Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.

Parallel photonic acceleration processor for matrix-matrix multiplication.

We propose and experimentally demonstrate a highly parallel photonic acceleration processor based on a wavelength division multiplexing (WDM) system and a non-coherent Mach-Zehnder interferometer (MZI) array for matrix-matrix multiplication. The dimensional expansion is achieved by WDM devices, which play a crucial role in realizing matrix-matrix multiplication together with the broadband characteristics of an MZI. We implemented a 2 × 2 arbitrary nonnegative valued matrix using a reconfigurable 8 × 8 MZI array structure. Through experimentation, we verified that this structure could achieve 90.5% inference accuracy in a classification task for the Modified National Institute of Standards and Technology (MNIST) handwritten dataset. This provides a new effective solution for large-scale integrated optical computing systems based on convolution acceleration processors.

A Middle Eocene lowland humid subtropical "Shangri-La" ecosystem in central Tibet.

Tibet's ancient topography and its role in climatic and biotic evolution remain speculative due to a paucity of quantitative surface-height measurements through time and space, and sparse fossil records. However, newly discovered fossils from a present elevation of ∼4,850 m in central Tibet improve substantially our knowledge of the ancient Tibetan environment. The 70 plant fossil taxa so far recovered include the first occurrences of several modern Asian lineages and represent a Middle Eocene (∼47 Mya) humid subtropical ecosystem. The fossils not only record the diverse composition of the ancient Tibetan biota, but also allow us to constrain the Middle Eocene land surface height in central Tibet to ∼1,500 ± 900 m, and quantify the prevailing thermal and hydrological regime. This "Shangri-La"-like ecosystem experienced monsoon seasonality with a mean annual temperature of ∼19 °C, and frosts were rare. It contained few Gondwanan taxa, yet was compositionally similar to contemporaneous floras in both North America and Europe. Our discovery quantifies a key part of Tibetan Paleogene topography and climate, and highlights the importance of Tibet in regard to the origin of modern Asian plant species and the evolution of global biodiversity.

Promotion Effect of Coexposure to a High-Fat Diet and Nano-Diethylnitrosamine on the Progression of Fatty Liver Malignant Transformation into Liver Cancer.

Overconsumption of high-fat foods increases the risk of fatty liver disease (FLD) and liver cancer with long pathogenic cycles. It is also known that the intake of the chemical poison nitrosamine and its nanopreparations can promote the development of liver injuries, such as FLD, and hepatic fibrosis, and significantly shorten the formation time of the liver cancer cycle. The present work confirmed that the coexposure of a high-fat diet (HFD) and nano-diethylnitrosamine (nano-DEN) altered the tumor microenvironment and studied the effect of this coexposure on the progression of fatty liver malignant transformation into liver cancer. Gene transcriptomics and immunostaining were used to evaluate the tumor promotion effect of the coexposure in mice. After coexposure treatment, tumor nodules were obviously increased, and inflammation levels were elevated. The liver transcriptomics analysis showed that the expression levels of inflammatory, fatty, and fibrosis-related factors in the coexposed group were increased in comparison with the nano-DEN- and high-fat-alone groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that coexposure aggravated the high expression of genes related to the carcinomatous pathway and accelerated the formation of the tumor microenvironment. The immunohistochemical staining results showed that the coexposure significantly increased the abnormal changes in proteins related to inflammation, proliferation, aging, and hypoxia in mouse liver tissues. The coexposure of high fat and nano-DEN aggravated the process of steatosis and carcinogenesis. In conclusion, the habitual consumption of pickled foods containing nitrosamines in a daily HFD significantly increases the risk of liver pathology lesions progressing from FLD to liver cancer.

Prognosis of traumatic spinal cord injury in children: Follow-up of 86 patients.

