Luciferase Reporter Assay for Determining the Signaling Activity of Interferons.

The classic dual luciferase reporter assay has been widely used to rapidly and accurately determine the transcriptional activity of a given promoter induced by certain signal pathways in the cells. In particular, the sensitive characteristics of luciferase highlight its significance in many experiments, such as weak promoter analysis, transfection studies using small amounts of DNA, and detection in cell lines with low transfection efficiency. This chapter presents detailed information and experimental procedures for measuring interferon (IFN)-induced Interferon-Stimulated Response Element (ISRE) promoter activity using the dual luciferase reporter assay.

Automatic Segmentation of Ultrasound-Guided Quadratus Lumborum Blocks Based on Artificial Intelligence.

Ultrasound-guided quadratus lumborum block (QLB) technology has become a widely used perioperative analgesia method during abdominal and pelvic surgeries. Due to the anatomical complexity and individual variability of the quadratus lumborum muscle (QLM) on ultrasound images, nerve blocks heavily rely on anesthesiologist experience. Therefore, using artificial intelligence (AI) to identify different tissue regions in ultrasound images is crucial. In our study, we retrospectively collected 112 patients (3162 images) and developed a deep learning model named Q-VUM, which is a U-shaped network based on the Visual Geometry Group 16 (VGG16) network. Q-VUM precisely segments various tissues, including the QLM, the external oblique muscle, the internal oblique muscle, the transversus abdominis muscle (collectively referred to as the EIT), and the bones. Furthermore, we evaluated Q-VUM. Our model demonstrated robust performance, achieving mean intersection over union (mIoU), mean pixel accuracy, dice coefficient, and accuracy values of 0.734, 0.829, 0.841, and 0.944, respectively. The IoU, recall, precision, and dice coefficient achieved for the QLM were 0.711, 0.813, 0.850, and 0.831, respectively. Additionally, the Q-VUM predictions showed that 85% of the pixels in the blocked area fell within the actual blocked area. Finally, our model exhibited stronger segmentation performance than did the common deep learning segmentation networks (0.734 vs. 0.720 and 0.720, respectively). In summary, we proposed a model named Q-VUM that can accurately identify the anatomical structure of the quadratus lumborum in real time. This model aids anesthesiologists in precisely locating the nerve block site, thereby reducing potential complications and enhancing the effectiveness of nerve block procedures.

Biosynthesis of nonnutritive monosaccharide d-allulose by metabolically engineered Escherichia coli from nutritive disaccharide sucrose.

Sucrose is a commonly utilized nutritive sweetener in food and beverages due to its abundance in nature and low production costs. However, excessive intake of sucrose increases the risk of metabolic disorders, including diabetes and obesity. Therefore, there is a growing demand for the development of nonnutritive sweeteners with almost no calories. d-Allulose is an ultra-low-calorie, rare six-carbon monosaccharide with high sweetness, making it an ideal alternative to sucrose. In this study, we developed a cell factory for d-allulose production from sucrose using Escherichia coli JM109 (DE3) as a chassis host. The genes cscA, cscB, cscK, alsE, and a6PP were co-expressed for the construction of the synthesis pathway. Then, the introduction of ptsG-F and knockout of ptsG, fruA, ptsI, and ptsH to reprogram sugar transport pathways resulted in an improvement in substrate utilization. Next, the carbon fluxes of the Embden-Meyerhof-Parnas and the pentose phosphate pathways were regulated by the inactivation of pfkA and zwf, achieving an increase in d-allulose titer and yield of 154.2% and 161.1%, respectively. Finally, scaled-up fermentation was performed in a 5 L fermenter. The titer of d-allulose reached 11.15 g/L, with a yield of 0.208 g/g on sucrose.

Latent trajectories of cerebral perfusion pressure and risk prediction models among patients with traumatic brain injury: based on an interpretable artificial neural network.

