Abstract Gallstones disease is classified as cholesterol, pigment and mixed gallstones. Pigment gallstones is a common disease, and some patients experienced complications such as biliary pain and cholecystitis. Defatted walnut powder extract (DWPE) is extracted from the main by-product after oil extraction of the functional food walnut and can treat cholesterol gallstones. However, the effect of DWPE on pigment gallstones has not been reported. Thus, this paper aimed at exploring the potential mechanism of alleviating pigment gallstones and the metabolism of DWPE in vitro by UPLC-Q-Exactive Orbitrap MS to elucidate potential pharmacodynamic substances. It was found that DWPE significantly reduced the incidence of gallstones, the contents of unconjugated bilirubin and calcium, the inflammation of gallbladder tissue, the edema and congestion of gallbladder tissue, and the infiltration of inflammatory cells. In metabolism, a total of 35 metabolites of DWPE, including its main compounds ellagic acid and glansreginin A, were characterized in the intestine with various metabolic reactions. Presumably, the small molecular compounds generated after the metabolism by intestinal bacteria may be the pharmacodynamic substances of DWPE on pigment gallstones. This study revealed the effect of DWPE in treating pigment gallstones and their metabolism in vitro.

ABSTRACT Purpose: To investigate the Shikonin (SHI) induce autophagy of hypertrophic scar-derived fibroblasts (HSFs) and the mechanism of which in repairing hypertrophic scar. Methods: This study showed that SHI induced autophagy from HSFs and repaired skin scars through the AMPK/mTOR pathway. Alamar Blue and Sirius red were used to identify cell activity and collagen. Electron microscopy, label-free quantitative proteomic analysis, fluorescence and other methods were used to identify autophagy. The differences in the expression of autophagy and AMPK/mTOR pathway-related proteins after SHI treatment were quantitatively analyzed by Western blots. A quantitative real-time polymerase chain reaction assay was used to detect the expression of LC3, AMPK and ULK after adding chloroquine (CQ) autophagy inhibitor. Results: After treatment with SHI for 24 hours, it was found that the viability of HSFs was significantly reduced, the protein expression of LC3-II/LC3-I and Beclin1 increased, while the protein expression of P62 decreased. The expression of phosphorylated AMPK increased and expression of phosphorylated mTOR decreased. After the use of CQ, the cell autophagy caused by SHI was blocked. The key genes LC3 and P62 were then reexamined by immunohistochemistry using a porcine full-thickness burn hypertrophic scar model, and the results verified that SHI could induce autophagy in vivo. Conclusions: These findings suggested that SHI promoted autophagy of HSFs cells, and the potential mechanism may be related to the AMPK/mTOR signal pathway, which provided new insights for the treatment of hypertrophic scars.

Abstract Objectives: Although the cause of Meniere’s disease (MD) is not fully understood, endolymphatic hydrops is widely believed to be responsible for MD. Previous studies have used Air-Conducted Sound (ACS)-induced Vestibular Evoked Myogenic Potentials (VEMPs) to evaluate otolithic function in patients with MD. However, the use of Galvanic Vestibular Stimulation-VEMPs (GVS-VEMPs) with other vestibular tests in MD has been rare. This study aimed to explore the application of galvanic VEMPs in assessing MD. Methods: Normal individuals and patients with unilateral definite MD were included in this retrospective study. All participants underwent pure tone audiometry. Ocular and cervical VEMPs induced by GVS, and ACS were recorded. The characteristic parameters of VEMPs (n1 latency, p1 latency, amplitude, and AR) were analyzed. Results: The provocation rates of GVS-VEMPs did not differ between MD patients and control individuals. Compared with ACS, GVS could evoke potentials with longer latencies. MD patients presented GVS-VEMPs with lower amplitudes and ACS-cVEMP with shorter latencies and had a higher response rate in GVS-oVEMP. However, no differences or correlations were found in the characteristic parameters of GVS-VEMPs among the different stages of MD. Conclusions: GVS is as effective as ACS for inducing VEMP, and GVS-VEMP recording can detect retrolabyrinthine degeneration in MD. Further research is needed to assess the utility of GVS-VEMP in the evaluation of MD severity. Level of evidence: Level 4.

Abstract Objective: Subjective Visual Vertical (SVV) and Subjective Visual Horizontal (SVH) values may reflect bilateral utricle asymmetry. Bilateral utricle static tension balance can be used to evaluate bilateral otolith lesions and otolith-related central neuropathy. Few studies have examined Virtual Reality (VR)-assisted SVV and SVH values at various head-tilt angles across age groups. The present study aimed to determine the effects of age on VR-assisted SVV and SVH values at different head-tilt angles. Methods: We divided 180 healthy subjects into 6 age groups (n = 30 in each group). VR-assisted SVV and SVH measurements were performed at 9 head-tilt angles (head held vertically, 0°; head tilted 30°, 45°, 60°, and 90° to the left/right) in the roll plane. Results: SVV and SVH values significantly differed with head-tilt angle (p < 0.05). No significant difference was detected in the SVH and SVV values between different age groups (p = 0.632 and p = 0.810, respectively), and no interaction between the age group and the head-tilt angle was found for the SVH and SVV values (p = 0.670 and p = 0.084, respectively). Conclusion: These results suggest that age may have little effect on VR-assisted SVV and SVH at different head-tilt angles. Therefore, VR-assisted SVV and SVH can be evaluated as an effective, fast, and simple way to evaluate utricle function. Level of Evidence: Level 4.

