ABSTRACT
BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.
Subject(s)
Disease Models, Animal , Inflammasomes , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Mice, Inbred C57BL , Mice, Knockout, ApoE , NLR Family, Pyrin Domain-Containing 3 Protein , Phenanthrenes , Signal Transduction , Syk Kinase , Vasodilation , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammasomes/metabolism , Syk Kinase/metabolism , Matrix Metalloproteinase 2/metabolism , Phenanthrenes/pharmacology , Male , Matrix Metalloproteinase 9/metabolism , Vasodilation/drug effects , Hyperlipidemias/drug therapy , Hyperlipidemias/physiopathology , Vasodilator Agents/pharmacology , Phosphorylation , Mice , Aorta/drug effects , Aorta/physiopathology , Aorta/metabolism , Aorta/enzymology , Apolipoproteins EABSTRACT
BACKGROUND: Recent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear. RESULTS: Here, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells. CONCLUSIONS: Our results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients.
Subject(s)
Gene Regulatory Networks , Pre-Eclampsia , RNA, Long Noncoding , Pre-Eclampsia/genetics , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Female , Pregnancy , Placenta/metabolismABSTRACT
Lilium lancifolium Thunb (L. lancifolium) is an important medicinal and edible plant with outstanding functionality for selenium (Se) biofortification. However, the molecular response of L. lancifolium to exogenous Se has not been fully elucidated. In this study, the effects of different levels of Se on L. lancifolium growth and quality were explored by transcriptome, metabolome and biochemical analyses. The results showed that the total Se and organic Se content in L. lancifolium bulbs increased with increasing Se dosage (0-8.0 mmol/L). Moreover, Se stimulated the growth of L. lancifolium at low level (2.0 mmol/L) but showed an inhibitory effect at high levels (≥4.0 mmol/L). Metabolomic and biochemical analyses revealed that the bulb weight and the content of amino acid, soluble sugar, and soluble protein were significantly increased in the 2.0 mmol/L Se treatment compared with those in the control (0 mmol/L Se). Transcriptome and metabolome analyses revealed that the significant upregulation of the GPD1, GPAT and ADPRM genes promoted glycerophospholipid accumulation. Additionally, the significantly upregulated glyA and downregulated asnB, nadB, thrA and SAT genes coordinate to the regulation of amino acid biosynthesis. The significantly upregulated SUS, bgl B, BAM, and SGA1 genes were involved in soluble sugar accumulation under Se treatment. In summary, this study identified the optimal Se concentration (2.0 mmol/L), which significantly improved the growth and nutritional quality of L. lancifolium and contributed to understanding the combined effects of Se treatment on the expression of genes and the accumulation of metabolites in L. lancifolium bulbs.
ABSTRACT
Electrical control of charge density waves has been of immense interest, as the strong underlying electron-lattice interactions potentially open new, efficient pathways for manipulating their ordering and, consequently, their electronic properties. However, the transition mechanisms are often unclear as electric field, current, carrier injection, heat, and strain can all contribute and play varying roles across length scales and timescales. Here, we provide insight on how electrical stimulation melts the room temperature charge density wave order in 1T-TaS_{2} by visualizing the atomic and mesoscopic structural dynamics from quasi-static to nanosecond pulsed melting. Using a newly developed ultrafast electron microscope setup with electrical stimulation, we reveal the order and strain dynamics during voltage pulses as short as 20 ns. The order parameter dynamics across a range of pulse amplitudes and durations support a thermally driven mechanism even for fields as high as 19 kV cm^{-1}. In addition, time-resolved imaging reveals a heterogeneous, mesoscopic strain response across the flake, including MHz-scale acoustic resonances that emerge during sufficiently short pulsed excitation which may modulate the order. These results suggest that metallic charge density wave phases like studied here may be more robust to electronic switching pathways than insulating ones, motivating further investigations at higher fields and currents in this and other related systems.
