Ultrahigh-energy photons up to 1.4 petaelectronvolts from 12 γ-ray Galactic sources.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3-6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

[The impact of non-HDL-C level on major adverse cardiovascular and cerebrovascular events and all-cause mortality after revascularization].

Objective: To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization. Methods: This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes. Results: A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [HR=0.62(95%CI: 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [HR=0.80(95%CI: 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P<0.001, non-linear association P=0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95%CI: 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [HR=0.85(95%CI: 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P=0.039, non-linear association P=0.174). Conclusion: The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.

Measurement of Ultra-High-Energy Diffuse Gamma-Ray Emission of the Galactic Plane from 10 TeV to 1 PeV with LHAASO-KM2A.

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

Cerebellar Transcranial Magnetic Stimulation (TMS) Impairs Visual Working Memory.

An increasing body of evidence points to the involvement of the cerebellum in cognition. Specifically, previous studies have shown that the superior and inferior portions of the cerebellum are involved in different verbal working memory (WM) mechanisms as part of two separate cerebro-cerebellar loops for articulatory rehearsal and phonological storage mechanisms. In comparison, our understanding of the involvement of the cerebellum in visual WM remains limited. We have previously shown that performance in verbal WM is disrupted by single-pulse transcranial magnetic stimulation (TMS) of the right superior cerebellum. The present study aimed to expand on this notion by exploring whether the inferior cerebellum is similarly involved in visual WM. Here, we used fMRI-guided, double-pulse TMS to probe the necessity of left superior and left inferior cerebellum in visual WM. We first conducted an fMRI localizer using the Sternberg visual WM task, which yielded targets in left superior and inferior cerebellum. Subsequently, TMS stimulation of these regions at the end of the encoding phase resulted in decreased accuracy in the visual WM task. Differences in the visual WM deficits caused by stimulation of superior and inferior left cerebellum raise the possibility that these regions are involved in different stages of visual WM.

Intranasal administration of Lactobacillus johnsonii attenuates hyperoxia-induced lung injury by modulating gut microbiota in neonatal mice.

BACKGROUND: Supplemental oxygen impairs lung development in newborn infants with respiratory distress. Lactobacillus johnsonii supplementation attenuates respiratory viral infection in mice and exhibits anti-inflammatory effects. This study investigated the protective effects of intranasal administration of L. johnsonii on lung development in hyperoxia-exposed neonatal mice. METHODS: Neonatal C57BL/6N mice were reared in either room air (RA) or hyperoxia condition (85% O2). From postnatal days 0 to 6, they were administered intranasal 10 µL L. johnsonii at a dose of 1 × 105 colony-forming units. Control mice received an equal volume of normal saline (NS). We evaluated the following four study groups: RA + NS, RA + probiotic, O2 + NS, and O2 + probiotic. On postnatal day 7, lung and intestinal microbiota were sampled from the left lung and lower gastrointestinal tract, respectively. The right lung of each mouse was harvested for Western blot, cytokine, and histology analyses. RESULTS: The O2 + NS group exhibited significantly lower body weight and vascular density and significantly higher mean linear intercept (MLI) and lung cytokine levels compared with the RA + NS and RA + probiotic groups. At the genus level of the gut microbiota, the O2 + NS group exhibited significantly higher Staphylococcus and Enterobacter abundance and significantly lower Lactobacillus abundance compared with the RA + NS and RA + probiotic groups. Intranasal L. johnsonii treatment increased the vascular density, decreased the MLI and cytokine levels, and restored the gut microbiota in hyperoxia-exposed neonatal mice. CONCLUSIONS: Intranasal administration of L. johnsonii protects against hyperoxia-induced lung injury and modulates the gut microbiota.

[Reinforced radiculoplasty for the treatment of symptomatic sacral Tarlov cysts: A clinical analysis of 71 cases].

