Targeting AQP9 enhanced the anti-TNF therapy response in Crohn's disease by inhibiting LPA-hippo pathway.

Although anti-TNF antibodies are extensively used to treat Crohn's disease (CD), a significant proportion of patients, up to 40%, exhibit an inadequate response to this therapy. Our objective was to identify potential targets that could improve the effectiveness of anti-TNF therapy in CD. Through the integration and analysis of transcriptomic data from various CD databases, we found that the expression of AQP9 was significantly increased in anti-TNF therapy-resistant specimens. The response to anti-TNF therapy in the CD mouse model was significantly enhanced by specifically inhibiting AQP9. Further experiments found that the blockade of AQP9, which is dominantly expressed in macrophages, decreased inflamed macrophage functions and cytokine expression. Mechanistic studies revealed that AQP9 transported glycerol into macrophages, where it was metabolized to LPA, which was further metabolized to LPA, resulting in the activation of the LPAR2 receptor and downstream hippo pathway, finally promoting the expression of cytokines, especially IL23 and IL1ß⊡ Taken together, the expansion of AQP9+ macrophages is associated with resistance to anti-TNF therapy in Crohn's disease. These findings indicated that AQP9 could be a potential target for enhancing anti-TNF therapy in Crohn's disease.

Treatment of multisystem inflammatory syndrome in children.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a relatively uncommon but severe pediatric complication, is associated with coronavirus disease 2019 (COVID-19). A variety of treatment approaches, including intravenous immunoglobulins (IVIGs), glucocorticoids (GCs) and biologic agents, such as anakinra and infliximab, have been described for the management of COVID-19-related MIS-C. Anticoagulant therapy is also important. However, a well-developed treatment system has not been established, and many issues remain controversial. Several recently published articles related to the treatment of MIS-C have been released. Hence, in this review, we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and systematically. DATA SOURCES: We reviewed the literature on the treatment of MIS-C through 20 September 2023. The PubMed/Medline, Web of Science, EMBASE, and Cochrane Library databases were searched with the combination of the terms "multisystem inflammatory syndrome", "MIS-C", "PIMS-TS", "therapy", "treatment", "drug", "IVIG", "GCs", "intravenous immunoglobulin", "corticosteroids", "biological agent", and "aspirin". RESULTS: The severity of MIS-C varies, and different treatment schemes should be used according to the specific condition. Ongoing research and data collection are vital to better understand the pathophysiology and optimal management of MIS-C. CONCLUSIONS: MIS-C is a disease involving multiple systems and has great heterogeneity. With the accumulation of additional experience, we have garnered fresh insights into its treatment strategies. However, there remains a critical need for greater standardization in treatment protocols, alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols. Supplementary file1 (MP4 208044 kb).

High spatiotemporal-resolution mapping for a seasonal erosion flooding inundation using time-series Landsat and MODIS images.

Seasonal erosion flooding events present a significant challenge for effective disaster monitoring and land degradation studies. This research addresses this challenge by harnessing the combined capabilities of time-series Landsat and MODIS images to achieve high spatiotemporal-resolution mapping of flooding during such events. The study underscores the critical importance of precise flood monitoring for disaster mitigation and informed land management. To overcome the limitations posed by the trade-off between spatial and temporal resolution in current satellite sensors, we emplyedand theflexible spatiotemporal data fusion (FSDAF) methods to produce synthetic flood images with enhanced spatiotemporal resolutions for mapping by using MODIS and Landsat data from August 29 to September 3, 2016. A comparison was made between flood maps from several post-disaster forecasts based on ground-obtained time-series images of the Tumen River flood in China. According to the FSDAF approach, the input Landsat image of March 25, 2016, and the fused results had a root mean square error (RMSE) of 0.0301, average difference of 0.001, r of 0.941, and structure similarity indexof 0.939, indicating that temporal variation data had been effectively incorporated into a forecast on August 16, 2016. Results also indicated that the FSDAF forecast values are lower than those from the actual Landsat image. The results of the study also showed that the generated images could be effectively used for flood mapping. By using our newly developed simulation model, we were able to produce a comprehensive map of the inundated areas during the event from August 29 to September 3, 2016. This shows that FSDAF holds great potential for flood prediction and study and has the potential to benefit further disaster-related land degradation by combining multi-source images to provide high temporal and spatial resolution remote sensing information.

