Transcriptome-wide profiling of A-to-I RNA editing by Slic-seq.

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional processing event involved in diversifying the transcriptome and is responsible for various biological processes. In this context, we developed a new method based on the highly selective cleavage activity of Endonuclease V against Inosine and the universal activity of sodium periodate against all RNAs to enrich the inosine-containing RNA and accurately identify the editing sites. We validated the reliability of our method in human brain in both Alu and non-Alu elements. The conserved sites of A-to-I editing in human cells (HEK293T, HeLa, HepG2, K562 and MCF-7) primarily occurs in the 3'UTR of the RNA, which are highly correlated with RNA binding and protein binding. Analysis of the editing sites between the human brain and mouse brain revealed that the editing of exons is more conserved than that in other regions. This method was applied to three neurological diseases (Alzheimer's, epilepsy and ageing) of mouse brain, reflecting that A-to-I editing sites significantly decreased in neuronal activity genes.

New Indole Diketopiperazine Alkaloids from Soft Coral-Associated Epiphytic Fungus Aspergillus versicolor CGF 9-1-2.

Two new indole diketopiperazine alkaloids (IDAs), (+)19-epi-sclerotiamide (1) and (-)19-epi-sclerotiamide (2), along with 13 known analogs (3-15), were isolated from a soft coral-associated epiphytic fungus Aspergillus versicolor CGF 9-1-2. The structures of two new compounds were established based on the combination of HR-ESI-MS, 1D and 2D NMR spectroscopy, optical rotation measurements and quantum chemical 13 C-NMR, the absolute configurations were determined by experimental and electronic circular dichroism (ECD) calculations. The results of molecular docking showed that all the compounds had a good binding with TDP1, TDP2, TOP1, TOP2, Ache, NLRP3, EGFR, EGFR L858R, EGFR T790M and EGFR T790/L858. Biological evaluation of compounds 3, 6, 8, 11 showed that 3 exerted a strong inhibitory effect on TDP2 with a rate of 81.72 %.

Preferences for end-of-life care and decision-making among Chinese community-dwelling older adults: A comparative cross-sectional study in Hong Kong and Wuhan in China.

This study aimed to describe and compare end-of-life care and decision-making preferences among Chinese community-dwelling older adults between Wuhan and Hong Kong in China. The study adopted a cross-sectional correlation design and recruited a convenience sample of 259 older adults, aged ≥65 years old from five community centers in Wuhan and Hong Kong. Participants completed a validated structured questionnaire that measured their end-of-life care and decision-making preferences. Multivariate logistic regression analyses were conducted. Results showed that Wuhan participants were significantly more likely to view "trying every means to extend the life span" as very important/important; and they perceived "support from religious personnel" as unimportant/very unimportant. Different from those older adults in Hong Kong, the Wuhan participants significantly chose their home as the preferred place for end-of-life care and death. They also tended to prefer family members to enact the decision-maker role in end-of-life decision situations. The study suggests older adults in Hong Kong and Wuhan have some differences in preferences for end-of-life care and decision-making, which provides the basis for future development of culturally relevant community-based end-of-life care.

Prediction and prognosis of adverse maternal and foetal/neonatal outcomes in pulmonary hypertension: an observational study and nomogram construction.

BACKGROUND: Pregnant women with pulmonary hypertension (PH) have higher mortality rates and poor foetal/neonatal outcomes. Tools to assess these risk factors are not well established. METHODS: Predictive and prognostic nomograms were constructed using data from a "Development" cohort of 420 pregnant patients with PH, recorded between January 2009 and December 2018. Logistic regression analysis established models to predict the probability of adverse maternal and foetal/neonatal events and overall survival by Cox analysis. An independent "Validation" cohort comprised data of 273 consecutive patients assessed from January 2019 until May 2022. Nomogram performance was evaluated internally and implemented with online software to increase the ease of use. RESULTS: Type I respiratory failure, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide [Formula: see text] 1400 ng/L, arrhythmia, and eclampsia with pre-existing hypertension were independent risk factors for maternal mortality or heart failure. Type I respiratory failure, arrhythmia, general anaesthesia for caesarean section, New York Heart Association functional class, and N-terminal pro-brain natriuretic peptide [Formula: see text] 1400 ng/L were independent predictors of pulmonary hypertension survival during pregnancy. For foetal/neonatal adverse clinical events, type I respiratory failure, arrhythmia, general anaesthesia for caesarean section, parity, platelet count, fibrinogen, and left ventricular systolic diameter were important predictors. Nomogram application for the Development and Validation cohorts showed good discrimination and calibration; decision curve analysis demonstrated their clinical utility. CONCLUSIONS: The nomogram and its online software can be used to analyse individual mortality, heart failure risk, overall survival prediction, and adverse foetal/neonatal clinical events, which may be useful to facilitate early intervention and better survival rates.