ABSTRACT
Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with progressive senescence in vascular smooth muscle cells (VSMCs). The vascular protective effect of FGF21 has gradually gained increasing attention, but its role in diabetes-induced vascular senescence needs further investigation. In this study, diabetic mice and primary VSMCs are transfected with an FGF21 activation plasmid and treated with a peroxisome proliferator-activated receptor γ (PPARγ) agonist (rosiglitazone), an NLRP3 inhibitor (MCC950), and a spleen tyrosine kinase (SYK)-specific inhibitor, R406, to detect senescence-associated markers. We find that FGF21 overexpression significantly restores the level of catalase (CAT), vascular relaxation, inhibits the intensity of ROSgreen fluorescence and p21 immunofluorescence, and reduces the area of SA-ß-gal staining and collagen deposition in the aortas of diabetic mice. FGF21 overexpression restores CAT, inhibits the expression of p21, and limits the area of SA-ß-gal staining in VSMCs under high glucose conditions. Mechanistically, FGF21 inhibits SYK phosphorylation, the production of the NLRP3 dimer, the expression of NLRP3, and the colocalization of NLRP3 with PYCARD (ASC), as well as NLRP3 with caspase-1, to reverse the cleavage of PPARγ, preserve CAT levels, suppress ROSgreen density, and reduce the expression of p21 in VSMCs under high glucose conditions. Our results suggest that FGF21 alleviates vascular senescence by regulating the SYK-NLRP3 inflammasome-PPARγ-catalase pathway in diabetic mice.
Subject(s)
Cellular Senescence , Diabetes Mellitus, Experimental , Fibroblast Growth Factors , Inflammasomes , Mice, Inbred C57BL , Muscle, Smooth, Vascular , NLR Family, Pyrin Domain-Containing 3 Protein , PPAR gamma , Signal Transduction , Syk Kinase , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Syk Kinase/metabolism , Syk Kinase/genetics , PPAR gamma/metabolism , PPAR gamma/genetics , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Inflammasomes/metabolism , Mice , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Male , Fibroblast Growth Factors/metabolism , Fibroblast Growth Factors/genetics , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathologyABSTRACT
To study the environmental responses of tropical cyclones (TCs) in continental shelf regions, TCs passing over the Yellow Sea and Bohai Sea (YBS) during 2002-2020 were investigated, with a special focus on how competition between ocean thermal structure and TC characteristics modulates ocean surface changes. The spatial distributions of the climatic mixed layer depth (MLD), accumulated wind forcing power index (WPi), accumulated sea surface temperature (SST) changes and accumulated chlorophyll (Chl-a) changes in the YBS were calculated. The linear regressions indicate that both the TC-induced SST cooling and TC-induced Chl-a increase are correlated with the TC wind speed rather than the translation speed, especially when the TC forcing depth (Zmixing) is greater than the MLD. Otherwise, both the changes in SST and Chl-a are correlated with the TC translation speed when Zmixing is shallower than the MLD. Further study has shown that whether TCs can break the MLD is also a key condition for oceanic responses. In the southern YBS, which has a deep-sea basin and MLD, the TC wind speed is the major factor affecting SST cooling and Chl-a increase, as TCs need more strength to reach the MLD. However, in the northern YBS, which has the shallowest sea basin and MLD, even weak TCs can easily break the MLD and reach the seabed; thus, ocean surface changes are associated mainly with the TC translation speed. The composite results reveal that both the maximum SST cooling center (1.64 °C) and the maximum Chl-a increasing center (0.14 log10(mg/m3)) are located on the right and behind the TC center, respectively. In addition, TC-induced SST cooling and Chl-a increase were initiated two days prior to TC passage and then reached their maximum values after 1 day. It takes approximately 7-8 days for the Chl-a concentration to recover, but it takes a much longer time (>15 days) for the SST to recover.
