2-c concentration in the first trimester was negatively correlated with the risk of LGA.

Comparison of hyperreflective foci in macular edema secondary to multiple etiologies with spectral-domain optical coherence tomography: An observational study.

BACKGROUND: Hyperreflective foci (HRF) features in macular edema associated with different etiologies may indicate the disease pathogenesis and help to choose proper treatment. The goal of this study is to investigate the retinal microstructural features of macular edema (ME) secondary to multiple etiologies with spectral-domain optical coherence tomography (SD-OCT) and analyze the origin of HRF in ME. METHODS: This was a retrospective study. SD-OCT images were reviewed to investigate macular microstructural features such as the number and distribution of HRF and hard exudates and the internal reflectivity of the cysts. The differences in microstructural features between groups and the correlations between the number of HRF and other parameters were analyzed. RESULTS: A total of 101 eyes with ME from 86 diabetic (diabetic macular edema, DME) patients, 51 eyes from 51 patients with ME secondary to branch retinal vein occlusion (branch retinal vein occlusion-macular edema, BRVO-ME), 59 eyes from 58 central retinal vein occlusion (central retinal vein occlusion-macular edema, CRVO-ME) patients, and 26 eyes from 22 uveitis (uveitic macular edema, UME) patients were included in this study. The number of HRF, the frequency of hard exudates and the enhanced internal reflectivity of the cysts were significantly different among the groups. The number of HRF in the DME group was significantly higher than that in the other groups (all P < 0.05). The frequency of hard exudates and enhanced internal reflectivity of the cysts in the DME group were significantly higher than ME secondary to other etiologies (all P < 0.001). Within the DME group, the number of HRF in the patients with hard exudates was significantly higher than that in the patients without hard exudates (P < 0.001). CONCLUSION: HRF detected with SD-OCT were more frequent in DME patients than in BRVO-ME, CRVO-ME, or UME patients. The occurrence of HRF was correlated with the frequency of hard exudates. HRF may result from the deposition of macromolecular exudates in the retina, which is speculated to be a precursor of hard exudates.

A novel sternoclavicular hook plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular join.

PURPOSE: The aim of this study was to explore the efficacy of sternoclavicular hook plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular joint. METHODS: Between October 2016 and December 2020, 16 cases (9 male and 7 female patient, with a mean age of (42 ± 10) years) of proximal clavicle fracture with dislocation of sternoclavicular joint were included in the study. Injured side, injury mechanism, time to surgery, Complications and duration of follow-up were recorded. The outcomes were evaluated with radiographic assessment, American Shoulder and Elbow Surgeons' Form (ASES). All the patients were evaluated on postoperative 3rd, 6th, and 12th months. RESULTS: According to the ASES scoring system, the average score was 49 ± 4 (preoperative score), 87 ± 5 (3 months follow-up), 88 ± 3 (6 months follow-up) and 91 ± 3 (12 months follow-up). Statistics differences was showed between preoperative and 3,6,12 months follow-up score of ASES score (p < 0.001). The postoperative physical function was better than the preoperative function. Internal fixation failure and fracture non-union complications in two patients. CONCLUSION: Our study indicates that open reduction and sternoclavicular hook plate fixation for the treatment of traumatic sternoclavicular fracture is a safe, relatively straightforward surgical procedure that can lead to satisfactory outcomes.

Chatbot as an emergency exist: Mediated empathy for resilience via human-AI interaction during the COVID-19 pandemic.