OBJECTIVE: This study aimed to characterize long-term cerebral perfusion pressure (CPP) trajectory in traumatic brain injury (TBI) patients and construct an interpretable prediction model to assess the risk of unfavorable CPP evolution patterns. METHODS: TBI patients with CPP records were identified from the Medical Information Mart for the Intensive Care (MIMIC)-IV 2.1, eICU Collaborative Research Database (eICU-CRD) 2.0 and HiRID dataset 1.1.1. The research process consisted of two stages. First, group-based trajectory modeling (GBTM) was used to identify different CPP trajectories. Second, different ANN algorithms were employed to predict the trajectories of CPP. RESULTS: A total of 331 eligible patients' records from MIMIC-IV 2.1 and eICU-CRD 2.0 were used for trajectory analysis and model development. Additionally, 310 patients' data from HiRID were used for external validation. The GBTM identified 5 CPP trajectory groups, group 1 and group 5 were merged into class 1 based on unfavorable in-hospital mortality. The best 6 predictors were invasive systolic blood pressure coefficient of variation (ISBPCV), venous blood chloride ion concentration, PaCO2, PT (Prothrombin Time), CPP coefficient of variation (CPPCV), and mean CPP. Compared with other algorithms, Scaled Conjugate Gradient (SCG) performed relatively better in identifying class 1. CONCLUSION: This study identified 2 CPP trajectory groups associated with elevated risk and 3 with reduced risk. PaCO2 might be a strong predictor for the unfavorable CPP class. The ANN model achieved the primary goal of risk stratification, which is conducive to early intervention and individualized treatment.

Symptom Dimensions and Cognitive Impairments in Individuals at Clinical High Risk for Psychosis.

OBJECTIVE: Understanding the intricate relationship between symptom dimensions, clusters, and cognitive impairments is crucial for early detection and intervention in individuals at clinical high-risk(CHR) for psychosis. This study delves into this complex interplay within a CHR sample and aims to predict the conversion to psychosis. METHODS: A comprehensive cognitive assessment was performed among 744 CHR individuals. The study included a three-year follow-up period to assess conversion to psychosis. Symptom profiles were determined using the Structured Interview for Prodromal Syndromes. By applying factor analysis, symptom dimensions were categorized as dominant negative symptoms(NS), positive symptoms-stressful(PS-S), and positive symptoms-odd(PS-O). The factor scores were used to define three dominant symptom groups. Latent class analysis(LCA) and factor mixture model(FMM) were employed to identify discrete clusters based on symptom patterns. The three-class solution was chosen for the LCA and FMM analysis. RESULTS: Individuals in the dominant NS group exhibited significantly higher conversion rates to psychosis than those in the other groups. Specific cognitive variables, including performance in the Brief Visuospatial Memory Test-Revised(Odd ratio, OR=0.702, p=0.001) and Neuropsychological Assessment Battery mazes(OR=0.776, p=0.024), significantly predicted conversion to psychosis. Notably, cognitive impairments associated with NS and PS-S affected different cognitive domains. LCA- and FMM-Cluster 1, characterized by severe NS and PS-O, exhibited more impairments in cognitive domains than other clusters. No significant difference in the conversion rate was observed among LCA and FMM clusters. CONCLUSIONS: These findings highlight the importance of NS in the development of psychosis and suggest specific cognitive domains that are affected by symptom dimensions.

Solvent-Controlled Divergent Cyclization of 3-Ylideneoxindoles with Ethyl 2-Diazoacetate: Access to Spirocyclopropyl and Spiropyrazolines Oxindoles.

Herein a catalyst-free solvent-controlled method for the divergent synthesis of spirocyclopropyl and spiropyrazoline oxindoles from 3-ylideneoxindoles and ethyl diazoacetate was developed. With ClCH2CH2Cl as the solvent, spirocyclopropyl oxindoles were obtained in moderate to excellent yields, whereas the use of MeOH as solvent afforded spiropyrazoline oxindoles in moderate to good yields. The readily available substrates, simple operation and various product transformations further highlighted the utility of this method.

Mycophenolate Mofetil and New-Onset Systemic Lupus Erythematosus: A Randomized Clinical Trial.

