Bipolar Electrode-based Sheath-Less Focusing and Continuous Acoustic Sorting of Particles and Cells in an Integrated Microfluidic Device.

Sheath-less focusing and sorting of cells or particles is an important preprocessing step in a variety of biochemical applications. Most of the previous sorting methods depend on the use of sheath flows to realize efficient cell focusing. The sheath flow dilutes the sample and requires precise flow control via additional channels. We, for the first time, reported a method of bipolar electrode (BPE)-based sheath-less focusing, switching, and tilted-angle standing surface acoustic wave-based sorting of cells and particles in continuous flow. The device consists of a piezoelectric substrate with a pair of BPEs for focusing and switching, and a pair of interdigitated transducers for cell sorting. Smaller cells experience a weak acoustic force and reach the lower outlet, whereas larger cells are subjected to a strong acoustic force such that they are propelled toward the upper outlet. We first validate the device functionality by sorting 5 and 8 µm PS beads with a high sorting efficiency. The working and deflection regions were increased by propelling the particle beam toward the bottom edge of BPE via changing the applied voltage of BPE, further improving the sorting performance with high efficiency (94%) and purity (92%). We then conducted a verification for sorting THP-1 and yeast cells, and the efficiency and purity reached 90.7 and 91.5%, respectively. This integrated device eliminates the requirement of balancing the flow of several sheath inlets and provides a robust and unique approach for cell sorting applications, showing immense promise in various applications, such as medical diagnosis, drug delivery, and personalized medicine.

Breathing Behavior and Superprotonic Conductivity of Two-Dimensional Flexible Metal-Organic Frameworks Tuned with Alkoxy Groups.

Flexible metal-organic frameworks (FMOFs) exhibit reversible structural transitions ("breathing" behaviors), which can regulate the proton transport passageway effectively. This property offers remarkable advantages for improving the proton conductivity. Our objective of this work is to design a single-variable flexibility synergistic strategy for the fabrication of FMOFs with high conductivity. Herein, four two-dimensional FMOFs, {[Co(4-bpdb)(R-ip)]·xsolvents}n (x = rich, 1-4), have been successfully designed and assembled (4-bpdb = 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene and R-ip = MeO/EtO/n-PrO/n-BuO-isophthalate). Upon the release and/or absorption of different solvent molecules, they display reversible breathing behaviors, thereby resulting in the formation of the partial and complete solvent-free compounds {[Co(4-bpdb)(R-ip)]·ysolvents}n (y = free or poor, 1A-4A). This breathing behavior involves the synergistic self-adaption of the dynamic torsion of alkoxy groups and reversible structural transformation, leading to remarkable changes in cell parameters and void space, as evidenced by single-crystal X-ray diffraction, powder X-ray diffraction, and N2 and CO2 adsorption analyses. At 363 K and 98% relative humidity, 2A exhibits the best proton conductivity among the FMOFs. Its conductivity reaches 4.08 × 10-2 S cm-1 and is one of the highest conductivities shown by reported unmodified MOF-based proton conductors.

Development and evaluation of nomograms for predicting osteoarthritis progression based on MRI cartilage parameters: data from the FNIH OA biomarkers Consortium.

