The effects of antioxidant supplementation on short-term mortality in sepsis patients.

Background: The occurrence and development of sepsis are related to the excessive production of oxygen free radicals and the weakened natural clearance mechanism. Further dependable evidence is required to clarify the effectiveness of antioxidant therapy, especially its impact on short-term mortality. Objectives: The purpose of this systematic review and meta-analysis was to evaluate the effect of common antioxidant therapy on short-term mortality in patients with sepsis. Methods: According to PRISMA guidelines, a systematic literature search on antioxidants in adults sepsis patients was performed on PubMed/Medline, Embase, and the Cochrane Library from the establishment of the database to November 2023. Antioxidant supplements can be a single-drug or multi-drug combination: HAT (hydrocortisone, ascorbic acid, and thiamine), ascorbic acid, thiamine, N-acetylcysteine and selenium. The primary outcome was the effect of antioxidant treatment on short-term mortality, which included 28-day mortality, in-hospital mortality, intensive care unit mortality, and 30-day mortality. Subgroup analyses of short-term mortality were used to reduce statistical heterogeneity and publication bias. Results: Sixty studies of 130,986 sepsis patients fulfilled the predefined criteria and were quantified and meta-analyzed. Antioxidant therapy reduces the risk of short-term death in sepsis patients by multivariate meta-analysis of current data, including a reduction of in-hospital mortality (OR = 0.81, 95% CI 0.67 to 0.99; P = 0.040) and 28-day mortality (OR = 0.81, 95% CI 0.69 to 0.95]; P = 0.008). Particularly in subgroup analyses, ascorbic acid treatment can reduce in-hospital mortality (OR = 0.66, 95% CI 0.90 to 0.98; P = 0.006) and 28-day mortality (OR = 0.43, 95% CI 0.24 to 0.75; P = 0.003). However, the meta-analysis of RCTs found that antioxidant therapy drugs, especially ascorbic acid, did substantially reduce short-term mortality(OR = 0.78, 95% CI 0.62 to 0.98; P = 0.030; OR = 0.57, 95% CI 0.36 to 0.91; P = 0.020). Conclusions: According to current data of RCTs, antioxidant therapy, especially ascorbic acid, has a trend of improving short-term mortality in patients with sepsis, but the evidence remains to be further demonstrated.

Trajectories and comorbid symptom networks of posttraumatic stress symptoms in frontline rescuers: A longitudinal study.

BACKGROUND: Previous research has largely lacked studies that explore the trajectories of Posttraumatic stress symptoms (PTSS) and the structure of comorbid psychiatric symptom networks following traumatic event, while controlling for the severity of traumatic exposure. The present study aims to explore the characteristic trajectories of PTSS, in the context of ensuring controlled levels of traumatic exposure. Furthermore, the PTSS, depressive, and anxiety comorbid symptom networks of different PTSS trajectory subgroups are also investigated. METHODS: A total of 296 frontline rescue personnel were enrolled into our study. In an effort to control for variations in traumatic exposure severity, this study ensured that all participants had same responsibilities and cumulative operational duration at the post-disaster rescue circumstance. Growth mixture models (GMMs) were employed to scrutinize the trajectories of PTSS. Additionally, network analysis was used to examine the comorbid symptom network of PTSS, depression, and anxiety. RESULTS: Four distinct PTSS trajectories were identified, namely Persisting Symptom, Gradual Recovery, Gradual Aggravation, and Asymptomatic. Although both the Persisting Symptom and Gradual Aggravation groups belong to the high-risk subgroups for persistent PTSS, they exhibit differences in core symptoms within their respective networks. The core symptom for the Persisting Symptom Network is flashbacks, while for the Gradual Aggravation Network, it is sleep disturbances. CONCLUSION: To the best of our knowledge, the present study represents the first research endeavor to integrate longitudinal trajectory analysis of PTSS with longitudinal symptom network analysis, clarifying the evolving features of PTSS but also offering valuable insights for early screening and intervention strategies.

Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor kappa-B p65/ß-catenin pathway.

