Allosteric inhibition of the IRE1α RNase preserves cell viability and function during endoplasmic reticulum stress.

Depending on endoplasmic reticulum (ER) stress levels, the ER transmembrane multidomain protein IRE1α promotes either adaptation or apoptosis. Unfolded ER proteins cause IRE1α lumenal domain homo-oligomerization, inducing trans autophosphorylation that further drives homo-oligomerization of its cytosolic kinase/endoribonuclease (RNase) domains to activate mRNA splicing of adaptive XBP1 transcription factor. However, under high/chronic ER stress, IRE1α surpasses an oligomerization threshold that expands RNase substrate repertoire to many ER-localized mRNAs, leading to apoptosis. To modulate these effects, we developed ATP-competitive IRE1α Kinase-Inhibiting RNase Attenuators-KIRAs-that allosterically inhibit IRE1α's RNase by breaking oligomers. One optimized KIRA, KIRA6, inhibits IRE1α in vivo and promotes cell survival under ER stress. Intravitreally, KIRA6 preserves photoreceptor functional viability in rat models of ER stress-induced retinal degeneration. Systemically, KIRA6 preserves pancreatic ß cells, increases insulin, and reduces hyperglycemia in Akita diabetic mice. Thus, IRE1α powerfully controls cell fate but can itself be controlled with small molecules to reduce cell degeneration.

Phosphorylation switches protein disulfide isomerase activity to maintain proteostasis and attenuate ER stress.

Accumulated unfolded proteins in the endoplasmic reticulum (ER) trigger the unfolded protein response (UPR) to increase ER protein folding capacity. ER proteostasis and UPR signaling need to be regulated in a precise and timely manner. Here, we identify phosphorylation of protein disulfide isomerase (PDI), one of the most abundant and critical folding catalysts in the ER, as an early event during ER stress. The secretory pathway kinase Fam20C phosphorylates Ser357 of PDI and responds rapidly to various ER stressors. Phosphorylation of Ser357 induces an open conformation of PDI and turns it from a "foldase" into a "holdase", which is critical for preventing protein misfolding in the ER. Phosphorylated PDI also binds to the lumenal domain of IRE1α, a major UPR signal transducer, and attenuates excessive IRE1α activity. Importantly, PDI-S359A knock-in mice display enhanced IRE1α activation and liver damage under acute ER stress. We conclude that the Fam20C-PDI axis constitutes a post-translational response to maintain ER proteostasis and plays a vital role in protecting against ER stress-induced cell death.

Mechanisms Underlying a Quantum Superposition Microscope Based on THz-Driven Coherent Oscillations in a Two-Level Molecular Sensor.

We report pump-probe measurements of a hydrogen molecule (H_{2}) in the tunnel junction of a scanning tunneling microscope coupled to ultrashort terahertz (THz) pulses. The coherent oscillation of the THz-induced dc tunneling current at a frequency of ∼0.5 THz fingerprints the absorption by H_{2} as a two-level system (TLS). Two components of the oscillatory signal are observed and point to both photon and field aspects of the THz pulses. A few loosely bound states with similar energies for the upper state of the TLS are evidenced by the coherent revival of oscillatory signal. Furthermore, the comparison of spectroscopic features of H_{2} with different tips provides an understanding of the TLS for H_{2}.

Single amino acid variation in MAB21L1 is dominantly associated with congenital eye defects.

BACKGROUND: Diagnosis of a genetic disease and determination of the causative molecular lesion rely on the availability of the disease-associated pedigrees. Microphthalmia is a congenital eye defect due to an insufficiently developed visual system; its prevalence is 1-3 in 10 000 live births. OBJECTIVE: We analysed a pedigree exhibiting autosomal dominant inheritance of microphthalmia to determine the genetic lesion; used AlphaFold2 to predict the changes in the protein's 3-Dimensional structure; and compared wild-type and variant proteins in cultured cells or Drosophila model was used to explore the cellular or developmental function of the encoded product. RESULTS: We identified a novel missense variation, F52L, in MAB21L1 that is absent in population databases and present exclusively in the individuals diagnosed with microphthalmia in this pedigree. Common structural changes were predicted for the disease-associated variants clustered at amino acids 49-52, and these variant products were also predominantly trapped in the cytoplasm of cultured human lens epithelia. To recapitulate its dominant effect in development, we expressed the Drosophila homologue corresponding to MAB21L1F52L and caused malformation of sensory organs. CONCLUSION: Mutations at the residues 49-52 of MAB21L1 compromise eye development. We recommend including MAB21L1 in the genetic testing panel for congenital eye disorders.

