This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C

This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

ObjectiveAngle-closure glaucoma (ACG) is one of the major eye-blinding diseases. To diagnose ACG, it is crucial to examine the anterior chamber angle. Current diagnostic tools include slit lamp gonioscopy, water gonioscopy, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT). Slit lamp and water gonioscopy allow convenient observation of the anterior chamber angle, but pose risks of invasive operation and eye infections. UBM can accurately measure the structure of the anterior chamber angle. However, it is complex to operate and unsuitable for patients, who have undergone trauma or ocular surgery. Although AS-OCT provides detailed images, it is costly. The aim of this study is to explore a non-invasive, non-destructive optical reflection tomography (ORT) technique. This technique can achieve low-cost three-dimensional imaging and full-field anterior chamber angle measurement of the porcine eye. MethodsThe experiment involved assembling an optical reflection tomography system, which included a complementary metal oxide semiconductor (CMOS) camera, a telecentric system, a stepper motor, and a white light source, achieving a spatial resolution of approximately 8.5 μm. The process required positioning the porcine eye at the center of the field of the imaging system and rotating it around its central axis using a stepper motor. Reflection projection images were captured at each angle with an exposure time of 1.0 ms and an interval of 2°. The collected reflection-projection data were processed using a filtered reflection tomography algorithm, generating a series of two-dimensional slice data. These slices essentially represented cross-sectional views of the three-dimensional structural image, and were reconstructed into a complete three-dimensional structural image. Based on the reconstructed three-dimensional structural image of the porcine eye, the anterior chamber angles at different positions were measured, and a distribution map of these angles was drawn. Simultaneously, the ORT measurements were compared with the standard results obtained from optical coherence tomography (OCT) to assess the accuracy of ORT measurements. ResultsIn this study, we successfully obtained the reflection projection data of a porcine eye using ORT technology, reconstructed its three-dimensional structural image, and measured the anterior chamber angle, generating the corresponding distribution map. To better distinguish the different structural parts of porcine eye, the three-dimensional structural image was marked with blue, green, and yellow dashed lines from the outer to the inner layers. The area between the blue and green dashed lines corresponded to the sclera. The area between the green and yellow dashed lines corresponded to the iris. The area inside the yellow dashed line corresponded to the pupil. The three-dimensional structural image clearly revealed the key anatomical features of the porcine eye. It was able to measure the anterior chamber angle at different positions. Additionally, the anterior chamber angle measurements of the porcine eye using ORT were compared with the measurements obtained using a TEL320C1 type OCT system, showing an average deviation of 0.51° and a mean square error MSE of 0.317. ConclusionORT is a non-invasive, non-destructive, low-cost, and high-resolution imaging technique capable of achieving three-dimensional structural imaging and full-field anterior chamber angle measurement of a porcine eye. This technology offers a new perspective for the diagnosis of angle-closure glaucoma and is significant for the screening, diagnosis, and monitoring of eye diseases, potentially benefiting clinics and small hospitals in remote areas in the future.