PURPOSE: The long-term situation of children with spinal cord injury (SCI) was investigated, and suggestions for helping them better return to the society were provided. METHODS: SCI patients less than 18 years old hospitalized in Beijing Boai Hospital from January 2011 to December 2020 were retrospectively analyzed. Information including motor function, complications, characteristic changes, self-care abilities, school attendance and social participation were collected by telephone interview and electronic questionnaire. All the answers were statistically analyzed. RESULTS: A total of 86 cases were enrolled, 77 girls and 9 boys, with a median injury age of 6 years and 2 months. The follow-up time was 3-130 months. The main cause of trauma in these children was sport injury (66.3%), the thoracic spinal cord was involved the most (91.9%), and complete SCIs accounted for the majority (76.7%). In terms of complications, children with complete SCIs were more likely to have urinary incontinence, constipation and characteristic changes (p < 0.05); whereas the incomplete SCIs often have spasticity (p < 0.05). As to the daily living abilities, children with incomplete lumbar SCIs were more capable to accomplish personal hygiene, transfer, and bathing independently than those with complete injuries, or cervical/thoracic SCIs, respectively (p < 0.05). Moreover, children older than 9 years care more able to dress and transfer independently than the youngers (p < 0.05). Wheelchair users accounted for 84.9% and more than half of them were able to propel wheelchair independently, and those who move passively in wheelchairs were mostly introverted kids (p < 0.05). Almost all (93.8%) children with incomplete injuries were able to walk independently. Most (79.1%) children continued to attending school, and 41.9% participated in interest classes. Unfortunately, 67.4% of the children spent less time playing with their peers than before the injury. CONCLUSION: SCIs impair physical structures and function of children, affect their independence in daily living, and restrict school attendance and social interaction. Comprehensive rehabilitation after injury is a systematic work. Medical staff and caregivers should not only pay attention to neurological function, but also help them improve self-care abilities. It is also important to balance rehabilitation training and school work and social participation.

Detection of target DNA with a visual CRISPR-associated hyperbranched rolling circle amplification technique.

This paper presents a novel clustered regularly interspaced short palindromic repeat (CRISPR)-associated HRCA technique (CART). During the entire detection process of CART, the target DNA is first specifically recognized and cleaved by a pair of Cas9/sgRNA complexes; then, the cleaved product is ligated into circular DNA as the template of HRCA, and the circular DNA is efficiently amplified by HRCA. Therefore, CART has the advantages of Cas9/sgRNA (single-base mismatch specificity) and HRCA (isothermal reaction temperature and high sensitivity). This technique has been verified by detecting various human papillomavirus (HPV) genes with numerous subtypes. In summary, this study provides a new and effective method for the detection of nucleic acids.

MicroRNA-762 Modulates Lipopolysaccharide-induced Acute Lung Injury via SIRT7.

BACKGROUND: Inflammation and oxidative stress contribute to the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury (ALI). MicroRNA-762 (miR-762) has been implicated in the progression of inflammation and oxidative stress; however, its role in ALI remains unclear. In this study, we aim to investigate the role and underlying mechanisms of miR-762 in LPS-induced ALI. METHODS: Mice were intravenously injected with miR-762 antagomir, agomir or the negative controls for 3 consecutive days and then received a single intratracheal instillation of LPS (5 mg/kg) for 12 h to establish ALI model. Adenoviral vectors were used to knock down the endogenous SIRT7 expression. RESULTS: An increased miR-762 expression was detected in LPS-treated lungs. miR-762 antagomir significantly reduced inflammation, oxidative stress and ALI in mice, while the mice with miR-762 agomir treatment exhibited a deleterious phenotype. Besides, we found that SIRT7 upregulation was essential for the pulmonoprotective effects of miR-762 antagomir, and that SIRT7 silence completely abolished the anti-inflammatory and anti-oxidant capacities of miR-762 antagomir. CONCLUSION: miR-762 is implicated in the pathogenesis of LPS-induced ALI via modulating inflammation and oxidative stress, which depends on its regulation of SIRT7 expression. It might be a valuable therapeutic target for the treatment of ALI.

The function and mechanism of microRNA-92a-3p in lipopolysaccharide-induced acute lung injury.