Quantitative evaluation of retinal and choroidal vascularity in systemic lupus erythematosus by SS-OCT/OCTA.

PURPOSE: To evaluate changes in retinal and choroidal vascularity using swept-source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (OCTA) in patients with systemic lupus erythematosus (SLE). METHODS: In this prospective, cross-sectional study, 48 SLE patients and 40 healthy control (group HC) participants were included. The SLE patients were divided into two subgroups: patients with SLE with no ocular disease (group I) and patients with SLE with signs of retinopathy (group II). The superficial vessel density (SVD), deep vessel density (DVD), peripapillary retinal vessel densities (pRVD), choroidal thickness (ChT), and choroidal vascularity including total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI) were measured using SS-OCT/OCTA. Physical and ophthalmic examinations as well as the assessments of immunological markers were performed. The results of SS-OCT/OCTA were compared between group I, group II, and group HC, while the correlations among the parameters were analyzed. RESULTS: The SVD, DVD, and pRVD were found to be significantly lower in SLE patients than group HC, especially in SLE patients with signs of retinopathy. ChT were found to be significantly higher in group II. CVI was positively correlated with SVD and DVD in the fovea, as well as the foveal and parafoveal thickness. A significant decrease in SVD and DVD in the fovea among subjects positive for anti-dsDNA antibodies was noted. CONCLUSIONS: The application of OCTA in the evaluation of microvasculature may be useful in subclinical changes. Retinal microvascular density decreased in patients with SLE with greater severity of SLE. Disturbed retinal circulation was related to SLE disease activity, disease duration, CVI, and being positive for anti-dsDNA antibodies. The study results also suggest that SLE with signs of retinopathy may affect the choroid with increases in LA, SA, TCA, and ChT.

The Therapeutic Effects of EFNB2-Fc in a Cell Model of Kawasaki Disease.

The EphrinB2/EphB4 signaling pathway involves the regulation of vascular morphogenesis and angiogenesis. However, little is known about EphrinB2/EphB4 in the pathogenesis of Kawasaki disease (KD) and coronary artery aneurysm formation. Hence, this study aimed to explore the role of EphrinB2/EphB4 and the potential therapeutic effect of EphrinB2-Fc in the coronary arterial endothelial injury of KD. The levels of EphB4 were compared between KD patients and healthy children. Human coronary artery endothelial cells (HCAECs) were stimulated with sera from acute KD patients to establish the KD cell model. The overexpression of EphB4 or treatment with EphrinB2-Fc was found to intervene in the cell model. The cell migration, angiogenesis, and proliferation ability were assessed, and the expression of inflammation-related factors was measured. Our study showed that EphB4 showed low expression in both KD patients and the cell model of KD. The EphB4 protein levels in the CECs of CAA+ KD patients were much lower than those in healthy children. EphrinB2-Fc treatment of KD sera-activated HCAECs suppressed cell proliferation, reduced the expression of inflammation-related factors (such as IL-6 and P-selectin), and elevated cell angiogenesis ability. The results reveal that EphrinB2-Fc has a protective function in endothelial cells and has promising clinical applications for protecting vascular endothelium in patients with KD.

Sialylated IVIg binding to DC-SIGN+ Hofbauer cells induces immune tolerance through the caveolin-1/NF-kB pathway and IL-10 secretion.

Although the use of IVIg has increased in various immune-driven diseases and even in pregnancy, the exact action mechanisms of IVIg are not fully understood. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) is a known receptor for α-2,6-sialylated IgG (sIVIg), which is responsible for the anti-inflammatory effect of IVIg. DC-SIGN is expressed on Hofbauer cells (HBCs) of the fetal villi of the placenta which act as an innate immune modulator at the maternal-fetal interface. Preeclampsia is a major complication in pregnancy and is related to IL-10, a cytokine with an important role in immune tolerance. DC-SIGN interaction with sIVIg in HBCs promoted IL-10 secretion through the activation of the caveolin-1/NF-κB pathway, especially in plasma lipid rafts. Consistent results were obtained for HBCs from patients with preeclampsia. Collectively, the stimulation of DC-SIGN+ HBCs with sIVIg enhanced immune tolerance in the feto-maternal environment, suggesting the therapeutic application of sIVIg to prevent preeclampsia.