Subject(s)
Cyclonic Storms , Temperature , Oceans and Seas , Chlorophyll , Linear ModelsABSTRACT
Importance: Electronic cigarettes (ECs) are often used by smokers as an aid to stopping smoking, but evidence is limited regarding their efficacy compared with nicotine replacement therapy (NRT), and no evidence is available on how their efficacy compares with that of varenicline. Objective: To evaluate whether ECs are superior to NRT and noninferior to varenicline in helping smokers quit. Design, Setting, and Participants: This was a randomized clinical trial conducted at 7 sites in China and including participants who were smoking at least 10 cigarettes per day and motivated to quit, not using stop-smoking medications or EC, and willing to use any of the study products. Participants were first recruited in May 2021, and data analysis was conducted in December 2022. Interventions: A cartridge-based EC (30 mg/mL nicotine salt for 2 weeks and 50 mg/mL after that), varenicline (0.5 mg, once a day for 3 days; 0.5 mg, twice a day for 4 days; and 1 mg, twice a day, after that), and 2 mg (for smokers of ≤20 cigarettes per day) or 4 mg (>20 cigarettes per day) nicotine chewing gum, all provided for 12 weeks and accompanied by minimal behavioral support (an invitation to join a self-help internet forum). Main Outcomes and Measures: The primary outcome was sustained abstinence from smoking at 6 months as validated by an expired-air carbon monoxide reading (<8 parts per million). Participants lost to follow-up were included as nonabstainers. Results: Of 1068 participants, 357 (33.5%) were female, and the mean (SD) age was 33.9 (3.1) years. A total of 409 (38.3%), 409 (38.3%), and 250 (23.4%) participants were randomized to the EC, varenicline, and NRT arms, respectively. The 6-month biochemically validated abstinence rates were 15.7% (n = 64), 14.2% (n = 58), and 8.8% (n = 22) in the EC, varenicline, and NRT study arms, respectively. The quit rate in the EC arm was noninferior to the varenicline arm (absolute risk reduction, 1.47%; 95% CI, -1.41% to 4.34%) and higher than in the NRT arm (odds ratio, 1.92; 95% CI, 1.15-3.21). Treatment adherence was similar in all study arms during the initial 3 months, but 257 participants (62.8%) in the EC arm were still using ECs at 6 months, with no further use in the 2 other study arms. The most common adverse reactions were throat irritation (32 [7.8%]) and mouth irritation (28 [6.9%]) in the EC arm, nausea (36 [8.8%]) in the varenicline arm, and throat irritation (20 [8.0%]) and mouth irritation (22 [8.8%]) in the NRT arm. No serious adverse events were recorded. Conclusions and Relevance: The results of this randomized clinical trial found that when all treatments were provided with minimal behavior support, the efficacy of EC was noninferior to varenicline and superior to nicotine chewing gum. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100048156.
Subject(s)
Electronic Nicotine Delivery Systems , Nicotine Chewing Gum , Smoking Cessation , Female , Humans , Adult , Male , Smoking Cessation/methods , Varenicline/therapeutic use , Nicotinic Agonists/adverse effects , Tobacco Use Cessation Devices , SmokingABSTRACT
Strong spin-lattice coupling in van der Waals (vdW) magnets shows potential for innovative magneto-mechanical applications. Here, nanoscale and picosecond imaging by ultrafast electron microscopy reveal heterogeneous spin-mediated coherent acoustic phonon dynamics in a thin-film cavity of the vdW antiferromagnet FePS3. The harmonics of the interlayer shear acoustic modes are observed, in which the even and odd harmonics exhibit distinct nanoscopic dynamics. Corroborated by acoustic wave simulation, the role of defects in forming even harmonics is elucidated. Above the Néel temperature (TN), the interlayer shear acoustic harmonics are suppressed, while the in-plane traveling wave is predominantly excited. The dominant acoustic dynamics shifts from the out-of-plane shear to the in-plane traveling wave across TN, demonstrating that magnetic properties can influence phonon scattering pathways. The spatiotemporally resolved structural characterization provides valuable nanoscopic insights for interlayer-shear-mode-based acoustic cavities, opening up possibilities for magneto-mechanical applications of vdW magnets.
ABSTRACT
The primary underlying contributor for cataract, a leading cause of vision impairment and blindness worldwide, is oxidative stress. Oxidative stress triggers protein damage, cell apoptosis, and subsequent cataract formation. The nuclear factor-erythroid 2-related factor 2 (Nrf2) serves as a principal redox transcriptional factor in the lens, offering a line of defense against oxidative stress. In response to oxidative challenges, Nrf2 dissociates from its inhibitor, Kelch-like ECH-associated protein 1 (Keap1), moves to the nucleus, and binds to the antioxidant response element (ARE) to activate the Nrf2-dependent antioxidant system. In parallel, oxidative stress also induces endoplasmic reticulum stress (ERS). Reactive oxygen species (ROS), generated during oxidative stress, can directly damage proteins, causing them to misfold. Initially, the unfolded protein response (UPR) activates to mitigate excessive misfolded proteins. Yet, under persistent or severe stress, the failure to rectify protein misfolding leads to an accumulation of these aberrant proteins, pushing the UPR towards an apoptotic pathway, further contributing to cataractogenesis. Importantly, there is a dynamic interaction between the Nrf2 antioxidant system and the ERS/UPR mechanism in the lens. This interplay, where ERS/UPR can modulate Nrf2 expression and vice versa, holds potential therapeutic implications for cataract prevention and treatment. This review explores the intricate crosstalk between these systems, aiming to illuminate strategies for future advancements in cataract prevention and intervention. The Nrf2-dependent antioxidant system communicates and cross-talks with the ERS/UPR pathway. Both mechanisms are proposed to play pivotal roles in the onset of cataract formation.