Background: Tolerogenic dendritic cells (DCs) are associated with poor prognosis of sepsis. Matrix metalloproteinases (MMPs) have been shown to have immunomodulatory effects. However, whether MMPs are involved in the functional reprogramming of DCs is unknown. The study aims to investigate the role of MMPs in sepsis-induced DCs tolerance and the potential mechanisms. Methods: A murine model of late sepsis was induced by cecal ligation and puncture (CLP). The expression levels of members of the MMP family were detected in sepsis-induced tolerogenic DCs by using microarray assessment. The potential roles and mechanisms underlying MMP8 in the differentiation, maturation and functional reprogramming of DCs during late sepsis were assessed both in vitro and in vivo. Results: DCs from late septic mice expressed higher levels of MMP8, MMP9, MMP14, MMP19, MMP25 and MMP27, and MMP8 levels were the highest. MMP8 deficiency significantly alleviated sepsis-induced immune tolerance of DCs both in vivo and in vitro. Adoptive transfer of MMP8 knockdown post-septic bone marrow-derived DCs protected mice against sepsis-associated lethality and organ dysfunction, inhibited regulatory T-cell expansion and enhanced Th1 response. Furthermore, the effect of MMP8 on DC tolerance was found to be associated with the nuclear factor kappa-B p65/ß-catenin pathway. Conclusions: Increased MMP8 levels in septic DCs might serve as a negative feedback loop, thereby suppressing the proinflammatory response and inducing DC tolerance.

Risk model for predicting mortality in patients with necrotizing soft tissue infections in the intensive care unit.

BACKGROUND: The goal of this study is to look into the factors that lead to death in patients with necrotizing soft tissue infections（NSTIs） in the intensive care unit and create a mortality risk model. METHODS: The clinical data of 106 patients with necrotizing soft tissue infections admitted to intensive care unit(ICU) of the First Affiliated Hospital of Wenzhou Medical University between January 2008 and December 2021 were retrospectively analyzed. Univariate analysis and multivariate analysis were performed to evaluate the risk factors impacting patient mortality. The regression coefficient in binary logistic regression analysis was converted into the item score in the model, and then the model score of each patient was calculated. Finally, an ROC curve was constructed to evaluate the efficiency of the model for predicting mortality. Thirteen patients with NSTIs admitted to ICU between January 2022 and November 2022 were used to validate the model. RESULTS: The death group had 44 patients, while the survival group had 62 patients. The overall mortality was 41.5%. Binary logistic regression analysis showed that risk factors for mortality were age≥ 60 years(OR:4.419; 95%CI:1.093-17.862; P = 0.037), creatinine ≥ 132µmol/L(OR:11.166; 95%CI:2.234-55.816; P = 0.003), creatine kinase ≥ 1104 U/L(OR:4.019; 95%CI:1.134-14.250; P = 0.031), prothrombin time ≥ 24.4 s(OR:11.589; 95%CI:2.510-53.506; P = 0.002), and invasive mechanical ventilation (OR:17.404; 95%CI:4.586-66.052; P＜0.000). The AUC of the model for predicting mortality was 0.940 (95% CI:0.894-0.986). When the cut-off value for the model was 4 points, the sensitivity was 95.5% and the specificity was 83.9%. CONCLUSION: The death risk model in this study for NSTIs patients in the intensive care unit shows high sensitivity and specificity. Patients with a score of ≥ 4 points have a higher risk of mortality.

Dynamic risk factors of psychiatric readmission for major depressive disorder: A longitudinal study on patients treated with mono-antidepressant.

In this comprehensive study, we sought to unravel the risk factors for recurrence in Major Depressive Disorder (MDD), uniquely focusing on patients undergoing mono-antidepressant treatment. By considering psychiatric readmission as a direct indicator of MDD recurrence, we meticulously analyzed the records of 1,456 inpatients from a Chinese mental health center from 2012 to 2020. Our follow-up periods, spanning 90, 180, and 365 days post-discharge, allowed for a nuanced understanding of the recurrence dynamics. We identified four critical risk factors: thyroid function (FT3 and TSH), high-density lipoprotein (HDL) levels, and region of residence. Notably, the study revealed an increasing risk of readmission associated with decreased FT3 and HDL over time, while elevated TSH and residing in another province 's impact diminished. The antidepressant type did not significantly alter readmission risks, providing a unique perspective on MDD management. This research contributes to the field by offering a deeper understanding of how demographic and biochemical factors influence the likelihood of MDD recurrence, guiding more effective treatment approaches.

Historical and projected evolutions of glaciers in response to climate change in High Mountain Asia.