Development of a fermentation strategy to enhance the catalytic efficiency of recombinant Escherichia coli for l-2-aminobutyric acid production.

Microbial fermentation for enzyme production and then whole-cell catalysis for l-2-aminobutyric acid (l-ABA) production have huge potential for industrial application, but the catalytic capacities of cells are directly related to the fermentation process. Using a 50 L fermenter, the effects of initial glycerol concentration in the medium and rotating speed on cell catalytic capacity were investigated. Fermentation cells showed the best catalytic activity when the initial glycerol concentration was 12 g/L and the rotating speed was 250 rpm. Furthermore, we studied the difference between glycerol and glycerol mixtures as fed-batch media in pH-stat fed-batch fermentation. Results showed that glycerol had better catalytic activity than the glycerol mixture, and the effect of fed-batch fermentation was better than batch fermentation. Meanwhile, the enzyme activities of leucine dehydrogenase and formate dehydrogenase reached 129.87 U/g DCW and 437.02 U/g DCW, respectively, and the intracellular NAD(H) concentration reached 14.94 µmol/g DCW. Using the optimized fermentation parameters, amplified fermentation was then carried out in a 5000 L fermenter to demonstrate the industrial production of l-ABA by Escherichia coli BL21.

Cluster of differentiation 19 chimeric antigen receptor T-cell therapy in pediatric acute lymphoblastic leukemia.

Chimeric antigen receptor (CAR) T cells have an unprecedented positive curative effect for hematological malignances. Most notably, cluster of differentiation 19 (CD19) CAR T-cell therapy for pediatric acute lymphoblastic leukemia is associated with a high complete remission rate and has aroused considerable attention in the medical field. However, it also causes a series of adverse reactions and increases the risk of recurrence. The present review examines the results of CD19 CAR T-cell therapy and lists its adverse effects. In addition, some of the mechanisms of recurrence are characterized and applicable strategies to address this challenging problem are proposed.

Management of isolated oligohydramnios in Korea: a questionnaire-based study of clinical practice patterns among the members of the Korean Society of Maternal Fetal Medicine.

OBJECTIVE: The aim of this survey was to investigate the recommendations and clinical practice patterns of the Korean Society of Maternal and Fetal Medicine (KSMFM) members, regarding management of isolated oligohydramnios (IO). METHODS: From December 2018 to February 2019, questionnaires were e-mailed to the KSMFM members at 257 institutes that are listed by the Korean Statistical Information Services (KOSIS) as suitable labor premises. Responses to the seven questions on the management of IO, from diagnosis to treatment, were evaluated. RESULTS: A total of 72 KSMFM members responded to this survey. Nearly all participants (90.1%) used the amniotic fluid index (AFI) as the primary method for estimating amniotic fluid volume. The majority of the participants (73.6%) believed that IO was a risk factor for adverse pregnancy outcomes, including abnormal fetal heart rate (73.6%), need for cesarean delivery (58.3%), intrauterine fetal demise (52.8%), and meconium aspiration syndrome (50%). Almost 70% of the participants believed that induction of labor might decrease perinatal morbidities, and that late-preterm to early-term period (36-38 gestational weeks) was a suitable timeframe for delivery, if the fetus was sufficiently grown and antenatal testing revealed reassuring results. Less than half of the participants (47.2%) believed that maternal oral or intravenous hydration was a useful intervention for IO management. CONCLUSIONS: KSMFM members preferred labor induction at late-preterm to early-term, to decrease perinatal morbidity in cases of IO, although it was still uncertain whether labor induction improved the outcomes. Further prospective studies are needed regarding IO management.

Evaluation of maternal rhesus blood type as a risk factor in adverse pregnancy outcomes in Korea: a nationwide health insurance database study.