What Is Different about Teratoma-Associated Anti-LGI1 Encephalitis? A Long-Term Clinical and Neuroimaging Case Series.

INTRODUCTION: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is clinically heterogeneous, especially at presentation, and though it is sometimes found in association with tumor, this is by no means the rule. METHODS: Clinical data for 10 patients with anti-LGI1 encephalitis were collected including one case with teratoma and nine cases without and compared for clinical characteristics. Microscopic pathological examination and immunohistochemical assay of the LGI1 antibody were performed on teratoma tissue obtained by laparoscopic oophorocystectomy. RESULTS: In our teratoma-associated anti-LGI1 encephalitis case, teratoma pathology was characterized by mostly thyroid tissue and immunohistochemical assay confirmed positive nuclear staining of LGI1 in some tumor cells. The anti-LGl1 patient with teratoma was similar to the non-teratoma cases in many ways: age at onset (average 47.3 in non-teratoma cases); percent presenting with rapidly progressive dementia (67% of non-teratoma cases) and psychiatric symptoms (33%); hyponatremia (78%); normal cerebrospinal fluid results except for positive LGI1 antibody (78%); bilateral hippocampal hyperintensity on magnetic resonance imaging (44%); diffuse slow waves on electroencephalography (33%); good response to immunotherapy (67%); and mild residual cognitive deficit (22%). Her chronic anxiety and presentation with status epilepticus were the biggest differences compared with the non-teratoma cases. CONCLUSION: In our series, anti-LGI1 encephalitis included common clinical features in our series: rapidly progressive dementia, faciobrachial dystonic seizures, behavioral disorders, hyponatremia, hippocampal hyperintensity on magnetic resonance imaging, and residual cognitive deficit. We observed some differences (chronic anxiety and status epilepticus) in our case with teratoma, but a larger accumulation of cases is needed to improve our knowledge base.

Asparaginase-related diabetic ketoacidosis: Analysis of the FDA Adverse Event Reporting System (FAERS) data and literature review.

WHAT IS KNOWN AND OBJECTIVE: Diabetic ketoacidosis (DKA) may occur during asparaginase use. However, limited by the study population, the association between asparaginase and DKA has not been elucidated. The purpose of this study was to determine the potential association between asparaginase and DKA and analyse related clinical characteristics and possible risk factor. METHODS: Disproportionality analysis with the reporting odd ratio (ROR) was used to detect the adverse reaction signals of asparaginase-associated DKA in Food and Drug Administration Adverse Event Reporting System (FAERS). A literature review was conducted to further analyse clinical characteristics, possible risk factor and something noteworthy in asparaginase-associated DKA. RESULTS AND DISCUSSION: A total of 12 reports of DKA associated with l-asparaginase (l-asp) and 6 reports associated with pegaspargase (PEG-asp) were extracted in FAERS, more than 50% of the cases were classified as serious adverse events. DKA was a positive signal of l-asp (ROR = 2.397, 95% CI 1.360-4.226), while not closely related to the use of PEG-asp (ROR = 1.602, 95% CI 0.719-3.570). Searched in PubMed, Embase and Web of Science, a total of eight patients were collected. The patients were mainly adolescent patients, aged between 11 and 25 years old with a median age of 16 years. Drug dosage form distribution is unbalanced, 7 patients received l-asp and only 1 received PEG-asp. WHAT IS NEW AND CONCLUSIONS: The ROR of KDA caused by l-asp was statistically significant, but there was not a statistical association for DKA caused by PEG-asp. Asparaginase dosage form may affect the occurrence of DKA, but further research is needed.

Effect of wearing personal protective equipment on acoustic characteristics and speech perception during COVID-19.