OBJECTIVE: To investigate the safety and efficacy of reinforced radiculoplasty in the treatment of symptomatic sacral Tarlov cysts (TCs). METHODS: A retrospective analysis was performed on the clinical data and follow-up data of 71 patients with symptomatic sacral TCs who underwent reinforced radiculoplasty in the Neurosurgery Department of Peking University Third Hospital from June 2018 to March 2021. All the operations were performed under neuroelectrophysiological monitoring. Intraoperative cyst exploration, partial resection of the cyst wall, narrowing of the leak, nerve root sleeve radiculoplasty and artificial dural reinforcement were performed. The incidence of postoperative complications and new neurological dysfunction was analyzed. Visual analogue scale (VAS) was used to assess the changes of pain before and after surgery. The Japanese Orthopedics Association (JOA) low back pain score was used to evaluate the changes in nerve function before and after surgery. RESULTS: In the study, 71 patients had 101 TCs, 19 (18.8%) TCs originated from the left S1 nerve, 26 (25.7%) originated from the left S2 nerve, 3 (3.0%) originated from the left S3 nerve, 14 (13.9%) originated from the right S1 nerve, 33 (32.7%) originated from the right S2 nerve, 6 (5.9%) originated from the right S3 nerve, all the TCs underwent reinforced radiculoplasty. Deep infection (1 case), subcutaneous effusion (1 case), fat li-quefaction (1 case) and urinary tract infection (4 cases) were recorded postoperatively. The patients were followed up for 12-43 months (median, 26 months). Two cases had new urinary retention after operation, and the catheter was removed at the end of the first and second months respectively. One case had new fecal weakness, which improved after 3 months. Compared with preoperation, VAS decreased significantly at the last follow-up [median, 6 (4-9) vs. 1 (0-5), Z=-7.272, P < 0.001], JOA score increased significantly [median, 20 (16-25) vs. 27 (18-29), Z=-7.265, P < 0.001]. There were 18 cured cases (25.4%), 41 excellent cases (57.7%), 8 effective cases (11.3%), and 4 invalid cases (5.6%). The total efficiency was 94.4% (67/71). Two (1.98%) cysts recurred. CONCLUSION: For patients with symptomatic sacral TCs, reinforced radiculoplasty can significantly improve the pain and nerve function, which is safe and reliable.

[The mediating effect of resilience on anxiety and subjective well-being in occupational population].

Objective: To explore the current situation of anxiety, subjective well-being in occupational population and the mediating effect of resilience. Methods: From March 24th to 26th, 2020, a cross-sectional survey was conducted among occupational population aged ≥18 years old using online questionnaires. A total of 2134 valid questionnaires were obtained, with respondents from 30 provinces, autonomous regions, and municipalities directly under the Central Government. Their general demographic data, subjective well-being, anxiety, and resilience were collected. Pearson χ(2) test and Spearson correlation analysis were used for data analysis, and structural equation model was used to explore the mediating effect of resilience on anxiety and subjective well-being. Results: The age of the respondents ranged from 18 to 60 years old, with an average age of (31.19±7.09) years old, including 1075 (50.4%) women and 1059 (49.6%) men. The positive rates of low subjective well-being and anxiety were 46.5% (992/2134) and 28.4% (607/2134), respectively. Anxiety scores were significantly negatively correlated with subjective well-being scores and resilience scores (r(s)=-0.52, -0.41, P<0.05), while resilience was significantly positively correlated with subjective well-being (r(s)=0.32, P<0.05). Structural equation models showed that anxiety had a negative predictive effect on subjective well-being, while resilience not only had a positive predictive effect on subjective well-being, but also played a mediating role between anxiety and subjective well-being, with a mediating effect of 9.9%. Conclusion: The situation of anxiety and well-being in the occupational population is still not optimistic, and resilience has a mediating effect between anxiety and subjective well-being.

Brain entropy, fractal dimensions and predictability: A review of complexity measures for EEG in healthy and neuropsychiatric populations.

