Early hyperbaric oxygen therapy through regulating the HIF-1α signaling pathway attenuates Neuroinflammation and behavioral deficits in a mouse model of Sepsis-associated encephalopathy.

BACKGROUND: Sepsis-associated encephalopathy (SAE) presents a significant clinical challenge, associated with increased mortality and healthcare expenses. Hyperbaric oxygen therapy (HBOT), involving inhaling pure or highly concentrated oxygen under pressures exceeding one atmosphere, has demonstrated neuroprotective effects in various conditions. However, the precise mechanisms underlying its protective actions against sepsis-associated brain injury remain unclear. This study aimed to determine whether HBOT protects against SAE and to elucidate the impact of the hypoxia-inducible factor-1α (HIF-1α) signaling pathway on SAE. METHODS: The experiment consisted of two parts. In the first part, C57BL/6 J male mice were divided into five groups using a random number table method: control group, sham surgery group, sepsis group, HBOT + sepsis group, and HBOT + sham surgery group. In the subsequent part, C57BL/6 J male mice were divided into four groups: sepsis group, HBOT + sepsis group, HIF-1α + HBOT + sepsis group, and HIF-1α + sepsis group. Sepsis was induced via cecal ligation and puncture (CLP). Hyperbaric oxygen therapy was administered at 1 h and 4 h post-CLP. After 24 h, blood and hippocampal tissue were collected for cytokine measurements. HIF-1α, TNF-α, IL-1ß, and IL-6 expression were assessed via ELISA and western blotting. Microglial expression was determined by immunofluorescence. Blood-brain barrier permeability was quantified using Evans Blue. Barnes maze and fear conditioning were conducted 14 days post-CLP to evaluate learning and memory. RESULTS: Our findings reveal that CLP-induced hippocampus-dependent cognitive deficits coincided with elevated HIF-1α and increased TNF-α, IL-1ß, and IL-6 levels in both blood and hippocampus. Observable activation of microglial cells in the hippocampus and increased blood-brain barrier (BBB) permeability were also evident. HBOT mitigated HIF-1α, TNF-α, IL-1ß, and IL-6 levels, attenuated microglial activation in the hippocampus, and significantly improved learning and memory deficits in CLP-exposed mice. Additionally, these outcomes were corroborated by injecting a lentivirus that overexpressed HIF-1α into the hippocampal region of the mice. CONCLUSION: HIF-1α escalation induced peripheral and central inflammatory factors, promoting microglial activation, BBB impairment, and cognitive dysfunction. However, HBOT ameliorated these effects by reducing HIF-1α levels in Sepsis-Associated Encephalopathy.

Effect of antipsychotics and mood stabilisers on metabolism in bipolar disorder: a network meta-analysis of randomised-controlled trials.

Background: Antipsychotics and mood stabilisers are gathering attention for the disturbance of metabolism. This network meta-analysis aims to evaluate and rank the metabolic effects of the commonly used antipsychotics and mood stabilisers in treating bipolar disorder (BD). Methods: Registries including PubMed, Embase, Cochrane Library, Web of Science, Ovid, and Google Scholar were searched before February 15th, 2024, for randomised controlled trials (RCTs) applying antipsychotics or mood stabilisers for BD treatment. The observed outcomes were twelve metabolic indicators. The data were extracted by two reviewers independently, and confirmed by another four reviewers and a corresponding author. The above six reviewers all participated in data analyses. Data extraction was based on PRISMA guidelines, and quality assessment was conducted according to the Cochrane Handbook. Use a random effects model for data pooling. The PROSPERO registration number is CRD42023466669. Findings: Together, 5421 records were identified, and 41 publications with 11,678 complete-trial participants were confirmed eligible. After eliminating possible sensitivity, risperidone ranked 1st in elevating fasting serum glucose (SUCRA = 90.7%) and serum insulin (SUCRA = 96.6%). Lurasidone was most likely to elevate HbA1c (SUCRA = 82.1%). Olanzapine ranked 1st in elevating serum TC (SUCRA = 93.3%), TG (SUCRA = 89.6%), and LDL (SUCRA = 94.7%). Lamotrigine ranked 1st in reducing HDL (SUCRA = 82.6%). Amisulpride ranked 1st in elevating body weight (SUCRA = 100.0%). For subgroup analyses, quetiapine is more likely to affect indicators of glucose metabolism among male adult patients with bipolar mania, while long-term lurasidone tended to affect glucose metabolism among female patients with bipolar depression. Among patients under 18, divalproex tended to affect glucose metabolism, with lithium affecting lipid metabolism. In addition, most observed antipsychotics performed higher response and remission rates than placebo, and displayed a similar dropout rate with placebo, while no between-group significance of rate was observed among mood stabilisers. Interpretation: Our findings suggest that overall, antipsychotics are effective in treating BD, while they are also more likely to disturb metabolism than mood stabilisers. Attention should be paid to individual applicability in clinical practice. The results put forward evidence-based information and clinical inspiration for drug compatibility and further research of the BD mechanism. Funding: The National Key Research and Development Program of China (2023YFC2506200), and the Research Project of Jinan Microecological Biomedicine Shandong Laboratory (No. JNL-2023001B).