With the COVID-19 pandemic, the usage of personal protective equipment (PPE) has become 'the new normal'. Both surgical masks and N95 masks with a face shield are widely used in healthcare settings to reduce virus transmission, but the use of these masks has a negative impact on speech perception. Therefore, transparent masks are recommended to solve this dilemma. However, there is a lack of quantitative studies regarding the effect of PPE on speech perception. This study aims to compare the effect on speech perception of different types of PPE (surgical masks, N95 masks with face shield and transparent masks) in healthcare settings, for listeners with normal hearing in the audiovisual or auditory-only modality. The Bamford-Kowal-Bench (BKB)-like Mandarin speech stimuli were digitally recorded by a G.R.A.S KEMAR manikin without and with masks (surgical masks, N95 masks with face shield and transparent masks). Two variants of video display were created (with or without visual cues) and tagged to the corresponding audio recordings. The speech recording and video were presented to listeners simultaneously in each of four conditions: unattenuated speech with visual cues (no mask); surgical mask attenuated speech without visual cues; N95 mask with face shield attenuated speech without visual cues; and transparent mask attenuated speech with visual cues. The signal-to-noise ratio for 50 % correct scores (SNR50) threshold in noise was measured for each condition in the presence of four-talker babble. Twenty-four subjects completed the experiment. Acoustic spectra obtained from all types of masks were primarily attenuated at high frequencies, beyond 3 kHz, but to different extents. The mean SNR50 thresholds of the two auditory-only conditions (surgical mask and N95 mask with face shield) were higher than those of the audiovisual conditions (no mask and transparent mask). SNR50 thresholds in the surgical-mask conditions were significantly lower than those for the N95 masks with face shield. No significant difference was observed between the two audiovisual conditions. The results confirm that wearing a surgical mask or an N95 mask with face shield has a negative impact on speech perception. However, wearing a transparent mask improved speech perception to a similar level as unmasked condition for young normal-hearing listeners.

Enhanced light extraction efficiency of an LED package by a surface-mounted amorphous photonic structure.

In this study, we propose a low-cost, simple and feasible post-processing approach to improve the light extraction efficiency (LEE) of LED packages. Amorphous photonic structures (APSs) with only short-range order are fabricated from anodic aluminum oxide (AAO) and transferred to intermediate polymer stamp (IPS) by nanoimprint technology. The IPS with APSs is directly mounted onto the surface of an LED package, where the LEE is achieved as 94.6%. The scanning electron microscope (SEM) images of AAO templates and imprinted IPS are analyzed by radial distribution function and diameter histogram. The far-field patterns of APS-mounted LED packages are measured in electroluminescence (EL). The three-dimensional finite-difference time-domain (3D-FDTD) calculations of transmittance of APSs confirm that they improve the light extraction above the critical angle. Two-dimensional Fourier power spectra from SEM images of APSs are also calculated. The LEE enhancement is attributed to that the APSs have short-range order on a length scale comparable to emission wavelength of LED. We provide novel multistage simulations in a simplified FDTD model for the LED package. Finally, we discuss the influence of the morphology of APSs on the LEE of the APS mounted LEDs.

Investigation on many-body effects in micro-LEDs under ultra-high injection levels.

Micro-LEDs can work under an extremely high injection level and are widely used in high-brightness micro-displays and visible light communication. With the increase of carrier concentration, many-body effects gradually become important factors affecting devices' characteristics. Considering the effects of carrier scattering, bandgap renormalization, and Coulomb enhancement (CE), changes in the electroluminescence spectra of micro-LEDs are analyzed as the current density increases from 49.2 to 358.2 kA/cm2, the latter representing an ultra-high injection level. Affected by plasma screening, CE decreases below about 150 kA/cm2. After that, polarization screening dominates and effectively alleviates the spatial separation of electrons and holes, which results in CE increases to the maximum injection level of 358.2 kA/cm2. It is established that CE promotes radiative recombination processes. Different from the traditional phenomenon of "efficiency droop", the enhanced attraction between carriers leads to an abnormal increase of external quantum efficiency at high current density.

Is obstructive sleep apnoea associated with hypoxaemia and prolonged ICU stay after type A aortic dissection repair? A retrospective study in Chinese population.

