Successful treatment of sepsis-induced cardiomyopathy with 36 hours refractory ventricular fibrillation: A case report.

Sepsis-induced cardiomyopathy (SIC) is generally characterized by decreased cardiac ejection fraction (EF) reversibility, less cardiac response to fluid resuscitation and catecholamine, and rarely complicated with refractory ventricular fibrillation (RVF). Once RVF is induced, the mortality rate of sepsis patients will be greatly increased. In this case, we reported a 26-year-old female patient who was diagnosed sepsis-induced cardiomyopathy (SIC), presented with RVF for 36 hours. The patient was maintained by the mechanical circulatory support (MCS) devices and experienced twice defibrillation. Finally, the patient was discharged without intracardial thrombosis and severe craniocerebral complications. This case suggested that early application of MCS and appropriate frequency of defibrillation may help the prognosis of SIC with RVF.

Nanoscale detection of carbon dots-induced changes in actin skeleton of neural cells.

Understanding the cytotoxicity of fluorescent carbon dots (CDs) is crucial for their applications, and various biochemical assays have been used to study the effects of CDs on cells. Knowledge on the effects of CDs from a biophysical perspective is integral to the recognition of their cytotoxicity, however the related information is very limited. Here, we report that atomic force microscopy (AFM) can be used as an effective tool for studying the effects of CDs on cells from the biophysical perspective. We achieve this by integrating AFM-based nanomechanics with AFM-based imaging. We demonstrate the performance of this method by measuring the influence of CDs on living human neuroblastoma (SH-SY5Y) cells at the single-cell level. We find that high-dose CDs can mechanically induce elevated normalized hysteresis (energy dissipation during the cell deformation) and structurally impair actin skeleton. The nanomechanical change highly correlates with the alteration of actin filaments, indicating that CDs-induced changes in SH-SY5Y cells are revealed in-depth from the AFM-based biophysical aspect. We validate the reliability of the biophysical observations using conventional biological methods including cell viability test, fluorescent microscopy, and western blot assay. Our work contributes new and significant information on the cytotoxicity of CDs from the biophysical perspective.

Near-Field Terahertz Morphological Reconstruction Nanoscopy for Subsurface Imaging of Protein Layers.

Protein layers formed on solid surfaces have important applications in various fields. High-resolution characterization of the morphological structures of protein forms in the process of developing protein layers has significant implications for the control of the layer's quality as well as for the evaluation of the layer's performance. However, it remains challenging to precisely characterize all possible morphological structures of protein in various forms, including individuals, networks, and layers involved in the formation of protein layers with currently available methods. Here, we report a terahertz (THz) morphological reconstruction nanoscopy (THz-MRN), which can reveal the nanoscale three-dimensional structural information on a protein sample from its THz near-field image by exploiting an extended finite dipole model for a thin sample. THz-MRN allows for both surface imaging and subsurface imaging with a vertical resolution of ∼0.5 nm, enabling the characterization of various forms of proteins at the single-molecule level. We demonstrate the imaging and morphological reconstruction of single immunoglobulin G (IgG) molecules, their networks, a monolayer, and a heterogeneous double layer comprising an IgG monolayer and a horseradish peroxidase-conjugated anti-IgG layer. The established THz-MRN presents a useful approach for the label-free and nondestructive study of the formation of protein layers.

Melittin acupoint injection in attenuating bone erosion in collagen-induced arthritis mice via inhibition of the RANKL/NF-κB signaling pathway.

Background: Rheumatoid arthritis (RA) is an autoimmune disease leading to chronic joint inflammation. Bone erosion is the most serious pathological condition of RA and the main cause of joint deformities and disability. Melittin acupoint injection (MAI) is an effective traditional Chinese medicine (TCM) method for RA treatment. This study aimed to investigate the effect of MAI on RA bone erosion and to elucidate the underlying mechanism. Methods: A collagen-induced arthritis (CIA) mouse model was established as the experimental subject. MAI was administrated once every other day for 28 days to mice with CIA. The effects of MAI on joint diseases were assessed by body weight, arthritis index (AI) score, swollen joint count (SJC) score, and hind paw thickness. Ankle radiological changes were captured by micro-computed tomography (micro-CT) and histological changes were observed by pathological staining. Organ histological changes, spleen index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Crea) levels of serum were tested to evaluate the toxicity of MAI. Cytokine expression levels were confirmed by enzyme-linked immunosorbent assay (ELISA) to evaluate the immunity of CIA mice. Results: MAI administration markedly improved the clinical signs of CIA in mice, including hind paw thickness, AI, and the number of swollen paw joints (most of them P<0.05 or even <0.01). According to histopathological analysis, MAI ameliorated inflammatory cell infiltration, synovial hyperplasia, pannus formation, and bone erosion (all P<0.01). Micro-CT and tartrate-resistant acid phosphatase (TRAP) staining (P<0.01) also revealed that MAI could relieve bone erosion via reducing the formation of osteoclasts. Not only could MAI relieve the immunological boost [P<0.05 for the high-dose MAI (HM) group], but also it had no liver or kidney side effects (P>0.05). In addition, it decreased the serum levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) and increased the serum levels of IL-4 and IL-10 (the majority of P<0.05 or even <0.01). Transcriptome sequencing results indicated that MAI affected the expression of osteoclast differentiation pathway genes, which was connected with the receptor activator of the nuclear factor κB ligand/nuclear factor kappa B (RANKL/NF-κB) pathway. Conclusions: Based on our findings, MAI could suppress joint inflammation and inhibit RANKL/NF-κB-mediated osteoclast differentiation to rescue bone erosion in CIA mice, suggesting that MAI can be a potentially therapeutic substance for RA.

