ObjectiveGastric hemorrhage is one of the most common and life-threatening emergencies of the upper digestive tract. Early identification and continuous monitoring are essential for reducing rebleeding rates and mortality, particularly within the critical early hours after onset. Although endoscopy and radiological imaging can accurately localize bleeding sites, these approaches are invasive, resource-intensive, and unsuitable for continuous bedside monitoring. Electrical impedance tomography (EIT), as a noninvasive and radiation-free functional imaging technique, offers real-time visualization of conductivity distribution and has the potential for detecting intragastric bleeding based on the electrical contrast between blood and surrounding gastric tissues. In this study, a three-dimensional gastric EIT (3D-gEIT) framework is proposed to achieve noninvasive, real-time, and dynamic monitoring of gastric hemorrhage, with emphasis on spatial localization and quantitative volume assessment. MethodsA three-dimensional upper-abdominal simulation model incorporating the stomach, gastric wall, gastric contents, and surrounding tissues was established. Three electrode configurations, namely the dual layer ring, the four layer staggered ring, and the opposed dual plane array, were designed and systematically compared to evaluate their influence on depth sensitivity and spatial resolution. Based on the Tikhonov-Noser hybrid regularization scheme, a region-clustering constraint was introduced to develop the TK-Noser-RCC algorithm. This approach aggregates spatially adjacent elements with similar conductivity variations, thereby enhancing structural continuity and suppressing isolated noise artifacts. To validate the proposed framework, an upper-abdominal physical phantom was constructed using agar to simulate background tissue conductivity. Hemispherical high-conductivity inclusions with volumes ranging from 10 ml to 50 ml were attached to the inner gastric wall to mimic localized bleeding under different gastric filling states. Boundary voltages were acquired under a 120 kHz excitation current and reconstructed using the TK-Noser-RCC algorithm. Furthermore, an in vivo animal experiment was performed using a porcine model with adult-scale abdominal dimensions. A total of 100 ml of autologous blood was injected incrementally into the stomach to simulate progressive gastric hemorrhage, and time-difference EIT reconstruction was conducted at each injection stage to assess the dynamic system response under physiological conditions. ResultsSimulation results demonstrated that the opposed dual-plane electrode array achieved superior depth sensitivity distribution and spatial resolution. For a 40 ml hemorrhage model, the average ICC and SSIM improved by 55.9% and 38.8% compared with the dual-layer ring configuration, and by 64.0% and 39.5% compared with the four-layer staggered configuration. The proposed region-clustering constraint significantly enhanced reconstruction stability. Under added Gaussian noise of 40 dB and 30 dB, ICC values remained approximately 0.85, indicating effective artifact suppression and preservation of boundary integrity. In physical phantom experiments, reconstructed hemorrhage volumes increased approximately linearly with the preset hemispherical volumes, and the reconstructed high-conductivity regions closely matched the actual bleeding locations. Both empty-stomach and full-stomach conditions were evaluated, demonstrating that the opposed dual-plane configuration maintained stable imaging performance across varying gastric contents. In the animal experiment, reconstructed low-impedance regions expanded progressively with increasing injected blood volume. The spatial localization of the hemorrhage remained stable throughout the procedure, and no significant artifacts were observed. Quantitative analysis showed that reconstructed volume and average conductivity variation exhibited an approximately linear growth trend with injected blood volume, confirming the sensitivity of the system to dynamic intragastric conductivity changes. ConclusionThe proposed 3D-gEIT framework enables quantitative reconstruction of gastric hemorrhage volume and spatial distribution with improved depth sensitivity, structural continuity, and noise robustness compared with conventional EIT approaches. By integrating optimized electrode configuration and a region-clustering-constrained reconstruction algorithm, the system provides stable dynamic monitoring under both controlled phantom conditions and in vivo physiological environments. This method offers a noninvasive, real-time, and low-cost imaging strategy for early diagnosis, postoperative monitoring, and bedside surveillance of gastric bleeding.

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

AIM To establish an HPLC-MS/MS method for the simultaneous residue determination of 11 plant growth regulators(PGRs)in Renshen Guben preparations,and to conduct a risk assessment.METHODS The analysis was performed on a 40 ℃ thermostatic ACQUITY UPLC ? Waters HSS T3 column(2.1 mm×100 mm,1.8 μm),with the mobile phase of acetonitrile-0.1％formic acid(containing 5 mmol/L ammonium formate)flowing at 0.30 mL/min in a gradient elution manner,and electro spray ionization was employed in both positive and negative ion scanning,with multiple reaction monitoring mode.The chronic and acute exposure risk values of the detected PGRs were calculated and assessed based on residue levels,health guidance values,and exposure estimates.RESULTS Eleven PGRs exhibited good linear relationships within their own ranges(R2 ≥ 0.990),whose average recoveries were 70.0％-120.0％,with RSDs all below 12.0％.In both oral liquid and pill forms,mepiquat chloride showed the highest average residue levels,while sodium 5-nitroguaiacolate exhibited the highest acute risk value(0.765 7,0.908 1)and chronic risk value(0.023 1,0.027 0).CONCLUSION Although PGRs residues are detected in Renshen Guben preparations,all levels remained within safe limits.

Objective:To investigate the views of doctors on the incidence and treatment tactics of mild progression after epithelial growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)treatment in lung adenocarcinoma and provide suggestions to optimize the counter-measure strategies.Methods:Convenience sampling was used to conduct an online questionnaire survey for doctors specializing in onco-logy and respiratory diseases.Results:584 valid questionnaires were collected,and all the doctors expressed concerns regarding mild tumor progression after EGFR-TKI treatment.The coping strategies included maintaining the original TKI treatment,adding other treatments to the original TKI,changing the regimen,and performing secondary tissue biopsy,among which,most doctors chose to add other treatments to the original TKI.Conclusions:Doctors have noticed the enlargement of target lesions in still stable disease(SD)and most frequently chose to add other treatments to the original TKI as a coping strategy.This finding can provide a reference for framing future guidelines for large sample prospective clinical studies that are needed to find the most effective synergistic treatment options.