Improvement of social functioning in patients with first-episode schizophrenia using blonanserin treatment: a prospective, multi-centre, single-arm clinical trial.

Objectives: This clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia. Methods: In this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed. Results: A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. Conclusion: Blonanserin treatment exhibited favourable effects on social functioning in individuals with first-episode schizophrenia. The results suggest that blonanserin was effective treatment options for patients with schizophrenia encountering functional impairments.

Efficacy and tolerability of FDA-approved atypical antipsychotics for the treatment of bipolar depression: a systematic review and network meta-analysis.

We employed a Bayesian network meta-analysis for comparison of the efficacy and tolerability of US Food and Drug Administration (FDA)-approved atypical antipsychotics (AAPs) for the treatment of bipolar patients with depressive episodes. Sixteen randomized controlled trials with 7234 patients treated by one of the five AAPs (cariprazine, lumateperone, lurasidone, olanzapine, and quetiapine) were included. For the response rate (defined as an improvement of ≥50% from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS]), all AAPs were more efficacious than placebo. For the remission rate (defined as the endpoint of MADRS ≤12 or ≤ 10), cariprazine, lurasidone, olanzapine, and quetiapine had higher remission rates than placebo. In terms of tolerability, olanzapine was unexpectedly associated with lower odds of all-cause discontinuation in comparison with placebo, whereas quetiapine was associated with higher odds of discontinuation due to adverse events than placebo. Compared with placebo, lumateperone, olanzapine, and quetiapine showed higher odds of somnolence. Lumateperone had a lower rate of ≥ weight gain of 7% than placebo and other treatments. Olanzapine was associated with a significant increase from baseline in total cholesterol and triglycerides than placebo. These findings inform individualized prescriptions of AAPs for treating bipolar depression in clinical practice.

A direct estrogenic involvement in the expression of human hypocretin.

Hypocretin is synthesized exclusively in the hypothalamus and distributes inputs to several areas of the brain, which may play an important role in depression. Our previous study showed that hypocretin-1 was increased in the lateral hypothalamus in female patients with depression compared to female controls. Estrogen acts through estrogen receptor (ER)α and ERß. We studied the possibility of a direct action of estrogen receptors on the expression of human hypocretin. We found that hypocretin-1 plasma levels were significantly higher in female patients with depression than in female controls. Female depression estrogen receptors and hypocretin are colocalized in the human lateral hypothalamus, PC12, and SK-N-SH cells. The estrogen receptor response elements (ERE) that exist in the hypocretin promoter region may directly regulate the gene expression of hypocretin. The synchronicity of change of hypocretin and estradiol both in hypothalamus and plasma was verified in female rats. In the presence of estradiol, specific binding occurs between the recombinant human ER and hypocretin-ERE. Expression of ER combined with estradiol repressed hypocretin promoter activity via the ERE. In conclusion, we found that estradiol may directly affect hypocretin neurons in the human hypothalamus via ER binding to the hypocretin-ERE, which may lead to the sex-specific pathogenesis of depression.

Clinical Characteristics of Asymptomatic Thromboembolism in Psychiatric Inpatients: A Retrospective Study.