OBJECTIVES: Sepsis-associated acute lung injury (ALI) is a clinically severe respiratory disorder and remains the leading cause of multiple organ failure and mortality. Herein, we used lipopolysaccharide (LPS) to generate sepsis-induced ALI and try to explore the role and mechanism of microRNA-92a-3p (miR-92a-3p) in this process. METHODS: Mice were intravenously injected with miR-92a-3p agomir, antagomir and negative controls for 3 consecutive days and then were intratracheally instillated by LPS (5 mg/kg) for 12 h. To knock down the endogenous A-kinase anchoring protein 1 (AKAP1), mice were intratracheally injected with recombinant adenovirus carrying the short hairpin RNA targeting AKAP1 (shAkap1) at 1 week before LPS administration. RESULTS: miR-92a-3p level was significantly upregulated in the lungs by LPS injection. miR-92a-3p antagomir reduced LPS-induced intrapulmonary inflammation and oxidative stress, thereby preventing pulmonary injury and dysfunction. In contrast, miR-92a-3p agomir aggravated LPS-induced intrapulmonary inflammation, oxidative stress, pulmonary injury and dysfunction. Moreover, we reported that AKAP1 upregulation was required for the beneficial effects of miR-92a-3p antagomir, and that AKAP1 knockdown completely abolished the anti-inflammatory and antioxidant capacities of miR-92a-3p antagomir. CONCLUSION: Our data identify that miR-92a-3p modulates LPS-induced intrapulmonary inflammation, oxidative stress and ALI via AKAP1 in mice.

Evaluation of CRISPR/Cas9 site-specific function and validation of sgRNA sequence by a Cas9/sgRNA-assisted reverse PCR technique.

The effective application of the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system in biology, medicine and other fields is hindered by the off-target effects and loci-affinity of Cas9-sgRNA, especially at a genome-wide scale. In order to eliminate the occurrence of off-target effects and evaluate loci-affinity by CRISPR/Cas9 site-specific detection and screening of high-affinity sgRNA sequences, respectively, we develop a CRISPR/Cas9-assisted reverse PCR method for site-specific detection and sgRNA sequence validation. The detection method based on PCR can be used directly in the laboratory with PCR reaction conditions, without the need for an additional detection system, and the whole process of detection can be completed within 2 h. Therefore, it can be easily popularized with a PCR instrument. Finally, this method is fully verified by detecting multiple forms of site mutations and evaluating the affinity of a variety of sgRNA sequences for the CRISPR/Cas9 system. In sum, it provides an effective new analysis tool for CRISPR/Cas9 genome editing-related research. A CRISPR/Cas9-assisted reverse PCR method was developed for Cas9/sgRNA site-specific detection and sgRNA sequence validation. The technique detects target DNA in three steps: (1) target DNA is specifically cut by a pair of Cas9/sgRNA complexes; (2) the cleaved DNA is rapidly linked by T4 DNA ligase; (3) the ligated DNA is efficiently amplified by PCR (PCR or qPCR).

Increased sagittal diameter of the vertebral arch aids in diagnosis of lumbar spondylolysis.

OBJECTIVE: To identify a diagnostic indicator of lumbar spondylolysis visible in plain X-ray films. METHODS: One hundred and seventy-two patients with low back pain who received X-ray and computerized tomography (CT) examinations were identified and studied. They were divided into three groups: the spondylosis without spondylolisthesis (SWS) group, comprising 67 patients with bilateral pars interarticularis defects at L5 and without spondylolisthesis, the isthmic spondylolisthesis (IS) group, comprising 74 patients with L5/S1 spondylolisthesis and bilateral L5 pars interarticularis defects, and the control group, comprising 31 patients with low back pain but without spondylolysis. The sagittal diameters of the vertebral arch (SDVAs) of L4 and L5 were measured in lateral X-ray image, and the differences in SDVA between L4 and L5 (DSL4-5) in each case were calculated and analyzed. RESULTS: There were no significant differences in demographic characteristics among the three groups. In the SWS and IS groups, the SDVA of L5 was significantly longer than the SDVA of L4 (p < 0.001), whereas no significant difference found in the control group (p > 0.05). DSL4-5, in which the SDVA of L4 was subtracted from the SDVA of L5, significantly differed among the three groups (p < 0.001), and the normal threshold was provisionally determined to be 1.55 mm. CONCLUSIONS: In bilateral L5 spondylolysis, the SDVA of L5 is wider than the SDVA of L4, and this difference is greater in isthmic spondylolisthesis. This sign in lateral X-rays may provide a simple and convenient aid for the diagnosis of spondylolysis.