BACKGROUND: Osteoarthritis (OA) is a leading cause of disability worldwide. However, the existing methods for evaluating OA patients do not provide enough comprehensive information to make reliable predictions of OA progression. This retrospective study aimed to develop prediction nomograms based on MRI cartilage that can predict disease progression of OA. METHODS: A total of 600 subjects with mild-to-moderate osteoarthritis from the Foundation for National Institute of Health (FNIH) project of osteoarthritis initiative (OAI). The MRI cartilage parameters of the knee at baseline were measured, and the changes in cartilage parameters at 12- and 24-month follow-up were calculated. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to extract the valuable characteristic parameters at different time points including cartilage thickness, cartilage volume, subchondral bone exposure area and uniform cartilage thickness in different sub regions of the knee, and the MRI cartilage parameters score0, scoreΔ12, and scoreΔ24 at baseline, 12 months, and 24 months were constructed. ScoreΔ12, and scoreΔ24 represent changes between 12 M vs. baseline, and 24 M vs. baseline, respectively. Logistic regression analysis was used to construct the nomogram0, nomogramΔ12, and nomogramΔ24, including MRI-based score and risk factors. The area under curve (AUC) was used to evaluate the differentiation of nomograms in disease progression and subgroup analysis. The calibration curve and Hosmer-Lemeshow (H-L) test were used to verify the calibration of the nomograms. Clinical usefulness of each prediction nomogram was verified by decision curve analysis (DCA). The nomograms with predictive efficacy were analyzed by secondary analysis. Internal verification was assessed using bootstrapping validation. RESULTS: Each nomogram included cartilage score, KL grade, WOMAC pain score, WOMAC disability score, and minimum joint space width. The AUC of nomogram0, nomogramΔ12, and nomogramΔ24 in predicing the progression of radiology and pain were 0.69, 0.64, and 0.71, respectively. All three nomograms had good calibration. Analysis by DCA showed that the clinical effectiveness of nomogramΔ24 was higher than others. Secondary analysis showed that nomogram0 and nomogramΔ24 were more capable of predicting OA radiologic progression than pain progression. CONCLUSION: Nomograms based on MRI cartilage change were useful for predicting the progression of mild to moderate OA.

Duck sewage source coliphage P762 can lyse STEC and APEC.

Multiple pathogenic types or serotypes restrict treatment for colibacillosis. In addition, rising antibiotic resistance has heightened public awareness to prevent and control pathogenic Escherichia coli. The bacteriophage is a viable technique to treat colibacillosis as an alternative to antibiotics. P762, a coliphage isolated from duck farm sewage, was demonstrated to cloud lyse Shiga toxin-producing Escherichia Coli serotypes O157 and non-O157 (17/39), Avian pathogenic E. coli covered serotype O78, O83, and O9 (5/19), and other pathogenic Escherichia coli (5/17). Additional fundamental biological characteristics analysis revealed that P762 is stable at pH 3 ~ 11 and temperature between 4 °C and 60 °C, and its optimum multiplicity of infection (MOI) is 0.1. The one-step curve of P762 exhibited three bursts of growth stage: two rapid and one slow stage. Furthermore, the first rapid burst size is 80 CFU/PFU, the burst size of the slow stage is 10 CFU/PFU, and the second rapid burst size is about 990 CFU/PFU. In addition, P762 can form a "halo" on a double agar plate, implying that the phage secretes depolymerase. With 95.14% identity and 90% query coverage, genome sequence analysis revealed that P762 is most closely related to Escherichia phage DY1, which belongs to the genus Kayfunavirus. After screening using RAST and VFDB, no virulence factors were discovered in P762. In vitro antibacterial tests revealed that P762 has high bactericidal activity in lettuce leaves contaminated with STEC. In conclusion, phage P762 might be employed in the future to prevent and control pathogenic Escherichia coli.

Comparing oblique lumbar interbody fusion with lateral screw fixation and percutaneous endoscopic transforaminal discectomy (OLIF-PETD) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the treatment of lumbar disc herniation complicated with lumbar instability.

OBJECTIVE: To evaluate the early clinical effect of oblique lumbar interbody fusion with lateral screw fixation and percutaneous endoscopic transforaminal discectomy (OLIF-PETD) in the treatment of lumbar disc herniation with lumbar instability. METHODS: A total of 22 patients with lumbar disc herniation and lumbar instability from August 2017 to August 2019 were enrolled in this retrospective study. The general information, perioperative indicators and complications were recorded. The clinical outcomes and radiological outcomes were evaluated before the operation, seven days after the operation, and at the last follow-up. Vertebral fusion and degree of multifidus muscle injury were evaluated at the last follow-up. RESULTS: In this study, OLIF + PETD showed shorter incision length compared to the MIS-TLIF (P < 0.001). In the two groups, the clinical outcomes and radiological outcomes were significantly improved compared with the preoperative (P < 0.001). At the seven days after the operation and the last follow-up, the VAS of OLIF + PETD group was lower than that of MIS-TLIF group (P < 0.05). OLIF + PETD could give superior outcome in restoring disc height (P < 0.001), but the fusion segment angle of OLIF + PETD group was larger compared to the MIS-TLIF group seven days after the operation and at the last follow-up (P < 0.05). In addition, the fusion rate was not significantly different between the two groups (P > 0.05), but OLIF + PETD could avoid the multifidus injury (P < 0.001). CONCLUSION: Compared to MIS-TLIF, OLIF-PETD can achieve satisfactory decompression effects and fusion rates with less multifidus injury and postoperative low back pain, which may be an alternative choice for the treatment of lumbar disc herniation combined with lumbar instability.