Purpose: Venous thromboembolism (VTE) poses a significant threat to individuals' health, yet its correlation with mental disorders remains underappreciated. Here, we conducted a retrospective analysis to explore the characteristics of psychiatric patients presenting with VTE. Methods: We retrospectively analyzed psychiatric inpatients with elevated plasma D-dimer levels at the Mental Health Center, First Affiliated Hospital, Zhejiang University School of Medicine, from January 2014 to January 2022. The inclusion criteria comprised comprehensive demographic and clinical profiles, including laboratory and imaging findings. Results: A cohort of 33 eligible patients was included, with plasma D-dimer levels ranging from 880 to 10,700 µg/L FEU. Significantly higher D-dimer levels were observed in patients diagnosed with severe mental disorders (SMD), such as schizophrenia and bipolar disorder, compared to those with mild mental disorders (MMD), including depression and anxiety disorders (p = 0.007). Furthermore, individuals receiving antipsychotic medications for less than one year exhibited elevated D-dimer levels compared to those on treatment for over one year (p = 0.005). However, normalization of D-dimer levels did not demonstrate a significant association with psychiatric diagnosis or treatment duration (p > 0.05). Conclusion: Our findings suggest that patients diagnosed with SMD or those undergoing antipsychotic treatment for less than one year may have elevated D-dimer levels, indicating a potential predisposition to VTE severity. This underscores the importance of recognizing VTE risk in individuals with severe mental disorders and warrants further investigation into the impact of antipsychotic treatment duration on thrombotic risk.

Task-state skin potential abnormalities can distinguish major depressive disorder and bipolar depression from healthy controls.

Early detection of bipolar depression (BPD) and major depressive disorder (MDD) has been challenging due to the lack of reliable and easily measurable biological markers. This study aimed to investigate the accuracy of discriminating patients with mood disorders from healthy controls based on task state skin potential characteristics and their correlation with individual indicators of oxidative stress. A total of 77 patients with BPD, 53 patients with MDD, and 79 healthy controls were recruited. A custom-made device, previously shown to be sufficiently accurate, was used to collect skin potential data during six emotion-inducing tasks involving video, pictorial, or textual stimuli. Blood indicators reflecting individual levels of oxidative stress were collected. A discriminant model based on the support vector machine (SVM) algorithm was constructed for discriminant analysis. MDD and BPD patients were found to have abnormal skin potential characteristics on most tasks. The accuracy of the SVM model built with SP features to discriminate MDD patients from healthy controls was 78% (sensitivity 78%, specificity 82%). The SVM model gave an accuracy of 59% (sensitivity 59%, specificity 79%) in classifying BPD patients, MDD patients, and healthy controls into three groups. Significant correlations were also found between oxidative stress indicators in the blood of patients and certain SP features. Patients with depression and bipolar depression have abnormalities in task-state skin potential that partially reflect the pathological mechanism of the illness, and the abnormalities are potential biological markers of affective disorders.

Gut microbial diversity moderates polygenic risk of schizophrenia.

Background: Schizophrenia (SCZ) is a heritable disorder with a polygenic architecture, and the gut microbiota seems to be involved in its development and outcome. In this study, we investigate the interplay between genetic risk and gut microbial markers. Methods: We included 159 first-episode, drug-naïve SCZ patients and 86 healthy controls. The microbial composition of feces was characterized using the 16S rRNA sequencing platform, and five microbial α-diversity indices were estimated [Shannon, Simpson, Chao1, the Abundance-based Eoverage Estimator (ACE), and a phylogenetic diversity-based estimate (PD)]. Polygenic risk scores (PRS) for SCZ were constructed using data from large-scale genome-wide association studies. Effects of microbial α-diversity, microbial abundance, and PRS on SCZ were evaluated via generalized linear models. Results: We confirmed that PRS was associated with SCZ (OR = 2.08, p = 1.22×10-5) and that scores on the Shannon (OR = 0.29, p = 1.15×10-8) and Simpson (OR = 0.29, p = 1.25×10-8) indices were inversely associated with SCZ risk. We found significant interactions (p < 0.05) between PRS and α-diversity indices (Shannon, Simpson, and PD), with the effects of PRS being larger in those exhibiting higher diversity compared to those with lower diversity. Moreover, the PRS effects were larger in individuals with a high abundance of the genera Romboutsia, Streptococcus, and Anaerostipes than in those with low abundance (p < 0.05). All three of these genera showed protective effects against SCZ. Conclusion: The current findings suggest an interplay between the gut microbiota and polygenic risk of SCZ that warrants replication in independent samples. Experimental studies are needed to determine the underpinning mechanisms.

Collaborative FFE-assisted simplified soft-output MLSE with LDPC for high-speed IM-DD transmissions.

