Cytoplasmic Escape of Mitochondrial DNA Mediated by Mfn2 Downregulation Promotes Microglial Activation via cGas-Sting Axis in Spinal Cord Injury.

Neuroinflammation is associated with poor outcomes in patients with spinal cord injury (SCI). Recent studies have demonstrated that stimulator of interferon genes (Sting) plays a key role in inflammatory diseases. However, the role of Sting in SCI remains unclear. In the present study, it is found that increased Sting expression is mainly derived from activated microglia after SCI. Interestingly, knockout of Sting in microglia can improve the recovery of neurological function after SCI. Microglial Sting knockout restrains the polarization of microglia toward the M1 phenotype and alleviates neuronal death. Furthermore, it is found that the downregulation of mitofusin 2 (Mfn2) expression in microglial cells leads to an imbalance in mitochondrial fusion and division, inducing the release of mitochondrial DNA (mtDNA), which mediates the activation of the cGas-Sting signaling pathway and aggravates inflammatory response damage after SCI. A biomimetic microglial nanoparticle strategy to deliver MASM7 (named MSNs-MASM7@MI) is established. In vitro, MSNs-MASM7@MI showed no biological toxicity and effectively delivered MASM7. In vivo, MSNs-MASM7@MI improves nerve function after SCI. The study provides evidence that cGas-Sting signaling senses Mfn2-dependent mtDNA release and that its activation may play a key role in SCI. These findings provide new perspectives and potential therapeutic targets for SCI treatment.

Decompression alone or decompression and fusion in degenerative lumbar spondylolisthesis.

Background: Clinically, there are substantive practice variations in surgical management of degenerative lumbar spondylolisthesis. We aimed at evaluating whether decompression alone outcomes for patients with degenerative lumbar spondylolisthesis are comparable to those of decompression with fusion. Methods: In this meta-analysis, the Embase, PubMed, and Cochrane Library databases were searched from inception to February 16th, 2022. Randomised controlled trials (RCTs) and cohort studies comparing decompression alone with decompression and fusion for patients with degenerative lumbar spondylolisthesis were included in this study. There were no language limitations. Odds ratio (OR), mean difference (MD) and 95% confidence interval (CI) were used to report results in the random-effects model. Main outcomes included Oswestry disability index (ODI), pain, clinical satisfaction, complication and reoperation rates. The study protocol was published in PROSPERO (CRD42022310645). Findings: Thirty-three studies (6 RCTs and 27 cohort studies) involving 94 953 participants were included. Differences in post-operative ODI between decompression alone and decompression with fusion were not significant. A small difference for back (MD, 0.13; [95% CI, 0.08 to 0.18]; I 2:0.00%) and leg pain (MD, 0.30; [95% CI, 0.09 to 0.51]; I 2:48.35%) was observed on the 3rd post-operative month. The results did not reveal significant differences in leg pain and back pain between decompression alone and fusion groups on the 6th, 12th, and 24th post-operative months. Difference in clinical satisfaction between decompression alone and decompression with fusion were not significant from RCTs (OR, 0.26; [95% CI, 0.03 to 1.92]; I 2:83.27%). Complications (OR, 1.54; [95% CI, 1.16 to 2.05]; I 2:48.88%), operation time (MD, 83.39; [95% CI, 55.93 to 110.85]; I 2:98.75%), intra-operative blood loss (MD, 264.58; [95% CI, 174.99 to 354.16]; I 2:95.61%) and length of hospital stay (MD, 2.85; [95% CI, 1.60 to 4.10]; I 2:99.49%) were higher with fusion. Interpretation: Clinical effectiveness of decompression alone was comparable to that of decompression with fusion for degenerative lumbar spondylolisthesis. Decompression alone is recommended for patients with degenerative lumbar spondylolisthesis. Funding: This work was supported by grants from the National Natural Science Foundation of China (No. 81871818), Tangdu Hospital Seed Talent Program (Fei-Long Wei), Natural Science Basic Research Plan in Shaanxi Province of China (No.2019JM-265) and Social Talent Fund of Tangdu Hospital (No.2021SHRC034).

Association of robot-assisted techniques with the accuracy rates of pedicle screw placement: A network pooling analysis.