Subject(s)
Antioxidants , Cataract , Humans , Antioxidants/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Endoplasmic Reticulum Stress/physiology , Oxidative Stress/physiology , Reactive Oxygen Species/metabolismABSTRACT
Understanding how microscopic spin configuration gives rise to exotic properties at the macroscopic length scale has long been pursued in magnetic materials1-5. One seminal example is the Einstein-de Haas effect in ferromagnets1,6,7, in which angular momentum of spins can be converted into mechanical rotation of an entire object. However, for antiferromagnets without net magnetic moment, how spin ordering couples to macroscopic movement remains elusive. Here we observed a seesaw-like rotation of reciprocal lattice peaks of an antiferromagnetic nanolayer film, whose gigahertz structural resonance exhibits more than an order-of-magnitude amplification after cooling below the Néel temperature. Using a suite of ultrafast diffraction and microscopy techniques, we directly visualize this spin-driven rotation in reciprocal space at the nanoscale. This motion corresponds to interlayer shear in real space, in which individual micro-patches of the film behave as coherent oscillators that are phase-locked and shear along the same in-plane axis. Using time-resolved optical polarimetry, we further show that the enhanced mechanical response strongly correlates with ultrafast demagnetization, which releases elastic energy stored in local strain gradients to drive the oscillators. Our work not only offers the first microscopic view of spin-mediated mechanical motion of an antiferromagnet but it also identifies a new route towards realizing high-frequency resonators8,9 up to the millimetre band, so the capability of controlling magnetic states on the ultrafast timescale10-13 can be readily transferred to engineering the mechanical properties of nanodevices.
ABSTRACT
BACKGROUND: Substantial studies have demonstrated that oxidative stress placenta and endothelial injury are considered to inextricably critical events in the pathogenesis of preeclampsia (PE). Systemic inflammatory response and endothelial dysfunction are induced by the circulating factors released from oxidative stress placentae. As a novel biomarker of oxidative stress, advanced oxidation protein products (AOPPs) levels are strongly correlated with PE characteristics. Nevertheless, the molecular mechanism underlying the effect of factors is still largely unknown. METHODS: With the exponential knowledge on the importance of placenta-derived extracellular vesicles (pEVs), we carried out lncRNA transcriptome profiling on small EVs (sEVs) secreted from AOPPs-treated trophoblast cells and identified upregulated lncRNA TDRKH-AS1 as a potentially causative factor for PE. We isolated and characterized sEVs from plasma and trophoblast cells by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. The expression and correlation of lncRNA TDRKH-AS1 were evaluated using qRT-PCR in plasmatic sEVs and placentae from patients. Pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs was performed to detect the TDRKH-AS1 function in vivo. To investigate the potential effect of sEVs-derived TDRKH-AS1 on endothelial function in vitro, transcriptome sequencing, scanning electron Microscopy (SEM), immunofluorescence, ELISA and western blotting were conducted in HUVECs. RNA pulldown, mass spectrometry, RNA immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP) and coimmunoprecipitation (Co-IP) were used to reveal the latent mechanism of TDRKH-AS1 on endothelial injury. RESULTS: The expression level of TDRKH-AS1 was significantly increased in plasmatic sEVs and placentae from patients, and elevated TDRKH-AS1 in plasmatic sEVs was positively correlated with clinical severity of the patients. Moreover, pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs exhibited a hallmark feature of PE with increased blood pressure and systemic inflammatory responses. Pyroptosis, an inflammatory form of programmed cell death, is involved in the development of PE. Indeed, our in vitro study indicated that sEVs-derived TDRKH-AS1 secreted from AOPPs-induced trophoblast elevated DDIT4 expression levels to trigger inflammatory response of pyroptosis in endothelial cells through interacting with PDIA4. CONCLUSIONS: Herein, results in the present study supported that TDRKH-AS1 in sEVs isolated from oxidative stress trophoblast may be implicated in the pathogenesis of PE via inducing pyroptosis and aggravating endothelial dysfunction.