Importance: Anti-double-stranded DNA (dsDNA) antibody has been reported to have a close relationship with systemic lupus erythematosus (SLE) flares and participates in the pathogenesis of lupus nephritis (LN) as well as causing damage to other organs. However, whether early use of mycophenolate mofetil (MMF) could prevent SLE flares is not clear. Objective: To assess the efficacy and safety of MMF plus prednisone and hydroxychloroquine sulfate compared with prednisone and hydroxychloroquine sulfate alone in patients with SLE. Design, Setting, and Participants: This investigator-initiated, multicenter, observer-blinded randomized clinical trial enrolled 130 participants aged 18 to 65 years and was conducted in 3 hospitals across China. Treatment-naive patients with newly diagnosed SLE, a high titer of anti-dsDNA antibody, and no major organ involvement were included. The study was started September 1, 2018, and the follow-up was completed September 30, 2021. Data were analyzed from December 1, 2021, to March 31, 2022. Interventions: Patients were randomized 1:1 to receive oral prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) (control group) or prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) plus MMF (500 mg twice daily) (MMF group) for 96 weeks. Main Outcomes and Measures: The primary outcome was the proportion of patients presenting with flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare Index. The secondary outcomes included the proportion with lupus low disease activity state at week 96, 36-Item Short Form Health Survey scores before and after treatment, proportion of adverse events (AEs), and changes in SLEDAI-2000 scores and prednisone doses. Results: Among 130 randomized patients (mean [SD] age, 34.5 [12.5] years; 112 [86.2%] women), 119 (91.5%) completed the follow-up. The risk of severe flare was significantly lower in the MMF group (7 of 65 [10.8%]) vs the control group (18 of 65 [27.7%]) (relative risk [RR], 0.39 [95% CI, 0.17-0.87]; P = .01). Additionally, 1 of 65 patients in the MMF group (1.5%) and 9 of 65 in the control group (13.8%) manifested LN (RR, 0.11 [95% CI, 0.01-0.85]; P = .008). Most common serious study drug-related AEs were infections (20 of 65 [30.8%] in the control group and 22 of 65 [33.8%] in the MMF group). Conclusions and Relevance: The findings of this randomized clinical trial suggest that MMF may reduce the rate of severe flare and lower the incidence of LN in patients with new-onset SLE and a high titer of anti-dsDNA antibody without major organ involvement. Trial Registration: Chinese Clinical Trial Registry: ChiCTR1800017540.

Immunization status and factors influencing hepatitis B vaccination of preterm infants in three provinces of China, 2019 to 2021.

BACKGROUND: Premature infants have less physiologic reserve and often delayed vaccination compared to full-term infants. The birth dose of hepatitis B vaccine (HepB-BD) is an essential measure to achieve the goal of "zero infections" of hepatitis B virus in all newborns. However, there are few investigations of hepatitis B vaccination of preterm infants, leading to uncertainty of coverage and insufficient knowledge of factors influencing timely vaccination of this important population. METHODS: We obtained hepatitis B vaccine (HepB) vaccination histories of premature infants born during 2019-2021 in three provinces from the respective provincial immunization information systems. Extracted data included date of birth, sex, region, and dates of HepB administration. We conducted descriptive analyses that included basic characteristics of the study subjects, HepB-BD administration, and full-series HepB vaccination. Factors potentially influencing HepB-BD and full series vaccination were analyzed by logistic regression. RESULTS: There were 1623 premature infants included in the analytic data set. Overall HepB-BD coverage was 71.41%; coverage among premature infants born to mothers with unknown hepatitis B surface antigen (HBsAg) status was 69.57%; coverage was higher at county-level-and-above hospitals (72.02%) than hospitals below county level (61.11%). Full-series HepB coverage was 94.15%; full-series coverage among preterm infants weighing less than 2000 g at birth was 76.92%. Logistic regression showed that the HepB-BD vaccination rate was positively associated with being born to an HBsAg-positive mother and being preterm with high birth weight. Regression analysis for factors influencing full-series HepB coverage showed that being born prematurely was positively associated with full-series coverage and being premature with a very low birth weight was negatively associated with full-series coverage. CONCLUSIONS: HepB-BD coverage levels in three provinces of China were less than the target of 90%, especially among premature infants born to mothers with unknown HBsAg status and at hospitals below the county level. Screening of pregnant women should be a universal normal standard. Hepatitis B vaccination training should be strengthened in hospitals to improve the HepB-BD vaccination rate of premature infants and to effectively prevent mother-to-child transmission of hepatitis B virus.

Construction and validation of a necroptosis-related prognostic signature in acute myeloid leukemia.