Background: Traditional paired meta-analyses have yielded inconsistent results for the safety and effectiveness of robotic-assisted pedicle screw placement due to the high heterogeneity within studies. This study evaluated the clinical effectiveness and safety of robotic-assisted pedicle screw placement. Methods: The Embase, PubMed, and Cochrane Library databases were searched with no language limitations from inception to Jan 4, 2022. Odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) were used to report results. The main outcomes were accuracy of pedicle screw placement, proximal facet joint violation, and complications. The study protocol was published in PROSPERO (CRD42022301417). Findings: 26 trials including 2046 participants evaluating robotic-assisted pedicle screw placement were included in this study. Our pooled results showed that Renaissance (OR 2.86; [95% CI 1.79 to 4.57]) and TiRobot (OR 3.10; [95% CI 2.19 to 4.40]) yielded higher rates of perfect pedicle screw insertion (Grades A) than the conventional freehand technique. Renaissance (OR 2.82; [95% CI 1.51 to 5.25]) and TiRobot (OR 4.58; [95% CI 2.65 to 7.89]) yielded higher rates of clinically acceptable pedicle screw insertion (Grades A+B). However, ROSA, SpineAssist, and Orthobot were not associated with higher perfect pedicle screw insertion and clinically acceptable pedicle screw insertion rates. Robot-assisted techniques were associated with low rates of proximal facet joint violation (OR 0.18; [95% CI 0.10 to 0.32]; I2:9.55%) and overall complications (OR 0.38; [95% CI 0.23 to 0.63]; I2:27.05%). Moreover, robot-assisted techniques were associated with lower radiation doses (MD -14.38; [95% CI -25.62 to -3.13]; I2:100.00%). Interpretation: Our findings suggest that only Renaissance and TiRobot systems are associated with high accuracy rates of pedicle screw placement. Robotic-assisted techniques hold great promise in spinal surgery due to their safety and effectiveness. Funding: This work was supported by grants from the National Natural Science Foundation of China (No. 81871818), Tangdu Hospital Seed Talent Program (Fei-Long Wei) and Natural Science Basic Research Plan in Shaanxi Province of China (No.2019JM-265).

Therapeutic Effect of Large Channel Endoscopic Decompression in Lumbar Spinal Stenosis.

Background: Percutaneous endoscopic decompression (PED) is a minimally invasive surgical technique that is now used for not only disc herniation but also lumbar spinal stenosis (LSS). However, few studies have reported endoscopic surgery for LSS. Therefore, we conducted this study to evaluate the outcomes and safety of large channel endoscopic decompression. Methods: Forty-one patients diagnosed with LSS who underwent PED surgery were included in the study. The estimated blood loss, operative time, length of hospital stay, hospital costs, reoperations, complications, visual analogue scale (VAS) score, Oswestry Disability Index (ODI) score, Japanese Orthopaedic Association (JOA) score and SF-36 physical-component summary scores were assessed. Preoperative and postoperative continuous data were compared through paired-samples t-tests. The significance level for all analyses was defined as p < 0.05. Results: A total of 41 consecutive patients underwent PED, including 21 (51.2%) males and 20 (48.8%) females. The VAS and ODI scores decreased from preoperatively to postoperatively, but the JOA and SF-36 physical component summary scores significantly increased. The VAS (lumbar) score decreased from 5.05 ± 2.33 to 0.45 ± 0.71 (P = 0.000); the VAS (leg) score decreased from 5.51 ± 2.82 to 0.53 ± 0.72 (P = 0.000); the ODI score decreased from 52.80 ± 20.41 to 4.84 ± 3.98 (P = 0.000), and the JOA score increased from 11.73 ± 4.99 to 25.32 ± 2.12 (P = 0.000). Only 1 patient experienced an intraoperative complication (2.4%; dural tear), and 1 patient required reoperation (2.4%). Conclusions: Surgical treatment for LSS is to sufficiently decompress and minimize the trauma and complications caused by surgery. This study did not reveal any obvious shortcomings of PED and suggested PED is a safe and effective treatment for LSS.

Comparison of Different Operative Approaches for Lumbar Disc Herniation: A Network Meta-Analysis and Systematic Review.