Trends of epidemiological characteristics of traumatic spinal cord injury in China, 2009-2018.

OBJECTIVE: We focus on providing the first comprehensive national dataset on the incidence, injury aetiology and mortality of TSCI in China. METHODS: A multi-stage stratified cluster sampling method was used. We included TSCI cases from all hospitals in three regions, nine provinces and 27 cities in China via search of electronic medical records and retrospectively analysed the characteristics of TSCI in China from 2009 to 2018. We estimated the incidence of TSCI in the total population and subgroups. RESULTS: There were 5954 actual cases in 2009, corresponding to a total estimated TSCI incidence of 45.1 cases per million population (95% CI, 44.0-46.3). There were 10,074 actual cases in 2018, corresponding to a total estimated TSCI incidence of 66.5 cases per million population (95% CI, 65.2-67.8) (P < 0.001; annual average percentage change (AAPC), 4.4%). From 2009 to 2018, the incidence of almost all sex/age groups showed an increasing trend over time (P < 0.001; AAPC, 0.7-8.8%). The elderly population (aged 65-74) displayed the highest incidence of TSCI (with an average annual incidence of 127.1 cases per million [95% CI, 119.8-134.3]). CONCLUSIONS: The TSCI incidence increased significantly from 2009 to 2018. The incidence in the elderly populations was consistently high and continues to increase over time. The mortality of TSCI patients in hospitals is relatively low and continues to decrease each year, but elderly individuals remain at a high risk of hospital death.

Novel nomogram for predicting the progression of osteoarthritis based on 3D-MRI bone shape: data from the FNIH OA biomarkers consortium.

BACKGROUND: Osteoarthritis(OA) is a major source of pain, disability, and socioeconomic cost in worldwide. However, there is no effective means for the early diagnosis of OA, nor can it accurately predict the progress of OA. To develop and validate a novel nomogram to predict the radiographic progression of mild to moderate OA based on three-dimensional(3D)-MRI bone shape and bone shape change during 24 months. METHOD: Analysis of publicly available data from the Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium. Radiographic progression was defined as minimum radiographic narrowing of the medial tibiofemoral joint space of ≥ 0.7 mm from baseline at 24, 36, or 48 months. There were 297 knees with radiographic progression and 303 without. The bone shapes of the tibia, femur, and patella were evaluated by 3D-MRI at the baseline and at 24 months. Two nomograms were separately established by multivariate logistic regression analysis using clinical risk factors, bone shape at baseline (nomogram 0), or bone shape change at 24 months (nomogram Δ24). The discrimination, calibration, and usefulness were selected to evaluate the nomograms. RESULTS: There were significant differences between groups in baseline Kellgren-Lawrence (KL) grade, gender, age, and tibia, femur, and patella shape. The areas under the curve (AUC) of nomogram 0 and nomogram Δ24 were 0.66 and 0.75 (p < 0.05), with accuracy of 0.62 and 0.69, respectively. Both nomograms had good calibration. The decision curve analysis ( DCA) showed that nomogram Δ24 had greater clinical usefulness than nomogram 0 when the risk threshold ranged from 0.04 to 0.86. CONCLUSIONS: Nomograms based on 3D-MRI bone shape change were useful for predicting the radiographic progression of mild to moderate OA.