Glacier changes are regarded as the conspicuous icon of climate change in High Mountain Asia (HMA) alpine environments. Multi-temporal glacier coverage is essential for mass balance estimations and understanding glacial changes in response to climate variability. However, consistent multi-temporal glacier area datasets across the HMA are limited due to challenges posed by seasonal snow and cloud cover in remote sensing satellite images. In this study, a new method is proposed to estimate glacier and nonseasonal snow (GNS) areas by combining the normalized difference snow index (NDSI) and bright temperature bands from Landsat remote sensing images in 1990s, 2000s, 2010s and 2020s. Meanwhile, the integrated ice dynamic Open Global Glacier Model (OGGM) is applied to simulate nine typical glaciers and project their changes using 15 general circulation models (GCMs) under four shared socioeconomic pathways (SSPs). The results showed that total GNS areas in HMA were estimated at 71.26 × 103 km2 in the 1990s, and decreased to 53.17 × 103 km2 in the 2020s. Massive proportions of GNS were mainly distributed in the southeast and northwest region. Tipping points of GNS indicating a transition from mass balance gain to loss during four periods were detected in the Upper Tarim basin, Inner Tibetan Plateau, Upper Yangtze river basin, Upper Brahmaputra river basin, and Upper Salween river basin. The reduction of total GNS area was attributed to significantly rising temperature and decreasing solid precipitation. The projections indicate that glacier shrinkages will be the dominant trend in the future, and most typical glaciers will experience a mass loss of 60% under SSP245 (SSP2-RCP4.5) and over 90% under SSP585 (SSP5-RCP8.5) by the end of the century. The response of glaciers to climate change is also found to be influenced by factors including local topography and elevation ranges. The findings of this study provides a better understanding of glacial dynamics in response to climate change and highlights the importance of making water resources management strategies to mitigate the influence of glacier retreat.

SUPPLEMENTATION WITH NICOTINAMIDE RIBOSIDE ATTENUATES T CELL EXHAUSTION AND IMPROVES SURVIVAL IN SEPSIS.

ABSTRACT: T cell exhaustion is the main cause of sepsis-induced immunosuppression and is associated with the poor prognosis. Nicotinamide adenine dinucleotide (NAD + ) is well known for its anti-aging effect, but its role in sepsis-induced T cell exhaustion remains to be elucidated. In the present study, using a classic septic animal model, we found that the levels of NAD + and its downstream molecule, which is sirtuins 1 (SIRT1), in T cells in sepsis were decreased. Supplementation with nicotinamide ribose (NR), the precursor of NAD + , right after cecal ligation and puncture significantly increased the levels of NAD + and SIRT1. Supplementation with NR alleviated the depletion of mononuclear cells and T lymphocytes in spleen in sepsis and increased the levels of CD3 + CD4 + and CD3 + CD8 + T cells. Interestingly, both Th1 and Th2 cells were expanded after NR treatment, but the balance of Th1/Th2 was partly restored. Nicotinamide ribose also inhibited the regulatory T cells expansion and programmed cell death 1 expression in CD4 + T cells in sepsis. In addition, the bacteria load, organ damage (lung, heart, liver, and kidney), and the mortality of septic mice were reduced after NR supplementation. In summary, these results demonstrate the beneficial effect of NR on sepsis and T cell exhaustion, which is associated with NAD + /SIRT1 pathway.

Administration of protopine prevents mitophagy and acute lung injury in sepsis.

Introduction: Sepsis is a severe life-threatening infection that induces a series of dysregulated physiologic responses and results in organ dysfunction. Acute lung injury (ALI), the primary cause of respiratory failure brought on by sepsis, does not have a specific therapy. Protopine (PTP) is an alkaloid with antiinflammatory and antioxidant properties. However, the function of PTP in septic ALI has not yet been documented. This work sought to investigate how PTP affected septic ALI and the mechanisms involved in septic lung damage, including inflammation, oxidative stress, apoptosis, and mitophagy. Methods: Here, we established a mouse model induced by cecal ligation and puncture (CLP) and a BEAS-2B cell model exposed to lipopolysaccharide (LPS). Results: PTP treatment significantly reduced mortality in CLP mice. PTP mitigated lung damage and reduced apoptosis. Western blot analysis showed that PTP dramatically reduced the expression of the apoptosis-associated protein (Cleaved Caspase-3, Cyto C) and increased Bcl-2/Bax. In addition, PTP decreased the production of inflammatory cytokines (IL-6, IL-1ß, TNF-α), increased glutathione (GSH) levels and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) levels. Meanwhile, PTP significantly reduced the expression of mitophagy-related proteins (PINK1, Parkin, LC-II), and downregulated mitophagy by transmission electron microscopy. Additionally, the cells were consistent with animal experiments. Discussion: PTP intervention reduced inflammatory responses, oxidative stress, and apoptosis, restored mitochondrial membrane potential, and downregulated mitophagy. The research shows that PTP prevents excessivemitophagy and ALI in sepsis, suggesting that PTP has a potential role in the therapy of sepsis.