A High-Performance Flexible Hydroacoustic Transducer Based on 1-3 PZT-5A/Silicone Rubber Composite.

In recent years, hydroacoustic transducers made of PZT/epoxy composites have been extensively employed in underwater detection, communication, and recognition for their high energy conversion efficiency. Despite the ease with which these transducers can be formed into complex shapes, their lack of mechanical flexibility limits their versatility across various sizes of underwater vehicles. This study introduces a novel flexible piezoelectric composite hydroacoustic transducer (FPCHT) based on a 1-3 PZT-5A/silicone rubber composite and an island-bridge flexible electrode, which can break the limitations of existing hydroacoustic transducers that do not have flexibility. The finite element method is used to optimize the structural parameters of high-performance 1-3 FPC. A large-sized (187 mm × 47 mm × 5.12 mm) FPC is fabricated using an improved cutting-filling method and packaged into the FPCHT. Compared with the planar rigid PZT/epoxy composite hydroacoustic transducer (RPCHT) of the same size, the TVR (186.5 db) of the FPCHT has increased by about 7 dB, indicating that it has better acoustic radiation performance and electroacoustic conversion efficiency. Furthermore, its electroacoustic performance exhibits excellent stability under different bending states. Therefore, the FPCHT with high electroacoustic performance is an ideal substitute for the existing RPCHT and promotes the development of hydroacoustic transducers towards flexibility and portability.

Investigating phase separation properties of chromatin-associated proteins using gradient elution of 1,6-hexanediol.

BACKGROUND: Chromatin-associated phase separation proteins establish various biomolecular condensates via liquid-liquid phase separation (LLPS), which regulates vital biological processes spatially and temporally. However, the widely used methods to characterize phase separation proteins are still based on low-throughput experiments, which consume time and could not be used to explore protein LLPS properties in bulk. RESULTS: By combining gradient 1,6-hexanediol (1,6-HD) elution and quantitative proteomics, we developed chromatin enriching hexanediol separation coupled with liquid chromatography-mass spectrometry (CHS-MS) to explore the LLPS properties of different chromatin-associated proteins (CAPs). First, we found that CAPs were enriched more effectively in the 1,6-HD treatment group than in the isotonic solution treatment group. Further analysis showed that the 1,6-HD treatment group could effectively enrich CAPs prone to LLPS. Finally, we compared the representative proteins eluted by different gradients of 1,6-HD and found that the representative proteins of the 2% 1,6-HD treatment group had the highest percentage of IDRs and LCDs, whereas the 10% 1,6-HD treatment group had the opposite trend. CONCLUSION: This study provides a convenient high-throughput experimental method called CHS-MS. This method can efficiently enrich proteins prone to LLPS and can be extended to explore LLPS properties of CAPs in different biological systems.

Deacetylase sirtuin 2 negatively regulates myeloid-derived suppressor cell functions in allograft rejection.