As a global health crisis, the COVID-19 pandemic has also made heavy mental and emotional tolls become shared experiences of global communities, especially among females who were affected more by the pandemic than males for anxiety and depression. By connecting multiple facets of empathy as key mechanisms of information processing with the communication theory of resilience, the present study examines human-AI interactions during the COVID-19 pandemic in order to understand digitally mediated empathy and how the intertwining of empathic and communicative processes of resilience works as coping strategies for COVID-19 disruption. Mixed methods were adopted to explore the using experiences and effects of Replika, a chatbot companion powered by AI, with ethnographic research, in-depth interviews, and grounded theory-based analysis. Findings of this research extend empathy theories from interpersonal communication to human-AI interactions and show five types of digitally mediated empathy among Chinese female Replika users with varying degrees of cognitive empathy, affective empathy, and empathic response involved in the information processing processes, i.e., companion buddy, responsive diary, emotion-handling program, electronic pet, and tool for venting. When processing information obtained from AI and collaborative interactions with the AI chatbot, multiple facets of mediated empathy become unexpected pathways to resilience and enhance users' well-being. This study fills the research gap by exploring empathy and resilience processes in human-AI interactions. Practical implications, especially for increasing individuals' psychological resilience as an important component of global recovery from the pandemic, suggestions for future chatbot design, and future research directions are also discussed.

Changes in serum TG levels during pregnancy and their association with postpartum hypertriglyceridemia: a population-based prospective cohort study.

BACKGROUND: Blood lipid increases during gestation are considered a physiological adaption, and decrease after delivery. However, some adverse pregnancy outcomes are thought to be related to gestational lipid levels. Therefore, it is necessary to have a reference range for lipid changes during gestation. The present study aims to describe triglyceride (TG) changes during pregnancy and 42 days postpartum and to find cut-off points for TG levels during the first, second, and third trimesters. METHODS: A total of 908 pregnant women were followed from recruitment to 42 days postpartum, and their serum lipids were collected at gestational weeks 6-8, 16, 24, and 36 and 42 days postpartum. The major outcome was postpartum hypertriglyceridemia. The association between gestational and postpartum TG levels was analysed by stepwise multiple linear regression. A two-stage approach including a linear mixed-effect model and linear or logistic regression was conducted to explore the contribution of the changes in TG over time in pregnancy to postpartum hypertriglyceridemia. Logistic regression was constructed to examine the association between gestational TG levels and postpartum hypertriglyceridemia. Cut-off points were calculated by receiver operating characteristic (ROC) curves. RESULTS: There was a tendency for serum TG to increase with gestational age and decrease at 42 days postpartum. Prepregnancy overweight, obesity, and GDM intensified this elevation. Higher TG levels at gestational weeks 6-8, 16, 24, and 36 were positively associated with a higher risk of postpartum hypertriglyceridemia [OR 4.962, 95 % CI (3.007-8.189); OR 2.076, 95 % CI (1.303-3.309); OR 1.563, 95 % CI (1.092-2.236); and OR 1.534, 95 % CI (1.208-1.946), respectively]. The trend of the change in TG over time was positively associated with the TG level and risk of postpartum hypertriglyceridemia [OR 11.660, 95 % CI (6.018-22.591)]. Based on ROC curves, the cut-off points of serum TG levels were 1.93, 2.35, and 3.08 mmol/L at gestational weeks 16, 24, and 36, respectively. Stratified analysis of prepregnancy body mass index (pre-BMI) and GDM showed that higher gestational TG was a risk factor for postpartum hypertriglyceridemia in women with normal pre-BMI and without GDM. CONCLUSIONS: Gestational TG and its elevation were risk and predictive factors of postpartum hypertriglyceridemia, especially in pregnant women with normal pre-BMI or without GDM.

Digital analysis of external fixation area of proximal humerus fractures in elderly patients.