Mutual promotion of mitochondrial fission and oxidative stress contributes to mitochondrial-DNA-mediated inflammation and epithelial-mesenchymal transition in paraquat-induced pulmonary fibrosis.

BACKGROUND: Pulmonary fibrosis (PF) is one of the main causes of death in patients with paraquat (PQ) poisoning. This study aimed to evaluate the relationship between mitochondrial fission and oxidative stress in PQ-induced epithelial-mesenchymal transition (EMT) and PF. METHODS: C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro. Histological changes in the lungs were examined by hematoxylin and eosin (H&E) staining. Mitochondrial morphology was detected by MitoTracker® Deep Red FM or transmission electron microscopy (TEM). Western blotting and immunofluorescence were used to determine the expression of protein. The migration ability of the cells was detected by the cell scratch test. Mitochondrial DNA (mtDNA) levels were assessed by real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) was applied to detect cytokine levels. Superoxide dismutase (SOD) activity and the levels of glutathione (GSH) and malondialdehyde (MDA) were detected by chemichromatometry. RESULTS: PQ exposure caused EMT and PF in vivo and in vitro. PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1 (Drp1), which were accompanied by oxidative stress. Inhibiting mitochondrial fission using mitochondrial division inhibitor-1 (Mdivi-1), a selective inhibitor of Drp1, attenuated PQ-induced EMT and oxidative damage. Treatment with N-acetyl-L-cysteine (NAC), an antioxidant, reduced Drp1 expression, attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF. Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release, the expression of Toll-like receptor 9 (TLR9) and phosphorylation (P)-NF-κB p65 as well as cytokines (interleukin 6 [IL-6], interleukin-1ß [IL-1ß], and tumor necrosis factor-α [TNF-α]) production. CONCLUSION: Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF, which is associated with the mtDNA/TLR9/NF-κB pathway.

Post-traumatic stress disorder and depressive symptoms among firefighters: a network analysis.

Background: Firefighters, as first responders with a high risk of occupational exposure to traumatic events and heavy working stress, have a high prevalence of PTSD symptoms and depressive symptoms. But no previous studies analyzed the relationships and hierarchies of PTSD and depressive symptoms among firefighters. Network analysis is a novel and effective method for investigating the complex interactions of mental disorders at the symptom level and providing a new understanding of psychopathology. The current study was designed to characterize the PTSD and depressive symptoms network structure in the Chinese firefighters. Method: The Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) and the Self-Rating Depression Scale (SDS) were applied to assess PTSD and depressive symptoms, respectively. The network structure of PTSD and depressive symptoms was characterized using "expected influence (EI)" and "bridge EI" as centrality indices. The Walktrap algorithm was conducted to identify communities in the PTSD and depressive symptoms network. Finally, Network accuracy and stability were examined using the Bootstrapped test and the case-dropping procedure. Results: A total of 1,768 firefighters were enrolled in our research. Network analysis revealed that the relationship between PTSD symptoms, "Flashback" and "Avoidance," was the strongest. "Life emptiness" was the most central symptom with the highest EI in the PTSD and depression network model. Followed by "Fatigue" and "Interest loss." Bridge symptoms connecting PTSD and depressive symptoms in our study were "Numb," "High alertness," "Sad mood," and "Compunction and blame," successively. The data-driven community detection suggested the differences in PTSD symptoms in the clustering process. The reliability of the network was approved by both stability and accuracy tests. Conclusion: To the best of our knowledge, the current study first demonstrated the network structure of PTSD and depressive symptoms among Chinese firefighters, identifying the central and bridge symptoms. Targeting interventions to the symptoms mentioned above may effectively treat firefighters suffering from PTSD and depressive symptoms.

Evaluating the impacts of sustainable land management practices on water quality in an agricultural catchment in Lower Austria using SWAT.