Although myeloid-derived suppressor cells (MDSCs) are critical for allograft survival, their regulatory mechanism remains unclear. Herein, our results showed that metabolism sensor sirtuin 2 (SIRT2) negatively regulates the functions of MDSCs in inducing allogeneic skin graft rejection. Genetic deletion of SIRT2 in myeloid cells (Sirt2Δmye) increased the number of CD11b+Gr1+ MDSCs in bone marrow, spleens, draining lymph nodes, and allografts, inhibited the production of proinflammatory cytokine tumor necrosis factor ɑ, enhanced the production of anti-inflammatory cytokine interleukin 10, and potentiated the suppressive activation of MDSCs in prolonging allograft skin survival. C-X-C motif chemokine receptor 2 is critical for mediating the recruitment and cytokine production of MDSCs induced by SIRT2. Mechanistically, Sirt2Δmye enhanced NAD+ levels, succinate dehydrogenase subunit A (SDHA) activities, and oxidative phosphorylation (OXPHOS) levels in MDSCs after transplantation. Pharmacologically blocking nicotinamide phosphoribosyltransferase effectively reverses the production of cytokines and suppressive activities of MDSC induced by Sirt2Δmye. Blocking OXPHOS with knockdown of SDHA or pharmacological blocking of SDHA significantly restores Sirt2Δmye-mediated stronger MDSC suppressive activity and inflammatory factor productions. Thus, our findings identify a previously unrecognized interplay between NAD+ and SDH-mediated OXPHOS metabolic pathways in regulating MDSC functions induced by the metabolic sensor SIRT2 in allogeneic transplantation.

Enhancing Crystallization in Hybrid Perovskite Solar Cells Using Thermally Conductive 2D Boron Nitride Nanosheet Additive.

Controlling crystallization and grain growth is crucial for realizing highly efficient hybrid perovskite solar cells (PSCs). In this work, enhanced PSC photovoltaic performance and stability by accelerating perovskite crystallization and grain growth via 2D hexagonal boron nitride (hBN) nanosheet additives incorporated into the active perovskite layer are demonstrated. In situ X-ray scattering and infrared thermal imaging during the perovskite annealing process revealed the highly thermally conductive hBN nanosheets promoted the phase conversion and grain growth in the perovskite layer by facilitating a more rapid and spatially uniform temperature rise within the perovskite film. Complementary structural, physicochemical, and electrical characterizations further showed that the hBN nanosheets formed a physical barrier at the perovskite grain boundaries and the interfaces with charge transport layers, passivating defects, and retarding ion migration. As a result, the power conversion efficiency of the PSC is improved from 17.4% to 19.8%, along with enhanced device stability, retaining ≈90% of the initial efficiency even after 500 h ambient air storage. The results not only highlight 2D hBN as an effective additive for PSCs but also suggest enhanced thermal transport as one of the pathways for improved PSC performance by 2D material additives in general.

Electrical Manipulation of Quantum Coherence in a Two-Level Molecular System.

We report the manipulation of ultrafast quantum coherence of a two-level single hydrogen molecular system by employing static electric field from the sample bias in a femtosecond terahertz scanning tunneling microscope. A H_{2} molecule adsorbed on the polar Cu_{2}N surface develops an electric dipole and exhibits a giant Stark effect. An avoided crossing of the quantum state energy levels is derived from the resonant frequency of the single H_{2} two levels in a double-well potential. The dephasing time of the initial wave packet can also be changed by applying the electric field. The electrical manipulation for different tunneling gaps in three dimensions allows quantification of the surface electrostatic fields at the atomic scale. Our work demonstrated the potential application of molecules as controllable two-level molecular systems.

E3 ubiquitin ligase NEURL3 promotes innate antiviral response through catalyzing K63-linked ubiquitination of IRF7.

Interferon regulatory factor 7 (IRF7), as the interferon-stimulated gene, maximally drives type I interferon (IFN) production. However, the mechanisms by which the biological function of IRF7 is regulated remain elusive. In this study, we found that IRF7 selectively interacted with the neuralized E3 ubiquitin-protein ligase 3 (NEURL3). In concomitant with IRF7 induction, NEURL3 is upregulated by NF-κB signaling in the late phase of viral infection. Moreover, NEURL3 augmented the host antiviral immune response through ubiquitinating IRF7. A mechanistic study revealed that NEURL3 triggered K63-linked poly-ubiquitination on IRF7 lysine 375, which in turn epigenetically enhanced the transcription of interferon-stimulated genes (ISGs) through disruption of the association of IRF7 with Histone Deacetylase 1 (HDAC1), consequently augmenting host antiviral immune response. Accordingly, Neurl3-/- mice produced less type I IFNs and exhibited increased susceptibility to viral infection. Taken together, our findings identify NEURL3 as an E3 ubiquitin ligase of IRF7 and shed new light on the positive regulation of IRF7 in host antiviral immune signaling.

