Bhlhe40 deficiency attenuates LPS-induced acute lung injury through preventing macrophage pyroptosis.

BACKGROUND: Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. Recently, increasing evidence supports activated inflammation and gasdermin D (GSDMD)-mediated pyroptosis in macrophage are closely associated with ALI. Basic helix-loop-helix family member e40 (Bhlhe40) is a transcription factor that is comprehensively involved in inflammation. However, there is little experimental evidence connecting Bhlhe40 and GSDMD-driven pyroptosis. The study sought to verify the hypothesis that Bhlhe40 is required for GSDMD-mediated pyroptosis in lipopolysaccharide (LPS)-induced inflammatory injury. METHOD: We performed studies using Bhlhe40-knockout (Bhlhe40 -/-) mice, small interfering RNA (siRNA) targeting Bhlhe40 and pyroptosis inhibitor disulfiram to investigate the potential roles of Bhlhe40 on LPS-induced ALI and the underlying mechanisms. RESULTS: Bhlhe40 was highly expressed in total lung tissues and macrophages of LPS-induced mice. Bhlhe40-/- mice showed alleviative lung pathological injury and inflammatory response upon LPS stimulation. Meanwhile, we found that Bhlhe40 deficiency significantly suppressed GSDMD-mediated pyroptosis in macrophage in vivo and in vitro. By further mechanistic analysis, we demonstrated that Bhlhe40 deficiency inhibited GSDMD-mediated pyroptosis and subsequent ALI by repressing canonical (caspase-1-mediated) and non-canonical (caspase-11-mediated) signaling pathways in vivo and in vitro. CONCLUSION: These results indicate Bhlhe40 is required for LPS-induced ALI. Bhlhe40 deficiency can inhibit GSDMD-mediated pyroptosis and therefore alleviate ALI. Targeting Bhlhe40 may be a potential therapeutic strategy for LPS-induced ALI.

Immune-Enhancing Treatment among Acute Necrotizing Pancreatitis Patients with Metabolic Abnormalities: A Post Hoc Analysis of a Randomized Clinical Trial.

Background/Aims: : Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immune-enhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients. Methods: : All data were obtained from the database for a multicenter randomized clinical trial that evaluated the efficacy of Tα1 in ANP patients. Patients who discontinued the Tα1 treatment prematurely were excluded. The primary outcome was 90-day infected pancreatic necrosis (IPN) after randomization. Three post hoc subgroups were defined based on the presence of hyperglycemia, hypertriglyceridemia, or both at the time of randomization. In each subgroup, the correlation between Tα1 and 90-day IPN was assessed using the Cox proportional-hazards regression model. Multivariable propensity-score methods were used to control potential bias. Results: : Overall, 502 participants were included in this post hoc analysis (248 received Tα1 treatment and 254 received matching placebo treatment). Among them, 271 (54.0%) had hyperglycemia, 371 (73.9%) had hypertriglyceridemia and 229 (45.6%) had both. Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. Additional multivariate regression models using three propensity-score methods yielded similar results. Conclusions: : Among ANP patients with hyperglycemia, immune-enhancing Tα1 treatment was associated with a reduced risk of IPN (ClinicalTrials.gov, Registry number: NCT02473406).

Plasma LTBP2 as a potential biomarker in differential diagnosis of connective tissue disease-associated interstitial lung disease and idiopathic pulmonary fibrosis: a pilot study.