AIM To establish the quality standard of the zhujieshen Formula Granules based on standard decoction.METHODS The contents and transfer rates of ginsenoside Ro and chikusetsu saponin Ⅳa in standard decoction and formula granules were determined by HPLC,after which the transfer rates were calculated.The HPLC characteristic chromatograms of standard decoctions were established,after which cluster analysis and principal component analysis were adopted.Then the HPLC characteristic chromatograms of formula granules were established.RESULTS Nine common peaks were found in the HPLC characteristic chromatograms of seventeen batches of standard decoctions with the similarities of more than 0.9(except for S6,S12),which were clustered into two categories,and the accumulative variance contribution rate of three principal components reached 86.7％.The contents of ginsenoside Ro in three batches of formula granules were 83.1-88.6 mg/g,and the transfer rates were 53.1％-55.5％.The contents of chikusetsusaponin Ⅳa were 14.8-15.0 mg/g,and the transfer rates were 47.4％-48.1％.Nine common peaks were found in the HPLC characteristic chromatograms of three batches of formula granules with the similarities of 0.998,0.998 and 0.999,respectively.CONCLUSION This reasonable and reliable method can comprehensively evaluate the quality of Zhujieshen Formula Granules,and provide a reference for the quality control.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Objective:To explore the influencing factors and the impact of artificial liver treatment on the prognosis and survival of patients with acute-on-chronic liver failure (ACLF).Methods:Clinical data from 201 cases with ACLF from January 2016 to December 2019 was retrospectively analyzed. The survival rate was calculated by the Kaplan-Meier method, the log-rank test of univariate analysis, and the multivariate analysis of the stepwise Cox regression forward method.Results:The median survival time of patients was 6 months, and the survival rates at 6, 9, and 12 months were 51.2%, 38.3%, and 29.9%, respectively. In univariate analysis, age, presence or absence of hypertension and upper gastrointestinal bleeding, treatment method, model for end-stage liver disease (MELD) score, and cholinesterase were associated with prognosis ( P < 0.05). Multivariate regression analysis results showed that MELD score was the main factor affecting the 1-year prognosis of ACLF patients ( P = 0.002). Artificial liver treatment was beneficial for the 1-year prognosis of ACLF patients aged < 50 years or with a MELD score of ≥20 ( P < 0.05 ). The relative risk ratio (RR) of mortality was 2.55 times higher in patients with advanced age (≥50 years old) than that of younger patients ( P < 0.001). Regression analysis was performed using age as a stratification factor, and upper gastrointestinal bleeding was related to the prognosis of younger patients, while choline esterase was related to the prognosis of advanced age. Regression analysis after stratified MELD score showed that age and hypertension were related to the prognosis of patients with MELD score < 20, and treatment method and age were related to the prognosis of patients with MELD score≥20. Conclusion:Artificial liver treatment is beneficial for the 1-year prognosis of ACLF patients. Age, MELD score, hypertension, and upper gastrointestinal bleeding are independent risk factors affecting the prognosis of ACLF patients.

Objective: Hyperlipidemia is closely related to premature acute myocardial infarction (AMI). The present study was performed to explore the correlation between various blood lipid components and the risk of premature AMI. Methods: This is a cross-sectional retrospective study. Consecutive patients with acute ST-segment elevation myocardial infarction (STEMI), who completed coronary angiography from October 1, 2020 to September 30, 2022 in our hospital, were enrolled and divided into premature AMI group (male<55 years old, female<65 years old) and late-onset AMI group. Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, lipoprotein (a) (Lp (a)), apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA-1), non-HDL-C/HDL-C and ApoB/ApoA-1 were analyzed. The correlation between the above blood lipid indexes and premature AMI was analyzed and compared by logistic regression, restricted cubic spline and receiver operating characteristic curve (ROC). Results: A total of 1 626 patients with STEMI were enrolled in this study, including 409 patients with premature AMI and 1 217 patients with late-onset AMI. Logistic regression analysis showed that the risk of premature AMI increased significantly with the increase of TG, non-HDL-C/HDL-C, non-HDL-C, ApoB/ApoA-1, TC and ApoB quintiles; while LDL-C, ApoA-1 and Lp (a) had no significant correlation with premature AMI. The restricted cubic spline graph showed that except Lp (a), LDL-C, ApoA-1 and ApoB/ApoA-1, other blood lipid indicators were significantly correlated with premature AMI. The ROC curve showed that TG and non-HDL-C/HDL-C had better predictive value for premature AMI. Inconsistency analysis found that the incidence and risk of premature AMI were the highest in patients with high TG and high non-HDL-C/HDL-C. Conclusion: TG, non-HDL-C/HDL-C and other blood lipid indexes are significantly increased in patients with premature AMI, among which TG is the parameter, most closely related to premature AMI, and future studies are needed to explore the impact of controlling TG on incidence of premature AMI.
Humans ; Male ; Female ; Middle Aged ; Aged ; Cross-Sectional Studies ; Cholesterol, LDL ; Retrospective Studies ; ST Elevation Myocardial Infarction ; Apolipoprotein A-I ; Myocardial Infarction ; Cholesterol ; Apolipoproteins B ; Triglycerides ; Cholesterol, HDL ; Lipids ; Lipoproteins