Design, synthesis and biological evaluation of novel fluoro-substituted benzimidazole derivatives with anti-hypertension activities.

A series of new fluoro-substituted benzimidazole derivatives were designed, synthesized and pharmacologically evaluated. All the target compounds were characterized by 1HNMR, 13CNMR, mass spectra and elemental analysis. The biological evaluation showed that most of the synthesized compounds displayed nanomolar affinity to the angiotensin II type 1 (AT1) receptor and could decrease blood pressure efficiently in spontaneously hypertensive rats. The maximal response of mean blood pressure (MBP) lowered 74.5 ± 3.5 mmHg (1g) and 69.2 ± 0.9 mmHg (2a) at 10 g/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than both losartan and telmisartan. So, compounds 1g and 2a may be considered as potential antihypertension drug candidates.

What is the difference in ablation zone of multi-bipolar radiofrequency ablation between liver cirrhosis and normal liver background? - a prospective clinical study.

PURPOSE: To explore the differences in ablation zone between liver cirrhosis and normal liver background and investigate the effect of hepatic blood flow on ablation zone of RFA. METHODS: Between 2017 and 2019, 203 patients who had liver malignancies and underwent percutaneous RFA with Celon bipolar electrodes enrolled into this study. There were 90 patients had liver cirrhosis and 113 patients had normal liver background. They were 63 females and 140 males with average age of 59.0 ± 10.9 years old. Contrast-enhanced CT/MRI was used to evaluate the ablation zone in one month after RFA. The hepatic flow measurements on CDFI and CEUS were performed before RFA. Correlations between ablation zone versus hepatic flow were assessed using multiple linear regression analysis. RESULTS: The average ablation zone in cirrhotic liver was significantly larger than those in normal liver background with 3 cm tip of RF electrodes (length 3.5 ± 0.5 vs 3.1 ± 0.4 cm, p = 0.001; width 2.6 ± 0.3 vs 2.2 ± 0.3 cm, p < 0.001; thickness 2.5 ± 0.3 vs 2.0 ± 0.2 cm, p < 0.001). The similar result was found with three 4 cm tip of RF electrodes (width 3.6 ± 0.5 vs 3.1 ± 0.5 cm, p = 0.019; thickness 3.3 ± 0.5 vs 2.7 ± 0.5 cm, p = 0.002). The multiple linear regression analysis showed arrive time of hepatic vein and portal vein was statistically associated with ablation zone with 3 cm electrodes (p < 0.001, p = 0.001), but explained part of the variance (Adjusted R2=0.294, adjusted R2=0.212). CONCLUSION: The ablation zones of RFA with multi-bipolar electrodes in liver cirrhosis were significantly larger than those in normal liver background, being up to 6 mm in thickness. The hepatic flow parameters partly contributed to the ablation zone.

Ischemic damage may play an important role in spinal cord injury during dancing.

STUDY DESIGN: Retrospective analysis. SETTING: China Rehabilitation Research Center, Beijing, China. OBJECTIVE: To explore possible mechanisms underlying spinal cord injury (SCI) in children caused by hyperextension of the spine while dancing. METHODS: The clinical records of 88 children with SCI (mean age, 5.97 years; age range, 4-10 years) admitted to our hospital from January 1989 to October 2019 were retrospectively reviewed. Computed tomography and magnetic resonance imaging were performed on the day of injury. The time from injury to development of paralysis, as well as post-injury activities were surveyed, while abnormal patterns on images, the range of the involved vertebrae, and the extents of edema and atrophy were assessed. RESULTS: Among the 88 patients, 6 (6.8%) were unable to move immediately after SCI, while paralysis occurred in 42, 23, and 17 patients at <30, 30-60, and >60 min after SCI, respectively. The neurological level of injury of 84 patients was between T4 and T12. On sagittal T2-weighted images (T2WIs), the longitudinal range of spinal cord edema was more than one vertebral body in 65 patients, while spinal cord atrophy below T8 was found in 40 patients. On axial T2WIs, although three patients had none, long T2 signals were found in the central gray matter of seven patients. Meanwhile, necrosis of the central area combined with the peripheral white matter was observed in 57 patients, while three patients had total involvement on a cross section. CONCLUSION: Ischemia-related damage, rather than direct trauma to the spinal cord, may play an important role in SCI due to spinal hyperextension during dancing.