Few biomarkers distinguish connective tissue disease-associated interstitial lung disease (CTD-ILD) from idiopathic pulmonary fibrosis (IPF). Latent transforming growth factor-ß binding protein-2 (LTBP2), a secreted extracellular matrix protein, is involved in pulmonary fibrosis. However, the role of LTBP2 in differentially diagnosing CTD-ILD and IPF is unclear. In this study, enzyme-linked immunosorbent assays quantified plasma LTBP2 concentrations in 200 individuals (35 healthy controls, 42 CTD patients without ILD, 89 CTD-ILD patients, and 34 IPF patients). CTD-ILD and IPF were further classified based on chest imaging pattern and pulmonary function test results. Plasma LTBP2 levels were significantly elevated in the IPF group compared with the CTD-ILD group. ROC analysis further suggested the possible value of LTBP2 in differentially diagnosing CTD-ILD and IPF. Additionally, CTD-ILD patients with progressive lung fibrosis had higher plasma LTBP2 concentrations than those who did not. Similarly, patients with IPF developing acute exacerbation showed higher plasma LTBP2 levels than those with stable IPF. This is the first study showing that LTBP2 was closely associated with the usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated ILD (RA-ILD). Moreover, the optimal cutoff values of LTBP2 for distinguishing IPF from CTD-UIP/RA-UIP were 33.75 and 38.33 ng/mL with an AUC of 0.682 and 0.681, respectively. Our findings suggest that plasma LTBP2 levels may differentially diagnose CTD-ILD and IPF, and assess their fibrotic activity. Additionally, clinical LTBP2 evaluation may be a great aid to identifying the presence of the UIP pattern in RA-ILD and to discriminating IPF from CTD-UIP, particularly RA-UIP.

Design and test of a FBG acceleration sensor based on multi-stage flexible hinges.

High-precision and high-sensitivity vibration acceleration sensors have been a research hotspot in engineering technology, which play an important role in engineering structural health monitoring, earthquakes, tsunamis, and geological exploration. A novel, to the best of our knowledge, fiber Bragg grating (FBG) acceleration sensor incorporating a mass block and flexible hinge was proposed against the low sensitivity and poor transverse interference resistance of existing FBG acceleration sensors. The FBG accelerometer with the multi-stage flexible hinge was modeled and theoretically analyzed, the structural parameters of the sensor were optimized and actual sensors were developed, and a sensor performance test experiment was carried out in the end. The result suggested that the sensor's natural frequency was as high as 1400 Hz, and its response was flat in the frequency range of 50-800 Hz; its sensitivity was 18.4 pm/g, linearity R 2 was 0.9983, and transverse interference immunity was below 3.2%. The research findings offered a new way of thinking about high-precision and high-sensitivity vibration measurement in engineering technology.

Association between serum albumin levels and survival in elderly patients with diffuse large B-cell lymphoma: a single-center retrospective study.

Background: In clinical hematology, diffuse large B-cell lymphoma (DLBCL) is notably heterogeneous and varies in prognosis. Serum albumin (SA) is considered a biomarker of prognostic value in a number of hematologic malignancies. However, current knowledge of the association between SA levels and survival is limited, especially in DLBCL patients aged ≥70 years. Thus, this study sought to assess the prognostic value of SA levels among this age group of patients. Methods: The data of DLBCL patients aged ≥70 years at the Shaanxi Provincial People's Hospital in China from 2010 to 2021 were retrospectively reviewed. The SA levels were measured using standard procedures. The Kaplan-Meier method was used to estimate survival time, and the Cox proportional hazards model for time-to-event data was used to identify potential risk factors. Results: The data of 96 participants were included in the study. The univariate analysis showed that B symptoms, Ann Arbor stage III or IV of the disease, high International Prognostic Index (IPI) scores, high NCCN-IPI scores, and low SA levels were prognostic factors for an undesirable overall survival (OS) rate. The multivariate analysis showed that a high SA level (hazard ratio: 0.43; 95% confidence interval: 0.2-0.88; P=0.022) was an independent prognostic factor of superior outcomes. Conclusions: An SA level ≥4.0 g/dL was identified as an independent biomarker of prognostic value for DLBCL patients aged ≥70 years.

Immune Molecules' mRNA Expression in Porcine Alveolar Macrophages Co-Infected with Porcine Reproductive and Respiratory Syndrome Virus and Porcine Circovirus Type 2.

Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus 2 (PCV2) are economically important pathogens in swine, and pigs with dual infections of PCV2 and PRRSV consistently have more severe clinical symptoms and interstitial pneumonia. However, the synergistic pathogenesis mechanism induced by PRRSV and PCV2 co-infection has not yet been illuminated. Therefore, the aim of this study was to characterize the kinetic changes of immune regulatory molecules, inflammatory factors and immune checkpoint molecules in porcine alveolar macrophages (PAMs) in individuals infected or co-infected with PRRSV and/or PCV2. The experiment was divided into six groups: a negative control group (mock, no infected virus), a group infected with PCV2 alone (PCV2), a group infected with PRRSV alone (PRRSV), a PCV2-PRRSV co-infected group (PCV2-PRRSV inoculated with PCV2, followed by PRRSV 12 h later), a PRRSV-PCV2 co-infected group (PRRSV-PCV2 inoculated with PRRSV, followed by PCV2 12 h later) and a PCV2 + PRRSV co-infected group (PCV2 + PRRSV, inoculated with PCV2 and PRRSV at the same time). Then, PAM samples from the different infection groups and the mock group were collected at 6, 12, 24, 36 and 48 h post-infection (hpi) to detect the viral loads of PCV2 and PRRSV and the relative quantification of immune regulatory molecules, inflammatory factors and immune checkpoint molecules. The results indicated that PCV2 and PRRSV co-infection, regardless of the order of infection, had no effect on promoting PCV2 replication, while PRRSV and PCV2 co-infection was able to promote PRRSV replication. The immune regulatory molecules (IFN-α and IFN-γ) were significantly down-regulated, while inflammatory factors (TNF-α, IL-1ß, IL-10 and TGF-ß) and immune checkpoint molecules (PD-1, LAG-3, CTLA-4 and TIM-3) were significantly up-regulated in the PRRSV and PCV2 co-infection groups, especially in PAMs with PCV2 inoculation first followed by PRRSV. The dynamic changes in the aforementioned immune molecules were associated with a high viral load, immunosuppression and cell exhaustion, which may explain, at least partially, the underlying mechanism of the enhanced pulmonary lesions by dual infection with PCV2 and PRRSV in PAMs.

Gradual Traction Reduction With the Ilizarov Method for Tile C1.2 Old Pelvic Fracture: A Case Report.

CASE: A 20-year-old man with a Tile C1.2 pelvic fracture was treated with skeletal traction. After 3 months, the patient was unable to stand and walk, and the right lower limb was shortened by 7 cm. Radiographs showed that the sacroiliac joint dislocation was not reduced. Gradual traction reduction with the Ilizarov method was used to correct sacroiliac joint dislocation, and open internal fixation was performed. Postoperatively, the old pelvic fracture was successfully reduced without sacral plexus injury. CONCLUSION: Gradual traction reduction with the Ilizarov method can reduce the risk of sacral plexus injury and achieve satisfactory reduction of Tile C1.2 old pelvic fractures.

Identification and characterization of two SERPINC1 mutations causing congenital antithrombin deficiency.

BACKGROUND: Antithrombin (AT) is the main physiological anticoagulant involved in hemostasis. Hereditary AT deficiency is a rare autosomal dominant thrombotic disease mainly caused by mutations in SERPINC1, which was usually manifested as venous thrombosis and pulmonary embolism. In this study, we analyzed the clinical characteristics and screened for mutant genes in two pedigrees with hereditary AT deficiency, and the functional effects of the pathogenic mutations were evaluated. METHODS: Candidate gene variants were analyzed by next-generation sequencing to screen pathogenic mutations in probands, followed by segregation analysis in families by Sanger sequencing. Mutant and wild-type plasmids were constructed and transfected into HEK293T cells to observe protein expression and cellular localization of SERPINC1. The structure and function of the mutations were analyzed by bioinformatic analyses. RESULTS: The proband of pedigree A with AT deficiency carried a heterozygous frameshift mutation c.1377delC (p.Asn460Thrfs*20) in SERPINC1 (NM000488.3), a 1377C base deletion in exon 7 resulting in a backward shift of the open reading frame, with termination after translation of 20 residues, and a different residue sequence translated after the frameshift. Bioinformatics analysis suggests that the missing amino acid sequence caused by the frameshift mutation might disrupt the disulfide bond between Cys279 and Cys462 and affect the structural function of the protein. This newly discovered variant is not currently included in the ClinVar and HGMD databases. p.Arg229* resulted in a premature stop codon in exon 4, and bioinformatics analysis suggests that the truncated protein structure lost its domain of interaction with factor IX (Ala414 site) after the deletion of nonsense mutations. However, considering the AT truncation protein resulting from the p.Arg229* variant loss a great proportion of the molecule, we speculate the variant may affect two functional domains HBS and RCL and lack of the corresponding function. The thrombophilia and decreased-AT-activity phenotypes of the two pedigrees were separated from their genetic variants. After lentiviral plasmid transfection into HEK293T cells, the expression level of AT protein decreased in the constructed c.1377delC mutant cells compared to that in the wild-type, which was not only reduced in c.685C > T mutant cells but also showed a significant band at 35 kDa, suggesting a truncated protein. Immunofluorescence localization showed no significant differences in protein localization before and after the mutation. CONCLUSIONS: The p.Asn460Thrfs*20 and p.Arg229* variants of SERPINC1 were responsible for the two hereditary AT deficiency pedigrees, which led to AT deficiency by different mechanisms. The p.Asn460Thrfs*20 variant is reported for the first time.