Defining matrix Gla protein expression in the Dunkin-Hartley guinea pig model of spontaneous osteoarthritis.

BACKGROUND: Matrix Gla (γ-carboxyglutamate) protein (MGP) is considered a strong inhibitor of ectopic calcification, and it has been associated with OA severity, although not conclusively. We utilized male Dunkin-Hartley (DH) guinea pigs to investigate the expression of MGP throughout aging and disease pathogenesis in a spontaneous model. METHOD: Twenty-five male DH guinea pigs were obtained and nurtured to several timepoints, and then randomly and equally divided by age into five subgroups (1-, 3-, 6-, 9-, and 12-months, with the 1-month group as the reference group). DH guinea pigs in each group were euthanized at the designated month-age and the left or right medial tibial plateaus cartilages were randomly excised. OA severity was described by modified Mankin Score (MMS) at microscopy (Safranin O/Fast Green stain). Proteomic evaluation using isobaric tags for relative and absolute quantification (iTRAQ) was performed to validate the age-related changes in the MGP profiles, and immunohistochemistry (IHC) methods were applied for semi-quantitative determination of MGP expression in articular cartilage. RESULTS: The histopathologic findings validated the increasing severity of cartilage degeneration with age in the DH guinea pigs. The MMS showed significant, stepwise (every adjacent comparison P < 0.05) disease progression with month-age. The iTRAQ indicated that MGP levels increased significantly with advancing age (P < 0.05), as supported by the IHC result (P < 0.05). CONCLUSION: Increased expression of MGP in male DH guinea pigs was present throughout aging and disease progression and may be link to increased OA severity. Further studies are needed to investigate and confirm the association between MGP levels and OA severity.

Percutaneous endoscopic posterior lumbar interbody fusion for the treatment of degenerative lumbar diseases: a technical note and summary of the initial clinical outcomes.

BACKGROUND: Percutaneous endoscopic lumbar interbody fusion was a new technique that leads to improved visualization, improved safety and less trauma than does the traditional procedure. The purpose of this study was to introduce the technique of percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) and determine its efficacy. METHODS: 35 patients with an average age of 52.3±13.7 years were treated with single-segment PE-PLIF. The perioperative parameters and the radiographic parameters were measured. The visual analog scale (VAS) score for low back pain, VAS score for leg pain and Oswestry disability index (ODI) score were used to assess the levels of pain and function. RESULTS: The mean estimated volume of blood loss was 68.6±32.3 ml, operative time was 179.6±31.0 minutes. PE-PLIF significantly reduced the VAS score for low back pain, VAS score for leg pain and ODI score, and improved the posterior disc height, lumbar lordosis angle and segmental lordosis angle (p < 0.05). The rate of satisfaction was 94.3%. One patient suffered a dural tear. There was one case of contralateral radiculopathy that was relieved after conservative treatment. CONCLUSIONS: This research suggests that PE-PLIF is a minimally invasive, safe, and effective treatment for degenerative lumbar diseases requiring interbody fusion.

Comprehensive analysis of differential immunocyte infiltration and the potential ceRNA networks during epicardial adipose tissue development in congenital heart disease.

BACKGROUND: To detect the development, function and therapeutic potential of epicardial adipose tissue (EAT); analyze a related gene expression dataset, including data from neonates, infants, and children with congenital heart disease (CHD); compare the data to identify the codifferentially expressed (DE) mRNAs and lncRNAs and the corresponding miRNAs; generate a potential competitive endogenous RNA (ceRNA) network; and assess the involvement of immunocyte infiltration in the development of the EAT. METHODS: Multiple algorithms for linear models for microarray data algorithms (LIMMA), CIBERSORT, gene-set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were used. The miRcode, miRDB, miRTarBase, and TargetScan database were used to construct the ceRNA network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DE mRNAs were performed. RESULTS: Thirteen co-DE mRNAs and 47 co-DE lncRNAs were subsequently identified. The related categories included negative regulation of myoblast differentiation, regulation of ion transmembrane transport, and heart development, which were primarily identified for further pathway enrichment analysis. Additionally, the hub ceRNA network in EAT development involving MIR210HG, hsa-miR-449c-5p, and CACNA2D4 was generated and shown to target monocyte infiltration. CONCLUSION: These findings suggest that the pathways of myoblast differentiation and ion transmembrane transport may be potential hub pathways involved in EAT development in CHD patients. In addition, the network includes monocytes, MIR210HG, and CACNA2D4, which were shown to target the RIG-I-like receptor signaling pathway and PPAR signaling pathway, indicating that these factors may be novel regulators and therapeutic targets in EAT development.