Curtanaerobium respiraculi gen. nov., sp. nov., a novel anaerobic bacterium isolated from human bronchoalveolar lavage fluid.

Two related anaerobic strains, designated as SWB101512T and SWB19611, were isolated from the bronchoalveolar lavage fluid of two lung cancer patients. Cells were Gram-stain-positive, non-motile and non-spore-forming. Growth could be observed at 26-45 °C (optimum, 37 °C), pH 5.0-8.5 (optimum, pH 7.0) and with 0.5-2.0 % (v/w) NaCl (optimum, 1.0%). The 16S rRNA gene sequences of SWB101512T and SWB19611 showed the highest similarities to Denitrobacterium detoxificans DSM 21843T (91.1 and 91.3 %, respectively). The phylogenetic tree based on the 16S rRNA gene sequences and the core genome sequences demonstrated that the two strains clustered together and formed a distinct lineage within the family Eggerthellaceae. The DNA G+C contents of strains SWB101512T and SWB19611 were 62.0 and 61.9 mol%, respectively. The predominant cellular fatty acids of strains SWB101512T and SWB19611 were C16 : 0 DMA (27.8 and 28.8 %, respectively). The respiratory menaquinone in both strains was menaquinone 6 and the polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, two phospholipids, three glycolipids and three unidentified lipids. Based on evidence from phenotypic, chemotaxonomic and genomic analyses, a new genus and species belonging to the family Eggerthellaceae, named Curtanaerobium respiraculi gen. nov., sp. nov. is proposed. The type strain is SWB101512T (=GDMCC 1.2991T=JCM 35330T).

MicroRNA-181a-5p alleviates acute liver failure in mice by inhibiting HMGB1.

MicroRNAs (miRNAs) control liver diseases, but the role of microRNA-181a-5p in acute liver failure (ALF) is unclear. In this study, the ALF model was generated by injection of D-galactosamine (D-GalN) and lipopolysaccharide (LPS). The levels of miRNAs were assessed by microarray and qRT-PCR. The expression of caspase 3 was detected as the marker of cell apoptosis in ALF by immunohistochemistry and western blot. The targeting of microRNA-181a-5p on the high mobility group box 1 (HMGB1) was verified by dual luciferase assay. The impact of microRNA-181a-5p and HMGB1 was explored by flow cytometry. Results showed that microRNA-181a-5p was significantly down-regulated by D-GalN/LPS in vivo and in vitro, while the level of HMGB1 was up-regulated after the challenge. Furthermore, microRNA-181a-5p overexpression attenuated cell apoptosis in D-GalN/TNF-treated BNLCL2 cells. MicroRNA-181a-5p could directly target HMGB1 mRNA and repress its expressions, in further HMGB1 is involved in microRNA-181a-5p effect on cell apoptosis of ALF. In conclusion, these findings demonstrate that microRNA-181a-5p regulates hepatocyte apoptosis via HMGB1 in the development of ALF, which may provide potential therapeutic targets for ALF. However, the precise underlying mechanism that connects microRNA-181a-5p and HMGB1 remains to be explored.

The role and molecular mechanism of metabolic reprogramming of colorectal cancer by UBR5 through PYK2 regulation of OXPHOS expression study.

Colorectal carcinoma (CRC) is the third most malignant tumor in the world, but the key mechanisms of CRC progression have not been confirmed. UBR5 and PYK2 expression levels were detected by RT-qPCR. The levels of UBR5, PYK2, and mitochondrial oxidative phosphorylation (OXPHOS) complexes were detected by western blot analysis. Flow cytometry was used to detect ROS activity. The CCK-8 assay was used to assess cell proliferation and viability. The interaction between UBR5 and PYK2 was detected by immunoprecipitation. A clone formation assay was used to determine the cell clone formation rate. The ATP level and lactate production of each group of cells were detected by the kit. EdU staining was performed for cell proliferation.Transwell assay was performed for cell migration ability. For the CRC nude mouse model, we also observed and recorded the volume and mass of tumor-forming tumors. The expression of UBR5 and PYK2 was elevated in both CRC and human colonic mucosal epithelial cell lines, and knockdown of UBR5 had inhibitory effects on cancer cell proliferation and cloning and other behaviors in the CRC process by knockdown of UBR5 to downregulate the expression of PYK2, thus inhibiting the OXPHOS process in CRC; rotenone (OXPHOS inhibitor) treatment enhanced all these inhibitory effects. Knockdown of UBR5 can reduce the expression level of PYK2, thus downregulating the OXPHOS process in CRC cell lines and inhibiting the CRC metabolic reprogramming process.