INTRODUCTION: The purpose is based on anatomical basis, combined with three-dimensional measurement, to guide the clinical repositioning of proximal humeral fractures, select the appropriate pin entry point and angle, and simulate surgery. METHODS: 11 fresh cadaveric specimens were collected, the distance of the marked points around the shoulder joint was measured anatomically, and the vertical distance between the inferior border of the acromion and the superior border of the axillary nerve, the vertical distance between the apex of the humeral head and the superior border of the axillary nerve, the vertical distance between the inferior border of the acromion and the superior border of the anterior rotator humeral artery, and the vertical distance between the apex of the humeral head and the superior border of the anterior rotator humeral artery were marked on the 3D model based on the anatomical data to find the relative safety zone for pin placement. RESULTS: Contralateral data can be used to guide the repositioning and fixation of that side of the proximal humerus fracture, and uniform data cannot be used between male and female patients. For lateral pining, the distance of the inferior border of the acromion from the axillary nerve (5.90 ± 0.43) cm, range (5.3-6.9) cm, was selected for pining along the medial axis of the humeral head, close to the medial cervical cortex, and the pining angle was measured in the coronal plane (42.84 ± 2.45)°, range (37.02° ~ 46.31°), and in the sagittal plane (28.24 ± 2.25)°, range (19.22° ~ 28.51°). The pin was advanced laterally in front of the same level of the lateral approach point to form a cross-fixed support with the lateral pin, and the pin angle was measured in the coronal plane (36.14 ± 1.75)°, range (30.32° ~ 39.61°), and in the sagittal plane (28.64 ± 1.37)°, range (22.82° ~ 32.11°). Two pins were taken at the greater humeral tuberosity for fixation, with the proximal pin at an angle (159.26 ± 1.98) to the coronal surface of the humeral stem, range (155.79° ~ 165.08°), and the sagittal angle (161.76 ± 2.15)°, with the pin end between the superior surface of the humeral talus and the inferior surface of the humeral talus. The distal needle of the greater humeral tuberosity was parallel to the proximal approach trajectory, and the needle end was on the inferior surface of the humeral talus. CONCLUSION: Based on the anatomical data, we can accurately identify the corresponding bony structures of the proximal humerus and mark the location of the pin on the 3D model for pin placement, which is simple and practical to meet the relevant individual parameters.

RCC2, a regulator of the RalA signaling pathway, is identified as a novel therapeutic target in cisplatin-resistant ovarian cancer.

Currently, cisplatin (DDP) is the first-line chemotherapeutic agent used for treatment of ovarian cancer, but gradually acquired drug resistance minimizes its therapeutic outcomes. We aimed to identify crucial genes associated with DDP resistance in ovarian cancer and uncover potential mechanisms. Two sets of gene expression data were downloaded from Gene Expression Omnibus, and bioinformatics analysis was conducted. In our study, the differentially expressed genes between DDP-sensitive and DDP-resistant ovarian cancer were screened in GSE15709 and GSE51373 database, and chromosome condensation 2 regulator (RCC2) and nucleoporin 160 were identified as 2 genes that significantly up-regulated in DDP-resistant ovarian cancer cell lines compared with DDP-sensitive cell lines. Moreover, RCC2, Ral small GTPase (RalA), and Ral binding protein-1 (RalBP1) expression was found to be significantly higher in DDP-resistant ovarian cancer tissues than in DDP-sensitive tissues. RCC2 plays a positive role in cell proliferation, apoptosis, and migration in DDP-resistant ovarian cancer cell lines in vitro and in vivo. Furthermore, RCC2 could interact with RalA, thus promoting its downstream effector RalBP1. RalA knockdown could reverse the effects of RCC2 overexpression on DDP-resistant ovarian cancer cell proliferation, apoptosis, and migration. Similarly, RalA overexpression could alleviate the effects of RCC2 knockdown in DDP-resistant ovarian cancer cells. Taken together, RCC2 may function as an oncogene, regulating the RalA signaling pathway, and intervention of RCC2 expression might be a promising therapeutic strategy for DDP-resistant ovarian cancer.-Gong, S., Chen, Y., Meng, F., Zhang, Y., Wu, H., Li, C., Zhang, G. RCC2, a regulator of the RalA signaling pathway, is identified as a novel therapeutic target in cisplatin-resistant ovarian cancer.

The Relationship Between Protein S-Nitrosylation and Human Diseases: A Review.

S-nitrosylation (SNO) is a covalent post-translational oxidative modification. The reaction is the nitroso group (-NO) to a reactive cysteine thiol within a protein to form the SNO. In recent years, a variety of proteins in human body have been found to undergo thiol nitrosylation under specific conditions. Protein SNO, which is closely related to cardiovascular disease, Parkinson's syndrome, Alzheimer's disease and tumors, plays an important role in regulatory mechanism of protein function in both physiological and pathological pathways, such as in cellular homeostasis and metabolism. This review discusses possible molecular mechanisms protein SNO modification, such as the role of NO in vivo and the formation mechanism of SNO, with particular emphasis on mechanisms utilized by SNO to cause certain diseases of human. Importantly, the effect of SNO on diseases is multifaceted and multi-channel, and its critical value in vivo is not well defined. Intracellular redox environment is also a key factor affecting its level. Therefore, we should pay more attention to the equilibrium relationship between SNO and denitrosylation pathway in the future researches. These findings provide theoretical support for the improvement or treatment of diseases from the point of view of SNO.