Acute myeloid leukemia (AML), an uncommonly low 5-year survival and high mortality rate, is a potentially catastrophic diagnosed subtype of leukemia. The development of new prognostic markers is urgently needed to guide its treatment. Necroptosis is a newly defined biological process for regulating cell death, and previous studies have confirmed that the abnormality of the physical function can lead to multiple malignancies. Here, we performed necroptosis-related genes (NRGs) to build a predictive model in the Cancer Genome Atlas (TCGA)-AML patients, thus exploring the correlation between the NRG prognosis signature (NRG score) of this model and immune infiltration, pathway activity, clinical features, and immunotherapy. Besides, we computed the statistical measure Spearman rank correlation between the NRG score and the Log IC50 values of therapeutic agents. Subsequently, we divided the TCGA-AML cohort into 2 groups, one with high scores and the other with low scores depending on the model score. AML patients with high NRG scores exhibited a lower estimated overall survival (OS) rate than those with low NRG scores, which was confirmed in the validation set. The prognostic value of the constructed NRG signature to the AML, independent of other variables, was demonstrated by uni- and multivariate stepwise regression analysis. When comparing the infiltrating states of specialized cells associated with immune system from the 2 groups, B cells naive, Plasma cells, and monocytes represented significant differences among various subgroups of samples. Moreover, the 30 hallmark-related pathways related to necroptosis characteristics were remarkably different between the high/low NRG score groups. And patients showed remarkable NRG score distribution in clinical features of bone marrow lymphocyte, category, and FAB classifications. Besides, we found that the BIRB0796, VX680, Vorinostat, and Axitinib positively related with NRG score, whereas CI. 1040, PD. 0325901, Z.L LNle. CHO, and AZD6244 negatively correlated with the NRG score. These drugs may provide a reference for subsequent treatment.

Long-Term Effects of Individualized Acupuncture for Chronic Neck Pain : A Randomized Controlled Trial.

BACKGROUND: Long-term effects of individualized acupuncture in persons with chronic neck pain (CNP) remain unknown. OBJECTIVE: To evaluate the efficacy and safety of pressure pain, sensory-based individualized acupuncture for relieving CNP. DESIGN: A 24-week multicenter randomized controlled clinical trial. (ChiCTR1800016371). SETTING: Outpatient settings at 4 clinical centers in China from May 2018 to March 2020. PARTICIPANTS: 716 participants with CNP. INTERVENTION: Participants were randomly assigned to a waiting list (WL) group or to 1 of 3 interventions, which consisted of 10 sessions over 4 weeks: higher sensitive acupoints (HSA), lower sensitive acupoints (LSA), and sham acupoints (SA) acupuncture groups. MEASUREMENTS: The primary outcome was the change in the visual analogue scale (VAS) score for neck pain (range, 0 to 100) from baseline to 4 weeks, with a difference of 10 points considered the minimum clinically important threshold. The VAS was also assessed every 4 weeks through 24 weeks. RESULTS: The modified intention-to-treat population included 683 participants. The mean baseline VAS was 50.36, 50.10, 49.24, and 49.16 for HSA, LSA, SA, and WL, respectively. Compared with a mean baseline to week 4 change of -12.16 in the HSA group, the mean changes were -10.19 in the LSA group (net difference [ND], -1.97 [95% CI, -5.03 to 1.09]), -6.11 in the SA group (ND, -6.05 [CI, -9.10 to -3.00]), and -2.24 in the WL group (ND, -9.93 [CI, -12.95 to -6.90]). The intervention effects persisted at 24-week follow-up. LIMITATION: Lack of complete blinding and limited generalizability. CONCLUSION: Individualized acupuncture interventions using high- or low-sensitivity acupuncture points were more effective in reducing CNP than SA and WL control groups sustained through 24 weeks, but the magnitude of relative improvement did not reach a minimal clinically important difference. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.