This paper compared the differences between two kinds of Bufonis Venenum produced by Bufo gargarizans gargarizans and B. gararizans andrewsi, and verified the rationality of the market value orientation of Bufonis Venenum based on the zebrafish mo-del. Twenty batches of Bufonis Venenum from Jiangsu province, Hebei province, Liaoning province, Jilin province, and Liangshan, Sichuan province, including B. gargarizans gargarizans and B. gararizans andrewsi, were collected. The UHPLC-LTQ-Orbitrap-MS combined with principal component analysis was used to compare the differences between two kinds of Bufonis Venenum. According to the limiting conditions of VIP>1, FC<0.5 or FC>2.0, and peak total area ratio>1%, 9 differential markers were determined, which were cinobufagin, cinobufotalin, arenobufagin, resibufogenin, scillaredin A, resibufagin, 3-(N-suberoylargininyl)-arenobufagin, 3-(N-suberoylargininyl)-marinobufagin, and 3-(N-suberoylargininyl)-resibufogenin. The content of 20 batches of Bufonis Venenum was determined according to the Chinese Pharmacopoeia(2020 edition) by high-performance liquid chromatography, and the 2 batches of Bufonis Venenum, CS7(8.99% of total content) and CS9(5.03% of total content), with the largest difference in the total content of the three quality control indexes of the Chinese Pharmacopoeia(bufalin, cinobufagin, and resibufogenin) were selected to evaluate their anti-liver tumor activity based on the zebrafish model. The tumor inhibition rates of the 2 batches were 38.06% and 45.29%, respectively, proving that only using the quality control indexes of the Chinese Pharmacopoeia as the value orientation of Bufonis Venenum market circulation was unreasonable. This research provides data support for the effective utilization of Bufonis Venenum resources and the establishment of a rational quality evaluation system of Bufonis Venenum.
Animals ; Zebrafish ; Bufanolides/analysis* ; Bufonidae ; Chromatography, High Pressure Liquid ; Quality Control ; Cell Line, Tumor

Objective: To explore the change of hearing threshold of workers exposed to noise, establish an individual-based hearing loss early warning model, accurately and differentiated the health of workers exposed to noise. Methods: In September 2019, all physical examination data of 561 workers exposed to noise from an enterprise were collected since their employment. Three indicators of average hearing threshold of the better ear, namely, at high frequency, 4000 Hz and speech frequency, were constructed. The generalized estimating equation (GEE) was used to adjust gender and age and establish the warning model of each indicator. Finally, sensitive indicators and warning models were screened according to AUC and Yoden index. Results: Among the 561 workers exposed to noise, 26 (4.6%) workers had hearing loss. The sensitivity indicators were the average hearing threshold at speech frequency ≥20 dB, high frequency ≥30 dB and 4000 Hz ≥25 dB. The AUC of each index was 0.602, 0.794 and 0.804, and the Youden indexes were 0.204, 0.588 and 0.608, respectively. In GEE of hearing loss warning models, high-frequency hearing threshold ≥20 dB and 4000 Hz hearing threshold ≥25 dB were the optimal models, with AUC of 0.862. Conclusion: Combined with the changes of individual hearing threshold over the years, can accurately assess the risk of individual hearing loss of workers exposed to noise.
Humans ; Hearing Loss, Noise-Induced/diagnosis* ; Noise, Occupational/adverse effects* ; Audiometry ; Deafness ; Employment ; Occupational Exposure/adverse effects* ; Occupational Diseases/diagnosis*