Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time， resulting in irreversible pathological changes that last longer than 6 months. Emodin （EMO） is a natural anthraquinone derivative derived from Rheum officinale， and its pharmacological effect has been extensively studied， exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases， and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy， EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism， in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.

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*

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

The study explores the traditional Chinese medicine （TCM） diagnostic and treatment approach to coronary microvascular disease （CMVD） from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective， different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice， four targeted treatment methods， i.e. warming， unblocking， tonifying， and activating， are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia， myocardial infarction， and coronary revascularization， with corresponding pathological mechanisms of latent pathogenic obstruction， toxic accumulation in the collaterals， and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation， staging， and transformation. Accordingly， treatment principles include warming to assist qi transformation， unblocking obstruction and dispelling turbidity， activating to disperse toxic stasis and invigorate collaterals， and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis， attention should be paid to the underlying disease， analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.

Objective To explore the expression level of plasma miRNA in patients with swallowing and cognitive dysfunction after ischemic stroke and its correlation with the severity of dysfunction.Methods A retrospective analysis was conducted on the clinical data of 109 patients with ischemic stroke who were hospitalized in the First Affiliated Hospital of Guangxi Medical University and the First Affiliated Hos-pital of Fujian Medical University from January 2023 to March 2024.The expression levels of plasma miR-140-5p,miR-17-5p,and miR-103a-3p were detected by RT-qPCR.The swallowing function was evaluated by the Wada Drinking Water Test and the Functional Oral Feeding Scale,and the cognitive function of stroke pa-tients was evaluated by the modified Rankin Scale(mRS)classification.According to the mRS rating criteria,the patients were divided into the good functional outcome group(grade≤2,n=50)and the poor functional outcome group(grade≥3,n=59).Analyzed the correlation between miRNA expression levels and the degree of functional impairment,compared the clinical characteristics of patients with different mRS grades,and used the receiver operating characteristic(ROC)curve and the area under the curve(AUC)to analyze the efficacy of miRNA in predicting the functional outcome of mRS evaluation.Results The results of Spearman correla-tion analysis showed that the expression level of miR-17-5p was negatively correlated with the classification of the Wada Drinking Water Test(r=-0.317)and the classification of the Functional Oral Feeding Scale(r=-0.457,P<0.05).Compared with the good functional outcome group,the poor functional outcome group had a lower proportion of males,shorter disease course,and higher expression level of miR-103a-3p,the differ-ences were statistically significant(P<0.05).The results of ROC curve analysis showed that miR-103a-3p(AUC=0.709,95%CI:0.611-0.808)had the ability to distinguish functional outcomes in mRS evaluation.However,miR-140-5p(AUC=0.514,95%CI:0.405-0.624)and miR-17-5p(AUC=0.527,95%CI:0.414-0.637)did not have the ability.Conclusion The expression level of plasma miR-17-5p is related to the severi-ty of dysphagia in patients in the recovery period of ischemic stroke,and miR-103a-3p is helpful for judging the functional outcomes of patients in the recovery period of ischemic stroke.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

Background: Hypertension is a major risk factor for cardiovascular diseases, including AF, which is one of the most common cardiac arrhythmias globally. AF is strongly associated with an increased risk of stroke, heart failure (HF), and cardiovascular mortality. Although intensive blood pressure lowering has been shown to reduce adverse cardiovascular events, its effect on the risk of AF remains debated. Some studies suggest a beneficial effect, whereas others are inconclusive. Therefore, a comprehensive review and meta-analysis are needed to clarify these effects. Objective: This study aims to evaluate the impact of intensive blood pressure lowering on the incidence of atrial fibrillation (AF) in hypertensive patients. Methods: We performed a systematic review and meta-analysis by searching PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library up to September 2, 2024, for randomized controlled trials comparing intensive blood pressure lowering with standard treatment in hypertensive patients. Studies were included if participants were 40 year or older with systolic blood pressure between 130 and 180 mm Hg (1 mm Hg≈0.133 kPa). Data extraction was conducted by 2 independent researchers, and statistical analysis was performed using Review Manager (RevMan) 5.4. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A random-effects model was applied if heterogeneity was detected (I > 50%). Results: A total of 6 randomized controlled trials involving 34,824 participants were included in the analysis. Intensive blood pressure lowering significantly reduced the risk of new-onset AF compared with standard treatment (RR = 0.76, 95% CI = 0.62-0.93, p < 0.01, I = 0%). Reductions were also observed in stroke (RR = 0.71, 95% CI = 0.58-0.87, p < 0.005, I = 7%), HF (RR = 0.67, 95% CI = 0.45-0.99, p = 0.05, I = 53%), and nonfatal coronary events (RR = 0.80, 95% CI = 0.70-0.92, p < 0.005, I = 39%). However, intensive blood pressure lowering had no significant effect on cardiovascular mortality or all-cause mortality compared with standard treatment. Discussion: Intensive blood pressure lowering significantly reduces the risk of AF and other cardiovascular events, such as stroke, HF, and nonfatal coronary events, particularly among high-risk hypertensive patients. These findings support the potential benefits of intensive blood pressure management in reducing AF incidence and improving overall cardiovascular outcomes, but the evidence is limited.