In this paper, we propose a feed-forward equalizer (FFE)-assisted simplified soft-output MLSE (sMLSE) by collaborating the maximum likelihood sequence estimation (MLSE) with soft-decision low-density-parity-check (LDPC) decoding. The simplified sMLSE results in undetermined log-likelihood ratio (LLR) magnitudes when the reserved level is less than or equal to the half of modulation order. This severely degrades the performance of soft-decision forward error correction (SD-FEC) decoding. In the FFE-assisted simplified sMLSE, we use the LLRs calculated from pre-set FFE to replace these undetermined LLRs of simplified sMLSE. Thus, the proposed method eliminates the SD-FEC decoding performance degradation resulted from simplification. We conduct experiments to transmit 184-Gb/s PAM-4 or 255-Gb/s PAM-8 signal in IM-DD system at C-band to evaluate the performance of the proposed sMLSE. The results show that the proposed sMLSE can effectively compensate for the degradation of LLR quality. For 255-Gb/s PAM-8 signal transmissions, the FFE-assisted simplified sMLSE achieves almost the same SD-FEC decoding performance as the conventional sMLSE but with 85% complexity reduction.

The impact of CYP3A5*3 on oral quetiapine: A population pharmacokinetic model in Chinese bipolar disorder patients.

BACKGROUND: There is great interindividual difference in the plasma concentration of quetiapine, and optimizing quetiapine therapy to achieve a balance between efficacy and safety is still a challenge. In our study, a population pharmacokinetic (PPK) model considering genetic information was developed with the expectation of comprehensively explaining this observation in Chinese patients with bipolar disorder. METHODS: Patients who were dispensed quetiapine and underwent the therapeutic drug monitoring (TDM) were included. The genotypes of CYP3A5*3, CYP2D6*10, and ABCB1 C3435T/G2677T were analyzed. Finally, a multivariable linear regression model was applied to describe the PPK of quetiapine considering the covariates weight, height and genotype information. RESULTS: A total of 175 TDM points from 107 patients were adopted for PPK model development. Resultantly, the CL/F of quetiapine in CYP3A5 expressers was 81.1 CL/h, whereas it was 43.6 CL/h in CYP3A5 nonexpressers. The interindividual variability in CL/F was 47.7 %. However, neither the ABCB1 nor CYP2D6 genotype was significantly associated with the predictor of quetiapine clearance in our study. LIMITATIONS: Only trough concentrations were collected, and the span between different points was relatively wide, impeding the application of the typical nonlinear compartment model for PPK analysis. In addition, this was a single-center study which limited the sample of wild-type CYP3A5 carriers. CONCLUSIONS: The currently established PPK model of quetiapine considering the contribution of the CYP3A5 genotype could efficiently predict the population and individual pharmacokinetic parameters of Chinese bipolar disorder patients, which could better guide the personalized therapy with quetiapine, thus to achieve the best clinical response.

Progress and Implications from Genetic Studies of Bipolar Disorder.

With the advancements in gene sequencing technologies, including genome-wide association studies, polygenetic risk scores, and high-throughput sequencing, there has been a tremendous advantage in mapping a detailed blueprint for the genetic model of bipolar disorder (BD). To date, intriguing genetic clues have been identified to explain the development of BD, as well as the genetic association that might be applied for the development of susceptibility prediction and pharmacogenetic intervention. Risk genes of BD, such as CACNA1C, ANK3, TRANK1, and CLOCK, have been found to be involved in various pathophysiological processes correlated with BD. Although the specific roles of these genes have yet to be determined, genetic research on BD will help improve the prevention, therapeutics, and prognosis in clinical practice. The latest preclinical and clinical studies, and reviews of the genetics of BD, are analyzed in this review, aiming to summarize the progress in this intriguing field and to provide perspectives for individualized, precise, and effective clinical practice.

Mapping the global, regional and national burden of bipolar disorder from 1990 to 2019: trend analysis on the Global Burden of Disease Study 2019.