Subject(s)
Extracellular Vesicles , Pre-Eclampsia , RNA, Long Noncoding , Female , Pregnancy , Humans , Animals , Mice , Endothelial Cells , Pyroptosis , Advanced Oxidation Protein Products , Trophoblasts , RNA-Binding Proteins , Transcription Factors , Protein Disulfide-IsomerasesABSTRACT
Rheumatoid arthritis (RA) is an autoimmune disorder that has been associated with the gut microbiota. However, whether and how the gut microbiota plays a pathogenic role in RA remains unexplored. Here, we observed that Fusobacterium nucleatum is enriched in RA patients and positively associated with RA severity. F. nucleatum similarly aggravates arthritis in a mouse model of collagen-induced arthritis (CIA). F. nucleatum outer membrane vesicles (OMVs) containing the virulence determinant FadA translocate into the joints, triggering local inflammatory responses. Specifically, FadA acts on synovial macrophages, resulting in the activation of the Rab5a GTPase involved in vesicle trafficking and inflammatory pathways and YB-1, a key regulator of inflammatory mediators. OMVs containing FadA and heightened Rab5a-YB-1 expression were observed in RA patients compared with controls. These findings suggest a causal role of F. nucleatum in aggravating RA and provide promising therapeutic targets for clinically ameliorating RA.
Subject(s)
Arthritis, Rheumatoid , Fusobacterium nucleatum , Animals , Mice , Fusobacterium nucleatum/metabolism , Virulence Factors/metabolismABSTRACT
The unique topology and physics of chiral superlattices make their self-assembly from nanoparticles highly sought after yet challenging in regard to (meta)materials1-3. Here we show that tetrahedral gold nanoparticles can transform from a perovskite-like, low-density phase with corner-to-corner connections into pinwheel assemblies with corner-to-edge connections and denser packing. Whereas corner-sharing assemblies are achiral, pinwheel superlattices become strongly mirror asymmetric on solid substrates as demonstrated by chirality measures. Liquid-phase transmission electron microscopy and computational models show that van der Waals and electrostatic interactions between nanoparticles control thermodynamic equilibrium. Variable corner-to-edge connections among tetrahedra enable fine-tuning of chirality. The domains of the bilayer superlattices show strong chiroptical activity as identified by photon-induced near-field electron microscopy and finite-difference time-domain simulations. The simplicity and versatility of substrate-supported chiral superlattices facilitate the manufacture of metastructured coatings with unusual optical, mechanical and electronic characteristics.
Subject(s)
Gold , Metal Nanoparticles , Electronics , PhysicsABSTRACT
Pancreatic cancer (PC) is burdened with a low 5-year survival rate and high mortality due to a severe lack of early diagnosis methods and slow progress in treatment options. To improve clinical diagnosis and enhance the treatment effects, we applied metabolomics using ultra-high-performance liquid chromatography with a high-resolution mass spectrometer (UHPLC-HRMS) to identify and validate metabolite biomarkers from paired tissue samples of PC patients. Results showed that the metabolic reprogramming of PC mainly featured enhanced amino acid metabolism and inhibited sphingolipid metabolism, which satisfied the energy and biomass requirements for tumorigenesis and progression. The altered metabolism results were confirmed by the significantly changed gene expressions in PC tissues from an online database. A metabolites biomarker panel (six metabolites) was identified for the differential diagnosis between PC tumors and normal pancreatic tissues. The panel biomarker distinguished tumors from normal pancreatic tissues in the discovery group with an area under the curve (AUC) of 1.0 (95%CI, 1.000-1.000). The biomarker panel cutoff was 0.776. In the validation group, an AUC of 0.9000 (95%CI = 0.782-1.000) using the same cutoff, successfully validated the biomarker signature. Moreover, this metabolites panel biomarker had a great capability to predict the overall survival (OS) of PC. Taken together, this metabolomics method identifies and validates metabolite biomarkers that can diagnose the onsite progression and prognosis of PC precisely and sensitively in a clinical setting. It may also help clinicians choose proper therapeutic interventions for different PC patients and improve the survival of PC patients.