Scopolamine for patients with motion sickness: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Scopolamine has been demonstrated to relieve motion sickness. However, repeated significance testing may increase false-positive results. OBJECTIVES: Review the efficacy and safety of scopolamine in the prevention of motion sickness by performing a meta-analysis with Trial Sequential Analysis (TSA). MATERIAL AND METHODS: Randomized controlled trials (RCTs) compared scopolamine with other medications or placebo were included. Primary outcomes were nausea reported and head movement time. RESULTS: Twenty studies with 753 participants were included. Scopolamine had a greater reported reduction in nausea than placebo (relative risk [RR] 0.35; 95% confidence interval [CI] 0.24 to 0.52; p<0.00001; I2 = 45%), while TSA showed the included sample size exceeded the required information size (RIS). There is no difference in head movement time between scopolamine and placebo (mean difference [MD] 2.02; 95% CI -1.2 to 5.25; p = 0.6; I2 = 0%), while the included sample size did not reach RIS. CONCLUSION: Scopolamine is effective for motion sickness nausea compared to placebo. The TSA recommends conducting more head movement trials to validate the objective efficacy of scopolamine. SIGNIFICANCE: Clarifying the efficacy of scopolamine for motion sickness, the TSA highlights the need for more prospective studies using head movement as an outcome.

Polyzwitterion-grafted decellularized bovine intercostal arteries as new substitutes of small-diameter arteries for vascular regeneration.

Coronary artery bypass grafting is acknowledged as a major clinical approach for treatment of severe coronary artery atherosclerotic heart disease. This procedure typically requires autologous small-diameter vascular grafts. However, the limited availability of the donor vessels and associated trauma during tissue harvest underscore the necessity for artificial arterial alternatives. Herein, decellularized bovine intercostal arteries were successfully fabricated with lengths ranging from 15 to 30 cm, which also closely match the inner diameters of human coronary arteries. These decellularized arterial grafts exhibited great promise following poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) grafting from the inner surface. Such surface modification endowed the decellularized arteries with superior mechanical strength, enhanced anticoagulant properties and improved biocompatibility, compared to the decellularized bovine intercostal arteries alone, or even those decellularized grafts modified with both heparin and vascular endothelial growth factor. After replacement of the carotid arteries in rabbits, all surface-modified vascular grafts have shown good patency within 30 days post-implantation. Notably, strong signal was observed after α-SMA immunofluorescence staining on the PMPC-grafted vessels, indicating significant potential for regenerating the vascular smooth muscle layer and thereby restoring full structures of the artery. Consequently, the decellularized bovine intercostal arteries surface modified by PMPC can emerge as a potent candidate for small-diameter artificial blood vessels, and have shown great promise to serve as viable substitutes of arterial autografts.

Clinical outcomes and ctDNA correlates for CAPOX BETR: a phase II trial of capecitabine, oxaliplatin, bevacizumab, trastuzumab in previously untreated advanced HER2+ gastroesophageal adenocarcinoma.

Preclinical studies suggest that simultaneous HER2/VEGF blockade may have cooperative effects in gastroesophageal adenocarcinomas. In a single-arm investigator initiated clinical trial for patients with untreated advanced HER2+ gastroesophageal adenocarcinoma, bevacizumab was added to standard of care capecitabine, oxaliplatin, and trastuzumab in 36 patients (NCT01191697). Primary endpoint was objective response rate and secondary endpoints included safety, duration of response, progression free survival, and overall survival. The study met its primary endpoint with an objective response rate of 81% (95% CI 65-92%). Median progression free and overall survival were 14.0 (95% CI, 11.3-36.4) and 23.2 months (95% CI, 16.6-36.4), respectively. The median duration of response was 14.9 months. The regimen was well tolerated without unexpected or severe toxicities. In post-hoc ctDNA analysis, baseline ctDNA features were prognostic: Higher tumor fraction and alternative MAPK drivers portended worse outcomes. ctDNA at resistance identified oncogenic mutations and these were detectable 2-8 cycles prior to radiographic progression. Capecitabine, oxaliplatin, trastuzumab and bevacizumab shows robust clinical activity in HER2+ gastroesophageal adenocarcinoma. Combination of VEGF inhibitors with chemoimmunotherapy and anti-PD1 regimens is warranted.

Clinical utility of a blood based assay for the detection of IDH1.R132H-mutant gliomas.