BACKGROUND: New approaches and technologies can be beneficial for patients but also bring corresponding complications. Traditional pairwise meta-analyses cannot be used to comprehensively rank all surgical approaches. OBJECTIVES: The purpose of this systematic review and network meta-analysis (NMA) was to compare the outcomes of different surgical approaches for lumbar disc herniation (LDH). STUDY DESIGN: NMA of randomized controlled trials (RCTs) for multiple treatment comparisons of LDH. METHODS: The PubMed, Embase, MEDLINE, Ovid, and Cochrane Library databases were searched for RCTs comparing different surgical approaches for patients with LDH from inception to February 10, 2020. The Markov chain Monte Carlo methods were used to perform a hierarchical Bayesian NMA in WinBUGS version 1.4.3 using a random effects consistency model. The primary outcomes were disability and pain intensity. The secondary outcomes were complications and reoperation. The PROSPERO number was CRD42020179406. RESULTS: A total of 22 trials including 2529 patients and all 5 different approaches (open discectomy or microdiscectomy [OD/MD], microendoscopic discectomy [MED], percutaneous endoscopic discectomy [PED], percutaneous discectomy [PD], and tubular discectomy [TD]) were retrospectively retrieved. PED had the best efficacy in improving patients' dysfunction with no statistical significance (probability = 50%). PD was significantly worse than OD/MD, MED, and PED in relieving patients' pain (standardized mean differences: 0.87 [0.03, 1.76], 0.94 [0.06, 1.88], and 1.02 [0.13, 1.94], respectively). There was no statistically significant difference between any 2 surgical approaches in dural tear; intraoperative, postoperative, and overall complications; or reoperation rate. PED had the lowest dural tear rate and the lowest intraoperative and overall complication rates (probability = 51%, 67%, and 33%, respectively). TD had the lowest postoperative complication and reoperation rates (probability = 35% and 39%, respectively). LIMITATIONS: The limitations of this NMA include the inconsistent follow-up times, the criteria for complications, and the reasons for reoperation. CONCLUSIONS: Compared with other approaches used to treat LDH, PED had the best safety and efficacy in general, and TD had the lowest reoperation rate. Finally, we recommended PED for LDH.

Management for lumbar spinal stenosis: A network meta-analysis and systematic review.

BACKGROUND: Conventional paired meta-analyses have shown inconsistent results regarding the safety and efficacy of different interventions. OBJECTIVE: To perform a network meta-analysis (NMA) and systematic review based on randomized controlled trials (RCTs) evaluating the efficacies of different interventions for lumbar spinal stenosis (LSS). METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, and major scientific websites from inception to October 10, 2019, for randomized controlled trials comparing the nine most commonly used interventions for LSS. The main outcomes were disability and pain intensity. The PROSPERO number was CRD42020154247. RESULTS: First, laminotomy was better in improving patients' short- and long-term dysfunction (probability 49% and 25%, respectively). Second, decompression, decompression plus fusion, endoscopic decompression, interspinous process spacer device implantation, laminectomy, laminotomy and minimally invasive decompression were significantly more efficacious in relieving pain than non-surgical interventions (mean difference in the short-term -21.82, -22.00, -16.68, -17.47, -17.75, -17.61 and -18.86; in the long-term -37.14, -34.04, -34.07, -39.79, -36.14, -32.75 and -39.14, respectively). Third, endoscopic decompression had a lower complication rate (probability 51%). In addition, laminotomy had a lower reoperation rate (probability 45%). Fourth, decompression plus fusion resulted in more blood loss than any other surgical intervention (probability 96%). Finally, endoscopic decompression had the shortest hospitalization time (probability 96%). CONCLUSIONS: There were no significant differences among the different interventions in improving patient function. Surgical interventions were associated with better pain relief but a higher incidence of complications. Decompression plus fusion is not necessary for patients. In addition, endoscopic decompression as a novel and less invasive surgical approach may be a good choice for LSS patients.

Management for lumbar spinal stenosis: Protocol for a network meta-analysis and systematic review.