There has been an increasing trend towards the use of complexity analysis in quantifying neural activity measured by electroencephalography (EEG) signals. On top of revealing complex neuronal processes of the brain that may not be possible with linear approaches, EEG complexity measures have also demonstrated their potential as biomarkers of psychopathology such as depression and schizophrenia. Unfortunately, the opacity of algorithms and descriptions originating from mathematical concepts have made it difficult to understand what complexity is and how to draw consistent conclusions when applied within psychology and neuropsychiatry research. In this review, we provide an overview and entry-level explanation of existing EEG complexity measures, which can be broadly categorized as measures of predictability and regularity. We then synthesize complexity findings across different areas of psychological science, namely, in consciousness research, mood and anxiety disorders, schizophrenia, neurodevelopmental and neurodegenerative disorders, as well as changes across the lifespan, while addressing some theoretical and methodological issues underlying the discrepancies in the data. Finally, we present important considerations when choosing and interpreting these metrics.

Exploring Lorentz Invariance Violation from Ultrahigh-Energy γ Rays Observed by LHAASO.

Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M_{Pl} and that the second-order LIV scale is >10^{-3}M_{Pl}. Both limits improve by at least one order of magnitude the previous results.

Constraints on Heavy Decaying Dark Matter from 570 Days of LHAASO Observations.

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9} GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

The power of heteronemin in cancers.

Heteronemin (Haimian jing) is a sesterterpenoid-type natural marine product that is isolated from sponges and has anticancer properties. It inhibits cancer cell proliferation via different mechanisms, such as reactive oxygen species (ROS) production, cell cycle arrest, apoptosis as well as proliferative gene changes in various types of cancers. Recently, the novel structure and bioactivity evaluation of heteronemin has received extensive attention. Hormones control physiological activities regularly, however, they may also affect several abnormalities such as cancer. L-Thyroxine (T4), steroid hormones, and epidermal growth factor (EGF) up-regulate the accumulation of checkpoint programmed death-ligand 1 (PD-L1) and promote inflammation in cancer cells. Heteronemin suppresses PD-L1 expression and reduces the PD-L1-induced proliferative effect. In the current review, we evaluated research and evidence regarding the antitumor effects of heteronemin and the antagonizing effects of non-peptide hormones and growth factors on heteronemin-induced anti-cancer properties and utilized computational molecular modeling to explain how these ligands interacted with the integrin αvß3 receptors. On the other hand, thyroid hormone deaminated analogue, tetraiodothyroacetic acid (tetrac), modulates signal pathways and inhibits cancer growth and metastasis. The combination of heteronemin and tetrac derivatives has been demonstrated to compensate for anti-proliferation in cancer cells under different circumstances. Overall, this review outlines the potential of heteronemin in managing different types of cancers that may lead to its clinical development as an anticancer agent.

A New Remote Guided Method for Supervised Web-Based Cognitive Testing to Ensure High-Quality Data: Development and Usability Study.

BACKGROUND: The global COVID-19 pandemic has triggered a fundamental reexamination of how human psychological research can be conducted safely and robustly in a new era of digital working and physical distancing. Online web-based testing has risen to the forefront as a promising solution for the rapid mass collection of cognitive data without requiring human contact. However, a long-standing debate exists over the data quality and validity of web-based studies. This study examines the opportunities and challenges afforded by the societal shift toward web-based testing and highlights an urgent need to establish a standard data quality assurance framework for online studies. OBJECTIVE: This study aims to develop and validate a new supervised online testing methodology, remote guided testing (RGT). METHODS: A total of 85 healthy young adults were tested on 10 cognitive tasks assessing executive functioning (flexibility, memory, and inhibition) and learning. Tasks were administered either face-to-face in the laboratory (n=41) or online using remote guided testing (n=44) and delivered using identical web-based platforms (Cambridge Neuropsychological Test Automated Battery, Inquisit, and i-ABC). Data quality was assessed using detailed trial-level measures (missed trials, outlying and excluded responses, and response times) and overall task performance measures. RESULTS: The results indicated that, across all data quality and performance measures, RGT data was statistically-equivalent to in-person data collected in the lab (P>.40 for all comparisons). Moreover, RGT participants out-performed the lab group on measured verbal intelligence (P<.001), which could reflect test environment differences, including possible effects of mask-wearing on communication. CONCLUSIONS: These data suggest that the RGT methodology could help ameliorate concerns regarding online data quality-particularly for studies involving high-risk or rare cohorts-and offer an alternative for collecting high-quality human cognitive data without requiring in-person physical attendance.