A terahertz near-field nanoscopy revealing edge fringes with a fast and highly sensitive quantum-well photodetector.

We demonstrate the successful implementation of a terahertz (THz) quantum-well photodetector (QWP) for effective signal collection in a scattering-type scanning near-field optical microscope (s-SNOM) system. The light source is an electrically pumped THz quantum cascade laser (QCL) at 4.2 THz, which spectrally matches with the peak photoresponse of THz QWP. The sensitive THz QWP has a low noise equivalent power (NEP) of about 1.1 pW/Hz0.5 and a spectral response range from 2 to 7 THz. The fast-responding capability of the THz QWP is vital for detecting the rapidly tip-modulated THz light which can effectively suppress the background noise. The THz images of the nanostructure demonstrate a spatial resolution of about 95 nm, corresponding to ∼λ/752 at 4.2 THz. We experimentally investigate and theoretically interpret the formation of the fringes which appear at the edge position of a gold stripe in the THz near-field image.

In Situ Ti6Al4V/TiB Composites Prepared by Hydrogen-Assisted Sintering of Blends Containing TiH2 and Ball-Milled Ti+TiB2 Powders.

In the present study, 98.6-99.5% dense in situ reinforced Ti6Al4V/TiB composites were manufactured with a newly developed approach based on hydrogen-assisted blended elemental powder metallurgy (BEPM). The approach includes the activation milling of titanium powder produced with hydrogenation-dehydrogenation (HDH-Ti powder) with finer TiB2 additives, following blending with TiH2 and master alloy (MA) powders, and final press-and-sinter operations. Scanning electron microscope (SEM) observations prove the formation of microstructures with improved density and homogeneous distribution of TiB reinforcements in a sintered Ti6Al4V matrix. Hardness and compressive tests validated the high mechanical characteristics of produced composites. The effect of preliminary milling time over 2-6 h and the ratio of hydrogenated and non-hydrogenated titanium powders used (TiH2 vs. HDH Ti) on microstructure and mechanical properties were studied to further optimize the processing parameters. Test results indicate the above approach can be regarded as a promising route for the cost-effective manufacturing of Ti6Al4V/TiB composite with reduced porosity, tailored microstructure uniformity, acceptable impurity level and, hence, mechanical characteristics sufficient for practice applications.

The spectrum characteristics of Parkinson's disease (PD) patients with sleep disorders.

OBJECTIVE: This study aimed to explore the spectrum characteristics of Parkinson's disease (PD) patients with sleep disorders. METHODS: This retrospective study included 101 PD patients who received treatment at our hospital between August 2018 and August 2020. According to the modified Hoehn-Yahr (H-Y) classification, the patients were divided into the early-stage (grade I and II) group (N=21), the mid-stage (grade III) group (N=28), and the late-stage (grade IV) groups (N=20). Detailed information including general data and clinical data was collected. RESULTS: Multivariate logistic regression analysis showed that lower total cholesterol, triglyceride, and uric acid levels were protective factors against the occurrence of sleep disorder, and increased Madopar dosage ≥ 600 mg, Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were risk factors for the occurrence of sleep disorder. The levels of total cholesterol, triglyceride, and uric acid, total sleep time, sleep efficiency, REM sleep latency score, minimum oxygen saturation, and Madopar dosage ≥ 600 mg in the late-stage group were lower than those in the mid-stage group. Meanwhile, homocysteine levels, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, SAS, SDS score, sleep latency score, hypopnea index, the number of times of waking up, and the number of episodes of hypopnea and apnea were higher than those in the mid-stage group. CONCLUSIONS: Decreased levels of total cholesterol, triglyceride, and uric acid were associated with the occurrence of PD. Lower Madopar doses and reducing anxiety and depression might control the occurrence and development of sleep disorders in PD patients.