Managing agricultural watersheds in an environmentally friendly manner necessitate the strategic implementation of well-targeted sustainable land management (SLM) practices that limit soil and nonpoint source pollution losses and translocation. Watershed-scale SLM-scenario modeling has the potential to identify efficient and effective management strategies from the field to the integrated landscape level. In a case study targeting a 66-hectare watershed in Petzenkirchen, Lower Austria, the Soil and Water Assessment Tool (SWAT) was utilized to evaluate a variety of locally adoptable SLM practices. SWAT was calibrated and validated (monthly) at the catchment outlet for flow, sediment, nitrate-nitrogen (NO3-N), ammonium nitrogen (NH4-N), and mineralized phosphorus (PO4-P) using SWATplusR. Considering the locally existing agricultural practices and socioeconomic and environmental factors of the research area, four conservation practices were evaluated: baseline scenario, contour farming (CF), winter cover crops (CC), and a combination of no-till and cover crops (NT + CC). The NT + CC SLM practice was found to be the most effective soil conservation practice in reducing soil loss by around 80%, whereas CF obtained the best results for decreasing the nutrient loads of NO3-N and PO4-P by 11% and 35%, respectively. The findings of this study imply that the setup SWAT model can serve the context-specific performance assessment and eventual promotion of SLM interventions that mitigate on-site land degradation and the consequential off-site environmental pollution resulting from agricultural nonpoint sources.

Stability of DNA and RNA hairpins: a comparative study based on ox-DNA.

Advances in single-molecule experiments on macromolecular crowding urgently need an efficient simulation method to resolve their discrepancies quantitatively. Ox-DNA model has been since reworked to treat the thermodynamics and mechanical properties of DNA/RNA hairpin at a stretching force. In hopping experiments, the critical forces of RNA hairpins at different temperatures are greater than those of DNA hairpins, in addition, the Gibbs free energy at a fixed temperature required to convert an RNA hairpin into a single-stranded molecule at zero force is obviously greater than that of DNA hairpin and gradually decreases by increasing the temperature. As far as force-ramping experiments are concerned, the first-rupture forces of RNA/DNA hairpins corresponding to the maximum probability density linearly pertain to the force-loading rate, with those of RNA hairpins being greater. The extended ox-DNA model could potentially identify the interaction between biologically inert polymer and RNA/DNA hairpins in crowded environments.

[Identification of Nitrate Source of Surface Water in a Typical Peri-urban Watershed in the Tableland of the Loess Plateau, China].

With the rapid development of industry and agriculture, nitrate pollution in surface water has become one of the serious environmental problems in the Loess Plateau region. In this study, Yanwachuan watershed, a typical suburban watershed in the gully region of a loess plateau, was selected as the research area. Using hydrochemical data and nitrogen and oxygen bistable isotopes, combined with the SIAR model, the contribution rates of different pollution sources of nitrate in surface water in the dry season and wet season were quantitatively identified, and the main reasons for seasonal differences in different pollution sources were clarified. The results showed that inorganic nitrogen mainly existed in the form of NO3--N and NO2--N, and the average concentration of NO3--N and NO2--N in the wet season was higher than that in the dry season, whereas NH4+-N showed the opposite characteristics. Nitrification was the main process of nitrate transformation in the surface water of the basin. In the wet season, the main sources of nitrate were manure and sewage, whereas in the dry season, manure, sewage, and soil N leaching were the dominant sources, followed by ammonium fertilizer. The contribution proportion of different pollution sources to nitrate in surface water of the watershed showed significant seasonal differences. The sewage had the highest contribution, accounting for 31.40% and 65.66% in the dry season and rainy season, respectively, and the contribution of sewage to NO3- in the wet season was much higher than that in the dry season. The increase in residential water consumption in summer led to a large amount of sewage discharge into the watershed.

PINK1 protects against dendritic cell dysfunction during sepsis through the regulation of mitochondrial quality control.