rs10865331 in 2p15 increases susceptibility to ankylosing spondylitis: a HuGE review and meta-analysis.

OBJECTIVES: 2p15 polymorphisms have been reported to increase ankylosing spondylitis (AS) susceptibility in several studies; however, when it comes to whether and how much of this risk exists, the results are inconclusive. The aim of this study is to investigate the correlation between rs10865331 in 2p15 and the risk of AS. METHODS: We conducted a HuGE review and meta-analysis of studies published through September 2019. Studies were identified in PubMed, Scopus, HuGE Navigator, Embase, and Web of Science databases. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk estimations were calculated. Sensitivity analysis, subgroup analysis and analysis for potential publication bias were also estimated. RESULTS: Eleven studies with 18555 AS patients and 43777 unrelated healthy individuals, each with a score greater than 6 on the Newcastle-Ottawa Scale (NOS), that investigated the association between rs10865331 in 2p15 and AS were included in our meta-analysis. Data were classified into the genotype analysis cohort, the OR-value cohort, and the pooled analysis cohort, and then a meta-analysis was performed. The OR value of the recessive model in the genotype analysis cohort was 1.376 (95% CI=1.204-1.572, p<0.001, I²=56.30%), and the OR value of the pooled analysis cohort was 1.295 (95% CI=1.228-1.365, p<0.001, I²=73.70%). These findings suggest that individual who carries this single nucleotide polymorphism (SNP) are about 30% more susceptible to developing AS. CONCLUSIONS: Our results suggest that rs10865331 is associated with a significantly higher risk of AS in all race and country subgroups that we have evaluated. Therefore, rs10865331 may be a useful genetic marker for predicting AS susceptibility. However, further studies are needed to confirm our findings.

Effect of posterior cervical expansive open-door laminoplasty on cervical sagittal balance.

PURPOSE: Posterior cervical expansive open-door laminoplasty (LAMP) is a mature surgical procedure for the treatment of cervical spondylotic myelopathy (CSM), but there are few studies on the changes in cervical sagittal balance. This study aimed to analyze the imaging and clinical data of patients who underwent LAMP and to explore the effect of this procedure on the cervical sagittal balance. METHODS: This was a retrospective study of the patients who underwent LAMP between 01/2014 and 12/2017. The C0-C2 Cobb angle, sagittal vertical angle (SVA), C2-C7 Cobb angle, and T1-slope were measured. The Japanese Orthopaedic Association (JOA) score, neck disability index (NDI), and visual analog scale (VAS) were used. RESULTS: There were 69 males and 39 females. The mean age was 61.3 ± 5.3 years. The C0-C2 Cobb angle increased from 11.3 ± 5.5° to 26.8 ± 4.8° (P = 0.186). The C2-C7 Cobb angle decreased from 13.9 ± 8.6° to 10.65 ± 10.7° P = 0.016). SVA increased from 21.0 ± 5.8 mm to 25.4 ± 11.5 mm (P = 0.001). The preoperative average JOA score was 11.1 ± 2.2 points, and the postoperative score was 14.0 ± 2.1 points, with an average improvement rate of JOA of 46.5 ± 3.8%. The NDI score decreased from preoperative 15.6 ± 5.4 points to 11.3 ± 7.9 points, and the VAS score was decreased from 4.6 ± 1.8 points to 3.3 ± 1.6 points (all P < 0.05). CONCLUSION: LAMP improved the neurological function and quality of life of patients with CSM. The cervical vertebrae show a tendency of tilting forward, suggesting that overextension of the upper cervical vertebra might be used to maintain the center of gravity of the skull and horizontal vision.