Abstract The contents of total phenol and flavonoid of 27 edible plants as well as their antioxidative and digestive enzymes inhibitory activities were evaluated. The total phenol content of the 27 plants ranged from 1.28-46.80 mg gallic acid equivalent/g. DPPH, ABTS and reducing power assay explored that Rubus idaeus Linn, Hibiscus sabdariffa Linn. and Crataegus pinnatifida Bge. exhibited stronger antioxidant capacity among the 27 plants. 4 plants showed inhibitory percentage more than 50% on pancreatic lipase. 10 plants showed inhibitory percentage more than 50% on α-glucosidase. 3 plants simultaneously possess significant inhibitory activities on pancreatic lipase and α-glucosidase, which were Alpinia officinarum Hance, Ginkgo biloba Linn. leaves and Vitis vinifera Linn. Seeds. Strong positive correlation between total phenol content and antioxidative capacity were found. However, digestive enzymes inhibitory activity was less correlated with total phenol and total flavonoids content.

ABSTRACT Purpose: To investigate the active ingredients of walnut ointment (WO) and its mechanism in repairing wounds. Methods: The ingredients of WO were detected by gas chromatography–mass spectrometry. The effect of linoleic acid (LA) was tested by in vitro Alamar Blue (AB) reagent. Image J software, histological and immunohistochemical analysis were used to confirm the healing effect of LA in the porcine skin model. The animals were euthanized after the experiment by injection of pentobarbital sodium. Results: LA, 24% in WO, promotes keratinocytes and fibroblasts proliferation, which were 50.09% and 15.07% respectively higher than control (p < 0.05). The healing rate of the LA group (96.02% ± 2%, 98.58% ± 0.78%) was higher than the saline group (82.11% ± 3.37%, 88.72% ± 1.73%) at week 3 and week 4 (p < 0.05). The epidermal thickness of the LA was 0.16 ± 0.04 mm greater and the expression of the P63 and CK10 proteins was stronger in the LA group than the control (p < 0.05). Conclusions: LA, which is the main components in WO can promote full-thickness burning wounds (FBWs) by stimulating cell proliferation and differentiation.

Abstract Limited initiation energy or external stimulation may cause incomplete detonation in a warhead. At present, there is no quantitative method to characterize the energy release of a warhead charge for incomplete detonation such as explosion and deflagration. We propose a method based on average fragment quality to characterize the energy released by a warhead charge. The theoretical study shows that the average fragment quality after warhead initiation is inversely proportional to the initial fragment velocity. The relationship between the average fragment quality and explosive energy release is established and verified by experiment. This relation can be used to determine the charge energy released after warhead initiation. It provides a theoretical basis for optimizing efficiency of charge energy use in high-energy conventional damage technology and warhead design, and provides a quantitative method for evaluating insensitive ammunition.

This study explores the safety and effect of acute cerebral infarction treatment by microcatheter injection of tirofiban combined with a Solitaire AB stent and/or stent implantation. Emergency cerebral angiograms showing the responsible vascular occlusion of 120 acute cerebral infarction patients who underwent emergency endovascular thrombectomy were included in the study. These patients were randomly divided into two groups using the random number table method: treatment group (n=60) that received thrombectomy (with cerebral artery stents) combined with intracerebral injection of tirofiban and control group (n=60) that only received thrombectomy (with cerebral artery stents alone). The baseline data, cerebral angiography before and after surgery, hospitalization, and follow-up results of patients in these two groups were compared. Furthermore, the incidence of major adverse cerebrovascular events of these two groups was compared (90-day modified Rankin scale, a score of 0–2 indicates a good prognosis). The difference between baseline clinical data and brain angiography between these two groups was not statistically significant. Patients in the treatment group had a higher prevalence of thrombolysis in cerebral infarction grade 2b/3 than patients in the control group (88.3% (53/60) vs 66.7% (40/60), P=0.036). Moreover, the National Institutes of Health Stroke Scale scores 7 days after surgery and the 90-day prognosis were all better for the patients who received tirofiban (P=0.048 and P=0.024). Mechanical thrombectomy with Solitaire AB stents in combination with the injection of tirofiban through a microcatheter appears to be safe and effective for the endovascular treatment of acute ischemic stroke.

OBJECTIVE: Bilirubin is considered an important antioxidant, anti-inflammatory factor and immunomodulator. The current investigation aimed to explore the association between bilirubin and white blood cell (WBC) count in a large Chinese cohort. METHODS: A total of 61091 participants (29259 males, 31832 females) were recruited from a Chinese tertiary hospital. Data were sorted by sex, and the association between bilirubin and WBC count was analyzed after dividing bilirubin levels into quartiles. RESULTS: Most parameters (including age, body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, total bilirubin, blood urea nitrogen, creatinine, uric acid, triglycerides and WBC count) were significantly higher in men than in women. Bilirubin displayed significant negative relationships with most other measured variables. Linear logistic regression analysis further indicated their negative relationships. Females showed a significantly higher frequency of leucopenia than males. Significant associations of leucopenia with high bilirubin quartiles were shown in binary logistic regression models for both sexes, with a much closer association in men than in women. For instance, for men with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.600-times higher than that of men with values in quartile 1. For women with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.135-times higher than that of women with values in quartile 1. CONCLUSION: Bilirubin is negatively related to WBC count. Significant associations exist between leucopenia and high bilirubin quartiles, and these associations are more obvious in men than in women.

Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.