Musculoskeletal Ultrasound Image-Based Radiomics for the Diagnosis of Achilles Tendinopathy in Skiers.

OBJECTIVES: Our study aimed to develop and validate an efficient ultrasound image-based radiomic model for determining the Achilles tendinopathy in skiers. METHODS: A total of 88 feet of skiers clinically diagnosed with unilateral chronic Achilles tendinopathy and 51 healthy feet were included in our study. According to the time order of enrollment, the data were divided into a training set (n = 89) and a test set (n = 50). The regions of interest (ROIs) were segmented manually, and 833 radiomic features were extracted from red, green, blue color channels and grayscale of ROIs using Pyradiomics, respectively. Three feature selection and three machine learning modeling algorithms were implemented respectively, for determining the optimal radiomics pipeline. Finally, the area under the receiver operating characteristic curve (AUC), consistency analysis, and decision analysis were used to evaluate the diagnostic performance. RESULTS: By comparing nine radiomics analysis strategies of three color channels and grayscale, the radiomic model under the green channel obtained the best diagnostic performance, using the Random Forest selection and Support Vector Machine modeling, which was selected as the final machine learning model. All the selected radiomic features were significantly associated with the Achilles tendinopathy (P < .05). The radiomic model had a training AUC of 0.98, a test AUC of 0.99, a sensitivity of 0.90, and a specificity of 1, which could bring sufficient clinical net benefits. CONCLUSIONS: Ultrasound image-based radiomics achieved high diagnostic performance, which could be used as an intelligent auxiliary tool for the diagnosis of Achilles tendinopathy.

Sulfur-driven autotrophic denitrification of nitric oxide for efficient nitrous oxide recovery.

Nitrous oxide (N2 O) was previously deemed as a potent greenhouse gas but is actually an untapped energy source, which can accumulate during the microbial denitrification of nitric oxide (NO). Compared with the organic electron donor required in heterotrophic denitrification, elemental sulfur (S0 ) is a promising electron donor alternative due to its cheap cost and low biomass yield in sulfur-driven autotrophic denitrification. However, no effort has been made to test N2 O recovery from sulfur-driven denitrification of NO so far. Therefore, in this study, batch and continuous experiments were carried out to investigate the NO removal performance and N2 O recovery potential via sulfur-driven NO-based denitrification under various Fe(II)EDTA-NO concentrations. Efficient energy recovery was achieved, as up to 35.5%-40.9% of NO was converted to N2 O under various NO concentrations. N2 O recovery from Fe(II)EDTA-NO could be enhanced by the low bioavailability of sulfur and the acid environment caused by sulfur oxidation. The NO reductase (NOR) and N2 O reductase (N2 OR) were inhibited distinctively at relatively low NO levels, leading to efficient N2 O accumulation, but were suppressed irreversibly at NO level beyond 15 mM in continuous experiments. Such results indicated that the regulation of NO at a relatively low level would benefit the system stability and NO removal capacity during long-term system operation. The continuous operation of the sulfur-driven Fe(II)EDTA-NO-based denitrification reduced the overall microbial diversity but enriched several key microbial community. Thauera, Thermomonas, and Arenimonas that are able to carry out sulfur-driven autotrophic denitrification became the dominant organisms with their relative abundance increased from 25.8% to 68.3%, collectively.

Novel Loss-of-Function Variant in HNF1a Induces ß-Cell Dysfunction through Endoplasmic Reticulum Stress.