INTRODUCTION: Lumbar spinal stenosis (LSS) is caused by structural changes of the spine, which lead to several severe symptoms, including back pain, leg pain, numbness and tingling in the legs, as well as reduced physical function. However, there is little evidence suggesting whether a patient with LSS should be treated with surgery. If surgery is recommended, which type of surgery benefits the patient most? To answer these questions, we will conduct a network meta-analysis and a systematic review to compare surgical and nonsurgical interventions in terms of efficacy as well as safety in adult patients with LSS. METHODS AND ANALYSIS: We will search the PubMed, Cochrane library, and EMBASE databases for articles published prior to October 10, 2019. We will search for randomized controlled trials assessing surgical and nonsurgical interventions for adult patients with degenerative LSS without any language restrictions. The primary outcome measures will be pain and disability. The secondary outcomes will include adverse events (number of events or number of people with each type of adverse event), reoperations, complications, blood loss and operation time. We will obtain the full texts of the potentially relevant studies and independently assess them. The quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation framework. A random-effects network meta-analysis will be performed to analyze all the evidence under the frequentist framework, and the ranking results will be presented. We will generate plots depicting the network geometry using Stata. The network meta-analysis will be performed according to the Bayesian framework. Ethics and dissemination Ethics approval is not required. The research will be published in a peer-reviewed journal.

Urachal adenocarcinoma that metastasized to breast was misinterpreted as primary breast mucinous carcinoma: A rare case report and literature review.

BACKGROUND: The urachus is a vestigial tubular structure that connects the urinary bladder to the allantois during early embryonic development. Urachal carcinoma develops in the urachus, which is an embryological remnant of the urogenital sinus and allantois. The estimated annual incidence of urachal carcinoma in the general population is 0.01% of all cancers in adults. Moreover, urachal carcinoma accounts for 0.34% to 0.7% of all bladder carcinoma cases. And breast metastasis is extremely rarer. METHODS AND RESULTS: A 42-year-old woman was admitted to our hospital with a palpable mass in the outer upper quadrant of the right breast, which was misinterpreted as a carcinoma that originated from the breast. Subsequently, she underwent surgery without any further meticulous examination. Immunohistochemistry analysis revealed positivity for CK20, Villin, and CDX-2 and negativity for CK7. After further inspection, a mass was found in the bladder dome using 18F-fluorodeoxyglucose positron emission tomography and computed tomography. The mass was surgically removed. CONCLUSION: Pathologic and immunohistochemical examination confirmed that the mass was urachal mucinous adenocarcinoma and mucinous adenocarcinoma to the right breast. The patient has been followed up without recurrence for 8 months.

Ertapenem versus piperacillin/tazobactam for diabetic foot infections in China: a Phase 3, multicentre, randomized, double-blind, active-controlled, non-inferiority trial.

OBJECTIVES: Few randomized controlled studies have compared antibiotic regimens against diabetic foot infections (DFIs) in Chinese patients. We evaluated the efficacy and safety of ertapenem versus piperacillin/tazobactam for the treatment of DFIs in Chinese patients. METHODS: Patients with moderate to severe DFIs requiring parenteral antibiotics were randomized in a 1 : 1 ratio to receive ertapenem (1.0 g once daily) or piperacillin/tazobactam (4.5 g every 8 h) by 30 min intravenous (iv) infusions for ≥5 days. The primary outcome was favourable clinical response at discontinuation of iv therapy (DCIV). An evaluable-patient population was identified for primary analysis of non-inferiority at -15%. Safety was assessed. ClinicalTrials.gov: NCT01370616. RESULTS: Of 565 patients randomized, 443 patients (ertapenem = 219 and piperacillin/tazobactam = 224) were clinically evaluable for primary analysis. In the clinically evaluable population, the proportions of patients with favourable clinical response at DCIV were 93.6% (205/219) and 97.3% (218/224) in the ertapenem and piperacillin/tazobactam groups, respectively (difference: -3.8%, 95% CI: -8.3%, 0.0%). Ertapenem had a significantly lower favourable clinical response rate (91.5% versus 97.2%, 95% CI for difference: -12.1%, -0.3%) at DCIV in severe DFI patients. In the modified ITT population, 88.8% (237/267) and 90.6% (241/266) of patients in the ertapenem and piperacillin/tazobactam groups, respectively, had favourable clinical responses at DCIV (difference: -1.9%, 95% CI: -7.3%, 3.3%). Microbiological eradications of causative pathogens and adverse events were similar between treatment groups. CONCLUSIONS: Treatment with ertapenem was non-inferior to piperacillin/tazobactam in Chinese patients with DFIs. Ertapenem treatment resulted in a markedly lower rate of clinical resolution in severe DFIs.