BACKGROUND: Although obstructive sleep apnoea (OSA) is prevalent among patients with aortic dissection, its prognostic impact is not yet determined in patients undergoing major vascular surgery. We aimed to investigate the association of OSA with hypoxaemia and with prolonged intensive care unit (ICU) stay after type A aortic dissection (TAAD) repair. METHODS: This retrospective study continuously enrolled 83 patients who underwent TAAD repair from January 1 to December 31, 2018. OSA was diagnosed by sleep test and defined as an apnoea hypopnea index (AHI) of ≥ 15/h, while an AHI of > 30/h was defined severe OSA. Hypoxaemia was defined as an oxygenation index (OI) of < 200 mmHg. Prolonged ICU stay referred to an ICU stay of > 72 h. Receiver operating characteristic curve analysis was performed to evaluate the predictive value of postoperative OI for prolonged ICU stay. Multivariate logistic regression was performed to assess the association of OSA with hypoxaemia and prolonged ICU stay. RESULTS: A total of 41 (49.4%) patients were diagnosed with OSA using the sleep test. Hypoxaemia occurred postoperatively in 56 patients (67.5%). Postoperatively hypoxaemia developed mostly in patients with OSA (52.4% vs. 83.0%, p = 0.003), and particularly in those with severe OSA (52.4% vs. 90.5%, p = 0.003). The postoperative OI could fairly predict a prolonged ICU stay (area under the receiver-operating characteristic curve, 0.72; 95% confidence intervals [CI] 0.60-0.84; p = 0.002). Severe OSA was associated with both postoperative hypoxaemia (odds ratio [OR] 6.65; 95% CI 1.56-46.26, p = 0.008) and prolonged ICU stay (OR 5.58; 95% CI 1.54-20.24, p = 0.009). CONCLUSIONS: OSA was common in patients with TAAD. Severe OSA was associated with postoperative hypoxaemia and prolonged ICU stay following TAAD repair.

A Cross-Language Comparison of Sentence Recognition Using American English and Mandarin Chinese HINT and AzBio Sentences.

OBJECTIVES: The aim of this study was to perform a cross-language comparison of two commonly used sentence-recognition materials (i.e., Hearing in Noise Test [HINT] and AzBio) in American English (AE) and Mandarin Chinese (MC). DESIGNS: Sixty normal-hearing, native English-speaking and 60 normal-hearing, native Chinese-speaking young adults were recruited to participate in three experiments. In each experiment, the subjects were tested in their native language. In experiments I and II, noise and tone vocoders were used to process the HINT and AzBio sentences, respectively. The number of channels varied from 1 to 9, with an envelope cutoff frequency of 160 Hz. In experiment III, the AE AzBio and the MC HINT sentences were tested in speech-shaped noise at various signal to noise ratios (i.e., -20, -15, -10, -5, and 0 dB). The performance-intensity functions of sentence recognition using the two sets of sentence materials were compared. RESULTS: Results of experiments I and II using vocoder processing indicated that the AE and MC versions of HINT and AzBio sentences differed in level of difficulty. The AE version yielded higher recognition performance than the MC version for both HINT and AzBio sentences. The type of vocoder processing (i.e., tone and noise vocoders) produced little differences in sentence-recognition performance in both languages. Incidentally, the AE AzBio sentences and the MC HINT sentences had similar recognition performance under vocoder processing. Such similarity was further confirmed under noise conditions in experiment III, where the performance-intensity functions of the two sets of sentences were closely matched. CONCLUSIONS: The HINT and AzBio sentence materials developed in AE and MC differ in level of difficulty. The AE AzBio and the MC HINT sentence materials are similar in level of difficulty. In cross-language comparative research, the MC HINT and the AE AzBio sentences should be chosen for the respective language as the target sentence-recognition test materials.

A meta-analysis on genetic associations between Transcription Factor 7 Like 2 polymorphisms and type 2 diabetes mellitus.

BACKGROUND: Some previous studies already explored associations of Transcription Factor 7 Like 2 (TCF7L2) polymorphisms with type 2 diabetes mellitus (T2DM), with conflicting findings. Here, we aimed to better analyze the relationship between TCF7L2 polymorphisms and T2DM in a larger combined population by performing a meta-analysis. METHODS: We searched Pubmed, Embase, Web of Science and CNKI for related articles. We calculated odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between TCF7L2 polymorphisms and T2DM. RESULTS: Totally 42 studies were included for this meta-analysis. The meta-analysis results demonstrated that TCF7L2 rs4506565, rs7901695, rs11196205 and rs12255372 polymorphisms were all significantly associated with susceptibility to T2DM in general population. Further subgroup analyses revealed similar significant findings in both Asians and Caucasians. CONCLUSIONS: Our findings supported that these TCF7L2 polymorphisms could be used to identify individuals at high risk of developing T2DM.