Plasma IL-36α and IL-36γ as Potential Biomarkers in Interstitial Lung Disease Associated with Rheumatoid Arthritis: a Pilot Study in the Chinese Population.

Interstitial lung disease (ILD) is a frequent extra-articular manifestation of rheumatoid arthritis (RA) and increases mortality in patients with RA. Early identification of ILD, especially the usual interstitial pneumonia (UIP) pattern with a poor prognosis, is important for guiding treatment of RA-ILD and preventing damage resulting from a delay in diagnosis. Interleukin-36 (IL-36) cytokines are involved in connective tissue diseases. However, IL-36 expression in RA-ILD is unknown. In this study, the clinical relevance of plasma IL-36 cytokines was evaluated in 39 patients with RA-ILD and three other groups (30 healthy controls [HCs], 35 RA patients without ILD, and 27 patients with idiopathic pulmonary fibrosis [IPF]) in the Chinese population. Plasma IL-36α and IL-36γ concentrations were elevated in patients with RA-ILD compared with those in HCs and patients with RA. RA-ILD patients with UIP pattern had higher plasma IL-36γ concentrations than those with RA-ILD without UIP, but these were lower than those in patients with IPF. Receiver operating curve analysis suggested that IL-36α and IL-36γ were potential biomarkers for identifying ILD in patients with RA. Additionally, the optimal cutoff value of IL-36γ for distinguishing RA-ILD with the UIP pattern from RA-ILD without UIP was 555.40 pg/mL and that for distinguishing RA-ILD from IPF was 655.10 pg/mL. No significant difference in plasma IL-36ß or IL-36Ra concentrations was found between patients with RA-ILD and the three other groups. We also found that the lungs originating from different types of patients with PF, including RA-ILD and IPF, and those from mice following bleomycin-induced PF were characterized by increased IL-36γ expression. Our findings suggest that using IL-36 cytokines to identify patients with RA for further ILD workups may provide additional diagnostic value to the current clinically available assays. Moreover, IL-36γ may help to identify the presence of the UIP pattern in patients with RA-ILD and to discriminate RA-ILD from IPF.

Interleukin-35 has a Protective Role in Infectious Mononucleosis-Induced Liver Inflammation Probably by Inhibiting CD8+ T Cell Function.

Interleukin (IL)-35 plays an immunosuppressive role in infectious diseases, autoimmune disorders, and cancers. However, IL-35 expression and its regulation of CD8+ T cells in infectious mononucleosis (IM) are not fully understood. In this study, three groups of participants were compared, including twenty-three patients of IM without liver inflammation, twenty-eight patients of IM with liver inflammation, and twenty-one controls. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. CD8+ T cells were purified. Plasma IL-35 was measured by ELISA. PBMCs and CD8+ T cells were stimulated with recombinant human IL-35 in vitro. Perforin and granzyme B secretion was assessed by ELISPOT. Immune checkpoint molecule expression was investigated by flow cytometry. CD8+ T cells were co-cultured with HepG2 cells in direct contact and indirect contact manner. The cytotoxicity of CD8+ T cells was calculated by measuring lactate dehydrogenase release and proinflammatory cytokine expression. There was no significant difference in plasma IL-35 levels between patients with IM without liver inflammation and the controls, but the IL-35 level was notably increased in patients with IM who presented with liver inflammation and negatively correlated with aminotransferase. CD8+ T cells in patients with IM with liver inflammation showed stronger cytotoxicity. IL-35 stimulation inhibited CD8+ T cell-induced target cell death in patients with IM, mainly through suppression of IFN-γ/TNF-α secretion and elevation of immune checkpoint molecule expression, but did not affect perforin or granzyme B secretion. The current data indicated that IL-35 dampened the cytotoxicity of CD8+ T cells in patients with IM probably via repression of cytokine secretion. Elevated IL-35 may protect against CD8+ T cell-induced liver inflammation in patients with IM.