OBJECTIVES: The current study aimed to investigate whether pregnancy outcomes are affected by maternal rhesus (Rh) status by comparing the primigravida pregnancy outcomes of Rh-negative women with those of Rh-positive women. METHODS: The study data were collected from the Korea National Health Insurance Claims Database and the National Health Screening Program for Infants and Children. In total, 1,664,882 primigravida women who gave birth between January 1, 2007 and December 31, 2014, were enrolled in this study. As the risk and severity of sensitization response increases with each subsequent pregnancy, only primigravida women were enrolled. The patients were divided into 2 groups according to Rh status, and the pregnancy outcomes were compared. RESULTS: In total, 1,661,320 women in the Rh-positive group and 3,290 in the Rh-negative group were assessed. With regard to adverse pregnancy outcomes, there was no statistically significant difference between the 2 groups in terms of the prevalence of preeclampsia, postpartum hemorrhage, abruptio placenta, placenta previa, and uterine artery embolization. A univariate analysis revealed that none of the adverse pregnancy outcomes were significantly correlated to Rh status (preeclampsia: odds ratio [OR], 1.00, 95% confidence interval [CI], 0.81-1.23; postpartum hemorrhage: OR, 1.10, 95% CI, 0.98-1.24; abruptio placenta: OR, 0.80, 95% CI, 0.46-1.37; and placenta previa: OR, 1.08, 95% CI, 0.78-1.42). The adjusted ORs of postpartum hemorrhage and preterm birth did not significantly differ. CONCLUSION: Maternal Rh status is not associated with adverse outcomes in primigravida women.

Efficacy of blood purification for severe pancreatitis and acute respiratory distress syndrome.

BACKGROUND: This study will assess the efficacy and safety of blood purification (BP) for severe pancreatitis (SP) and acute respiratory distress syndrome (ARDS). METHODS: We will search the following electronic databases of Ovid MEDLINE, EMBASE, Web of Science, Cochrane Library, Scopus, Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and WANGFANG from inception to the present without language restriction. A systematic review and data synthesis will be carried out of randomized controlled trials of BP for the treatment of patients with SP and ARDS. RevMan 5.3 software will be used for statistical analysis. RESULTS: This systematic review will evaluate the efficacy and safety of BP for the treatment of patients with SP and ARDS. The primary outcome includes respiratory indexes, blood biochemical and inflammatory factors. The secondary outcomes consist of complications, sepsis, abdominal hemorrhage, renal failure, length of hospital stay, and mortality. CONCLUSION: This study will provide up-to-date evidence of BP for the treatment of patients with SP and ARDS. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019139467.

Investigation of a Signal Demodulation Method based on Wavelet Transformation for OFDR to Enhance Its Distributed Sensing Performance.

Optical fiber distributed sensing that is based on optical frequency domain reflectometer (OFDR) is a promising technology for achieving a highest spatial resolution downwards to several millimeters. An OFDR signal demodulation method that is based on Morlet wavelet transformation (WT) is demonstrated in detail to improve the resolution of distributed sensing physical quantity under a high spatial resolution, aiming at the trade-off between spatial and spectrum resolution. The spectrum resolution, spatial interval of the measured gauges, and spatial resolution can be manually controlled by adjusting the wavelet parameters. The experimental results that were achieved by the wavelet transformation (WT) method are compared with these by short time Fourier transformation (STFT) method and they indicate that significant improvements, such as strain resolution of 1 µÎµ, spatial resolution of 5 mm, average repeatability of 4.3 µÎµ, and stability of 7.3 µÎµ within one hour, have been achieved. The advantages of this method are high spatial and spectral resolution, robust, and applicability with current OFDR systems.

Efficacy of erlotinib and celecoxib for patients with advanced non-small cell lung cancer: A retrospective study.