Therapeutic effects of human umbilical cord mesenchymal stem cells transplantation on hypoxic ischemic encephalopathy.

OBJECTIVE: Human umbilical cord mesenchymal stem cells (hUC-MSCs) hold substantial promise for the treatment of ischemic neurological disease, but few clinical data are currently available about its therapeutic effects in hypoxic ischemic encephalopathy (HIE). This study is to evaluate the effects of hUC-MSCs transplantation on patients with HIE. Methods A total 22 patients with HIEwere randomly divided into hUC-MSCs transplantation group (n = 12) and control group (n = 10). After isolation, hUC-MSCs were cultured for 3 to 5 passages in vitro and then intravenously administered to HIE patients in the transplantation group, while the control group received routine treatment only. The outcomes of HIE patients were evaluated at designated time points by clinical assessment scales, including NIHSS, Barthel Index, MMSE, HAMA24, HAMD14 and UPDRS. RESULTS: hUC-MSCs were identified by morphological analysis and flow cytometry assays before clinic transplantation. No significant differences of demographic characteristics were observed between the two groups of subjects. Compared to the control group, hUC-MSCs transplantation markedly improved the outcomes of HIE patients leading to better recovery of neurological function, cognition ability, emotional reaction and extrapyramidal function. No significant adverse effects were found in subjects with hUC-MSCs transplantation during a 180-day follow-up period. CONCLUSION: These data suggest that hUC-MSCs therapy markedly improves the outcomes of patients with HIE, which is potential for the routine treatment of ischemic neurological disease.

Effects of Astragalus polysaccharides on memory impairment in a diabetic rat model.

OBJECTIVE: Astragalus polysaccharides (APS) are active constituents of Astragalus membranaceus. In this study, we aimed to investigate the effects of APS on memory impairment in a diabetic rat model and their mechanisms. METHODS: A diabetic model was established in 50 male Wistar rats with streptozotocin intra-peritoneal injection. A blood glucose level higher than 16.7 mmol/L obtained 72 hours after the injection was regarded as a successful diabetic model. The modeled rats were divided into model group, high, medium, and low doses of APS, and piracetam groups (positive control). A group of ten rats without streptozotocin-induced diabetes were used as a normal control. After respective consecutive 8-week treatments, the levels of blood fasting plasma glucose, insulin, hemoglobin A1c, memory performance, hippocampal malondialdehyde, and superoxide dismutase were determined. RESULTS: After the 8-week APS treatment, serum fasting plasma glucose, hemoglobin A1c, and insulin levels were decreased compared with those of the model group (P<0.05). Importantly, memory impairment in the diabetic model was reversed by APS treatments. In addition, hippocampal malondialdehyde concentration was lowered, whereas that of superoxide dismutase was higher after APS treatments. CONCLUSION: APS are important active components responsible for memory improvement in rats with streptozotocin-induced diabetes. The potential mechanism of action is associated with the effects of APS on glucose and lipid metabolism, and antioxidative and insulin resistance. APS are constituents of A. membranaceus that are potential candidate therapeutic agents for the treatment of memory deficit in diabetes.

Efficient differentiation of neural stem cells induced by the rat bone marrow stromal cells.

Neural stem cells (NSCs) are valuable self-renewing cells that can maintain the capacity to differentiate into specific brain cell types. NSCs may repair and even replace the brain tissue, and ultimatley promoting the central nervous system regeneration. Therefore, it is important, for scientists and pjysicians, to study the method for efficient culture and differentiation of NSCs. Our previous study demonstrated that Bone Marrow Stromal Cells (BMSCs) can directly regulate the differentiation of NSCs into neurons, and soluble molecules excreted by BMSCs played a key role in this process. Hereby, we further identified the BMSCs-induced neurons could form the synapses, convey dopamine and express voltage-depend and receptor-depend calcium channels. Moreover, the extracellular signal-regulated protein kinase ERK1/2 pathway was founded to be involved in the process of neuron differentiation and proliferation by the in vitro experiments. Finally, by using protein array, we, for the first time, found that the cytokine-induced neutrophil chemoattractant-3 (CINC-3, a small molecule cytokine) can promote the leukocytes invasion into the inflammation site, and have the ability to induce mesencephal NSCs into neurons. Consequently, these positive findings suggested that our BMSCs-induced culture system could provide a useful tool to investigate the molecular mechanisms of neural differentiation of NSCs, which may be benifical for neurodegenerative diseases in the near future.