Ginsenoside Rd attenuates Aß25-35-induced oxidative stress and apoptosis in primary cultured hippocampal neurons.

One of the most common pathological changes in Alzheimer's disease (AD) brain is the large number of amyloid ß (Aß) peptides accumulating in lesion areas. Ginsenosides are the most active components extracted from ginseng. Ginsenoside Rd (GRd) is a newly discovered saponin that has a stronger pharmacological activity than other ginsenosides, especially in neuroprotection. Here we examined the neuroprotective effects of GRd against neuronal insults induced by Aß25-35 in primary cultured hippocampal neurons. A 10µM GRd treatment significantly prevented the loss of hippocampal neurons induced by Aß25-35. In addition, GRd significantly ameliorated Aß25-35-induced oxidative stress by decreasing the reactive oxygen species (ROS) production and malondialdehyde (MDA) level, and increasing the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px); which is similar in treatments with 10µM of probucol (PB) and 100µM of edaravone (EDA). Moreover, our present study demonstrated that GRd significantly enhanced the expression of Bcl-2 mRNA, and decreased the expressions of Bax mRNA and Cyt c mRNA. GRd also downregulated the protein level of cleaved Caspase-3 compared to controls. These results highlighted the neuroprotective effects of GRd against Aß25-35-induced oxidative stress and neuronal apoptosis, suggesting that this may be a promising therapeutics against AD.

[94 km Brillouin distributed optical fiber sensors based on ultra-long fiber ring laser pumping].

A novel optical amplification configuration based on ultra-long fiber laser with a ring cavity was proposed and applied to Brillouin optical time-domain analysis (BOTDA) sensing system, in order to extend the measurement distance significantly. The parameters used in the experiment were optimized, considering the main limitations of the setup, such as depletion, self-phase modulation (SPM) and pump-signal relative intensity noise (RIN) transfer. Through analyzing Brillouin gain spectrum, we demonstrated distributed sensing over 94 km of standard single-mode fiber with 3 meter spatial resolution and strain/temperature accuracy of 28 /1. 4 degree C.

Distributed Raman amplification using ultra-long fiber laser with a ring cavity: characteristics and sensing application.

Distributed Raman amplification (DRA) based on ultra-long fiber laser (UL-FL) pumping with a ring cavity is promising for repeaterless transmission and sensing. In this work, the characteristics (including gain, nonlinear impairment and noise figure) for forward and backward pumping of the ring-cavity based DRA scheme are fully investigated. Furthermore, as a typical application of the proposed configuration, ultra-long-distance distributed sensing with Brillouin optical time-domain analysis (BOTDA) over 142.2 km fiber with 5m spatial resolution and ± 1.5 °C temperature uncertainty is achieved, without any repeater. The key point for the significant performance improvement is the system could offer both of uniform gain distribution and considerably suppressed pump-probe relative intensity noise (RIN) transfer, by optimized design of system structure and parameters.

Hybrid distributed Raman amplification combining random fiber laser based 2nd-order and low-noise LD based 1st-order pumping.

A configuration of hybrid distributed Raman amplification (H-DRA), that is formed by incorporating a random fiber laser (RFL) based 2nd-order pump and a low-noise laser-diode (LD) based 1st-order pump, is proposed in this paper. In comparison to conventional bi-directional 1st-order DRA, the effective noise figure (ENF) is found to be lower by amount of 0 to 4 dB due to the RFL-based 2nd-order pump, depending on the on-off gain, while the low-noise 1st-order Raman pump is used for compensating the worsened signal-to-noise ratio (SNR) in the vicinity towards the far end of the fiber and avoiding the potential nonlinear impact induced by excess injection of pump power and suppressing the pump-signal relative intensity noise (RIN) transfer. As a result, the gain distribution can be optimized along ultra-long fiber link, due to combination of the 2nd-order RFL and low-noise 1st-order pumping, making the transmission distance be extended significantly. We utilized such a configuration to achieve ultra-long-distance distributed sensing based on Brillouin optical time-domain analysis (BOTDA). A repeater-less sensing distance record of up to 154.4 km with 5 m spatial resolution and ~ ± 1.4 °C temperature uncertainty is successfully demonstrated.

[The safety and effectiveness of once daily detemir in patients with type 2 diabetes previously failing oral agents: the Chinese cohort from SOLVE(TM) observational study].