[Effectiveness analysis of disposable skin stretch closure in treatment of difficult to close skin and soft tissue defects].

Objective: To observe the effectiveness of disposable skin stretch closure in the treatment of wounds with skin and soft tissue defects that were difficult to close. Methods: The clinical data of 13 patients with skin and soft tissue defects that were difficult to close treated with disposable skin stretch closure and met the selection criteria between July 2021 and February 2022 were retrospectively reviewed. There were 9 males and 4 females, the age ranged from 15 to 71 years with a mean of 39.8 years. The causes of injury included falling injury in 5 patients, traffic accident injury in 5 patients, and falling from height injury in 3 patients. The causes of skin soft tissue defects included open fractures in 4 patients, wound infection in 4 patients, osteomyelitis in 3 patients, degloving injury in 1 patient, and necrosis of skin graft in 1 patient. The injury was located at calf in 8 patients, calcaneus in 3 patients, pelvis in 1 patient, and plantar in 1 patient. The skin and soft tissue defects ranged from 5.0 cm×2.0 cm to 10.5 cm×6.5 cm. Wound conditions (wound closure and wound healing) and the presence or absence of complications were recorded. Results: All 13 patients were followed up 32-225 days with a median of 164 days. The wound closure time ranged from 5 to 14 days, with a mean of 8.8 days. The wound closure speed ranged from 0.7 to 13.7 cm 2/day, with a mean of 3.6 cm 2/day. All wounds healed at grade A, and no complication such as skin edge injury, wound necrosis, infection, dehiscence, and edema occurred. No patient complained of pain or discomfort, and no obvious scarring was found during follow-up. The wound healing time ranged from 17 to 28 days, with a mean of 21.7 days. One of them was transferred to other department due to lung cancer condition changes after using disposable skin stretch closure, and the wound had directly healed without suturing at 17 days after operation. Conclusion: The effectiveness of disposable skin stretch closure in the treatment of wounds with skin and soft tissue defects that were difficult to close was exact, with short wound closure time, few complications, and easy operation.

circSTRN3 aggravates sepsis-induced acute kidney injury by regulating miR-578/ toll like receptor 4 axis.

Sepsis is a systemic inflammatory response caused by infection, and severe sepsis is commonly associated with the development of acute kidney injury (AKI). Accumulating evidence has revealed the implication of circular RNAs in AKI. In this study, we explored the potential engagement and the underlying mechanism of hsa_circ_010157 (circSTRN3) in sepsis-induced AKI. CircSTRN3 levels in HK2 cells and serum samples of patients were determined by RT-PCR. The protein levels of TLR4 (Toll Like Receptor 4), bax (Bcl-2-associated X protein), cleaved caspase 3 and bcl-2 (B-cell lymphoma-2) were detected by Western blotting (WB), and the levels of proinflammatory cytokines were detected by ELISA. The molecular interactions between mir-578/TLR4 and circSTRN3/miR-578 were analyzed by dual luciferase reporter assay as well as RNA pull-down experiment. Lipopolysaccharide (LPS) treated HK2 cells were used as an in vitro model to investigate the functional interaction of circSTRN3/miR-578/TLR4 axis. We found that the expression level of circSTRN3 in patients with sepsis-induced AKI and LPS-induced HK2 cells was higher. Silencing cicrSTRN3 alleviated LPS-induced cell proliferation, and suppressed the inflammatory response and apoptosis in LPS-treated HK2 cells. In contrast, the overexpression of circSTRN3 aggravated the cellular damages induced by LPS treatment. CircSTRN3 targeted miR-578/TLR4 axis to influence the damage effect induced by LPS. miR-578 inhibitor or TLR4 overexpression impaired the rescue effect of circSTRN3 knockdown. These results indicate that circSTRN3 upregulation in sepsis-induced AKI modulates miR-578/TLR4 axis to promote the pathogenesis of AKI, which could serve as future therapeutic targets for AKI treatment.