Sandbur Drought Tolerance Reflects Phenotypic Plasticity Based on the Accumulation of Sugars, Lipids, and Flavonoid Intermediates and the Scavenging of Reactive Oxygen Species in the Root.

The perennial grass Cenchrus spinifex (common sandbur) is an invasive species that grows in arid and semi-arid regions due to its remarkable phenotypic plasticity, which confers the ability to withstand drought and other forms of abiotic stress. Exploring the molecular mechanisms of drought tolerance in common sandbur could lead to the development of new strategies for the protection of natural and agricultural environments from this weed. To determine the molecular basis of drought tolerance in C. spinifex, we used isobaric tags for relative and absolute quantitation (iTRAQ) to identify proteins differing in abundance between roots growing in normal soil and roots subjected to moderate or severe drought stress. The analysis of these proteins revealed that drought tolerance in C. spinifex primarily reflects the modulation of core physiological activities such as protein synthesis, transport and energy utilization as well as the accumulation of flavonoid intermediates and the scavenging of reactive oxygen species. Accordingly, plants subjected to drought stress accumulated sucrose, fatty acids, and ascorbate, shifted their redox potential (as determined by the NADH/NAD ratio), accumulated flavonoid intermediates at the expense of anthocyanins and lignin, and produced less actin, indicating fundamental reorganization of the cytoskeleton. Our results show that C. spinifex responds to drought stress by coordinating multiple metabolic pathways along with other adaptations. It is likely that the underlying metabolic plasticity of this species plays a key role in its invasive success, particularly in semi-arid and arid environments.

Single-Molecule Frequency Fingerprint for Ion Interaction Networks in a Confined Nanopore.

The transport of molecules and ions through biological nanopores is governed by interaction networks among restricted ions, transported molecules, and residue moieties at pore inner walls. However, identification of such weak ion fluctuations from only few tens of ions inside nanopore is hard to achieve owing to electrochemical measurement limitations. Here, we developed an advanced frequency method to achieve qualitative and spectral analysis of ion interaction networks inside a nanopore. The peak frequency fm reveals the dissociation rate between nanopore and ions; the peak amplitude am depicts the amount of combined ions with the nanopore after interaction equilibrium. A mathematical model for single-molecule frequency fingerprint achieved the prediction of interaction characteristics of mutant nanopores. This single-molecule frequency fingerprint is important for classification, characterization, and prediction of synergetic interaction networks inside nanoconfinement.

Optical and frequency degradation behavior of GaN-based micro-LEDs for visible light communication.

In this study, optical power and frequency response degradation behavior of GaN-based micro-LEDs with bandwidth up to 800MHz were investigated under different modes, including direct current (DC) mode, alternating current (AC) mode and DC plus AC small signal mode at room temperature. The electroluminescence (EL), current-voltage (I-V) characteristics and small signal frequency response were measured during the stress. The results show that micro-LEDs under AC mode have better reliability because of the decreased junction temperature, but the high current density would still generate some defects within or around the active region, which can increase the trap-assisted tunneling (TAT) current and non-radiative recombination. The electrical stress-related defects not only reduce the effective carrier concentration injected into QWs but also increase the carrier lifetime for radiative recombination and Auger recombination and decrease the modulation bandwidth. These results will help to understand and improve the reliability of micro-LEDs operated under high current density and promote the application of micro-LEDs for visible light communication.

Characteristics of corneal high-order aberrations in adolescents with mild to moderate myopia.