This study evaluated the efficacy and toxicity of erlotinib and celecoxib (EC) for treating Chinese patients with advanced non-small cell lung cancer (ANSCLC) and epidermal growth factor receptor (EGFR) wild type.Totally, 75 subjects with ANSCLC and EGFR wild type were included. They all underwent EC treatment. The outcome measurements consisted of progression-free survival (PFS), overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), and disease control rate (DCR). Additionally, adverse events were also documented.Two-year CR, PR, SD, PD, and DCR were 4.0%, 6.7%, 42.6%, 46.7%, and 53.3% respectively. The median PFS was 3.4 months, the median OS was 10.0 months. Additionally, acceptable toxicities were recorded in this study.The results showed that EC may be efficacious for patients with ANSCLC and EGFR wild type only, and acceptable toxicity among the Chinese Han population.

Enhancement of the Performance and Data Processing Rate of an Optical Frequency Domain Reflectometer Distributed Sensing System Using A Limited Swept Wavelength Range.

A novel optical frequency domain reflectometer (OFDR) processing algorithm is proposed to enhance the measurable range and data processing rate using a narrow swept spectrum range and reducing the time consuming of the process distributed sensing results. To reduce the swept wavelength range and simultaneously enhance strain measurable range, the local similarity characteristics of Rayleigh scattering fingerprint spectrum is discovered and a new similarity evaluation function based on least-square method is built to improve the data processing rate and sensing performance. By this method, the strain measurable range is raised to 3000 µÎµ under a highest spatial resolution of 3 mm when the swept spectrum range is only 10 nm and the data processing rate is improved by at least 10 times. Experimental results indicate that a nonlinearity of less than 0.5%, a strain resolution of better than 10 µÎµ, a repeatability at zero strain of below ±0.4 GHz and a full-scale accuracy is lower than 0.85 GHz under a highest spatial resolution of 3 mm can be achieved. Advantages of this method are fast processing rate, large strain measurable range, high SNR, and applicability with current OFDR systems.

Investigation of a Three-Dimensional Micro-Scale Sensing System Based on a Tapered Self-Assembly Four-Cores Fiber Bragg Grating Probe.

Three-dimensional micro-scale sensors are in high demand in the fields of metrology, precision manufacturing and industry inspection. To extend the minimum measurable dimension and enhance the accuracy, a tapered four-cores fiber Bragg grating (FBG) probe is proposed. The sensing model is built to investigate the micro-scale sensing characteristics of this method and the design of the tapered stylus is found to influence the accuracy. Therefore, a π/2 phase-shift point is introduced into the FBGs comprised in the probe to suppress spectrum distortion and improve accuracy. Then, the manufacturing method based on capillary self-assembly is proposed to form the probe and the critical length to form a square array for four cylindrical fibers is verified to be effective for the tapered fibers. Experimental results indicate that the design of the tapered stylus can extend the minimum measurable dimension by twofold and has nearly no influence on its sensitivity. The three-dimensional measurement repeatability is better than 31.1 nm and the stability is better than 200 nm within once measuring process. Furthermore, the measurement precision of the three-dimensional micro-scale measurement results is less than 150 nm. It would be widely used in measuring micro-scale features for industry inspection or metrology.

Improvement of the strain measurable range of an OFDR based on local similar characteristics of a Rayleigh scattering spectrum.

The decrease of overlap between the reference spectrum and measurement spectrum (ReS and MeS) is found to limit the strain measurable range of the optical frequency domain reflectometer (OFDR) and signal-to-noise ratio (SNR) of cross-correlation results. In this Letter, the local similar characteristics of Rayleigh scattering (RS) fingerprint spectrum are discovered and, thus, an improved OFDR based on local similarity of RS spectrum is proposed to ensure the feasibility of the OFDR during measuring a large distribution strain with a high spatial resolution. The normalized length and location of the local spectrum are optimized to obtain a high spectral similarity between the ReS and MeS and achieve a robust suppression on cross-correlation fake peaks and multi-peaks. By this method, four times enhancement of similarity is experimentally achieved, compared to conventional OFDR methods when the measured distribution strain varies from 0 to 3000 µÏµ with a 3 mm long fiber gauge. The experimental results verify that it effectively avoids influences of fake peaks and multi-peaks. The advantages of this method are a large strain measurable range, robust performance, a high SNR, and applicability with current OFDR systems.