[Surgical treatment of large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading].

OBJECTIVE: To investigate the surgical strategy for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. METHODS: The clinical data of 16 patients with large and giant recurrent meningioma in the middle and posterior third part of the superior sagittal sinus with extracranial invasion who underwent surgery in the Department of Neurosurgery of Peking University Third Hospital from May 2019 to May 2022 were retrospectively analyzed. All the patients underwent brain-enhanced magnetic resonance imaging (MRI), magnetic resonance venography (MRV), computed tomography angiography (CTA) and three-dimensional skull computed tomography (CT) before, to evaluate the extent of tumor invasion, the edema of brain tissue, the degree of skull damage, the blood supply of the tumor, and the degree of compression of the superior sagittal sinus, etc, and to formulate an individualized surgical plan. The neurological function of the patients was evaluated 1 week, 1 month, and 3 months after the operation, and the tumor condition was evaluated by brain-enhanced MRI 3 months, 6 months, and 1 year after the operation. RESULTS: The tumors in the 16 patients were all located in the middle and posterior 1/3 part of the superior sagittal sinus and invaded extracranially. Among them, 8 cases were operated for the second time, 6 cases for the third time, and 2 cases for the fourth time; In the last operation, the bone flap was used to repair the skull in 4 cases, and the titanium mesh was used in 12 cases; Tumor arterials of 3 cases were embolized under digital subtraction angiography (DSA). Tumors of 10 cases were resected at Simpson grade Ⅰ, and 6 cases at Simpson grade Ⅱ; 2 cases underwent decompressive craniectomy during operation, and 14 cases underwent cranioplasty at the same time; scalp incisions of 14 cases were directly sutured, and flap transposition was used in 14 cases. When evaluating nerve function after operation, the limb muscle strength was improved compared with that before operation, and the Karnofsky performance scale (KPS) score reached 100 points 3 months after operation. During the follow-up, 1 patient's tumor recurred after 1 year and received Gamma Knife treatment, and the rest of the patients had no recurrence during the follow-up period. CONCLUSION: Surgical treatment is the first choice for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. It is a safe and effective surgical method to take individualized surgical plan after detailed preoperative assessment of cerebral edema, tumor blood supply, venous sinus compression, and scalp invasion.

[Effects of subanesthetic dose of esketamine on opioid consumption after thoracoscopic surgery].

Objective: To investigate the effect of continuous intravenous infusion of subanesthetic dose of esketamine intraoperatively on postoperative opioid consumption in patients undergoing thoracoscopic surgery. Methods: A total of 71 patients with elective thoracoscopic lung surgery in the First Affiliated Hospital of Zhengzhou University from December 2020 to December 2021 were selected. Patients who were classified as grade Ⅰ or Ⅱ by the American Society of Anesthesiologists (ASA) and aged 18-70 years were included, including 32 males and 39 females, with a body mass index (BMI) of 18.5-30.0 kg/m2. The patients were randomly divided into three groups: (1) Control group (group C, n=24): continuous intravenous infusion of normal saline at the same rate during surgery; (2) Subanesthetic dose of esketamine 0.125 mg·kg-1·h-1 group (group ES1, n=23): continuous intravenous infusion of esketamine at a rate of 0.125 mg·kg-1·h-1 during surgery; (3) Subanesthetic dose of esketamine 0.250 mg·kg-1·h-1 group (group ES2, n=24): continuous intravenous infusion of esketamine at a rate of 0.250 mg·kg-1·h-1 during surgery. The main outcome measures were the total consumptions of hydromorphone of 3 groups within 24 and 48 hours after surgery. The secondary outcome measures were the extubation time, length of postanesthesia care unit (PACU) stay, the time of first feeding, and the incidences of adverse effects within 24 h after surgery in 3 groups. Results: The 24 h postoperative consumption of hydromorphone in group C, ES1 and ES2 was (5.4±1.0) mg, (4.5±1.5) mg and (4.0±0.8) mg, respectively. Likewise, the 48 h postoperative consumption of hydromorphone was (9.7±2.2) mg, (9.0±3.0) mg and (7.7±1.8) mg, respectively. Compared with group C, the 24 h postoperative hydromorphone consumptions were significantly reduced in group ES1 and ES2 (both P<0.05). The extubation time, length of PACU stay and the time of first feeding after surgery in group C were (23±10) min,(70±12) min,(17±3) h,in group ES1 were (22±4) min,(69±11) min,(14±5) h,in group ES2 were (16±8) min,(58±12) min,(14±3) h, respectively. Compared with group C and group ES1, both of the extubation time and length of PACU stay were shortened in group ES2 (both P<0.05). Compared with group C, the first postoperative feeding time of group ES1 and ES2 was shortened (both P<0.05). There were no differences in the incidences of adverse effects at postoperative 24 h among 3 groups (all P>0.05). Conclusion: Continuously intravenous infusion of subanesthetic esketamine at a rate of 0.250 mg·kg-1·h-1 can significantly reduce the postoperative opioid consumption and improve the patient's outcomes.