Fusion Protein Cleavage Site Containing Three Basic Amino Acids Attenuates Newcastle Disease Virus in Chicken Embryos: Use as an in ovo Vaccine.

In ovo vaccination is an attractive immunization strategy for the poultry industry. However, although most live Newcastle disease virus (NDV) vaccine strains, such as LaSota and V4, can be used after hatching, they are pathogenic to chicken embryos when administered in ovo. We have previously reported that NDV strain TS09-C is a safe in ovo vaccine in specific-pathogen-free and commercial chicken embryos because it is attenuated in chicken embryos. However, the molecular basis of its attenuation is poorly understood. In this study, we firstly evaluated the safety of chimeric NDV strains after exchanging genes between strains TS09-C and LaSota as in ovo vaccines, and demonstrated that the attenuation of NDV in chicken embryos was dependent upon the origin of the fusion (F) protein. Next, by comparing the F protein sequences of TS09-C strain with those of LaSota and V4 strain, the R115 in cleavage site and F379 were found to be unique to TS09-C strain. The mutant viruses were generated by substituting one or two amino acids at position 115 and 379 in the F protein, and their safety as in ovo vaccine was evaluated. Mutation in residue 379 did not affect the viral embryonic pathogenicity. While the mutant virus rTS-2B (R115G mutation based on the backbone of TS09-C strain) with two basic amino acids in F cleavage site, was pathogenic to chicken embryos and similar with rLaSota in its tissue tropism, differing markedly from rTS09-C with three basic amino acids in F cleavage site. Together, these findings indicate that the F protein cleavage site containing three basic amino acids is the crucial determinant of the attenuation of TS09-C in chicken embryos. This study extends our understanding of the pathogenicity of NDV in chicken embryos and should expedite the development of in ovo vaccines against NDV.

Dec1 Deficiency Ameliorates Pulmonary Fibrosis Through the PI3K/AKT/GSK-3ß/ß-Catenin Integrated Signaling Pathway.

Tissue remodeling/fibrosis is a main feature of idiopathic pulmonary fibrosis (IPF), which results in the replacement of normal lung parenchyma with a collagen-rich extracellular matrix produced by fibroblasts and myofibroblasts. Epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells is a key process in IPF, which leads to fibroblasts and myofibroblasts accumulation and excessive collagen deposition. DEC1, a structurally distinct class of basic helix-loop-helix proteins, is associated with EMT in cancer. However, the functional role of DEC1 in pulmonary fibrosis (PF) remains elusive. Herein, we aimed to explore DEC1 expression in IPF and bleomycin (BLM)-induced PF in mice and the mechanisms underlying the fibrogenic effect of DEC1 in PF in vivo and in vitro by Dec1-knockout (Dec1 -/-) mice, knockdown and overexpression of DEC1 in alveolar epithelial cells (A549 cells). We found that the expression of DEC1 was increased in IPF and BLM-injured mice. More importantly, Dec1 -/- mice had reduced PF after BLM challenge. Additionally, DEC1 deficiency relieved EMT development and repressed the PI3K/AKT/GSK-3ß/ß-catenin integrated signaling pathway in mice and in A549 cells, whereas DEC1 overexpression in vitro had converse effects. Moreover, the PI3K/AKT and Wnt/ß-catenin signaling inhibitors, LY294002 and XAV-939, ameliorated BLM-meditated PF in vivo and relieved EMT in vivo and in vitro. These pathways are interconnected by the GSK-3ß phosphorylation status. Our findings indicated that during PF progression, DEC1 played a key role in EMT via the PI3K/AKT/GSK-3ß/ß-catenin integrated signaling pathway. Consequently, targeting DEC1 may be a potential novel therapeutic approach for IPF.