BACKGROUND: Data on trends in the epidemiological burden of bipolar disorder are scarce. AIMS: To provide an overview of trends in bipolar disorder burden from 1990 to 2019. METHOD: Revisiting the Global Burden of Disease Study 2019, we analysed the number of cases, calculated the age-standardised rate (per 100 000 population) and estimated annual percentage change (EAPC) of incidence, prevalence and years lived with disability (YLDs) for bipolar disorder from 1990 to 2019. The independent effects of age, period and cohort were estimated by the age-period-cohort modelling. RESULTS: Globally, the bipolar disorder-related prevalent cases, incident cases and number of YLDs all increased from 1990 to 2019. Regionally, the World Health Organization Region of the Americas accounted for the highest estimated YLD number and rate, with the highest age-standardised prevalence rate in 1990 and 2019 and highest EAPC of prevalence. By sociodemographic index (SDI) quintiles, all five SDI regions saw an increase in estimated incident cases. Nationally, New Zealand reported the highest age-standardised rate of incidence, prevalence and YLDs in 1990 and 2019. The most prominent age effect on incidence rate was in those aged 15-19 years. Decreased effects of period on incidence, prevalence and YLD rates was observed overall and in females, not in males. The incidence, prevalence and YLD rates showed an unfavourable trend in the younger cohorts born after 1990, with males reporting a higher cohort risk than females. CONCLUSIONS: From 1990 to 2019, the overall trend of bipolar disorder burden presents regional and national variations and differs by age, sex, period and cohort.

Multiomics Analyses Reveal Microbiome-Gut-Brain Crosstalk Centered on Aberrant Gamma-Aminobutyric Acid and Tryptophan Metabolism in Drug-Naïve Patients with First-Episode Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia (SCZ) is associated with complex crosstalk between the gut microbiota and host metabolism, but the underlying mechanism remains elusive. Investigating the aberrant neurotransmitter processes reflected by alterations identified using multiomics analysis is valuable to fully explain the pathogenesis of SCZ. STUDY DESIGN: We conducted an integrative analysis of multiomics data, including the serum metabolome, fecal metagenome, single nucleotide polymorphism data, and neuroimaging data obtained from a cohort of 127 drug-naïve, first-episode SCZ patients and 92 healthy controls to characterize the microbiome-gut-brain axis in SCZ patients. We used pathway-based polygenic risk score (PRS) analyses to determine the biological pathways contributing to genetic risk and mediation effect analyses to determine the important neuroimaging features. Additionally, a random forest model was generated for effective SCZ diagnosis. STUDY RESULTS: We found that the altered metabolome and dysregulated microbiome were associated with neuroactive metabolites, including gamma-aminobutyric acid (GABA), tryptophan, and short-chain fatty acids. Further structural and functional magnetic resonance imaging analyses highlighted that gray matter volume and functional connectivity disturbances mediate the relationships between Ruminococcus_torgues and Collinsella_aerofaciens and symptom severity and the relationships between species Lactobacillus_ruminis and differential metabolites l-2,4-diaminobutyric acid and N-acetylserotonin and cognitive function. Moreover, analyses of the Polygenic Risk Score (PRS) support that alterations in GABA and tryptophan neurotransmitter pathways are associated with SCZ risk, and GABA might be a more dominant contributor. CONCLUSIONS: This study provides new insights into systematic relationships among genes, metabolism, and the gut microbiota that affect brain functional connectivity, thereby affecting SCZ pathogenesis.

The impact of quetiapine monotherapy or in combination with lithium on the thyroid function in patients with bipolar depression: A retrospective study.

OBJECTIVE: This study aims to investigate whether quetiapine monotherapy or in combination with lithium significantly disturbs thyroid function in depressed patients with bipolar disorder (BD), and whether difference exists in the post-treatment thyroid function between the two therapies. METHODS: Based on the electric medical records, outpatients and inpatients with a current depressive episode of BD from January 2016 to December 2022 were screened. All patients were treated with quetiapine monotherapy or in combination with lithium. In addition to the demographic data and depression scale, thyroid profiles including total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TGAb) were recorded, analyzed, and compared before and after the treatment. RESULTS: Totally, 73 eligible patients were enrolled, including 53 in the monotherapy group (MG) and 20 in the combined therapy group (CG). No significant differences in thyroid profiles were detected between the two groups at the baseline (p > 0.05). After one-month treatment, in the MG, serum levels of TT4, TT3, FT4, and FT3 reduced significantly (p < 0.05), while TSH, TPOAb, and TGAb increased significantly (p < 0.05). In the CG, serum levels of TT4, TT3, and FT4 reduced and TSH increased following one-month treatment (p < 0.05), with no significant change in FT3, TPOAb, or TGAb (p > 0.05). After one-month treatment, no difference of TT4, TT3, FT4, FT3, and TSH was found between the two groups (p > 0.05). CONCLUSION: Both quetiapine monotherapy and a combined therapy with lithium significantly disturbed thyroid function in patients with bipolar depression, while quetiapine monotherapy seems to be associated with immune dysregulation in the thyroid.