A novel xenograft mouse model for testing approaches targeting human kappa light-chain diseases.

Patients with immunoglobulin (Ig) light-chain (LC) diseases such as LC light-chain amyloidosis die with organ failure and need new therapies. We sought a model to test anti-LC siRNA delivery to human plasma cells, requiring circulating LC, in vivo indicators of tumor presence, and capacity for multiple injections of delivery vehicle. The JJN-3 human myeloma reporter cell line expressing firefly luciferase (FFL) implanted intraperitoneally (IP) in the NOD scid γ (NSG) mouse has a 90% prompt tumor-take, rapid LC production, and in vivo indicators of tumor measurable on day 5 post-implant (κ LC, bioluminescent signal, and soluble B-cell maturation antigen [sBCMA]) with median day 5 serum levels of κ LC of 1482 ng/mL (range, 255-4831) and robust correlations with all in vivo indicators. In preliminary attempts to deliver siRNA against κ LC constant region mRNA, we identified the 306-O18B3 lipidoid nanoparticle (LNP) as promising, safe and efficient in vitro. In vivo in the JJN-3 NSG IP model, after daily IP 306-O18B3:siRNA injections on days 5-10, a reduction in κ LC was observed on day 8 between control and test groups that continued through day 12 at sacrifice. This model is potentially useful as a platform for refining anti-LC therapies.

Rab7 delays intervertebral disc degeneration through the inhibition of the p38MAPK pathway.

The objective of this study is to determine whether Rab7 could delay intervertebral disc degeneration and study the mechanism. We chose old mice to established intervertebral disc degeneration model and study the effect of Rab7 on intervertebral disc by western blotting, quantitative real-time PCR, immunohistochemistry et al. Nucleus pulposus cells were cultured to study the exact mechanism. Expression of Rab7 was decreased in degenerative human nucleus pulposus tissues. With the aging of mice, the degree of intervertebral disc degeneration was aggravated and the expression of Rab7 was decreased. In addition, overexpression of Rab7 can reduce the degeneration of nucleus pulposus cells and reduce the levels of p38 and p-p38. Rab7 is a protective factor for intervertebral discs and could delays intervertebral disc degeneration through the inhibition of the p38MAPK pathway.

A human behavior integrated hierarchical model of airborne disease transmission in a large city.

Epidemics of infectious diseases such as SARS, H1N1, and MERS threaten public health, particularly in large cities such as Hong Kong. We constructed a human behavior integrated hierarchical (HiHi) model based on the SIR (Susceptible, Infectious, and Recovered) model, the Wells-Riley equation, and population movement considering both spatial and temporal dimensions. The model considers more than 7 million people, 3 million indoor environments, and 2566 public transport routes in Hong Kong. Smallpox, which could be spread through airborne routes, is studied as an example. The simulation is based on people's daily commutes and indoor human behaviors, which were summarized by mathematical patterns. We found that 59.6%, 18.1%, and 13.4% of patients become infected in their homes, offices, and schools, respectively. If both work stoppage and school closure measures are taken when the number of infected people is greater than 1000, an infectious disease will be effectively controlled after 2 months. The peak number of infected people will be reduced by 25% compared to taking no action, and the time of peak infections will be delayed by about 40 days if 90% of the infected people go to hospital during the infectious period. When ventilation rates in indoor environments increase to five times their default settings, smallpox will be naturally controlled. Residents of Kowloon and the north part of Hong Kong Island have a high risk of infection from airborne infectious diseases. Our HiHi model reduces the calculation time for infection rates to an acceptable level while preserving accuracy.

Inhibition of HMGB1 reduces rat spinal cord astrocytic swelling and AQP4 expression after oxygen-glucose deprivation and reoxygenation via TLR4 and NF-κB signaling in an IL-6-dependent manner.