The Structure of Chaos: An Empirical Comparison of Fractal Physiology Complexity Indices Using NeuroKit2.

Complexity quantification, through entropy, information theory and fractal dimension indices, is gaining a renewed traction in psychophsyiology, as new measures with promising qualities emerge from the computational and mathematical advances. Unfortunately, few studies compare the relationship and objective performance of the plethora of existing metrics, in turn hindering reproducibility, replicability, consistency, and clarity in the field. Using the NeuroKit2 Python software, we computed a list of 112 (predominantly used) complexity indices on signals varying in their characteristics (noise, length and frequency spectrum). We then systematically compared the indices by their computational weight, their representativeness of a multidimensional space of latent dimensions, and empirical proximity with other indices. Based on these considerations, we propose that a selection of 12 indices, together representing 85.97% of the total variance of all indices, might offer a parsimonious and complimentary choice in regards to the quantification of the complexity of time series. Our selection includes CWPEn, Line Length (LL), BubbEn, MSWPEn, MFDFA (Max), Hjorth Complexity, SVDEn, MFDFA (Width), MFDFA (Mean), MFDFA (Peak), MFDFA (Fluctuation), AttEn. Elements of consideration for alternative subsets are discussed, and data, analysis scripts and code for the figures are open-source.

Menthol in Combination with Iontophoresis Promotes Natamycin Penetration through the Cornea: In Vitro and In Vivo Studies.

We studied whether menthol can promote penetration of natamycin, a representative antifungal macrolide agent, through the cornea. Natamycin penetration was examined using an in vitro iontophoresis system that simulates clinical scenario; menthol (0.1-0.3%, w/v) was added to the donor reservoir of a standard Franz diffusion chambers. In vivo effects of menthol on natamycin penetration were examined in a set of bioassays using rabbits inoculated with Aspergillus fumigatus in the right eye. Potential irritation to the rabbit eye was examined using a standard test. Menthol significantly (p<0.05) potentiated the effects of iontophoresis on natamycin penetration. The optimal combination seemed to be 0.2% menthol in combination with 3 mA/cm2 iontophoresis.

[Correlation of nonalcoholic fatty liver disease at different ages of onset with new-onset diabetes mellitus].