BACKGROUND: This study investigated the characteristics of corneal higher-order aberrations (HOAs) of the anterior surface, posterior surface, and total cornea in adolescents with mild to moderate myopia. METHODS: A total of 183 patients with myopia (183 eyes) aged 8 to 18 years were enrolled in this study. The axial length (AL) of the eyes was measured by an IOL-Master, and corneal curvatures (K-values) and HOAs were measured by a Pentacam anterior segment diagnostic analyzer. RESULTS: Results of this study showed that the anterior, posterior and total corneal horizontal coma Z31 were - 0.1249 ± 0.105 µm, 0.0009 ± 0.001 µm, and - 0.1331 ± 0.116 µm, respectively; the anterior, posterior and total corneal vertical coma Z3- 1 were - 0.0212 ± 0.164 µm, 0.0003 ± 0.043 µm, and - 0.0216 ± 0.168 µm, respectively; and spherical aberration (SA) Z40 values were 0.2244 ± 0.091 µm, 0.1437 ± 0.029 um, and 0.1889 ± 0.090 µm, respectively. Total corneal Z31 was statistically correlated with posterior corneal astigmatism (K2b - K1b) (p = 0.038). Total corneal Z3- 1 was correlated with anterior corneal astigmatism (K2f - K1f) (p = 0.027). Anterior, posterior, and total corneal Z40 were correlated with anterior and posterior corneal curvature (K1f, K2f, K1b, K2b) (p = 0.001). Posterior corneal Z40b was also significantly correlated with AL. CONCLUSIONS: In adolescents with mild to moderate myopia, the posterior corneal surface shape may play a compensatory role in the balance of corneal aberrations, and the posterior corneal SA tended to become less negative as the AL increased. The corneal coma may also play a compensatory role in posterior corneal surface astigmatism, which was valuable for the treatment for improving visual quality. This conclusion still needs to be verified.

Tracheal Ultrasound for the Accurate Confirmation of the Endotracheal Tube Position in Obese Patients.

OBJECTIVES: Obesity is a serious disorder that may lead to numerous difficulties in endotracheal tube (ETT) management. This study investigated the potential of tracheal ultrasound (TUS) for the accurate confirmation of the ETT position in obese patients. METHODS: A total of 68 obese patients undergoing tracheal intubation were enrolled in this study from January 2017 to June 2018. All patients received auscultation and TUS to evaluate the ETT position, which was ultimately verified by bronchoscopy. A correct position of the ETT was defined as placement at the trachea, whereas placement at the right/left main bronchus was classified as an incorrect position. RESULTS: We found 58 correct placements of the ETT at the trachea, 8 incorrect placements at the right main bronchus, and 2 incorrect placements at the left main bronchus. Compared with auscultation, TUS showed higher accuracy (85.29% versus 67.65%; P = .005), sensitivity (84.48% versus 67.24%; P = .005), and specificity (90.00% versus 70.00%; P < .001), as well as lower rates of false-positive (10.00% versus 30.00%; P < .001) and false-negative (15.52% versus 32.76%; P = .005) results for detecting the correct placement of the ETT, defined as placement at the trachea. CONCLUSIONS: Tracheal ultrasound is highly sensitive and specific in confirming the ETT position in obese patients.

An improved LC-MS/MS method for determination of docetaxel and its application to population pharmacokinetic study in Chinese cancer patients.

Because of its unpredictable side effects and efficacy, the anticancer drug docetaxel (DTX) requires improved characterisation of its pharmacokinetic profiles through population pharmacokinetic studies. A sensitive and rugged LC-MS/MS method for the detection of DTX in human plasma was developed and optimised using paclitaxel as an internal standard (IS). The plasma samples underwent rapid extraction using hybrid solid-phase extraction-protein precipitation. The analyte and IS were separated with an isocratic system on a Zorbax Eclipse Plus C18 column using water containing 0.05% acetic acid along with 20 µM of sodium acetate and methanol (30/70, v/v) as the mobile phase. Quantification was performed using a triple quadrupole mass spectrometer through multiple reaction monitoring in positive mode, using the m/z 830.3 → 548.8 and m/z 876.3 → 307.7 transitions for DTX and paclitaxel, respectively. The range of the calibration curve was 1-500 ng/mL for DTX, and the linear correlation coefficient was >0.99. The accuracies ranged from -4.6 to 4.2%, and the precision was no higher than 7.0% for the analytes. No significant matrix effect was observed. Both DTX and the IS showed considerable recovery. This method was finally applied to the establishment of a population pharmacokinetic model to optimise the clinical use of DTX.

Distinct fusion intersegmental parameters regarding local sagittal balance provide similar clinical outcomes: a comparative study of minimally invasive versus open transforaminal lumbar interbody fusion.