Glioma represents the most common central nervous system neoplasm in adults. Current classification scheme utilizes molecular alterations, particularly IDH1.R132H, to stratify lesions into distinct prognostic groups. Identification of the single nucleotide variant through traditional tissue biopsy assessment poses procedural risks and does not fully reflect the heterogeneous and evolving tumor landscape. Here, we introduce a liquid biopsy assay, mt-IDH1dx. The blood-based test allows minimally invasive detection of tumor-derived extracellular vesicle RNA using only 2 ml plasma volume. We perform rigorous, blinded validation testing across the study population (n = 133), comprising of IDH1.R132H patients (n = 80), IDH1 wild-type gliomas (n = 44), and age matched healthy controls (n = 9). Results from our plasma testing demonstrate an overall sensitivity of 75.0% (95% CI: 64.1%-84.0%), specificity 88.7% (95% CI: 77.0%-95.7%), positive predictive value 90.9%, and negative predictive value 70.1% compared to the tissue gold standard. In addition to fundamental diagnostic applications, the study also highlights the utility of mt-IDH1dx platform for blood-based monitoring and surveillance, offering valuable prognostic information. Finally, the optimized workflow enables rapid and efficient completion of both tumor tissue and plasma testing in under 4 hours from the time of sampling.

Engineering Escherichia coli for D-allulose biosynthesis from glycerol.

D-allulose, a naturally occurring monosaccharide, is present in small quantities in nature. It is considered a valuable low-calorie sweetener due to its low absorption in the digestive tract and zero energy for growth. Most of the recent efforts to produce D-allulose have focused on in vitro enzyme catalysis. However, microbial fermentation is emerging as a promising alternative that offers the advantage of combining enzyme manufacturing and product synthesis within a single bioreactor. Here, a novel approach was proposed for the efficient biosynthesis of D-allulose from glycerol using metabolically engineered Escherichia coli. FbaA, Fbp, AlsE, and A6PP were used to construct the D-allulose synthesis pathway. Subsequently, PfkA, PfkB, and Pgi were disrupted to block the entry of the intermediate fructose-6-phosphate (F6P) into the Embden-Meyerhof-Parnas (EMP) and pentose phosphate (PP) pathways. Additionally, GalE and FryA were inactivated to reduce D-allulose consumption by the cells. Finally, a fed-batch fermentation process was implemented to optimize the performance of the cell factory. As a result, the titer of D-allulose reached 7.02 g/L with a maximum yield of 0.287 g/g.

The role of lncRNAs related ceRNA regulatory network in multiple hippocampal pathological processes during the development of perioperative neurocognitive disorders.

Background: Perioperative neurocognitive disorders (PND) refer to neurocognitive abnormalities during perioperative period, which are a great challenge for elderly patients and associated with increased morbidity and mortality. Our studies showed that long non-coding RNAs (lncRNAs) regulate mitochondrial function and aging-related pathologies in the aged hippocampus after anesthesia, and lncRNAs are associated with multiple neurodegenerations. However, the regulatory role of lncRNAs in PND-related pathological processes remains unclear. Methods: A total of 18-month mice were assigned to control and surgery (PND) groups, mice in PND group received sevoflurane anesthesia and laparotomy. Cognitive function was assessed with fear conditioning test. Hippocampal RNAs were isolated for sequencing, lncRNA and microRNA libraries were constructed, mRNAs were identified, Gene Ontology (GO) analysis were performed, and lncRNA-microRNA-mRNA networks were established. qPCR was performed for gene expression verification. Results: A total of 312 differentially expressed (DE) lncRNAs, 340 DE-Transcripts of Uncertain Coding Potential (TUCPs), and 2,003 DEmRNAs were identified in the hippocampus between groups. The lncRNA-microRNA-mRNA competing endogenous RNA (ceRNA) network was constructed with 29 DElncRNAs, 90 microRNAs, 493 DEmRNAs, 148 lncRNA-microRNA interaction pairs, 794 microRNA-mRNA interaction pairs, and 110 lncRNA-mRNA co-expression pairs. 795 GO terms were obtained. Based on the frequencies of involved pathological processes, BP terms were divided into eight categories: neurological system alternation, neuronal development, metabolism alternation, immunity and neuroinflammation, apoptosis and autophagy, cellular communication, molecular modification, and behavior changes. LncRNA-microRNA-mRNA ceRNA networks in these pathological categories were constructed, and involved pathways and targeted genes were revealed. The top relevant lncRNAs in these ceRNA networks included RP23-65G6.4, RP24-396L14.1, RP23-251I16.2, XLOC_113622, RP24-496E14.1, etc., and the top relevant mRNAs in these ceRNA networks included Dlg4 (synaptic function), Avp (lipophagy), Islr2 (synaptic function), Hcrt (regulation of awake behavior), Tnc (neurotransmitter uptake). Conclusion: In summary, we have constructed the lncRNA-associated ceRNA network during PND development in mice, explored the role of lncRNAs in multiple pathological processes in the mouse hippocampus, and provided insights into the potential mechanisms and therapeutic gene targets for PND.