Using epidemiological data to identify needs for child-rearing support among Chinese parents: a cross-sectional survey of parents of children aged 6 to 35 months in 15 Chinese cities.

BACKGROUND: The quality of the family environment-in particular, the kind of parenting children receive in their early years-plays a critical role in influencing children's growth and development. To facilitate the development and delivery of appropriate parenting and family interventions for Chinese parents, this study explores the prevalence of the difficulties that may arise in the course of child-rearing, the associated sociodemographic factors and parents' help-seeking behavior. METHODS: A cross-sectional self-reporting survey was conducted with a sample of 2229 parents of children between 6 and 35 months of age. Using a stratified random-digit design, parents from 15 Chinese cities were surveyed to determine their child-rearing difficulties, support-seeking behavior and their preferences for service delivery. The sociodemographic factors that influenced major child-rearing difficulties were analyzed using bivariate and logistic analyses. RESULTS: The majority (87.5%) of Chinese parents of children aged 6-35 months reported experiencing child-rearing difficulties. Nearly one third (31.5%) of parents reported experiencing major difficulties. Feeding and sleep problems were most often reported. Regression analysis revealed that major child-rearing difficulties most often involved male children (OR = 1.35, 95% CI 1.11-1.64), single-child households (OR = 1.38, 95% CI 1.07-1.77), and households with financial problems (OR = 1.40, 95% CI 1.06-1.85). Just over one third of parents (33.44%) sought professional support, while 21.37% had attended a parenting course in the past year. Prefer ways of sourcing parental support included professional online platform (69.24%), self-help books (43.70%), face-to-face consultation (24.99%), and attending lectures (36.57%). CONCLUSIONS: Child-rearing difficulties are common among parents of children between 6 and 35 months of age in Chinese cities. The family with boys, single-child, financial problems, and father not joining in child-rearing may face the high risk to major child-rearing difficulties. The national initiative to provide more guidance and support for child-rearing difficulties is worthwhile, as is the development of online parenting programs.

Heterogeneity among traumatic spinal cord injuries at the thoracolumbar junction: helping select patients for clinical trials.

STUDY DESIGN: Retrospective analysis. SETTING: China Rehabilitation Research Center, Beijing, China. OBJECTIVE: A retrospective study that documents the modalities and clarifies the heterogeneity among spinal cord injuries (SCIs) caused by trauma to the thoracolumbar vertebral junction. METHODS: X-ray and MRI imaging, neurological records, and the urodynamics results of 190 patients were reviewed and used to categorize different SCI modalities. First, injuries were divided into complete and incomplete injuries using the International Standard for Neurological Classification of Spinal Cord Injury. Next, the complete injuries were further grouped using the neurological level of injury and Long T2 signal from mid-sagittal MRI images, whereas the bulboconvernosus reflexes were also used as a reference to detect injury to the sacral cord. RESULTS: The SCI modalities were classified into five categories: pure complete epiconus lesion with caudal cord intact (G1), complete epiconus injury with conus medullaris (CM) totally involved in the lesion (G2), CM syndrome, cauda equine syndrome without sacral sparing (G3 and G4), and incomplete injury (G5). CONCLUSIONS: The heterogeneity of SCIs at the thoracolumbar junction was documented, a criterion we propose to be of great significance when selecting patients for clinical trials. In particular, the G2 group, which comprises nearly one third of the patients with epiconus lesions, is sometimes mistaken as G1, an observation that has thus far received insufficient attention.