BACKGROUND: Dendritic cell (DC) dysfunction plays a central role in sepsis-induced immunosuppression. Recent research has indicated that collective mitochondrial fragmentation contributes to the dysfunction of immune cells observed during sepsis. PTEN-induced putative kinase 1 (PINK1) has been characterized as a guide for impaired mitochondria that can keep mitochondrial homeostasis. However, its role in the function of DCs during sepsis and the related mechanisms remain obscure. In our study, we elucidated the effect of PINK1 on DC function during sepsis and its underlying mechanism of action. METHODS: Cecal ligation and puncture (CLP) surgery and lipopolysaccharide (LPS) treatment were used as in vivo and in vitro sepsis models, respectively. RESULTS: We found that changes in mitochondrial PINK1 expression of DCs paralleled changes in DC function during sepsis. The ratio of DCs expressing MHC-II, CD86, and CD80, the mRNAs level of dendritic cells expressing TNF-α and IL-12, and the level of DC-mediated T-cell proliferation were all decreased, both in vivo and in vitro during sepsis, when PINK1 was knocked out. This suggested that PINK1 knockout prevented the function of DCs during sepsis. Furthermore, PINK1 knockout inhibited Parkin RBR E3 ubiquitin protein (Parkin)-dependent mitophagy and enhanced dynamin-related protein 1 (Drp1)-related mitochondrial fission, and the negative effects of PINK1 knockout on DC function following LPS treatment were reversed by Parkin activation and Drp1 inhibitor. Knockout of PINK1 also increased apoptosis of DCs and the mortality of CLP mice. CONCLUSION: Our results indicated that PINK1 protected against DC dysfunction during sepsis through the regulation of mitochondrial quality control.

A new criteria for acute on preexisting kidney dysfunction in critically ill patients.

Critically ill patients with preexisting kidney dysfunction (PKD) are at high risk for acute kidney injury (AKI). Nevertheless, there is no criteria for screening and classifying AKI in patients with PKD. In this study, after assessing relationship between the change in SCr from baseline and in-hospital mortality, a new criteria, named APKD, for identifying AKI in PKD was proposed. APKD defined AKI in critically ill patients with PKD as an absolute increase of ≥ 0.2 mg/dL in SCr within 48 h or an increase in SCr ≥ 1.1 times over baseline within 7 d. APKD detected more AKI among PKD patients compared with the other criteria. Additionally, the AKI patients identified by APKD but missed by the other criteria had higher mortality than those without AKI. APKD shows higher sensitivities than KDIGO criteria in predicating in-hospital mortality. APKD, but not the KDIGO, is effective for staging the severity of AKI in patients with PKD. In conclusion, APKD is more effective in screening and classifying AKI in critically ill patients with PKD compared with the earlier criteria, and it may helpful in guiding clinical treatment and predicting prognosis.

Orai1 overexpression improves sepsis-induced T-lymphocyte immunosuppression and acute organ dysfunction in mice.

Immune paralysis induced by sepsis, especially dysfunction of CD4+ T cells, leads to an increased risk of infection. In sepsis, abnormal differentiation of T lymphocytes is associated with multiorgan dysfunction syndrome. In T lymphocytes, the Orai1/nuclear factor of activated T Cells (NFAT) pathway is a critical mediator of infection, inflammation, and autoimmunity. In this study, we confirmed immunosuppression of splenic CD4+ T cells and abnormal differentiation of T lymphocytes in septic mice. Furthermore, we found that the Orai1/NFAT signaling pathway was inhibited in septic mice; however, the overexpression of Orai1 not only improved immune function of T cells in sepsis but also reduced the mortality and organ damage in septic mice. Moreover, the overexpression of Orai1 could reverse the increases in the numbers of T regulatory and T helper 17 cells in septic mice. These data suggest that the Orai1-mediated NFAT signaling pathway can improve sepsis-induced T-lymphocyte immunosuppression and acute organ dysfunction.

Neural activity changes in first-episode, drug-naïve patients with major depressive disorder after transcutaneous auricular vagus nerve stimulation treatment: A resting-state fMRI study.