BACKGROUND: Most contemporary studies suggested that intersegmental parameters including disc height and local lordosis contribute to the sagittal balance of fused lumbar. Although similar clinical outcomes following MIS- and Open-TLIF were reported essentially at the early postoperative time, the comparison of local balance variables after these two different techniques was lack. The radiological differences maybe not relevant to the postoperative efficacy at an earlier post-operation stage. But during the long-term follow-up, the complications with regards to the sagittal imbalance might occur due to the distinct biomechanical properties of fusion level after MIS- and Open-TLIF. METHODS: The patients who underwent a single-level MIS- and Open-TLIF were reviewed retrospectively. The anterior disc height (ADH), posterior disc height (PDH), and segmental lordosis (SL) of the fusion segment were measured using recognition technical fluoroscopy. The mean disc height (MDH) was calculated by (ADH + PDH)/2. The relative DH was normalized by the anterior height of the upper vertebrae. The body mass index (BMI), the pain score of low back and leg visual analogue scale (VAS), Oswestry disability index (ODI), estimated blood loss, and hospital stay length was collected. RESULTS: A total of 88 patients undergoing a single-level TLIF (MIS and Open) were included. The pre- and post-operative ADH, PDH, MDH, and SL of MIS-TLIF group were 1.57 ± 0.33 cm, 0.79 ± 0.20 cm, 1.18 ± 0.21 cm, 7.36 ± 3.07 and 1.63 ± 0.30 cm, 1.02 ± 0.28 cm, 1.32 ± 0.24 cm, 10.24 ± 4.79 respectively. Whereas, the pre- and post-operative ADH, PDH, MDH, and SL of Open-TLIF group were 1.61 ± 0.40 cm, 0.77 ± 0.21 cm, 1.19 ± 0.24 cm, 9.05 ± 5.48 and 1.81 ± 0.33 cm, 0.98 ± 0.24 cm, 1.39 ± 0.24 cm, 12.34 ± 4,74 respectively. MIS- and Open-TLIF group showed no significant differences in low back VAS, leg VAS, and ODI both in pre-operation and post-operation (P > 0.05). The estimated blood loss and hospital stay length in the MIS-TLIF group were significantly lower than those in the Open-TLIF group (P < 0.05). CONCLUSION: MIS- and Open-TLIF provided similar clinical outcomes as the respect of low back VAS, leg VAS, and ODI. MIS-TLIF significantly reduced the blood loss and length of hospital stay though. The intervertebral parameters of DH and SL were both increased significantly, Open-TLIF group presented better sagittal balance in term of ADH and SL variables. The contrast investigation of intersegmental parameters may help the surgeons to figure out the further advantages of MIS-TLIF technique, and then better manage the rehabilitation and prevent the reoperation.

LL-37 and its analog FF/CAP18 attenuate neutrophil migration in sepsis-induced acute lung injury.

INTRODUCTION: Sepsis can result in acute lung injury. LL-37 is a small cationic host defense peptide involved in anti-inflammatory. In the current study, it was hypothesized that antimicrobial peptide LL-37 could play a protective role in attenuating the progression of sepsis-induced acute lung injury. METHODS: Forty male C57BL/6 mice were induced into sepsis using cecal ligation and puncture, and subsequently administered with recombinant mouse osteopontin. Peptides LL-37, the LL-37 analog (FF/CAP18, called sLL-37), or normal saline was intravenously administered into septic mice for 20 hours. Then, proinflammatory cytokines (IL-6 and IL-1ß), acute lung injury markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and lactate dehydrogenase [LDH]), the neutrophil infiltration marker (myeloperoxidase [MPO]), and neutrophil infiltration were detected. Furthermore, the neutrophil migration and expression of migration-related factors (focal adhesion kinase [FAK], ERK, and P38) in differentiated HL-60 cells were detected. RESULTS: Septic mice had upregulated IL-6, IL-1ß, ALT, AST, LDH, MPO, p-FAK, p-ERK, and p-P38, infiltrated neutrophils, and migrated neutrophil-like HL-60 cells. In contrast, the administration of peptide LL-37 and sLL-37 inhibited all these changes. Compared with septic mice, it was found that proinflammatory cytokines, lung injury markers, MPO, and infiltrated neutrophils decreased in mice treated with LL-37 and sLL-37. In addition, the migrated neutrophil-like HL-60 cells and activated p-FAK, p-ERK, and p-P38 proteins were suppressed by LL-37 and sLL-37 treatments. CONCLUSIONS: Peptide LL-37 and its analog sLL-37 attenuated the progression of sepsis-induced acute lung injury by inhibiting neutrophil infiltration and migration through the FAK, ERK, and P38 pathways.