Efficacy of acupuncture in the management of post-apoplectic aphasia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Aim of this study was to evaluate the effectiveness of scalp, tongue, and Jin's 3-needle acupuncture for the improvement of postapoplectic aphasia. METHOD: PubMed, Cochrane, Embase databases were searched using index words to identify qualifying randomized controlled trials (RCTs). Meta-analyses of odds ratios (OR) or standardized mean differences (SMD) were performed to evaluate the outcomes between investigational (scalp / tongue / Jin's 3-needle acupuncture) and control (traditional acupuncture; TA and/or rehabilitation training; RT) groups. RESULTS: Thirty-two RCTs (1310 participants in investigational group and 1270 in control group) were included. Compared to TA, (OR 3.05 [95% CI: 1.77, 5.28]; p<0.00001), tongue acupuncture (OR 3.49 [1.99, 6.11]; p<0.00001), and Jin's 3-needle therapy (OR 2.47 [1.10, 5.53]; p = 0.03) had significantly better total effective rate. Compared to RT, scalp acupuncture (OR 4.24 [95% CI: 1.68, 10.74]; p = 0.002) and scalp acupuncture with tongue acupuncture (OR 7.36 [3.33, 16.23]; p<0.00001) had significantly better total effective rate. In comparison with TA/RT, scalp acupuncture, tongue acupuncture, scalp acupuncture with tongue acupuncture, and Jin's three-needling significantly improved ABC, oral expression, comprehension, writing and reading scores. CONCLUSION: As treatments to postapoplectic aphasia, scalp / tongue acupuncture and Jin's Three-needling are found better than TA and/or RT in yielding total effective rate and improving ABC, oral expression, comprehension, reading and writing scores.

Comparison of clinical outcomes of expansive open-door laminoplasty with unilateral or bilateral fixation and fusion for treating cervical spondylotic myelopathy: a multi-center prospective study.

BACKGROUND: The present study evaluated the clinical outcomes and safety of expansive open-door laminoplasty, when securing with C4 - C6 lateral mass screw and fusion. METHODS: A total of 110 patients with cervical spondylotic myelopathy (CSM) were enrolled. There were 88 male and 22 female, with mean age at 60.55 ± 10.95 years. All of the patients underwent expansive open-door laminoplasty with unilateral or bilateral C4-6 lateral mass screws fixation and fusion. Clinical data, including age, gender, operation-related information, pre- and post-operation Japanese Orthopedic Association (JOA) scores, and cervical curvatures were collected. RESULTS: The mean follow-up time of the cohort was 13.61 ± 9.53 months. Among the 110 patients, 33 of them were allocated to Unilateral group, and 77 of them were in Bilateral group. The mean JOA score of the 110 patients before surgery was 10.07 ± 2.39, and the score was improved significantly to 12.85 ± 2.45 after surgery. There were no reported cases of neurological deterioration or symptom worsening. Patients in both the Unilateral group and Bilateral groups had significant improvement of JOA scores. Among all patients, the most frequently observed complications were axial symptoms (n = 7). The average preoperative cervical curvature among all patients was 15.17 ± 5.26, and the post-surgery curvature was 14.41 ± 4.29. Similar observations were found between Unilateral and Bilateral groups. CONCLUSION: The modified surgical approach provided satisfactory clinical outcome in patients with CSM. The unilateral and bilateral fixation appeared to provide similar outcomes, in terms of cervical curvature maintenance and improvement of clinical symptoms. However, the examination of the exact differences between the two fixation methods await further biomechanical studies.

Association of Systemic Inflammation Score With Atrial Fibrillation: A Case-Control Study With Propensity Score Matching.

