OBJECTIVE: This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis (AD), focusing on its ability to alleviate chronic pruritus (CP) and the underlying molecular mechanisms. METHODS: In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene (DNCB)-induced AD mouse model and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) stimulated huma immortalized epidermal (HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence staining. RESULTS: Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness AD-like mice. It also reduced the levels of interleukin (IL)-31 and IL-31 receptor A (IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65 (p-p65) and phosphor-inhibitor of nuclear factor kappa-Bα (p-IκBα). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and PPARγ in HaCaT cells. CONCLUSION These findings indicated that osthole effectively inhibited CP in AD by activating PPARα, PPARγ, repressing the NF-κB signaling pathway, as well as the expression of IL-31 and IL-31 RA.

OBJECTIVES: To evaluate the causal association between circulating levels of zinc, magnesium, and other minerals and autism spectrum disorder (ASD). METHODS: A two-sample Mendelian randomization (MR) analysis was performed using summary statistics from large-scale genome-wide association studies of European populations, including 18 382 ASD cases and 27 969 controls. Genetic data for iron, calcium, and magnesium were obtained from the UK Biobank, and data for zinc and selenium were sourced from an Australian-British cohort. A total of 351 genetic instrumental variables were selected. Causal inference was performed using inverse-variance weighting as the primary analysis method. Sensitivity analyses were performed by Cochran's Q test and MR-PRESSO global test to assess the robustness of the findings. RESULTS: No statistically significant causal effect was observed for circulating zinc, magnesium, calcium, selenium, or iron levels on ASD risk (all P>0.05). The odds ratios and 95% confidence intervals from the inverse-variance weighting analysis were 0.934 (0.869-1.003) for zinc, 1.315 (0.971-1.850) for magnesium, 1.055 (0.960-1.159) for calcium, 1.015 (0.953-1.080) for selenium, and 0.946 (0.687-1.303) for iron. Sensitivity analysis revealed significant heterogeneity in the causal association between circulating calcium and ASD (P=0.006), while the effect estimate remained stable after MR-PRESSO correction (P=0.487). The causal effect estimates for the remaining minerals demonstrated good robustness. CONCLUSIONS This study did not find significant evidence supporting a causal association between circulating zinc, magnesium, calcium, selenium, or iron levels and ASD risk, providing important clues for the etiology of ASD and precision nutritional interventions.
Humans ; Mendelian Randomization Analysis ; Autism Spectrum Disorder/genetics* ; Magnesium/blood* ; Zinc/blood* ; Minerals/blood* ; Genome-Wide Association Study ; Selenium/blood*

Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

OBJECTIVE: This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction (MI) in patients with both coronary heart disease (CHD) and type 2 diabetes (T2D). METHODS: We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen, China. Patients were categorized into 6 groups based on baseline fasting plasma glucose (FPG) levels and diabetes duration (from the date of diabetes diagnosis to the baseline date) to examine their combined effects on subsequent MI. Cox proportional hazards regression models were used, with further stratification by age, sex, and comorbidities to assess potential interactions. RESULTS: Over a median follow-up of 2.4 years, 2,110 patients experienced MI. Compared to those with optimal glycemic control (FPG < 6.1 mmol/L) and shorter diabetes duration (< 10 years), the fully-adjusted hazard ratio ( HR) (95% Confidence Interval [95% CI]) for those with a diabetes duration of ≥ 10 years and FPG > 8.0 mmol/L was 1.93 (95% CI: 1.59, 2.36). The combined effects of FPG and diabetes duration on MI were largely similar across different age, sex, and comorbidity groups, although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation. CONCLUSION Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D. Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
Humans ; Diabetes Mellitus, Type 2/blood* ; Male ; Female ; Middle Aged ; Aged ; Coronary Disease/complications* ; Myocardial Infarction/etiology* ; Retrospective Studies ; China/epidemiology* ; Glycemic Control ; Blood Glucose ; Adult ; Risk Factors ; Time Factors

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To investigate the pharmacological mechanism through which total flavonoids extracted from Xiaobuxin-Tang(XBXT-2)affects neural network activities in the frontal cortex by focusing on the effects of XBXT-2 on the cortical field potentials in the frontal association cortex(FrA)in mice.Methods Cortical electrodes were implanted into the skull of C57BL/6J mice targeting the FrA.After a 7-day recovery period,the mice were administered XBXT-2 intragastrically at a dose of 100 mg/kg,and 1 hour later,local field potential(LFP)in the FrA were recorded for 30 minutes.Spectral analysis of the data was performed using Neuro Explorer software.Changes in the power spectral density of α,β,θ,γ,and δ frequency bands before and after drug administration were analyzed using GraphPad Prism 10.3.Phase-amplitude coupling of θ and γ oscillations was analyzed using Matlab 2021 software.Results It was found that the oral administration of XBXT-2 significantly suppressed high-frequency γ oscillations while simultaneously enhancing θ,β,α,and δ oscillations in FrA of mice compared to the control.Furthermore,XBXT-2 treatment markedly strengthened the phase-amplitude coupling between θ and γ oscillations.Conclusion XBXT-2 possibly affects emotional and cognitive functions by modulating neural network activity in FrA and enhancing θ-γ phase-amplitude coupling in mice.