Circulating T-cell subsets discrepancy between bipolar disorder and major depressive disorder during mood episodes: A naturalistic, retrospective study of 1015 cases.

AIMS: We aimed to investigate whether peripheral T-cell subsets could be a biomarker to distinguish major depressive disorder (MDD) and bipolar disorder (BD). METHODS: Medical records of hospitalized patients in the Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2015 to September 2020 with a discharge diagnosis of MDD or BD were reviewed. Patients who underwent peripheral blood examination of T-cell subtype proportions, including CD3+, CD4+, CD8+ T-cell, and natural killer (NK) cells, were enrolled. The Chi-square test, t-test, or one-way analysis of variance were used to analyze group differences. Demographic profiles and T-cell data were used to construct a random forest classifier-based diagnostic model. RESULTS: Totally, 98 cases of BD mania, 459 cases of BD depression (BD-D), and 458 cases of MDD were included. There were significant differences in the proportions of CD3+, CD4+, CD8+ T-cell, and NK cells among the three groups. Compared with MDD, the BD-D group showed higher CD8+ but lower CD4+ T-cell and a significantly lower ratio of CD4+ and CD8+ proportions. The random forest model achieved an area under the curve of 0.77 (95% confidence interval: 0.71-0.83) to distinguish BD-D from MDD patients. CONCLUSION: These findings imply that BD and MDD patients may harbor different T-cell inflammatory patterns, which could be a potential diagnostic biomarker for mood disorders.

Targeted LC-MS/MS profiling of bile acids reveals primary/secondary bile acid ratio as a novel biomarker for necrotizing enterocolitis.

Bile acids (BAs) are involved in the development of necrotizing enterocolitis (NEC), which mainly occurs in preterm infants. We aim to identify the change of BAs in preterm infants and validate its potential value in the detection of NEC. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure the plasma BAs in healthy preterm infants and patients with NEC. By analyzing the level of BAs in healthy preterm infants, we found that the plasma concentrations of BAs were related to sex, gestational/postnatal age, birth weight, mode of birth, and feeding type after birth. The plasma levels of TCA, GCA, TCDCA, GCDCA, primary BAs, and total BAs and the primary/secondary BA ratio were decreased, while DCA, UDCA, and secondary BAs were increased in NEC. The primary/secondary BA ratio (cutoff point 62.9) can effectively differentiate NEC from healthy preterm infants, with an AUC of 0.9, a sensitivity of 94.5%, and a specificity of 78.1%. Combining the ratio with high-risk factors of NEC can better distinguish between NEC and control, with an AUC of 0.95. Importantly, significantly lower levels of primary/secondary BA ratio were found in infants with surgical NEC than in nonsurgical NEC cases. The cutoff point of 28.7 identified surgical NEC from nonsurgical NEC with sensitivity and specificity of 76.9% and 100%. Thus, our study identified that the primary/secondary BA ratio in the plasma can differentiate NEC from healthy preterm infants and effectively differentiate the surgical NEC from nonsurgical NEC. Therefore, LC-MS/MS was expected to be a novel measurement platform used to distinguish infants who are most in need of close monitoring or early surgical intervention.

Low complexity MIMO equalization for long-haul SDM systems.

Space-division multiplexing (SDM) has been expected to support the continuous growth of transmission capacity. However, it suffers from high computation complexity that limits its physical implementations. In this paper, we propose and experimentally demonstrate a low-complexity MIMO equalization method to leverage the sparsity of weights and reduce the complexity by L1&L2-regularization in long-haul space-division multiplexing (SDM) systems. The L1-regularization finds the sparse solution of equalizer filters and substitutes it for optimal solution, reducing the complexity with performance degradation. On the other hand, the L2-regularization tends to produce a smoother estimation than L1 regularization and is therefore more robust to large variance. We conduct a 39.87-GBaud QPSK coherent optical transmission experiment based on a 4-core coupled-core fiber with the transmission distance from 1206-km to 7236-km. Comparisons on the equalization performance and computational complexity show that the sparse equalizer using L1&L2-regularization achieves a 30% reduction in complexity at the similar system performance, compared with the traditional time-domain MIMO.