Objective:To understand the usage situation of e-cigarettes among residents aged 18-65 in Beijing, explore the relationship between e-cigarette use and cigarette smoking as well as smoking cessation behaviors, and provide scientific support for the developing and improving policies and measures related to e-cigarettes.Methods:Using 19 684 residents data from the Beijing Non-communication Chronic Disease and Risk Factors Surveillance in 2022, complex sampling weighted methods were used to estimate proportions, and complex sampling logistic regression analysis was applied to explore the relationship between e-cigarette use, cigarette smoking, and smoking cessation.Results:Among all study participants, the proportion of those who had ever used e-cigarettes was 3.36%, with the current e-cigarette use at 1.26%. The proportion of current e-cigarette users (1.87%) and the former e-cigarette users (3.47%) were higher ( χ2=64.70, P<0.001) among males compared to females (0.60% and 0.64% respectively). The top three reasons for using e-cigarettes were wanting to quit smoking, perceiving e-cigarettes as less harmful, and enjoying the flavors of e-cigarettes. 83.54% of e-cigarette users started with cigarettes. The results of the complex sampling multivariable logistic regression analysis showed that current smoking ( OR=61.35, 95% CI: 36.98-101.76) and former smoking ( OR=31.20, 95% CI: 15.52-62.71) were positively associated with e-cigarette, while current e-cigarette use ( OR=0.13, 95% CI: 0.04-0.39) was negatively associated with quitting cigarette smoking. Conclusions:The proportion of e-cigarette use in Beijing was relatively low. E-cigarette use was associated with cigarette use and was not conducive to smoking cessation. Therefore, stronger regulatory measures and health education campaigns regarding the risks of e-cigarettes should be implemented.

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Background: Influenza A viruses (IAVs) are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications. Isorhamnetin, an abundant natural flavonoid in fruits and medicinal plants, has recently been shown to have strong antioxidative, anti-inflammatory, and antiviral effects. Objective: This study investigated the pharmacological effects of isorhamnetin on viral pneumonia and explored the underlying mechanisms by in vivo and in vitro experiments. Materials and methods: In the present study, the protective effect of isorhamnetin against IAV was evaluated by the cytopathogenic effect assay, cell counting kit-8 assay, real-time polymerase chain reaction, and immunofluorescence assay in vitro. Then the pathological damage associated with pneumonia was examined by calculating the pulmonary index and performing micro-CT and hematoxylin-eosin staining in vivo. Thereafter, the related protein or gene levels of factors in the mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathways were determined by Western blot and immunofluorescence staining. Results: Isorhamnetin exerted significant anti-influenza effects and inhibited the expression of viral RNA in A549 cells, counteracting oxidative stress and apoptosis by suppressing the production of reactive oxygen species and caspase-3. The in vivo experiment results showed that isorhamnetin (20 and 40 mg/kg) caused a significant decrease in the pulmonary index, ameliorated pathological damage in the lung tissue, decreased viral load and NA activity, and reduced cytokines and nuclear factors. Furthermore, isorhamnetin could counteract the B cell lymphoma-2/B cell lymphoma-2–associated X protein (Bax) imbalance induced by PR8, suppress activation of the MAPK pathway, and upregulate the expression of Nrf2 and HO-1. Conclusions: Isorhamnetin can protect against viral pneumonia by activating the Nrf2/HO-1 pathway and suppressing the MAPK path-way. This study deciphers the pharmacological mechanism of isorhamnetin in alleviating pathological damage in viral pneumonia and provides rationale for the application of isorhamnetin in influenza treatment.

Background: Influenza A viruses (IAVs) are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications. Isorhamnetin, an abundant natural flavonoid in fruits and medicinal plants, has recently been shown to have strong antioxidative, anti-inflammatory, and antiviral effects. Objective: This study investigated the pharmacological effects of isorhamnetin on viral pneumonia and explored the underlying mechanisms by in vivo and in vitro experiments. Materials and methods: In the present study, the protective effect of isorhamnetin against IAV was evaluated by the cytopathogenic effect assay, cell counting kit-8 assay, real-time polymerase chain reaction, and immunofluorescence assay in vitro. Then the pathological damage associated with pneumonia was examined by calculating the pulmonary index and performing micro-CT and hematoxylin-eosin staining in vivo. Thereafter, the related protein or gene levels of factors in the mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathways were determined by Western blot and immunofluorescence staining. Results: Isorhamnetin exerted significant anti-influenza effects and inhibited the expression of viral RNA in A549 cells, counteracting oxidative stress and apoptosis by suppressing the production of reactive oxygen species and caspase-3. The in vivo experiment results showed that isorhamnetin (20 and 40 mg/kg) caused a significant decrease in the pulmonary index, ameliorated pathological damage in the lung tissue, decreased viral load and NA activity, and reduced cytokines and nuclear factors. Furthermore, isorhamnetin could counteract the B cell lymphoma-2/B cell lymphoma-2–associated X protein (Bax) imbalance induced by PR8, suppress activation of the MAPK pathway, and upregulate the expression of Nrf2 and HO-1. Conclusions: Isorhamnetin can protect against viral pneumonia by activating the Nrf2/HO-1 pathway and suppressing the MAPK path-way. This study deciphers the pharmacological mechanism of isorhamnetin in alleviating pathological damage in viral pneumonia and provides rationale for the application of isorhamnetin in influenza treatment.