Heterozygous variants in the hepatocyte nuclear factor 1a (HNF1a) cause MODY3 (maturity-onset diabetes of the young, type 3). In this study, we found a case of novel HNF1a p.Gln125* (HNF1a-Q125ter) variant clinically. However, the molecular mechanism linking the new HNF1a variant to impaired islet ß-cell function remains unclear. Firstly, a similar HNF1a-Q125ter variant in zebrafish (hnf1a+/-) was generated by CRISPR/Cas9. We further crossed hnf1a+/- with several zebrafish reporter lines to investigate pancreatic ß-cell function. Next, we introduced HNF1a-Q125ter and HNF1a shRNA plasmids into the Ins-1 cell line and elucidated the molecular mechanism. hnf1a+/- zebrafish significantly decreased the ß-cell number, insulin expression, and secretion. Moreover, ß cells in hnf1a+/- dilated ER lumen and increased the levels of ER stress markers. Similar ER-stress phenomena were observed in an HNF1a-Q125ter-transfected Ins-1 cell. Follow-up investigations demonstrated that HNF1a-Q125ter induced ER stress through activating the PERK/eIF2a/ATF4 signaling pathway. Our study found a novel loss-of-function HNF1a-Q125ter variant which induced ß-cell dysfunction by activating ER stress via the PERK/eIF2a/ATF4 signaling pathway.

The initial CT blend sign is not associated with poor patient outcomes after stereotactic minimally invasive surgery.

BACKGROUND: The initial CT blend sign is an imaging marker that has been used to predict haematoma expansion and poor outcomes in patients with small-volume intracerebral haemorrhage (ICH). However, the association of the blend sign with the outcomes of patients undergoing surgery remains unclear. The present study aimed to retrospectively evaluate the influence of the initial CT blend sign on short-term outcomes in patients with hypertensive ICH after stereotactic minimally invasive surgery (sMIS). METHODS: We enrolled 242 patients with spontaneous ICH. The patients were assigned to the blend sign group (91 patients) or non-blend sign (control) group (151 patients) based on the initial CT features. The NIHSS, GCS and mRS were used to assess the effects of sMIS. The rates of severe pulmonary infection and cardiac complications were also compared between the two groups. RESULTS: Statistically significant differences in the NIHSS and GCS scores were not observed between the blend sign group and the control group. No significant differences in the proportion of patients with good outcomes during the follow-up period were observed between the two groups. A higher rate of re-haemorrhage was noted in the blend sign group. Significant differences in the rates of severe pulmonary infection and cardiac complications were not observed between the two groups. CONCLUSIONS: The initial CT blend sign is not associated with poor outcomes in patients with hypertensive ICH after sMIS. ICH patients with the CT blend sign should undergo sMIS if they are suitable candidates for surgery.

Biological Reduction of Nitric Oxide for Efficient Recovery of Nitrous Oxide as an Energy Source.

Chemical absorption-biological reduction based on Fe(II)EDTA is a promising technology to remove nitric oxide (NO) from flue gases. However, limited effort has been made to enable direct energy recovery from NO through production of nitrous oxide (N2O) as a potential renewable energy rather than greenhouse gas. In this work, the enhanced energy recovery in the form of N2O via biological NO reduction was investigated by conducting short-term and long-term experiments at different Fe(II)EDTA-NO and organic carbon levels. The results showed both NO reductase and N2O reductase were inhibited at Fe(II)EDTA-NO concentration up to 20 mM, with the latter being inhibited more significantly, thus facilitating N2O accumulation. Furthermore, N2O accumulation was enhanced under carbon-limiting conditions because of electron competition during short-term experiments. Up to 47.5% of NO-N could be converted to gaseous N2O-N, representing efficient N2O recovery. Fe(II)EDTA-NO reduced microbial diversity and altered the community structure toward Fe(II)EDTA-NO-reducing bacteria-dominated culture during long-term experiments. The most abundant bacterial genus Pseudomonas, which was able to resist the toxicity of Fe(II)EDTA-NO, was significantly enriched, with its relative abundance increased from 1.0 to 70.3%, suggesting Pseudomonas could be the typical microbe for the energy recovery technology in NO-based denitrification.

Regular-Shaped Hematomas Predict a Favorable Outcome in Patients with Hypertensive Intracerebral Hemorrhage Following Stereotactic Minimally Invasive Surgery.