ABSTRACT
INTRODUCTION: This study developed and validated a nomogram for predicting the risk of second surgery in patients with concomitant esotropia (CE) based on a cohort in Beijing. METHODS: In this retrospective cohort study, the inpatient and outpatient medical records of 419 patients with CE who underwent surgery at the Peking University First Hospital between January 1, 2005 and December 31, 2009 were collected. A total of 357 CE cases were included. For those cases 70% were randomly assigned to the training set (n = 234) and 30% to the validation set (n = 123). Demographic and clinical variables were ascertained at hospital admission and discharge and screened using multivariate Cox proportional hazards regression analysis to construct predictive models and generate a 1-, 4-, and 8-year overall survival nomogram. This nomogram provided an estimate of the risk of second surgery in patients with surgically treated CE. Internal validation was conducted using the concordance index (C-index) and calibration curve for the training and validation sets. RESULTS: Six independent prognostic factors were identified, namely age at surgery, age at onset, amblyopia, deviation angles, surgical amount, and deviation angles 1 week after surgery, and these were entered into the nomogram. The proposed nomogram showed favorable discrimination and accuracy in the training and validation sets. The C-indexes of the training and validation sets were 0.84 (95% CI 0.79-0.89) and 0.80 (95% CI 0.78-0.82), respectively. CONCLUSIONS: The proposed nomogram can serve as a predictive tool for prognostic evaluation of CE surgery.
ABSTRACT
Graves' disease (GD) is an autoimmune thyroid disease (AITD), which is one of the most common organ-specific autoimmune disorders with an increasing prevalence worldwide. But the etiology of GD is still unclear. A growing number of studies show correlations between gut microbiota and GD. The dysbiosis of gut microbiota may be the reason for the development of GD by modulating the immune system. Metabolites act as mediators or modulators between gut microbiota and thyroid. The purpose of this review is to summarize the correlations between gut microbiota, microbial metabolites and GD. Challenges in the future study are also discussed. The combination of microbiome and metabolome may provide new insight for the study and put forward the diagnosis, treatment, prevention of GD in the future.
ABSTRACT
Many reports have shown that patients with Hp-associated chronic gastritis exhibit anxiety and poor sleep quality. However, less is known about the effects and specific manifestations of Hp-associated chronic gastritis on autonomous activity and sleep quality in animals. Here, we investigated the effect of Helicobacter pylori (Hp)-associated chronic gastritis on autonomous activity and sleep quality in mice. To do this, a Hp-associated chronic gastritis mouse model was first established, then analyzed for autonomous activity, relative to controls, for 15 min using an autonomous activity tester. Next, sleep quality of mice was detected by sodium pentobarbital-induced sleep experiment and results compared between groups. The results showed that male mice in the model group exhibited higher activity counts but lower forelimb lift counts, relative to those in the control group, although there were no significant differences (all p > .05). Conversely, female mice in the model group recorded lower activity counts, albeit at no significant difference (p > .05), and significantly lower counts of forelimb lift (p < .05), relative to those in the control group. Notably, male mice in the model group had longer sleep latency and shorter sleep duration than those in the control group, albeit at no significant differences (all p > .05). On the other hand, female mice in the model group recorded significantly longer sleep latency as well as shorter sleep duration compared to those in the control group (all p < .01). We conclude that Hp-associated chronic gastritis exerts certain effects on autonomous activity and sleep quality of mice in a gender-dependent manner. Notably, female mice with Hp-associated chronic gastritis had lower activity and forelimb lift counts, as well as prolonged sleep latency, and shortened sleep duration. These effects were all statistically significant except for activity counts.
ABSTRACT
While blended learning has been growing in popularity in recent years, the effectiveness of this procedure remains controversial. In this report, we assess the effectiveness of blended learning of embryology within international medical students. The participants were international medical students taking embryology in the Bachelor of Medicine and Bachelor of Surgery program. The blended learning group (BLG) consisted of students (n = 43) in the 2018-2019 academic year, taught with blended learning model via a customized small private online course (SPOC). The control traditional teaching group (TTG) consisted students (n = 48) in the 2017-2018 academic year, taught with traditional teaching model. Academic performance, including mean scores and passing ratios on the final exam of two groups were compared and analyzed with a t-test. In addition, a questionnaire directed toward evaluating student's perceptions with the blended learning was administered to students in BLG. The majority of students in BLG actively participated in online self-study activities and discussion in face-to-face class sessions. The mean score and passing ratio were significantly greater than those of students in TTG (p < 0.01). Results from the questionnaire revealed that the majority of BLG students felt that this method was beneficial for their learning of human embryology. The blended learning model, that integrates SPOC with face-to-face class lectures proved a more effective means for the teaching of embryology than the traditional lecture-based teaching model. This blended learning method may serve as a feasible model that can be readily applied for use in other medical courses.