BACKGROUND: Spinal cord astrocyte swelling is an important component to spinal cord edema and is associated with poor functional recovery as well as therapeutic resistance after spinal cord injury (SCI). High mobility group box-1 (HMGB1) is a mediator of inflammatory responses in the central nervous system and plays a critical role after SCI. Given this, we sought to identify both the role and underlying mechanisms of HMGB1 in cellular swelling and aquaporin 4 (AQP4) expression in cultured rat spinal cord astrocytes after oxygen-glucose deprivation/reoxygenation (OGD/R). METHODS: The post-natal day 1-2 Sprague-Dawley rat spinal cord astrocytes were cultured in vitro, and the OGD/R model was induced. We first investigated the effects of OGD/R on spinal cord astrocytic swelling and HMGB1 and AQP4 expression, as well as HMGB1 release. We then studied the effects of HMGB1 inhibition on cellular swelling, HMGB1 and AQP4 expression, and HMGB1 release. The roles of both toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and interleukin-6 (IL-6) in reducing cellular swelling resulting from HMGB1 inhibition in spinal cord astrocytes after OGD/R were studied. Intergroup data were compared using one-way analysis of variance (ANOVA) followed by Dunnett's test. RESULTS: The OGD/R increased spinal cord astrocytic swelling and HMGB1 and AQP4 expression, as well as HMGB1 release. Inhibition of HMGB1 using either HMGB1 shRNA or ethyl pyruvate resulted in reduced cellular volume, mitochondrial and endoplasmic reticulum swelling, and lysosome number and decreased upregulation of both HMGB1 and AQP4 in spinal cord astrocytes, as well as HMGB1 release. The HMGB1 effects on spinal cord astrocytic swelling and AQP4 upregulation after OGD/R were mediated-at least in part-via activation of TLR4, myeloid differentiation primary response gene 88 (MyD88), and NF-κB. These activation effects can be repressed by TLR4 inhibition using CLI-095 or C34, or by NF-κB inhibition using BAY 11-7082. Furthermore, either OGD/R or HMGB1 inhibition resulted in changes in IL-6 release. IL-6 was also shown to mediate AQP4 expression in spinal cord astrocytes. CONCLUSIONS: HMGB1 upregulates AQP4 expression and promotes cell swelling in cultured spinal cord astrocytes after OGD/R, which is mediated through HMGB1/TLR4/MyD88/NF-κB signaling and in an IL-6-dependent manner.

Anterior cervical discectomy and fusion versus cervical arthroplasty for the management of cervical spondylosis: a meta-analysis.

PURPOSE: The aim of this study was to compare the efficacy and safety of anterior cervical discectomy and fusion (ACDF) and cervical arthroplasty for patients with cervical spondylosis. METHODS: PubMed, Embase, and Cochrane Library were used to search for relevant articles published prior to April 2016 to identify studies comparing ACDF and cervical arthroplasty involving patients with cervical spondylosis. Relative risks (RR) and mean differences (MD) were used to measure the efficacy and safety of ACDF and cervical arthroplasty using the random effects model. RESULTS: The meta-analysis of 17 studies involved 3122 patients diagnosed with cervical spondylosis. Patients undergoing ACDF showed lower overall success rate (RR 0.84; 95 % CI 0.77-0.92; P < 0.001), higher VAS score (MD 0.36; 95 % CI 0.08-0.64; P = 0.011), and shorter mean surgical duration (MD -1.62; 95 % CI -2.80 to -0.44; P = 0.007) when compared with cervical arthroplasty. However, the association between ACDF therapy and the risk of mean blood loss (MD -0.16; 95 % CI -0.34 to 0.02; P = 0.082), mean hospitalization (MD 0.02; 95 % CI -0.31 to 0.36; P = 0.901), patient satisfaction (RR 0.96; 95 % CI 0.92-1.00; P = 0.066), neck disability index (MD 0.20; 95 % CI -0.05 to 0.44; P = 0.113), reoperation (RR 1.25; 95 % CI 0.64-2.41; P = 0.514), or complication (RR 1.17; 95 % CI 0.90-1.52; P = 0.242) was not statistically significant. CONCLUSIONS: Patients undergoing ACDF therapy tended to exhibit lower overall success rate, higher VAS score, and decreased mean surgical duration when compared with patients treated with cervical arthroplasty.