Effect of hypoproteinemia on the mortality of sepsis patients in the ICU: a retrospective cohort study.

The objective of the study was to evaluate the effect of hypoproteinemia on the prognosis of sepsis patients and the effectiveness of exogenous albumin supplementation. A retrospective cohort study was conducted in adult ICUs. The subjects were 1055 sepsis patients in MIMIC III database from June 2001 to October 2012. There were no interventions. A total of 1055 sepsis patients were enrolled and allocated into two groups based on the lowest in-hospital albumin level: 924 patients were in the hypoproteinemia group (the lowest in-hospital albumin ≤ 3.1 g/dL) and 131 patients were in the normal group (the lowest in-hospital albumin > 3.1 g/dL). A total of 378 patients [331 (35.8%) were in the hypoproteinemia group, and 47 (35.9%) were in the normal group] died at 28 days, and no statistically significant difference was found between the two groups (P = 0.99). The survival analysis of the 28-day mortality rate was performed using the Cox proportional risk model and it was found that the lowest in-hospital albumin level showed no significant effect on the 28-day mortality rate (P = 0.18, 95%CI). Patients in the hypoproteinemia group exhibited a longer length of stay in ICU and hospital and more complications with AKI than those in the normal group. However, multivariate regression analysis found that there was no statistical significance between the two groups. In addition, multivariate regression analysis showed that patients in the hypoproteinemia group had a shorter time without vasoactive drugs and time without mechanical ventilation than those in the normal group (P < 0.01). In the subgroup analysis, univariate analysis and multivariate regression analysis showed that there was no significant difference in the 28-day mortality rate (39.6% vs 37.5%, P = 0.80), the proportion of mechanical ventilation time (P = 0.57), and vasoactive drug time (P = 0.89) between patients with and without albumin supplementation. However, patients in the albumin supplementation group had a longer length of ICU stay and hospital stay than those in the non-supplementation group (P < 0.01). Albumin level may be an indicator of sepsis severity, but hypoproteinemia has no significant effect on the mortality of sepsis patients. Despite various physiological effects of albumin, the benefits of albumin supplementation in sepsis patients need to be evaluated with caution.

Improved Resolution and Cost Performance of Low-Cost MEMS Seismic Sensor through Parallel Acquisition.

In earthquake monitoring, an important aspect of the operational effect of earthquake intensity rapid reporting and earthquake early warning networks depends on the density and performance of the deployed seismic sensors. To improve the resolution of seismic sensors as much as possible while keeping costs low, in this article the use of multiple low-cost and low-resolution digital MEMS accelerometers is proposed to increase the resolution through the correlation average method. In addition, a cost-effective MEMS seismic sensor is developed. With ARM and Linux embedded computer technology, this instrument can cyclically store the continuous collected data on a built-in large-capacity SD card for approximately 12 months. With its real-time seismic data processing algorithm, this instrument is able to automatically identify seismic events and calculate ground motion parameters. Moreover, the instrument is easy to install in a variety of ground or building conditions. The results show that the RMS noise of the instrument is reduced from 0.096 cm/s2 with a single MEMS accelerometer to 0.034 cm/s2 in a bandwidth of 0.1-20 Hz by using the correlation average method of eight low-cost MEMS accelerometers. The dynamic range reaches more than 90 dB, the amplitude-frequency response of its input and output within -3 dB is DC -80 Hz, and the linearity is better than 0.47%. In the records from our instrument, earthquakes with magnitudes between M2.2 and M5.1 and distances from the epicenter shorter than 200 km have a relatively high SNR, and are more visible than they were prior to the joint averaging.

Study of Building Safety Monitoring by Using Cost-Effective MEMS Accelerometers for Rapid After-Earthquake Assessment with Missing Data.