ObjectiveTo use the maternal morbidity WOICE Tool（Chinese version）to investigate the maternal morbidity in Shanghai， and to examine the current situation and associated factors of adverse symptoms and impaired functioning in the third trimester and postpartum period. MethodsPregnant women who made their initial visit and established a medical record at a tertiary obstetrics and gynecology hospital in Shanghai from March to August 2021 were recruited and a baseline survey was completed. The prevalence of maternal morbidity was surveyed in the third trimester and first 6 weeks postpartum. ResultsSelf-reported adverse physical symptoms were observed in 89.8% of women in the third trimester and 86.1% in first 6 weeks postpartum. The prevalence rates of anxiety and depression were 4.1% and 6.2% in the third trimester， and 6.2% and 7.5% in first 6 weeks postpartum， respectively. The proportions of women reporting impaired functioning were 80.3% in the third trimester and 64.1% in first 6 weeks postpartum， respectively. Physical symptoms were associated with parity， education， the newborn’s health status， and risk of experiencing violence. Psychological symptoms were associated with age， household responsibilities， employment status， the newborn’s health status， pre-pregnancy body mass index （BMI）， and risk of experiencing violence. Functionality was associated with the type of registered residence， education level， household responsibilities， and risk of experiencing violence. ConclusionThe physical health status of pregnant and postpartum women in Shanghai is better than that in the middle-income regions abroad， with anxiety and depression at average levels compared to national statistics in China. Physical， psychological， and functional status are affected by multiple factors including personal， health， family， and work conditions. Preventive measures should be taken from various perspectives to mitigate adverse symptoms and impaired functioning， and to improve the positive experience of pregnancy and childbirth.

Objective:To construct a virtual-real interactive system HE-01 for the treatment of microtia based on HoloLens and verify the feasibility of applying HE-01 in ear reconstruction.Methods:Six volunteers (3 males and 3 females, average age: 20.5 years old) and six patients with microtia(3 males and 3 females, average age: 7.6 years old) were recruited from Plastic Surgery Hospital of Chinese Academy of Medical Sciences from August to September 2021. The Mimics Research 21.0 software and 3-matic research software were used to construct a virtual three-dimensional auricle model. Based on HoloLens and occlusal splint navigation marker device, the virtual-real interactive system HE-01 for the treatment of microtia was constructed. The registration accuracy, tracking delay and display effect of different colors (red, green, blue and skin color) of HE-01 were evaluated through repeated experiments of volunteers. The operation process was defined through repeated experiments of patients and the feasibility of applying HE-01 in auricular reconstruction was verified.Results:HE-01 was built successfully and the operation flow was clear. The experiment of six volunteers (12 ears) showed a high registration accuracy (average error rate 2.3%-2.4%, less than 2.7% of the bilateral auricle size difference of normal people), low tracking delay (six volunteers were all less than 0.1 s), and best green and red display effect of virtual auricle guide under different angles (-60°, -30°, 0°, 30°, 60°). Experiments of patients with microtia showed that HE-01 could be applied to auricular reconstruction, and there were no obvious complications in wearing the navigation marker device, which had repeatability and stability.Conclusion:This study has completed the conceptual design of augmented-reality assisted auricular reconstruction based on navigation device, CT data and HoloLens. HE-01 has good registration accuracy, tracking speed and display effect, laying a good foundation for further software development and clinical transformation.

Objective:To construct a virtual-real interactive system HE-01 for the treatment of microtia based on HoloLens and verify the feasibility of applying HE-01 in ear reconstruction.Methods:Six volunteers (3 males and 3 females, average age: 20.5 years old) and six patients with microtia(3 males and 3 females, average age: 7.6 years old) were recruited from Plastic Surgery Hospital of Chinese Academy of Medical Sciences from August to September 2021. The Mimics Research 21.0 software and 3-matic research software were used to construct a virtual three-dimensional auricle model. Based on HoloLens and occlusal splint navigation marker device, the virtual-real interactive system HE-01 for the treatment of microtia was constructed. The registration accuracy, tracking delay and display effect of different colors (red, green, blue and skin color) of HE-01 were evaluated through repeated experiments of volunteers. The operation process was defined through repeated experiments of patients and the feasibility of applying HE-01 in auricular reconstruction was verified.Results:HE-01 was built successfully and the operation flow was clear. The experiment of six volunteers (12 ears) showed a high registration accuracy (average error rate 2.3%-2.4%, less than 2.7% of the bilateral auricle size difference of normal people), low tracking delay (six volunteers were all less than 0.1 s), and best green and red display effect of virtual auricle guide under different angles (-60°, -30°, 0°, 30°, 60°). Experiments of patients with microtia showed that HE-01 could be applied to auricular reconstruction, and there were no obvious complications in wearing the navigation marker device, which had repeatability and stability.Conclusion:This study has completed the conceptual design of augmented-reality assisted auricular reconstruction based on navigation device, CT data and HoloLens. HE-01 has good registration accuracy, tracking speed and display effect, laying a good foundation for further software development and clinical transformation.

Epileptic seizures and the interictal epileptiform discharges both have similar waveforms. And a method to effectively extract features that can be used to distinguish seizures is of crucial importance both in theory and clinical practice. We constructed state transfer networks by using visibility graphlet at multiple sampling intervals and analyzed network features. We found that the characteristics waveforms in ictal periods were more robust with various sampling intervals, and those feature network structures did not change easily in the range of the smaller sampling intervals. Inversely, the feature network structures of interictal epileptiform discharges were stable in range of relatively larger sampling intervals. Furthermore, the feature nodes in networks during ictal periods showed long-term correlation along the process, and played an important role in regulating system behavior. For stereo-electroencephalography at around 500 Hz, the greatest difference between ictal and the interictal epileptiform occurred at the sampling interval around 0.032 s. In conclusion, this study effectively reveals the correlation between the features of pathological changes in brain system and the multiple sampling intervals, which holds potential application value in clinical diagnosis for identifying, classifying, and predicting epilepsy.
Humans ; Electroencephalography/methods* ; Epilepsy/diagnosis* ; Signal Processing, Computer-Assisted ; Brain/physiopathology* ; Seizures/diagnosis* ; Algorithms