A Transdiagnostic Network Analysis of Childhood Trauma and Psychopathology.

BACKGROUND AND HYPOTHESIS: Psychiatric comorbidities suggest that symptoms overlap across different diagnoses; the transdiagnostic network approach is valuable for studying psychopathology. Childhood trauma is a common transdiagnostic risk factor for psychiatric disorders, but the complex relationship between childhood trauma and psychopathology has seldom been investigated using a large cross-sectional transdiagnostic sample. STUDY DESIGN: This study recruited 869 patients with different diagnoses, including 418 schizophrenia, 215 bipolar disorder, and 236 major depressive disorder. Participants completed psychiatric interviews and self-report questionnaires. We constructed dimension- and item-level Least Absolute Shrinkage and Selection Operator-based (LASSO) networks to explore the relationship between childhood trauma, psychopathology, and duration of illness. Moreover, we constructed directed acyclic graphs (DAGs) to tentatively clarify the potential directions of associations among these variables. Network Comparison Tests (NCTs) were conducted for different diagnostic groups and gender-stratified groups. STUDY RESULTS: The transdiagnostic LASSO networks showed that different types of childhood trauma exerted distinct impacts on various psychopathological dimensions. Emotional abuse was linked to depressive symptoms, physical abuse to excited symptoms, sexual abuse to positive and disorganized symptoms, emotional neglect to depressive symptoms and motivation and pleasure (MAP) deficits factor of negative symptoms, and physical neglect to MAP factor. The DAG findings generally concurred with the LASSO network. The NCT showed comparable networks. CONCLUSIONS: Our findings suggest that childhood trauma is significantly associated with the development of psychopathology across different diagnostic groups. The affective pathway model suggests that early identification and tailored interventions would be needed for people with a history of childhood trauma.

Glymphatic function and its influencing factors in different glucose metabolism states.

BACKGROUND: Dysfunction of the glymphatic system in the brain in different stages of altered glucose metabolism and its influencing factors are not well characterized. AIM: To investigate the function of the glymphatic system and its clinical correlates in patients with different glucose metabolism states, the present study employed diffusion tensor imaging along the perivascular space (DTI-ALPS) index. METHODS: Sample size was calculated using the pwr package in R software. This cross-sectional study enrolled 22 patients with normal glucose metabolism (NGM), 20 patients with prediabetes, and 22 patients with type 2 diabetes mellitus (T2DM). A 3.0T magnetic resonance imaging was used to evaluate the function of the glymphatic system. The mini-mental state examination (MMSE) was used to assess general cognitive function. The DTI-ALPS index of bilateral basal ganglia and the mean DTI-ALPS index was calculated. Further, the correlation between DTI-ALPS and clinical features was assessed. RESULTS: The left-side, right-side, and mean DTI-ALPS index in the T2DM group were significantly lower than that in the NGM group. The right-side DTI-ALPS and mean DTI-ALPS index in the T2DM group were significantly lower than those in the prediabetes group. DTI-ALPS index lateralization was not observed. The MMSE score in the T2DM group was significantly lower than that in the NGM and prediabetes group. After controlling for sex, the left-side DTI-ALPS and mean DTI-ALPS index in the prediabetes group were positively correlated with 2-hour postprandial blood glucose level; the left-side DTI-ALPS index was negatively correlated with total cholesterol and low-density lipoprotein level. The right-side DTI-ALPS and mean DTI-ALPS index were negatively correlated with the glycosylated hemoglobin level and waist-to-hip ratio in the prediabetes group. The left-side, right-side, and mean DTI-ALPS index in the T2DM group were positively correlated with height. The left-side and mean DTI-ALPS index in the T2DM group were negatively correlated with high-density lipoprotein levels. CONCLUSION: Cerebral glymphatic system dysfunction may mainly occur in the T2DM stage. Various clinical variables were found to affect the DTI-ALPS index in different glucose metabolism states. This study enhances our understanding of the pathophysiology of diabetic brain damage and provides some potential biological evidence for its early diagnosis.