Suffering from structural deterioration and natural disasters, the resilience of civil structures in the face of extreme loadings inevitably drops, which may lead to catastrophic structural failure and presents great threats to public safety. Earthquake-induced extreme loading is one of the major reasons behind the structural failure of buildings. However, many buildings in earthquake-prone areas of China lack safety monitoring, and prevalent structural health monitoring systems are generally very expensive and complicated for extensive applications. To facilitate cost-effective building-safety monitoring, this study investigates a method using cost-effective MEMS accelerometers for buildings' rapid after-earthquake assessment. First, a parameter analysis of a cost-effective MEMS sensor is conducted to confirm its suitability for building-safety monitoring. Second, different from the existing investigations that tend to use a simplified building model or small-scaled frame structure excited by strong motions in laboratories, this study selects an in-service public building located in a typical earthquake-prone area after an analysis of earthquake risk in China. The building is instrumented with the selected cost-effective MEMS accelerometers, characterized by a low noise level and the capability to capture low-frequency small-amplitude dynamic responses. Furthermore, a rapid after-earthquake assessment scheme is proposed, which systematically includes fast missing data reconstruction, displacement response estimation based on an acceleration response integral, and safety assessment based on the maximum displacement and maximum inter-story drift ratio. Finally, the proposed method is successfully applied to a building-safety assessment by using earthquake-induced building responses suffering from missing data. This study is conducive to the extensive engineering application of MEMS-based cost-effective building monitoring and rapid after-earthquake assessment.

Effects of the Pars Plana Vitrectomy on the Chronic Total Rhegmatogenous Retinal Detachment in the Young Adults.

Objective: To observe the characteristics and evaluate the efficacy and safety of the chronic total rhegmatogenous retinal detachment (RRD) treatment by the 23-gauge pars plana vitrectomy (PPV) in young adults and to analyze the related factors. Methods: A retrospective chart review was performed for the young adults who underwent the 23-gauge PPV for the chronic total RRD at the Tianjin Medical University General Hospital from 2011 to 2018. A total of 54 eyes of 48 patients were included in this study. The preoperative vision ranged from 2.00 to 1.00. The mean duration of RRD was 9 ± 0.6 months with a range from 4 to 18 months. The proliferative vitreoretinopathy (PVR) grade D1 and grade D2 was diagnosed in 48 eyes and 6 eyes, respectively. About 37 eyes were filled with C3F8 and 17 eyes were filled with silicone oil tamponade. The follow-up ranged from 9 to 78 months with a mean of 23 ± 2.2 months. Results: The postoperative visual acuity increased in all the eyes at the final observation. The retinal attachment was achieved in 49 eyes (90.7%) in the primary PPV. Five eyes (9.3%) with the failed retinal attachment finally achieved the attachment after the second procedure. The postoperative complications mainly included temporary intraocular pressure (IOP) elevation, hyphema, and retinal redetachment. Conclusion: Chronic total RRD can be treated via the 23-gauge PPV with a great anatomical and visual prognosis in the young adult. The successful treatment of the chronic total RRD in young adults is mainly associated with the complete dissection of the severe vitreoretinopathy, especially for the epiretinal membrane at the retinal breaks and degenerations and the subretinal proliferation during surgery.

Design of a Low-Cost Small-Size Fluxgate Sensor.

Traditional fluxgate sensors used in geomagnetic field observations are large, costly, power-consuming and often limited in their use. Although the size of the micro-fluxgate sensors has been significantly reduced, their performance, including indicators such as accuracy and signal-to-noise, does not meet observational requirements. To address these problems, a new race-track type probe is designed based on a magnetic core made of a Co-based amorphous ribbon. The size of this single-component probe is only Φ10 mm × 30 mm. The signal processing circuit is also optimized. The whole size of the sensor integrated with probes and data acquisition module is Φ70 mm × 100 mm. Compared with traditional fluxgate and micro-fluxgate sensors, the designed sensor is compact and provides excellent performance equal to traditional fluxgate sensors with good linearity and RMS noise of less than 0.1 nT. From operational tests, the results are in good agreement with those from a standard fluxgate magnetometer. Being more suitable for modern dense deployment of geomagnetic observations, this small-size fluxgate sensor offers promising research applications at lower costs.