Introduction: Major depressive disorder (MDD) is a disease with prominent individual, medical, and economic impacts. Drug therapy and other treatment methods (such as Electroconvulsive therapy) may induce treatment-resistance and have associated side effects including loss of memory, decrease of reaction time, and residual symptoms. Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel and non-invasive treatment approach which stimulates brain structures with no side-effects. However, it remains little understood whether and how the neural activation is modulated by taVNS in MDD patients. Herein, we used the regional homogeneity (ReHo) to investigate the brain activity in first-episode, drug-naïve MDD patients after taVNS treatment. Materials and methods: Twenty-two first-episode, drug-naïve MDD patients were enrolled in the study. These patients received the first taVNS treatment at the baseline time, and underwent resting-state MRI scanning twice, before and after taVNS. All the patients then received taVNS treatments for 4 weeks. The severity of depression was assessed by the 17-item Hamilton Depression Rating Scale (HAMD) at the baseline time and after 4-week's treatment. Pearson analysis was used to assess the correlation between alterations of ReHo and changes of the HAMD scores. Two patients were excluded due to excessive head movement, two patients lack clinical data in the fourth week, thus, imaging analysis was performed in 20 patients, while correlation analysis between clinical and imaging data was performed in only 18 patients. Results: There were significant differences in the ReHo values in first-episode, drug-naïve MDD patients between pre- or post- taVNS. The primary finding is that the patients exhibited a significantly lower ReHo in the left/right median cingulate cortex, the left precentral gyrus, the left postcentral gyrus, the right calcarine cortex, the left supplementary motor area, the left paracentral lobule, and the right lingual gyrus. Pearson analysis revealed a positive correlation between changes of ReHo in the right median cingulate cortex/the left supplementary motor area and changes of HAMD scores after taVNS. Conclusion: The decreased ReHo were found after taVNS. The sensorimotor, limbic and visual-related brain regions may play an important role in understanding the underlying neural mechanisms and be the target brain regions in the further therapy.

[Value of vascular endothelial-cadherin in evaluating the severity of patients with sepsis].

OBJECTIVE: To explore the value of vascular endothelial-cadherin (VE-cad) in evaluating the severity of sepsis. METHODS: A prospective study was conducted to select 85 patients with sepsis treated in the emergency ward of the First Affiliated Hospital of Wenzhou Medical University from June 1, 2015 to November 1, 2017. The gender, age, medical history, first infection site, number of affected organs, laboratory indexes, acute physiology and chronic health evaluation II (APACHE II), simplified acute physiology score II (SAPS II), sequential organ failure assessment (SOFA) and the total length of stay, emergency intensive care unit (EICU) length of stay, 28-day at admission and survival during hospitalization were measured, and the VE-cad level within 24 hours at admission was measured. The patients were divided into sepsis group and septic shock group according to the progress of the disease. The patients were divided into multiple organ dysfunction syndrome (MODS) group and non MODS group according to whether they were accompanied by MODS. The differences of the above indexes in patients with different disease progression, MODS and different prognosis were analyzed and compared. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the value of VE-cad in evaluating the severity of sepsis. RESULTS: A total of 85 patients were included, mainly respiratory tract infection. Among them, 38 cases were sepsis and 47 cases were septic shock, 39 cases had MODS, 46 cases had no MODS, 64 cases survived and 21 cases died within 28 days after admission. Compared with sepsis group, the number of affected organs in septic shock group was greater [3 (2, 4) vs. 1 (0, 2)], APACHE II score [13 (10, 21) vs. 7 (5, 12)], SAPS II score [35 (31, 55) vs. 7 (5, 12)], SOFA score [7.0 (5.0, 10.0) vs. 3.0 (0, 5.0)], blood lactic acid [Lac (mmol/L): 3.5 (2.4, 6.2) vs. 1.9 (1.2, 2.2)], C-reactive protein [CRP (mg/L): 90.0 (58.1, 90.0) vs. 50.5 (38.0,90.0)] and VE-cad levels [mg/L: 1.427 (1.141, 2.150) vs. 1.195 (0.901, 1.688)] were significantly increased, while platelet count [PLT (×109/L): 113.4±67.2 vs. 202.5±109.5] and hemoglobin (Hb) levels (g/L: 106.3±36.3 vs. 118.6±18.0) were significantly decreased (all P < 0.05). Compared with non MODS group, APACHE II score [14 (10, 22) vs. 8 (6, 13)], SAPS II score [36 (32, 56) vs. 29 (24, 35)], SOFA score (7.9±3.9 vs. 4.0±3.8), in-hospital mortality [53.8% (21/39) vs. 0% (0/46)], Lac [mmol/L: 3.1 (2.3, 6.3) vs. 2.1 (1.4, 4.6)] and VE-cad levels [mg/L: 1.427 (1.156, 1.937) vs. 1.195 (0.897, 1.776)] in MODS group were significantly higher, the length of stay in EICU was significantly longer [days: 6 (3, 12) vs. 3 (0, 7)], and the PLT level was significantly lower (×109/L: 118.2±80.0 vs. 182.5±104.0, all P < 0.05). Compared with the death group, the number of affected organs in the survival group was fewer [2 (1, 3) vs. 3 (1, 5)], APACHE II score [9 (6, 13) vs. 21 (13, 25)], SAPS II score [31 (25, 36) vs. 55 (35, 63)] and SOFA score (4.7±3.7 vs. 8.9±4.5) were significantly reduced, and the length of stay in EICU [days: 4 (1, 8) vs. 8 (3, 15)] was significantly shorter (all P < 0.05). ROC curve analysis showed that area under the ROC curve (AUC) of VE-cad, SOFA score and VE-cad combined with SOFA score in evaluating the severity of sepsis were 0.632 [95% confidence interval (95%CI) was 0.513-0.750], 0.830 (95%CI was 0.744-0.916) and 0.856 (95%CI was 0.779-0.933), respectively. When the cut-off value of VE-cad was 1.240 mg/L, the sensitivity was 68.1% and the specificity was 55.3%, the sensitivity of VE-cad combined with SOFA score was 85.1%, the specificity was 73.7%. CONCLUSIONS: VE-cad has a certain evaluation value for the severity of sepsis, and the evaluation value of VE-cad combined with SOFA score is better than that of VE-cad single index.