Accuracy of continuous glucose monitoring in the hospital setting: an observational study.

AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) improves glycaemic outcomes in the outpatient setting; however, there are limited data regarding CGM accuracy in hospital. METHODS: We conducted a prospective, observational study comparing CGM data from blinded Dexcom G6 Pro sensors with reference point of care and laboratory glucose measurements during participants' hospitalisations. Key accuracy metrics included the proportion of CGM values within ±20% of reference glucose values >5.6 mmol/l or within ±1.1 mmol/l of reference glucose values ≤5.6 mmol/l (%20/20), the mean and median absolute relative difference between CGM and reference value (MARD and median ARD, respectively) and Clarke error grid analysis (CEGA). A retrospective calibration scheme was used to determine whether calibration improved sensor accuracy. Multivariable regression models and subgroup analyses were used to determine the impact of clinical characteristics on accuracy assessments. RESULTS: A total of 326 adults hospitalised on 19 medical or surgical non-intensive care hospital floors were enrolled, providing 6648 matched glucose pairs. The %20/20 was 59.5%, the MARD was 19.2% and the median ARD was 16.8%. CEGA showed that 98.2% of values were in zone A (clinically accurate) and zone B (benign). Subgroups with lower accuracy metrics included those with severe anaemia, renal dysfunction and oedema. Application of a once-daily morning calibration schedule improved accuracy (MARD 11.4%). CONCLUSIONS/INTERPRETATION: The CGM accuracy when used in hospital may be lower than that reported in the outpatient setting, but this may be improved with appropriate patient selection and daily calibration. Further research is needed to understand the role of CGM in inpatient settings.

The impact of diabetes, hypercholesterolemia, and low-density lipoprotein (LDL) on the survival of cervical cancer patients.

BACKGROUND: Cervical cancer is a prevalent malignancy and an important health concern worldwide. Recent research has highlighted the potential impact of metabolic factors, such as hyperlipidemia and diabetes, on cancer progression, increased mortality, and patient outcomes. However, insufficient data have been reported regarding their relationship with cervical cancer. This study aimed to investigate the relationships between metabolic disorders, including dyslipidemia, dysglycemia, and metabolic syndrome, and survival in patients with cervical cancer. METHODS: We retrospectively analyzed demographic information, clinical characteristics, and metabolic health indicators of patients with cervical cancer. Patients were categorized into groups based on specific metabolic conditions: high triglyceride, high low-density lipoprotein, high cholesterol, and diabetes groups. Additionally, the presence of metabolic syndrome and other metabolic comorbidities was recorded. The log-rank test was used to compare survival rates between different patient groups and identify associated risk factors. Survival curves generated via the Cox proportional hazards model were used to evaluate the associations between metabolic parameters and survival. RESULTS: The Cox proportional hazards model was used to analyze data from 840 patients with cervical cancer between 28 and 72 years old who underwent surgery. The hazard ratio (HR) of mortality was 1.804 (95% CI 1.394-2.333, p < 0.001) in the high-density lipoprotein group, 0.758 (95% CI 0.558 to 1.030, p < 0.001) in the high-triglyceride group, 1.794 (95% CI 1.304-2.470, p < 0.001) in the high low-density lipoprotein group, and 0.011 (95% CI 0.005-0.025, p < 0.001) in the diabetes group. These factors were significantly associated with reduced survival in patients with cervical cancer, and these associations persisted after adjusting for age, cancer stage, treatment type, and the presence of metabolic syndrome or other comorbidities. CONCLUSION: This study highlights the importance of metabolic health and the significance of controlling metabolic disorders, including hyperlipidemia, diabetes, and metabolic syndrome, to improve survival outcomes in patients with cervical cancer. Future research should explore the impact of managing multiple metabolic conditions on the prognosis of these patients.