One siRNA pool targeting the λ constant region stops λ light-chain production and causes terminal endoplasmic reticulum stress.

In systemic light-chain amyloidosis, λ light chains produced by clonal plasma cells cause organ damage and early death. In pursuit of novel therapy, we developed 1 pool of short interfering RNA (siRNA) targeting the constant region of λ light chains that substantially and promptly reduces λ-light-chain production and secretion by human plasma cells regardless of sequence diversity. In clones producing intact immunoglobulin G (IgG) λ antibodies (containing paired heavy and light chains), the secretion of intact antibodies is reduced, and all 3 branches of the unfolded protein response are activated by accumulation of unpaired IgG heavy chains in the endoplasmic reticulum (ER). Moreover, an ER stress response can then become terminal with effector caspase activity mediated in part by the transcription of the Bcl-2 homology 3 domain only family member NOXA. This pool of siRNA can be used to reduce pathological λ-light-chain production and cause apoptosis in human plasma cells making intact IgGλ antibodies.

Association between neutrophilic granulocyte percentage and depression in hospitalized patients with heart failure.

BACKGROUND: Previous researches reveal that depression is associated with increased inflammatory markers. As a simple and cheap inflammatory marker, we hypothesize that neutrophilic granulocyte percentage is associated with depression in hospitalized heart failure patients, whose prevalence of depression is at a very high level. METHODS: Three hundred sixty-six cases of hospitalized heart failure patients with left ventricular ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. All the enrolled patients received Hamilton Rating Scale for Depression (24-items) (HAM-D24). The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with HAM-D24 depression index. The significantly correlated factors were enrolled as independent variables in Logistic regression to determine the risk or protective factors for depression, which was taken as dependent variable. RESULTS: Two hundred ten cases of hospitalized heart failure patients (57.4%) had depression. Among them, 134 patients (63.8%) had mild depression, 58 patients (27.6%) had moderate depression and 18 patients (8.6%) had severe depression. Pearson simple linear correlation revealed that in hospitalized patients with heart failure, the neutrophils granulocyte percentage was positively correlated with the HAM-D24 depression index (r = .435, p < .001). After the adjustment of age, BMI, number of members of the household, smoking index, New York Heart Association (NYHA) classification, hemoglobin, TC, LDL-C, creatinine, cystatin-C, TBIL and albumin, the neutrophils granulocyte percentage is still significantly associated with depression in hospitalized heart failure patients (OR = 1.046, p < .001). CONCLUSIONS: The neutrophils granulocyte percentage may be used as a new marker for depression in hospitalized heart failure patients.

Complex cervical spondylotic myelopathy: a report of two cases and literature review.

STUDY DESIGN: A report of two cases with complex cervical spondylotic myelopathy (CSM) and review of the literature. OBJECTIVE: To describe two unique patients with complex CSM due to simultaneous anomalies as anteroposterior compressions of the spinal cord in both upper and lower cervical spine, caused by hypertrophic transverse ligament of atlas (TLA), dysplasia of the posterior arch of atlas, disc herniation, hypertrophic ligamentum flavum and osteophytes. METHODS: We present such two cases with clinical, imageological presentations, and describe the surgical procedure, to which both patients responded favorably. RESULTS: The neurological functions of both patients gradually improved according to the JOA scores and VAS scores in preoperative clumsiness and gait disturbance during the mean follow-up period lasted for 18 months. The latest plain radiographs and computed tomography (CT) revealed good fusion without instrumental failure and magnetic resonance imaging (MRI) showed good decompression of C1-7 spinal cord of both patients. Both patients are progressively followed-up. CONCLUSION: Posterior surgical approach as C1-7 laminectomy with fixations or occipital-cervical fusions may obtain better reconstructions of the cervical spine and good neurological recovery for the patients with complex CSM we present. However, the incidence and ethnic predisposition for the patients with complex CSM are still unclear.