Exposure pathways, levels and toxicity of polybrominated diphenyl ethers in humans: A review.

Polybrominated diphenyl ethers (PBDEs) are extensively used as brominated flame retardants (BFRs) in different types of materials, which have been listed as Persistent Organic Pollutants (POPs) by the Stockholm Convention in 2009 and 2017. Due to their ubiquities in the environment and toxicities, PBDEs have posed great threat to both human health and ecosystems. The aim of this review is to offer a comprehensive understanding of the exposure pathways, levels and trends and associated health risks of PBDEs in human body in a global scale. We systematically reviewed and described the scientific data of PBDE researches worldwide from 2010 to March 2020, focusing on the following three areas: (1) sources and human external exposure pathways of PBDEs; (2) PBDE levels and trends in humans; (3) human data of PBDEs toxicity. Dietary intake and dust ingestion are dominant human exposure pathways. PBDEs were widely detected in human samples, especially in human serum and human milk. Data showed that PBDEs are generally declining in human samples worldwide as a result of their phasing out. Due to the common use of PBDEs, their levels in humans from the USA were generally higher than that in other countries. High concentrations of PBDEs have been detected in humans from PBDE production regions and e-waste recycling sites. BDE-47, -153 and -99 were proved to be the primary congeners in humans. Human toxicity data demonstrated that PBDEs have extensively endocrine disruption effects, developmental effects, and carcinogenic effects among different populations.

Quantitative analysis of retinal and choroidal microvascular parameters using optical coherence tomography angiography in children with nephrotic syndrome: a pilot study.

PURPOSE: To study the retinal and choroidal microvascular parameters in children with nephrotic syndrome (NS). METHODS: This is a cross-sectional study. Optical coherence tomography angiography was used to evaluate the changes of retinal and choroidal microvessels in patients with NS. Thirty NS children and 20 normal controls were included in this study. The macular vessel density (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choroid capillary plexus (CCP), and foveal avascular zone (FAZ) area of the SCP and DCP was quantitatively calculated. Clinical data including serum protein, blood lipid, uric acid, urea, serum creatinine, urinary protein concentration, urinary creatinine, 24-h urine volume, 24-h urinary total protein, 24-h creatinine clearance rate, and urinary albumin to creatinine ratio were collected. RESULTS: The VDs of the DCP and CCP in children with NS were significantly lower than those in controls (59.35 ± 2.45 vs. 61.15 ± 1.53, p = 0.002, 66.34 ± 1.43 vs. 67.16 ± 1.23, p = 0.042, respectively). The VD of the SCP in children with NS had a tendency to decrease compared with that in controls, but there were no significant differences. There were also no significant differences in FAZ area between the two groups. The VD of the SCP was positively correlated with serum total protein (ρ = 0.446, p = 0.014), serum albumin (ρ = 0.431, p = 0.017), and 24-h urine volume (ρ = 0.389, p = 0.034) but negatively correlated with triglyceride (ρ = - 0.450, p = 0.013), low-density lipoprotein cholesterol (ρ = -0.432, p = 0.017), urinary protein concentration (ρ = - 0.606, p < 0.001), and 24-h urinary total protein (ρ = - 0.517, p = 0.004). The VDs of the SCP, DCP, and CCP were negatively correlated with the urinary albumin to creatinine ratio (ρ = - 0.473, p = 0.008, ρ = - 0.438, p = 0.015, ρ = -0.467, p = 0.009, respectively). CONCLUSIONS: Retinal and choroidal VDs were decreased in children with NS and paralleled the severity of kidney disease. Optical coherence tomography angiography can be used as a noninvasive method for evaluating renal injury in patients with NS.