BACKGROUND: Stereotactic minimally invasive surgery (sMIS) has been used in the treatment of intracerebral hemorrhage (ICH) in recent years and has obtained promising results. However, the outcomes of patients are associated with many factors. The aim of the present study was to retrospectively observe the relationship between hematoma shape features and the outcome of patients with spontaneous ICH following sMIS. METHODS: One hundred eighty-three patients with hypertensive ICH who underwent sMIS were enrolled. Based on hematoma shape features, the patients were assigned to a regular-shaped hematoma group (RSH group, including 121 patients) or an irregular-shaped hematoma group (ISH group, including 62 patients). The Glasgow Coma Scale (GCS) score and the National Institutes of Health Stroke Scale (NIHSS) score were assessed on admission and at 1 week and 2 weeks after surgery. The rates of severe pulmonary infection, cardiac complications, and postoperative rebleeding during the hospital stay were also recorded for comparison. The functional outcome assessed by using the modified Rankin scale score was determined at discharge. A multivariate logistic regression analysis was performed for predictors of good outcome in patients with ICH who underwent sMIS. A receiver operating characteristic curve was also used to confirm the results. RESULTS: Compared to the ISH group, the RSH group showed increased median GCS scores at one week and two weeks after surgery. The RSH group showed significantly decreased NIHSS scores at one week and two weeks after surgery compared with the ISH group at the same time point. Significant differences in the GCS score and the NIHSS score at 1 week (P < 0.05) and 2 weeks (P < 0.05) after surgery were observed between the RSH group and the ISH group. The RSH group showed lower rates of severe pulmonary infection, heart failure, and postoperative rehemorrhage than the ISH group (P < 0.05). Of the total patients with good outcomes, the RSH group accounted for 84.6%, and just 15.4% were from the ISH group. The multivariate logistic regression analysis demonstrated that regular-shaped hematoma (P < 0.0001) was an independent predictor of good outcome. The postoperative residual hematoma volume (P < 0.05) predicted a poor outcome. The sensitivity, specificity, and positive and negative predictive values of regular-shaped hematomas for the prediction of a favorable outcome in patients were 0.667, 0.846, 0.917, and 0.542, respectively. Additionally, the Youden index was 0.513. CONCLUSIONS: Patients with regular-shaped hematomas exhibited more favorable outcomes. Irregular-shaped hematomas and postoperative residual hematoma volume predicted a poor outcome in patients with ICH following sMIS.

Is the CT Blend Sign Composed of Two Parts of Blood with Different Age?

BACKGROUND: Blend sign on initial computed tomography (CT) is associated with poor outcome in patients with intracerebral hemorrhage (ICH). However, the mechanisms underlying the blend sign formation are poorly understood. The present study aimed to explore the possible mechanism of the CT blend sign in patients with ICH. METHODS: Seventy healthy rabbits were selected to prepare an ICH model. The animals were assigned to a whole blood group + whole blood group (ww group, 50 rabbits), a whole blood + plasma group (wp group, 10 rabbits) or a whole blood + serum group (ws group, 10 rabbits). The animals of the ww group were allocated to five subgroups based on the interval between the first infusion of blood and the second one. The subgroups included ww 1 h group (with an interval of 1 h), ww 2 h group, ww 3 h group, ww 4 h group and ww 5 h group. The rabbits from each group received first infusion of 0.3 mL of whole blood into the basal ganglia area to form a hematoma. Then, they received a second infusion of the same amount of whole blood, plasma or serum into the brain to form another hematoma adjacent to the first one. RESULTS: A hematoma with two densities on brain CT could be formed in each group after a second infusion of blood into the brain. A significant difference in CT attenuation values was observed between the hyperattenuation and the hypoattenuation in all the groups. However, only the morphological features of the hematoma in the ww group was in accordance with the CT blend sign observed in humans. The CT attenuation values in the hypodensity area of the ww 4 h group or the ww 5 h group were decreased compared with the ww 1 h group to the ww 3 h group. CONCLUSIONS: The CT blend sign observed in humans might be composed of two parts of blood with different ages. The hypodense area might be blood with older age and the hyperdense area might be new bleeding.