OBJECTIVE: Study of Once-daily LeVEmir(®) (SOLVE(TM)) was a 24-week international observational study to evaluate the safety and effectiveness of initiating once-daily insulin detemir (Levemir) as add-on therapy in patients with type 2 diabetes mellitus (T2DM) who failed treatment of oral anti-diabetic drugs (OAD). METHODS: The present study was derived from the data of Chinese cohort. A total of 3272 patients with T2DM failing OAD were enrolled in the study. Determir were prescribed to the patients by the decision of the physician. Clinical data were collected at baseline, week 12 and week 24 to evaluate the safety and effectiveness of detemir. RESULTS: The age of the patients was (56.2 ± 10.8) years with a diabetes duration of (7.1 ± 5.2) years. Their BMI was (25.3 ± 3.3) kg/m(2). No patient experienced any major or nocturnal hypoglycaemic event during the study. After 24 weeks of treatment, the glycosylated hemoglobin A1c (HbA1c) decreased from (8.33 ± 1.69)% to (7.16 ± 1.18)% with a mean change of -1.17%, the fasting plasma glucose decreased from (9.52 ± 2.59) mmol/L to (6.84 ± 1.42) mmol/L with a mean change of -2.7 mmol/L, and the 7-point blood glucose profile improved overall. Totally 49.1% of patients achieved HbA1c < 7%. The mean body weight decreased by 0.15 kg. CONCLUSIONS: Insulin detemir administered once daily as add-on therapy in patients with T2DM failing OAD regimen significantly reduces the risk of major hypoglycemia, improves glycemic control, increases the percentage of patients achieving treatment target with neutral effect on body weight.

Residue depletion of nifuroxazide in broiler chicken.

BACKGROUND: Several nitrofuran drugs have been prohibited for use in food producing animals due to their carcinogenic and mutagenic effects. However, one of the nitrofurans, nifuroxazide, is still used as a veterinary drug in some countries. This study was conducted to investigate the residue depletion of nifuroxazide in broiler chicken. Chickens were fed with dietary feeds containing 50 mg kg⁻¹ of nifuroxazide for seven consecutive days. Liver, kidney, muscle and plasma samples were collected at different withdrawal periods, and the residues of parent nifuroxazide and its acid-hydrolysable side chain, 4-hydroxybenzhydrazide (HBH), in these samples were determined. RESULTS: Nifuroxazide was metabolised in vivo and its metabolite HBH was formed. Parent nifuroxazide was not detectable in these samples after 14 days of cessation. HBH was detectable in these samples even after 28 days of cessation and the total HBH residues were higher than 1.0 ng g⁻¹. Furthermore, the residue level of tissue bound HBH was much higher than that of free HBH. CONCLUSION: The tissue-bound HBH could be used as a marker to monitor the residue of nifuroxazide in chicken and the best target tissue should be liver. This is the first paper reporting the residue depletion of nifuroxazide in chicken.

Effects of Astragalus polysaccharide on immune responses of porcine PBMC stimulated with PRRSV or CSFV.

BACKGROUND: Astragalus polysaccharide (APS) has been used as an immunomodulator that can enhance immune responses, whereas the immunomodulatory effects of APS on porcine peripheral blood mononuclear cells (PBMCs) exposed to porcine reproductive and respiratory syndrome virus (PRRSV) and classical swine fever virus (CSFV) have not been investigated. METHODOLOGY/PRINCIPAL FINDINGS: Porcine PBMCs were cultured in complete RPMI media in the presence of the R98-strain of PRRSV (5×10(4) TCID(50)/ml) or C-strain of CSFV (10(3) TCID(50)/ml) with or without APS. The expression of mRNA for CD28, cytotoxic T-lymphocyte antigen 4 (CTLA-4), transforming growth factor-ß (TGF-ß), interleukin 2 (IL-2) and IL-10 was assayed by TaqMan real-time RT-PCR. The expression of mRNA for CD28 and CTLA-4 increased at 24 h after stimulation of PBMCs with CSFV and the increased production of CTLA-4 was confirmed by western blot analysis, whereas the increases were inhibited by the addition of APS. In addition, APS alone upregulated IL-2 and TGF-ß mRNA expression in PBMCs and the addition of APS had the capacity to prevent a further increase in IL-2 mRNA expression in PBMCs during CSFV or PRRSV infection, but had no effect on TGF-ß mRNA expression. The production of tumor necrosis factor-alpha (TNF-α) increased at 12 h after stimulation with PRRSV or CSFV, but not with PRRSV plus APS or CSFV plus APS, whereas the addition of APS to PBMCs infected with PRRSV or CSFV promoted IL-10 mRNA expression. CONCLUSIONS: We suggested that APS had immunomodulatory effects on cells exposed to PRRSV or CSFV. It might be that APS via different mechanisms affects the activities of immune cells during either PRRSV or CSFV infection. This possibility warrants further studies to evaluate whether APS would be an effective adjuvant in vaccines against PRRSV or CSFV.