BACKGROUND: Inflammation plays a key role in the initiation and progression of atrial fibrillation (AF). We developed a novel systemic inflammation score (SIS) based on integration of biomarkers used routinely in clinical settings. We aim to explore the association between SIS and AF. METHODS: A matched case-control study with 376 pairs of AF cases and controls was performed using a propensity score matching system. The SIS was developed by integrating albumin (ALB), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocytes to monocytes ratio (LMR). Univariate and multivariate analyses were performed to examine the association of each marker and SIS with AF. RESULTS: The conditional multivariate logistic regression analysis showed that elevated levels of ALB and LMR were significantly associated with decreased risk of AF with an OR of 0.74 (95% CI: 0.65, 0.85) and 0.73 (95% CI: 0.64, 0.83), respectively. Patients with elevated SIS had a significantly higher risk of AF. Compared to the patients with SIS equal to 1, the patients with SIS equal to 3 and 4 had an OR of 2.16 (95% CI: 1.40 3.32), and 2.55 (95% CI: 1.66, 3.92), respectively. The SIS was positively correlated with left atrial diameter and right atrial diameter in patients with AF. CONCLUSIONS: In conclusion, this study provides further clinical epidemiological evidence that systemic inflammatory status was correlated with AF. The SIS, as an index to evaluate the intensity of systemic inflammatory status, could be useful for early prediction of AF development and understanding of AF mechanism.

Conditional knockout of Fgf13 in murine hearts increases arrhythmia susceptibility and reveals novel ion channel modulatory roles.

The intracellular fibroblast growth factors (iFGF/FHFs) bind directly to cardiac voltage gated Na+ channels, and modulate their function. Mutations that affect iFGF/FHF-Na+ channel interaction are associated with arrhythmia syndromes. Although suspected to modulate other ionic currents, such as Ca2+ channels based on acute knockdown experiments in isolated cardiomyocytes, the in vivo consequences of iFGF/FHF gene ablation on cardiac electrical activity are still unknown. We generated inducible, cardiomyocyte-restricted Fgf13 knockout mice to determine the resultant effects of Fgf13 gene ablation. Patch clamp recordings from ventricular myocytes isolated from Fgf13 knockout mice showed a ~25% reduction in peak Na+ channel current density and a hyperpolarizing shift in steady-state inactivation. Electrocardiograms on Fgf13 knockout mice showed a prolonged QRS duration. The Na+ channel blocker flecainide further prolonged QRS duration and triggered ventricular tachyarrhythmias only in Fgf13 knockout mice, suggesting that arrhythmia vulnerability resulted, at least in part, from a loss of functioning Na+ channels. Consistent with these effects on Na+ channels, action potentials in Fgf13 knockout mice, compared to Cre control mice, exhibited slower upstrokes and reduced amplitude, but unexpectedly had longer durations. We investigated candidate sources of the prolonged action potential durations in myocytes from Fgf13 knockout mice and found a reduction of the transient outward K+ current (Ito). Fgf13 knockout did not alter whole-cell protein levels of Kv4.2 and Kv4.3, the Ito pore-forming subunits, but did decrease Kv4.2 and Kv4.3 at the sarcolemma. No changes were seen in the sustained outward K+ current or voltage-gated Ca2+ current, other candidate contributors to the increased action potential duration. These results implicate that FGF13 is a critical cardiac Na+ channel modulator and Fgf13 knockout mice have increased arrhythmia susceptibility in the setting of Na+ channel blockade. The unanticipated effect on Ito revealed new FGF13 properties and the unexpected lack of an effect on voltage-gated Ca2+ channels highlight potential compensatory changes in vivo not readily revealed with acute Fgf13 knockdown in cultured cardiomyocytes.

The dark side of "the force" - lipid nanoparticles enhance the oncogenesis of diethylnitrosamine and result in liver cancer in mice.

Nano-carriers, especially lipid nanoparticles have been used widely in "a good manner", for instance in the treatment of cancer, by enhancing the targetability and reducing required dose. Here in the contrary, we presented a new possibility: nanoDEN, a nanoparticle-packed "bad guy", which is more effective and efficient in generating liver tumor in mice. We have shown that nanoDEN, same as diethylnitrosamine (DEN), induced overexpression of multiple pivotal factors (including COX-2, ß-catenin and PCNA) during oncogenesis. Moreover, nanoDEN increased the apoptosis of liver cells compared with DEN alone. This apoptotic effect of nanoDEN is more efficient on normal cells than on cancer cells. Taken into consideration the fact that there are endogenous nanoparticles naturally formed inside our body, our research enlarged our views of all the aspects of oncogenic chemicals, while also established a better method of producing animal model of liver cancer, which has future investigational and therapeutical potential.