Objective: To investigate the effect of nonalcoholic fatty liver (NAFLD) at different ages of onset with new-onset diabetes mellitus. Methods: The cohort study was conducted in Kailuan Group Company. Active and retired employees were used as study subjects. After excluding NAFLD diagnosed at baseline, previous history of diabetes mellitus, and long-term history of heavy drinking, 43 317 cases were finally included in the cohort. The study subjects were divided into five groups according to age (<30 years old as group 1, 30-39 years old as group 2, 40-49 years as group 3, 50-59 years as group 4, and ≥60 years as group 5). The prevalence and incidence density of new-onset diabetes mellitus were compared between each NAFLD and non-fatty liver population group. The effect of NAFLD at different ages of onset with new-onset diabetes mellitus was analyzed by multivariate Cox's regression model. Statistical analysis was performed using one-way ANOVA, χ2 test or multivariate Cox's regression model. Results: The prevalence and incidence density of diabetes mellitus was significantly higher in NAFLD than non-fatty liver population. The prevalence of diabetes mellitus in different age groups were 6.45%, 6.88%, 9.94%, 10.83%, and 11.43%, respectively. The incidence density of each age group was 9.21/1 000 person-years, 11.10/1 000 person-years, 16.17/1 000 person-years, 18.72/1 000 person-years, and 22.13/1 000 person-years, and the differences were statistically significant (P<0.001). Multivariate Cox's regression model result showed that after adjusting for confounding factors such as gender, systolic blood pressure, and fasting blood glucose, the HRs (95%CI) for diabetes mellitus in each age group were 3.992 (1.897, 8.400), 2.321 (1.589, 3.392), 2.041 (1.667, 2.500), 2.007 (1.708, 2.360), and 1.908 (1.570, 2.319), and the differences were statistically significant (P＜0.001). Conclusion: Newly developed NAFLD is an independent risk factor for new-onset diabetes mellitus. Early exposure to NAFLD increases the risk of developing diabetes mellitus compared with the same age group. Younger age of onset of NAFLD should be given attention and active treatment.

[Association between high-density lipoprotein cholesterol level and cardiovascular disease and all-cause mortality in the elderly population].

Objective: To investigate the relationship between high density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) and all-cause mortality in the elderly population. Methods: A total of 14 355 elderly persons aged ≥65 years, who participated in the annual physical examination in Kailuan Group in 2006 were included in this prospective cohort study. According to HDL-C level, the participants were divided into 4 groups: low-level group (HDL-C<1.30 mmol/L), intermediate-level group (1.30 mmol/L ≤HDL-C≤1.54 mmol/L), medium-high-level group (1.55 mmol/L ≤HDL-C≤1.80 mmol/L), high-level group (HDL-C≥1.81 mmol/L). Baseline data such as age, sex and blood lipid levels were collected and compared. Inpatient medical records and death information were obtained through the social security system, and CVD and all-cause mortality were analyzed. After adjusting for confounding factors, the medium-high-level group was used as the reference group. Cox proportional risk regression model was used to evaluate the impact of HDL-C on CVD and all-cause mortality events. The linear or nonlinear relationship between HDL-C level and CVD and all-cause mortality events was evaluated by restricted cubic spline regression model. Death competitive risk analysis was conducted, and sensitivity analysis was performed after excluding subjects with CVD or all-cause mortality within 1 year of follow-up and female participants. Results: The average age of this cohort was (71.5±5.5) years and follow-up time was (10.9±3.3) years. Compared with medium-high-level group, Cox proportional risk regression analysis showed that the HR (95%CI) of CVD and all-cause mortality in low-level group were 1.21 (1.06-1.38) (P<0.05) and 1.02 (0.95-1.11) (P>0.05), respectively; the HR (95%CI) of CVD events in high-level group was 1.17 (1.03-1.33) (P<0.05), and there was a marginal significant association with all-cause mortality, the HR (95%CI) was 1.07 (1.00-1.16) (0.050.1). Conclusions: In the elderly population, the risk of CVD is lowest when the HDL-C level is 1.55-1.80 mmol/L, either high or low HDL-C is a risk factor for CVD. High HDL-C tends to be related to increased risk of all-cause mortality and low HDL-C is not related to increased risk of all-cause mortality.

[A case of poisoning caused by oral and inhalation of high concentration glutaraldehyde].

Glutaraldehyde is a kind of volatile and irritating aldehyde organic compound, which belongs to high-efficiency disinfectant. It has a strong stimulating effect on the mucous membranes of the eyes, respiratory tract and digestive tract, and skin causing denaturation, liquefaction and necrosis of mucous membrane proteins. This article analyzes the treatment process of a patient with high-concentration glutaraldehyde poisoning by oral and inhalation, and discusses the clinical manifestations and prognosis of high-concentration glutaraldehyde poisoning, so as to provide a basis for clinical treatment.