Alterations of ADAMTSs and TIMP-3 in human nucleus pulposus cells subjected to compressive load: Implications in the pathogenesis of human intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) pertains to the loss of extracellular matrix (ECM), particularly the early loss of aggrecan, the turnover of which is regulated by ADAMTSs. Amongst the etiological factors of IDD, mechanical stress plays an important role in the physiological and pathological processes of nucleus pulposus (NP) cells. However, the role of ADAMTSs and their inhibitor in human NP cells under mechanical stress has not been elucidated to date. The purpose of this study was to investigate the role of ADAMTSs and TIMP-3 in NP cells under mechanical stress. Human NP cells isolated from non-degenerative and degenerative discs were subjected to dynamic compressive load. The expression of ADAMTSs, aggrecan, and TIMP-3 was detected by quantitative real-time PCR and/or Western blot. Consequently, the gene expression of ADAMTS-1, 4, and 5 increased significantly in loaded NP cells compared with not-loaded cells from either non-degenerative or degenerative discs, whereas the gene expression of aggrecan decreased significantly. Moreover, Western blot indicated increased protein levels of ADAMTSs-1, 4, and 5. However, the expression of TIMP-3 altered insignificantly. Together, this study is the first addressing the underlying mechanisms of compressive load as a contributing factor to IDD in terms of ADAMTSs. Our results suggest that compressive load leads to the increase in ADAMTS-1, 4, and 5 that contributes to the decrease of aggrecan and IDD via TIMP-3 independent machinery.

[The baseline characteristics of patients with type 2 diabetes initiating insulin detemir : the Chinese cohort from the SOLVE(TM) study].

OBJECTIVE: To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVE(TM) study. METHODS: Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study. Data on demographics, medical history, glycemic profile and treatment regimen at baseline were collected by physicians. RESULTS: A total of 3272 patients [female 42%, male 58%, mean age (56.2 ± 10.8) years] were included in the study. Their BMI was (25.3 ± 3.3) kg/m(2). The duration of diabetes was 4.0 (0.1 - 27.0) years, and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0 (0.0 - 20.2) years. The proportions of subjects with diabetic macro- and micro-vascular complications were 15.8% (515 cases) and 27.1% (866 cases), respectively. The hemoglobin A1c (HbA1c) at baseline was (8.33 ± 1.70)%, and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L. CONCLUSIONS: A large proportion of patients with type 2 diabetes remain in poor glycemic control, and the prevalence of diabetic complications is high, which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.

Residue depletion of nitrovin in chicken after oral administration.

In this study, the residue depletion of nitrovin in chicken was studied after feeding the birds with dietary feeds containing 10 mg/kg of nitrovin for 7 consecutive days. Tissues (muscle, fat, kidney, and liver) and plasma were collected at different withdrawal periods and determined by a high-performance liquid chromatography-ultraviolet (HPLC-UV) method. The limit of detection for nitrovin in tissue and plasma samples was 0.1 ng/(g or mL), and the inter- and intrarecoveries from the blank fortified samples were in the range of 71.1-85.7%. At the withdrawal period of 0 days, the residue concentration of nitrovin in plasma was the highest (average of 84.98 ng/mL) compared to those in muscle, fat, liver, and kidney (average of 21.04, 61.18, 24.04, and 68.28 ng/g, respectively). At the withdrawal period of 28 days, the residue levels of nitrovin in muscle, fat, liver, and plasma were all higher than 1.0 ng/(g or mL) and the highest concentration was in liver (average of 5.8 ng/g). These data are in support of the ban of nitrovin as a feed additive in food-producing animals.