Factors related to the length of stay for major depressive disorder patients in China: A real-world retrospective study.

Background: As numerous patients with depression have to be hospitalized because of various reasons, the demand far exceeds the limited bed count in the psychiatry department. Controlling the length of stay (LOS) of the patient is gradually being considered an effective method to alleviate this problem. Given the lack of statistical evidence of the LOS of patients with major depressive disorder (MDD) in China and the strain on the limited psychiatric resources, the purpose of our study was to investigate the LOS of patients with MDD among in-patient samples and to analyze related factors of the LOS in China by building a regression model. Method: The data were exported from the electronic medical record system. A total of three categories of independent variables were enrolled in our study, namely, demographic, clinical, and biochemical. Univariate analysis and binominal regression analysis were applied comprehensively to find the factors related to the LOS among MDD samples. The discrimination accuracy of the model was evaluated by the receiver operating characteristic (ROC) analysis. ROC analysis indicated that the discrimination accuracy of our model was acceptable (AUC = 0.790, 95% CI = 0.714-0.865, P < 0.001). Result: A total of 254 patients were finally brought into analysis after filtering. Regression analysis indicated that abnormal LDL was the only risk factor of long LOS (OR = 3.352, 95% CI = 1.087-10.337, P = 0.035) among all the kinds of variables. Notably, in the statistically irrelevant factors of the LOS, the category of anti-depressant drugs [serotonin-norepinephrine reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI)] prescribed to patients with MDD was not associated statistically with the LOS, which was against our initial hypothesis that the LOS of patients with MDD treated with SNRI would vary from that of the patients treated with SSRI. Conclusion: Up to our knowledge, our research is the first study to show the potential factors related to the LOS from various domains, especially biochemical indexes, and the effect of drugs, among clinical patients with MDD in China. Our results could provide a theoretical reference for efficient psychiatry hospitalization management and prioritization of allocating medical resources. Future studies are required for updating independent variables which are potentially related to the LOS and verifying existing results in a larger sample.

Red Blood Cell Membrane-Camouflaged PLGA Nanoparticles Loaded With Basic Fibroblast Growth Factor for Attenuating Sepsis-Induced Cardiac Injury.

Cardiac injury is recognized as a major contributor to septic shock and a major component of the multiple organ dysfunction associated with sepsis. Emerging evidence shows that regulation of the intramyocardial oxidative stress and inflammatory response has a promising prospect. Basic fibroblast growth factor (bFGF) exhibits anti-inflammatory and antioxidant properties. In this study, red blood cell membrane-camouflaged poly (lactide-co-glycolide) nanoparticles were synthesized to deliver bFGF (bFGF-RBC/NP) for sepsis-induced cardiac injury. The in vitro experiments revealed that bFGF-RBC/NP could protect cardiomyocytes from oxidative and inflammatory damage. In addition, the antioxidant and anti-inflammatory properties of bFGF-RBC/NP against cardiac injury were validated using data from in vivo experiments. Collectively, our study used bFGF for the treatment of sepsis-induced cardiac injury and confirmed that bFGF-RBC/NP has therapeutic benefits in the treatment of myocardial dysfunction. This study provides a novel strategy for preventing and treating cardiac injury in sepsis.